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NMSK Exam 3 > Chapter 26 > Flashcards

Chapter 26 Flashcards

1
Q
A
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2
Q

Disorders of NMJs present with what?

A

Painless muscle weakness

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3
Q

Disease of NMJ are most often due to what?

A

AutoAB that inhibit AChR, which are responsible for intiating signals that cause contraction of muscle.

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4
Q

What toxins can cause damage to NMJ?

A
  1. Clostridium botulinum, botox blocks release of acetylcholine
  2. Curare muscle relaxant blocks AChR → flaccid paralysis
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5
Q

2 Diseases of NMJ caused by autoAb that affect AChR

A
  1. Myasthenia gravis (grave weakness)
  2. Lambert-Eaton
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6
Q

When is Myasthenia Gravis most common and in whom?

A

Bimodal age

  1. Younger adults = more common in W
  2. Older adults = more common in M
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7
Q

Myastheina Gravis is caused by what?

A

AutoAB against:

  1. Post-synaptic ACh-R (85% cases)
  2. Muscle-specific receptor tyrosine kinase (15%)
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8
Q

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

Why>

A
  • Thymic abnormalities: Thymoma (benign tumor of thyroid) and Thymic hyperplasia (often in younger patients)
  • Thymoma and hyperplasia disrupt function of thymus, causing autoimmunity againt AChR in thymic myoid cells.
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9
Q

Histology of thymic hyperplasia in patients with Myasthenia Gravis

A
  1. B-cell follicles in thymus
    2.
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10
Q

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

A

Fluctuating generalized weakness that worsens with exertion and over course of day

  1. Begins with extraocular muscles: ptosis (drooping eyelids) and diplopia
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11
Q

What feature of Myashtenia Gravis is not seen in any other myelopathies?

A

Weakness of extraocular muscles => ptsosis and diplopia

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12
Q

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

A
  • M.G. = ↓↓↓ muscle responses (blinking) after repeated stimulation

- L.E.M.S = ↑↑↑ muscle response (blinking) after repeated stimulation

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13
Q

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

A
  1. 1st line = AChE inhibitors-> INC 1/2 life of ACh.
  2. Plasmapheresis and immunosuppressives (glucocorticoids, cyclosporine, rituximab) –> ↓ autoAb titers
  3. Thymectomy for those with thymoma
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14
Q

How do patients with autoAB to AChR differ from those with Ab to muscle specific tyrosine kinase in Myasthenia Gravis?

A

Ab to muscle specific tyrosine kinase => more focal muscle involvement(neck, shoulder, facial, respiratory and bulbar muscles)

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15
Q

Lambert-Eaton Myasthenic Syndrome is what?

A

An AI disorder OR paraneoplstic syndrome caused be Ab that block ACh release by inhibiting pre-synaptic Ca2+ channel

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16
Q

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

A

A paraneoplastic syndrome due to cancer (small-cell carcinoma of lung)

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17
Q

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

A

Weakness of the proximal extremities and autonomic dysfunction

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18
Q

Durning embryogenesis, how does skeletal muscle develop?

A
  • Mononucleated precursor cells (myoblasts) fuse ==> multinucleated myotubes
  • Later mature into myofibers (muscle fibers) that vary in length and have thousands of nuclei
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19
Q

In adult tissue, how are skeletal muscle myofibers arranged?

A

Fascicles, each associated with a small pool of tissue stem cells (satellite cells), that help with muscle regeneration after injury

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20
Q

Types of skeletal muscle fibers and how are they arranged

A

Type I and type II, which are admixed in a checkerboard pattern in normal skeletal muscle

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21
Q

What determines whether a skeletal myofiber is type 1 or 2?

A

Signal from the innervating motor neuron, meaning that all muscle fibers in a motor unit are the SAME type

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22
Q
  1. What surrounds an individual muscle fiber/cell?
  2. What surrounds fascicles?
  3. What surrounds skeletal muscle (group of fascicles)?
A
  1. Endomysium
  2. Perimysium
  3. Epimysium
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23
Q

What causes skeletal muscle atrophy?

A
  1. Loss of innervation
  2. Disuse
  3. Cachexia
  4. Old age
  5. Primary myopathies
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24
Q

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

A
  1. Prolonged corticosteroid therapy
  2. Disuse
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25
Q

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

A

Neurogenic diseases

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26
Q

How can skeletal muscle myofibers be injured?

A
  1. Directly injured (myopathic injury)
  2. Disruption of muscle innervation (neurogenic disease), which leads to fiber type grouping and grouped atrophy
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27
Q

Myopathic injury (directly injury) to skeletal muscles causes what changes in the muscle?

A
  1. Segmental myofiber degeneration and regeneration
  2. Hypertrophy of myofiber = adaptation to exercise or chronic myopathic conditions
  3. Cytoplasmic inclusions, like vacuoles, aggregates of protein, clusters of organnelles.
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28
Q

What is a marker for damage to skeletal muscle?

