Oligoepilepsy and lifelong seizure susceptibility in epilepsy with generalized tonic-clonic seizures alone: Experience at an adult tertiary center.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is the least studied syndrome within the idiopathic generalized epilepsy (IGE) spectrum. We characterize a large cohort of adult patients with GTCA to understand natural history and drug responsiveness. METHODS: In this retrospective single-center study using our epilepsy electronic record, we evaluated clinical characteristics, seizure outcomes, anti-seizure medication (ASM) response including seizure recurrence after ASM withdrawal, and sex differences in a cohort of GTCA patients aged ≥17 years. RESULTS: Within a cohort of 434 IGE patients, 87 patients (20 %) with GTCA were included. The mean age was 34.9 years (range 17-73 years). Forty-six patients (52.8 %) were females. Seventy-two patients (82.8 %) were seizure-free and 15 (17.2 %) had active epilepsy over the previous 12 months. Thirty-four patients (39.1 %) had ≤5 lifetime seizures, aligning with a prior definition of 'oligoepilepsy'. Sixty-five patients (74.7 %) were treated with monotherapy, 19 (21.8 %) were treated with polytherapy, and three were not taking any ASM. Levetiracetam (37.9 %) was the most commonly prescribed ASM, followed by lamotrigine (32.1 %) and valproate (31 %). Seventeen patients (19.5 %) attempted to withdraw their ASM. The rate of seizure recurrence after ASM withdrawal was 88.2 % (15/17), including two patients who relapsed more than 20 years after ASM discontinuation. Females had more seizures in their lifetime and had trialed more ASM compared to males. SIGNIFICANCE: GTCA has a relatively good prognosis, with most patients becoming seizure-free on monotherapy. The high rate of seizure recurrence after ASM withdrawal supports lifetime seizure susceptibility. We found potential sex differences in seizure outcomes and ASM response, although further research is needed to validate this finding.

Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.

BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.

Antiseizure medication withdrawal in adult patients with idiopathic generalized epilepsy: Performance of two seizure recurrence prediction models.

PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.

Outcomes and predictors of seizure recurrence in post-stroke epilepsy, a retrospective hospital-based study.

BACKGROUND: The occurrence of seizures following a stroke is a well-recognized complication associated with a significant increase in morbidity and mortality. Despite the numerous studies examining outcomes and risk factors related to post-stroke seizures (PSS), there remains a lack of clarity regarding the clinical characteristics, treatment, and PSS recurrence (PSSR) rates in patients experiencing their initial episode of PSS. PURPOSE: This study aimed to determine the risk factors for developing recurrent seizures after first PSS and their effects on functional outcomes and mortality. METHODS: All patients underwent an electroencephalography (EEG) and were monitored for a minimum of 24 months following the first PSS. The primary endpoint was the recurrence of seizures. Predictive factors for PSSR were determined by using the Cox-proportional hazards model, and the cumulative latency of recurrence at 90, 180, 360, and 720 days was estimated using Kaplan-Meier analysis. RESULTS: Seizure recurred in 36.8% (39/106). Significant association of PSSR was noted with female gender, use of older anti-seizure medications (ASMs) (p<0.001), EEG findings as focal slow wave activity (p<0.001), Ictal epileptiform abnormalities (p=0.015), status epilepticus (p=0.015), and with severe disability (p=0.008). However, multivariate cox-proportional hazards model showed significant association of female gender (HR=3.28; 95% CI: 1.42-7.58; p=0.006). Hazard ratio (HR) was increased with older ASMs use, focal aware seizure types, Ictal EAs, and periodic discharges on EEG; though, statistically significant. CONCLUSION: Factors such as the type of ASMs, EEG findings, and seizure type were significantly linked to PSSR. Female gender was the only independent predictor established. Additionally, significant functional decline was reported with recurrence.

Perampanel for the treatment of epilepsy with genetic aetiology: Real-world evidence from the PERMIT Extension study.

Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology. Assessments included retention rate (evaluated at 3, 6 and 12 months), effectiveness (responder and seizure freedom rates; evaluated at 3, 6, 12 months and the last visit [last observation carried forward) and tolerability (adverse events [AEs]). Of the 6822 people with epilepsy included in PERMIT Extension, 1012 were presumed to have a genetic aetiology. The most common genetic aetiologies were idiopathic generalised epilepsy (IGE; 58.2%), tuberous sclerosis (1.1%), Dravet syndrome (0.8%) and genetic epilepsy with febrile seizures plus (GEFS+; 0.5%). Retention rates at 3, 6 and 12 months in the total genetic aetiology population were 89.3%, 79.7% and 65.9%, respectively. In the total genetic aetiology population, responder rates at 12 months and the last visit were 74.8% and 68.3%, respectively, and corresponding seizure freedom rates were 48.9% and 46.5%, respectively. For the specific aetiology subgroups, responder rates at 12 months and the last visit were, respectively: 90.4% and 84.4% (IGE), 100% and 57.1% (tuberous sclerosis), 100% and 71.4% (Dravet syndrome), and 33.3% and 20.0% (GEFS+). Corresponding seizure freedom rates were, respectively: 73.1% and 64.6% (IGE), 33.3% and 22.2% (tuberous sclerosis), 20.0% and 28.6% (Dravet syndrome), and 0% and 0% (GEFS+). The incidence of AEs was 46.5% for the total genetic aetiology population, 48.8% for IGE, 27.3% for tuberous sclerosis, 62.5% for Dravet syndrome, and 20% for GEFS+. Tolerability findings were consistent with PER's known safety profile. PER was effective and generally well tolerated when used in individuals with a presumed genetic epilepsy aetiology in clinical practice. PER was effective across a wide range of genetic aetiologies.

Benzodiazepines for the Treatment of Seizure Clusters.

Patients with epilepsy may experience seizure clusters, which are described by the US Food and Drug Administration (FDA) as intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. Untreated seizure clusters may increase the risk for status epilepticus, as well as decrease quality of life and increase burden on patients and care partners. Benzodiazepine therapies are the mainstay for acute treatment of seizure clusters and are often administered by nonmedical care partners outside a healthcare facility. Three rescue therapies are currently FDA-approved for this indication, with diazepam rectal gel being the first in 1997, for patients aged ≥  2 years. Limitations of rectal administration (e.g., positioning and disrobing the patient, which may affect ease of use and social acceptability; interpatient variation in bioavailability) led to the investigation of the potential for nasal administration as an alternative. Midazolam nasal spray (MDS) was approved by the FDA in 2019 for patients aged ≥  12 years and diazepam nasal spray (DNS) in 2020 for patients aged ≥  6 years; these two intranasal therapies have differences in their formulations [e.g., organic solvents (MDS) vs. Intravail and vitamin E for absorption and solubility (DNS)], effectiveness (e.g., proportion of seizure clusters requiring only one dose), and safety profiles. In clinical studies, the proportion of seizure clusters for which only one dose of medication was used varied between the three approved rescue therapies with the highest single-dose rate for any time period for DNS; however, although studies for all three preparations enrolled patients with highly intractable epilepsy, inclusion and exclusion criteria varied, so the three cannot be directly compared. Treatments that have been used off-label for seizure clusters in the USA include midazolam for injection as an intranasal spray (indicated for sedation/anxiolysis/amnesia and anesthesia) and tablet forms of clonazepam (indicated for treatment for seizure disorders) and lorazepam (indicated for anxiety). In the European Union, buccal and intranasal midazolam are used for treating the indication of prolonged, acute convulsive seizures and rectal diazepam solution for the indication of epileptic and febrile convulsions; duration of effectiveness for these medications for the treatment of seizure clusters has not been established. This paper examines the literature context for understanding seizure clusters and their treatment and provides effectiveness, safety, and administration details for the three FDA-approved rescue therapies. Additionally, other medications that are used for rescue therapy in the USA and globally are discussed. Finally, the potential benefits of seizure action plans and candidates for their use are addressed. This paper is intended to provide details about the unique characteristics of rescue therapies for seizure clusters to help clarify appropriate treatment for individual patients.

