Risk Of Seizures Research Articles

Patient-Centered Management of Brain Tumor-Related Epilepsy.

Brain tumor-related epilepsy is a heterogenous syndrome involving variability in incidence, timing, pathophysiology, and clinical risk factors for seizures across different brain tumor pathologies. Seizure risk and disability are dynamic over the course of disease and influenced by tumor-directed treatments, necessitating individualized patient-centered management strategies to optimize quality of life. Recent translational findings in diffuse gliomas indicate a dynamic bidirectional relationship between glioma growth and hyperexcitability. Certain non-invasive measures of hyperexcitability are correlated with survival outcomes, however it remains uncertain how to define and measure clinically relevant hyperexcitability serially over time. The extent of resection, timing of pre-operative and/or post-operative seizures, and the likelihood of tumor progression are critical factors impacting the risk of seizure recurrence. Newer anti-seizure medications are generally well-tolerated with similar efficacy in this population, and several rapid-onset seizure rescue agents are in development and available. Seizures in patients with brain tumors are strongly influenced by the underlying tumor biology and treatment. An improved understanding of the interactions between tumor cells and the spectrum of hyperexcitability will facilitate targeted therapies. Multidisciplinary management of seizures should occur with consideration of tumor-directed therapy and prognosis, and anti-seizure medication decision-making tailored to the individual priorities and quality of life of the patient.

Management of alcohol withdrawal syndrome (AWS)

Alcohol withdrawal syndrome (AWS) is a complex set of symptoms that occur in alcohol-dependent individuals after sudden withdrawal or a significant reduction in alcohol consumption. AWS symptoms occur in about 50% of alcohol abusers. These symptoms may include restlessness, tremor, nausea, nervousness, tachycardia, elevated blood pressure, hyperhidrosis, insomnia, hyperactivity, and hallucinations. In some cases, seizures may occur and delirium tremens may develop, which is life-threatening and an absolute indication for hospitalization of the patient. Effective treatment of AWS is the key to prevent complications and to reduce the risk of death. Treatment of alcohol withdrawal syndrome requires a complex approach that combines properly performed diagnosis, careful monitoring of the patient's condition, pharmacotherapy, equalization of electrolyte disorders, adequate hydration of the patient, supplementation of thiamine deficiencies and, in the case of symptoms of alcoholic delirium, intensive medical care. Pharmacological treatment plays a key role, with the first line of treatment being benzodiazepines, which reduce the risk of epileptic seizures and delirium tremens, and reduce mortality in the course of AWS. Individualized therapy adjustment and patient monitoring are crucial to ensure effective and safe treatment.

Pro-inflammatory cytokine activity: The root cause of catamenial seizures

About 40% of women with epilepsy experience catamenial seizures, which can be mentally and physically debilitating. Catamenial epilepsy (CE) refers to the relationship between the timing of a woman’s seizures and the monthly hormonal changes that occur throughout her menstrual cycle. The prevailing hypothesis theorizes that these hormonal changes cause CE seizures. However, researchers have not isolated the catamenial seizure neurological trigger mechanism; as a result, standard anti-seizure medications (ASMs) mostly are ineffective. Recent research substantiates the significant role inflammatory cytokines play in epilepsy, menstrual disorders, and the female reproductive system. This paper poses a new hypothesis that the direct trigger of catamenial seizures is an increase in pro-inflammatory cytokines that occurs at several times during the menstrual cycle. The hypothesis is evaluated using published evidence that the occurrences of catamenial seizures during the menstrual cycle align temporally with the surges in pro-inflammatory cytokines. Consequently, the anti-inflammatory benefits of exercise, endocannabinoid-based drugs and safe, neuroprotective dietary supplements could enable hundreds of thousands of women with catamenial epilepsy to enjoy more productive lives from a much reduced risk of seizures.

Glycogenolysis-Induced Astrocytic Serping1 Expression Regulates Neuroinflammatory Effects on Hippocampal neuron.

