A 61-year-old man was admitted to the hospital because of increasing weakness in all his extremities.The patient had been in good health until five years earlier, when weakness developed in the distal portion of the left leg, with mild pain in the left hip. He began to limp because of the weakness. There were severe muscle cramps in the leg, which subsided approximately two years later. Three years before admission a neurologist found distal muscular atrophy of the left leg, with normal reflexes and sensation, and normal cranial-nerve functions. Motor-nerve conduction velocities and sensory-nerve action potentials were normal. A magnetic resonance imaging (MRI) scan of the lumbar spine showed a very slight posterior bulge of the L3-4 disk space and herniations at the L4-5 and L5-S1 disk spaces. An MRI scan of the cranium was said to reveal a tiny area of bright signal in the left anterior parietal white matter close to its junction with the gray matter; no other abnormality was detected. Electromyographic examination showed spontaneous activity and denervation and reinnervation in both legs and in the right arm. A test for anti-GM-1 ganglioside antibodies was negative.One year before admission the patient was admitted to another hospital because of increasing weakness in the left leg. Examination revealed wasting and marked muscle weakness in the left leg and moderate weakness in the right leg and both arms. The tendon reflexes were normal except that the ankle jerks were absent. The plantar responses were flexor. Sensation was normal. Motor-nerve conduction velocities and sensorynerve action potentials remained normal. Electromyographic examination disclosed changes characteristic of denervation. The results of routine hematologic and blood-chemistry studies were normal, as were the values for vitamin B 12 , folic acid, thyroid-stimulating hormone, and creatine kinase; the results of serum and urinary immunoelectrophoresis; and the serum concentrations of lead, mercury, and arsenic. The cerebrospinal fluid contained 1 white cell per cubic millimeter; the protein concentration was 65 mg per deciliter, and the glucose concentration was 61 mg per deciliter (3.4 mmol per liter). A computed tomographic study of the abdomen was normal. Microscopical examination of a specimen from a gastrocnemius-muscle biopsy revealed evidence of chronic and ongoing denervation; a suralnerve biopsy was negative.Six months before admission the patient became wheelchair-bound. Three months later he was first seen at this hospital. He was a retired warehouse supervisor. The limb weakness was asymmetric but severe and involved both proximal and distal muscles. He had had fasciculations in all extremities and in the face for about one year and had lost approximately 32 kg in weight during the three or four years before admission. There was no history of hypertension, diabetes mellitus, fever, chills, sweats, dysarthria, dysphagia, headache, sensory symptoms, or incontinence of the bladder or bowel, and there was no family history of neurom...