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There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D is actively under investigation as a potential intervention for epilepsy. Vitamin D is fat soluble steroid which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D may reduce seizures, and animal data support the efficacy of Vitamin D in rat and mouse models of epilepsy. Very little clinical data exists to support the treatment of human epilepsy with Vitamin D, but positive findings from preliminary clinical trials warrant larger Phase I and II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D as a treatment for human epilepsy.

The study of large-scale functional interactions in the human brain with fMRI extends almost to the first applications of this technology. Due to historical reasons and preconceptions about the limitations of this brain imaging method, most studies have focused on assessing connectivity over extended periods of time. It is now clear that fMRI can resolve the temporal dynamics of functional connectivity, like other faster imaging techniques such as EEG and MEG (albeit on a different temporal scale). However, the indirect nature of fMRI measurements can hinder the interpretability of the results. After briefly summarizing recent advances in the field, we discuss how the simultaneous combination of fMRI with electrophysiological activity measurements can contribute to a better understanding of dynamic functional connectivity in humans both during rest and task, wakefulness and other brain states.

Parkinson’s disease (PD) adversely affects timing abilities. Beat-based timing is a mechanism that times events relative to a regular interval, such as the ‘beat’ in musical rhythm, and is impaired in PD. It is unknown if dopaminergic medication influences beat-based timing in PD. Here we tested beat-based timing over two sessions in participants with PD (OFF then ON dopaminergic medication), and unmedicated control participants. People with PD and control participants completed two tasks. The first was a discrimination task in which participants compared two rhythms and determined whether they were the same or different. Rhythms either had a beat structure (metric simple rhythms), or did not (metric complex rhythms), as in previous studies. Discrimination accuracy was analyzed to test for the effects of beat structure, as well as differences between participants with PD and controls, and effects of medication (PD group only). The second task was the Beat Alignment Test (BAT), in which participants listened to music with regular tones superimposed, and responded as to whether the tones were ‘on’ or ‘off’ the beat of the music. Accuracy was analyzed to test for differences between participants with PD and controls, and for an effect of medication in patients.Both patients and controls discriminated metric simple rhythms better than metric complex rhythms. Controls also improved at the discrimination task in the second vs. first session, whereas people with PD did not. For participants with PD, the difference in performance between metric simple and metric complex rhythms was greater (sensitivity to changes in simple rhythms increased and sensitivity to changes in complex rhythms decreased) when ON vs. OFF medication. Performance also worsened with disease severity. For the Beat Alignment Test, no group differences or effects of medication were found. Overall, these findings suggest that timing is impaired in PD, and that dopaminergic medication influences beat-based and non-beat-based timing differently. Judging the beat in music does not appear to be affected by PD or by dopaminergic medication.

ObjectiveTo develop and validate a method for the detection of binding anti-drug antibodies (ADAs) against interferon beta (IFN-β) in human serum as part of a European initiative (ABIRISK) aimed at the prediction and analysis of clinical relevance of anti-biopharmaceutical immunization to minimize the risk.MethodA two-tiered bridging enzyme-linked immunosorbent assay (ELISA) format was selected and validated according to current recommendations. Screening assay: ADA in serum samples form complexes with immobilized IFN-β and biotinylated IFN-β, which are then detected using HRP labeled Streptavidin and TMB substrate. Confirmation assay: Screen “putative positive” samples are tested in the presence of excess drug (preincubation of sera with 0.3 µg/mL of soluble IFN-β) and percentage of inhibition is calculated.ResultsThe assay is precise, and the sensitivity of the assay was confirmed to be 26 ng/mL using commercially available polyclonal rabbit antihuman IFN-β in human sera as the positive control.ConclusionAn ultrasensitive ELISA for IFN-β-binding ADA testing has been validated. This will form the basis to assess anti-biopharmaceutical immunization toward IFN-β with regards to its clinical relevance and may allow for the development of predictive tools, key aims within the ABIRISK consortium.

Background: Despite the wide availability of novel anti-seizure medications (ASMs), 30% of patients with epilepsy retain persistent seizures with a significant burden in comorbidity and an increased risk of premature death. This review aims to discuss the therapeutic strategies, both pharmacological and non-, which are currently in the pipeline. Methods: PubMed, Scopus, and EMBASE databases were screened for experimental and clinical studies, meta-analysis, and structured reviews published between January 2018 and September 2021. The terms “epilepsy,” “treatment” or “therapy,” and “novel” were used to filter the results. Conclusions: The common feature linking all the novel therapeutic approaches is the spasmodic rush toward precision medicine, aiming at holistically evaluating patients, and treating them accordingly as a whole. Toward this goal, different forms of intervention may be embraced, starting from the choice of the most suitable drug according to the type of epilepsy of an individual or expected adverse effects, to the outstanding field of gene therapy. Moreover, innovative insights come from in-vitro and in-vivo studies on the role of inflammation and stem cells in the brain. Further studies on both efficacy and safety are needed, with the challenge to mature evidence into reliable assets, ameliorating the symptoms of patients, and answering the challenges of this disease.