Chapter 27: Diseases of the NMJ and Skeletal Muscle Flashcards

1
Q

Disorders of NMJs present with what?

A

Painless muscle weakness

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2
Q

Myastheina Gravis is associated with autoantibodies against what?

A
  • ACh receptors on post-synaptic membrane (85% cases)
  • Muscle-specific receptor tyrosine kinase (15%)
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3
Q

There is a strong association with tht AChR autoantibodies seen in Myathenia Gravis and which abnormalities?

A

Thymic abnormalities: Thymoma and Thymic hyperplasia

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4
Q

Myasthenia gravis patients with AChR autoantibodies usually present with what signs/sx’s?

A
  • Fluctuating weakness that worsens with exertion and over course of day
  • Diplopia** and **ptosis due to involvement of extra-ocular muscles
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5
Q

What electrophysiologic findings help distinguish Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome?

A
  • M.G. = Diminished muscle responses after repeated stimulation
  • L.E.M.S = Increased muscle response after repeated stimulation
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6
Q

What is 1st line tx for Myasthenia Gravis and what other tx’s can be used to control the sx’s?

A
  • 1st line = Acetylcholinesterase inhibitors
  • Plasmapheresis and immunosuppressives (glucocorticoids, cyclosporine, rituximab) –> ↓ autoAb titers
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7
Q

Lambert-Eaton Myasthenic Syndrome is an autoimmune disorder due to what?

A

Antibodies block ACh release by inhibiting pre-synaptic Ca2+ channel

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8
Q

50% of Lambert-Eaton Myasthenic Syndrome cases are associated with what underlying condition?

A

Malignancy; most often small-cell carcinoma of lung

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9
Q

Pt’s with Lambert-Eaton Myasthenic Syndrome typically present with what sx’s?

A

Weakness of the extremities and autonomic dysfunction

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10
Q

Type II fiber atrophy with sparing of type I fibers is seen with what?

A

Prolonged corticosteroid therapy or disuse

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11
Q

Clusters or groups of atrophic skeletal muscle fibers are seen in which disorders?

A

Neurogenic diseases

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12
Q

Regenerating myofibers are rich in what and stain how in H&E stained sections; characteristic nuclei and nucleoli that are seen?

A
  • RNA and stain basophilic
  • Enlarged nuclei and prominent nucleoli
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13
Q

Which autoantibody type in Dermatomyositis is associated with prominent Gottron papules and heliotrope rash?

A

Anti-Mi2 antibodies

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14
Q

Which autoantibody type in Dermatomyositis is associated with interstitial lung disease, non-erosive arthritis, and a rash known as “mechanic’s hands?”

A

Anti-Jo1 antibodies

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15
Q

Which autoantibody type in Dermatomyositis is associated with paraneoplastic and juvenile cases?

A

Anti-P155/P140 antibodies

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16
Q

Myofiber atrophy accentuated at the periphery of fascicles known as perfascicular atrophy is seen with what disorder?

A

Dermatomyositis

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17
Q

Biopsies and immunohistochemical studies of muscle and skin in Dermatomyositis will show deposition of what?

A

Complement MAC (C5b-9) within capillary beds + infiltrate rich in CD4+ T helper cells

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18
Q

What are the signs and sx’s of dermatomyositis and some complications which may be seen?

A
  • Slow onset symmetric muscle weakness often w/ myalgias affecting the proximal ms. 1st
  • 10% of pt’s have dysphagia and another 10% with interstitial lung disease —> can cause death
  • Cardiac involvement = common, rarely leads to failure
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19
Q

What is the most common inflammatory myopathy in children and average age of onset?

A

Juvenile Dermatomyositis; average age 7 y/o

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20
Q

Juvenile Dermatomyositis is more likely to have what findings compared to the adult-type; how does this affect prognosis?

A

Calcinosis and lipodystrophy; have a better prognosis

21
Q

Various rashes have been described in Dermatomyositis, but which 2 are the most characteristic?

A
  • Heliotrope rash: Lilac colored discoloration of upper eyelids assoc. w/ periorbital edema
  • Gottron papules: scaling erythematous eruption or dusky patches over knuckles, elbows and knees
22
Q

Which inflammatory myopathy is more associated with perimysial infiltration vs. endomysial infilatration?

A
  • Dermatomyositis = perimysial (CD4+ T cells)
  • Polymyositis and Inclusion body myositis = endomysial (CD8+ T cells)
23
Q

When is the onset of Polymyositis and what are the signs/sx’s; how is it distinguished from Dermatomyositis?

A
  • Adult onset w/ myalgia and weakness; NO cutaneous features
  • Symmetrical proximal muscle involvement
24
Q

When does Inclusion Body Myositis typically present?

A
  • Disease of late adulthood; typically >50 y/o
  • Most common cause of inflammatory myopathy in pt’s >65 y/o
25
Q

What are the typical signs/sx’s of Inclusion Body Myositis?

A
  • Slowly progressive muscle weakness most severe in quadriceps and distal upper extremities; asymmetric
  • Dysphagia is not uncommon
26
Q

What are 4 morphological changes that are specific for Inclusion Body Myositis?

