NEURO PERIPHERAL NEUROPATHY: DRA.

DAVID, 9-10-12 and 9-12-12

PERIPHERAL NEUROPATHY
LMN lesion flaccid
Reflexes lost early on in disease =peripheral nerve
injury
Acute spinal cord injury =areflexia

PERIPHERAL NERVOUS SYSTEM
- All neural structures outside the brain and spinal cord
- Includes sensory receptors, peripheral nerves,
associated ganglia and motor endings
- Provides links to and fromthe external environment

SPINAL NERVE
- Inside vertebral foramen
- Root affected =radiculopathies
- Disc herniation

FUNCTIONAL ANATOMY
- Dendrites
Receives incoming synaptic signals
- Soma/cell body
Receives incoming synaptic signals
- Initial segment/axon hillock
Concentrated Na+channels
Trigger zone
- Axon
Conducts action potential
- Axon terminal
Site of signal transmission



MICROSCOPIC ANATOMY
3 levels of organization
- Epineurium
Dense connective tissue
Continuous with dura mater
- Perineurium
Organizes nerve fascicles
Inner layer continuous with pia/arachnoid
- Endoneurium
Directly surrounds myelinated and unmyelinated
axons

MYELIN
- Produced in PNS by Schwann cell
Average Schwann cel covers ~1mm of axon
internode
~1umgap of unmyelinated axon occurs between
Schwann cels Node of Ranvier









TYPES OF FIBERS





SEGMENTAL DEMYELINATION
- Focal degeneration of the myelin sheath with
sparing of the axon
- Disappearance of the sheath over segments of
variable length, bounded on each end by a
preserved segment of myelin

WALLERIAN DEGENERATION
- A reaction of both the axon and myelin distal to
the site of disruption of an axon
- Described as dying forward, a process in which
the nerve degenerates from th point of axonal
damage outward

AXONAL DEGENERATION
- Dying back phenomenon
- Axon is affected progressively fromthe distal most
site to the proximal
- Dissolution of myelin that occurs roughly in parallel
with the axonal change

THE TEN PS
- Pattern
Temporal
Anatomical
- Population of neurons
- Part of neuron
- Physiology
- Pathology
- Prickling
- Phenomena
- Pedigree
- Plasma
- Pharmacology

(Need picture of the algorithm!)

- Guillain-Barre Syndrome
IMMUNE-MEDIATED NEUROPATHIES
- Chronic Inflammatory Demyelination
- Bells Palsy

GUILLAIN BARRE SYNDROME
- Acute autoimmune inflammatory polyneuropathy
(AIDP)
- Acute monophasic paralyzing _______
NEURO PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12

- Provoked by preceding infection

HISTORY
1859
- ascending paralysis
1916
- Motor weakness
- Areflexia
- Albuminocytologic dissocation

EPIDEMIOLOGY
Incidence
- 1 to 2 per 100,000 per year
- Mean age: 40 yrs old
- Slight male preponderance

ANTECEDENT EVENTS
Infection
- Viral
Epstein-barr virus
Cytomegalovirus
HIV
Influenza
Herpes simplex
Coxsackie
- Bacterial
Campylobacter jejuni
Mycoplasma pheumoniae
Escherichia coli
- Parasitic
Malaria
Toxoplasmosis
Systemic Illness
- Hodgkins disease
- Chornic lymphocytic leukemia
- Hyperthyroidism
- Collagen vascular disease
- Sarcoidosis
- Renal disease
Other Medical Conditions
- Pregnancy
- Surgical procedures
- Bone marrow transplantation
- Immunization
- Envenomization
- Drug ingestion

CLINICAL MANIFESTATION
- Paresthesias
- Sensory loss
- Pain
- Weakness
Ascends fromlower extremities
Symmetrical
Bilateral facial
Eye movement
Respiratory muscles
- Reflexes
- Autonomic involvement
Labile blood pressure
Tachycardia
Postural hypotension
Cardiac arrhythmias
Tachycardia
Bradycardia, _____ heart block
Urinary incontinence
Constipation

COURSE
- Peak: 2 weeks
- Nadir: 4 weeks
- Onset of recovery: 28 days
- Recovery period: 6 months

PATHOGENESIS
1. Complement component are deposited on the outer
surface of the myelin fiber
2. Complement induces vesicular myelin degeneration
3. Schwann cells are invaded by macrophages
4. Macrophages penetrate the basal lamina and strip off
the myelin

VARIANTS
- Weakness is predominant
Acute inflammatory demyelination (AIDP)
Acute motor axonal neuropathy
(AMAN)
Acute motor sensory axonal neuropathy
(AMSAN)
- Weakness is NOT predominant
Fisher syndrome
Acute panautonomic neuropathy?
Pure sensory neuropathy

AXONAL VARIANT
- Commonly preceeded by history of diarrhea,
especially
- Muscle atrophy became apparently relatively early
related to Campylobacter jejuni
- Recovery is prolonged and complete resolution of
weakness is uncommon
- Immune attack is directed at

axon plasmalemma
AUTOANTIBODIES
The one Dra. emphasized fromthe table is:

GBS Subtype Autoantibody
*Miller Fisher Syndrome GQ1b, GT1a

DIAGNOSTIC EVALUATION
- Cerebrospinal fluid analysis
Elevated protein
Cell count
Normal
Pleocytosis >10 cells/mm3
- Nerve conduction studies
Demyelinating
Conduction block is the hallmark of _____
lesion
Prolonged distal motor and F wave latencies
Axonal
Marked reduction in _____ amplitude
- Electrophysiologic studies
Eletromyographic findings
Demyelinating
Fibrillations and sharp waves (second week)
Axonal
Fibrillation and sharp waves

TREATMENT
- Supportive care
ICU monitoring
Respiratory
Cardiac
Hemodynamic
Prophrylaxis for DVT
Bladder and bowel care
Physical and occupational tx
- Intubate!



NEURO PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12

IMMUNOTHERAPY FOR GUILLAIN-BARRE
SYNDROME
1. Treatment wth plasma exchange (PE) or
immunoglobulin (IVIg)
2. PE and IVIg are
hastens recovery
equally effective
3. PE may carry a greater risk of side effects and
more difficult to aminister
in patients with
advanced GBS symptoms
4. Combining the two treatments is
5.
NOT
recommended
Steroid treatment is

NOT beneficial

Did my best to transcribe this one Good luck!

- Acquired immune-mediated neuropathy with
clnical progression for longer than 8-12 weeks
CHRONIC INFLAMMATORY DEMYELINATING
POLYNEUROPATHY (CIDP)
- Separated fromGBS by Austin in 1958 on the
basis of
Prolonged and relapsing course
Enlargement of nerves
Responsiveness to corticosteroids
- Antecedent infection usually NOT identified
- Peak incidence in the 40-60 year age group
CLINICAL FEATURES
- Slowly progressive or relapsing and symmetric
proximal and distal weakness
- Distal panmodality sensory loss
- Depressed/absent muscle stretch reflexes
- Elevated spinal fluid protein w/o pleocytosis
PROGNOSIS
- Approximately 90% of patients will show initial
______

VARIANTS
- Multifocal motor neuropathy (MMN)
- Lewis-Sumner syndrome
Multifocal acquired demyelinating
sensory and motor neuropathy
(MADSAM)
Distal acquired demyelinating sensory
neuropathy (DADS)

- Courses 1 side of the face to be partly or
completely paralyzed resulting in:
BELLS PALSY
Eyebrow sagging
Drooping of eye and corner of mouth
One eye will not close completely

TREATMENT
- Mainstay of pharmacologic treatment: early short
termoral glucocorticoid
- Eye care artificial tears should be applied every
our while the patient is awake
In severe cases of Bells Palsy, _____

PROGNOSIS
- Related to the severity of lesion
- Incomplete lesion _____

- Polyneuropathy that advances slowly over 10
years or more
HEREDITARY NEUROPATHIES
- Time of onset usually early in life but often
cannot be dated with certain by the patient or
family

- Hereditary motor and sensory neuropathies
(HMSN) ______
CHARCOT-MARIE TOOTH DISEASE
(nice to know!)

- CMT1 dominantly inherited myelinopathies
- CMT2 dominantly inherited axonopathies
- CMT3 contenital myelinopathies (infancy
onset)
- CMT4 recessive inherited myelino-
axinopathy

CMT1
CLINICAL FEATURES
- Distal muscle weakness and atrophy (inverted
champagne bottle)
- Clawing of the finger (severe cases)
- Loss of muscle stretch reflex.

CMT2.

CMT3
- Dejerine-Sottas Disease
- Rag doll appearance lots of head lag
- Onset at birth or early childhood..

- Elevated CSF protein (enlarged spinal roots)
- Motor NCV slowed usually under 10 m/s in legs
and 20 m/s in arms
- Mutation in PMP22.

PATHOLOGY
- Onion bulb deformity
- Repeated cycles of demyelination and
remyelination result in nerve fibers.

TREATMENT
- Rehab measures
- Ankle-foot orthoses

- Multiple focal thickenings of myelin sheaths,
each termed a fomaculum
HEREDITARY NEUROPATHY WITH LIABILITY
TO PRESSURE PALSIES (HNPP)

HEREDITARY SENSORY AND AUTONOMIC
NEUROPATHY (HSAN)..


VASCULITIC NEUROPATHIES
VASCULITIS
- Inflammation and structural damage to blood
vessel walls that lead to ischemic hemorrhagic
and thrombotic damage to the tissues supplied by
those vessels.

