Risk Of Seizures Research Articles

Seizure outcomes following single-fraction versus hypofractionated radiosurgery for brain metastases: a single-center experience.

Although seizures are a relatively common phenomenon in the setting of brain metastases (BMs), there are no discrete recommendations regarding the use of antiepileptic drugs (AEDs) in this population, either in general or in the context of treatment. The authors' aim was to better understand the underlying pathological factors as well as the therapeutic techniques that may lead to seizures following the radiosurgical treatment of BMs with the goal of guiding appropriate AED prophylaxis. Adult patients with BMs diagnosed from 2013 to 2020 at a single academic institution and treated with radiation therapy were included in this study. The authors evaluated factors associated with the incidence of seizures throughout the disease course, with a focus on seizures in the 90-day period following stereotactic radiosurgery (SRS). Four hundred forty-four patients with newly diagnosed BMs were identified, 10% of whom had seizures at the time of presentation and 28% of whom had a seizure at any point during the study period. Tumor histology was significantly associated with initial seizure risk. AED use was highly variable. In the 90-day post-SRS period, the summed total planning target volume (PTV) was independently predictive of post-SRS seizures, regardless of the fractionation scheme (single fraction vs hypofractionated) and other clinical factors. The number of supratentorial BMs was not predictive of post-SRS seizures. PTV is a superior predictor of post-SRS seizures relative to the number of supratentorial BMs, as it serves as a volumetric proxy for intracranial disease burden. A larger PTV, alongside tumor histology and prior seizure history, should be considered in the decision-making process for AED use following radiosurgery.

Increased hippocampal cannabinoid 1 receptor expression is associated with protection from severe seizures in pregnant mice with reduced uterine perfusion pressure.

Eclampsia, new-onset seizures in pregnancy, can complicate preeclampsia, a hypertensive pregnancy disorder. The mechanisms contributing to increased risk of seizures in preeclampsia are not fully known. One mechanism could be abnormal endocannabinoid system (ECS) activity and impaired neuromodulation. Indeed, increased placental cannabinoid receptor 1 (CB1R) expression and reduced serum anandamide, a CB1R ligand, have been reported in preeclampsia patients. We hypothesized that reduced uterine perfusion pressure (RUPP), used to mimic preeclampsia, leads to changes in hippocampal CB1R expression, and that manipulating CB1R activity will change seizure severity in RUPP mice. Pregnant mice underwent sham or RUPP surgery on gestational day (GD)13.5. On GD18.5, mice received: no drug treatment, pentylenetetrazol (PTZ, 40 mg/kg), Rimonabant (10 mg/kg) + PTZ, or 2-AG (1 mg/kg) + PTZ. Behaviors were video recorded (15 min for Rimonabant and 2-AG, followed by 30 min for PTZ), and the hippocampus was harvested. The expression of CB1R and ECS proteins was measured in hippocampal homogenates, synaptosomes, and cytosol. Hippocampal CB1R increased in homogenates and cytosolic fraction, and was unchanged in synaptosomes of RUPP mice. Increased CB1R colocalization on glutamate-releasing neurons within hippocampal CA1 was observed in RUPP mice. Rimonabant modestly increased seizure scores over time in RUPP mice. PTZ after rimonabant pretreatment increased seizure scores and duration, while reducing latency in sham mice, with little to no change in RUPP mice. Furthermore, RUPP mice had lower seizure scores over time than sham following CB1R blockade and activation. These data suggest that RUPP modifies CB1R activity prior to seizure induction, which protects mice from worse seizure outcomes.

