Unrecognized Focal Nonmotor Seizures in Adolescents Presenting to Emergency Departments.

BACKGROUND AND OBJECTIVES: Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents. METHODS: This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants' initial diagnosis and management. RESULTS: A total of 83 adolescents were enrolled between 12 and 18 years. Fifty-eight (70%) presented to an ED before diagnosis of epilepsy. Although most ED presentations were for motor seizures (n = 52; 90%), many patients had a history of nonmotor seizures (20/52 or 38%). Adolescents with initial nonmotor seizures were less likely to present to EDs (26/44 or 59% vs 32/39 or 82%, p = 0.02), and nonmotor seizures were less likely to be correctly identified (2/6 or 33% vs 42/52 or 81%, p = 0.008). A history of initial nonmotor seizures was not recognized in any adolescent who presented for a first-lifetime motor seizure. As a result, initiation of treatment and admission from the ED was not more likely for these adolescents who met the definition of epilepsy compared with those with no seizure history. This lack of nonmotor seizure history recognition in the ED was greater than that observed in the adult group (0% vs 23%, p = 0.03) and occurred in both pediatric and nonpediatric ED settings. DISCUSSION: Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.

Epilepsia partialis continua: A review.

Epilepsia partialis continua (EPC) is a rare type of focal motor seizure characterized by continuous, involuntary muscle contractions in a specific part of the body. These contractions usually involve rhythmic, twitching movements and can last for several hours to days. The seizures are usually limited to one part of the body and can be clonic or dystonic. EPC can affect people of all ages but is more common in children and adolescents. The pathophysiology of EPC is complex and depends on the cause. There are several possible causes of EPC including structural brain abnormalities, infections, metabolic and genetic disorders, inflammatory conditions, traumatic brain injury, and vascular causes. The work-up of EPC includes electroencephalography (EEG), magnetic resonance imaging (MRI) of the brain, position emission tomography (PET) scan of the brain, autoimmune antibodies, infection work-up, and metabolic and genetic work-up. The management of EPC can be challenging. Antiseizure medications (ASDs) including benzodiazepines are an integral part of the management of EPC. Immunotherapy trials are recommended in resistant cases. Epilepsy surgery is one of the effective modalities in some surgically amenable cases. This article reviews the topic of EPC and summarizes diagnostic and .treatment recommendations.

Stereoelectroencephalography-guided radiofrequency thermocoagulation of the epileptogenic zone: a potential treatment and prognostic indicator for subsequent excision surgery.

PURPOSE: To evaluate the safety and efficacy of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) for drug-resistant focal epilepsy and investigate the relationship between post-RFTC remission duration and delayed excision surgery effectiveness. METHODS: We conducted a retrospective analysis of 43 patients with drug-resistant focal epilepsy who underwent RFTC via SEEG electrodes. After excluding three, the remaining 40 were classified into subgroups based on procedures and outcomes. Twenty-four patients (60%) underwent a secondary excision surgery. We determined the predictive value of RFTC outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the duration of seizure freedom after RFTC were assessed. RESULTS: Among 40 patients, 20% achieved Engel class I with RFTC alone, while 24 underwent delayed secondary excision surgery. Overall, 41.7% attained Engel class I, with a 66.7% success rate combining RFTC with delayed surgery. Seizure freedom duration was significantly longer in the success group (mean 4.9 months, SD = 2.7) versus the failure group (mean 1.9 months, SD = 1.1; P = 0.007). A higher proportion of RFTC-only and delayed surgical success group patients had preoperative lesional findings (p = 0.01), correlating with a longer time to seizure recurrence (p < 0.05). Transient postoperative complications occurred in 10%, resolving within a year. CONCLUSION: This study demonstrates that SEEG-guided RFTC is a safe and potential treatment option for patients with drug-resistant focal epilepsy. A prolonged duration of seizure freedom following RFTC may serve as a predictive marker for the success of subsequent excision surgery.

Long-term effects of adjunctive eslicarbazepine acetate in adult Asian patients with refractory focal seizures: Post hoc analysis of a phase III trial.

