External Topography of the Brain

1. For labs and dissections, refer to Lecture Notes posted on Sakai

2. Divisions of the nervous system
a. CNS: Brain and spinal cord
b. PNS: Cranial nerves, spinal nerves, ganglia (everything else)
3. Subdivisions of the brain (5)
a. Forebrain →
i. Telencephalon → Cerebral hemispheres
ii. Diencephalon → Thalamus and hypothalamus
b. Midbrain →
i. Mesencephalon → Midbrain
c. Hindbrain →
i. Metencephalon → Pons and cerebellum
ii. Myelencephalon → Medulla

4. Functional neural systems

a. Motor system
b. Sensory systems
c. Autonomic nervous system
d. Limbic system (emotions, memory, behavior)
5. Neuroanatomical directions
a. Above midbrain/diencephalon junction: Rostral = anterior; Caudal = posterior;
Dorsal = superior; Ventral = inferior
b. Below midbrain/diencephalon junction: Rostral = superior; Caudal = inferior;
Dorsal = posterior; Ventral = anterior
6. Planes of section
a. Horizontal plane: parallel to ground
b. Sagittal plane: perpendicular to horizontal plane
c. Coronal plane: perpendicular to sagittal plane
7. Cerebral cortex

1
 a. Gyri ridges
b. Sulci/fissures
8. Hemispheric functions
a. Crossed representation: each cerebral hemisphere carries out motor and
sensory functions related to the other side of the body.
b. Some higher functions are lateralized: one side of brain takes of the function; ex:
language, left side of brain controls language function
c. Dominance is established by which side of brain controls language (usually left)
d. Non dominant side is for non-verbal functions (spatial, orientation, attention)
9. Lobes of the cerebral hemisphere (4)
a. Frontal Lobe: rostral to central sulcus and dorsal to lateral sulcus
b. Parietal lobe: rostral to parieto-occipital sulcus, caudal to central sulcus, and
dorsal to lateral sulcus
c. Temporal lobe: ventral to lateral sulcus
d. Occipital lobe: caudal to parieto-occipital sulcus
e. Insula: buried within lateral fissure
10. Cerebral Cortex: Gyri and Sulci; gray matter
a. Precentral sulcus: in front of and parallel to central sulcus
b. Precentral gyrus: primary motor cortex
i. Neurons in primary motor cortex are known as upper motor neurons
1. (Lower motor neurons directly innervate muscle)
ii. Controls movement on contralateral side of body
iii. Somatotopic organization: discrete regions responsible for controlling
discrete regions of movement in body.
iv. Trunk, arm, hand, and face are from superior to inferior on lateral aspect
v. Lower extremity and external genitalia on the medial aspect
vi. Face, fingers, and hands get more area due to fine movement
c. Superior frontal gyrus
d. Middle frontal gyrus
e. Inferior frontal gyrus
i. Pars orbitale: most rostral, sits on orbit
ii. Pars triangularis: middle
iii. Pars opercularis: most caudal
iv. Broca’s area: p. triangularis and opercularis on dominant hemisphere
1. Function: motor mechanisms of speech; producing speech
2. Lesions → nonfluent aphasia (can’t speak); able to understand
f. Postcentral sulcus: caudal to and parallel to central sulcus
g. Postcentral gyrus: primary somatosensory cortex
i. Sensory information from contralateral side of body arrives here
ii. Similar somatotopic organization to primary motor cortex
iii. Higher sensory acuity requires greater area of postcentral gyrus
h. Intraparietal sulcus divides parietal lobe into two lobules
i. Superior parietal lobule
j. Inferior parietal lobule

2
 i. Supramarginal gyrus: wraps around lateral fissure
ii. Angular gyrus: wraps around superior temporal sulcus
iii. Inferior parietal lobule lesions differ depending on hemisphere
1. Dominant hemisphere: Agraphia (can’t write), acalculia (difficulty
with mathematical equations), impaired language comprehension
2. Non-dominant hemisphere: contralateral hemineglect (patient
ignores left half of the world)
k. Occipital Lobe → Occipital Gyri
l. Superior temporal gyrus
i. Transverse gyri of Heschl: primary auditory cortex
1. Located on dorsal aspect within the lateral fissure
ii. Wernicke’s area: language comprehension
1. Posterior part of superior temporal gyrus and inferior parietal
lobule
2. Lesion → fluent, but nonsensical (gibberish)
m. Middle temporal gyrus
n. Inferior temporal gyrus
11. Cerebral Hemisphere: Ventral surface
a. Gyrus rectus: most medial
b. Olfactory sulcus: has olfactory bulb and tract
c. Orbital gyri: lateral to gyrus rectus
d. Lateral fissure: divides frontal lobe and temporal lobe
e. Collateral sulcus: most medial sulcus in temporal lobe
f. Inferior temporal sulcus: lateral sulcus in temporal lobe
g. Inferior temporal gyrus: most lateral
h. Occipitotemporal gyrus: medial to inferior temporal gyrus
i. Parahippocampal gyrus: most medial gyrus
i. Uncus: rostral portion that bulges out in front of midbrain; amygdala is in it
12. Hemisected brain: medial surface
a. Corpus callosum: large white matter landmark, commissural fibers (connects
hemispheres)
i. Rostrum: point of the hook
ii. Genu: the bend
iii. Body: long part
iv. Splenium: the tail part
b. Cingulate gyrus: just external to corpus callosum;
i. Subcallosal gyrus is part that is below corpus callosum
ii. Isthmus is thin part behind corpus callosum
c. Cingulate sulcus: external to cingulate gyrus
i. Marginal sulcus: part that turns upward in parietal lobe
d. Paracentral lobule: lies rostral to marginal sulcus, motor and sensory area of
lower limb
e. Superior frontal gyrus: lies rostral to paracentral lobule
f. Parieto-occipital sulcus: caudal to marginal sulcus, ends in calcarine sulcus

3
 g. Calcarine sulcus: horizontal sulcus, landmark for primary visual cortex which lies
just above and just below the sulcus
i. Lesion → Contralateral homonymous hemianopsia: patient unable to see
anything on contralateral visual field.
h. Precuneus: region between marginal and parieto-occipital sulcus
i. Cuneus: region between parieto-occipital and calcarine sulcus
j. Lingual gyrus: just under the calcarine sulcus

Internal Topography of the Brain

1. Subcortical Telencephalic Structures
a. Septum pellucidum: thin membrane under the corpus callosum
b. Body of Fornix: fiber bundle over the thalamus
c. Column of Fornix: curves over in front of the thalamus
d. Anterior commissure: just rostral to the column of fornix; connects temporal lobes
e. Lamina terminalis: thin membrane coming down from anterior commissure
i. Adult remnant of site where neural tube closed
2. Diencephalic Structures
a. Thalamus: large egg shaped mass in center of brain in front of splenium of CC
i. Principle source of input to cerebral cortex
b. Massa intermedia: connects thalamus, 20% of brains don’t have this
c. Hypothalamus: ventral to thalamus
d. Pineal body: posterior aspect of thalamus
e. Posterior commissure: just in front and below pineal body
f. Optic Chiasm: ventral hypothalamus
g. Infundibulum
h. Mammillary bodies
3. Brain stem boundaries and subdivisions
a. Midbrain
b. Pons
c. Medulla
4. Brainstem longitudinal regions
a. Midbrain: Crus Cerebri, Tegmentum, Tectum (superior and inferior colliculi)
b. Pons: Basilar Pons, Pontine Tegmentum
c. Medulla: Pyramid, Dorsal Medulla
5. Ventricular system
a. Interconnected fluid-filled cavity
b. Lateral ventricles in telencephalon
i. Anterior horn: located in frontal lobe, anterior to thalamus
ii. Body: located in parietal lobe, above thalamus
iii. Posterior horn: located in occipital lobe
iv. Inferior horn: located in temporal lobe
v. Trigone: intersection of body, posterior horn, and inferior horn
c. Third ventricle: associated with diencephalon
i. Connects to lateral ventricle via interventricular foramen

4
 ii. Located ventral to lateral ventricle
d. Cerebral aqueduct
i. Third ventricle drains into cerebral aqueduct, narrow channel located
between tectum and tegmentum of midbrain
e. Fourth ventricle
i. Where the cerebral aqueduct drains; Dorsal to pons and medulla
ii. Has three openings which allows CSF to drain into subarachnoid space
1. Foramen of Luschka: lateral openings
2. Foramen of magendie: medial opening
f. Central Canal: thin channel in lower medulla
6. Choroid plexus: makes CSF
a. Located in roof of third ventricle, interventricular foramen, body, trigone, and
inferior horn of lateral ventricle, in fourth ventricle and foramen of Luschka
b. Not in anterior or posterior horn
c. CSF Flow: produced in lateral ventricle → III Ventricle through IVF → cerebral
aqueduct → IV Ventricle, leaves ventricles through foramen of Magendie and
Foramen of Luschka, flows through SAS
d. CSF reabsorbed via arachnoid villi into dural sinus (superior sagittal sinus)
7. 3 Important principles
a. C-Shaped growth of telencephalon: cerebral cortex, lateral ventricles,
i. Caudate nucleus: head (in front of thalamus, in lateral wall of anterior
horn of LV); body (above thalamus, in lateral wall of body of LB), tail
(temporal lobe, in roof of inferior horn of LV); tail ends and merges with
amygdala
ii. Fornix: fiber bundle that originates in hippocampus, floor of inferior horn
of lateral ventricle, arches over thalamus down to mammillary body
b. Core structure of the brain is made of three things:
i. Lentiform nucleus: just deep to insula;
1. Putamen: lateral piece, rostral part merges with head of caudate
2. Globus pallidus: medial part; has a lateral and medial part
ii. Thalamus
iii. Internal capsule: collections of fibers coming down from cerebral cortex to
brainstem; between lentiform nucleus and thalamus and caudate
1. Anterior limb: lateral to head of caudate, medial to lentiform nuc.
2. Posterior limb: lateral to body of caudate and thalamus
8. Three Key Concepts
a. Many telencephalic structures are C-Shaped
i. Lateral ventricle
ii. Caudate nucleus
b. Core of brain is made up of three major structures
i. Lentiform nucleus (Putamen and Globus Pallidus)
ii. Thalamus
iii. Internal capsule: anterior limb (anterior to thalamus), posterior limb
(lateral to thalamus and caudate and medial to lentiform nucleus), Genu

5
 (bend)
c. Medial Temporal Lobe contains 2 major gray matter structures
i. Amygdala: almond shaped; deep to the uncus at rostral tip of the inferior
horn of the lateral ventricle
ii. Hippocampus: located in the floor of the inferior horn of the lateral
ventricle
1. Gives rise to the fornix

Scalp, Cranial Cavity, and Meninges

1. Scalp
a. Layers: Skin, Connective tissue, Aponeurosis, Loose Areolar tissue, Pericranium
b. Skin: hair, sweat, and sebaceous glands; common site for sebaceous cysts
(caused by obstruction of sebaceous gland ducts)
c. Connective Tissue (dense): contains vessels and nerves of scalp; superficial
scalp wounds bleed profusely because collagen fibers attach to the arteries in
this layer and prevent their retraction after a laceration.
d. Aponeurosis: epicranial aponeurosis and occipitofrontalis muscle (nerve = CN
VII)
i. Frontalis muscle: anterior border, raises eyebrow and wrinkle forehead
ii. Occipitalis: superior nuchal line, mastoid, temporal bone, pulls scalp back
iii. Deep scalp wounds gape widely if aponeurosis is severed in coronal
plane since frontalis and occipitalis pulls aponeurosis in opposite direction
e. Loose areolar layer: provides mobility to scalp
i. Danger area of the scalp since blood of pus spreads easily throughout the
layer. Accumulation of blood here is called subgaleal hematoma
ii. Infection can spread from this layer into the cranial cavity through
emissary veins (veins passing through foramina to connect to dural sinus)
f. Pericranium: periosteum of skull bones; adheres loosely to skull except at
sutures, where it attaches firmly
i. Cephalohematoma: is a benign complication of birth injury to skull.
Bleeding occurs between pericranium and skull bone. Hematoma outlines
the affected bone since firm attachments at sutures limits spread of blood.
2. Blood supply of scalp
a. Scalp is supplied by 5 arteries
i. 2 most anterior arteries are from internal carotid arteries via ophthalmic
artery: supratrochlear and supraorbital arteries
ii. 3 most posterior arteries are direct branches of the external carotid artery:
superficial temporal, posterior auricular, occipital arteries
iii. Arteries course in dense CT layer with abundant anastomoses
3. Nerve supply of scalp
a. Trigeminal nerve innervates from ear forward
i. V1 Ophthalmic nerve (supraorbital and supratrochlear branches):
innervates forehead and anterior part of scalp until vertex
ii. V2 Maxillary nerve (zygomaticotemporal branch) anterior temple region

