Uncontrolled Seizures Research Articles

Long-term Cenobamate for Uncontrolled Focal Seizures in Patients Living in a Group Home or With Developmental Disability (P4-1.006)

Long-term Cenobamate for Uncontrolled Focal Seizures in Patients Living in a Group Home or With Developmental Disability (P4-1.006)

Predictors of Sustainability of Response With Cenobamate: Post-hoc Subset Analysis of a Phase 3, Open-Label, Study (P14-1.005)

Predictors of Sustainability of Response With Cenobamate: Post-hoc Subset Analysis of a Phase 3, Open-Label, Study (P14-1.005)

Concomitant Drug Load Reduction During Adjunctive Cenobamate Therapy: Post-hoc Analysis of a Phase 3, Open-Label Study (P11-1.006)

<h3>Objective:</h3> Changes in concomitant antiseizure medication (ASM) drug load after adding cenobamate were evaluated post-hoc in a subset of the open-label, phase 3 safety study. <h3>Background:</h3> Many patients with epilepsy require adjunctive therapy, which can increase their ASM drug load. <h3>Design/Methods:</h3> Patients 18–70 years old with uncontrolled focal seizures taking stable doses of 1–3 ASMs were enrolled. Total concomitant ASM drug load (not including cenobamate) was calculated by dividing the patient’s prescribed dose for each ASM by its defined daily dose, a World Health Organization standardized daily maintenance dose, then summing the ratios. Changes in concomitant ASM drug load were measured from baseline in 3-month intervals up to 24 months by both total and class-specific ASM drug load. Subgroups of interest included: older adults (65–70 years), prior epilepsy-related surgery vs none, and baseline seizure frequency &lt;3 vs ≥3 seizures/28 days. <h3>Results:</h3> Data from 240 patients were available (median exposure duration 30.2 months, mean age 41.8 years, mean baseline drug load 3.57). Following cenobamate initiation, mean percent reductions in concomitant ASM drug load occurred at Month 12 (29.44%) and 24 (31.82%), and in all assessed ASM drug classes, with the largest reduction in benzodiazepines (55.24% at Month 24). All assessed patient subgroups exceeded 30% reduction in concomitant ASM drug load at Month 24. Patients with low (−0.25 to &lt;0), moderate (−0.59 to −0.25), or high (−3.3 to −0.59) change in concomitant ASM drug load vs no change, respectively, had similar maintenance of ≥50% (89.29%, 86.42%, 90.57% vs 85.99%) and 100% response rates (80.65%, 84.29%, 70.00% vs 82.00%). <h3>Conclusions:</h3> Adding cenobamate led to reduced mean concomitant ASM drug load during Year 1 and Year 2. Reductions occurred regardless of ASM drug class, patient age, or epilepsy disease characteristics. Reductions in ASM drug load did not impact maintenance of response rates. See also abstract by O’Dwyer et al. <b>Disclosure:</b> Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. Louis Ferrari has received personal compensation for serving as an employee of SK Life science. Mr. Stern has received personal compensation for serving as an employee of SK Life Science. Mr. Wade has nothing to disclose. Dr. Weingarten has received personal compensation for serving as an employee of SK Life Science. The institution of Dr. Connor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for SK Life Sciences. The institution of Dr. Connor has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Sciences. The institution of Dr. Rosenfeld has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for SK Life Science. Dr. Rosenfeld has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Science. The institution of Dr. Rosenfeld has received research support from SK Life Science. The institution of Dr. Rosenfeld has received research support from UCB Pharma.

Online CME-Certified Expert Panel Discussion Improves Awareness Among Neurologists Regarding Seizure Freedom in Patients with Epilepsy (P14-2.003)

