Hans Faber

Prolonged and symptomatic bradycardia following a single dose of fingolimod.

Fingolimod-related bradycardia is usually asymptomatic, reaches its nadir within 6 hours post-dose and recovers spontaneously. Here we report the case of a 30-year-old MS patient with vagotonia who developed symptomatic bradycardia with 33 beats per minute at nadir 39 hours after a single dose of fingolimod. Bradycardia was responsive to atropine, but returned within 2 hours. Overall, it took a week until the patient recovered. Extended monitoring is advised in patients with symptomatic bradycardia.

Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects

Background Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently. Methods We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments. Results Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively). Conclusion Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.

Interferon β‐1a reduces increased interleukin‐16 levels in multiple sclerosis patients

There is convergent evidence for an important role of interleukin‐16 (IL‐16) in the pathogenesis of multiple sclerosis (MS). IL‐16 serves as a chemoattractant for different immune cells that are involved in developing lesions. Here, we compared IL‐16 levels of MS patients and controls and addressed the long‐term effect of IFN‐β, the most common immunomodulatory MS therapy, on IL‐16 serum levels in MS patients over 2 years. Beyond this, we analysed the expression of IL‐16 in two CD4+ T‐cell subsets, Th1 and Th17 cells, which are important autoimmune mediators and affected by IFN‐β treatment, derived from myelin‐specific T‐cell transgenic mice.

Spontaneous and induced experimental autoimmune encephalomyelitis (EAE) models in mice culminate in common pathways

© 2013 SAGE Publications 48 Intracortical laminar pathology in the motor cortex is associated with proximal underlying white matter injury in multiple sclerosis: a multimodal 7 T and 3 T MRI study C. Louapre (1), S.T. Govindarajan (1), C. Giannì (1), J. Cohen-Adad (2), S.M. Tobyne (3), R.P. Kinkel (4), C. Mainero (1) (1)Athinoula A. Martinos Center for Biomedical Imaging (Charlestown, US); (2)Ecole Polytechnique de Montréal (Montreal, CA); (3)Massachusetts General Hospital (Charlestown, US); (4)Beth Israel Deaconess Medical Center (Boston, US)