Detection of focal to bilateral tonic-clonic seizures using a connected shirt.

OBJECTIVE: This study was undertaken to develop and evaluate a machine learning-based algorithm for the detection of focal to bilateral tonic-clonic seizures (FBTCS) using a novel multimodal connected shirt. METHODS: We prospectively recruited patients with epilepsy admitted to our epilepsy monitoring unit and asked them to wear the connected shirt while under simultaneous video-electroencephalographic monitoring. Electrocardiographic (ECG) and accelerometric (ACC) signals recorded with the connected shirt were used for the development of the seizure detection algorithm. First, we used a sliding window to extract linear and nonlinear features from both ECG and ACC signals. Then, we trained an extreme gradient boosting algorithm (XGBoost) to detect FBTCS according to seizure onset and offset annotated by three board-certified epileptologists. Finally, we applied a postprocessing step to regularize the classification output. A patientwise nested cross-validation was implemented to evaluate the performances in terms of sensitivity, false alarm rate (FAR), time in false warning (TiW), detection latency, and receiver operating characteristic area under the curve (ROC-AUC). RESULTS: We recorded 66 FBTCS from 42 patients who wore the connected shirt for a total of 8067 continuous hours. The XGBoost algorithm reached a sensitivity of 84.8% (56/66 seizures), with a median FAR of .55/24 h and a median TiW of 10 s/alarm. ROC-AUC was .90 (95% confidence interval = .88-.91). Median detection latency from the time of progression to the bilateral tonic-clonic phase was 25.5 s. SIGNIFICANCE: The novel connected shirt allowed accurate detection of FBTCS with a low false alarm rate in a hospital setting. Prospective studies in a residential setting with a real-time and online seizure detection algorithm are required to validate the performance and usability of this device.

Sudden unexpected death in epilepsy (SUDEP): A bibliometric analysis.

OBJECTIVE: The literature on sudden unexpected death in epilepsy (SUDEP) has been evolving at a staggering rate. We conducted a bibliometric analysis of the SUDEP literature with the aim of presenting its structure, performance, and trends. METHODS: The Scopus database was searched in April 2023 for documents explicitly detailing SUDEP in their title, abstract, or keywords. After the removal of duplicate documents, bibliometric analysis was performed using the R package bibliometrix and the program VOSviewer. Performance metrics were computed to describe the literature's annual productivity, most relevant authors and countries, and most important publications. Science mapping was performed to visualize the relationships between research constituents by constructing a country collaboration network, co-authorship network, keyword co-occurrence network, and document co-citation network. RESULTS: A total of 2140 documents were analyzed. These documents were published from 1989 onward, with an average number of citations per document of 25.78. Annual productivity had been on the rise since 2006. Out of 6502 authors, five authors were in both the list of the ten most productive and the list of the ten most cited authors: Devinsky O, Sander JW, Tomson T, Ryvlin P, and Lhatoo SD. The USA and the United Kingdom were the most productive and cited countries. Collaborations between American authors and European authors were particularly rich. Prominent themes in the literature included those related to pathophysiology (e.g., cardiac arrhythmia, apnea, autonomic dysfunction), epilepsy characteristics (e.g., epilepsy type, refractoriness, antiseizure medications), and epidemiology (e.g., incidence, age, sex). Emerging themes included sleep, genetics, epilepsy refractoriness, and non-human studies. SIGNIFICANCE: The body of literature on SUDEP is rich, fast-growing, and benefiting from frequent international collaborations. Some research themes such as sleep, genetics, and animal studies have become more prevalent over recent years.

Unexpected cardiorespiratory findings postictally and at rest weeks prior to SUDEP.

