Effects of vagus nerve stimulation on the quality of sleep and sleep apnea in patients with drug-resistant epilepsy: A systematic review.

OBJECTIVE: The objective was to systematically evaluate the current evidence surrounding the effect of vagus nerve stimulation (VNS) on quality of sleep and obstructive sleep apnea (OSA) among patients with epilepsy. METHODS: A literature search was conducted using the Embase and MEDLINE databases. Studies were included if they involved patients with drug-resistant epilepsy treated with VNS and used validated tools to report on quality of sleep or sleep apnea. The literature search yielded 112 citations related to VNS and sleep quality, and 82 citations related to sleep apnea. Twelve articles were included in the review, of which five measured quality of sleep among patients who underwent VNS, six studies measured sleep apnea, and one study measured both outcomes. RESULTS: Studies measuring quality of sleep used different methods, including sleep quality questionnaires and the percentage of sleep in each cycle. Studies also varied in patient populations, the use of control groups, and whether multiple measurements were taken for each patient. Some studies found improved sleep quality after VNS, whereas others found reductions in deep sleep stages. Additionally, mixed results in sleep quality were found when comparing patients with epilepsy who received VNS treatment versus patients with epilepsy who did not receive VNS treatment. Variables such as VNS intensity and age could potentially confound quality of sleep. Studies measuring sleep apnea consistently found increased proportions of patients diagnosed with OSA or increased sleep index scores after VNS implantation. SIGNIFICANCE: Overall, the effect of VNS on quality of sleep remains unclear, as studies were very heterogeneous, although the effect on sleep apnea has consistently shown an increase in sleep apnea severity indices after VNS implantation. Future studies with consistent measures and discussions of confounding are required to determine the effect of VNS on quality of sleep, and the effect of VNS parameters should be further explored among patients who develop sleep apnea.

Disrupting the epileptogenic network with stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a treatment option for focal drug-resistant epilepsy. In previous studies, this technique has shown seizure reduction by ≥50% in 50% of patients at 1 year. However, the relationship between the location of the ablation within the epileptogenic network and clinical outcomes remains poorly understood. Seizure outcomes were analyzed for patients who underwent SEEG-guided RF-TC and across subgroups depending on the location of the ablation within the epileptogenic network, defined as SEEG sites involved in seizure generation and spread. Eighteen patients who had SEEG-guided RF-TC were included. SEEG-guided seizure-onset zone ablation (SEEG-guided SOZA) was performed in 12 patients, and SEEG-guided partial seizure-onset zone ablation (SEEG-guided P-SOZA) in 6 patients. The early spread was ablated in three SEEG-guided SOZA patients. Five patients had ablation of a lesion. The seizure freedom rate in the cohort ranged between 22% and 50%, and the responder rate between 67% and 85%. SEEG-guided SOZA demonstrated superior results for both outcomes compared to SEEG-guided P-SOZA at 6 months (seizure freedom p = .294, responder rate p = .014). Adding the early spread ablation to SEEG-guided SOZA did not increase seizure freedom rates but exhibited comparable effectiveness regarding responder rates, indicating a potential network disruption.

Management of patients with epilepsy and Intellectual disabilities in group homes vs. Family Homes: Insights into polypharmacy and seizure characteristics.

