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- Congenital myopathies
Muscular Dystrophieshistologic myopathic changes group atrophy and type grouping / central nuclear migration / hypertrophy / fiber type predominance / split fibers, basophilic fibers, target fibers, interstitial changes (fibrosis) Duchenne muscular dystrophy XLR / altered dystrophin protein / progressive debilitation until early death (20s) Becker’s muscular dystrophy milder form Emery-Dreifuss myopathy early onset / shoulders, calves, heart atrophy Autosomal dominant dystrophies AD / atrophy of face, shoulders (but not deltoid), calves / slowly progressive, prolonged survival Myotonic dystrophy and non-dystonic myotonias cranial changes, cataracts, small testes, endocrine disturbances (diabetes) / central nuclei / may develop slowly progressive respiratory failure (abnormal sleep study may be earliest indicator) Congenital muscular dystrophy – same as floppy baby? neonatal hypotonia Bethlem muscular dystrophy defective collagen 6 / contractures Late-onset muscular dystrophies Oculopharyngeal dystrophy late onset / opthalmoplegia and dysphagia / rimmed vacuoles Facioscapularhumeral dystrophy Congenital myopathiesNemaline myopathy intracytoplasmic rods / variable inheritance Centronuclear myopathy selective hypertrophy of type I fibers Central core disease AD / type one fibers devoid of mitochondrial enzymes centrally / predisposes to malignant hyperpyrexia
rare AD inheritance / called Kearns-Sayre syndrome if onset in childhood Mechanism: myotonia (prolongation of muscle contraction)
limb girdle myopathy presenting in 2nd decade Glycogen storage diseases (see McArdle’s) Inflammatory myopathies Prevalence of Antibodies Anti Jo-1 (20-30%) Anti-Mi-2 (8%, 20% of DM) Histone (17%) U1-RNP (12%) Ro (10%)
Pm-Scl (8%) Polymyositis (see other) proximal, painful muscle weakness / autoimmune, ANA / biopsy NOT always conclusive Myasthenia Gravis 1 in 7500 / women: 20-30s, men: 50-60s Associations: hyperthyroidism (3-8%) and thymomas (~10-15%) Presentation: weakness and fatigue / early: cranial, facial (ptosis, diplopia, dysarthria, nasal speech) / later: generalized (85%) / proximal limb weakness (may be asymmetrical) Diagnosis: AChE inhibitor (IV edrophonium) test / repetitive nerve stimulation gives decremental response / ACh receptor antibodies (80%) / thoracic CT or MR to detect thymoma Treatment: Mild AChE inhibitors (stigmines) Severe prednisone, plasmapheresis, Cyclosporin A, Immuran, Cellcept Younger pts remove thymus to decrease production of anti-ACh antibodies Older pts thymus often removed prophylactively / always remove if a tumor is present
Mechanism: IgG against voltage-gated calcium channel receptors at NMJ prevents ACh release; generally, this is a paraneoplastic syndrome / ~50% of cases have associated cancer (usu. small cell carcinoma of lung); may allow earlier detection of cancer, but cancer is less likely in patients < 40 yrs Diagnosis: EMG readily distinguishes from MG as well as PM Treatment: pyridostigmine, guanidine, diaminopyridine, plasmapheresis, immunosuppressive therapy (maybe) Inclusion body myositis progressive, painless weakness (distal) Mechanism: CD8 T-cells involved / exact sequence of events unclear (could be response to primary degeneration of muscle) Genetics: 2-3 fold prevalence of DR1 Pathology: enzyme tests suggest neurogenic picture / rimmed vacuoles containing amyloid (ability to eliminate amyloid is lost), mononuclear cell invasion of nonnecrotic muscle fibers and/or 15-18 nm tubulofilaments by EM Malignancy: relative risk 2.4 (no particular type) Treatment: try steroids because they occasionally help, but not generally / some are trying IVIG sporadic (SIBM) most common inflammatory myopathy in over 50 population / males 2-3x females / more in Caucasians / painless proximal muscle weakness, progresses over yrs, distal involvement in 50% (predominant in 30%) / has characteristic, often asymmetrical pattern that is clinically distinguishable (if you grab the textbook) / CK normal in 20% (usu. does not exceed 12 x normal) / EMG atypical in 30% (i.e. may look like neuropathy or seem normal) hereditary (HIBM) 20s to 30s / AR and AD forms / slowly progressive / early involvement of distal muscles / absence of inflammation on biopsy Eosinophilic Fasciitis (Schulman syndrome) – great prognosis Presentation: edema of lower extremities and taut skin, flexion contractures / no primary muscle involvement (can extend from fascia to muscle) Acute (short prodrome) low-grade fever, myalgias, and fatigue, thickening of subcutaneous tissues ensues, sparing of face, pitting edema Over weeks limited ROM in small joints and large joints (less)
