Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013-2022). Epilepsy and DRE prevalence and incidence in children <18 years old were estimated over time and by age and sex. Results showed that the age-standardized prevalence and incidence rates of epilepsy increased. The age-standardized prevalence rate of DRE increased, while the age-standardized incidence rate remained unchanged. The standardized prevalence rate of DRE was 0.26 per 1000 persons, and the average standardized incidence rate of DRE was 0.06 per 1000 persons. The prevalence rate of DRE gradually increased with age, with age 0 demonstrating the highest incidence rate. The prevalence of generalized DRE was the highest across all ages, and incidence was the highest at 0 years. Conversely, the incidence of focal DRE did not change with age. Our study revealed a stable incidence rate of DRE in Korea, despite increased prevalence. DRE incidence was the highest in the first year of life, with the generalized type being the most prevalent.

If the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes Nav1.1 protein, undergoes pathological mutation, it results in a wide range of epileptic syndrome, including febrile seizure, genetic epilepsy with febrile seizure plus (GEFS+), and developmental and epileptic encephalopathy (DEE), including Dravet syndrome. We present the case of a five-and-a-half-month-old boy with SCN1A gene-related epileptic seizures, starting as focal seizures and progressing to generalized tonic-clonic seizures. Despite treating the seizures with multiple antiepileptic drugs, including phenytoin, sodium valproate, levetiracetam, perampanel, and clobazam, it was very difficult to control the seizures, and genetic testing was suggested. The SCN1A mutation leads to either loss of function, including GEFS+ and Dravet syndrome, or gain of function, including familial hemiplegic migraine type 3. The case emphasizes the importance of genetic testing in refractory epilepsy management to provide medical strategies for the diagnosis. It focuses on the difficulties faced in diagnostic and treatment strategies for the management of SCN1A-related epilepsy. It emphasizes the importance of monitoring and personalized treatment strategies to reduce the incidence of refractory epilepsy.

Cerebral folate transport deficiency due to folate receptor 1 gene (FOLR1) gene mutation results from impaired folate transport across the blood: choroidplexus: cerebrospinal fluid (CSF) barrier. This leads to low CSF 5-methyltetrahydrofolate, the active folate metabolite. We are reporting two children with this treatable cerebral folate transport deficiency. Eight years and 9-month-old female presented with delayed milestones followed by regression, seizures, and intention tremors. On examination child had microcephaly, generalized hypotonia, hyperreflexia, unsteady gait, and incoordination. Magnetic resonance imaging (MRI) of brain revealed dilated ventricular system and cerebellar atrophy. Computed tomography (CT) of brain showed brain calcifications. Whole exome sequencing was finally performed, revealing homozygous nonsense pathogenic variant in FOLR1 gene in exon 3 c.C382T p.R128W, confirming the diagnosis of cerebral folate deficiency. Twelve-year-old female child presented with global developmental delay since birth, myoclonic jerks and cognitive regression. Child had generalized hypotonia and hyperreflexia. Her coordination was markedly affected with intention tremors andunbalanced gait. CT brain showed bilateral basal ganglia and periventricular calcifications with brain atrophic changes. MRI brain showed a prominent cerebellar folia with mild brain atrophic changes. Genetic testing showed a homozygous pathogenic variant was identified in FOLR1 C.327_328 delinsAC, p.Cys109Ter. Both patients were started on intramuscular folinic acid injections with a decrease in seizure frequency. However, their seizures did not stop completely due to late initiation of therapy. In conclusion, cerebral folate transport deficiency should be suspected in every child with global developmental delay, intractable myoclonic epilepsy, ataxia with neuroimaging suggesting cerebellar atrophy and brain calcifications. Response to folinic acid supplementation is partial if diagnosed late and treatment initiation is delayed.

Objectives This study aimed to describe the clinical characteristics, investigational results, and management strategies in patients with drug-resistant epilepsy (DRE). Methods This retrospective cohort study included all adult and adolescent patients (aged 14 years or older) diagnosed with DRE who visited the adult neurology clinic at King Abdulaziz Medical City, Jeddah, Saudi Arabia from January 2019 to December 2021. DRE was defined as failure to achieve seizure freedom despite undergoing adequate trials of two well-tolerated and appropriately selected antiseizure medications. Results This study included 299 patients with DRE. Most patients were in their second to fourth decade, with a mean age of 37 ± 17 years. Focal onset epilepsy was diagnosed in 52.5% of the patients, and an etiology for epilepsy was determined in 44.1% of the patients. Findings in brain magnetic resonance imaging were abnormal in 49% of the patients, whereas abnormal findings in electroencephalograms were found in 27.5%. The most common antiseizure medication was levetiracetam (67.6% of cases). Conclusion The findings of this study confirm the challenges in diagnosing and managing patients with DRE and emphasize the necessity for careful and comprehensive patient evaluation. Further research is needed to investigate the effectiveness, safety, and accessibility of diagnostic and therapeutic resources for patients with DRE.

