pathology (muscle)

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pathology (muscle)
2013-09-18 15:29:45
pathology muscle

pathology (muscle)
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  1. What is a motor unit?
    (1) a lower motor neuron in the anterior horn of the spinal cord or cranial nerve motor nucleus in the brain stem, (2) the axon of that neuron, and (3) the multiple muscle fibers it innervates
  2. How does Schawnn cell cover myelinated and unmyelinated fibers?
    • A single Schwann cell supplies the myelin sheath for each internode.
    • Unmyelinated axons are far more numerous than myelinated axons, and the cytoplasm of one Schwann cell envelops a variable number of unmyelinated fibers (5 to 20 axons in humans).
  3. What are the three major connective tissue components of peripheral nerve? .
    • the epineurium, which encloses the entire nerve;
    • the perineurium, a multilayered concentric connective tissue sheath that encloses each fascicle;
    • and the endoneurium, which surrounds individual nerve fibers
  4. What are the abnormal motor units?
    • Normal motor units: Two adjacent motor units are shown (red and green neurons, red and pale-pink myocytes). Segmental demyelination: Random internodes of myelin are injured and are remyelinated by multiple Schwann cells, while the axon and myocytes remain intact. Axonal degeneration: The axon and its myelin sheath undergo anterograde degeneration (shown for the green neuron), with resulting denervation atrophy of the myocytes within its motor unit (pale-pink myocytes). Reinnervation of muscle: Sprouting of adjacent (red) uninjured motor axons leads to fiber type grouping of myocytes, while the injured axon attempts axonal sprouting. Myopathy: Scattered myocytes of adjacent motor units are small (degenerated or regenerated), whereas the neurons and nerve fibers are normal.
  5. How is two main responses of peripheral nerve to injury determined?
    • By the target of the injury: either the Schwann cell or the axon.
    • Diseases that affect primarily the Schwann cell lead to a loss of myelin, referred to as segmental demyelination.
    • Primary involvement of the neuron and its axon leads to axonal degeneration. In some diseases axonal degeneration may be followed by axonal regeneration and reinnervation of muscle.
  6. What are the causes of segmental demyelination?
    • Dysfunction of the Schwann cell (HSMN)
    • Damage to the myelin sheath (GBS
    • there is no primary abnormality of the axon.
  7. What is the histological hallmark of segmental demyelination?
    • With sequential episodes of demyelination and remyelination, there is an accumulation of tiers of Schwann cell processes that, on transverse section, appear as concentric layers of Schwann cell cytoplasm and redundant basement membrane surrounding a thinly myelinated axon (onion bulbs)
  8. What is the response of a nerve fiber to segmental demyelination?
    The disintegrating myelin is engulfed initially by Schwann cells and later by macrophages. The denuded axon provides a stimulus for remyelination. A population of precursor cells within the endoneurium has the capacity to replace injured Schwann cells. These cells proliferate and encircle the axon and, in time, remyelinate the denuded portion
  9. What are the features of newly myelinated fibers after demyelination?
    Newly formed myelinated internodes are shorter than normal, and several are required to bridge the demyelinated region. The new myelin sheath is also thin in proportion to the diameter of the axon.
  10. What is the major complication of chronic demyelinating neuropathy?
    Axonal injury
  11. What is the cause of axonal degenration?
    • Primary destruction of the axon, with secondary disintegration of its myelin sheath.
    • Damage to the axon may be due to a focal event occurring at some point along the length of the nerve (such as trauma or ischemia) or to a more generalized abnormality affecting the neuron cell body(neuronopathy) or its axon (axonopathy).
  12. What is the hallmark of the axon response to focal axonal degeneration?
    Wallerian degenerationof the distal portion
  13. What is the histological specific finding in Wallerian degeneration?
    Within a day the axon begins to break down, and the affected Schwann cells begin to catabolize myelin and later engulf axon fragments, forming small oval compartments (myelin ovoids).
  14. How does Wallerian degeneration occur?
    • Within a day the axon begins to break down, and the affected Schwann cells begin to catabolize myelin and later engulf axon fragments, forming small oval compartments (myelin ovoids).