Analysis of seizure-cluster circadian periodicity from a long-term, open-label safety study of diazepam nasal spray.

OBJECTIVE: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters. METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed. RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h. SIGNIFICANCE: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.

Evaluating fenfluramine hydrochloride as an oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome.

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by treatment-refractory seizures, including tonic/atonic 'drop' seizures, and intellectual impairment and slow spike-wave discharges on the electroencephalogram. Fenfluramine, previously prescribed as a weight-loss drug but then withdrawn, has recently been approved in the US, EU, and UK for the adjunct treatment of seizures associated with LGS. AREAS COVERED: The authors review the efficacy and safety findings from clinical trials of fenfluramine in LGS. The authors then discuss the evidence for adverse effects that may be of particular concern to fenfluramine, namely cardiac abnormalities, and weight loss, in the context of the use of fenfluramine for the treatment of the refractory seizures in LGS. EXPERT OPINION: Fenfluramine has demonstrated efficacy in reducing the frequency of seizures in LGS, notably drop seizures, in short-term and long-term clinical trials. Valvular heart disease and pulmonary hypertension have not been reported at the low doses (≤26 mg/day) used in these studies, however, data are limited. Due to its novel mechanism of action, fenfluramine may be of benefit in LGS which has not responded adequately to other antiseizure medications. However, none of these medications, including fenfluramine, achieves the ultimate goal of seizure freedom in most cases.

Long-term outcomes after new onset seizure in children living with HIV: A cohort study.

OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

Cognitive and psychological dysfunction is present after a first seizure, prior to epilepsy diagnosis and treatment at a First Seizure Clinic.

OBJECTIVE: Neuropsychological comorbidities found in chronic epilepsy have also been reported earlier in the disease course. However, recurrent seizures, antiseizure medication (ASM), and adjustment to a chronic diagnosis remain potential confounds of this literature. It thus remains unclear whether these comorbidities are primary or secondary attributes of epilepsy. To capture individuals as close to disease onset as possible, we studied the cognitive and psychological functioning in adults after their first seizure, yet prior to epilepsy diagnosis and treatment. METHODS: Using a telehealth-based prospective design, we screened cognition, mood, and anxiety symptoms in adult patients referred to a First Seizure Clinic (FSC), who were over 18 years, English-speaking and not taking ASM. We screened cognition via telephone, and psychological symptoms via online questionnaires, all prior to the patients' diagnostic evaluation. Data were collected on 32 individuals subsequently diagnosed with epilepsy at the FSC, and 30 healthy controls from the community, who were matched to the epilepsy group for age, gender, and education. RESULTS: A multivariate analysis of variance revealed that the groups differed significantly on combined cognitive measures with a large effect size (F[1,56] = 5.75, p < 0.001, η2 = 0.45). Post-hoc analyses showed that performances on measures of verbal memory, working memory, and executive functions were significantly worse for the newly diagnosed epilepsy group than controls. The epilepsy group also exhibited higher rates of clinically significant depressive and anxiety symptoms. SIGNIFICANCE: Cognitive and psychological dysfunction is prevalent in people with epilepsy as early as the first seizure event, before the influence of diagnosis, ASM and recurrent seizures. Their neuropsychological profile parallels that seen in chronic epilepsy, showing that this dysfunction is already present at the very onset of the disease. The current study demonstrates the viability of telehealth neuropsychological screening for all new epilepsy cases. PLAIN LANGUAGE STATEMENT: The results of this study show, using telephone-based cognitive assessment and online questionnaires, that people with newly diagnosed epilepsy can experience problems with their thinking and memory skills, and low mood and anxiety, as early as after their first seizure. These issues are apparent at the very beginning of the disease, before an epilepsy diagnosis is made and before antiseizure medication is commenced, which suggests that they are due to the underlying brain disturbance, rather than the secondary effects of seizures, treatment, or lifestyle changes. Telehealth-screening of thinking skills and mental health for all new epilepsy cases is recommended to promote early management of such problems.