CLASSIFICATION
- Direct infection
Bacterial, fungal, viral (e.g. lyme
disease, TB, HSV, CMV, HIV)
- Immunological mechanism
Systemic necrotizing vasculitis
Hypersensitivity vasculitis
Giant cell artertitis
Localized vasculitis (non-systemic
vasculitis)

SYSTEMIC NECROTIZING VASCULITIS
- Classic polyarteritis nodosa (PAN)
- Antineutrophil cytoplasmic antibody (ANCA)
associated with:
Microscopic polyangitis
NEURO PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12

Churg-Strauss syndrome
Wegener granulomatosis
- Polyangiitis overlap syndrome
- Vasculitis with connective tissue disease

VASCULTIC NEUROPATHY PATHOLOGY
- Early active lesion

TOXIC NEUROPATHIES

PRINCIPLES OF GENERAL NEUROGOXICOLOGY
1. Strong dose-response relationship
2. Proximity to exposure
3. Coasting
4. Most chemicals that trigger structural damage to
the nervous systemproduce a consistent pattern
of disease commensurate with dose and duration
of exposure

TOXIC NEUROPATHIES
- Peripheral neuropathy of the distal axonopathy
type is the most common form of neurotoxic
disease
- Most instances are caused by pharmaceutical
agents (1-6-12) or substance abuse (alcohol)
- Occupational neuropathies are relatively
infrequent

NEUROTOXIC DRUGS
(drugs that Dra. emphasized are underlined)
- Amphiphilic cationic drug
Amiodarone, chloroquine
- Chemotherapeutic agents
Vinca alkaloids
- Nucleoside analog
, cisplatin, paclitaxel
Zalcitabine, didanosine
- Antibiotics
Dapsone, isoniazid, ethambutol,
- anticonvulsants

nitrofurantoin, metronidazole,
chloramphenicol

- vitamin B6
phenytoin
- colchicine

ARSENIC
METAL TOXICITY
CLINICAL FEATURES
- length dependent sensory-motor neuropathy
(entire length of nerve affected)
- Mees lines in fingernails


LAB FEATURES
- Normal biopsy

LEAD
- Uncommon cause of peripheral neuropathy
- Neruotoxic effect in both organic and inorganic
forms.
- Sources of exposure: industrial plants, batteries,
welding, paint, gas

CLINICAL FEATURES
- Predominantly motor neuropathy primarily
involving the upper limbs
- Radial innervated.


DIABETIC NEUROPATHIES
DIABETES MELLITUS
- Most common cause of polyneuropathy in
general clinical practice
- Approximately 15% of patients have symptoms
of polyneuropathy
- Both type 1 and 2 diabetic patients are
susceptible
- Most important factor

: duration of diabetes
DIABETIC NEUROPATHIES
- Diabetic polyneuropathy
- Diabetic cranial neuropathies
- Acute mononeuropathy of limbs/trunk
- Diabetic amyotrophy (muscles shrink)
- Autonomic neuropathy

PATHOGENESIS
- Metabolic factors
Accumulation of advanced
glycosylation end products
Increase oxidative stress

DIABETIC POLYNEUROPATHY
- Most common type of polyneuropathy
- Distal and symmetrical, primarly sensory formof
polyneuropathy
- stocking glove sensory loss
- Mild muscle weakness of distal lower limb

DIABETIC CRANIAL NEUROPATHY
- **third and sixth cranial nerves most often
affected**
- Diabetic third nerve palsy (opthalmoplegia)
Usually in diabetics over age 50
Retro/supraorbital pain often precedes
the opthalmoplegia
Pupillary sparing = hallmark of the
condition
- Patients will recover as long as you treat the
diabetes

DIABETIC AMYOTROPHY
- Diabetic lumbosacral radiculoplexus neuropathy
- Bruns-Garland syndrome
- ***mostly thigh muscles affected***

TREATMENT
- Antidepressants.

- Caused by direct invasion of nerves by the acid
fast bacilli.
LEPROSY

- Compression injuries to a specific region/regions
of a nerve predisposition by...
ENTRAPMENT NEUROPATHIES

MEDIAN NERVE
- Receives contributions fromC6, C7, C8, T1
- Distal muscles affected fromwrist

ANTERIOR INTEROSSEUS NERVE

ULNAR NERVE
- Compressed at wrist/elbow
- Median nerve =numbness of first 3 fingers and
of 4
th
- Ulnar nerve =numbness of of 4
finger
th
and 5
th
digit
NEURO PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12



MERALGIA PARESTHETICA: LATERAL FEMORAL
CUTANEOUS NERVE ENTRAPMENT
- Most common in obese individuals and people
who wear tight pants/underwear

DUCHENNE-ERB PARALYSIS
PLEXUS
- .
- Waiters or bellhops tip position

KLUMPKES PARALYSIS
- .
- Weakness of medial wrist flexion and of most
finger movements including
Finger extension, flexion and abduction

DERMATOME
RADICULOPATHIES
- Cutaneous innvervation by a root segment

MYOTOME
- Muscular innvervation by a root segment

CAUSES
- Degeneration and structural compression,
myeloradiculopathy
-

Median n.
Ulnar n.