Priscilla’s Neurology, Haematology &

Dermatology
Table of Contents
Neuroanatomy .................................................................................................................................................... 5
Neuroanatomy = The Sensory System ........................................................................................................... 5
Neuroanatomy = The Motor System (Pyramidal, Extrapyramidal and Cerebellum) .................................... 7
Neuroanatomy = Cerebral Topography ....................................................................................................... 10
Neuroanatomy = Brainstem ......................................................................................................................... 13
Neuroanatomy = Spinal Cord ...................................................................................................................... 18
Neuroanatomy = Dermatomes and crossings .............................................................................................. 19
Cranial Nerves ................................................................................................................................................. 20
Neurological examination: Cranial Nerves .................................................................................................. 20
Principles of Cranial Nerves ...................................................................................................................... 25
1st Cranial Nerve (Olfactory Nerve) ............................................................................................................ 26
2nd Cranial Nerve (Optic Nerve) .................................................................................................................. 27
3rd Cranial Nerve (Occulomotor nerve) ....................................................................................................... 29
4th Cranial Nerve (Trochlear Nerve) ......................................................................................................... 30
5th Cranial Nerve (Trigeminal Nerve) ....................................................................................................... 30
6th Cranial Nerve (Abducens Nerve) ......................................................................................................... 31
7th Cranial Nerve (Facial Nerve) ............................................................................................................... 31
8th cranial nerve (Vestibule-cochlear nerve) ................................................................................................ 32
9th and 10th cranial nerves (Glossopharyngeal and Vagus nerve) ................................................................ 32
11th cranial nerve (Accessory nerve) ........................................................................................................... 32
12th Cranial Nerve (Hypoglossal nerve) ...................................................................................................... 33
Cranial Nerve Lesions...................................................................................................................................... 34
Approach to 7th nerve palsy ........................................................................................................................ 34
Cerebellopontine Angle Lesion ................................................................................................................... 38
Pseudo-bulbar and Bulbar Palsy .................................................................................................................. 39
Upper and lower limbs ..................................................................................................................................... 40
Examination of the Upper Limbs ................................................................................................................. 40
Upper Limb Nerves...................................................................................................................................... 42
Median Nerve............................................................................................................................................... 44
Median Nerve Palsy ..................................................................................................................................... 44
Ulnar Nerve Palsy ........................................................................................................................................ 45
Radial Nerve Palsy....................................................................................................................................... 46
Examination of the Lower Limbs ................................................................................................................ 47

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 Neurology of the Lower Limb ..................................................................................................................... 49
Foot drop ...................................................................................................................................................... 50
Brain and the Higher Centers ........................................................................................................................... 51
Gait ............................................................................................................................................................... 51
Tremors ........................................................................................................................................................ 52
Examination of Higher Centers ................................................................................................................. 53
Glasgow Coma Scale ................................................................................................................................... 55
Assessing Speech ......................................................................................................................................... 56
Examination of the Cerebellar System ........................................................................................................ 58
Neurology Pathologies ..................................................................................................................................... 60
Stroke – History-taking ................................................................................................................................ 60
Stroke – Presentation and management ....................................................................................................... 62
Transient Ischaemic Attack (TIA) ............................................................................................................... 69
Stroke - Stroke Syndromes .......................................................................................................................... 70
Intracerebral Haemorrhage .......................................................................................................................... 72
Subarachnoid Haemorrhage ......................................................................................................................... 74
Subdural Haemorrhage ................................................................................................................................ 76
Extradural (epidural) Haemorrhage ............................................................................................................. 77
Spinal cord syndromes ................................................................................................................................. 78
Case 35 | Syringomyelia .............................................................................................................................. 82
Myasthenia Gravis I ..................................................................................................................................... 83
Myasthenia Gravis II.................................................................................................................................... 85
Multiple Sclerosis ........................................................................................................................................ 89
Guillain Barré Syndrome (GBS) .................................................................................................................. 92
Motor Neuron Disease ................................................................................................................................. 95
Parkinson’s disease ...................................................................................................................................... 97
Parkinson’s disease (History-Taking) ........................................................................................................ 102
Parkinsonism (short-case) .......................................................................................................................... 104
Epilepsy...................................................................................................................................................... 106
Approach to numbness and weakness........................................................................................................ 111
Hemiplegia ................................................................................................................................................ 113
Spastic Paraparesis .................................................................................................................................. 114
Hereditary ataxias ...................................................................................................................................... 116
Friedreich’s ataxia ...................................................................................................................................... 118
Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy) ............................................... 119
Muscle disorders (Myopathies).................................................................................................................. 120
Myotonic dystrophy (Dystrophia myotonica) ............................................................................................ 121
Metabolic Myopathies/Periodic Paralysis.................................................................................................. 122
Polymyositis & Dermatomyositis .............................................................................................................. 124

2
 Dermatomyositis ........................................................................................................................................ 124
Polymyositis ............................................................................................................................................... 125
Eye ................................................................................................................................................................. 126
Examination of the Eye .............................................................................................................................. 126
Eye Signs ................................................................................................................................................... 128
Visual field defects .................................................................................................................................... 130
3rd nerve palsy ............................................................................................................................................ 132
6th nerve palsy ............................................................................................................................................ 133
Horner’s Syndrome .................................................................................................................................... 134
Ptosis .......................................................................................................................................................... 136
Conjugate Eye Movements ........................................................................................................................ 137
Haematology .................................................................................................................................................. 141
Approach to anaemia ................................................................................................................................. 141
Haemolytic anaemia................................................................................................................................... 145
Diminished Erythropoiesis......................................................................................................................... 148
Macrocytic Anaemia .................................................................................................................................. 150
Thrombocytopenia ..................................................................................................................................... 152
Idiopathic Thrombocytopenic Purpura (ITP)............................................................................................. 155
Leukemias .................................................................................................................................................. 156
Hodgkin’s Lymphoma ............................................................................................................................... 159
Myeloproliferative Disorders ..................................................................................................................... 160
Multiple Myeloma ..................................................................................................................................... 161
Coagulation disorders ................................................................................................................................ 162
Oncologic emergencies .............................................................................................................................. 163
Deep Vein Thrombosis .............................................................................................................................. 164
Pulmonary Embolism................................................................................................................................. 168
Dermatology .................................................................................................................................................. 173
Basic Dermatology..................................................................................................................................... 173
Cutaneous Lesions ..................................................................................................................................... 174
Erythema Multiforme................................................................................................................................. 175
Erythema Nodosum ................................................................................................................................... 177
Steven-Johnsons Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS) ........................................... 178
Psoriasis ..................................................................................................................................................... 180
Alopecia ..................................................................................................................................................... 183

3
Acknowledgements

Written by:
Dr Priscilla Phoon & her team of original authors

Transcribed by Class of 2013:

Amelia Yeap
Ma Wai Wai Zaw
Lucy Davis
Choo Yun Song
Cherlyn Ong
Caroline Choong
Jasline Chua
Arjun Bolem
John Loh
Wong Jiayi
Chew Bao Li
Nanthini
Ong Eng Hui

Edited and formatted by:

James Lee (Class of 2013)
Ong Eng Hui (Class of 2013)

Last Updated:
24th Febuary 2011

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Neuroanatomy
Neuroanatomy = The Sensory System
1. General sensory modalities
(a) crude touch and pressure
(b) pain and temperature
(c) fine touch and pressure
(d) vibration
(e) proprioception (conscious)
(f) proprioception (subconscious)

2. General pathway
- peripheral processes of 1 sensory neurones synapse with receptors
- central processes enter dorsal root of spinal cord
- 2 sensory neurones located either in spinal cord or brain stem
- axons cross midline and ascend in CNS
- synapse with 3 sensory neurones in thalamus
- eventually reaches sensory cortex (post-central gyrus of parietal lobe)

3. Main somatosensory systems

(a) spinothalamic (anterior → crude touch and pressure; lateral → pain and temperature)
st
- 1 -order neurone = dorsal root ganglion
nd
- 2 -order neurone = dorsal horn neurone
axons cross midline in front of the central canal
rd
- 3 -order neurone = thalamus
- sensory cortex
(b) dorsal column medial lemniscus
st
- 1 -order neurone = dorsal root ganglion
ascend in dorsal column (fasciculus gracilis and fasciculus cuneatus)
nd
- 2 -order neurone = medulla oblongata (gracile and cuneate nuclei)
axons cross midline to form medial lemniscus
rd
- 3 -order neurone = thalamus
- sensory cortex
(c) spinocerebellar
st
- 1 -order neurone = dorsal root ganglion
nd
- 2 -order neurone = dorsal root neurone
axons do not cross midline
- terminates in vermis of cerebellum via superior and inferior peduncles
(d) trigeminothalamic

4. Thalamus
rd
- location = large mass of grey matter in lateral wall of 3 ventricle and floor of lateral ventricles
lies between midbrain and cerebral hemisphere
hypothalamus lies just inferiorly
- function = sensory (receives all contralateral general sensory fibres from spinal cord and brain stem;
receives visual and auditory input)
motor (receives afferents from cerebellum, basal nuclei and motor cortex)
cognitive
- sensory fibres ascend through the brain stem → synapse in the thalamus → relayed to the sensory
cortex via internal capsule (motor fibres are relayed to the brainstem via internal capsule without
passing through the thalamus)
- lesions to VPL (ventral posterior lateral) and VPM (ventral posterior medial) nuclei can cause loss of all
sensation on contralateral side of body
- thalamic strokes are not known for motor manifestations

Issues to discuss
1. Positive Romberg can occur in proprioceptive or vestibular defects
- maintaining balance requires at least 2 out of the 3 senses = vision, vestibular sense and proprioception
- these 3 modalities feed into the cerebellum
5
 - patient with a pure cerebellar lesion will not have a positive Romberg = will sway with or without eyes closed

2. Lesion in the dorsal column

- causes sensory ataxia = movement disorder resulting from a sensory impairment
- Can only stand unsupported min = Feet well apart
Broad based gait
Gaze directed downwards
Stamping action (maximizes remaining proprioceptive function)

- Testing of the dorsal column loss

o Romberg’s sign and gait disturbances
o 2 – point discrimination (fine touch and pressure)
o Vibration sense
o Proprioceptive loss

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Neuroanatomy = The Motor System (Pyramidal, Extrapyramidal and Cerebellum)
1. Lower motor neurone
- motor neurons in the spinal cord/brain stem that supply skeletal muscles directly
- receive information from = pyramidal tract
extra-pyramidal tract
spinal cord inter-neurones
peripheral sensory organs (muscle spindles)
- clinical features = flaccid paralysis/hypotonia
muscle atrophy (anterior horn cells produce nourishing factor that is conveyed to the
muscles by axonal transport)
fasciculations
hyporeflexia/areflexia

2. Upper motor neurone

- motor neurons in the cerebral cortex (primary motor cortex) and other motor nuclei in other parts of the
brain/brainstem
- ultimately influence LMN
- types of descending motor pathways
(a) conscious voluntary pathways (pyramidal tract)
* corticospinal tract
* corticobulbar (brainstem) tract
(b) postural pathways (extrapyramidal tract)
* rubrospinal tract (red nucleus in midbrain)
* vestibulospinal tract (vestibular nuclei in pons)
* tectospinal tract (superior colliculus in midbrain)
* reticulospinal tract (reticular formation in pons and medulla)
* basal ganglia
- clinical features = initial flaccid paralysis and hyporeflexia
clasp-knife spasticity (increased tone in UL flexors and LL extensors due to destruction
of corticoreticulospinal tract stretch reflex hyperactivity)
muscle weakness (UL extensors/abductors and LL flexors/abductors)
little muscle atrophy (unless severe disuse atrophy)
clonus
hyper-reflexia but absent superficial reflexes (abdominal)
up-going plantar response (Babinski’s positive)

3. Corticospinal tract
- function = voluntary control of discrete/skilled movements
- UMN originate from cerebral cortex (pre-central gyrus – 1 motor cortex
supplementary motor area – 2 motor cortex
post-central gyrus – sensory cortex [modulate afferent inputs])
axons of UMN pass through corona radiata
internal capsule
midbrain (crus cerebri)
pons
medulla (90% decussate in the pyramids to form lateral corticospinal tract; 10% do not decussate and
form anterior corticospinal tract which eventually decussate at the spinal cord)
synapse with anterior horn cells (spinal grey matter) just prior to leaving the cord

7
4. Corticobulbar (corticonuclear) tract
- function = controls muscles of the face, head and neck
influences CN 3-12 except vestibulocochlear nerve (no motor function)
- UMN originate from cerebral cortex
crosses midline just above motor nuclei
terminate in brainstem motor nuclei
- innervates cranial nerve nuclei bilaterally except lower facial nucleus (contralateral innervation)
* unilateral damage to the corticobulbar tract does not cause massive dysfunction
* bilateral lesions of the corticobulbar tracts result in pseudobulbar palsy

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5. Extra-pyramidal system
- descending pathways that influence muscle tone, posture and movement
- affects LMN by modifying and adjusting influence of pyramidal system
- basal ganglia disorders are characterised by meaningless unintentional movements that occur
unexpectedly
- clinical features = increased tone that is continuous throughout the range of movement (rigidity)
involuntary movement (tremor, tics, dystonia, chorea, athetosis, hemiballismus, myoclonus)
cogwheel rigidity (tremor + rigidity)
bradykinesia
postural instability

6. Cerebellum
- function = balance, muscle tone, coordination of voluntary movements on ipsilateral side
- located in posterior cranial fossa between temporal lobe, occipital lobe and brainstem
- lesion in a cerebellar hemisphere causes lack of coordination on the ipsilateral side
- clinical features = dysdiadochokinesia
ataxia (truncal)
slurred speech
hypotonia
intention tremor (initial part of movement is normal until target is approached)
nystagmus
gait (ataxic = broad-based, tendency to veer to the side of the lesion)
- central vermis of the cerebellum is concerned with coordination of gait and posture
lesions affecting here produces characteristic ataxic gait

7. Summary
* ‘plegia’ = paralysis
‘paresis’ = weakness
(a) monoplegia (paralysis affecting only 1 limb) = partial internal capsule lesion
motor cortex
(b) hemiplegia = corona radiata
internal capsule
crus cerebri of midbrain
pons
medulla oblongata
high cervical cord (ipsilateral hemiplegia)
(c) paraplegia (paralysis affecting both lower limbs) = cortical paraplegia
thoracic cord leison
(d) quadriplegia (paralysis affecting all 4 limbs) = high cervical cord lesion
brainstem lesion (basilar artery thrombosis)

9
Neuroanatomy = Cerebral Topography

10
11
12
Neuroanatomy = Brainstem

1. Structure
- made up of the midbrain, pons and medulla oblongata
- location = extends between the thalamus and spinal cord
begins at the foramen magnum
anterior to the cerebellum and connected to it by 3 cerebellar peduncles (superior, middle, inferior)
- contains 10 cranial nerve nuclei (except CN 1,2)
apparatus for controlling eye movements (CN 3,4,6)
ascending and descending pathways
reticular formation

2. Ascending pathways
(a) spinothalamic tract
(b) dorsal column medial lemniscus
st
- 1 -order neurones synapse in the ipsilateral dorsal column nuclei (gracile and cuneate nuclei)
nd
- 2 -order neurones decussate in the medial lemniscus and ascend on the contralateral side to
synapse in the thalamus

3. Descending pathways
(a) corticospinal tract

4. Midbrain

- cerebral aqueduct = continuation of the central canal in the spinal cord

13
 - superior colliculus = afferent fibres for pupillary light reflex synapse here before terminating in the EW
nucleus
(a) Perinaud’s syndrome = lesions affecting the area of the midbrain just below the superior colliculus
produce difficulty with upward gaze, nystagmus on attempted convergence
and poor pupillary reaction to light but not to accommodation
- red nucleus = involved in motor control; lesions here produce contralateral ataxia and tremor
- substantia nigra = synthesizes dopamine; degeneration associated with Parkinson’s disease
- crus cerebri = contains descending corticospinal tract

5. Pons

- medial longitudinal fasciculus = lesions here result in internuclear ophthalmoplegia

- lateral gaze centre = lesions here result in ipsilateral gaze palsy
- trigeminal nerve nucleus = exits at the level of mid-pons
(a) high pontine lesions = contralateral pain and sensory loss both in the face and extremities
(b) medulla/lower pontine lesions = ipsilateral pain and sensory loss in the face
contralateral pain and sensory loss in the extremities

14
15
6. Medulla

16
 th
- medial structures = pyramidal tract, dorsal column and 12 nerve nucleus
(a) medial medullary syndrome = ipsilateral tongue paralysis
contralateral hemiplegia
contralateral loss of touch, vibration and proprioception
- lateral structures = sympathetics, vestibular + CN 9 + CN 10 nuclei, spinothalamic tract, spinal trigeminal
nucleus, spinocerebellar tract
(a) lateral medullary syndrome (Wallenberg’s syndrome) = contralateral pain and sensory loss in extremities
ipsilateral pain and sensory loss in the face
ipsilateral Horner’s syndrome
ipsilateral cerebellar signs
vertigo, nausea, nystagmus
dysphagia, impaired gag reflex, dysarthria
vocal cord paralysis, hoarseness
- descending sympathetics
(a) Horner’s syndrome = ptosis, miosis, facial anhidrosis

7. Blood supply
- arterial supply by the vertebro-basilar system
(a) midbrain (cerebral peduncles) = central arteries from the circle of Willis
anterior choroidal artery
(b) midbrain (tectum) = posterior cerebral artery
posterior choroidal artery
superior cerebellar artery
(c) pons = pontine arteries
(d) medulla (medial) = medullary branches of verterbral arteries
(e) medulla (lateral) = posterior inferior cerebellar artery
- drains into 2 internal cerebral veins → great cerebral vein → straight sinuses

8. Summary
- cerebral lesion = entire contralateral side of body
- brainstem lesion = crossed symptoms (ipsilateral face and contralateral extremities)
- spinal cord lesion = sparing of cranial nerves
paraparesis (LL), quadriparesis (UL+LL), sensory dissociation

17
Neuroanatomy = Spinal Cord

1. Structure
- caudal extension of the brain that is located in the vertebral column
- 31 pairs of spinal nerves attached to it via dorsal and ventral nerve roots
* exit vertebral column through intervertebral foramina
- ends at L1/L2 level in adults
- forms cauda equina below termination
- pia mater ends as filum terminale which anchors spinal cord to the coccyx
* dura and arachnoid mater end at S2/S3 level
- spinal segment does not correlate with vertebral segment due to differential growth (latter grows
faster than former)
- central grey matter contains neuronal cell bodies and synapses
peripheral white matter contains ascending and descending nerve fibres

2. Arterial supply
(a) anterior and posterior spinal arteries
- given off by vertebral arteries before they merge to form the basilar artery
- anterior spinal artery supplies the entire cord except for the dorsal columns
* anterior spinal artery thrombosis = paralysis and loss of pain and temperature sensation
intact vibration and proprioception
(b) segmental arteries
- enter vertebral column through intervertebral foramina

Issues to discuss
1. Hemisection of the spinal cord at the level of T1 actually produces contralateral loss of pain and temperature
of T3 dermatome and below as the fibres usually ascend 1-2 segments before crossing over

18
Neuroanatomy = Dermatomes and crossings

19
Cranial Nerves
Neurological examination: Cranial Nerves
Start
1. Introduce yourself, shake the patient’s hand and explain your purpose (myotonic dystrophy)
2. Assess for hoarseness of voice (recurrent laryngeal nerve lesion)
3. Ask the patient to sit at the edge of the bed/chair

General Inspection
1. Look at the patient’s head, face and neck
 Hydrocephalus (in infancy before the closure of sutures -> resemble inverted triangle)
 Acromegaly
 Facial asymmetry
 Eyes = ptosis, proptosis, squint ( head tilt)
 Skin lesions
a. Neurofibromata + axillary freckling + café au lait patches (NF type 1)
b. Herpes zoster
c. Haemangioma in the distribution of trigeminal nerve (Sturge-Weber syndrome)
d. Hypopigmented macules (tuberous sclerosis)
2. Look at the upper and lower limbs
 Posture = hemiplegic
st
1 Cranial Nerve (Olfactory Nerve) Not tested usually unless patient complains of loss of smell (anosmia) or there are
signs of frontal/temporal lobe lesion

1. Ask patient if he has noticed any change in smell recently

 If yes = take a bedside object (fruits or soap, etc) and test one nostril at a time
 If there is a loss of smell = examine nasal passages for polyps and mucosal thickening
nd
2 Cranial Nerve (Optic Nerve) Visual acuity, visual fields, fundi

Visual Acuity
1. Ask the patient to put on his glasses (if he uses them)
2. Test visual acuity of BE before testing each eye separately
 Instruct patient to cover R eye with R hand and vice versa
 Ask him to count fingers
 If cannot = wave your hand and ask if he can see that
 Still cannot = test for light perception with pen torch

Visual fields
1. Patient’s head should be at arm’s length away from you
2. Test each eye separately by asking patient to cover R eye with R hand. At the same time, cover your opposite eye and ask
patient to look you in the other eye
3. Position your finger halfway between the patient and yourself and bring it in from just outside your peripheral vision and
ask if the patient can see
 Patient must be looking directly at your eye
 Test all 4 quadrants

Fundoscopy
1. Dim the room
2. Instill tropicamide if needed (mydriatic)
3. Tell the patient “I am going to use this instrument to look into your eye. To do so, I will have to come very close to you so
please do not be alarmed. There will be a bright light shining into your eyes so if at any point in time you feel uncomfortable
please let me know okay? Can you please now look straight ahead in front of you.”
4. Use your right eye to look into the patient’s right eye and vice versa
5. Look at the cornea, iris and the lens (absence of orange-red reflex -> cataracts)
6. Search for the optic disc (follow a large retinal vein back towards the disc)

20
  Blurred margins -> papilloedema (indicates raised ICP; examine retinal veins for spontaneous pulsations = presence
excludes raised ICP but absence does not exclude it), papillitis (demyelination of anterior part of optic nerve)
 Pale and white -> optic atrophy (disc should be yellow normally)
7. Estimate the cup:disc ratio (>0.6 may indicate glaucoma)
8. Examine each of the 4 quadrants for abnormalities
 Diabetic retinopathy (haemorrhages, hard exudates, cotton wool spots, maculopathy, neovascularisation, laser scars)
 Hypertensive changes (silver wiring, AV nipping, flame haemorrhages and cotton wool spots, papilloedema)
 Retinal detachment
 Retinitis pigmentosa (most common form of retinal dystrophy; scattering of black pigment in a criss-cross pattern in the
periphery of the retina; causes loss of peripheral vision and night blindness)
 Fundus appears milky-white -> central retinal artery occlusion (retinal oedema; arteries greatly reduced in diameter;
cherry–red spot)
rd th th
3 , 4 , 6 Cranial Nerves Pupillary reflex, Marcus-Gunn sign, accommodation, eye movements, nystagmus

Pupillary reflex
1. Observe for ptosis (levator palpebrae superioris and Mueller’s muscle)
2. Ask the patient to look straight ahead and examine pupils for size, shape and equality by shining the pen torch upwards
from below the patient’s chin
3. Shine the pen torch from the side into one of the pupils and observe direct response. Do it again and look into the other eye
for consensual response
 Repeat the same procedure in the other eye
 Optic nerve lesion = no papillary response bilaterally when light is shone in affected eye bilateral papillary response
when light is shone in normal eye

Marcus-Gunn sign
1. Swing the torch rapidly from one eye to the other and observe for RAPD
 Affected eye will dilate paradoxically (optic atrophy/severely reduced visual acuity)

Accomodation (especially if reaction to light is poor)

1. Ask the patient to look straight ahead and shine light from above him. Then ask him to focus his eyes on your finger close to
his face)
 Normal response is papillary constriction
 Loss of papillary reflex but intact accommodation =
a. Midbrain lesion (Argyll-Robertson pupil)
b. Ciliary ganglion lesion (Adie’s pupil)
c. Parinaud’s syndrome (loss of vertical gaze a/w nystagmus on attempted convergence)

Eye movements
1. Ask the patient to follow your finger moving in a “H” pattern with both eyes without moving the head and to indicate if
double images are seen
 Note failure of eye movement and nystagmus
 If any abnormality detected, each eye must be tested separately
2. Diplopia (early sign of ocular muscle weakness)
 Ask patient if images are side by side (lateral/medial recti) or one above the other (obliques/superior and inferior recti)
 Ask in which direction is there maximum image separation (greatest in the direction in which the weak muscle has its
purest action) --- determine which pair of muscles is responsible
 At the point of maximum separation, cover one eye and ask which image disappears. Loss of the outermost image
indicates that covered eye is responsible

Example: diplopia is maximal when eyes deviate to the right and downwards weak right inferior rectus OR left
superior oblique

Testing of eye movements

 Lateral rectus = abduction
 Medial rectus = adduction
 Superior rectus = up and out (action is in and up)
 Inferior rectus = down and out (action is in and down)
 Superior oblique = down and in (action is down and out)

21
  Inferior oblique = in and up (action is up and out)

Diplopia (monocular, binocular)

 False image paler, blurrer and always more peripheral than the real image
 False image arises from the affected eye
 Monocular diplopia = astigmatism, dislocated lens, hysteria

3. Nystagmus
 Involuntary jerky eye oscillations with a slow drift in one direction (pathological brainstem lesion) followed by a fast
corrective movement in the opposite direction (frontal control)
 Maximal when the eyes are turned in the direction of the fast gaze
 Note direction of fast phase and gaze direction when nystagmus is maximal
 Physiological nystagmus =  2 beats or at extremes of gazes
 Horizontal nystagmus
a. Vestibular lesion (a/w deafness and tinnitus)
i. Acute = away from the lesion
ii. Chronic = towards the lesion
b. Cerebellar lesion
i. Towards the lesion
c. Medial longitudinal fasciculus lesion = internuclear opthalmoplegia (eg MS)
d. Toxic causes = alcohol, phenytoin, benzodiazepine, barbiturates

 Vertical nystagmus (central lesion) gaze-dependent, vertical, rotatory, unilateral nystagmus

th
a. upbeat nystagmus = lesion in the midbrain or base of 4 ventricle
b. downbeat nystagmus = lesion in the foramen magnum/cerebellar
c. toxic causes = alcohol, phenytoin, benzodiazepines, barbiturates
 Varies with head position = BPPV
th th th
5 , 7 , 8 Cranial Nerves and cerebellum (latter if indicated)
th
1. 5 cranial nerve
 Use sharp toothpick and poke anterior chest wall first (reference point), then poke forehead, cheeks and lower jaw.
Compare both sides.
 An area of dull sensation should be mapped out by testing pin-prick sensation progressively from the dull area
to a sharp area
 Inspect for wasting of the temporalis and masseter muscles
 Ask patient to:
 Clench teeth and palpate contraction of masseter muscles
 Open mouth and note jaw deviation to the side of the lesion (pterygoid muscles) “Don’t let me close your
mouth”
th
2. 7 cranial nerve
 Inspect for facial asymmetry (unilateral drooping of corner of mouth, smoothing of wrinkled forehead and nasolabial
fold)
 Ask patient to:
 Look up and wrinkle forehead (frontalis) = unaffected in UMN 7 nerve palsy
th

 Shut eyes tightly (orbicularis oculi) = may be occasionally unaffected in UMN 7 nerve palsy
th

i. Eyelash sign (can bury eyelashes?)

th
ii. Bell’s phenomenon = present in everyone, only visible in LMN 7 nerve palsy, upward movement of the
eyeball with incomplete eye closure
 Puff up cheeks (buccinator)
i. Tap with finger over each cheek to detect ease of air expulsion on the affected side
 Smile and show teeth (orbicularis oris)


th
UMN 7 nerve palsy – contralateral lower quadrant of face
th
LMN 7 nerve palsy – ipsilateral half of face
 LMN lesion  check for ear and palatal vesicles of herpes zoster (Ramsay Hunt syndrome)

th
In cases of 7 nerve palsy – check CN 5, 6, 8 and cerebellum
 UMN lesion (internal capsule lesion) – don’t need to test cerebellum

22
  LMN lesion – test cerebellum
 In both lesions must check neurological status of upper and lower limbs
th
3. 8 cranial nerve
 Tell the patient that he will hear a sound and to indicate to you when it starts and stops
 Ask if the 2 sounds are the same
 Use the 512 Hz tuning fork
 If hearing is impaired  do Weber’s test

Weber’s Test
Place the base of the tuning fork in the middle of forehead and ask which ear it is louder in.
 Normal – sound heard in centre of the forehead
 Conductive deafness – deaf ear louder
 Sensorineural deafness – normal ear louder

Rinne’s Test (not usually done)

Hold tuning fork on mastoid process (bone conduction) and in front of ear (air conduction). Ask patient which sound is louder.
Normally air conduction is better than bone.
 Conductive deafness – bone conduction better
 Sensorineural deafness – as per normal (both are reduced equally)

4. Cerebellum – balance and coordination

 Tap hands back and forth repeatedly (Dysdiadochokinesia)
 Patient’s arm must be in “chicken-stance” and ask him to touch nose with index finger, then twist outwards and extend
arm to touch your finger. Change the position of your finger (intention tremors and dysmetria)
th th th
9 , 10 and 12 Cranial Nerves
th
1. 12 cranial nerve
 inspect tongue at rest on the floor of mouth and look for wasting and fasciculations
 ask patient to stick out tongue (deviates to affected side)
o usually indicates unilateral LMN lesion
o unilateral UMN lesion does not cause deviation secondary bilateral cortical innervation
 ask him to push tongue against cheek to test power. Repeat on the other side.
th
2. 10 cranial nerve
 inspect the palate and ask the patient to say “ah”. Observe the arches to detect asymmetry (deviates to normal side)
 ask the patient to speak to assess hoarseness and then to cough (bovine cough occurs with recurrent laryngeal nerve
lesions)
th
3. 9 cranial nerve
 gag reflex
th
11 Cranial Nerve (central division supplies motor fibres to CN10; spinal division supplies
trapezius and sternomastoid muscles)

1. Inspect for wasting of muscles

2. Ask patient to raise shoulders and try to push them down (trapezius)
3. Ask patient to turn his head to the side against your hand (sternomastoid). Repeat on the other side. The muscle tested is
the one on the opposite side

End
st th
1. Corneal reflex (1 to be lost in 5 nerve palsy)
Ask the patient to look in the opposite direction while you touch the cornea with a wisp of cotton wool brought to the eye from
the other side. Reflex blinking of both eyes is a normal response. Ask the patient if can feel touch of cotton wool. Repeat it on
the other eye. Sensory component mediated by ophthalmic division of CN5, while motor component mediated by CN7
(innervates orbicularis oculi).

23
2. Gag Reflex
Touch the back of the pharynx on each side with a cotton bud. Ask the patient if he can feel each time. Normal response is reflex
contraction of soft palate. CN 9 is the sensory component while CN10 is the motor component.

3. Jaw Jerk
Place your finger on the patient’s chin and hit downards with the tendon tapper. In normal individuals, the jaw jerk is not usually
observed. It is, however, exaggerated in a UMN lesion (pseudo-bulbar palsy). If present, it indicates a lesion above the mid-pons.
The jaw jerk is due to the action of the masseter muscles which is supplied by the trigeminal nucleus.

4. Pronator drift

5. Babinski sign (UMN sign)

6. Walk the patient (long tract signs)

“This patient is a pleasant looking middle-aged Chinese gentleman who appears to be alert, well, orientated and comfortable at
rest. On general inspection, I do not/do note facial asymmetry, ptosis, strabismus or neurocutaneous skin lesions.”

24
Principles of Cranial Nerves
1. All come from the brainstem except for cranial nerves 1 and 2
- mid-brain = CN 3 + 4
- pons = CN 5 + 6 + 7
- ponto-medullary junction = CN 8
- medulla = CN 9 + 10 + 11 + 12
* always examine long tracts (descending pyramidal and ascending spinothalamic tracts),
cerebellar signs and tremors (red nucleus in mid-brain)

2. All must pass through the meninges as they exit the brainstem
- can be affected in meningitis or meningeal metastases
- chronic meningitis (TB, fungal, malignant) tends to pick off the lower cranial nerves one by one

3. All occur in groups

- CN 3+4+51+6 = cavernous sinus (aneurysm, tumour, thrombosis)
superior orbital fissure (Tolosa-Hunt syndrome)
- CN 2+3+4+6 = orbital apex
- CN 5+6 = petrous temporal bone
- CN 5+7+8 and cerebellum = cerebellopontine angle (acoustic neuroma)
- CN 9+10+11 = jugular foramen
- CN 9+10+12 = post-NPC radiation
bulbar palsy (bilateral LMN involvement)
pseudobulbar palsy (bilateral UMN involvement)

4. Can be affected as part of a systemic disease e.g. DM, MS, GBS, sarcoidosis, peripheral neuropathy,
vasculitis (PAN, SLE), syphilis

25
1st Cranial Nerve (Olfactory Nerve)
1. Anatomy
- purely a sensory nerve
- fibres arise in the mucous membranes of the nose  pass through cribriform plate of the ethmoid bone
 synapse in the olfactory bulb  olfactory tract runs under the frontal lobe  terminates in ipsilateral medial
temporal lobe

2. Unilateral loss of smell

(i) head trauma without a fracture
(ii) early meningioma of the olfactory groove

3. Bilateral loss of smell

(i) URTI (sinusitis, rhinitis)
(ii) ethmoid tumours
(iii) frontal lobe tumours
(iv) frontal fractures or after pituitary surgery
(v) congenital (Kallmann’s syndrome)
(vi) meningioma of the olfactory groove
(vii) meningitis (give dexamethasone)

26
2nd Cranial Nerve (Optic Nerve)

Anatomy
- purely a sensory nerve
- passes through the orbital apex close to the ophthalmic artery and joins the nerve from the other side to
form the optic chiasm
- fibres from the temporal visual fields (nasal halves of the retina) cross in the chiasm while those from the
nasal visual fields (temporal halves of the retina) do not fibres from the left visual field terminate in
the right occipital lobe and vice versa
- fibres for the light reflex from the optic chiasm finish in the superior colliculus  synapse with both the
3rd nerve nuclei in the midbrain
- fibres leaving the optic chiasm are concerned with vision  travel in the optic tract  lateral geniculate
body in the thalamus  internal capsule  optic radiation  visual cortex of the occipital lobe
- fibres serving the lower quadrants end in the parietal lobe homonymous inferior quadrantanopia
fibres serving the upper quadrants end in the temporal lobe homonymous superior quadrantanopia

Visual acuity changes

- bilateral blindness of sudden onset = bilateral occipital lobe infarction (posterior circulation)
bilateral occipital lobe trauma
bilateral optic nerve damage (methylalcohol poisoning)
hysteria
- unilateral blindness of sudden onset = central retinal artery / vein occlusion
temporal arteritis (ischaemia of posterior ciliary artery)
non-arteritic ischaemic optic neuropathy
optic neuritis
- bilateral blindness of gradual onset = cataracts
acute glaucoma
macular degeneration
ischaemic neuropathy
diabetic retinopathy (vitreous hb, retinal detachment)
bilateral optic nerve or chiasmal compression
bilateral optic atrophy (chronic papilloedema, MS, Friedrich’s ataxia,
retinitis pigmentosa, glaucoma, optic nerve
compression by SOL)

Visual pathway lesions

- lead to visual field defects
- can occur following damage at optic nerve, optic chiasm, optic tract, optic radiation and visual cortex
- Types of defects:
(a) Monocular blindness = unilateral optic nerve damage e.g. vascular, tumour
(b) Bitemporal hemianopia = optic chiasm lesion e.g. pituitary adenoma, craniopharyngioma, suprasellar
meningioma, ICA aneurysm
(c) Binasal hemianopia = very rare, due to bilateral lesions affecting uncrossed optic fibres e.g. ICA atheroma
(d) Homonymous hemianopia = loss of vision in the entire contralateral visual field
lesions in optic tract, optic radiation and visual cortex e.g. vascular, tumour
(e) Homonymous quadrantanopia = lesion in temporal/parietal lobes e.g. vascular, tumour
(f) Homonymous hemianopia with macular sparing = lesions in visual cortex e.g. ischaemia
* due to dual blood supply from MCA and PCA
* not the case if a destructive process is responsible e.g. tumour, abscess, haemorrhage

27
Causes of papilloedema
1. Raised ICP
(a) space-occupying lesion (tumour, abscess)
(b) hydrocephalus (enlarged ventricles)
- Obstruction e.g. tumour, aqueduct stenosis
- Increased formation of CSF e.g. choroid plexus papilloma
- Decreased absorption of CSF e.g. tumour causing venous compression, meningitis
(c) benign intracranial hypertension (small/normal-sized ventricles)
- idiopathic, OC, steroids, head trauma, Addison’s disease

2. Retro-orbital lesion
(a) cavernous sinus aneurysm/tumour/thrombosis

3. Grade 4 hypertension

4. Central retinal vein thrombosis

5.
Papilloedema Papillitis
usually bilateral involvement usually unilateral involvement
gradual onset sudden onset
swollen optic disc without venous pulsations swollen optic disc
normal visual acuity (early on) poor visual acuity
large blind spot large central scotoma
peripheral constriction of visual fields pain on eye movement
normal colour vision colour vision affected (esp red desaturation)

6. Optic neuritis
- causes = MS
infective (infectious mononucleosis, syphilis, sinusitis)
drugs (ethambutol, chloroquine, alcohol)
metabolic (vitamin B12 deficiency)
ischaemia (DM, temporal arteritis)
- clinical features = pain on eye movement
loss of central and colour vision
RAPD
papillitis

28
3rd Cranial Nerve (Occulomotor nerve)
1. Actions
a. Pupillary constriction
b. Levator palpebrae superioris
c. Extraocular muscles except superior oblique (CN IV) and lateral rectus (CN VI)

2. Pupillary reflex
a. Afferent limb = optic n.; efferent limb = occulomotor n.
b. Depends on a balance of parasympathetic and sympathetic innervations
c. Parasympathetic innervations supplied by Edinger-Westphal nucleus  constriction; sympathetic innervations
 dilation
d. Optic n.  optic chiasm  optic tract  superior colliculus  EW nucleus in the midbrain  efferent motor
fibres from occulomotor nucleus travel in the wall of cavernous sinus together with CN IV, V 1, VI 
iridoconstrictor fibres terminate in the ciliary ganglion
nd
e. Sympathetic fibres from hypothalamus  ciliospinal centre in the spinal cord at C8, T1 & T2  synapse  2
rd
order neurons exit thoracic cord  synapse at superior cervical ganglion  3 order neurons travel with ICA
to the eye

rd
3. Clinical features of 3 nerve palsy
a. Complete ptosis (partial ptosis with incomplete lesion)
b. Divergent squint (eye is down & out)
c. Dilated pupil (unreactive to light & accommodation)

rd
4. Medical versus surgical 3 nerve palsy
rd rd
Medical 3 Surgical 3
6 conditions to fulfil Dilated and sluggish pupil
1. Pupillary sparing x 2/52 - 90% pupil involvement, 10% pupil sparing
rd
2. Complete 3 nerve palsy (eye is ‘down and out’; complete - Causes: aneurysm (PCA aneurysm), tumour
ptosis) (NPC), abscess, ↑ICP if bilateral involvement
rd th
3. Isolated 3 nerve palsy (exclude 4 nerve involvement by (Hutchinson’s pupil = uncal herniation through
asking patient to look down & out  look for intortion) the tentorium compressing the nerve)
4. Risk factors: DM, HTN, hyperlipidemia, age, smoking,
vasculitis
5. Complete recovery within 12 weeks
6. No aberrant regeneration

Pupillary sparing
rd
- Pupillary fibres located on the outer surface of 3 nerve
- Tends to be affected in compressive situations, i.e. surgical
rd
3
rd
- Unlikely to be affected in medical 3 = rich anastomoses
supplying these fibres; inner fibres affected first
- 80% pupil sparing, 20% pupil involvement
rd
5. Approach to isolated 3 nerve palsy

Pupil Ptosis Investigations

Dilated Partial CT/MRI  4-vessel angiogram
Complete
Spared Partial Serial observation of pupil for 1 week (could be a growing aneurysm)
MRI if no improvement within 12 weeks (look for superior division paresis [superior division divides at
superior orbital fissure]  supplies levator palpebral superioris and superior rectus)
Complete Observation
MRI if no improvement in 12 weeks (e.g. multiple sclerosis)
rd
*NB. Aneurysms in the cavernous sinus can compress both sympathetic and 3 nerve :. pupil ‘spared’