A

Creatine Kinase

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29
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 randomly distributed in cytoplasm
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30
Q

Name 3 primary Non-Infectious Inflammatory Myopathies

A
  1. Polymyositis
  2. Dermatomyositis
  3. Inclusion body myositis
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31
Q

What is Dermatomyositis?

When does it MC occur?

A
  • Systemic AI disease that involves skin and muscle
  • Adults: 40s-60s
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32
Q

Skin changes in Dermatomyositis

A
  1. Distinctive skin rash: lilac or heliotrope discoloration of eyelids + periorbital edema
  2. Telangiectasies (dilated capillaries) in nail folds, eyelids and gums
  3. Grotten lesions: scaling erythemous patches over the knuckles, elbows and knees.
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33
Q

Muscle changes in Dermatomyositis

A
  1. Weakness of proximal muscles 1st => difficulty rising from chair, climbing stairs
  2. 1/3 dev dysphagia (oropharyngeal & esophageal m) => problem swallowing
  3. 10% interstitial lung dz, vasculitis
  4. Cardiac involvement common, rarely leads to cardiac failure
34
Q

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

A

Anti-Mi2 antibodies

35
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 Ab

36
Q

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

A

Anti-P155/P140 Ab

37
Q

Histology in Dermatomyositis?

A
  1. Perfascicular atrophy = atrophic myofiber grouped periphery of fascicles
    * Mononuclear infiltrate perimysial CT
38
Q

Patients with dermatomyositis have ↑ of?

A

↑ risk of visceral cancer

15-24% adults with dermatomyositis have an assoc malignancy, may be viewed as paraneoplastic

39
Q

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

A

Juvenile Dermatomyositis; average age 7YO

40
Q

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

A
  1. GI involvement
  2. Calcinosis and lipodystrophy (have a better prognosis)
41
Q

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

A
  1. Adult onset w/ myalgia and weakness; NO cutaneous features
  2. Symmetrical proximal muscle involvement
42
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 mononuclear infiltrate of (CD8+ T cells), affecting random fibers
43
Q

When does Inclusion Body Myositis typically present?

A

- Late adulthood; typically >50 y/o

  • Most common cause of inflammatory myopathy in pt’s >65 y/o
44
Q

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

A
  1. Slowly progressive asymmetric muscle weakness, most severe in quadriceps (knee extensors) and distal upper extremities (flexors of wrist and fingers)
  2. Dysphagia is not uncommon
45
Q

Morphological changes that are specific for Inclusion Body Myositis?

A
  1. - “Rimmed vacuoles” = cytoplasmic inclusions with red/granular rimming + basophilic granules around periphery + endomysial fibrosis
46
Q

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

A

Corticosteroids

47
Q

Which drugs cause drug-induced lysosomal storage myopathy => with slowly progressive muscle weakness which predominantly affects type I fibers?

A

Anti-malarial drugs: Chloroquine and hydroxychloroquine

48
Q

Myopathy is a common compliation of what drugs, not related to the dose or type?

A

Statin: atorvastatin, simvastatin, pravastatin.

49
Q

What is ICU myopathy (aka myosin deficit myopathy)?

A

Critical illness + corticosteroid treatment

50
Q

Thyrotoxic myopathy causes what?

A
  1. Acute or chronic proximal muscle weakness
  2. Exopthalmic opthalmoplregia: swelling of eyelids, conjunctiva and diplopia
  3. Hypothryoirism
51
Q

Binge drinking can cause what myopathy?

A
  1. Rhabdomyolysis
  2. Myoglobinuria
  3. Renal failure
  4. Acute myalgia
52
Q

Types of Inherited Diseases of Skeletal Muscle

When do they present?

A
  1. Congenital myopathies = persent in infancy with muscle defects that are static or get better over time
  2. Muscular dystrophies = progressive muscle damage that appears AFTER infancy, often associated with developmental abnormalities of the CNS + progressive muscle damage
53
Q
  1. What is the inheritance and gene is affected in Duchene and Beckers muscular dystropgy?
  2. Most commonly sporadic or familial?
  3. Both have INC risk of developing what?
A
  • X-linked
  • DMD gene on Xp21 => encodes dystrophin
  • 2/3 = familial
  • Cardiomyopathy
54
Q

How do the type of mutations of 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
55
Q

Which is more common and more severe: Duchenne or Becker?