The bacterial pathogen, lipopolysaccharide (LPS), elicits microglial response and induces cytokine secretion that subsequently activates astrocytes. Recent findings have indicated that LPS-induced activation of postnatal glial cells has led to alterations in synapse formation in hippocampal and cortical neurons, thereby resulting in a prolonged increased risk for seizure or depression. Nevertheless, its mechanisms remain to be fully elucidated. Cellular metabolism has recently gained recognition as a critical regulatory mechanism for the activation of peripheral immune cells, as it supplies the requisite energy and metabolite for their activation. In the present study, we report that LPS did not change the expression of reported astrocyte-derived synaptogenic genes in the postnatal hippocampus; however, it induced upregulation of astrocytic complement component regulator Serping1 within the postnatal hippocampus. As a regulatory mechanism, activation of glycogen degradation (glycogenolysis) governs the expression of a subset of inflammatory-responsive genes including Serping1 through reactive oxygen species (ROS)-NF-κB axis. Our study further demonstrated that glycogenolysis is implicated in neurotoxic phenotypes of astrocytes, such as impaired neuronal synaptogenesis or cellular toxicity. These findings suggested that activation of glycogenolysis in postnatal astrocytes is an essential metabolic pathway for inducing responses in inflammatory astrocytes.

Critical dynamics and interictal epileptiform discharge: a comparative analysis with respect to tracking seizure risk cycles.

Epilepsy is characterized by recurrent, unprovoked seizures. Accurate prediction of seizure occurrence has long been a clinical goal since this would allow to optimize patient treatment, prevent injuries due to seizures, and alleviate the patient burden of unpredictability. Advances in implantable electroencephalographic (EEG) devices, allowing for long-term interictal EEG recordings, have facilitated major progress in this field. Recently, it has been discovered that interictal brain activity demonstrates circadian and multi-dien cycles that are strongly aligned, or phase locked, with seizure risk. Thus, cyclical brain activity patterns have been used to forecast seizures. However, in the effort to develop a clinically useful EEG based seizure forecasting system, challenges remain. Firstly, multiple EEG features demonstrate cyclical patterns, but it remains unclear which feature is best suited for predicting seizures. Secondly, the technology for long-term EEG recording is currently limited in both spatial and temporal sampling resolution. In this study, we compare five established EEG metrics:synchrony, spatial correlation, temporal correlation, signal variance which have been motivated from critical dynamics theory, and interictal epileptiform discharge (IED) which are a traditional marker of seizure propensity. We assess their effectiveness in detecting 24-h and seizure cycles as well as their robustness under spatial and temporal subsampling. Analyzing intracranial EEG data from 23 patients, we report that all examined features exhibit 24-h cycles. Spatial correlation, signal variance, and synchrony showed the highest phase locking with seizures, while IED rates were the lowest. Notably, spatial and temporal correlation were also found to be highly correlated to each other, as were signal variance and IED-suggesting some features may reflect similar aspects of cortical dynamics, whereas others provide complementary information. All features proved robust under subsampling, indicating that the dynamic properties of interictal activity evolve slowly and are not confined to specific brain regions. Our results may aid future translational research by assisting in design and testing of EEG based seizure forecasting systems.

