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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).

Objectives The purpose of our study was to investigate the association between repetitive head impact (RHI) exposure and postural control. Design Systematic review. Methods PubMed, Embase and PsycInfo were searched using a self-developed search term including the keywords balance OR postural control AND repetitive OR sub-concussive head impacts. Twenty-one studies excluding non-peer reviewed studies, secondary studies, cross-sectional studies, animal studies, and studies investigating concussion were included for further analyses. We rated Level of Evidence and quality using the Centre for Evidence-Based Medicine tool, the Quality Assessment for the Systematic Review of Effectiveness, and the Sub-concussion Specific Tool. Results All included studies were grouped into Category I and II studies. Category I included trials investigating the effects of controlled soccer heading on postural control (n = 8) and Category II studies were cohort studies investigating on-the-field changes between preseason and postseason assessments on postural control measures (n = 13). Findings were heterogeneous, with a tendency towards no effects of RHI on clinical postural control measures. Most laboratory studies in Category I used instrumented assessments whereas on-the-field studies in Category II used both instrumented and non-instrumented assessments. Conclusions Due to heterogeneous findings, future studies aiming to investigate the effects of RHI on different athlete populations are needed on other participant cohorts. Furthermore, the combination of objective clinical balance measures may be a promising approach to accurately measure how, and to what degree, postural control may be affected by RHI.

Zusammenfassung Einleitung Im Rahmen der Demenz vom Alzheimer-Typ (DAT) zeigt sich eine gestörte neuronale Netzwerkorganisation, welche sich unter anderem auch im Default Mode Netzwerk (DMN) widerspiegelt. Multimodale Interventionen, wie zum Beispiel Golf, können einen positiven Einfluss auf die funktionelle Integrität der Netzwerke haben. Methodik Im Rahmen einer Pilotstudie wurde der Einfluss des Erlernens der Sportart Golf bei sieben älteren Menschen (> 60 Jahre) mit subjektiven Gedächtnisbeschwerden auf die funktionelle Konnektivität des DMN untersucht. Die Probanden haben 22 Wochen unter Anleitung eines professionellen Golftrainers dreimal wöchentlich je 60 min trainiert. Vor (Messzeitpunkt 0, MZP0) und nach der Intervention (Messzeitpunkt 1, MZP1) wurde eine Elektroenzephalografie (EEG)-Messung unter Ruhebedingungen (resting-state) durchgeführt. Die EEG-Daten wurden mit einem Magnetresonanztomographie-Template koregistriert. Die Konnektivitätsanalyse wurde in 15 Regionen des DMN durchgeführt und im Längsschnitt verglichen. Dabei wurden die Frequenzbänder beta (14–29 Hz) und theta (5–7 Hz) berücksichtigt. Ergebnisse Nach der Intervention wurde eine höhere funktionelle Konnektivität im gesamten DMN bei 5 / 7 Teilnehmenden im beta Frequenzband bzw. bei 6 / 7 Probanden im theta Frequenzband zu MZP1 im Vergleich zu MZP0 gemessen. Im anterioren DMN war bei allen Probanden und Probandinnen die funktionelle Konnektivität im beta Frequenzband zu MZP1 im Vergleich zu MZP 0 höher, während sie im theta-Band bei 6 von 7 Teilnehmenden niedriger war. Im posterioren DMN war bei 6 von 7 (beta), bzw. 5 von 7 (theta) Probanden und Probandinnen die funktionelle Konnektivität zu MZP1 höher als zu MZP0. Spearman-Korrelationsanalysen zeigen zudem einen Zusammenhang zwischen der Teilnahmehäufigkeit und der prozentualen Veränderung der funktionellen Konnektivität im gesamten DMN des beta Frequenzbandes (r = 0,786, p = 0,036) und im anterioren DMN des theta Frequenzbandes (r = –0,821, p = 0,023). Fazit Auf Basis der vorliegenden Daten lässt sich vermuten, dass das Erlernen der Sportart Golf einen Einfluss auf das DMN haben könnte. Die Ergebnisse bilden die Grundlage für die Planung einer Studie mit einer größeren Kohorte und randomisierten kontrollierten Design.

