Risk of Autism Spectrum Disorder According to the Dose and Trimester of Exposure to Antiseizure Medications: A Systematic Review and Meta-Analysis

Background: The association between prenatal exposure to antiseizure medications (ASM) and autism spectrum disorder has been documented. This study sought to examine and synthesize evidence from studies that have evaluated these associations, with particular focus on the trimester of pregnancy and dosage of exposure. Methodology: PubMed, Embase, and PsycINFO databases were searched following strict inclusion/exclusion criteria. 10 studies were recruited involving children born to mothers with epilepsy who took ASM during pregnancy as cases, and those with epilepsy who did not take any ASM in pregnancy. Results: The relative risk of developing ASD among children exposed to valproic acid (RR, 3.90 [95% CI: 2.36 - 6.44], p < 0.006), was twice higher than that of carbamazepine (RR, 1.65 [95% CI: 0.62 - 4.37], p < 0.0001), or lamotrigine (RR, 1.60 [95% CI: 0.77 - 3.32], p = 0.006). The trimester of exposure and dosage of ASM administered were not significant. Conclusion: In summary, prenatal exposure to ASM increased the risk of developing ASD in children. The relative risk was twice as high in those exposed to valproic acid compared to those exposed to carbamazepine or lamotrigine. Trimester of pregnancy and dosage of ASM used by the mothers were not significant.

Electroencephalogram and phenotype patterns in neuronopathic Gaucher disease patients-ten years of experience in a single center

Background This study aimed to investigate the unique electroencephalography(EEG)patterns in neuronopathic Gaucher disease(GD)patients and explore the correlations between EEG findings and neurological phenotypes so as to optimize clinical outcomes.Methods A retrospective analysis was conducted on 74 EEG recordings from 50 GD patients between January 2012 and July 2022.Results Twenty-three patients exhibited abnormal EEG recordings,including 11 of the GD1 type(the transitional type)and 12 with neuronopathic GD.Of the 12 neuronopathic GD patients,9 patients with epilepsy were analysed specifically in terms of the clinical course.The primary waveform observed in the neuronopathic EEG recordings was the spike-and-wave complex(SWC)during both awake and sleep states.This was significantly different from sharp waves observed only during sleep in the patients of the transitional type(P=0.0230).The abnormal discharges in the neuronopathic patients were most commonly located in the bilateral Rolandic areas,while the transitional type commonly involved the bilateral frontal regions.Three patients with an epileptic EEG pattern reported their initial seizures years later.Seizures in the neuronopathic patients were effectively controlled with anti-seizure medications(ASMs),despite the ongoing presence of abnormal EEG patterns.The EEG patterns during ocular symptoms were characterized by sporadic or continuous unilateral SWC during sleep.Conclusions Patients with neuronopathic GD exhibit distinct EEG patterns that can help differentiate them from GD1 patients.Early treatment with ASMs can effectively control seizures.EEG plays a crucial role in monitoring seizures and can facilitate prompt intervention for GD patients.

Differences and potential mechanisms of theta oscillation and temporoparietal and temporal-central networks in temporal lobe epilepsy patients with unilateral hippocampal sclerosis

Background There is a lack of further exploration of the epileptogenic network of specific types of epilepsy,such as unilateral hippocampal sclerosis(HS),and there is an urgent need to find exact evidence to confirm the consistency of its brain network changes.Methods We enrolled 22 mesial temporal lobe epilepsy with hippocampal sclerosis(mTLE-HS)patients to compare the differences in brain activity between 22 healthy controls(HCs)and them.Resting-state electroencephalography(EEG)was also measured.Then,we calculated the power spectral density and phase locking values in and between these electrodes.Results The results showed the increased theta power was related to the high severity of epilepsy in the temporal,parietal,and central regions in mTLE-HS patients,and there were positive correlations between theta power in the contralateral temporal region and seizure frequency.Theta power in the ipsilateral parietal lobe is positively correlated with the number of anti-seizure medications(ASMs),but not with the usage of third-generation ASMs.Meanwhile,the temporal lobe of mTLE-HS patients had more connectivity with parietal lobe and central region.