The Predictors of Seizures in Patients with Encephalocele: An 11-Year Experience from a Tertiary Hospital

Introduction: The aim of the study was to investigate and identify the predictors associated with the incidence of seizures in patients with encephalocele (EC). Methods: A retrospective analysis was undertaken of patients treated for EC at a tertiary medical center in Tehran between 2010 and 2021. Data including age at presentation, gender, location, size, and content of EC, ventriculomegaly, hydrocephalus, associated anomalies, and neurodevelopmental delay (NDD) were evaluated for their prognostic value. In addition, univariate and multivariate analyses were performed to identify the correlation between independent predictors and seizure incidence. Results: One hundred and two cases of EC were identified. Seventy-one ECs (69.6%) were posterior ECs, while 31 (30.4%) were anterior. Neural tissue was found in 43 (42.2%) of the ECs. Thirty-three patients (32.4%) had ventriculomegaly, of which 90.9% underwent shunt placement for progressive or symptomatic hydrocephalus. Seizure was found in 26 (25.5%) patients. On univariate analysis, presence of other anomalies, postoperative infections, and NDD were associated with seizures (p < 0.05). When the anomalies were categorized into intracranial and extracranial groups in univariate analysis, none was associated with statistically significant increase in seizure (p values of 0.09 and 0.61, respectively). Although according to multivariate analysis, only the association between other associated anomalies and seizure was near significant (OR: 2.0, 95% CI: 0.95–4.2, p = 0.049). Children with NDD and postoperative infection were, respectively, 3.04 and 1.3 times more at risk to experience seizures compared to other patients. Conclusion: We found a rate of 25.5% risk of seizure in patients with EC. This study could not find any significant predictors of seizure in children with EC. However, pediatric patients with postoperative infections including sepsis, wound infection, and NDD require more consideration to reduce the risk of seizure.

Perampanel’s forgiveness factor in a variable medication adherence paradigm in a rat model of chronic epilepsy

BackgroundPoor medication adherence contributes to increased morbidity and mortality in patients with epilepsy and may be under-addressed in clinical practice. Ethical concerns make it impossible to study the impact of medication nonadherence in clinical trials, but our previous work emphasizes the importance of using preclinical approaches to address these questions. With over 30 clinically available antiseizure medicines (ASM’s), it remains an important question to understand the relationship between poor adherence and seizure incidence across mechanistically distinct ASM’s, including the broad-spectrum ASM, perampanel (PER).MethodsWe formulated PER into chow pellets to deliver to rats in a 100% fully adherent or 50% variable nonadherent paradigm via our novel automated medication-in-food delivery system. Chronic oral dosing was initiated in male rats with chronic epilepsy while monitoring 24/7 for videoEEG evidence of seizures during a 4-week placebo baseline and 4-week treatment phase. PER concentrations were monitored in plasma at 1-week intervals and correlated with degree of seizure control. The relationship between missed doses and extended patterns of nonadherence were correlated with breakthrough seizures.ResultsFully adherent rats demonstrated a median reduction in seizure frequency of 50%, whereas nonadherent rats had a median increase of 54%. Plasma concentrations of PER were stable over the 4-week treatment period in both fully adherent and nonadherent groups, with levels being twice as high in fully adherent animals. There was no correlation between a single missed dose or series of missed doses and the incidence of breakthrough seizures. However, those animals in the nonadherent group that received PER for every meal during a 24-h period had a reduced likelihood of seizure incidence.ConclusionsIf our preclinical data is supported in the clinic, PER’s favorable pharmacokinetic profile in humans, combined with a lowered risk of breakthrough seizures suggests that it may provide a certain forgiveness factor if a dose is missed within a 24-h window.

Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study

BackgroundAcute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%.MethodsInclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey.ResultsEleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate.ConclusionsEven in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature.

Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature. The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype-phenotype correlations. We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non-polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance. CCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.

New Onset Seizures in Hospitalized COVID-19 Patients; A Systematic Review and Meta-Analysis.