29
4th Cranial Nerve (Trochlear Nerve)
1. Innervates superior oblique muscle of the eye
- test by asking the patient to adduct the eye and then look down (‘look towards your nose’)

2. Clinical presentation
(a) diplopia on looking down and in (often noticed on descending stairs)
(b) head tilt to the contralateral shoulder (ocular torticollis)
th
3. Causes of 4 nerve palsy (rare)
(i) idiopathic
(ii) congenital form decompensated by minor head injury
(iii) trauma
(iv) vascular

5th Cranial Nerve (Trigeminal Nerve)

1. Anatomy
- contains both sensory and motor fibres
- motor part of the nerve supplies muscles of mastication
- motor nucleus confined to the pons; sensory nucleus extends from spinal cord to midbrain
- nerve itself leaves the pons from the cerebellopontine angle  runs over temporal lobe in the middle cranial
fossa  trigeminal ganglion at the petrous temporal bone  3 sensory divisions arise
rd th th
* V1 (ophthalmic division) --- runs in the cavernous sinus with 3 , 4 and 6 cranial nerve; emerges from
the superior orbital fissure to supply skin of forehead, cornea and
conjunctiva
* V2 (maxillary division) --- emerges from infraorbital foramen to supply skin in the middle of the face and
mucous membranes of the upper part of the mouth, palate and nasopharynx
* V3 (mandibular division) --- largest division; runs with motor nerve; emerges from foramen ovale to
supply skin of lower jaw and mucous membranes of the lower part of the
mouth
- pain and temperature fibres from the face  trigeminal ganglion  spinal trigeminal nucleus  2 -order
nd

neurones descend in the medulla  upper cervical cord  ascend as trigeminothalamic tract  cross at
mid-pons  thalamus  sensory cortex
- total loss of sensation in all 3 divisions = lesion is at the ganglion or sensory root
- total loss of sensation in only 1 division = post-ganglionic lesion
th
2. Causes of 5 nerve palsy
(a) Central (pons, medulla, upper cervical cord) = vascular, tumour
(b) Cavernous sinus = aneurysm, tumour, vascular
(c) Peripheral (middle fossa) = aneurysm, tumour (NPC), chronic meningitis, # middle fossa
(d) Trigeminal ganglion = trigeminal neuroma, meningioma, acoustic neuroma, herpes zoster

3. Herpes zoster affects V1 (ophthalmic branch)

- can cause blindness (V1 supplies the cornea) = examine tip of the nose to see if it has been affected as well
(supplied by the same nasociliary branch)
- refer ophthalmologist
- treated with acyclovir 800mg 5x/day (8am, 12pm, 4pm, 8pm, 12am)

4. Trigeminal neuralgia
- clinical features = sudden severe shooting pain in the distribution of part of the trigeminal nerve
more commonly in elderly people (occurrence in a young woman suggests MS)
usually precipitated by an activity e.g. brushing teeth, eating
intact sensation
- causes = pontine lesion
compression of trigeminal nerve by vascular abnormality
- differentials = sinusitis
dental abscess
herpes zoster
30
6th Cranial Nerve (Abducens Nerve)
1. Innervates lateral rectus muscle of the eye
- test by asking the patient to look outwards (i.e. abduction)
th
2. Causes of 6 nerve palsy
th
(a) True 6 nerve palsy
- DM = mononeuritis multiplex
- inflammation = MS, GBS
- tumour = NPC
- vascular = pontine infarction, vasculitis, aneurysm
- infective = chronic meningitis (TB, fungal infection, malignancy)
- trauma
- Wernicke’s encephalopathy (syndrome of ophthalmoplegia, confusion and ataxia a/w Korsakoff’s
psychosis 2 thiamine deficiency; bilateral involvement)
- idiopathic (unilateral involvement)
th
(b) Pseudo-6 nerve palsy
- muscle (myositis, thyroid eye disease, entrapment)
- NMJ (myasthenia gravis)
- false-localising sign (raised ICP)
th
- congenital absence of 6 nerve nucleus

7th Cranial Nerve (Facial Nerve)

1. Anatomy
th th
- 7 nerve nucleus lies in the pons next to the 6 nerve nucleus
- nerve leaves the pons through the cerebellopontine angle  enters facial canal  becomes
geniculate ganglion  leaves skull via stylomastoid foramen  parotid gland  5 terminal branches
(temporal, zygotic, buccal, mandibular and cervical)
th
- supplies stapedius muscle, taste fibres from anterior 2/3 of the tongue (via chorda tympani which joins 7
nerve in the facial canal), lacrimation glands and muscles of facial expression dysarthria, drooling of saliva,
facial asymmetry
th
2. Causes of 7 nerve palsy
(a) UMN lesions
(i) Recovering bell’s palsy (recovers top down)
(ii) Vascular ( stroke)
(iii) Tumour

(b) LMN lesions

(i) pons (a/w 5 and 6 nerve lesions)  vascular, tumour, MS
th th

(ii) posterior fossa  acoustic neuroma, meningioma, chronic meningitis

(iii) petrous temporal bone  Bell’s palsy, #, Ramsay-Hunt syndrome, otitis media, GBS
(iv) parotid  tumour, parotiditis, sarcoidosis, parotid surgery/biopsy (look for scars)

3. Bell’s palsy
- most common cause of 7th nerve palsy
- acute unilateral inflammatory lesion of the facial nerve along its course through the skull
- clinical features = ear pain
facial weakness
absent corneal reflex
hyperacusis
loss of taste in anterior 2/3s of tongue

31
8th cranial nerve (Vestibule-cochlear nerve)
1. Anatomy
- Cochlear fibres for hearing; vestibular fibres for balance
- Fibres for hearing originate in the organ of corti  cochlear nucleus in the pons  bilateral transmission to medial
geniculate bodies  superior gyrus of temporal lobes
- Fibres for balance begin in the utricle and semicircular canals  join auditory fibres in auditory canal enter pons at
cerebello pontine angle  brainstem and cerebellum
- Nucleus at the ponto medullary junction

2. Causes of deafness
i) Conduction deafness  ear wax, NPC (Chronic otitis media/ glue ear), otosclerosis
ii) Sensorineural deafness  acoustic neuroma, noise induced deafness, drugs (aminoglycosides, alcohol, diuretics),
aging (presbycusis), herpes zoster, brainstem CVA, meniere’s disease, congenital, infection (syphilis, rubella), # petrous
bone

3. Causes of vertigo
i) Urticle = BPPV
- hallpike manoeuvre
- diagnostic features = short latent period
Nausea, vertigo, nystagmus towards affected (lower most) ear
Fatigability (occur for several seconds and abate, not reproducible for 10-15 min
- Caused by concretions in the semicircular canals
ii) labryinthe = acute labrynthitis
streptomycin toxicity
iii) Vestibular nerve = vestibular neronitis
iv) Brainstem = MS, vascular, tumour, demyelination
v) Cerebellum = metastatic carcinoma

9th and 10th cranial nerves (Glossopharyngeal and Vagus nerve)

1. Anatomy
- Motor sensory and autonomic functions
- Nuclei located in the medulla  emerge from the skull through jugular foramen
th
- 9 nerve receives sensory fibres from nasopharynx, pharynx, middle and inner ear and taste fibres from posterior 1/3
of the tongue; secretory fibres to parotid gland
th
- 10 nerve receives sensory fibres from pharynx and larynx; motor fibres to muscles of pharynx; larynx and palate
th th
2. causes of 9 and 10 nerve palsy
i) Central = vascular e.g.lateral medullary syndrome, stroke,
tumours
motor neurone disease e.g. pseudobulbar palsy (UMN)
ii) Peripheral = aneurysm, tumours, chronic meningitis, GBS

11th cranial nerve (Accessory nerve)

1. Anatomy
-central portion arises in the medulla; spinal portion arises from c1-c5 segments
th th
-leaves the skull with the 9 and 10 nerves through the jugular foramen
-central division provides motor fibres to the vagus nerve
-spinal division innervates trapezius and sternocleidomastoid muscles
th
2. Causes of 11 nerve palsy
-Unilateral = trauma (#base of skull), basilar invagination, tumours
-Bilateral = motor neurone disease, polio, GBS, muscular dystrophy

32
12th Cranial Nerve (Hypoglossal nerve)
1. Anatomy
a. Nucleus found in medial medulla
b. Leaves the skull via hypoglossal foramen
c. Motor nerve for the tongue

th
2. Causes of 12 nerve palsy
a. Unilateral
i. Central  vascular (thrombosis of vertebral artery, carotid dissection, aneurysm)
ii. Peripheral
1. Posterior fossa  tumours, chronic meningitis, vascular (aneurysm), trauma, Arnold-Chiari
malformation, osteomyelitis
2. Neck  tumours, LAD
b. Bilateral
i. UMN  motor neurone disease, vascular, tumour
ii. LMN  motor neurone disease, GBS, polio, Arnold-Chiari malformation

3. Arnold-Chiari malformation
a. Congenital malformation of the base of skull with herniation of tongue of cerebellum and medulla into the
spinal canal
b. Usually associated with syringomyelia and spina bifida
c. Clinical features: Lower cranial nerve palsies
Cerebellar limb signs
UMN signs in the LL

33
Cranial Nerve Lesions
Approach to 7th nerve palsy
1. Anatomy
th th
a. 7 nerve nucleus lies in the pons next to the 6 nerve nucleus
b. Nerve leaves the pons through cerebellopontine angle  enters internal auditory meatus  facial canal 
becomes geniculate ganglion  leaves skull via stylomastoid foramen  parotid gland  5 terminal branches
(TZBMC = temporal, zygomatic, buccal, mandibular, cervical)
c. Motor component = nerve to stapedius muscle
muscles of facial expression
(frontalis, orbicularis oculi & oris, buccinators etc.)
th
d. Sensory component = taste fibres from anterior 2/3 of tongue (via chorda tympani which joins 7 nerve in the
facial canal)
e. Parasympathetic component = lacrimal glands

th
2. Unilateral 7 nerve palsy
th
UMN 7 nerve
a. Etiology
i. Cortical / subcortical stroke
ii. Recovering Bell’s palsy (recovers top down)
b. Request to examine
i. Corneal reflex
ii. Other cranial nerve involvement
iii. Long tract signs (ipsilateral hemiplegia and hemisensory loss)
c. Complications
i. Exposure keratitis
ii. Evidence of tarsorrhaphy
th
LMN 7 nerve
a. Etiology
i. Pons
 CVA
 Tumour
 MS
ii. Posterior fossa
 CPA lesion (meningioma, medulloblastoma, haemangioblastoma, acoustic neuroma, NPC  loss
of V2 sensation, lymphomatous deposits, cholesteatoma, aneurysm of basilar artery)
 Chronic meningitis (TB, fungal, base of skull metastatic deposits)
iii. Petrous temporal bone
 Bell’s palsy
 Ramsay-Hunt syndrome (herpes zoster of geniculate ganglion), GBS, #, otitis media
iv. Parotid
 Cancer/sarcoidosis/amyloidosis
 Parotid surgery/biopsy
v. Mononeuritis complex
1. DM/PAN/RA/SLE/Wegener’s/sarcoidosis/amyloidosis/leprosy
b. Request to examine
i. Corneal reflex
ii. Other cranial nerve involvement
iii. Long tract signs (ipsilateral hemiplegia and hemisensory loss)
iv. Ears (vesicles on external auditory meatus for Ramsay-Hunt syndrome; otoscope for otitis media; scars for
previous trauma; scar behind ear  mastoid process surgery)
v. Palate (vesicles for Ramsay-Hunt syndrome)
34
 vi. Parotid (enlargement for cancer/sarcoidosis/amyloidosis; scars for previous surgery)
c. Questions to ask
i. Dry eyes
ii. Hyperacusis (facial canal)
iii. Loss of taste over anterior 2/3 of tongue (facial canal)
d. Complications
i. Exposure keratitis
ii. Evidence of tarsorrhaphy

th
3. Bilateral 7 nerve palsy (LMN)
a. Physical findings
i. Expressionless facies (wasting of temporalis muscle  myopathy)
ii. Bilateral ptosis
iii. Tent-shaped mouth (unable to close mouth fully)  drooling of saliva
b. Etiology
i. Isolated
ii. Systemic
1. Myopathy – myotonia dystrophica, fasciohumeroscapular dystrophy
2. NMJ – myasthenia gravis
3. Peripheral nerves – AIDP (GBS), CIDP
4. Anterior horn cell – motor neurone disease
c. Request to examine
i. Corneal reflex
ii. Other cranial nerve involvement
iii. Long tract signs (myopathy, NMJ, peripheral nerve & AHC involvement)
iv. Lid fatigability (myasthenia gravis)
v. Parotid (enlargement for amyloidosis/sarcoidosis)
d. Complications
i. Exposure keratitis
ii. Evidence of tarsorrhaphy

4. Bell’s palsy (idiopathic)

th
a. Acute unilateral inflammation of 7 nerve in facial canal
b. Epidemiology
th
i. Most common cause of LMN 7 nerve palsy
ii. Peak incidence: 10-40yo
iii. Incidence increases with age
iv. More common in diabetics (10% of cases) and pregnant women
v. Males = females; left = right
c. Pathogenesis = evidence for HSV type 1 infection
d. Clinical features
i. Acute onset followed by worsening of symptoms over 3-72h
ii. Mastoid pain preceding/accompanying weakness
iii. Facial weakness, inability to close eyes fully, excessive tearing, drooling of saliva, dysarthria
iv. Ear pain, hyperacusis (intolerance of high-pitched sounds), disturbance of taste
v. Absent corneal reflex
e. Investigation = electroneurography (identify axonal degeneration)
f. Management
i. 50-60% of patients recover spontaneously without deficits (incomplete paralysis; no axonal degeneration)
ii. May be complicated by aberrant reconnections  facial synkinesis
1. Eye blinking accompanied by synchronous upturning of mouth
iii. Dexamethasone  only in those with clinically complete deficit or severe pain; reduces nerve oedema
iv. Physiotherapy  massage, electrical stimulation, splint to prevent drooping of lower part of face
35
 v. Protection of eye  artificial tears, regular eyelid closure by pulling down lid by hand, tape eye shut at
night, lateral tarsorrhaphy (severe ectropion)
vi. Acyclovir  effective in improving volitional muscle activity

5. Reflexes involving facial nerve

a. Corneal reflex
b. Palmomental reflex
c. Suck reflex
d. Snout reflex
e. Glabellar reflex

36
37
Cerebellopontine Angle Lesion
Cerebellopontine angle
- Shallow triangular fossa lying between cerebellum, lateral pons and petrous temporal bone
- Relations
a) superior = trigeminal nerve
b) inferior = glossopharyngeal nerve
c) medial = abducens nerve
- Facial and cochlear nerves traverse angle to enter internal auditory meatus

Pathology
Cranial nerves
- CN 5
o Loss of corneal reflex (earliest sign)
o Facial numbness
- CN 6
o Failure of eye abduction
o Diplopia
- CN 7
o LMN facial nerve palsy
- CN 8
o Tinnitus + deafness  vertigo

Cerebellar signs

Causes
- primary neoplasia = meningioma, haemangioblastoma, medulloblastoma, acoustic neurome (NF type 2)
- secondary neoplasia = lymphomatous deposits
- NPC (loss of V2 sensation and corneal reflex)
- Cholesteatoma
- Aneurysm of basilar artery

38
Pseudo-bulbar and Bulbar Palsy
Pseudobulbar Palsy (UMN) Bulbar Palsy (LMN)
Prevalence Common Rare
Lesion Bilateral lesions above mid-pons Myopathy
NMJ disorders
Peripheral neuropathy
Anterior horn cell
Cranial nerve nuclei in brainstem
Structures - Tongue - Tongue
involved - Muscles of mastication - Muscles of mastication
- Muscles of swallowing - Muscles of swallowing
- Facial muscles - Facial muscles
Clinical features - Spastic tongue (cannot say ‘lalala’) - Flaccid and fasciculating tongue
- No tongue wasting - Tongue wasted
- Spastic dysarthria (Donald duck) – slow thick and - Flaccid dysarthria (nasal speech)
indistinct - Absent jaw jerk and gag reflex
- Brisk jaw jerk and gag reflex - Nasal regurgitation prominent
- Nasal regurgitation not prominent - LMN signs in limbs (if not BS
- UMN signs in limbs lesion)
Causes - bilateral CVA - Myopathy
- Multiple sclerosis - Myasthenia gravis
- Motor neuron disease - GBS
- MND
- Polio
- Syringobulbia
- Brainstem tumours
- Central pontine myelinolysis
Examination - quality of speech (nasal/Donald duck)
- cranial nerve exam (wrt CN 5,6,7,8,9,10,11,12)
- jaw jerk
- gag reflex
- fasciculations elsewhere
- UMN/LMN signs in the limbs
Management Refer speech therapist
Assess swallowing – barium swallow with videofluoroscopy

39
Upper and lower limbs
Examination of the Upper Limbs
Motor Function

General
1. Shake hands with the patient and introduce yourself
- cannot relax hand grip  myotonia dystrophica
2. Ask patient to undress so that arms and shoulders are well-exposed  assess functional level
3. General inspection
- myopathic facies = myasthenia gravis, myotonia dystrophica
- face = ptosis, strabismus, facial asymmetry
- lower limbs = hemiplegic posture, muscle wasting, deformities
- neurocutaneous signs = NF type 1, tuberous sclerosis

Inspection of the upper limbs

- resting posture = UMN lesion (shoulder adducted, forearm pronated, elbow/wrist/fingers flexed)
- muscle wasting = LMN lesion, disuse atrophy, myopathy
- contractures
- surgical scars
- skin lesions = herpes zoster, neurocutaneous signs

4. Ask the patient to hold his arms stretched out in front and close his eyes  pronator drift
- UMN lesion = downwards, slow pronation
- cerebellar lesion = upwards, slow pronation
5. Look for fasciculations by flicking your fingers on muscles  LMN lesion

Tone
“Relax your arms and let me move them for you”
1. Flex and extend elbow, pronate and supinate forearm
- clasp-knife spasticity (UMN) = increased tone in flexors > extensors
- lead-pipe rigidity (extrapyramidal) = rigidity throughout full range of motion
2. Flex and extend wrist
- cogwheel rigidity (Parkinson’s Disease) = rigidity broken up by tremors

Reflexes
1. Biceps jerk (C5)
2. Triceps jerk (C7)
3. Supinator jerk (C6) = elbow flexion, forearm supination and finger flexion
# Inversion of supinator reflex = finger flexion is the only response
associated with absence of biceps jerk and exaggerated triceps jerk
~ LMN lesion at C6 and UMN lesion below this level
4. Hoffmann’s sign (equivalent of Babinksi’s reflex in UL) = flick distal phalanx of middle finger to elicit flexion of the
thumb
# If reflexes are absent = reinforce by clenching teeth or pulling fingers in opposite direction

Power
1. Shoulder abduction (C5+C6)
2. Shoulder adduction (C7)
3. Elbow flexion (C5+C6)
4. Elbow extension (C7)
5. Wrist flexion (C7+C8)
6. Wrist extension (C7)
7. Hand grip (C8)
8. Finger extension (C8)
9. Finger abduction (T1) = adduct patient’s index and little fingers at proximal phalanges

40
# Grading of power (Medical Research Council Scale)
 0 = complete paralysis
 1 = some flicker of contraction
 2 = movement possible if gravity removed
 3 = movement possible against gravity but not against resistance
 4 = movement possible against gravity and some resistance
 5 = normal power

# if power is reduced = symmetrical/asymmetrical

proximal/distal/generalised
UMN pattern/motor nerve root/peripheral nerve/muscle group

Coordination (test of cerebellar disease  at least grade 3 power)

1. Finger-nose test = intention tremor, dysmetria (past-pointing)
2. Rapidly alternating movements = dysdiadochokinesia

Sensory Function

Pinprick sensation (spinothalamic tract)

1. Ask patient if there is any numbness
2. Use toothpick and poke a normal area first. Ask patient if pin prick feels sharp or dull
3. Poke thumb (C6) and compare with first point (if same  new control)
rd
- 3 finger (C7)
- little finger (C8)
- medial aspect of elbow (T1)
- axilla (T2)
- shoulder tip (C4)
- radial aspect of arm (C5)
- radial aspect of forearm (C6)
Compare left and right sides

Proprioception (dorsal column)

1. Fix patient’s wrist joint and with his eyes open, move the thumb up and down to demonstrate these positions
2. Have the patient close his eyes and repeat the positions randomly. Ask him to report the final position
- DIP of thumb  wrist  elbow  shoulder

Vibration (dorsal column)

1. Use a 128 Hz vibration fork
2. Test on the sternum first so that patient can recognise vibration
3. Ask patient to close his eyes and place vibrating tuning fork on DIP joint. Deaden the tuning fork with your hand and
patient should say exactly when this occurs
4. Compare one side with the other
- DIP of thumb  ulnar head  olecranon  shoulder

Light touch (dorsal column)

1. Test each dermatome comparing left and right sides

41
Upper Limb Nerves
Region Action Muscle Nerve Nerve Root Branch
Shoulder Abduction Deltoid Axillary n. C5, C6 Post cord
Supraspinatus Suprascapular C5, C6 Up trunk
Adduction Pectoralis mjr Med + Lat pectoral C6, C7, C8 Lat cord
Lats dorsi Thoracodorsal C6, C7, C8 Post cord
Elbow Flexion Biceps Musculocutaneous C5, C6 Lat cord
Brachialis Musculocutaneous C5, C6 Lat cord
Extension Triceps Radial nerve C7, C8 Post cord
Wrist Flexion Flexor carpi ulnaris Ulnar nerve C8, T1 Med cord
Flexor carpi radialis Median nerve C6, C7 Med+Lat root
Extension Extensor carpi group Radial nerve C7, C8 Post cord
Fingers Extension Extensor digitorium, ext Radial (deep) C7, C8
indicis, ext digiti minimi
Flexion Flexor digitorum profundus Ulnar nerve (med) + Median C8. T1 Med cord
(lat)
Flexor digitorum superficialis
Median nerve C7, C8 Med cord
Abduction Dorsal interossei (DAb) Ulnar nerve C8, T1 Med cord
Adduction Palmar interossei (PAd) Ulnar nerve C8, T1 Med cord
Thumb Oppose Opponens pollicis Median nerve C8, T1 Med, lat cord
Abduct Abs pollicis brevis Median nerve C8, T1 Med, lat cord

1. Radial Nerve (Posterior Cord)

I. Motor Function:
i. Supplies: Triceps, brachioradialis, extensor muscles of the hand
ii. ActionL Flex elbow, pronate forearm, extend wrist and fingers
iii. Characteristic deformity: wrist drop
iv. Level of lesion above upper third of upper arm, triceps muscle affected
II. Sensation:
i. Supplies: Area of anatomical snuffbox
ii. Level of lesion: before bifurcation at elbow
2. Median Nerve (Medial + Lateral Cord)
I. Motor Function:
i. Supplies: ALL muscles on front of forearm except FCU and ulnar half of FDP. LOAF.
ii. Level of lesion:
1. At wrist (carpal tunnel) – Pen touch test for APB. Absent if lesion above wrist.
2. At cubital fossa – Ochsner’s clasping test
II. Sensation
i. Supplies: Radial 3½ fingers
ii. Level of lesion: Palm spared in median nerve lesion in carpal tunnel.
3. Ulnar Nerve (Medial cord)
I. Motor Function
i. Supplies: ALL small muscles of the hand ( except LOAF), FCU, ulnar half of FDP
ii. Action: do Froment’s sign. Finger abduction/adduction.
iii. Characteristic deformity: Wasting of small muscles of hand (guttering of the intrinsic muscles), Ulnar
claw hand
iv. Level of lesion: Ulnar paradox with lesions above the elbow having lesser deformity due to loss of
FDP.
II. Sensation
i. Supplies: Palmar and dorsal aspects of the little finger and medial half of ring finger
III. Causes of a true claw hand:
i. Ulnar and median nerve lesion
ii. Brachial plexus lesion: in medial cord; Klumpke’s paralysis (lower brachial plexus)
iii. Neurological diseases: polio, syringomyelitis, lateral sclerosis

42
iv. Severe Volkman’s ischaemic contracture
v. Rheumatoid Arthritis

43
Median Nerve
1. Origin
I. Medial and Lateral cords of brachial plexus (C5-T1)

2. Course
rd
I. Axilla = lies lateral to 3 part of axilla artery
II. Arm = crosses brachial artery from lateral to medial side at level of insertion of coracobrachialis
III. Cubital fossa = most medial structure of importance (MBTR)
IV. Forearm = passes between 2 heads of pronator teres. Gives off anterior interosseous nerve.
i. Muscular supply  Pronator teres, FCR, FDS, Palmaris longus
ii. Sensory supply  Lateral aspect of palm (given off at wrist before flexor retinaculum)
iii. Anterior interosseous nerve  FPL, lateral ½ FDP, pronator quadratus
V. Hand = travels under flexor retinaculum in carpal tunnel
i. Muscular supply  thenar muscles (APB, FPB, Opponens pollicis), lateral 2 lumbricals. (LOAF)
ii. Sensory supply  lateral 3½ fingers (palmar aspects) till PIPJ on dorsal aspect

Median Nerve Palsy

Can be high (elbow), low (wrist), AIN palsy, carpal tunnel syndrome

1. Fully expose patient’s chest and upper limbs

 Scars  elbow, wrist, flexor retinaculum (from previous CTS surgery)
 Wasting of thenar muscles with sparing of hypothenar muscles & interosseous muscles
2. Hello

Make a fist  No benediction sign  Low lesion (wrist)

↓ ↓
Benediction sign Carpal tunnel syndrome
↓ ↓
High lesion (elbow) OR AIN palsy No lesion
↓ ↓
Test motor function Test motor function
↓ ↓
Lumbricals = radial 2 lumbricals (✓ Lumbrical = X
palsy)
Opponens = √ in AIN palsy Opponens = X
APB = √ in AIN palsy, Abductor = X
Supination of thumb during opposition
‘OK’ sign = terminal phalanges of thumb & ‘OK’ sign = X
index finger extended (AIN palsy)
FPL/FPB of thumb and FDP of index finger (X Flexor = √
in both)
↓ ↓
Test sensory function Test sensory function
↓ ↓
Radial palm (√ in AIN palsy) Radial palm (reserved in CTS)
Radial 3½ fingers (Palmar aspect to DIPJ on Radial 3½ fingers = X
dorsal aspect) = √ in AIN palsy
↓
Phalen’s / Tinels
↓
+ve for CTS

Differentials: C6/C7 radiculopathy

 Test biceps jerk  Musculocutaneous nerve (C5, C6)
 Test elbow flexion  Musculocutaenous nerve (C5, C6)
 No splitting of sensation of ring finger

44
Ulnar Nerve Palsy
1. See an ulnar claw hand
 Fully expose patient’s chest (males) and upper limbs
* scar over supraclavicular area = brachial plexopathy
* scar over medial epicondyle
* scar over wrist
 Hold arms up = cubitus valgus deformity (leads to tardive ulnar nerve palsy)
= large carrying angle (repeated flexion and extension can damage olecranon
and ulnar nerve

2. Confirm ulnar nerve palsy

 Clawing = hyperextension at 4 and 5 MCPJ
th th

 Wasting of hypothenar muscles with sparing of thenar eminence

 Wasting of dorsal interosseous muscles (guttering)
 F= Flexor digitorium profundus (flexion of 4 and 5 DIPJ)  intact in wrist lesions
th th

A= Adductor pollicis (Froment’s sign)

I= Interosseous (finger abduction)
L= medial 2 Lumbricals (salute sign)
 Sensation: medial ½ of palm
palmar aspect of little finger
split sensation of ring finger (rule out C8/T1 radiculopathy)
medial ½ of dorsum intact in wrist lesions

3. Tinel’s test in traumatic nerve injury (over scar at medial epicondyle and anterior forearm)

* Distinguishing factors between elbow and wrist lesions

th th
(a) Ulnar nerve paradox: more flexion at 4 and 5 DIPJ in wrist lesions (looks more serious)
(b) Intact FDP in wrist lesions
(c) Intact sensation over medial ½ of dorsum (because dorsal cutaneous branch given off)

* Differentials
(a) C8/T1 radiculopathy – wasting of thenar muscles
– no split sensation of ring finger
– Horner’s syndrome
(b) Syringomyelia – dissociated sensory loss
– Horner’s syndrome

45
Radial Nerve Palsy
1. Expose patient’s chest and upper limb
* scars : back of humerus
elbow
* wasting of triceps (axilla lesion)

Hold arms out in front : palms up  down  lock wrists

2. Wrist drop: axilla

: spiral groove
(a) elbow extension (triceps)= lost in axilla
= intact in spiral groove
(b) flexion in forearm in mid-pronated position (brachioradialis) = not possible in both
(c) finger extension = not possible in both
(d) EPL = not possible in both

3. Sensation
 axilla = loss over posterior arm, posterior forearm, 1 dorsal web space
st

 spiral groove = loss over 1 dorsal web space

st

 PIN palsy = no sensory loss

4. Test triceps jerk

* differential: C7 radiculopathy – loss of: shoulder adduction

wrist flexion
sensation over middle finger
– similarities to radial nerve palsy: loss of elbow extension
loss of triceps jerk
wasting of triceps

46
Examination of the Lower Limbs
Motor Function
General
1. Shake hands with patient and introduce yourself
2. Request to remove pants so that thighs and legs are well-exposed
3. General inspection
- myopathic facies = myasthenia gravis, myotonia dystrophica
- face = ptosis, strabismus, facial asymmetry
- upper limbs = hemiplegic posture, muscle wasting, deformities
- neurocutaneous signs = NF type 1, tuberous sclerosis

Inspection of the lower limbs

- resting posture = UMN hemiplegia (hip and knee extension, foot drop)
hypotonia (hip abduction and flexion, knee flexion)
- muscle wasting = LMN lesion, disuse atrophy, myopathy
- contractures
- surgical scars = tendon release scars, muscle biopsy (thighs, calves), nerve biopsy (sural nerve over lateral
malleolus)
- deformities = pes cavus (peripheral neuropathy, Friedreich’s ataxia, Charcot-Marie-Tooth disease)
- skin changes = trophic nail changes, diabetic dermopathy, shiny hairless skin

4. Look for fasciculations by flicking your fingers on muscles  LMN lesion, motor neurone disease

Tone
“Relax your legs and let me move them for you”
1. Ask if there is any hip pain
2. Leg roll
3. Support the knee from below and pull it up quickly
- clasp-knife spasticity (UMN) = increased tone in extensors > flexors
4. Ankle clonus = rotate thigh externally, ask patient if ankle hurts then dorsiflex ankle and look for clonus
> 3 rhythmic downward beats of the foot  UMN lesion

# most common cause of spasticity with hyporeflexia is an unrelaxed patient!

Reflexes
1. Knee jerk (L3,L4)
2. Ankle jerk (S1,S2)
3. Babinski’s reflex (L5,S1,S2) = UMN lesion (big toe extensor response with fanning of the other toes)
- Chaddock = run orange stick along lateral border of foot
- Oppenhiam = run orange stick along tibial shaft
- Gordon = squeeze the calf
# If reflexes are absent = reinforce by clenching teeth or pulling fingers in opposite direction

Power
1. Hip flexion (iliopsoas = L1+L2)
2. Hip extension (gluteus = L5+S1)
3. Knee extension (quadriceps = L3+L4)
4. Knee flexion (hamstrings = L5+S1)
5. Ankle dorsiflexion (tibialis anterior = L5)
6. Ankle plantarflexion (gastrocnemius = S1)
7. Big toe flexion (FHL = S1)
8. Big toe extension (EHL = L5)

# Grading of power (Medical Research Council Scale)

 0 = complete paralysis
 1 = some flicker of contraction
 2 = movement possible if gravity removed
 3 = movement possible against gravity but not against resistance
 4 = movement possible against gravity and some resistance
47
 5 = normal power

# if power is reduced = symmetrical/asymmetrical

proximal/distal/generalised
motor nerve root/peripheral nerve/muscle group
UMN pattern of weakness (hip flexion, knee flexion, ankle dorsiflexion)

Coordination (test of cerebellar disease  at least grade 3 power)

1. Heel-shin test
2. Toe-finger test = patient to lift the foot with the knee bent and touch examiner’s finger with big toe

Sensory Function

Pinprick sensation (lspinothalamic tract)

4. Ask patient if there is any numbness
5. Use toothpick and poke a normal area first. Ask patient if pin prick feels sharp or dull
st
6. Poke 1 interdigital cleft (L5) and compare with first point (if same  new control)
- plantar surface of big toe (S1)
- lateral aspect of foot (S1)
- medial aspect of leg (L4)
- lateral aspect of leg (L5)
- front of knee (L3)
- upper anterior thigh (L2)
- groin (L1)
Compare left and right sides

Proprioception (dorsal column)

1. Fix ankle joint and test using the big toe. With his eyes open, hold the toe from the sides and move it up and down to
demonstrate these positions
2. Have the patient close his eyes and repeat the positions randomly. Ask him to report the final position
- DIP of big toe  ankle  knee  hip

Vibration (dorsal column)

5. Use a 128 Hz vibration fork
6. Test on the sternum first so that patient can recognise vibration
7. Ask patient to close his eyes and place vibrating tuning fork on the medial malleolus. Deaden the tuning fork with your
hand and patient should say exactly when this occurs
8. Compare one side with the other
- medial malleolus  tibial tuberosity  ASIS

Light touch (dorsal column)

2. Test each dermatome comparing left and right sides

~ Other additional steps ~

1. Assess gait
2. Examine UL and cranial nerve
3. PR examination and percuss for palpable bladder
4. Examine the back
- surgical scars
- neurocutaneous signs
- spina bifida
- palpate for tenderness over the vertebral bodies
5. CVS system = AF, carotid bruits, murmurs, BP, stigmata of hyperlipidaemia

48
Neurology of the Lower Limb

1. Sciatic nerve (L4-S3)

a. Largest branch of sacral plexus in pelvis
b. Tibial component of sciatic nerve  hamstrings (long head of biceps femoris, semitendinosus,
semimembranosus, hamstring part of adductor magnus)
c. Common peroneal component of sciatic nerve  short head of biceps femoris
d. Sciatic nerve palsy
i. Foot drop (paralysis of muscles below knee)
ii. Loss of ankle reflex (S1)
iii. Loss of hip extension & knee flexion
iv. Loss of sensation below the knee except medial aspect of lower leg up to ball of big toe (supplied by
saphenous nerve)

2. Tibial nerve (L4-S3)

a. Motor = supplies posterior compartment muscles (gastrocnemius, soleus, popliteus, plantaris)
i. Ankle plantarflexion
ii. Foot inversion
b. Sensory = posterior and lateral aspects of lower leg
Sural nerve
lateral border of foot to little toe
sole of foot

3. Common peroneal nerve (L4-S2)

a. Superficial peroneal nerve
i. Motor = lateral compartment muscles (peroneus longus & brevis)
 foot eversion
ii. Sensory = anterior aspect of lower leg
dorsum of foot
st
dorsal surfaces of all toes except 1 interdigital cleft (DPN)
th
and lateral border of 5 toe (sural nerve)
b. Deep peroneal nerve
i. Motor = anterior compartment muscles (TA, EDL, EDB, EHL)
 ankle dorsiflexion
st
ii. Sensory = 1 interdigital cleft

4. Femoral nerve (L2-4)

a. Largest branch of lumbar plexus
b. Motor = quadriceps femoris
pectineus
sartorius
c. Sensory = anteromedial aspect of thigh
medial aspect of lower leg to ball of big toe (saphenous nerve)

49
Foot drop

1. Aetiology
a. Bilateral foot drop
i. Spastic paraparesis
ii. Peripheral neuropathy = Charcot-Marie-Tooth disease
b. Unilateral foot drop
i. Peripheral neuropathy
ii. Common peroneal nerve palsy = mononeuritis multiplex
tibia/fibula #
plaster casts
leprosy
iii. Sciatic nerve palsy
iv. L5 radiculopathy
v. Anterior horn cell = poliomyelitis
motor neurone disease

2. Approach to foot drop

Confirm foot drop = weak ankle dorsiflexion

Ankle plantarflexion

Weak Strong

Sciatic nerve palsy Check foot inversion Check knee flexion (L5, S1)

- Absent ankle jerk Strong Weak Intact Weak

- Loss of hip extension
& knee flexion CPN palsy L5 radiculopathy Check for numbness Check hip internal rotation
Tibial n. palsy & abduction (superficial
- Loss of sensation
gluteal nerve)
below the knee
except medial aspect Distal & symmetrical L5 dermatome
of lower leg up to ball Weak
of big toe (supplied Peripheral neuropathy CPN palsy
by saphenous nerve) Check numbness

None
3. Management L5 dermatome
a. Nerve conduction study Polio L5 radiculopathy
b. Conservative = 90˚ night splint & caliper shoes
c. Surgery (for transacted nerve)

50
Brain and the Higher Centers
Gait
Gait examination
Ensure that patient’s pants are secured
Obtain adequate exposure by exposing up to level of mid-thigh

1. Get the patient to stand and assess for

(a) postural instability  parkinsonism, gait apraxia
(b) truncal ataxia  cerebellar syndrome
(c) broad-based stance  cerebellar syndrome
(c) Romberg’s sign  dorsal column loss

2. Walk in a straight line (walk  stop  walk  turn  walk  stop  walk  stop)

Types of Gait Aetiology Characteristics

Hemiplegic gait UMN pattern of weakness  foot is plantar-flexed and leg is swung in a lateral arc
(circumduction)
 fingers, wrist and elbow are flexed with shoulder
adducted
Ataxic gait cerebellar syndrome (refer)  broad-based gait
 veering to one side
 cannot do tandem walking
Festinating gait parkinsonism  lack of arm swing, hunched posture, paucity of facial
expression, resting tremor
 hesitancy, short and shuffling steps, festinating gait,
turning by numbers
 propulsion, retropulsion
Magnetic gait normal pressure hydrocephalus  instability on getting up from sitting position
(gait apraxia) multi-infarcts in pre-frontal area  feet appear glued to the floor (magnetic)
 ignition failure = responds to visual cues
 request to examine MMSE (NPH)
High-stepping gait foot-drop (refer)
Sensory ataxia dorsal column loss (refer)  bilateral broad-based gait
 high-stepping and slapping down of feet
Scissoring gait spastic paraplegia (refer)
Trendelenburg gait hip girdle weakness (refer)
Waddling gait proximal myopathy (refer)

3. Tandem (heel-to-toe) walking  cerebellar syndrome

4. Walk on toes  S1 weakness

5. Walk on heels  L5 weakness

6. Squat and stand up repeatedly  proximal myopathy

Investigations
Bloods Imaging
FBC AP pelvis and lateral hip
U/E/Cr lumbar spine X-ray (AP, lateral)
ESR/CRP MRI spine
serum vit B12 and folate levels CT head
VDRL
PSA, serum acid phosphatase, LFT, CXR, urine and serum protein electrophoresis Nerve conduction studies

Muscle biopsy EMG

51
Tremors
1. Resting tremors
- Are there tremors while watching TV?
- decreases with voluntary action

2. Postural tremors Suspect Wilson’s

- tremors while maintaining a certain posture e.g. holding hands out disease or
- coarse tremors thyrotoxicosis in
- accentuate by abducting fingers
a young patient
3. Essential tremors
- no apparent cause
- positive family history
- occurs around 40 years old and worsens with age
- improves with beer

4. Intention tremors
- marked increase in tremor amplitude during a terminal portion of targeted movement
- due to weakness or cerebellar lesion

5. Task-specific tremors
- occurs during a specific activity e.g. writing (writer’s tremor)

6. Fasciculation tremors
- occurs in motor neurone disease
- associated with fatigue and muscle wasting

7. Alcoholic tremors
- very coarse tremors

8. Asterixis
- flapping tremor
- associated with major organ failure e.g. liver failure, heart failure

52
Examination of Higher Centers
General signs
1. Level of consciousness (GCS)
2. Neck stiffness
- meningism = resistance to neck flexion due to painful spasm of extensor neck muscles
 infective meningitis
~ Kernig’s sign (pain on extending knee with hip flexed)
~ Brudzinski’s sign (hip flexion on neck flexion)
 subarachnoid haemorrhage