A post hoc analysis of data from Asian patients included in the study BIA-2093-304 was conducted to evaluate the long-term safety/tolerability and efficacy of adjunctive eslicarbazepine acetate (ESL) in adult Asian patients with refractory focal seizures. Part I was a randomized controlled trial, in which patients received ESL (800 or 1200 mg once daily [QD]) or placebo, assessed over a 12-week maintenance period. Patients completing Part I could enter two open-label extension periods (Part II, 1 year; Part III, ≥2 years), during which all received ESL (400-1600 mg QD). Safety/tolerability was assessed by evaluating treatment-emergent adverse events (TEAEs). Efficacy assessments included responder and seizure freedom rates. The safety population included 125, 92, and 23 Asian patients in Parts I, II, and III, respectively. Incidence of ESL-related TEAEs was 61.3%, 45.7%, and 17.4% during Parts I, II, and III, respectively. ESL-related TEAEs (most commonly, dizziness, somnolence, and headache) were consistent with ESL's known safety profile. During Part I, responder rates were higher with ESL 800 (41.7%) and 1200 mg QD (44.4%) versus placebo (32.6%), although not statistically significant. Seizure freedom rates with ESL 800 (5.5%) and 1200 mg QD (11.1%) were also higher versus placebo (0%) (p < 0.05 for ESL 1200 mg QD versus placebo). At the end of Part II, responder and seizure freedom rates were 60.3% and 14.7%, respectively. In summary, adult Asian patients with refractory focal seizures were responsive to treatment with ESL as adjunctive therapy and generally showed treatment tolerance well for up to 3 years. No new/unexpected safety findings were observed.

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

INTRODUCTION: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). METHODS: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. DISCUSSION: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Systematic Analysis of the Relationship Between Elevated Zinc and Epilepsy.

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.

Multisensory flicker modulates widespread brain networks and reduces interictal epileptiform discharges.

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect of sensory flicker exposure on local field potential (LFP) power and interictal epileptiform discharges (IEDs) as primary and secondary outcomes, respectively. Flicker focally modulated local field potentials in expected canonical sensory cortices but also in the medial temporal lobe and prefrontal cortex, likely via resonance of stimulated long-range circuits. Moreover, flicker decreased interictal epileptiform discharges, a pathological biomarker of epilepsy and degenerative diseases, most strongly in regions where potentials were flicker-modulated, especially the visual cortex and medial temporal lobe. This trial met the scientific goal and is now closed. Our findings reveal how multi-sensory stimulation may modulate cortical structures to mitigate pathological activity in humans.

Multimodal Approach for the Treatment of Complex Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are rare congenital lesions formed by heterotopic neuronal and glial cells attached to the mammillary bodies, tuber cinereum, and hypothalamus.They often present with an intractable epilepsy typically characterized by gelastic seizures but commonly associated with other types of refractory seizures. The clinical course is progressive in most of the cases, starting with gelastic seizures in infancy and deteriorating into complex seizure disorders that result in catastrophic epilepsy associated with cognitive decline and behavioral disturbances.Hamartomas are known to be intrinsically epileptogenic and the site of origin for the gelastic seizures. As antiepileptic drugs are typically ineffective in controlling HH-related epilepsy, different surgical options have been proposed as a treatment to achieve seizure control. Resection or complete disconnection of the hamartoma from the mammillothalamic tract has proved to achieve a long-lasting control of the epileptic syndrome.Usually, symptoms and their severity are typically related to the size, localization, and type of attachment. Precocious puberty appears mostly in the pedunculated type, while epileptic syndrome and behavioral decline are frequently related to the sessile type. For this reason, different classifications of HHs have been developed based on their size, extension, and type of attachment to the hypothalamus.The bigger and more complex hypothalamic hamartomas typically present with severe refractory epilepsy, behavioral disturbances, and progressive cognitive decline posing a formidable challenge for the control of these symptoms.We present here our experience with the multimodal treatment for complex hypothalamic hamartomas. After an in-depth review of the literature, we systematize our approach for the different types of hypothalamic hamartomas.

Lesion volume and spike frequency on EEG impact perfusion values in focal cortical dysplasia: a pediatric arterial spin labeling study.