OBJECTIVES: This study aimed to investigate the differences in ASMs prescription, seizure characteristics and predictors of polypharmacy in patients with epilepsy and Intellectual disabilities (IDs) residing in group homes versus family homes. METHODS: This nine-year retrospective study analyzed patients with epilepsy and IDs who were admitted to the EMU, epilepsy clinics at LHSC and rehabilitation clinics for patients with IDs at Parkwood Institution. The study included individuals aged 16 years and older residing in either group homes or family homes. Data on demographics, epilepsy characteristics, and ASMs use were collected and analyzed using the Statistical Package for Social Sciences. The study utilized binary logistic regression to identify predictors of polypharmacy in patients with epilepsy and IDs. RESULTS: The study enrolled a total of 81 patients, of which 59.3 % resided in family homes. Group home residents were significantly older (41 vs. 24.5 years; p = 0.0001) and were prescribed more ASMs (3 vs. 2; p = 0.002). Specific ASMs were more common in group homes, including valproic acid (54.5 % vs. 25.0 %), lacosamide (54.5 % vs. 22.9 %), topiramate (33.3 % vs. 14.6 %), and phenytoin (30.3 % vs. 6.2 %). Admission to the EMU was more prevalent in group homes (93.9 % vs. 52.1 %; p = 0.0001). Living in a group home increased the risk of polypharmacy (OR = 10.293, p = 0.005), as did older epilepsy onset age (OR = 1.135, p = 0.031) and generalized or focal & generalized epilepsy (OR = 7.153, p = 0.032 and OR = 10.442, p = 0.025, respectively). SIGNIFICANCE: Our study identified notable differences in the demographic and clinical characteristics of patients with epilepsy and IDs living in group homes versus family homes. Age of epilepsy onset, EMU admissions, epilepsy types, and residency setting were significant predictors of polypharmacy. These findings highlight the need for personalized care strategies and increased awareness of the potential risks associated with polypharmacy.

Real-world practices in reproductive health and counselling for women with epilepsy: A Canadian perspective.

Canadian women of reproductive potential living with epilepsy present unique care challenges due to the complex interplay of hormones, seizures, and medications. This study explores reproductive health practices and counselling for women with epilepsy. Through a questionnaire developed by the Canadian League Against Epilepsy women with epilepsy (WWE) workgroup, we are the first to report demographic and real-world practice characteristics of Canadian healthcare professionals providing care for WWE with specific focus on family planning, birth plans, and postpartum care counselling. Among respondents, 76.9% routinely reviewed contraception with patients and an intrauterine device (IUD) was the most popular recommended method (85.3%). With regards to preconception planning, 50% of respondents routinely had a preconception drug level prior to pregnancy. A significant proportion, 44.9%, reported not communicating a neurology-informed birth plan to obstetrical health practitioners. The majority recommended breastfeeding for WWE on anti-seizure medications (92.3%) and regularly provided safety counselling for women in the postpartum period (84.6%). Overall, our study demonstrates that Canadian practice patterns conform reasonably well to existing evidence and guidelines, although important gaps in care exist.

Real-world practices for the care of women with epilepsy during pregnancy: A Canadian perspective.

OBJECTIVE: Approximately 150,000 Canadian women live with epilepsy, a population that presents with unique challenges. Our objective was to capture demographic and real-world practice characteristics of Canadian healthcare professionals providing care for women with epilepsy (WWE) with specific focus on reproductive considerations to identify potential gaps in knowledge and care. METHODS: A questionnaire developed by the Canadian League Against Epilepsy WWE workgroup was distributed to Canadian healthcare professionals from February 2021 to October 2022 to capture participant demographic characteristics and practice patterns in key areas of the reproductive cycle in WWE. RESULTS: A total of 156 participants completed the questionnaire, most being physicians (81.4%), epilepsy specialists (69.0%), and those who cared for adult patients (86.5%), with a significant proportion based at an academic center (65.4%). The majority of participants counselled on folic acid supplementation (89.7%). Participants selected lamotrigine and levetiracetam most frequently for either focal or generalized epilepsies during pregnancy. Additionally, 85.9% performed therapeutic drug monitoring during pregnancy. Almost all practitioners always or often counseled WWE on valproic acid on the benefits of switching to a less teratogenic medication (96.2%). Some geographic variability in practice patterns was noted with valproic acid being one of the top three medications selected for patients with generalized epilepsies in Western regions, although participants in Eastern regions had brivaracetam more commonly included as one of their top three agents for this population. SIGNIFICANCE: This is the first report of real-world Canadian practices in epilepsy care for women in pregnancy. Overall, our study reports that Canadian practice patterns conform well to current evidence and best-practice guidelines. Important variations in antiseizure medication selection across different regions were identified.

Adults with tuberous sclerosis complex: A distinct patient population.