Higher centres
1. Introduce yourself, shake patient’s hand and ask permission to examine
2. “Please tell me your name. How old are you? What do you work as? Which hand do you use to write?”
 dysphasia = non-fluent  expressive/global dysphasia
fluent  receptive dysphasia
3. Orientation (T,P,P)
- “Do you know what day/date/month/year today is?”
- “Do you know where are you now?”
- “Do you know who I am?”
4. Short term memory
 “What did you have for breakfast this morning?”
 “Please remember ‘red, cat and ball’. I will ask you about them later.”
5. Long term memory
 “Who is the current PM of Singapore?”
 “When did Singapore gain independence?”
6. Attention (serial 3s)
7. Language
 follow 3-step command
 name 2 objects
 repeat “Today is a sunny day. No, ifs and or buts.”
 write a sentence (do not dictate)
8. Executive functioning
 “You’re in Orchard Road but you have lost your bag, wallet and handphone. How will you go home?”
9. Interpret proverbs in light of social and educational background
10. Ask patient about side effects and complications of therapy
11. Family history of illness (are you the only one affected? are there more males than females affected?)
12. Remember the 3 items

Localising hemispheric signs

# parietal, temporal and frontal lobe functions are tested if patient is
(a) disorientated
(b) dysphasic (no need to go on further if patient has Wernicke’s)
(c) demented

Parietal lobe

Dominant hemispheric parietal lobe signs Non-localising parietal lobe signs

Gerstmann’s syndrome Visual fields
 acalculi (inability to do simple arithmetic)  assess for visual field defect
- “What is 1+2? 2+3?” - contralateral homonymous hemianopia
dyscalculi (able to do simple but not complex - contralateral homonymous lower
arithmetics) quadrantanopia
- “What is 5x3?”164?”
 agraphia (inability to write)
- “Please write your name.”
 finger agnosia (inability to name fingers)
 left-right disorientation
- “Please show me your right hand. Please show
me your left hand. Please use your right hand
to touch your left ear. Please use your left
hand to touch your right ear.”
53
Dysphasia Neglect
 visual neglect (line bisection)
- assess visual fields first
- hold stethoscope vertically and ask patient to
point out the middle (should be normal)
- hold stethoscope horizontally and ask patient to
point out the middle
 sensory neglect
- normal when 1 arm/leg is tested (abnormal when
both are tested at the same time)
Loss of 2-point sensory discrimination
Optokinetic nystagmus
“Please look at this point and do not move your head.”
- slow pursuit movement which follows tape measure
followed by a quick saccade back to fixation point
- impaired OKN when tape measure pulled towards
side of lesion indicates parietal lobe dysfunction
Agraphaesthesia (inability to appreciate number
drawn on hand)
 “Please close your eyes. I am going to write a
number on your palm. Tell me the number.”
Astereognosis (tactile agnosia; inability to appreciate
object placed in hand)
 pen
 notebook
Dressing apraxia
 take off patient’s top, turn it inside out and ask
patient to put it back on
Constructional apraxia
 copy your hand movements (2 ok signs 
interlocking ok signs)
 copy object that you have drawn (star)
# Agnosia = failure to recognise objects despite having intact sensory pathways for sight, sound and touch
# Apraxia = inability to perform purposeful movements in absence of motor weakness, sensory deficits or severe
incoordination

Temporal lobe
 Short-term memory
 Long-term memory
 Visual fields = contralateral homonymous upper quadrantanopia

Frontal lobe
 Inspection = akinetic mutism
unkempt
emotional lability
disinhibition
perseveration
apathy
 urinary incontinence (on pampers or urinary catheter)
 LL hemiplegia and sensory loss
 anosmia (loss of smell)
 primitive reflexes = palmomental reflex, grasp reflex, glabellar tap, snout(pout) reflex, rooting/sucking reflex
 gait apraxia (magnetic gait)
 expressive dysphasia (Broca’s dysphasia)
 interpret proverb = “Please tell me the meaning of the phrase – time and tide wait for no man.”
 executive functioning = ”You are in orchard road but you realise that your bag, wallet and handphone are lost.
How will you go back home?”
 request to do fundoscopy
- optic atrophy on side of frontal lobe SOL
- papilloedema on opposite side due to secondarily raised ICP (Foster-Kennedy syndrome)

Occipital lobe
 Visual fields = contralateral homonymous hemianopia

54
Glasgow Coma Scale
1. Motor Response (6)
6 = obeys commands
5 = localizing response to pain
- apply painful stimulus to supraorbital nerve
- patient should respond by bringing hand up beyond the chin
4 = withdraws to pain
3 = flexor response to pain
- apply pressure on nailbed
- results in decorticate posture
2 = extensor response to pain
- apply pressure on nailbed
- results in decerebrate posture
1 = no response

2. Verbal Response (5)

5 = oriented
4 = confused/disoriented
3 = utters occasional words rather than sentences
2 = groaning/moaning; no words
1 = none

3. Eye Opening (4)

4 = spontaneous
3 = to words
2 = to pain
1 = none

55
Assessing Speech
SPEECH DISTURBANCES

Dysarthria Dysphonia Dysphasia

Articulation Phonation Language

Dysphasia
 disorders with language
 classification
Types
Broca’s/Expressive
dysphasia
Wernicke’s/Receptive
dysphasia
Global aphasia
Conductive dysphasia
Nominal dysphasia
Site of lesion/Areas Fluency Comprehension Repetition Naming Hemiplegia
44, 45 (frontal lobe) – + – – contralateral
22, 39, 40 (superior temporal + – – – absent
gyrus of parietal lobe)
Broca’s and Wernicke’s – – – – contralateral
arcuate fasciculus + + – – absent
posterior temporo-parietal area + + + – absent

Transcortical (motor) near Broca’s – + + – contralateral

Transcortical (sensory) near Wernicke’s + – + – absent

 laterality of dominance
- right-handed people  97% have left dominant hemisphere
- left-handed people  50% have left dominant hemisphere
 dominant hemisphere controls language and mathematical functions
- localizing signs = Gerstmann’s syndrome (acalculi, finger agnosia, left-right disorientation)
dysphasia
 multi-lingual patients
- mother tongue in childhood > resistant to damage
- language more familiar to patients will recover first
- language written, read and well-spoken recover faster than those spoken
 special situations
(a) global aphasia without hemiparesis  exclude embolic causes
(b) dysphasia without hemiparesis  anterior thalamic/basal ganglia lesion
partial seizures

Examining speech
1. Introduce yourself to the patient
Ask for permission to examine
2. “Please tell me your name. How old are you? What do you work as? Which hand do you use to write?”
 dysphonia (hoarse voice) = recurrent laryngeal nerve palsy (CN 10)
 dysphasia = non-fluent  expressive/global dysphasia
fluent  receptive dysphasia
3. Assess for dysarthria
 lalala  cerebellar dysarthria (loud jerky explosive speech)
 bababa  facial weakness (CN 7)
 kakaka  palatal, pharyngeal and laryngeal weakness (CN 9+10  look for CN 12 weakness as well)

# nasal speech (bulbar palsy)

# hot potato (pseudobulbar palsy)

4. Comprehension (receptive/global dysphasia)

 1-step command = “Please close your eyes.”
 2-step command = “Please close your eyes and stick out your tongue.”
 3-step command = “Please close your eyes, stick out your tongue and lift up your hands.”
5. Naming objects (nominal dysphasia)
 pen
56
  watch
 watch strap
 watch buckle
6. Repeat sentences (only possible in transcortical dysphasia)
 “Today is a sunny day.”
 “No, ifs ands or buts.”
7. Writing a sentence (do not dictate)

Request to examine
(a) MMSE
(b) expressive dysphasia  hemiplegia
(c) receptive dysphasia  parietal lobe signs
(d) CVS examination  AF, murmurs, carotid bruit

57
Examination of the Cerebellar System
“DASHING” = Dysdiadochokinesia; Ataxia (Truncal); Slurred speech (cerebellar dysarthria); Hypotonia;
Intention tremor; Nystagmus; Gait abnormality

Head
1. Multi-directional gaze-dependent nystagmus
- test visual acuity first
 jerky horizontal nystagmus with an increased amplitude on looking towards the side of the lesion
2. Slurred speech (cerebellar dysarthria)
- ask the patient to say “Lalalalala” (fast and loud)
- speech will be irregular in both volume (loud + soft) and rhythm (fast + slow)
 jerky, loud and explosive with an irregular separation of syllabus

Hand
1. Pronator drift
- downwards and slow pronation = UMN lesion (likely ataxic hemiparesis)
- upwards and slow pronation = cerebellar hypotonia (Holmes’ rebound phenomenon = inability to arrest
strong contraction on sudden removal of resistance)
2. Finger-nose test
- elbow must be up at right angles to patient’s torso
- place your finger at around one arm’s length from the patient
- patient touches the nose, rotates his finger and touches your finger
- look at the patient’s eye  patient not blinking implies that he knows he won’t hit his own eye (hysteria)
- note intention tremor and past-pointing (dysmetria)
3. Disdiadochokinesia
- rapidly alternating movements of the hands

Legs
# Ask the patient to lift LL one at a time  assess adequate power first
1. Heel-shin test
(1) Lift your leg straight up
(2) Touch your knee with your heel
(3) Slide your heel down your shin
(4) Place your leg back on the bed
2. Toe-finger test
- Look for intention tremor and past-pointing (dysmetria)

Sit the patient up at the edge of the bed

1. Truncal ataxia
2. Pendular jerks (not useful clinically but must still perform in exam)
- knee jerk  lower leg continues to swing a number of times before coming to rest

Get the patient to stand

# make sure that patient’s pants are secured, roll up the ends and ensure no joint pain
1. Observe patient’s stance and for truncal ataxia
* Broad-based = wider than shoulder
* Patient cannot stand properly or may start swaying from side to side

Get the patient to walk

1. Walk in a straight line
* Broad-based gait
* Patient staggers toward the affected side
2. If gait appears steady  heel-toe (tandem) walking

Request to examine
1. Full neurological examination of upper and lower limbs
- UMN signs = spasticity, hyper-reflexia, UMN pattern of weakness (ataxic hemiparesis)
- sensory loss = contralateral loss of pain and temperature (lateral medullary syndrome)
peripheral neuropathy (alcoholism)

58
2. Cranial nerves
- CN 5, 6, 7, 8 = cerebellopontine angle tumour (acoustic neuroma)
- Horner’s syndrome, CN 5, 9, 10 = lateral medullary syndrome
3. Fundoscopy
- RAPD = impaired direct light reflex with intact consensual light reflex (MS)
- optic atrophy (MS and FA)
- retinitis pigmentosum (FA)
4. CVS examination
- AF, murmurs, carotid bruit

Localisation of cerebellar signs (don’t need to know!)

1. Gait ataxia (inability to do tandem walking), UL spared  anterior lobe
2. Truncal ataxia (drunken gait, titubation)  posterior lobe
3. UL ataxia  lateral lobes

Causes

Unilateral Bilateral
Isolated cerebellar signs (no weakness!) Friedreich’s ataxia
 cerebellar stroke (infarct, haemorrhage) - pes cavus
 posterior fossa SOL (tumour, abscess) - distal muscle wasting
- loss of ankle and knee jerks but Babinski’s reflex
present
- pyramidal weakness
- dorsal column loss
Cerebellar signs + cranial nerve involvement Infections
 ataxic hemiparesis  viral encephalitis = HIV, enteroviruses
th
- contralateral UMN 7 lesion
- contralateral UMN pattern of weakness
- contralateral cerebellar signs Multiple sclerosis
 lateral medullary syndrome - UMN pattern of weakness
- ipsilateral facial loss of pain with - cerebellar signs
contralateral loss of pain in extremities Alcoholism
- ipsilateral cerebellar signs - peripheral neuropathy
- ipsilateral Horner’s syndrome - proximal myopathy
th th
- ipsilateral CN 9 and 10 lesions - cerebellar syndrome
- no weakness - bilateral 6
th
nerve palsy (Wernicke’s
 acoustic neuroma encephalopathy)
th th th th
- ipsilateral CN 5 , 6 , 7 , 8 lesions - recent memory loss and confabulation
- ipsilateral cerebellar signs (Korsakoff’s
- no weakness psychosis)
 jugular foramen malformation (Arnold-Chiari malformation; Dandy- Drug-induced toxicity
Walker syndrome)  anti-convulsants = phenytoin, carbamazepine
th th
- ipsilateral CN 9 -12 lesions  lithium
- ipsilateral cerebellar signs
Metabolic
 hypothyroidism (reversible cause)
 Wilson’s disease
Cerebellar signs + UMN pattern of weakness Paraneoplastic syndrome
 multiple sclerosis  Ca lung
 Ca ovary

59
Neurology Pathologies
Stroke – History-taking
Age/race/gender
Occupation
Handedness (determines dominant hemisphere)

Presenting complaint
When did it happen?
What were you doing at the time of onset?
Sudden/gradual onset?
Duration? (Differentiate TIA from CVA)

Weakness
- pattern (localized, hemiplegia, quadriplegia, face, UL, LL)
- Equally affected? UL>LL? LL>UL?
- Progressively worsening?
Numbness and parasthesiae
Haemorrhagic stroke
- severe headache (can also be a warning sign especially in large vessel occlusion)
- projectile vomiting
- meningism (photophobia, neck stiffness)
- coma within a few hours

brainstem lesion
- giddiness
- vertigo (+nausea and vomiting)
- drowsiness + LOC (reticular activating system affected)
- diplopia
- visual loss (cortical lesion)
- tinnitus
- facial numbness
- facial weakness
- drooling of saliva
- dysarthria/slurred speech
- dysphonia
- dysphagia

Subcortical lesion (internal capsule, basal ganglia, thalamus)

- involuntary movements (extrapyramidal)
- gait disturbances (+ cerebellum)
- poor balance (+ cerebellum)

Cortical lesion
- urinary incontinence
- dysphasia (did you understand others? Did others understand you?)
- cognitive impairment (were you able to count?)

Aetiology
- neck pain (carotid dissection)
- head injury
- preceding seizures (seizures, epilepsy, CNS infections)
- fever (CNS infections, infective endocarditis)
- LOA, LOW, fatigue (CNS malignancy)
- Hypoglycaemia

Systems review
Chest pain, sob, bladder/bowel function
Bladder – spinal cord pathology
60
Bowel – melena/haematochezia (BGIT may contraindicate use of aspirin)

Current management

Is this the first episode? Has it happened before? Describe previous incidents.

Past medical history

DM, HTN, HCL, AMI, Valvular heart problems, AF
CVA
Cancer
Seizures, epilepsy
Bleeding coagulopathy
PUD

Drug History
OCP
TCA overdose
Anti-coagulants – aspirin, warfarin

Social History
Smoking,
Drinking
Main caregiver
ADL
Family finances
Lift landing

Family History
DM, HTM, HCL, AMI
CVA
Berry aneurysms

If patient cannot give a history, suspect:

1) dysphasia – cortical stroke
2) dysarthria – brainstem lesion affecting cranial nerves 7, 9, 10, 12 (9, 10, 12 affected in pseudobulbar palsy)
3) drowsy – brainstem/thalamic/massive cortical lesion – affecting reticular activating system, or sepsis from nosocomial
infection

intra cranial haemorrhage

- occurs during waking hours
- known hypertensive patient or in a patient with bleeding tendency
- full deficit seldom present at onset (gradually develops over mins – hours)
- decreased consciousness
- warming symptoms rarely present

subarachnoid haemorrhage
- sudden severe “worst headache of my life”
- onset usually during exertion
- a/w signs of meningism (stiff neck, photophobia)
- ‘sentinal’ headache may occur days-weeks before major event

embolic stroke
- occurs during waking hours
- maximal deficit at onset (may improve in hours)
- may present with headache/focal seizures

thrombotic stroke
- occurs during sleep or present on awakening
- usually progresses in a stepwise fashion (takes hrs-days to develop full deficit)
- history of TIA

61
Stroke – Presentation and management
Focal neurological deficit of vascular origin developing acutely over minuts and lasting:
- <24h – TIA
- >24h – Stroke
rd
3 most common cause of death in Singapore

Types of stroke
Ischaemia (80%) Thrombotic Large artery disease (Extracranial – carotid Non-modifiable risk factors
artery stenosis; intracranial) - age (elderly)
- gender (male)
Modifiable risk factors
- smoking
- physical inactivity
- obesity
- DM
- Hypertension
- Hypercholesterolaemia
- Homocystenemia
- Prothrombotic states
Small artery disease (Lacunar) Chronic Hypertension
- hypertrophy of media
- fibrinoid deposition in wall
(lipohyalinosis)
Hypoperfusion Anaemia
GI bleeding/Haemorrhage
Embolic Heart (Cardiogenic) Hx/PE
Artery - Atrial Fibrillation (5x)
Resp - Mitral Stenosis
- Cardiomyopathy
- Prosthetic valve
- Recent AMI (<6mths)
- Infective Endocarditis
2D Echo
- Patent foramen ovale
- Akinetic segment
- Diffuse hypokinesia
- Ejection fraction <30%
- Mural thrombus
- Dilated LA
- Vegetations
Haemorrhagic Berry aneurysm (cortical)
(20%) AVM (young <40y) (cortical)
Amyloid angiopathy (cortical)
Hypertension (subcortical)
Trauma
Coagulopathy
Substance abuse
Haemorrhagic conversion of infarct

Non-atherosclerotic vasculopathy (5% of ischaemic strokes)

- vasculitis: SLE, giant cell arteritis, syphilis
- Prothrombotic state: Factor V Leiden mutation, Protein C/S deficiency, anti-thrombin III deficiency, antiphospholipid
syndrome, hyperhomocystinaemia

62
Aims to answer 6 questions from history/PE
1. Is it a stroke?
2. Where is the stroke?
3. Ischaemic or haemorrhagic?
4. Mechanism of stroke?
5. Risk factors?
6. Functional impairment

1. Is it a stroke?
Differential diagnoses:
- Space occupying lesion
a) Aneurysm
b) AVM
c) Tumour (slow progression of symptoms, mets more common than primary)
- Head injury (subdural haemorrhage)
- Infection (Encephalitis; abscess esp if patient has brochiectasis or IE)
o Fever & seizures
- Seizure
- Todd’s paresis (Epilepsy)
o Post-seizure hemiplegia (usually <3days)
o Preceded by seizure
- Migraine
o Preceded by headache
o Hemiplegia usually lasts <24h
- Metabolic
o Hyponatraemia
o Hypoglycaemia
o Hypo/Hyperkalemia (periodic paralysis)
o Hypercapnia
- Drugs (TCA overdose)
- Multiple Sclerosis
- Neuromuscular disorders
o Myasthenia
o Guillain-Barre Syndrome
- Labyrinthine disorders
o Vestibular neuronitis (viral)
o BPPV (vertigo on changing head position)

2. Where is the stroke?

Large vessel (atherosclerosis, embolic) vs small vessel (arteriosclerosis)
Brainstem vs subcortical vs cortical

ACA territory Contralateral LL weakness and sensory deficit (LL>UL)

Urinary incontinence
MCA territory superior division
contralateral face and UL weakness and sensory deficit (UL>LL)
Broca’s dysphasia (dominant hemisphere)

Inferior division
Contralateral homonymous hemianopia
Wernicke’s dysphasia (dominant hemisphere)
Neglect (common to both lobes)
Dressing and constructional apraxia (non-dominant
hemisphere)

Lenticulostriate branches
Contralateral hemiplegia and sensory deficit
PCA territory Contralateral homonymous hemianopia with macular sparing
rd
Ipsilateral 3 nerve palsy with contralateral hemiplegia (mid-

63
 brain)
Nominal dysphasia (dominant hemisphere)
Lacunar syndrome (Basal ganglia, Internal capsule, thalamus, - pure motor (dense hemiplegia)
pons) - pure sensory
- sensorimotor
- alert - ataxic hemiparesis (dentate-rubro-thalamic tract)
- no cognitive impairment - clumsy hand dysarthria (genu of IC)

Vertebrobasilar circulation Drowsiness

- PCA territory Lower cranial nerve palsies (crossed neuro signs)
- Brainstem Ataxia
- Cerebellum Spastic hemi/quadriplegia
Hemi/total sensory deficit

3. Ischaemia or haemorrhagic?

Ischaemic Haemorrhagic
Thrombotic Embolic Coagulopathy
old AF Examination may reveal raised ICP
male MS Altered mental state
hypertensive Prosthetic valve Severe headache
smoking Cardiomyopathy Vomiting
hypercholesterolaemia Recent MI Papilloedema
DM Hypertension (cushing’s reflex)

Investigations
CT brain (without contrast – may be misleading)
- mainly for excluding haemorrhagic stroke especially if thrombolysis is being considered
- Identifies nearly 100% of parenchymal haemorrhage only within 5-7 days of stroke
- Only 50% of infarcts seen (and only after 24-48 hours later)
- After 7 days, haemorrhage is distinguishable from infarcts

4. Mechanism of stroke?
a) embolus
b) extracranial thrombosis
c) intracranial thrombosis (presence of atherosclerotic risk factors + absence of cardioembolic source + absence of carotid
stenosis)

History
Physical Exam
- AF, MS suggest embolus
- Carotid bruit suggests thrombosis
Investigations
- ECG
- 2D Echo:
o Patent foramen ovale
o Akinetic segment
o Diffuse hypokinesia
o Poor ejection fraction <30%
o Mural thrombus (post MI)
o Dilated left atrium (secondary AF)
o Vegetations (IE, SBE)
# indications = abnormal auscultations/ECG/CXR findings
???
isolated wedge-shaped cortical infarct
absence of atherosclerotic risk factors

- Trans-oesophageal (bubble) echocardiogram (for patent foramen ovale)

- Blood tests (BSL, fasting lipids)
64
 - Duplex Doppler carotid ultrasound (carotid artery stenosis)
o Only for patients with non-disabling partial anterior circulation stroke who is fit for operation and agreeable to
endarterectomy
- Cerebral angiogram
o To quantify degree of carotid stenosis and status of intracranial circulation
- Transcranial doppler ultrasound
o Evidence of intracranial atherosclerosis
o Usually not done now due to MRA (less operator dependent, able to visualize entire circle of willis)

5. Risk Factors?

6. Functional impairment?
- Activities of daily living
o Transfer
o Feeding
o Toileting/continence
o Bathing
o Grooming
o Dressing
- impairment (eg. Severe hemiparesis) = NIH Stroke Scale
- Disability (eg. Unable to walk) = Barthel’s index
- Handicap (eg. Unable to attend to own needs) = Modified Rankin’s Score, social aspect to disability

INVESTIGATIONS

Bloods FBC Anaemia (contributory factor,

influences used of anticoagulants)
Polycythaemia (hyperviscosity)
Leukostasis (hyperviscosity)
Thrombocytopenia/Thrombocytosis
U/E/Cr Exclude metabolic causes
PT/PTT Coagulopathy (if want to start on anti-
coagulation)
ESR CNS infection, inflammation,
malignancy, vasculitis
Fasting lipids Risk factor
Fasting glucose, HbA1c Risk factor
Young stroke Factor 5 Lieden mutation
Protein C/S deficiency
Anti-thrombin III deficiency
APS (lupus anticoagulant, anti-
cardiolipin antibodies)
SLE (ANA, anti-dsDNA)
Tertiary syphilis (VDRL)
Fasting homocysteinaemia
Radiology CXR & ECG (AF) Cardiomegaly (cardiac disease, HPT)
st
CT brain Exclude haemorrhagic stroke, 1 invx
to order
MRI brain Posterior fossa lesions
Late presentation of stroke (>7days)
(T2 for chronic)
Acute ischaemic stroke (MRI – DWI)
2D echo/TEE Evidence of embolic stroke
Carotid Doppler U/s Establish carotid thrombosis/stenosis
No point doing it if it is a posterior
circulation stroke (not supplied by
carotid)
Cerebral angiogram (MRA – Quantify degree of carotid stenosis
non-invasive) Status of intracranial circulation
AVM/aneurysms
65
 Carotid dissection (MRA is diagnostic)
Transcranial Doppler u/s Evidence of intracranial
atherosclerosis
ECG Atrial Fibrillation (do TFT)

1) MANAGEMENT
- Manage within specialised stroke unit if possible
o Reduce mortality and morbidity
o Reduce secondary complications of stroke
o Reduce need for institutional care by reducing disability
- Aims
o prevent/reverse acute brain injury
o prevent further neurological injury

- General management
Resuscitation Airway
Breathing (may have to intubate in large cortical strokes, increased ICP or vertebrobasilar
ischaemia = respiratory depression)
Circulation
Hypertension: Do not lower too rapidly or may exacerbate stroke due to global hypoperfusion
Only treat if there is aortic - SBP > 200mmHg or DBP > 110mmHg
dissection or AMI a) IV nitroprusside/labetalol (avoid oral nifedipine as effect is unpredictable)
b) Lower BP by 10-20% over 2 hours
c) Lower BP to 160/100 over ~ days
Hourly Parameters HR, RR, BP (hold off anti-HPTs unless SBP > 220mmHg), GCS, ICP (important to monitor in
large strokes with cerebral oedema = coning)
IV Fluids Avoid dextrose and excessive fluid  cerebral oedema
IV isotonic saline
Nil by mouth NBM due to risk of aspiration especially in
- massive haemorrhagic stroke
- brainstem stroke
- pseudobulbar palsy
get speech therapy to assess swallowing
Prevent hyperthermia Exacerbation of ischaemic neuronal injury
Increased M&M
Prevent hyperglycaemia Increased M&M

# monitor daily for any complications/progression of stroke

(a) haemorrhagic conversion of infarcts
(b) seizures/epilepsy
(c) DVT prophylaxis – moribund patients, grade 2 power and below
# decrease in GCS
- extension of brainstem lesion, haemorrhagic conversion (restoration of blood flow into infracted area via damaged
vascular endothelium following lysis of thrombus), raised ICP, coning, cerebral edema

Specific management
Ischaemic Stroke
Aspirin (300mg/24hours) Initiate ASAP (within 48 hours) – safe even during acute phase
Reduces recurrence of stroke

Thrombolysis (must rule out haemorrhage) IV r-tPA (within 3 hours) or intra-arterial pro-urokinase (within 6 hours)
Decreases risk of adverse events by 12%
Streptokinase is contraindicated in view of lack of beneficial effect
Runs the risk of catastrophic ICH therefore should not be routinely used

Haemorrhagic stroke
- Measures to decrease ICP
o Raise head of bed
o Mechanical hyperventilation
o IV mannitol

66
 - Stop all thrombolytics, antiplatelets and anticoagulants
- Withhold anti-hypertensives unless SBP > 200mmHg
o Acute BP reduction may reduce re-bleeding and haematoma expansion BUT may exacerbate ischaemia in
regions adjacent to haematoma
- Correct coagulation defects
- Monitor hypertensive organ failure
Neurosurgery
- intraparenchymal haematomas: surgical evaluation if there is a clinical deterioration
- Pure cerebellar infarct: posterior cranial fossa decompression (potential herniation due to small space; patients make
good recovery)
- Hydrocephalus (compression of aqueduct of Sylvius by blood/edema, a/w cerebellar stroke): ventricular
shunting/decompression
- Raised ICP with much cerebral edema: craniectomy
- Clipping of aneurysms

2) Secondary prevention (risk factor management)

Anti-platelet (aspirin) - long term treatment reduces risk of serious vascular events
- Aspirin 75-150mg/day
- Alternatives = Ticlodipine (ticlid), clopidogrel (plavix), dipyridamole (persantin)
Anti-coagulation - Indications: AF, valvular heart disease, recent MI, APLs, dilated cardiomyopathy with low EF,
(Warfarin) brainstem CVA
- Target INR: 2-3
- SE: haemorrhagic conversion (start 5 days post-CVA)
Carotid - For moderate to severe carotid artery stenosis (>60%) with ipsilateral carotid territory TIA or
endarterectomy non-disabling ischaemic stroke
- Only for surgically fit patients and under experienced surgeons
Hypertension - All stroke patients (regardless of type of stroke or pre-stroke BP status)
- Start only after acute phase of stroke (prevent hypoperfusion) 1-2 weeks later
Dyslipidaemia Statins
Diabetes Insulin
OHGAs
Stop smoking, optimize BMI

3) Rehabilitation
Multidisciplinary care (specialized Rehabilitation medicine unit)
a) physiotherapy
b) occupational therapy
c) speech therapy

Long term complications of immobility

1. DVT
2. Constipation  acute retention of urine  UTI
3. Bed sores
4. Pneumonia
5. Depression
6. ?

Assessing rehab potential

1. Pre-morbid status
2. Social support, home environment, finances
3. Severity of stroke (lacunar – good, cortical - +/-, brainstem – poor)
4. Co-morbidities
5. Education background
6. Age of patient

67
Young stroke

Aetiology
1. Metabolic: homocystinuria, hyperhomocystinaemia, premature atherosclerosis
2. Vasulitis: Syphillis, SLE
3. Hypercoaguable states: Factor 5 Leiden mutation, Protein C/S deficiency, anti-thrombin III deficiency, APS, SLE
4. Drugs: OCP, amphetamines, cocaine, heavy alcohol consumption, smoking
5. Hypertension: renal artery stenosis, pheochromocytoma, coarctation of aorta
6. Carotid dissection: spontaneous, trauma, cervical manipulation, neck exercise
7. Cardiac: infective endocarditis, prosthetic valve, mitral valve prolapse, patent foramen ovale, cardiomyopathy
8. Berry aneurysm, AVM

Young stroke work up

a) Bloods = FBC, ESR, PT/PTT, fasting lipids + as above
b) Drug screen (cocaine, amphetamines, alcohol)
c) 2D Echo/TEE
d) MRA = carotid dissection, berry aneurysm, AVM

Prognosis
- immediate outcome
o Haemorrhagic: mortality ~ 50%
o Infarct: mortality < 20%
- Long term outcome
o Haemorrhagic: depends on cause and function
o Infarct:
 recurrence ~ 5-15% per year
 at risk of AMI and IVD
 5-year mortality ~ 40%

68
Transient Ischaemic Attack (TIA)
Definition = sudden onset of focal neurological deficit resolving within 24 hours
Pathology = due to temporary occlusion of the cerebral circulation usually by an embolus
Clinical importance = harbingers of CVA and AMI

Clinical Presentation
1. Attacks can be single/multiple
2. Symptoms may be the same/different on each occasion
3. A stroke usually occurs within 2 days of the TIA if not treated

Physical Examination
1. No CNS signs 24 hours after an attack
2. Pulse – AF
3. Murmurs – valvular heart disease, prosthetic valves, infective endocarditis
4. Carotid bruit (absence does not rule of a carotid source of emboli – tight stenoses often have no bruit)
5. Fundoscopy (during TIA) – retinal artery emboli (patient experiences amaurosis fugax)

Aetiology
1. Atherothromboembolism
a. Carotid stenosis
b. AF
c. Post-MI mural thrombus
d. Prosthetic valve
e. Valvular heart disease
2. Hyperviscosity
a. Polycythaemia
b. Leukostasis (may need urgent chemotherapy)
c. Multiple myeloma
3. Vasculitis
a. SLE
b. Giant cell arteritis
c. Syphilis

Investigations
Similar to those for stroke

Treatment
# begin after the first attack (don’t wait for another)
1. Control risk factors = smoking, hypertension, dyslipidaemia, DM, obesity, physical inactivity)
2. Life-long antiplatelet therapy (aspirin)
3. Anti-coagulation if AF, recent MI, valvular heart disease
4. Carotid endarterectomy

Prognosis
Risk of CVA/AMI is 7% per year each

Features of Carotid TIA

Hemiparesis
Aphasia
Loss of vision?

Features of VB TIA
Vertigo
Dysphagia
Ataxia
Sudden bilateral blindness

69
Stroke - Stroke Syndromes
1. Lacunar syndromes
- Pathology
o caused by small-vessel disease leading to thrombotic infarction in the internal capsule, basal ganglia,
thalamus and pons
o small well circumscribed lesions
- Commonly seen in patients with hypertension, dyslipidaemia and diabetes
- Associated with chronic hypertension
o Hypertrophy of media
o Fibrinoid deposition in vessel wall (lipohyalinosis)

- Clinical types
# patient is alert and there is no cognitive impairment
a) pure motor
o lesion is in the pons or internal capsule
o no sensory deficit
b) pure sensory
o lesion is in the thalamus
o no motor deficit
c) sensorimotor
o lesion is in the internal capsule
d) ataxic hemiparesis
o lesion is in the pons or internal capsule (dentato-rubro-thalamic tract)
e) clumsy-hand dysarthria
o lesion is in the pons or internal capsule
o slurred speech & weakness/clumsiness of one arm

- Management
o control of risk factors
o smoking cessation
o use of anti-platelet agents

2. Anterior cerebral artery syndrome

a. Unilateral lesion
o contralateral motor and sensory loss in LL
o urinary incontinence
o Broca’s dysphasia (dominant hemisphere)
b. Bilateral lesion
o bilateral motor and sensory loss in LL
o urinary incontinence
o primitive reflexes (frontal lobe release)
 palmomental reflex, grasp reflex (clenching, inability to let go), glabellar tap, snout (pout) reflex,
rooting/sucking reflexes
o changes in personality and behavior
 apathy, disinhibition, emotional lability, preservation, akinetic mutism – does not move or talk)
o gait apraxia

3. Middle cerebral artery syndrome

a. Superior division
o contralateral motor and sensory loss in face and UL (>LL)
o Broca’s dysphasia (dominant hemisphere)

b. Inferior division
o contralateral homonymous hemianopia
o gaze deviation towards the side of the lesion
o wernickes’s dysphasia (dominant hemisphere)
o neglect (common to both)
o agraphsthesia, astereognosis, OKN, apraxia

c. Lenticulostriate branches

70
 o contralateral hemiplegia and sensory loss

4. Posterior cerebral artery syndrome

a. Cortical branches
o contralateral homonymous hemianopia with macular sparing
o nominal aphasia (dominant hemisphere)

b. Perforating branches
rd
o midbrain (weber’s syndrome) – ipsilateral 3 nerve palsy with contralateral hemiplegia
o thalamus – contralateral hemisensory deficit

5. Lateral medullary syndrome

- Pathology = thrombotic occlusion of posterior inferior cerebellar artery causing infarction of lateral medulla and
inferior surface of cerebellum
- Most common posterior circulation stroke (possible diagnosis in a patient on NGT)

- Clinical presentation (no limb weakness!)

a) sympathetics
o ipsilateral Horner’s syndrome
b) vestibular nucleus
o vertigo, nausea, vomiting, nystagmus (rotatory)
th th
c) 9 and 10 cranial nerve nuclei
o dysarthria, dysphagia, dysphonia, decreased gag reflex, palatal weakness
d) descending spinal tract of trigeminal nucleus
o ipsilateral pain and temperature loss of face
e) spinothalamic tract
o contralateral pain and temperature loss of body below face
f) spinocerebellar tract
o ataxic gait, poor balance, ipsilateral cerebellar signs
th
may present with an ipsilateral UMN 7 nerve palsy due to an aberrant corticobulbar tract (arises from medulla instead of pons)

6. Medial medullary syndrome

- Pathology = occlusion of medullary branches of vertebral artery
- Clinical presentation
a) corticospinal tract  contralateral hemiplegia
th
b) 12 cranial nerve nucleus  ipsilateral tongue paralysis with fasciculations
c) dorsal column medical lemniscus  contralateral vibration and proprioception loss

7. Medial pontine stroke

- Clinical presenation
a) Medial longitudinal fasciculus  internuclear opthalmoplegia
b) Lateral gaze centre  ipsilateral gaze palsy (eyes deviate away from side of lesion)
c) Corticospinal tract  contralateral hemiplegia
d) Medial lemniscus  contralateral vibration and proprioceptive loss

8. Lateral pontine stroke

- Clinical presentation
a) spinothalamic tract  contralateral sensory deficit
b) spinocerebellar tract  ipsilateral cerebelllar signs
c) CN 5,6,7,8

9. Massive pontine stroke

- Clinical presentation
o Comatose
o Small and pinpoint pupils (reactive to light)
o Quadriparesis with upgoing toes
o Doll’s negative
o Locked-in syndrome (conscious but unable to move to show consciousness, may retain ability to look up
and down)
- Poor prognosis

71
Intracerebral Haemorrhage
1. Aetiology
a. Hypertension
b. Trauma
c. Blood dyscrasia
d. Side-effect of anti-coagulant therapy
e. Berry aneurysm
f. AVM/amyloid angiopathy
g. Haemorrhagic conversion of infarct
h. Substance abuse = cocaine, amphetamines, alcohol

2. Pathophysiology
- explosive entry of blood into brain parenchyma causes immediate cessation of function in that area (neurones are
structurally disrupted and white matter tracts are split open)
- Rim of cerebral edema forms around resulting blood clot  mass effect and raised ICP
- Results in
o Shift of intracranial contents (midline shift)
o Transtentorial coning (hutchinson’s pupil, respiratory depression)
o Coma and rapid death
- Haematoma gradually absorbed  haemosiderin-lined slit in the brain parenchyma

3. Clinical presentation
- usually no warning signs
- occurs during waking hours
- usually in a known hypertensive patient or in a patient with a bleeding tendency
- full deficit seldom present at onset (develops gradually over mins-hours)  decreased consciousness
- focal signs usually present

Putamen
- hemiplegia
- gaze deviation to the side of the brain
- headache
- field defect
- cortical deficits as haemorrhage progresses

Thalamus
- eyes look down at nose
- impaired vertical gaze
- small and non-reactive pupil
- marked hemisensory loss

Pons
- comatose
- small pinpoint pupils
- quadriparesis with upgoing toes
- Doll’s negative
- Locked-in syndrome: conscious but unable to move to show consciousness, may retain ability to look up and down

4. Investigations
CT-head
- detect parenchymal haemorrhage with near 100% accuracy within 7-10 days from onset
- beyond 10 days  cannot distinguish haemorrhage from infarct

5. Management
a. Resuscitate (intubate if necessary)
b. Avoid excessive IV hydration
Keep NBM
Avoid hyperthermia and hyperglycaemia
c. Stop all thrombolytic, antiplatelets and anticoagulants

72
 Correct coagulation defects
d. Withhold antihypertensives unless SBP > 220/130 mmHg
e. Decrease ICP
i. Raise head of bed
ii. Mechanical hyperventilation
iii. IV mannitol
f. Refer neurosurgery – surgical evacuation of clot
g. Place on head chart (monitory HR, RR, BP, Pupils, GCS, ICP)
Monitor for hypertensive organ failure
h. Complete rest in bed + stool softeners

73
Subarachnoid Haemorrhage
1. Aetiology
(a) Berry aneurysm (85%)
~ bulging from the bifurcations of the cerebral arteries particularly in the Circle of Willis (junction of
posterior communicating artery with ICA / anterior communicating artery with ACA / bifurcation of
MCA)
~ develop from medial defects in the arterial wall
~ increased risk in association with APKD, coarctation of the aorta, Ehlers-Danlos syndrome
(b) AVM (5%)
(c) Non-aneurysmal haemorrhage (10%)

2. Clinical presentation
- risk factors = family history of berry aneurysm
gender (female)
th
age (esp 4 decade)
history of collagen vascular disorder, coarctation of the aorta, APKD
- may have ‘sentinel’ headache days-weeks beforehand
- sudden severe onset of ‘worst headache of my life’ (usually occipital) occurring during exertion
severity is maximal at onset
- usually no focal deficits unless artery ruptures into brain parenchyma
arterial vasospasm 2 presence of blood in subarachnoid space (usually begins 3-
14 days later)
rebleeding
hydrocephalus
- symptoms of raised ICP = projectile vomiting, neck stiffness (takes 6 hrs to develop), photophobia
- rapid progression into coma
- clinical signs = low GCS (intubate if GSC score < 8)
severe hypertension
high diastolic pressure (> 80mmHg) a/w bradycardia (Cushing’s reflex)
meningism (positive Brudzinski and Kernig’s sign)
papilloedema / subhyaloid haemorrhage

3. Differentials (only 25% of those with sudden severe headache have SAH)
(a) meningitis
(b) migraine
(c) intracerebral haemorrhage
(d) cerebral venous thrombosis
(e) idiopathic

4. Complications
(a) Acute = transtentorial coning, brainstem herniation, coma, death
neurogenic pulmonary oedema (increase in pulmonary interstitial and alveolar fluid)
cardiac arrhythmias
hydrocephalus
(b) Subacute = hydrocephalus
arterial vasospasm
rebleeding
hyponatraemia (SIADH, cerebral salt-wasting syndrome)
(c) Chronic = complications of immobility
persistent neurological deficits
recurrence

5. Investigations
(a) CT head = abnormal in 90% of cases of SAH (10% false-negative rate do LP)
(b) Lumbar puncture = bloody CSF
elevated pressure
xanthochromia (yellowish tinge to CSF due to RBC breakdown)
raised protein levels
bilirubin (excludes ‘bloody’ tap)
74
 (c) 4-vessel angiogram (alternative is CTa/MRA) = locate source of bleeding

5. Management
(a) Resuscitate (intubate if necessary)
(b) Avoid excessive IV hydration
Keep NBM
Avoid hyperthermia and hyperglycaemia
(c) Stop all thrombolytics, antiplatelets and anticoagulants
Correct coagulation defects
(d) Analgesia (pain)
Nimodipine (CCB to prevent arterial vasospasm)
Withhold anti-hypertensives unless SBP>220/130mmHg
(e) Decrease ICP = raise head of bed
mechanical hyperventilation
IV Mannitol
(f) Refer neurosurgery = surgical clipping of aneurysm (SE=post-craniotomy epilepsy)
(g) Place on head chart (monitor HR, RR, BP, pupils, GCS, ICP)
Monitor for hypertensive organ failure (U/E/Cr)
(h) Complete rest in bed (CRIB) + stool softeners

6. Prognosis
- most common cause of death is rebleeding (30%)

Grade Signs Mortality (%)

I none 0
2 neck stiffness, CN palsies 11
3 drowsiness 37
4 drowsiness, hemiplegia 71
5 prolonged coma 100
st
- almost all the mortality occurs in the 1 month
st
- if survive 1 month → 90% survive a year or more

7. Preventive surgery
- usually done only in young patients = more years at risk
higher risks if done > 45 yrs old
or if aneurysm > 7mm in diameter (esp with risk factors of hypertension or prior history of bleeding)
- best in those with few/no symptoms (grades 1/2)

hyperdense area corresponding to blood in the

subarachnoid basal cisterns

75
Subdural Haemorrhage
1. Usually due to head trauma (shearing forces)

2. Pathology
Tearing of bridging veins between cortex and venous sinuses (vulnerable to deceleration injury)
- haematoma formation between dura and arachnoid mater (sub-dural)
- ICP gradually increases  midline shift away from clot  tentorial herniation  coning  coma  death

3. Risk Factors
a. Elderly  brain shrinkage makes bridging veins more vulnerable
b. Long term anticoagulation
c. Prone to falls (epileptics, alcoholics)

4. Clinical presentation
- insidious onset (low pressure veins bleed more slowly)
- fluctuating consciousness
- physical and intellectual slowing
- sleepiness
- headache
- change in personality
- unsteadiness

5. Clinical signs
- raised ICP
- focal neurological deficits occur late and often long after injury

6. Differential diagnosis
a. Evolving stroke
b. Dementia
c. Cerebral tumour

7. Investigations
CT-head
- crescent shaped haematoma over 1 hemisphere
- midline shift

8. Management
Surgical evacuation via burr holes

9. Prognosis
Excellent if treated promptly!

76
Extradural (epidural) Haemorrhage
1. Aetiology
Trauma

2. Pathology
- laceration of the middle meningeal vessels due to a fracture temporal/parietal bone
- typically after trauma to a temple just lateral to the eye
- blood accumulates between bone and the dura

3. Clinical presentation
- typical ‘lucid interval’ pattern  deterioration of consciousness after any head injury that initially produced to
LOC/after resolution of post-injury drowsiness; may last a few hours-days
- deteriorating level of consciousness caused by rising ICP
- headache, vomiting, altered mental state, seizures  hemiparesis, hyper-reflexia, upgoing plantars  ipsilateral
pupil dilation, bilateral spastic paraparesis, deep and irregular breathing, coma deepens  bradycardia,
hypertension  death secondary to respiratory arrest

4. Investigations
a. X-ray skull = normal or # crossing the course of the middle meningeal vessels (skull # after trauma greatly
increases the risk of EDH)
b. CT head = lens-shaped haematoma over 1 hemisphere (biconvex as touch dural attachments to the skull keep
the haematoma localized; rarely crosses a cranial suture)
# LP is contraindicated!