6
 iii. V3 Mandibular nerve (Auriculotemporal branch) posterior temple region
iv. Cervical spinal nerves (C2 and C3)
1. Lesser occipital nerve: area behind and above ear
2. Greater occipital nerve: scalp of back of head
b. Posterior scalp is innervated by cervical spinal nerve
i. Great auricular nerve: ear
ii. Lesser occipital nerve: behind ear
iii. Greater occipital nerve: back of head
4. Cranial cavity
a. Pterion:
i. Junction of frontal, parietal, temporal, and sphenoid
ii. Middle meningeal artery is deep to the pterion
iii. Skull fracture at pterion → epidural hematoma
5. Cranial fossae
a. Anterior cranial fossae
b. Middle cranial fossae
c. Posterior cranial fossae
d. Bones of the cranial fossa:
i. Frontal
ii. Temporal
iii. Ethmoid bone: made up of crista galli and cribriform plates
1. Cribriform plates support olfactory bulbs and transmits CN I
iv. Temporal bone: Squamous part, Petrous part, mastoid part
e. Sphenoid Bone
i. Greater wing
ii. Lesser wing
iii. Body
f. Sella Turcica: Made up of portions of body of sphenoid
i. Tuberculum sellae: anterior knob
ii. Hypophysial fossa: saddle part, where pituitary sits
iii. Dorsum sellae: posterior knob
g. Clivus: flat part of bone just anterior to foramen magnum; supports brainstem
6. Openings in anterior cranial fossa
a. Cribriform plate: foramina transmit filaments of CN I Olfactory nerve
b. Optic canal: transmits CN II Optic nerve and Ophthalmic artery (comes off ICA)
c. Superior orbital fissure: Superior orbital fissure: transmits CN III Oculomotor
nerve, CN IV Trochlear nerve, CN V1 Ophthalmic nerve, CN VI Abducens nerve,
Ophthalmic veins
d. Foramen rotundum: transmits CN V2 Maxillary nerve
e. Foramen ovale: CN V3 Mandibular nerve
f. Foramen spinosum: transmits Middle meningeal artery enters, V3 meningeal
g. Foramen lacerum: covered by cartilage
7. Foramina of posterior cranial fossa

7
 a. Foramen magnum: brainstem/spinal cord junction, spinal accessory nerve
entering, vertebral arteries.
b. Internal acoustic meatus: CN VII Facial, CN VIII Vestibulocochlear
c. Jugular foramen: CN IX Glossopharyngeal, CN X Vagus, Spinal accessory
nerve, Inferior petrosal sinus, jugular bulb
d. Hypoglossal canal: CN XII hypoglossal nerve
8. Basilar skull fracture
a. Racoon eyes
b. Nasal discharge
c. Battle’s sign: bruising behind ear
9. Dura mater
a. Just beneath bone of cranial cavity
b. Two layers: Periosteal layer, meningeal layer
c. Epidural space is between periosteal dura layer and skull bone, potential space
i. Epidural hematoma: high pressure bleeding of middle meningeal artery
ii. Rapid deterioration, about 4 hours to fix it
10. Arachnoid and Pia Mater
a. Arachnoid does not dip into sulci
b. Pia mater does go into sulci and can not be separated from brain
c. Subdural space is between meningeal dura and arachnoid mater, potential space
i. Subdural hematoma: bleeding from cerebral veins
ii. Low pressure venous bleeding, mild trauma, long time for blood to
develop
d. Subarachnoid space is a real space, contains CSF
i. Subarachnoid hematoma: bleeding from rupture of cerebral artery
ii. Patients describe it as worst headache of his/her life
iii. MRI shows blood in sulci and lumbar puncture shows yellow/red
11. Formations of dural partitions
a. Falx cerebri: vertical partition between longitudinal fissure
b. Tentorium cerebelli: horizontal partition forms partial roof above posterior fossa
i. Supratentorial and infratentorial: above and below this
c. Falx cerebelli: between cerebellum
d. Diaphragma Sellae: partial roof over hypophyseal fossa, pituitary gland sits
below
12. Elevated intracranial pressure
a. Compensated mass: ventricles shrink to compensate
b. Uncompensated mass: too large
c. Brain herniation: ↑ ICP causing parts of brain to move to different compartments
i. Transtentorial herniation: when uncus herniates down below tentorium
cerebelli → compresses Oculomotor CN III at base of midbrain → loss of
eye movement and pupillary control
ii. Subfalcine herniation: cingulate gyrus under falx cerebri → compresses
anterior cerebral artery → weakness of lower limb

8
 iii. Tonsillar herniation: Cerebellar tonsil (and brainstem) through foramen
magnum → damaged respiratory control centers in lower medulla
13. Dural venous sinuses
a. Dural venous sinus in fixed border of dural partition
b. Cerebral vein, bridging veins, emissary veins drains into dural venous sinuses
c. CSF also percolates through arachnoid granulations and drains into sinuses
d. Superior sagittal sinus drains to confluence of sinuses
e. Inferior sagittal sinus: in free border of falx cerebri
f. Straight sinus is at junction between falx cerebri and tentorium cerebelli
g. Occipital sinus in the fixed border of falx cerebelli
h. Transverse sinus: outward along occipital bone
i. Sigmoid sinus: curves downward at petrous part of temporal bone
j. Cavernous sinus drains to superior and inferior petrosal sinus; sits right on lateral
sphenoid bone; CN III, VN IV, CN V1, and CN V2, ICA run through it

Introduction of Clinical Neurology

1. Refer to Introduction to Neurologic Diagnosis handout
2. Diagnostic Challenge
a. Only behavior and cognition can be studied directly
b. Ulnar nerve is the only structure that can be palpated
c. Optic nerve head is the only structure that can be seen
3. Solving the puzzle
a. Babinski’s sign proves that the weakness is central nervous system
b. Split sensory loss suggests a spinal cord disorder
c. Loss of pain in left hand (as opposed to the right) identifies where in the spinal
cord the trouble was (anatomic diagnosis)
d. Insidious development suggests tumor syndrome (tumor = mass)
e. Outcomes: herniated disc compressing the spinal cord
4. Think neurology when patient has chief complaint of:
a. Some part of body is weak, clumsy, or moves funny
b. Numb tingling feelings
c. Something wrong with vision
d. Headaches
e. Strange spells
f. Dizziness
g. Bad memory
h. Child is not developing as expected
5. Anatomy of something not moving right:
a. Weakness
i. Upper motor neuron
ii. Motor unit: Nerve or Muscle
b. Unwanted Movement and Clumsiness
i. Cerebellum
ii. Basal Ganglion

9
6. Voluntary Movements
a. Cerebral Precentral Gyrus: controls all voluntary movements
b. Basal ganglia: resting tremor, rigidity, chorea and athetosis, unstable gait
c. Cerebellum: action tremor, broad based gait, dysmetria and ataxia, nystagmus
d. Brain stem: CN VII, reflexes
e. Spinal cord anterior horn cells: weakness (paresis), reflex changes, and paralysis
7. Anatomy of I have numb and tingling feelings
a. CNS
i. Sensory Tracts
ii. Cortical
b. PNS
i. Large Fiber
ii. Small Fiber
8. Anatomy of Something wrong with vision
a. Things blurred → refractive error
b. Loss of vision
i. Structural Eye disease
ii. Field cut on examination: Central (optic nerve) or Hemianopsia (optic
tracts of cortical)
c. Seeing double
i. Extraocular muscle
ii. CN III, IV, VI
iii. Brain stem
9. Clinical diagnosis of headaches
a. Recurrent headaches: Migraine; Tension; Cluster; Behavioural
b. Non recurrent (more serious)
i. Meningeal irritation: Meningitis, Hemorrhage
ii. Meningeal traction: tumors, edema
iii. Incidental: infection, withdrawal, post-trauma
10. Strange spells
a. Epilepsy
i. Generalized
ii. Partial: simple, complex
iii. Partial with secondary generalization
11. Dizziness
a. Rapid onset, single event, persistent: acute vestibulitis, acoustic neuronitis
b. Multiple attacks: Meniere’s disease, benign positional vertigo (most common)
c. Presyncope: orthostatic, cardiac
d. Spatial differentiation: drugs and medications, sensory deprivation
12. Memory troubles
a. Gradual onset (dementia)
i. Any age: head injury, hepatic/renal, endocrine, brain tumor, drug/alcohol
ii. Elderly: Alzheimer’s, Lewy body, vascular, fronto-temporal., normal
pressure hydrocephalus

10
 b. Rapid onset (delirium)
i. Drugs/alcohol acute and withdrawal
ii. Infections: non specific fever, encephalitis
13. Neurologic disorders flow sheet
a. CNS
i. Focal
1. Acute: Stroke syndrome (Ischemic or hemorrhagic)
2. Chronic: Tumor syndrome (neoplasms, granulomas, orthopedic,
Multiple sclerosis)
ii. Diffuse/bilateral
1. Acute: Encephalopathy syndrome (meningitis, encephalitis,
anoxia, traumatic, intoxication and poisoning, subarachnoid
hemorrhage)
2. Chronic: Degeneration syndrome (Alzheimer’s, Parkinson’s, ALS,
chronic infections, toxic and metabolic disorders)
b. PNS
i. Focal
1. Acute: Traumatic nerve or root
2. Chronic: Compression syndrome
ii. Diffuse/bilateral
1. Acute: Guillain Barre Syndrome
2. Chronic: Peripheral neuropathy syndrome
c. Spells
i. Notes: To qualify for this category the patient must have a normal
neurologic exam at the time of examination. If neurologic findings are
present, they must be addressed first
ii. Epilepsies: generalized, partial
iii. Headaches
iv. Vascular: syncope, TIA
v. Some of the dizzies
vi. Psychological disorders

Mental Status Exam

1. Mental status exam
a. The psychiatric exam (not the MMSE or MOCA)
b. Series of observations of the patient and how they interact with their environment
c. An attempt to describe the recent and current state of the patient in written form
d. Much like other types of exams, the MSE helps substantiate a diagnosis and
determine treatment as well as convey information to another provider
e. While there are usual descriptions for an MSE you can use your own words
f. Not inherently complicated or involved
g. There are four main dimensions within the MSE
h. These four dimensions cover the majority of the MSE
2. The 4 Dimensions

11
 a. General
i. Appearance: age, apparent age, ethnicity, gender, build, grooming, dress
ii. Behavior: eye contact, gait, adherence to social conventions, interaction
with interviewer, psychomotor activity
iii. Speech: quality, rate, volume, fluency or rhythm
b. Mood
i. Mood: subjective portion, patient’s answer to “how are you feeling?” often
written as “patient states his/her mood is…”
ii. Affect: the examiner’s inference of patient’s emotional state
1. Range: variation in behavior/emotion during interview
2. Intensity: power of emotion coming from patient
3. Lability: speed and intensity of swings in emotion during interview
4. Appropriateness: most commonly included portion of affect when
writing an MSE; an assessment of congruence
c. Thought
i. Thought Process
1. Coherence: does it make sense to listener
2. Logical: are the patient’s conclusions based on sound logic?
3. Goal directed (tangential, circumstantial)
4. Associations (blocking, looseness of associations, flight of ideas)
5. Logical: A → B
6. Linear: A → B → C → D
7. Goal Directed: A → D
ii. Thought content
1. Perceptions: hallucinations, illusions, ideas of reference, thought
broadcasting, thought insertion
2. Delusions: fixed false beliefs
3. Dangerousness/Safety (recent and current)
a. Suicidal/homicidal ideation: intent, plan, method, access
d. Cognition
i. Knows person, place, time and event (x4) or person, place, time (x3)
ii. If a MOCA or MMSE is performed, it would go here. Total score followed
by information on any items missed
e. Insight/Judgement
i. Insight: ability to understand illness that you have (good, fair, poor)
ii. Judgement: making good decisions (intact, poor)
iii. Impulse control: (intact, poor)
3. Safety (General, Mood, Thought all tie into safety)

Nervous Tissue and Cellular Function

1. Neuron
a. Cell body: contains nucleus
b. Dendrites: receives input
c. Axons: transmit information in form of action potential