Antiepileptic Drugs as Prophylaxis for Seizures after Excision of Brain Tumors

Abstract Background Seizures are the most common & most serious side effect of cranial surgery. The latter condition requires chronic treatment with Antiepileptic drugs (AEDs) and comes with relevant socioeconomic sequelae. The routine prophylactic use of AEDs for people undergoing tumor resection has remained controversial due to the risk of postoperative seizures. Some Neurosurgeons are advocates to the use of AEDs to reduce the risk of these seizures. Objective To evaluate the efficacy of prophylactic AEDs routinely in brain tumor patients without previous history of seizures. Primary objective has been to identify the efficacy of AEDs in perioperative seizure prophylaxis. Secondary objective has been to highlight the most common type of post-operative AEDs. Methods All available studies from 2000-2021 including randomized or non-randomized clinical trials, prospective or retrospective observational cohort studies, and case series of six or more cases that address these criteria have been collected. Results Our search concluded that the most common type of post-operative seizure is the Early seizure which is of total 87 patients representing 12.3% of seizure reported patients, yet when comparing the P-value between the Early & late seizure it has a P-value of 0.415 which is nonsignificant rendering the comparison redundant. The Most common types of AED used are Phenytoin (PHT) 89 (71.8%) & Levetiracetam (LEV) 109 (81.8%). To measure the efficacy of AEDs two groups of patients with no history of AED administration or seizures preoperatively were created, one the control group of 268 participants were not administered AEDs postoperatively only 32 (11.94%) of them suffered from seizures postoperatively. The other group of 171 participants were administered the AEDs postoperatively only 25 (14.62%) of these participants suffered from postoperative seizure. Comparing both of these results statistically it had a P-value of 0.416 which is non-Significant statistically. On interpreting these results was that the AED have no influence in controlling the seizures. Conclusion Postoperative seizures are one of the main complications of brain tumor surgery. Neurosurgeons have a strong belief more of tradition that preventing seizures with Anti-Epileptic Drugs (AEDs) as a sort of seizure prophylaxis is not only effective but also necessary. Finally, there is not enough evidence of sufficient quality available to suggest that antiepileptic drugs AEDs treatment can or cannot be recommended to reduce Post-craniotomy seizures.

MTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.

Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear. Brain EC-specific CCM3-deficient (Pdcd10BECKO) mice were generated by crossing Pdcd10fl/fl mice with Mfsd2a-CreERT2 mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches. Single-cell RNA-sequencing analyses from P10 Pdcd10BECKO mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier-associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6 Pdcd10BECKO brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the Pdcd10BECKO model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in Pdcd10BECKO mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins. CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss-induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.

Not All Patients with a Headache need a CT Scan, but they should be Listened to, and also with a Stethoscope: A Report of a Large Arteriovenous Malformation with a Loud Cranial Bruit.

Arteriovenous malformations (AVMs) are abnormal direct connections between arterial and venous systems, without an interposed capillary bed. This permits high-flow arteriovenous shunting, which precipitates structural changes in the afferent and efferent vessels, namely arterial smooth muscle hyperplasia and thinning of venous walls. Patients with intracranial AVMs typically present with a haemorrhage, headache or seizure. Treatment is either via medical management aimed at control of seizures, headache and blood pressure, or interventional via surgical, radiation or radiologically guided embolisation. We report the case of a woman in her early 40s presenting with a tonic-clonic seizure against a background of a 31-year history of migraine and an 18-month history of tremors in her right arm. The clinical examination was remarkable for an extremely loud cranial bruit and a right homonymous hemianopia. Imaging diagnosed an 8 cm Martin-Spetzler grade V intracranial arteriovenous malformation in her left parietal lobe, which was deemed unsuitable for operative or radiotherapy-based intervention. The patient was managed through observation and relatively good control of her breakthrough seizures was achieved through the addition of brivaracetam to her lamotrigine and carbamazepine-based therapy, six years after her initial presentation. Arteriovenous malformations may go undetected for decades.The presence of a cranial bruit is an important sign and tool in diagnosing an intracranial arteriovenous malformation. The presence of a homonymous hemianopia, of which a patient may be unaware, helps to localise an intracranial lesion.The risks of operative or radiological intervention must be balanced with the risks of haemorrhage or refractory seizure when adopting a strategy for the treatment of an intracranial arteriovenous malformation. Good control of epileptic symptoms in those deemed not suitable for operative or radiological intervention can be achieved by careful titration of anti-seizure medications.

Characteristics of Stroke-related Seizures and their Predictive Factors: A Tertiary Care Center Experience.

