Myasthenia gravis

Objectives:•introduction•Definition •Clinical features •Diagnosis•Treatment

introduction•Neuromuscular junction : the synapse

between motor neuron and muscle fiber is called the neuromuscular junction.

•Motor end plate contain nicotinic receptors, and the Ach binds to these receptors leads to conformational changes,

the channels opens & permeability of motor end plate to Na+ & K+ increases.

Myasthenia gravis:•Is an acquired autoimmune disorder.•Is caused by autoantibodies that block the

function of postsynaptic Ach receptors at motor end plate.

•Some 60% of cases are associated with a peculiar reactive hyperplasia of intrathymic B cells.

•And another 20% are associated with thymoma.

Clinical features

Myasthenia gravis can involve either the external ocular muscle selectively (ocular MG) or the general voluntary muscle system (generalized MG) ,the symptoms usually fluctuate tending to be worse later in the day (diurnal fluctuation) .

they are worsened by exertion

•Ocular muscle involvement is usually bilateral and asymmetrical and typically is associated with ptosis and diplopia.

•Ocular muscles are affected in nearly all patients after a year of disease.

•weakness of other muscles innervated by cranial nerves result in loss of facial expression.

•Abnormal fatigability of the limb muscles difficulty in combing the hair, lifting objects repeatedly ,climbing stares, walking, and running.

•The symptoms are ocular in 40% ,•And are generalized in 40%,• involve only the extremities in 10%• and involve only bulbar or bulbar and eye

muscles in another 10%.

•In about 10% the MG is associated with another autoimmune disease, circulating Ach receptor antibodies can be detected in most infants born to myasthenic mothers, but only 12% of such children develop transit neonatal MG,usually during the first few hours of life.

•The disease is caused by transfer of Ach receptor antibodies is self limited

Diagnosis

Anticholinesterase tests(tensilon test)

Edrophonium given intravenously acts within a few seconds and lasts for a few minutes. Two milligrams of the drug are injected intravenously over 15 seconds. If no response occurs in 30 to 45 seconds, an additional 8 mg is injected. The evaluation of the response requires objective assessment of one or more signs not easily influenced by motivation, such as degree of ptosis and range of ocular movements.

Anticholinesterase tests(tensilon test) cont.

Possible cholinergic side effects of the drug include fasciculations, flushing, lacrimation, abdominal cramps, nausea, vomiting, and diarrhea. The drug must be given cautiously to patients with cardiac disease because it may cause sinus bradycardia, atrioventricular block, and, rarely, cardiac arrest. Atropine should be available during the test. Edrophonium should not be given to patients having respiratory difficulty.

Repetitive Nerve Stimulation

Supramaximal stimulation of a motor nerve at 2 or 3 Hz results in a 10% or greater decrement of the amplitude of the evoked compound muscle action potential from the first to the fifth response. The test is positive in about 75% with generalized MG, provided that two or more distal and two or more proximal muscles are examined. It is less frequently abnormal (approximately 50%) in purely ocular MG.

Single Fiber Electromyography

Single fiber electromyography (SFEMG) is currently the most sensitive method for diagnosis of MG and reveals increased jitter and blocking in 99% of patients with generalized MG and in 97% of those with purely ocular MG when a weak muscle is tested. SFEMG is usually available only in specialized EMG laboratories

Blood Tests and Radiography

The AChR antibody test measures the binding of antibody to AChR labeled with radioactive αbungarotoxin. The antibody-binding test result is positive in nearly all adults with moderately severe or severe MG, in 80% with mild generalized MG, and in 50% with ocular MG. Some patients without AChR have abnormal antibodies to MuSK, a muscle-specific tyrosine kinase with a role in aggregation of AChR and the end plate. Striated muscle antibodies also occur in MG patients. Their role is unknown, but they are often associated with thymoma. Because of the frequency of thymomas, chest x-ray studies and chest computed tomography (CT) scanning are indicated.

TREATMENT

Oral anticholinesterases

Pyridostigmine (60 mg tablet) is widely used. The duration of action is 3–4 hours, the dose (usually 4–16 tablets daily) determined by response. Pyridostigmine prolongs acetylcholine action by inhibiting cholinesterase. Overdose of anticholinesterases causes severe weakness (cholinergic crisis). Muscarinic side-effects, e.g. colic and diarrhoea, are common; oral atropine (antimuscarinic) 0.5 mg helps to reduce this. Anticholinesterases help weakness but do not alter the natural history of myasthenia.

Immunosuppressant drugs

•These drugs are used in patients who do not respond to pyridostigmine or who relapse on treatment. Steroids are often used. There is improvement in 70%, although this may be preceded by an initial relapse. Azathioprine, mycophenolate and other immunosuppressants are also used.

•Plasmapheresis and intravenous immunoglobulin

•During exacerbations these interventions are of value.

Thymectomy

•Thymectomy improves prognosis, more so in women than men below 50 years with positive AchR antibodies, even in patients without a thymoma. Cases positive for anti-MuSK antibodies tend not to improve following thymectomy. When a thymoma is present, the potential for malignancy also makes surgery necessary.

Reference •Andreoli and Carpenter’s cecil essentials

of Medicine 8th edition

by: Thomas E. Andreoli, Ivor J. Benjamin, Ropert C. Griggs, Edward J. wing

•Robbins Basic Pathology 9th edition

Vinay Kumar, Abul K. Abbas, Jon C. Aster•Kumar & Clark’s Clinical Medicine 8th

edition• by Parveen Kumar and Michael Clark•  published by Elsevier