Focal electroclinical features in generalized tonic-clonic seizures: Decision flowchart for a diagnostic challenge.

OBJECTIVE: Bilateral tonic-clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal EEG or semiology. METHODS: We retrospectively analyzed video-EEG recordings of 101 bilateral tonic-clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1-year follow-up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. RESULTS: Focal semiology in IGE was observed in 75% of seizures and 77.8% of patients, most often corresponding to forced head version (66.7%). In patients with multiple seizures, direction of head version was consistent across seizures. Focal interictal epileptiform discharges (IEDs) were observed in 61.1% of patients with IGE, whereas focal ictal EEG onset only occurred in 13% of seizures and 16.7% of patients. However, later during the seizures, a reproducible pattern of 7-Hz lateralized ictal rhythm was observed in 56% of seizures, associated with contralateral head version. We did not find correlation between presence of focal features and therapeutic response in IGE patients. Our decision flowchart distinguished between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal features with an accuracy of 96.6%. SIGNIFICANCE: Focal semiology associated with bilateral tonic-clonic seizures and focal IEDs are common features in patients with IGE, but focal ictal EEG onset is rare. None of these focal findings appears to influence therapeutic response. By assessing the concordance between interictal and ictal EEG findings, one can accurately distinguish between focal and generalized epilepsies.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

Effects of valproic acid and levetiracetam monotherapy on balance functions in patients with generalized epilepsy.

BACKGROUND: It is reported that antiepileptic drugs have an effect on balance functions. The aim of the study was to evaluate and compare the effects of valproic acid and levetiracetam monotherapy on balance functions in patients with generalized epilepsy using objective test methods. METHODS: The study included 43 generalized epilepsy patients aged 18-60 years, including 20 patients receiving valproic acid monotherapy, 23 patients receiving levetiracetam monotherapy, and 25 healthy individuals as controls, in the Neurology Clinic of a university hospital in eastern Turkey. The demographic data form was filled out and the Video Head Impulse Test and Vestibular Evoked Myogenic Potentials test were performed. RESULTS: Statistically significant differences were obtained between the groups in lateral, posterior, and anterior semicircular canal gains and RALP and LARP asymmetry values in the V-HIT test (p < 0.05). Statistically significant differences were obtained between the groups in P1, N1 latency and asymmetry values in the C-VEMP test and in N1, P1 latency, amplitude, and asymmetry values in the o-VEMP test (p < 0.05). CONCLUSION: Valproic acid and levetiracetam may affect the vestibulocular and vestibulocolic reflex pathways negatively. In this cohort, valproic acid had more pronounced adverse effects on balance functions as compared to levetiracetam.

Evaluating the Potential of Light Exposure on Reducing the Frequency of Epileptic Seizures.

Epilepsy is one of the most common and devastating neurological disorders that causes unprovoked, recurrent seizures arising from excessive synchronized neuronal discharging. Although antiepileptic drugs (AEDs) reduce the frequency of epilepsy seizures, drug-refractory epileptic patients exert resistance to AEDs, resulting in treatment difficulty. Moreover, pharmacological treatments do not show satisfactory results in response to photosensitive epilepsy. In the recent era, light therapy emerged as a potential non-pharmacological approach for treating various diseases, including depression, seasonal affective disorders, migraine, pain, and others. Several studies have also shown the potential of light therapy in treating epilepsy. In addition, Red light evokes epilepsy seizures. Blue lenses filter the red light and significantly suppress the frequency of epilepsy seizures. However, the effects of green light on the frequency of epileptic seizures are not studied yet. In addition, light-activated gene therapy or optogenetics also emerged as a possible option for epilepsy treatment. Animal models have shown the therapeutic possibilities of optogenetics and light therapy; however, human studies addressing this possibility are still vague. This review provides the beneficial effects of light in reducing seizure frequency in epilepsy patients. A limited number of studies have been reported so far; therefore, light therapy for treating epilepsy requires more studies on animal models to provide precise results of light effects on seizures.

