Persistent Seizures Research Articles

MNGA-01 ÉPILEPSIE LIÉE AU MÉNINGIOME: À PROPOS DE DEUX CAS

Abstract BACKGROUND Meningiomas are the most common intracranial primary neoplasms. Seizures are a common manifestation of these tumors (10% to 50%). PURPOSE To present 2 cases of meningioma-related epilepsy and discuss the predictive factors for preoperative and postoperative seizures, their physiopathology and their management. CASE REPORTS The first patient is a 36-years-old male with a 16 years history of epilepsy revealing an underlying left frontoparietal meningioma which benefited from a Simpson grade 1 surgical resection with a seizure free postoperative outcome. The second patient is a 46-years-old man with a 6 months history of seizures revealing a right parieto-occipital meningioma requiring surgical removal with persistence of seizures on postoperative follow-up. CONCLUSION Seizures are a common occurrence both prior to and after meningioma resection, and can have a significant negative impact on patient quality of life. Further efforts are required for better understanding and predicting seizures in meningioma as well as plan their medical treatment.

Beyond seizure freedom: Reduction in anti-seizure medication after epilepsy surgery

IntroductionPatients considering therapeutic epilepsy surgery often seek to decrease the number of anti-seizure medications (ASMs) they need. Predicting such reductions remains challenging. Although predictors of seizure freedom after epilepsy surgery are well-established, long-term outcomes remain modest and factors associated with ASM reduction, even in the absence of seizure freedom, may improve surgical planning to align with patient goals. MethodsWe studied a large multi-institutional cohort of patients who underwent epilepsy surgery between 2001 and 2022, with a minimum of two years follow-up. Preoperative features, including duration of epilepsy, epilepsy etiology, non-invasive investigation data, and total number of ASMs prescribed immediately prior to surgery were extracted for each patient. Primary endpoints included likelihood of ASM reduction and ASM freedom at multiple post-operative time points up to 15 years and stratified by seizure control. ResultsA total of 250 patients were followed for a median of 6.0 (range 2, 22) years after intracranial EEG (iEEG) surgery. Significant ASM reduction was only observed in those who underwent subsequent resection, whereas those undergoing neuromodulation saw their ASM usage maintained. Engel I outcomes were the strongest driver of ASM reduction. In patients with persistent seizures, patients with lateralized seizure onset zones (SOZs) also achieved sustained ASM reduction over time. Similarly, an increased number of preoperative ASMs also corresponded to a higher likelihood of ASM reduction across all follow-up periods. Other preoperative factors, including seizure etiology, did not independently influence ASM reduction. ConclusionsEven patients with persistent seizures after epilepsy surgery can observe meaningful ASM reduction during long-term follow-up. ASM reduction may be a relevant secondary outcome measure for epilepsy surgery.

Exploring seizure characteristics in individuals with autoimmune encephalitis: A comprehensive retrospective study in a low-middle-income country setting

IntroductionSeizures and epilepsy are well-documented in association with autoimmune encephalitis. Despite this, a notable gap exists in understanding the persistence of seizures beyond the acute phase, particularly within the context of low- and low-middle-income settings. ObjectiveTo evaluate the frequency, clinical characteristics, diagnosis, and potential factors associated with the occurrence and persistence of seizures in autoimmune encephalitis patients. MethodsThis was a retrospective, cross-sectional study. Patients diagnosed with possible, probable or confirmed autoimmune encephalitis according to the Graus criteria at the “Instituto Nacional de Ciencias Neurológicas” in Lima, Peru, were included between January 2018 and April 2023. Demographic, clinical, diagnosis, and management information was recorded. A bivariate analysis was performed considering the persistence of seizures at one-year follow-up and a second analysis was performed to compare the groups according to the anti N-methyl-D-aspartate receptor (NMDAR) antibody results. ResultsSixty patients predominantly male (40; 66.7 %) were included. Only 36 (60 %) patients were tested for antibodies, 16 (44.4 %) were NMDAR positive. 46 (76.7 %) patients had at least one seizure and 13 (37.1 %) had seizures after 1 year of follow-up. Patients with seizure relapse were younger, 20 (IQR: 18–28) versus 29.5 years (IQR: 21–48), p=0.049. Four (44.4 %) patients with persistent seizures had positive NMDAR results. Similar sex distributions, no differences in seizure characteristics, and higher CSF cell count in the NMDAR-positive group were observed. Neuroimaging, EEG findings, and follow-up times were comparable between the groups. ConclusionsWe found a 37.1 % seizures rate after one year of follow-up, predominantly in younger patients.

