Marieke van Rosmalen

Clinical outcomes in MMN 35 2 with MMN and found a slowly worsening of muscle weakness, i.e. a change in neurological impairment score (NIS) of 1.3 points/year. 14 We performed multiple linear regression analysis to determine predictors of a progressive disease course and found that absence of at least one reflex and a lower MRC sum score at baseline were associated with a larger decrease of the MRC sum score over time. This amounted to a difference of 1.36 MRC point decrease of the MRC sum score per year in patients with generalized areflexia compared to those with normal reflexes. These findings can help to identify patients with a more progressive disease course. Until the development of more effective treatment strategies for MMN, the identification of patients at greater risk may ultimately help to tailor the dosing or frequency of immunoglobulin treatment in the future. We used two approaches to analyze cross sectional data. First, we compared patients with a diagnosis before and after 2007, and thereby with longer and shorter disease duration. The distribution pattern of muscle weakness in patients with shorter and longer disease duration was similar but the severity of weakness of hand and lower leg/foot muscles was significantly increased in the latter. This finding supports the longitudinal data and also shows that proximal muscle groups are relatively spared. The second approach consisted of multiple linear regression analysis to determine factors that were associated with more severe weakness. Previous studies showed that axonal damage is highly associated with muscle weakness and therefore we performed the analysis without axonal damage as an independent factor. 15 We found that presence of anti-GM1 IgM antibodies and ‘years untreated’ were associated with more severe weakness, which is similar to findings of smaller previous studies. 24–26 These data imply that to prevent permanent weakness, reducing time to diagnosis and providing earlier treatment are crucial. Increased awareness of MMN and possibly the extension of reliable diagnostic tools, such as nerve ultrasound might serve this goal. We think that MMN should also be actively excluded in older patients or those with asymmetric weakness in a leg. The follow-up data showed that almost all outcome measures significantly deteriorated over time. However, there were some exceptions, most notably vigorimetry of the left hand. Although we cannot explain this finding, we previously observed that weakness is more common in the dominant hand. 11 This has also been reported for other inflammatory asymmetric syndromes such as neuralgic amyotrophy. 27 Moreover, fatigue seemed to improve over time. Fatigue is a common symptom of chronic immune-mediated disorders but without intervention, at best remains stable but often deteriorates over time. 28,29 A possible explanation for the improvement of fatigue in MMN could be that patients get used to the feeling of fatigue or adapted by changing frequency or intensity of their daily activities (e.g. change or quit their jobs, improve their lifestyles). We do not think that immunoglobulin therapy provides an explanation for the reduction in reported fatigue, since both in 2007 and in 2015 approximately 85% of the patients received maintenance therapy.