Diseases of Muscle Flashcards
Clinical Features
Weakness is usually proximal, no sensory loss, usually no pain
Classes of Muscle disease
Dystrophies - heterogenous group of inherited disorder muscle disorders; Clinical onset in infancy, childhood or adulthood, classification is based on genetics and abnormalities of muscle proteins
Duchenne and Becker Muscular Dystrophy
X-linked recessive, 1/3 spontaneous
Frequency of DMD 1/3500; BMD is 1/35000
Abnormality of gene coding for the muscle membrane protein dystrophin (usually a large deletion, but may be a point mutation or substitution) - Dystrophin is virually absent in DMD and decreased or altered in BMD
Clinical features of DMD - onset early in childhood, proximal weakness (gower’s maneuver), large calves, toe walking, increased lumbar lordosis, falling by age 6-7, can’t walk by age 12, cardiomyopathy is common, death by respiratory failure of CMO by age 20
Evaluation - CK markedly elevated, EMG is myopathic, Dx is commonly made by genetic testing (muscle bx for others)
Becker Muscular dystrophy - Simialr to DMD but milder with a later onset, diagnosed in the same manner as DMD
Treatment of DMD and BMD - corticosteriods (usually initiated after age 5, slows progression, side effects -> growth retardation, weight gain, changes in behavior) Symptomatic Tx - > bracing, wheelchairs, therapy to prevent contractures, Genetic counseling is important
Fasciopulohumeral (FSH) Muscular Dystrophy
Weakness of proximal limbs and of distal lower extremities (joint contractures are common)
Cardiac involvement is common (conduction block, CMO) - monitor heart closely adn tx CHF (heart is major cause of death in these patients), pacemaker is commonly needed
Usually X-linked, but may be dominant
Diagnosed via DNA testing
Symptomatic tx of weakness -> assistive devices, therapy, wheelchairs
Oculopharyngeal Muscular Dystrophy
Late onset (5th or 6th decade) Clinical -> eye muscle weakness and ptosis initially, difficulty swallowing, facial weakness, proximal limb weakness Autosomal dominant Rimmed vacuoles on muscle bx Diagnosed via DNA testing
Limb-Girdle Muscular Dystrophies
Mildly or severely increased CK
May be AD or AR
Abnormalities in a variety of muscle membrane constituents
usually diagnosed via muscle bx
Congenital Myopathies
Always present at birth (unlike muscular dystrophies). Defined based on the histological appearance of their muscle biopsies -> central core disease, nemaline myopathy, centronuclear myopathy, congenital fiber-type diproportion, myofibrillar myopathy
See page 14 pictures
Usually these are “floppy babies”
Some are sever resulting in respiratory distress and death; others go on to become weak children and adults with relatively nonprogressive disorders
Polymyositis
Clinical Features - Relatively rapid onset of weakness over days to weeks, predominantly arms and legs, no sensory loss, often no pain, but pain may occur with CT disease (not uncommon), Other organ involvement -> myocarditis with CHF, ILD (anti-Jo-1 antibodies)
Diagnostic evaluation - increased serum CK level (50x normal), EMG ->myopathic featurs, Muscle bx (definitive) -> inflammation, muscle fiber destruction, necrosis
Tx and Prognosis - Mechanism - cell-mediated response against muscle fibers; Tx- immunosuppressive drugs (prednisone, azathioprine, methotrexate); outcome - good to excellent recover (unless muscle necrosis has been severe)
Dermatomyositis
Clinical Features - Most frequent in childhood, rash (heleotrope - eyelids) -> sun-sensitive areas, progressive weakness over weeks to months, calcifications in subCu tissue, more commonly in children, increased incidence of malignanc in adults
Diagnostic evaluation - increased serum CK level (50x normal), EMG - myopathic features, Muscle bx- perifascicular atrophy, pervascular inflammation
Treatment and prognosis - Mechanism - humorally-mediated microangiopathy (around blood vessels), Tx - immunosuppressive drgus (prednisone, azathioprine, methotrexate, IVIG), Outcome - good to excellent recovery generally
Inclusion body myositis
Individuals over 50 years of age, very slowly progressiver over many years, finger flexors, quadriceps most affected, CK modestly elevated, inflammation and rimmed vacuoles (inclusion bodies) - not specific, probabaly not autoimmune but may be degenerative (due to amyloid deposition), Tx - generally responds poorly to immunosuppressive therapy, otucome - progresses slowly over many years
Endocrine myopathies
Hyperthyroidism - proximal weakness and opthalmoplegia
Hypothyroidism - muscle aching, cramps, fatigue, elevated CK
Disorders of glycogen metabolism
muscle pain with exertion (McArdle’s dx)
Mitochondrial
Kearns-Sayre Sydnrome -> progressive external opthalmoplegia (PEO), retinitis pigmentosa, heart block, increased CSF protein, Myoclonus epilepsy with ragged red fibers, Mt encephalopathy with lactic acidosis and stroke-like episodes, Pure PEO, Pure skeletal myopathy
Myotonic Dystrophy
Clinical Features - Temporalis and masseter wasting, wasting of the sternocleidomastoid muscle -> swan neck deformity, Ptosis, weakness -> facial, distal, proximal; grip weakness and myotonia; gradual progression over years; autosomal dominant inheritance; mental retardation (mild to severe); cardiac dysfxn -> conduction defect; cataracts, frontal balding; Endocrine abnormalities -> abnormal GTT, gynecomastia, testicular atrophy; GI motility disturbances
Electrodiagnostic studies -> myotonic discharges on needle exam
Etiology and Genetics - Type I (repeated trinucleotide sequence (CTG) in a gene on chromosome 19 which codes for a protein kinase (more repeats - more sever disease; anticipation in successive generations) Type II (proximal myotonic myopathy (repeat expansion in the zinc finger on protein 9 gene on chromosome 3q)
