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Compared to relapsing-remitting multiple sclerosis (MS), progressive MS is characterized by a lack of spontaneous recovery and a poor response to pharmaceutical immunomodulatory treatment. These patients may, therefore, particularly benefit from interventions that augment training-induced plasticity of the central nervous system. In this cross-sectional double-blind cross-over pilot study, effects of transcranial direct current stimulation (tDCS) on motor sequence learning were examined across four sessions on days 1, 3, 5, and 8 in 16 patients with progressive MS. Active or sham anodal tDCS of the primary motor cortex was applied immediately after each training session. Participants took part in two experiments separated by at least four weeks, which differed with respect to the type of posttraining tDCS (active or sham). While task performance across blocks of training and across sessions improved significantly in both the active and sham tDCS experiment, neither online nor offline motor learning was modulated by the type of tDCS. Accordingly, the primary endpoint (task performance on day 8) did not differ between stimulation conditions. In sum, patients with progressive MS are able to improve performance in an ecologically valid motor sequence learning task through training. However, even multisession posttraining tDCS fails to promote motor learning in progressive MS.

Objective To report pregnancy outcomes and disease activity (DA) in women with MS, neuromyelitis optica spectrum disorders (NMOSDs), and other neuroimmunologic diseases (ONID) after treatment with rituximab (RTX)/ocrelizumab (OCR) 12 months before or during pregnancy. Methods Data were collected in the German MS and pregnancy registry and centers from the Neuromyelitis Optica Study Group. Sixty-eight known outcomes of 88 pregnancies from 81 women (64 MS, 10 NMOSD, and 7 ONID) were included and stratified in 3 exposure groups: >6M-group = RTX/OCR >6 but ≤12 months before the last menstrual period (LMP) (n = 8)

Background and ObjectivesTo determine the real-world use of rituximab in autoimmune encephalitis (AE) and to correlate rituximab treatment with the long-term outcome.MethodsPatients with NMDA receptor (NMDAR)-AE, leucine-rich glioma-inactivated-1 (LGI1)- AE, contactin-associated protein-like-2 (CASPR2)-AE, or glutamic acid decarboxylase 65 (GAD65) disease from the GErman Network for Research on AuToimmune Encephalitis who had received at least 1 rituximab dose and a control cohort of non–rituximab-treated patients were analyzed retrospectively.ResultsOf the 358 patients, 163 (46%) received rituximab (NMDAR-AE: 57%, CASPR2-AE: 44%, LGI1-AE: 43%, and GAD65 disease: 37%). Rituximab treatment was initiated significantly earlier in NMDAR- and LGI1-AE (median: 54 and 155 days from disease onset) compared with CASPR2-AE or GAD65 disease (median: 632 and 1,209 days). Modified Rankin Scale (mRS) scores improved significantly in patients with NMDAR-AE, both with and without rituximab treatment. Although being more severely affected at baseline, rituximab-treated patients with NMDAR-AE more frequently reached independent living (mRS score ≤2) (94% vs 88%). In LGI1-AE, rituximab-treated and nontreated patients improved, whereas in CASPR2-AE, only rituximab-treated patients improved significantly. No improvement was observed in patients with GAD65 disease. A significant reduction of the relapse rate was observed in rituximab-treated patients (5% vs 13%). Detection of NMDAR antibodies was significantly associated with mRS score improvement. A favorable outcome was also observed with early treatment initiation.DiscussionWe provide real-world data on immunosuppressive treatments with a focus on rituximab treatment for patients with AE in Germany. We suggest that early and short-term rituximab therapy might be an effective and safe treatment option in most patients with NMDAR-, LGI1-, and CASPR2-AE.Class of EvidenceThis study provides Class IV evidence that rituximab is an effective treatment for some types of AE.