<h3>Objective:</h3> An online CME-certified activity was developed to educate neurologists on the importance of achieving seizure freedom and clinical data on seizure freedom for anti-seizure medications (ASMs), particularly among patients refractory to treatment. <h3>Background:</h3> The primary goals of epilepsy treatment are to achieve seizure freedom without side effects. However many patients with epilepsy continue to experience seizures and are not offered therapeutic options that may offer greater seizure control. <h3>Design/Methods:</h3> The online CME activity consisted of a 30-minute video discussion between three expert epileptologists. Educational effect was assessed by comparing neurologists’ pre- and post-activity responses to four questions. A paired-samples t-test was used to assess significant differences between pre- and post-assessment responses. Cohen’s <i>d</i> was used to calculate the effect size of the online education. Data were collected between April 6, 2022 and June 29, 2022. <h3>Results:</h3> Among neurologists who participated in the activity, a small educational effect was observed (n=133; <i>d</i>=.34, <i>P</i>&lt;.001). The following areas showed significant (<i>P</i> &lt;.05) pre- vs post-educational improvements: patient-related consequences of uncontrolled seizures and the seizure-freedom rate reported in a clinical trial of an ASM in patients with treatment refractory focal seizures. There was a non-significant pre-vs post educational improvement on a question asking about how to address dosing when a new ASM is added to an existing ASM. Participation in the activity resulted in 32% of neurologists reporting an increase in confidence regarding their ability to optimize the dosing of ASMs to maximize the chance of achieving seizure freedom. <h3>Conclusions:</h3> The results indicated that a CME-certified 30-minute video activity was effective at improving knowledge among neurologists’ regarding seizure freedom in patients with epilepsy. Given the lack of a significant educational effect on ASM dosing, future education should continue to address dosing in the setting of combination ASM therapy. <b>Disclosure:</b> Dr. Finnegan has nothing to disclose. Jovana Lubarda has nothing to disclose. The institution of Dr. Chung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ucb pharma. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SK Life sciences. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for ucb. Dr. Chung has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for SK Life sciences. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for sunovion.

Early and Sustained Treatment Effect of Adjunctive Perampanel in Patients with Seizures Associated with Lennox-Gastaut Syndrome (LGS): A Post Hoc Analysis (P11-1.004)

<h3>Objective:</h3> To report a post hoc analysis of efficacy and safety data from Phase III Study 338 (NCT02834793) by treatment period, assessing early and sustained treatment effect of adjunctive perampanel. <h3>Background:</h3> Study 338 evaluated long-term effects of perampanel in patients with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS). <h3>Design/Methods:</h3> Patients with LGS receiving 1–4 concomitant anti-seizure medications and an average of ≥2 drop seizures/week during baseline were enrolled. The study consisted of a randomized, placebo-controlled Core Study (6-week Titration, 12-week Maintenance) and Extension Phase (6-week Conversion, 46-week Maintenance). During the Extension Phase, all patients received perampanel treatment. The primary endpoint was change from baseline in drop seizure frequency/28 days during the Core Study. Secondary endpoints included 50% responder rates and safety outcomes. Outcomes were assessed in prior perampanel vs prior placebo groups during Titration (Core Study Titration vs Extension Phase Conversion), Maintenance (Core Study Maintenance vs initial 12-week Extension Phase Maintenance), and Long-Term Treatment (52-week Extension Phase vs remaining 34-week Extension Phase Maintenance) Periods. <h3>Results:</h3> In the Extension Phase, 58 patients received perampanel (prior perampanel, n=26; prior placebo, n=32). During Titration, Maintenance, and Long-Term Treatment Periods, the median percent reduction in drop seizures/28 days were 33.4%, 42.1%, and 34.3%, respectively; similarly, the 50% responder rates were 29.3%, 37.9%, and 32.8%, respectively. Treatment-emergent adverse events (TEAEs) occurred in &gt;60% of patients throughout the study; the incidence of treatment-related TEAEs peaked during the Titration Period and subsequently declined over time. The most common TEAEs during each treatment period were somnolence (12.1%; Titration), upper respiratory tract infection (9.3%; Maintenance), and nasopharyngitis and pyrexia (9.8% each; Long-Term Treatment). <h3>Conclusions:</h3> Adjunctive perampanel demonstrated early-onset efficacy that was sustained long term (≥46 weeks) and was well tolerated in patients with LGS. <b>Disclosure:</b> Anna Patten, 14934 has received personal compensation for serving as an employee of Eisai Ltd. An immediate family member of Dr. Morita-Sherman has received personal compensation for serving as an employee of Forrester Research. Dr. Morita-Sherman has received personal compensation for serving as an employee of Eisai Inc.. An immediate family member of Dr. Morita-Sherman has stock in Forrester Research. The institution of Dr. Morita-Sherman has received research support from Cleveland Clinic. Dr. Ngo has received personal compensation for serving as an employee of Eisai Inc..

