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Wearable devices and mobile health software applications have a great potential for improving epilepsy-related health outcomes and contributing to personalized medical care for persons with epilepsy. With limitations and challenges, they can be used for tracking seizure occurrence and for seizure detection, prediction, and forecasting in hospital and ambulatory settings. They can also help promote self-monitoring and self-management and thereby contribute to patient empowerment. In this review, we provide an overview of current wearable devices and mobile health software applications for epilepsy. We focus on clinically validated devices, their clinical applications, the challenges faced when using these devices in real-world settings, and how these devices may be optimized in the future.

Background Subjective Memory Complaints (SMC) in elderly people due to preclinical Alzheimer’s Disease may be associated with dysregulation of the Kynurenine Pathway (KP), with an increase in neurotoxic metabolites that affect cognition. Golf is a challenging sport with high demands on motor, sensory, and cognitive abilities, which might bear the potential to attenuate the pathological changes of preclinical AD. This trial investigated the feasibility of learning to play golf for elderly with cognitive problems and its effects on cognitive functions and the KP. Methods In a 22-week single-blinded randomized controlled trial, elderly people with SMC were allocated to the golf (n = 25, 180 min training/week) or control group (n = 21). Primary outcomes were feasibility (golf exam, adherence, adverse events) and general cognitive function (Alzheimer’s Disease Assessment Scale). Secondary outcomes include specific cognitive functions (Response Inhibition, Corsi Block Tapping Test, Trail Making Test), KP metabolites and physical performance (6-Minute-Walk-Test). Baseline-adjusted Analysis-of-Covariance was conducted for each outcome. Results 42 participants were analyzed. All participants that underwent the golf exam after the intervention passed it (20/23). Attendance rate of the golf intervention was 75 %. No adverse events or drop-outs related to the intervention occurred. A significant time*group interaction (p = 0.012, F = 7.050, Cohen’s d = 0.89) was found for correct responses on the Response Inhibition task, but not for ADAS-Cog. Moreover, a significant time*group interaction for Quinolinic acid to Tryptophan ratios (p = 0.022, F = 5.769, Cohen’s d = 0.84) in favor of the golf group was observed. An uncorrected negative correlation between attendance rate and delta Quinolinic acid to Kynurenic acid ratios in the golf group (p = 0.039, r=-0.443) was found as well. Conclusions The findings indicate that learning golf is feasible and safe for elderly people with cognitive problems. Preliminary results suggest positive effects on attention and the KP. To explore the whole potential of golfing and its effect on cognitive decline, a larger cohort should be studied over a longer period with higher cardiovascular demands. Trial registration The trial was retrospectively registered (2nd July 2018) at the German Clinical Trials Register (DRKS00014921).

People with epilepsy (PWE) are less fit and have an increased risk of sudden cardiac death. Imbalances within the autonomic nervous system (ANS) are believed to mediate some of those effects. However, results are mostly derived from patients whose seizures are refractory to medical therapy. In this study, an exhaustive bicycle ergometer test was delivered to 25 PWE (19 seizure free in the last 6 months) recruited in a community-based setting and 25 age-, sex-, and BMI-matched healthy controls. During the exercise test a 12-channel ECG was recorded and spirometry was carried out to determine the maximal oxygen uptake (VO

Purpose of ReviewThe incidence of sport-related concussion (SRC) has been increasing in different sports and its impact on long-term cognitive function is increasingly recognized. In this study, we review the epidemiology, neuropathophysiology, clinical symptoms, and long-term consequences of SRC with a specific focus on cognition.Recent FindingsRepeated concussions are associated with an increased risk of several neurologic diseases and long-term cognitive deficits. To improve cognitive outcomes in athletes with SRC, standardized guidelines for the assessment and management of SRC are vital. However, current concussion management guidelines lack procedures for rehabilitating acute and long-term cognitive symptoms.SummaryIncreased awareness for the management and rehabilitation of cognitive symptoms in SRC is needed in all clinical neurologists treating professional and amateur athletes. We propose cognitive training as a prehabilitation tool to alleviate the severity of cognitive symptoms and as a rehabilitative tool to improve cognitive recovery postinjury.