rare disease, more in men, 30 to 60 years, half with intense exertion prior to the onset Presentation: low-grade fever, transient maculopapular rash, muscle pains, and cramps and weakness of the extremities +/- paresthesias / can have predominance of fasciitis, myositis, peripheral neuropathy or combination Note: severity peripheral eosinophilia correlates with level of tissue inflammation Complications: Diffuse fasciitis Proximal muscle weakness and elevated CK (+/- neuropathy) CNS: neurocognitive deficits and peripheral neuropathy (neurotoxins? MBP?) / can occur 1 to 23 months after onset / less likely to respond to therapy CVS: heart block, arrhythmias, and pulmonary infiltrates, resulting in death Esophageal motility Diagnosis: history, organ involvement, serologic studies Labs: serum CK (can be normal with EF, usu. normal or minimal elevation with EMS), RF may be present (unlike eosinophilic fasciitis), ESR often moderately elevated (similar to others) EMG: myopathic pattern with eosinophilic myositis (less common with EF), may show axonal or demyelinative lesions Biopsy: muscle Bx can aid in the diagnosis of eosinophilic myositis / tissue biopsy shows infiltrates of vessels and connective tissues with everything but eosinophils (similar to toxic oil syndrome from rapeseed oil) Ddx: PAN, RA, allergic granulomatosis, hypersensitivity vasculitis, scleroderma, or parasitic infections Treatment: high-dose prednisone at 1 mg/kg/d +/- cytoxic agents Eosinophilia-myalgia syndrome and toxic oil syndrome Presentation: insidious onset of fatigue, myalgias, peripheral eosinophilia associated with the chronic ingestion of L-tryptophan or oil products containing bad things like certain aniline derivatives / mostly in white women Polymyalgia rheumatica (PMR) 1 in 133 of > 50 yrs population (peak 80-90 yrs) / women > men 2:1 / not a true myopathy and no joint erosions (synovitis, bursitis and not so much actual joints), can have swelling of joints/bursa [pic] / 15-20% have giant cell arteritis (r/o if any symptoms present) Presentation: acute onset ( < 2 wks) of severe myalgias (shoulder > pelvis, neck > torso, proximal arms, thighs) / morning stiffness > 30 mins / 1/3 have fever, malaise, fatigue, anorexia, weight loss Ddx: RA, PM, fibromyalgia, malignancies, RS3PE, infections, depression Labs: ESR normal to elevated (> 40) / usu. normal CK and EMG / biopsy normal (not usually performed) Treatment: NSAIDS or low-dose steroids (15-20 mg/d) usually rapidly effective (different treatment regimen from GCA) RS3PE seronegative, symmetric synovitis with pitting edema / acute onset bilateral, diffuse, symmetric swelling of wrists/hands with marked, pitting edema of dorsum of hands > feet / persistently seronegative for RF / responds rapidly to small doses of steroids Other Causes of Myopathy (~weakness) Hypothyroidism (see endocrine) cramps, pain, stiffness / proximal muscle weakness (33%), muscle enlargement / elevated CK Hyperthyroidism (see endocrine) proximal muscle weakness and atrophy / brisk reflexes / bulbar/proximal or generalized pattern / decreased CK Hyperparathyroidism (see endocrine) CK normal or elevated / proximal muscle weakness, wasting, brisk reflexes / Ca and PO4 do not correlate with disease / may be primary or secondary to renal failure Polyneuropathy of Diabetes Mellitus (see endocrine) Hyperaldosteronism (Conn’s) (see endocrine) Addison’s Acromegaly Excess steroid (exogenous or Cushing’s) normal CK / EMG unremarkable / hyperglycemia? Vitamin D deficiency Uremic polyneuropathy? Botulism dilated pupils / repetitive nerve stimulation gives incremental response Myopathy of Systemic Disease (lung, heart, liver) Non-dystrophic myopathies (Channelopathies) Sodium channel disease (hyperkalemic periodic paralysis, paramyotonia congenital) and chloride channel disease (Thompsen’s, Becker’s) Treatment: quinine, procainamide, phenytoin Metabolic myopathies Disorders of carbohydrate and lipid metabolism Chronic Drug-Induced Myopathy Causes: HMGCoA reductase or statins (< 1%, lovastatin is worst, risk increased with elevated drug levels via P450 interactions), gemfibrozil, nicotinic acid, clofibrate (more than statins), alcohol, aminocaproic acid, procainamide, zidovudine, L-tryptophan, colchicine Rhabdomyolysis (pigment-induced ATN) Causes: Drugs: alcohol, cocaine, amphetamines, LSD, heroin, PCP Medications: diuretics, narcotics, barbiturates, anesthetics (halothane), Succinylcholine, Aminocaproic acid, terbutaline, quinine, TCA’s, phenothiazides, theophylline, steroids) Prolonged immobility (including surgery), strenuous exercise, seizures, crush injury, malignant hyperthermia, heat stroke Electrolytes: hypokalemia, hypophosphatemia, hyperosmolar states, hyperglycemia, hypernatremia Infections (viral): Coxsackie, Echo, Influenza, Measles, Infections (bacterial): Clostridium, Staphylococcus, Legionella, Typhoid, Tularemia Toxins