Hypothalamic Hamartoma in an 11-Year-Old Female: Clinical Presentation, Diagnostic Evaluation, and Management Strategies – A Case Report and Literature Review

Background: Hypothalamic hamartomas (HH) are rare, benign brain tumors that can cause severe neurological symptoms, including epilepsy. This report presents a case of an 11-year-old female with HH, highlighting the clinical presentation, diagnostic workup, and management strategies. Case Presentation: An 11-year-old female with no prior medical history presented with generalized tonic-clonic seizures during sleep, characterized by convulsions, cyanosis, tongue biting, frothing at the mouth, and loss of consciousness lasting 1-2 minutes. Subsequent episodes included focal Jacksonian seizures involving the face and right eye myoclonus, progressing to generalized convulsions. Neurological examination and development were normal, with no family history of epilepsy. MRI revealed a sessile lesion in the left hypothalamus with T2/FLAIR hyperintensity and T1 hypointensity. Laboratory tests, including thyroid function, gynecological ultrasound, and various blood tests, were normal. A 48-hour video EEG indicated sensorimotor cortex involvement in both hemispheres, likely linked to the hypothalamic lesion. Management: Initial management involved observation without antiepileptic medications. Due to persistent seizures, the treatment plan included oxcarbazepine, titrated to 1200 mg/day, and Keppra (levetiracetam) 1000 mg/day. Efforts were made to discontinue Keppra and maintain monotherapy with oxcarbazepine. Given the small size of the lesion and effective seizure control with medication, surgical intervention was not pursued. Conclusion: This case underscores the importance of comprehensive diagnostic evaluation and individualized treatment plans for patients with HH. While medical management can be effective for small lesions, surgical options reported in the literature provide alternative strategies for larger or treatment-resistant cases. A multidisciplinary approach is crucial in managing the complex presentation of HH to optimize patient outcomes and improve quality of life.

Real-world use of the updated refractory epilepsy screening tool for Lennox-Gastaut syndrome.

To evaluate the Refractory Epilepsy Screening Tool for Lennox-Gastaut Syndrome (REST-LGS) for real-world identification of LGS in adults and to develop a scoring system for the tool. A retrospective chart review of adults with drug resistant epilepsy (DRE) and intellectual development disorder (IDD) was conducted by 2 primary care providers blinded to diagnosis. The REST-LGS was designed via the Modified Delphi Consensus and was previously validated. This tool consists of 8 criteria (4 major, 4 minor) considered indicative of LGS. To account for missing data in the earlier validation study and to evaluate applicability in a real-world setting, the REST-LGS was refined to include a scoring system in which major criteria were more heavily weighted than minor criteria, producing categories of "likely" (>11 points), "possible" (8-11 points), and "unlikely" (<8 points) LGS. Statistical analyses were descriptive. Of the 100 patients included in the analysis, data for slow spike-waves in electroencephalography and seizure onset age - both major REST-LGS criteria - were missing for 46% and 42% of patients, respectively. The majority of patients met 4 of the 8 REST-LGS criteria (cognitive impairment since childhood, 71%; persistent seizures despite a trial of ≥2 antiseizure medications, 65%; seizure onset before the age of 12 years, 57%; ≥2 seizure types, 56%). All 4 major criteria were met in 22 patients (22%). The percentages of patients considered "likely," "possible," or "unlikely" to have LGS were 26%, 30%, and 44%, respectively. Of the 74 patients without a previous LGS diagnosis, 42 (57%) were identified as "possible" or "likely" to have LGS using REST-LGS. In this analysis, the validated REST-LGS was evaluated in a real-world setting. The majority of previously undiagnosed patients were identified via REST-LGS as "possible" or "likely" to have LGS. Extensive missing data highlights challenges of LGS diagnosis in adults. There is a need to identify adult patients with Lennox-Gastaut syndrome (LGS) so they can receive appropriate treatment. The Refractory Epilepsy Screening Tool for LGS (REST-LGS) questionnaire was designed by experts to identify whether patients with seizures that are not controlled by medications may have LGS. In this study, 2 physicians completed the REST-LGS using charts for 100 patients who experience seizures not controlled by medications. Of the patients who were previously diagnosed as not having LGS, the majority were "likely" or "possible" to have LGS based on the REST-LGS; therefore, the REST-LGS can identify patients for further evaluation.