In sport science, athlete tracking and motion analysis are essential for monitoring and optimizing training programs, with the goal of increasing success in competition and preventing injury. At present, contact-free, camera-based, multi-athlete detection and tracking have become a reality, mainly due to the advances in machine learning regarding computer vision and, specifically, advances in artificial convolutional neural networks (CNN), used for human pose estimation (HPE-CNN) in image sequences. Sport science in general, as well as coaches and athletes in particular, would greatly benefit from HPE-CNN-based tracking, but the sheer amount of HPE-CNNs available, as well as their complexity, pose a hurdle to the adoption of this new technology. It is unclear how many HPE-CNNs which are available at present are ready to use in out-of-the-box inference to squash, to what extent they allow motion analysis and if detections can easily be used to provide insight to coaches and athletes. Therefore, we conducted a systematic investigation of more than 250 HPE-CNNs. After applying our selection criteria of open-source, pre-trained, state-of-the-art and ready-to-use, five variants of three HPE-CNNs remained, and were evaluated in the context of motion analysis for the racket sport of squash. Specifically, we are interested in detecting player’s feet in videos from a single camera and investigated the detection accuracy of all HPE-CNNs. To that end, we created a ground-truth dataset from publicly available squash videos by developing our own annotation tool and manually labeling frames and events. We present heatmaps, which depict the court floor using a color scale and highlight areas according to the relative time for which a player occupied that location during matchplay. These are used to provide insight into detections. Finally, we created a decision flow chart to help sport scientists, coaches and athletes to decide which HPE-CNN is best for player detection and tracking in a given application scenario.

The present study aimed to investigate time trends of head injuries and their injury mechanisms since a rule change as monitoring may help to identify causes of head injuries and may advance head injury prevention efforts. Based on continuously recorded data from the German football magazine “kicker Sportmagazin®” as well as other media sources, a database of head injuries in the 1st German male Bundesliga was generated comprising 11 seasons (2006/07–2016/17). Injury mechanisms were analysed from video recordings. Injury incidence rates (IR) and 95% confidence intervals (95% CI) were calculated. Time trends were analysed via linear regression. Two hundred thirty-eight match head injuries occurred (IR 1.77/1000 match hours, 95% CI 1.56–2.01). There were no significant seasonal changes, expressed as annual average year-on-year change, in IRs over the 11-year period for total head injuries (p=0.693), facial/head fractures (p=0.455), lacerations/abrasions (p=0.162), and head contusions (p=0.106). The annual average year-on-year increase for concussion was 6.4% (p=0.004). Five head injury mechanisms were identified. There were no seasonal changes in injury mechanisms over the study period. The concussion subcategory increased slightly over the seasons, which may either be a result of increasing match dynamics or raised awareness among team physicians and players.

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.

SARS‐CoV‐2 infection has emerged as not only a pulmonary but also potentially multi‐organ disease, which may cause long‐term structural damage of different organ systems including the lung, heart, vasculature, brain, liver, kidney, or intestine. As a result, the current SARS‐CoV‐2/COVID‐19 pandemic will eventually yield substantially increased numbers of chronically diseased patients worldwide, particularly suffering from pulmonary fibrosis, post‐myocarditis, chronic heart failure, or chronic kidney disease. Exercise recommendations for rehabilitation are complex in these patients and should follow current guidelines including standards for pre‐exercise medical examinations and individually tailored exercise prescription. It is of utmost importance to start exercise training at an early stage after COVID‐19 infection, but at the same time paying attention to the physical barriers to ensure safe return to exercise. For exercise recommendations beyond rehabilitation programs particularly for leisure time and elite athletes, more precise advice is required including assessment of sports eligibility and specific return‐to‐sports exercise programs. Because of the current uncertainty of long‐term course of SARS‐CoV‐2 infection or COVID disease, long‐term follow‐up seems to be necessary., publishedVersion