Introduction: Mechanisms underlying sudden unexpected death in epilepsy (SUDEP) are unclear, but autonomic disorders are thought to play a critical role. However, those dysfunctions have mainly been reported in the peri-ictal context of generalized tonic-clonic seizures. Here, we explored whether heart rate variability (HRV), heart rate (HR), and breathing rate (BR) changes could be observed perictally during focal seizures with or without impaired awareness as well as interictally to assess the risk of SUDEP. We report the case of a 33-year-old patient with drug-resistant bilateral temporal lobe epilepsy who died at home probably from an unwitnessed nocturnal seizure ("probable SUDEP"). Methods: Ictal and interictal HRV as well as postictal cardiorespiratory analyses were conducted to assess autonomic functions and overall SUDEP risk. The SUDEP patient was compared to two living male patients from our local database matched for age, sex, and location of the epileptic focus. Results: Interictal HRV analysis showed that all sleep HRV parameters and most awake HRV parameters of the SUDEP patient were significantly lower than those of our two control subjects with bitemporal lobe epilepsy without SUDEP (p < 0.01). In two focal with impaired awareness seizures (FIAS) of the SUDEP patient, increased postictal mean HR and reduced preictal mean high frequency signals (HF), known markers of increased seizure severity in convulsive seizures, were seen postictally. Furthermore, important autonomic instability and hypersensitivity were seen through fluctuations in LF/HF ratio following two seizures of the SUDEP patient, with a rapid transition between sympathetic and parasympathetic activity. In addition, a combination of severe hypopnea (202 s) and bradycardia (10 s), illustrating autonomic dysfunction, was found after one of the SUDEP patient's FIAS. Discussion: The unusual cardiorespiratory and HRV patterns found in this case indicated autonomic abnormalities that were possibly predictive of an increased risk of SUDEP. It will be interesting to perform similar analyses in other SUDEP cases to see whether our findings are anecdotal or instead suggestive of reliable biomarkers of high SUDEP risk in focal epilepsy, in particular focal with or without impaired awareness seizures.

Novel NALCN variant linked to temporal lobe epilepsy.

The sodium leak channel (NALCN) gene encodes a sodium leak channel that plays an important role in the regulation of the resting membrane potential and the control of neuronal excitability. Mutations in the NALCN gene have been reported in patients with infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of the limbs and face with hypotonia and developmental delay (CLIFAHDD syndrome). We describe the case of a father with drug-resistant left temporo-orbitofrontal epilepsy and his son with mildly-symptomatic temporal epilepsy (only recurrent déjà vu auras) whose genetic panels identified a likely pathogenic deletion of exon 27 on the NALCN gene. Our study helps broaden the clinical spectrum of diseases associated with mutations in the NALCN gene.

Use of non-medical cannabis in epilepsy: A scoping review.

Objective: The use of medical cannabis among people with epilepsy (PWE) has been garnering increasing interest. In this scoping review, we aimed to summarize the literature on recreational/non-medical cannabis (NMC) use in PWE, focusing on the experience, habits, and beliefs of PWE regarding NMC. Methods: Four databases (OVID Medline, OVID Embase, Ovid APA PsycInfo, and Web of Science) were searched for studies describing NMC use in PWE. NMC was defined as cannabis products procured from sources other than by prescription. Studies that consisted in original research and that detailed the experience, habits, and/or beliefs of PWE regarding NMC use were included in the analysis. Data pertaining to study identification, demographics, NMC use, and epilepsy characteristics were extracted. Descriptive statistical analyses and reflexive thematic analyses were performed to map these data. Results: In total, 3,228 records were screened, and 66 were included for analysis: 45 had mainly adult samples, whereas 21 had mainly pediatric samples. Most studies were published after 2010, originated from the USA, and were cross-sectional. The median number of PWE using cannabis in these studies was 24.5 (1-37,945). No studies showcased elderly PWE, and most had predominantly Caucasian samples. The lifetime prevalence of NMC use in PWE was variable, ranging between 0.69 and 76.8%. Factors frequently associated with NMC use in PWE were male sex, younger adult age, and lower education status. Children with epilepsy took NMC primarily for seizure control, using high CBD/THC ratios, and only orally. Adults with epilepsy took NMC for various reasons including recreationally, using variable CBD/THC ratios, and predominantly through smoking. The majority of PWE across all studies perceived that NMC aided in seizure control. Other aspects pertaining to NMC use in PWE were rarely reported and often conflicting. Conclusion: The literature on NMC use in PWE is sparse and heterogeneous, with many salient knowledge gaps. Further research is necessary to better understanding the experience, habits, and beliefs of PWE pertaining to NMC.

Epilepsy and cerebral developmental venous anomalies (DVAs): A systematic review.

