Spindle-locked ripples mediate memory reactivation during human NREM sleep.

Memory consolidation relies in part on the reactivation of previous experiences during sleep. The precise interplay of sleep-related oscillations (slow oscillations, spindles and ripples) is thought to coordinate the information flow between relevant brain areas, with ripples mediating memory reactivation. However, in humans empirical evidence for a role of ripples in memory reactivation is lacking. Here, we investigated the relevance of sleep oscillations and specifically ripples for memory reactivation during human sleep using targeted memory reactivation. Intracranial electrophysiology in epilepsy patients and scalp EEG in healthy participants revealed that elevated levels of slow oscillation - spindle activity coincided with the read-out of experimentally induced memory reactivation. Importantly, spindle-locked ripples recorded intracranially from the medial temporal lobe were found to be correlated with the identification of memory reactivation during non-rapid eye movement sleep. Our findings establish ripples as key-oscillation for sleep-related memory reactivation in humans and emphasize the importance of the coordinated interplay of the cardinal sleep oscillations.

Electrophysiological signatures of veridical head direction in humans.

Information about heading direction is critical for navigation as it provides the means to orient ourselves in space. However, given that veridical head-direction signals require physical rotation of the head and most human neuroimaging experiments depend upon fixing the head in position, little is known about how the human brain is tuned to such heading signals. Here we adress this by asking 52 healthy participants undergoing simultaneous electroencephalography and motion tracking recordings (split into two experiments) and 10 patients undergoing simultaneous intracranial electroencephalography and motion tracking recordings to complete a series of orientation tasks in which they made physical head rotations to target positions. We then used a series of forward encoding models and linear mixed-effects models to isolate electrophysiological activity that was specifically tuned to heading direction. We identified a robust posterior central signature that predicts changes in veridical head orientation after regressing out confounds including sensory input and muscular activity. Both source localization and intracranial analysis implicated the medial temporal lobe as the origin of this effect. Subsequent analyses disentangled head-direction signatures from signals relating to head rotation and those reflecting location-specific effects. Lastly, when directly comparing head direction and eye-gaze-related tuning, we found that the brain maintains both codes while actively navigating, with stronger tuning to head direction in the medial temporal lobe. Together, these results reveal a taxonomy of population-level head-direction signals within the human brain that is reminiscent of those reported in the single units of rodents.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy.

Objective: Heterozygous mutations within the voltage-gated sodium channel α subunit (SCN1A) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches. Methods: We investigated SCN1A mRNA expression and expression of two SCN1A related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against SCN1A specific antisense RNAs on SCN1A expression was tested. Results: The SCN1A related antisense RNAs SCN1A-dsAS (downstream antisense, RefSeq identifier: NR_110598) and SCN1A-usAS (upstream AS, SCN1A-AS, RefSeq identifier: NR_110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA SCN1A-usAS with SCN1A mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against SCN1A-dsAS was associated with a significant enhancement of SCN1A mRNA expression and reduction in SCN1A-dsAS transcripts. Conclusion: These findings support the role of SCN1A-dsAS in the suppression of SCN1A mRNA generation. Considering the haploinsufficiency in genetic SCN1A related DS, SCN1A-dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance SCN1A expression in DS.

Association between retinal thickness and disease characteristics in adult epilepsy: A cross-sectional OCT evaluation.