Low-grade epilepsy-associated tumors: Epilepsy outcome and antiseizure medication discontinuation after lesionectomies as first-line surgical approach in pediatric population.

This study aimed to evaluate epilepsy outcome and antiseizure medication (ASM) discontinuation after lesionectomies as first surgical approach in pediatric population diagnosed with low-grade epilepsy-associated neuroepithelial tumors (LEATs). We conducted a retrospective study. Thirty-six consecutive patients with histological diagnoses of LEATs who underwent surgery between 2018 and 2021 at our institution were included. The clinical and surgical data were retrospectively analyzed. Thirty (83.3%) of 36 patients are free of disabling seizures (Engel class I) and 19 (63,4%) of them are classified as Engel Ia. In 17 (47.2%) patients, ASM could be discontinued. The mean age at surgery was 8.6 years (±4.04) and the mean age at onset of epilepsy was 7.2 years (±3.8), whereas the mean duration of epilepsy in months at the time of surgery was 21.3 months (±23.7). The epileptogenic tumor was in the temporal lobe in 20 (55.5%) patients. Because of seizure persistence, a second or a third surgery was necessary for six patients (16.7%) and four of them had residual lesions (three in temporal and one in extratemporal site). No perioperative complications were recorded, including acute seizures, with a median hospitalization time of 7 days. Shorter epilepsy duration at time of surgery as long as a single ASM was significantly correlated with an Engel class I outcome (p-value = .01 and p-value = .016, respectively). Focal seizure semeiology was associated with an increased probability of antiseizure medication discontinuation (p-value = .042). Our findings confirm that shorter epilepsy disease duration, monotherapy before surgery, and seizure semeiology are determinant factors for a positive seizure outcome and medication discontinuation, also with less invasive surgical approaches such as lesionectomies. However, considering the intrinsic multifactorial epileptogenic nature of LEATs, a tailored surgical approach should be considered to optimize clinical and seizure outcome, especially for lesions located in the temporal lobe.