Seizures in COVID-19 patients continue to be a common reason for consulting the neurology service in the inpatient setting. This paper assesses the frequency of new onset seizures in adult hospitalized COVID-19 patients. PubMed and EMBASE were searched, with fifteen cohort studies identified to calculate the primary outcome, which was the frequency of new onset seizures in hospitalized COVID-19 patients. An inverse variance meta-analysis of single proportions with a random effects model was applied to these cohort studies to calculate the primary outcome. Risk of bias in individual studies was assessed using the 10-item risk of bias tool for prevalence studies. The meta-analysis revealed a frequency of .71% (95% confidential interval: .32-1.25, I2 = 89%, 147/28242 patients) for acute symptomatic seizures in patients with COVID-19. For secondary outcomes, the risk of seizures in patients who had EEG completed was 8.49% (95% confidential interval: .62-24.07, I2 = 14%, 44/535 patients). Slightly less than half of patients with COVID-19 and seizures were reported to have acute imaging abnormalities (45.7%) with acute vascular insults being commonly reported. Only a small percentage of COVID-19 patients with seizures (2.8%) met the criteria for COVID-19 encephalitis as determined by the international encephalitis consortium. The frequency of seizures in COVID-19 was .71% (95% confidential interval: .32-1.25). Slightly less than half of COVID-19 patients had head imaging abnormalities as a complication of COVID-19 infection. Only a small percentage of patients with seizures and COVID-19 met the criteria for COVID-19 encephalitis.

P09.01.A IMPACT OF TIMING OF ANTISEIZURE MEDICATION WITHDRAWAL ON SEIZURE RECURRENCE IN GLIOMA PATIENTS: A RETROSPECTIVE OBSERVATIONAL STUDY

Abstract BACKGROUND Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk of recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. MATERIAL AND METHODS In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥3 months, but &amp;lt;12 months; medium-term as 12-24 months; and long-term as ≥24 months seizure freedom from the date of last antitumour treatment. RESULTS This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 44% (15/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR]=0.65 [95%CI=0.29-1.46]) and long-term group (cause-specific aHR=1.04 [95%CI=0.52-2.09]). CONCLUSION Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.

P11.61.B TUMOR ASSOCIATED EPILEPSY AND RESTRICTION OF DRIVING PRIVILEGES IN THE FIRST YEAR AFTER BRAIN TUMOR SURGERY

Abstract BACKGROUND In most countries, the risk of postoperative seizures prompts regulations restricting driving privileges at least temporarily following brain tumor operations. The present study investigated the frequency of epileptic seizures and driving habits in the first year after brain tumor operations in a prospective and a retrospective patient cohort. MATERIAL AND METHODS The authors studied overall 523 patients undergoing surgery for a brain tumor at the authors’ institution (prospective cohort, 09/2021-09/2022: N=313 and retrospective cohort, 01/2020-12/2020: N=210). Clinical data were obtained by reviewing patient charts and through (telephone) interviews. RESULTS The cohort included 160 (30.6%) meningiomas, 135 (25.6%) glioblastomas, 111 (21.2%) metastases and 56 (10.7%) other gliomas. 135/523 (25.8%) presented with seizure(s). At 3 months (excluding early post operative seizures) overall 57 (10.9%; prospective vs. retrospective cohort: 13.2 vs. 8.1%) patients reported seizure(s). The seizure incidence at 1 year was 18.4% (prospective vs. retrospective cohort: 18.7 vs. 18.2%). 22/173 (12.7%) patients reported de-novo seizures at 1 year. Significant predictors of seizures at 1 year included preoperative seizures (p&amp;lt;0.001), an adverse preoperative and postoperative KPI (p=0.038 and p=0.001) as well as postoperative NANO (p&amp;lt;0.001) score and histology (e.g. meningiomas: 7.5%, metastases: 22.0%, glioblastomas: 38.5%, other gliomas: 18.8%; p&amp;lt;0.001). 219/318 (69.9%) assessable patients were not driving in 3 months. Reasons included no driver’s license (6.3%), death (7.9%), neurological deficits (38.4%), epilepsy (9.0%), and personal choice (12.9%). 91.3% of glioblastoma patients did not drive in 3 months (cf. metastases: 77.8%, other gliomas. 72.4%, meningiomas: 43.8%; p&amp;lt;0.001). CONCLUSION We documented a high incidence of postoperative seizures and potential risk factors in patients following brain tumor surgery. Our figures support postoperative restriction of driving privileges even in seizure-naive patients (12.7% de-novo seizures at 1 year). Of note, epilepsy was the reason for not driving after surgery for a brain tumor only in 9.0%.