OBJECTIVE: Thinning of the peripapillary retinal nerve fiber layer (p-RNFL), as measured by optical coherence tomography (OCT), was recently introduced as a promising marker for cerebral neuronal loss in people with epilepsy (PwE). However, its clinical implication remains to be elucidated. We thus aimed to (1) systematically characterize the extent of the retinal neuroaxonal loss in a broad spectrum of unselected PwE and (2) to evaluate the main clinical determinants. METHODS: In this prospective study, a spectral-domain OCT evaluation was performed on 98 well-characterized PwE and 85 healthy controls (HCs) (18-55 years of age). All inner retinal layers and the total macula volume were assessed. Group comparisons and linear regression analyses with stepwise backward selection were performed to identify relevant clinical and demographic modulators of the retinal neuroaxonal integrity. RESULTS: PwE (age: 33.7 ± 10.6 years; 58.2% female) revealed a significant neuroaxonal loss across all assessed retinal layers (global pRNFL, P = 0.001, Δ = 4.24 µm; macular RNFL, P < 0.001, Δ = 0.05 mm3 ; ganglion cell inner plexiform layer, P < 0.001, Δ = 0.11 mm3 ; inner nuclear layer, INL, P = 0.03, Δ = 0.02 mm3 ) as well as significantly reduced total macula volumes (TMV, P < 0.001, Δ = 0.18 mm3 ) compared to HCs (age: 31.2 ± 9.0 years; 57.6% female). The extent of retinal neuroaxonal loss was associated with the occurrence and frequency of tonic-clonic seizures and the number of antiseizure medications, and was most pronounced in male patients. SIGNIFICANCE: PwE presented an extensive retinal neuroaxonal loss, affecting not only the peripapillary but also macular structures. The noninvasive and economic measurement via OCT bears the potential to establish as a practical tool to inform patient management, as the extent of the retinal neuroaxonal loss reflects aspects of disease severity and sex-specific vulnerability. PLAIN LANGUAGE SUMMARY: The retina is an extension of the brain and closely connected to it. Thus, cerebral alterations like atrophy reflect also on the retinal level. This is advantageous, as the retina is easily accessible and measureable with help of the optical coherence tomography. Here we report that adults with epilepsy have a significantly thinner retina than healthy persons. Especially people with many big seizures and a lot of medications have a thinner retina. We propose that measurement of the retina can be useful as a marker of disease severity and to inform patient management.

Quantitative analysis of the morphometric analysis program MAP in patients with truly MRI-negative focal epilepsy.

OBJECTIVE: In the presurgical evaluation of epilepsy, identifying the epileptogenic zone is challenging if magnetic resonance imaging (MRI) is negative. Several studies have shown the benefit of using a morphometric analysis program (MAP) on T1-weighted MRI scans to detect subtle lesions. MAP can guide a focused re-evaluation of MRI to ultimately identify structural lesions that were previously overlooked. Data on patients where this additional review after MAP analysis did not reveal any lesions is limited. Here we evaluate the diagnostic yield of MAP in a large group of truly MRI-negative patients. METHODS: We identified 68 patients with MRI-negative focal epilepsy and clear localization of the epileptogenic zone by intracranial EEG or postoperative seizure freedom. High resolution 3D T1 data of patients and 73 healthy controls were acquired on a 3 T scanner. Morphometric analysis was performed with MAP software, creating five z-score maps, reflecting different structural properties of the brain and a patient's deviation from the control population, and a neural network-based focal cortical dysplasia probability map. Ten brain regions were specified to quantify whether MAP findings were located in the correct region. Receiver operating characteristic (ROC) analyses were performed to identify the optimal thresholds for each map. RESULTS: MAP-guided visual re-evaluation of the original MRI revealed overlooked lesions in three patients. The remaining 65 truly MRI-negative patients were included in the statistical analysis. At the optimal thresholds, maximum sensitivity was 84 %, with 35 % specificity. Balanced accuracy (arithmetic mean of sensitivity and specificity) of the respective maps ranged from 51 % to 60 %, creating three to six times more false positive than true positive findings. CONCLUSION: This study confirms that MAP is useful in detecting previously overlooked subtle structural lesions. However, in truly MRI-negative patients, the additional diagnostic yield is very limited.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Seizure-free outcome and safety of repeated epilepsy surgery for persistent or recurrent seizures.

