A Protean Protein

A 39-year-old man presented to a neurologist with three weeks of progressive leg weakness associated with numbness in his feet and fingertips. His medical history included hypertriglyceridemia, hypogonadism, and gout. He was taking fenofibrate and colchicine as needed. There was no family history of neurologic issues. He did not smoke or drink alcohol.

The patient appeared well with a heart rate of 76 beats per minute, blood pressure 133/72 mm Hg, temperature 36.6°C, respiratory rate 16 breaths per minute, and oxygen saturation 100% on room air. His cardiopulmonary and abdominal examinations were normal. His skin was warm and dry without rashes. On neurologic examination, upper extremity strength and sensation was normal. Bilateral hip flexion, knee flexion, and knee extension strength was 4/5; bilateral ankle dorsiflexion and plantar flexion strength was 3/5. Reflexes were trace in the arms and absent at the patellae and ankles. He had symmetric, length-dependent reduction in vibration, pinprick, and light touch sensation in his legs.

Peripheral neuropathy presenting with ascending symmetric motor and sensory deficits progressing over three weeks raises the suspicion of an acquired inflammatory demyelinating polyneuropathy (AIDP), a variant of Guillain-Barre Syndrome. Alternative causes of acute polyneuropathy include thiamine (B1) deficiency, vasculitis, sarcoidosis, or malignancy, particularly lymphoma and multiple myeloma. Further evaluation should include electromyography, nerve conduction studies, lumbar puncture with cerebrospinal fluid (CSF) protein, glucose, and cell count differential. Follow-up laboratory testing based on results of the above may include serum protein electrophoresis (SPEP), serum free light chains (sFLC), vitamin B12, human immunodeficiency virus (HIV), hepatitis B and C testing, antinuclear antibody, and erythrocyte sedimentation rate.

Electromyography and nerve conduction studies revealed a sensorimotor mixed axonal/demyelinating polyneuropathy in all extremities. CSF analysis found one white cell per mm³, glucose of 93 mg/dL, and protein of 313 mg/dL. Magnetic resonance imaging (MRI) of the spine without contrast showed normal cord parenchyma. The vitamin B12 level was 441 pg/mL (normal >200 pg/mL). Antibodies to HIV-1, HIV-2, hepatitis C virus, and Borrelia burgdorferi were negative. Serum protein electrophoresis (SPEP) and immunofixation were normal.

The patient received two courses of intravenous immunoglobulin (IVIG) for suspected AIDP. His weakness progressed over the next several weeks to the point that he required a wheelchair.

Progression of symptoms beyond three weeks and lack of response to IVIG are atypical for AIDP. Alternate diagnoses for a sensorimotor polyneuropathy should be considered. Causes of subacute or chronic demyelinating polyneuropathy include inflammatory conditions (chronic inflammatory demyelinating polyneuropathy [CIDP], connective-tissue disorders), paraprotein disorders (myeloma, amyloidosis, lymphoplasmacytic lymphoma), paraneoplastic syndromes, infectious diseases (HIV, Lyme disease), infiltrative disorders (sarcoidosis), medications or toxins, and hereditary disorders. Of these etiologies, the first three seem the most likely given the history and clinical course, the negative HIV and Lyme testing, and the absence of exposures and family history. Normal SPEP and immunofixation make paraprotein disorders less likely, but sFLC testing should be sent to evaluate for a light chain-only paraprotein. A paraneoplastic antibody panel and a CT of the chest, abdomen, and pelvis should be ordered to evaluate for sarcoidosis, lymphoma, or other malignancies. Although a peripheral nerve biopsy would further classify the polyneuropathy, it is of low diagnostic yield in patients with subacute and chronic distal symmetric polyneuropathies and is associated with significant morbidity. In the absence of history or physical exam findings to narrow the differential diagnosis for polyneuropathy, testing for paraneoplastic antibodies and imaging is appropriate.

The patient tested negative for antiganglioside GM1 and antimyelin-associated glycoprotein antibodies. Urine arsenic, lead, and mercury levels were normal. Tests for serum antinuclear antibody, rapid plasmin reagin, and a paraneoplastic neuropathy panel including amphiphysin antibody, CV2 antibody, and Hu auto-antibody were negative. Repeat electrodiagnostic testing was consistent with CIDP. The patient received prednisone 60 mg daily for six weeks and was then tapered to 30 mg daily over six weeks. Concurrently, he underwent twelve cycles of plasma exchange. His strength improved, and he could walk with a cane; however, weakness recurred when steroids were further tapered.