How have the recent updated epilepsy classifications impacted on diagnosis and treatment?

ABSTRACT Introduction Epilepsies are a diverse group of disorders which differ regarding prognosis for seizure control and associated comorbidities. Accurate classification is critical to choose the highest yield investigations and best therapeutic options and to provide the most accurate prognoses regarding the expected degree of seizure control, possible remission, and risk of associated comorbidities to patients and their families. This article reviews the recent updates in epilepsy classification to illustrate how accurate classification impacts care for persons with epilepsy. Areas Covered The authors discuss the ILAE 2017 Classification of the Epilepsies along with the modification of the classification for neonatal seizures and epilepsies. They also discuss the ILAE position papers on Epilepsy syndromes in neonates and infants and children of variable age and the Idiopathic Generalized Epilepsies. Expert opinion Accurate epilepsy classification allows selection of the highest yield investigations, choice of optimal therapies, and accurate prognostication of seizures (likelihood of response to antiseizure treatments and likelihood of remission with age), as well as comorbidities (likelihood, type, and severity). As we move into the era of disease modifying therapy, early accurate identification of underlying causes with timely introduction of specific treatments will be crucial to lessen the severity of epilepsy, with improved seizure control and attenuation of associated comorbidities.

P11.12.B SEIZURES IN PATIENTS WITH BRAIN METASTASES FROM BREAST CANCER: RESULTS FROM A RETROSPECTIVE SINGLE-CENTRE STUDY

Abstract BACKGROUND Seizures may be a symptom of brain metastases (BrMs) from breast cancer. Gross-total resection (GTR) is known to correlate with a better seizure control, while the impact of radiotherapy (RT) and chemotherapy (CT) still remains uncertain. In this study, we aimed to explore which clinical and molecular factors might affect seizure control in a cohort of patients with BrMs from breast cancer. Patients and METHODS We retrospectively included patients ≥18 with surgically resected BrMs from primary breast cancer treated in our Institution from 1991 to 2022. RESULTS We included 79 patients in the analysis. Thirty-three (41.7%) had a history of seizures. Seizures prevailed in patients &amp;lt; 50 vs ≥ 50 (59.0% vs 32.0%, p=0.021), and they were not associated with BrMs location, number, or morphology (cystic vs non-cystic; bleeding vs non-bleeding). Patients with low (score 0-1) vs high (score 2-3) STAT3 expression in the peritumoural reactive astrocytes (RAs) had a slightly higher incidence of seizures (50.0% vs 35.0%, p=0.337). Seizure incidence did not differ between HER2+, HR+/HER2- and TNBC patients. Seizures tended to be more common after non-GTR as compared with GTR (21.0% vs 11.0%, p=0.293). RT and CT did not affect seizure control. CONCLUSION Younger age was associated with a higher risk of seizures, whereas different molecular subgroups (HER2+, HR+/HER2-, TNBC) or STAT3 expression in the RAs were not. To our knowledge, this is the first real-life study investigating the correlation between seizures and clinical and molecular factors in patients with BrM from breast cancer.

