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BackgroundFor most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis.MethodsWe conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used.ResultsWe included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033–0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events.ConclusionData on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.

Background Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. Methods We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. Results We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected ( p  = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. Conclusions Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.

BackgroundClinicians have questioned whether any disorder involving seizures and neural antibodies should be called “(auto)immune epilepsy.” The concept of “acute symptomatic seizures” may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses.MethodsRetrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years.ResultsPatients had surface antibodies against the N-methyl-d-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P < 0.001) and terminal seizure-freedom (80% vs. 7%, P < 0.001) more frequently. The time to first and terminal seizure-freedom and the time to freedom from ASM were shorter in the surface antibody group (Kaplan–Meier curves: P < 0.0001 for first seizure-freedom; P < 0.0001 for terminal seizure-freedom; P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time.ConclusionSeizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses.

Oral administration of N,N-Dimethylglycine (DMG), a tertiary amino acid, presumably enhances oxygen utilization by tissue and complex with free radicals. Beneficial effects are improved endurance performance and reduction fatigue in humans and animals. This pilot study reports the results over a one-year double-blind, placebo-controlled trial of DMG in 30 randomized patients with progressive multiple sclerosis. No treatment effects were found between the placebo group and the DMG group for disability, fatigue, cognitive, or gait parameters.

Post-stroke Epilepsy (PSE) is one of the most common forms of acquired epilepsy, especially in the elderly population. As people get increasingly older, the number of stroke patients is expected to rise and concomitantly the number of people with PSE. Although many patients are affected by post-ischemic epileptogenesis, not much is known about the underlying pathomechanisms resulting in the development of chronic seizures. A common hypothesis is that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing. Here, we summarize the clinical features of PSE and describe in detail the inflammatory changes after an ischemic stroke as well as the chronic changes reported in epilepsy. Moreover, we discuss alterations and disturbances in blood-brain-barrier leakage, astrogliosis, and extracellular matrix changes in both, stroke and epilepsy. In the end, we provide an overview of commonalities of inflammatory reactions and cellular processes in the post-ischemic environment and epileptic brain and discuss how these research questions should be addressed in the future.

The use of Brain–Computer Interfaces (BCI) as rehabilitation tools for chronically ill neurological patients has become more widespread. BCIs combined with other techniques allow the user to restore neurological function by inducing neuroplasticity through real-time detection of motor-imagery (MI) as patients perform therapy tasks. Twenty-five stroke patients with gait disability were recruited for this study. Participants performed 25 sessions with the MI-BCI and assessment visits to track functional changes during the therapy. The results of this study demonstrated a clinically significant increase in walking speed of 0.19 m/s, 95%CI [0.13–0.25], p  < 0.001. Patients also reduced spasticity and improved their range of motion and muscle contraction. The BCI treatment was effective in promoting long-lasting functional improvements in the gait speed of chronic stroke survivors. Patients have more movements in the lower limb; therefore, they can walk better and safer. This functional improvement can be explained by improved neuroplasticity in the central nervous system.

Background Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are applied in epilepsy mostly during presurgical assessment. Nonlesional focal epilepsy is very challenging for presurgical evaluation in cases of refractory epilepsy. Objectives We aimed to investigate the contribution of PET and SPECT to focus localization in nonlesional epilepsy. Methods The basic principles of SPECT and PET including different tracers were reviewed. The literature and the most recent publications are discussed in view of findings in nonlesional epilepsy. Results Ictal SPECT shows a high sensitivity of over 80% for ictal onset zone in nonlesional epilepsy. Postprocessing with subtraction ictal SPECT co-registered with MRI (SISCOM) or statistical parametric mapping are the gold standard. Histopathological findings in nonlesional epilepsies with concordant ictal SPECT imaging show focal cortical dysplasia in up to 75% of cases. Ictal injection is unsuccessful in approximately 20% of cases and the procedure is very time consuming and labor intensive. Fluorodeoxyglucose (FDG)-PET in nonlesional epilepsy shows variable sensitivity of 46–76%. As with ictal SPECT, it benefits from postprocessing of co-registration with magnetic resonance imaging (MRI) or even statistical parametric mapping. Hybrid PET/magnetic resonance imaging (MRI) scanners provide additional benefits for identifying lesions. Other PET tracers ( 11 C‑Flumazenil (FMZ), α- 11 C‑methyl-L-tryptophane (AMT)) are clinically applied in special cases only. Both procedures contribute complementary information in multimodal imaging diagnostics. Conclusions Ictal SPECT and PET are optional diagnostic tools for presurgical assessment in nonlesional epilepsies. They may reverse nonlesional to lesional epilepsy status and identify nonlesional epileptic foci with a fair chance of seizure freedom after epilepsy surgery.