12
 d. Nerve terminals: releases neurotransmitters
e. Three different types of neurons
i. Bipolar: one axon and one dendrite
ii. Multipolar: one axon and two or more dendrite; majority of neurons
iii. Pseudounipolar: one axon with two long process but no dendrites
iv. The majority of bipolar and pseudounipolar neurons are sensory
2. Glial cells
a. Non-neuronal cells that maintain homeostasis in CNS
b. Forms myelin, provides structural and metabolic support for neurons
c. 4 types in CNS
i. Astrocytes: provides scaffolds for growing axons and migrating neurons,
anchor neurons to blood supply, contributes to blood brain barrier
ii. Microglia: specialized macrophages capable of phagocytosis
iii. Ependymal: lines fluid filled cavities (ventricles) of brain and spinal cord,
creates cerebrospinal fluid (CSF); beats cilia to circulate CSF
iv. Oligodendrocytes: coat axons in CNS with myelin sheath
d. 2 types in PNS
i. Schwann cell: myelinate axons of peripheral nerves, plays a role in nerve
regeneration following injury
ii. Satellite cells: surround and support nerve cell bodies in peripheral
ganglia
3. Processing information and integrative function of CNS
a. CNS are miniature computational units that integrate inputs from many sources
i. Many presynaptic inputs to postsynaptic cell are required to activate it
ii. Has excitatory and inhibitory inputs (creates EPSP or IPSP)
iii. Various chemical transmitters interacting with different receptor types
iv. Many action potentials firing synchronously to get an AP in target neuron
b. CNS Synapses:
i. Intercellular junctions specialized for transmission of nerve impulses
ii. Interaction is chemically mediated via neurotransmitters (NTs)
iii. Synaptic potentials are graded changes in postsynaptic membrane
iv. Most are at axon-dendrite, but can also be at axon-soma or axon-axon
v. Neurotransmitters released by presynaptic neuron can depolarize (EPSP)
or hyperpolarize (IPSP) postsynaptic neuron
vi. Factors influencing the size of the graded potential:
1. Amount of neurotransmitter released
2. Density of receptors on postsynaptic membrane
c. Integration of synaptic inputs
i. Graded PSP spread passively and decay over time and space in soma
1. Synapses closer to axon hillock have greater effect
ii. Axon hillock is the site of integration of graded PSP (trigger zone for AP)
iii. AP occurs when multiple subthreshold EPSPs sum to bring membrane
potential to threshold
iv. 2 Types of integration:

13
 1. Temporal summation: consecutive EPSPs at the same site sum to
depolarize membrane toward threshold
2. Spatial summation: simultaneous EPSPs at different synapses on
same neuron sum to depolarize membrane toward threshold
d. Arrangements of local synaptic connections
i. Divergence: 1 neuron contacts many neurons
ii. Convergence: Many neurons contact one neuron
e. Presynaptic modulation of synaptic transmission
i. Axoaxonic synapse type 1: cell A influences membrane potential at the
axon hillock and alters the likelihood of generating an AP in cell B
ii. Axoaxonic synapse type 2: cell A influences membrane potential at the
axon terminal and alters the amount of Ca2+ present in cell B → alters
amount of neurotransmitter released by cell B onto cell C.
1. Presynaptic facilitation: activity in axon terminal of cell A → ↑ Ca2+
in axon terminal of cell B → ↑ neurotransmitter release by cell B →
↑ EPSP or IPSP size in cell C
2. Presynaptic inhibition: activity in axon terminal of cell A → ↓ Ca2+
in axon terminal of cell B → ↓ neurotransmitter release by cell B →
↓ EPSP or IPSP size in cell C
f. Neuronal Circuits
i. CNS executes its complex functions using combination of a few basic
pattern of connections between neurons
ii. Feedforward excitation: three excitatory neurons connected in series,
when Cell A fires AP → Cell B fires AP → Cell C fires AP
iii. Feedforward inhibition: neuron A fires AP but neuron B is inhibitory →
reduces firing rate of neuron C
iv. Disinhibition: excitatory presynaptic cell A is connected to two inhibitory
neurons in series → cell A fires AP → cell B inhibits the inhibitor cell C →
allows cell D to fire
4. Neurotransmitters in synaptic communication
a. Amino acids: GABA (main inhibitor), Glutamate (main exciter), Glycine
b. Amines: ACh, dopamine, norepinephrine, histamine, serotonin
c. Neuropeptides: enkephalins, substance P
5. Co-localization of glutamate and neuropeptide substance P
a. Co-localization modulates the action of the transmitter on postsynaptic cell
6. Degeneration and regeneration
a. PNS has an intrinsic ability for repair and regeneration
b. CNS, for the most part, is incapable of self-repair and regeneration
c. Neuronal reactions: morphological changes that can be observed microscopically
after damage to the axon of a neuron
d. Anterograde reaction: if axon is cut, the part distal to the cut degenerates
(wallerian degeneration) because materials for maintaining axon are formed in
cell body and can no longer be transported down axon
i. Clearance of distal axon to allow of potential regeneration

14
 ii. Schwann cells in region de-differentiate and divide
iii. PNS injury: schwann cells and macrophages phagocytose debris
iv. CNS injury: microglia, astrocytes, and macrophages phagocytose
e. Retrograde reaction:
i. Swelling of the cell body and nucleus
ii. Displacement of nucleus from center of cell to eccentric location
iii. Dispersion of Nissl substance into fine, homogenous particles of
decreased basophilia (chromatolysis)
iv. Ribosome-studded reticulum are dispersed and replaced with
polyribosomes
f. Regeneration of peripheral nerve
i. Nerve’s ability to repair itself, including re-establishment of connections
ii. Sprouting: tips of the proximal stumps form enlargements (growth cones)
iii. Growth cones sprout initially at nearest node of Ranvier of proximal
segment, and grow across injury site into schwann cell guidance tunnels.
iv. When growing axons contact Schwann cells, a second wave of Schwann
cell proliferation occurs
v. Schwann cells from secondary proliferation form guidance tunnels
vi. Elongation of axons innervate target tissue, myelinate; recovery occurs
vii. Failure of regenerating axonal sprouts results in neuroma formation
1. The permanently denervated muscle fibers severely atrophy
7. PNS regeneration and reinnervation can occur but influenced by several factors:
a. Type of Nerve injury:
i. Crush: endoneurial sheaths remain intact (better prognosis)
ii. Transection: continuity of axoplasm lost, misalignment of axons with
original pathway (worse prognosis)
1. suture ends of nerve together → ↑ chance of recovery
b. Site of injury: damage close to target site have higher chance of regeneration
c. Age: younger → regenerative activity is greater
8. CNS damage; axons do initially sprout from proximal segment, but regrowth through
injury site is limited by several factors:
a. Loss of molecules that promote axonal growth
b. Expression of molecules that inhibit axonal growth
c. Oligodendroglia do not form guidance tunnels
d. Development of glial scar at injury site impedes growth of axons due to
proteoglycan production that inhibits sprouting

Psychiatric Interview Assessment/Diagnosis

1. Psychiatric History
a. Identifying data
b. Chief complaint
c. HPI: onset, precipitating factors
d. Past psychiatric plus psych ROS
e. Past medical/surgical

15
 f. Social: substance, occupational, marital, military, educational, current living
situation, religion, sexual, legal
g. Developmental: prenatal, infancy/early childhood, middle childhood,
adolescence, young/middle adult
h. Family psychiatric and medical
i. Review of systems
j. At a minimum capture:
i. Course
ii. Signs/symptoms
iii. Degree of impairment
k. With few exceptions, it is not a disorder unless there is evidence of impairment
2. Psychiatric History in the real world
a. Workflows
b. Questionnaires/screening tools: opportunity for patient input, symptoms tracking
c. Validated instruments; but do not diagnose
i. PHQ-2/PHQ-9: depression
ii. AUDIT-C/AUDIT: Alcohol
3. Mental Status Exam
a. Evaluation of patient’s mental functioning at a point in time
b. Combines observations with series of formal question
c. Interpret patient’s communication, verbal and nonverbal
d. Rapport and observational skills essential
e. Two processes occurring at once
i. Open-ended, unstructured: appearance, behavior, attitude, speech,
affect, thought form, thought content, insight, judgement
ii. Directed, focused: mood, suicidal and homicidal ideation, perceptions and
cognitive functioning
4. Assessment Tools
a. Cognitive screening tests: help detect mild cognitive impairment (MCI) in adults
i. Montreal cognitive assessment (MoCA)
ii. Standardized mini-mental state exam (SMMSE)
b. Good for following cognitive symptoms
c. But does not replace full MSE
5. Shortcomings in DSM-IV
a. High rates of comorbidity
b. High use of Not Otherwise Specified (NOS) category
c. Treatment non-specificity
d. Inability to find a laboratory marker/test
e. DSM is starting to hinder research progress
6. New directions
a. Pressures to improve validity
b. Move from strictly categorical to more etiologically informed classification
c. Serve as bridge so that data in various life science areas can contribute to
ongoing development and refinement of diagnoses

16
 7. DSM-5 Organization
a. Section I: Basics
b. Section II: Essential Elements: Diagnostic Criteria and Codes
c. Section III: Emerging Measures and Models
d. Appendix
e. Index
8. DSM-5 Elements of diagnosis
a. Diagnostic criteria: guidelines to make diagnosis/inform clinical judgement
b. Specifiers: define grouping that share similar features; not mutually exclusive
(more than one can be assigned)
c. Subtype: increases specificity; mutually exclusive phenomenological subgrouping
9. DSM-5: Structure of disorder chapters
a. Criteria
b. Subtypes and/or specifiers
c. Severity: codes and recording procedures
d. Explanatory text: diagnostic and associated features; prevalence; development
and course; risk and prognosis; culture and gender related factors; diagnostic
markers; functional consequences; differential diagnosis; comorbidity
10. Assessment Measures
a. Assess characteristics not necessarily included in diagnostic criteria; but relevant
to prognosis, treatment planning and outcome:
i. Items that have support for clinical use but require further research
b. Cross-cutting symptom measures: Level 1 and Level 2
c. Diagnosis-specific severity ratings
d. WHODAS disability ratings
11. Bio-Psycho-Social Formulations
a. Organizes assessment/planning in an efficient, global, and illustrative manner
b. Consider 4Ps:
i. Predisposing: historical and constitutional vulnerabilities
ii. Protective: characteristic strengths
iii. Precipitating: why now?
iv. Perpetuating: sustain, maintain, or extend duration, severity of illness
v. Goal: systematically assess each factor from biological, psychological
and social perspective
12. DSM-5: Making a diagnosis
a. Cross-cutting symptom assessments: Level I and II suggested
b. WHODAS 2.0 suggested
c. Clinical interview (informed by assessment scores)
d. Diagnosis is given
e. Develop treatment plan and outcome monitoring approach

Cerebrospinal Fluid
1. CSF
a. Forms a crucial component of the CNS system environment

17
 b. Bathes the brain and spinal cord
c. Production, circulation and absorption affect homeostasis of CNS
d. Clear and colorless fluid
e. Percolates through ventricles and out into subarachnoid space
f. Actively secreted into ventricles by choroid plexus epithelium (ependymal cells)
2. Subarachnoid space (SAS)
a. Space between the arachnoid and pia mater filled with CSF
b. In certain regions the SAS is expanded to form cisterns, which have more CSF
i. Cerebellomedullary cistern/Cisterna Magna; Superior cistern/Cisterna
ambiens; Pontine cistern, Chiasmatic cistern, Cistern of lamina terminalis
3. Choroid plexus
a. Forms and secretes most of CSF
b. Consists of:
i. Capillary network core lined with fenestrated endothelium (blood provides
nutrients and hydrostatic pressure)
ii. Choroid ciliated tight-junction epithelium (simple cuboidal) surrounding
the interstitial fluid and vascular core
c. Separates CSF in the ventricles from blood of the vascular plexus
d. CSF formation involves:
i. Filtration through fenestrated endothelium ( → interstitial fluid)
ii. Active secretion by choroidal epithelium → CSF
4. CSF Flow
a. CSF made my ependymal cells of the choroid plexus
b. Flows into lateral ventricle → interventricular foramen (of Monro) → 3rd ventricle
→ Cerebral Aqueduct (of Sylvius) → 4th ventricle → Foramen of Luschka
(Lateral) or Foramen of Magendie (Medial) → subarachnoid space
c. CSF in subarachnoid space is reabsorbed by arachnoid granulations
d. Then drains into dural venous sinuses
5. Extrachoroidal sources of CSF
a. Cerebral capillary walls
b. Metabolic generation of water by the complete oxidation of glucose
6. Volume of CSF in the ventricular and subarachnoid spaces
a. Total CSF = 140 ml
b. Rate of CSF formation = 500 ml/day
c. Ventricles = 30 ml
d. Brain SAS = 80 ml (brain has majority of CSF in it)
e. Spinal SAS = 30 ml
7. Functions of CSF
a. Maintains constant external environment for neurons and glia
b. Removes harmful brain metabolites
c. Distributes neuroactive hormones throughout the nervous system
d. Protects CNS from trauma via the buoyant effect
8. Comparison of CSF and serum composition
a. Osmolarity and Na+ levels are equal