    • Macrophages are recruited into the area and participate in the phagocytosis of axonal and myelin-derived debris.
    • The stump of the proximal portion of the severed nerve shows degenerative changes involving only the most distal two or three internodes and then undergoes regenerative activity.
  15. What happens in the slowly evolving neuronopathies or axonopathies regarding axonal regeneration?
    Evidence of axonal degeneration is scant because only a few fibers are actively degenerating at any given time
  16. What happens following axonal degeneration in the muscle innervated by that axon?
    • The muscles undergo denervation atrophy. Breakdown of myosin and actin, with a decrease in cell size and resorption of myofibrils, but cells remain viable.
    • In cross-section, the atrophic fibers are smaller than normal and have a roughly triangular (“angulated”) shape.
    • There is also cytoskeletal reorganization of some muscle cells, which results in a rounded zone of disorganized myofibers in the center of the fiber (target fiber).
  17. What is the histological evidence for axonal regeneration?
    The presence of multiple closely aggregated, thinly myelinated small-caliber axons is evidence of regeneration (regenerating cluster)
  18. How does axonal regeneration occur?
    • The proximal stumps of degenerated axons sprout and elongate, and they may develop new growth cones during the process of axonal regeneration.
    • These growth cones use the Schwann cells vacated by the degenerated axons to guide them.
    • The presence of multiple closely aggregated, thinly myelinated small-caliber axons is evidence of regeneration (regenerating cluster).
    • This regrowth of axons is apparently limited by the rate of the slow component of axonal transport, and the movement of tubulin, actin, and intermediate filaments, proceeding at about 1 mm per day. 
    • May cause some functional recovery
  19. How is the muscle fiber type determined?
    By the neuron of the motor unit
  20. What is the distribution of fiber type in a given motor unit?
    Since the motor neuron determines fiber type, all muscle fibers of a single unit are of the same type
  21. What are the features of type 1 muscle fibers?
    “one (type 1 fiber) slow (twitch) fat (lipid-rich) red (appearance) ox (oxidative)” 
  22. What are the differences between type one and two fibers?
    • Type 1 fibers (red) are high in myoglobin and oxidative enzymes and have many mitochondria, high lipid and low glycogen content in keeping with their ability to perform tonic contraction; operationally, they are most often defined by their dark staining for adenosine triphosphatase (ATPase) at pH 4.2 but light staining at pH 9.4. (Wide Z band)
    • Type 2 fibers (white)are rich in glycolytic enzymes and are involved in rapid phasic contractions, have low myoglobin, mitochondria, lipid and high glycogen; they are dark staining on ATPase stain performed at pH 9.4 but light staining at pH 4.2. (Narrow Z band)
  23. How are fiber types distributed across a muscle before and after degeneration/regeneration?
    • The fibers of a single motor unit are distributed across the muscle, giving rise to a checkerboard pattern of alternating fiber types, as is demonstrated especially well with staining for ATPase/ The result of reinnervation is the loss of the checkerboard pattern and the occurrence of a patch of contiguous myocytes having the same histochemical type (type grouping
  24. What is the type of newly adopted reinnervated fibers?
    Furthermore, since muscle fiber type is imparted by the innervating neuron, the newly adopted reinnervated fibers assume the fiber type of their neighboring new siblings.
  25. What are the causes for type 2 atrophy?
    Inactivity or disuse--> after fracture of a limb and application of a plaster cast, in pyramidal tract degeneration, or in neurodegenerative diseases, “steroid myopathy.”
  26. What is the hallmark of steroid myopathy?
    Type 2 atrophy
  27. What are the reactions of muscle fiber to injury?
    • Segmental necrosis, destruction of a portion of the length of a myocyte, may be followed by myophagocytosis as macrophages infiltrate the region. The loss of muscle fibers in time leads to extensive deposition of collagen and fatty infiltration.  
    • Vacuolation, alterations in structural proteins or organelles, and accumulation of intracytoplasmic deposits may be seen in many diseases.  
    • Regeneration occurs when satellite precursor cells proliferate and reconstitute the destroyed portion of the fiber. The regenerating portion of the muscle fiber has large internalized nuclei and prominent nucleoli, and the cytoplasm, laden with RNA, is basophilic.  