P11.23.A GLIOBLASTOMA MOLECULAR CORRELATES OF SEIZURE OCCURRENCE/RECURRENCE AFTER SURGERY: THE ROLE OF P53 MUTATION

Abstract BACKGROUND The integration of molecular data and histology changed the diagnostic approach and prognostic characterization for patients with brain tumors. The aim of this study is identify molecular risk factors associated with seizure occurrence and/or recurrence after surgery in patients with brain glioblastoma. MATERIAL AND METHODS Patients with brain glioblastoma were consecutively enrolled and underwent brain surgery, followed by histopathological and molecular evaluation. Immuno-histochemical, molecular (synaptophysin, GFAP, ATRX, p53, ki67 index and MGMT gene promoter methylation) and clinical (age, sex and seizure occurrence/recurrence before and/or after surgery) data were collected. Histopathological and molecular features were compared between patients with and without seizure occurrence/recurrence after surgery. A step-backward logistic regression was performed to investigate the association between molecular features and seizure occurrence/recurrence. RESULTS 100 patients (age 59.51±1.23, 65 males) were enrolled. Forty-nine patients had seizures before surgery. After surgery, 40 patients (age 59.43±1.64, 27 males) had seizure occurrence/recurrence, while 60 (age 59.57±1.75, 38 males) had not. Patients with epilepsy (i.e., seizures before and/or after surgery) had lower synaptophysin (33.33%, p=0.008) and higher p53 (85%, p=0.038) mutation rate compared with patients without epilepsy. In the whole sample, seizure occurrence/recurrence after surgery was significantly associated with p53 mutation (OR: 3.9, CI 1.12-13.50, p=0.032) and seizure occurrence before surgery (OR: 5.3, CI 2.15-13.08, p&amp;lt;0.001). In patients without seizures before surgery, p53 mutation perfectly predicted seizure occurrence, therefore the OR was not computable. In fact, all patients without p53 mutation didn’t have seizure after surgery, while all patients that had seizure after surgery, also had p53 mutation (p=0.028). However, to note 71% patients with p53 mutation didn’t have seizure after surgery. CONCLUSION The p53 mutation is related with a high risk of seizure occurrence/recurrence after surgery in brain glioblastoma, even in patients that didn’t have seizures before surgery. Conversely, the absence of p53 mutation appears to protect against the occurrence of seizures. If confirmed, this result may help in the management of anti-seizure treatment after surgery in brain glioblastoma patients.

CLOZAPINE INDUCED EXTRAPYRAMIDAL SYMPTOMS FOLLOWING ALCOHOL CONSUMPTION IN PATIENT WITH SCHIZOPHRENIA AND ALCOHOL DEPENDENCE SYNDROME: A CASE REPORT OF SIALORRHEA, ACUTE AKATHISIA AND DYSTONIA

Clozapine (CLZ), a second-generation or atypical antipsychotic, although not recommended as the first-line drug of choice in the treatment of schizophrenia and schizoaffective disorders; however, it is recommended in the treatment of Treatment-Resistant Schizophrenia and in schizophrenic patients to decrease the recurrent risk of suicidal behavior. For the cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4, CLZ serves as a substrate. CLZ also exhibits drug-food interaction with alcohol leading to an increase in the risk of seizures and extrapyramidal symptoms. A case of a 36-year-old male patient with a known history of paranoid schizophrenia and alcohol dependence syndrome came with complaints of dystonia and hypersalivation 1 day following the consumption of alcohol after ingestion of tablet CLZ. After clinical pharmacist intervention, the doses were titrated and the patient improved gradually. With this, it can be postulated that the concomitant use of alcohol with CLZ can be a predisposing factor for drug toxicity in the patients and hence patients should be monitored and counseled to abstain from the use of alcohol while on CLZ therapy.

An information-motivation-behavioral skills model-based intervention for patients with epilepsy