OBJECTIVE: Cerebral developmental venous anomalies (DVAs) are frequent and rarely symptomatic. When symptomatic, DVAs may present with seizures; however, little is known about the characteristics of DVA-related epilepsy. In this systematic review, we aim to describe the clinical and paraclinical features of patients with DVA-related epilepsy. METHODS: This review was registered on PROSPERO (CRD42021218711). We searched the MEDLINE/PubMed and Scopus databases for case reports/series on patients with DVAs complicated by seizures. Studies describing patients with a potentially epileptogenic comorbid lesion close to their seizure focus were excluded. Descriptive statistical analyses were performed to synthetize patient characteristics. The methodological quality of each study was evaluated using a standardized appraisal tool. RESULTS: In total, 66 patients were included from 39 articles. The frontal lobe was the most common location for DVAs. The superior sagittal sinus drained half of the DVAs. Seizures were inaugural in most cases, and the most common manifestations accompanying seizures were headaches. EEG was abnormal in 93% of cases, but only 26% had characteristic epileptic spikes. More than half the patients suffered a medical complication due to their DVA, with hemorrhage and thrombosis being the most common. Refractory seizures were encountered in 19% of individuals. At 12 months of follow-up, 75% of patients were seizure free. Most included studies were at low risk of bias. SIGNIFICANCE: Epilepsy can be a complication of DVAs; these DVAs are mostly frontal or parietal, draining via the superior sagittal sinus or the vein of Galen.

Usage of Genetic Panels in an Adult Epilepsy Clinic.

BACKGROUND: There is limited data on the utility, yield, and cost efficiency of genetic testing in adults with epilepsy. We aimed to describe the yield and utility of genetic panels in our adult epilepsy clinic. METHODS: We performed a retrospective, cross-sectional study of all patients followed by an epileptologist at a Canadian tertiary care centre's epilepsy clinic between January 2016 and August 2021 for whom a genetic panel was ordered. A panel was generally ordered when the etiology was unknown or in the presence of a malformation of cortical development. We determined the yield of panel positivity and of confirmed genetic diagnoses. We also estimated the proportion of these diagnoses that were clinically actionable. RESULTS: In total, 164 panels were ordered in 164 patients. Most had refractory epilepsy (80%), and few had comorbid intellectual disability (10%) or a positive family history of epilepsy (11%). The yield of panel positivity was 11%. Panel results were uncertain 49% of the time and negative 40% of the time. Genetic diagnoses were confirmed in 7 (4.3%) patients. These genetic conditions involved the following genes: SCARB2, DEPDC5, PCDH19, LGI1, SCN1A, MT-TL1, and CHRNA7. Of the seven genetic diagnoses, 5 (71%) were evaluated to be clinically actionable. CONCLUSION: We report a lower diagnostic yield for genetic panels in adults with epilepsy than what has so far been reported. Although the field of the genetics of epilepsy is a fast-moving one and more data is required, our findings suggest that guidelines for genetic testing in adults are warranted.

Déjà-vu evoked by electrical stimulation of the insula.

OBJECTIVE: Déjà-vu is a mental phenomenon commonly experienced during temporal lobe seizures and can be evoked by electrical stimulation of the temporal lobe. We analyzed reproducible déjà-vu experiences evoked by stimulating the insula in two patients with pharmacoresistant temporal lobe epilepsy. METHODS: We reviewed video-electroencephalography (EEG) recordings from extraoperative electrical cortical stimulation sessions. In addition, we performed the directed transfer function (DTF) effective connectivity measure of monopolar signals in Patient 1. To highlight elective changes due to each stimulation, we subtracted pre-stimulation DTF matrices from early poststimulation matrices. This analysis was performed for both non-inducing-déjàvu stimulation (control matrix) and déjà-vu-inducing stimulation (active matrix). Finally, the control matrix was subtracted from the active matrix. RESULTS: Comparison of effective connectivity during control stimulation versus déjà-vu-inducing stimulation revealed a reversal of connectivity levels in three main regions: the contralateral inferior insula (the ipsilateral insula could not be analyzed), bilateral mesiotemporal regions and the ipsilateral superior frontal gyrus. The drivers of evoked déjà-vu were the mesiotemporal regions (mainly ipsilateral) and the ipsilateral superior frontal gyrus. SIGNIFICANCE: Although our findings are possibly anecdotal, the insula may (in rare instances) remotely generate unexpected déjà-vu. If confirmed by further studies, this might change the assessment strategy for possible causes of anterior temporal lobectomy failure.