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

A better understanding of the early detection of seizures is highly desirable as identification of an impending seizure may afford improved treatments, such as antiepileptic drug chronotherapy, or timely warning to patients. While epileptic seizures are known to often manifest also with autonomic nervous system (ANS) changes, it is not clear whether ANS markers, if recorded from a wearable device, are also informative about an impending seizure with statistically significant sensitivity and specificity. Using statistical testing with seizure surrogate data and a unique dataset of continuously recorded multi-day wristband data including electrodermal activity (EDA), temperature (TEMP) and heart rate (HR) from 66 people with epilepsy (9.9 ± 5.8 years; 27 females; 161 seizures) we investigated differences between inter- and preictal periods in terms of mean, variance, and entropy of these signals. We found that signal mean and variance do not differentiate between inter- and preictal periods in a statistically meaningful way. EDA signal entropy was found to be increased prior to seizures in a small subset of patients. Findings may provide novel insights into the pathophysiology of epileptic seizures with respect to ANS function, and, while further validation and investigation of potential causes of the observed changes are needed, indicate that epilepsy-related state changes may be detectable using peripheral wearable devices. Detection of such changes with wearable devices may be more feasible for everyday monitoring than utilizing an electroencephalogram.

Background For many years, people with epilepsy were advised not to engage in sports. In this systematic review, we investigated whether persons with epilepsy exercise less than the general population, and what effect physical activity has on epilepsy. Methods A literature search was carried out in PubMed and the Web of Science, and 14 269 studies were entered into the selection process. The selected studies were assessed for their methodological quality and accordingly assigned an evidence level. Results 42 studies were included in the review; 10 were classified as evidence level 3, 27 as evidence level 2-, 2 as evidence level 2+, and 3 as evidence level 1-. Persons with epilepsy are less physically active and less physically fit than the general population. Reduced physical activity is associ- ated with a higher frequency of comorbidities and lower quality of life. Physical interventions can improve quality of life. In most cases, physical exercise did not increase seizure frequency. Conclusion There is no reason to forbid persons with epilepsy to participate in sports; they should, rather, be encour- a particular type of sport should, however, be taken individually in each case.

Trail running places specific physiological demands on the human body due to its uphill and downhill running sections. We developed and investigated a more sport-specific trail exercise test protocol (inclination and speed incremental protocol), and compared it to two standard exercise test protocols (horizontal step and ramp protocol) in thirteen highly trained trail runners (age 31±6 years, height 179±6.4 cm, weight 69.2±7.9 kg, BMI 21.6±2.1 kg/m2). The maximum oxygen uptake (VO2max) measured during the trail test (62.5±5.9 ml·kg−1·min−1, [95% CI: 59.0-66.1]) was significantly higher compared to both the step test (60.1±5.3 ml·kg−1·min−1, [95% CI: 56.8-63.3], p=0.024) and the ramp test (59.7±5.5 ml·kg−1·min−1, [95% CI: 56.4-63.0], p=0.028). Time to task failure was significantly shorter in the trail test (557±73 s, [95% CI: 512-601]) compared to both the step test (1378±152 s, [95% CI: 1286-1470], p

Purpose: Running an ultramarathon can be considered as a multifaceted, intense stressor inducing changes within the autonomic nervous system (ANS). The aim of this study was to examine chan...

