Neuro Shelf - skeletal muscle

At the presynaptic bouton, secretory vesicles containing Ach concentrated at active zones formed by P/Q type voltage-gated Ca channels, which leads to Ca influx, which triggers release of Ach

Ach binds at the postsynaptic cleft, which generates an inward Na current through the Ach-receptor ion pore, which leads to depolarization of the muscle endplate

antibodies directed against the postsynaptic nicotinic Ach receptor

bimodal peak (20-30, 80-90)

earlier -onset MG associated with thymic hyperplasia, whereas thymoma associated with pts with later onset

fatigable muscle weakness, ocular involvment (pstosis, diplopia), bulbar muscle weakness (dysarthria or dysphasia), limb weakness is proximal and symmetric

be sure to check pulmonary function bc even those who don't look like it could be in crisis

Dx with edrophonium chloride (anti-choniesterase agent) should help

Tx with pyridostigmine (antiacetylcholinesterase)

*associated with small cell carcinoma of the lung*

antibodies directed against the presynaptic P/Q-type voltage-gated Ca channel, reducing release of Ach

fatigable proximal muscle weakness, reduced DTRs. Unlike MG, bulbar and ocular symptoms rare, but autonomic complaints (dry eyes, dry mouth, impotence) common. Muscle strenth increases with brief intense exercise

mutations of dystrophin (allelic), x-linked inheritance (usually in young boys)

onset in childhood, may use an arm to push down on thighs when arising from floor (Gowers sign), pseudohypertrophy of calf muscles, proximal muscle weakness (including neck flexors), usually sparing of ocular and bulbar muscles

in DMD, death around age 20 due to respiratory insufficiency and aspiration

CK very elevated (normal CK strongly against diagnosis), muscle biopsy shows dystrophic features with absent or reduced staining for dystrophin

proximal muscles of arms and legs affected predominantly, sparing of other structures. Shoulder and hip girdle weakness, may require muscle biopsy to distinguish from muscular dystrophy

CK usually elevated

most common inherited skeletal muscle disorder affecting adults. inheritance is AD - genetic defect either unstable CTG expansion in DMPK gene or CCTG expansion in the ZNF9 gene

weakness and stiffness of distal muscles present in young adults, action and percussion myotonia, proximal weakness develops later. Cataracts, ptosis, arrhythmias, dysphagia, insulin resistance, testicular atrophy, frontal balding, neurobehavioral changes

CK normal or mildly elevated, Cardiac evaluation important to prevent arrhythmias

Phenytoin and carbamazepine may reduce myotonia

mutations in emerin (transnuclear membrane protein) gene on x-chromosome (AD form rare, mutations in lamin A and C genes on chromosome 1)

early onset of joint contractures (elbows, ankles, c-spine), slowly pregressive humeroperoneal pattern of weakness and atrophy, and cardiomyopathy (conduction abnormalities). Key is appearance of contractures prior to onset of weakness)

although femal carriers do not develop weakness or atrophy, they are at risk for the cardiac complications

CK mildly to moderately elevated

AD conditions with episodic muscle weakness. attacks of weaknessassociated with change in serum K concentration

hypokalemic pp - mutation in pore-forming alpha IS-subunit of skeletal muscle Ca channel that causes secondary dysfunction of the NA,K ATPase

hyperkalemic pp - mutation in skeletal muscle voltage-gated Na channel

co-occurance of a myopathy with a peripheral neuropathy. serum lactate and pyruvate often increased

polymyositis - proximal muscle weakness, often associated with other autoimmune diseases (crohns disease, vasculitis, sarcoidosis, MG, etc). mediated by CD8 T lymphocytes

dermatomyositis - antibodies against intramuscular blood vessels, inflammation due to muscle ischemia. proximal muscle weakness. purplish discoloration of eyelids (heliotrope) and papular erythematous scaly lesions over the knuckles (Gottron patches). Cardiac manifestations, interstitial lung disease (anti-Jo-1 antibodies), increased risk of malignancy

inclusion body myositis - inflammatory and neurodegenerative. assymmetric, both proximal and distal muscles (early selective involvement of forearm and finger flexors as well as knee extensors and ankle extensors. usually diagnosed when pts thought to have PM fail to respond to steroids . Endomysial inflammation and basophilic rimmed vacuoles

in all - CK elevated (amount doesn't correlate with degree of weakness), muscle pain and weakness

proximal muscle weakness and atrophy with normal or brisk reflexes, ck normal

tx underlying thyrotoxic state with beta-blockers, will improve muscle strength

proximal muscle weakness, fatigue, myalgias, and cramps. muscle reflexes may show delayed relaxation, associated distal polyneuropathy

CK elevated, weakness improves following thyroid replacement

due to inreased glucocorticoids

weakness proximal, wparing of ocular, bulbar, and facial muscles, ck and emg normal

drug/toxin -HMG-CoA reductase inhibitors, cyclosporin, propofol, alcohol

clinical - proximal muscle weakness, ck elevated

drug/toxin - zidovudine

clinical - proximal muscle weakness, ck normal or mildly elevated

drug/toxin - cimetidine, procainamide, l-dopa, phenytoin, lamotrigine, d-penicillamine

clinical - proximal muscle weakness, CK increased

drug/toxin - corticosteroids plus neuromuscular blocking agents in pts with sepsis

clinical - generalized weakness, ck normal or elevated