Epileptic Amnesia as an Alzheimer’s Disease Mimic (P2-6.004)

<h3>Objective:</h3> To present a case of amnestic dementia that was caused as a result of mesial temporal lobe epilepsy. <h3>Background:</h3> Memory impairments have been reported as a result of mesial temporal lobe epilepsy. Dementia as a result of long term uncontrolled seizures has been reported. Here we report a patient presenting for evaluation of dementia - diagnosed with uncontrolled mesial temporal lobe epilepsy. <h3>Design/Methods:</h3> A 76 year old male presented to the cognitive clinic for evaluation of amnestic problems that started approximately 4 years prior. The patient reported problems with both long-term and short-term memory–such as details of family vacations, weddings, names of acquaintances. He additionally reported mild word finding abnormalities and spatial difficulty. Neuropsychological testing revealed problems in non contextual verbal learning and memory. The patient notably reported stereotyped events which also started around 4 years prior.–which he described as getting a sense of deja vu followed by tingling in all 4 limbs, nausea and a changed sense of smell. These events occurred around 10 times a month. MRI brain performed 4 years prior had revealed some small vessel ischemic changes and diffuse volume loss. An EEG obtained at the time had been unremarkable. Repeat MRI brain was significant for left hippocampal atrophy with bilateral hippocampal T2 signal hyperintensities. Ambulatory EEG monitoring was significant for transient epileptiform discharges. Lumbar puncture was unremarkable with tau /amyloid profiles not consistent with Alzheimer9s pathology. The patient was started on Levetiracetam with cessation of his episodes of deja vu, tingling and nausea. <h3>Results:</h3> NA <h3>Conclusions:</h3> Uncontrolled mesial temporal lobe epilepsy can result in hippocampal atrophy and cause amnestic problems. Epilepsy should be a diagnostic consideration in patients who present for evaluation of dementia. <b>Disclosure:</b> Dr. Philip has nothing to disclose. Dr. Chabrashvili has nothing to disclose.

Glycolysis inhibition partially resets epilepsy-induced alterations in the dorsal hippocampus-basolateral amygdala circuit involved in anxiety-like behavior

Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapies. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel interventions, including glycolysis inhibition, on epilepsy-induced alterations. Here, we investigated kainic acid-induced changes in the dorsal hippocampus (dHPC) and basolateral amygdala (BLA) circuit and the efficiency of a glycolysis inhibitor, 2-deoxy D-glucose (2-DG), in resetting such alterations using simultaneous local field potentials (LFP) recording and elevated zero-maze test. dHPC theta and gamma powers were lower in epileptic groups, both in the baseline and anxiogenic conditions. BLA theta power was higher in baseline condition while it was lower in anxiogenic condition in epileptic animals and 2-DG could reverse it. dHPC-BLA coherence was altered only in anxiogenic condition and 2-DG could reverse it only in gamma frequency. This coherence was significantly correlated with the time in which the animals exposed themselves to the anxiogenic condition. Further, theta-gamma phase-locking was lower in epileptic groups in the dHPC-BLA circuit and 2-DG could considerably increase it.

A Preoperative Scoring System to Predict Function-Based Resection Limitation Due to Insufficient Participation During Awake Surgery.

Failure in achieving a function-based resection related to the insufficient patient's participation is a drawback of awake surgery. To assess preoperative parameters predicting the risk of patient insufficient intraoperative cooperation leading to the arrest of the awake resection. Observational, retrospective, multicentric cohort analysis enrolling 384 (experimental dataset) and 100 (external validation dataset) awake surgeries. In the experimental data set, an insufficient intraoperative cooperation occurred in 20/384 patients (5.2%), leading to awake surgery failure in 3/384 patients (ie, no resection, 0.8%), and precluded the achievement of the function-based resection in 17/384 patients (ie, resection limitation, 4.4%). The insufficient intraoperative cooperation significantly reduced the resection rates (55.0% vs 94.0%, P < .001) and precluded a supratotal resection (0% vs 11.3%, P = .017). Seventy years or older, uncontrolled epileptic seizures, previous oncological treatment, hyperperfusion on MRI, and mass effect on midline were independent predictors of insufficient cooperation during awake surgery ( P < .05). An Awake Surgery Insufficient Cooperation score was then assessed: 96.9% of patients (n = 343/354) with a score ≤2 presented a good intraoperative cooperation, while only 70.0% of patients (n = 21/30) with a score >2 presented a good intraoperative cooperation. In the experimental data set, similar date were found: 98.9% of patients (n = 98/99) with a score ≤2 presented a good cooperation, while 0% of patients (n = 0/1) with a score >2 presented a good cooperation. Function-based resection under awake conditions can be safely performed with a low rate of insufficient patient intraoperative cooperation. The risk can be assessed preoperatively by a careful patient selection.