CLINICAL AND SURGICAL APPROACH TO EPILEPSY REFRACTORY

Refractory epilepsy is characterized by the persistence of epileptic seizures even after adequate use of at least two antiepileptic drugs. This condition represents a significant challenge in the treatment of epilepsy, requiring a more assertive clinical and, in some cases, surgical approach. This study aims to review and explore the clinical and surgical approach to refractory epilepsy, highlighting the available treatment options, indications, benefits and challenges faced by patients and health professionals. This is a bibliographic review, using qualitative premises, with the PubMed, Scopus, Web of Science and Scielo databases. To better refine the research, the health descriptors “epilepsy”, “surgical treatment”, “neurostimulation” and “refractory epilepsy” were used. The clinical approach to refractory epilepsy involves careful assessment of the patient, including a detailed clinical history, complete physical examination and complementary tests such as electroencephalogram (EEG), magnetic resonance imaging (MRI) and computed tomography (CT) of the brain. The aim is to identify the origin of the epileptic seizures and determine the best therapeutic strategy. Clinical treatment usually involves optimizing drug therapy, with adjustments to the doses of existing drugs or the introduction of new drugs. However, in many cases, the response to drug treatment is unsatisfactory, leading to consideration of surgical options. Surgery for refractory epilepsy can include removing the brain tissue responsible for epileptic seizures (temporal lobectomy, focal resection, etc.), deep brain stimulation or other less invasive techniques. These procedures aim to reduce the frequency and severity of epileptic seizures, improving the patient’s quality of life. The approach to refractory epilepsy requires a multidisciplinary and individualized assessment, taking into account the clinical characteristics and specific needs of each patient. Although clinical treatment is the first line of approach, surgery can be a viable option for those who do not respond adequately to antiepileptic drugs. It is essential that patients with refractory epilepsy are referred to specialized centers for a complete and appropriate evaluation of their case.

1238 Next Generation Sequencing of Gliomas to Identify Predictors of Time to Postoperative Epilepsy

INTRODUCTION: Seizures during the course of disease for patients with diffuse gliomas is common. As genetic characterization of gliomas has improved, how a tumors mutational profile influences the timing of postoperative seizures, and if postoperative seizures relate to survival and tumor progression, is poorly understood. METHODS: A retrospective review of consecutive adults from 2017 to 2020 who underwent resection of gliomas with next generation sequencing of tumors at a single institution was performed. Cox proportional hazards regression was performed to identify factors associated with time to postoperative seizures. Seizures within 72 hours of surgery were excluded. RESULTS: 363 patients with newly diagnosed or recurrent tumor tissue genotyped via next generation sequencing were included. Median follow-up time was 37.4 months, median time to seizure after surgery was 39.2 months (95% CI 34.6 – 60.8), and IDH-mutant tumors comprised 38.3% of the cohort. Patients with IDH-mutant tumors were more likely to have non-immediate postoperative seizures (p = 0.031) and more persistent postoperative seizures (p = 0.004) compared to IDH-wildtype tumors. PDGFRA mutation was associated with shorter time to seizure in IDH-mutant gliomas (p = 0.033), with no such genetic factors in IDH-wildtype tumors. Among IDH-mutant and wildtype tumors, patients with shorter seizure freedom had significantly shorter overall and progression-free survival. CONCLUSIONS: PDGFRA mutation is associated with earlier seizures after resection of IDH-mutant diffuse gliomas. Earlier first non-immediate postoperative seizure after resection is associated with worse overall and progression-free survival.

Adherence to Epilepsy's Medical Recommendations.

The primary problem in the treatment of epilepsy is poor seizure control. Several studies have shown that non-adherence to doctors' recommendations regarding drug dosage, time of drug administration as well as lifestyle modifications are the most frequent causes of the persistence or reoccurrence of seizures, other than cases of misdiagnosis and poor drug selection. The aim of this study was to assess the prevalence of non-compliance with medical recommendations, both in relation to medicine dosage, regularity of administration and lifestyle, and also to determine the factors affecting patients with diagnosed epilepsy. This study was carried out on a total of 169 patients diagnosed with epilepsy who were under the care of an outpatient neurology clinic. The assessment of compliance was performed using the Patient Rating of Compliance Scale (PRCS), Clinician Rating Scale (CRS) and authors' scale. Depending on the scale used, varying degrees of non-compliance were noted. They were as follows-65.3% on the authors' scale, 10% on the PRCS and 9% on the CRS. The following factors influenced compliance with doctors' recommendations: type of epilepsy, consumption of alcoholic beverages, frequency of follow-up visits to the neurology clinic, type of pharmacotherapy and number of medicines taken.