Arterial spin labelling (ASL), an MRI sequence non-invasively imaging brain perfusion, has yielded promising results in the presurgical workup of children with focal cortical dysplasia (FCD)-related epilepsy. However, the interpretation of ASL-derived perfusion patterns remains unclear. Hence, we compared ASL qualitative and quantitative findings to their clinical, EEG, and MRI counterparts. We included children with focal structural epilepsy related to an MRI-detectable FCD who underwent single delay pseudo-continuous ASL. ASL perfusion changes were assessed qualitatively by visual inspection and quantitatively by estimating the asymmetry index (AI). We considered 18 scans from 15 children. 16 of 18 (89%) scans showed FCD-related perfusion changes: 10 were hypoperfused, whereas six were hyperperfused. Nine scans had perfusion changes larger than and seven equal to the FCD extent on anatomical images. Hyperperfusion was associated with frequent interictal spikes on EEG (p = 0.047). Perfusion changes in ASL larger than the FCD corresponded to larger lesions (p = 0.017). Higher AI values were determined by frequent interictal spikes on EEG (p = 0.004). ASL showed FCD-related perfusion changes in most cases. Further, higher spike frequency on EEG may increase ASL changes in affected children. These observations may facilitate the interpretation of ASL findings, improving treatment management, counselling, and prognostication in children with FCD-related epilepsy.

Familial occurrence of seizure disorders across MRI defined structural focal epilepsy etiology.

BACKGROUND: Previous studies have established familial occurrence of epilepsy and seizure disorders and early age of epilepsy onset as predictors of genetic epilepsy, but have not evaluated the rate of their occurrence in patients with different epilepsy etiology. Our study determines the distribution of familial occurrence and age of epilepsy onset across structural focal epilepsy (FE) etiology in a large FE cohort. METHODS: Records of 1354 consecutive patients evaluated for epilepsy and seizure disorders in The Neurology Clinic, University Clinical Center of Serbia from 2008 to 2019 were screened for FE. Structural etiology, lobar diagnosis, familial occurrence, and age at epilepsy onset were determined. Patients with a. nonlesional focal epilepsy (NLFE), b. hippocampal sclerosis (HS) and c. congenital or perinatal etiology (CPE) were classified as NAFE, while patients with an identified acquired focal epilepsy (AFE) constituted the control group. RESULTS: We identified 965 patients with FE, 329 (34.1 %) with NLFE, 213 (22.1 %) with HS, 174 (18.0 %) with CPE and 249 (25.8 %) with AFE. Familial occurrence was identified in 160 (16.6 %), 19.1 % of patients with NAFE and 9.2 % of AFE (p = 0.003). Patients with NAFE had a younger age of epilepsy onset (13 vs. 18 years, p < 0.001). The highest proportion of familial occurrence was found in patients with NLFE (23.7 %), while the youngest median age of epilepsy onset was identified in patients with HS (12 years) and CPE (11 years). CONCLUSION: Patients with NAFE frequently have familial occurrence of epilepsy and have an earlier age of epilepsy onset than patients with AFE.

The latest advances in the pharmacological management of focal epilepsies in children: a narrative review.

INTRODUCTION: Focal epilepsy constitutes the most common epilepsy in children, and medical treatment represents the first-line therapy in this condition. The main goal of medical treatment for children and adolescents with epilepsy is the achievement of seizure freedom or, in drug-resistant epilepsies, a significant seizure reduction, both minimizing antiseizure medications (ASM)-related adverse events, thus improving the patient's quality of life. However, up to 20-40% of pediatric epilepsies are refractory to drug treatments. New ASMs came to light in the pediatric landscape, improving the drug profile compared to that of the preexisting ones. Clinicians should consider several factors during the drug choice process, including patient and medication-specific characteristics. AREAS COVERED: This narrative review aims to summarize the latest evidence on the effectiveness and tolerability of the newest ASMs administered as monotherapy or adjunctive therapy in pediatric epilepsies with focal onset seizures, providing a practical appraisal based on the existing evidence. EXPERT OPINION: The latest ASMs have the potential to be effective in the pharmacological management of focal onset seizures in children, and treatment choice should consider several drug- and epilepsy-related factors. Future treatments should be increasingly personalized and targeted on patient-specific pathways. Future research should focus on discovering new chemical compounds and repurposing medications used for other indications.

[The relationship between immunological and psychopathological characteristics in patients with focal epilepsy depending on the profile of interhemispheric asymmetry]. / Vzaimosvyaz' immunologicheskikh i psikhopatologicheskikh kharakteristik u bol'nykh fokal'noi epilepsiei v zavisimosti ot profilya mezhpolusharnoi asimmetrii.