A Clinical Case Report About an Intracranial Lipoma

Intracranial lipoma is a uncommon congenital malformation, represent less than 0.1% of all intracranial tumors. Result from abnormal persistence and mal-differentiation of meninx primitiva, during embryogenesis. The cases in which the tumor presents an extracranial component are caused by a secondary dehiscence of the skull with evagination of a small tuft of primitive meninges. These lesions are frequently located in the inter-hemispheric fissure in the pericallosal region in 50% of cases, other locations as ambient or quadrigeminal cisterns present an incidence about 20-25%. In half of cases the patients present associate midline brain malformations of varying severity, the most frequent is the agenesia of the corpus callosus. The most accepted theory states that in embryonic phases, mesenchymal alterations at the level of the cranial sutures in the sagittal plane can cause anomalies of the SSS, sinus rectum, tentorium, and parietal bones that would explain the associated anomalies. Majority of intracranial lipomas are detected incidentally, being a third of the asymptomatic cases. As in all other pathologies certain localizations cause specific symptomatology of the involved area. The most common clinical manifestations are headache, epilepsy, mental dysfunctions and cranial nerve deficits. The clinical diagnosis is unclear and it is necessary release complementary exams in every suspected cases. Neuroimaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI) make possible identify these lesions. We describe a clinical case about a 79-year-old woman with headache without any other symptoms. Was done CT and MRI that showed a inter-hemispheric lesion located in the pericallosal region, without any other abnormality associated. The development, during the last decades, of neuroimaging and histogenesis techniques increased the knowledge about this pathology and modified the management in recent times. The surgery is contraindicated in the majority of the cases, however still play a role in some cases especially in presence of hydrocephalus, uncontrollable seizures, and bony affectation with cosmetic influence. The medical control of the epilepsy is mandatory. We present a clinical case about pericallosal intracranial lipoma and review the current literature. Taking in account the clinical situation and the imaging findings, we decide for a conservative approach with clinical/neurological and radiological follow-up.

Chronic seizures induce sex-specific cognitive deficits with loss of presenilin 2 function.

Patients with early-onset Alzheimer's disease (EOAD) are at elevated risk for seizures, including patients with presenilin 2 (PSEN2) variants. Like people with epilepsy, uncontrolled seizures may worsen cognitive function in AD. While the relationship between seizures and amyloid beta accumulation has been more thoroughly investigated, the role of other drivers of seizure susceptibility in EOAD remain relatively understudied. We therefore sought to define the impact of loss of normal PSEN2 function and chronic seizures on cognitive function in the aged brain. Male and female PSEN2 KO and age- and sex-matched wild-type (WT) mice were sham or corneal kindled beginning at 6-months-old. Kindled and sham-kindled mice were then challenged up to 6weeks later in a battery of cognitive tests: non-habituated open field (OF), T-maze spontaneous alternation (TM), and Barnes maze (BM), followed by immunohistochemistry for markers of neuroinflammation and neuroplasticity. PSEN2 KO mice required significantly more stimulations to kindle (males: p<0.02; females: p<0.02) versus WT. Across a range of behavioral tests, the cognitive performance of kindled female PSEN2 KO mice was most significantly impaired versus age-matched WT females. Male BM performance was generally worsened by seizures (p=0.038), but loss of PSEN2 function did not itself worsen cognitive performance. Conversely, kindled PSEN2 KO females made the most BM errors (p=0.007). Chronic seizures also significantly altered expression of hippocampal neuroinflammation and neuroplasticity markers in a sex-specific manner. Chronic seizures may thus significantly worsen hippocampus-dependent cognitive deficits in aged female, but not male, PSEN2 KO mice. Our work suggests that untreated focal seizures may worsen cognitive burden with loss of normal PSEN2 function in a sex-related manner.

