Registration is a key step in many automatic brain Magnetic Resonance Imaging (MRI) applications. In this work we focus on longitudinal registration of brain MRI for Multiple Sclerosis (MS) patients. First of all, we analyze the effect that MS lesions have on registration by synthetically eliminating some of the lesions. Our results show how a widely used method for longitudinal registration such as rigid registration is practically unconcerned by the presence of MS lesions while several non-rigid registration methods produce outputs that are significantly different. We then focus on assessing which is the best registration method for longitudinal MRI images of MS patients. In order to analyze the results obtained for all studied criteria, we use both descriptive statistics and statistical inference: one way ANOVA, pairwise t-tests and permutation tests.