A Man With Progressive Neuropathy and Congestive Heart Failure

A 59-year-old man presented with a 3-year history of paresthesias in the legs, feet, and thighs and weakness in the legs, with difficulty going up stairs and getting up from a chair. He developed severe leg weakness and atrophy in the hands for approximately 6 months prior. He had an MRI of the lumbosacral spine that showed spinal stenosis.

The family history was positive. His father died of tuberculosis and a brother died at age 50 of congestive heart failure after a 6-year history that included peripheral neuropathy and carpal tunnel syndrome (CTS).

Past medical history was positive for a nonspecific lung nodule, for which he received isoniazide for 1 month until the results of the biopsy were reported negative for tuberculosis and otherwise nonspecific. He had hypertension and congestive heart failure from cardiomyopathy and had been previously operated on for a right carpal tunnel. He also had hiatal hernia, irritable bowel, chronic low back pain, and depression.

Physical examination revealed normal mentation and cranial nerves except for a dry tongue and mild decreased tearing in the eyes. Pupillary light responses were mildly sluggish. No cataracts or corneal opacities were detected. The fundi and extraocular movements were normal. Strength was normal in the neck and upper extremities, except 3+/5 in the hand muscles. Hip flexors were 4−/5, extensors 4/5; foot dorsiflexors were 3−/5, feet flexors 4/5. He had wasting in the hands and feet and was areflexic without pathologic reflexes. Sensory examination revealed a stocking/glove deficit to pain and temperature to the midforearm and midlegs with absent vibration sense in the toes and ankles. The rest of the examination was unremarkable.

This case was studied with Dr. Lance Wright.

What is the Differential Diagnosis?

This patient presented with a progressive sensorimotor neuropathy with an apparent cardiomyopathy, autonomic dysfunction, and a history of CTS. There was no history of exposure to drugs, except for isoniazide, which can cause a neuropathy, ¹ but he only took this medicine for 1 month, and his symptoms started years after its discontinuation. There was no exposure to alcohol or other toxins. He had a history of lumbar spinal stenosis, but this does not explain the upper extremity findings.

Diabetes is a primary consideration in a patient with this presentation, and patients with diabetic polyneuropathy have a predisposition to CTS. ² It is also possible that the cardiac involvement was secondary to arteriosclerotic coronary disease related to diabetes, but he had no history of diabetes.

Another consideration would be neuropathy associated with monoclonal gammopathy with antibodies against myelin-associated glycoprotein, a sensorimotor neuropathy of older persons that shows predominantly distal demyelination (DADS). ³ This patient’s neuropathy appeared to involve large and small nerve fibers.

Finally, the history of a lung mass could suggest the possibility of a paraneoplastic neuropathy ⁴ or Wegener granulomatosis. ⁵ Neither cancer nor inflammation was demonstrated by his biopsy.

The history of neuropathy in a brother with a similar presentation suggests a hereditary condition, such as Charcot–Marie–Tooth disease. ⁶ However, his problems appeared to have a late onset as opposed to that typically seen in these patients and would not explain the cardiomyopathy or his autonomic dysfunction, and prominent sensory findings are unusual in those.

The family history, cardiovascular manifestations, autonomic involvement, and CTS suggest familial amyloidosis, particularly the transthyretin (TTR) or Andrade type. ⁷