Biallelic OTUD6B variants associated with a Kabuki syndrome-like disorder in three siblings: A clinical report and literature review.

Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies, seizures, and distal limb abnormalities. Physical differences described for affected individuals suggest that the disorder may be clinically recognizable, but previous publications have reported an initial clinical suspicion for Kabuki syndrome (KS) in some affected individuals. Here, we report on three siblings with biallelic variants in OTUD6B co-segregating with neurodevelopmental delay, shared physical differences, and other clinical findings similar to those of previously reported individuals. However, clinical manifestations such as long palpebral fissures, prominent and cupped ears, developmental delay, growth deficiency, persistent fetal fingertip pads, vertebral anomaly, and seizures in the proband were initially suggestive of KS. In addition, previously unreported clinical manifestations such as delayed eruption of primary dentition, soft doughy skin with reduced sweating, and mirror movements present in our patients suggest an expansion of the phenotype, and we perform a literature review to update on current information related to OTUD6B and human gene-disease association.

Metabolomic changes in adults with status epilepticus: Ahuman case-control study.

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure that affects ~40 per 100 000 people yearly worldwide. The persistence of seizures may lead to excitotoxic processes, neuronal loss, and neuroinflammation, resulting in long-term neurocognitive and functional disabilities. A better understanding of the pathophysiological mechanisms underlying SE consequences is crucial for improving SE management and preventing secondary neuronal injury. We conducted a comprehensive untargeted metabolomic analysis, using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS), on plasma and cerebrospinal fluid (CSF) samples from 78 adult patients with SE and 107 control patients without SE, including 29 with CSF for both groups. The metabolomic fingerprints were compared between patients with SE and controls. Metabolites with differences in relative abundances that could not be attributed to treatment or nutrition provided in the intensive care unit were isolated. Enrichment analysis was performed on these metabolites to identify the most affected pathways. We identified 76 metabolites in the plasma and 37 in the CSF that exhibited differential expression in patients with SE compared to controls. The enrichment analysis revealed that metabolic dysregulations in patients with SE affected primarily amino acid metabolism (including glutamate, alanine, tryptophan, glycine, and serine metabolism), pyrimidine metabolism, and lipid homeostasis. Specifically, patients with SE had elevated levels of pyruvate, quinolinic acid, and keto butyric acid levels, along with lower levels of arginine, N-acetylaspartylglutamate (NAAG), tryptophan, uracil, and uridine. The tryptophan kynurenine pathway was identified as the most significantly altered in SE, resulting in the overproduction of quinolinic acid, an N-methyl-d-aspartate (NMDA) receptor agonist with pro-inflammatory properties. This study has identified several pathways that may play pivotal roles in SE consequences, such as the tryptophan kynurenine pathway. These findings offer novel perspectives for the development of neuroprotective therapeutics.

Spike ripples localize the epileptogenic zone best: an international intracranial study.

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.

Correlation between serum galanin and neuron-specific enolase levels with EEG abnormalities in pediatric convulsive status epilepticus and the efficacy of triple drug therapy.