OBJECTIVES: There are few data on adults living with tuberous sclerosis complex (TSC), with most studies focusing on pediatric populations. The objective of our study was to examine a large national cohort of adults with TSC, and to describe the clinical characteristics of these adults and the nature of the multidisciplinary care that they receive. METHODS: Six Canadian medical centers collaborated in this study. Data were collected using a standardized form, and descriptive statistics were used for the analyses. RESULTS: Our study included 181 adults with definite TSC (mean age = 33.6 years [SD = 13.7]). More than 40% (n = 75) had family members affected by TSC. Forty-six percent (n = 83) of individuals had intellectual disability. Nearly 30% (n = 52) of individuals reported living alone or with a partner/spouse. Seventy-six percent (n = 138) of people had epilepsy, 43% (n = 59) of whom had drug-resistant epilepsy, and 21% (n = 29) had undergone epilepsy surgery. Neuropsychiatric disease (n = 128) and renal angiomyolipomas (n = 130) were both present in approximately 70% of people. Renal imaging was performed in 75.7% (n = 137) of participants within the past 3 years. Renal and pulmonary function tests, as well as electrocardiograms, were recently performed in a minority of individuals. SIGNIFICANCE: Our cohort of adults with TSC showed that an important proportion have a milder phenotype, and are more frequently familial, as compared to children with TSC (and differing from prior reports in adult cohorts). Drug-resistant epilepsy, neuropsychiatric comorbidities, and renal angiomyolipoma are challenging factors in adults with TSC. Our participating medical centers generally followed recommended screening strategies, but there remain important gaps in care. Multidisciplinary and structured TSC care centers offering service to adults may help to improve the health of this important patient population.

Canadian epilepsy priority-setting partnership: Toward a new national research agenda.

BACKGROUND: Health research agendas are often set by researchers or by industry and may not reflect the needs and priorities of end users. This priority-setting partnership (PSP) for epilepsy was undertaken to identify the most pressing unanswered questions about epilepsy and seizures from the perspective of people with epilepsy (PWE) and their care providers. METHODS: Using the methodology developed by the James Lind Alliance (JLA), evidence uncertainties were gathered via online surveys from stakeholders across Canada. Submissions were formed into summary questions and checked against existing evidence to determine if they were true uncertainties. Verified uncertainties were then ranked by patients, caregivers, and healthcare providers and a final workshop was held to reach a consensus on the top 10 priorities. RESULTS: The final top 10 list reflects the priority areas of focus for research as identified by the Canadian epilepsy community, including genetic markers for diagnosis and treatment, concerns about living with the long-term effects of epilepsy, and addressing knowledge gaps in etiology and treatment approaches. CONCLUSION: This project represents the first systematic evidence of patient- and clinician-centered research priorities for epilepsy. The results of this priority-setting exercise provide an opportunity for researchers and funding agencies to align their agendas with the values and needs of the epilepsy community in order to improve clinical outcomes and quality of life (QOL) for PWE.

Vagus nerve stimulation does not alter brainstem nuclei morphology in patients with refractory epilepsy.

OBJECTIVE: To describe morphological characteristics of the brainstem nuclei in response to chronic vagus nerve stimulation (VNS) in patients with refractory epilepsy. BACKGROUND: VNS is a treatment option for individuals with medically refractory epilepsy. While treatment with VNS may achieve up to 50% seizure reduction and is protective against sudden unexpected death in epilepsy (SUDEP), its mechanism of action is not fully understood. Long-term structural and cellular changes in response to VNS have rarely been addressed in humans. METHODS: Four autopsy cases with history of chronic epilepsy treated with VNS (VNS+) and 4 age- and sex-matched chronic epilepsy-related death cases without VNS (VNS-) were included. Detailed clinical and postmortem data were obtained. Serial horizontal sections of the brainstem were prepared and stained with hematoxylin, eosin, and luxol fast blue (HE/LFB). Three regions of interest (ROIs) were delineated, including nucleus tractus solitarius (NTS), locus coeruleus (LC), and the rostral pontine group of raphe nuclei (rRN). Immunohistochemistry studies were performed using antibodies to GFAP, NeuN, HLA-DR, and IBA-1. Immunolabeling index was analyzed. RESULTS: Three of the 4 VNS+ patients and all 4 control (VNS-) patients died of SUDEP. There was no laterality difference in the NeuN, GFAP, HLA-DR and IBA-1 expression in LC and NTS of VNS+ patients. Similarly, there was no difference in the rRN, LC, and NTS between the VNS+ and VNS- groups. CONCLUSION: This study represents the first histopathological study of the long-term effects of VNS therapy in the human brain. There was no difference observed in the neuronal cell number, degree of astrocytosis, and neuroinflammation in the main brainstem vagal afferent nuclei after prolonged VNS treatment in patients with refractory epilepsy.

Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy: A Canadian Experience.

OBJECTIVE: To describe the experience with Anterior Nucleus of the Thalamus-Deep Brain Stimulation (ANT-DBS) for the treatment of epilepsy at a Canadian Center. METHODS: All patients who underwent ANT-DBS implantation between 2013 (first patient implanted at our center) and 2020 were included. These patients had therapy-resistant epilepsy (TRE), were not candidates for resective surgery, and failed vagus nerve stimulation (VNS) treatment. Baseline of monthly seizure frequency was calculated within 3 months prior to VNS placement. Monthly seizure frequency was assessed at different points along the timeline: 3 months before ANT-DBS implantation as well as 3, 6, 12, 24, 36, 48, 60, and 72 months after ANT-DBS device placement. At each time point, seizure frequency was compared to baseline. RESULTS: Six patients were implanted with ANT-DBS. Three (50%) patients had multifocal epilepsy, one (16.6%) had focal epilepsy, and two (33.4%) had combined generalized and focal epilepsy. Two patients with multifocal epilepsy experienced a seizure reduction >50% in the long-term follow-up. Three (50%) patients did not showed improvement: two with combined generalized and focal epilepsy and one with focal epilepsy. There were not surgical or device-related side effects. Two (33.3%) patients presented mild and transient headaches as a stimulation-related side effect. CONCLUSION: ANT-DBS is an effective and safe treatment for focal TRE. Our experience suggests that patients with multifocal epilepsy due to regional lesion may benefit from ANT-DBS the most. Further investigations are required to determine optimal parameters of stimulation.

Impact of 24-Hour On-Call Shifts on Headache in Medical Residents: A Cohort Study.

BACKGROUND: During 24-hour on-call shifts medical residents are exposed to diverse circumstances such as sleep deprivation and stress. OBJECTIVE: Our aim is to assess the effect of 24-hour on-call shifts on medical residents' headache-related disability. METHODS: The Migraine Disability Assessment Scale (MIDAS), the Headache Impact Test (HIT-6), the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS) questionnaires were administered to medical residents who had never performed on-call shifts at baseline and 6 months after beginning 24-hour on-call shifts. Scores were compared. RESULTS: About 66 medical residents completed this study. About 21.2% (n = 14) had history of migraine, 42.4% (n = 28) had a history of tension-type headache (TTH) and 12.1% (n = 8) had a history of both migraine and TTH. Among medical residents with migraine, the median MIDAS score was significantly higher after starting 24-hour on-call shifts than at a baseline (4.0 vs 8.0; Wilcoxon, P = .001), meaning that, on average, disability increased from little or no disability, to moderate disability. No difference in HIT-6 scores was found. The median score of PSQI and HADS was higher at 6 months (PSQI: 7.0 vs 8.0; P = .003), (HADS: 5.0 vs 8.0; P < .001) for the general group. CONCLUSIONS: In medical residents with migraine, migraine-related disability increased after starting 24-hour on-call shifts. We also found a worsening in depression and anxiety symptoms and self-reported sleep quality in medical residents with and without headache history.

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy.

BACKGROUND: For patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox-Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE). METHODS: We identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications. RESULTS: A total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8-31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31-112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic-clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE). CONCLUSIONS: Vagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.

Seizure Freedom in Temporal Plus Epilepsy Surgery Following Stereo-Electroencephalography.