Prevalence of Bipolar Symptoms or Disorder in Epilepsy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: This systematic review with meta-analysis (PROSPERO: CRD42021249336) was performed to estimate the pooled lifetime prevalence of bipolar symptoms (BS) and bipolar disorder (BD) in people with epilepsy (PWE). METHODS: A search was performed on June 5, 2021, in 4 databases (MEDLINE/PubMed, Ovid EMBASE, Ovid APA PsycInfo, and Web of Science) for original research reporting on BS/BD in PWE, with no restriction on language or time of publication. Inclusion criteria were as follows: (1) original research, (2) cross-sectional study design component, (3) reported lifetime prevalence of BS/BD or enough information to calculate an estimate, and (4) reported the method by which participants were deemed bipolar. Studies based on an exclusively pediatric population were excluded. To calculate pooled lifetime prevalence of BS/BD, 2 meta-analytic random-effects models were fitted, one for BS and the other for BD. Risk of bias was assessed using a standardized appraisal tool for studies reporting prevalence. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: A total of 750 records were screened and 17 studies were included for analysis: 7 provided prevalence estimates for only BS, 8 for only BD, and 2 for both BS and BD. After outlier exclusion and subgroup analysis using screening method as a moderator, the pooled prevalence of BS in PWE was 12.3% (95% CI 10.6%-14.1%) (7,506 PWE). The pooled prevalence of BD in PWE was 4.5% (95% CI 2.2%-7.4%) (48,334 PWE). Considerable heterogeneity was present, more so for BD than for BS, and could be explained through differences in population demographics and study methodology. DISCUSSION: This study's main limitation was regarding the certainty of evidence. However, our estimates of prevalence should prompt further research on BS/BD in PWE. Given the significant morbidity associated with BD, clinicians should carefully screen PWE for BS.

Insular Involvement in Cases of Epilepsy Surgery Failure.

BACKGROUND: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. METHODS: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004-2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. RESULTS: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). CONCLUSIONS: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes.

Déjà-vu evoked by electrical stimulation of the insula: Stimulation-induced insular déjà-vu.

OBJECTIVE: Déjà-vu is a mental phenomenon commonly experienced during temporal lobe seizures and can be evoked by electrical stimulation of the temporal lobe. We analyzed reproducible déjà-vu experiences evoked by stimulating the insula in two patients with pharmacoresistant temporal lobe epilepsy. METHODS: We reviewed video-electroencephalography (EEG) recordings from extraoperative electrical cortical stimulation sessions. In addition, we performed the directed transfer function (DTF) effective connectivity measure of monopolar signals in Patient 1. To highlight elective changes due to each stimulation, we subtracted pre-stimulation DTF matrices from early poststimulation matrices. This analysis was performed for both non-inducing-déjàvu stimulation (control matrix) and déjà-vu-inducing stimulation (active matrix). Finally, the control matrix was subtracted from the active matrix. RESULTS: Comparison of effective connectivity during control stimulation versus déjà-vu-inducing stimulation revealed a reversal of connectivity levels in three main regions: the contralateral inferior insula (the ipsilateral insula could not be analyzed), bilateral mesiotemporal regions and the ipsilateral superior frontal gyrus. The drivers of evoked déjà-vu were the mesiotemporal regions (mainly ipsilateral) and the ipsilateral superior frontal gyrus. SIGNIFICANCE: Although our findings are possibly anecdotal, the insula may (in rare instances) remotely generate unexpected déjà-vu. If confirmed by further studies, this might change the assessment strategy for possible causes of anterior temporal lobectomy failure.

Epilepsy and Pregnancy: An Audit of Specialized Care.

BACKGROUND: Caring for women with epilepsy (WWE) during pregnancy poses unique challenges. We conducted an audit of the care our epilepsy clinic provided to pregnant WWE. METHODS: We performed a retrospective study on all pregnancies followed by an epileptologist at a Canadian tertiary care centre's epilepsy clinic between January 2003 and March 2021. Among 81 pregnancies in 53 patients, 72 pregnancies in 50 patients were analyzed to determine patient-related, follow-up-related, antiseizure-medication-related, and child-related pregnancy characteristics. Univariate analyses were performed to explore if these characteristics were associated with disabling seizure occurrence during pregnancy. RESULTS: Most pregnancies were intended (72%) and occurred in women who used folic acid pre-pregnancy (76%) and who followed recommended blood tests for antiseizure medication (ASM) levels (71%). In 49% of pregnancies, ASM dosage was modified; 53% of these modifications were made in response to ASM blood levels. Most often used ASMs were lamotrigine (43%), followed by carbamazepine (32%) and levetiracetam (13%). One child was born with a thyroglossal duct cyst; our congenital malformation rate was thus 2%. Disabling seizures occurred in 24% of pregnancies. Exploratory analyses suggested that disabling seizure occurrence during pregnancy was associated with younger patient age (p = 0.018), higher number of ASMs used during pregnancy (p = 0.048), lamotrigine usage in polytherapy (p = 0.008), and disabling seizure occurrence pre-pregnancy (p = 0.027). CONCLUSION: This Canadian audit provides an in-depth description of pregnancies benefiting from specialized epilepsy care. Our results suggest an association between disabling seizure occurrence during pregnancy and lamotrigine usage in polytherapy that warrants further evaluation.

