Marieke van Rosmalen

Chapter 2 28 Neurological examination and questionnaires We documented clinical characteristics of patients with MMN (including but not limited to site of onset and age at symptom onset) using a standardized questionnaire and collected the Overall Disability Sum Score (ODSS), the Self-Evaluation Scale (SES), the Rasch-built Overall Disability Score for MMN (MMN-RODS) and the Fatigue Severity Scale (FSS). 16–20 All patients underwent a standardized neurological examination ( Supplemental table 2.1 ). This consisted of bilateral grading of motor function of 18 muscle groups using the Medical Research Council (MRC) scale to calculate the MRC sum score with a maximum of 180 points. Sensory function was tested using a Rydell-Seiffer tuning fork to assess vibration sense in arms and legs bilaterally. Vibration sense was graded from normal (grade 0) to abnormal at the acromioclavicular joint or anterior superior iliac spine (grade 4). 21 Tendon reflexes of biceps, triceps, knee and ankle were performed on both sides and scored as normal, brisk or absent. We used data obtained during a previous study in 2007 as baseline data. 11 To minimize inter-observer variability, one of the authors (EAC) who collected clinical data during the 2007 study trained the author (BAJ) who performed the clinical examination in 2015 – 2016, with special emphasis on the interpretation of MRC and Rydell-Seiffer scales. Nerve conduction studies and other ancillary investigations One of the authors (HSG) evaluated available nerve conduction study results using the EFNS/PNS criteria for CB and other abnormalities. 5 All patients underwent nerve conduction studies (NCS) using a standardized protocol and stimulation was up to Erb’s point. 22 CB was defined as definite CB (compound muscle action potential (CMAP) area reduction of at least 50%) or probable CB (CMAP area reduction of 30-50%), and axonal loss as a decreased distal CMAP (distal CMAP amplitude below the lower limit of normal) in ≥ 1 nerves, including the median, ulnar, radial, musculocutaneous, peroneal, and tibial nerves. 5,23 We also collected all available results of laboratory studies (in particular the presence of anti-GM1 IgM antibodies in serum and analysis of cerebrospinal fluid) and of MRI of the brachial plexus. Statistical analyses MMN cohort data We stratified the patients with MMN into two groups: (1) patients diagnosed before our previous study in 2007, and (2) patients diagnosed after 2007) to explore differences in clinical characteristics. Depending on the distribution of the variable, we compared groups using the Mann-Whitney U test (for continuous data) and the χ 2 test (for categorical data). To account for right skew in time- related covariates, we log-transformed (natural) duration of treatment, months untreated and time to diagnosis. Univariate linear regression analyses were performed to identify changes in clinical characteristics over calendar time. Dependent variables were age at diagnosis, time to diagnosis (log-transformed) and age at onset of symptoms. The independent variable was the year of diagnosis. Subsequently, we calculated the mean MRC score per muscle group for patients with longer and shorter disease duration (defined as equal to or larger than the median disease duration). We corrected