This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE) and their relationship with abnormal electroencephalogram (EEG) patterns. Additionally, the study assessed the effectiveness of a combination therapy involving midazolam, diazepam, and phenobarbital in treating CSE. The research involved 100 children diagnosed with CSE and included a control group of 50 healthy children. Serum GAL and NSE levels were measured, and EEGs were analyzed for abnormalities in the CSE group. Comparisons were made between the healthy control group and the CSE group, particularly within the first 24 hours after persistent seizures. The severity of EEG abnormalities was correlated with GAL and NSE levels. The treatment consisted of an observation group that received the triple therapy of midazolam, diazepam, and phenobarbital, while a control group received diazepam and phenobarbital. Clinical efficacy, symptom improvement, Status Epilepticus Severity Score (STESS), and adverse reactions were evaluated. The results indicated elevated levels of GAL and NSE in the CSE group, with higher levels noted within 24 hours after persistent seizures. Furthermore, a positive correlation was observed between the severity of EEG abnormalities and GAL and NSE levels. The group receiving the triple therapy demonstrated superior efficacy, faster resolution of seizures and fever, reduced STESS scores, and fewer adverse reactions than the control group. In conclusion, this study highlights the positive correlation between serum GAL and NSE levels and the severity of EEG abnormalities in pediatric CSE. The triple therapy approach is effective in treating CSE, leading to improved clinical symptoms, reduced brain damage, and enhanced safety. The study concludes that serum GAL and NSE levels in children with convulsive status epilepticus are positively correlated with the degree of EEG abnormalities. The combination therapy involving midazolam, diazepam, and phenobarbital is effective in treating children with convulsive status epilepticus, significantly improving clinical symptoms, reducing brain damage, and ensuring safety.

An exploration of anomia rehabilitation in drug-resistant temporal lobe epilepsy

Around 40% of patients who undergo a left temporal lobe epilepsy (LTLE) surgery suffer from anomia (word-finding difficulties), a condition that negatively impacts quality of life. Despite these observations, language rehabilitation is still understudied in LTLE. We assessed the effect of a four-week rehabilitation on four drug-resistant LTLE patients after their surgery. The anomia rehabilitation was based on cognitive descriptions of word finding deficits in LTLE. Its primary ingredients were psycholinguistic tasks and a psychoeducation approach to help patients cope with daily communication issues. We repeatedly assessed naming skills for trained and untrained words, before and during the therapy using an A-B design with follow-up and replication. Subjective anomia complaint and standardized language assessments were also collected. We demonstrated the effectiveness of the rehabilitation program for trained words despite the persistence of seizures. Furthermore, encouraging results were observed for untrained items. Variable changes in anomia complaint were observed. One patient who conducted the protocol as self-rehabilitation responded similarly to the others, despite the different manner of intervention. These results open promising avenues for helping epileptic patients suffering from anomia. For example, this post-operative program could easily be adapted to be conducted preoperatively.

GS-441524 and molnupiravir are similarly effective for the treatment of cats with feline infectious peritonitis.

Although not registered for feline infectious peritonitis (FIP) in Japan, nucleoside analogs have shown efficacy and we have been offering them to owners of cats with FIP at our clinic since January 2020. The aim of this study was to investigate outcomes in cats with FIP who received GS-441524 or molnupiravir. Diagnosis of FIP was based on clinical signs, laboratory test results, and the presence of feline coronavirus RNA in blood or effusion aspirate. After providing verbal and written information, owners of cats with a presumptive diagnosis of FIP with a were offered antiviral treatment with commercially sourced GS-441524 from June 2020, and either GS-441524 or compounded molnupiravir from January 2022. Dosing was 12.5-25 mg/kg/day for GS-441524 and 20-40 mg/kg/day for molnupiravir, depending on the presence of effusion and neurological and/or ocular signs, and continued for 84 days. Overall, 118 cats with FIP (effusive in 76) received treatment, 59 with GS-4421524 and 59 with molnupiravir. Twenty cats died, 12/59 (20.3%) in the GS-441524 group and 8/59 (13.6%) in the molnupiravir group (p = 0.326), with most deaths within the first 10 days of starting treatment. Among survivors, neurological and ocular signs resolved in all but one cat, who had persistent seizures. Of the cats completing treatment, 48/48 in the GS-441524 group and 51/52 in the molnupiravir group achieved remission. Laboratory parameters normalized within 6 to 7 weeks of starting drug administration. Adverse events, such as primarily hepatic function abnormalities, were transient and resolved without specific intervention. Our data indicate that GS-441524 and molnupiravir show similar effects and safety in cats with FIP.