Intracranial EEG seizure onset and termination patterns and their association.

OBJECTIVE: The study of seizure onset and termination patterns has the potential to enhance our understanding of the underlying mechanisms of seizure generation and cessation. It is largely unclear whether seizures with distinct onset patterns originate from varying network interactions and terminate through different termination pathways. METHODS: We investigated the morphology and location of 103 intracranial EEG seizure onset and termination patterns from 20 patients with drug-resistant focal epilepsy. We determined if seizure onset patterns were associated with specific termination patterns. Finally, we looked at network interactions prior to the generation of distinct seizure onset patterns by calculating directed functional connectivity matrices. RESULTS: We identified nine seizure onset and six seizure termination patterns. The most common onset pattern was Low-Voltage Fast Activity (36 %), and the most frequent termination pattern was Burst Suppression (44 %). All seizures with fast (>13 Hz) termination patterns had a fast (>13 Hz) onset pattern type. Almost any onset pattern could terminate with the Burst Suppression and rhythmic Spike/PolySpike and Wave (rSW/rPSW) termination patterns. Seizures with a fast activity onset had higher inflow to the seizure onset zone from other regions in the gamma and high gamma frequency ranges prior to their generation compared to seizures with a slow onset. SIGNIFICANCE: Our observations suggest that different mechanisms underlie the generation of different seizure onset patterns although seizure onset patterns can share a common termination pattern. Possible mechanisms underlying these patterns are discussed.

Intervention Time and Adverse Events in a Canadian Epilepsy Monitoring Unit.

BACKGROUND: Intervention time (IT) in response to seizures and adverse events (AEs) have emerged as key elements in epilepsy monitoring unit (EMU) management. We performed an audit of our EMU, focusing on IT and AEs. METHODS: We performed a retrospective study on all clinical seizures of admissions over a 1-year period at our Canadian academic tertiary care center's EMU. This EMU was divided in two subunits: a daytime three-bed epilepsy department subunit (EDU) supervised by EEG technicians and a three-bed neurology ward subunit (NWU) equipped with video-EEG where patients were transferred to for nights and weekends, under nursing supervision. Among 124 admissions, 58 were analyzed. A total of 1293 seizures were reviewed to determine intervention occurrence, IT, and AE occurrence. Seizures occurring when the staff was present at bedside at seizure onset were analyzed separately. RESULTS: Median IT was 21.0 (11.0-40.8) s. The EDU, bilateral tonic-clonic seizures (BTCS), and the presence of a warning signal were associated with increased odds of an intervention taking place. The NWU, BTCS, and seizure rank (seizures were chronologically ordered by the patient for each subunit) were associated with longer ITs. Bedside staff presence rate was higher in the EDU than in the NWU (p < 0.001). AEs occurred in 19% of admissions, with no difference between subunits. AEs were more frequent in BTCS than in other seizure types (p = 0.001). CONCLUSION: This study suggests that close monitoring by trained staff members dedicated to EMU patients is key to optimize safety. AE rate was high, warranting corrective measures.

Are Sub-Saharan epileptic people less photosensitive? A Senegalese study of photoparoxysmal response in a reference epilepsy centre.