Poor Seizure Control Among Children Attending a Tertiary Hospital in South Western Uganda - A Retrospective Study.

Seizure control among children with epilepsy (CWE) receiving anti-seizure medications (ASMs) remains a challenge in low-resource settings. Uncontrolled seizures are significantly associated with increased morbidity and mortality among CWE. This negatively impacts their quality of life and increases stigma. This study determined seizure control status and described the factors associated among CWE receiving ASMs at Mbarara Regional Referral Hospital (MRRH). In a retrospective chart review study, socio-demographic and clinical data were obtained from 112 medical records. CWE receiving ASMs for at least six months and regularly attending the clinic were included in the study. Physical or telephone interviews were conducted with the immediate caregivers of the CWE to establish the current seizure control status of the participants. A total of 112 participants were enrolled. Of these, three-quarters had generalized onset seizures, 23% had focal onset seizures, while 2% had unknown onset motor seizures. About 60.4% of the study participants had poor seizure control. Having a comorbidity (p-value 0.048, AOR 3.2 (95% CI 1.0-9.9)), history suggestive of birth asphyxia (p-value 0.014, AOR 17.8 (95% CI 1.8-176.8)), and being an adolescent (p-value 0.006, AOR 6.8 (95% CI 1.8-26.6)) were significantly associated with poor seizure control. Seizure control among CWE receiving ASMs at MRRH remains poor. Efforts geared to addressing seizure control and optimizing drugs are needed, especially among children with comorbidities, those with history of birth asphyxia, and adolescents.

Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis.

Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy. We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome. Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73-11.54) and 4.71 (95% CI 0.57-39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33-5.02) and 0.50 (95% CI 0.031-7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89-3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93-14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment. Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.

Ring chromosome 14 syndrome: what the dentist should know to manage children with r(14) effec-tively

Ring chromosome 14 syndrome, or r(14), is a rare genetic disorder characterized by distinctive facial features, intractable epilepsy, delayed development, intellectual disability, and autism spectrum disorder. With less than 100 documented cases worldwide, the disease is not well known or fully studied. Furthermore, the literature offers little guidance to aid dentists in the management of these patients as r(14) remains undocumented in the dental literature. To investigate the manifestations and challenges faced by a group of subjects suffering from r(14), to raise awareness of this syndrome, and to provide tips and suggestions that dentists may find helpful to manage r(14) children effectively. A voluntary survey was administered to the caretakers of 13 r(14) patients who, as of 2019, were registered in the NORD (National Organization for Rare Diseases) global data bank (Ring 14 USA Outreach). The patients were assessed for age, gender, geographic distribution, phenotype, physical appearance, maxillofacial characteristics, presence of oral conditions and abnormalities, malocclusion, epileptic seizures, cognitive abilities, speech, muscle tone, nutrition, autism, and other developmental and behavioral points of interest. Of the 13 patients queried, 7 were male and 6 were female. The age of the patients ranged from 5 to 49 years. Ten patients were of European ancestry and three were Hispanic, all residing across the U.S. The majority of patients were diagnosed as infants, shortly after commencement of uncontrollable seizures. All the patients had microcephaly and presented with Class II malocclusions. More frequent occlusal anomalies and conditions included diastemata of the anterior teeth, congenitally missing teeth, crowding, and drooling. The majority of subjects was unable to speak, suffered from intractable seizures, and frequently exhibited behavioral outbursts. A child with r(14) may present a considerable challenge to the dentist and staff, but the dental problems of r(14) children are, for the most part, like those of any other patient and can often be handled by the dentist. Depending on the severity of symptoms, some children with r(14) may be as treatable in the dental office as any other child.