18
 b. CSF has less glucose, K+, Ca2+, pH (more acidic), and 200x less protein
c. CSF has more water, lactate, Mg2+, and Cl-
9. Lumbar puncture from lumbar cistern
a. Between L2-L4
10. Diagnostic significance of composition and appearance of CSF
a. Clear and colorless = normal
b. Bloody or yellow = hemorrhage
c. 150 mg/dl protein = bilirubin from plasma
d. 500 mg/dl protein = solid tumor, meningeal cancer, or compressing lesions
e. WBC > 4 /ml = infection
f. ↓ glucose = acute bacterial infection
g. γ-globulin in CSF but normal blood γ globulin: multiple sclerosis, other
inflammatory diseases
11. Hydrocephalus
a. Excess CSF can increase intracranial pressure and in adult the ventricles expand
at the expense of surrounding brain
b. Characterized by an increase in volume of cerebral ventricles and is cause by:
i. Oversecretion of CSF i
ii. Impaired absorption of CSF
iii. Obstruction of CSF circulation
c. Communicating hydrocephalus: occurrence of oversecretion and/or impaired
absorption; ventricles are in communication with subarachnoid space
i. Communicating hydrocephalus: ↓ CSF reabsorption by arachnoid
granulation → ↑ intracranial pressure, papilledema, and herniation
1. Ex: arachnoid scarring post-meningitis
ii. Normal pressure hydrocephalus: results in ↑ in subarachnoid space
volume but no increase in CSF pressure.
1. Expansion of ventricles distorts the fibers of the corona radiata
2. Clinical triad of: urinary incontinence, ataxia, and cognitive
dysfunction (sometimes reversible)
iii. Hydrocephalus ex vacuo: appearance of ↑ CSF in atrophy (ex:
Alzheimer’s disease, advanced HIV, Pick’s disease)
1. ICP is normal and triad is not seen
2. Increase is CSF observed on imaging due to decreased neural
tissue due to neuronal atrophy
d. Noncommunicating hydrocephalus: occurrence of obstruction
i. Due to a structural blockage of CSF circulation within ventricular system
ii. Ex: stenosis of the aqueduct of Sylvius
12. Fluid compartments of the CNS
a. Vascular (blood)
b. CSF
c. Extracellular (interstitial)
13. Barriers
a. Blood-CSF barrier

19
 b. Blood-Brain barrier
c. CSF-Brain barrier: no tight junction, not regulated well
14. Blood-Brain Barrier
a. Prevents circulating blood substances from reaching the CSF/CNS
i. Maintains microenvironment
ii. Transports: glucose, amino acids, ribonucleotides
iii. Lipid soluble molecules can cross rapidly via diffusion
iv. 90% of small molecules do not cross BBB; no large molecules pass
v. Transport mechanisms across BBB: diffusion for small lipid soluble;
passive and active carriers; ion channels and ion-exchangers
b. Formed by 3 structures
i. Tight junctions between non fenestrated capillary endothelial cells
ii. Basement membrane
iii. Astrocyte foot processes
c. Helps prevent bacterial infection from spreading into CNS
d. Also restricts drug delivery to brain
15. Breakdown of BBB
a. Primary and secondary brain tumors with excessively leaky vessels cause
accumulation of interstitial fluid (vasogenic edema)
b. Stroke and bacterial meningitis can also destroy endothelial cell tight junctions
c. Multiple sclerosis: T lymphocytes enter CNS through BBB attacking myelin in the
brain and spinal cord
d. Disruption of BBB because of inflammation triggers chronic or acute seizures and
causes the onset of epilepsy
e. Failure of BBB can also exacerbate the neurological consequences of TBI
f. Contributes to HIV associated dementia, hypertension, brain hemorrhage,
exposure to radiation and nerve gases.
16. Drug delivery to the brain
a. Simple diffusion of lipid soluble molecules (ex: heroin, morphine)
b. Temporary opening of BBB by hypertonic solution
c. Piggyback via existing membrane carriers or transcytosis of membrane receptors
d. Implanted intraventricular reservoirs
17. Circumventricular organs
a. Areas of specialized tissue that lack BBB located in close proximity to ventricles
18. Brain edema
a. Increased brain volume due to increased water content
b. 2 types of brain edema: vasogenic and cytotoxic
c. Vasogenic brain edema:
i. Cause: increased permeability of BBB and capillary walls
ii. Manifestations: increase in brain interstitial fluid, increased intracranial
pressure, smaller ventricles
iii. Occurs during: ischemia, head trauma, meningitis
d. Cytotoxic brain edema:
i. Net shift of water from extracellular space to interior of brain cells

20
 ii. Manifestations: cell swelling, increased intracellular fluid volume due to a
failure of energy-dependent mechanisms leading to accumulation of
water inside cells, with a simultaneous decrease in brain interstitial fluid,
elevated intracranial pressure and reduction of ventricle size
iii. Due to drug poisoning, hyponatremia, water intoxication,
hypoxia/ischemia

CNS Vasculature
1. Stroke (now called Cerebral vascular accident)
a. Disturbance of blood supply
b. Two general types of strokes: bleeds or blocks
i. Bleed: leakage of blood from vessels (30%, but higher mortality)
ii. Block: blood can’t get through vessels (70%)
2. Bleeding = hemorrhagic stroke
a. Ruptured vessel: blood leaks into CNS
b. Vulnerable vascular structures:
i. Aneurysm: abnormal expansion weakens vessel, especially at
bifurcations
ii. Arteriovenous malformation: abnormal connection of arteries and veins
3. Blockage = Ischemic stroke
a. Thrombosis:
i. Block from clot formed in vessel due to atherosclerotic plaque
ii. Develops slowly
b. Stenosis
i. Arteriosclerosis: gradual thickening of vessel walls
c. Embolism:
i. Dislodged clot, air bubble, fat particle; most often clot from atrial fibrillation
ii. Develops rapidly
4. Cerebral vascular accident and cardiac arrest
a. Cardiac arrest: cessation of blood flow to CNS
b. 10 seconds of consciousness
c. Lack of ATP to maintain ion pumps in membranes
d. Cytotoxic Edema: swelling of cells in brain
5. Cerebral hypoperfusion
a. Transient ischemic attacks (TIAs)
i. Similar to stroke but temporary (resolves within a day)
ii. Focal neurologic dysfunction: deficits due to focal ischemia
1. Motor or sensory symptoms
2. Visual
3. Memory (transient global amnesia - hippocampus)
iii. Negative MRI
iv. Warning sign for thrombotic stroke: clinical follow up is very important
v. Concerns: atherosclerosis and cardiovascular disease
6. Mass effect from CVA

21
 a. Early: hematoma enlargement causes midline shift
b. Late: edema causes midline shift
c. Temporal progression of CVA
i. Hemorrhage
ii. Hours: infarction
iii. Hours to days: mass effect hematoma
iv. Weeks: mass effect edema
7. Two main arterial sources of CNS: Vertebral and Internal Carotid Artery
8. Vertebral artery: supplies posterior circulation
a. Branches: Anterior spinal artery, bulbar branches, posterior inferior cerebellar
artery (PICA), basilar artery formed by 2 vertebral arteries
b. Anterior spinal artery
i. Supplies the ventral portion of the spinal cord
ii. Lateral corticospinal tract lesion → contralateral hemiparesis of lower limb
iii. Medial lemniscus lesion → ↓ contralateral proprioception
iv. Caudal medulla-hypoglossal nerve lesion → ipsilateral hypoglossal
dysfunction (tongue deviates ipsilaterally)
v. Stroke commonly bilateral
vi. Medial medullary syndrome: caused by infarct of paramedian branches of
ASA and vertebral arteries
c. Basilar artery branches: basilar, anterior inferior cerebellar artery (AICA),
labyrinthine, posterior cerebral, superior cerebellar, circumferential
i. Anterior inferior cerebellar artery
1. Supplies the pons, CN VII, and inferior surface of cerebellum
2. Lateral pons lesion (cranial nerve; vestibular, facial, spinal
trigeminal, and cochlear nuclei, sympathetic fibers →
a. Vomiting, vertigo, nystagmus, paralysis of face, ↓
lacrimation, salivation, ↓ taste from anterior ⅔ of tongue, ↓
corneal reflex
b. Face: ↓ pain and temperature sensation. Ipsilateral ↓
hearing. Ipsilateral Horner’s syndrome
3. Lateral pontine syndrome: facial nucleus effects are specific to
AICA lesions. Facial droop = AICA is bad
4. Middle and inferior cerebellar peduncles lesion →
a. Ataxia, dysmetria
ii. Labyrinthine: inner ear (deafness; vertigo)
iii. Paramedian: medial pons (CST, VI N. and nuc.)
iv. Circumferential: Lateral pons (V N, VII N, STT)
d. Posterior inferior cerebellar artery
i. Lateral medulla (vestibular nuclei, lateral spinothalamic tract, spinal
trigeminal nucleus, nucleus ambiguus, sympathetic fibers, inferior
cerebellar peduncle) lesion →
1. Vomiting, vertigo, nystagmus; ↓ pain and temperature sensation to
limb/face; dysphagia and hoarseness, ↓ gag reflex; ipsilateral

22
 Horner’s syndrome; ataxia, dysmetria
ii. Lateral medullary (Wallenberg's) syndrome: nucleus ambiguus effects are
specific to PICA lesions → dysphagia and hoarseness
e. Posterior Cerebral Artery
i. Occipital cortex, visual cortex lesions → contralateral hemianopia with
macular sparing
f. Paramedian brain stem infarcts causes
i. Medial lemniscus (ML): contralateral loss of tactile discrimination
ii. Contralateral spastic hemiparesis (paralysis of arms, legs, trunk)
iii. General somatic efferent CN: ipsilateral impairment of CN XII, VI, III
iv. CST + GSE CN XII, VI, III = alternating hemiplegia (hemiplegia in
ipsilateral and contralateral side of different parts of body)
g. Lateral brain stem infarcts
i. Spinothalamic tract: contralateral loss of pain/temp sensation
ii. CN V: trigeminal sensory loss
iii. Ipsilateral special visceral efferent: Dysphagia (pharynx), dysphonia
(larynx)
iv. Descending autonomics: Horner’s syndrome
9. Internal carotid artery supplies anterior circulation
a. 4 Segments:
i. Cervical: from carotid bifurcation until it enters carotid canal
ii. Petrous: inside petrous part of temporal bone
iii. Cavernous: surrounded by cavernous sinus
iv. Supraclinoid: begins after cavernous sinus
b. 5 Branches
i. Ophthalmic artery
ii. Anterior cerebral artery:
1. Supplies medial portions of frontal lobe and superior medial
parietal lobes, corpus callosum, olfactory bulb
2. Motor cortex (lower limb) lesion → contralateral paralysis
3. Sensory cortex (lower limb) lesion: contralateral loss of sensation
iii. Middle cerebral artery:
1. supplies lateral cerebral cortex (motor and somatosensory cortex,
broca’s, auditory, and Wernicke’s area)
2. Motor cortex (upper limb and face): contralateral paralysis
3. Sensory cortex (upper limb, face): contralateral loss of sensation
4. Temporal lobe (Wernicke’s area); frontal lobe (Broca’s area) →
aphasia if in dominant (left) hemisphere. Hemineglect if non.
5. Sylvian triangle: angiogram shows a triangle; displacement of
triangle indicates space occupying lesion (mass effect)
iv. Anterior choroidal artery
v. Posterior communicating artery
c. Circle of Willis
i. Arterial wreath to equalize blood flow

23
 ii. Anterior and posterior cerebral
1. Anterior: Callosomarginal; Frontopolar; Pericallosal
2. Posterior: Calcarine artery, Posterior cerebral
iii. Anterior and posterior communicating
1. Anterior communicating: common site of berry aneurysm →
impingement on cranial nerves → visual field defects
2. Posterior communicating: common site of berry aneurysm → CN
III palsy (eye is down and out)with ptosis and pupil dilation
iv. Small segment of internal carotid
v. Branches:
1. Cortical branches to cortical surface
2. Central branches to deep structures
10. Effects of Strokes
a. Middle cerebral artery
i. Affects motor and sensory of lateral cortex → contralateral paralysis and
loss of sensation of upper limb and face
ii. Affects temporal lobe (Wernicke’s area) or frontal lobe (Broca’s area) →
aphasia if in dominant (left) hemisphere. Hemineglect if nondominant
iii. Does not affect legs (supplied by anterior cerebral artery) or capsule
b. Anterior cerebral artery
i. Affects motor and sensory of medial cortex → contralateral paralysis and
loss of sensation of leg and foot
ii. All other motor areas intact
c. Lateral striate artery
i. Affects striatum and internal capsule → contralateral hemiparesis
ii. Common location of lacunar infarcts secondary to unmanaged HTN
11. Lesion localization
a. Differential diagnosis for lesions of:
i. Anterior cerebral artery: foot and leg motor and sensory
ii. Middle cerebral artery: face and arm (everything except foot and leg)
iii. Capsular infarcts: internal capsule → leg, arm, and face

