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ObjectiveThis study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom.MethodsWe conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method.ResultsData for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique.SignificanceThis pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

Children with tuberous sclerosis complex (TSC), may experience a variety of seizure types in the first year of life, most often focal seizure sand epileptic spasms. Drug resistance is seen early in many patients, and the management of TSC associated epilepsy remain a major challenge for clinicians. In 2018 clinical recommendations for the management of TSC associated epilepsy were published by a panel of European experts. In the last five years considerable progress has been made in understanding the neurobiology of epileptogenesis and three interventional randomized controlled trials have changed the therapeutic approach for the management of TSC associated epilepsy. Pre-symptomatic treatment with vigabatrin may delay seizure onset, may reduce seizure severity and reduce the risk of epileptic encephalopathy. The efficacy of mTOR inhibition with adjunctive everolimus was documented in patients with TSC associated refractory seizures and cannabidiol could be another therapeutic option. Epilepsy surgery has significantly improved seizure outcome in selected patients and should be considered early in all patients with drug resistant epilepsy. There is a need to identify patients who may have a higher risk of developing epilepsy and autism spectrum disorder (ASD). In the recent years significant progress has been made owing to the early identification of risk factors for the development of drug-resistant epilepsy. Better understanding of the mechanism underlying epileptogenesis may improve the management for TSC-related epilepsy. Developmental neurobiology and neuropathology give opportunities for the implementation of concepts related to clinical findings, and an early genetic diagnosis and use of EEG and MRI biomarkers may improve the development of pre-symptomatic and disease-modifying strategies. • Three interventional RCTs have changed the therapeutic approach in patients with TSC. • Early identification of risk factors of (drug resistant) epilepsy is critical for an optimal management of TSC patients. • Pre-symptomatic treatment with vigabatrin is recommended as early as possible when epileptiform EEG activity is recorded. • Epilepsy surgery should be considered early in all TSC patients with drug resistant epilepsy. • Clinical, EEG, MRI and genetic predictors of drug resistant epilepsy guides treatment choices. [ABSTRACT FROM AUTHOR]

Purpose: Several antiseizure drugs (ASD), especially Valproic acid (VPA), influence platelet counts and coagulation parameters. The ketogenic diet (KD), established in drug-resistant epilepsy, is combined with ASDs. Bruising and prolonged bleeding times during KD have been described, but whether hemostatic changes result from the KD or from concomitant ASDs, remains unclear. Aim of the present study was to evaluate bleeding, platelet counts and global coagulation tests prior to and during KD in childhood epilepsy.Method: Consecutive children treated with KD were systematically observed for bleeding. Serial measurements of platelet counts and global coagulation tests (APTT, PT and fibrinogen) were obtained at baseline and during KD (at 1, 3, 6 and 12 months). Children with KD monotherapy, concomitant VPA, or other ASDs were compared.Results: Among 162 children receiving KD, we observed neither bleeding in daily life nor perioperative bleeding in those undergoing surgery (n = 25). Most children had normal platelet counts and coagulation parameters. Only a few had transient mild thrombocytopenia and mildly prolonged APTT values, not indicative of a bleeding risk. Even KD combined with VPA did not cause relevant coagulopathy. Unexpectedly, we found mild thrombocytosis in 24 % of patients prior to KD, which was most pronounced in yet untreated epilepsy. Thrombocytosis steadily resolved during KD.Conclusions: During KD treatment of childhood epilepsy, we observed neither bleeding symptoms nor laboratory results indicating a bleeding risk. Unexpectedly, mild thrombocytosis was present in 24 % at baseline, normalising during KD. Thrombocytosis may reflect the underlying inflammatory process of untreated epilepsy and requires further study. [ABSTRACT FROM AUTHOR]