Multiple Sclerosis (MS) is a chronic neurodegenerative disease in which the immune system attacks the myelin sheaths around nerves. People with MS (pwMS) often experience pain, fatigue, cognitive dysfunction, and reduced mobility. Today, MS is incurable, and treatments can at best slow the progression of the disease and manage symptoms. We conducted a preliminary, single-arm study using a motor-imagery brain-computer interface (MI-BCI) with functional electrical stimulation (FES) and virtual reality avatar targeting gait in pwMS. Twenty-six pwMS were enrolled; 24 completed 30 BCI sessions. Outcomes were assessed at Baseline, immediately post-treatment (Post1, week 13) and during follow-up (Post2, week 17; Post3, week 37). Change from baseline was analyzed using mixed models for repeated measures (with log-ratio models for skewed measures) and multiplicity control. This uncontrolled study is hypothesis-generating. Patients treated with the BCI-based intervention obtained significant improvements that were largely maintained to 6 months after the therapy. The walking endurance, assessed by the 6-minute walking test (6MWT), increased by 37.3 m (95% CI 21.50-53.10) after the treatment ( < 0.001), exceeding the minimal clinically important difference (MCID). This improvement in the walking endurance was maintained during the following 6 months after the intervention. Mobility/speed improved: TUG and T25FW times decreased by -15.5% and -16.4% after the last BCI session (both < 0.001), with benefits persisting after 6 months. Spasticity (MAS) declined by about 1 point, and patient-reported outcomes improved statistically and clinically (MSIS-29 10.18 points, MFIS 7.29 points). Pairwise post-visit contrasts were not significant, consistent with maintenance. Exploratory models found no consistent MS-subtype effect on 6MWT change and suggested larger gains with higher baseline EDSS. Two discontinuations were due to participant availability, not concerns with fatigue or safety. In this preliminary, single-arm study, a MI-BCI + FES system was associated with statistically significant, clinically meaningful gains in gait endurance, mobility/speed, spasticity, and patient-reported outcomes, sustained up to 6 months after the intervention.

Akut symptomatische Anfälle sind definiert durch einen engen zeitlichen Zusammenhang zwischen einem akuten Ereignis, welches einen negativen Einfluss auf das Gehirn hat, und dem daraus resultierenden Auftreten von epileptischen Anfällen. Diesem akuten Ereignis können neben einer strukturellen Hirnschädigung (z. B. traumatisch, vaskulär) unter anderem auch Entgleisungen im Rahmen internistischer Erkrankungen oder Einfluss von externen Noxen wie Medikamenten, Alkohol oder Drogen zugrunde liegen. In weiterer Folge beschreiben wir die häufigsten internistischen Ursachen, welche zu akut symptomatischen Anfällen führen können. Das Risiko von Elektrolytentgleisungen, Leber- und Nierenerkrankungen, Darmerkrankungen, Diabetes mellitus und der Einfluss unterschiedlicher Medikamente wird diskutiert.

Stroke is one of the leading causes of acquired epilepsy in adults. An instrument to predict whether people are at high risk of developing post-stroke seizures is not available. We aimed to develop and validate a prognostic model of late (>7 days) seizures after ischaemic stroke. In this multivariable prediction model development and validation study, we developed the SeLECT score based on five clinical predictors in 1200 participants who had an ischaemic stroke in Switzerland using backward elimination of a multivariable Cox proportional hazards model. We externally validated this score in 1169 participants from three independent international cohorts in Austria, Germany, and Italy, and assessed its performance with the concordance statistic and calibration plots. Data were complete for 99·2% of the predictors (99·2% for Switzerland, 100% for Austria, 97% for Germany, and 99·7% for Italy) and 100% of the outcome parameters. Overall, the risk of late seizures was 4% (95% CI 4–5) 1 year after stroke and 8% (6–9) 5 years after stroke. The final model included five variables and was named SeLECT on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). The lowest SeLECT value (0 points) was associated with a 0·7% (95% CI 0·4–1·0) risk of late seizures within 1 year after stroke (1·3% [95% CI 0·7–1·8] within 5 years), whereas the highest value (9 points) predicted a 63% (42–77) risk of late seizures within 1 year (83% [62–93] within 5 years). The model had an overall concordance statistic of 0·77 (95% CI 0·71–0·82) in the validation cohorts. Calibration plots indicated high agreement of predicted and observed outcomes. This easily applied instrument was shown to be a good predictor of the risk of late seizures after stroke in three external validation cohorts and is freely available as a smartphone app. The SeLECT score has the potential to identify individuals at high risk of seizures and is a step towards more personalised medicine. It can inform the selection of an enriched population for antiepileptogenic treatment trials and will guide the recruitment for biomarker studies of epileptogenesis. None.