Energy Metabolism in the Brain

1. Importance of glucose homeostasis
a. 80 mg/100 mL = normal level
b. 65 mg = release of glucagon, epinephrine
c. 60 mg = decreased attention, motor skills, sweating, hunger ,drowsiness
d. 40 mg = lethargy, coma
e. 25 mg = convulsions
f. 15 mg = permanent damage, death
2. Distinguishing features of brain energy metabolism
a. Brain requires some glucose all the time
i. 85% of glucose is used for ATP production
ii. 15% of the glucose is used for biosynthetic reactions (neurotransmitters,

24
 nonessential amino acids, NADPH, glycogen synthesis, membrane lipids)
b. Cannot use long chain fatty acids as an energy source due to BBB
c. Brain consumes 20% daily calories (much higher % in an infant)
i. Greatest energy demand is to maintain electrochemical gradients in
neuron via ion pumps, especially Na/K ATPase
ii. Requires continuous supply of oxygen
iii. Glucose is major fuel of brain, but ketone bodies used during starvation
d. Early fasting state:
i. Pancreas secretes glucagon → stimulates glycogenolysis
ii. Gluconeogenesis from muscle breaking down to amino acid (alanine)
e. Fasting state:
i. Gluconeogenesis from muscle breaking down to amino acid (alanine)
ii. Fat is being broken down to fatty acids and glycerol → ketone bodies
1. Ketone bodies: Acetoacetate; D-β-Hydroxybutyrate; Acetone
3. Glucose homeostasis in the newborn
a. Before birth, fetus relies on mother for glucose
b. At birth, newborn’s glucose falls → hormonal stress response
i. Most important hormonal response is surge of glucagon →
glycogenolysis and gluconeogenesis
c. Ketogenesis is very active; KB needed to supplement glucose as fuel for the
brain
d. Babies have more active KB production/utilization than adult, even when well fed
4. Three energy systems of muscle and brain
a. Immediate: phosphagens (ATP and phosphocreatine)
i. Phosphocreatine + ADP → ATP + Creatine
ii. Bursts of pumping ions across membrane of neuron cause transient drop
in ATP level and rise in ADP level → Shifts reaction to the right
iii. During recovery phase: ATP levels rise and ADP levels decrease →
reaction moves to the left
b. Short term: anaerobic glycolysis; Glucose/glycogen → Lactate
i. Pyruvate + NADH → Lactate + NAD+
ii. Astrocytes produce lactate and send it to neurons
c. Long term: Aerobic
i. Aerobic glycolysis: Glucose + O2 → CO2 + H2O
ii. Fatty acid oxidation: FA + O2 → CO2 + H2O
iii. Ketone bodies: KBs + O2 → CO2 + H2O
5. Transport through the blood brain barrier
a. Impermeable to most fatty acids (fatty acid oxidation not a source of ATP in
brain)
b. Permeable to glucose (main fuel usually) via GLUT1 and GLUT3 transporters
c. Permeable to alternate fuels: ketone bodies, lactate, acetate and pyruvate; via
monocarboxylate transporter
i. Transporter is induced during ketosis or hypoglycemia
d. Permeable to selected amino acids, essential fatty acids

25
 6. Glutamate is major excitatory NT in brain
a. α-Ketoglutarate + Aspartate → Glutamate + Oxaloacetate; E: transaminase, PLP
i. Transamination reaction trades amino group for carbonyl group

ii.
b. α-ketoglutarate + NADPH → glutamate + NADP; E: glutamate dehydrogenase
c. Glutamate + Amine at carboxy terminal side chain; E: glutamine synthetase
d. Glutamine → Glutamate; E: glutaminase
7. Excitotoxicity
a. Caused by over-accumulation of glutamate in synaptic cleft
b. Very common, usually due to ATP depletion from hypoglycemia or hypoxia
c. Will be discussed in lecture 3

Introduction to CNS Pharmacology

1. Review of synaptic transmission (CNS drugs exert effects at one more general sites)
a. NT synthesized in nerve terminals and stored in vesicles
b. AP propagate down axon and depolarize nerve terminal
c. Terminal depolarization causes Ca2+ influx
d. Ca2+ influx leads to vesicles fusion and NT into synaptic cleft
e. Released NT binds to its receptors which mediate response
f. NT cleared from synaptic cleft by diffusion, re-uptake, metabolism, or
degradation
g. Synaptic vesicles lipids and proteins are endocytosed and recycled
2. Types of ion channels and receptors in CNS
a. Voltage-gated ion channel: fast drug action, drug modulates ion channels,
directly affects neuronal function
b. Ligand-gated ion channels: fast drug action (ligand → drug directly opens →
modulates ligand-gated ion channels)
c. G-protein coupled receptors (GPCRs): slower, multiplicity of action: ligand/drug
modulates many systems; amplification
3. Amplification
a. Signal amplification: signal produces many molecules of diffusible messengers
b. Space amplification: signal not limited to immediate receptor site

26
 c. Time amplification: signals can be long-lasting
4. Neurotransmitters
a. Small molecules: amino acids, acetylcholine, monoamines
b. Peptides: opioid peptides, orexin, CGRP, substance P
c. Endocannabinoids: anandamide, 2-arachidonoylglycerol
5. Glutamate (amino acid)
a. Most abundant excitatory NT in CNS
b. Most excitatory synapses in CNS are glutamatergic
c. Glutamate synthesized from glutamine in nerve terminal mitochondria
d. Glutamate transporters clear glutamate from synapse
e. Glutamate receptors
i. Metabotropic receptors: presynaptic and/or postsynaptic, modulate
intracellular signal transduction
ii. Ionotropic receptors: KAR (Na channel), AMPAR(Na channel), NMDAR
(Na and Ca channel, requires glycine and depolarization); cation
channels
6. GABA
a. Most inhibitory synapses in CNS are GABAergic
b. Synthesized in nucleus accumbens
c. Decreased in anxiety and Huntington’s
d. GABA synthesized from glutamate by glutamic acid decarboxylase (GAD)
e. GABA transporters clear GABA from synapse
f. GABA catabolized to glutamine by GABA-transaminase (GABA-T) in
mitochondria
g. GABA receptors (2)
i. GABAA receptors: postsynaptic ionotropic receptor, ligand-gated ion
channel, Cl- in → hyperpolarizes cell
ii. GABAB receptors: metabotropic receptor (GPCR); presynaptic: inhibits
adenylyl cyclase, hyperpolarizes cell, and ↓ Ca into cell; postsynaptic:
inhibits adenylyl cyclase and hyperpolarizes cell
7. Acetylcholine
a. Primary neurotransmitter in ANS and NMJ; also in CNS
b. Implicated in Alzheimer’s, Huntington’s and Parkinson’s diseases, normal sleep-
wake cycle, pain perception, and hallucination
c. Synthesized in basal nucleus of Meynert
d. Ionotropic receptors (nicotinic receptors; nAChRN)
e. Metabotropic receptors (GPCR; muscarinic receptors; mAChR; M1-4)
8. Monoamines
a. Catecholamines: dopamine, norepinephrine, epinephrine
i. Tyrosine (E: tyrosine hydroxylase) → DOPA (dopa decarboxylase) →
dopamine (E: dopamine β-hydroxylase) → NE (phentolamine N-
methyltransferase) → EPI
b. Dopamine (DA)
i. Mostly from substantia nigra; Synthesized from tyrosine

27
 ii. ↑ in schizophrenia, ↓ in depression, anxiety and ↓ Parkinson’s disease
iii. DA loaded into vesicles via vesicular monoamine transporters (VMAT)
iv. Catabolized by monoamine oxidase (MAO), inactivated by COMT
v. DA transporters (DAT) clear DA from synapse
vi. All receptors are metabotropic (GPCR)
c. Norepinephrine
i. Most CNS regions receive diffuse NE inputs, more prevalent in
hypothalamus, amygdala, and dentate gyrus
ii. Synthesized in locus coeruleus (pons)
iii. NE systems implicated in sleep-wake cycle, attention, feeding,
depression
1. ↑ in anxiety and ↓ in depression
d. Serotonin (5-hydroxytryptamine; 5HT)
i. Synthesized from tryptophan (E: tryptophan hydroxylase) → 5-
hydroxytryptophan (E: L-amino acid decarboxylase) → Serotonin
ii. Synthesized in raphe nuclei or midline regions of pons/upper brainstem
iii. Most CNS regions receive diffuse serotonergic inputs; more prevalent in
cerebral cortex, limbic system, and diencephalon
iv. ↓ in depression, anxiety, stress, schizophrenia, hallucinations, OCD,
substance abuse; migraine, sleep, temperature, neuroendocrine control
v. Loaded into vesicles via VMAT, catabolized by MAO
vi. 5HT transporters (SERT) clear 5HT from synapse
vii. Receptors (15 subtypes)
1. 5HT3: ligand-gated cation channel; mediates EPSPs, emesis and
anti-nociception
2. All remaining are GPCR
9. Neuropeptides
a. Opioid peptides (enkephalin, endorphin, dynorphin), substance P, orexin, CGRP
b. Neuropeptides differ from classical NT:
i. Prepropeptides synthesized in rough ER, cleaved and transported to
release sites
ii. Needs high frequency stimulation (one AP not enough to release it)
iii. Slow and far reaching
10. Endocannabinoids
a. Receptors (CB1, CB2) are metabotropic (GPCR)
b. CB1 is primary receptor in CNS; inhibits adenylyl cyclase and Ca2+ conductance
c. Implicated in memory, cognition and pain perception
d. Not stored in synaptic vesicles
e. Endogenous brain lipids synthesized after neuronal depolarization and Ca2+
influx
f. Can act as retrograde transmitters; released from postsynaptic neuron and
activate receptors on presynaptic terminal

Metabolism of the Nervous System

28
1. The role of some cofactors in amino acid and nitrogen metabolism
a. Pyridoxal phosphate (PLP)
i. The quintessential coenzyme (Everywhere in AA pathways)
ii. Carries out >10 types of reactions
1. Decarboxylation of amino acids (most important) → amine
2. Transamination
3. Racemization
4. γ-elimination
5. β-elimination
b. Tetrahydrobiopterin (BH4)
i. Catalyzes ring hydroxylations (attaches OH to rings)
ii. Ex: Phenylalanine → Tyrosine
iii. Phenylketonuria: inability to convert phenylalanine → tyrosine
c. S-Adenosylmethionine (SAM)
i. Methylating agent (adds CH3)
ii. Examples of most common reactions
1. RNH3 + SAM → RNH2-CH3 + SAH
2. ROH + SAM → ROCH3 + SAH
3. SAH = S-Adenosylhomocysteine (SAM minus 1 CH3)
2. Catecholamines
a. Synthesis:
i. Phenylalanine → Tyrosine; E: Phenylalanine hydroxylase, BH4
ii. Tyrosine → DOPA; E: Tyrosine hydroxylase, BH4
iii. DOPA → Dopamine; E: DOPA decarboxylase, cofactor PLP
iv. Dopamine → Norepinephrine; E: Dopamine β-hydroxylase, Cu, Vit C
v. Norepinephrine → Epinephrine; phenylalanine N-methyltransferase, SAM
b. Key enzymes of inactivation
i. Catechol-O-methyltransferase (COMT)
1. Reaction: SAM + ROH → ROCH3 + SAH
2. SAM resynthesis requires folate, B12
ii. Monoamine oxidase (MAO)
1. Two isoforms, MAO-A and MAO-B with different specificities
2. Reaction:
a. RCH2NH2 + O2 and FAD → FADH2 + H2O2 + RCH=NH
b. RCH=NH + H2O → RCH=O + NH3
3. Metabolism of Serotonin
a. Synthesis
i. Tryptophan → 5-Hydroxytryptophan; E: Tryptophan hydroxylase, BH4
ii. 5-Hydroxytryptophan → Serotonin; E: DOPA decarboxylase, PLP
b. Inactivation
i. Serotonin → 5-hydroxyindole-acetaldehyde; E: MAO-A
ii. 5-hydroxyindole-acetaldehyde → 5-hydroxyindole acetic acid
4. Metabolism of histamine
a. Synthesis: Histidine → Histamine; E: histidine decarboxylase, PLP