PurposeSelf-management is crucial for patients with epilepsy (PWE) as it can effectively control the condition, improve treatment outcomes, and reduce the risk of seizures. The objective of this study was to evaluate the effectiveness of health education based on the Information-Motivation-Behavioral Skills (IMB) model in improving self-management, quality of life, and medication adherence among PWE. MethodThis study was conducted in a district in Shanghai, China, from September 2022 to March 2023. A total of 90 PWE were randomly assigned to an intervention group or a control group. Patients in the intervention group received health education based on the IMB model, whereas those in the control group received routine medical treatment only. The effectiveness of the intervention was evaluated by measuring self-management ability, quality of life, and medication adherence at three months and six months after the intervention. ResultsThe study included a total of 90 PWE; among them, 55 patients (61.11%) were male, divided into two groups: 45 participants in the control group and 45 participants in the intervention group. After 3 and 6 months of intervention, the self-management scores of the intervention group were significantly higher than those of the control group (t = 14.274, 12.448; P < 0.05). After 6 months of the intervention, the quality-of-life scores of the intervention group were significantly higher than those of the control group (t = 2.025, P < 0.05), and the medication adherence in the intervention group was significantly higher than that in the control group (X2 = 9.003, P < 0.05). ConclusionHealth education based on the IMB model is a promising approach to improving self-management, quality of life, and medication adherence among PWE. It provides personalized, patient-centered interventions that consider patients' knowledge, motivation, and behavior skills, and could be a useful tool for healthcare providers in developing comprehensive care plans for individuals with epilepsy.

Nocturnal seizure detection: What are the needs and expectations of adults with epilepsy receiving secondary care?

IntroductionSeizure detection devices (SDDs) may lower the risk of sudden unexpected death in epilepsy (SUDEP) and provide reassurance to people with epilepsy and their relatives. We aimed to explore the perspectives of those receiving secondary care on nocturnal SDDs and epilepsy in general. Materials and methodsWe recruited adults with tonic or tonic-clonic seizures who had at least one nocturnal seizure in the preceding year. We used semi-structured interviews and questionnaires to explore their views on SDDs and their experiences of living with epilepsy. None of the participants had any previous experience with SDDs. We analyzed the data using qualitative content analysis. ResultsEleven participants were included with a nocturnal seizure frequency ranging from once every few weeks to less than once a year. Some participants experienced little burden of disease, whereas others were extremely impaired. Opinions on the perceived benefit of seizure detection varied widely and did not always match the clinical profile. Some participants with high SUDEP risk displayed no interest at all, whereas others with a low risk for unattended seizures displayed a strong interest. Reasons for wanting to use SDDs included providing reassurance, SUDEP prevention, and improving night rest. Reasons for not wanting to use SDDs included not being able to afford it, having to deal with false alarms, not having anyone to act upon the alarms, having a relative that will notice any seizures, not feeling like the epilepsy is severe enough to warrant SDD usage or not trusting the device. ConclusionsThe interest in nocturnal seizure detection varies among participants with low seizure frequencies and does not always match the added value one would expect based on the clinical profile. Further developments should account for the heterogeneity in user groups.

A novel approach to seizures in neonates.

Recognition of seizures in neonates remains the foremost challenge to overcome. All neonates at risk for seizures, especially the critically ill, should undergo video-EEG monitoring. The initial step toward an accurate diagnosis is the accurate description and interpretation of the electro-clinical phenotype. THE IMPORTANCE OF SEIZURE SEMIOLOGY AND ASSOCIATION WITH ETIOLOGY: The early distinction between acute provoked seizures and neonatal-onset epilepsies serves as the primary determinant for guiding management, treatment choices, and duration. Seizures in neonates should be seen as a symptom, not a disease, and their semiology may suggest the etiology. Neonates with hypoxic-ischemic encephalopathy respond best to phenobarbital, while levetiracetam is a better choice for neonates with congenital heart diseases. Anti-seizure medication can be discontinued after 72h of seizure freedom, before discharge from the hospital. Neonates with epilepsy usually require a personalized, etiology-based approach in terms of choice and duration of treatment. Neonates with channelopathies tend to respond to sodium channel blockers such as carbamazepine, oxcarbazepine, or phenytoin. The surgical option should be considered early in cases of large brain malformations, such as hemimegalencephaly.

Intracranial intraoperative radiotherapy (IORT): evaluation of electrocorticography and peri-operative seizure risk.

