By Michael Rubin, MD

Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

SYNOPSIS: Peripheral neuropathy is uncommon at presentation in patients with myeloma, and may be complicated by vitamin D deficiency and the neurotoxic effects of chemotherapy.

SOURCE: Leone C, Federico V, La Cesa S, et al. An observational study assessing peripheral neuropathy related to multiple myeloma. Neurol Sci 2016;37:1141-1143.

Lumbosacral and thoracic radiculopathies are the most common neurologic complications of multiple myeloma, resulting from compression of nerve roots by collapsed bone or paravertebral plasmacytoma. Approximately 5% of patients experience spinal cord compression, a neurologic emergency, usually from vertebral body fracture with resultant bone fragment extrusion or from extramedullary plasmacytoma. Peripheral neuropathy is uncommon in multiple myeloma, except in those with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), and usually is due to amyloidosis. What is the prevalence of peripheral neuropathy in newly diagnosed, untreated patients with multiple myeloma?

To address this question, 180 newly diagnosed multiple myeloma patients seen at the Hematology Department, Sapienza University, Rome, between March 2006 and December 2014, were evaluated by the Department of Neurology. Patients were excluded if they had any pre-existing condition associated with neuropathy, including diabetes, alcoholism, prior cancer, hepatitis C virus, or vitamin deficiency, leaving 153 patients for study. All patients underwent a thorough neurologic history, including questioning regarding dysautonomia and DN4 questionnaire for distinguishing nociceptive and neuropathic pain, and complete neurologic examination with careful attention to the sensory components. Standard sensory and motor nerve conduction studies were performed on all patients, encompassing the sural, ulnar, and radial sensory nerves, and peroneal, tibial, and ulnar motor nerves, with the median nerve omitted because of the high prevalence of incidental carpal tunnel syndrome in the general population. Additionally, skin punch biopsy, 10 cm proximal to the lateral malleolus, was performed on patients with distal paresthesiae but normal nerve conduction studies. Primary outcome measures for defining peripheral neuropathy required symptoms consistent with neuropathy in conjunction with abnormal nerve conduction studies, or, where nerve conduction studies were normal, skin biopsy abnormalities to diagnose small fiber neuropathy. Statistical analysis comprised the Mann-Whitney and Fisher’s exact tests, with P < 0.05 considered statistically significant.

Peripheral neuropathy was found in 7.2% (n = 11), was equally distributed between men and women, was more frequent in older patients (68.7 years vs. 63.2 years), and was large fiber in all but one, who had pure small fiber neuropathy. Negative symptomatology, sensory hypesthesia in the feet, was predominant, with absent Achilles’ deep tendon reflexes and decreased sural sensory nerve action potential amplitudes on electrodiagnostic studies. Motor compound muscle action potential amplitudes were spared in all, despite the occasional presence of very mild extensor digitorum brevis weakness on examination. Neuropathy at time of myeloma diagnosis is uncommon, but raises the possibility that these patients may be at greater risk of developing chemotherapy-induced neuropathy as treatment is initiated.

COMMENTARY

In a non-randomized, six-center study across the United States, encompassing 111 multiple myeloma patients treated with bortezomib or thalidomide for at least 12 weeks, symptoms of peripheral neuropathy were present in 58%, and vitamin D levels were found to be deficient (< 20 ng/mL) or insufficient (20-29.9 ng/mL) in 42%. Although vitamin D levels among these patients were similar to those found in the general adult population and no correlation was evident between vitamin D levels and neuropathy, sensory and motor peripheral neuropathy was more severe in vitamin D-deficient patients, and sensory peripheral neuropathy was more severe in vitamin D-insufficient patients. Low vitamin D levels are associated with more severe neuropathy in myeloma patients and should be monitored and supplemented where necessary.1

REFERENCE

  1. Wang J, Udd KA, Vidisheva A, et al. Low serum vitamin D occurs commonly among multiple myeloma patients treated with bortezomib and/or thalidomide and is associated with severe neuropathy. Support Care Cancer 2016;24;3105-3110.