Thalidomide Neuropathy

Abstract & Commentary

Source: Isoardo G, et al. Thalidomide neuropathy: Clinical, electrophysiological and neuroradiological features. Acta Neurol Scand. 2004;109:188-193.

Six patients are the focus of this report defining the neuropathic side effects of thalidomide treatment in multiple myeloma. All subjects underwent evaluation prior to commencing thalidomide treatment, including neurological examination focusing on motor and sensory function, nerve conduction studies of bilateral median, ulnar, peroneal, and tibial motor, and median, ulnar, and sural sensory nerves, and somatosensory evoked potential studies of the median and tibial nerves. Blood studies included glucose, thyroid, liver, and renal function tests, vitamin E, B12, cryoglobulins, hepatitis B and C, HIV, multiple antibody studies, Shirmer testing, and fat and bone marrow biopsy. MRI of the cervical and thoracic spine was performed using a 1-Tesla magnet.

All patients developed a pure or predominant sensory polyneuropathy while on thalidomide. Family history excluded hereditary neuropathy in all, and none had spinal cord compression. Symptoms included pain, paresthesiae, and imbalance, and examination demonstrated distal impairment of touch, vibration, and pain sensitivity, distal or total areflexia, Romberg sign, and gait ataxia. Electrophysiological studies were consistent with a sensory axonal neuropathy or neuronopathy, with decreased or absent sensory responses, mild loss of motor amplitudes, and normal or mildly decreased conduction velocity not into the demyelinating range. MRI demonstrated posterior column high-signal intensity on T2-weighted sequences in the cervical region in only 1 patient. With discontinuation or lowering of thalidomide dosage from 200 mg/d to 100 mg/d or 50 mg/d, symptoms improved or resolved in 3 of 6 patients, although the clinical examination did not change by 6 months. Thalidomide can induce an axonal sensory neuropathy or, infrequently, a ganglionopathy. Discontinuation of medication does not guarantee reversibility.


Given its anti-inflammatory, anti-angiogenic, and immunomodulatory properties, thalidomide is finding ever-increasing indications.1 Its mechanism of action remains uncertain but may include inhibition of tumor necrosis factor-alpha production and interference with leukocyte integrin membrane receptor expression. Dermatologic conditions, including erythema nodosum leprosum, pyoderma gangrenosum, aphthous stomatitis, and Behcet disease, as well as non-dermatologic conditions encompassing systemic lupus erythematosus, graft-vs-host disease, multiple myeloma, myelofibrosis, and Rasmussen encephalitis, have responded to thalidomide, warranting that its neurological complications should be familiar to all neurologists. — Michael Rubin, MD Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus and Assistant Editor of Neurology Alert.


1. Nasca MR, et al. Ann Pharmacother. 2003;37:1307-1320.