The photoparoxysmal response (PPR) is defined as the occurrence of generalized spike, spike-wave or polyspike-wave discharges consistently elicited by intermittent photic stimulation (IPS). PPR is not well studied in Sub-Saharan African people. We prospectively studied the epidemiological, clinical, and EEG characteristics of PPR among consecutive patients recorded at the clinical neurophysiology unit of Fann University Hospital (Dakar, Senegal). Among 6,808 EEG recordings including 3,065 pathological EEGs, we collected 56 EEGs with PPR (0.8% of all recorded EEGs and 1.8% of anormal EEGs), from 31 women and 25 men (sex ratio: 0.8). The mean age was 13.3 years (range: 8 months to 59 years). The peak of photosensitivity was found in the range of 6 to 10 years. Of the PPR cases, 12 had clinical manifestations during IPS. Generalized epilepsy was diagnosed in 23 (41%) patients and 18 (32%) had focal epilepsies. The most epileptogenic stimulation frequencies were between 12 and 24 Hz (range: 1-28 Hz). PPR were mainly triggered during eye closure (64%), and 41 patients (73% of PPR cases) were classified as Type 4 (Waltz classification). Our results confirm lower rates of photosensitivity in African Sub-Saharan people compared with others. Although the current data do not support a role of short-term ambient light levels, subject to consistent data from larger cohorts, it may be interesting to study the probable epigenetic-mediated protective role of sunshine against photosensitivity.

Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: A critical review.

Three decades after its introduction as an adjuvant therapeutic option in the management of selective drug-resistant epilepsy cases (DRE), vagus nerve stimulation (VNS) retains growing interest. An implantable device was first approved for epilepsy in Europe in 1994 and in the United States (US) in 1997. Subsequent modifications improved the safety and the efficacy of the system. The most recent application of vagal neurostimulation is represented by transcutaneous devices that are claimed to have strong therapeutic potential. In this review, we sought to analyze the most meaningful available data describing the indications, safety and efficacy of the different approaches of VNS in clinical practice. Therefore, we identified studies reporting VNS efficacy and/or safety in epilepsy and its comorbidities from January 1990 to February 2020 from various databases including PubMed, Scopus, Cochrane, US government databases and VNS manufacturer published resources. In general, VNS efficacy becomes optimal around the sixth month of treatment and a 50-100 % seizure frequency reduction is achieved in approximately 45-65 % of the patients. However, some clinically relevant differences have been reported with specific factors such as epilepsy etiology or type, patient age as well as the delay of VNS therapy onset. VNS efficacy on seizure frequency has been demonstrated in both children and adults, in lesional and non-lesional cases, in focal and generalized epilepsies, on both seizures and epilepsy comorbidities. Regarding the latter, VNS can lead to an improvement of about 25-35 % in depression scores, 35 % in anxiety scores and 25 % in mood assessment scores. If non-invasive devices are undeniably safer, their efficacy is limited due to the scarcity of large cohort studies and the disparity of methodological approaches (study design and stimulation parameters). Overall, we believe that there is a progress margin for improving the safety of implantable devices and, above all, the effectiveness of the various VNS approaches.

Identification of global and local states during seizures using quantitative functional connectivity and recurrence plot analysis.

INTRODUCTION: As a dynamical system, the brain constantly modulates its state and epileptic seizures have been hypothesized to be low dimensional periodic states of the brain. With this assumption, seizures have previously been investigated to identify patterns of these recurrent states; however, these attempts have generated conflicting results. These discrepant observations led us to reconsider the dynamic of state transitions during seizures. METHODS: Using intracerebral recordings of 17 refractory epilepsy patients assessed prior to surgery, we studied ictal states with several state-of-the-art methods in order to investigate their dynamics. Global states were identified based on distinct functional connectivity measures in the time domain, frequency domain, and phase-space. We further investigated the state transitions in different brain regions locally using a univariate measure based on dynamical system analysis named the Recurrence Plot (RP). RESULTS: For the ictal period, we detected lower global state transition rates compared to pre- and post-ictal periods (p < 0.05 for seizure-free (SF) and p > 0.05 for non-seizure-free (NSF) groups post-surgery); however, the structure of RPs pointed towards higher state transition rates in some regions like the seizure-onset-zone (p < 0.001 for SF and p > 0.05 for NSF group). Moreover, a direct comparison of state transition dynamics between SF and NSF patients revealed different patterns for local state transitions between SF and NSF patients (p < 0.05 for seizure-onset-zone while p > 0.05 for other regions) and no significant difference in global state transition rates (p > 0.05). CONCLUSION: Our findings pointed to distinct dynamics for state transitions at different spatial scales. While the pattern of global state transitions led to the conclusion that the brain changes state less frequently during ictal activity, locally, it experienced a higher rate of state transition. Furthermore, our results for different patterns of state transitions in the seizure-onset-zone between SF and NSF patients could have a practical application in predicting surgical outcome.

Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.

PURPOSE: Our purpose was to determine the role of CHRNA4 and CHRNB2 in insular epilepsy. METHOD: We identified two patients with drug-resistant predominantly sleep-related hypermotor seizures, one harboring a heterozygous missense variant (c.77C>T; p. Thr26Met) in the CHRNB2 gene and the other a heterozygous missense variant (c.1079G>A; p. Arg360Gln) in the CHRNA4 gene. The patients underwent electrophysiological and neuroimaging studies, and we performed functional characterization of the p. Thr26Met (c.77C>T) in the CHRNB2 gene. RESULTS: We localized the epileptic foci to the left insula in the first case (now seizure-free following epilepsy surgery) and to both insulae in the second case. Based on tools predicting the possible impact of amino acid substitutions on the structure and function of proteins (sorting intolerant from tolerant and PolyPhen-2), variants identified in this report could be deleterious. Functional expression in human cell lines of α4ß2 (wild-type), α4ß2-Thr26Met (homozygote), and α4ß2/ß2-Thr26Met (heterozygote) nicotinic acetylcholine receptors revealed that the mutant subunit led to significantly higher whole-cell nicotinic currents. This feature was observed in both homo- and heterozygous conditions and was not accompanied by major alterations of the current reversal potential or the shape of the concentration-response relation. CONCLUSIONS: This study suggests that variants in CHRNB2 and CHRNA4, initially linked to autosomal dominant nocturnal frontal lobe epilepsy, are also found in patients with predominantly sleep-related insular epilepsy. Although the reported variants should be considered of unknown clinical significance for the moment, identification of additional similar cases and further functional studies could eventually strengthen this association.

Utility of magnetic source imaging in nonlesional focal epilepsy: a prospective study.

OBJECTIVE: For patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone may be more arduous than for other types of epilepsy and frequently requires information from multiple noninvasive presurgical modalities and intracranial EEG (icEEG). In this prospective, blinded study, the authors assessed the clinical added value of magnetic source imaging (MSI) in the presurgical evaluation of patients with NLRFE. METHODS: This study prospectively included 57 consecutive patients with NLRFE who were considered for epilepsy surgery. All patients underwent noninvasive presurgical evaluation and then MSI. To determine the surgical plan, discussion of the results of the presurgical evaluation was first undertaken while discussion participants were blinded to the MSI results. MSI results were then presented. MSI influence on the initial management plan was assessed. RESULTS: MSI results influenced patient management in 32 patients. MSI results led to the following changes in surgical strategy in 14 patients (25%): allowing direct surgery in 6 patients through facilitating the detection of subtle cortical dysplasia in 4 patients and providing additional concordant diagnostic information to other presurgical workup in another 2 patients; rejection of surgery in 3 patients originally deemed surgical candidates; change of plan from direct surgery to icEEG in 2 patients; and allowing icEEG in 3 patients deemed not surgical candidates. MSI results led to changed electrode locations and contact numbers in another 18 patients. Epilepsy surgery was performed in 26 patients influenced by MSI results and good surgical outcome was achieved in 21 patients. CONCLUSIONS: This prospective, blinded study showed that information provided by MSI allows more informed icEEG planning and surgical outcome in a significant percentage of patients with NLRFE and should be included in the presurgical workup in those patients.

Ictal asystole with intercurrent cardiopathy: a complex combination leading to delayed diagnosis.

Ictal asystole is a rare epileptic phenomenon, though usually self-limiting, which has been associated with an increased risk of sudden death in epileptic patients. Although early recognition is desirable, the diagnosis can be delayed until prolonged video-EEG monitoring is completed. We report a case of ictal asystole in a 74-year-old patient with co-morbid cardiac conditions leading to a delay in diagnosis of approximately 10 years. Indeed, multiple cardiac investigations and EEGs failed to reveal that the recurrent syncope was seizure induced. A detailed description of the case with an emphasis on the prolonged diagnostic process, as well as the clinical and EEG findings, is provided. This case highlights the complexity of the diagnosis of some ictal asystole cases and the need to perform continuous video-EEG monitoring for confirmation. [Published with video sequence].