Marieke van Rosmalen

Chapter 2 36 Median age at onset of symptoms and age of diagnosis significantly increased over time. The higher median age at diagnosis could be explained by an already increased awareness of MMN, resulting in more frequent clinical suspicion in older patients presenting with asymmetric weakness. Moreover, the addition of novel diagnostic techniques other than nerve conduction studies such as nerve ultrasound or the more frequent use of immunoglobulin trials to assess response to treatment could have led to the higher median age at diagnosis. The cause of the increase of age at onset is unknown although it is not unique for MMN. Similar trends have been observed in amyotrophic lateral sclerosis (ALS) (unpublished data of ALS cohort of 2900 patients in UMC Utrecht The Netherlands). 30 We can therefore not exclude the possibility that this trend is caused by changes in an altered referral pattern of patients with motor neuron disorders in our center. Despite the fact that MMN is considered a pure motor neuropathy, we found vibration sense abnormalities in 57% of the patients. These deficits were confined to the feet in 97% of the patients and in general occurred in patients with longer disease duration. Vibration sense also significantly deteriorated over time, which is similar to previous studies that showed reduced sensory nerve action potentials years after MMN onset. 31,32 Our study has some limitations. Neurological examination at both study visits was performed by different investigators. However, the authors who performed neurological examination were trained prior to the second tier of the study to minimize differences in performance, evaluation and interpretation of the MRC and Rydell-Seiffer scales. The large majority of patients received immunoglobulin maintenance treatment, which will have attenuated the true progression of MMN. Moreover, the relation of disease course with immunoglobulin therapy was not a primary aim of our study. We usually tailor treatment dose and frequency to maintain stable function between gifts. Although we found a significant increase in dose of immunoglobulin over time, possible relations between the therapy and progression should be a topic for future studies. Our study shows that MMN is a progressive disorder in the large majority of patients despite immunoglobulin maintenance treatment. Diagnostic delays are more common in older patients or with onset of weakness in one of the legs. Absence of reflexes and lower MRC sum score at baseline predict a more progressive disease course. Whether these patients would benefit from more aggressive treatment approaches with immunoglobulins needs to be established.