    • Fiber hypertrophy occurs in response to increased load, either in the setting of exercise or in pathologic conditions in which muscle fibers are injured. Large fibers may divide longitudinally (muscle fiber splitting), so that in cross-section, a single large fiber contains a cell membrane traversing its diameter, often with adjacent nuclei.
  28. How is trichinosis transmitted?
    ingestion of larvae in undercooked meat from infected animals (usually pigs, boars, or horses)
  29. What is the life cycle of Trichinella?
    In the human gut, T. spiralis larvae develop into adults that mate and release new larvae, which penetrate into the tissues.
  30. What are the symptoms of acute trichinosis?
    • Larvae disseminate hematogenously and penetrate muscle cells, causing fever, myalgias, marked eosinophilia, and periorbital edema.
    • Much less commonly, patients develop dyspnea, encephalitis, and cardiac failure
  31. Which infection is capable of involving all three kinds of muscles?
    Chagas (T. Cruzi)
  32. What modifications occur by Trichinella larvae in skeletal muscle?
    loses its striations, gains a collagenous capsule, and develops a plexus of new blood vessels around itself
  33. What are the symptoms of intramuscular trichinosis?
  34. How is trichinosis serodiagnosed?
    Antibodies to larval antigens, which include an immunodominant carbohydrate epitope called tyvelose, may reduce reinfection and are useful for serodiagnosis of the disease
  35. What is the immune response in Trichinellosis?
    Trichinella spiralis and other invasive nematodes stimulate a TH2 response, with production of IL-4, IL-5, IL-10, and IL-13. The cytokines produced by TH2 cells activate eosinophils and mast cells, and increase contractility of the intestine, which expels adult worms from the gut and subsequently reduces the number of larvae in the muscles
  36. What is the morphology of trichinella in heart, lung and brain?
    • In the heart there is a patchy interstitial myocarditis characterized by many eosinophils and scattered giant cells. The myocarditis can lead to scarring. Larvae in the heart do not encyst (cannot be identified).
    • In the lungs, trapped larvae cause focal edema and hemorrhages, sometimes with an allergic eosinophilic infiltrate.
    • In the CNS, larvae cause a diffuse lymphocytic and eosinophilic infiltrate, with focal gliosis in and about small capillaries of the brain.
  37. Trichinella spiralis preferentially encysts in which striated skeletal muscles?
    Those with the richest blood supply, including the diaphragm and the extraocular, laryngeal, deltoid, gastrocnemius, and intercostal muscles
  38. What is the histology of trichinosis in striated muscle?
    • Coiled larvae are approximately 1 mm long and are surrounded by membrane-bound vacuoles within nurse cells, which in turn are surrounded by new blood vessels and an eosinophil-rich mononuclear cell infiltrate.
  39. What is the DOC for trichinosis?
    Albendazole (+steroid in severe cases)
  40. Which viral muscle infection can cause severe pain?
    coxsackievirus B (pleurodynia)
  41. What is the mcc of pyomyositis?
  42. What is the mcc of pyomyositis +toxicity?
    Strep.pyogenes (staph aureus--> not toxic)
  43. What are the features of strep.pyogenes myositis?
    • Associated with TSS (pyrogenic exotoxin A)
    • Associated with necrotizing fasciitis 
    • Severe toxicity
  44. How is SMA inherited?
  45. What is the involved gene in SMA?
    SMN1 (chromosome 5)-->AR (deletion)
  46. What is the role of SMN2 gene in SMA?
    • Chromosome 5 also contains variable numbers of copies of a second highly homologous gene, SMN2.
    • The number of copies of the homologous SMN2 modifies the clinical phenotype, with more copies being associated with milder neurologic phenotype
  47. What is the hallmark of SMA?
    Selective destruction of the anterior horn cells in the spinal cord and cranial nerve motor neurons
  48. What is the role of SMN?
    SMN protein is critical for normal axonal transport and integrity of neuromuscular junctions, and thus promotes survival of motor neurons.
  49. What is the histological finding in SMA?
    • Large numbers of atrophic fibers
    • This is unlike the groups of angulated atrophic fibers seen in denervation atrophy of muscle in adults.