Non-discontinuation of antiseizure medication in seizure-free epilepsy patients.

BACKGROUND AND PURPOSE: In patients with epilepsy and sustained seizure freedom, guidelines recommend considering discontinuation of antiseizure medication (ASM) based on shared decision-making. This study aims to identify factors associated with non-discontinuation of ASM in seizure-free patients. METHODS: Retrospective data from three sites of an academic outpatient clinic were analyzed. Adult patients with epilepsy who have been seizure-free for ≥24 months on ASM monotherapy were included. The primary end-point was non-discontinuation of ASM, defined as no discontinuation or no dose reduction of ≥25% at the last outpatient clinic visit in the ultimate seizure-free interval. Secondary end-points included frequency of discussion on discontinuation attempts between patients and physicians, adherence to ASM discontinuation decisions, and post-discontinuation seizure outcomes. RESULTS: Out of 338 included patients, 81.7% did not discontinue ASM and did not reduce its dose, 11.5% discontinued ASM and 6.8% had a significant dose reduction. Factors independently associated with non-discontinuation of ASM were history of focal to bilateral or generalized tonic-clonic seizures (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.08-5.06), history of breakthrough seizures (OR 3.32, 95% CI 1.10-10.04), history of failed attempts to discontinue or reduce the ASM dose (OR 4.67, 95% CI 1.03-21.11) and higher ASM load at the index visit (OR 6.10, 95% CI 2.09-17.78). Discontinuation attempts were made during the entire period of seizure freedom and were most commonly undertaken ≥10 years after the last seizure. CONCLUSIONS: This study provides insights into factors associated with the shared decision-making process regarding ASM discontinuation in seizure-free patients and highlights the importance of considering individual patient characteristics and seizure history.

The role of angiotensin receptor blockers in treating epilepsy: a review.

Epilepsy is a chronic brain disease with a global prevalence of 70 million people. According to the World Health Organization, roughly 5 million new cases are diagnosed every year. Anti-seizure drugs are the treatment of choice. However, in roughly one third of the patients, these drugs fail to produce the desired effect. As a result, finding novel treatments for epilepsy becomes inevitable. Recently, angiotensin receptor blockers have been proposed as a treatment to reduce the over-excitation of neurons in epilepsy. For this purpose, we conducted a review using Medline/PubMed and Google Scholar using the relevant search terms and extracted the relevant data in a table. Our review suggests that this novel approach has a very high potential to treat epilepsy, especially in those patients who fail to respond to conventional treatment options. However, more extensive and human-based trials should be conducted to reach a decisive conclusion. Nevertheless, the use of ARBs in patients with epilepsy should be carefully monitored keeping the adverse effects in mind.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. METHODS: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. RESULTS: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. SIGNIFICANCE: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Generalized onset seizures with focal evolution (GOFE) - a largely unknown ictal variation in genetic generalized epilepsies.

