Unprovoked Seizures Research Articles

The bidirectional role of music effect in epilepsy: Friend or foe?

Epilepsy is a prevalent neurological disease that impacts around 70 million individuals globally. Anti-seizure medications (ASMs) are the first choice for clinicians to control unprovoked epileptic seizures. Although more than 30 ASMs are available in the market, patients with epilepsy (PWEs) still show poor responses to adequate drug treatment. Meanwhile, long-term medications not only bring heavy financial burdens but also lead to undesirable side effects. Music, a ubiquitous art form throughout human history, has been confirmed as therapeutically effective in various neurological conditions, including epilepsy. This alternative therapy offers convenience and a relatively safe approach to alleviating epileptic symptoms. Paradoxically, besides anti-convulsant effect, some particular music would cause seizures inversely, indicating the pro-convulsant effect of it. Considering that investigating the impact of music on epilepsy emerges as a compelling subject. In this review, we tried to present the following sections of content on this topic. Initially, we overviewed the impact of music on the brain and the significant progress of music therapy in central neurological disorders. Afterward, we classified the anti-convulsant and pro-convulsant effects of music in epilepsy, relying on both clinical and laboratory evidences. Finally, possible mechanisms and neural basis of the music effect were concluded, and the translational potentials and some future outlooks about the music effect in epilepsy were proposed. PLAIN LANGUAGE SUMMARY: Epilepsy is an extremely severe neurological disorder. Although anti-seizure medications are preferred choice to control seizures, the efficacy is not satisfied due to the tolerance. Anecdotal music effect had been deemed functional diversity but not clarified on epilepsy, pro-convulsive, or anti-convulsive. Here, we reviewed this interesting but puzzling topic, as well as illustrating the potential mechanisms and its translational potential.

Unravelling the neuroimmune nexus: insights into epilepsy pathology and the role of S100b protein in brain-gut axis modulation: a literature review.

Epilepsy, a chronic neurological condition marked by recurrent, unprovoked seizures, involves complex pathophysiological mechanisms. Recent advancements have expanded our understanding from traditional neuronal dysfunction to include neuroimmune interactions and the influence of the brain-gut-bio-axis. This review explores the role of the S100b protein within these contexts, noted for its involvement in neuroinflammatory processes and as a potential biomarker. Furthermore, it discusses the emerging significance of the gut microbiome in modulating neuroimmune responses and seizure activity. The review integrates findings from recent studies, emphasizing the critical role of the S100b signalling pathway and the gut-brain axis in epilepsy pathology. The interplay between neuroimmune mechanisms and gut microbiota offers novel insights and potential therapeutic targets, underlining the need for further research to exploit these connections for clinical benefit.

Plasma neurofilament heavy chain is a prognostic biomarker for the development of severe epilepsy after experimental traumatic brain injury.

This study was undertaken to test whether the postinjury plasma concentration of phosphorylated neurofilament heavy chain (pNF-H), a marker of axonal injury, is a prognostic biomarker for the development of posttraumatic epilepsy. Tail vein plasma was sampled 48 h after traumatic brain injury (TBI) from 143 rats (10 naïve, 21 controls, 112 with lateral fluid percussion injury) to quantify pNF-H by enzyme-linked immunosorbent assay. During the 6th postinjury month, rats underwent 30 days of continuous video-electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T2 magnetic resonance imaging were performed to assess comorbidities and lesion severity. Of the 112 TBI rats, 25% (28/112) developed epilepsy (TBI+) and 75% (84/112) did not (TBI-). Plasma pNF-H concentrations were higher in TBI+ rats than in TBI- rats (p < .05). Receiver operating characteristic curve analysis indicated that plasma pNF-H concentration distinguished TBI+ rats from TBI- rats (area under the curve [AUC] = .647, p < .05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (≥3 seizures/month) with all other TBI rats (AUC = .732, p < .01). Plasma pNF-H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, p < .05). Higher plasma pNF-H concentration on D2 after TBI correlated with lower neuroscores on D2 (p < .001), D6 (p < .001), and D14 (p < .01). Higher pNF-H concentration on D2 correlated with greater T2 signal abnormality volume on D2 (p < .001) and D7 (p < .01) and larger cortical lesion area on D182 (p < .01). Plasma pNF-H concentration on D2 did not correlate with Morris water maze performance on D37-D39. Plasma pNF-H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters.

