Polyneuropathy

Question 1

Definition of polyneuropathy

Answer 1

Syndrome of dysfunction or disease of peripheral nerves
Similar presentation regardless of etiology (most pts will present with both motor and sensory symptoms that usually start in the feet and can go on to involve the hands or arms)

Question 2

Acute vs Chronic

Answer 2

Acute (uncommon) - GBS, porphyria, diptheria, drugs, toxins, tick paralysis, vasculitis or CT disease
Chronic (months - years with insidious onset)

Question 3

Progression

Answer 3

Steady (most common)
Stepwise (mononeuritis multiplex)
Relapsing-remitting (would suggest chronic demyelinating neuropathy or intermittent exposures/toxic exposures)

Question 4

Determine the Fiber types involved

Answer 4

Fiber types - nerve fibers are classified by fiber side and modality carried
small sensory - unmyelinated fibers that convey pain and temperature
large sensory - myelinated, convey proprioception, touch, vibration
Motor - large diameter, myelinated, activate muscle contraction
Autonomic - small, unmyelinated
Useful to determine which fiber type is involved by looking at positive vs negative symptoms
Negative (lack of function) - weakness, atrophy, sensory loss, hyporeflexia, hypotension, anhidrosis
Positive (over-functioning) - cramping, fasciculations, burning sensations, hyperhyrosis, parasthesias

Question 5

Pure sensory neuropathies

Answer 5

uncommon and usually indicate damage to the dorsal root ganglion; when they do occur, they are subacute and are classified as one of four types: Paraneoplastic syndrome, Postinfectious processes, Sjogren’s syndrome, Pyridoxine (B6) intoxication

Question 6

Pure motor neuropathy

Answer 6

Hereditary neuropathies, Pb poisoning, porphyrias, and GBS

Question 7

Small sensory neuropathy

Answer 7

DM, amyloid, toxins (EtOH), drugs (antiretrovirals), hereditary diseases

Question 8

Distribution of polyneuropathy

Answer 8

Distal>proximal gradients (classic) - due to axonal damage, length dependent, dying back pattern - longest nerves are affected first resulting in a “stocking glove” pattern
Nearly all polyneuropathies are symmetric
Asymmetric neuropathies rule out toxic, metabolic and genetic conditions
Asymmetric neuropathy suggests mononeuritis multiplex or superimposed radiculopathy - Mononeuritis mutliplex ->asymmetric nerve involvement with step-wise progression (Ddx - vasculitis, DM, inflammatory demyelination PN, multiple entrapments (hereditary vs acquired), Cryoglobulinemia, Infectious (lyme, leprosy), infiltration (granulomatous dx, CA)

Question 9

Determine the underlying nerve pathology

Answer 9

Axonal - most common (DM most common etiology) - most are chronic and progressive
Demyelinating - damage to myelin sheath (marked slowing of conduction velecities) - demonstrated by electrodiagnostic testing or bx, indicates a favorable process, common demyelinating polyneuropathies (Hereditary -> HMSN (hereditary motor and sensory neuropathy), Acquired -> AIDP (GBS), CIDP, Multifocal Motor neuropathy, Diptheria, Toxic)
Mixed

Question 10

Family History of Neuropathy?

Answer 10

Clinical clues - these are common in neuropathies
Foot deformity ( pes cavus, hammer toes)
Long-standing PN
Very slow progression
Few positive symptoms
Family history

Question 11

Medical conditions highly associated with PN

Answer 11

DM, CA, CT dx, HIV and deficiency states

Question 12

Diabetic Neuropathy

Answer 12

Most common cause of neuropathy
Pathogenesis - polyol pathway - microvascular ischemia, advanced glycosylation end products, inflammation, growth factor/insulin deficiency, ion channel dysfunction, dysfunctional fatty acid metabolism
Leading cause of all 3 major categories of polyneuropathy - generalized neuropathies (large, small, and autonomic involvement); Compressive focal neuropathies (carpal tunnel syndrome, ulnar neuropathy, peroneal neuropathy of fibular head); Non-compressive focal /mulcifocal (amyotrophy, cranial neuropathies, CN VI, mononeuritis multiplex)

Question 13

Hereditary neuropathies

Answer 13

HMSN (Hereditary Motor Sensory Neuropathy) = CMT (Charcot Marie Tooth)
HSAN - hereditary sensory and autonomic neuro
HMN - hereditary motor neuro
CMTX - charcot-marie-tooth, x-linked

Question 14

HMSN I

Answer 14

Most common subtype
Key pathologic feature -> demyelinating neuropathy
Genetics -> autosomal dominant with variable phenotypes
Onset before age 20
Duplication of the PMP22gene (opposite of HNPP)
Positive family history
Clinical features - distal weakness, peroneal atrophy, distal and symmetric sensory loss -> loss of vibration and proprioception distally, decreased DTRS, not hyperrefflexic, Pes cavus -> high-arched feet with “hammer toes”, bilateral foot drop, palpable nerves
Electrodiagnostic testing -> slowed conduction
Nerve Bx- hypertrophic nerves with onion bulb formation (attempt to remyelinate)

Question 15

HMSN II

Answer 15

key pathologic feature -> axonal loss
Clinical features (similar presentation to CMT I) - middle-aged patient (d/o of adulthood), slowly progressive weakness and atrophy, positive FH, distal muscle weakness and atrophy, distal and symmetrical sensory loss (stocking glove), decreased DTRs, do not see + symptoms as in acquired PN
Electrodiagnostic testing -> normal nerve conduction with decrease sensory and motor amplitudes
Genetics - multiple gene mutations with AD inheritance

Question 16

HMSN III (Dejerines Sottas)

Answer 16

Key pathologic feature -> demyelinating PN
Clinical features -> childhood onset, proximal and truncal weakness, sensory ataxia, absent DTRS
Nerve Bx - absent or very thin myelin sheaths with onion bulb formation
Electrodiagnostic testing - very slow (or unillicitable) conduction velocities
Genetics - all types of inheritance (AD, AR, sporadic)

Question 17

HMSN IV

Answer 17

Rare, autosomal recessive, early onset, slow nerve conduction

Question 18

CMT - X

Answer 18

considered to be an “intermediate” for CMT
genetics - most cases are linked to connexin 32 mutaions (X-linked females are asymptomatic carriers)
Clinical features -> similar features as CMT I (childhood onset, slowing of lower extremities>upper extremities)
Pathology - onion bulbs are NOT seen

Question 19

HNPP (Hereditary Neuropathy with Liability to Pressure Palsies)

Answer 19

Recurrent, painless, focal mononeuropathies
Genetics - AD (PMP 22 gene deletion)
Onset can be at any age (commonly after age 20)
Electrodiag testing - slowing at site of nerve entrapment
Nerve Bx - swelling of nerve fibers

Question 20

HSAN

Answer 20

5 major subtypes
Most subtypes are recessive except for the most common subtype (which is dominant)
Congenital insensitiivy to pain, sensory neuropathies, painless ulcers of feet, charcot joints, bony deformities, fevers of unknown origin (autonomic dysfunction)