    • In SMA the muscle fiber atrophy often involves an entire fascicle, a feature known as panfascicular atrophy.
    • There are also scattered large fibers that are two to four times normal size.
  50. What is the mc finding in SMA?
    SMA1 --> mc. onset at birth or within the first 4 months of life with severe hypotonia (lack of muscle tone and “floppiness”).
  51. What distinguishes dystrophies from myopathies ?
    in advanced cases of dystrophies muscle fibers undergo degeneration and are replaced by fibrofatty tissue and collagen
  52. What is the course of DMD?
    becomes clinically manifest by the age of 5 years. It leads to wheelchair dependence by 10 to 12 years of age, and thereafter progresses relentlessly
  53. What is the major problem in gene therapy of DMD?
    Large gene size
  54. What is the genetic abnormality in DMD and BMD?
    • X chromosome--> mc deletion
    • BMD--> reduced size and abnormal function
    • DMD--> absence
  55. What are the features of female carriers of DMD?
    • Elevated CK
    • Risk of DCMP in adulthood
  56. What is the function of dystrophin?
    • Dystrophin is a cytoplasmic protein located adjacent to the sarcolemmal membrane in myocytes.
    • It is concentrated at the plasma membrane over Z-bands, where it forms a strong mechanical link to cytoplasmic actin. Thus, dystrophin and the dystrophin-associated protein complex form an interface between the intracellular contractile apparatus and the extracellular connective tissue matrix.
    • The role of this complex of proteins in transferring the force of contraction to connective tissue has been proposed to be the basis for the myocyte degeneration that occurs in the absence of dystrophin[
  57. What are the involved genes in limb girdle muscular dystrophy?
    caveolin and sarcoglycan
  58. What are the histological features common to DMD and BMD?
    • (1) variation in fiber size 
    • (2) increased numbers of internalized nuclei 
    • (3) degeneration, necrosis, and phagocytosis 
    • (4) regeneration 
    • (5) proliferation of endomysial connective tissue 
    • (6)fibrous and fatty replacement
    • (7) involvement of both type I and II
  59. What histological feature in unique to DMD compared with BMD?
    DMD cases also often show enlarged, rounded, hyaline fibers that have lost their normal cross-striations; such fibers, believed to be hypercontracted, are rare in BMD.
  60. What is the histology of heart in DMD?
    interstitial fibrosis, which is more prominent in the subendocardium.
  61. What is the features of patients with DMD early in development?
    • Boys with DMD are normal at birth, and early motor milestones are met on time. Walking, however, is often delayed
    • First indications of muscle weakness are clumsiness and inability to keep up with peers.
    • Weakness begins in the pelvic girdle muscles and then extends to the shoulder girdle.
    • Other findings(late)--> lordosis, Gower
  62. In DMD where do first weakness begin?
    Pelvic girdle
  63. What is the cause of pseudohypertrophy in DMD?
    increase in the size of the muscle fibers and then, as the muscle atrophies, by an increase in fat and connective tissue
  64. What are the clinical manifestations of heart involvement in DMD?
    heart failure or arrhythmias
  65. What is the mcc of muscular dystrophy?
  66. What happens to CNS in DMD?
    Cognitive problem and MR
  67. What is the course of CK in DMD?
    Serum creatine kinase is elevated during the first decade of life but returns to normal as muscle mass decreases
  68. What is the mcc of death in DMD?
    respiratory insufficiency, pulmonary infection, and cardiac decompensation
  69. What are some other muscular dystrophies?
    • Fascioscapulohumeral muscular dystrophy--> AD
    • Oculopharyngeal (rimmed vacuoles in type 1 fibers)--> AD
    • Emery-Dreifuss--> XL prominent contractures, especially of elbows and ankles
    • Limb girdle (AR, AD)-->Sarcoglycan interact with dystrophin through another transmembrane protein, β-dystroglycan
  70. What is myotonia?
    the sustained involuntary contraction of a group of muscles, is the cardinal symptom in this disease. Patients often complain of “stiffness” and have difficulty in releasing their grip, for instance, after a handshake. Myotonia can often be elicited by percussion of the thenar eminence.