OBJECTIVE: Reoperation may be an option for select patients with unsatisfactory seizure control after their first epilepsy surgery. The aim of this study was to describe the seizure-free outcome and safety of repeated epilepsy surgery in our tertiary referral center. METHODS: Thirty-eight patients with focal refractory epilepsy, who underwent repeated epilepsy surgeries and had a minimum follow-up time of 12 months after reoperation, were included. Systematic reevaluation, including comprehensive neuroimaging and noninvasive (n = 38) and invasive (n = 25, 66%) video-electroencephalography monitoring, was performed. Multimodal 3D resection maps were created for individual patients to allow personalized reoperation. RESULTS: The median time between the first operation and reoperation was 74 months (range 5-324 months). The median age at reoperation was 34 years (range 1-74 years), and the median follow-up was 38 months (range 13-142 months). Repeat MRI after the first epilepsy surgery showed an epileptogenic lesion in 24 patients (63%). The reoperation was temporal in 18 patients (47%), extratemporal in 9 (24%), and multilobar in 11 (29%). The reoperation was left hemispheric in 24 patients (63%), close to eloquent cortex in 19 (50%), and distant from the initial resection in 8 (21%). Following reoperation, 27 patients (71%) became seizure free (Engel class I), while 11 (29%) continued to have seizures. There were trends toward better outcome in temporal lobe epilepsy and for unilobar resections adjacent to the initial surgery, but there was no difference between MRI lesional and nonlesional patients. In all subgroups, Engel class I outcome was at least 50%. Perioperative complications occurred in 4 patients (11%), with no fatalities. CONCLUSIONS: Reoperation for refractory focal epilepsy is an effective and safe option in patients with persistent or recurrent seizures after initial epilepsy surgery. A thorough presurgical reevaluation is essential for favorable outcome.

Novel 3D video action recognition deep learning approach for near real time epileptic seizure classification.

Seizure semiology is a well-established method to classify epileptic seizure types, but requires a significant amount of resources as long-term Video-EEG monitoring needs to be visually analyzed. Therefore, computer vision based diagnosis support tools are a promising approach. In this article, we utilize infrared (IR) and depth (3D) videos to show the feasibility of a 24/7 novel object and action recognition based deep learning (DL) monitoring system to differentiate between epileptic seizures in frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE) and non-epileptic events. Based on the largest 3Dvideo-EEG database in the world (115 seizures/+680,000 video-frames/427GB), we achieved a promising cross-subject validation f1-score of 0.833±0.061 for the 2 class (FLE vs. TLE) and 0.763 ± 0.083 for the 3 class (FLE vs. TLE vs. non-epileptic) case, from 2 s samples, with an automated semi-specialized depth (Acc.95.65%) and Mask R-CNN (Acc.96.52%) based cropping pipeline to pre-process the videos, enabling a near-real-time seizure type detection and classification tool. Our results demonstrate the feasibility of our novel DL approach to support 24/7 epilepsy monitoring, outperforming all previously published methods.

Teaching distinguishing semiological features improves diagnostic accuracy of seizure-like events by emergency physicians.

BACKGROUND: Misdiagnosis of seizure-like events (SLE) in emergency situations is common. Here, we evaluate whether a single, video-based lesson highlighting distinguishing semiological features can improve the diagnostic accuracy of emergency physicians for epileptic seizures (ES), psychogenic non-epileptic seizures (PNES) and syncopes (SY). METHODS: 40 emergency physicians (24 anesthetists, nine surgeons and seven internal medicine specialists by primary specialty) participated in a prospective trial on the diagnostic accuracy of SLE. They assessed video-displayed SLE at two time points: before and after a lecture on distinguishing semiological features. In the lecture, semiological features were demonstrated using patient videos, some were acted by the instructor in addition. The increase in correct diagnoses and recognition of distinguishing semiological features were analyzed. RESULTS: Before the lesson, 45% of 200 SLE-ratings were correct: 15% of SY (n = 40), 30% of PNES (n = 40), 59% of ES (n = 120, focal to bilateral tonic-clonic seizures (FBTCS) 87.5% (n = 40), focal impaired aware seizures (FIAS) 45% (n = 80)). Semiology teaching increased both the rate of correct diagnoses of SLE to overall 79% (p < 0.001) (ES 91% (p < 0.001), FBCTS 98% (n.s.), FIAS 88% (p < 0.001), PNES 88% (p < 0.001), SY 35% (p < 0.001)), and the number of recognized distinguishing semiological features. We identified several semiological features with high entity specific positive predictive values (> 0.8). CONCLUSIONS: A single 45-min video-based lesson highlighting distinguishing semiological features improves the diagnostic accuracy of ES, PNES and SY by emergency physicians. We expect that including this aspect into the curriculum of emergency physicians will lead to better individual patient treatment in pre-hospital medicine and more appropriate subsequent use of clinical resources.

