Peripheral Neuropathy
- Wallerian
degeneration –
loss of axis cylinder and myelin distal to site of axonal interruption
- Segmental
demyelination
– axon is spared; no muscle atrophy
- Axonal
degeneration –
distal degeneration of myelin and axis cylinder due to neuronal disease
- Recurrent
demyelination and remyelination leads to “onion bulb” formations and
enlargement of nerves
- Toxic – vincristine, mercery,
actinomycin D
- Thallium
Salt Toxicity (resembles GBS)
- Abdominal
pain, vomiting, diarrhea, then weakness progressing distal to proximal
- Decreased
DTR’s
- Decreased
pain sensation; acral pain with allodynia
- Cranial
nerve palsies
- Rapid
loss of hair, painful paresthesias, sensory loss, pain in
joints/back/chest
- Drug
Induced Neuropathy – usually sensory
- Isoniazid – sensory loss progressing
to distal weakness and loss of DTR’s
- Due to
interference with pyridoxine metabolism
- Prevent
with pyridoxine
- Disulfuram
- Vincristine
- Toxol/Cisplatin – sensory, acrochymia, color
changes of fingers and toes, sensory ataxia and athetosis
- Nitrofurantoin
- Amiodarone
- Dilantin – distal sensory loss, loss
of DTR’s
- Neuronal
Dysfunction produced by drugs:
- Transcription
– actinomycin D
- Translation
– methylmercury
- Microtubule
– vincristine, vinblastine
- Oxidative
phosphorylation – dinitrophenol
- Turnaround
– acrylamide, diabetes
- Hexachloropheme
and lead produce a demyelinating polyneuropathy
- Diphtheric
polyneuropathy
- 5-8
weeks after infection, there is acute limb weakness with paresthesias and
distal loss of vibratory and position sense
- demyelination
seen without inflammatory reaction of spinal roots, ganglia, and
nerves
- Metabolic
- Diabetes – ischemia of vaso nervorum;
painful pupil-sparing CNIII palsy (center of nerve); ischemic femoral
neuropathy; distal symmetric sensory loss
- Acute
Diabetic Mononeuropathy – due to nerve infarction
- Diabetic
ophthalmoplegia – isolated CN III palsy (rarely CN IV)
- Femoral
and sciatic neuropathy
- Multiple
Mononeuropathy and Radiculopathy – painful, asymmetric
- pain
in low hip radiating to thigh
- weakness,
atrophy, loss of DTR’s on affected side
- recovery
over months to years
- Distal
Polyneurophaty – distal, symmetric, primarily sensory form; absent DTR’s
- Autonomic
Neuropathy
– papillary and lacrimation dysfunction, impaired sweating and vascular
reflex, nocturnal diarrhea, atonicity of GI and bladder, impotence,
postural hypotension
- Amyloid
–
immunoglobulin light chain forms extracellular beta-sheets; congo red dye
green with polarized light
- Porphyria
– rapid
symmetric
- Motor
> sensory
- Abdominal
pain, psychiatric changes, seizures
- Axon
and myelin degeneration without inflammation
- Autosomal
dominant
- Deficiency
of hydroxymetylbilane synthase – causes increased production and
excretion of porphybilinogen and delta-aminolevulinic acid
- Signs/Symptoms
- Abdominal
pain, constipation, nausea/vomiting, tachycardia, hypertension, urine
discoloration, fever, psychosis
- Hyponatremia,
limb weakness, delirium, hyporeflexia, seizures
- Peripheral
neuropathy with segmental demyelination
- Autonomic
neuropathy with ganglionic and postganglionic involvement
- SIADH
with hyponatremia (loss of cells in supraoptic and paraventricular
hypothalamic nuclei
- Polyneuropathy
– motor greater than sensory
- May
have facial paralysis, dysphagia, ocular palsies
- Truncal
sensory loss
- Tachycardia,
hypertension
- Starts
in upper extremity
- Many
symptoms and signs may be caused by damage to vagus nerve (abdominal
pain, constipation, sinus tachycardia, hypertension, hyperhidrosis, and
sphincter bladder problems)
- Uremia – painless, symmetric, worse
in lower extremities