OBJECTIVE: To identify the possible influence of cellular immunity parameters and neurobiological variables (frequency of seizures of various semiotics and their severity) on comorbid psychopathological symptoms depending on the profile of interhemispheric asymmetry in patients with focal forms of epilepsy. MATERIAL AND METHODS: The study included 92 patients with epilepsy (38 men, 54 women, mean age 38.7+8.45 years). Focal temporal lobe epilepsy was diagnosed in 36 patients, focal frontal lobe epilepsy in 16 patients, and temporal-frontal lobe epilepsy in 40 patients. For each type of seizure, severity was assessed according to the National Seizure Severity Scale (NHS3). The mental status of patients was assessed using the SCL-90 self-report questionnaire. The Annette scale was used to assess the profile of interhemispheric asymmetry. The number of different clusters of lymphocytes was studied, including the number of T-lymphocytes (CD3+), T-helpers (CD3+CD4+), T-cytotoxic (CD3+CD8+), T-NK (natural killers CD3+CD16+CD56+), B-lymphocytes (CD3-CD19+), as well as immunoregulatory index (CD4/CD8 ratio). In order to identify any possible relationships between neurobiological and immune variables, on the one hand, and the SCL-90 constructs, on the other hand, a separate correlation analysis of Spearman ranks within the left-handed group and the right-handed group was carried out. RESULTS: We revealed the differences between groups of patients with epilepsy with right and left profiles of hemispheric asymmetry regarding the relationship between the frequency of seizures, their severity and accompanying psychopathological variables, on the one hand, and between immunity indices and psychopathological constructs, on the other hand. It has been established that neurobiological and immune variables in left-handers can determine the psychopathological structure of the comorbid mental disorder. CONCLUSION: Prediction of concomitant psychopathological syndromes in patients with epilepsy on the basis of clinical data and data on immunity is quite possible, but only in left-handed patients.

Genetic causal association between physical activities and epilepsy: A Mendelian randomization study.

BACKGROUND: Despite numerous investigations into the relationship between physical activities (PA) and epilepsy, the causal effects remain contentious. Thus, we conducted a two-sample Mendelian randomization (MR) study to assess the potential causality. METHODS: Single-nucleotide polymorphisms (SNPs) predisposed to self-reported moderate and vigorous physical activities (MPA and VPA) and overall acceleration average (OAA) calculated through wrist-worn accelerometers were selected as exposure instrumental variables. Five subtypes of epilepsy, including all epilepsy, focal epilepsy and generalized epilepsy (with or without each other), focal epilepsy-strict definition and generalized epilepsy-strict definition (without overlap), were chosen as the outcomes. The MR study utilized the inverse-variance weighted (IVW) method as the primary analytical tool, supplemented by MR-Egger, simple mode, weighted mode, and weighted median methods. Cochran's Q and MR-Egger intercept tests were employed to assess heterogeneity and pleiotropy, while MR pleiotropy residual sum and outlier and leave-one-out analyses were conducted to identify potential SNP outliers. RESULTS: The study indicated that OAA was genetically linked to a decreased risk of both focal epilepsy (OR = 0.812, 95% CI: 0.687-0.960, p = .015, IVW) and focal epilepsy-strict definition (OR = 0.732, 95% CI: 0.596-0.900, p = .003, IVW; OR = 0.749, 95% CI: 0.573-0.979, p = .035, Weighted median). Genetically predicted MPA and VPA did not exhibit a causal association with all epilepsy or its subtypes (p>.05). No evidence of heterogeneity, pleiotropy, or SNP outlier was observed. CONCLUSIONS: Our findings suggested that PA with accelerometer monitoring may potentially reduce the risk of focal epilepsy, while there is no evidence supporting causal association between self-reported MPA or VPA and either focal or generalized epilepsy.

Effectiveness analysis of three-drug combination therapies for refractory focal epilepsy.

Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann-Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini-Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n â€‹= â€‹95). At the last clinical visit, 14.9% (n â€‹= â€‹48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17-0.85; adjusted P â€‹< â€‹0.001) and 0.63 (IQR, 0.21-1.04; adjusted P â€‹< â€‹0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR â€‹= â€‹0.67; adjusted P â€‹= â€‹0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.

Transient postictal dysphagia in older adults with focal structural epilepsy.