A seizure is a strong central stimulus that affects multiple subsystems of the autonomic nervous system (ANS), and results in different interactions across ANS modalities. Here, we aimed to evaluate whether multimodal peripheral ANS measures demonstrate interactions before and after seizures as compared to controls to provide the basis for seizure detection and forecasting based on peripheral ANS signals.Continuous electrodermal activity (EDA), heart rate (HR), peripheral body temperature (TEMP), and respiratory rate (RR) calculated based on blood volume pulse were acquired by a wireless multi-sensor device. We selected 45 min of preictal and 60 min of postictal data and time-matched segments for controls. Data were analyzed over 15-min windows. For unimodal analysis, mean values over each time window were calculated for all modalities and analyzed by Friedman's two-way analysis of variance.Twenty-one children with recorded generalized tonic-clonic seizures (GTCS), and 21 age- and gender-matched controls were included. Unimodal results revealed no significant effect for RR and TEMP, but EDA (p = 0.002) and HR (p 0.001) were elevated 0-15 min after seizures. The averaged bimodal correlation across all pairs of modalities changed for 15-min windows in patients with seizures. The highest correlations were observed immediately before (0.85) and the lowest correlation immediately after seizures. Overall, average correlations for controls were higher.Multimodal ANS changes related to GTCS occur within and across autonomic nervous system modalities. While unimodal changes were most prominent during postictal segments, bimodal correlations increased before seizures and decreased postictally. This offers a promising avenue for further research on seizure detection, and potentially risk assessment for seizure recurrence and sudden unexplained death in epilepsy.

OBJECTIVE Daytime and nighttime patterns affect the dynamic modulation of brain and body functions and influence the autonomic nervous system response to seizures. Therefore, we aimed to evaluate 24-hour patterns of electrodermal activity (EDA) in patients with and without seizures. METHODS We included pediatric patients with (a) seizures (SZ), including focal impaired awareness seizures (FIAS) or generalized tonic-clonic seizures (GTCS), (b) no seizures and normal electroencephalography (NEEG), or (c) no seizures but epileptiform activity in the EEG (EA) during vEEG monitoring. Patients wore a device that continuously recorded EDA and temperature (TEMP). EDA levels, EDA spectral power, and TEMP levels were analyzed. To investigate 24-hour patterns, we performed a nonlinear mixed-effects model analysis. Relative mean pre-ictal (-30 min to seizure onset) and post-ictal (I: 30 min after seizure offset; II: 30 to 60 min after seizure offset) values were compared for SZ subgroups. RESULTS We included 119 patients (40 SZ, 17 NEEG, 62 EA). EDA level and power group-specific models (SZ, NEEG, EA) (h = 1; P

ObjectiveThe aim of this pilot study is to explore changes in EEG derived functional connectivity of the default mode network in response to physical exercise during return-to-sports (RTS) after sports related concussion (SRC).BackgroundThe rehabilitation of athletes with SRC is challenging. Presently, there are no objective biomarkers to predict effects of exercise during RTS. SRC associated diffuse axonal injuries predominantly affect the Default Mode Network (DMN). Assessing exercise induced changes in functional connectivity of the DMN may therefore be a potential target.Design/MethodsEleven athletes were examined during the early stages of RTS after SRC (age: 23.90 ± 4.81) and compared to 13 control athletes (age: 24.00 ± 4.90). Resting state 128-channel EEGs were collected before and after a progressive ergometer exercise protocol working up to 70% of the maximal heart rate. DMN connectivity was assessed by calculating the phase locking value (PLV) in 3 frequency bands (theta: 3–7, alpha: 7–13, beta: 14–25). Wilcoxon Signed Rank Tests were used to explore statistical significance between pre- and post-exercise.ResultsIn SRC athletes PLV within the alpha band decreased significantly post-exercise (median [Mdn] = 0.445, interquartile range [IQR = 0.069) in comparison to pre-exercise (Mdn = 0.436, IQR = 0.047; Z = −1.956, p < 0.05), whereas no difference was observed in the control group (post-exercise [Mdn = 0.476, IQR = 0.072] compared to pre-exercise [Mdn = 0.461, IQR = 0.100; Z = −0.175, p = 0.86]). PLVs in the theta and beta band before and after exercise differed neither in the patient nor in the control group.ConclusionsExercise induced changes of functional connectivity of the DMN within the alpha band were only present in post-concussed athletes and may be suitable as a potential objective marker to reflect pathophysiologic changes in further clinical studies to guide RTS.

