Authors
R.M. van den Berg-Vos, M.D.

Clinical features
MMN is clinically characterised by a slowly progressive, asymmetrical, predominantly distal weakness that develops insidiously or in a stepwise manner over several years. The commonest presenting clinical features are wrist drop, foot drop and grip weakness. Symptoms and signs of distal muscles prevail for a long time. In our recent study of 38 patients, 22 had onset of disease in the arms. In 14 of the 16 patients with onset in the legs, the arms were also affected at a later stage and in five of these, weakness in the arms predominated. 14 Proximal muscle weakness in deltoid and biceps muscles has been described. Read more

Natural course and prognosis
The majority of patients with MMN respond to IVIg treatment. A prospective study on the natural course of MMN is therefore not feasible. In retrospective studies we and others have shown that the disease runs a slowly progressive course, although most patients are impaired in their daily life by reduced dexterity in manual activities. 14,54 . Occasionally, a step-wise 55,56  or spontaneously remitting course 1,57  have been described. Read more

Epidemiology
The incidence and prevalence of MMN are unknown, but probably low. In the literature one MMN patient for every 50 patients with ALS⁵¹, a disease with a reported incidence of 1.5 -2 :100.000^52,53, has been described. In the Netherlands, we estimate the number of patients with MMN at approximately 100, giving a prevalence of 0.7: 100.000. With an approximate ratio of 2.6 : 1, men are more frequently affected than women.⁸ The mean age at onset is 40 years, with a range of 20 – 65 years.¹⁶

Differential diagnosis
The differential diagnosis of MMN includes (lower) motor neuron disease ((L)MND) 17,18  on one hand and demyelinating neuropathies on the other. In some patients MMN may appear similar to amyotrophic lateral sclerosis (ALS) with predominantly lower motor neuron signs and axonal changes on nerve conduction studies. The rapidly progressive disease course and the presence -or development during the disease course- of upper motor neuron signs as hyperreflexia, spasticity and/or bulbar signs may point to a diagnosis of ALS. The difference with LMND may be more difficult as a subgroup of patients with adult-onset, sporadic LMND may have a benign disease course. The clinical phenotype of several subtypes may be helpful in differentiating from MMN. Read more

Ancillary investigations
Evidence of motor conduction block (CB) is considered to be the electrodiagnostic hallmark of MMN. CB has been defined as a reduction in the amplitude or area of the compound muscle action potential (CMAP) obtained by proximal versus distal stimulation of motor nerves exceeding the CMAP reduction caused by increased temporal dispersion in demyelinating disorders or polyphasic motor-unit potentials in axonal degeneration. 21 The degree of CMAP reduction which is necessary to diagnose CB varies considerably from author to author. Our criterion for definite CB (area reduction P/D at least 50%) is based on the finding that computer simulation of temporal dispersion of biphasic MUPs yields an area reduction P/D of no more than 50%. 22 With more polyphasic MUPs, the CMAP reduction P/D is possibly greater. Read more

Therapy
Based on the assumption that MMN may be immune-mediated, several immune therapies have been used. Prednisolone and plasma exchange are ineffective in most patients with MMN. 20,58  Of the immunosuppressants, only cyclophosphamide seems to be consistently effective. 3,59  Unfortunately, the considerable side effects of cyclophosphamide, especially the increased risk of the development of neoplasms 60-62 , may limit its utility. More recently, various open and placebo-controlled studies have shown that treatment with high-dose IVIg leads to improvement of muscle strength in patients with MMN. Read more

References
1.        Chad DA, Hammer K, Sargent J. Slow resolution of multifocal weakness and fasciculation: a reversible motor neuron syndrome. Read more