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Flashcards in Neuro Deck (229)
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211

Fascioscapulohumeral Muscular Dystrophy

  • autosomal dominant.
  • type 1A: deletions from D4Z4 on 4q35.
  • type 1B: mutated FSHMD1B.
  • morphology: dystropic myopathy with inflammatory infiltrates in muscle.
  • presentation: age 10-30yrs, weakness of muscles of face, neck, shoulder girdle.

212

Oculopharyngeal Muscular Dystrophy

  • autosomal dominant
  • mutated PABP-2 gene.
  • morphology; dystrophic myopathy with rimmed vacuoles in type 1 fibers.
  • presentation: onset in mid adult life, ptosis and weakness of extraocular muscles, difficulty swallowing.

213

Emery-Dreifuss Muscular Dystrophy

  • X-linked.
  • mutated emerin (EMD1) gene
  • morphology: mild myopathic changes, absent emerin.
  • presentation: onset 10-20yrs, prominent contractures especially at elbows and ankles.

214

Congenital Muscular Dystrophies

  • autosomal recessive
  • three types: MDC1A = type 1a, merosin deficient (laminin alpha 2 gene).
    • MDC1B = type 1b, 1q42.
    • MDC1c = type 1c, fukutin related protein gene.
  • morphology: variable fiber size, extensive endomysial fibrosis.
  • presentation: neonatal hypotonia, respiratory insufficiency, delayed motor milestones

215

Congenital Muscular Dystrophy with CNS Manifestations

  • aka Fukuyama type.
  • autosomal recessive.
  • mutated fukutin.
  • morphology: variable muscle fiber size and endomysial fibrosis, CNS malformations (polymicrogyria)
  • presentation: neonatal hypotonia and mental retardation.

216

Congenital Muscular Dystrophy with CNS and Ocular Manifestations

  • aka Walker-Warburg type.
  • mutated POMT1, POMT2.
  • morphology: variable muscle fiber size and endomysial fibrosis, CNS and ocular malformations
  • presentation: neonatal hypotonia and mental retardation with cerebral and ocular malformations.

217

Lipid Myopathies

  • abnormalities of carnitine transport system or deficiency of mitochondrial dehydrogenase enzyme systems ⇒ block fatty acid catabolism, muscle lipid accumulation.
  • limited ATP generation when exercising ⇒ pain, tightness, myoglobinuria.
  • can have cardiomyopathies and fatty liver.

218

Mitochondrial Myopathies

  • oxidative phosphorylation diseases.
  • from mutations in nuclear and mitochondrial genes.
  • morphology: aggregates of abnormal mitochondria ⇒ irregular muscle fiber contour (ragged red fibers), 
    • ↑ # and abnormalities in shape and size of mitochondria

    • may contain paracrystalline arrays (parking lot inclusions) or alterations in cristae structure.

  • presentation: young adults, proximal muscle weakness, severe eye muscle dysfunction.  neurologic symptoms, lactic acidosis, cardiomyopathy.  

    • from mtDNA mutation have maternal inheritance.

    • from pt mutations in mtDNA ⇒ myoclonic epilepsy, Leber hereditary optic neuropathy, MELAS.

    • from deletions or duplications of mtDNA ⇒ chronic progressive external ophthalmoplegia or Kearns-Sayer syndrome.

    • from mutated nuclear DNA = X-linked or autosomal dominant/recessive.  subacute necrotizing encephalopathy, exertional myoglobinuria, X-linked cardioskeletal myopathy.

219

Central Core Disease

  • autosomal dominant
  • mutation RYR1 gene.
  • morphology: cytoplasmic cores slightly eosinophilic and distinct from sarcoplasm.  in type I fibers on NADH stain.
  • presentation: early onset hypotonia, nonprogressive weakness, skeletal deformities, sometimes malignant hyperthermia.

220

Nemaline Myopathy

  • autosomal dominant or recessive.
    • dominant = NEM1-TPM3 gene (tropomysin 3)
    • recessive = NEM2-NEB gene (nebulin)
    • dominant or recessive = ACTA1 gene (skeletal muscle actin alpha 1)
  • morphology: aggregates of nemaline rods (subsarcolemmal spindle-shaped particles), in type I fibers, from alpha-actinin in Z-band.  see on Gomori stain.
  • presentation: weakness, hypotonia, delayed motor development in childhood (sometimes adults).  
    • nonprogressive.  
    • involves proximal limb muscles most.
    • can have skeletal abnormalities.