Mechanism: ARF from myoglobin damaging renal tubules and causing tubular obstruction and all exacerbated by hypovolemia from fluid sequestration into necrotic muscle Complications (in addition to renal failure): hypercalcemia may occur 2-3 weeks after acute muscle injury as deposited calcium dissociates from deposited CaPO4 salts Labs: muscle breakdown directly causes elevated CK, ↑ uric acid, ↑ K, ↑ PO4; low Ca results from binding to PO4 and low vitamin D levels; Cr may rise more than BUN (unlike prerenal); (+) anion gap acidosis; UA shows (+) blood (↑ hemosiderin), myoglobinuria without RBC’s on exam (unless there is an additional reason for RBC’s) Treatment: aggressive fluid resuscitation, hydration (as much as tolerated by cardiopulmonary status, e.g. 200 cc/hr ½ NS; diuretics may worsen situation) / alkalinization of urine not proven to prevent tubular damage from rhabdomyolysis and pigmenturia and may increase risk of hypocalcemia 9/06 Neuroleptic malignant syndrome (NMS) Mechanism: effect of using anti-dopamine agents or sudden withdrawal dopaminergic agent (Parkinson’s patients who abruptly stop levodopa) Usual drugs: haldol, thiothixine but also prochlorperazine, promethazine, droperidol, and metoclopramide Note: can occur any time during treatment (doesn’t matter how long they’ve been on it) / not result of overdose (serum levels of drug do not correlate with NMS) Risk factors: prominent psychomotor agitation, higher doses, increased dose in short time (< 5 days), IV administration, organic brain abnormalities (infection, encephalitis, AIDS, tumors, etc.), dehydration, history of increased CK with neuroleptics / Note: NMS less common with atypical antipsychotics than typical Presentation: altered mental status (confusion, delirium, stupor, coma) motor symptoms (rigidity, tremor, akinesia, bradykinesia, dystonia, mutism, dysarthria, involuntary movements) hyperthermia (38 to 41oc) autonomic instability (respiratory irregularities, incontinence, cardiac arrhythmias, labile blood pressure) Ddx: non-NMS drug effect, encephalitis, other neurological condition, mood disorder with catatonia Labs: ↑ WBC (10-40K), elevated CK , ↑ LDH, ↑ AST, ↑ ALT, ↑ alk phos, hypocalcemia (sequestration in muscle), ↓ pH Course: usually evolves over 24 to 72 hours (rarely, slower onset over a few days may occur), usually lasts 7-10 days / usually MS changes 1st then rigidity ~fever ~ANS findings Complications: renal failure (from rhabdomyolysis), DVT (stasis, hypercoagulable state), multiple system failure (respiratory, cardiac, SZ, DIC), residual catatonia may last weeks to months Treatment: supportive (needs ICU, IV fluid, temp, alkalinize urine, DVT prophylaxis) pharmacologic (believed to reduce duration by a few days) bromocriptine – central dopamine agonist / only PO (titrate up to 60mg/d) / dose-limiting hypotension, psychosis, nausea dantrolene – skeletal muscle relaxation by inhibition of Ca release from SR / PO (50-200 mg/d) or IV (2-10 mg/kg/d) / hepatotoxicity (esp. > 10 mg/kg/d) can give either alone or give IV dantrolene followed by PO bromocriptine / must continue treatment at least 10 days after resolution of episode (and then slowly taper off treatment)Other agents used: amantadine, apomorphine (not available in U.S.), PO or IV levodopa, IV clonidine (for BP control) ECT – useful in refractory cases (consider if no improvement after 48 hrs of supportive/pharmacotherapy) / also good for ALC or residual psychosis following NMS episode Note: must distinguish whether caused by stopping neuroleptic or dopaminergic agent (must restart comparable agent following day) or starting/changing neuroleptic (must discontinue offending agent) Recurrence: 40% risk on rechallenge (much lower if you wait longer before restarting), concomitant lithium increases risk Download 3.95 Mb. Share with your friends:
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