Abstract Patients with tuberous sclerosis complex (TSC) are at very high risk for developing epilepsy, and the majority experience seizure onset during the first year of life. Early targeted interventions increase the probability of seizure-freedom and may protect neurodevelopment. In 2012, clinical recommendations for the management of epilepsy in patients with TSC were published by a panel of European experts. Since that time novel studies, reports, and expert opinions in preclinical and clinical TSC-related sciences prompted the need for updated recommendations, including epileptogenesis in TSC, the potential role of predictive biomarkers, the possible benefits of presymptomatic diagnosis and preventive treatment, and new treatment options including mTOR inhibitors. A reconvened panel reviewed the current literature to answer specific questions and five panelists discussed the findings, followed by a general discussion during which all issues were debated to achieve consensus regarding recommendations. A draft manuscript based on these discussions and recommendations was then circulated several times among the panelists, who added their own comments. All the panelists/authors agreed with the final manuscript, which was then submitted for publication. The panel concluded that the need for early diagnosis of TSC-associated seizures is now established, electroencephalographic monitoring has good predictive value for epilepsy before seizure onset in TSC, and, until conclusive data from the EPISTOP trial are available, administration of vigabatrin may be considered in children with subclinical epileptiform EEG discharges. The panel also supported the role of adjunctive everolimus for TSC-associated drug-refractory seizures and emphasized the necessity of early surgical evaluation. Highlights • Parental education is crucial to early recognize infantile spasms and focal seizures. • Early EEG monitoring significantly improves the outcomes of infants with epilepsy. • Certain EEG patterns can be predictive of subsequent seizure presentation. • Vigabatrin may be considered if ictal discharges without clinical seizures occur. • mTOR inhibition should be considered early for refractory seizures. [ABSTRACT FROM AUTHOR]

Background To describe the rates and types of psychiatric disorders among adolescents with chronic symptomatic epilepsies and to evaluate syndrome-specific differences between temporal lobe (TLE) and frontal lobe (FLE) epilepsies. Methods A cross-sectional single-center study design applying the Youth Self Report (YSR) to investigate psychopathological symptoms and the Weinberger Adjustment Inventory (WAI) to investigate personality dimensions was used. Consecutive adolescents between 14 and 18 years of age with drug-resistant symptomatic TLE and FLE were investigated during pre-surgical evaluation prior to epilepsy surgery. Data from twenty-eight patients (19 with TLE and 9 with FLE) were analyzed for this report. Results Compared with the test norm, higher prevalence rates and a wider range of psychopathological symptoms were seen in patients with TLE. This result was not seen in patients with FLE. Concerning personality dimensions, significantly higher values of repressive defensiveness and significantly lower values of positive emotion and confidence were found in patients with TLE. In contrast, significantly lower levels of distress and significantly higher levels of repressive defensiveness and denial of distress were seen in patients with FLE. Comparing TLE with FLE, a significantly higher mean score for distress, and a significantly lower mean score for positive emotion and denial of distress were found in patients with TLE. Conclusion In summary, psychiatric comorbidity was frequently found in this sample of youths with chronic drug-resistant localization-related epilepsies. Although results have to be interpreted with caution because of the small sample size, psychiatric symptomatology was significantly different between TLE and FLE. Our results show that continuous and syndrome-specific psychiatric monitoring is essential in young patients with epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies. Methods: Data from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as ≥50% seizure reduction. Treatment effects on EEG, developmental outcome and the “outcome-predictive” value of various clinical factors were also assessed. Results: 50 children (22 boys; mean age 4.5 years±3.55) were included. Mean follow-up was 3.93±2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly (p =0.014) and a significantly lower rate of epileptic discharges (p =0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress (p =0.038). Favourable treatment outcome was associated with a shorter disease duration (p =0.025) and generalised tonic clonic seizures (p =0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome. Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate (p =0.001) and valproate (p =0.046). Conclusion: Despite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development. [ABSTRACT FROM AUTHOR]

Objective: To correlate fetal brain magnetic resonance imaging (MRI) findings with epilepsy characteristics and neurodevelopment at 2 years of age in children with tuberous sclerosis complex (TSC) to improve prenatal counseling.Study Design: This retrospective cohort study was performed in a collaboration between centers of the EPISTOP consortium. We included children with definite TSC, fetal MRIs, and available follow-up data at 2 years of age. A pediatric neuroradiologist masked to the patient's clinical characteristics evaluated all fetal MRIs. MRIs were categorized for each of the 10 brain lobes as score 0: no (sub)cortical lesions or doubt; score 1: a single small lesion; score 2: more than one small lesion or at least one large lesion (>5 mm). Neurologic manifestations were correlated to lesion sum scores.Results: Forty-one children were included. Median gestational age at MRI was 33.3 weeks; (sub)cortical lesions were detected in 97.6%. Mean lesion sum score was 4.5. At 2 years, 58.5% of patients had epilepsy and 22% had drug-resistant epilepsy. Cognitive, language, and motor development were delayed in 38%, 81%, and 50% of patients, respectively. Autism spectrum disorder (ASD) was diagnosed in 20.5%. Fetal MRI lesion sum scores were significantly associated with cognitive and motor development, and with ASD diagnosis, but not with epilepsy characteristics.Conclusions: Fetal cerebral lesion scores correlate with neurodevelopment and ASD at 2 years in children with TSC. [ABSTRACT FROM AUTHOR]