Vagus nerve stimulation in lesional and Non-Lesional Drug-Resistant focal onset epilepsies.

PURPOSE: Drug-resistant epilepsy (DRE) affects one-third of patients with focal epilepsy. A large portion of patients are not candidates for epilepsy surgery, thus alternative options, such as vagus nerve stimulation (VNS), are proposed. Our objective is to study the effect of vagus nerve stimulation on lesional versus non-lesional epilepsies. METHODS: This is a retrospective cohort study in a single center in London, Ontario, which includes patients with DRE implanted with VNS, implanted between 1997-2018 and the date of analysis is December 2023. PARTICIPANTS: Patients implanted with VNS were classified by lesional (VNS-L) and non-lesional (VNS-NL) based on their MRI head findings. We further subdivided the VNS groups into patients with VNS alone versus those who also had additional epilepsy surgeries. RESULTS: A total of 29 patients were enrolled in the VNS-L, compared to 29 in the VNS-NL. The median age of the patients in the study was 31.8 years, 29.31 % were men (N = 17). 41.4 % (n = 12) of the patients were VNS responders (≥50 % seizure reduction) in the VNS-L group compared to 62.0 % (n = 18) in the VNS-NL group (p = 0.03). When other epilepsy surgeries were combined with VNS in the VNS-L group, the median rate of seizure reduction was greater (72.4 (IQR 97.17-45.88) than the VNS-NL group 53.9 (IQR 92.22-27.92); p = 0.27). CONCLUSIONS: VNS is a therapeutic option for patients with lesional epilepsy, with slightly inferior results compared to patients with non-lesional epilepsy. Patients implanted with VNS showed higher seizure reduction rates if they had previous epilepsy surgeries. This study demonstrates that VNS in lesional epilepsies can be an effective treatment.

Low Yield of Routine Cerebrospinal Fluid Analysis to Assess for An Autoimmune Etiology in Patients with Chronic Seizures of Unknown Cause.

In this study, we examined the yield of routine cerebrospinal fluid (CSF) analysis to assess for an autoimmune etiology in patients with chronic seizures of unknown cause. Forty-seven patients were included. Six of 47 (13%) had inflammation on routine CSF analysis, none of whom were diagnosed with seizures related to autoimmune encephalitis (AE). Meanwhile, 2/47 (4%) were diagnosed with seizures related to AE, neither of whom had inflammation on routine CSF analysis. Routine CSF analysis to assess for an autoimmune etiology in patients with chronic seizures of unknown cause is low yield, and has suboptimal specificity and sensitivity for seizures related to AE.

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.

Association of outdoor air and noise pollution with unprovoked seizures and new onset epilepsy: A systematic review and meta-analysis.

Research has indicated that certain environmental exposures may increase the risk of unprovoked seizures and new onset epilepsy. This study aimed to synthesize the literature that has estimated the associations between short- and long-term exposure to outdoor air and noise pollution and the risk of unprovoked seizures and new onset epilepsy. We searched Embase, MEDLINE, Scopus, Web of Science, BIOSIS Previews, Latin American and Caribbean Health Sciences Literature, Proquest Dissertations and Theses, conference abstracts, and the gray literature and conducted citation tracing in June 2023. Observational and ecological studies assessing the associations of air and noise pollution with unprovoked seizures or new onset epilepsy were eligible. One reviewer extracted summary data. Using fixed and random effects models, we calculated the pooled risk ratios (RRs) for the studies assessing the associations between short-term exposure to air pollution and unprovoked seizures. Seventeen studies were included, 16 assessing the association of air pollution with seizures and one with epilepsy. Eight studies were pooled quantitatively. Ozone (O3; RR = .99, 95% confidence interval [CI] = .99-.99) and nitrogen dioxide (NO2) exposure adjusted for particulate matter (RR = 1.02, 95% CI = 1.01-1.02) on the same day, and carbon monoxide (CO) exposure 2 days prior (RR = 1.12, 95% CI = 1.02-1.22), were associated with seizure risk. A single study of air pollution and epilepsy did not report a significant association. The risk of bias and heterogeneity across studies was moderate or high. Short-term exposure to O3, NO2, and CO may affect the risk of seizures; however, the effect estimates for O3 and NO2 were minimal. Additional research should continue to explore these and the associations between outdoor air pollution and epilepsy and between noise pollution and seizures and epilepsy.

Epilepsy surgery in adults older than 50 years: A systematic review and meta-analysis.