Seizures Are the Main Sign of Epilepsy: Stages of Seizures

A common neurological condition known as epilepsy is characterized by recurrent bouts of uncontrollable body movements that affect only a portion of the body (partial) or the full body (generalized), occasionally accompanied by loss of consciousness and control over bowel or bladder function. Uncontrolled seizures are linked to medical and psychological illness, dependent behavior, a low quality of life, and a higher risk of untimely death. Epilepsy affects people of all ages, ethnicities, sexes, levels of education, socioeconomic status, and social classes worldwide. The prodrome phase is a pre-epileptic feeling or experience that might start hours, days, or even weeks in advance of the actual seizure. The most prevalent prodromal phase symptoms include difficulties maintaining focus, tension, exhaustion, sleep disruptions, behavioral changes (differently smelling, tasting, having ringing in the ears, feeling queasy, etc.), restlessness, and others. The ictal phase defined as spans the interval between the start of a seizure and its conclusion. The phrase "interictal" refers to a phase that occurs between seizures or headaches. "Postictal" refers to the period following a seizure. The duration of postictalphase varies from minutes to hours depending on the type of seizure, the frequency and intensity of seizures, and the length of the seizure.

Seizure control during pregnancy and postpartum period in women with epilepsy: an Egyptian prospective study

BackgroundProper seizure control during pregnancy and postpartum is essential to optimize the outcome of women with epilepsy (WWE). The current work aimed to address factors related to seizure occurrence during pregnancy and postpartum.MethodsOne hundred twenty-five WWE, compliant with their anti-seizure medications (ASMs) regimen, were prospectively evaluated for seizure control and ASMs changes all through the pregnancy up to 4 weeks postpartum.ResultsMost of the patients, 73 (58.4%), completed their pregnancy without seizures, while 52 (41.6%) had seizures. Only one case developed one episode of convulsive status epilepticus in the third trimester. Due to breakthrough seizures, the ASM dose was increased from the first to the third trimester in 19.2% of pregnancies, while another ASM was added in 8 pregnancies. Uncontrolled seizures during the six months before pregnancy were associated with a four-fold increase in the risk of seizures during pregnancy (95% CI 2.476–6.695). The latter nearly doubled the risk of seizures during the postpartum period (RR 1.978) (95% CI 1.44 -2.717). Furthermore, genetic etiology would increase the risk of seizures during the postpartum period by 2.7 times more than the unknown etiology (RR 2.778, 95%CI 1.156–6.679).ConclusionWomen with epilepsy should be counselled that proper seizure control six months before pregnancy is necessary to pass their pregnancy and the postpartum period without seizures.

Magnitude of uncontrolled seizures and associated factors among people with epilepsy. Data from a major teaching hospital in Southwest Ethiopia

BackgroundEpilepsy is a major public health problem affecting 70 million people worldwide. 90% of global people with epilepsy were living in developing regions like Ethiopia. Due to the lack of clear guidelines for treatment selection and the difficulty of individualizing care in resource-poor settings, achieving seizure control can be challenging. Seizure control status among epileptic patients is affected by different factors. Accordingly, this study aimed to assess the magnitude of uncontrolled seizures and associated factors among people with epilepsy attending the outpatient clinic of Jimma Medical Center, Southwest Ethiopia. MethodsA hospital-based retrospective chart review and a respective patient interview conducted among people with epilepsy from October 2020 to June 2021. Sociodemographic, behavioral-related factors, medication adherence, and medication belief were obtained through patient interviews. Seizure control status in the last two years before the study period was retrospectively evaluated and recorded from the charts. Data were entered into Epi Data manager version 4.6 and then exported to SPSS version 23.0 for analysis. A backward logistic regression analysis was done to identify factors associated with uncontrolled seizures. ResultsFrom a total of 314 medical charts reviewed, 149(47.5 %) of patients were with uncontrolled seizures. 28.7 %,12.8 %, and 6 % of the patients experienced 1–5,6–10, and >10 seizure episodes during the last two years respectively. Comorbidity [adjusted odds ratio [(AOR): 2.13, 95 % confidence interval (CI):1.26–3.58], nonadherence [AOR: 2.41, 95 %CI: 1.46–3.9], possible adverse drug reaction (ADR) [AOR:1.79, 95 %CI: 1.107–3.01], and drug interaction [AOR: 3.06, 95 %CI: 1.24–7.57] were associated with an uncontrolled seizure. Conclusion and recommendationOur study showed that a substantial proportion of the patients were with uncontrolled seizures. Epileptic patients with comorbidities, nonadherence, adverse drug reactions, and drug interactions were more prone to have uncontrolled seizures. Hence, to overcome these problems, strategies like community-based education, treatment intensification, and routine assessment of adverse drug reactions and drug interaction may help to improve seizure control status.