  71. What is the genetic of MD?
    • AD
    • CTG trinucleotide repeat expansion on chromosome 19q.
    • This expansion affects the mRNA for the dystrophia myotonia protein kinase (DMPK)
    • Anticipation
  72. What is the only dystrophy that shows pathologic changes in the intrafusal fibers of muscle spindles?
    Myotonic dystrophy
  73. What are the histological hallmarks of MD?
    • Striking increase in the number of internal nuclei, which on longitudinal section may form conspicuous chains.  
    • Ring fiber, with a subsarcolemmal band of cytoplasm that appears distinct from the center of the fiber. The rim contains myofibrils that are oriented circumferentially around the longitudinally oriented fibrils in the rest of the fiber.
    • The ring fiber may be associated with an irregular mass of sarcoplasm (sarcoplasmic mass) extending outward from the ring. These sarcoplasmic masses stain blue with hematoxylin and eosin, red with Gomori trichrome.
    • Relative atrophy of type I
    • Pathologic changes in the intrafusal fibers of muscle spindles
  74. What is the first muscle involvement in MD?
    Dorsiflexors of foot
  75. Which extramuscular involvement is present in 100% of patients with MD?
    Cataract and hypogonadism
  76. What is the hallmark of muscle involvement in MD?
    Involvement of small muscles first in the disease
  77. What are the other features of MD?
    • Atrophy of muscles of the face and ptosis
    • Cataracts
    • Frontal balding, gonadal atrophy, cardiomyopathy, smooth muscle involvement, decreased plasma IgG, and abnormal glucose tolerance, cognitive abnormality
  78. What are the features of ion channel myopathies, or channelopathies?
    • are a group of familial diseases featuring myotonia, relapsing episodes of hypotonic paralysis (induced by vigorous exercise, cold, or a high-carbohydrate meal), or both.
    • Hypotonia variants associated with elevated, depressed, or normal serum potassium levels at the time of the attack are called hyperkalemic, hypokalemic, and normokalemic periodic paralysis,
  79. What is the major genetic defect in hyper and hypokalemic periodic paralysis?
    • Hyperkalemic --> sodium channel
    • Hypokalemic--> voltage-gated L-type calcium channel.
  80. What are the features of malignant hyperthermia?
    • Marked hypermetabolic state (tachycardia, tachypnea, muscle spasms, and later hyperpyrexia) triggered by anesthetics, most commonly halogenated inhalational agents and succinylcholine.
    • The clinical syndrome may occur in predisposed individuals with hereditary muscle diseases.
    • L-type voltage-dependent calcium channel, notably the rynodine receptor (RyR1).
    • Upon exposure to anesthetic, the mutant receptor allows uncontrolled efflux of calcium from the sarcoplasm. This leads to tetany, increased muscle metabolism, and excessive heat production.
  81. What are the features of congenital myopathies?
    • Onset in early life
    • nonprogressive or slowly progressive course
    • proximal or generalized muscle weakness,
    • hypotonia.
    • Those affected at birth or in early infancy may present as “floppy infants” or arthrogryposis
  82. What are the important subtypes of congenital myopathies?
    • Distinguished by histology, all type I dominant
    • 1. Central-core disease; autosomal dominant (Ryanodine receptor)--> risk of MH: Cytoplasmic cores are lightly eosinophilic and distinct from surrounding sarcoplasm
    • 2. Nemaline myopathy (AR AD--> Actin, Troponin, Tropomyosin): Aggregates of subsarcolemmal spindle-shaped particles (nemaline rods)
    • 3. Myotubular (centronuclear) myopathy: Abundance of centrally located nuclei involving the majority of muscle fibers
  83. What is the hallmark symptom of lipid myopathies?
    • Muscle pain, tightness, and myoglobinuria following prolonged exercise or exercise during fasting states.
    • Fatty acids provide energy for muscle contraction, especially when glycogen stores are depleted (as in fasting). With a metabolic block in fatty acid oxidation, the required energy is not available, resulting in symptoms
  84. What is the defect in lipid myopathies?
    Abnormalities of carnitine transport or deficiencies of the mitochondrial dehydrogenase enzyme systems can lead to blocks in fatty acid oxidation and accumulation of lipid droplets within muscle (lipid myopathies).