The human thalamus orchestrates neocortical oscillations during NREM sleep.

A hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak -50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak -100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.

Kinesigenic dyskinesias after ENT surgery misdiagnosed as focal epilepsy.

We describe a man in his 30s who presented with paroxysmal right-sided dyskinesias of the arm and neck, misdiagnosed with drug-resistant focal epilepsy. Two months earlier he had undergone surgery for chronic sinusitis. Immediately after this procedure, he developed hemiparesis, hemiataxia, paresthesias and disturbances in verbal fluency. Cranial MRI revealed a disruption of the left lamina cribrosa and an intracerebral injury resembling a branch canal spanning to the left dorsal third of the thalamus. Single-photon emission tomography imaging demonstrated malperfusion of the left ventral thalamus, left-sided cortex and right cerebellar hemisphere. During continuous video-EEG monitoring, three dyskinetic episodes with tremor of the right arm and dystonia of the finger and shoulder could be recorded. The paroxysmal dyskinesias did not improve with carbamazepine, valproate and tiapride. This case demonstrates an unusual symptomatic cause of a thalamic movement disorder misdiagnosed as focal epilepsy and highlights the postoperative complications, diagnostic and treatment efforts.

Seizure prevalence in neurodegenerative diseases-a study of autopsy proven cases.

BACKGROUND AND PURPOSE: Knowledge about the seizure prevalence in the whole symptomatic course, from disease onset to death, in neurodegenerative diseases (ND) is lacking. Therefore, the aim was to investigate seizure prevalence and associated clinical implications in neuropathologically diagnosed ND. METHODS: Clinical records of cases from the Neurobiobank Munich, Germany, were analyzed. Neuropathological diagnoses of the assessed cases included Alzheimer disease (AD), corticobasal degeneration (CBD), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Seizure prevalence during the whole symptomatic disease phase was assessed and compared amongst ND. Associations between first clinical symptom and seizure prevalence and between seizures and disease duration were examined. RESULTS: In all, 454 patients with neuropathologically diagnosed ND and with available and meaningful clinical records were investigated (AD, n = 144; LBD, n = 103; PSP, n = 93; FTLD, n = 53; MSA, n = 36; CBD, n = 25). Seizure prevalence was 31.3% for AD, 20.0% for CBD, 12.6% for LBD, 11.3% for FTLD, 8.3% for MSA and 7.5% for PSP. Seizure prevalence was significantly higher in AD compared to FTLD (p = 0.005), LBD (p = 0.001), MSA (p = 0.005) and PSP (p < 0.001). No other significant differences regarding seizure prevalence were found between the studied ND. Cognitive first symptoms in ND were associated with an increased seizure prevalence (21.1% vs. 11.0% in patients without cognitive first symptoms) and motor first symptoms with a decreased seizure prevalence (10.3% vs. 20.5% in patients without motor first symptoms). Seizures were associated with a longer disease duration in MSA (12.3 vs. 7.0 years in patients without seizures; p = 0.017). CONCLUSIONS: Seizures are a clinically relevant comorbidity in ND, particularly in AD. Knowledge of the first clinical symptom in ND may allow for estimation of seizure risk.

Do all patients in the epilepsy monitoring unit experience the same level of comfort? A quantitative exploratory secondary analysis.

AIMS: To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit. DESIGN: Exploratory, quantitative study design. METHODS: Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses. RESULTS: Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students ≥18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels. CONCLUSION: When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students ≥18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely. IMPACT: Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.

Unilateral Blinking: Insights from Stereo-EEG and Tractography.

To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies.

OBJECTIVE: To evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies. METHODS: Cathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS. RESULTS: TDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: -30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events. CONCLUSIONS: The spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction. SIGNIFICANCE: Spaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.

A Systematic Review of Seizure-Freedom Rates in Patients With Benign Epilepsy of Childhood With Centrotemporal Spikes Receiving Antiepileptic Drugs.