Physical exercise has been shown to modulate activity within the autonomic nervous system (ANS). Considering physical exercise as a holistic stimulus on the nervous system and specifically the ANS, uni- and multimodal analysis tools were applied to characterize centrally driven interactions and control of ANS functions. Nineteen young and physically active participants performed treadmill tests at individually determined moderate and high intensities. Continuous electrodermal activity (EDA), heart rate (HR), and skin temperature at wrist (Temp) were recorded by wireless multisensor devices (Empatica® E4, Milan, Italy) before and 30 min after exercise. Artifact-free continuous 3 min intervals were analyzed. For unimodal analysis, mean values were calculated, for bimodal and multimodal analysis canonical correlation analysis (CCA) was performed. Unimodal results indicate that physical exercise affects ANS activity. More specifically, Temp increased due to physical activity (moderate intensity: from 34.15°C to 35.34°C and high intensity: from 34.11°C to 35.09°C). HR increased more for the high (from 60.76 bpm to 79.89 bpm) than for the moderate (from 64.81 bpm to 70.83 bpm) intensity. EDA was higher for the high (pre: 8.06 μS and post: 9.37 μS) than for the moderate (pre: 4.31 μS and post: 3.91 μS) intensity. Bimodal analyses revealed high variations in correlations before exercise. The overall correlation coefficient showed varying correlations in pretest measures for all modality pairs (EDA-HR, HR-Temp, Temp-EDA at moderate: 0.831, 0.998, 0.921 and high: 0.706, 0, 0.578). After exercising at moderate intensity coefficients changed little (0.828, 0.744, 0.994), but increased substantially for all modality pairs after exercising at high intensity (0.976, 0.898, 0.926). Multimodal analysis confirmed bimodal results. Exercise-induced changes in ANS activity can be found in multiple ANS modalities as well as in their interactions. Those changes are intensity-specific: with higher intensity the interactions increase. Canonical correlations between different ANS modalities may therefore offer a feasible approach to determine exercise induced modulations of ANS activity.

Interictal spikes (IIS) are bursts of neuronal depolarization observed electrographically between periods of seizure activity in epilepsy patients. However, IISs are difficult to characterize morphologically and their effects on neurophysiology and cognitive function are poorly understood. Currently, IIS detection requires laborious manual assessment and marking of electroencephalography (EEG/iEEG) data. This practice is also subjective as the clinician has to select the mental threshold that EEG activity must exceed in order to be considered a spike. The work presented here details the development and implementation of a simple automated IIS detection algorithm. This preliminary study utilized intracranial EEG recordings collected from 7 epilepsy patients, and IISs were marked by a single physician for a total of 1339 IISs across 68 active electrodes. The proposed algorithm implements a simple threshold rule that scans through iEEG data and identifies IISs using various normalization techniques that eliminate the need for a more complex detector. The efficacy of the algorithm was determined by evaluating the sensitivity and specificity of the detector across a range of thresholds, and an approximate optimal threshold was determined using these results. With an average true positive rate of over 98% and a false positive rate of below 2%, the accuracy of this algorithm speaks to its use as a reliable diagnostic tool to detect IISs, which has direct applications in localizing where seizures start, detecting when seizures start, and in understanding cognitive impairment due to IISs. Furthermore, due to its speed and simplicity, this algorithm can be used for real-time detection of IIS that will ultimately allow physicians to study their clinical implications with high temporal resolution and individual adaptation.

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 To identify risk situations promoting head injuries in professional male football (soccer) and to investigate the impact of a rule change in 2006 punishing elbow-head contacts. Design Analysis of video sequences of head events leading to head injury. Participants Professional football players of the first male German Bundesliga. Main outcome measures Observational criteria of head impacts on video recordings (players' actions preceding head injuries, foul play-referee's decision and assessment of rater, ball possession, on-pitch medical treatment, and consequences of head impact). Results Three hundred thirty-four head injuries were reported in kicker Sportmagazin corresponding to an incidence rate of 2.25 (95% confidence interval 2.01-2.51) per 1000 player match hours. The injured player predominantly jumped (60%), headed the ball (36%), or ran forwards (20%); the noninjured players mainly jumped (64%), headed the ball (27%), or raised the elbow to the head (23%). Free ball situations (2 players challenge for the ball) caused most of the head injuries (81%). The players' action "raising the elbow" during a head injury seemed to be lower after the rule change. Conclusions Jumping for the ball with the intention of heading is the predominant action associated with head injury risk. Head injuries occur most often when players challenge for the ball in a header duel. As head injuries bear the potential risk of long-term health sequelae, the identification of situational circumstances is essential to develop preventative means in the future.

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.

Several sources of media seem to agree that football (soccer) impairs brain health due to repeated head collisions and headers. Unfortunately, some of our scientific colleagues contribute to this v...

