Peripheral Neuropathy (Week 1--Andersson)

Question 1

Different types of injury to the peripheral nervous system

Answer 1

Root injury: radiculopathy; motor and sensory deficits in segmental distribution

Plexus injury: plexopathy; in the distribution of its organizational anatomy

Peripheral nerve injury in particular nerve distribution can either be neuronopathy (injury to nerve cell body; motor neuron disease for motor, or sensory ganglionopathy for sensory) or peripheral neuropathy (injury to the the peripheral process)

Question 2

Polyneuropathy

Answer 2

Common (2.4%, and 8% over 55 years old)

Multiple nerves, contiguous, typically length dependent (stocking-glove)

Question 3

Example of motor neuronopathy

Answer 3

ALS

SMA

Question 4

Different types of peripheral nerve injury (peripheral neuropathy)

Answer 4

1) Mononeuropathy: focal; carpal tunnel syndrome, seen in pregnancy with fluid retention
2) Mononeuritis multiplex: focally but multiply; vasculitis
3) Polyneuropathy: diffuse; chronic ethanol toxicity

Question 5

Three things to consider when diagnosing a peripheral neuropathy

Answer 5

1) Injury to axon or myelin?
2) Is the modality affected motor, sensory or autonomic?
3) Injury to large or small fibers?

Question 6

Symptoms with motor nerve injury

Answer 6

Loss of function (negative symptoms): wasting, hypotonia, weakness, hyporeflexia, orthopedic deformity

Altered function (positive symptoms): fasciculations, cramps

Question 7

Symptoms with LARGE sensory nerve injury

Answer 7

Loss of function (negative symptoms): decreased vibration, decreased proprioception, hyporeflexia, sensory ataxia (problem with coordination when eyes closed)

Altered function (positive symptoms): paresthesias

Question 8

Symptoms with small sensory nerve injury

Answer 8

Loss of function (negative symptoms): decreased pain, decreased temperature

Altered function (positive symptoms): dysthesias, allodynia

Question 9

Symptoms with autonomic nerve injury

Answer 9

Loss of function (negative symptoms): decreased sweating, hypotension, urinary retention, impotence, vascular color changes

Altered function (positive symptoms): increased sweating, hypertension

Question 10

Axonal degeneration and reinnervation attempts

Answer 10

Histologically, see denervation atrophy and axon dropout with degeneration and regenerating sprouts for reinnervation

Electrodiagnostically see reduced compound muscle action potential amplitude (CMAP) with reduced recruitment of muscle fibers on EMG with degeneration and large motor unit potentials on EMG for reinnervation

Clinically see weakness with atrophy with axonal degeneration

Question 11

Demyelinating neuropathy signs

Answer 11

Histopathologically: loss of myelin and onion bulb formation

Electrodiagnostically: slowed conduction velocity (uniform in hereditary and non-uniform in acquired), EMG reduced recruitment but motor units normal size and amplitude, little or no signs of reinnervation on EMG

Clinically: weakness but NO wasting, tendency for predominant motor over sensory deficits and generalized arreflexia, may have palpably hypertrophic peripheral nerves (greater auricular nerve)

Question 12

Nerve conduction study to tell if it is axonal degeneration or demyelinating neuropathy

Answer 12

Axonal degeneration = low = fewer “wires”

Demyelinating neuropathy = slow (because demyelination reduces conduction veolcity) and also low

Question 13

Are the majority of peripheral neuropathies axonopathies or demyelinating neuropathies?

Answer 13

Majority are axonopathies (low)

CMAPs decreased 80% lower limit of normal

Legs more than arms

EMG: signs of devervation (acute, chronic) and reinnervation

Question 14

Myelinopathies

Answer 14

Clinically: hypertrophic nerves, arreflexia, weakness w/o wasting, motor more than sensory deficits, NCS can distinguish inherited from acquired

NCS: distal motor latency prolonged (>125% ULN), conduction velocities slowed (<80% LLN), may have conduction block

EMG: reduced recruitment without much denervation

Question 15

Examples of different causes of peripheral neuropathy (there are many!)

Answer 15

Inherited: Charcot-Marie-Tooth disease (HMSN)

Infectious: leprosy

Inflammatory: Guillain Barre syndrome (acute inflammatory demyelinating polyneuropathy)

Neoplastic: monoclonal gammopathy

Metabolic: diabetes

Drug: vincristine

Toxic: ethanol

Question 16

How to tell if large or small fibers are affected

Answer 16

Motor fibers are large and myelinated

Autonomic fibers are small and mostly unmyelinated

Sensory fibers can be large (proprioception, vibration and touch) or small (pain and temperature)

Question 17

6 D’s of diagnosing peripheral neuropathy

Answer 17

1) Distribution of deficits
2) Duration
3) What are the deficits (which fibers involved)
4) What is disease pathology (axonal, demyelinating or mixed)
5) Is there a developmental (inherited) neuropathy
6) Is there drug/toxin exposure

Question 18

1) Distribution

Answer 18

Asymmetry: mononeuropathy, mononeuritis multiplex (vasculitis)

Symmetric (glove/stocking): polyneuropathy

Question 19

2) Duration

Answer 19

Acute is 4 weeks; subacute is 8 weeks; chronic is >8 weeks

Most polyneuropathies are chronic

Acute polyneuropathies include Guillain Barre, vasculitis

If relapses and remissions, think intermittent toxin exposure

Question 20

3) Deficits (which fibers affected)

Answer 20

If motor, think Guillain Barre, lead toxicity, Charcot-Marie-Tooth disease

If pure sensory/severe proprioceptive, think carcinoma (paraneoplastic), vitamin B6 toxicity

If autonomic, think diabetes, amyloid, drugs like vincristine, ddI, ddC

Question 21

4) What is disease pathology

Answer 21

Majority are axonal

If demyelination uniform, then hereditary (Charcot-Marie-Tooth type I)

If chronic sensorimotor axonal polyneuropathy, exclude alcohol, diabetes, hypothyroidism, uremia, B12 deficiency, monoclonal gammopathy (simple blood test and account for majority of neuropathies!)

Question 22

5) Developmental (inherited) neuropathy

Answer 22

Among most common

Clues: orthopedic deformities, long duration, indolent progression, few “positive” symptoms, examine family members!

Question 23

6) Drug or toxin exposure

Answer 23

Demyelinating neuropathy could be due to glue sniffing, arsenic

Axonal neuropathy could be due to cancer drugs like vincristine and paclitaxel, antibiotics like chloroquine, ethambutol, isonaizid and metronidazole, or cardiac medications like amiodarone

Question 24

Ethanol neuropathy

Answer 24

Common axonal neuropathy

Among most common neuropathies worldwide

Chronic

Numbness, paresthesias, pain in stocking distribution

Sensory more than motor, loss of ankle reflexes

Question 25

Guillain Barre Syndrome

Answer 25

Common demyelinating polyneuropathy

Rapid, severe, typically ascending paralysis

Post infectious in 60%

Paresthesias, pain, numbness

Symmetric across midline, typically ascending

Autonomic nerves

Reflexes lost

Cytoalbuminologic dissociation in CSF

Question 26

Diabetic polyneuropathy

Answer 26

Common mixed axonal and demyelinating polyneuropathy

Sensory more than motor

Stocking numbness in all modalities to the ankles; absent ankle reflexes

Autonomic involvement is common

CSF protein frequently elevated