PURPOSE: At onset of generalized seizures, focal electroclinical features are commonly seen, while generalized onset seizures with focal evolution (GOFE) are largely unknown bearing the risk of misclassification. METHODS: In two German epilepsy-centers, patients with GOFE documented by video-EEG monitoring (VEM) between 2017 and 2022 were identified retrospectively. In addition to analysis of ictal electroclinical features, detailed epilepsy and family history, response to antiseizure medication (ASM), and findings from neuroimaging were considered. RESULTS: We identified five patients with GOFE, three females, age 14 to 22 years. All patients developed genetic generalized epilepsy in childhood or adolescence, each presenting with two or three generalized seizure types. In each of the five patients, one GOFE was recorded by VEM. At onset, EEG seizure patterns were characterized by generalized spike-wave discharges at 2.5 to 3.5/sec for 9 to 16 s followed by focal evolution of the discharges. Interictally, all patients presented with generalized spike-wave discharges without focal abnormalities. Semiology at onset was behavioral arrest in two patients and generalized increase in tone in one, while two onsets were clinically inapparent. Semiological signs during focal evolution were variable, comprising head and body version, figure 4 sign, unilateral arm clonic activity, and staring with oral automatisms. In one case, focality involved both hemispheres successively. CONCLUSION: Prominent focal semiological features in GOFE carry a high risk of misclassification as focal seizures and epilepsy and thus wrong choice of ASM. This calls for low-threshold VEM if any doubts of focal genesis of seizures exist.

Intracerebral electrographic activity following a single dose of diazepam nasal spray: A pilot study.

OBJECTIVE: Rescue benzodiazepine medication can be used to treat seizure clusters, which are intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. The NeuroPace RNS® System is a device that detects abnormal electrographic activity through intracranial electrodes and administers electrical stimulation to control seizures. Reductions in electrographic activity over days to weeks have been associated with the longer-term efficacy of daily antiseizure medications (ASMs). In this pilot study, electrographic activity over hours to days was examined to assess the impact of a single dose of a proven rescue therapy (diazepam nasal spray) with a rapid onset of action. METHODS: Adult volunteers (>18 years old) with clinically indicated RNS (stable settings and ASM usage) received a weight-based dose of diazepam nasal spray in the absence of a clinical seizure. Descriptive statistics for a number of detections and a sum of durations of detections at 10-min, hourly, and 24-h intervals during the 7-day (predose) baseline period were calculated. Post-dose detections at each time interval were compared with the respective baseline-detection intervals using a 1 SD threshold. The number of long episodes that occurred after dosing also were compared with the baseline. RESULTS: Five participants were enrolled, and four completed the study; the excluded participant had recurrent seizures during the study. There were no consistent changes (difference >1 SD) in detections between post-dose and mean baseline values. Although variability was high (1 SD was often near or exceeded the mean), three participants showed possible trends for reductions in one or more electrographic variables following treatment. SIGNIFICANCE: RNS-assessed electrographic detections and durations were not shown to be sensitive measures of short-term effects associated with a single dose of rescue medication in this small group of participants. The variability of detections may have masked a measurable drug effect. PLAIN LANGUAGE SUMMARY: Rescue drugs are used to treat seizure clusters. Responsive neurostimulation (RNS) devices detect and record epilepsy brain waves and then send a pulse to help stop seizures. This pilot study looked at whether one dose of a rescue treatment changes brain activity detected by RNS. There was a very wide range of detections, which made it difficult to see if or how the drug changed brain activity. New studies should look at other types of brain activity, multiple doses, and larger patient groups.

What are the considerations when initiating treatment for epilepsy in children?

INTRODUCTION: There is a very wide spectrum of epilepsies and developmental and epileptic encephalopathies that affect children, from self-limited forms, not necessarily requiring treatment, to severe drug-resistant ones. AREAS COVERED: In this perspective, the authors discuss the main factors to consider before drug prescription in children, considering the most recent clinical research, including age, seizure type, epilepsy syndrome, etiology, efficacy and safety profile, comorbidities, gender, available formulations, costs and drug coverage, and regulatory issues. The literature search was conducted through a PubMed search on antiseizure medications for patients aged 0-18, with respect to each of the aforementioned factors, and by checking the reference lists of relevant papers. EXPERT OPINION: The most expanding field of research and innovation for clinical practice is precision medicine, which addresses the holistic treatment of genetic epilepsies and developmental and epileptic encephalopathies. It achieves this by addressing their detrimental effects on synapses, neurotransmission, and cellular signaling pathways with the double aim to treat seizures and to rescue neurodevelopmental trajectories, but also the issue of adverse events and drug resistance through pharmacogenomics.