5. Management
Clot evacuation +/- ligation of bleeding vessel

6. Prognosis
Excellent if early diagnosis and operation

77
Spinal cord syndromes
Brown-Sequard syndrome
 pathology = hemisection of spinal cord
 aetiology
(a) Vascular = angioma
subdural/epidural haematoma
haematomyelia
(b) Infective = syphilis
HIV/HSV/VZV
meningitis
(c) Trauma = bullet/stab wounds
(d) Autoimmune = multiple sclerosis
(e) Metabolic = subacute combined degeneration of cord
(f) Infiltrative = syringomyelia
(g) Neoplasia = multiple myeloma
spinal cord tumour
 clinical features
(a) motor = ipsilateral LMN signs at level of lesion
ipsilateral UMN signs below level of lesion
(b) sensory = ipsilateral loss of vibration and proprioception
contralateral loss of pain and temperature 2-3 segments below level of lesion
 request to examine
(a) abdomen  palpable bladder
PR examination  lax anal tone
(b) back  trauma
kyphosis, tenderness on deep percussion of vertebral column (multiple myeloma)
(c) cerebellar signs  multiple sclerosis
(d) eyes for RAPD, INO, one-and-a-half syndrome, optic atrophy  multiple sclerosis

Subacute combined degeneration of the cord

 pathology = axonal degeneration of both the corticospinal and dorsal column tracts
peripheral neuropathy
 aetiology = vitamin B12 deficiency (vegan diet, alcohol consumption, pernicious anaemia, gastrectomy,
Crohn’s disease, celiac disease)
 consider vitamin B12 deficiency as a differential in all spinal cord, peripheral nerves and neuropsychiatric disorders
 clinical features
(a) motor = spastic paraparesis
absent ankle jerks with brisk knee jerks
Babinski’s reflex present
(b) sensory = loss of vibration and proprioception
(c) gait = positive Romberg’s sign
sensory ataxia
 request to examine
(a) eyes  conjunctival pallor
Argyll-Robertson pupil (tabes dorsalis is a differential)
optic atrophy
(b) abdominal scar  previous gastrectomy
(c) mini-mental state examination  dementia
 investigations
(a) FBC = macrocytic anaemia
(b) PBF
(c) serum vitamin B12 and folate levels
(d) serum iron, ferritin, TIBC
(e) pernicious anaemia = anti-IF Ab, anti-parietal cell Ab, Schilling test
(f) MRI
 avoid giving PCT before replacing vit B12  will irreversibly worsen neurological manifestations
 variable response to vit B12 therapy = improve, remain unchanged or deteriorate
# sensory improve > motor
# peripheral neuropathy improve > myelopathy
78
Syringomyelia
 rare disorder
 epidemiology = no gender predilection
age of onset (40-50 yrs old)
 pathology
- syrinx development (fusiform cyst) in or beside central canal of cervical cord
- may extend into brainstem above and distal cord below
- as syrinx enlarges and expands into adjacent grey and white matter
# decussating anterior spinothalamic fibres in anterior white commissure  dissociated sensory loss
segmental sensory loss
band of numbness/pain
# anterior horn cells at level of syrinx  LMN signs
# corticospinal tract below level of syrinx  UMN signs
# spinothalamic tract  total loss of pain and temperature below level of lesion
# cervical sympathetics at C8, T1  Horner’s syndrome
- symptoms may worsen during coughing/sneezing = acute rise in venous pressure  syrinx extension
- cavity of syrinx contains fluid similar to CSF but with higher protein content
 associated with = Arnold-Chiari malformation
spina bifida
bony defects around foramen magnum
hydrocephalus
spinal cord tumours
 aetiology
(a) primary = Arnold-Chiari malformation
(b) secondary = trauma, intramedullary tumour, infection (arachnoiditis, TB)
(c) idiopathic
 clinical features
(a) motor (late sign)
# LMN signs in upper limbs = wasting of small muscles of hands, hypotonia, hyporeflexia
# UMN signs in lower limbs = spastic paraparesis
spasticity, hyper-reflexia, Babinski’s reflex
(b) sensory = loss of pain and temperature over neck, shoulders and arms (cape-like distribution)
intact vibration and proprioception (‘dissociated sensory loss’)
# classically = painless burns
Charcot’s joints (DM  toes and ankles; tabes dorsalis  hips and knees)
(c) Horner’s syndrome
(d) lower brainstem (extension above C5 to pons)  syringobulbia
# medial longitudinal bundle = nystagmus, ataxia
# spinal tract of CN V = dissociated sensory loss of face of ‘onion-skin’ pattern
# base of skull = CN 9,10,11,12
(e) others = scoliosis
hydrocephalus (25%)
 investigations
(a) MRI

Anterior spinal artery syndrome

 rare disorder
 pathology = occlusion of anterior spinal artery which supplies 2/3 of spinal cord except dorsal columns
usually affects thoracic cord
 clinical features
(a) motor = spastic paraplegia with urinary incontinence
(b) sensory = sensory level can usually be found
 good prognosis

Tabes dorsalis
 pathology = form of tertiary syphilis
demyelination of axons in dorsal column
 epidemiology = common in HIV patients
 5 clinical patterns of neurosyphilis
(a) meningovascular disease = 3-4 yrs after primary infection
79
(b) tabes dorsalis = 10-40 yrs after primary infection
(c) generalized paralysis of the insane = 10-15 yrs after primary infection
(d) taboparesis = combination of (b) + (c)
(e) localized gummata
 clinical presentation
(a) motor = absent knee jerks and extensor plantar response
(b) sensory = loss of vibration and proprioception
Charcot’s joints affecting hips and knees
neuropathic ulcers
(c) gait = positive Romberg’s sign
sensory ataxia
high-stepping gait
(d) eyes = Argyll-Robertson pupil (unreactive to light but reactive to accommodation)
optic atrophy
(e) others = acute abdominal pain (lightning pains)
constipation (present as a rule)
loss of bladder sensation  overflow incontinence
impotence
 diagnosis = VDRL
 treatment
(a) IV penicillin
# Jarisch-Herxheimer reaction = acute hypersensitivity reaction caused by toxins from killed
spirochaetes  can be fatal  steroids given during first few days
of penicillin therapy

Peripheral neuropathy
 peripheral neuropathy (mainly sensory)
A = alcohol
autoimmune (RA, SLE)
B = vitamin B12 deficiency
C = CIDP
cancer (ca lung, Hodgkin’s lymphoma)
D = diabetes mellitus
drugs (isoniazid, phenytoin, nitrofurantoin, chloroquine, penicillamine, vincristine)

peripheral neuropathy (mainly motor)

(a) heavy metal poisoning = lead, arsenic, mercury
(b) Guillain-Barre syndrome
(c) porphyria
 clinical presentation
(a) motor = ascending distal weakness
(b) sensory = progressive and symmetrical numbness in ‘glove and stocking’ distribution
sensory loss for all modalities (pain, vibration, proprioception)
Charcot’s joints (toes and ankles)
 request to examine
(a) diabetes = diabetic dermopathy
(b) alcoholic liver disease = palmar erythema, spider naevi, hepatomegaly, duputyren’s contracture,
parotidomegaly
(c) vitamin B12 deficiency = conjunctival pallor, atrophic glossitis
(d) rheumatoid hands
 types of neuropathy in DM
(a) mononeuropathy
(b) sensory polyneuropathy (symmetrical)
(c) motor polyneuropathy (asymmetrical  diabetic amyotrophy)
(d) mononeuritis multiplex
(e) autonomic neuropathy
 Mx for painful neuropathy = TCA
carbamazepine
gabapentin

80
Summary

Spinothalamic loss only Dorsal column loss only

Brown-Sequard syndrome (contralateral limb)
Syringomyelia
Anterior spinal artery thrombosis
Lateral medullary syndrome
Peripheral neuropathy
Multiple sclerosis
Brown-Sequard syndrome (ipsilateral limb)
Tabes dorsalis
Subacute combined degeneration of cord
Medial medullary syndrome
Peripheral neuropathy
Multiple sclerosis

 dissociated sensory loss

(a) syringomyelia
(b) anterior spinal artery thrombosis
(c) diabetic neuropathy
(d) leprosy

81
Case 35 | Syringomyelia
Record

This patient (with kyphoscoliosis) shows wasting and weakness of the small muscles of the hands (sometimes there is curling of
the fingers), flattening of the muscles of the ulnar border of the forearm and the upper limb reflexes are absent (conspicuous
fasciculation is uncommon). There is dissociated sensory loss* over (one or both of) the upper limbs and the upper chest** and
there are scars (from painless burns and cuts) on the hands. Ths lower limb reflexes are exaggerated and the plantars are
extensor. A Horner’s syndrome is (may be) present (involvement of sympathetic neurones especially at C8/T1).

These findings suggest syringomyelia (? Nystagmus, which may occur with lesions from C5 upwards – i.e. involving the medial
longitudinal bundle).

Syringobulbia. Syrinx may involve upper cervical and bulbar segments (usually an extension of syringomyelia but it may begin in
the brainstem) and cause

 Nystagmus

 Ataxia

 Facial dissociated sensory loss (initial onion skin loss over the outer part of the face, from involvement of the lower part
of the Vth nucleus in the cord, may occur before the syrinx reaches the medulla)

 Bulbar palsy (wasted fasciculated tongue, palatal paralysis, nasal dysarthria, dysphasia, weakness of sternomastoids
and trapezius from XIth nerve involement, etc)

Trophic and vasomotor disturbances are common in syringomyelia, e.g.:

 Areas of loss of, or excessive, sweating

 La main succulente (ugly, cold, puffy, cyanosed hands with stumpy fingers and podgy soft palms)

 Coarse, thickened skin over the hands with callosities over the knuckles and scars from old injuries

 Slow healing and indolence ulceration of the digits

Charcot’s joints may occur, usually at the elbow or shoulder. Tabes dorsalis (knees, hips) and diabetes mellitus (toes, ankles) are
the other causes of Charcot’s joints.

Skeletal abnormalities which may be associated with syringomyelia

 (Kypho)scoliosis (mild, very common)

 Short neck (e.g. fusion of the cervical vertebrae; Klippel-Feil syndrome

 Asymmetrical thorax

 Sternal depression or proinence

 Cervical ribs (may cause diagnostic difficulty)

*Analgesia and thermoanaesthesia, but light touch and propioception intact. In the early stages cold stimuli may be perceived
but not warm stimuli

** Due to destruction by the syrinx of crossing axons carrying pain and temperature sensation. The area affected depends on
the length of the syrinx – e.g. lower cervical and upper thoracic. Separate from this effect on crossing axons, the syrinx may also
involve one or both spinothalamic tracts producing dissociated sensory loss in one or both lower limbs.

Station 3: Central nervous system | 249

82
Myasthenia Gravis I
History
name/age/ethnicity/gender/occupation
drug allergy
past medical history
date of admission

History of presenting complaint

Presenting complaint
1. Ocular involvement
- ptosis = duration
unilateral vs bilateral
complete vs partial
aggravated by  glare, exercise, as day progresses
improves with  rest
alternating sites
- strabismus
- diplopia = monoocular vs binocular
horizontal/vertical images
worse in which direction of gaze
near (severe) or far (mild) vision
2. Generalised
- bulbar = dysarthria
dysphonia (nasal speech)
difficulty chewing food
dysphagia (able to initiate swallowing, choke/cough on swallowing, nasal regurgitation,
liquids worse than solids, aspiration pneumonia)
- respiratory muscles = dyspnoea/orthopnoea
hoarse voice (vocal cord paralysis, RLN palsy)s
- proximal myopathy = difficulty washing hair, hanging clothes, getting up from sitting position,
climbing stairs
- no pain, numbness or parasthesiae

Associations
1. thyrotoxicosis = polyphagia, LOW, diarrhoea, heat intolerance, sweating, irritable, insomnia,
tremors, palpitations, amenorrhoea, infertility, neck mass
2. RA = joint pain and swelling
3. SLE = joint pain and swelling, malar rash
4. IDDM = symptoms of hyperglycaemia
5. pernicious anaemia = pallor, exertional chest pain/SOB, giddiness, palpitations, fatigue
6. IBD = chronic bloody diarrhoea

Complications
1. Aspiration pneumonia
2. Respiratory failure  requiring O2 therapy
3. Acute myasthenic crisis

Systemic review
1. fever, LOA, LOW
2. bladder and bowel control

Management prior and during admission

1. When was diagnosis made?
- presenting complaint
- investigations done = bloods, CXR/CT thorax, Tensilon test, EMG, lung spirometry
- treatment = medications (type, dose, recent changes, compliace)
surgery (thymoma)
- f/u with whom? compliance?
- number of relapses
83
Is this the first time? Describe prior episodes

Past medical history

Drug history
1. use of D-penicillamine for RA  can cause MG

Social history

Family history

Physical examination
Inspection
 ptosis = unilateral vs bilateral
complete vs partial
 strabismus

Ocular MG
If patient presents with ptosis
(a) can ptosis be overcome voluntarily
rd
# yes MG, 3 nerve palsy
rd
# no Horner’s syndrome, 3 nerve palsy
(b) pupillary size at rest (ask the room to be dimmed)
rd
# normal MG, medical 3 nerve palsy
# constricted  Horner’s syndrome
rd
# dilated  surgical 3 nerve palsy
(c) pupillary light reflex and accommodation
# Horner’s syndrome  constricted pupil that reacts to light and accommodation
rd
# 3 nerve palsy  dilated pupil that do not react to light and accommodation
# MG  normal pupils that react to light and accommodation
(d) involvement of extraocular eye muscles  ask about diplopia
 all eye movement abnormalities sparing the pupil is MG until proven otherwise!
 hold still at extremities of gaze and wait for diplopia to develop due to fatigability
(e) special manoeuvres
# lid fatigability = look upwards
hold up contralateral lid
shine light into affected eye to induce glare
# eye-lash sign = ask patient to close eyes as tightly as he can (eye lashes should be buried)
# Bell’s phenomenon
# Cogan’s lid-twitch sign = rapid downward gaze and return to primary horizontal position
eyelid will twitch in MG

Generalized MG
(a) facial weakness
# expressionless facies
# on smiling  myasthenic snarl (mid-lip rises but outer corners fail to move; due to weakness of
buccinator muscles)
# masseter weakness but pterygoids normal
(b) weakness of neck flexion
(c) proximal myopathy
# shoulder abduction = test first  flap up and down 20x  weaker compared to before
# finger abduction = spared (affected in oculo-pharyngeal muscular dystrophy)
# test deep tendon reflexes = depressed/absent in LEMS
# squat and stand repeatedly
(d) examine neck for
# tracheostomy scar
# thymectomy scar = midline sternotomy scar
small scar (minimally invasive Sx if non-invasive thymoma)
# thymoma = percussion

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 Pemberton’s sign
(e) request to examine for
# goitre
# rheumatoid hands
# vitiligo
# malar rash

Myasthenia Gravis II
Introduction
 2 peaks = 20-30 (females)
60-70 (males)
 autoimmune NMJ disease due to circulating antibodies against post-synaptic ACh receptors
- results in complement-mediated destruction of receptors
 other mechanisms involved = reduced receptor synthesis
antagonistic action
 associated with AI diseases (5-10%) = Graves’ disease, Hashimoto’s thyroiditis, RA, SLE, pernicious anaemia,
IBD, IDDM, dermatomyositis

Classification
 Osserman’s grading of severity
# Class 1 = ocular muscles only
# Class 2 = mild generalized weakness
# Class 3 = moderate generalized and mild-moderate ocular-bulbar weakness
# Class 4 = severe generalized and ocular-bulbar weakness
# Class 5 = myasthenic crisis
 Newsom-Davies clinical subgroups
 important to distinguish between ocular and generalized MG
- ocular MG = 1/3 will progress to generalized MG
no risk of myasthenic crisis
only ocular muscles affected
- generalized MG = risk of myasthenic crisis

Clinical presentation
muscle weakness (extraocular  bulbar  face  neck  limb girdle distal limb trunk)
exacerbated by fatigue, exercise, infection, pregnancy and drugs (aminoglycosides, propanolol, morphine, barbiturates,
procainamide, quinidine)

 extraocular = ptosis, strabismus, diplopia

- worsens as day progresses
- improves with rest
- can present with compensatory lid retraction of the unaffected eye (overactive frontalis  ‘proptosis’)
 bulbar = dysarthria, dysphonia (nasal speech), difficulty chewing food, dysphagia
 respiratory muscles = dyspnoea, orthopnoea
vocal cord paralysis  acute respiratory failure
 proximal myopathy
- difficulty washing hair, hanging clothes, getting up from chair and climbing stairs
- worsens as day progresses
- improves with rest
- little muscle wasting and no sensory deficits
 complications = aspiration, respiratory failure

Cardinal features
 fatigability
 variability = worsens as day progresses and improves with rest
 fluctuating/alternating sites

Differential diagnosis
1. Chronic progressive external ophthalmoplegia (CPEO)

85
 - mitochondrial disease aka Kearns-Sayre syndrome
- clinical features = complete ophthalmoplegia, no diplopia
2. Oculo-pharyngeal muscular dystrophy
- clinical features = ptosis, dysphagia, proximal + distal muscle weakness
3. Drugs/Toxins = botulism, snake bites, organophosphates
4. Lambert-Eaton myasthenic syndrome (LEMS)
- paraneoplastic syndrome = associated with small cell lung cancer
- unlike MG
(a) ocular involvement rare
(b) autonomic involvement common (esp dry mouth)
(c) hyporeflexia (cardinal feature)
(d) slight response to Tensilon test
(e) incremental response on EMG following repeated stimulation
(f) Ab against pre-synaptic VGCC
- Mx = regular CXR (symptoms may predate lung cancer by > 4 years)
5. Multiple Sclerosis

Investigations
Diagnosis
(a) anti-ACh receptor Ab
- present in 90% of patients with MG
(b) anti-skeletal muscle Ab
- associated with thymoma
- if +ve but CT –ve  do serial imaging
- raised levels after surgery may suggest recurrence
(c) Tensilon test
- contraindications = bradycardia, asthma/COPD, mild ptosis
- ensure that there is a panel of independent and masked observers
- outcome measure = relief of ptosis (improvement occurs within seconds and lasts for only 2-3 mins)
- conducted with N/S as control
(a) give 1ml N/S  wait 30s and comment on effect  give 3ml
(b) give 1ml edrophonium  wait 30s and comment on effect (make sure no adverse reaction)  3ml
- edrophonium comes in 1ml  dilute to 10ml
- precautions = monitor ECG for 20 mins
watch out for laryngeal oedema and increased bronchial secretions
- ensure that resuscitation facilities and atropine are available

Ice-pack test
- ptosis improves by > 2mm after ice is applied to affected lid for > 2mins
- NMJ transmission increases at low temperatures

(d) CXR and CT thorax

- thymoma (15% of cases)
- small-cell lung carcinoma
(e) EMG
- 10 quick successive shocks applied to deltoid muscle  look at motor amplitudes
- decremental response on repeated stimulation
(f) vital capacity

Associated AI disorders
 fasting glucose and HbA1c = IDDM
 FBC = pernicious anaemia
 TFT = Graves’ disease, Hashimoto’s thyroiditis
 ESR, CRP, anti-ds DNA, ANA, C3/C4 = SLE
 rheumatoid factor = RA

Treatment
Ocular MG
 acetylcholinesterase inhibitor  pyridostigmine
86
 - fast onset = within days (TCU x 1/52)
- S/E = diarrhoea, abdominal pain, sweating, lacrimation
 corticosteroids  prednisolone
- dosage = 1mg/kg/day
- slower onset = within weeks
- initial exacerbation of myasthenia common  initiate Rx in hospital
- monitor closely in first week for immune suppression and glucose control
Generalized MG
 acetylcholinesterase inhibitor  pyridostigmine
 corticosteroids  prednisolone
 immune modulators  azathioprine, cyclosporine A
- indications = resistant to steroids
steroid toxicity
- AZP = slow onset (within 6 mths)
check FBC and LFT for agranulocytosis and hepatotoxicity
- CsA = faster onset (within 2-3 mths)
more expensive
 thymectomy
- a must in generalized MG esp if patient is young (even in absence of tumour)
- response seen in years (long-term remission)
- invasive thymoma = surgery and radiotherapy
 long-term O2 therapy
- if patient cannot maintain saturations

Acute myasthenic crisis

 acute exacerbation of generalized MG
- occurs in those with bulbar and respiratory muscle involvement  prone to respiratory tract infections
 clinical presentation
(a) respiratory failure
# dyspnoea and orthopnoea due to diaphragmatic weakness
# precipitated by lying down (abdominal contents push against diaphragm)
(b) generalized weakness
 differentials
(a) neurotoxins e.g. botulism and snake venoms (toxicology screen)
(b) drugs e.g. organophosphates and aminoglycosides
 management
- A = secure airway; B = make sure patient is breathing; C = restore circulation
- intubate and ventilate if necessary  send patient to neuro-ICU
- identify and treat precipitating cause = infection, drug OD
 treatment
(a) IV neostigmine
(b) IV prednisolone
(c) IV immunoglobulin
- mainstay of treatment
- 2g/kg over 5 days (0.4g/kg/day)
- expensive and effects only last 4 weeks
- screen for Ig A deficiency first (contraindication to IVIG) = anti-Ig A Ab may react with IVIG/plasma
causing anaphylaxis
- S/E = anaphylaxis, hyperviscosity, ARF
(d) plasmapheresis
- requires large amounts of plasma
- longer recovery
- expensive and effects only last 4 weeks
- Cx = hypotension, metabolic disturbances, thromboembolic phenomenon
- Mx = call BTS MO
insert femoral line
 distinguish from cholinergic crisis (large doses of acetylcholinesterase inhibitor)
- clinical presentation = progressive weakness
increased sweating, saliva and bronchial secretions
small pupils (miosis)

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 respiratory failure
- important to distinguish from myasthenic crisis as management differs! (cannot give neostigmine)

Prognosis
 50% have remission after treatment
 5-10% die from respiratory failure

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Multiple Sclerosis
Introduction
 relapsing and remitting disorder
- time = distinct episodes of neurological deficits lasting for days-weeks followed by gradual partial
remission
- space = multiple plaques of demyelination throughout CNS (PNS not involved)
 3 subtypes
(a) relapsing and remitting (non-progressive)
(b) chronic progressive = primary progressive
secondary progressive (on and off  progressive)

Epidemiology
 more common in females
 age of onset = 20-40 yrs old
 predisposing factors
(a) infection = EBV
(b) family history

Pathology
 immune-mediated demyelinating disease
- directed against myelin components of CNS = myelin damage with relative sparing of axons
 characterized by plaque formation
- sharply defined areas of grey discolouration of white matter throughout CNS
- commonly found = peri-ventricular area
optic nerves
brainstem and cerebellar connections
cervical spinal cord (corticospinal tracts, dorsal columns)
- active plaques = myelin breakdown with lipid-laden macrophages
relative axonal preservation
inflammatory infiltrate (lymphocytes and mononuclear cells)
inactive plaques = no inflammatory infiltrate
unmyelinated axons

Clinical presentation
Symptoms
 spinal cord = limb weakness (usually spastic paraparesis)
pain, numbness, parasthesiae
urge incontinence, constipation, impotence
 brainstem = vertigo, diplopia, facial numbness and asymmetry, dysarthria, drooling of saliva, dysphagia
 cerebellum = gait disturbances
 eyes = visual loss, pain on EOM, impaired colour vision
 psychological = depression, dementia
 exacerbated by heat (exercise, hot bath  Uhthoff’s symptom)
 incomplete remissions  disability accumulates
Steinberg’s triad = urinary incontinence + impotence + constipation

Signs
 limb examination = tone (spasticity, ankle clonus)
power (spastic paraparesis)
reflexes (hyper-reflexia, present Babinski response)
coordination (cerebellar signs = dysdiadochokinesia, intention tremor, dysmetria, ataxic
gait)
sensory (affected)
 abdominal reflexes (absent/diminished in 80% of cases)
 neck = positive Lhermitte’s sign (also present in cervical myelopathy + subacute degeneration of cord)
 eyes = optic atrophy
optic neuritis (decreased VA, RAPD, pain on EOM, impaired central vision, impaired colour vision)

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 diplopia
nystagmus
INO
one-and-a-half syndrome

Differentials
1. Spinal cord compression
- must be ruled out in patients with sensory level, LL weakness, bladder and bowel disturbances
2. Other demyelinating disorders
- leukodystrophy = disorder of fatty acid deposition in lipid-containing tissues
can cause spastic paraparesis and mimic chronic progressive MS
3. Degenerative conditions = Friedrich’s ataxia
4. Sarcoidosis
5. Behcet’s syndrome

Diagnosis
 Clinical = demonstrate lesions are disseminated in time and space
unattributable to other causes
 Proposed McDonald criteria

Clinical Presentations Additional Information

≥ 2 relapses lasting > 1hr with ≥ 2 objective None
clinical lesions Clinical diagnosis  do imaging for consistency
≥ 2 relapses with 1objective clinical lesion Dissemination in space shown by
1) MRI
2) +ve CSF and ≥ 2 MRI lesions consistent with MS
3) Further attacks involving different sites
1 attack with ≥ 2 objective clinical lesions Dissemination in time shown by
1) MRI
nd
2) 2 clinical attack
1 attack with 1 clinical lesion (monosymptomatic) Show dissemination in time and space
Insidious neurolo ical progression suggestive of Positive CSF (oligoclonal IgG bands) AND
MS dissemination in space shown by
1) MRI evidence of ≥ 9 T2 brain lesions OR
2) ≥ 2 cord lesions OR
3) 4-8 brain and 1 cord lesion OR
4) +ve VER with 4-8 MRI lesions OR
5) +ve VER with < 4 brain lesions & 1 cord lesion AND
dissemination in time (MRI or progression in ≥ 1 year)

Investigations
 lumbar puncture
- raised CSF protein
- raised Ig G level
- Ig G oligoclonal bands on electrophoresis
 MRI brain and spinal cord (T2-weighted scan)
- hyperintense focal periventricular lesions (plaque)
- spinal cord compression
 visual-evoked potential
- may indicate optic neuropathy
 ESR, CRP
 serum vit B12 level
- rule out subacute degeneration of the cord

Management
1. Immunosuppressants
(a) IV Methyprednisolone
- for acute relapses

90
 - reduces severity of acute attack but does not affect long-term prognosis
- alternative = plasmapheresis (enhances recovery in patients with no response to high-dose steroids)
(b) immune-modulators
- indications = resistant to steroid therapy
steroid toxicity
- CsA
- cyclophosphamide

2. -interferon
- indications =  2 relapses in a 2-yr period
- advantages = decreases rate of relapse in relapsing-remitting MS by 1/3
decreases plaque formation
- disadvantages = expensive ($3000/mth)

3. Adjuvant therapy
(a) physiotherapy
(b) muscle relaxants (Baclofen, BZP) = for spasticity
(c) urinary incontinence = post-void RU > 100ml  CISC
< 100ml  oxybutynin (anti-cholinergic)
detrusitol (-adrenergic antagonist)

Prognosis
 poor prognostic factors
- male gender
- motor and cerebellar signs at presentation
- frequent relapses in early disease
- progressive disease from onset of symptoms
- multiple cranial lesions on T2-weighted MRI at presentation
 causes of death = pneumonia
uraemia

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Guillain Barré Syndrome (GBS)
Introduction
- Aka acute inflammatory demyelinating polyneuropathy (AIDP)
o If symptoms persist more than 8 weeks  CIPD
o Generally characterised by motor, sensory and autonomic disturbances
- Epidemiology: males > females
bimodal distribution (young adults: 15-35; elderly: 50-75)
- Miller-Fisher variant of GBS
o Rare proximal variant of GBS
o Ophthalmoplegia + ataxia + areflexia
o Anti-GQ1b Ab
o Recovery within 1-3 months

Pathology
- Immune-mediated demyelinating process involving nerve roots and peripheral nerves
o Demyelination starts at nerve roots
- Antecedent infection (URTI/GE) triggers immune system to attack components of peripheral nerve due to molecular
mimicry (sharing of cross-reactive epitopes)
o Invastion by activated T cells  macrophage-mediated demyelination  complement & Ig deposition on
myelin and Schwann cells
o C. Jejuni infection = generates anti-ganglioside Abs (shared ganglioside Ag between peripheral nerve
components & lipo-ligosaccharide coat of bacterium)
- Disease course
o Progresses over 2 weeks
o Plateaus by 4 weeks
o 85% make full functional recovery = complete paralysis compatible with complete recovery
o 10-40% have permanent neurological sequelae
o 5-10% mortality = severe autonomic instability, cardiac arrest, respiratory failure, sepsis, PE

Clinical presentation
- Varied clinical spectrum of presentation
o Mild cases = little disability with spontaneous recovery
o Severe cases (20%)
 Muscle weakness
 Begins distally and asends to involve proximal muscles over several days to weeks (ascending
paralysis)
 Length-dependent (legs  thighs  fingers  arms  face)
 Proximal muscles more affected
 Associated with pain, numbness and paresthesiae
 Respiratory muscles = dyspnoea, orthopnoea, respiratory failure, dysphonia
 Bulbar muscles = dysarthria, difficulty chewing food, dysphagia, aspiration
th
 Facial muscles = 7 nerve palsy (facial asymmetry, drooling)
 Extraocular muscles = ptosis, strabismus, diplopia
- Autonomic disturbances
o CVS (tachycardia, bradycardia, dysrhythmia, postural hypotension)
o GUT (urinary retention, impotence, erectile dysfunction)
o GIT (nocturnal diarrhoea, constipation, gastroparesis, paralytic ileus)
o Others (loss of sweating, facial flushing)
- Usually occurs 1-3 weeks later
o Infection
 URTI: EBV, CMV, HSV
 GE: Campylobacter jejuni
 UTI
 HIV: sexual history, IVDA, HIV status
o Flu vaccine
o Surgery
- Physical examination
o Vital signs = HR, RR, BP, T˚, pain score, SpO2
o Limb examination = tone (hypotonia)
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 reflexes (hyporeflexia, areflexia)
power (symmetrical weakness; proximal > distal)
coordination (may be affected in MF variant)
sensation (numbness, loss of vibration & proprioception)
th
o Cranial nerve involvement = LMN 7 nerve palsy (may mimic Bell’s palsy)
pupillary involvement
ophthalmoplegia
dysarthria
dysphagia
o Respiratory = poor inspiratory effort / diminished breath sounds
atelectasis
signs of aspiration pneumonia
o Abdomen = diminished/absent breath sounds (paralytic ileus)
palpable or percussible bladder (urinary retention)
o Autonomic involvement = postural BP

Differentials
1. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
a. Mixed sensorimotor polyneuropathy similar to GBS
b. Slower onset and recovery ( chronic)
c. Multiple relapses and remissions
d. Pathology of peripheral nerves = recurrent demyelination and remyelination  onion bulb appearance
e. Mx = steroids; IVIG used during acute exacerbations
2. Poliomyelitis
3. Peripheral neuropathy
4. Myopathy
5. Botulism

Investigations
Diagnosis
1. Lumbar punctures
a. CSF albumin-cytologic dissociation = cell count normal but protein concentration frequently raised
b. Differentials = CIDP
infective myeloradiculitis (EBV, CMV, HIV)
Lyme’s disease
sarcoidosis
c. Protein levels may not be raised in 10% :. Cannot rule out with negative sample
2. Nerve conduction studies (NCS)
a. Nerve conduction velocity slowed

Others
1. Severity of respiratory depression
a. ABG = respiratory acidosis
b. Vital capacity
2. Underlying aetiology
a. HIV serology
b. Stool c/s

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Management
1. Stabilise patient’s vitals
a. A = secure airway
B = make sure patient is breathing
C = restore circulation
b. Intubate & ventilate for severe paralysis involving respiratory muscles
2. Immune therapy
a. IVIG
i. Mainstay of therapy = decreases duration & severity of disease
ii. 2g/kg over 5 days (0.4g/kg/day)
iii. Expensive
iv. Screen for IgA deficiency first (contraindication to IVIG) = anti-IgA may react with IVIG/plasma causing
anaphylaxis
v. Side effects = anaphylaxis, hyperviscosity, ARF
b. Plasmaphresis
i. Decreases duration of disease
ii. Requires large amount of plasma and central line to be inserted
iii. Expensive
Combination of a & b has no significant additional advantage
c. IV corticosteroids
i. Given but no proven benefit
3. Adjuvant therapy
a. Neuropathic pain = gabapentin, carbamazepine
b. DVT prophylaxis = TED stockings
adequate hydration
subcutaneous heparin
4. PT/OT after acute phase

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Motor Neuron Disease
1. Pathophysiology
- caused by degeneration of neurons in motor cortex, cranial nerve nuclei and anterior horn cells
- Excessive activation of glutamate receptors  increased influx of intracellular Ca  increased free
radical formation  apoptosis
- can affect both UMN and LMN

2. Aetiology
- unknown but there are several possibilities:
(a) Genetic (5-10%)
 autosomal dominant inheritance
 due to mutations in the SOD1 gene (produces the enzyme superoxide dismutase)
 SOD = removes toxic superoxide radicals
 accumulation of superoxide radicals leads to anterior horn cell death
(b) Viral
(c) Toxins e.g. lead, selenium, mercury and manganese etc

3. Subtypes of MND
UMN signs LMN signs Prognosis
Amyotrophic Lateral Sclerosis (ALS) Upgoing plantars Fasciculations 2-5 years
* most common form (80%) Spastic weakness Muscle wasting/atrophy
* Amyotrophy = muscle atrophy Hyperreflexia Weakness
* Lateral sclerosis = disease of lateral Hyporeflexia
corticospinal tracts
spastic paraparesis
Primary Lateral Sclerosis (2%) + - Life span could be
* Corticospinal tract affected normal (depends if it
* slowly progressive remains a pure PLS
* rarest form of MND or progresses to
ALS)
Progressive Muscular Atrophy (7%) - + Better than ALS
* anterior horn cell affected
* distal > proximal weakness
* atrophy, weakness and fasciculations
Progressive Pseudo-bulbar palsy (7%) + - Poorer prognosis
* Corticobulbar tract affected
* difficulty chewing (muscles of
mastication affected)
* expressionless (muscles of expression
affected)
* Spastic tongue (huge, beefy)
* Dysarthria (Donald Duck speech)
* Dysphagia
* Palatal weakness (nasal regurgitation)
* Brisk jaw jerk & gag reflex
Progressive Bulbar Atrophy - + Poorer prognosis
* Cranial nerve nuclei affected
* atrophy
* fasciculations
* absent jaw jerk and gag reflex
* All will eventually progress to ALS

4. Epidemiology
- prevalence of 6 per 100,000
- mean age of onset is 55 years
- 2 peaks = 30-50 & 70-80 years old
- male:female ratio is 3:2

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5. Clinical Features
- weakness e.g. foot drop, wrist drop, weak grip
- spastic gait
- progressive dysarthria and dysphagia with nasal regurgitation
- difficulty chewing on food
- respiratory = SOB on exertion, orthopnoea, aspiration pneumonia, respiratory failure
- NO sensory loss or sphincter disturbance (distinguish from MS and polyneuropathies)
- Extra-ocular eye movements are not affected (distinguish from MG)

6. Investigations
- MRI brain and cord  r/o structural causes
- LP  r/o inflammatory causes
- Nerve conduction studies  normal velocities, r/o multifocal motor neuropathy
- EMG  denervation with fibrillation
- Vital capacity  monitor lung function

7. Diagnosis
- clinical diagnosis = mixture of UMN and LMN signs
NO sensory involvement
- strongly supported by = progressive UMN+LMN signs with involvement of  2 limbs OR
limb and bulbar weakness

8. Differential diagnosis
(a) Cervical cord compression
 mixture of UMN and LMN signs
 do MRI spine to exclude
(b) Cervical-medullary junction lesion (may have numbness)
(c) Multifocal motor neuropathy
 due to an autoimmune nerve conduction problem
 Rx = IVIG
(d) Spinal Muscular Atrophy (SMA)
 can mimic progressive muscular atrophy form of MND
(e) Bulbar MG
 similar to MND in early stages
 but ocular movements are affected in MG