Background In multiple sclerosis (MS), neurological disability results from incomplete remission of relapses and from relapse-independent progression. Intravenous high dose methylprednisolone (IVMP) is the established standard treatment to accelerate clinical relapse remission, although some patients do not respond. Most studies of relapse treatment have been performed when few patients received disease-modifying treatment and may no longer apply today. Methods We prospectively assessed, over one year, the course of patients who presented with a clinically isolated syndrome (CIS) or MS relapse, documenting demographic, clinical, treatment and outcome data. A standardized follow-up examination was performed 10–14 days after end of relapse treatment. Results We documented 119 relapses in 108 patients (31 CIS, 77 MS). 114 relapses were treated with IVMP resulting in full remission (29.2%), partial remission (38.7%), no change (18.2%) or worsening (4.4%). In 27 relapses (22.7%), escalating relapse treatment was indicated, and performed in 24, using double-dose IVMP (n = 18), plasmapheresis (n = 2) or immunoadsorption (n = 4). Conclusions Standardised follow-up visits and outcome documentation in treated relapses led to escalating relapse treatment in every fifth relapse. We recommend incorporating scheduled follow-up visits into routine relapse management. Our data facilitate the design of prospective trials addressing methods and timelines of relapse treatment.

We performed a genome-wide association study in 1,194 controls and 150 patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n = 96) or anti-leucine-rich glioma-inactivated1 (anti-LGI1, n = 54) autoimmune encephalitis. Anti-LGI1 encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs) in the HLA-II region (leading SNP rs2858870 p = 1.22 × 10

Die KE-Familie ist das am ausführlichsten untersuchte Beispiel für eine angeborene spezifische Sprachstörung. Die Sprachstörung in dieser Familie wird durch eine heterozygote Punktmutation im FoxP2-Gen hervorgerufen, die R553H-Mutation. Die betroffenen Mitglieder der Großfamilie haben Defizite beim Erlernen komplexer orofazialer Bewegungsabläufe als Grundlage des fließenden Sprechens und zeigen Störungen beim Sprachverständnis und beim Schreiben. Untersuchungen an der KE-Familie und an Knockout-Tieren hatten Hinweise auf eine Beteiligung des Kleinhirns an der Sprachstörung der KE-Familie geliefert. Entsprechend war zu erwarten, dass genauere Kenntnisse über den Einfluss vom FoxP2-Gen auf Entwicklung und Funktion des Kleinhirns helfen könnten, die Funktion von FoxP2 und seine Rolle bezüglich dieser Sprachstörung, aber auch in Hinblick auf die Sprachfähigkeit des Menschen weiter aufzuschlüsseln. Die Experimente, die der vorliegenden Promotionsarbeit zu Grunde liegen, erforschten erstmals den Einfluss der KE-Mutation im FoxP2-Gen auf synaptischer Ebene durch Untersuchungen am in der Literatur ausführlich beschriebenen erregenden Schaltkreis im Kleinhirnkortex von heterozygoten R552H-Mäusen. Elektrophysiologische Messungen dienten dazu, die Verschaltung der Parallelfasern und Kletterfasern auf die Purkinjezelle auf Veränderungen der Übertragungseigenschaften zu prüfen. Durch Induktion von Langzeitdepression und Paarpulsbahnung an der Parallelfaser-Purkinjezell-Synapse sollte die synaptische Plastizität untersucht werden. Es zeigten sich eine intakte Verschaltung der erregenden Eingänge auf die Purkinjezelle, jedoch Veränderungen der Langzeit- und der Kurzzeitplastizität: Nach Induktion von Langzeitdepression entwickelte sich diese signifikant schneller. Die Paarpulsbahnung war bei kurzen Interstimulusintervallen signifikant verstärkt. Die Befunde sprechen für einen Einfluss des FoxP2-Gens auf die synaptischen Eigenschaften im Kleinhirnkortex. Die Aufschlüsselung dieses Einflusses und seine Bedeutung für die Sprachstörung der KE-Familie und die Sprachentwicklung beim Menschen ist Gegenstand weiterer Forschung.