Risk of recurrence after a first unprovoked seizure with different risk factors: A 10-year prospective cohort study

ObjectiveTo evaluate the recurrence risk following a first unprovoked seizure using both single-factor and multiple-factor approaches, as well as to further analyze the potential risk factors associated with recurrence. MethodsIn a prospective cohort study, a total of 201 individuals who experienced their initial unprovoked seizure were recruited from January 2010 to December 2019. The cumulative recurrence rates were calculated by Kaplan–Meier survival curves. Multivariate analyses for recurrence risk were conducted utilizing the Cox regression model. Additionally, interaction effects were evaluated by quantifying the attributable proportion due to interaction (AP). ResultsThe cumulative recurrence rates were as follows: 29.4 % at 6 months, 35.8 % at 1 year, 41.1 % at 2 years, 47.9 % at 5 years, and 57.5 % at 10 years. Notably, the majority of recurrences, specifically 61.2 %, manifested within the initial 6 months following the onset, with 74.4 % occurring within the first year, and 82.6 % within the initial 2 years. The recurrence risk of patients with epileptic abnormal discharges on VEEG, nocturnal seizure, abnormal MRI, prior brain insult and focal seizure was 71.9 %, 61.4 %, 61.5 %, 75.0 %, and 69.7 %, respectively. Epileptiform discharges (RR 2.5, 95 % CI 1.4–4.3, P=0.001) and prior brain insult (RR 2.1, 95 % CI 1.2–3.7, P=0.007) were predictors of recurrence. Interaction analysis showed the combination of epileptiform discharges and prior brain insult was associated with a 7-fold increased risk of recurrence (RR 7.0, 95 %CI 3.5–14.2)，with AP estimated at 0.34, the combination of epileptiform discharges and nocturnal seizure was associated with a 4-fold increased risk of recurrence(RR 4.3, 95 %CI 2.4–7.4), with AP estimated at −0.25,and the combination of prior brain insult and nocturnal seizures was associated with a 4-fold increased risk of recurrence(RR 4.1, 95 %CI 1.9–8.9), with AP estimated at −0.03. ConclusionsPatients with epileptiform discharges VEEG, nocturnal seizures, abnormal MRI findings, prior brain insult, or focal seizures exhibited a substantial recurrence rate. Specifically, the presence of epileptiform discharges in VEEG recordings, and a history of prior brain insult were identified as independent risk factors associated with recurrence following an initial unprovoked seizure. Notably, individuals with multiple risk factors exhibited a significantly higher recurrence risk compared to those with no or a single risk factor.

Seizure recurrence following the first unprovoked seizure: Risk factors among children in UAE.

In a retrospective study of paediatric and adolescent patients in Abu Dhabi, UAE, who experienced their first unprovoked seizure between March 2016 and March 2020, with a minimum one-year follow-up, we identified significant risk factors associated with seizure recurrence. Among 317 patients, 96.2% experienced seizure recurrence, with the majority (68.8%) occurring within the first 6-month follow-up period. Notable risk factors for recurrence included focal seizures, symptomatic seizure causes, abnormal initial electroencephalogram (EEG) findings, abnormal brain magnetic resonance imaging results, and the presence of neurological disorders. Interestingly, the type of epileptiform activity in the initial EEG did not predict recurrence risk. Over a 3-year period, the overall recurrence risk was 98.4%, particularly higher in cases with symptomatic seizures compared to idiopathic (genetic) ones. These findings underscore the importance of vigilant monitoring, particularly in the early post-seizure follow-up period, and advocate for initial EEG assessments, especially in cases of remote symptomatic first unprovoked seizures.

Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients. We employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus-induced rotary saturation contrast (SIRS) at spin-lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls. The SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age- or sex-related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz. SIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy-related magnetic field perturbations may serve as a-at this stage experimental-diagnostic test in first seizure patients to complement EEG findings as a standard screening test. Routine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time-sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

Prediction begins with diagnosis: Estimating seizure recurrence risk in the First Seizure Clinic

ObjectivesTo assess the feasibility of using a seizure recurrence prediction tool in a First Seizure Clinic, considering (1) the accuracy of initial clinical diagnoses and (2) performance of automated computational models in predicting seizure recurrence after first unprovoked seizure (FUS). MethodsTo assess diagnostic accuracy, we analysed all sustained and revised diagnoses in patients seen at a First Seizure Clinic over 5 years with 6+ months follow-up (‘accuracy cohort’, n = 487).To estimate prediction of 12-month seizure recurrence after FUS, we used a logistic regression of clinical factors on a multicentre FUS cohort (‘prediction cohort’, n = 181), and compared performance to a recently published seizure recurrence model. ResultsInitial diagnosis was sustained over 6+ months follow-up in 69% of patients in the ‘accuracy cohort’. Misdiagnosis occurred in 5%, and determination of unclassified diagnosis in 9%. Progression to epilepsy occurred in 17%, either following FUS or initial acute symptomatic seizure.Within the ‘prediction cohort’ with FUS, 12-month seizure recurrence rate was 41% (95% CI [33.8%, 48.5%]). Nocturnal seizure, focal seizure semiology and developmental disability were predictive factors. Our model yielded an Area under the Receiver Operating Characteristic curve (AUC) of 0.60 (95% CI [0.59, 0.64]). ConclusionsHigh clinical accuracy can be achieved at the initial visit to a First Seizure Clinic. This shows that diagnosis will not limit the application of seizure recurrence prediction tools in this context. However, based on the modest performance of currently available seizure recurrence prediction tools using clinical factors, we conclude that data beyond clinical factors alone will be needed to improve predictive performance.

Preliminary development and validation of the Indonesian Pediatric Epilepsy Questionnaire (INA-PEPSI) to determine epilepsy and distinguish focal and generalized epilepsy in infants and children with unprovoked seizure in low-resource settings.

To outline the preliminary development and validation of a questionnaire for diagnosing epilepsy and distinguishing focal and generalized epilepsy among infants and children in Indonesia, where electroencephalography and pediatric neurologists are generally not available. A 10-question questionnaire comprising of 43 items was developed through literature review and expert panel discussions. Then, the questionnaire was administered by pediatricians to 75 children aged 1 month to 18 years old presenting with >1 episode of unprovoked seizures at an interval of >24 h. Subsequently, the questionnaire was assessed for content validity with item-level and scale-level content validity indices and ratio, construct validity with item-total correlation tests, criterion validity with diagnostic parameter assessments, and inter-rater reliability using Cohen's kappa (κ) and internal consistency with Cronbach's alpha (α) coefficient. The questionnaire exhibited favorable internal validity and reliability in diagnosing epilepsy and distinguishing focal and generalized epilepsy, with excellent content (both indices and ratio at 1) and construct validity (rcount > rtable at p < 0.001), inter-rater reliability (κ = 0.86 and κ = 0.84), and internal consistency (α = 0.634 and α = 0.806). The questionnaire had a sensitivity and specificity of 96.4% (95%CI 89.1-99.5%) and 95.0% (79.5-99.6%) (area under the curve [AUC] 0.946 [0.900-0.992, p < 0.001]) in diagnosing epilepsy and 80.0% (57.4-95.7%) and 97.4% (89.7-99.2%) (AUC 0.889 [0.783-0.995, p < 0.001]) in distinguishing focal and generalized epilepsy, with a misdiagnosis rate of 4.0%. The questionnaire shows promising potential in diagnosing epilepsy and distinguishing focal and generalized epilepsy. Further external validation studies in larger and more diverse populations are required to confirm our findings. The diagnosis of epilepsy in children is challenging, particularly in resource-limited settings such as Indonesia, where advanced diagnostic tests and pediatric neurologists are scarce. The Indonesian Pediatric Epilepsy Questionnaire (INA-PEPSI) is designed to address these limitations by enabling healthcare professionals in Indonesia to diagnose epilepsy and classify its types without relying on advanced diagnostic tools. Although the questionnaire is still in the early stages of development and validation, this study demonstrates that the questionnaire exhibits good overall diagnostic performance in diagnosing epilepsy and distinguishing epilepsy types among Indonesian children.