OBJECTIVES: The objective of this study was to evaluate seizure remission rates in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) receiving antiepileptic drugs. METHODS: PubMed and Web of Science were searched for studies on pharmacotherapy in patients with BECTS using free search terms or Medical Subject Headings. Only studies that used seizure-freedom rates as an indicator for pharmaceutical efficacy were considered. Different antiepileptic drugs were compared using the Fisher exact test for seizure-freedom rates. RESULTS: A total of 19 studies were included, 6 of them being randomized controlled trials. The randomized controlled trials included a total of 308 patients and covered sulthiame (n = 52), topiramate (n = 45), levetiracetam (n = 43), oxcarbazepine (n = 31), carbamazepine (n = 68), and clobazam (n = 18) as well as placebo (n = 35) and untreated control groups (n = 16). Treatment success rates were significantly higher in those children treated with sulthiame, levetiracetam, and clobazam compared with the children treated with carbamazepine, oxcarbazepine, or topiramate. CONCLUSIONS: The available literature suggests the use of sulthiame, levetiracetam, or clobazam as first-line agents for the treatment of BECTS.

An integrative method to quantitatively detect nocturnal motor seizures.

In this proof-of-concept investigation, we demonstrate a marker-free video-based method to detect nocturnal motor seizures across a spectrum of motor seizure types, in a nighttime setting with a single adult female with refractory epilepsy. In doing so, we further explore the intermediate biosignals, visually mapping seizure "fingerprints" to seizure types. The method is designed to be flexible enough to generalize to unseen data, and shows promising performance characteristics for low-cost seizure detection and classification. The dataset contained recordings from 27 recorded nights. Seizure events were observed in 22 of these nights, with 36 unequivocally confirmed seizures. Each seizure was classified by an expert epileptologist according to both the ILAE 2017 standard and the Lüders semiological classification guidelines, yielding 5 of the ILAE-recognized seizure types and 7 distinct seizure semiologies. Evaluation was based on inference of motion, oscillation, and sound signals extracted from the recordings. The model architecture consisted of two feature extraction and event determination layers and one thresholding layer, establishing a simple framework for multimodal seizure analysis. Training of the optimal parameters was done by randomly resampling the event hits for each signal, and choosing a threshold that kept an expected 90 % sensitivity for the sample distribution. With the cut-off values selected, statistical performance was calculated for two target seizure groups: those containing a clonic component, and those containing a tonic component. When tuned to 90 % sensitivity, the system achieved a very low false discovery rate of 0.038/hour when targeting seizures with a clonic component, and a clinically-relevant rate of 1.02/hour when targeting seizures with a tonic component. These results indicate a sensitive method for detecting various nocturnal motor seizure types, and a high potential to differentiate motor seizures based on their video and audio signal characteristics. Paired with the low cost of this technique, both cost savings and improved quality of care might be achieved through further development and commercialization of this method.

Hemispheric differences in the duration of focal onset seizures.

OBJECTIVE: To assess hemispheric differences in the duration of focal onset seizures and its association with clinical and demographic factors. METHODS: A retrospective analysis was performed on adult patients with drug-resistant unifocal epilepsy, who underwent intracranial EEG recording between 01/2006 and 06/2016. Seizure duration was determined based on the subdural and/or stereo-EEG (sEEG) recordings. Hemispheric differences in seizure duration were statistically evaluated with regard to clinical and demographic data. RESULTS: In total, 69 patients and 654 focal onset seizures were included. The duration of seizures with left-hemispheric onset (n = 297) was by trend longer (91.88 ± 93.92 s) than of right-hemispheric seizures (n = 357; 71.03 ± 68.53 s; p = .193). Significant hemispheric differences in seizures duration were found in temporal lobe seizures (n = 225; p = .013), especially those with automotor manifestation (n = 156; p = .045). A prolonged duration was also found for left-hemispheric onset seizures with secondary generalized commencing during waking state (n = 225; p = .034), but not during sleep. A similar hemispheric difference in seizure duration was found in female patients (p = .040), but not in men. CONCLUSIONS: Hemispheric differences in seizure duration were revealed with significantly longer durations in case of left-hemispheric seizure onset. The observed differences in seizure duration might result from brain asymmetry and add new aspects to the understanding of seizure propagation and termination.