Acta Epileptologica最新文献

Epilepsy is one of the most common neurological disorders, affecting more than 50 million people worldwide. Management is particularly complex in individuals with intellectual disabilities, who are at a much higher risk of having severe seizures compared to the general population. People with intellectual disabilities are regularly excluded from epilepsy research, despite having significantly higher risks of negative health outcomes and early mortality. Recent advances in artificial intelligence (AI) have shown great potential in improving the diagnosis, monitoring, and management of epilepsy. Machine learning techniques have been used in analysing electroencephalography data for efficient seizure detection and prediction, as well as individualised treatment, which facilitates timely and customised intervention for individuals with epilepsy. Research and implementation of AI-based solutions for people with intellectual disabilities and epilepsy still remains limited due to a lack of accessible long-term clinical data for model training, difficulties in communicating with people with intellectual disabilities, and ethical challenges in ensuring the safety of the AI systems for this population. This paper presents an overview of recent AI applications in epilepsy and for people with intellectual disabilities, highlighting key challenges and the necessity of including people with intellectual disabilities in research on AI and epilepsy, and potential strategies to promote the development and use of AI applications for this vulnerable population. Given the prevalence and consequences associated with epilepsy in people with intellectual disabilities, the application of AI in epilepsy care has the potential to have a significant positive impact. To achieve this impact and to avoid increasing existing health inequity, there is an urgent need for greater inclusion of people with intellectual disabilities in research around the application of AI to epilepsy care and management.

Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy, with FCD type II (FCD II) being the most common subtype. FCD II is characterized by cortical dyslamination accompanied by dysmorphic neurons (DNs). Identifying the molecular alterations and targetable biomarkers is pivotal for developing therapies. Here, we provide a detailed description of the neuropathological manifestations of FCD II, including morphological alterations and immunophenotypic profiles, indicating that abnormal cells exhibit a diverse spectrum of mixed differentiation states. Furthermore, we summarize current research on the pathogenetic mechanisms, indicating that gene mutations, epigenetic alterations, cortical developmental protein disturbances, inflammatory processes, and extrinsic damages may lead to abnormal neuronal proliferation and migration, thereby contributing to the emergence and progression of FCD II. These findings not only enhance our understanding of the pathogenesis of FCD II but also offer new directions for clinical diagnosis and treatment. Future research should further explore the interactions among these factors and employ multidisciplinary approaches to advance our understanding of FCD II.

Background: Hemorrhagic stroke has a high incidence, often leaving patients with significant complications such as limb mobility disorders after treatment. Traditional treatment methods for stroke patients mainly include limb function exercises and hyperbaric oxygen therapy, which have shown effective results. In recent years, there have been reports utilizing vagus nerve stimulation (VNS) to treat limb paralysis in ischemic stroke patients, achieving encouraging outcomes. However, there are rare related reports on hemorrhagic stroke.

Case presentation: This report presents a case of a patient who developed left upper limb hemiplegia and recurrent seizures after a hemorrhagic stroke. The patient showed a poor response to standard anti-epileptic treatment and was diagnosed with stroke-related epilepsy. To manage the recurrent seizures, VNS was performed. After the device was activated, the patient reported a significant reduction in abnormal muscle tone and increased mobility impairment in the affected upper limb. Parameters were adjusted, and intermittent stroke electrical stimulation was combined with upper limb rehabilitation exercises. After three months of active treatment, the patient's seizures were well controlled, and there was significant improvement in upper limb function.

Conclusions: VNS has potential in the rehabilitative treatment of stroke patients with upper limb dysfunction. It is hoped that more patients will benefit from this advanced treatment method in the future, regaining their health and vitality. Additionally, future research needs to further explore the mechanisms and methods of brain remodeling to provide theoretical support and more effective treatment options for stroke patient rehabilitation.

Background: The ketogenic diet (KD) therapy is a primary treatment for drug-resistant epilepsy, and beta-hydroxybutyrate (BHB) is the main ketone produced during KD. However, the pattern of increase in BHB levels is not well understood, and the reference range for BHB need to be defined. The aim of this study was to evaluate the BHB levels in the first three months, especially one week, after KD initiation, and to explore the physiological reference range for BHB.

Methods: In our study, a fasting initiation strategy was used for the majority of patients (252/300, 84%) who underwent fasting for 24-48 h, the rest fasted for at least 12 h. The concentration of blood BHB was measured four times a day during the first week, at one month and three months. Seizure frequency was recorded at one week, one month and three months. Responders were defined as those with a seizure reduction 50% or more compared to baseline. BHB levels were compared between responders and non-responders. The BHB levels of responders were used to calculate the reference range.

Results: A total of 300 patients were recruited, of whom 172 (57%) had accessible BHB data. BHB levels rapidly rose to 2.0 mmol/L at 19 h, peaked at 4.2 mmol/L at 43 h of therapy, and stabilized by three months. The reference range for BHB was 1.1 to 4.9 mmol/L.

Conclusions: BHB levels increased rapidly following fasting, reaching the peak at day 2, stabilizing from the end of the first week through three months. The lower reference limit for BHB to ensure KD efficacy should be set at 1.1 mmol/L.

Genetic developmental and epileptic encephalopathies (DEE) are often associated with movement disorders. Accurate identification and classification of movement disorders are essential for management of these diseases. In this review, we describe the characteristics of various movement disorders associated with DEE and summarize the distribution of common DEE-related gene mutations reported in previous studies, aiming to provide references for the diagnosis and treatment of these disorders.

