An Elderly Woman With Asymmetric Weakness and a Monoclonal Gammopathy

A 70-year-old woman was evaluated for a 1-year history of weakness and numbness that manifested initially in the legs and in the left hand and for the last 6 weeks also in the right hand. She developed mild bilateral footdrop in the last month.

Past medical history included mild glucose intolerance for which she took glyburide for several months. She had had two C-sections, appendectomy, hemorrhoidectomy, and three ear surgeries, as she also had a chronic history of left otitis and mastoiditis for which she received antibiotics periodically and had hearing loss on the left.

General physical examination revealed mild splenomegaly. Mentation and cranial nerves were normal, except for decreased hearing in the left ear. Facial muscle strength was normal. She had weakness of finger extensors of both hands, with significant weakness of the interosseous and thenar muscles on the left. Neck and proximal upper extremity muscles were normal. She had moderate proximal leg weakness of 3+/5, foot dorsiflexors, evertors, and toe extensors 3− bilaterally. Foot flexors were minimally weak. She was areflexic and had no pathologic reflexes.

Vibration sense was absent in the toes and decreased in the fingers and ankles; position sense was minimally decreased in the toes. Pinprick, temperature, and touch sensations were decreased up to the ankles, all symmetrically. Reflexes were absent throughout. No fasciculations were seen. There were no Babinski signs. Romberg’s test was negative; coordination and gait were normal.

What is the Differential Diagnosis?

This woman had progressive, asymmetric weakness with more severe involvement of the left upper extremity. A spinal canal disease causing a C8 radiculopathy could explain the hand findings, but not her generalized areflexia and weakness with sensory deficits in the legs, unless she had two disorders. Because of the sensory findings, a motor neuron disorder is also unlikely. The asymmetric presentation could suggest a vasculitic neuropathy, but the slow progression is somewhat unusual for this. She could have a polyneuropathy such as from diabetes, with a superimposed radiculopathy or a left brachial plexus lesion. Her neuropathy could also have other causes, such as being associated with a monoclonal gammopathy or a connective tissue disease. Thyroid disease and B ₁₂ deficiency neuropathy do not present with prominent weakness, unless there is evidence of combined degeneration of the spinal cord in the latter. Acquired demyelinating inflammatory neuropathies are usually symmetrical, but sometimes patients might have an asymmetric presentation and could have predominant involvement of the upper extremities. ¹ The chronic recurrent infections could suggest a secondary amyloidosis, but her degree of weakness was out of proportion to the sensory findings, which are more prominent in amyloidosis. A multifocal motor and sensory neuropathy, or Lewis–Sumner syndrome, is a possibility, particularly with the more prominent manifestations in the left hand. This condition is multifocal and affects mainly the upper extremities, ² however, and she also had symmetrical leg findings. Distal demyelinating neuropathy associated with a monoclonal gammopathy occurs in elderly persons, mainly in men, and is more symmetrical.