Various risk factors have been described in the literature that increase the risk of seizures associated with stroke. This study was aimed to determine the occurrence rate of poststroke seizures (PSSs) and the associated risk factors in Arab population. Study included all stroke patients aged >18 years with a minimum follow-up of 24 months following stroke to identify seizure occurrence. Patient's hospital records for all admissions and clinic visits were reviewed. Seizures were classified into early PSS if they occur within 1 week of stroke, and late PSS if they occur after 1 week of stroke. Out of 594 patients, 380 were males. Seizure occurrence was higher in anterior circulation infarctions (94.8%, P < 0.05), cortical location (80.5%, P < 0.05), large artery atherosclerosis (63.8%, P < 0.05), lower activated partial thromboplastin time (APTT) (P = 0.0007), patients with ischemic heart disease (IHD) (P = 0.01), and those who underwent craniotomy (P = 0.001). Nonhigh-density lipoprotein cholesterol was inversely related to PSS (P = 0.01). Higher stroke severity (89%) and confusion (67%) at the time of presentation were independently related to PSS. Eighty-two (13.8%) patients had PSS. Greater stroke severity at presentation with altered sensorium was independent risk factors for the development of PSS. Patients with underlying IHD, lower APTT, and undergoing neurosurgical intervention require vigilant monitoring for PSS.

Medication Reconciliation Errors on Discharge for Epilepsy Monitoring Unit Patients.

Medication errors are common in the inpatient setting. Epilepsy patients who miss doses of their antiseizure medications are at risk for breakthrough seizures and subsequent complications. The purpose of this study was to quantify and characterize anti-seizure medications reconciliation errors on discharge from the epilepsy monitoring unit (EMU). Consecutive admissions to an academic medical center EMU were retrospectively reviewed. Medication reconciliation errors on discharge, including drug errors, dosing errors, and dose timing errors, were recorded. Associations between medication errors and clinical and demographic variables were analyzed using binary logistic regression for continuous variables and Fisher exact tests for categorical variables. One hundred and eleven admissions between January 1, 2021 and December 31, 2021 were identified. Fourteen anti-seizure medication reconciliation errors were recorded during 11 unique admissions (9.9% of admissions). The most common error type was dosing error (10/14 errors; 71.4%). Number of antiseizure medications on admission (p=0.004), total number of medications on admission (p=0.013), number of medication changes during admission (p=0.0007), and length of stay (p=0.0001) were associated with increased likelihood of errors. Medication reconciliation errors upon discharge from the EMU occur during approximately 10% of admissions. A higher number of preadmission antiseizure medications, higher total number of preadmission medications, higher number of medication changes during admission, and longer length of stay are associated with increased risk of discharge medication reconciliation errors. Careful attention should be paid to patients with these risk factors.

Risk of breakthrough seizures depends on type and etiology of epilepsy.

This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure-free for at least 12 months varies among different types and etiologies of epilepsy. Given the relative ease of achieving seizure freedom with ASM in patients with post-ischemic stroke epilepsy, we hypothesized that this etiology is associated with a reduced risk of breakthrough seizures. We defined a breakthrough seizure as an unprovoked seizure occurring while the patient was taking ASM after a period of at least 12 months without seizures. Data were analyzed retrospectively from a tertiary epilepsy outpatient clinic. Patients were eligible for inclusion if they either had a breakthrough seizure at any time or a seizure-free interval of at least 2 years. Our primary endpoint was rate of breakthrough seizures. We conducted univariable and multivariable analyses to identify variables associated with breakthrough seizures. Of 521 patients (53% females, median age = 49 years) included, 29% had a breakthrough seizure, which occurred after a median seizure-free interval of 34 months (quartiles = 22, 62). When controlling for clinically relevant covariates, breakthrough seizures were associated with post-ischemic stroke epilepsy (odds ratio [OR] = .267, 95% confidence interval [CI] = .075-.946), genetic generalized epilepsy (OR = .559; 95% CI = .319-.978), intellectual disability (OR = 2.768, 95% CI = 1.271-6.031), and the number of ASMs previously and currently tried (OR = 1.203, 95% CI = 1.056-1.371). Of the 151 patients with breakthrough seizures, 34.3% did not reachieve terminal 12-month seizure freedom at the last visit. This is the first study to show an association between type and etiology of epilepsy and risk of breakthrough seizures. Our data suggest that epilepsies in which seizure freedom can be obtained more easily also exhibit a lower risk of breakthrough seizures. These findings may help to better counsel seizure-free patients on their further seizure prognosis.

Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises

BackgroundThis retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA. MethodsMedical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently. ResultsEighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 μmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 μmol/L increase in glutamine. ConclusionsThis study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.

The course of tumor-related epilepsy in glioblastoma patients: A retrospective analysis

PurposeMany patients with glioblastoma suffer from tumor-related seizures. However, there is limited data on the characteristics of tumor-related epilepsy achieving seizure freedom. The aim of this study was to characterize the course of epilepsy in patients with glioblastoma and the factors that influence it. MethodsWe retrospectively analyzed the medical records of glioblastoma patients treated at the University Hospital Erlangen between 01/2006 and 01/2020. ResultsIn the final cohort of patients with glioblastoma (n = 520), 292 patients (56.2 %) suffered from tumor-related epilepsy (persons with epilepsy, PWE). Levetiracetam was the most commonly used first-line antiseizure medication (n = 245, 83.9 % of PWE). The onset of epilepsy was preoperative in 154/292 patients (52.7 %). 136 PWE (46.6 %) experienced only one single seizure while 27/292 PWE (9.2 %) developed drug-resistant epilepsy. Status epilepticus occurred in 48/292 patients (16.4 %). Early postoperative onset (within 30 days of surgery) of epilepsy and total gross resection (compared with debulking) were independently associated with a lower risk of further seizures. We did not detect dose-dependent pro- or antiseizure effects of radiochemotherapy. ConclusionTumor-related epilepsy occurred in more than 50% of our cohort, but drug-resistant epilepsy developed in less than 10% of cases. Epilepsy usually started before tumor surgery.

Natural History and Predictors for Hemorrhage in Supratentorial Brain Arteriovenous Malformations.

Background/Objectives: Approximately half of the patients harboring supratentorial brain arterio-venous malformations (stAVMs) present with hemorrhage, and another considerable proportion suffer from epileptic seizures. An important milestone in the management of this vascular pathology is acknowledging their natural history, especially across long periods of time. The aim of this study was to assess the predictive factors for hemorrhage and for epileptic seizures as presenting symptoms in stAVMs. Methods: We retrospectively analyzed patients with stAVMs admitted to our institution between 2012 and 2022 and evaluated predictive factors for hemorrhage and the risk factors associated with epileptic seizures. Results: The cohort included 169 patients, 78 of them (46.2%) presenting with intracerebral hemorrhage (ICH). Seventy-seven (45.5%) patients suffered from epileptic seizures. The annual hemorrhagic rate was 1.28%/year. Unruptured lesions (p = 0.001, OR 3.1, 95% CI 1.6-6.2), superficial venous drainage (p = 0.007, OR 2.7, 95% CI 1.3-5.7) and large nidus size (p = 0.025, OR 4, 95% CI 1.2-13.5) were independently associated with seizures. Among unruptured lesions, superficial venous drainage (OR 2.6, p = 0.036, 95% CI 1.06-6.3) and frontal/temporal/parietal location (OR 2.7, p = 0.040, 95 CI% 1.04-6.9) significantly increased the risk of seizures as a presenting symptom in multivariate analysis. Patients younger than 18 (p = 0.003, OR 4.5, 95% CI 1.6-12.2), those with AVMs < 3 cm (p = 0.03, OR 2, 95% CI 1.07-3.9) or those with deep located AVMs (p = 0.035, OR 2.3, 95% CI 1.06-5.1) presented statistically more often with ICH in multivariate regression. Small size (HR 1.8, 95% CI 1.09-3, p = 0.022) and exclusively deep venous drainage (HR 2.2, 95% CI 1.2-4, p = 0.009) were independent predictors for ICH, in time-dependent birth-to-diagnosis analysis. After shifting the birth-to-diagnosis curve by 10 years, unique arterial feeder demonstrated a positive correlation with ICH presentation as well. Conclusions: Small AVMs, those with exclusively deep venous drainage, unique arterial feeder or deep location may pose higher hemorrhagic risks for the patient, and therapeutic strategies should be tailored accordingly. When managing unruptured brain AVMs, it is important to consider the risk of developing seizures, in addition to the lifelong risk of hemorrhage, in determining the optimal treatment approach for each patient.