A

Duchenne: more common = more severe

56
Q

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

A

↑↑↑ CK

57
Q

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

A
  • Females carriers = asymptomatic
  • Symptoms appear before 5YO
    • Begins in pelvic girdles -–> extends to shoulder girdles
    • Pseudohypertrophy of calves: enlargement of lower leg muscles due to weakness: initially => ↑ bulk due to ↑ size of muscle fibers initially; later => muscle is replaced by ↑ fat & CT
  • Wheelchair bound by 10-12 YO
58
Q

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

A
  1. Begins in late childhood/adolescene
    1. Begins in pelvic girdles —> extends to shoulder girdles
    2. Pseudohypertrophy of calves often present (same as Duchennes)
  2. Nearly NL lifespan
  3. INC risk of cardiac disease
59
Q

Histology of DMD and BMD

A
  1. Variation in fiber size
  2. ↑ # internalized nuclei
  3. Degeneration, necrosis, & phagocytosis of muscle fibers
  4. Regeneration of muscle fibers
  5. Proliferation of endomysial connective tissue
  6. occasionally (DMD), enlarged, rounded hyaline fibers that have lost their cross-striations (rare in BMD)

7.Later stages, muscle almost totally replaced by fat & connective tissue

60
Q

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

A
  • Duchenne: absence of normal dystrophen staining pattern
  • Becker: shows reduced staining
61
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”

62
Q

What is a key feature of Myotonic Dystrophy?

A

Myotonia: sustained involuntary contraction of a group of muscles; elicited by percussing the thenar eminence => “Stifness or difficulty releasing grip”

63
Q

Myotonic dystrophy is caused by what?

A

AD: expansions of CTG triplet repeats in 3’-noncoding region of DMPK gene

64
Q

How does Myotonic Dystrophy present signs and sx’s?

A
  1. Gait, then atrophy of facial muscles = ptosis and “hatchet face,”
  2. Frontal balding,
  3. Cataracts,
  4. Cardiomyopathy
  5. Endocrinopathy
65
Q

Histology in Myotonic Dystropgy

A
  1. Ring fiber
  2. Sarcoplasmic Mass
66
Q

What are diseases of lipid and glycogen metabolism?

A

Inborn errors of lipid or glycogen metabolism affect SKM

  1. Carnitine palmitoyltransferase II
  2. McArdle Dz (myophosphorylase def)
  3. Pompe Dz (Acid maltase def)
67
Q

When does a patient with a disease of lipid/glycogen metabolism get symptoms of muscle dysfunction?

A
  1. Exercise or fasting
  2. Or slowly progressive muscle damage
68
Q

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

A
    • Episodic muscle damage with exercise and fasting
69
Q

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

A

Myopathy preferentially involving respiratory and truncal muscles

70
Q

Severe acid maltase deficiency causes what?

A

Pompe disease => generalized glyocogenesis of infancy

71
Q

Skeletal muscle involvement in Mitochondrial Myopathies, which cause problems making ATP, can manifest with what findings; involvement of what is common and can be a clue to the diagnosis?

A
    • Weakness + ↑ CK or rhabdomyolysis
    • Extraocular muscle involvement = common and clue to dx
    • Chronic progressive external opthalmoplegia = common feature
72
Q

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

A

Ragged red fibers: Abnormal aggregates of mitochondria under the sarcolemma (red) + distortion of myofibrils (ragged)

- Trimchrome stain*

73
Q

On EM, ragged red fibers seen in skeletal muscle due to Mitochondrial Myopathies are described how?

A

Paracrystalline parking lot inclusions

74
Q

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

A
  • Destruction of anterior horn motor neurons in the spinal cord => muscle weakess and atropgy
  • Onset at birth: generalized hypotonia (floppy infant), death <3 yo
  • Initially => muscle weakness of truncal and extremity ms ==> followed by chewing, swallowing and breathing difficulties
75
Q

Spinal Muscular Atrophy is also called what?

Inheritance

A

Infantile Motor Neuron Disease

  • AR mutation of Survival Motor Neuron 1 (SMN1) on Chr 5
76
Q

Characteristic morphological changes seen with Spinal Muscular Atrophy (SMA)?

A
  • Mix of:
    • Large zones of round atrophic myofibers (panfascicular atrophy)
    • Scattered NL sized fibers or hypertrophied myofibers that are STILL innervated, found individually or in small groups
77
Q

Ion channel myopathies are what?

Inheritance?

Symptoms?

A
  • Mutations affecting function of ion channel proteins
  • Most AD
  • SX:
    • epilepsy,
    • migraine,
    • movement DOs with cerebellar dysfunction,
    • peripheral n dzs
    • muscle dz
    • •↑ or ↓ excitability → hypotonia or hypertonia
78
Q

What triggers malignant hyperthermia in patients with RYR1 mutation?

A

Anesthetics (usu halogenated inhalational agents) ==> ↑efflux of Ca⁺² from sarcoplasmic reticulum→ tetany & excessive heat production

79
Q

What is an ion channel myopathy (channelopathy)?

A

Malignant Hyperthermia due to a RYR1 mutation

80
Q

RYR1 mutations are associated with what?

A

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

81
Q

Ion channel myopathies that cause hypotonia may have what associated findings?

A
  1. ↑,↓ or NL serum K+ (potassium)
82
Q
A

NMSK Exam 3 (17 decks)

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