Resective Epilepsy Surgery after Corpus Callosotomy in Children with Lennox-Gastaut Syndrome

Purpose: This study examined the characteristics and outcomes of resective epilepsy surgery following corpus callosotomy (CC) in children with Lennox-Gastaut syndrome (LGS).Methods: We retrospectively analyzed 17 children with LGS who underwent resective surgery (RS) after CC over a span of 10 years, with a minimum of 2 years of follow-up, at a single tertiary epilepsy center in Korea.Results: Of the 17 patients, 13 (73.5%) demonstrated favorable surgical outcomes (Engel class I or II) at 1 year after RS, and eight (47.1%) were ultimately free of seizures 2 years after surgery. A significantly larger decrease in the number of anti-seizure medications taken from before to 2 years after the final surgical procedure was observed in the group that became seizure-free than in the group with persistent seizures (&lt;i&gt;P&lt;/i&gt;=0.062). Furthermore, a significantly greater decline in daily adaptive function was found in the persistent seizure group (&lt;i&gt;P&lt;/i&gt;=0.059). The baseline characteristics, results of presurgical evaluation, and treatment-related factors assessed prior to surgery showed no significant differences between the seizure-free group and the group with persistent seizures.Conclusion: In conclusion, RS may be a viable option for patients with LGS who exhibit lateralization and/or localization on presurgical evaluation after CC, as the procedure may reveal a concealed primary focus. The proactive implementation of two-stage epilepsy surgery could provide significant seizure reduction and preservation of cognitive function in carefully selected patients with LGS.

Tuberculosis Meningitis in a 9‐Month‐Old Girl during the COVID‐19 Pandemic

Tuberculous meningitis (TBM) is a serious form of TB disease that can result in high morbidity and mortality, particularly if there are delays in diagnosis and treatment. In this case report, a 9‐month‐old girl was admitted with persistent vomiting and focal seizures. On examination, she was found to have a right‐side hemiparesis. Brain imaging showed intense nodular leptomeningeal enhancement, hydrocephalus, a hypolucent lesion in the left basal ganglia, arterial stenosis and vasculitis, and an old ischemic insult. The patient was initially diagnosed with an acute ischemic stroke and was treated with aspirin and antiepileptic drugs. The patient’s condition failed to improve despite initial treatment, leading to further diagnostic procedures. The results uncovered a diagnosis of TBM. The case highlights the importance of considering TBM as a possible cause of neurological symptoms, especially during the coronavirus disease 2019 (COVID‐19) pandemic where similar symptoms can be present in cases of neurological complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and multisystem inflammatory syndrome in children (MIS‐C).

Stroke-related epilepsy in the rehabilitation setting: Insights from the inpatient post-stroke rehabilitation study – RIPS

In stroke survivors, persistent seizure activity could be associated with poor functional outcomes. At the same time, antiepileptic over-treatment could hamper post-stroke recovery. We systematically investigated the occurrence of seizures, the prevalence of epileptic discharges, and delta slow waves on electroencephalogram (EEG) and anti-seizure medication (ASM) management in relation to clinical manifestations and EEG abnormalities. This was a multi-centre prospective study involving two intensive rehabilitation units (IRUs). Clinical and EEG data were acquired at admission to the IRU, discharge (T1), and six-month follow-up (T2). A total of 163 patients underwent EEG recording upon admission to the IRU, while 149 were available for analysis at discharge from the IRU. Eighteen patients were treated with ASMs upon IRU admission despite only five of these patients having early seizures. Among the 145 patients not treated upon admission to the IRU, eight had late seizures, of which six were during the IRU stay, while two were after discharge from the IRU. During IRU stay, ASMs were generally discontinued in patients with no early seizures reported and were started in patients with late seizures. Among the 18 patients treated with ASMs at admission to the IRU, only six maintained the therapy also at T2. Our results suggest that post-acute inpatient rehabilitation is a proper setting to observe patients treated with ASMs after stroke and provide personalized post-stroke epilepsy management.