Background: Autosomal recessively inherited progressive myoclonic epilepsy of Lafora, which is also known as Lafora disease, is a fatal neurodegenerative disorder. It affects individuals in late childhood or early adolescence and presents with symptoms of progressive mental and physical deterioration. This disease is caused by pathogenic genetic variants in either of two genes: EPM2A on chromosome 6q24, encoding laforin, or NHLRC1 (EPM2B) on chromosome 6p22, encoding malin.

Case presentation: In this study, we report a clinical and molecular investigation of Lafora disease segregating in a consanguineous Pakistani family. The proband presented with symptoms of rapidly progressive myoclonic epilepsy, but laboratory studies were negative for Lafora bodies and ragged red fibres. Sanger DNA sequencing of the genomic DNA of the proband for EPM2A and NHLRC1 identified a previously reported pathogenic nonsense variant in NHLRC1 (NM_198586.3:c.793C > T), which encodes the E3 ubiquitin ligase called malin. The NHLRC1 variant was found in a homozygous state in the proband, predicting a premature stop codon at position 265 (NP_940988.2:p.Arg265Ter). If the mRNA escaped nonsense-mediated decay, it would result in a truncated protein lacking 130 amino acids, including three NHL (NCL-1, HT2A, LIN-41) repeats.

Conclusions: Our study emphasizes the role of molecular genetic testing in patients presenting with symptoms of progressive myoclonic epilepsy.

Background: Electronic medical records (EMR) can be utilized to understand the impact of the disruption in care provision caused by the pandemic. We aimed to develop and validate an algorithm to identify persons with epilepsy (PWE) from our EMR and to use it to explore the effect of the pandemic on outpatient service utilization.

Methods: EMRs from the neurology specialty, covering the period from January 2018 to December 2023, were used. An algorithm was developed using an iterative approach to identify PWE with a critical lower bound of 0.91 for negative predictive value. Manual internal validation was performed. Outpatient visit data were extracted and modeled as a time series using the autoregressive integrated moving average model. All statistical analyses were performed using STATA version 14.2 (Statacorp, USA).

Results: Four iterations resulted in an algorithm, with a negative predictive value 0.98 (95% CI: 0.95-0.99), positive predictive value of 0.98 (95% CI: 0.85-0.99), and an F-score accuracy of 0.96, which identified 4474 PWE. The outpatient service utilization was abruptly reduced by the pandemic, with a change of -902.1 (95%CI: -936.55 to -867.70), and the recovery has also been slow, with a decrease of -5.51(95%CI: -7.00 to -4.02). Model predictions aligned closely with actual visits with median error of -3.5%.

Conclusions: We developed an algorithm for identifying people with epilepsy with good accuracy. Similar methods can be adapted for use in other resource-limited settings and for other diseases. The COVID pandemic appears to have caused a lasting reduction of service utilization among PWE.

Background: Epilepsy is a common neurological disorder. The homologous to E6-AP carboxy terminus (HECT) E3 ligase is associated with epilepsy. NEDD4-like ubiquitin protein ligase-1 (NEDL1) is a HECT E3 ligase that is highly expressed in the brain. This study aimed to investigate the involvement of NEDL1 in epilepsy and the potential effect of NEDL1 on the cognitive ability.

Methods: The pilocarpine-induced epileptic mouse model was used to assess cognitive functions in Barnes maze, the pathological changes, and the activation of astrocytes and microglia in wild-type (Nedl1^+/+) and Nedl1 knockout (Nedl1^-/-) mice. The RNA-seq method was used to analyze differentially expressed genes and explore the brain pathophysiology after epilepsy development.

Results: Nedl1 knockout resulted in a protective effect against epilepsy. The Nedl1^-/- mice showed improved spatial learning and memory, alleviation of pathological damage in the hippocampus induced by epilepsy, and reduced microglial activation in the hippocampus. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes also revealed several prominently enriched T-cell-related pathways.

Conclusions: Nedl1 knockout reduces seizures and alleviates neuroinflammation. The potential functional link between NEDL1 and epilepsy provides a new approach to the treatment and intervention of epilepsy.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epilepsy syndrome with unclear pathogenesis, characterized by fever-induced, super-refractory status epilepticus and high mortality. Studies have shown that ketogenic diet (KD) is effective in controlling convulsions in FIRES, but its mechanisms are unclear. This paper intends to summarize the mechanisms by which KD may exert effects against FIRES. Clinical studies have shown that patients with FIRES have elevated levels of various inflammatory factors such as interleukin (IL)-6, IL-8, IL-10, and so on. KD may exert anti-FIRES effects through several potential inflammatory pathways, including nuclear factor -κB (NF-κB) and NLR family pyrin domain containing 3 (NLRP3). Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) network suggested that KD may play an anti-inflammatory role through several pathways such as cellular senescence and neutrophil extracellular trap formation. These mechanisms need to be further investigated.

Ablation of seizure foci represents a crucial therapeutic approach for epilepsy. Traditionally, the seizure foci are predominantly located in the anterior hippocampus and amygdala. However, recent research by Ivan Soltesz and his colleagues described the posterior hippocampal fasciola cinereum (FC) as a region activated during seizures. Their findings demonstrate that inhibition and ablation of FC reduce seizures frequency. Therefore, FC emerges as a critical seizure node within the posterior hippocampus, playing an important role in epilepsy treatment.