The goal of this study was to evaluate and summarize the current literature on multimodal changes of the autonomic nervous system (ANS) in people with epilepsy (PWE). We included studies reporting ANS measures of at least two modalities and with a minimum of one group of people with epilepsy. We screened two hundred eighty-three abstracts and sixty-six full texts, of which twenty-two met our inclusion criteria. Eleven studies reported ictal and interictal cardiac and respiratory changes. Three studies investigated the correlation between cardiac and respiratory markers, whereby two found no correlation and one showed a relation. Six studies evaluated electrodermal and cardiac parameters and showed effects on both ANS subsystems that jointly indicate a shift toward increased sympathetic activity for people with epilepsy during rest and during activity. Two studies assessed three modalities and reveal epilepsy-related alterations within the ANS. In summary, there is a growing interest in multimodal monitoring approaches, such as combining at least two ANS modalities, to describe epilepsy-related changes in ANS activity and to test for the potential to use ANS markers for seizure detection and prediction. Most studies report multiple unimodal analyses while only few studies analyzed multimodal patterns. Patterns of changes depend on the type of epilepsy and differ on an individual level; therefore, a multimodal approach might offer an approach to more individualized monitoring and, ultimately, management.

Objective Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in “hub” areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We aim to clarify these associations using connectivity measures specifically sensitive to hubs. Methods Connectivity between 1000 cortical surface parcels was determined in 49 TLE patients and 23 controls with diffusion and resting-state functional magnetic resonance imaging. Two types of hub connectivity were investigated across multiple brain modules (the DMN, motor system, etcetera): (1) within-module connectivity (a measure of local importance that assesses a parcel's communication level within its own subnetwork) and (2) between-module connectivity (a measure that assesses connections across multiple modules). Results In TLE patients, there was lower overall functional integrity of the DMN as well as an increase in posterior hub connections with other modules. Anatomical between-module connectivity was globally decreased. Higher DMN disintegration (DD) coincided with higher anatomical between-module connectivity, whereas both were associated with increased seizure frequency. DD related to seizure frequency through mediating effects of anatomical connectivity, but seizure frequency also correlated with anatomical connectivity through DD, indicating a complex interaction between multimodal networks and symptoms. Interpretation We provide evidence for dissociated anatomical and functional hub connectivity in TLE. Moreover, shifts in functional hub connections from within to outside the DMN, an overall loss of integrative anatomical communication, and the interaction between the two increase seizure frequency.

SummaryObjective New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Methods Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic–clonic seizures and 49 focal to bilateral tonic–clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. Results The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy.

BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI ≥0.10 or ≤−0.10 was considered left- or right-hemisphere dominance, respectively; a LI between −0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients.

SUMMARY The special requirements for a seizure detector suitable for everyday use in terms of cost, comfort, and social acceptance call for alternatives to electroencephalography (EEG)–based methods. Therefore, we developed an algorithm for automatic detection of generalized tonic– clonic (GTC) seizures based on sympathetically mediated electrodermal activity (EDA) and accelerometry measured using a novel wrist-worn biosensor. The problem of GTC seizure detection was posed as a supervised learning task in which the goal was to classify 10-s epochs as a seizure or nonseizure event based on 19 extracted features from EDA and accelerometry recordings using a Support Vector Machine. Performance was evaluated using a double cross-validation method. The new seizure detection algorithm was tested on >4,213 h of recordings from 80 patients and detected 15 (94%) of 16 of the GTC seizures from seven patients with 130 false alarms (0.74 per 24 h). This algorithm can potentially provide a convulsive seizure alarm system for caregivers and objective quantification of seizure frequency.

We investigated the safety, tolerability, and effectiveness of lacosamide (LCM) in patients with acute recurrent seizures or with periodic epileptiform activity captured during continuous EEG monitoring. A total of 17 patients received LCM; 12 patients received LCM as a second or third antiepileptic drug (AED), one patient as a fourth AED, and one patient as a fifth AED. No additional AEDs were introduced after LCM in 15 patients. Twelve patients responded to LCM with improvement in the seizures or periodic epileptiform activity. Two patients required further AED management or burst suppression. No adverse effects, including symptomatic bradycardia and allergic reactions, were seen for intravenous infusion dosages up to 300 mg. Eleven patients were eventually discharged on LCM. LCM is an important new AED in the add-on treatment of acute recurrent seizures and periodic epileptiform activity in critically ill patients.

