Clinical background of the multifocal motor neuropathy: the Lausanne experience

Abstract

In this review we describe patients examined in Lausanne in whom a diagnosis of multifocal motor neuropathy (MMN) with conduction block (CB) was made, the basis of a discussion of the literature. Thirteen patients are described with their clinical features and the results of their laboratory and neuroimaging characteristics. There were 3 women and 10 men followed over a mean period of 7.3 years. Diagnosis was established after a mean period of 1.9 years. The location of the blocked nerve was predominantly observed in the upper limbs. Thirty per cent of the patients were considered as non-responders to treatment, including infusions of immunoglobulins (IVIg), cyclophosphamide or mycophenolate mofetil, and 70% of the patients were responders to IVIg infusions given repetitively. IVIg response was maintained during a mean period of time of 4.7 years in 8 patients. Only one patient is considered as cured following the associated treatment after 10 IVIg monthly courses associated with interferon alpha given subcutaneously over 16 months. The natural history of multifocal motor neuropathy is of a slowly progressive motor neuropathic process. Most patients have progression over many years, with treatment having persistent effects in the responders, but not curing the disease. The predilection for the upper limbs and in particular the handy muscles results in neurologic disability in the majority of the patients. Some patients are disabled by fatigue. The aetiology and pathogenesis of multifocal motor neuropathy remain unresolved, in part because the neuropathy runs an indolent course rarely justifying motor nerve biopsy and because there are no animal models of the disease. Nevertheless, it is widely believed that multifocal motor neuropathy is an autoimmune disorder. Recent excitability measurements of the nerves showed that there is axonal hyperpolarisation adjacent to sites with conduction block secondary to intraaxonal sodium accumulation. In conclusion, multifocal motor neuropathy is a disease that is slowly progressive but not benign, nerves showing conduction block develop axonal changes, and markers for this disease are needed. There are therefore open questions in this peripheral nerve disorder, the two most crucial being lack of real knowledge of the pathophysiological mechanisms of this peripheral nerve channelopathy and need of alternative treatments to IVIg infusions to cure this disease.