Cardiovascular risk factor assessment in late-onset seizures: A study protocol to assess the value of structured intervention.

A growing body of evidence suggests patients with late-onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new-onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow-up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study. Participating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged ≥50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register-based cohort study examining the long-term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics. The primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register. Swedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer-reviewed scientific publications. The study will be registered at clinicaltrials.gov. A first seizure in a middle-aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.

Prospective study of epilepsy with generalized tonic-clonic seizures alone: Clinical features, response to treatment, and likelihood of medication withdrawal.

This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic-clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse. The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new-onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3-h sleep-deprived video-EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow-up. Cumulative time-dependent probabilities of seizure recurrence were calculated using Kaplan-Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper. Eighty-nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike-wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p < 0.00001). ASM discontinuation was attempted in 50 patients after a median treatment duration of 3 years, with 44% experiencing a recurrence. Patient-initiated taper and a mixed circadian seizure pattern independently predicted a higher likelihood of recurrence post-ASM discontinuation. Our findings underscore the importance of prompt treatment upon the diagnosis of EGTCA. Notably, lifelong treatment may not be imperative; patients seizure-free for at least 2 years, with the absence of GSWD on EEG, often maintained seizure freedom after ASM withdrawal, especially with physician-initiated tapering. Seizures in individuals diagnosed with "epilepsy with generalized tonic-clonic seizures alone" (EGTCA) typically start during adolescence and often respond well to antiseizure medications. An electroencephalogram, which measure brain waves, will show abnormal discharges in most patients with EGTCA. Lifelong treatment with antiseizure medication is not necessary for everyone with EGTCA; approximately, 40% can successfully stop treatment without facing seizure recurrence. Patients who stop medication on their own have a higher risk of seizures returning compared with those who undergo cessation under a doctor's supervision.

Epilepsy after acute central nervous system complications of pediatric hematopoietic cell transplantation: A retrospective, multicenter study

BackgroundAcute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT. MethodsThis retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up. ResultsNinety-four patients (63 males, 31 females, median age 10 years, range 1–21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87–68.97). ConclusionsA higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT.

GABA(A) Receptor Subunit (γ2, δ, β1-3) Variants in Genetic Epilepsy: A Comprehensive Summary of 206 Clinical Cases.

Epilepsy is identified in individuals who experienced 2 or more unprovoked seizures occurring over 24 hours apart, which can have a profound impact on a person's neurobiological, cognitive, psychological, and social well-being. Epilepsy is considerably diverse, with classifications such as genetic epilepsy that result directly from a known or presumed genetic variant with the core symptoms of seizures. The GABAA receptor primarily functions as a heteropentamer, containing 3 of 8 subunit types: α, β, γ, δ, ε, π, θ, and ρ. In the adult brain, the GABAA receptor is the primary inhibitory component in neural networks. The involvement of GABAA receptors in the pathogenesis of epilepsy has been proposed. We extensively reviewed all relevant clinical data of previously published cases of GABAA receptor subunit γ2, δ, β1-3 variants included in PubMed up to February 2024, including the variant types, loci, postulated mechanisms, their relevant regions, first onset ages, and phenotypes. We summarized the postulated mechanisms of epileptic pathogenesis. We also divided the collected 206 cases of epilepsy into 4 epileptic phenotypes: genetic generalized epilepsies, focal epilepsy, developmental and epileptic encephalopathies, and epilepsy with fever sensibility. We showed that there were significant differences in the likelihood of the γ2, β2, and β3 subunit variants causing genetic generalized epilepsies, focal epilepsy, developmental and epileptic encephalopathies, and epilepsy with fever sensibility. Patients with the β3 subunit variant seemed related to an earlier first onset age. Our review supports that GABAA receptor subunit variants are a crucial area of epilepsy research and treatment exploration.

