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Flashcards in Neuro Deck (229)
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181

Diphtheria Neuropathy

  • from diphtheria exotoxin
  • segmental demyelination
  • presentation: paresthesias and weakness

182

Varicella-Zoster Virus Neuropathy

  • latent infection of spinal cord and brain stem sensory ganglia
  • reactivation ⇒ shingles.  trigeminal or thoracic nerve distribution.
  • neuronal destruction with associated mononuclear cell infiltrates.  peripheral nerves have axonal degeneration.

183

Hereditary and Sensory Autonomic Neuropathies

  • HSANs.  5 types.
  • presentation: numbness, pain, autonomic dysfunction.

184

HSAN Type I

  • autosomal dominant.
  • mutated SPTLC-1 gene.
  • presentation: young adults.  sensory neuropathy.  axonal degeneration of myelinated fibers.

185

HSAN Type II

  • autosomal recessive.
  • mutated HSN2 gene.
  • presentation: in childhood.  sensory neuropathy.  axonal degeneration of myelinated fibers.

186

HSAN Type III

  • aka Riley-Day syndrome, familial dysautonomia.
  • autosomal recessive.
  • mutated IKAP gene.
  • presentation: Jewish kids.  autonomic neuropathy.  axonal degeneration of unmyelinated fibers, atrophy and loss of sensory and autonomic ganglion cells.

187

HSAN Type IV

  • autosomal recessive dysautonomia type II
  • mutated NTRK1 gene.
  • presentation: infants.  insensitivity to pain and anhidrosis.  almost complete loss of small myelinated and unmyelinated fibers.

188

HSAN Type V

  • autosomal recessive
  • mutated NGFB gene.
  • presentation: infants.  insensitivity to pain and temperature.  nearly complete loss of small myelinated fibers.

189

Familial Amyloid Polyneuropathies

  • autosomal dominant.
  • deposition of amyloid in PNS.
  • mutated transthyretin (transports thyroxine and retinol).
  • amyloid fibrils made of transthyretin.
  • morphology: amyloid deposits in vessel walls and CT with axonal degeneration.
  • presentation: numbness, pain, autonomic dysfunction.

190

Adrenoleukodystrophy

  • X-linked. 4% female carriers symptomatic.
  • mutated ABCD1.
  • morphology: segmental demyelination, onion bulbs, axonal degeneration (myelinated and unmyelinated).
    • linear inclusions in Schwann cells.
  • presentation: mixed motor and sensory neuropathy, adrenal insufficiency, spastic paraplegia.
    • onset btw 10-20 yrs in men with leukodystrophy, 20-40 yrs in women with myeloneuropathy

191

Porphyria (AIP or Variegate Coproporphyria)

  • autosomal dominant
  • mutated enzymes in heme synthesis
    • AIP = porphobilinogen
  • morphology: acute and chronic axonal degeneration, regenerating clusters.
  • presentation: acute episodes neuro dysfunction, psychiatric disturbances, abd pain, seizures, proximal weakness, autonomic dysfunction.
    • may be precipitated from drugs.

192

Refsum Disease

  • autosomal recessive.
  • mutated PAHX gene.
  • morphology: severe onion bulb formation.
  • presentation: mixed motor and sensory neuropathy with palpable nerves, ataxia, night blindness, retinitis pigmentosa, ichthyosis.
    • onset before age 20.

193

Charcot-Marie-Tooth Disease

  • aka hereditary motor and sensory neuropathy (HMSN) type I.
  • autosomal dominant demyelinating disorder.
  • pathogenesis: HMSN-1A has duplicated segment on chrom 17 ⇒ ↑ PMP-22 that compacts myelin as Schwann cells wrap around axons.
    • HMSN-1B = mutated MPZ.
    • mutations in connexin 32, protein degradation pathway, and myelination induction genes.
  • morphology: segmental demyelination and onion bulb.
  • presentation: young adults with distal muscle weakness and calf atrophy.