BACKGROUND: "Temporal plus" epilepsy (TPE) is a term that is used when the epileptogenic zone (EZ) extends beyond the boundaries of the temporal lobe. Stereotactic electroencephalography (SEEG) has been essential to identify additional EZs in adjacent structures that might be part of the temporal lobe/limbic network. OBJECTIVE: We present a small case series of temporal plus cases successfully identified by SEEG who were seizure-free after resective surgery. METHODS: We conducted a retrospective analysis of 156 patients who underwent SEEG in 5 years. Six cases had TPE and underwent anterior temporal lobectomy (ATL) with additional extra-temporal resections. RESULTS: Five cases had a focus on the right hemisphere and one on the left. Three cases were non-lesional and three were lesional. Mean follow-up time since surgery was 2.9 years (SD ± 1.8). Three patients had subdural electrodes investigation prior or in addition to SEEG. All patients underwent standard ATL and additional extra-temporal resections during the same procedure or at a later date. All patients were seizure-free at their last follow-up appointment (Engel Ia = 3; Engel Ib = 2; Engel Ic = 1). Pathology was nonspecific/gliosis for all six cases. CONCLUSION: TPE might explain some of the failures in temporal lobe epilepsy surgery. We present a small case series of six patients in whom SEEG successfully identified this phenomenon and surgery proved effective.

Epilepsy-associated death in the Southwestern Ontario: A clinicopathological correlation study.

Patients with epilepsy are at elevated risk for premature mortality, of which sudden unexpected death in epilepsy (SUDEP) is one of the leading causes. SUDEP incidence varies significantly depending on the population and the methods used to document the cause of death. We performed retrospective case review at the London Health Sciences Centre for the period of 2000 to 2018. Clinical information, scene investigations, general pathology findings, toxicology, and neuropathology findings were obtained, examined, and confirmed by two neuropathologists and one epileptologist. The characteristics were compared and summarized. We also evaluated the impact of 2010 revision of Ontario Coroner Act Regulation, which significantly limited whole brain examination. Among the 12,206 cases reviewed, we identified 152 cases with a known history of epilepsy. Ninety-seven cases (64%) were classified as SUDEP. There were significantly more SUDEP decedents found dead unwitnessed at night in prone position, than non-SUDEP. Generalized seizures were strongly associated with SUDEP. A male predominance was observed in SUDEP group between 15 and 35 years old. Near half of the brains examined were "unremarkable." There was no difference in neuropathology findings between SUDEP and non-SUDEP groups. After implementation of the 2010 revision of Ontario Coroner Act Regulation, fixed whole brain examination was reduced from 88% to 7% of the epilepsy-related death investigation. Except a lower diagnosis rate of "inflammatory/infectious changes," there were no significant differences in neuropathology findings. This is the first detailed clinical-pathological study on epilepsy-related death based on a Canadian cohort. This study reinforces the previously reported findings in SUDEP and highlights the importance of clinicopathological correlation for accurate classification of epilepsy-related death.

Involvement of the posterior cingulate gyrus in temporal lobe epilepsy: A study using stereo-EEG.

OBJECTIVE: To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS). METHODS: We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled. RESULTS: Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up. CONCLUSION: We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome.

Nationwide Study of Postlegalization Marijuana Use Among Patients With Epilepsy in Canada.

