Weekly Clinicopathological Exercises

A 23-year-old man was seen in the clinic because of progressive weakness and paresthesias. He had been well until six months earlier, when he began to have difficulty climbing a flight of stairs quickly and noted intermittent tingling of the soles of his feet and toes. Two months later, he had increasing weakness in his legs, pain in the lower back, stiffness of the hands, and intermittent numbness of the toes and fingertips. Three months before this visit to the clinic, a tremor developed in the arms. The weakness worsened, and the feet and calves became numb, with tingling in the feet and fingertips. The patient’s balance was poor, particularly with his eyes closed. There was no history of visual symptoms, dysphagia, slurred speech, dyspnea, sphincteric disturbances, muscle cramps, fasciculations or pain in the arms or legs, transient neurologic symptoms, weight loss, anorexia, skin changes, fever, chills, recent infection, risk factors for human immunodeficiency virus (HIV) infection, tick bite, allergies, recent immunization, exposure to neurotoxic chemicals, use of tobacco or illicit drugs, or excessive use of alcohol. The patient’s father had a mild tremor, but there was no family history of other neurologic disorders. On examination, the pulse was 72, and the blood pressure was 110/65 mm Hg. The patient was unable to stand on his toes or heels, and a Romberg sign was present. Cranial-nerve functions were preserved, and the optic disks were normal. No muscle atrophy was seen; muscle tone was normal. Motor function was graded as follows (right/left): neck flexion and extension, 5/5; extensor hallucis longus, 4/4; extensor digitorum brevis, 4/4; ankle dorsiflexion and plantar flexion, 4 /4 ; hip flexion and extension, 4 /4 ; elbow flexion, 4 /4; abductor pollicis brevis, 4/5; first dorsal interosseus muscle, 5/4; and abductor digiti minimi, 5/4. The remaining muscles were normal. Vibratory sensation was decreased in the ankles and feet; sense of position was impaired in the toes; sensitivity to pinprick was reduced distally in the legs, with a proximal-to-distal gradient; and sensation of cold was normal. There was a postural tremor in the arms without dysdiadochokinesia or dysmetria. Tendon reflexes were absent at the ankles and hypoactive elsewhere. No hypertrophied nerves were palpated. A lumbar puncture performed one month earlier showed a total protein concentration of 290 mg per deciliter, with a normal cell count. The results of serum protein electrophoresis with immunofixation and concentrations of IgG, IgM, and IgA were normal. Tests for antinuclear antibodies; antibodies to HIV, Borrelia burgdorferi, and hepatitis A, B, and C; and antibodies to myelin-associated glycoprotein (MAG), sulfatide, Hu, and ganglioside GM 1 were negative. Conduction studies of the median and ulnar nerves performed six weeks before the current visit showed prolonged motor distal latencies, normal motor-nerve conduction velocities, the absence of sensory potentials, prolonged F responses, and normal electromyographic findings in the intrinsic hand muscles. The results of a magnetic resonance imaging (MRI) study of the brain, performed before and after the administration of contrast material, were normal. Routine and electron-microscopical examination of a specimen from a sural-nerve biopsy showed axonal degeneration and changes suggestive of remyelination. A diagnostic procedure was performed.