29
 b. Inactivation: SAM and MAO
5. Metabolism of acetylcholine
a. Synthesis
i. Acetyl CoA + Choline → Acetylcholine + CoA; E: choline
acetyltransferase
ii. Acetyl CoA from glucose; Choline mainly from diet
b. Inactivation: Acetylcholine → Acetic acid + Choline; E: acetylcholinesterase
6. γ-Amino Butyric Acid (GABA) metabolism
a. Glutamate: amino acid with CH2CH2COOH side chain
b. Glutamate → GABA + CO2; E: Glutamic acid decarboxylase, PLP
c. GABA → Glutamate; E: GABA transaminase (by glial cells)
d. Glutamate is converted to glutamine to be transported back to neuron

Introduction to Neuroimaging
1. What am I looking at
a. CT scan: bone is white (look for petrous bone)
b. MR scan: bone is black
i. If white matter is white → T1 weighted
ii. If not; is CSF/eyeballs white?
1. Yes → T2-weighted (ADC)
2. No → FLAIR, DWI, GRE
iii. Fuzziness = ADC or DWI

c.
2. Basic Approach
a. Location of lesion:
i. Boundary between intra and extra is pia; gray matter at skull
ii. Intraaxial: lesion is within brain parenchyma
iii. Extraaxial: lesion is outside brain parenchyma; gray matter being pushed

30
 away from skull (Example: meningioma, can be removed by surgery)
iv. Intraventricular
v. Supratentorial: above tentorium cerebelli
vi. Infratentorial: below tentorium cerebelli
b. Age of patient
i. Child
ii. Adult
c. Sex of patient
3. Brain concentric layers
a. Scalp and skull
b. Epidural space
c. Dura and arachnoid
d. Pia
e. Brain:
i. Cortex (gray matter)
ii. White
iii. Deep Nuclei (gray matter)
iv. Ventricles: Ependyma and CSF
4. Cortical Tubers
a. Big lumpy gray matter but the inside looks like white matter = loss of myelin
b. Cortical islands with unmyelinated axons
5. Acute neuroimaging: scan 3 key slices

a.

31
 b.
i. Star is suprasellar cistern
ii. Smile is quadrigeminal plate cistern

c.
6. Epidural hematoma
a. Usually acute clinical presentation
b. Young male patients, usually <40 (dura firmly fixed in older patients)
c. Usually unilateral
d. Usually associated with skull fracture
e. Lucid interval: patient wakes up, 40% (talk and die patients)
f. Does not cross sutures, and convex towards brain
g. Significant trauma
h. Fracture and concussion (loss of consciousness)
i. Delayed neurologic symptoms (hours later)
j. Herniation, coma and death
7. Subdural hematoma
a. On top of arachnoid
b. Concave towards brain
c. Source of blood
i. Laceration of cortical artery and vein; Direct: penetrating injury
ii. Large contusion; direct/indirect: pulped brain

32
 8. Belly of Pons
a. Dunlop’s disease: belly of pons lopped over medulla

Bacterial Meningitis
1. Infections of the CNS
a. Categorized by anatomic part of brain affected
i. Brain parenchyma = encephalitis or brain abscess
ii. Meninges = meningitis
iii. Spinal cord tissue = myelitis
2. Definition of meningitis
a. An inflammation of the meninges with the exudative response in the CSF
b. Agents include bacteria, viruses and fungi
c. Meninges are the 3 membranes that cover the brain and spinal cord (dura mater,
pia mater, and arachnoid mater)
d. Causes of bacterial meningitis: streptococcus pneumoniae (58%), neisseria
meningitidis (14%), Group B Streptococcus (18%), haemophilus influenzae (7%),
listeria monocytogenes (3%)
3. Review of Streptococcus pneumoniae
a. Gram +, cocci, catalase negative, α hemolytic, bile soluble, optochin sensitive
b. Primary virulence: capsule; conjugate vaccine against capsule
c. Leading cause of death in US: pneumonia, bacteremia, meningitis, otitis media
4. Conditions that predispose patients to bacterial meningitis
a. Age: very young or very old
b. Immunocompromised
c. Basal skull fracture
d. Head trauma, post neurosurgery
e. Cerebrospinal fluid shunt
5. Etiology by age
a. Newborns (0-6 months): Group B strep, E. coli, Listeria monocytogenes
b. Children (6 months - 6 years): S. pneumoniae, Neisseria meningitidis, H.
influenzae, enteroviruses
c. 6-60 years: S. pneumoniae, N. meningitidis (#1 in teens) , mycobacteria,
enteroviruses, HSV
d. 60+: S. pneumoniae, gram-negative rods, listeria
6. Key steps in development of bacterial meningitis
a. Hematogenous delivery of bacteria to subarachnoid space
b. Host immune response
c. Edema
d. Increased intracranial pressure
e. Decreased cerebral blood flow
f. Damage, seizures, herniation
7. Sign and symptoms
a. Classic triad: sudden onset of fever, headache, and nuchal rigidity (stiff neck)
b. Kernig’s sign: inability to straighten knee when hip is flexed at 90

33
 c. Brudzinski’s sign: while flat on back, flexion of neck causes patient to flex knees
d. Also often accompanied by: nausea, vomiting, increased sensitivity to light
(photophobia), altered mental status (confusion)
8. Diagnostic laboratory tests
a. Examination of the CSF is the most important test
b. Cell count, gram stain, antigen tests; culture is gold standard
c. Typical CSF findings in various types of meningitis
i. Normal: < 5 WBCs in adults and <20 WBCs in newborn
ii. Bacterial meningitis: > 1000 WBC, PMNs, ↑ protein, ↓ CSF glucose
iii. Viral: <100 WBC, lymphocytes, ↑/normal protein, normal CSF glucose
iv. Fungal and Tubercular: ↑ lymphocytes, ↑ protein, ↓ CSF glucose
9. Neisseria Meningitidis
a. Overview
i. Gram negative diplococci; maltose and glucose fermenter
ii. Oxidase positive; has cytochrome C oxidase → reduction of dye to blue
iii. Aerobic but will multiply under microaerophilic conditions; chocolate agar
b. Major virulence factor
i. Polysaccharide Capsule: antiphagocytic, interferes with complement
deposition and prevents C3b mediated uptake by phagocytes
ii. 12 serogroups for capsule: in US, Group B and C most often cause
meningitis; in Africa, group A and W-135.
iii. Antibodies to type B capsule cross-react with E.coli K1 capsule
iv. No vaccine for Group B capsule due to cross reaction with own tissue
v. Abs against capsular polysaccharide are bactericidal with complement
c. Other virulence determinants
i. Produces IgA proteases; a similar protease made by H. influenzae, S.
pneumoniae, and N. gonorrhoeae
ii. LOS: toxic properties of the meningococcus reside in LOS
d. Clinical spectrum
i. Asymptomatic pharyngeal carrier ( = focus of infection)
1. 5-10% of population are carriers
2. In closed populations (ex: barracks/dorms) carrier rate increased
3. Overall, low incidence of disseminated disease after colonization
in adults, higher incidence in children <5 years
ii. Meningococcemia = meningococci in blood; may occur with or without:
1. Petechiae and/or purpura (hallmark or Neisseria Meningitidis)
2. Waterhouse-Friderichsen syndrome: shock, disseminated
intravascular coagulation, bilateral destruction of adrenal glands
3. Meningitis
4. Chronic recurring meningococcal disease: rare; associated with
complement deficiency (C6, C7, or C8)
e. Epidemiology
i. Spreads through respiratory and oral secretions
ii. Age: unvaccinated 6 month to 3 years of age; #1 cause in teens

34
 iii. Serogroup: incidence varies with serogroup and location of outbreak.
1. Serogroup A causes epidemics in less developed nations (Africa)
2. Serogroup B vaccine 4CMenB used at Princeton and UCSB
f. Immunity
i. Tetravalent conjugate vaccine called MCV4
ii. Recommended for persons aged 2-10 and 19-55 at increased risk:
1. College freshmen living in dorms
2. Microbiologists
3. Military recruits
4. Travelers to or residents of countries that have N. meningitidis
5. Persons with terminal complement component deficiencies or with
anatomic or functional asplenia.
10. Group B streptococci (Streptococcus agalactiae)
a. Overview
i. Most common cause of neonatal meningitis
ii. Colonizes vagina
iii. Pregnant women are tested for Group B strep at 35-37 week
b. Laboratory identification
i. Gram + cocci, catalase -, β hemolytic and bacitracin resistant
ii. CAMP test positive: CAMP factor is extracellular protein that reacts
synergistically with β-lysin of S. aureus
iii. Confirm group B strep by detection of group B-specific cell wall antigen
c. Infections
i. Neonatal: early onset (acquired in utero or at birth) and late onset
(outside)
ii. Adults
1. Pregnant or postpartum: bacteremia
2. Non-pregnant adults (most commonly elderly or individuals with
chronic, underlying diseases): bacteremia, meningitis, cellulitis.
Adults are more likely to die from group B strep than infants
d. Prevention
i. Penicillin G iv during labor (or ampicillin) to women with positive test
11. Listeria monocytogenes
a. Overview
i. Vaginal transmission during birth
ii. Food-borne pathogen (ex: soft cheese, deli meats, hot dogs)
iii. Can cause miscarriage and stillbirths in pregnant women, severe
systemic disease in immunosuppressed, and gastroenteritis in healthy
b. Properties
i. Organism is psychrophilic (grows at cold temperatures) or mesophilic
(grows at moderate temperatures) and widely distributed in nature
ii. Gram positive rod, motile, non-sporulating, aerobic to microaerophilic,
and catalase and CAMP positive; β hemolytic on blood agar
c. Cellular pathogenesis of L. monocytogenes

35
 i.Facultative intracellular pathogen
ii.Essential virulence factor: listeriolysin (LLO), promotes release of bacteria
from phagosomes into the cytoplasm, hemolytic factor on blood agar
iii. After bacteria escapes from phagosomes, organism multiplies in
cytoplasm and move within cell by mechanism that involved host actin
polymerization mediated by ActA produced by L. monocytogenes
1. Actin rockets to move from cell to cell
iv. Bacteria then spread directly from cell to cell without re-entering the
extracellular space
v. Characteristic tumbling motility
d. Disease:
i. Spontaneous abortion in pregnant women
ii. Neonatal meningitis and meningitis immunocompromised patients
iii. Mild gastroenteritis in healthy individuals
e. Immunity
i. Infections are terminated by cell-mediated immune response of host
ii. Immunosuppressed patients at high risk; should not each lunch meat
iii. Pregnant women should not eat lunch meat either, baby is susceptible

Viral Infections of CNS

1. Viral infections of CNS
a. Functions of CNS and its metabolic requirements can be disrupted by virus
b. Routes of infections: Blood-borne or Neuronal spread
i. Viremia: hematogenous spread (circulating through blood)
1. Infect capillary endothelial cells of blood brain barrier
2. Directly infect glial cells then infect neuron
3. Leukocyte-associated
4. Agents: Enteroviruses, systemic paramyxoviruses, arboviruses
ii. Neuronal spread → encephalitis
1. Agents: Herpes virus, Rabies virus
2. Direct neuron killing
c. Clinical features: Acute meningitis or encephalitis
2. Major agents
a. Picornavirus family: enteroviruses; most common cause of meningitis
b. Paramyxovirus family: Mumps virus; Measles virus
c. Herpesvirus family: HSV-1 and 2; VZV, CMV
d. Arboviruses
i. WEE, EEE, VEE (alphaviruses)
ii. St. Louis, West Nile (Flaviviruses)
iii. California/La Crosse (Bunyaviruses)
e. Rabies
f. HIV
3. Clinical manifestations/pathogenesis
a. Often parenchymal disease → direct viral infection and killing of neurons