9. Treatment (e) Hospice care and social services

- unsatisfactory at best
- Pharmacological
(a) Antiglutamate drugs e.g. Riluzole
 highly expensive (S$2000/mth)
 only for mild to moderate conditions
 prolongs survival by only 2 months
(b) Treat spasticity
(c) Drooling  amitriptyline
- Non-pharmacological
(a) Patient education
(b) Dysphagia  blended food; NG tube; PEG
(percutaneous endoscopic gastrostomy)
(b) Respiratory failure  non-invasive ventilation :
Bi-pap, C-pap ; mechanical ventilation
(c) Dysarthria  speech and language therapy
(d) Muscle weakness  physiotherapy, occupational
therapy, walking aids
- explore end-of-life issues
 discuss invasive (e.g. for bulbar palsy  PEG for
feeding, mechanical ventilation) OR
non-invasive (hospice care) plans
10. Prognosis
- incurable = usually die of respiratory failure
- fatal within 5 years from diagnosis (mean survival is 3
years)
- worse with bulbar-onset disease  respiratory
infection (aspiration pneumonia)
 death < 1.5 years from diagnosis
- if only 1 limb is affected  monolimbic ALS (good
prognosis)

96
Parkinson’s disease
Introduction
 epidemiology = presents at around 50-70 years old
1% prevalence in those > 60 years old
 pathogenesis
- progressive extra-pyramidal neurodegenerative disorder associated with loss of dopaminergic neurons in the
substantia nigra
- results in = dopamine deficiency supraspinal excitatory overdrive
excess cholinergic activity in striatum
 pathology
- presence of lewy bodies
- loss of pigmented dopaminergic neurones in substantia nigra
 ~ 60-80% of dopaminergic neurones lost before clinically evident

Stages of development (Hoehn-Yahr staging)

Stage 1  unilateral involvement (newly diagnosed)
Stage 2  bilateral involvement ) moderately severe
Stage 3  loss of postural reflexes )
Stage 4  non-dependent ) advanced disease
Stage 5  fully dependent )

Aetiology
 Primary parkinsonism
- features = asymmetrical involvement, tremors present, good response to L-dopa
(a) idiopathic parkinson’s disease
(b) juvenile parkinsonism
 Secondary parkinsonism
- features = symmetrical involvement, absent tremors, no response to L-dopa
(a) vascular  multi-infarct
- due to repeated subcortical strokes
- stepwise worsening of motor function with each subsequent episode
(b) infective  post-encephalitis, SSPE, CJD, prion disease, HIV
(c) trauma  pugilist’s encephalopathy
(d) toxins  MPTP neurotoxin, CO, mercury, manganese, cyanide, methanol, ethanol
(e) drugs  dopamine-receptor blockers (anti-psychotics + anti-emetics), reserpine, lithium, methyldopa
(f) others  brain tumour, normal-pressure hydrocephalus
 Heredodegenerative parkinsonism
(a) Wilson’s disease
(b) Huntington’s disease
 Parkinsonism-plus syndrome
- 10% of parkinsonian patients
- associated with poorer prognosis and response to drug therapy
(a) striatonigral degeneration (+ pyramidal signs = spasticity, hyper-reflexia, UL flexors>extensors + LL extensors>flexors)
(b) olivo-ponto-cerebellar atrophy (+ cerebellar signs)
(c) Shy-Drager syndrome (+ autonomic signs)
- autonomic involvement = urinary retention  overflow incontinence
nocturnal diarrhoea
gastroparesis
erectile dysfunction
postural giddiness
- Invx = long ECG trace of lead 2 (loss of R-R interval variability on Valsalva manoeuvre due to denervated heart;
normal individuals  decreased R-R interval due to increased HR)
(d) progressive supranuclear palsy (+ loss of vertical gaze)
- aka Steele-Richardson-Olszewski syndrome
- vertical ocular gaze paresis = loss of downward gaze  upward gaze  horizontal gaze
- overcome by passive head movement which activates oculocephalic reflexes
(e) corticobasal ganglionic degeneration
- usually presents with limb apraxia and dystonia
97
 - less common  sensory symptoms, speech and behavioural changes

Olivo-ponto-cerebellar atrophy

+ cerebellar signs

Shy-Drager syndrome
Striato-nigral
degeneration

+ autonomic signs + pyramidal signs

Multisystem atrophy

Postural MSA

 Multisystem atrophy = poorly responsive to L-dopa therapy

varying degrees of cerebellar, pyramidal and autonomic dysfunction
rapidly progressive and fatal

Clinical features
 4 cardinal signs (2 out of first 3 criteria needed to make diagnosis)
(a) tremors
- rest tremor (‘pill-rolling’ of thumb over fingers)
o usually unilateral at onset
o usually starts in upper limbs (can involve legs and jaw)
o coarser than cerebellar tremor (4-6 Hz)
o disappears on action and during sleep
o if not seen at rest  stress the patient (count down from 100)
- postural tremor (not diagnostic)
(b) rigidity
- ‘lead-pipe’ rigidity = increased resistance to passive stretch of muscles throughout ROM (cf spasticity)
characteristic of extra-pyramidal tract lesions, CJD and Wilson’s disease
- cog-wheeling = rigidity broken up by tremors
if not significant  ask patient to wave contralateral hand, look from side to side or talk to him
(c) bradykinesia
- appearance = paucity of facial expression, drooling,  blink rate,  spontaneous movement
- movement = progressively slower with smaller amplitudes, fusion of final actions
- eyes = EOM slower, impaired saccades (tends to undershoot when asked to look quickly from 1 point to
another then corrects; cerebellar  overshoots then corrects)
- speech = soft, slow and monotonous
- handwriting = micrographia
- gait = hesitancy, stooped posture, lack of arm-swing, short and shuffling steps, festinant
- GIT (decreased peristalsis) = dysphagia, constipation
(d) postural instability (emerges late in disease  usually after  8 yrs)
- turning by numbers
- propulsion/retropulsion
- freezing

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Complications
 recurrent falls
- source of morbidity and mortality
- usually end up with head injuries as patients are unable to break their fall (normal elderly  Colles’ fracture)
- 3 common causes = Parkinson’s disease
normal-pressure hydrocephalus (gait apraxia, urinary incontinence, dementia)
cervical myelopathy
 depression
- causes = brain cognitively impaired  may be ignored by other people
body slow to do what the mind wants
- Tx = anti-depressants (TCA/SSRI)  contraindicated in patients on selegiline (may cause psychosis by  dopamine)
 dementia
- occurs in 20% of patients with PD
- may be caused by degeneration of cholinergic neurones
- results in = memory loss, getting lost in familiar places, lack of grooming and hygiene, poor executive functioning,
behavioural changes
 sleep disturbances
- results in poor sleep quality
- occurs in 2 forms
(a) periodic limb movement disorder (akin to ‘restless leg syndrome’)
(b) REM sleep behavioural disorder = patient acts out vivid dreams  may cause harm to self and others
should be atonic during REM sleep normally
- strongly a/w PD
- may precede diagnosis especially in young patients
- Tx = benzodiazepine (BZP)
 psychosis
- occurs halfway into course of disease (~ 10 yrs later)
st
- if occurring during 1 year  consider Lewy body dementia (Parkinsonism, Hallucinations, Delusions)
- clinical features = visual hallucinations, persecutory delusions, morbid jealousy
- differentials = psychosis in PD
drug-induced
sepsis
- management
o exclude intercurrent infection and sepsis
o review medications (withdraw/reduce)  amitriptyline, anti-cholinergics, L-dopa, dopamine agonists
(bromocriptine, pergolide), selegiline
o start on atypical anti-psychotics  quetiapine (Seroquel) is the drug of choice
clozapine not used as patient requires frequent FBC (blood dyscrasia)
risperidone, amisulpride and olanzepine are not really atypical!

Differentials
1. space-occupying lesion
2. normal-pressure hydrocephalus
3. essential tremors
4. Wilson’s disease (esp if patient is young!)

Investigations
1. CT head = rule out SOL and normal-pressure hydrocephalus
2. work-up for Wilson’s disease in patients < 50 yrs old = deranged LFT
low serum ceruloplasmin
high 24hr urinary copper
slit-lamp examination (Kayser-Fleischer rings)
liver biopsy (high hepatic copper content)

Management
 non-pharmacological
(a) encourage ambulation
- if not = constipation  ARU/UTI
aspiration pneumonia
99
 - continue with pre-morbid activities
- encourage patient to go out of the house = ‘forces’ patient to make an attempt to groom
(b) aggressive rehabilitation
- indication = moderate-severe stiffness
- involve PT, OT and speech therapist
 pharmacological
- indications = significant disability interfering with function
- aims at restoring dopamine levels  does not halt disease progression
- determine lowest possible dose needed for symptom relieve to avoid S/E
(a) dopaminergic drugs
- types
o L-dopa = precursor of dopamine
oral administration  > 90% decarboxylated peripherally in liver before reaching CNS
must give with peripheral dopamine decarboxylase inhibitor  increases [L-dopa]CNS, reduces
peripheral S/E (N/V, hypotension)
decarboxylase inhibitor does not cross BBB with L-dopa
central S/E = dyskinesia, on-off phenomenon, depression, hallucinations, delusions
not started early due to S/E and beneficial effects wearing off with time
dosage must be titrated carefully = too much  dyskinesia; too little  stiffness/freezing
o Madopa (1 part benserazide : 4 parts L-dopa)
- not advisable to start in young patients unless function is severely affected
- contraindicated in melanoma

Motor complications of Levo-dopa

 ‘wearing-off’ phenomenon
- occurs at a predictable timing after dose (hence timing of drug impt!)
- clinical features
(a) return of PD symptoms
(b) sensory = pain, parasthesiae
motor = decreased movement
behavioural = anxiety, panic, akathisia (inner urge to move around, restless)
- may result in dopamine addiction (dopamine dysregulation syndrome)  takes more dopamine for relief
 ‘on-off’ phenomenon
- unable to predict timing
- SubQ apomorphine may help rescue patient rapidly from ‘off’ period
 dyskinesia
At peak dose (predictable) OR Biphasic
- P–I–D–I–P - P–D–I–D–P
- choreoathetosis, ballistic movements,
myoclonus, obsessive manipulation of P: Parkinson symptoms
objects repetitively (starts from foot) D: dyskinesis
- ventral lateral part of striatum degenerates I: improvement
st
1 (representative of foot)

 risk factors
(a) longer duration on L-dopa
(b) higher dosage of L-dopa
(c) early disease onset
(d) genetic predisposition

(b) dopamine agonists

- used frequently to (a) prolong effects of L-dopa  decrease dosage and frequency
(b) reduces motor fluctuations when used with L-dopa
- less powerful than L-dopa in controlling features of parkinsonism but less likely to cause dyskinesia
- types
o older drugs = pergoline, bromocriptine, subQ apomorphine
o newer drugs = ropinirole, prampexole
- S/E = postural hypotension, hallucinations, delusions, sedation
(c) COMT (catechol-O-methyl transferase) inhibitors  tolcapone, entacapone
- prevents breakdown of dopamine

100
 - used frequently to (a) prolong effects of L-dopa  decrease dosage and frequency
(b) increases ‘on’ time and reduces duration of ‘off’ time
(d) monoamine-oxidase B inhibitor  Selegiline
- prevents breakdown of dopamine
- retards progression of early parkinsonism and delays initiation of L-dopa therapy
(e) anti-cholinergics  Benzhexol, Ophenadrine
- reduces cholinergic overdrive 2 decreased dopaminergic activity
- indications = (a) tremors
(b) drug-induced parkinsonism where reduction/withdrawal of culprit drug may have adverse
effects e.g. anti-psychotics in schizophrenia
- S/E = hallucinations, dry mouth, blurred vision, urinary retention, constipation
(f) amantidine
- helps with rigidity

No clinically significant disability Clinically significant disability

selegiline Job security/health threatened  L-dopa  dopamine
agonists/COMT inhibitors
Job security/health NOT threatened  anti-cholinergics
amantidine
Older patients  dopamine agonists, COMT inhibitors
Very elderly (> 80 yrs)  L-dopa  dopamine agonists/COMT
inhibitors

tremors anti-cholinergics
bradykinesia L-dopa with peripheral decarboxylase inhibitor
dopamine agonists
COMT inhibitors
amantidine
rigidity amantidine

 surgery
(a) non-lesional = deep-brain stimulation
- uses implanted electrode to deliver continuous high-frequency electrical stimulation to
(i) globus pallidus = dyskinesia, tremors
(ii) subthalamic nucleus = bradykinesia, tremors, rigidity
(iii) thalamus = disabling tremors
- helps shut down cells and rebalance connections between movement control centres
(b) lesional = tremors and dystonia  ventral medial thaladotomy
akinesia  medial pallidotomy

Prognosis
 improved survival with L-dopa
- 3x higher mortality without treatment
- nearly normal lifespan with treatment

101
Parkinson’s disease (History-Taking)
name/age/ethnicity/gender/occupation
date of admission

Presenting complaint
st
 1 presentation = tremors, stiffness (from rigidity), slowness in movement/lack of coordination/difficulty initiating movement,
changes in handwriting, instability, recurrent falls, sleep disturbances
 tremors = location, resting, disappears on action
rigidity = stiffness
bradykinesia = slowness in movement/lack of coordination/difficulty initiating movement
drooling
change in handwriting
change in voice
constipation, dysphagia
gait disturbances
postural instability = able to get up from chair properly

Aetiology
 secondary parkinsonism = history of CVA
history of encephalitis
history of repeated head trauma
drug history
history of brain tumour (headache, nausea, vomiting, focal neurological deficits)
 heredodegenerative parkinsonism = Wilson’s disease
Huntington’s disease
 parkinsonism plus syndrome = autonomic dysfunction (postural giddiness, urinary retention with overflow incontinence,
constipation, gastroparesis, erectile dysfunction)
Complications
 recurrent falls
 sleep disturbances
 psychosis
 depression
 dementia = behavioural changes, getting lost in a familiar neighbourhood, neglecting own hygiene

Systemic review

Management prior and during admission

Has this happened before

History of presenting complaint

When was diagnosis made? initial presentation? investigations done? management?
F/U with whom? frequency? compliance? What did doctor say at last visit?
Management = non-pharmacological (PT, OT, speech therapist)
pharmacological (what kind of meds? when was it started? any recent changes? control of symptoms?
side-effects?)
Currently = control of symptoms
complications of disease (recurrent falls, sleep disturbances, psychosis, depression)
functional status

Past medical history

DM, HPT, HCL, IHD, AMI, CVA  vascular cause
schizophrenia (on anti-psychotics)
history of liver disease (esp if young patient)

Drug history
anti-psychotics (haloperidol, chlorpropamide)
anti-emetics (metoclopramide, prochlorperazine)
lithium

102
methyldopa
reserpine (anti-hypertensive and anti-psychotic)

Social history
smoker
alcoholic drinker
lives with whom? main caregiver?
type of housing? lift-landing?
finances?
home modifications?

Family history
history of parkinson’s disease  familial PD
history of liver disease  Wilson’s disease (esp if young patient)

103
Parkinsonism (short-case)
General inspection (stand at the foot of the bed)
 appearance = paucity of facial expression
lack of spontaneous movement
decreased blink rate (normal 6x/min)
drooling
 rest tremor (usually ‘pill rolling’)
 urinary catheter (sign of autonomic involvement)

Say = “This patient has features suggestive of parkinsonism as evidenced by ….. I would like to examine him for the other
features of parkinsonism.”

Ask the patient to (a) wave his hands

(b) tap his thumb and index finger repeatedly
 bradykinesia = difficulty initiating movement
movements become progressively slower
smaller amplitudes
final actions fused together

Upper limb Head

 assess for lead-pipe rigidity  Glabellar tap
 assess for cog-wheeling - keep finger out of patient’s line of vision and tap
- if not evident = ask patient to wave contralateral centre of forehead
hand, look from side to side or ask patient questions - positive if patient continues to blink as long as
 assess speech = soft, slow, monotonous, palilalia (repetition examiner taps (Myerson’s sign)
of end of word), echolalia (repeat question before answering)  assess eye movements for failure of upward gaze 
progressive supranuclear palsy

Ask the patient to get up from the chair → Walk (start, stop, start) → Turn quickly → Walk (stop, start)
(a) Stand the patient up
 hesitancy
 unsteadiness while standing  postural instability
(b) Gait
 stooped posture
 hesitancy in initiating gait
 lack of arm-swing
 short and shuffling gait (small steps with feet barely lifting off the ground)
 festinant gait (always a step behind one’s centre of gravity)
 turning by numbers (sign of postural instability)
 difficulty stopping
 worsening of resting tremor
(c) Retropulsion
 abnormal if patient takes > 2 steps to compensate

Go on to examine
 pyramidal signs  pronator drift, supinate forearm and extend wrist for increased tone, test reflexes and Babinski’s
 cerebellar signs  dysdiadochokinesia, finger-nose test

Request to examine
 handwriting  micrographia
 palmomental reflex  frontal lobe release
 postural BP  autonomic involvement, L-dopa treatment
 higher mental state/MMSE and ask about hallucinations and psychosis  Lewy body dementia, PD dementia, progressive
supranuclear palsy, CJD, Wilson’s disease
 limb apraxia  corticobasal ganglionic degeneration
- show me how do you make a ‘keep quiet’ sign (test both sides)
- show me how do you comb your hair (test both sides)
- follow my actions = ‘ok’ sign, interlocking fingers
- constructional apraxia (draw a star and ask patient to copy)

104
 take a detailed drug history

105
Epilepsy
Introduction
 definition = abnormal brain activity resulting in electrical discharges and seizure
 consider epilepsy = sudden onset
LOC
stereotyped movements

Classification

Generalized
1. Generalized tonic-clonic  pre-ictal = aura
 ictal = loss of consciousness
up-rolling of eyes
foaming at mouth
clenching of teeth
tongue biting
apnoea  cyanosis
tonic  clonic
incontinence
 post-ictal = slow recovery
weakness/headache/drowsiness/confusion
2. Tonic
3. Atonic
4. Absence (petit mal)  can present as
(a) generalized
(b) complex partial seizures = staring spells
 characteristics = children < 12 years old
short duration < 20 secs
many episodes in a day
no automatism
no post-ictal drowsiness
5. Myoclonic
Partial
1. Simple partial  no LOC
2. Complex partial  impaired level of consciousness
 typically associated with aura in temporal lobe epilepsy
- déjà vu, jamais vu, hallucinations
- emotional changes (fear, sexual arousal)
- visceral sensation (nausea, epigastric discomfort)
- alterations in sensations (taste, smell, sound)
 psychomotor phenomenon
- lip smacking
- repetitive stereotyped movements
- automatisms (non-purposeful manner)
3. Partial with 2 generalisation

Aetiology

CNS Metabolic Infections

 CVA  hypoglycaemia  encephalitis/meningitis
 space-occupying lesion  hyperglycaemia  brain abscess
 head injury  hyponatraemia Others
 SAH  hypernatraemia  cardiac arrhythmias
 hypertensive  hypocalcaemia - VT/VF
encephalopathy  hypomagnesaemia - torsades de pointes
 scar epilepsy  uraemic encephalopathy - bradyarrhythmias
 neurocutaneous  hepatic encephalopathy

106
 syndromes  alcohol withdrawal
 substance abuse (TCA
OD, cocaine,
amphetamines, BZP
withdrawal)

Differentials
Convulsive syncope

Convulsive Syncope Seizures

Trigger Common Rare
Prodromal symptoms Almost always (pre-syncope) Aura
Onset Gradual (often minutes) Sudden (often seconds)
Duration Shorter (1-30s)
Convulsive Jerks Common (brief)
Urinary incontinence Uncommon Common
Lateral biting of tongue Rare Common
Post-ictal drowsiness Rare (e.g. wakes up on floor) Common (e.g. wakes up in ambulance)
Recovery Rapid Gradual
Patient profile NS man, Elderly

 vasovagal syncope
- triggers = emotion, pain, fear, prolonged standing
- due to reflex bradycardia  peripheral vasodilatation
- often preceded by nausea, pallor, sweating and closing in of visual fields (pre-syncope)
- cannot occur if lying down
- sequence of events = patient falls to the ground
LOC ~ 2 mins
urinary incontinence rare
brief jerking of limbs uncommon
no prolonged confusion/amnesia after attack
 situational syncope
- cough syncope
- micturition syncope = mostly men and occurs at night
- cardiac syncope = usually on exercise e.g. AS, HOCM
- carotid sinus syncope = carotid sinus hypersensitivity e.g. head-turning or shaving neck

Oculogyric crisis
 cause = cough mixtures
anti-emetics
 Tx = anti-cholinergics (Artane)
BZP (Flumenazil)

Pseudo-seizure
 characteristics = wild thrashing movements
eyes tend to be closed (vs opened eyes in true seizures)
less/no incontinence or tongue biting
 normal EEG
 either psychological (commonly sexual abuse) or can co-exist with epilepsy

Rigors

History
name/age/race/gender/occupation/handedness
past medical history
drug allergy
date of admission

Presenting complaint
107
1. Seizure
- frequency
- prior episodes
- pre-ictal = aura
- ictal = duration
loss of consciousness
up-rolling of eyes
foaming at mouth
clenching of teeth
tongue biting
apnoea  cyanosis
tonic  clonic
incontinence
- post-ictal = any injuries sustained
speed of recovery
drowsiness/confusion/weakness/headache

Aetiology
(a) Is this a seizure?
1. Convulsive syncope
- triggers = prolonged standing, emotion, fear, coughing fit, micturition, exercise, head-turning
- pre-syncope = nausea, pallor, sweating and closing in of visual fields
2. Oculogyric crisis
- recent drug ingestion = cough mixtures, anti-emetics

(b) If it is a seizure  what is the underlying cause?

1. CNS
- CVA = headache, vomiting, sudden weakness/numbness, BOV, tinnitus, vertiginous giddiness, diplopia,
dysarthria, dysphonia, dysphagia, gait abnormalities, impaired cognition
- tumour = history of cancer, LOA, LOW, early morning headache/vomiting, systemic review
- recent head injury
- CNS infections = fever, photophobia, neck stiffness, headache, projectile vomiting
2. Metabolic
- hypoglycaemia = hunger, diaphoresis, giddiness, tremors
- recent alcohol/drug withdrawal
- liver/renal impairment
3. Cardiac
- chest pain, SOB, palpitations

Complications
1. Fall  injuries sustained

Systemic review

Management prior and during admission

Has this happened before?

Past medical history

- developmental history = full term/premature baby
developmental milestones
history of fits
IQ

Drug history

Social history

Family history
- epilepsy

108
- psychiatric problems
- substance abuse

Physical examination
Neurocutaneous syndromes
(a) Neurofibromatosis
(b) Tuberous sclerosis
(c) Sturge-Weber syndrome

Genetic syndromes
(a) Down syndrome

Neurological examination

Investigations
Metabolic screen
 hypocount
 U/E/Cr = electrolyte abnormalities, uraemia, glucose
 Ca/Mg/albumin
 LFT = liver failure
 ABG = hypoxia
 serum/urine toxicology

Exclude other causes

 ECG = arrhythmias
 CXR = suppurative lung conditions
 FBC, ESR, CRP = infectious and inflammatory causes
 skull X-ray = history of HI
 CT head with contrast/MRI = mesotemporal sclerosis (esp in elderly)
latter preferred if there is focal seizures
 LP = infection suspected

Compliance
 drug levels

EEG

st
Management of patient with 1 fit
Counselling
 everyone allowed 1 fit in his/her lifetime
nd
 if tests all normal  70% will never get another fit (20-50% may get 2 fit  epilepsy  treat)
 risk of recurrence after 2 unprovoked seizures = 73%
 warn patient against driving and swimming alone
 avoid triggers = lack of sleep
stress
flickering lights
alcohol consumption
fever/URTI

Pharmacological
First-line drugs
(a) Carbamazepine
- indications = generalized and partial seizures
- S/E = somnolence
cognitive impairment
delayed hypersensitivity reactions (SJS)
agranulocytosis
teratogenicity
hepatotoxicity

109
(b) Sodium valproate (the only enzyme inhibitor!)
- indications = generalized seizures, absence seizures, juvenile myoclonic seizures
- S/E = weight gain
alopecia
teratogenicity (neural tube defects, spina bifida)
hepatotoxicity (monitor LFT)
- drug levels do not correlate to therapeutic and adverse effects  not useful!

Second-line drugs
(a) Phenytoin
- convenient dosing
- narrow therapeutic index = acne, hirsutism, coarse facies, gum hypertrophy, mouth ulcers, LAD, ataxia,
peripheral neuropathy
st
- not suitable as 1 -line due to side-effects

(b) Phenobarbitone
- suitable for children due to sedative effects

Third-line drugs
(a) Lamotrigine
- inhibits glutamate release

(b) Gabapentin
- GABA-nergic compounds

 early treatment with anti-epileptic drugs after first seizure halves recurrence risk BUT does not alter long-term prognosis
 may consider stopping medications after 2-yr seizure free period = 60% remain seizure free
- withdrawal should be a gradual process occurring over a few months
- recurrence = anti-convulsants given for another 3 yrs before attempting to stop again
 monitoring of drug levels
- compliance issues
- toxicity on normal dose
- high doses
- polypharmacy
- management of status epilepticus

Immediate management of seizure

First-aid
 remove hazards from immediate surroundings
 protect patient from falling unsupported to the ground or striking objects
 lie patient on left lateral position  give high-flow oxygen
 suction secretions if possible
 monitor SpO2
 administer 5-10 mg rectal diazepam if seizures > 5 mins
 call EMS if = seizures > 5 mins
injury during seizure
status epilepticus
 stat hypocount
 create IV access

Pregnancy and seizures

 pre-conceptual counselling
 pregnant patient
- make sure seizures are well-controlled  fetal hypoxia
- all medications are teratogenic BUT carbamazepine is the safest!
- start folate supplementation at least 3 months before pregnancy till the first trimester
- work closely with O&G  regular U/S to monitor for fetal defects
- do not change medications abruptly  may trigger status epilepticus
- can still breastfeed

110
Approach to numbness and weakness
Questions to ask
1. Is there weakness?
a. flaccid (LMN) = lesion at anterior horn cell, nerve plexus/roots, peripheral nerves, neuromuscular junction
(NMJ), muscles
b. spastic (UMN) = lesion at spinal cord, brainstem, subcortical or cortical
2. Is there numbness?
a. If present with flaccid paralysis, can rule out myopathies and disorders of NMJ
3. Other parts affected?
a. cranial nerve palsies/cortical signs – help in localization

Basic Principles
1. All hemipareses are UMN lesions at the spinal cord level or above  spastic paralysis
2. Hemiparesis & ipsilateral sensory loss = lesion at brainstem or above
Hemiparesis & contralateral sensory loss = lesion at spinal cord
3. A nerve root supplies more than 1 nerve; a nerve receives supply from more than 1 nerve root.
a. To distinguish between weakness/numbness caused by a nerve or a nerve root, find another muscle that is
supplied by the same nerve root BUT different nerve, e.g. weakness in arm abduction (supplied by axillary
nerve: C5-6)  test biceps flexion (supplied by musculocutaneous nerve: C5-6) since both supplied by the
same nerve roots
4. Myopathies and NMJ disorders affect ALL 4 limbs.

Conus Medullaris
1. Junction between spinal cord and cauda equina (ventral and dorsal nerve roots)
2. Lesion at this level results in a mixture of UMN (upgoing plantars; cut above L5 nerve root) and LMN (flaccid paralysis)
signs
3. However, commonest cause for a mixed UMN and LMN picture is an elderly diabetic with cervical spondylosis and
concurrent diabetic peripheral neuropathy.

Can a wasted hand be due to cervical spondylosis?

No! Intrinsic muscles of the hand supplied by T1, hence thoracic spondylosis is responsible.
Differentials
1. Acute onset – vascular (eg stroke), trauma, seizure
2. Subacute onset – infection (eg spinal cord abscess), inflammatory (eg SLE, transverse myelitis)
3. Insidious – neoplasm, space-occupying lesion (eg hydrocephalus, prolapsed intervertebral disc), degenerative (eg
Alzheimer’s), demyelination (eg Guillain-Barre Syndrome, multiple sclerosis)
4. Variable – metabolic (eg hypercalcemia, uremia, hypoglycemia, Vitamin B12 deficiency), toxic, paraneoplastic

Appraoches
Bilateral Lower Limb Weakness
Flaccid Spastic
Numbness No Numbness Numbness No Numbness
 Ipsilateral  Myelopathy  Frontal lobe lesion
lumbosacral plexus  Multiple sclerosis  Parasaggital
 Tumour impinging on meningioma
cauda equina  Motor neuron
 Conus medullaris disease
syndrome (upgoing
plantars)
 Cervical myelopathy
with peripheral
neuropathy

111
 Generalised Weakness
Flaccid Spastic
Numbness No Numbness  Cervical cord
Peripheral Neuropathy  Myopathy  Brainstem
A  Alcoholism  NMJ Disorders  Subcortical region
 Acute  Peripheral o Normal pressure hydrocephalus
inflammatory Neuropathy (mainly o Parkinson’s disease
demyelinating motor) o Chronic hypertension causing white matter
neuropathy o Heavy metal degeneration
 Autoimmune poisoning eg Pb,  Cortex
B Vitamin B12 Hg, As
deficiency o Guillain-Barre
C  Chronic Syndrome
inflammatory o Porphyria
demyelinating
neuropathy
 Cancer
D  Diabetes
mellitus
 Drugs
F Familial (eg
Charcot Marie
Tooth)

Hemiparesis (always UMN)

Numbness No Numbness
Ipsilateral Contralateral  Brainstem
 Brainstem Brown-Sequard  Subcortical Region
 Subcortical region Syndrome  Cortex
 Cortex

1. Flaccid UL & Spastic LL  Lesion at C5/6/7 levels

2. Proximal flaccid weakness
a. Myopathy
b. NMJ disorder
c. Exceptions: Guillain-Barre Syndrome, Kennedy Syndrome, SMA Type 3 (Krukenberg-Welander Syndrome)
3. Distal flaccid weakness
a. Peripheral neuropathy (heavy metal poisoning, Guillain-Barre Syndrome, porphyria)
b. Exceptions: myotonia dystrophica, distal myopathy of Gower, Duchenne muscular dystrophy
4. Spastic weakness of bilateral UL = lesion in medulla where arm fibres decussate
5. Flaccid weakness of 1 hand = mononeuropathy, polyneuropathy, monoradiculopathy, polyradiculopathy, cortical lesion
6. Dissociated sensory loss = loss of pain and temperature with preservation of proprioception and vibration
Segmental sensory loss = no loss above and below the segment affected
Central cord syndrome: intramedullary tumour, syringomyelia (when syrinx is small)
7. Brachiofacial weakness = subcortex, brainstem, cortex (superior division of MCA)

112
Hemiplegia
Localisation
 high cervical cord lesion
 brainstem
 subcortical
 cortical

Approach to physical examination

Inspection Request to examine
 hemiplegic posture  fundoscopy = papilloedema (SOL  differential for cortical
 facial asymmetry stroke)
 on NGT diabetic/hypertensive retinopathy
optic atrophy/RAPD (multiple sclerosis)
Pronator drift (confirm UMN lesion)  CVS examination = AF, murmurs, carotid bruit, blood
pressure
LL examination  stigmata of hyperlipidaemia = xanthoma, xanthelasma,
 motor examination thickened tendo Archilles
(a) spastic tone urinalysis = glycosuria (DM)
(b) ankle clonus
(c) hyperreflexia
(d) Babinski’s reflex present
(e) UMN pattern of weakness (LL extensors > flexors)
 cerebellar examination (do not test  UL dysmetria
faster)
 sensory testing

UL examination
 motor examination
(a) spastic tone
(b) wrist clonus
(c) hyperreflexia
(d) Hoffmann’s reflex present
(e) UMN pattern of weakness (UL flexors > extensors)
 cerebellar examination (if present  ataxic
hemiparesis)
 sensory testing (do not test  already tested in LL)

Cranial nerves (involvement may suggest brainstem CVA)

 CN 3 = Weber’s syndrome (+ crossed hemiplegia)
th
 CN 6 + LMN 7 lesion = Millard-Gubler syndrome (+
crossed hemiplegia)
th
 UMN 7 lesion = subcortical stroke

Cortical
 dominant hemispheric signs
(a) Gerstmann’s syndrome
(b) dysphasia
 common to both hemispheres
(a) visual field defects
(b) neglect (sensory and visual)
(c) loss of 2-point discrimination  usually not done
(d) OKN
(e) agraphasthesiae  usually not done
(f) astereognosis  usually not done
(g) dressing apraxia  usually not done
(h) constructional apraxia  usually not done

113
 Spastic Paraparesis
# lesion is usually in the spinal cord or frontal/parasagittal area
(a) associated with numbness → spinal cord
(b) no numbness associated → bilateral frontal lobe lesion; parasaggital meningioma

Young Adult Elderly

Spinal cord
Friedrich’s ataxia
Hereditary paraparesis

Spinal cord compression (myelopathy)

V  epidural haematoma, angioma
I  epidural abscess
T  vertebral body #, PID (L1-L2 or higher)
M  acromegaly, Paget’s disease
N  primary (multiple myeloma, Hodgkin’s lymphoma)
secondary (bone mets)
spinal cord tumour (astrocytoma, ependymoma, haemagioblastoma, neuroma(fibroma))
syringomyelia

Spinal cord infarction

V  ASA thrombosis, PAN, syphilis, AAA dissection
T  trauma

Myelitis
I  tabes dorsalis, HIV
I  multiple sclerosis
M  subacute combined degeneration of cord
Cortex Cortex
Spastic diplegia (CP) ACA infarct
Pasasagittal meningioma
Disseminated disease
Motor neurone disease

Request to examine
1. Sensory modalities
 sensory level (spinal cord lesion)
# sacral sparing with intrinsic cord compression
# PR for lax anal tone
# percuss for enlarged bladder
# examine back for spinal tenderness/deformity
 loss of vibration and proprioception (dorsal column loss)  tabes dorsalis
subacute combined degeneration of cord
multiple sclerosis
# gait  sensory ataxia
# Romberg’s test
# check eyes  Argyll-Robertson pupil (syphilis)
pallor (SCDC)  examine abdomen for splenomegaly
 dissociated sensory loss  syringomyelia
2. Cerebellar signs  multiple sclerosis, Friedrich’s ataxia
3. Full neurological examination of UL
 UMN signs  cervical myelopathy, bilateral CVA, syringomyelia, motor neurone disease, multiple sclerosis
4. Jaw jerk
 if positive  lesion above level of mid-pons

History
- gradual/acute onset
- speed of progression
- spastic/flaccid paralysis
114
- spinal cord = history of trauma
back pain
radicular pain
a/w numbness or parasthesiae
urinary retention  overflow incontinence
faecal incontinence
- cortex = change in personality/behaviour
urinary incontinence

Findings
# LL spasticity only = lesion of thoracic cord (T2-L1)
# mixed UMN and LMN signs = lesion of conus medullaris (L2-S2)
motor neurone disease
# Babinksi’s reflex present + absent ankle/knee jerks (‘MAST’) = motor neurone disease (fasciculations)
Friedrich’s ataxia
subacute combined degeneration of the cord
tabes dorsalis
peripheral neuropathy in a stroke patient
conus medullaris lesion

Investigations
(a) FBC = megaloblastic anaemia (subacute combined degeneration of the cord)
leucocytosis (transverse myelitis)
(b) serum vitamin B12 levels = subacute combined degeneration of the cord
(c) ESR = inflammatory process (tabes dorsalis, transverse myelitis, multiple sclerosis)
(d) VDRL = tabes dorsalis
(e) elderly = PSA, serum acid phosphatase, serum protein electrophoresis (myeloma), CXR
(f) suspect spinal cord pathology = x-ray
MRI (definitive imaging)
CT myelography
(g) suspect cortical pathology = CT head
(h) suspect MS = lumbar puncture (oligoclonal bands)

115
Hereditary ataxias
Common features
 pes cavus
 distal muscle wasting
 loss of knee and ankle jerks (Babinski’s reflex present in FA but absent/equivocal in CMTS)
 loss of proprioception  sensory ataxia

Friedreich’s ataxia
Introduction
 autosomal recessive inheritance
 expansions of trinucleotide repeat GAA in the frataxin gene located on Chr 9
 Harding’s criteria used for diagnosis

Clinical features
 age of onset ~ 8-16 yrs old (same in each family)
 physical examination
(a) pes cavus
(b) neurological signs = pyramidal weakness in LL (spastic paraparesis)
cerebellar signs
dorsal column loss (loss of vibration/proprioception, sensory ataxia, Romberg’s +ve)
peripheral neuropathy (Babinski’s reflex present with absent knee/ankle jerks)
distal muscle wasting

Request to examine
 heart  HOCM, CCF
 eyes  optic atrophy, retinitis pigmentosum
 spine  kyphoscoliosis
 urine  glycosuria (DM)
 IQ  mental retardation

Differentials
1. Multiple sclerosis = mixture of cerebellar, pyramidal and dorsal column signs
2. Charcot-Marie-Tooth syndrome

Prognosis
 usually progresses slowly
 few patients live more than 20 yrs after onset of symptoms (die at ~ 50 yrs old)

Charcot-Marie-Tooth disease
Introduction
 also known as peroneal muscular atrophy
 3 recognised forms = HMSN 1, HMSN 2, distal spinal muscular atrophy
 CMT1A (mutation in myelin gene on Chr 17)is the most common form  AD inheritance
 strong family history

Clinical features
 age of onset ~ puberty
 marked muscle wasting
- peroneal muscles first to atrophy  hands  arms
- affects distally first then spreads proximally
 physical examination
(a) pes cavus, clawing of toes, marked distal wasting, contractures of Archilles tendon
(b) bilateral foot drop
(c) ‘inverted champagne bottle’ legs = wasting of calves and thigh muscles which stop abruptly in lower
third of thigh
(d) weakness of ankle dorsiflexion
(e) absent ankle and knee jerks with absent/equivocal Babinski’s reflex)
(f) sensory neuropathy
(g) gait = high-stepping gait (due to foot drop)
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Request to examine
 thickened peripheral nerves (seen in type 3 CMTD  AR inheritance)
(a) lateral popliteal nerve
(b) greater auricular nerve
 hands  distal muscle wasting, clawing
 spine  kyphoscoliosis
 eyes  optic atrophy, retinitis pigmentosum

Prognosis
 disability is minimal despite marked deformity
 usually arrests in middle life

117
Friedreich’s ataxia
 A hereditary spinocerebellar degeration condition
 Due to an autosomal recessive trinucleotide repeat disorder with a GAA unstable expansion in the long arm of chromosome
9
 Fully-fledged syndrome is rare among affected family members who more commonly show slight signs of abnormality in the
lower limbs: mainly pes cavus and absent reflexes
 Major classic ataxic conditions (MS and tabes dorsalis) need to be differentiated from Friedreich’s ataxia

Features to differentiate the major ataxic conditions

Friedreich’s ataxia Multiple sclerosis Tabes dorsalis
Family history Major Minor None
Onset before age 15 Usual Rare Rare
Knee and ankle jerks Absent Usually exaggerated Absent
Spine (kypho) scoliosis Normal Normal
Feet shape Pes cavus Normal Normal
Pupils Normal Normal Argyll Roberston
Plantars ↑ ↑ ↓ or → (unless taboparesis)
Pain and deep pressure Normal Normal Absent
Romberg’s sign ± - +

Other conditions which may have features of Friedreich’s ataxia (all recessive)
Bassen-Kornzweig syndrome Steatorrhoea, acanthosis, pigmentary retinal degeneration and a spinocerebellar degeneration
which resembles Friedreich’s ataxia
Refusum’s disease Papillary abnormalities, optic atrophy, deafness, pigmentary retinal degeneration,
cardiomyopathy, icthyosis, and a Friedreich-like ataxia
Roussy-Levy syndrome Ataxia, areflexia, pes cavus and kyphoscoliosis BUT absence of nystagmus, dysarthria, extensor
plantar responses and posterior column sign

There is a pes cavus, (kypho)scoliosis and (may be) a deforemed high-arched palate. The patient is ataxic and clumsy with an
intention tremor and his head shakes. There is nystagmus (often slow and coarse and observed before formal examination) and
dysarthria (slow and slurred or scanning and explosive). There is (?gross) bilateral impairment of rapid alternate motion, finger-
nose and hell-shin tests. Knee and ankle jerks are absent and the plantor responses are extensor. Position and vibration sense
are diminished in the feet.
This diagnosis is Friedreich’s ataxia.

