Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

The clinical significance of incidental white-matter foci seen on MRI is controversial. Mainly using a computer-assisted neuropsychological test battery, we tested the hypothesis that there is a clinical correlate of these foci. We studied 41 individuals aged 45-65 years with no history of neurological or psychiatric disorder, in whom no indication of central nervous system abnormalities was found on standardised neurological examination. A computer-assisted neuropsychological test battery, with the advantage of precise measuring of both time and deviation (e.g. in position memory tests), and rating scales for emotional dysfunction were administered; selected soft neurological signs were assessed. In 16 subjects (39%) MRI showed high-signal foci in the white matter on spin-echo sequences. White-matter foci not adjacent to the lateral ventricles were found to be related to performance on immediate visual memory/visuoperceptual skills, visuomotor tracking/psychomotor speed and, to a lesser degree, learning capacity and abstract and conceptual reasoning skills. Subtle cognitive dysfunction would appear to be a clinical correlate of punctate white-matter foci on MRI of otherwise "healty" individuals.

The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a neuropsychological screening battery, often applied in multiple sclerosis (MS) patients. It is almost exclusively administered in trials and not in the daily practice routine because of the lack of normative values. Using a stepwise linear regression analysis, the dependence of test results on age, gender, and education of 241 healthy control subjects was investigated. Z-values of -1.68 or less were considered pathological. Based on the normative values, the proportions of cognitively impaired patients with relapsing-remitting MS (RRMS, n=43) and secondary progressive MS patients (SPMS, n=60) were calculated. The regression model explained 2.7-25.0% of the variance of test performances. Cognitive impairment occurred in 38% and in 47% of the RRMS and the SPMS groups, respectively. In both groups attention and concentration impairment was prominent, while in the SPMS group memory was also frequently affected. The proportion of cognitively impaired MS patients reflected the figures that could be found in the literature.

This prospective, multicentre, international, observational, cohort study compared injection site pain (ISP) and injection site reactions (ISRS) between interferon beta-1b (IFNB-1b; Betaferon) 250 microg subcutaneously every other day and interferon beta-1a (IFNB-1a; Rebif) 44 microg subcutaneously three times weekly in patients with relapsing-remitting MS. Patients started treatment within 3 months before recruitment and were on full dose of therapy at inclusion. Patients self-injected IFNB and self-assessed ISP for 15 consecutive injections immediately, 30 and 60 min after injection, using a visual analogue scale diary. Study staff assessed ISRS. Of 445 patients (valid cases), approximately 90% used autoinjectors. More patients were pain-free at all timepoints with IFNB-1b than with IFNB-1a (eg, 30 min: 42.6% versus 19.7%; P<0.0001). The mean proportion of pain-free injections was greater for IFNB-1b (eg, 30 min: 79.0%) than for IFNB-1a (53.3%; P<0.0001). The proportion of patients without ISRS was greater for IFNB-1b (second visit 51.8% versus 33.8%; P<0.0001). Compared with IFNB-1a, more IFNB-1b patients either had no pain or their ISP had no influence on treatment satisfaction (76.9% versus 64.1%; P=0.006). The impact on tolerability and patient acceptability of any new IFNB product formulations would, however, have to be evaluated in comparative studies.