Segmentation and quantification of venous structures and perivascular spaces in the thalamus in epilepsy using 7 Tesla MRI

Background and purposeEpilepsy is a complex neurological disorder affecting 50 million people worldwide. Persistent seizures may correlate with neural network, microstructural, and vascular changes within the thalamus. These thalamic changes may result from seizure activity or broader alterations involving neuronal vasculature and neuroinflammatory processes linked to glymphatic drainage. Improved resolution with Ultra-high field (UHF) magnetic resonance imaging (MRI) may be useful in identifying possible thalamic vascular abnormalities not otherwise detectable at lower field strengths. Materials and methodsWe outline a novel method which leverages UHF neuroimaging for detection and quantification of vessels and perivascular spaces (PVS) within the thalamus in 25 epilepsy patients and 16 controls, to uncover possible underlying imaging biomarkers of epilepsy. In our analysis, we optimize a MATLAB-based Frangi-based detection tool called Perivascular Space Semi-Automated Segmentation (PVSSAS) to detect thalamic PVSs, and additionally use a second Frangi-based segmentation tool method to automate detection of vascular structures in the thalamus. The resulting PVS and vessel masks were used to quantify differences in the number of vessels, PVS, overlaps, and number of PVS overlaps per vessel detected between groups, using a Hessian detection filter linked on an 18-connected network. ResultsWe found significantly more thalamic PVS (p = 0.0307) and a significant increase in the number of thalamic vessels (p = 0.038) in patients compared to controls. ConclusionHere we have developed a novel process which leverages UHF MRI to quantify and detect thalamic vessels and PVS that may provide a potential neuroimaging biomarker of epilepsy. Statement of SignificanceWe use 7T, ultra-high field MRI and employed an innovative combination of semi-automated perivascular space segmentation and automated vessel segmentation to visualize and quantify vessels and perivascular spaces (PVS) within the thalamus, a highly cited region of interest in epilepsy. To our knowledge, this is the first study to semi-automatically visualize and segment PVS in the thalamus and automatically detect thalamic vessels. We uncovered detectable differences in thalamic vasculature and PVS. These findings suggests that increases in the number of thalamic PVS and vessels may be a potential neuroimaging biomarker in epilepsy. This tool may be useful in the detection of subtle vascular changes in other regions of the brain related to epilepsy or can be employed in other neurological conditions.

Management strategies for refractory status epilepticus

Refractory status epilepticus (RSE) is defined as the persistence of either clinical or electrographic seizures despite the administration of appropriate doses of an initial benzodiazepine and suitable second-line antiepileptic drugs (AEDs). The Neurocritical Care Society and the American Epilepsy Society have proposed a treatment paradigm for the management of convulsive status epilepticus (CSE). The third-line therapy in refractory CSE may involve general anesthesia using intravenous midazolam, propofol, or other agents, while recent evidence supports the use of ketamine to manage RSE in both adults and children. However, although these treatment strategies are frequently employed in nonconvulsive status epilepticus (NCSE), the efficacy of AEDs and anesthetics in NCSE has not been thoroughly investigated. Recent evidence has demonstrated the safety and efficacy of newer AEDs, including levetiracetam and lacosamide, in the treatment of status epilepticus (SE) and RSE, which also encompasses NCSE. Use of multiple combinations of various intravenous AEDs can also be considered in NCSE before the administration of general anesthesia. In addition, AEDs alone exhibit limited effectiveness in managing SE for new-onset RSE (NORSE) and its subset, febrile infection-related epilepsy syndrome. Therefore, in cases of refractory status, it is imperative to explore treatment options beyond AEDs, including immunotherapy and the incorporation of a ketogenic diet. The present review suggests treatment approaches for RSE based on subgroups, including CSE, NCSE, and NORSE. A discussion of recent clinical studies on AEDs and anesthetics in the management of RSE, as well as proposed treatment methods for NORSE, is also provided.