- Leukodystrophy – central and peripheral
- Fabry’s
disease
- Viramin
deficiency
- Hypothyroid
- Autoimmune
- Guilliane-Barre – idiopathic polyneuritis;
rapid onset, often after trauma, surgery, infection, immunization, or
neoplasm
- Acute,
frequently severe and fulminant demyelinating polyneuropathy
- Also
called acute inflammatory demyelating polyradiculopathy (AIDP)
- Autoimmune
cell mediated reaction to myelin basic protein 2
- Incidence
is 1.8/100,000 population with male predominance
- Symptoms:
mostly motor and autonomic
- Often
prodomal viral illness or surgical procedure (1-4 weeks prior to
onset), ascending areflexic motor paralysis with only mild sensory
disturbance, maximum deficit usually with 4 weeks of onset, 10-20% require
mechanical ventilation
- weakness,
lower > upper, distal then proximal, progresses over days to
respiratory paralysis
- paresthesias
progress to numbness over 1-2 weeks
- greatly
decreased or absent DTR’s
- facial
diplegia, cranial nerve palsies late
- Autonomic
dysfunction common,
including urinary retention
- 10-14
days to peak; usually monophasic but can recur
- CSF
acellular with dramatically increased protein after 5 weeks
- Nerve
conduction studies are consistent with peripheral demyelination, prolonged
F response, and prolonged latencies (decreased velocity and amplitude of
conduction)
- Pathology:
Endoneurial perivascular mononuclear and lymphocytic cell infiltration
(usually perivenous) with widespread multifocal segmental demyelination
and Wallerian degeneration
- Treatment:
Supportive care
- Immune
globulin or plasmapheresis speed recovery
- Steroids
have no role
- Prognosis:
85% make complete or near complete recovery
- Bad
prognostic factors: Age >40 years, need for ventilatory support,
maximum deficit in <7 days, amplitude of distal M responses on EMG
<20% of normal
- Chronic
Inflammatory Demyelating Polyneuropathy (CIDP)
- Characteristics
different from GBS:
- Chronic
relapsing
- Nerves
enlarged
- Responds
to steroids
- Characteristics
similar to GBS:
- CSF
cytoalbuminologic dissociation
- Decreased
conduction velocity, partial conduction block consistent with
demyelination
- Inflammatory
changes
- Mixed
sensorimotor involvement
- CSF
protein elevated in 80%; some have papilledema and pseudotumor when protein
> 1000; protein increase due to CSF gamma globulin and mild
lymphocyte pleocytosis
- Can
treat with plasmapheresis and IVIG; steroids work but are used as a last
resort (require chronic treatment)
- Ischemic
- Polyarteritis
nodosa – most
common vasculitis affecting central nervous system
- Mononeuritis
multiplex from obstruction of vaso nervorum
- Axonal
degeneration
- Vessel
walls show intimal proliferation with infiltration of polys, lymph,
eosinophils
- Skin
purpura, renal problems
- Diffuse,
asymmetric, due to multiple nerve infarctions (like a polyneuritis)
- Can
also look like a mononeuritis multiples (random infarction of two or
more individual nerves) – produces abrupt onset of pain or numbness in
distribution of affected nerve
- Infectious – nerves usually protected by
perineurium
- Zoster – hemorrhagic
ganglioradiculitis/myelopathy
- Leprosy
- HSV
- Diphtheria – inhibits Schwann cell
myelin synthesis – demyelinating peripheral neuropathy
- Hereditary (onion bulb) – demyelination
and remyelination with decreased nerve conduction velocities
- Peroneal
muscular atrophy (Charcot-Marie-Tooth disease or hereditary motor sensory
neuropathy (HMSN type I or II))
- Autosomal
dominant, usually on chromosome 17
- Type I
– slow conduction velocity in median and ulnar nerve (<38 m/sec)
- Type II
– normal conduction velocity
- Symptoms:
- Chronic