36
 i. Pathologic findings unique for different viruses
b. Viral meningitis: fever, vomiting, headache, nuchal rigidity and photophobia
c. Viral encephalitis: fever, headache; but also: alterations in consciousness,
confusion, seizures, paralysis, changes in sensation or vision
d. Examples of direct infection with killing of neural cells (encephalitis):
i. Herpes (HSV): hemorrhagic necrosis w/ inflammation and neuronophagia
ii. Poliovirus: destruction motor neurons in spinal cord and brainstem
iii. Rabies virus: infects and destroy neurons
4. Major initial symptoms
a. Viral: headache, fever, vomiting
b. Bacterial: headache, fever
c. CSF:
i. Viral: <100 WBC, lymphocytes, ↑/normal protein, normal CSF glucose
ii. Bacterial: 1000-5000 WBC, elevated protein, + gram stain and culture
d. Rapid diagnosis: CSF IgM titers and PCR techniques for viral
e. Presence of pathogen-specific IgG in CNS at levels similar or higher than in
serum will often be diagnostic
f. In chronic infections, pathogen-specific CSF IgG is more useful than serum
5. Picornaviruses family
a. Non-enveloped, icosahedral structure, Positive ssRNA (RNA is infectious)
b. RNA translated into 1 large polypeptide → cleaved by proteases into viral
proteins
c. Enterovirus members spread fecal-orally: Poliovirus, Echovirus, Coxsackievirus
d. Causes aseptic (viral) meningitis
6. Pathogenesis of enterovirus infection
a. The target tissue infected by enterovirus determines the predominant disease
b. Brain (encephalitis): polio, coxsackie
c. Meninges: Echo, polio, coxsackie
7. Poliovirus
a. Background
i. 3 serotypes (1, 2, and 3) but no common antigen (vaccine for each)
ii. Have identical properties but only share 50% nucleotide homology
iii. Humans are the only susceptible hosts
iv. Polioviruses are distributed globally. Before vaccines, almost 100% of
population in developing countries became infected before age 5
v. Poliovirus is on course to be eradicated worldwide
b. Transmission
i. Infection spreads through the GI route
ii. Reproduces in lymphoid tissue
iii. Secondary viremia spreads infection to CNS
iv. Mainly affects motor neurons of the anterior horn of the spinal cord
c. Clinical Presentation
i. Subclinical infection (95%); mild: viral syndromes (fever, malaise, emesis)
ii. Severe: asymmetric motor paralysis with intact sensation during fever

37
 1. Anterior horn cells (motor neurons) → flaccid paralysis, medulla
infection may lead to respiratory paralysis and death
iii. Aseptic meningitis, urinary retention, muscle spasm may also be seen
d. Vaccines
i. Salk (IPV)
1. Inactivated (killed) polio vaccine: first poliovirus vaccine
2. Stimulates serum antibody formation and secretory IgA antibody
3. Induces systemic serum antibody levels but not gut immunity
4. Currently used for immunosuppressed patients
5. Given as multiple doses (4 doses)
ii. Sabin (OPV)
1. Oral polio vaccine: attenuated (live) for all 3 serotypes
2. Attenuation achieved by passage in tissue culture
3. Induces mucosal IgA response and systemic immunity
4. Induces a cellular response
5. Rarely associated with paralytic poliomyelitis
6. Attenuation and reversion to wild-type virus is a risk of Sabin
a. Type 1: replicates most efficiently
b. Type 2: fewer mutations
c. Type 3: fewest mutations; reacquires 5’ wild type sequence
iii. Both vaccines cause serum and secretory antibody response; IgA
8. Arboviruses viruses: bunyaviruses, togaviruses, flaviviruses
a. Background
i. Arbo = arthropod borne viruses; uses insects as a vector
ii. Transmission by mosquitoes and ticks; reservoir is an animal
iii. All cause encephalitis
iv. All are enveloped RNA viruses
v. Flavivirus: West nile, St. Louis, Japanese encephalitis
vi. Togavirus: Eastern equine encephalitis (EEE), Western (WEE),
Venezuelan (VEE)
vii. Bunyavirus: California Encephalitis/La Crosse, Jamestown Canyon
b. Disease symptoms
i. Flu-like symptoms: usually non-specific, resembling other viral illnesses
such as influenza (fever, rash, aches, chills)
ii. Patients may progress to encephalitis
iii. Encephalitis: EEE/WEE/VEE, West Nile, St. Louis, California, Japanese
c. Diagnosis
i. Serology: usually used to diagnoses arbovirus infections
ii. Direct detection tests also: PCR
d. Prevention
i. Surveillance: vector/reservoir populations
ii. Control of vector: pesticides
iii. Personal protection: screening of houses
iv. Vaccination: available for some

38
9. Flavivirus: West Nile Virus
a. Mild infection: most infections subclinical
b. Symptoms: Fever, weakness, rash on neck, trunk, arms or legs
c. Neurologic: myelitis, ataxia, seizures, optic neuritis, mental status change
d. Clinical suspicion of West Nile infection:
i. Adults (>50) developing unexplained encephalitis in Summer/Fall
ii. Presence locally of WNV in birds, animals, human cases
e. Diagnosis (state labs): ELISA for IgM in serum or CSF within 8 days
f. Treatment: supportive; hospitalization, fluid and respiratory support
g. Most significant risk for severe neurological disease is advanced age
10. Flavivirus: Japanese encephalitis
a. First discovered and originally restricted to Japan, now epidemic occurs in China,
India and other parts of Asia
b. Transmission cycle involves culex mosquitoes, birds, and pigs
c. Most infections are subclinical: 1 in 300 develops encephalitis
d. Diagnosed by serology; no specific therapy available
e. Single Culex has flight range of 20 km, local control measures fail
f. Effective killed virus vaccine available
11. Togaviruses: equine encephalitis viruses
a. Enveloped viruses transmitted by insects; equine encephalitis viruses
b. Pathology of WEE/EEE/VEE: flu-like symptoms can progress to encephalitis 3-10
days post-infection. Generally resolves without sequelae, but can cause
paralysis, mental disorders, death.
c. Eastern EE/Western EE: mosquito - bird - mosquito cycle
d. EEE is most infrequent; majority are asymptomatic or nonspecific fever
e. WEE is more frequent, infants prone to more severe brain damage; 60% of
survivors have neurologic impairment
f. VEE, wide distribution in Americas; used as biological weapon during Cold War
12. Bunyaviruses
a. California serogroup: California encephalitis, La Crosse, and others
b. Transmitted by Aedes mosquito
c. La Crosse Virus:
i. Most important cause of pediatric arbovirus encephalitis in US
ii. Localized in Midwest states
iii. Most infections are subclinical; disease in 5-18 year old
13. Seasonal Clues
a. Enterovirus peaks in summer time
b. Herpesvirus is all year round
14. Rabies
a. Background
i. Rhabdovirus; Enveloped, negative-sense ssRNA, bullet-shaped
ii. Causes acute encephalitis in warm-blooded host; fatal if untreated
b. Transmission
i. Animal reservoirs: raccoons, skunks, foxes, and coyotes, bats

39
 ii. Spread from saliva of host from bite then through neurons to brain
1. Also mucous membranes, aerosol, corneal and organ transplant
iii. Goes to CNS by migrating in retrograde fashion up peripheral nerve
axons
iv. Long incubation period (weeks to months) before symptom onset
c. Symptom progression:
i. Initially: fever and headache; 50% with tingling pain, itching at bit site
ii. Then: agitation, photophobia, hydrophobia, hypersalivation, hyperactivity
iii. Finally: paralysis, coma → death (100% death if untreated)
iv. Paralytic rabies: rapid progression of encephalitis, no hyperactivity
d. Diagnosis:
i. Negri bodies are characteristic inclusion bodies in infected neurons;
commonly found in Purkinje cells of cerebellum
e. Treatment
i. Postexposure treatment: wound cleansing and vaccination +/- rabies
immune globulin
ii. Recombinant vaccine
15. Paramyxovirus: Measles and Mumps
a. Enveloped, negative sense ssRNA
b. Contains surface F (fusion) protein, infects respiratory epithelial cells and causes
fusion and formation of multinucleated (syncytial) cells.
16. Mumps virus
a. Background
i. Mumps virus was the most common cause of encephalitis until 1975
ii. Systemic infection incubation period (3 weeks); 30% are subclinical
iii. Major morbidity due to meningitis, encephalitis, and orchitis
iv. Peak risk in post-pubertal boys that are unvaccinated
b. Clinical Presentation:
i. Starts in respiratory tract → viremia → spreads to different epithelial cells
ii. Most common sites of spread: Parotitis (inflammation of parotid glands);
Orchitis (inflammation of testes; usually unilateral)
iii. Aseptic meningitis
iv. Can cause sterility; especially after puberty
c. Vaccine
i. Live-attenuated vaccine → humoral and cell-mediated immune response
ii. Infants are protected for 6 months by maternal antibodies
17. Measles
a. Background
i. Remains leading cause of death among young children, despite vaccine
ii. One of the most contagious disease known; almost all non-immune
children contract measles if exposed
iii. Incubation period is 2 weeks: infects via respiratory tract, replicates
locally, spreads to lymphoid tissue by viremia, infects other organs
b. Clinical Presentation

40
 i. Symptoms due to immune response: rash from cell-mediated immunity
ii. Koplik spots (red spots with blue-white center on buccal mucosa)
iii. Descending maculopapular rash: presents from head to toe; includes
hands and feet
iv. SSPE (subacute sclerosing panencephalitis) occurs years later;
encephalitis, and giant cell pneumonia are possible sequelae
c. Vaccine
i. Live attenuated; given in Mumps, Rubella vaccine (MMR vaccine)
18. Herpes Simplex Virus
a. HSV-1 latent infection tends to reside in trigeminal ganglia
b. HSV-2 tends to reside in sacral ganglia → neonatal herpes
c. Most common and gravest form of acute encephalitis
i. HSV-1 most common cause; except in neonatal where type-2 dominates
d. HSV Identification
i. PCR is test of choice
ii. Tzanck test: smear of opened skin vesicle to detect multinucleated cells
iii. Infected cells also have intranuclear Cowdry A inclusions
e. Symptoms can reflect propensity to involve frontal and temporal lobes
(hallucinations, seizures, personality changes, and aphasia)
19. Congeital Infections
a. Maternally transmitted infections: transplacental mostly; or via delivery (HSV-2)
b. TORCH pathogens: Toxoplasma, Other (group B strep, E. coli, Listeria
monocytogenes), Rubella (togavirus), Cytomegalovirus (herpesvirus), Herpes
simplex type 2 also HIV-1, Syphillis
c. Congenital infections of the brain can produce diffuse, parenchymal inflammation
with microcephaly, brain atrophy, hydrocephalus, neuronal migrational anomalies
and cerebral calcifications
d. Earlier in gestation CNS involvement → worst brain destruction
20. Cytomegalovirus (CMV)
a. A herpesvirus which subclinically infects large portions of the population
b. Most frequent cause of a congenital viral infection
c. Congenital infection can occur after primary or secondary (reactivation) maternal
infection, virus reaches fetus via transplacental route
d. Earlier the infection = more severe and persistent neurologic sequelae
e. Causes diffuse encephalitic infectious process → multifocal destructive changes
in brain → calcifications and microcephaly
f. Infected cells have characteristic owl’s eye inclusions
g. Latent in mononuclear cells
21. Herpes Simplex Virus
a. Most cases of neonatal herpes encephalitis is HSV-2
b. Infection is most commonly acquired during delivery, although hematogenous
transmission through placenta can also occur
c. If infants surve early hematogenous infection, panencephalitis can cause
microcephaly, cerebral atrophy and necrosis, and intracranial calcification

41
 d. Drugs: Acyclovir and Ganciclovir
i. Mechanism: inhibition of viral DNA synthesis → block DNA replication
ii. Viral thymidine kinase
e. HIV-1
i. Majority of cases transmitted hematogenously through placenta
ii. Infants infected with HIV are asymptomatic at birth, presenting in time
with developmental delay and recurrent infections
iii. At 2-3 years of age, a progressive clinical syndrome evolves: seizures,
motor deficits, microcephaly, and behavioral and cognitive decline
22. Progressive Multifocal Leukoencephalopathy (PML)
a. JC virus (john cunningham)
b. PML is a disorder characterized by widespread foci of demyelination caused by
reactivation of a latent Polyomavirus
c. Most cases occur in setting of immunocompromised host secondary to
neoplasia, chemotherapy, or AIDS
d. Lesions are initially round or oval, then larger and more confluent in time
e. Initially subcortical white matter then spreads to deeper white matter
23. Meningoencephalitis
a. Dementia, ataxia, and paresthesias are common features
b. Due to enteroviruses
c. Now referred to as X-linked agammaglobulinemia (XLA), mapped to gene
encoding Bruton tyrosine kinase

Depressive Disorders
1. Age of onset of major psychiatric disorders
a. Bipolar I: 18
b. Bipolar II: 21.7
c. Major depressions: 26.5
2. Comorbidities
a. Anxiety
b. Substance abuse
c. Personality disorder
d. Eating disorders
e. Psychosis
3. Clinical evaluation of mood symptoms
a. Symptoms: mood, anhedonia, cognitive, sleep and energy, weight and appetite
b. Severity
c. Duration
d. Rule out other causes: medical condition, medication effect, alcohol, drugs
4. DSM-5: Diagnosis of disorders
a. Criteria (DSM-5 Section II)
b. Subtypes and/or specifiers
c. Severity: codes and recording procedures