Intra-operative radiotherapy (IORT) for brain metastases (BMs) and primary brain tumors has emerged as an adjuvant radiation modality that allows for consolidation of care into a single anesthetic episode with surgical resection. Yet, there is a paucity of data regarding the impact that IORT may have on peri-operative and long-term seizure risk. A retrospective analysis of patients receiving IORT during tumor resection was performed via registry including data regarding peri-operative anti-seizure medications and anesthetic agents. Intra-operative neuromonitoring was performed using electrocorticography (ECoG) captured before-, during-, and after-IORT then analyzed for evidence of seizure or significant baseline changes. Kaplan-Meir estimations were used for overall survival analysis relative to documented clinical seizure incidence post-IORT. Of the 24 consecutive patients treated with IORT during tumor resection included, 18 (75%) patients were diagnosed with BMs while 6 (25%) had newly-diagnosed glioblastoma. Mean and median survival times were 487 and 372 days, respectively. Clinical seizures occurred in 3 patients post-IORT, 2 BMs patients within 9 months and 1 glioblastoma patient at 14 months. IORT time represented 9.5% of anesthetic time. ECoG recordings were available for 5 patients (4 BMs; 1 glioblastoma), with mean recording durations of 13% of the total anesthetic time and no evidence of high-frequency oscillations or seizure activity. IORT is an option for delivery of definitive radiation in surgically resected brain tumors without increasing the peri-operative or long-term risk of seizure. ECoG data during the delivery of radiation fail to demonstrate any electrophysiological changes in response to ionizing radiation.

Early-infantile developmental and epileptic encephalopathy: the aetiologies, phenotypic differences and outcomes—a prospective observational study

Abstract In this study, we have evaluated the underlying aetiologies, yield of genetic testing and long-term outcomes in patients with early-infantile developmental and epileptic encephalopathies. We have prospectively studied patients with seizure onset before 3 months of age. Based on the clinical details, neuroimaging, metabolic testing and comprehensive genetic evaluation, patients were classified into different aetiological groups. The phenotypic differences between genetic/unknown groups and remaining aetiologies were compared. Factors that could affect seizure control were also assessed. A total of 80 children (M:F ratio—1.5:1) were recruited. The median seizure onset age was 28 days (range, 1–90 days). The aetiologies were confirmed in 66 patients (83%). The patients were further classified into four aetiological groups: genetic (50%), structural (19%), metabolic (14%; all were vitamin responsive) and unknown (17%). On comparing for the phenotypic differences between the groups, children in the ‘genetic/unknown’ groups were more frequently observed to have severe developmental delay (Odds Ratio = 57; P &amp;lt; 0.0001), autistic behaviours (Odds Ratio = 37; P &amp;lt; 0.0001), tone abnormalities (Odds Ratio = 9; P = 0.0006) and movement disorder (Odds Ratio = 19; P &amp;lt; 0.0001). Clonic seizures were more common in the vitamin responsive/structural groups (Risk Ratio = 1.36; P = 0.05) as compared to patients with ‘genetic/unknown’ aetiologies. On the contrary, vitamin responsive/structural aetiology patients were less likely to have tonic seizures (Risk Ratio = 0.66; P = 0.04). Metabolic testing was diagnostic in three out of 41 patients tested (all three had biotinidase deficiency). MRI was abnormal in 35/80 patients (malformation observed in 16/35; 19/35 had non-specific changes that did not contribute to underlying aetiology). A molecular diagnosis was achieved in 53 out of 77 patients tested (69%). Next-generation sequencing had a yield of 51%, while microarray had a yield of 14%. STXBP1 was the most common (five patients) single-gene defect identified. There were 24 novel variants. The mean follow-up period was 30 months (range, 4–72 months). On multivariate logistic regression for the important factors that could affect seizure control (seizure onset age, time lag of first visit to paediatric neurologist and aetiologies), only vitamin responsive aetiology had a statistically significant positive effect on seizure control (P = 0.02). Genetic aetiologies are the most common cause of early-infantile developmental and epileptic encephalopathies. Patients in the genetic/unknown groups had a more severe phenotype. Patients with vitamin responsive epilepsies had the best probability of seizure control.

