Bulbar-Predominant Weakness

A 61-year-old man sought care for recurrent episodes of dysarthria for about 1 year. This symptom was more common after prolonged speaking. Six months before his evaluation he had significant slurring of his speech after talking for 3½ hours at work about a new project. This led to emergency evaluation and his symptoms were thought to represent a transient ischemic attack; he started aspirin and a statin. The episodes continued to recur. He also experienced intermittent binocular double vision, which did not improve with new eyeglasses, and a sensation that chewing and swallowing was more effortful. He noted that his arms and legs felt “heavy” at times. All these symptoms tended to occur later in the day or after exertion. Neurologic examination was remarkable for binocular double vision with prolonged gaze upward or to the far right. He could squat and rise 5 times but with difficulty by the 5th attempt. The patient’s symptoms suggested myasthenia gravis. The differential diagnosis for autoimmune myasthenia gravis, particularly with prominent ocular and facial muscle involvement, can include central nervous system disorders, motor neuron disease, and myopathy. Serologic evaluation showed positivity for acetylcholine receptor-binding antibody and acetylcholine receptor-modulating antibody. Striated muscle antibody was also positive. Thiopurine S-methyltransferase activity was low. Repetitive stimulation studies showed a decrement in the right facial nerve, which partially improved after exercise. Routine needle examination showed motor unit variation in the right orbicularis oculi. Single-fiber electromyography showed increased jitter in the right orbicularis oculi. Chest computed tomography showed scattered tiny pulmonary nodules but no evidence of thymoma or other neoplasm. The clinical diagnosis was autoimmune generalized myasthenia gravis, seropositive for acetylcholine receptor antibody, without evident thymoma or other neoplasm. The patient was initially treated with oral pyridostigmine with some symptomatic benefit. Oral prednisone was then initiated; symptoms resolved when the dose was titrated. Calcium and vitamin D supplements, as well as Pneumocystis prophylactic therapy, were initiated concurrently. Mycophenolate mofetil was added as a steroid-sparing agent. On thoracic surgery consultation, thymectomy was recommended. Autoimmune myasthenia gravis is a disorder of impaired neuromuscular transmission caused by immunoglobulin G-mediated attack on a critical component of the acetylcholine receptor signaling complex in the muscle’s postsynaptic membrane. The most commonly identified antibodies, target the nicotinic acetylcholine receptor.