OBJECTIVE: Despite the general safety and efficacy of epilepsy surgery, there is evidence that epilepsy surgery remains underutilized. Although there are an increasing number of studies reporting epilepsy surgery in older adults, there is no consensus on whether epilepsy surgery is efficacious or safe for this population. Our objective was to systematically assess the efficacy as well as safety of resective surgery in people aged 50 years or older with drug-resistant epilepsy. METHODS: We considered studies that examine the efficacy and safety of epilepsy surgery in adults aged 50 years and older. Study eligibility was limited to studies carried out after 1990, with a minimum of 10 participants and 6 months of follow-up. We searched the following databases for published studies: Ovid MEDLINE, Ovid Embase, Cumulative Index to Nursing and Allied Health Literature, PsychInfo, and Web of Science Conference Proceedings Citation Index - Science. The risk of bias of each included study was independently assessed by two reviewers using the MINORS (Methodological Index for Non-Randomized Studies) instrument. RESULTS: Eleven case series and 14 cohort studies met the criteria for inclusion, for a total of 1111 older adults who underwent epilepsy surgery along with 4111 adults younger than 50 years as control groups. The pooled cumulative incidence of older adults achieving seizure freedom after resective surgery was 70.1% (95% confidence interval [CI] = 65.3-74.7). There was no evident difference in the incidence of seizure freedom among older adults as compared to younger adults (risk ratio [RR] = 1.05, 95% CI = .97-1.14) in cohort studies. The pooled cumulative incidence of perioperative complications in older adults was 26.2% (95% CI = 21.3-31.7). Among them, 7.5% (95% CI = 5.8-9.5) experienced major complications. Older adults were significantly more at risk of experiencing any complication than younger adults (RR = 2.8, 95% CI = 1.5-5.4). SIGNIFICANCE: Despite important considerations, epilepsy surgery may be considered appropriate among carefully selected individuals older than 50 years.

Evaluating the Current State of Epilepsy Care in the Province of Ontario.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Incidence of First-Episode Status Epilepticus and Risk Factors in Ontario, Canada.

BACKGROUND: Status epilepticus (SE) is a neurological emergency characterized by prolonged seizures. However, the incidence of first-episode SE is unclear, as estimates vary greatly among studies. Additionally, SE risk factors have been insufficiently explored. Therefore, the objectives of this study were to estimate the incidence of first-episode SE in Ontario, Canada, and estimate the associations between potential sociodemographic and health-related risk factors and first-episode SE. METHODS: We conducted a population-based retrospective cohort study using linked health administrative datasets. We included individuals who completed Canada's 2006 Census long-form questionnaire, lived in Ontario, were between 18 and 105, and had no history of SE. A Cox proportional hazards regression model was used to estimate the hazard ratios for SE within three years associated with each potential risk factor. RESULTS: The final sample included 1,301,700 participants, 140 of whom were hospitalized or had an emergency department visit for first-episode SE during follow-up (3.5 per 100,000 person-years). Older age was the only significant sociodemographic SE risk factor (HR = 1.35, 95% CI = 1.33, 1.37), while health-related risk factors included alcohol or drug abuse (HR = 1.05, 95% CI = 1.02, 1.08), brain tumour or cancer (HR = 1.14, 95% CI = 1.12, 1.15), chronic kidney disease (HR = 1.32, 95% CI = 1.29, 1.36), dementia (HR = 1.42, 95% CI = 1.36, 1.48), diabetes (HR = 1.11, 95% CI = 1.09, 1.12), epilepsy or seizures (HR = 1.05, 95% CI = 1.01, 1.09) and stroke (HR = 1.08, 95% CI = 1.05, 1.11). CONCLUSION: The estimated incidence of SE in a sample of Ontario residents was 3.5 per 100,000 person-years. Older age and several comorbid conditions were associated with higher first-episode SE risk.

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed.

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.

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.

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.

Seizures and epilepsy associated with central nervous system tuberculosis.

Central nervous system (CNS) tuberculosis is a life-threatening condition that usually presents with seizures, particularly in children and HIV-infected patients. Tuberculous meningitis (TBM) and tuberculomas are the two forms of CNS tuberculosis that can present with seizures. Seizures usually resolve after successful treatment of the underlying infection. However, the success of the treatment is usually based on an early diagnosis. Delay in the treatment of CNS tuberculosis increases the risk of its associated complications, such as stroke. This would lead to the development of epilepsy. Early seizures may be related to meningeal irritation and cerebral edema, whereas late seizures are often associated with structural brain lesions that generally require more advanced and prolonged treatment. Risk factors associated with the development of epilepsy include young age, refractory seizures, tuberculoma, cortical involvement, epileptiform discharges, and residual lesions. Treatment of CNS tuberculosis is based on early initiation of appropriate anti-tuberculous drugs, antiseizure medications, and correction of associated predisposing factors. Finally, further research into the mechanisms of seizures and the development of epilepsy in CNS tuberculosis could help improve management of these conditions.

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.

Pearls & Oy-sters: Salt and Pepper Sign, PLNTY for Drug-Resistant Epilepsy.

Drug-resistant epilepsy, defined as the failure of 2 or more antiseizure medications to achieve seizure freedom, is responsible for 2/3 of epilepsy cases. Tumors are responsible for up to 15% of all adult onset and up to 6% of childhood onset epilepsies. Among these tumors, commonly known subtypes DNET, ganglioglioma, and low-grade astrocytoma are often suspected. New advances in tumor classification have been made, with genetics playing a key role in tumor classification. Polymorphic low-grade neuroepithelial tumor of the young (PLNTY) is a highly epileptogenic subtype of tumors that may mimic low-grade gliomas but offer pathologic and genetic clues: oligodendroglioma-like cellular components and infiltration patterns and strong CD34-immunopositive stain. In addition, a key finding is radiologic: a unifocal abnormality best seen on MRI brain in FLAIR sequence as the "salt and pepper sign" and calcifications appreciated on CT head.