Disturbances of the autonomic nervous system (ANS) are common in neuropsychiatric disorders. Disease specific alterations of both sympathetic and parasympathetic activity can be assessed by heart rate variability (HRV), whereas electrodermal activity (EDA) can assess sympathetic activity. In posttraumatic stress disorder (PTSD), parasympathetic HRV parameters are typically decreased and EDA is increased, whereas in major depressive disorder (MDD) and dissociation, both parasympathetic and sympathetic markers are decreased. ANS abnormalities have also been identified in psychogenic nonepileptic seizures (PNES) by using HRV, indicating lower parasympathetic activity at baseline. In addition to reviewing the current literature on ANS abnormalities in PTSD, MDD, and disorders with prominent dissociation, including borderline personality disorder (BPD), this article also presents data from a pilot study on EDA in patients with PNES. Eleven patients with PNES, during an admission to our epilepsy monitoring unit (EMU), were compared with 9 with generalized tonic-clonic seizures (GTCS). The area under the EDA curve, the number of EDA responses lasting longer than 2 seconds, and the number of EDA surges during sleep (sympathetic sleep storms) were calculated on ictal and interictal days by an automated algorithm. EDA changes in PNES patients did not follow a systematic pattern of sympathetic hyperarousal (like EDA after GTCS) but were more variable. How specific PNES semiologies, and/or underlying neuropsychiatric disorders, may influence ictal and interictal EDA patterns, and lead to a novel diagnostic biomarker remains to be evaluated in future larger studies.

Objective Sudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients. Methods Patients admitted to the epilepsy monitoring unit were prospectively recruited, and wore an electrodermal activity (EDA) wrist sensor that continuously measured sympathetic activity while being monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as a measure of sympathetic activity. Peri-ictal parasympathetic activity was determined through the high frequency component (HF) analysis of heart rate variability (HRV). The duration of post-ictal generalized EEG suppression (PGES) was also documented. Results Twenty patients with GTCS were included in the study on whom 30 GTCS were recorded. PGES duration strongly correlated with age ( r =0.62, p =0.004) and measures of the EDA response. After controlling for PGES duration, we found pediatric patients had greater sympathetic activation measured as log rising portion of the area under the curve of the EDA response ( β =+0.67, p =0.034) and a higher degree of vagal suppression measured as maximal percentage change of HF power ( β =−12.65, p =0.0036). Conclusion Sympathetic activity can be measured in the peri-ictal period, and directly correlates with PGES duration. Age is a significant determinant of the sympathetic and parasympathetic response following a GTCS; given the same PGES duration, pediatric patients demonstrate stronger sympathetic activation and higher vagal suppression. However, the increase in PGES duration with age and the associated autonomic dysregulation may provide clues as to why there is a variable vulnerability to SUDEP across age groups.

Psychogenic nonepileptic seizures (PNES) remain poorly understood neurobiologically. Previously reported work suggests that adjunct ictal heart rates (HRs) may differentiate PNES from complex partial seizures (CPS). We retrospectively reviewed and compared preictal, ictal, and postictal HR differences in patients with PNES (n=42) and CPS controls (n=46) electively admitted for video/EEG monitoring to further characterize PNES autonomic patterns. Statistically significant preictal HR increases (P=0.006) and postictal (P=0.015) HR reductions normalized to baseline were identified in subjects with PNES compared with CPS controls. Ictal HRs were not found to differentiate between PNES and CPS events. This pattern of pre-event HR increases and postevent HR decreases in patients with PNES compared with those with CPS suggests frontolimbic neural circuit dysfunction and merits further exploration.