Other features (if asked)

1. Cardiomyopathy (may cause sudden death)
2. Optic and retinal atrophy
3. Diabetes mellitus
4. Mild dementia

118
Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy)
 Patters of inheritance are variable
 Degree of disability is commonly surprising slight in spite of the remarkable deformities
 Toe retraction and talipes equinovarus may occur and fasciculation (much less apparent than in motor neuron disease) is
sometimes seen
 Degeneration is mainly in the motor nerves.
o Sometimes also found in the dorsal roots and dorsal columns
o Slight pyramidal tract degeneration is often seen (however in classic cases, extensor plantars are not found)
 The condition usually becomes arrested in mid-life
 Other members of the patient’s family may have formes fruste and show just minor signs such as pes cavus and absent
ankle jerks only

Features
 Muscle wasting stops in the tights
 Foot drop
 Pes cavus
 Wasting of the small muscles of the hand
 Distal wasting in the upper limbs

There is distal wasting of the lower limb muscles with relatively well-preserved thigh muscles. The feet show pes cavus and
clawing of the toes, and there is weakness of the extensors of the toes and feet. The ankle jerks are absent and the plantar
reflexes show no response. There is only slight distal involvement of superficial modalities of sensation (although occasionally
marked sensory loss may lead to digital trophic ulceration). The lateral popliteal (?and ulnar) nerves are palpable (in some
families only). The patient has a steppage gait (bilateral foot drop). There is (may be) wasting of the small muscles of the hand.

This diagnosis is Charcot-Marie-Tooth disease.

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Muscle disorders (Myopathies)
1. History taking
 Is the weakness myopathic?
o Gradual onset
 Sudden onset → toxic, drug or metabolic cause
o Symmetrical distribution
o Proximal weakness
 Affecting esp shoulder and pelvic girdle muscles
 Difficulty climbing stairs, squatting, getting up from a chair, combing hair etc
o No sensory symptoms (pain, numbness, parasthesiae)
 Pain at rest → inflammatory myopathy
 Pain on exercising → ischaemic or metabolic myopathy
o Sparing of bladder and bowel function
o Worse after exercising or at the end of the day
 Rule out NMJ disorders
o Fatigability
o Variability
o Fluctuating
o Associated symptoms = diplopia, dysarthria, dysphonia, dysphagia, SOB
 Age of onset (congenital vs acquired)
 Acquired → part of systemic disease
 Drug and alcohol history
 Family history of similar disorders (e.g. muscular dystrophies)

2. Physical examination
 Common features
o Proximal weakness = shoulder abduction, shoulder flexion, hip flexion, neck flexion
 Neuropathies = distal weakness, sensory symptoms, hyporeflexia
o Muscle wasiting
o No loss of reflexes (slightly reduced in later stages of muscle weakness)
o Sensation intact
 Distinguishing features
o Facial muscle involvement = fascioscapulohumeral dystrophy
 E.g. shut eyes tightly, puff out cheeks, attempt to whistle
o Mainly pelvic and thigh muscles involvement = limb-girdle dystrophy
o Myotonia (delayed muscular relaxation after contraction) = myotonic disorders
 E.g. myotonia congenital, myotonia dystrophica
 E.g. shake patient’s hand and see if patient has difficulty letting go
o Diplopia, ptosis, fatigability, facial weakness, dysarthria, dysphonia = NMJ disorders (e.g. MG)
o Pseudohypertrophy and contractures = Duchenne’s muscular dystrophy

3. Investigations
 Muscle enzymes (aldolase, creatine phosphokinase) = elevated
 Lumbar puncture = CSF normal
 EMG
 Nerve conduction studies = normal
 Muscle biopsy = reserved when genetic tests are non-diagnostic
 DNA analysis

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Myotonic dystrophy (Dystrophia myotonica)
 Affects males > females
 Autosomal dominant
 Condition may show ‘anticipation’
o Progressive worsening of signs and symptoms in succeeding generations
o Genetic testing can be confirmatory; demonstrating expanded trinucleotide repeats in region on chromosome 19
in myotonin protein kinase gene

Features
 Cardio myopathy
o ? small volume pulse
o Low blood pressure
o Splitting of first heart sound in mitral area
o Low voltage P wave
o Prolonged PR interval
o Notched QRS
o And prolonged QTc
o Dysrthymias (sudden death may occur)
 Intellect and personality deterioration
 Slurred speech due to combined tongue and pharyngeal yotonia
 Testicular atrophy (small soft testicle but secondary sexual characteristic preserved usually develops after the patient has
had children and thus the disease is perpetuated; evidence regarding ovarian atrophy is indefinite)
 Diabetes mellitus (end organ unresponsiveness to insulin)
 Nodular thyroid enlargement
 Small pituitary fossa but normal pituitary function
 Dysphagia
 Abdominal pain
 Hypoventilation
 Postanaesthetic respiratory failure may also occur

The patient has myopathic facies (drooping mouth and long, lean, sad, lifeless, some-what sleepy expression), frontal balding (in
the male), ptosis (may be unilateral) and wasting of the facial muscles, temporalis, masseter, sternomastoids, shoulder girdle
and quadriceps. The forearms and legs are involved and the reflexes are lost. The patient has cataracts. After he made a fist, he
was unable to quickly open it, especially when asked t o do this repetitively (this gets worse in the cold and with excitement). He
has difficulty opening his eyes after firm closure. When he shook hands there was a delay before he released his grip* (these are
features of myotonia). When dimples and depressions are induced in his muscles by percussion, they fill only slowly (percussion
myotonia – e.g. tongue and thenar eminence)

The diagnosis is myotonic dystrophy.

*There may be absence of grip myotonia in advanced disease because of progressive muscle wasting. Though myotonia can be
relieved by phenytoin, quinine or procainamide, it is weakness (for which there is no treatment for) rather than the myotonia
which is the main cause of disability in myotonic dystrophy.

Myotonia congenital (Thomsen’s disease)

 There is difficulty in relaxation of a muscle after forceful contraction (myotonia)
 BUT none of the other features of myotonic dystrophy (e.g. weakness, cataracts, baldness, gonadal atrophy)
 Reflexes are normal
 Some patients have a ‘herculean’ appearance from very developed musculature (?related to repeated involuntary isometric
exercise)
 Disease is usually autosomal dominant but autosomal recessive forms are also recognized
 Due to disorders of ion challes (channelopathies)
o The finding of paramyotonia (myotonia worsening with exercise and cold) may be useful clinically in differentiating
various subtypes of channelopathy

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Metabolic Myopathies/Periodic Paralysis
Introduction
 Heterogeneous group of muscle diseases
 Characterised by episodes of flaccid muscle weakness occurring at regular intervals.
 Strength is normal b/w attacks, though fixed weakness may develop later in some forms
 a/w changes in serum potassium concentrations
 General characteristics of Primary PP:
i) Hereditary
+
ii) Most are a/w alterations in serum K levels
iii) Myotonia sometimes co-exist
iv) Both myotonia and PP result from defective ion channels

Classification
Primary Periodic Paralysis Secondary Periodic Paralysis
Hypokalemic Hyperkalemic
1. Hypokalemic PP 1. Drugs 1. Drugs
+
2. Hyperkalemic PP - Diuretics - K sparing diuretics
3. Paramyotonia congenita - Amphotericin B
4. Anderson-Tawil syndrome - Barium
- K+ channel mutation - Corticosteroids
+
- Variable expression of Triad 2. Urinary K wasting syndromes 2. Potassium Load
i. Dysmorphism - Hyperaldosteronism
 Short stature, - Conn syndrome
hypertelorism, low set ears, - Bartter syndrome
micrognathia, scoliosis - Licorice intoxication
+ +
ii. Periodic Paralysis 3. GI K wasting syndromes 3. GI K wasting syndromes
 Not a/w myotonia - Laxative abuse - Ileostomy with tight stoma
iii. Cardiac Arrythmias: - Severe diarrhoea
 Prolonged QT 4. Alcoholism 4. Alcoholism
 Vent. arrythmias 5. Renal tubular acidosis 5. Chronic Renal Failure
6. Endocrine 6. Endocrine
- Thyrotoxic PP - Addison disease
(most common)

Pathophysiology
+ 2+ + +
 Principal defects = Na , Ca , K channelopathies. Not the alteration of serum K levels (it is the result of PP)
 Physiological basis of flaccid weakness: aberrant depolarisation  inexcitability of muscle membrane
+
 In primary and Thyrotoxic PP, flaccid paralysis occurs with relatively small changes in serum K levels
 HypoK PP shows the clearest r/ship b/w episodic weakness and alterations in K levels
+ +

 HyperK PP is a “K sensitive” periodic paralysis, as weakness can be provoked by K admin, but serum K levels
+ + +

may only rise mariginally during spontaneous attacks

+
 In secondary PP, serum K levels are markedly abnormal

Clinical features
 Eyes: Interictal lid lag, eyelid myotonia
 Fixed proximal weakness
 Diminished stretch reflexes during attacks
 Normal sensation

General Principles of Management

 ABCs, Continuous ECG monitoring
+
 Serial serum K monitoring
 During attacks, oral potassium supplementation is preferred to IV (only for impaired swallowing/nausea/vomitting)
+
 Oral K salts  Dose: 0.25mEq/kg every 30mins till weakness improves
 Prophylaxis:
st
 1 line: Acetazolamide (Carbonic anhydrase inhibitor) 125-1500mg/day in divided doses
 MOA = In hypoK PP, it may decrease K inflow to muscle, because of metabolic acid
+ +
+
In hyperK PP, kaliopenic effect may be beneficial
2+ +
Recent data suggest activation of skeletal muscle BK channel (Ca -activated K channels)
nd + st
 2 line: K -sparing diuretics (spironolactone, triamterene)  in worsening weakness or no resp to 1 line
+
May not need to give additional K supplements
122
Syndrome Hyperkalemic PP Hypokalemic PP Normokalemic PP Paramyotonia congenita Thyrotoxic periodic
paralysis
Inheritance AD, AR AD AD - Occurs mainly in Asians
Chromosome 17 1 17 (same gene as HyperK) - M: F = 20:1
Underlying Na+ channel gene defect Mutations resulting in voltage-gated Impaired inactivation of skeletal muscle Na+
defect Ca2+ channel (dihydropyridine) channels
defect
nd rd th
Age of onset Infancy Onset in 2 decade Onset in infancy 3 and 4 decade
First decade of life Majority <16yrs old First decade of life
rd
(Childhood – 3 decade)
Precipitating - Low carbohydrate intake - High carbohydrate meals - Fasting - (same as hypoK PP)
factors - Fasting - Hyperinsulinemia
- Cold - Cold - Cold
- Rest after exercise - Early morning attacks occur after - Rest after exercise
- Alcohol prev day’s physical activity
- Infection
- Emotional Stress
- Trauma
- Menses
Clinical - Starts in proximal lower - Starts in proximal lower limbs - Episodic weakness in which no - Starts in proximal muscles (similar to HypoK+ PP)
features limbs - Evolves rapidly to become alterations in serum K levels are - Paradoxical myotonia
(thigh, calfarm, neck) generalised found o Myotonia worsens with activity
- Evolves rapidly - Onset usually in morning on - Sensitive to oral K+ salts admin Repetitive mus contractions ↑
wakening stiffness
- Urine output ↓ during attack
(H20 accumulates intracellularly)
Duration <1hr (few min - <2hrs) 4 – 24 hrs (few hrs to 1 wk) 2-24hrs Few hrs – 7 days
Severity Rarely severe Severe, Complete Paralysis Rarely severe (same as hypoK PP)
Associated - Perioral and limb - Bulbar and resp muscles - Pseudohypertrophy of muscles - HypoK during attacks
features paresthesias unaffected - Fixed weakness rare - Fixed muscle weakness
- Myotonia - Occasional myotonic lid lag may develop
- Occasional muscle - Myotonia b/w attacks rare
Pseudohypertrophy - Unilateral, partial monomelic
- Fixed muscle weakness late in
disease
Lab results - K+ only rises slightly from - K+ as low as 1.5mEq/L - Normal serum levels - EMG: marked spontaneous activity on limb
baseline, may not >normal - CPK ↑↑ during attacks - Muscle Biopsy: occasional/few muscle cooling
- CPK ↑ during attacks - ECG: flattened T wave, ST seg vacuoles, prominent tubular
- ECG: Tall T waves dep, U wave in II, V2,3,4 aggregates
- Muscle biopsy: vacuoles in
muscle fibres
Management - Acute: - Acute: Oral KCl - No resp to Acetazolamide - Na+ channel blockers - Control thyrotoxicosis
-Mild: high-carbo foods - Prophylactic: acetazolamide, - (Rest similar to HyperK PP Mx) - Tocainide - β-blockers: propanolol
-IV Ca2+ gluconate, IV NaCl low carbo, high K diet - Mexiletine (CI: heart block) - Oral K+ supplements
- Prophylactic: Acetazolamide - Prophylaxis

123
Polymyositis & Dermatomyositis
 Non-suppurative inflammation of the muscles
 Polymyositis: CD8 cell-mediated necrosis
 Dermatomyositis: B-cell and CD4 immune complex mediated

Clinical features of BOTH conditions

 Onset = 40 to 50 years old
 Autoimmune = respond to immunotherapy, a/w immunological disorders e.g. SLE, RA, elevated IgG in blood and presence
of circulating autoantiboides
 May follow systemic infection
 Symmetrical, proximal muscle weakness
o E.g. difficulty in rising up from chair, climbing stairs, lifting things
 ± pain, tenderness and induration
 Raynaud’s phenomenon
 Photosensitive rash
 Disease course: Progressive
o Widespread weakness and wasting
o Dysphagia
o Dysphonia
o Respiratory muscle weakness
o Cardiac involvement: CMP, arrhythimias
 No ocular muscle involvement
 Reflexes are intact (if involved → consider underlying carcinoma with added neuropathy)
 Rarely fatal

Dermatomyositis
 Inflammation of skin and muscles (more severe and acute)
 a/w malignancy (9-23%) in adults, vasculitis/ calcinosis in juvenile patients (screen for testicular cancer)

Skin changes
 Macular rash:
 Heliotrope rash:
 Gottron’s papules:
 Nail-fold erythema:
 Mechanic’s hands:
Shawl sign +ve over back and shoulders; v-sign if over chest
Lilac purple rash over cheeks, eyelids, light-exposed areas
Roughed red papules over extensor surfaces of IPJ, MCPJ, elbow or knee joint
Pathognomonic if CK ↑ + muscle weakness
Dilated capillary loops (peri-ungal telangiectasia)
Rough, cracked skin on lateral and palmar surfaces of fingers and hands with irregular
‘dirty’ horizontal lines

Systemic signs
 Fever
 Raynaud’s phenomenon
 Respiratory involvement (20%) = interstitial lung disease, aspiration pneumonia
 CVS: CMP, arrhythmias
 Eye: retinitis (e.g. cotton-wool patches)
 GIT: dysphagia, gut dysmotility

Investigations
1. ESR: ↑
2. Serum muscle enzymes: Creatine phosphokinase, ALT, aldosoe, LDH ↑↑
3. EMG: Myopathic changes → short duration, spiky polyphasic APs, fibrillations
4. Muscle biopsy: Perivascular inflammatory infiltrates, fibre atrophy, necrotic fibres
5. Tumor markers: Investigate extensively fro malignancy (breast, colorectal, lung, ovarian)
Differentials
1. Muscular dystrophies: but they rarely progress so rapidly, no muscle pain involved
2. Motor neuron disease: UMN sign and prominent fasciculations seen

124
Treatment
1. Corticosteriods: prednisolone
2. Immunosuppressants: azathioprine, cyclophosphamide, cyclosporine
3. High dose IVIG
4. Malignancy surveillance
a. Detailed history & physical examination (breast, pelvic, rectal exam)
b. Invx= CXR, abdo/pelvic ultrasound, mammogram, pap smear, FOBT

Polymyositis
 Muscles may be painful and tender (due to non-suppurative inflammation of skeletal muscles)
 Pathogenesis: immune cell-mediated damage of myocytes
 a/w skin changes (e.g. dermatomyositis), connective tissue diseases (e.g. scleroderma, SLE, RA)
 Histology:
o Endomysial inflammatory infiltrates
o Scattered necrotic fibres
o NO fibre atrophy or perivascular inflammation (unlike in dermatomyositis)

125
Eye
Examination of the Eye
1. Inspection
(a) ptosis = unilateral vs bilateral
complete vs partial
(b) strabismus
(c) exophthalmos + lid retraction  look from above for proptosis
# unilateral proptosis = Graves’ disease
retro-orbital tumour (primary or metastatic)
retro-orbital granulomatous infiltration (Wegener’s)
cavernous sinus thrombosis
carotico-cavernous fistula (visible pulsations; bruit heard on auscultation)
orbital cellulitis
# investigations = thyroid function test
orbital U/S
CT head

2. Visual acuity
 counting fingers
 hand movement
 light perception

3. Visual fields

4. Examine eyes with pen-torch

rd
(a) pupillary size = normal (medical 3 nerve palsy, MG)
rd
dilated (surgical 3 nerve palsy)
constricted (Horner’s syndrome)
anisocoria
rd
(b) pupillary light reflex = 3 nerve palsy  both direct and consensual impaired
optic nerve palsy  direct impaired, consensual intact
(c) relative afferent pupillary defect (Marcus-Gunn pupil) = impaired direct light reflex with an intact
consensual light reflex resulting in paradoxical
dilatation when light is shown into affected eye

5. Accommodation

6. Extra-ocular eye movements

(a) paralysis
(b) diplopia
(c) nystagmus
(d) INO
(e) horizontal/vertical gaze palsy

7. Special manoeuvres
(a) lid lag – thyroid eye disease
(b) lid fatigability – myasthenia gravis

Request to do
1. Fundoscopy
 Marcus-Gunn pupil = optic atrophy
 visual field defects = papilloedema
rd
 medical 3 nerve palsy = diabetic/hypertensive retinopathy

2. Corneal reflex – CN 5,7

3. Other cranial nerve involvement

(a) cavernous sinus and superior orbital fissure syndrome – CN 3, 4, 51, 6
126
 (b) orbital apex – CN 2, 3, 4, 6
(c) petrous apex – CN 5, 6
(d) cerebello-pontine angle – CN 5, 6, 7, 8, cerebellum

4. Neurological examination
(a) motor and sensory deficits
(b) cerebellar signs

# Suspect that patient may have glass eye = zero visual acuity + absent light reflex
malignant melanoma liver palpable

Ophthalmoplegia
 muscle = myopathy
entrapment
thyroid eye disease
 neuromuscular junction = myasthenia gravis
 peripheral nerve
(a) mononeuritis multiplex = Vascular  PAN
Infective  leprosy, Lyme disease
Autoimmune  Wegener’s granulomatosis, Sjogren’s syndrome
Metabolic  DM, HPT
Infiltrative  amyloidosis, sarcoidosis
(b) chronic meningitis = carcinoma
lymphoma
infective (TB, fungal, HIV, syphilis)
 brainstem = stroke
SOL (tumour, abscess)
multiple sclerosis

127
Eye Signs
1. Localisation in visual impairment
- visual impairment + impaired pupil response = lesion anterior to lateral geniculate body
- homonymous hemianopia + sensory and cognitive deficit = parieto-temporal lesion
- isolated homonymous hemianopia = occipital lesion

Dilated pupil
1. Causes
rd
(a) 3 nerve lesion = failure of pupil to constrict to light regardless of where light is shown
(b) Holmes-Adie syndrome
- lesion = degeneration of the nerve to the ciliary ganglion
- benign condition (must not be mistaken for Argyll-Robertson pupil)
- clinical presentation = usually in a young woman
pupil is large, regular/irregular, oval/circular
myotonic pupil (failure to react to light immediately but may constrict after
strong and prolonged exposure; dilates slowly when light
stimulus is removed)
delayed accommodation
absent ankle reflexes
- history = a/w dysautonomias (impaired sweating in Ross’s syndrome; palpitations from cardiac
arrhythmias )
- different from Adie’s tonic pupil = due to damage to parasympathetic fibres in the ciliary ganglion
ankle jerks are PRESENT!
(c) drugs (atropine, cocaine, amphetamines)
(d) trauma to the iris = iridectomy, blunt trauma
(e) deep coma and death

Constricted pupil
1. Causes
(a) Horner’s syndrome
(b) Argyll-Robertson pupil (prostitute’s pupil)
- lesion = pretectal area of the superior colliculus in the midbrain
- causes = neurosyphilis (tabes dorsalis)
diabetes mellitus (causing autonomic neuropathy)
multiple sclerosis
pinealoma
Lyme’s disease
brainstem encephalitis
- clinical presentation = constricted pupils that do not react to light but react to accommodation
show little response to atropine, physostigmine or methacholine
- history = lacinating pains
history of MS, syphilis, sarcoidosis
gait disturbances
- request to examine = vibration and proprioception (decreased/absent)
Romberg’s sign (positive)
deep tendon reflexes (decreased)
syphilitic serology
urine dipstick for diabetes
- ‘reversed’ Argyll-Robertson pupil = reacts to light but not to accommodation
seen in Parkinsonism caused by encephalitis lethargica
(c) drugs (opiates, pilocarpine)
(d) pontine lesion

2. Life-threatening causes of anisocoria = Horner’s syndrome with carotid dissection

rd
surgical 3 nerve palsy

Marcus-Gunn pupil
1. Causes
(a) optic neuritis (multiple sclerosis; infective = IM, syphilis, sinusitis; temporal arteritis; metabolic = DM,

128
 vitamin B12 deficiency; drugs = ethambutol, chloroquine, alcohol)
(b) optic atrophy (optic nerve compression, multiple sclerosis, chronic glaucoma, retinitis pigmentosa,
Friedrich’s ataxia)
(c) vascular occlusion of the retinal vessels (CRAO, CRVO, BRVO)
(d) ischaemic optic neuropathy
(e) severe retinal detachment

129
Visual field defects

1. Monocular blindness = optic neuritis (multiple sclerosis)

vascular (thrombotic occlusion of ICA → gives off ophthalmic artery; CRAO; CRVO;
temporal arteritis; ischaemic optic neuropathy)
optic nerve compression (optic glioma, abscess)

2. Bitemporal hemianopia
- caused by median lesions of the optic chiasm
- initial involvement of upper quadrants suggests that there is compression from below
(a) pituitary adenoma = macroadenoma (> 10mm in diameter; causes local pressure effects; requires
surgery via trans-sphenoidal approach)
microadenoma (< 10mm in diameter; causes hormonal effects; responds well
to dopamine agonists)
(b) NPC
(c) sphenoid sinus mucocele
initial involvement of lower quadrants suggests that there is compression from above
(a) craniopharygioma
(b) suprasellar meningioma
rd
(c) 3 ventricular tumour
(d) ICA aneurysm
- history = insidious onset of visual field defects
hypogonadism (impotence in males, amenorrhoea in females) → precede by many years
- request to examine = local pressure effects (CN 1, 3,4,6)
fundoscopy for optic atrophy
hands and face for acromegaly
signs of hypopituitarism (pallor, soft skin, paucity of axillary/pubic hair, breast/testicular
atrophy, postural hypotension)
- investigations = formal visual field testing (Humpfrey)
serum prolactin
skull x-ray (lateral skull → calcification of craniopharygioma, size of pituitary fossa)
CT/MRI head

3. Homonymous hemianopia
- lesion = optic tract, thalamus, internal capsule, optic radiation and visual cortex
- superior quadrantanopia = lesion in the temporal lobe
inferior quandrantanopia = lesion in the parietal lobe
with macular sparing = ischaemic lesion in the occipital lobe (dual blood supply from MCA and PCA)
- history = bumps into things on one side (patient may insist that he/she has one ‘bad’ eye → blindness in
1 eye causes impairment in perceiving distances but normal eye
will provide full field of vision on both sides and prevent patient

130
 from bumping into objects)
reading difficulty (cannot scan along line to the next word or find beginning of next line)
aware of defect (unaware → visual neglect, macular sparing)
- request to examine = double simultaneous visual stimulation
if neglect is found → higher centre testing
- aetiology = stroke, intracranial tumour
- investigations = formal visual field testing (Humpfrey)
CT/MRI head

131
3rd nerve palsy
1. Clinical presentation = complete ptosis (partial ptosis with incomplete lesion)
eye is ‘down and out’ (divergent squint)
dilated pupil that is unreactive to light and accommodation
impaired EOM with diplopia in all directions (except on abduction)
rd
2. Approach to 3 nerve palsy
(a) Are pupils dilated
rd
(b) isolated 3 (orbital apex → CN 2, 3, 4, 6;
cavernous sinus → CN 3, 4, 51, 6;
superior orbital fissure syndrome → CN 3, 4, 51, 6 + unilateral recurrent retro-orbital pain due
to inflammation of the cavernous sinus)
(c) Is there midbrain involvement
(a) contralateral hemiparesis (corticobulbar tract) → Weber’s syndrome
(b) contralateral ataxia + involuntary movements (tremor, chorea, athetosis) (red nucleus) → Benedikt’s
syndrome
(c) contralateral hemisensory loss (spinothalamic and medial meniscus)
rd
3. Medical vs Surgical 3 nerve
rd
Medical (Ischaemic 3 )
6 Conditions to fulfill
2
 pupil sparing x /52
rd
 complete 3 nerve palsy (eye is ‘down and out’; complete ptosis)
rd th
 isolated 3 nerve palsy (exclude 4 nerve involvement)
 vascular risk factors (e.g. HPT, HCL, DM, age, smoking, vasculitis)
 complete recovery within 12 weeks
 no aberrant regeneration

Pupillary sparing
rd
- pupillary fibres located on the outer surface of the 3 nerve
rd
- tends to be affected in compressive situations i.e. surgical 3
rd
- unlikely to be affected in medical 3 = rich anastomoses supplying these fibres; inner fibres affected first
- 80%  pupil sparing
20%  pupil involvement
rd
Surgical 3
Dilated and sluggish pupil + painful ophthalmoplegia
- 90%  pupil involvement
10%  pupil sparing
- causes = aneurysm (P. comm. aneurysm), tumour (NPC), abscess, raised ICP if bilateral involvement
(Hutchinson’s pupil = uncal herniation through the tentorium compressing the nerve)

4. Investigations
(a) Exclude other differential diagnosis = edrophonium test (myasthenia gravis esp if pupil is spared)
TFT + orbital U/S (thyroid eye disease in Graves’)
(b) BP (HPT)
(c) BSL and urine dipstick (DM)
(d) fasting lipid panel (HCL)
(e) ESR (giant cell arteritis in the elderly)
rd
(f) lumbar puncture if 3 nerve lesion cannot be localized
Pupil Ptosis Investigations
Dilated Partial CT/MRI  4 vessel angiogram
Dilated Complete CT/MRI  4 vessel angiogram
Spared Partial Serial observation of pupil for 1 week (could be a growing aneurysm)
MRI if no improvement in 12 weeks (look for superior division paresis 
supplies levator palpebral superioris and superior rectus)
rd
* Aneurysms in the cavernous sinus can compress both the sympathetics and the 3 nerve
 pupil ‘spared’
Spared Complete Observation
MRI if no improvement in 12 weeks (e.g. multiple sclerosis)

132
6th nerve palsy
1. Clinical presentation = convergent squint
impaired abduction of affected eye with horizontal diplopia
may be a/w hearing loss

2. Proceed with
(a) Other cranial nerve involvement
(i) cavernous sinus (CN 3, 4, 51, 6)
(ii) superior orbital fissure syndrome (CN 3, 4, 51, 6 + retro-orbital pain)
(iii) orbital apex (CN 2, 3, 4, 6)
(iv) petrous bone (CN 5, 6)
(v) cerebello-pontine angle (CN 5, 6, 7, 8 + cerebellum) → TEST CORNEAL REFLEX AND HEARING
(b) Fundoscopy for papilloedema (false-localising sign in raised ICP)
(c) Pontine involvement
(i) corticospinal tract
(ii) spinothalamic tract
(iii) medial meniscus
(iv) spinocerebellar tract
(v) INO
(vi) lateral gaze palsy
th
(d) Isolated 6 nerve palsy → check for NPC (ask about epitaxis and hearing loss; examine for cervical LAD)

3. Investigations
(a) BP (HPT)
(b) BSL and urine dipstick (DM)
(c) fasting lipid panel (HCL)
(d) CT/MRI head
(e) LP if chronic meningitis suspected
(f) ENT referral if necessary

133
Horner’s Syndrome
If got wasted hand (C8, T1)  Examine for Horner’s Syndrome

1. Neuroanatomy
a. Hypothalamus  brainstem  cervical spinal cord (C8, T1)  out the roots to near the lung apex  superior
cervical ganglion  up the carotid sheath with the ICA and later ophthalmic artery  pupils, levator palpebrae
and sweat glands of the face
b. Interruption of the sympathetic innervations of the eye at any point  Horner’s syndrome

2. Clinical presentation (ipsilateral signs)

a. Partial ptosis
b. Slight elevation of lower eyelid covering lower limbus (‘upside down ptosis’)  paralysis of lower tarsal
muscles
c. Enophthalmos
d. Miosis
e. Anhidrosis (absence of sweating)

3. Aetiology
Location Examples
Brainstem Vascular (especially lateral medullary syndrome)
Tumour
Syringobulbia
Cervical cord Syringomyelia (rare)
Tumour
Multiple sclerosis
Neck Tumour (thyroid ca)
Trauma (cervical sympathectomy)
Lymphadenopathy
Carotid aneurysm / dissection / tumour (post-ganglionic)
Lower trunk Trauma
brachial plexus Tumour
Lung Pancoast tumour (SCC)

4. Physical Examination
Confirm that it is Horner’s syndrome
rd
(a) Partial ptosis (TRO 3 nerve palsy & myasthenia gravis)
(b) Constricted pupil that is reactive to light and accommodation
(c) Facial anhidrosis = decreased sweating over each eyebrow (test with the back of the finger) --- may indicate level of
lesion

Aetiology
(a) Lung
- Hoarseness from recurrent laryngeal nerve palsy
- Clubbing, HOPA, small muscle wasting, weakness of finger abduction (if any of these signs is present 
dullness to percussion over supraclavicular area, tracheal deviation)
(b) Neck
- Inspect for surgical scars and neck masses
- Palpate for thyroid mass, cervical lymphadenopathy and carotid aneurysm (pulsatile neck mass)
- Auscultate for carotid bruit
(c) Brainstem (test cranial nerves, motor, sensory, cerebellum)
- Hx: vertigo, nausea, vomiting, dysarthria, dysphagia, hoarseness

134
 - Cranial n. testing: nystagmus to the side of the lesion (CN 8)
decreased gag reflex (CN 9 + 10) CN9, 10 LMS
palatal weakness (CN 10) Sensory loss
hoarseness (CN 10) Nystagmus LMS
- Motor testing: not affected in lateral medullary syndrome (LMS) Multiple sclerosis
- Sensory testing: ipsilateral pain & temperature loss of the Pronator drift Multiple sclerosis
Syringomyelia
face
contralateral pain & temperature loss of the extremities
- Cerebellar testing: ipsilateral cerebellar signs
(d) Spinal cord
- Syringomyelia:
i. Dissociated sensory loss (loss of pain & temperature over the neck, shoulders & arms in a ‘cape’
distribution; intact vibration & proprioception)
ii. UL LMN weakness with LL UMN weakness
iii. Can cause bilateral Horner’s syndrome

Level of lesion
(a) Central = anhidrosis over ipsilateral half of head, arm and upper trunk
(b) In the neck & proximal to superior cervical ganglion = anhidrosis over face
(c) In the neck & distal to superior cervical ganglion = no anhidrosis

135
Ptosis
1. Definition = refers to drooping of the upper eyelid due to abnormalities of the muscles that usually
rd
elevate it i.e. levator palpebrae superioris (3 nerve) and Mueller’s muscle (sympathetics)

2.
Causes of unilateral ptosis
Muscle myotonia dystrophica
NMJ myasthenia gravis
Peripheral nerve Horner’s syndrome
rd
3 nerve palsy
Congenital ptosis

Causes of bilateral ptosis

Muscle myotonia dystrophica
ocular myopathy
mitochondrial dystrophy
NMJ myasthenia gravis
Peripheral nerve bilateral Horner’s syndrome (syringomyelia)
rd
bilateral 3 nerve palsy
tabes dorsalis
Miller-Fisher syndrome
Congenital ptosis
rd
3. Physical examination (3 common exam cases = Myasthenia gravis, Horner’s syndrome, 3 nerve palsy)
(a) Inspection
rd rd
- complete (3 nerve palsy) vs partial (3 nerve, MG, Horner’s)
- unilateral vs bilateral
rd
- strabismus = 3 nerve palsy, MG
- slight elevation of lower eyelid (upside down ptosis) = Horner’s
(b) Ask the patient to open his eye voluntarily
- correctable = Horner’s, MG
rd
- non-correctable = 3 nerve palsy, MG
(c) Examine pupil size and pupillary reflex to light
rd
- dilated and sluggish = 3 nerve palsy
- constricted but reactive = Horner’s
rd
- normal and reactive = MG, 3 nerve palsy
(d) Examine extra-ocular movements (ask about diplopia)
rd
- impaired = MG, 3 nerve palsy
- normal = Horner’s
(e) Test for fatigability (MG)
* prolonged upward gaze for 1 min
* hold up contralateral (unaffected) upper eyelid
* shine light into affected eye

136
Conjugate Eye Movements

1. Types of movements
Scanning Flick from one visual target to another in high-speed movements Frontal lobe
called saccades
Tracking Follow an object of interest across the visual field in smooth pursuit Occipital lobe
Compensation Gaze held on an object of interest during movements of the head Vestibulo-ocular
reflex
Optokinetic Follow objects in motion when the head remains stationary Optokinetic reflex

2. Scanning
a. 4 separate gaze centres in the brainstem (left, right, up, down)
i. Located in the reticular formation
ii. Contain burst cells
b. Lateral gaze centre located in paramedian pontine reticular formation (PPRF)
c. Vertical gaze centre located in rostral interstitial nucleus of MLF (riMLF)
d. Automatic scanning = activated by superior colliculus
e.g. to objects moving in peripheral visual field
e. Voluntary scanning = initiated in frontal eye fields
fibres decussate before terminating in gaze centres

3. Damage to the motor areas of the cerebral cortex results in a loss of ability of either eye to look in the
contralateral direction
E.g. lesion in right visuo-motor area  patient cannot look to the left, :. eyes tend to deviate to the right

137
 a. Pathway from the left hemisphere innervates the right lateral rectus m. and the left medial rectus m. :. both
direct the eyes to the right
b. Lesion to the MLF results in weak adduction because it supplies medial rectus m.  internuclear
ophthalmoplegia (INO)
c. Damage to the abducens nucleus will result in ipsilateral gaze palsy
d. Right gaze preference
i. Right frontal lesion: destructive (vascular tumour) versus irritative (epileptic focus) lesion
ii. Left pontine lesion (PPRF, abducens nucleus)

CONJUGATE GAZE PALSY = SUPRANUCLEAR PALSY

4. One-and-a-half syndrome
a. Characterised by lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other (divergent
squint in contralateral eye)
b. Due to unilateral pontine lesion (affecting lateral gaze centre in PPRF) and ipsilateral MLF OR abducens
nucleus lesion and ipsilateral MLF
c. Main causes: Stroke (2˚ pontine infarct/haemorrhage)
Multiple sclerosis
Tumours
Tuberculomas
Ischaemia (posterior circulation / basilar artery)

BETWEEN 3RD TO 6TH NERVES

5. Internuclear ophthalmoplegia (INO)
a. Occurs when MLF is affected :. Affected eye cannot adduct + divergent squint
b. MLF runs from pons to midbrain
:. To distinguish a pontine lesion vs. Midbrain lesion, test for convergence and upward gaze (midbrain
functions)
c. Pure left INO:

One-and-a-half syndrome. This results from a pontine lesion (shaded area) involving the paramedian pontine reticular formation
(lateral gaze center) and medial longitudinal fasciculus, and sometimes also the abducens (VI) nucleus, and affecting the neuronal
pathways indicated by dotted lines.

Attempted gaze away from the lesion (A) activates the uninvolved right lateral gaze center and abducens (VI) nucleus; the right lateral
rectus muscle contracts and the right eye abducts normally. Involvement of the medial longitudinal fasciculus interrupts the pathway
to the left oculomotor (III) nucleus, and the left eye fails to adduct.

On attempted gaze toward the lesion (B), the left lateral gaze center cannot be activated, and the eyes do not move. There is a
complete (bilateral) gaze palsy in one direction (toward the lesion) and one-half (unilateral) gaze palsy in the other direction (away
from the lesion), accounting for the name of the syndrome.

