From Biology to Treatment of Monoclonal Gammopathies of Neurological Significance

Abstract

Monoclonal gammopathy and peripheral neuropathy are common diseases of elderly patients, and almost 10% of patients with neuropathy of unknown cause have paraprotein. However, growing evidence suggests that several hematological malignancies synthesize and release monoclonal proteins that damage the peripheral nervous system through different mechanisms. The spectrum of the disease varies from mild to rapidly progressive symptoms, sometimes affecting not only sensory nerve fibers, but also motor and autonomic fibers. Therefore, a multidisciplinary approach, mainly between hematologists and neurologists, is recommended in order to establish the correct diagnosis of monoclonal gammopathy of neurological significance and to tailor therapy based on specific genetic mutations. In this review, we summarize the spectrum of monoclonal gammopathies of neurological significance, their distinctive clinical and neurophysiological phenotypes, the most relevant pathophysiological events and new therapeutic approaches.

Keywords

• monoclonal gammopathies of neurological significance (MGNS)
• anti-myelin-associated-glycoprotein (MAG) polyneuropathy
• POEMS syndrome
• Castleman’s disease
• ibrutinib
• rituximab