Background and Objectives: Patients with epilepsy have long sought alternatives to conventional antiseizure medications (ASMs) for the treatment of their epilepsy and to improve the significant side effect burden of ASMs and comorbidities. It was established before the legalization of marijuana in Canada in 2018 that many patients with epilepsy use marijuana to treat their seizures or for recreational purposes. However, there exists no current data on the prevalence and habits of marijuana use in the Canadian epilepsy population since legalization. Methods: We conducted a nationwide cross-sectional survey of patients recruited through health care providers or epilepsy organizations to investigate marijuana usage habits and perceptions. Results: From 395 responses obtained through the survey, 221 responses stated that they used marijuana within the past year. A history of seizures for more than 10 years was noted in 50.7% (n = 148) patients with generalized seizures being the most common type (n = 169; 57.1%). Most of them (n = 154; 52.0%) had tried 3 or more ASMs, and 37.2% (n = 110) used various other treatments (ketogenic diet, vagus nerve stimulation, or resective surgery) indicating a proportion with drug-resistant epilepsy. This subgroup was more likely to have started using marijuana for drug-resistant epilepsy (p < 0.001). Current marijuana use for epilepsy management was endorsed by 47.5% (n = 116). Marijuana was "somewhat" to "very" effective at reducing seizure frequency for 60.1% (n = 123). The main side effects of marijuana were impaired thinking (n = 40; 17.17%), anxiety (n = 37; 15.74%), and altered hunger (n = 36; 15.32%). Marijuana was used at least once daily by 70.3% (n = 168) with the median amount per week being 5.0 g (IQR = 1-10), and the preferred method of consumption was smoking (n = 83; 34.7%). The participants expressed concerns regarding financial strain (n = 108; 36.5%), lack of recommendation from a doctor (n = 89; 30.1%), and lack of information (n = 56; 18.9%) surrounding marijuana use. Discussion: This study reveals a high prevalence of marijuana use among patients with epilepsy living in Canada particularly when seizures are drug resistant. A significant proportion of patients reported improvement of seizures with marijuana use, consistent with previous studies. With the increased accessibility of marijuana, it is imperative that physicians are aware of marijuana usage habits among patients with epilepsy.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Long-term outcomes after NORSE: Treatment with vagus nerve stimulation.

New-onset refractory status epilepticus (NORSE) is associated with high mortality, therapy-resistant epilepsy (TRE), and poor cognitive and functional outcomes. Some patients develop multifocal TRE, for whom surgery with a curative intention, is not an option. In these patients, vagus nerve stimulation (VNS) is performed as a palliative treatment. We report the long-term outcomes regarding seizure frequency, functional and cognitive outcome, and effectiveness of VNS in two patients with TRE as a consequence of NORSE. In the first patient with cryptogenic NORSE, VNS implantation occurred during the acute stage, probably contributing to the cessation of her status epilepticus. However, in the long-term follow-up, the patient persisted with daily multifocal seizures. In the second patient, VNS implantation was delayed to manage his epilepsy when the NORSE, ultimately due to autoimmune encephalitis, had resolved. During long-term follow-up, no reduction in seizure frequency was achieved. This evidence supporting the use of VNS in patients with TRE after NORSE warrants further investigation.

Waveform detection by deep learning reveals multi-area spindles that are selectively modulated by memory load.

Sleep is generally considered to be a state of large-scale synchrony across thalamus and neocortex; however, recent work has challenged this idea by reporting isolated sleep rhythms such as slow oscillations and spindles. What is the spatial scale of sleep rhythms? To answer this question, we adapted deep learning algorithms initially developed for detecting earthquakes and gravitational waves in high-noise settings for analysis of neural recordings in sleep. We then studied sleep spindles in non-human primate electrocorticography (ECoG), human electroencephalogram (EEG), and clinical intracranial electroencephalogram (iEEG) recordings in the human. Within each recording type, we find widespread spindles occur much more frequently than previously reported. We then analyzed the spatiotemporal patterns of these large-scale, multi-area spindles and, in the EEG recordings, how spindle patterns change following a visual memory task. Our results reveal a potential role for widespread, multi-area spindles in consolidation of memories in networks widely distributed across primate cortex.