Unraveling the Shared Genetic Elements Among COVID-19 and Epilepsy: A Computational and Bioinformatics Analysis

The outbreak of COVID-19 linked to the SARS-CoV-2 virus has raised worries about its potential to worsen pre-existing health issues such as autoimmune conditions. One common autoimmune condition seen across all individuals is epilepsy. Our detailed computational study examined the complex connection between COVID-19 and epilepsy, with a focus on their possible impact on neurodegenerative disorders. Leveraging transcriptome analysis, we aimed to interpret shared pathways and molecular biomarkers between COVID-19 and epilepsy using RNA-seq datasets. Cutting-edge bioinformatics tools facilitated Network, Enrichment, and route analysis, along with the identification of pivotal gene signatures, notably through comprehensive exploration of machine learning methods and protein-protein interactions. This work identified 1040 common differentially expressed genes (DEGs), forming the basis for unraveling shared pathways and potential drug targets. By employing statistical methods and diverse network analyses, we meticulously identified genetic elements shared between COVID-19 and epilepsy. The analysis reveals that 10 key genes, including CATIP, CDC25C, GPR132, NTS, PDE8B, PLK1, SLC12A9, SPC25, TUBAIA, and TYMS, are crucial in bridging transcriptomic alterations across various scenarios. A subset of these genes exhibited existence within distinct regulatory networks, signifying their significant role in the shared disease mechanisms of COVID-19 and epilepsy. Notably, CDC25C, PLK1, and TYMS emerged as prominent genes within the COVID-19 and epilepsy networks, strongly suggesting their vital roles in connecting regulatory mechanisms across these conditions. Further validation through molecular docking studies will confirm the significance of CDC25C, PLK1, and TYMS, potentially shedding light on new opportunities for targeted therapeutic interventions aimed at reducing the risk of seizures in individuals affected by COVID-19 and epilepsy.

First-ever seizure and eligibility for commercial motor vehicle driving

BackgroundAfter a first-ever seizure, 6 months of seizure freedom is usually required before returning to driving a private motor vehicle, after which the annual risk of seizure recurrence has fallen...

Effects of ambient temperature on pediatric incident seizure: A case-crossover analysis using distributed lag non-linear models

ObjectiveEmerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. Material and methodsData on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51% < 5 years old and 26.49 % ≥ 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). ResultsWe observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20 °C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0–21 days preceding the onset at the 5th percentile of the temperature (3 °C) and at the 95th percentile (29 °C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1 °C increases in TV0–7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. ConclusionBoth low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.

Children with ADHD and EEG abnormalities at baseline assessment, risk of epileptic seizures and maintenance on methylphenidate three years later

PurposeThis study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance on methylphenidate (MPH) over a three-year period.MethodsA total of 517 ADHD children aged 6–14 years were included. Baseline assessments included the identification of EEG-ab, ADHD inattentive subtype (ADHD-I), comorbid epilepsy, the use of antiepileptic drugs (AEDs) and the use of MPH. At the 3-year follow-up, assessments included the presence of EEG-ab, maintenance on MPH, AED usage, SZ risk in cases with EEG-epileptiform abnormalities (EEG-epi-ab), compared with control ADHD cases without EEG-epi-ab matched for age and gender.ResultsEEG-ab were identified in 273 (52.8%) cases. No statistically significant differences were observed between the EEG-ab and EEG-non-ab groups in terms of age, gender, ADHD-I type or initial use of MPH. EEG non-epileptiform abnormalities (EEG-non-epi-ab) were found in 234 out of 478 (49%) cases without EEG-epi-ab. Notably, EEG-non-epi-ab occurred more frequently in the group of 39 cases with EEG-epi-ab (30/39 (76.9%) vs. 9/39, (21.3%), a subset selected for 3-year follow-up. At 3-year-follow-up no statistically significant difference was found in maintenance on MPH in ADHD cases with and without EEG-epi-ab. Nobody of ADHD cases without comorbid epilepsy or with comorbid epilepsy with achieved SZ freedom developed new SZ. Only 3 children with drug resistant epilepsy experienced SZs, without increase in SZ frequency. The disappearance rate of EEG-epi-ab was higher than that EEG-non-epi-ab (71.8% vs. 33.3%).ConclusionsChildren with and without EEG-ab exhibited similar patterns of MPH use (initial use, positive response, and maintenance on MPH). The presence of comorbid epilepsy and EEG-ab, with or without EEG-epi-ab, was not associated with an increased risk of SZ despite the use of MPH.