degeneration of peripheral nerves and roots resulting in distal muscle
atrophy
- Feet
and legs involved before hands
- Equinovarous
deformity (pied en griffe) – “stork” legs
- Eventual
inability to plantarflex
- Claw
hands (main en griffe)
- Rarely
extends above elbows or midthighs
- Sensory
loss distally
- Affects
anterior horn, posterior column, dorsal root ganglion
- Both
axon and myelin affected
- Atrophy
of feet and hands (pes cavus, clawhand)
- No autonomic
changes, CSF normal
- Sensory
changes and weakness
- Ataxia
- Pathology
– degeneration of nerves (axons and myelin), especially motor nerves and
dorsal root ganglion
- Hypertrophic
Neuropathy of Infancy (Dejerine-Sottas Disease, HMSN type III)
- Usually
autosomal recessive
- 1st
decade of life
- Pain
and paresthesias of feet, progressive symmetric weakness and distal
wasting
- DTR
absent
- Ataxia,
nystagmus
- Enlarged
nerves (feel like ropelike tendons)
- Greatly
increased CSF protein because of involvement of roots
- Disabling
– usually wheelchair bound
- Clawfoot/hand,
weakness,wasting, foot parasthesia
- Enlarged
nontender ulnar/median/radial/peroneal nerves
- Hereditary
Areflexic Dystonia (Ramsey-Levy Syndrome)
- Sensory
ataxia with pes cavus and areflexia, atrophy
- Distinct
from Friedrich’s ataxia, which has faster course,
cerebellar/brainstem/corticospinal signs, and NO atrophy
- Distinct
from peroneal muscular atrophy, which has later onset, lacks sensory
ataxia, and lacks kyphoscoliosis
- Refsum’s
disease (HMSN type IV)
- Autosomal
recessive
- due to
phytanic acid oxidase deficiency, accumulate phytanic acid
- Distal
symmetric sensorimotor
- Retinitis
pigmentosa, cerebellar ataxia of gait (prominent finding), chronic
polyneuropathy
- Increased
levels of phytanic acid in blood
- Cardiomyopathy
and neurogenic deafness (congenital)
- Anosmia
and night blindness
- Decreased
sensation, distal weakness, onion bulbs, absent DTR’s
- Amyloid
Neuropathies
- Autosomal
dominant
- Amyloid
infiltration and deposition in small diameter sensory and autonomic
nerves
- Traumatic
- Neuropraxia
– injury to nerve with intact fibers; motor > sensory, recover in 6-8
weeks
- Axonotmesis
– fibers severed with intact sheath, so grow back (takes much longer – 1
mm/day)
- Neurotmesis
– nerve totally disrupted; unlikely to recover
- Morton
neuroma – traumatic neuroma (digital neuroma between toes)
- Paraneoplastic
polyneuropathy
- Distal, symmetric,
sensorimotor, weakness, atrophy, ataxia, sensory loss of limbs
- Associated
with Anti-Hu antibody in serum and CSF; typically small cell of
lung
- Seen in
2-5% of patients with cancer
- Treatment
– gamma globulin
- Seen
frequently in multiple myeloma and other paraproteinemias due to antimylein
antibodies (IgM against myelin associated glycoprotein); see deep
sensory loss with imbalance, Romberg sign
- Sarcoidosis
- Facial
palsy or multiple cranial nerve palsies
- Involvement
of muscles (polymyositis) or CNS (stalk of pituitary, cerebellum)
- Non-caseating
granulomas in lymph nodes, lung, skin, eyes, salivary gland, liver
- 5% have
CNS involvement (esp CN VII)
- can get
meningitis, pituitary dysfunction, hydrocephalus, hypothalamic granuloma,
myelopathy, neuropathy, myopathy
- ACE
levels increased
- Lyme
Disease
- Cranial
nerves sometimes involved
- Painful
radiculitis or dermatome of insect bite (Bannworth syndrome, cauda equina
syndrome)
- Usually
presents with fever, erythema chronicum migrans, lymphadenopathy, and
joint symptoms
- Facial
palsy, sensory neuropathy
- Polyradiculopathy
- More patchy
than polyneuropathy; proximal = distal, muscles of a common root
innervation (e.g., hamstring/gastrocnemius, or
iliopsoas/quadriceps/obturator)