221

Myotubular Myopathy

  • aka centronuclear.
  • X-linked, autosomal dominant, autosomal recessive.
    • X-linked = MTM1 gene.
    • autosomal dominant = MYF6 gene
    • autosomal recessive = unknown.
  • morphology: abundance of centrally located nuclei involving majority of muscle fibers, in type I fibers with small diameter, can be in type II fibers.
  • presentation: X-linked: infancy with hypotonia, poor prognosis.
    • autosomal = limb weakness, slowly progressive.
      • recessive = intermediate in severity and prognosis.

222

Dermatomyositis

  • lilac discoloration of upper eyelids and periorbital edema before or with weakness.
  • Grotton lesions = scaling, erythematous patches over knuckles, elbows, knees.
  • slow onset muscle weakness, bilaterally symmetric, proximal muscles first.
    • dysphagia in 1/3.
  • may have interstitial lung disease, vasculitis, myocarditis.
  • 25% have cancer.
  • juvenile pts: GI symptoms, 1/3 have calcinosis.
  • targets capillaries.
  • morphology: perivascular inflammatory infiltrates, scattered necrotic muscle fibers and muscle fiber atrophy at periphery of fascicles from hypoperfusion.
  • tx: immunosuppression.

223

Polymyositis

  • in adults.
  • cytotoxic T cell driven myocyte damage
  • autoAb against tRNA synthetases.
  • slow onset muscle weakness, bilaterally symmetricproximal muscles first.
  • morphology: endomysial inflammation, scattered necrotic muscle fibers, no vascular injury (perifascicular atrophy)
  • tx: immunosuppression.

224

Inclusion Body Myositis

  • starts with distal muscle involvement (extensors of knee, flexors of wrist).
  • can be asymmetric.
  • insidious onset, age > 50 yrs.
  • CD8+ T cells present but immunosuppression not effective.
  • intracellular deposits of beta-amyloid and hyperphosphorylated tau = abnormal protein folding.
  • morphology: endomysial inflammatory infiltrates, rimmed vacuoles (clear cytoplasm with thin rim basophilic material), contain amyloid.

225

Thyrotoxic Myopathy

  • proximal muscle weakness, can precede clinical thyroid dysfunction.
  • myofiber necrosis, regeneration, interstitial lymphocytosis.
  • hypothyroidism: muscle cramping and slow movements from fiber atrophy, ↑ # internal nuclei, glycogen aggregates.

226

Ethanol Myopathy

  • binge drinking ⇒ acute toxic syndrome of rhabdomyolysis with myoglobulinemia.
  • can cause renal failure.

227

Drug-Induced Myopathies

  • Cushing syndrome or corticosteroids ⇒ proximal muscles weakness and atrophy in type II fibers
  • chloroquine proximal myopathy with autophagic membrane-bound vacuoles and intracellular curvilinear lamellar bodies.
  • Statin-induced myopathy in 1-2%.

228

Myasthenia Gravis

  • autoAb against skeletal muscle Ach receptors.
  • women < 40 yrs.  m=f in elderly.
  • pathogenesis: AchR autoAb ⇒ complement fixation and direct postsynaptic membrane damage, accelerate internalization and down-regulation of AchR, or block Ach binding.
  • morphology: LM unremarkable, junctional folds reduced or gone at NMJ, ↓ AchR expression.
  • Presentation: easy fatigability, ptosis, and diplopia.  worsen with repeated stimulation.
    • thymic hyperplasia in 65%.
    • thymomas in 15%.
    • thymic resection can improve it.
  • tx: anticholinesterase agents, prednisone, plasmapheresis.

229

Lambert-Eaton Myasthenic Syndrome

  • weakness and autonomic dysfunction.
  • mostly paraneoplastic from small cell lung carcinoma.
  • autoAb against pre-synaptic voltage gated Ca channel ⇒ ↓ amount synaptic vesicles released.
  • improves with repeated stimulation.