Snapshot A 62-year-old man presents to his primary care physician for "seeing double." He reports that he has been experiencing these symptoms for a few months. His diplopia is worse after reading a book or watching television. He says that at times he notices his left eyelid "droops" at the end of the day and improves after waking up from sleep. He notes episodes of fluctuating weakness when chewing harder foods. On physical examination, there is left-sided ptosis. Pupillary reflex is intact. A plastic glove with ice is applied on the ptosis for approximately 2 minutes and the ptosis markedly improves. Serology is positive for anti-acetylcholine receptor antibodies and preparations are made for a computerized tomography scan of the chest. Introduction Clinical definition autoimmune disorder of the neuromuscular junction Associated conditions thymoma thymic hyperplasia Epidemiology Incidence has a bimodal distribution more common in younger women (< 40 years of age) and older men (> 50 years of age) Risk factors HLA-B8 medications penicillamine aminoglycosides Pathogenesis Autoantibodies directed against a protein of the neuromuscular junction autoantibodies can be directed against nicotinic acetlycholine receptor (AChR) more common muscle-specific receptor tyrosine kinase (MuSK) categorized as a type II hypersensitivity reaction T-cells play a role as well thought to stimulate B-cell antibody production Presentation Symptoms general feature fluctuating muscle weakness most commonly weakness is worse with continued use e.g., worse at the end of the day true muscle fatigue secondary to decreasing contractile muscle force ocular symptoms most common presenting symptoms ptosis diplopia bulbar symptoms dysphagia dysarthria fatigable chewing proximal muscle weakness Physical exam ice-pack test place ice on the patient's ptosis → ptosis improves low temperatures change the kinetics of acetylcholinesterase, decreasing its activity this increases the amount of acetylcholine in the synaptic cleft edrophonium chloride (Tensilon test) only used in patients with ptosis or ophthalmoparesis this allows for improvement in muscle strength to be observed edrophonium is an acetylcholinesterase inhibitor that has a short duration of action this increases the amount of acetylcholine in the synaptic cleft may result in false positives or cause life threatening bradycardia; thus, this test is rarely performed Imaging Computerized tomography (CT) scan indication to rule out a thymoma view chest Studies Labs serologic testing for autoantibodies anti-AChR this is the initial laboratory test to confirm the diagnosis anti-MuSK Electromyogram (EMG) decremental decrease in the compound muscle action potential (CMAP) Differential Lambert-Eaton myasthenic syndrome (LEMS) differentiating factor muscle weakness that improves with use autonomic manifestations Botulism differentiating factor poor or impaired pupillary response to light Thyroid ophthalmopathy Treatment Medical corticosteroids indication a chronic immunotherapy agent drugs oral prednisone acetylcholinesterase inhibitors indication considered first-line for symptomatic management drugs pyridostigmine adverse effects abdominal cramping and diarrhea bradycardia sweating bronchial secretion Procedural intravenous immunoglobulins (IVIg) or plasmapheresis indication rapid immunotherapy for myasthenic crisis Surgical thymectomy indication in patients with a thymoma, irrespective if the patient has myasthenia gravis or not associated with increased remission rates in patients with myasthenia gravis Complications Myasthenic crisis respiratory weakness secondary to myasthenia gravis Prognosis Most patients with ocular involvement progress to generalized myasthenia gravis