New valproate regulations, informed choice and seizure risk

Valproate is the most effective medication for generalised epilepsies, and several specific epilepsy syndromes. For some people, it will be the only medication to establish seizure remission, and withdrawing it carries risks of seizure recurrence and Sudden Unexpected Death in Epilepsy (SUDEP). It is also of proven efficacy for bipolar disorder and migraine prevention. Guidelines based on observational and epidemiological studies stress that maternal valproate related teratogenicity and neurodevelopmental effects are significantly higher than for other antiseizure medications (ASMs). It should, therefore, only be used if other medications are ineffective and after balancing the teratogenicity risk. Regulatory restrictions have changed prescribing practices and reduced valproate use. The number of other medications that must be trialled in the different conditions for which valproate has effectiveness and the consequences of the lack of efficacy of those drugs leading to significant harm including death remains unexplored. Risk minimisation measures (RMMs) for valproate, chiefly Pregnancy Prevention practices (PPP), consider foetal risk and not risk to people living with epilepsy. In the United Kingdom (UK), limitations relating to valproate use in all people < 55 years commenced in January 2024. While the evidence in child-bearing women is not disputed, the data in males are based on animal models, case reports, and one commissioned, unpublished, non-peer reviewed report unavailable to the UK public, stakeholder charities or professionals. Evidence suggests that 30–40% of people switching from valproate have breakthrough seizures. Thus, an estimated 21,000–28000 people in the UK will imminently be exposed to the potential hazards of breakthrough seizures, including death. There is little government investment in monitoring the effects of these changes to valproate prescribing on patient health and quality of life. This review summarises the history of valproate regulation, evidence underpinning it and argues how the latest regulations in the UK do not align with the country’s medical regulatory bodies ethical principles nor with the Montgomery principles of informed patient choice and autonomy. It dissects how such regulations infringe Common Law principles, nor give due regard for patient outcomes beyond reproduction. The paper looks to provide recommendations to redress these concerns while appreciating the core need for such governance to emerge in the first place.

Factors Affecting Outcome of Traumatic Brain Injury in Alcohol Dependence in the Absence of Intoxication: A Study from Goa

Abstract Background Alcohol dependence is common in certain parts of the world and it contributes to increased incidence of head injury. The effect of alcohol dependence on head injury outcome separate from intoxication has not received much attention. Aims We evaluate the factors affecting outcome in head injury patients with a history of alcohol dependence. Materials and Methods A prospective study of alcohol-dependent patients with head injury was conducted. The patients were treated using standard head injury protocols and information regarding duration of alcohol use was assessed with investigations relating to alcoholic liver disease. The outcome was measured up to 1 month and analyzed with respect to the factors measured. Results The Extended Glasgow Outcome Score at 1 month was lower in patients with increasing duration of alcohol use. Increased duration of alcohol use also led to increased incidence of liver disease and coagulopathy, which independently affected the outcome negatively. Higher duration of alcohol use also resulted in increased risk of seizures and infection. Conclusion Alcohol dependence negatively affects head injury outcome at 1 month. In addition, increased duration of alcohol use shows a linear trend with poor outcome. Although the exact mechanisms for this are not clear, detection and management of complications like coagulopathy may improve outcome.