194

HMSN II

  • autosomal dominant
  • axonal loss without demyelination
  • presents younger than HMSN type I.
  • mutated kinesin.

195

Déjérine-Sottas Neuropathy

  • aka HMSN III.
  • autosomal recessive.  infantile.
  • progressive upper and lower extremity weakness and muscle atrophy, enlarged palpable nerves.
  • mutated PMP-22 or MPZ.
  • severe segmental demyelination, onion bulbs, axonal loss.

196

Peripheral Neuropathy in Adult-Onset DM

  • present in about 50% DM.
  • from nonenzymatic protein glycation and polyol-mediated damage.
  • diabetic microvascular disease with secondary ischemic injury.
  • types: distal symmetric sensory or sensorimotor neuropathy, autonomic neuropathy, focal or multifocal asymmetric neuropathy.

197

Distal Symmetric Sensory or Sensorimotor Neuropathy

  • axonal neuropathy with loss of small fibers.
  • sensory loss > motor loss.
  • loss of pain ⇒ cutaneous ulcers, heal poorly from diabetic microvascular disease.

198

Autonomic Neuropathy

  • 20-40% diabetics.
  • presentation: postural hypotension, incomplete bladder emptying, sexual dysfunction.

199

Focal or Multifocal Asymmetric Neuropathy

  • ex. unilateral ocular nerve palsy.
  • secondary to vascular insufficiency of peripheral nerves.

200

Metabolic and Nutritional Peripheral Neuropathies

  • from renal failure
    • presents with distal symmetric sensory and motor neuropathy.
  • from chronic liver disease, respiratory insufficiency, thyroid dysfunction.
  • from deficiencies of thiamine, B6, B12, or E.
  • from excessive alcohol consumption by ethanol toxicity and thiamine deficiency.

201

Direct Infiltration or Nerve Compression

  • by tumor ⇒ mononeuropathy, brachial plexopathy, cranial nerve palsy, or polyradiculopathy of lower extremities (meningeal carcinomatosis of cauda equina)

202

Paraneoplastic Syndrome of PNS

  • progressive sensorimotor neuropathy (lower extremities) in 2-5% lung cancer.
  • loss of dorsal root ganglia ⇒ sensory neuropathy
    • circulating Ab against RNA-binding protein shared by neurons and tumor cells.
  • deposition of light-chain amyloid in pts with plasma cell dyscrasias
  • secondary to autoantibodies against myelin-associated glycoprotein

203

Toxic Neuropathies

  • from exposure to industrial/environmental chemicals, biologic toxins, heavy metals (lead, arsenic), therapeutic drugs.

204

Traumatic Neuropathies

  • lacerations cutting a nerve
  • avulsions when nerve under pressure
  • traumatic neuromas from nerve transection or damage.  painful nodules of tangled axons and CT from regenerating axonal sprouts.
  • compression neuropathy = nerve compressed.
    • Carpal Tunnel Syndrome: median nerve entrapped in wrist.  see in edema, pregnancy, degenerative joint disease, hypothyroidism, amyloidosis, excessive wrist use.
    • other nerves: ulnar nerve at elbow, peroneal nerve at knee, radial nerve in upper arm.
    • compression neuropathy of foot in women.
    • Morton neuroma: involves interdigital nerve at intermetatarsal sites ⇒ pain

205

Spinal Muscular Atrophy

  • autosomal recessive motor neuron diseases, onset in childhood or adolescence.
  • mutations of SMN1 gene on chromosome 5
    • # copies homologous SMN2 gene modifies gene severity.
    • SMN for axonal transport, NMJ integrity.
      • loss ⇒ neuronal cell death.
  • morphology: large numbers of extremely atrophic muscle fibers, involve entire fascicle of muscle
  • presentation: SMA type I = Werdnig-Hoffman disease: presents first 4 months of life with hypotonia and death by age 3 yr.
    • SMA type 2: presents later, die as kid after age 4.
    • SMA type 3: survive to adulthood.