138
 Right Left

nystagmus

d. Investigations: MRI
Edrophonium (TRO myasthenia gravis)
e. Check for evidence of multiple sclerosis (RAPD; optic atrophy; cerebellar, cranial nerves & long-tract signs),
drug use (phenytoin; carbamazepine), neurofibromatosis (brainstem stroke/glioma)
f. Multiple sclerosis can cause bilateral INO (either eye cannot look medially but can converge)

6. Doll’s reflex [also known as oculo-vestibular reflex (brainstem reflex)]

a. Important in maintaining gaze on a fixed object (image directed towards the fovea)
b. On turning to the left  left vestibular apparatus fires signals to the ipsilateral vestibular nucleus  sends fibres
that cross over to the contralateral abducens nerve nucleus, :. Eyes look to the right
c. Doll’s reflex should be present if brainstem function is intact!
d. Patient is asked to fixate on examiner’s face and the head is briskly rotated by the examiner from side to side
(horizontal doll’s) or up & down (vertical doll’s)
e. Doll’s reflex preserved in supranuclear gaze palsy
f. Caloric tests used to demonstrate:
i. Stimulus is maximal with the head supported 30˚ from the horizontal
:. lateral semicircular canal in a vertical plane
ii. Water at 30˚C irrigated into external auditory meatus
1. Nystagmus develops after 20s and lasts for >1min
2. Cold water reduces the vestibular output from one side
:. Eye drift towards the irrigated side
Fast component in the direction of the opposite ear
iii. Water at 44˚C increases vestibular output
:. Eye drift away from irrigated side
Fast component in the same direction
iv. In brain-dead patients  use ice-water
1. No fast component of nystagmus seen! (fast component under frontal control)
2. Eyes may still drift to irrigated ear if brainstem is intact

139
←nystagmus

Hot water
440C
→nystagmus

140
Haematology
Approach to anaemia
Definition
 Reduction in O2-transporting capacity of blood due to reduction in total circulating RBC mass OR increase in plasma volume
 Males = 13-18g/dL
Females = 11-16g/dL

Classification by pathogenesis

Anaemia

Blood loss Increased destruction Decreased Production

1. Acute
1. BM failure
2. Chronic Intrinsic Extrinsic  Hypoplastic/aplastic
abnormalities causes 2. BM suppression
 Tumour infiltration
 Myelofibrosis
1. Immune-mediated 3. Anaemia of chronic disease
Hereditary Acquired  ABO incompatibility  Chronic renal failure
 Rh incompatibility  Chronic inflammation
 Drug-induced  Chronic infection
Membrane defects  Malignancy
1. Membrane defects  SLE
 Spherocytosis - paroxysmal nocturnal 4. Defective DNA synthesis
haemoglobinuria  Idiopathic
 elliptocytosis 2. Mechanical trauma  Folate deficiency
2. Enzyme defects  Prosthetic valves  Vit B12 deficiency
 Pyruvate kinase  Microangiopathy 5. Defective Hb synthesis
 G6PD deficiency 3. Infections  Iron deficiency
3. Hb synthesis defects  Malaria  Globin deficiency
 Globin deficiency  Mycoplasma (thalassemia)
(thalassemia) 4. Hypersplenism
 Globin structural
abnormality (sickle
cell)

Classification by morphology Anaemia

Peripheral blood film Macrocytic

Microcytic
Normocytic Megaloblastic
1. Iron deficiency Non-
 ↓intake 1. Vit B12 deficiency
megaloblastic
Reticulocytosis
 ↓absorption  ↓intake (vegans)
 ↑demand  ↓absorption 1. Alcohol
(pregnancy) No  Pernicious anaemia 2. Hypothyroidism
 Chronic blood loss
reticulocytosis  Post-gastrectomy 3. Liver disease
2. Thalassemia 4. Myelodysplastic
2. Folate deficiency
3. Sideroblastic
 ↓intake syndrome
 ↑demand 5. Compensatory
1. Anaemia of
1. Acute blood loss (pregnancy) reticulocytosis
chronic disease
2. Haemolytic 2. BM failure  Drugs
anaemia 3. BM suppression (methotrexate,
valproate)

141
  Subjective RBC indices (seen on peripheral blood film)
o Size = compared with lymphocyte
o Colour = central pallor should not be more than 1/3 RBC diameter
o Shape
 Objective RBC indices (measured and reported in full blood count)
o Mean cell volume (MCV) = average volume of a RBC (femtolitres)
o Mean cell haemoglobin (MCH) = average mass of haemoglobin per RBC (pictograms)
o Mean cell haemoglobin concentration (MCHC) = average Hb conc in given vol of packed cells (g/dL)
o Red cell distribution width (RDW) = co-efficient of variation in RBC volume

Pathogenesis
 Decreased tissue oxygen tension triggers increased erythropoietin production
- exception = CRF (lost the ability to produce erythropoietin)
 Results in = compensatory hyperplasisa of erythroid precursors in bone marrow
Extramedullary haematopoiesis in secondary hematopoietic organs (spleen, liver)
 Increased reticulocytes released into circulation
- exception = BM failure

Clinical features of anaemia

History
Name/age/ethnicity/gender/occupation (ethnicity important in thalassemia)
Past medical history

Presenting complaint
Symptoms of anaemia = pallor, chest pain, SOB, giddiness, palpitations, fatigue

Aetiology
Chronic blood loss = haematemesis, melena, epigastric pain, history of PUD
Haematochezia, changes in bowel habit, tenesmus, abdominal pain
Menorrhagia
Haemolytic anaemia = associated with jaundice
# intrinsic causes = history of thalassemia and G6PD deficiency
# extrinsic causes = recent blood transfusion
Recent drug intake
Autoimmunity (rash, joint pain, h/o SLE)
History of renal impairment = changes in urine output
Lower limb swelling
BM pathology = thrombocytopenia (petechial rash, easy bruisability, epistaxis, gum bleeding, haematuria)
Leucopenia (increased susceptibility to infections)
LOA, LOW, fever, night sweats (B symptoms)
Exposure to chemicals/noxious substances

Past medical history

Heart valve replacement
Hypothyroidism
Gastrectomy
IBD (terminal ileitis)

Drug history
Drug allergies
Recent ingestion of NSAIDs, warfarin, aspirin, heparin, steroids, TCM

Social history
Alcoholic drinker
Dietary habits

Family history

142
Physical examination
General condition
- pallor
- jaundice  haemolytic anaemia
- nutritional status  cachexic
- chipmunk facies, frontal bossing  thalassemia
- receiving any transfusions  indicates severity
- hypotensive, sweaty  hypovolemic shock
- postural BP (indicates severity)

Hands
- koilonychia (spooning) and brittle nails  iron deficiency
- clubbing  infective endocarditis
- tachycardia

Eyes
- conjunctival pallor
- scleral icterus  haemolytic or pernicious anaemia (due to ineffective erythropoiesis)
- retinal haemorrhages

Mouth
- glossitis, small and smooth tongue  vit B12 deficiency
- angular stomatitis  severe malnutrition, iron deficiency
- oral ulcers  neutropenia

Others
- LN (neck, axilla, inguinal)  metastases, lymphoproliferative disorders, haematological malignancy
- skin  bruising (BM suppression, leukaemia, aplastic anaemia)
- chest scars  artificial heart valves
- CVS  tachycardia, bounding pulse, systolic flow murmur at the apex (hyperdynamic circulation)
- abdomen  splenomegaly (infection, haemolytic anaemia, hypersplenism, haematological malignancy); other masses
(malignancy)
- PR  haemorrhoids
Colorectal cancer

Investigations for MCHC or NCNC anaemia

 FBC
 Hb
 MCV and MCHC
 WBC and platelets (may suggest haematological pathology)
 Reticulocyte count = ↑ in acute blood loss and haemolysis
↓ in iron deficiency
If suspect haemolysis = haptoglobin (↓), LDH (↑), indirect bilirubin (↑), direct Coombs’ test (+ve in AIHA)
Cold agglutinins
Anti ds-DNA, ANA
Osmotic fragility test (not usually done now)
Enzyme assay
Flow cytometry (PNH)

 Peripheral blood film

 Spherocytes
 Teardrop cells = myelofibrosis
 Basophils and eosinophils = myeloproliferative disorders
 Target cells = post-splenectomy, thalassemia, iron deficiency
 Golf-ball inclusion bodies = HbH disease
 Sickle cells = sickle cell anaemia
 Iron studies
 Low serum iron, low serum ferritin, high TIBC = iron deficiency ((serum iron TIBC) <15% )

143
  Low serum iron, high serum ferritin, low TIBC = anaemia of chronic disease (ferritin
is acute phase reactant, raised in
inflammation)

Interpreting plasma iron studies

Iron TIBC Ferritin
Fe deficiency ↓ ↑ ↓
Anaemia of chronic dz ↓ ↓ ↑
Chronic haemolysis ↑ ↓ ↑
Haemchromatosis ↑ ↓/N ↑
pregnancy ↑ ↑ N
Sideroblastic anaemia ↑ N ↑

 Hb electrophoresis
 ↑ HbA2 = -thalassemia
 Normal HbA2 = -thalassemia (requires gene probe)
 U/E/Cr (chronic renal failure)
 ESR/CRP
 GXM (in case patient requires blood transfusion)
 Stool OB x 3
 OGD KIV colonoscopy  if patient refuses = barium meal and enema
 Bone marrow aspirate and trephine (latter can be done when aspiration gives a ‘dry tap’)

Investigations for macrocytic anaemia

 FBC
 Hb
 MCV
 WBC and platelets (may suggest haematological pathology)
 Reticulocyte count
 ↑ in compensatory reticulocytosis (reticulocytes are larger than RBC)
 Look out for reactive thrombocytosis as well
 Peripheral blood film
 Hypersegmented neutrophils (> 5 lobes) = most common cause is CRF  megaloblastic anaemia
 Serum Vit B12 and folate
 Pernicious anaemia screen = anti parietal Ab, anti-IF Ab
Schilling test (+ve)
 Thyroid function test
 Liver function test
 Bone marrow aspirate and trephine

Indications for transfusion

 Acute blood loss > 20% total blood volume (normal = 70ml/kg)
 Hct < 30% & risk of ischemia (IHD, CVA); symptomatic anaemia
 Hb < 7g/dL

144
  RBC lose membrane fragments after release into peripheral circulation but retain
Haemolytic anaemia most of their volume  decreased SA:VR  assume spherical shape to maintain
maximum stability
General concepts  Spherical shape and reduced plasticity  great difficulty leaving splenic cords 
 Characteristic features sequestered  phagocytosis
- increased rate of RBC destruction
- compensatory increase in erythropoiesis  reticulocytosis Morphology
- extramedullary haematopoiesis  Peripheral blood film
- retention of iron - RBC lack centrol zone of pallor
- reticulocytosis
Pathogenesis
 Intravascular haemolysis Clinical features
- causes = (a) mechanical trauma  History
(b) complement fixation - asymptomatic
- results in = haemoglobinemia and haemoglobinuria - symptoms of anaemia
Haemosiderinuria  Physical examination
Low serum haptoglobin - pallor
- complications = raised unconjugated bilirubin  jaundice - jaundice
ATN - splenomegaly (more so than any other form of haemolytic anaemia)
 Extravascular haemolysis (more common)
- occurs within cells of reticuloendothelial system Complications
- injured or immunologically altered RBC have reduced deformability  difficult  Splenomegaly
passage through splenic sinusoids (requires extreme alterations of shape)   Systemic haemosiderosis
splenic sequestration of RBC  phagocytosis  Cholelithiasis (extravascular haemolysis)
- NORMAL haptoglobin (because haemoglobin is not released into the circulation,  Aplastic crises
so haptoglobin is not consumed – contrast w/ intravascular) - transient cessation of RBC production triggered by parvovirus infections
- complications = formation of bilirubin-rich pigment stones  gallstones; - self-limiting in most cases
splenomegaly - may require blood transfusions

Hereditary spherocytosis Investigations

 Peripheral blood film
Inheritance  Increased osmotic fragility
 congenital  1%; acquired (AIHA)  99%
 autosomal dominant form most common and less severe Management
 25% have autosomal recessive form which is much more severe  No treatment available
 Splenectomy beneficial  remove major site of destruction
Pathogenesis Glucose-6-phosphate Dehydrogenase deficiency
 Mutations disrupt interactions between spectrin and other intrinsic proteins 
results in reduced membrane stability Inheritance
 X-linked recessive
145
 - affected males more vulnerable to oxidant injury
- carrier females are asymptomatic except those with high proportion of enzyme-
deficient RBC (due to unfavourable lynonisation)
Pathogenesis
 Intracellular reduced glutathione (GSH) inactivates oxidants normally
 Enzymatic abnormalities reduce ability of RBC to protect themselves from
oxidative injury
 Sources of oxidative stress
(a) Drugs = anti-malarials
Sulphonamides
Nitrofuratoin Morphology
(b) Toxins
(c) Infections (trigger release of toxic radicals from phagocytes)
 Asymptomatic unless patient exposed to oxidative stress
 Effects of oxidative stress
- oxidation of GSH to oxidized glutathione (GSSG) through H2O2 production Clinical features
- G6PD-deficient cells unable to regenerate GSH
- accumulation of H2O2 denatures globin chains
- denatured Hb precipitated within RBC  Heinz bodies
 Causes of haemolysis
- Heinz bodies damage cell membrane and causes intravascular haemolysis
- RBC membrane less deformable + splenic phagocytes attempt to ‘pluck’ out Investigations
inclusions to form ‘bite’ cells  extravascular haemolysis
Morphology
 Peripheral blood film
- RBC contain Heinz bodies (revealed by special staining)
- ‘bite’ cells
Immunohaemolytic anaemias
 Classification (based on nature of antibody)
(a) Warm antibody type (eg lymphoma, CLL, SLE, drugs)
 IgG produced
 Binds to RBC at 37°C
 Causes opsonisation  phagocytosis by splenic macrophages
(b) Cold antibody type (eg EBV, mycoplasma, Hep C)
 IgM produced
 Binds to RBCs at T< 30°C
 Fixation of complement  coats RBC with complement  weakly
bound IgM released  RBC left with coating of C3b  phagocytosis
 Peripheral blood film
- spherocytes = parts of cell membrane removed during attempted phagocytosis
of antibody-coated cells, therefore ↓ SA:VR
 History
- severity quite variable = most have chronic mild anaemia
 Physical examination
- splenomegaly
 Direct Coombs test
- antibodies raised in sheep targeted against human anti-RBC Ig
- positive result = RBC agglutination upon adding sheep antibodies
 Indirect Coombs test
- normal RBC incubated with patient’s serum
- direct Coombs test performed
- positive result indicates presence of anti-RBC immunoglobulins in
patient’s serum

Pathogenesis Management
 Antibody formation which react against normal or altered RBC membranes No treatment required
 Causes
(a) Idiopathic Anaemia due to trauma of RBC
(b) Drugs = methyldopa, ponstan, penicillin, quinidine
(c) Autoimmune = SLE, RA Pathogenesis
(d) Infection = mycoplasma  Cardiac valve prostheses
(e) Malignancy = B-cell lymphoma (esp in males)
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 - damaged by shear stresses from turbulent blood flow and abnormal pressure
gradients caused by valves
 Microangiopathic haemolytic anaemia
- narrowing/partial obstruction of vasculature results in mechanical damage
- causes = DIVC
Malignant hypertension
SLE
Haemolytic-uraemic syndrome

Post-splenectomy blood film

Morphology
 Target cells
 Acanthocytosis = speculated RBC
 Howell-Jolly bodies – nuclear remnants

- defective RBC seen as spleen has been removed (normally removes these)
- IBD, celiac disease and sickle cell disease can cause “medical” splenectomy due
to repeated splenic infarct

147
 - low serum iron
Diminished Erythropoiesis - low serum ferritin
- high TIBC
Iron Deficiency Anaemia
Management
Epidemiology  Iron-rich diet = liver, beans, red meat, poultry, fish
 Most common form of nutritional deficiency  Iron supplements
 Treat underlying cause
Normal iron storage and metabolism
Iron storage Anaemia of chronic disease
 Approximately 80% of functional body iron found in Hb
 Remainder found in myoglobin and iron-containing enzymes Pathogenesis
 Stored iron found in liver, spleen, bone marrow and skeletal muscle  Inflammation-induced iron sequestration within cells of reticulo-endothelial
 Serum ferritin good indicator of iron stores (also an acute phase reactant) system
 Iron transported in plasma by transferrin (iron-binding protein)  Transfer of iron from mononuclear phagocyte storage pool to erythroid
precursors hindered
Iron metabolism  Inadequate compensatory rise in erythropoietin
 No regulated pathway for excretion  limited to shedding of epithelial cells
 Iron balance maintained largely by regulating iron absorption in duodenum Investigations
 Absorption is increased in iron deficiency  FBC
- normocytic normochromic anaemia
Causes - microcytic hypochromic anaemia
(a) Decreased intake  Peripheral blood film
- vegans  Iron studies
rd - low serum iron
- malnutrition (3 world countries)
(b) Decreased absorption - high ferritin
- celiac disease - low TIBC
- post-gastrectomy (achlorhydria)  U/E/Cr
(c) Increased demand  ESR/CRP
- pregnancy
(d) Chronic blood loss (most common cause) Management
- BGIT = PUD, CRC, Haemorrhoids, parasites  Treat underlying cause
- menorrhagia  CRF/ESRF  erythropoietin

Investigations Aplastic anaemia

 FBC
- microcytic hypochromic anaemia Pathogenesis
- Mentzer index = MCV/RBC (< 13  thalassemia; > 13  iron deficiency)  Pancytopenia = anaemia, leucopenia, thrombocytopenia
 Peripheral blood film  Causes
 Iron studies (a) Primary (> 50% idiopathic)
148
 (b) Secondary - misshapen and immature RBCs  teardrop shaped
- Fanconi’s anaemia (autosomal recessive) - immature erythrocytic and granulocytic precursors
- radiation  Bone marrow biopsy
- drugs = chemotherapy agents, TCM, benzene, chloramphenicol, - replaced by neoplastic or inflammatory elements
carbimazole
- virus = parvovirus B19, EBV, HIV Management
- autoimmune = SLE - treat underlying cause

Morphology Sideroblastic Anaemia

 Peripheral blood film Pathogenesis
- normocytic normochromic  Abnormal RBC production as part of myelodysplastic syndrome
- reticulocytes ABSENT  Failure to completely form heme  deposits of iron in mitochondria that form
 Bone marrow biopsy a ring around nucleus of developing RBC
- hypocellular (> 90% of intertrabecular space occupied by fat)  Causes
(a) Congenital = X-linked ALA synthase deficiency
Clinical features (b) Drugs = ethanol, isoniazid, chloramphenicol
 History (c) Toxin = lead, zinc
- features of anaemia = weakness, pallor, dyspnoea (d) Nutritional = pyridoxine or copper deficiency
- features of leucopenia = frequent and persistent minor infections  Complications = haemosiderosis (endocrine, liver and cardiac damage)
- features of thrombocytopenia = petechiae and ecchymoses
 Physical examination Investigations
- splenomegaly ABSENT  FBC
- low Hb
Management - normocytic, microcytic or macrocytic
 Withdrawal of toxic drugs  Peripheral blood film
 Immunosuppression therapy (directed against T cells) - Perl’s stain = ringed sideroblasts
- cyclosporin A  Iron studies
- antithymocyte globulin - high serum iron
 Bone marrow transplantation - high serum ferritin
- low TIBC

Myelophthisic anaemia

Pathogenesis
 Extensive replacement of BM by fibrosis and tumours (primary or mets from
thyroid, breast, lung or prostate)

Morphology
 Peripheral blood film

149
 # Schilling test = helps identify the cause (absorption? Lack of IF?)
Macrocytic Anaemia Compares proportion of oral dose of radioactive vit B12 excreted in urine with/without
concurrent administration of IF (supersaturate blood first with IM Vit B12)
Definition
 Megaloblastic anaemia Vitamin B12 deficiency
- MCV > 110fL  Metabolism
- causes = vit B12 deficiency - found in liver and all animal products
Folate deficiency - body stores sufficient for 3yrs
 Non-megaloblastic anaemia - site of secretion  gastric parietal cells
- MCV 100-110fL - IF binds with vit B12  IF-vit B12 complex carried to terminal ileum  binds to
- causes = compensatory reticulocytosis (active blood loss, haemolysis) IF-receptor on luminal surface of ileal cells  absorbed
Alcohol intake  Aetiology
Chronic liver disease (a) Diet = vegans, alcoholism
Hypothyroidism (b) Impaired absorption from stomach = pernicious anaemia
Myelodysplastic syndrome Gastrectomy (lack of IF
production, achlorhydia)
# megaloblast = a cell in which cytoplasmic and nuclear maturation are out of phase due Chronic gastritis
to slow nuclear maturation (c) Impaired absorption from small bowel = Crohn’s disease
Celiac disease
Investigations (d) Impaired absorption from pancreas = chronic pancreatitis
 FBC  Clinical presentation
- Hb (a) Anaemia
- MCV (b) Tingling distal parasthesiae (peripheral neuropathy)
- WBC and platelets (megaloblastic anaemia presents as pancytopenia (c) Dementia
rather than isolated anaemia)  Should consider vit B12 deficiency as a differential in all spinal cord, peripheral
 Reticulocyte count nerve and neuropsychiatric disorders
- ↑ in compensatory reticulocytosis (reticulocytes are larger than RBC)  Tx = Vit B12 rich diet (meat, liver, seafood, dairy products)
- look out for reactive thrombocytosis as well IM Vit B12 injection 1mg x 3/7  every 3 months
 Peripheral blood film - avoid giving PCT before replacing Vit B12  may worsen neurological
- ovalocytes and hypersegmented neutrophils (> 5 lobes) = megaloblastic manifestations and ppt heart failure
- target cells = chronic liver disease - variable response = improve, remain unchanged, deteriorate
- polychromiasia +/- spherocytes = haemolytic anaemia - sensory improve > motor
- varying degrees of poikilocytosis = myelodysplastic syndrome Peripheral neuropathy > myelopathy
 Serum vitamin B12 and folate Folate deficiency
 Pernicious anaemia screen = anti-parietal Ab, anti-IF Ab, Schilling test (+ve)
 Thyroid function test  Metabolism
 Liver function test - found in green vegetables, fruits and liver
 Bone marrow aspirate and trephine - synthesized by gut bacteria
- indication = no definite cause found with above tests - body stores sufficient for 3 months
 Aetiology
150
 (a) Diet = alcoholics
(b) Malabsorption = celiac disease, drugs (methotrexate, phenytoin, TMP)
(c) Increased demand = pregnancy, haemolysis, malignancy
 RBC folate may be more reliable than serum folate (spuriously normal/raised  Fundus/body = IF and acid-secreting gastric parietal cells
after folate-rich diet) Pepsinogen-secreting zymogenic cells
 Tx = folate-rich diet (asparagus, broccoli, spinach, lettuce, fruits) Antrum = gastric-secreting G cells
Folate supplements  Progression from type A CAG  gastric atrophy  clinical anaemia spans
20-30 yrs (pathology can be reversed by treatment with steroids/AZP)
Pernicious anaemia
 Epidemiology  Clinical presentation
- most common cause of vit B12 deficiency  Pancytopenia = anaemia, leucopenia and thrombocytopenia
- median age of diagnosis = 60years  GIT = atrophic glossitis (smooth and beefy red tongue), diarrhoea
- females > males  Retinal haemorrhages
- strong family history  CNS = subacute combined degeneration of the cord
- associated with blood group A Peripheral neuropathy
 Incidence of gastric adenocarcinoma and carcinoid tumour 3 and 13 times higher Mild personality defects, memory loss, dementia, frank
respectively than that in general population, therefore low threshold for OGD psychosis
 Associated with other autoimmune disorders
o Thyroid disease (Graves’, Hashimoto’s)  Childhood pernicious anaemia = not a/w CAG or achlorhydria; genetic failure to
o Vitiligo secrete IF or secretion of defective IF
o Addison’s disease
o Type 1 DM
o Primary hypoparathyroidism
o LEMS
o Myasthenia gravis
 IF antibodies
- seen in 50% of patients with pernicious anaemia
- type 1  prevents vit B12 from binding to IF
Type 2  reacts with IF or IF-Vit B12 complex
 Pathophysiology
 Affects all cells in body  thymidine and DNA synthesis affected
 Major organs affected (high cell turnover) = bone marrow, GIT

Type A Affects fundus, body but Pernicious anaemia

(autoimmune)
not antrum
Chronic atrophic gastritis
(loss of gastric mucosal
folds and thinning of
gastric mucosa) Affects fundus, body and H. pylori gastritis
Type B 151
(non-autoimmune) antrum
Thrombocytopenia

1. distributional = congestive splenomegaly

2. Dilutional = aggressive hydration
PCT transfusion
3. Pseudo-thrombocytopenia = inadeq Platelet count < 140 x 109
coagulation, EDTA-induced plt clumping Thrombocytopenia

↓ed production ↑ed destruction ↓ed function

 Bone marrow suppression/failure  Immune-mediated  Uraemia
o Congenital = Fanconi anaemia, TAR o Autoimmune  Von Willebrand disease
syndrome o Drug-induced (heparin, quinine, valproate)  Anti-platelet agents
o Aplastic anaemia = o Infective  Glanzmann disease
 Autoimmune o Idiopathic (ITP)
 Infective (HIV/EBV)
 Drug-induced  Infection
 Toxin/chemicals o Malaria
 Idiopathic o Dengue
o Malignant infiltration o HIV
 Primary o EBV, CMV, VZV, parvovirus
 Secondary
 Mechanical trauma
 Decreased DNA synthesis o MAHA (TTP, HUS, DIVC)
o Vitamin B12 deficiency
o Folate deficiency  Hypersplenism
o Portal hypertension

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History taking Retro orbital headache, myalgia, arthralgia, fever
(dengue)
Name/age/race/gender/occupation Recent travel history (malaria)
Past medical history  Metabolic = dietary history
Drug allergy Liver disease (Hep B/C (Hx of transfusion?),
Date of admission jaundice, abdominal
distension, LL edema)
Presenting complaint 4. Management
1. Petechial rash 5. Systemic review
 Acute/gradual onset 6. Past medical history
 Duration 7. Drug history
 Distribution = generalized 8. Social history
Localized  history of trauma; appeared immediately  Alcoholism
 Areas of purpura/ecchymoses 9. Family history
2. Bleeding tendencies  Bleeding disorders
 Easy bruisability = immediately after trauma  Autoimmune disorders
 Prolonged bleeding
 Epistaxis BLEEDING DISORDERS
 Gum bleeding Clinical features CLOTTING FACTOR
 Haematuria PLATELET defect
deficiency
 Menorrhagia
Skin, mucous membranes
 Haemetemesis/ haematochezia/melena Site of bleeding (gingivae, nares, GI and
Deep in soft tissues
 Joint swelling  rule out haemarthrosis (coagulation disorders) genitourinary tract)
(joints, muscles)
3. Aetiology
Bleeding after minor cuts Yes Not usually
 Congenital = previous bleeding tendencies?
Problems with tooth extractions or immunizations Petechiae Present Absent
 Acquired Ecchymoses Small, superficial Large, palpable
 BM involvement = symptoms of anaemia Haemarthroses, muscle
↑ed susceptibility to infection Rare Common
haematomas
LOA, LOW, night sweats, fever, fatigue (B
Bleeding after surgery Immediate, mild Delayed, severe
symptoms)
Enlarged lumps on body
 Drugs = history of chemotherapy/radiotherapy
Antiplatelet agents (aspirin, NSAIDS, Glycoprotein
IIB/IIIA inhibitors.
Steroids, quinine, valproate, heparin, TCM)
 Autoimmune = history of SLE
Rash, joint pain and swelling
 Infections = recent URTI (CMV, EBV)

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Physical examination Atypical presentation

 Petechial rash = use ruler to test if it is blanchable Cytology/Histology Diagnosis

Should not be palpable  vasculitis Normal to ↑ numbers of megakaryocytes Increased peripheral destruction of
 General inspection = pallor plts
Cachexia ↓↓megakaryocytes, overall ↓/absent cellularity ↓BM production (eg Aplastic
Jaundice (MAHA) anaemia)
 UL = stigmata of chronic liver disease Hypercellular marrow, megaloblastic changes in Vitamin B12, folate deficiency
 Head & neck = conjunctival pallor red cell and granulocytic series
Sclera icterus Hypercellular marrow Myelodysplastic disorder
Buccal & gingival bleeding Dysplastic changes in red cell, granulocytic,
 Abdomen = hepatosplenomegaly (haematological malignancy) megakaryocytic lineages
Signs of portal HTN Presence of granulomata, increased reticulin, Marrow invasion: granulomatous infx
 Generalized lymphadenopathy collagen fibrosis (TB), fibrosis, tumour
Infiltration with malignant cells
If in paediatrics = haemangioma Overall BM cellularity normal. Normal ITP
Skeletal (TAR syndrome) erythropoiesis and myelopoiesis
Megakaryocytes normal/ ↑ in number
Request:
 Fundoscopy (raised ICP)
 FOBT (BGIT)
 Vitals

Investigations

1. FBC = platelet ↓ (thrombocytopenia)

Hb Platelet clumping (satellitism) = EDTA-induced clumping
Normal in ITP
WBC Inadequate coagulation

2. PBF = platelet morphology Circulating blast cells

Involvement of cell lines
Macrocytic RBC, hypersegmented neutrophils = Vit B12/folate
3. PT/PTT – rule out coagulation defects deficient
4. Infective = dengue screen
HIV screen (HIV ELISA) Fragmented RBC = MAHA
Liver cirrhosis = LFT, Hep B serology DIVC
Autoimmune = ANA, anti-dsDNA

5. BM aspirate/trephine
 Indications = refractory to treatment
154
Idiopathic Thrombocytopenic Purpura (ITP)
Introduction

 Common acquired bleeding disorder

 Diagnosis of exclusion
 Paediatric patients: 2-10 years of age, boys>girls
 Adult patients: 30-40 years of age, females>males
 Pathogenesis: anti-platelet Ab directed against platelet membrane glycoproteins, antibody-coated
platelets have shortened t1/2 - accelerated clearance by tissue macrophages
Clinical presentation

 Bleeding disorder
 Antecedent viral illness
 No systemic symptoms
 P/E = no LAD, no palpable spleen/liver
Investigations

 FBC = PH↓, Hb and WBC normal

 PBF = RBC normal, plt number ↓ but bigger in size
 Bone marrow = megakaryocytes ↑
Diagnosis

 Satisfy 2 criteria
o Isolated thrombocytopenia
o No clinically apparent associated conditions
Management

 Aim: safe platelets count to prevent major bleeds

 Mild, asymptomatic = monitor only
 Moderate to severe thrombocytopenia with bleeding:
o Corticosteroids = PO prednisolone 1mg/kg/day, IV hydrocortisone 100mg q 6hrly (response
seen within 2 weeks)
o Chronic management = steroids, immunosuppressants (AZP, CSA, cyclophosphamide),
splenectomy (after 2 relapses; vaccinate first)  50-60% go into remission
 Severe bleeds = platelet transfusion
o IV pulse methylprednisolone
o IVIg (expensive; ↑platelet within several days but ↓ within 2-3 weeks)

Prognosis

 Spontaneous remission rare (compared with children) usually treat in adults

 Usually becomes chronic ITP (>6 weeks)

155
Leukemias
Pathophysiology
 Acute leukemia:
o Aggressive and malignant transformation of haemopoietic stem cells
o Can present within weeks
o Possible cure
o Defined as bone marrow having >/= 30% blasts
 Chronic leukaemia:
o Presents within several months
o Cure is difficult
 Results in:
o Increased proliferation (clonal expansion)
o Reduced apoptosis
o Block in cellular differentiation
o And eventually, the accumulation of blast cells suppressed normal haematopoietic stem cells

Predisposing factors
 Genetic defects (Down’s syndrome, Fanconi anaemia)
 Oncogenes
 Radiation
 Cytotoxic drugs (nitrogen mustard)
 Chemicals (benzene)
 Viral infections (EBV, HTLV, HIV)

Complications
 Bone marrow failure: anemia, leucopenia, thrombocytopenia
 Peripheral WBC:
o Leucopenia occurs first because there is no capacity to generate WBC
o Leukocytosis occus later as there is a release of blast cells  Hyperviscosity syndrome
 Organ infiltration: skin, lymph nodes, spleen, liver, CNS, testes
 Increased cell turnover  hyperuricaemia  gout and renal failure

Investigations
Confirm diagnosis
1. FBc
2. PBF
3. Bone marrow study (aspirate/trephine)
 BM aspirate:
o cells aspirated and spread on slide (takes 1-2 hours)
o Cell morphology
o Cytochemical staining (if diagnosis is in doubt, allow subtype identification)
 BM trephine:
o Requires fixation in formalin (1-7 days)
o Canot see individual cell detail
o Can see marrow cellularity, overall architecture and fibrosis
4. Cytogenetics
 Diagnosis
 Prognostication
 Detection of minimal residual disease
5. Flow cytometry/immunophenotyping

Assess complications
1. U/E/Cr: renal impairment
2. Serum uric acid : hyperuricaemia
3. Serum phosphate: raised
4. PT/PTT: DIVC (esp AML M3)
5. CT head: CNS involvement
6. CT thorax: mediastinal involvement and enlarged thymus ( T cell ALL)

156
Assess fitness for treatment
1. U/E/Cr
2. LFT

ACUTE LYMPHOBLASTIC LEUKEMIA

Epidemiology
 Most common childhood malignancy (makes up 80%)
 2/3 occur in children; 1/3 occurs in adults
 Pead incidenct: 3-7 years old

Clinical features
 Abrupt and aggressive onset
 Bone marrow suppression:
o Anaemia (pallor, exertional chest pain/ SOB, giddiness, palpitations, fatigue)
o Leucopenia (increased susceptibility to infections)
o Thrombocytopenia (petechial rash, bleeding disorders)
 Peripheral WBC
o Hyperviscosity syndrome (focal neurological deficit, sudden loss of vision)
 Organ infiltration:
o Body lumps (generalized LAC)
o Abdominal discomfort and distension ( hepatosplenomegaly)
o Bone/back pain (marrow expansion/infiltration)
o CNS (headache, vomiting, nerve palsies  more common in ALL)
o Testicular swelling
 Constitutional symptoms: LOA, LOW, night sweats

Treatment
 Supportive
o Treatment of anemia: PCT
o Prophylaxis and treatment of infections
 Isolation, prophylactic antibiotics, surveillance
 Cultures/CXR
o Prophylaxis and treatment of haemorrhage
 Platelet transfusion, PCT, FFP
 Specific
o Aim: to reduce population of blast cells to allow reconstitution of remaining normal stem cells
st nd
o Takes 2 years: 1 year intensive, 2 year maintenance
o Principle: induction  consolidation  CNS maintenance arm  maintenance
 Induction
- Rapidly kill tumour cells to get patient into remission
- Remission is defined as <5% blasts in bone marrow + normal cell counts
 Consolidation:
- High dose multi dug chemotherapy used to reduce/eliminate tumour
 CNS maintenance arm:
- High levels of relapses in CNS
 Maintenance:
- Daily oral mercaptopurine/methotrexate for a few years
o Stem cell transplant (autologous/ allogenic/ matched unrelated donor)

Prognosis
 High success rates: >90%
 Prognostic factors
o 2-10 years old
o Precursor B cell tumours
o No Philadelphia chromosome translocation
o Females
o Lower leukocyte count at presentation

157
ACUTE MYELOID LEUKEMIA
Epidemiology
 2/3 occur in adults; 1/3 occur in children
 Primary AML: arises de novo
 Secondary AML: myelodysplasia, myeloproliferative disease

Management
 Supportive
o Treatment of anemia: PCT
o Prophylaxis and treatment of infections
 Isolation, prophylactic antibiotics, surveillance
 Cultures/CXR
o Prophylaxis and treatment of haemorrhage
 Platelet transfusion, PCT, FFP
 Specific
o Aim: to reduce population of blast cells to allow reconstitution of remaining normal stem cells
o Takes 6 months
o Principle: induction  consolidation
o Stem cell transplant (autologous/ allogenic/ matched unrelated donor)

Morphological differences
 ALL:
o Stains with PAS,
o Nucleoli are fewer and less prominent, no cytoplasmic granules, coarse clumped chromatin
 AML
o Stains with myeloperoxidase
o Prominent multiple nucleoli, cytoplasmic granules, red Auer rods, finer chromatin

CHRONIC MYELOID LEUKAEMIA

Epidemiology
 Usually affects middle-aged adults (40-60 years old)

Pathophysiology
 Philadelphia (Ph) chromosome translocation
o Chr 22  9 translocation  proto-oncogene c-ABL on Chr 9 moved to BCR gene on Chr 22
o BCR-ABL chimeric gene encodes fusion protein with dysregulated tyrosine kinase activity
o Highly characteristic of CML but can also occur in adult ALL
o Worse prognosis if without Ph translocation
 No block in maturation of leukaemic stem cells in CML (cf. AML)

Clinical features/ course

 Slow and gradual onset
 Similar symptoms to acute leukaemias
 MASSIVE splenomegaly
 Blast crisis – accelerated phase where there is failure of response to treatment, worsening anaemia/thrombocytopenia
and transformation into AML.

Treatment
 Chronic phase
o Gleevac (tyrosine kinase inhibitor)  excellent response
o Stem cell transplant  patients who fail Gleevac
o Allopurinol  gout

Prognosis
 Mortality
o Blast crisis
o Intercurrent infections

158
Hodgkin’s Lymphoma
Distinguishing features:
Caused by EBV infection
Reed Stemberg cells
- mirror-image nuclei
- admixed with variable reactive backgrounds (first 2 have good prognoses)
1. nodular sclerosis
2. mixed cellularity
3. lymphocyte-rich
4. lymphocyte-depleted
Arise from single lymph nodes OR chain of nodes  spreads to anatomically contiguous nodes
B symptoms = fever, night sweats, LOW (>10kg over 6 months)
Not as aggressive as Non-Hodgkin’s Lympoma (NHL)

Clinical Presentation:
History
- 2 peaks of incidence  young adults, elderly
- males > females
- enlarged painless nodules of rubbery consistency
- B symptoms
Physical examination
- cachexia
- anaemia
- hepatosplenomegaly Long term survivors at increased risk for:
- generalised lymphadenopathy - breast cancer
- lung cancer
Investigations:
- NHL
Diagnosis
1. FBC = NCNC anaemia - myelodysplasia
WBC variable - acute myeloid laukaemia (AML)
2. PBF
3. Lymph node biopsy
4. Bone marrow aspirate/trephine
Assess severity and complications
1. ESR
2. U/E/Cr
3. Serum uric acid
4. Serum phosphate
Assess spread
1. CT thorax/abdomen/pelvis
Staging:
Ann Arbor Classification
Stage Distribution of disease
I Confined to single lymph node region
II Involvement of 2 or more lymph nodes on same side of diaphragm
III Involvement of nodes on both sides of diaphragm
IV Spread beyond lymph nodes
Further divided into absence (A) or presence (B) of one or more B symptoms
Prognosis:
Clinical staging is the most important prognostic factor
Good prognosis = Stage IA and stage IIA have almost 100% 5-year survival rates
Stage IV has 50% 5-year survival rates

159
Myeloproliferative Disorders
Suspect this when peripheral blood film (PBF) shows basophils and eosinophils

4 diagnostic entities:
 Predominantly RBC  Polycythaemia rubra vera
Hb >20.0
WBC >12,000
Plt >600

 Predominantly WBC  Chronic myeloid leukaemia

Hb 10.0 (N)
WBC >22,000 Neutrophils 50%
Blasts 1% (therefore not acute leukaemia)
Plt >600

 Predominantly platelets  Essential thrombocytosis

Hb >14.0
WBC >15,000
Plt >1300

 No predominant cell types  myelofibrosis (elderly patient, tear drop sign)

Hb 12
WBC >15,000
Plt >700

Myelodysplasia

1. Bone marrow  normo/hypo-cellular

FBC  pancytopaenia
non-megaloblastic macrocytic anaemia

2. Increased risk of transformation to AML because genetically unstable

3. Poor response to chemotherapy

160
Multiple Myeloma
Pathology
Malignant B-cel lymphoproliferative disorder of bone marrow
- Clonal proliferation of plasma cells (IgG)
Results In monoclonal immunoglobulin band (m component)
- Differentials: Malignant – multiple myeloma, lymphoma, leukaemia, amyloidosis
Benign – monoclonal gammopathy of undetermined significance
Secretes cytokines that enhance osteoclastic activity, hence increasing bone resorption
- Resulting in: osteoporosis
discrete lytic lesions throughout skeleton (myelomatosis)
- Compression fracture
* osteoporosis
* multiple myeloma
* metastasis to bone

Clinical Presentation
Epidemiology: 45-65 years old
no gender predilection
Pathological fracture with history of chronic back pain
Constitutional symptoms: fever, LOW, LOA, fatigue, symptoms of anaemia, thrombocytopaenia and leukaemia
Complications:
(a) bone marrow suppression
(b) hypercalcaemia symptoms: polyuria, polydipsia, increased thirst, stones, moans, groans
(c) renal impairment (nephrocalcinosis, ureteric stones, light chain excretion, amyloidosis)
(d) gout
(e) hyperviscosity syndrome

Investigations
FBC: NCNC anaemia, low pH, low WBC count
ESR: raised
PBF: Rouleaux formation due to high ESR
LFT: total protein, albumin
U/E/Cr: renal impairment
Serum calcium: hypercalcaemia
Serum β2-microglobulin: useful prognostic indicator
Serum uric acid: raised
Serum/urine protein electrophoresis
Urine Bence Jones proteins (precipitate at 60°C, dissolve at 90°C) = prognostic
Skeletal survey: osteoporosis, discrete lytic lesions, pepper-pot skull
Bone marrow biopsy: increased plasma cell (>20%)

Diagnosis
Depends on principle findings: monoclonal proteins in serum/urine
increased plasma cells in bone marrow
related organ/tissue damage (renal failure, lytic bone lesion, anaemia,
hypercalcaemia)

Treatment
Supportive: adequate analgesia
treat pathological fracture (internal fixation)
treat hypercalcaemia (reduce calcium intake, increase hydration, bisphosphonates)
treat gout (allopurinol)
treat anaemia and infections
Specific: chemotherapy
stem cell transplant

161
Coagulation disorders
Extrinsic coagulation cascade:

 7  10  5 2

 Factor 7 measured by PT

Intrinsic coagulation cascade:

 12  11  9 8 10  5 2

 Factors 12 and 11 rare in causing bleeding tendencies

 Factors 12, 11, 9 and 8 are measured by aPTT

Common pathway

 Factors 10, 5 and 2 are reflected by both PT and aPTT

Monitoring warfarin therapy: PT/INR

Monitoring unfractionated heparin therapy: aPTT

*no need to monitor LMW hepatin unless severly obese or patient has poor renal function
- advantages: wider therapeutic index, less pharmacodynamic variability and no need to monitor aPTT.