  85. What is the genetic defect in mitochondrial myopathies?
    both nuclear and mitochondrial genes
  86. What are the common features of mitochondrial myopathies?
    • Young adulthood 
    • Proximal muscle weakness
    • Severe involvement of the extraocular muscles involved in eye movements (external ophthalmoplegia).
    • May be accompanied by other neurologic symptoms, lactic acidosis, and cardiomyopathy
  87. What are the pathological finding in mitochondrial myopathies?
    • The most consistent pathologic finding in skeletal muscle is aggregates of abnormal mitochondria that are demonstrable only by special techniques (under the sarcolemma in early stages)
    • Distortion of the myofibrils, the muscle fiber contour becomes irregular on cross-section (ragged red fibers) 
    • Electron microscopy shows increased numbers of mitochondria with irregular shapes (paracrystalline parking lot inclusions or alterations in the structure of cristae
    • Cytochrome oxidase–negative fibers
  88. What are the three types of mitochondrial myopathies?
    • 1) Point mutations in mtDNA. maternal pattern of inheritance; include myoclonic epilepsy with ragged red fibers, Leber hereditary optic neuropathy, and mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes. As in other diseases caused by mutations in mtDNA, the expression of the disease is quite variable due to unequal distribution of mtDNA in affected cells 
    • 2) Nuclear DNA and shows AR, AD. 
    • 3) Deletions or duplications of mtDNA: chronic progressive external ophthalmoplegia,  Kearns-Sayre syndrome, (ophthalmoplegia, pigmentary degeneration of the retina and complete heart block)
  89. What are the hallmarks of mtDNA inheritance?
    • Maternal
    • Variable expression due to unequal distribution of mtDNA in affected cells
  90. What are the clinical features of dermatomyositis?
    • Skin rash may accompany or precede the onset of muscle disease.
    • The classic rash takes the form of a lilac or heliotrope discoloration of the upper eyelids associated with periorbital edema 
    • Scaling erythematous eruption or dusky red patches over the knuckles, elbows, and knees (Grotton lesions). 
    • Muscle weakness is slow in onset, bilaterally symmetric, and often accompanied by myalgias. It typically affects the proximal muscles first (getting up from a chair and climbing steps become increasingly difficult)
    • Dysphagia 
    • ILD
    • Vasculitis
    • Myocarditis
    • Accompanied by SS or SLE
    • Visceral malignancy (ovarian mc) in 25%
  91. What are the features of JDM?
    • Weakness and rash
    • Abdominal pain and involvement of the gastrointestinal tract.
    • Mucosal ulceration, hemorrhage, and perforation ( vasculopathy).
    • Calcinosis (uncommon in adult)
  92. What is antisynthetase syndrome?
    • DM or PM
    • Anti aminoacyl-tRNA synthetase Ab
    • ILD
    • Acute onset
    • Raynaud
    • Mechanic hand
    • Nonerosive arthritis
  93. What is the difference between DM, PM, and IBM?
    • DM and PM--> proximal symmetric
    • IBM--> distal asymmetric
  94. What is different in PM relative to DM?
    It differs from dermatomyositis by the lack of cutaneous involvement and its occurrence mainly in adults
  95. What are the clinical features of IBM?
    • Begins with the involvement of distal muscles, especially extensors of the knee (quadriceps) and flexors of the wrists and fingers.
    • Weakness may be asymmetric.
    • After 50 years
  96. What are the pricipal pathogenic mechanisms in DM, PM, and IBM?
    • DM--> Main target:capillaries, antibody mediated (B, CD4), perifasicular, vascular injury, paucity of lymphocyte in the area of injury
    • PM--> CD8 and MQ direct damage to muscles, increased MHC I and II on muscle, no vascular damage
    • IBM-->CTL is found in the muscle but no response to immunosuppressive therapy/ IC deposits of β-amyloid protein, amyloid β–pleated sheet fibrils, and hyperphosphorylated tau protein-->aging. The protein deposition may result from abnormal protein folding.