Overnight Electroencephalogram to Forecast Epilepsy Development in Children with Autism Spectrum Disorders

ObjectiveTo establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). Study designA single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule (ADOS) data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. ResultsAmong 151 patients, 17.2% (n=26) developed unprovoked seizures (Sz group), while 82.8% (n=125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs. 20.0%, p=0.01). The Sz group also exhibited a greater frequency of slowing (42.3% vs. 13.6%, p < 0.01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, p=0.01) or any slowing (HR 2.78, 95% CI 1.02-7.58, p=0.046 significantly increased the risk of developing unprovoked seizures. ConclusionLong-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.

Effects of acute administration of 4-allyl-2,6-dimethoxyphenol in mouse models of seizures

Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked seizures, presents a substantial challenge in approximately one-third of cases exhibiting resistance to conventional pharmacological treatments. This study investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound derived from various natural sources, in different models of induced seizures and its impact on animal electroencephalographic (EEG) recordings. Adult male Swiss albino mice were pre-treated (i.p.) with a dose curve of 4-allyl-2,6-dimethoxyphenol (50, 100, or 200 mg/kg), its vehicle (Tween), or standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice were subjected to different seizure-inducing models – pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock seizure (MES). EEG analysis was performed on other animals surgically implanted with electrodes to evaluate brain activity. Significant results revealed that animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total duration of tonic-clonic seizures in the PTZ and PILO models; decreased intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase in the percentage of total power attributed to beta waves following 4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected from behavioral and electrographic seizures in the PTZ model, preventing increases in the average amplitude of recording signals while also inducing an increase in the participation of theta and gamma waves. These findings suggest promising outcomes for the tested phenolic compound across diverse pre-clinical seizure models, highlighting the need for further comprehensive studies to elucidate its underlying mechanisms and validate its clinical relevance in epilepsy management.

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.

The diagnostic value of MRI findings in pediatric idiopathic intracranial hypertension: a case-control study.

Idiopathic intracranial hypertension (IIH) is a rare medical condition in children. Based on the different radiological findings reported in various studies in pediatric IIH, this study was conducted to determine the diagnostic value of MRI findings in diagnosing IIH in children. In this retrospective study, the medical records of all children aged 1 to 18 years who visited Ghaem Hospital in Mashhad, Iran, between 2012 and 2022 and were diagnosed with IIH were gathered. Forty-nine cases of children with IIH and 48 control cases of children with the first unprovoked seizure with no indications of increased intracranial pressure for comparison were selected. Patient demographic information and MRI findings were extracted. The comparison between different MRI findings in the case and control groups was conducted using statistical tests. In the case group, the mean diameter of the subarachnoid space expansion around the optic nerve was 5.96 ± 1.21, compared to 4.79 ± 0.33 in the control group, with statistically significant difference (P < 0.001). All the patients with flattening of the posterior globe or transverse sinus stenosis were in the case group, and the frequency of these findings in the case group was significantly higher than in the control group (P < 0.001). The majority of patients (95.5%) classified under category 3 and 4 of empty sella were part of the case group, and the statistical test results indicated a significant difference between the two groups (P < 0.001). The optic nerve sheath diameter cut-off of 5.35 mm, when used for expansion of the subarachnoid space around the optic nerve, with a sensitivity of 82% and a specificity of 100% in diagnosing IIH. The most reliable diagnostic indicators for diagnosing IIH in children are perioptic subarachnoid space expansion with high sensitivity, and posterior globe flattening and transverse sinus stenosis with high specificity.