206

Duchenne Muscular Dystrophy

  • most severe and most common form muscular dystrophy.
  • X-linked.  1/3500 males.
  • DMD gene at Xp21 encodes dystrophin that transduces contractile forces from intracellular sarcomeres to ECM.
    • 2/3 familial.  1/3 de novo
    • no detectable dystrophin
  • morphology: enlarged, rounded, hyaline fibers lacking normal cross striations.
    • variation in myofiber diameter, ↑ internalized nuclei, degeneration/necrosis/phagocytosis of muscle fibers, regeneration of muscle fibers, proliferation of endomysial CT, muscles replaced by fat and CT, involves type I and type II fibers.
  • presentation: by age 5, wheelchair by 10-12. death in early 20's.
    • weakness in pelvic girdle muscles
    • pseudohypertrophy: lower muscles hypertrophied with weakness.
    • heart failure and arrhythmia, risk of cardiomyopathy
    • cognitive impairment
    • death from respiratory insufficiency, pulmonary infection, cardiac decompensation.

207

Becker Muscular Dystrophy

  • X-linked muscular dystrophy.
  • starts later than DMD, not as severe.
  • mutated DMD gene at Xp21 encoding dystrophin
    • 2/3 familial, 1/3 de novo.
    • ↓ amounts dystrophin that has abnormal molecular weight.

  • morphology: variations in myofiber diameter, ↑ internalized nuclei, degeneration/necrosis/phagocytosis of muscle fibers, regenerated muscle fibers, proliferation of endomysial CT, muscle replaced by fat and CT, type I and type II fibers involved.

  • presentation: weakness in pelvic girdle muscles, pesudohypertrophy, heart failure and arrhythmia, cardiomyopathy, cognitive impairment.

    • death by respiratory insufficiency, pulmonary infection, cardiac decompensation.

208

Limb Girdle Muscular Dystrophy

  • autosomal muscular dystrophy.
  • affects proximal trunk and limb musculature.
  • mutations of transmembrane sarcoglycan complex of proteins that link dystrophin with ECM.

209

Myotonic Dystrophy

  • autosomal dominant
  • ↑ in severity and appear at younger age in successive generations = anticipation.

  • myotonia = sustained involuntary muscle contraction.  cardinal neuromuscular symptom.

  • pathogenesis: CTG trinucleotide repeat expansion on 19q13. affects mRNA for DMPK.

  • morphology: fiber size heterogeneity, ↑ numbers internal nuclei and ring fibers (subsarcolemmal band of cytoplasm with rim of myofibrils that wrap around longitudinally oriented fibrils).

    • changes in muscle spindles: fiber splitting, necrosis, regeneration.

  • presentation: abnormalities in gait from foot dorsiflexor weakness, weakness in intrinsic hand muscles and wrist extensors, facial muscle atrophy, ptosis.

    • cataracts, frontal balding, gonadal atrophy, cardiomyopathy, smooth muscle involvement, ↓ plasma IgG, abnormal glucose tolerance test.

210

Channelopathies

  • familial disease with myotonia and/or hypotonic palsies
    • hypotonic can be hyper, hypo, or normokalemic.
  • hyperkalemic periodic paralysis: mutated SCN4A sodium channel protein - regulates Na entry during muscle contraction.
  • hypokalemic periodic paralysis: mutated gene for voltage gated L-type Ca channel.
  • malignant hyperpyrexia (malignant hyperthermia): dramatic hypermetabolic state triggered by anesthesia.  mutated gene for voltage gated L-type Ca channel (ryanodine receptor).
    • anesthetic ⇒ uncontrolled sarcoplasmic Ca efflux ⇒ tetany, ↑ muscle metabolism, excess heat production.
    • tachycardia, tachypnea, muscle spasms, hyperpyrexia later.