42
 d. Explanatory text: diagnostic and associated features; prevalence; development
and course; risk and prognosis; culture and gender related factors; diagnostic
markers; functional consequences; differential diagnosis; comorbidity
5. Depressive disorders (unipolar)
a. Disruptive mood dysregulation disorder
b. Major depressive disorder
c. Persistent depressive disorder
d. Premenstrual dysphoric disorder
e. Substance/medication-induced depressive disorder
f. Depressive disorder due to another medical condition
g. Other specified depressive disorder
h. Unspecified depressive disorder
6. Major depressive episode (MDE)
a. 5 or more symptoms present nearly every day for at least 2 weeks and
represents change from previous functioning; at least one symptom is either
depressed mood or loss of interest/pleasure
i. Sleep disturbance: Insomnia or hypersomnia
ii. Loss of interest or pleasure in all or almost all activity
iii. Feelings of worthlessness or excessive or inappropriate guilt
iv. Fatigue or loss of energy
v. Diminished ability to think or concentrate, or indecisiveness
vi. Significant weight loss or appetite change
vii. Psychomotor agitation or retardation
viii. Recurrent thoughts of death, recurrent SI, suicide attempt or plan
ix. Depressed mood for most of the day
x. SIGECAPS: sleep; interest; guilt; energy; concentration; appetite;
psychomotor; suicidality
b. Symptoms cause clinically significant distress or impairment in social,
occupational areas
c. Episode not due to physiologic effects of substance or another medical condition
7. Major Depressive Disorder
a. MDE not better explained by psychotic spectrum disorder
b. There has never been a history of manic or hypomanic episode
8. Persistent depressive disorder (dysthymia)
a. Depressed mood for at least 2 years
b. At least 2 associated SIGECAPS symptoms while depressed
c. Not symptom free for >2 months
d. Criteria for Major Depressive Disorder may be continually present for 2 years
e. Criteria for Manic/Hypomanic Episode, or Cyclothymic Disorder never met
f. Not better explained by psychotic spectrum disorder
g. Not due to physiologic effects of substance or another medical condition
h. Symptoms cause clinically significant distress or impairment in social,
occupational areas
9. Premenstrual dysphoric disorder

43
 a. In majority of menstrual cycles, at least 5 symptoms must be present in final
week before onset of menses, start to improve within a few days after menses,
and become minimal in the week post menses
b. One or more of the following symptoms must be present: marked affective
lability, irritability, depressed mood or anxiety
c. One or more additional symptoms must be present
d. Symptoms cause clinically significant distress or impairment in social,
occupational areas
e. Symptoms not an exacerbation of another disorder
f. Criterion A should be confirmed by prospective daily rating for 2 cycles
g. Not due to physiologic effects of substance or another medical condition
10. Substance/Medication Induced Depressive Disorder
a. Predominant and persistent mood disturbance
b. Evidence from history, physical or labs that criterion A symptoms developed
during or soon after substance intoxication/withdrawal or exposure and the
involved substance is capable of producing Criterion A symptoms
c. Not due to physiologic effects of substance or another medical condition
d. Symptoms cause clinically significant distress or impairment in social,
occupational areas
11. Depressive Disorder Due to Another Medical Condition
a. Predominant and persistent mood disturbance
b. Evidence from history, physical or labs that disturbance is the direct
pathophysiological consequence of another medical condition
c. Not better explained by another mental disorder
d. Does not occur exclusively during course of delirium
e. Symptoms cause clinically significant distress or impairment in social,
occupational areas
12. Other specific depressive disorder
a. Symptoms are characteristic of depressive disorder, but do not meet full criteria
for any named disorder
b. Used in situations where clinician chooses to communicate specific reason why
presentation does not meet criteria for a specific depressive disorder
i. Recurrent brief depression
ii. Short-duration depressive episode
iii. Depressive episode with insufficient symptoms
13. Unspecific depressive disorder
a. Symptoms are characteristic of depressive disorder, but do not meet full criteria
for any named disorder
b. Used in situations where clinician chooses not to specify why presentation does
not meet criteria for a specific depressive disorder
14. Depressive disorder specifiers
a. With anxious distress: at least 2 symptoms (tense, restless, worry, impending
doom, might lose control)
b. With mixed features: at least 3 manic/hypomanic symptoms during MDE

44
 c. With melancholic features: at least 1 symptoms (loss of pleasure or lack of
reactivity); 3 or more
d. With atypical features: mood reactivity; 2 or more (weight gain, hypersomnia,
leaden paralysis, longstanding rejection sensitivity)
e. With psychotic features (delusions and/or hallucinations)
i. Mood congruent: content c/w depressive themes
ii. Mood incongruent: content now c/w depressive themes
f. With catatonia
g. With peripartum onset: onset during pregnancy or in 4 weeks following delivery
h. With seasonal pattern
15. Bipolar and Depressive Disorders
a. Defined by presence at least 1 manic (Bipolar I) or hypomanic (bipolar II) episode
b. Depressive symptoms always occur eventually
i. Patient’s mood and functioning returns to normal between episodes
c. Use of antidepressants can lead to switch to mania
d. High suicide risk
e. Cyclothymic disorder: dysthymia and hypomania; milder form of bipolar lasting at
least 2 years,
f. Disorders with unipolar depression
i. Major depressive disorder
ii. Persistent depressive disorder (Dysthymia)
iii. Other/Unspecified depressive disorder
iv. Depressive disorder due to another medical condition
v. Substance/medication induced depressive disorder
g. Disorders with/without major depressive episode (MDE)
i. Required:
1. Major depressive disorder
2. Bipolar II
ii. May be characterized by:
1. Bipolar I disorder
2. Other/Unspecified depressive disorder
3. Depressive disorder due to another medical condition
4. Substance/medication induced depressive disorder
iii. Does not have MDE
1. Cyclothymic disorder
16. Antidepressant treatment guidelines
a. Antidepressant titrated to maximum recommended dosage for minimum of 4-6
weeks for an adequate trial
b. Patients who show clinical improvement on a low dose of antidepressant may
continue at that dose
c. Treatment should continue for at least 6-9 months after stabilization
d. Antidepressants should typically be tapered at time of discontinuation
17. Adjunctive medications
a. Lithium

45
 b. Thyroid supplement
c. Stimulants (Ritalin, Dextroamphetamine)
i. Elderly
ii. Medically/Terminally ill
d. Atypical antipsychotics
e. Mood stabilizers
18. Course and prognosis
a. Average 5-6 episodes over 20 year
b. 10% depressive disorders later diagnosed as bipolar spectrum
c. 15% suicide
d. Relapse rate increases after each episode:
i. 40% after 1st episode
ii. 55% after 2nd episode
iii. 80% after 3rd episode
e. 20% chronic

Somatic Symptom Disorders

1. Somatic Symptom Disorders
a. Characterized by physical symptoms, but cannot be explained by medical
condition, effect of a substance, or another mental disorder.
b. One or more somatic symptoms that are distressing or causing significant
disruption of function
c. + excessive and disproportion thought (catastrophization), feelings (anxiety),
behavior (time or energy spent)
d. + Symptomatic for at least 6 months (state of being symptomatic)
e. Will be an overly utilized diagnosis
2. Somatic symptom disorder risk factors
a. Major Axis I: panic disorders, phobias, PTSD, major depressive disorder, etc.
b. Personality disorders
c. History of abuse (patient did not learn empathy)
d. Defense denial or hostility
e. History of chronic illness in patient or family member (saw sickness = attention)
f. Personality traits
g. Masochistic: recount wounds, sacrifice; only time they experienced love and care
is when they were sick
3. Differential diagnosis: Multiple sclerosis; SLE; Endocrine disorders; Delusional disorder,
somatic subtype; GAD, panic disorder; adjustment disorder; MDD; Functional
neurological symptom disorder (loss of function rather than distress)
4. Somatization disorder
a. Variety of complaints in multiple organ systems (at least 4 pain, 2 GI, 1 sexual, 1
pseudoneurologic) over a period of years, developing before age 30 years
5. Functional neurological symptom disorder
a. One or more symptoms of altered voluntary motor or sensory function
b. Not explained by anatomical pathway or physiological mechanisms

46
 c. Motor symptoms: balance, seizures (poor prognosis), tremors (poor prognosis),
paralysis (good prognosis)
d. Sensory symptoms: blind, diplopia, deafness, hallucinations, anesthesia
e. Symptoms are incompatible with a recognized neurological or medical condition
6. Conversion disorder
a. Sudden loss of sensory or motor function (ex: paralysis, blindness, mutism),
often following an acute stressor
b. Patient is aware of but sometimes indifferent toward symptoms (la belle
indifference)
c. Most common somatic symptom disorder
d. Females more affected than male; onset of non-epileptic attacks in 3rd decade
(20s), onset of motor symptoms in 4th decade (30s)
e. Unconscious
f. Precipitated by acute stressor not necessary
g. Chronic and fluctuating course
h. Differential: neurologic disorders, factitious disorder and malingering, somatic
symptom disorder, dystonia, GMC, substance induced, dissociative disorders,
body dysmorphic disorders
i. Comorbidities: anxiety, depressive, personality, substance use, neurological and
medical conditions
7. Psychogenic nonepileptic seizures
a. Not pseudoseizures
b. Respond to command (saying it will not stop)
c. Cannot open eyes
d. No change in skin color
e. No incontinence
f. Gas, corneal, and pupil reflexes are intact
g. Talks during the seizure
h. Audience
i. Slow to begin and to end
j. Inconsistent presentation
k. Prolactin: increases with real seizures, but remains normal psychogenic
nonepileptic seizures
8. Psychogenic gait Astasia Abasia
a. Comorbid depression and pain disorder
b. Exaggerated effort, extreme slowness, variability throughout day, collapse,
tremors, no secondary gain
c. Other maneuvers
i. Hoover’s sign: counter pressure of “paralyzed” leg when lifting other leg
ii. Weakness of ankle plantar-flexion in an individual that can walk on tiptoes
iii. Tremor entrainment test: patient can copy movements while tremoring
iv. Dropping patient’s arm over their face: patient will avoid hitting face
v. Geotropic eye test: patient able to move eye
vi. Sternal rub: patient reacts to pain

47
 vii. Tuning fork: patient tricked into thinking tuning fork can stop seizure
viii. Abductor sign
ix. Tubular vision:
9. Illness Anxiety Disorder (previously called hypochondria)
a. Complete absence of somatic symptoms, if present are very mild
b. Preoccupation with having or acquiring a serious illness
c. Anxiety acquiring a severe condition
d. Excessive related behavior such as checking for symptoms or signs, information-
seeking reassurance or maladaptive avoidance
e. Not due to another disorder like panic disorder or GAD
f. 6 month duration of concerns but the specific illness may change over that time
g. Specify if care-seeking or care-avoidant type
h. Treatment: Cognitive behavioral therapy, SSRIs, exposure-response prevention
10. New factitious disorder
a. Falsification of physical or psychological symptoms, or induction of injury or
disease, associated with identified deception to get attention (1O gain)
b. Presents as ill, impaired, injured
c. No obvious external reward
d. Not better accounted for by another medical condition
11. Munchausen’s syndrome
a. Chronic factitious disorder with predominantly physical signs and symptoms
b. Characterized by history of multiple hospital admissions and willingness to
receive invasive procedures
12. Factitious disorder imposed on another (Munchausen’s syndrome by proxy)
a. Production or feigning of physical or psychological symptoms in another person
b. Motivation is to assume a sick role by proxy
c. 1000 of 3 million cases of child abuse reported each year
d. Time to diagnosis 15 months
e. 9% present with life threatening episode requiring CPR
f. Often a sibling died of unknown cause
g. Psychodynamics: projective identification (her need to be nurtured), parents
narcissism,sadistic impulses
h. Protection for liability is an external reward so does not meet criterion C (the
deceptive behavior is evident even in the absence of external rewards)
13. Psychological factors affecting other medical conditions
a. Medical symptom or condition is present
b. Psychological or behavioral factor adversely affect the medical condition by
interfering with the treatment of the medical condition, constitution of additional
well-established health risks, influence of the underlying pathophysiology, close
temporal relationship between the psychological factors and the exacerbation, or
delayed recovery of the condition
14. Malingering
a. Patient consciously fakes or claims to have a disorder in order to attain a specific
secondary gain (ex: avoiding work, obtaining drugs)

48
 b. Poor compliance with treatment or follow-up of diagnostic tests
c. Complaints ceases after gain (vs. factitious disorder)
15. Principles of management
a. Provide positive explanation of symptoms
b. Ensure regular follow up
c. Treat comorbid mood and anxiety disorders
d. Minimize polypharmacy
e. Provide specific therapy when indicated
f. Change social dynamics that reinforce symptoms
g. Resolve difficulties in doctor-patient relationships
h. Recognize and control negative reactions or counter transference
i. Cognitive behavioral therapy
j. Pharmacotherapy

49