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...

Let’s Talk About Epilepsy

Epilepsy, a brain disorder marked by recurrent, unprovoked seizures, affects over 50 million people globally according to the WHO. Modern medicine has evolved to offer various antiepileptic medications and precision-targeted medicine, highlighting the critical role of continued research and financial investment in developing innovative treatments. Brazilian Ronaldo Nazario, who is one of the greatest football players, had seizures throughout his career. The most critical seizure that he had was during the final of the FIFA World Cup in 1998, which affected his performance and led to his team’s defeat. Legends with epilepsy did not let epilepsy define them; they struggled and believed that they could. After all, NO PAIN, NO GAIN. While legal advancements, such as amendments to the Hindu Marriage Act in India, which permits those with epilepsy to marry, have been made, challenges persist. Today, there are restrictions on obtaining a driving license, illustrating the ongoing battle against societal barriers. Purple Day, observed annually on March 26, symbolizes a global effort to raise epilepsy awareness. The choice of purple is related to the lavender flower, which is associated with solitude – a reflection of the isolation that people with epilepsy may feel. Stigma leads to depression, and a decline in self-esteem, underlining the importance of comprehensive support systems. Epilepsy may bring challenges, but it also brings strength and resilience. As health-care workers, we are bound to help in spreading awareness, alleviate the stigma, and provide holistic care to those with epilepsy. The love and support that we render will help them take more steps forward and come out with flying colors in this battle against epilepsy. Let us help them “Seize the day.” “Courage is not having the strength to go on, it is going on when you don’t have the strength.”–Theodore Roosevelt

Characteristics and treatment of midlife-onset epilepsy: A 24-year single-center, retrospective study.

This study aimed to analyze the clinical characteristics, etiology, and treatment of midlife-onset epilepsy in a real-world setting at a single center in China. The clinical data of patients who attended the epilepsy clinic of the Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023 were retrospectively analyzed. The clinical characteristics, etiology, and risk factors for midlife-onset epilepsy over the past 24 years were analyzed. Of the 969 patients with onset at 45-64 years of age, 914 were diagnosed with epilepsy with at least two unprovoked seizures 24 h apart. Of those, 99.7% (911) were of focal origin. The median duration from the initial seizure to follow-up treatment was 2 months (interquartile range [IQR]: 1.0-6.0 months). Before commencing treatment, 30.2% (207/683) of patients experienced more than two seizures. A structural etiology was found in 66.3% (606/914) of patients. Cerebrovascular disease (CVD) and traumatic brain injury (TBI) accounted for 19.9% (182/914) and 16.6% (152/914) of the cases, respectively. Logistic regression analysis showed that patients with abnormal imaging (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.25-3.32; p = .004), focal seizures (OR 2.98; 95%CI 1.82-4.87; p < .001), and seizure clusters (OR 2.40; 95%CI 1.21-4.73; p = .01) had poor drug responses. Treatment outcomes were generally better in patients with epilepsy after CVD (OR .49; 95%CI .28-.85; p = .01). Treatment initiation after two seizures (OR .70; 95%CI .42-1.15; p = .16) or 6 months after the first seizure (OR 1.17; 95%CI .66-2.09; p = .58) did not result in poor drug effectiveness. Midlife-onset epilepsy is typically of focal etiology, with CVD being the most common cause, and tends to respond well to medication. The median duration from the initial seizure to follow-up treatment was 2 months. Over 30% of patients experienced more than two seizures before commencing treatment, but this did not affect subsequent outcomes.

Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications.

Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.