162
Oncologic emergencies

1. Hypercalcemia
 Defined as corrected calcium > 2.75 mmol/L
 Causes:
o Metastasis to bone
o Myeloma
o Non small cell lung cancer
o (primary hyperparathyroidism)
 Management
o Stabilize patient
 Assess airway
 Supplemental O2, monitor SpO2
 ECG: cardiac arrhythmias (short OT interval)
 Create IV access
o IV fluid hydration (4-6L)
 Ensure food cardiac function first
o IV diuretics (Lasix  Avoid _______)
o Monitor I/O, vitals, ECG and Calcium
o If ARF, dialysis is definitive treatment
 Can start patient on bisphosphonates after acute setting
o Slow onset (5-7 days)
o Contraindicated in ARF.
2. Tumour lysis syndrome
 2 conditions to be fulfilled
o High tumour burden (e.g in acute leukemias, small cell lung cancer, germ cell tumours, lymphomas)
o Highly sensitive to chemotherapy
 Results in
o Hyperuricaemia  obstructive uropathy, renal failure
o Hyperkalaemia  cardiac arrhythmias
o Hyperphosphataemia  may exacerbate renal failure
o Metabolic acidosis  cardiac arrhythmias
o Hypocalcaemia  cardiac arrhythmias
 Management
o Stabilize patient
o IV hyperhydration
o Correct electrolyte abnormalities
 Clinical manifestations
o CNS
o pulmonary

163
Deep Vein Thrombosis
History
Name/age/race/gender/occupation
Past medical history
Drug allergy
Date of admission

Presenting complaint
1. Symptoms
a. Unilateral swollen leg
 Onset (acute/gradual)
 Duration
 Pain
 Increasing warmth
 Incrasing erythema
 Progression since day 1
b. Fever
c. Chest pain, dyspnoea, haemoptysis
d. Lower limb numbness and weakness (implies severe obstruction impeding arterial inflow as well)
2. Aetiology
a. History of trauma
b. Endothelial damage = history of recent surgery (< 4 weeks)
c. Venous stasis = prolonged immobilization, recent long-haul flight
d. Coagulopathy =
 LOW, LOW, fatigue, PR bleeding, change in bowel habits, PMB, IMB
 Use of OCP/HRT
 Rash, joint pain or swelling, history of SLE, recurrent miscarriages
3. Management
4. Has this happened before? Describe previous episodes

Past Medical History

 CVA, AMI, TIA
 PUD = Contraindication to thrombolysis
 Prior hospitalisations and surgeries

Drug History

Social History
 Smoking

Family history

Risk factors: Virchow’s triad

COAGULOPATHY VENOUS STASIS ENDOTHELIAL DAMAGE

1. Malignancy 1. Age > 65 1. Trauma
2. Pregnancy 2. Obesity 2. Surgery
3. OCP/HRT 3. Prolonged immobility 3. Atherosclerosis
4. Congenital deficiences a. Major surgies within 4 4. Pacing wires
a. Protein C def weeks (ortho, pelvic, 5. Central venous catheters
b. Protein S def urology) 6. Local damage due to previous
c. Antithrombin III def b. CVA: bedbound damage
d. Leidgen Factor V def c. Long-haul flights 7. History of thromboembolism
e. Homocystinuria 4. History of varicose veins
5. Myeloproliferative disorders: 5. Induction of anaestheisa
Polycythemia, leukocytosis,
thrombocytosis
6. Antiphospholipid antibodies
7. Haemoconcentration – nephritic syndrome

164
Differentials
1. DVT
2. Cellulitis
3. Lymphoedema
4. Ruptured Baker’s cyst

Physical Examination

General Inspection
 Mental state
 Vital signs: Tachypnoea, dyspnoea

Lower limb
 Inspection
o Unilateral swollen limb = until what level
o Erythema
o Engorged collateral superficial veins
o Chronic venous insufficiency  suggests previous DVT
o Sites of entry (especially between toes)  cellulitis
 Measure circumference of thigh girth or calf muscles
o Significant if change is > 3cm
 Palpation
o Increased warmth
o Pitting oedema
o Tenderness of calf muscles
o Capillary refill time, Pulses (indicate severity)
Request
1. Homans’ sign (pain on passive dorsiflexion)
2. Abdomen: Organomegaly, ascites, inguinal lymphadenopathy, digital rectal examination
3. Lungs: Pleural effusion

Investigations

Active diagnosis
1. D-dimer
a. Screening in the acute setting  Decide if you want to do duplex ultrasound
2. Venous duplex ultrasound

Determine underlying aetiology

1. FBC
a. Coagulopathy: Polycythemia, leukocytosis, thrombocytosis
b. Anaemia: Influences use of thrombolytic/anticoagulant therapy
2. Pre-coagulant screen
a. Protein C
b. Protein S
c. Anti-thrombin 3
d. Leiden 5 mutation (not done in Chinese)
e. Homocystinuria
f. Anti-phospholipids = anti-cardiolipin Ab, lupus anticoagulants
3. Autoimmune screen
a. ANA
b. Anti-dsDNA
c. Anti-Ro Ab
d. Anti-La Ab

Assess severity and complications

1. Spiral CT
2. V/Q scan
3. Pulmonary angiogram
4. ECG: Sinus tachycardia, Right axis deviation, RBBB, S1Q3T3, S1S2S3, P-Pulmonale

165
 5. CXR
6. ABG: Type 1 respiratory failure

Others
1. PT/PTT: Baseline before starting anticoagulation
2. U/E/Cr: Heparin metabolized in kidneys

Wells Clinical Score for DVT

Active Cancer (ongoing treatment or w/in 6mths or palliative +1 Total of Above Score
Paralysis or recent plaster immobilization of lower extemities +1
Recenty bedridden for >3d of Major surgery <4 weeks +1 > 2 = High Probability
Localised tenderness along distribution of deep venous system +1 1 or 2 = Moderate Probability
Entire leg swelling +1 < 1 = Low Probability
Calf swelling >3cm compared to asymptomatic leg +1
Pitting edema (greater in symptomatic leg) +1
Prev DVT documented +1
Collateral superficial veins (non-varicose) +1
Alternative diagnosis (as likely or less that of DVT) -2

Management of DVT

General
 Rest in bed: Avoid dislodging clot
 Elevate foot of bed
 After DVT resolves  ambulation with TED stockings X 1 year (minimize post-phlebitic complications)

Medical
1. Anticoagulation
a. Depends on the location of clot.
i. Proximal: Anticoagulation
ii. Distal: Analgesia
b. Contraindications: Recent surgery, haemorrhagic stroke, active bleeding
c. Prescription orders
i. Subcutaneous Fraxiparine 0.1ml/10kg BW BD
ii. Start warfarin at the same time
 5mg PO (1 and 2 day)  Check PT/INR (target 2.5)
st nd

 Lower dose given: elderly patients, liver disease, high risk of bleeding
 Heparin should be overlapped with warfarin for a minimum of 4 – 5 days until INR has been in
therapeutic range for 2 days
 Continue warfarin for 6 months
2. Thrombolysis
a. In acute severe PE (cardiogenic shock, right heart failure)
b. In massive iliofemoral thrombosis  at risk of venous gangrene
Surgical
1. Operative thrombolectomy
 Indication: limb salvage in impending venous gangrene
2. IVC filter
o Indications
 Contraindication to anticoagulation
 Recurrent PE despite anticoagulation
 Complication of anticoagulation requiring withdrawal immediately after pulmonary embolectomy
o 2 forms
 Removable (for short term use for 2 months)
 Indication: waiting for acute clot to stabilize
 Indication: temporary contraindication to anticoagulation
 Permanent
 For those requiring life-long anticoagulation due to higher risk of thrombosis
 Complications: Perforation, migration, infection, thrombus formation, obstruction, bleeding

166
 HEPARIN WARFARIN
Mechanism of action  Binds and activates AT-III  Blocks carboxylation of glutamate
 Stimulates tissue factor pathway residues in prothrombin, factor II,
inhibitor (TFPI) release from VII, I, X, protein C, protein S
endotheliunm  Decreases pool of Vitamin K by
inhibiting vitamin K epoxide
reductase
Note: initially procoagulant
Route IV (infusion pump), SC Oral
Onset IV: immediate; SC: 20 – 60min Slow (8-12 hours), peak in 1-3 days
T1/2 About 1.5hours (UFH); 4 hours (LMWH) 36 hours
Duration 5 – 8 hours 4 – 5 ays
SE Bleeding, allergy, thrombocytopenia, Narrow therapeutic index, bleeding,
paradoxical thromboembolism, alopecia, teratogen (fetal warfarin syndrome),
osteoporosis, sponteanous fractures, cutaneous necrosis
increased lipids, mineralocorticoid
deficiency
Antidote Protamine sulphate Vitamin K, FFP, Recombinant Factor VIIa
+ IV Vit K

167
Pulmonary Embolism
Predisposing Factors
- prolonged bed rest, immobilisation
- surgery, trauma, fractures
- previous stroke or thromboembolism
- congestive cardiac failure
- disseminated cancer
- pregnant women
- antiphospholipid syndrome
- Drugs: OCP
- Smoking
- Genetic: Factor V Leiden mutation, thrombophilias

Pathogenesis
- Thrombi from deep veins of leg (95% from popliteal or veins above it)
- Clots break off and embolize to the lungs
- Large embolus obstructing the main pulmonary artery  increased PA pressure due to blockage of flow + vasospasm
due to release of mediators/neurogenic mechanisms  leads to hypoxaemia, acute cor pulmonale (when more than
60% of vasculature is obstructed) and death
- Small thrombi may be clinically silent cos they are rapidly removed by fibrinolytic activity and the bronchial circulation
maintains the viability of the affected parenchyma until this is achieved
- Smaller thrombi continue travelling distally and are more likely to produce pleuritic chest pain, by initiating an
inflammatory response adjacent to the parietal pleura
- Pulmonary infarction may occur rarely (less likely due to dual blood supply)
- Multiple small emboli may lead to pulmonary hypertension  decreased cardiac output

Clinical Syndromes of PE
Massive pulmonary embolism
- PE associated with a systolic BP < 90 mmHg or a drop in systolic BP of >/= 40 mmHg from baseline for a period > 15
minutes, which is not otherwise explained by hypovolemia, sepsis or a new arrhythmia
- A catastrophic entity that often results in acute RV failure and death

Submassive pulmonary embolism

- All PE not meeting the definition of massive PE are considered submassive PE

Pulmonary infarction
- infarction only occurs if bronchial circulation is impaired
- the more peripheral the embolic occlusion, the more likely is infarction

Chronic pulmonary embolism

- occurs when acute PE does not resolve, lasts for years
- may lead to pulmonary hypertension

Clinical features
History
- Acute breathlessness, pleuritic chest pain, hemoptysis, dizziness, syncope
- Risk factors
- LL swelling (DVT)

Physical Examination
- Tachypnoea, pyrexia, tachycardia, hypotension
- Cyanosis
th
- Raised JVP, loud P2, 4 heart sound
- Pleural rub or effusion
- Signs of DVT
- Recent surgical scar

168
Clinical scoring

Wells score
Previous DVT/PE 1.5 0-2 Low probability
Immobilization or surgery in previous 1 month 1.5 3-6 Mod probability
Malignancy 1 > 6 High probability
Clinical symptoms of DVT 3
Hemoptysis 1
Heart rate > 100 1.5
Other diagnosis less likely than PE 3

Geneva score
Age > 65 1
Previous DVT/PE 3 0-3 Low probability
Surgery under GA or LL fracture within 1 month 2 4-10 Mod probability
Active malignant condition or cured in <1 year 2 > 10 High probability
Unilateral LL pain 3
Pain on LL deep venous palpation and unilateral 4
edema
Hemoptysis 2
Heart rate 75-94bpm 3
Heart rate >/= 95 bpm 5

Investigations
Non-specific lab findings
- ESR raised
- BNP raised
- Trop T raised
Specific investigations
- CXR
o Normal
o Atelectasis
o Oligaemia of affected segment (westermark sign)
o Dilated pulmonary artery
o Small effusion
o Wedge-shaped opacities (hamptom’s hump – apex pointing to hilum)
- ECG
o S1Q3T3 pattern, RV strain, new incomplete RBBB (classical but rare)
o Atrial arrhythmias
o T wave inversion, ST changes
- D Dimer degradation product of cross-linked fibres
- VQ perfusion scan
o Look for perfusion defects without corresponding ventilation defects
- CT pulmonary angiography/Spiral CT
- Lower limb Doppler ultrasound

Differential diagnosis
PE
- Acute coronary syndrome
- COPD
- Myocarditis
DVT
- cellulitis
- Superficial thrombophlebitis
- Ruptured baker’s cyst

169
Algorithm for diagnosis of PE

Suspicion of PE

Perform
Wells/Geneva
Score

Low/Intermediate
High Probability
probability

D-dimer assay Start treatment

D Dimer negative D Dimer positive CTPA

No treatment CTPA CTPA negative CTPA positive

Lower limb DVT Continue

CTPA negative CTPA positive
scan treatment

No treatment Start treatment Scan negative Scan positive

Continue
Stop treatment
treatment

170
Management
- Assess ABCs
- Stabilise the patient
o Supportive measures eg. Supplemental O2
o Cautiously administer intravenous fluids (avoid ppting right heart failure)
o Vasopressor therapy
- Anticoagulation
o Reduces mortality by preventing recurrent PE
o In those with high probability of PE, start anticoagulation before investigations
o Greatest efficacy if therapeutic heparin levels are initiated within 24 hours
o In haemodynamically stable patients with PE, SC LMWH is preferred
o Patients in whom anticoagulation was initiated during the resuscitative period should remain anticoagulated
during the diagnostic evaluation. Anticoagulation should be discontinued if PE is excluded.
o Long term anticoagulation with warfarin is indicated if PE is confirmed
- Inferior vena caval filter placement should be considered if anticoagulation is contraindicated (patient has active
bleeding), fails or causes complications (eg. Severe bleeding)
o Results in less recurrence of PE
o But recurrent DVT was more common among patients who received an IVC filter
- Thrombolysis should be considered once PE is confirmed
o Accelerates the lysis of acute pulmonary emboli
o Increased likelihood of major haemorrhage
o If thrombolysis is chosen, anticoagulation should be temporarily discontinued then resumed
o No mortality benefit, but shown to improve RV function
o Persistent hypotension due to massive PE is a widely accepted indication for thrombolysis
- Embolectomy
o Removal of embolus using catheters or surgically
o When thrombolysis either fails or is contraindicated
o Catheter embolectomy: injecting pressurized saline through the catheter’s distal tip, which macerates the
embolus. The saline and fragments of clot are then sucked back into an exhaust lumen of the catheter for
disposal
- Preventive management
o Elastic stockings, leg exercises, ambulation, long term anticoagulation with warfarin

Anticoagulation regimes
DRUG THERAPY
- LMWH (fraxiparin, enoxaparin)
o Results in lower mortality, fewer recurrent thrombotic events, and less major bleeding than UFH
o Greater bioavailability, one or twice daily administration, fixed dosing (ie. Dose does not require adjustment),
no required lab monitoring, and decreased likelihood of thrombocytopenia
o Exception: patients who are pregnant or have severe renal failure require anti-Xa assay monitoring after
administration of SC LMWH

- Unfractionated heparin (continuous IV infustion)

o Preferred in patients with persistent hypotension due to massive PE; severe renal failure (aPTT monitoring is
easier than anti-Xa assay)
o Target 1.5-2.3x the control aPTT
o Protamine sulphate is the antidote for heparin (cannot fully reverse LMWH’s anti Xa effects)

- Fondaparinux (new)
o Synthetic heparin pentasaccharides that catalyse factor Xa inactivation by antithrombin, without inhibiting
thrombin
o May be a viable alternative to unfractionated heparin

- Warfarin
o Risk factors for bleeding: age > 75, concurrent aspirin therapy, hypertension, CVA, renal insufficiency, heart
disease, cancer
o Vit K and FFP are antidotes for warfarin

171
 First episode of Recurrent Episode
PE/DVT of PE/DVT

Reversible risk Irreversible risk

No identifiable risk
factor (eg. recent factor (eg. ptn C Indefinite therapy
factor
surgery) deficiency, APS)

Warfarin 6-12 Warfarin 6-12

Warfarin 3-6
months, consider months, consider
months
indefinite therapy indefinite therapy

- Treatment duration among patients with a first episode of PE or DVT is determined by whether a risk factor can be
identified, and if so, whether the risk factor is reversible.
- Reversible risk factors: immobilization, surgery, trauma  warfarin for 3-6 months
- No identifiable risk factors: idiopathic PE/DVT  at least 6-12 months, consider indefinite anticoagulation
- Irreversible risk factors: protein C/S deficiency, Factor V Leiden gene mutation  at least 6-12 months, consider
indefinite anticoagulation
- Indefinite therapy should be administered to patients with recurrent DVT/PE

Prognosis
- 30% chance of developing a second embolus
- Mortality rate of approximately 30% without treatment, due mainly to recurrent embolism
- Accurate diagnosis followed by effective therapy with anticoagulants decreases the mortality rate to 2-8%

172
Dermatology
Basic Dermatology
Koebner phenomenon
 Occurs in:
o vitiligo
o lichen planus
o psoariasis
o viral warts
 development of lesions along lines of trauma

Annular lesions
= circular / ovoid macules/papules with erythematous periphery and central clearing
1. dermatophytosis (tinea corporis)
2. erythema multiforme
3. granuloma annulare
4. urticaria
5. secondary syphillis
6. pityriasis rosea
7. Hansen’s disease
8. discoid lupus erythematosus
9. sarcoidosis

Papulosquamous disorders
characterised by primary lesions of scaly papules
Major entities
 psoriasis
 pityriasis rosea
 lichen planus
 pityriasis lichenoides et varioliformis acuta & chronica
 secondary syphilis
 seborrhoeic dermatitis
 dermatophytosis
 drug eruption
 lichen amyloidosis

STD screening
Bloods: HIV, Hep B, RPR, HSV
Females : swab for gonorrhoea, chlamydia, trichomonas, bacterial vaginosis, candida
 Normal saline preparation
 gram staining
 c/s
 pH
 pap snear
Males:
 Urethral smear
 Urethral c/s
 Urine PCR for chlamydia
173
Cutaneous Lesions
1. Acanthosis nigricans
description: Velvety black overgrowth seen in the axillae, neck, umbilicus, nipples, groin
Associations:
a. Insulin resistance
i.type II DM
ii.Obesity
b. Endocrinopathies
i.cushing’s syndrome
ii.hypo/hyper thyroidism
iii.acromegaldy
iv.PCOS (polycystic ovarian syndrome)
c. adenocarcinoma
i.especially intra-abdominal: stomach, GIT, uterus
ii.abnormal production of EGF (epidermal growth factor)
iii.may precede neoplasm > 5 years
2. necrobiosis lipoidica diabeticorum
a. description: sharply demarcated oval plaque with yellow atrophic centres & brownish-red margins, usually
over skin, arms or back
b. exclusively seen in diabetes
c. females > males
d. Cx = ulceration
3. pyoderma gangrenosum
a. description: necrotic ulcer with violaceous margins
b. associations:
i.inflammatory bowel disease: UC, CD
ii.RA
iii.leukaemia: AML, CML, hairy cell leukemia
iv.haematologicall malignancy:
1. PRV
2. multiple myeloma
3. IgA monoclonal gammopathy

174
Erythema Multiforme
(type 4 hypersensitivity reaction)

Classical description
 Target lesions usually over the limbs, may appear annular
 central dark purple area / blister
 pale oedematous round zone
 peripheral erythematous rim
 polymorphic eruption with macule, papules & bullae

Request to examine:
 mucous membranes of eyes and oral cavity (SJS / erythema multiforme major)
 external genitalia for ulcers (SJS / erythema multiforme major)

Aetiology:
 Infections
o streptococcal
o mycoplasma
o herpes simplex
 Drugs
o sulphonamides (bactim)
o penicillin
o anti-epileptics (phenytoin, carbamazepine)
o anti-malarials
o NSAIDs
 Collagen vascular disease
o SLE
o Dermatomyosistin
o PAN (polyarteritis nodosa)
 Neoplasia
o multiple myeloma
o lymphoma
 idiopathic (50%)

Investigations
 Initial:
o HSV serology
o complement fixation test for mycoplasma
o anti-streptolysin O titres
 If above tests -ve:
o anti-dsDNA, ANA, C3/C4
o protein electrophoreis

Management
 symptomatic
o IV hydration
o anti-pyretics
o antibiotics if secondary bacterial infection
o anti-histamines if itchy
 systemic corticosteroids
 immunosuppression
175
 o AZP
o CSA
o Methotrexate
o IVIG
 Local
o topical antibiotics
o sterile dressing
o artifical tears for eye involvement

176
Erythema Nodosum
Classical description:
 Poorly defined & tender erythematous nodules
 usually found over shins

Aetiology
 idiopathic (50%)
 infections
o yersinia enterocolitica
o TB, leprosy
o strep pneumoniae
o toxoplasmosis
 drugs
o sulphonamides
o OCP
 Inflammatory
o Inflammatory bowel disease
o Behcet’s disease
 neoplasia
o lymphoma
 Infiltrative
o sarcoidosis
o (lefgren’s syndrome = erythema nodosum + bilateral hilar lymphadenopathy+ arthritis)

Investigations
 skin biopsy
o panniculitis (subcutaneous fat inflammation)
o vasculitis
Management
 Local: hot / cold compress
 systemic: analgesia, steroids

177
Steven-Johnsons Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS)

Dermatological emergency
 SJS = erythema multiforme major
o target skin lesions + involvement of >= 2 mucosal surfaces + epidermal detachment < 10% BSA
o 5% mortality
 TENS = extension of SJS - epidermal detachment > 30% BSA
o tender confluent erythema and large sheets of epidermal sloughing (postive Nikosky’s sign)
o 30-50% mortality
 SJS-TENS overlap = epidermal detachment 10-30% BSA
Drug history is crucial - 1-4 weeks after initial drug intake
 anti-convulsants = phenytoin, carbamazepine
 sulphonamides
 penicillin
 NSAIDs
 anti-malarials
Investigations
 Bloods
o FBC
o U/E/Cr
o LFT
 Imaging
o CXR
 Bacteriology
o swabs from denuded skin and mucous erosions (oral cavity, conjunctiva, anal, urethral, genitalia)
o if febrile:
 blood c/s
 UFEME and urine c/s
 skin biopsy if diagnosis is doubtful
Management
 Stop offending drug
 Pharmacotherapy
o systemic corticosteroids
 IV hydrocotisone 100mg q6H
 PO prednisolone 1g/kg/day
 may relieve fever and systemic toxicity
 use is controversial as may increase risk of septicaemia (given only early in disease course)
o IV immunoglobulin 1.0g/kg for 2-5 days
 indications: pregressing from SJS to TENS, early TENS
 may arrest further progression of disease
o IV cyclosporin 3.5mg/kg
o prophylactic broad spectrum IV antibiotics
 indications = patient is febrile and toxic
 possble agents: cloxacillin, ceftriaxone, augmentin, erythromycin in penicillin allergy
o anti-pyretrics
o analgesia
 Supportive therapy
o environmental
 nurse in isolation room
 severe TENS - admit burns unit

178
 o skin care
o potassium permanganate astringets for oozy wounds
o paraffin dressings
o topical antibiotics
o lip emollient
o orased gel or kenalog paste for painful oral erosions
o antiseptic mouthwash
o occular lubricants
 nuitrition and hydration
o insert NGT early for enteral feeding - refer dietician
o suction oral secretions to prevent aspiration pneumonia
o IV hydration
 others
o eye consult to rule out corneal eriosions
Complications
 Sepsis
 Fluid and electrolyte disturbances
 thermoregulatory disturbances
 ARDS
 MODS

179
Psoriasis
1. Definition
- chronic inflammatory skin disorder leading to hyperproliferation of the epidermis resulting in well define erythematous
plaque surrounded by silvery scales
- Th1 mediated disease
 genetic predisposition - ⅓ have positive family history
 environmental triggers

2. Epidemiology
- prevalence rate: 1-2%
- no gender predilection
- significantly higher in Indians
- 2 peaks:
 20-30 years old (+ve family history, more severe)
 50-60 years old (smaller peak, no family history, indolent course)
- Median age of onset: 34 years

3. Precipitating Factors
- mechanical trauma (Koebner phenomenon)
- streptococcal throat infection = triggers guttate psoriasis
- drugs: ACE inhibitors, beta-blockers, withdrawal of systemic steroids, alcohol, lithium
 systemic steroids over use in the treatment of psoriasis - rebound phenomenon
- endocrine: pregnancy (improves and deteriorates after delivery)
- HIV infection (worsens during early HIV and improves in late HIV)
- Stress

4. Types
- Psoriasis vulgaris (chronic plaque type)
 affected sites: scalp, hairline, extensor surfaces of elbows & knee, back, umbilicus, sacrum, gluteal cleft
 description: symmetrical, well-defined erythematous plaques with silvery scales
 Auspitz’s sign: removal of scales reveals small bleeding points
- Inverse psoriasis
 affected sites: intertriginous areas (axilla, groin)
 description: well defined glassy erythematous plaques
 lack silver scaly appearance due to moisture & maceration
- Guttate psoriasis
 appearance: raindrop erythematous papules with silvery scapes emptying over body surface
 usually shows streptococcal throat infection
 differentials: pityriasis rosea, secondary syphillis
- Pustular psoriasis (dermatological emergency!)
 can be localized or generalized
 Differentials: herpetics whitlow (localized), pustular drug eruption (generalized)
 associated with fevers & hypocalcaemia
- Erythrodermic psoriasis (aka generalized exfoliative dermatitis)
 can be life threatening (dermatological emergency!)
 appearance: generalized erythema & scaling involving at least 90% BSA
 associated with:
 thermoregulatory problems
 fluids and electrolyte imbalances
 cardiac decompensation (high output cardiac failure)

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  susceptibility to infections
 protein loss
 hypovolaemic shock
 treatment
 topical steroids
 emollients
 1/4 strength beclomethasone
 excoriations
 ? S. auerues infections
 differentials: severe endogenous eczema, soeborrhoeic dermatitis, norwegian scabies, adverse drug
eruption, cutaneous T-cell lymphomas (sezary syndrome), idiopathic erythroderma
 prophylactic antibiotics:
 cloxacillin
 ceftriaxone
 augmentin
 erythromycin
 management
 IV hydration
 topical steroids
 emollients
 monitor vital regularly
 refer dermatology
 oral steroids not indicated in psoriasis (only for sever eczema and adverse drug eruptions)
5. Extracutaneous manifestations
- Nail changes (25-50%)
 pitting = corase irregular pattern
 onycholysis
 transverse ridging
 yellow-brown spot on nail bed (oil droplet sign)
 subungal hyperkeratosis
 nail dystrophy
- psoriatic arthropathy (10-20%)
 oligoarticular, asymmetrical arthritis (70%)
 RA-type arthritis (15%)
 OA-type arthritis (5%)
 spinal form resembling ankylosing spondylitis (5%)
 arthritis mutilans (5%)

6. Bazex syndromes
- psoriasiform lesions seen on nose, ears, fingers & toes
- paraneoplastic syndrome
- underlysing SCC of oropharynx, trachobronchial tree & oesophagus

7. Management
- Patient education
 incurable disease
 not infectious
 suppresion of disease is possible
- Specific therapy
 Topical
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  Emollients: aqueous cream, white soft paraffin
 keratolytic agents: salicylic acid
 coal tar: inhibits mitosis & anti-inflammatory
o complications - staining, smell, oil folliculitis
 dithranol (anthralin): inhibits mitosis
o complications: staining, irritation of surrounding normal skin
o stick application for 30 minutes (short contact anthralin therapy)
 topical steroids: for scalp, face, palms, soles & flexures
o advantages: cosmetically elegant, odourless
o complications: tachyphylaxis, rebound phenomenon, allergic contact dermatitis, skin atopy,
striae, easy bruising, telangiectasia, systemic side effects
 calcipotriol (vit D derivative): increase Ca2+ therefore increase differentiation and decrease
proliferation. excellent alternative to steroids
o side effects: hypercalcaemia, skin irritation
 phototherapy: narrow band UVB 2-3x/week for 30s to 5 minutes
 if failed: photochemotherapy (PUVA = psoralen + UVA)
 acute side effects: pigmentation, pruritis, erythema, nausea (due to psoralen)
 chronic side effects: photoaging, skin cancers (especially SCC)
 systemic
 methotrexate: inhibits dihydrofolate reductase
o weekly dose, given together with folate acid
o reserved for extensive / erythrodermic / pustular / arthropathic psoriasis
o monitor FBC & LFT
o measure U/E/Cr - renal excretion
o once cummulative dose of 1.5g/kg reaches, offer liver biopsy for liver fibrosis/cirrhosis
o side effects: n/v, GIT effects, pancytopenia, hepatotoxicity
 cyclosporin A: inhibits Tn cell activation
o reserved for reactive psoriasis
o monitor BP & U/E/Cr
o not to be used for more than 1 year
o Side effets: nephrotoxicity, gingival hyperplasia, hypertrichosis
 retinoids (acitretin)
o induces desquamation
o reserved for pustular & palmoplantar psoriasis
o monitor LFT & lipids
o biologics (TNF/TNF-a inhibitors): last resort

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Alopecia Alopecia Areata
 Localised loss of hair (round/oval areas) w/o visible inflammation of skin in hair-
Biology of Hair Growth bearing areas
 Hair growth on scalp occurs in cycles of intermittent activity  Most common presenting site: scalp
 Phases of hair growth are followed by periods of quiescence  AA totalis (AAT): total absence of terminal scalp hair
 Anagen (growing phase) = phase of normal active growth  AA universalis (AAU): total loss of terminal body and scalp hair
 Catagen = Brief transition phase (b/w anagen and telogen) during which hair growth  Ophiasis: Bandlike pattern of hair loss over scalp periphery
stops
 Telogen (Resting phase) Epidemiology
 Exogen (Falling phase) = hair shedding (r/ship b/w hair shaft and base of telogen  Young adults (<25yrs old)
follicle)  Male = Female

Alopecia Etiology/Pathogenesis
 Effluvium = Shedding of Hair  Autoimmune process affecting the hair bulb
 Resulting in a condition of hair loss  Alopecia  Not a sign of multisystemic disease
 a/w AI disorders: thyroid disease, vitiligo, Addison’s disease, Mucocutaneous
Non-Cicatricial (Non-scarring) Alopecia Cicatricial (Scarring) Alopecia candidiasis
Clinically no signs of tissue inflammation, scarring Evidence of tissue inflammation,  Follicular damage occurs in anagen phase, followed by rapid transformation to
or skin atrophy atrophy and scarring telogen
Diffuse/Global Patchy/Localised/Focal
Clinical History
Failure of follicle Production decline Neutrophilic
 Duration of hair loss = gradual over wks to mths
production - Triangular alopecia - Folliculitis decalvans
Patches of AA can be stable & show spontaneous regrowth
- Pattern hair loss (AGA) - Dissecting folliculitis (cellulitis)
over mths
Hair shaft Hair breakage Lymphocytic
(new patches appear while others resolve)
abnormalities - Trichotillomania - Chronic cutaneous/discoid lupus
 No skin symptoms
- Traction Alopecia erythematousus
 Associated with Hashimoto’s thyroiditis, vitiligo, MG
- Tinea capitis - Lichen planopilaris (LPP)
- 1° or acquired hair - Alopecia mucinosa
Physical Examination
shaft
Hair  Alopecia: sharply defined patches
abnormality
 Normal appearing skin with follicular opening present
AbN hair cycling Unruly hair Mixed
 No scarring
- Telogen effluvium - Folliculitis Keloidalis
 No atrophy
- Anagen effluvium - Folliculitis necrotica
 Occasional Exclamation Mark Hairs (!!): diagnostic broken-off stubby
- Loose anagen synd - Erosive pustular dermatosis
hairs where distal ends are broader than proximal ends
- Alopecia Areata
 Regrowth of new hair = fine, white/grey
AbN hair cycling Non-specific
 Sites of predilection: scalp, eyebrows, eyelashes, pubic hair, beard
- Alopecia Areata
Skin  None
- Syphilis
 Minimal Erythema in areas of hair loss
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 Nails  Fine pitting (“hammered brass”) of dorsal nail plate Telogen Effluvium
 Trachyonychia: rough nails Epidemiology
nd
 2 most common cause of alopecia after AGA
D/D of Non-scarring alopecia  Age of onset = any age
1. Secondary syphilis: moth-eaten appearance in beard/scalp  Females > Males: due to cessation of OCP, pregnancy, crash dieting
2. White patch tinea capitis
3. Trichotillomania Etiology
4. Traction alopecia Endocrine  Hypo-or Hyperthyroidism
5. Early chronic cutaneous lupus erythematosus  Postpartum (3-4 mths after childbirth)
6. Androgenetic Alopecia  Peri- or postmenopausal state
Nutritional  Deficiency: Fe, Zn, Essential fatty acids, biotin
Labs  Deprivation: Protein, Calorie
 Blds = ANA (r/o SLE), Rapid plasma regin (r/o syphilis) Drugs  Antimiotic agents: chemotherapy
 Fungal scrape = r/o tinea capitis  Antihypertensives: ACE inhibitors, Beta-blockers
 Dermatopathology  Anticoagulants
 Interferon
Course/Prognosis  CNS drugs: lithium, valproic acid
 Spontaneous remission is common in patchy AA, but less with AAT, AAU  Hormonal: OCP (2-3mths after cessation of OCP)
 Poor prognosis with ophiasis  Retinoid effect: vitamin A excess, retinoids
Physical stress  Anemia
Management  Surgery
 Treatment is directed at inflammatory infiltrate and growth inhibitor factors  Systemic Illness
produced by inflammation Psychological
 No curative treatment available at present stress
 Steroids: Idiopathic
 Topical: high potency
 Intralesional triamcinolone acetonide: injected into dermis of affected patches Pathogenesis
 Systemic: usually induce regrowth, but recurs on discontinuation  Ppting stimuli  accelerated shift of anagen (growth phase) into catagen and
 Systemic cyclosporine: usually induce regrowth, but recurs on discontinuation telogen
 Induction of Allergic contact dermatitis  Results in a premature shift of anagen follicles into telogen phase
 DCP/Diphencyprone  Transient increased hair shedding of normal telogen hairs from resting scalp follicles
 Start off initially with test dose of 0.25%  Increased daily hair loss and, if severe, diffuse thinning of scalp hair
 Tailor dose to patient’s response
 ADR: local discomfort, swelling of regional LNs Clinical History
 Photochemotherapy (Oral PUVA)  Increased hair loss on scalp + varying degrees of hair thinning
 Precipitating event typically precedes TE by 6-16 wks

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Physical Examination Pathogenesis
Skin  No abnormalities on scalp  AE occurs after any insult to hair follicle that impairs its mitotic/metabolic activity
Hair  Diffuse shedding of scalp hair, over sides and back too  Results from a rapid growth arrest or damage to anagen hairs that skip catagen &
 Gentle hair pull test  several telogen hairs telogen phases  anagen hair broken off  shed
 Short regrowing new hairs are close to scalp: finer with tapered  Inhibition/arrest of cell division in hair matrix  thin, weakened hair shaft
ends
Nails  Beau’s lines (transverse lines/grooves on fingernail, toenail Clinical Features
plates  Diffuse hair loss/balding, involves entire scalp
 Onset rapid and extensive
D/D of ↑↑ shedding of scalp hair +/- non-scarring alopecia Skin Normal scalp and skin
1. AGA Hair Breaks off or shed at level of scalp
2. Diffuse-patch AA Extensive with generalised lodd of scalp, eyebrows, beard
3. Hyper/hypothyroidism Nails Transverse banding/ridging (after successive rounds of chemotherapy)
4. SLE Course/Prognosis
5. Secondary syphilis  Regrowth of hair occurs rapidly after discontinuation of chemotherapy
6. Drug-induced alopecia
Androgenetic Alopecia (AGA)
Labs  Clinical diagnosis based on history, pattern of alopecia, and FHx
 Hair pull test  Most common progressive balding that occurs through combined effects of
 Bloods: FBC, Fe panel, TFT, ANA 1. genetic predisposition
 Scalp Biopsy 2. action of androgen on scalp hair follicles
 Variants of Pattern/extent of hair loss in males
Course/Prognosis 1. bitemporal recession
 Complete regrowth of hair is the rule/to be expected *reversible* 2. frontal and/or vertex thinning
 However, if severe and recurs after several pregnancies, regrowth may never 3. loss of all hair except those along occipital and temporal margins (Hippocrath’s
complete wreath)

Management Epidemiology
 No intervention is needed  Age of onset: Males  any time after puberty, full-blown in 40; Females  60 yrs
old
Anagen Effluvium  Males >> Females
Etiology
Drugs Cancer chemotherapy (antimetabolites, alkylating agents) Etiology
-- Severity is dose-dependent  Genetics: AD, polygenic, inherited from either/both parents
Deficiencies Severe protein deficiency  Effects of androgen on genetically predisposed hair follicles
Intoxications Mercury, Boric acid, thallium, colchicines
Radiation therapy to Pathogenesis
head  In genetically predisposed individuals, DHT causes terminal follicles to transform
into vellus-like follicles, which in turn undergoes atrophy
 During successive follicular cycles, hairs produced are shorter & decreasing diameter
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Clinical History Course/Prognosis
 Receding of anterior hairline, esp. in parietal regions  M-shaped recession  Gradual over years to decades
 Following this, a bald spot may appear on vertex
 As AGA progresses, may c/o increasing falling out of hair Management
 Syst r/v = manifestations of androgen excess (acne, hirsutism, irregular menses,  Oral Finesteride: 1mg PO qd
virilisation)  Competitively inhibits 5α-reductase and hence the conversion of testosterone
to DHT, ↓↓ serum and scalp levels of DHT
Physical Examination  BUT has no affinity for androgen receptors and hence does not block impt
Skin  Scalp skin is normal action of testosterone (growth of phallus, scrotum, spermatogenesis, libido)
 In advanced AGA, scalp is smooth and shiny  Improvement seen around 3-6mths after initiating treatment
 Orifices of follicles not visible to unaided eye  Topical Minoxidil
Hair  Hair in AGA areas: finer in texture, shorter lengths, reduced  Antiandrogens (ONLY in females!!)
diameters  Surgical treatment: hair transplantation, scalp reduction/rotation flaps
 Hair becomes vellus  atrophies completely
 Distribution in males: Laboratory investigations
- Males: patterned loss in frontotemporal and vertex area 1. Hair Pull Test
- End result: rim of residual hair on lateral and posterior scalp (hair  Scalp is gently pulled
never falls out these areas in AGA)  Normal = 3-5 strands are dislodged
- Paradoxically, males with extensive AGA may have excess growth  More than that  pathology
of 2° sexual hair 2. Trichogram (Anagen/Telogen ratio)
 Classification: Hamilton’s (males), Ludwig’s (females)  Determines the number of anagen and telogen hairs
Systemic  In young women, look for signs of virilisation (acne, excess  Epilate/Pluck 50 hairs or more with needleholder and count no. of
facial/body hair) - anagen hairs: growing hairs with long encircling hair sheath
- telogen hairs: resting hairs with inner root sheath, roots largest at base
D/D of Diffuse non-scarring alopecia  Nomally, 80-90% of hair are in telogen phase
1. Alopecia Areata with diffuse pattern hair loss 3. Scalp Biopsy: insight into pathogenesis of alopecia
2. Telogen effluvium 4. Bloods: Alopecia Screen
3. Secondary syphilis FBC Hb, MCV, MCH (Fe-def anaemia)
4. Iron deficiency TWC, Plts (SLE)
5. SLE Fe panel Fe, Ferritin, TIBC
6. Hypo/HyperThyroidism TFT Thyroid disease
7. Trichotillomania ESR, ANA SLE
8. Seborrhoeic dermatitis FBG DM

Labs History Taking to Alopecia

 Trichogram: increase in % of telogen hairs (earliest changes in AGA)
 Age/Gender/Occupation
 Dermatopathology
 Hair loss
 Hormone studies: Testosterone (total & free), DHEAS, Prolactin
 Amt/Quantity: combing/in the shower/on the pillow
 Bloods: FBC, TFT, Fe panel, ANA
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  Distribution: focal/diffuse
 Other sites of hair loss: eyebrows/lashes, axilla, pubic hair
 Aetiology
 Stressful events: physical, psychological
 Fever
 Acute illness/Recent infections
 Crash diets
 Post-partum: 2-4mths
 Post-surgery
 Drugs: cessation of OCP
 Systemic review
 Anemia
 LOW, LOA
 Menstrual cycle
 PMHx:
 AI disease: SLE
 Thyroid disease
 PSHx:
 DHx: OCP, antihypertensives, anticonvulsants, chemotherapy
 FHx: Alopecia
 SHx: Diet (Vegetarian)

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