  97. What is the main target tissue in DM and PM?
    • DM--> capillaries
    • PM--> myocyte
  98. What are the histological hallmark of DM?
    • Inflammatory infiltrates around small blood vessels and in the perimysial connective tissue.
    • Atrophic fibers are particularly prominent at the periphery of fascicles.
    • This “perifascicular atrophy” is sufficient for diagnosis, even if the inflammation is mild or absent
    • Marked reduction in the intramuscular capillaries (due to EC injury)
  99. What are the histological features of PM?
    • The inflammatory cells are found in the endomysium.
    • CD8+ lymphocytes and other lymphoid cells surround and invade healthy muscle fibers.
    • No perifascicular atrophy
    • No vascular injury.
  100. What are the histological features of IBM?
    • Presence of rimmed vacuoles (basophilic granules at their periphery.) 
    • The vacuolated fibers may also contain IC amyloid deposits that reveal typical staining with Congo red.
    • Under the electron microscope, tubular and filamentous inclusions are seen in the cytoplasm and the nucleus that are composed of β-amyloid or hyperphosphorylated tau.
    • CD8+
  101. How is inflammatory myopathy diagnosed?
    • clinical symptoms, electromyography (mixed neurogenic myopathic), elevated creatinine kinase in serum, and biopsy
    • Biopsy is required for diagnosis
  102. What is the most important diagnostic feature of DM?
    The presence of perifascicular atrophy is diagnostic of DM, even in the absence of inflammation.
  103. Immunosuppressive therapy is beneficial in which type of inflammatory myopathy?
    Immunosuppressive therapy is beneficial in adult and juvenile dermatomyositis and in polymyositis but not in inclusion-body myositis.
  104. What is the common feature of toxic myopathies?
    Proximal weakness
  105. What is the feature of alcoholic myopathy?
    • Proximal
    • After binge drink
    • Associated with myoglobinuria
    • Myopathy+neuropathy
  106. What is the feature of Grave's myopathy?
  107. What are the features of steroid myopathy?
    • Type II
    • Proximal
    • Dilation of the sarcoplasmic reticulum and thickening of the basal laminae.
  108. What is the hallmark of Chloroquine myopathy?
    • Proximal
    • Vacuoles within myocytes (type I)
    •  (1) autophagic membrane-bound vacuoles containing membranous debris; and (2) curvilinear bodies with short curved membranous structures with alternating light and dark zones
    • May cause necrosis
  109. All myopathies are associated with both type or type I atrophy except...
  110. The myopathy of statin is dose....
  111. What is the mc thymic abnormality in Myasthenia gravis?
  112. What is the epidemiology of Myasthenia gravis?
    When arising before age 40 years it is most commonly seen in women, but it occurs equally in both sexes in older patients
  113. What is the major change in AchR in MG?
    Reduction in number
  114. How does anti AchR antibodies affect function?
    (1) fixing complement and causing direct injury to the postsynaptic membrane, (2) increasing the internalization and degradation of the receptors, and (3) inhibiting binding of acetylcholine
  115. Which neural functions are spared in MG?
    • CNS
    • ANS
    • Sensory
    • NCV
  116. What is the finding in EMG-NCV of MG?
    diminished motor responses after repeated stimulation; nerve conduction is normal
  117. What is the main finding in LM of MG?
  118. What is the first muscle that is involved in MG?
  119. What is the hallmark of symptoms in MG?
  120. What are the exacerbators of MG?
    • Aminoglycoside
    • Beta blocker
    • Type I anti arrhythmics
    • quinolone
  121. What are the treatments for MG?
    anticholinesterase drugs, prednisone, plasmapheresis, and thymectomy when thymic lesions are present
  122. What are the features of Eaton Lambert syndrome?
    • Paraneoplastic process(SCC of lung).
    • Proximal muscle weakness and autonomic dysfunction.
    • No clinical improvement by anticholinesterase
    • EMG-NCV show evidence of enhanced neurotransmission with repetitive stimulation
    • The content of anticholinesterase is normal in neuromuscular junction synaptic vesicles, and the postsynaptic membrane is normally responsive to anticholinesterase
    • Fewer vesicles are released in response to each presynaptic action potential.
    • Antibodies to presynaptic PQ-type voltage-gated calcium channels