A
  • Abnormal cytoplasmic inclusions, “rimmed vacuoles”
  • Tubulofilamentous inclusions in myofibers
  • Cytoplasmic inclusions containing beta-amyloid, TDP-43, and ubiquitin
  • Endomysial fibrosis and fatty replacement
27
Q

What is the first-line tx for inflammatory myopathies (i.e., dermatomyositis and polymyositis)?

A

Corticosteroids

28
Q

Which drugs are associated with slowly progressive muscle weakness which predominantly affects type I fibers?

A

Chloroquine and hydroxychloroquine

29
Q

Ullrich congenital muscular dystophy (UCMD) is due to mutations in what; what is a morphological hallmark?

A
  • Mutations in one of thre collagen VI alpha genes
  • Hallmark: mismatched expression of normally co-localized matrix proteins perlecan and collagen VI
30
Q

How do the type of mutations of Dystrophin differ between Duchenne and Becker muscular dystrophy?

A
  • Duchenne: deletions or frame shift mutations –> total absence
  • Becker: synthesis of a truncated version, which retains some function
31
Q

What will immunohistochemical staining for dystrophin show in Duchenne vs. Becker muscular dystrophy?

A
  • Duchenne: absence of normal sarcolemmal staining pattern
  • Becker: shows reduced staining
32
Q

What morphological changes are seen with disease progression in Duchenne and Becker muscular dystrophy?

A

Muscle tissue is replaced by collagen and fat cells = Fatty replacement or change”

33
Q

Where does weakness associated with Duchenne muscular dystrophy begin and how does it progress?

A
  • Begins in pelvic girdles —> extends to shoulder girdles
  • Pseudohypertrophy of calves often present
  • Wheel-chair bound around age 9.5
34
Q

Which lab value can aid in the diagnosis of Duchenne and Becker muscular dystrophy?↑↑

A

↑↑↑ CK

35
Q

What is a key feature of Myotonic Dystrophy?

A

Myotonia: sustained involuntary contraction of a group of muscles; can be elicited by percussion on thenar eminence

36
Q

Myotonic dystrophy is caused by what?

A

Expansions of CTG triplet repeats in 3’-noncoding region of DMPK gene

37
Q

How does Myotonic Dystrophy present signs and sx’s?

A

Gait, then atrophy of facial muscles = ptosis and “hatchet face,” frontal balding, cataracts, cardiomyopathy

38
Q

What is the triad of findings seen with Emery-Dreifuss Muscular Dystrophy?

A

1) Slowly progressive humeroperoneal weakness
2) Cardiomyopathy w/ conduction defects
3) Early contractures of the achilles, spine, and elbows

39
Q

Emery-Dreifuss Muscular Dystrophy is due to mutations in genes that encode what and what is the inheritance of EMD1 and EMD2?

A
  • Genes that encode nuclear lamina proteins
  • X-linked = EMD1
  • Autosomal dominant = EMD2
40
Q

Carnitine palmitoyltransferase II deficiency is associated with what pattern of muscle damage?

A
  • Episodic muscle damage with exercise and fasting
  • Defect in transport of FFAs —> mitochondria
41
Q

Milder deficiencies of acid maltase lead to what type of myopathy in adults?

A

Myopathy preferentially involving respiratory and truncal muscles

42
Q

Skeletal muscle involvement in Mitochondrial Myopathies can manifest with what findings; involvement of what is common and can be a clue to the diagnosis?

A
  • Weakness + ↑ CKorrhabdomyolysis
  • Extraocular muscle involvement = common and clue to dx
  • Chronic progressive external opthalmoplegia = common feature
43
Q

Morphologically what is the most consistent pathologic change seen in skeletal muscle of the Mitochondrial Myopathies; which stain can be used?

A
  • Abnormal aggregates of mitochondria under the sarcolemma producing appearance of “ragged red fibers”
  • Trimchrome stain*
44
Q

Which syndrome due to deletions or duplications in mtDNA is characterized by ophthalmoplegia, pigmentary degeneration of the retina, and complete heart block?

A

Kearns-Sayre syndrome

45
Q

Point mutations in mtDNA can lead to which two mitochondrial myopathies?

A
  • Myoclonic epilepsy w/ ragged red fibers
  • Leber hereditary optic neuropathy
46
Q

Wernig-Hoffman (SMA type 1) is due to destruction of what and what is the presentation?

A
  • Destruction of anterior horn cells in the spinal cord
  • Onset at birth, floppy baby, death <3 yo
  • Muscle weakness of truncal and extremity ms. initially; followed by chewing, swallowing and breathing difficulties
47
Q

What are the characteristic morphological changes seen with Spinal Muscular Atrophy (SMA)?

A

Large zones of severely atrophic myofibers mixed with scattered normal sized fibers or hypertrophied myofibers, found individually or in small groups

48
Q

Missense mutations in CACNA1S (subunit of muscle Ca2+ channel) are the most common cause of what?

A

Hypokalmemic paralysis

49
Q

RYR1 mutations are associated with what?

A

Malignant hyperthermia –> hypermetabolic state: tachycardia + tachypnea + muscle spasms and later hyperpyrexia