BackgroundAbsolute numbers of head injuries in football (soccer) are considerable because of its high popularity and the large number of players. In 2006 a rule was changed to reduce head injuries. Players were given a red card (sent off) for intentional elbow-head contact.AimsTo describe the head injury mechanism and examine the effect of the rule change.MethodsBased on continuously recorded data from the German football magazine “kicker”, a database of all head injuries in the 1st German Male Bundesliga was generated comprising seasons 2000/01-2012/13. Injury mechanisms were analysed from video recordings. Injury incidence rates (IR) and 95% confidence intervals (95% CI) as well as incidence rate ratios (IRR) to assess differences before and after the rule change were calculated.Results356 head injuries were recorded (IR 2.22, 95% CI 2.00 to 2.46 per 1000 match hours). Contact with another player caused most head injuries, more specifically because of head-head (34%) or elbow-head (17%) contacts. After the rule change, head injuries were reduced by 29% (IRR 0.71, 95% CI 0.57 to 0.86, p=0.002). Lacerations/abrasions declined by 42% (95% CI 0.39 to 0.85), concussions by 29% (95% CI 0.46 to 1.09), contusions by 18% (95% CI 0.43 to 1.55) and facial fractures by 16% (95% CI 0.55 to 1.28).ConclusionsThis rule change appeared to reduce the risk of head injuries in men’s professional football.

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.

Aims Neurological outcome prognosis remains challenging in patients undergoing therapeutic hypothermia (TH) after cardiac resuscitation. Technological advances allow for a novel wrist-worn device to continuously record electrodermal activity (EDA), a measure of pure sympathetic activity. Methods A prospective cohort study was performed to determine the yield of continuous EDA in patients treated with TH for coma after cardiac arrest during hypothermia and normothermia. Association between EDA parameters (event-related and nonspecific electrodermal responses (ER-EDR, NS-EDR)) and outcome measures (cerebral performance category [CPC]) (Full Outline in UnResponsivenss (FOUR) score) were assessed. Results Eighteen patients were enrolled. Total number of EDR (66.4 vs 12.0/24h, p =0.02), ER-EDR (39.5 vs 11.2/24h, p =0.009), median amplitude change of all EDR (0.08 vs 0.03μSI, p =0.03) and ER-EDR (0.14 vs 0.05μSI, p =0.025) were higher in patients with favorable (CPC 1–2) versus poor outcome (CPC 3–5) during hypothermia. Greater differences in EDA parameters were observed during hypothermia than normothermia. The FOUR score was correlated to the number of all EDR and median amplitudes. Conclusions Continuous EDA potentially opens a new avenue for autonomic function monitoring in neurocritically ill patients. It is feasible in the ICU setting, even during hypothermic states. As a measure of a complete neurophysiological circuit, it may be a novel neurophysiologic biomarker of outcome after cardiac resuscitation.

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.

PURPOSE: To study differences in the whole-brain structural connectomes of patients with left temporal lobe epilepsy (TLE) and healthy control subjects.MATERIALS AND METHODS: This study was approved by the institutional review board, and all individuals gave signed informed consent. Sixty-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) magnetic resonance imaging volumes were analyzed in 24 patients with left TLE and in 24 healthy control subjects. MP-RAGE volumes were segmented into 1015 regions of interest (ROIs) spanning the entire brain. Deterministic white matter tractography was performed after voxelwise tensor calculation. Weighted structural connectivity matrices were generated by using the pairwise density of connecting fibers between ROIs. Graph theoretical measures of connectivity networks were compared between groups by using linear models with permutation testing.RESULTS: Patients with TLE had 22%-45% reduced (P < .01) distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with that in healthy subjects. However, local connectivity, as measured by means of network efficiency, was increased by 85%-270% (P < .01) in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE as compared with healthy subjects.CONCLUSION: This study suggests that TLE involves altered structural connectivity in a network that reaches beyond the temporal lobe, especially in the default mode network.

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.

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.