SummaryThe influence of smoking on lamotrigine (LTG) serum levels in 44 patients with epilepsy treated with LTG in monotherapy was examined. Fifteen patients were smokers (range: three cigarettes per month – three packages per day) and 29 were non-smokers. Analyzing 204 samples, smokers had a significantly lower serum level-to-dose ratio than non-smokers (0.0657mmolmg/l (smokers) vs. 0.0785mmolmg/l (non-smokers)) (p=0.0014). Analyzing only male patients, the same relationship with an almost equally high level of significance could be demonstrated (p=0.008). Our data indicate that the demonstrated effect of smoking on LTG metabolism is likely to be mediated via UDPGT2B7, as LTG is not a substrate of cytochrome P450 isoenzymes and UDPGT1A4 activity may not be affected by nicotine, but the exact mechanism underlying the demonstrated effect remains uncertain. These findings are likely to be independent from hormonal changes, as they could also be reproduced in the group of male patients. Therefore, the effect of smoking on blood levels of LTG has to be taken into account in the evaluation of treatment with this drug.

1. Massachusetts Institute of Technology (MIT), email: picard@media.mit.edu 2. Empatica, Inc, Cambridge, MA and Milan, Italy 3. Department of Neurology, New York University Langone Medical Center 4. Edward B. Bromfield Epilepsy Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 5. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 6. Institute of Sports Medicine, University of Paderborn, Germany 7. Epileptology Clinic, University of Bonn, Germany

Objective: To examine whether the corticospinal system emanating from the primary motor cortex may be organized to facilitate generation of dystonic movements. Methods: In this cross-sectional observational study, finger movement (FM) representations were assessed in 10 patients with focal hand dystonia (FHD) and 10 matched healthy controls by transcranial magnetic stimulation during rest. Evoked finger movements of the right hand were recorded using an instrumented data glove. Patterns of finger joint movements were analyzed using cluster analysis. Principal component analysis and centers of gravity for finger movement representations and motor evoked potentials recorded from the abductor pollicis brevis and abductor digiti minimi muscles were computed. For comparison, high-resolution somatosensory evoked potentials (SSEP) were recorded after electrical stimulation of the thumb (D1) or little finger (D5) in the same patients. Source reconstruction for the N20 SSEP component was performed using a dual-dipole model. Results: Stimulation of the resting motor cortex did not reveal overt abnormalities in FHD, neither with respect to finger joint movement patterns nor with respect to the topologic organization of finger movements or intrinsic hand muscle representations. However, in line with previous reports, the distance between the dipole sources of D1 and D5 in the somatosensory cortex (S1) was smaller in patients with FHD, suggesting disruption of homuncular finger representations in S1. Conclusions: Our findings may imply that abnormality of motor organization in focal hand dystonia arises principally only during activation, when abnormal somatosensory representations are functionally integrated.

The interictal EEG is a noninvasive and useful test for selecting candidates for resective epilepsy surgery, although it has many pitfalls. It is an essential test for the most common drug-resistant epilepsy, mesial temporal sclerosis, and predicts good outcome when interictal epileptiform discharges are concordant with unilateral hippocampal atrophy or sclerosis, and predicts poor outcome when interictal epileptic discharges are discordant with the lesion. Its role in other types of epilepsy surgery, including nonlesional cases and corpus callosotomy, is less clear. Future research gathering large multicenter prospective data is needed to maximize the role of this classic neurophysiological test in the evaluation of candidates for epilepsy surgery.

We investigated a patient with severe catatonic schizophrenia (manneristic catatonia according to Karl Leonhard) treated with electroconvulsive therapy (ECT) after pharmacological approaches did not result in any clinical improvement. Before and after nine ECT sessions a double-pulse transcranial magnetic stimulation (TMS) paradigm was used to measure intracortical inhibition (ICI) which has been shown to be reduced in a significant proportion of patients with schizophrenia. Although the patient showed no remission regarding some psychomotor aspects after ECT, we found an increase in ICI and a remarkable clinical improvement of catatonic omissions which might be due to changes in the GABAergic system.