The brain processes memories as we sleep, generating rhythms of electrical activity called 'sleep spindles'. Sleep spindles were long thought to be a state where the entire brain was fully synchronized by this rhythm. This was based on EEG recordings, short for electroencephalogram, a technique that uses electrodes on the scalp to measure electrical activity in the outermost layer of the brain, the cortex. But more recent intracranial recordings of people undergoing brain surgery have challenged this idea and suggested that sleep spindles may not be a state of global brain synchronization, but rather localised to specific areas. Mofrad et al. sought to clarify the extent to which spindles co-occur at multiple sites in the brain, which could shed light on how networks of neurons coordinate memory storage during sleep. To analyse highly variable brain wave recordings, Mofrad et al. adapted deep learning algorithms initially developed for detecting earthquakes and gravitational waves. The resulting algorithm, designed to more sensitively detect spindles amongst other brain activity, was then applied to a range of sleep recordings from humans and macaque monkeys. The analyses revealed that widespread and complex patterns of spindle rhythms, spanning multiple areas in the cortex of the brain, actually appear much more frequently than previously thought. This finding was consistent across all the recordings analysed, even recordings under the skull, which provide the clearest window into brain circuits. Further analyses found that these multi-area spindles occurred more often in sleep after people had completed tasks that required holding many visual scenes in memory, as opposed to control conditions with fewer visual scenes. In summary, Mofrad et al. show that neuroscientists had previously not appreciated the complex and dynamic patterns in this sleep rhythm. These patterns in sleep spindles may be able to adapt based on the demands needed for memory storage, and this will be the subject of future work. Moreover, the findings support the idea that sleep spindles help coordinate the consolidation of memories in brain circuits that stretch across the cortex. Understanding this mechanism may provide insights into how memory falters in aging and sleep-related diseases, such as Alzheimer's disease. Lastly, the algorithm developed by Mofrad et al. stands to be a useful tool for analysing other rhythmic waveforms in noisy recordings.

Extraoperative electrical stimulation mapping in epilepsy presurgical evaluation: a proposal and review of the literature.

BACKGROUND: Electrical stimulation mapping (ESM) is an important tool for the localization of the seizure onset zone (SOZ) in patients with medically resistant epilepsy (MRE). ESM is the gold standard for the identification of eloquent cortex in epilepsy surgery candidates. However, there is no standard protocol outlining how to perform ESM, to obtain the most useful information possible. The objective of this study, after reviewing the literature concerning ESM, is to propose a unifying technique to validate reliable data across different centers. METHODS: In this manuscript we summarize this technique from its origin to present, and review protocols used in other centers. We also describe a protocol that has been used in our institution, which utilizes depth electrodes. RESULTS: The most common type of ESM uses a "close-loop" system, bipolar and high frequency stimulation (50 Hz). We propose to use a pulse width of 300 µs, current spanning 1-6 mA in depth electrodes and 1-11 mA in subdural-grids. Stimulation time of 5 s maximum and at least 10 s break in between the stimulations. CONCLUSIONS: ESM is a useful tool for understanding eloquent cortex as well as the epilepsy network, although there is no clear consensus regarding how it should be performed.

Auditory verbal hallucinations as ictal phenomena in a patient with drug-resistant epilepsy.

PURPOSE: The presence of verbal auditory hallucinations is often associated with psychotic disorders and rarely is considered as an ictal phenomena. The aim of this paper is to describe the anatomical structures involved in the genesis of this ictal symptom during epileptic seizures and direct cortical stimulation using stereo encephalography (SEEG). METHOD: The case is of a 31-year-old right-handed female, bilateral speech representation, schizophrenia and with drug-resistant epilepsy and focal aware sensory seizures characterized by ictal verbal auditory hallucinations. She was implanted with depth electrodes, and she was monitored using SEEG recordings. RESULTS: She had focal aware sensory seizures characterized by verbal auditory hallucinations, with the following features: hearing numerous voices (both male and/or female), talking at the same time (not able to distinguish how many). The voices were inside her head, consisted of negative content, and lasted up to two minutes. Some of her focal aware sensory seizures evolved to focal motor seizures and rarely progressed to bilateral tonic clonic seizures. Her neurological examination, her brain MRI and her interictal SPECT were unremarkable. Her PET scan identified mild hypo metabolism over the right temporal and right frontal lobes. Her neuropsychological evaluation showed language laterality undetermined but her functional MRI showed bilateral language representation. On her video-EEG, three seizures were captured with a right posterior temporal onset. A subsequent SEEG showed thirteen typical seizures originating from the posterior temporal neocortical region. The cortical stimulation of the right posterior temporo-parietal neocortical region and right amygdala triggered her typical phenomena, which was multiple voices, inside her head, speaking in the second person, negative content, unable to identify gender, in English, and no side lateralization. CONCLUSION: Verbal auditory hallucinations should be analyzed carefully because they can be part of the seizure presentation. Our case supports the localization of these hallucinations in the right posterior neocortical temporal regions.