Neurosurgical Aspect of Management of Movement Disorders

Background People with movement disorders can experience involuntary movement such as tremor, abnormal posture, slowness, walking difficulty, and stiffness due to neurological conditions. Aim of the Work to conduct a meta-analysis of surgical treatment of patients with movement disorder diseases and help patients for living normal life and performing all sports and hand skill work without any limitation of movement, and improve surgical management, learn indication of surgery, patient selection, techniques, and complications among functional neurosurgeons. Methods Searching procedures will be conducted focusing on the following sources: electronic databases: Medline; 2) Bibliographies and 3) Hand searches of journals: -Online internet search from the electronic database of Medline via PubMed, “Related articles” function will be used to obtain any relevant articles. Additionally, references of the articles included in the analysis were reviewed for any other citations. After screening full text of the included studies the following data was extracted from each primary study: study design, full reference of article including author, year and source, population description: criteria for diagnosis, severity of disease. Intervention: Thalamotomy and DBS alone. Comparative Group (if relevant) and outcome. Results The efficacy in reducing drug-resistant tremor was non-significantly equal among DBS group and thalamotomy group. Cognitive changes were nonsignificantly less among DBS than thalamotomy groups. Gait disturbances were non-significantly lower among DBS than among thalamotomy group. Ataxia risk was non-significantly lower among DBS than among thalamotomy group. Dysarthria risk was non-significantly different among DBS and thalamotomy groups. Hypresthesia risk was non-significantly lower among DBS than among thalamotomy groups. Seizures risk was non-significantly higher among DBS group than among thalamotomy group. Paresis risk was non-significantly lower among DBS than among thalamotomy groups. Psychiatric disturbances risk was non-significantly different among DBS and thalamotomy groups. Intracerebral hemorrhage was significantly lower among DBS than among thalamotomy. That mean DBS is Equal in efficacy and less adverse effects but more expensive than thalamotomy. Conclusion Net result of complications of Thalamic stimulation is less than thalamotomy due to our meta-analysis which show that the incidence of intra cerebral hemorrhage is more in thalamotomy than thalamic stimulation, and the incidence of ataxia, gait disturbance, hypoesthesia and paresis are more in thalamotomy than thalamic stimulation but the incidence of seizers is higher in thalamic stimulation than thalamotomy. But there are another complication which is different in results between both such as dysarthria and psychiatric disturbance.

Treatment of Refractory Epilepsy With MEK Inhibitor in Patients With RASopathy

BackgroundSeveral specific syndromes within the RASopathies spectrum lead to an increased risk of seizures up to developing refractory epileptic encephalopathy. Management remains symptomatic. MethodsHere we report two patients treated with trametinib, a MEK1-2 inhibitor, as a precision strategy for drug-resistant epilepsy. Patient 1 is a six-year-old girl with cardiofaciocutaneous syndrome (BRAF p.F595L, germline mutation), and Patient 2 is a 14-month-old boy with Schimmelpenning syndrome (KRAS p.G12D, postzygotic somatic mutation). Trametinib was initiated at a dosage of 0.025 mg/kg/day. ResultsPatient 1 had multiple seizures per day, multifocal motor to bilateral tonic-clonic. Electroencephalography (EEG) showed a dramatic reduction in EEG discharges three months after trametinib onset, while a marked clinical improvement occurred after about five months, at the same dosage, and the girl is currently seizure-free for more than six months.Patient 2 had left cerebral hemiatrophy leading to right focal motor seizures, multiple per week to multiple per day, since the age of three months. On trametinib, he experienced an early benefit, remaining seizure-free for more than three months. However, after six months we observed recurrence of seizures. After 22 months of treatment, trametinib was discontinued because of a suspected drug-induced inflammatory colitis. After discontinuation, we observed a significant clinical and EEG “rebound effect.” ConclusionsWe provide proof of concept that MEK inhibition is a promising approach for the treatment of patients with refractory epilepsy with selected germline and mosaic RASopathies. Future trials are encouraged to better investigate their potentials and limitations.