Fighting Epilepsy with Nanomedicines-Is This the Right Weapon?

Epilepsy is a chronic and complex condition and is one of the most common neurological diseases, affecting about 50 million people worldwide. Pharmacological therapy has been, and is likely to remain, the main treatment approach for this disease. Although a large number of new antiseizure drugs (ASDs) has been introduced into the market in the last few years, many patients suffer from uncontrolled seizures, demanding the development of more effective therapies. Nanomedicines have emerged as a promising approach to deliver drugs to the brain, potentiating their therapeutic index. Moreover, nanomedicine has applied the knowledge of nanoscience, not only in disease treatment but also in prevention and diagnosis. In the current review, the general features and therapeutic management of epilepsy will be addressed, as well as the main barriers to overcome to obtain better antiseizure therapies. Furthermore, the role of nanomedicines as a valuable tool to selectively deliver drugs will be discussed, considering the ability of nanocarriers to deal with the less favourable physical-chemical properties of some ASDs, enhance their brain penetration, reduce the adverse effects, and circumvent the concerning drug resistance.

Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery. We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls. Nine centers from 3 continents contributed 206 patients operated for drug-resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss-of-function (LoF) variants (odds ratio [OR]=2.6, 95% confidence interval [CI]=1.9-3.5, p= 1.3E-09) and in genes encoding voltage-gated cation channels (OR=2.4, 95% CI=1.4-3.8, p= 2.7E-04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between-group differences. Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision-making and counseling. ANN NEUROL 2022.

Role of Neurogenesis and Oxidative Stress in Epilepsy (Study on Plasma Brain Derived Neurotrophic Factor and Malondialdehyde Level)

BACKGROUND: Epilepsy is a neurological disorder. Its incidence in Indonesia was 700,000–1,400,000 cases and 40–50% occurred in children. About 30–40% of cases in children had uncontrolled seizures. Biomarkers are needed to assess the prognostic value of patients with uncontrolled epilepsy. Malondialdehyde (MDA) and brain-derived neurotrophic factor (BDNF) are one of the prognostic biomarkers related to uncontrolled epilepsy to see the effect of oxidative stress and neuroplasticity. AIM: The objective of the study was to examine cut off value of plasma BDNF and MDA level; and to compare plasma BDNF and MDA levels in uncontrolled and controlled epilepsy patients. METHODS: The research usedanalytic observational with cross-sectional approach. Number of respondents was 30 patients of epilepsy who came to Ulin Hospital Banjarmasin. Respondents were divided into two groups (controlled and uncontrolled epilepsy). Blood plasma was examined for MDA with a spectrophotometer and BDNF with ELISA. Data were analyzed by t-test with 95% confidence level. RESULTS: 11 children were found in the uncontrolled epilepsy group and 19 children with controlled epilepsy. The result showed that there were significant differences between type of therapy and developmental disorders/other diseases with epilepsy status. There was no significant differences of plasma BDNF in epilepsy status (controlled and uncontrolled epilepsy), and there was also no significant differences of plasma MDA in epilepsy status (controlled and uncontrolled epilepsy). CONCLUSION: There were no significant differences of plasma BDNF and MDA in epilepsy status.

Efekat transkranijalne stimulacije direktnom strujom na kontrolu napada i prevenciju epilepsije

Introduction. Epilepsy is one of the most common neurological diseases. It is an uncontrollable neuronal activity of different parts of the brain leading to convulsion and/or fainting. Although epileptic seizure control and therapeutics have significant advances, 20% -30% of individuals still have uncontrolled seizures. Patients under the medication's control are not free from the drug's side effects and complications. Epileptic patients experience many different challenges. Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation method applied in drug-resistant seizures and epilepsies. It transmits positive/negative electrical current toward deep brain parts, modulating their electrical activity. Methods. This is a review article. All relevant articles which were accessible were reviewed. The effectiveness of tDCS in preventing epilepsy in patients undergoing seizures was reviewed in this article. Conclusion. According to the studies, this method can probably be an auxiliary method in preventing and treating seizures. As epileptic seizures were induced and confirmed in some studies after the application of tDCS, the method should be cautiously applied.