Die Applikation von kontinuierlicher Theta-Burst Stimulation (cTBS), einem neuen Protokoll der repetitiven transkraniellen Magnetstimulation (TMS), uber dem primaren Motorkortex kann die kortikospinale Exzitabilitat fur mehrere Minuten herabsetzen (Huang et al., 2005). Wir stellten uns die Frage, zu welchem Grad die Wirkung von cTBS von dem vorhergehenden Aktivierungszustand des konditionierten Motorkortex abhangig ist. Es wurde die Wirkung von funf verschiedenen Interventionen auf die Amplitude der motorischen evozierten Potenziale (MEPs) des rechten M. abductor pollicis brevis (APB) nach einzelnen TMS Reizen uber dem linken M1 bis zu 24 Minuten nach der Intervention untersucht. In den Experimenten 1 bis 3 wurden schwache (25% der maximalen Kraft), isometrische Kontraktionen des APB Muskels fur eine Dauer von 0min (ACT0), 1,5min (ACT1,5) und 5min (ACT5) durchgefuhrt. Daraufhin wurden hochfrequente (50Hz) Folgen von drei TMS Reizen in 5Hz Intervallen fur 20s uber dem linken M1 bei einer Intensitat von 70% der Ruheschwelle (cTBSRMT) appliziert. Experiment 4 war identisch zu ACT0+TBSRMT, mit dem einzigen Unterschied, dass die Stimulationsintensitat auf 80% der aktiven Schwelle (TBSAMT) gesetzt wurde. In Experiment 5 fuhrten die Probanden ohne anschliesende Intervention eine funfminutige isometrische Kontraktion durch (ACT5 ohne TBS). Nach ACT0+TBSRMT konnte keine Veranderung der MEP Amplituden beobachtet werden. ACT5 ohne TBS fuhrte zu einem Anstieg (nach 6min: 130±22%; p=0,005), wahrend durch ACT1,5+TBSRMT (nach 2min: 71±22%; p=0,019; nicht aber nach 6min: 100±36%; p=0,496), ACT5+TBSRMT (nach 6min: 65±26%; p=0,004) und TBSAMT (nach 6min: 75±23%; p=0,015) die MEP Amplituden vermindert wurden (ANOVA; ZEIT*INTERVENTION: F=1,573; p=0,012). Die Reduktion der MEP Amplituden war bei langerer Voraktivierung ausgepragter. Die Verminderung der kortikospinalen Exzitabilitat durch cTBS ist abhangig von der vorangehenden Aktivierung des Zielkortex. Diese Ergebnisse sind relevant fur die Anwendung von cTBS als eine „virtuelle Lasions-“Technik. Ref.: Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201–6. Unterstutzt durch gemeinnutzige Hertie-Stiftung, Deutschland.

Objective: Sudden unexpected death in epilepsy (SUDEP) poses a poorly understood but considerable risk to people with uncontrolled epilepsy. There is controversy regarding the significance of postictal generalized EEG suppression as a biomarker for SUDEP risk, and it remains unknown whether postictal EEG suppression has a neurologic correlate. Here, we examined the profile of autonomic alterations accompanying seizures with a wrist-worn biosensor and explored the relationship between autonomic dysregulation and postictal EEG suppression. Methods: We used custom-built wrist-worn sensors to continuously record the sympathetically mediated electrodermal activity (EDA) of patients with refractory epilepsy admitted to the long-term video-EEG monitoring unit. Parasympathetic-modulated high-frequency (HF) power of heart rate variability was measured from concurrent EKG recordings. Results: A total of 34 seizures comprising 22 complex partial and 12 tonic-clonic seizures from 11 patients were analyzed. The postictal period was characterized by a surge in EDA and heightened heart rate coinciding with persistent suppression of HF power. An increase in the EDA response amplitude correlated with an increase in the duration of EEG suppression ( r = 0.81, p = 0.003). Decreased HF power correlated with an increase in the duration of EEG suppression ( r = −0.87, p = 0.002). Conclusion: The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures. These results provide autonomic correlates of postictal EEG suppression and highlight a critical window of postictal autonomic dysregulation that may be relevant in the pathogenesis of SUDEP.

We report an unusual case of a 43-year old female patient suffering from multiple sclerosis, who was treated with mitoxantrone. Few weeks after treatment initiation a hyperpigmentation of the patient’s left thumb and index was noted. Following dose-reduction (from 12 to 10 mg/m2) and over the further course of mitoxantrone treatment the discoloration slightly faded. Although mitoxantrone is known to cause hyperpigmentation of various tissues this is the first report of melanonychia without hyperpigmentation of other tissue. Albeit speculative, pathogenesis of selective melanonychia by mitoxantrone could involve selective activation of nail matrix melanocytes or endocrine disturbances involving melanocyte stimulating hormone.