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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.

Multiple sclerosis (MS) is a neurological disorder characterised by inflammatory demyelination and neurodegeneration in the central nervous system (CNS). Until recently, disease modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya®) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from 10 Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.

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.

The pattern of epileptic seizures is often considered unpredictable, and the interval between events without correlation. A number of studies have examined the possibility that seizure activity, both in terms of event magnitude and inter-event intervals, respect a power-law relationship. Such relationships are found in a variety of natural and man-made systems, such as earthquakes or Internet traffic, and describe the relationship between the magnitude of an event and the number of events. We postulated that human inter-seizure intervals would follow a power law relationship, and furthermore that evidence for the existence of a long memory process could be established in this relationship. We studied 8 patients who had long-term ambulatory EEG data recorded as part of the assessment of a novel seizure prediction device, in which data was sufficiently stationary in 6. We demonstrated that a power law relationship could be established in these patients, β=1.5. In 5/6 subjects we found evidence of long memory process, spanning time scales from 30 minutes to 40 days, using a wavelet based analysis technique. The Hurst exponent values ranged from 0.5 to 0.76. We conclude there is evidence of long memory processes in adult human epilepsy, with a heterogeneous range of time scales demonstrated between individuals. This finding may provide evidence of phase-transitions underlying the dynamics of epilepsy.

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.

Introduction: 18F-FDG-PET is widely used to help localize the hypometabolic epileptogenic focus for presurgical evaluation of drug-refractory epilepsy patients. Two voxel-based brain mapping methods to interpret 18F-FDG-PET, statistical parametric mapping (SPM), and three-dimensional stereotactic surface projection (3D-SSP), improve the detection rate of seizure foci. This study aimed to compare the consistency of epileptic focus detection between SPM and 3D-SSP for 18F-FDG-PET brain mapping analysis. Methods: We retrospectively reviewed the clinical, electroecephalographic, and brain imaging results of 35 patients with refractory epilepsy. 18F-FDG-PET studies were revaluated by SPM, 3D-SSP, and visual assessment, and the results were compared to the MRI lesion location and to the presumed epileptogenic zone (PEZ) defined by video-EEG and other clinical data. A second consistency study compared PET analyses to histopathology and surgical outcomes in the 19 patients who underwent lesion resection surgery. Results: Of the 35 patients, consistency with the PEZ was 29/35 for SPM, 25/35 for 3D-SSP, 14/35 for visual assessment, and 10/35 for MRI. Concordance rates with the PEZ were significantly higher for SPM and 3D-SSP than for MRI (P0.05). A favorable Engel outcome (class I/II) was found in 16 of 19 cases (84%), and failure of seizure control was found in 3 of 19 patients (class III/IV). Conclusion: Voxel-based 18F-FDG-PET brain mapping analysis using SPM or 3D-SSP can improve the detection rate of the epileptic focus compared to visual assessment and MRI. Consistency with PEZ was similar between SPM and 3D-SSP; According to their own characteristics, 3D-SSP is recommended for primary evaluation due to greater efficiency and operability of the software, while SPM is recommended for high-accuracy localization of complex lesions. Therefore, joint application of both software packages may be the best solution for FDG-PET analysis of epileptic focus localization. Keywords: Epilepsy; Statistical Parametric Mapping; 18F-FDG-PET; 3D-SSP; Epileptic focus

Moyamoya disease is a slowly progressing steno-occlusive condition affecting the cerebrovascularture. Affecting the terminal internal carotid arteries (ICA) and there branches, bilaterally, a resulting in a fine vascular network in the base of the brain to allow for compensation of the stenosed vessels. While there is obvious evidence of the involvement of inflammatory proteins in the condition, this has historically not been acknowledged as a causal factor. Here we describe the fundamental histopathology, genetics and signaling cascades involved in moyamoya and debate whether these factors can be linked as causal factor for the condition or whether they are simply a secondary result of the ischemia described in the condition. A particular focus has been placed on the multitude of signaling cascades linked to the condition as these are viewed as having the greatest therapeutic potential. As such we hope to draw some novel insight into potential diagnostic and therapeutic inflammatory targets in the condition.

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

IntroductionVisual impairment, specifically eye movement disorders and vestibular dysfunction may have a negative influence on the functional recovery in post-stroke patients. This type of sensory dysfunction may further be associated with poor functional outcome in patients’ post-stroke.MethodsIn phase 1, a cross-sectional survey (n = 100) will be conducted to determine the prevalence of eye movement disorders and vestibular dysfunction in patients who sustained a stroke. A cross-sectional clinical trial (n = 60) will be conducted during phase 2 of the study to determine the effect of the combination of vestibular rehabilitation therapy (VRT) and visual scanning exercises (VSE) (experimental group) integrated with task-specific activities compared with the effect of task-specific activities as an intervention (control group) on patients who present with eye movement impairment and central vestibular dysfunction post-stroke. An audiologist will assess (a) visual acuity (static and dynamic), (b) nystagmus, (c) saccadic eye movements, (d) smooth pursuit eye movements, (e) vestibulo-ocular reflex, and (f) saccular, utricular, and vestibular nerve function. An independent physiotherapist will assess (1) cognitive function, (2) residual oculomotor visual performance, (3) visual–perceptual system, (4) functional balance, (5) gait, (6) functional ability, (7) presence of anxiety and/or depression, and (8) level of participation in physical activity.Ethics and disseminationEthics approval has been obtained from the Ethics Committee of the Faculty of Health Sciences at the University of Pretoria (UP) (374/2015). The study will be submitted as fulfillment for the PhD degree at UP. Dissemination will include submission to peer-reviewed professional journals and presentation at congresses. Training of rehabilitation team members on the integration of VSE and VRT into task-specific activities in rehabilitation will be done if the outcome of the experimental group’s functional performance is clinically and statistically significantly better than the control group on the Barthel Index.Trial RegistrationPan African Clinical Trials Registry (PACTR201509001223262).