Hippocampal sclerosis in women with temporal lobe epilepsy:seizure and pregnancy outcomes

Background Temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)is typically resistant to pharmacological interventions;however,achieving seizure freedom is possible through surgery.Our objective was to focus on the pregnancy and seizure outcomes during pregnancy of women with TLE-HS,and aim to identify predictors of seizure control.Methods The West China Registry of Pregnancy of Women with Epilepsy(WCPR_EPi)was a monocentric prospective cohort study of women with epilepsy(WWE).We screened women with TLE-HS in this database.Their clinical profile,anti-seizure medication(ASM)use,and pregnancy outcomes were extracted from the records of the registry(2010–2023).Results Out of 2320 WWE followed up,47 pregnancies in women with TLE-HS were identified and analyzed.Seizure exacerbation occurred in 40.4%of pregnancies,and seizure freedom was present in 34.0%of these during pregnancy.Factors associated with seizure exacerbation during pregnancy was ASM non-adherence(odds ratio[OR]=7.00,95%confidence interval[CI]1.43–34.07,P=0.016).The surgery group showed a significantly higher seizure freedom rate(OR=6.87,95%CI 1.02–46.23,P=0.016)and lower rate of induced labor(0.0%vs 26.5%,P=0.047)compared to the medically-treated group alone.Caesarean section was chosen in 77.1%of cases due to seizure concerns,with comparable in epilepsy-related(n=20)and obstetric causes(n=24).No major congenital malformations were reported.Conclusions Surgical treatment before pregnancy appears to offer a higher chance of seizure freedom compared to medication alone.Most of women with TLE-HS can deliver healthy offspring regardless of suboptimal seizure control and unwarranted concerns.

Therapeutic efficacy of voltage‑gated sodium channel inhibitors in epilepsy

Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological insults,imposing psychological,cognitive,social and also economic burdens to the sufferer.Voltage-gated sodium channels(VGSCs)are essential for the generation and propagation of action potentials throughout the central nervous system.Dysfunction of these channels has been implicated in the pathogenesis of epilepsy.VGSC inhibitors have been demonstrated to act as anticonvulsants to suppress the abnormal neuronal firing underlying epileptic seizures,and are used for the management and treatment of both genetic-idiopathic and acquired epilepsies.We discuss the forms of idiopathic and acquired epilepsies caused by VGSC mutations and the therapeutic efficacy of VGSC blockers in idiopathic,acquired and pharmacoresistant forms of epilepsy in this review.We conclude that there is a need for better alternative therapies that can be used alone or in combination with VGSC inhibitors in the management of epilepsies.The current anti-seizure medications(ASMs)especially for pharmacoresistant epilepsies and some other types of epilepsy have not yielded expected therapeutic efficacy partly because they do not show subtype-selectivity in blocking sodium channels while also bringing side effects.Therefore,there is a need to develop novel drug cocktails with enhanced selectivity for specific VGSC isoforms,to achieve better treatment of pharmacoresistant epilepsies and other types of epileptic seizures.

Withdrawal seizures vs on-medication seizures:an intracranial EEG recording case report

Background It has long been an interesting question of whether withdrawal seizures in epileptic patients differ from habitual seizures in terms of semiology and electrophysiology.Case presentation Here,we addressed this issue in a 40 year-old woman with drug-resistant focal epilepsy monitored by presurgical intracranial EEG.As a part of this routine pre-operative investigation,anti-seizure medications(ASMs)were halted;as a result,multiple withdrawal seizures were recorded before ASM readministration.During 4 days of invasive monitoring,we noticed three different phases in seizure organization:Acute withdrawal seizure(AWS):The first recorded seizure 10h after the implantation;the stabilized withdrawal seizures(SWS):seven habitual seizures recorded from 24h post implantation to readministration of ASMs;and the Non-withdrawal seizures(NWS):ten seizures recorded 24h after readministration of ASMs.AWS and SWS had the same semiology and same epileptic network,but the propagation time from the temporal pole to the para-hippocampal gyrus(PHG)and hippocampus ranged from no latency in AWS to up to 50 s in SWS.NWS were electrographic seizures,without any apparent clinical manifestation.Seizure onset in this type of seizure,as in the first two types,was in the temporal pole.However,NWS could last up to 3 min without involving the PHG or hippocampus.Conclusions We concluded that in acute withdrawal seizures the propagation time of epileptic activity is significantly reduced without affecting ictal organization network or semiology.Furthermore,ASM in this case had a remarkable influence on propagation rather than initiation of epileptic activity.