OBJECTIVE: Seizures can cause transient neurological symptoms, such as hemiparesis and aphasia. However, temporary swallowing changes leading to postictal dysphagia have not been previously described. Therefore, this study evaluated the presence of swallowing disorders following seizure. In addition, dysphagia severity and duration of any recovery from dysphagic symptoms were investigated. METHODS: The local clinical database of all fiberoptic endoscopic evaluation of swallowing (FEES) examinations performed from 2008 to 2019 was screened for patients diagnosed with seizures, but excluding patients with intensive care unit admission or intubation >24 h. Patient charts were evaluated to identify preexisting dysphagia or potential concurrent medical causes for dysphagia, including hyponatremia, increased intracranial pressure, sepsis, or other encephalopathies associated with infections, or other possible causes at the time of admission. Patients receiving >.5 defined daily doses of benzodiazepines or neuroleptics were also excluded. Age, sex, seizure semiology and etiology, comorbidities, concurrent pneumonia, and dysphagia course during hospitalization were evaluated as predictors of the occurrence of dysphagia or its potential duration. RESULTS: We identified 41 patients with dysphagia following a seizure, without evidence of any concurrent cause of swallowing dysfunction. These patients all presented with focal structural epilepsy, they had a mean age of 79 ± 11.3 years (range = 44-95 years), and 21 were women. The mean Elixhauser Comorbidity Score was 4.8. Hospital-acquired pneumonia was detected in 21 patients (51.2%). FEES diagnosed mild and severe dysphagia in 21 (51.2%) and 20 (48.8%) patients, respectively. Dysphagia improved significantly (p = .001) during hospitalization, persisting for an average of 3.9 days (median = 3 days, SD = 2.07 days, range = 1-8 days). SIGNIFICANCE: Dysphagia is a potential transient neurological deficit following seizure. Our findings suggest that older patients, with focal structural epilepsy, are at risk for postictal dysphagia. Further studies are needed to ascertain the prevalence, complications, and predictors of postictal dysphagia. Dysphagia screening may improve early detection in patients with relevant risk factors, as well as reduce the occurrence of aspiration pneumonia.

Specific consistency score for rational selection of epilepsy resection surgery candidates.

OBJECTIVE: Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. METHODS: This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. RESULTS: A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8-8.9] vs. 4.9 [95% CI = 4.3-5.5] points; p < .001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2-9.3] vs. 6.4 [95% CI = 4.5-8.3] points; p = .008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3-9.2] vs. 5.4 [95% CI = 3.5-7.3] points; p = .004). Multivariate analysis revealed areas under the curve of .843, .825, and .881 for Parameters 1, 2, and 3, respectively. SIGNIFICANCE: SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy.

Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies.

OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.

Comprehensive review of status gelasticus: Diagnostic challenges and therapeutic insights.

Status gelasticus is a rare form of status epilepticus characterized by prolonged and/or clustered gelastic seizures. The review encompasses an analysis of cases reported in the literature, focusing on causes, clinical-electroencephalographic features, and therapeutic interventions. The study reveals the challenges in defining and understanding status gelasticus due to its diverse etiologies and limited reported cases. The association with hypothalamic hamartomas and other brain abnormalities underscores the importance of thorough evaluations. The review also discusses new treatments, including medications and less invasive surgeries. While progress has been made, the study points out challenges in diagnosing and managing this complex condition, highlighting the importance of ongoing research.

Functional brain connectivity in children with focal epilepsy: A systematic review of functional MRI studies.

Epilepsy is increasingly recognised as a brain network disorder and many studies have investigated functional connectivity (FC) in children with epilepsy using functional MRI (fMRI). This systematic review of fMRI studies, published up to November 2023, investigated profiles of FC changes and their clinical relevance in children with focal epilepsy compared to healthy controls. A literature search in PubMed and Web of Science yielded 62 articles. We categorised the results into three groups: 1) differences in correlation-based FC between patients and controls; 2) differences in other FC measures between patients and controls; and 3) associations between FC and disease variables (for example, age of onset), cognitive and seizure outcomes. Studies revealed either increased or decreased FC across multiple brain regions in children with focal epilepsy. However, findings lacked consistency: conflicting FC alterations (decreased and increased FC) co-existed within or between brain regions across all focal epilepsy groups. The studies demonstrated overall that 1) interhemispheric connections often displayed abnormal connectivity and 2) connectivity within and between canonical functional networks was decreased, particularly for the default mode network. Focal epilepsy disrupted FC in children both locally (e.g., seizure-onset zones, or within-brain subnetworks) and globally (e.g., whole-brain network architecture). The wide variety of FC study methodologies limits clinical application of the results. Future research should employ longitudinal designs to understand the evolution of brain networks during the disease course and explore the potential of FC biomarkers for predicting cognitive and postsurgical seizure outcomes.

Feasibility study of microburst VNS therapy in drug-resistant focal and generalized epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. OBJECTIVE: To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (µVNS). µVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. METHODS: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of µVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. RESULTS: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of µVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). CONCLUSION: Overall, µVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.