Epilepsy is a noncommunicable chronic neurological disorder affecting people of all ages, with the highest prevalence in low and middle-income countries. Despite the pharmacological armamentarium, the plethora of drugs in the market, and other treatment options, 30%-35% of individuals still show resistance to the current medication, termed intractable epilepsy/drug resistance epilepsy, which contributes to 50% of the mortalities due to epilepsy. Therefore, the development of new drugs and agents is needed to manage this devastating epilepsy. We reviewed the pipeline of drugs in \"ClinicalTrials. gov,\" which is the federal registry of clinical trials to identify drugs and other treatment options in various phases against intractable epilepsy. A total of 31 clinical trials were found regarding intractable epilepsy. Among them, 48.4% (15) are about pharmacological agents, of which 26.6% are in Phase 1, 60% are in Phase 2, and 13.3% are in Phase 3. The mechanism of action or targets of the majority of these agents are different and are more diversified than those of the approved drugs. In this article, we summarized various pharmacological agents in clinical trials, their backgrounds, targets, and mechanisms of action for the treatment of intractable epilepsy. Treatment options other than pharmacological ones, such as devices for brain stimulation, ketogenic diets, gene therapy, and others, are also summarized.

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Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies. This comprehensive review aims to provide valuable insights on present and future use of neuromodulation.

While most children with epilepsy find their seizures manageable through medication, some continue to experience seizures despite trying multiple drugs. Failure of medical treatment often becomes apparent early on, and for these cases, it is advisable to seek further treatment options at a specialized epilepsy center. Such centers offer additional treatments like epilepsy surgery, vagus nerve stimulation, and ketogenic diets. There is no universal definition for what constitutes \"medically intractable\" epilepsy. A proposal by a task force from the International League Against Epilepsy suggests that drug-resistant epilepsy could be defined as the inability to control seizures even after two adequate treatment attempts with well-chosen and tolerated medications, either alone or in combination. In this review, the authors discussed the management of intractable epilepsy in children.

UNASSIGNED: This study aims to analyze key factors affecting the surgical outcome of children with intractable epilepsy caused by focal cortical dysplasia, providing more effective clinical guidance.
UNASSIGNED: We conducted a study from March 2019 to February 2021, selecting 80 children with intractable epilepsy caused by focal cortical dysplasia who underwent surgical treatment. Comprehensive inclusion criteria were met. We collected general information and treatment outcomes before and after surgery, with a two-year postoperative follow-up. Patients were categorized into good and poor outcome groups based on outcomes. Various factors including pathological types, age of onset, seizure frequency, and extent of resection were selected as variables. Logistic regression analysis investigated predictive factors.
UNASSIGNED: Engel class I included 53 cases, class II had 16 cases, class III had 9 cases, and class IV had 2 cases. Thus, 53 cases were in the good outcome group, and 27 in the poor outcome group. General data showed no significant differences between the groups (p > 0.05). Single-factor analysis revealed statistically significant risk factors: FCD classification, MRI results, age of onset, seizure frequency, and extent of resection (p < 0.05). Logistic multifactor analysis indicated seizure frequency. acute postoperative seizures (APSO) and extent of resection as independent influencing factors (p < 0.05).
UNASSIGNED: Seizure frequency, extent of resection, and APSO are key independent factors for surgical outcome in children with intractable epilepsy caused by focal cortical dysplasia. Clinicians should consider these factors when planning treatment to improve success rates and outcome, enhancing quality of life for affected children.

MicroRNA-134 (miRNA134) has emerged as a critical regulator in the pathogenesis of epilepsy, particularly in intractable cases resistant to conventional therapies. This review explores the multifaceted roles of miRNA134 in epileptogenesis, focusing on its influence on dendritic spine morphology and synaptic plasticity. Through its interactions with proteins such as LIM kinase 1 (LIMK1), Pumilio 2 (PUM2), and Tubby-like protein 1 (TULP1), miRNA134 modulates various molecular pathways implicated in epilepsy development. Preclinical studies have shown pro-mising results in targeting miRNA134 for mitigating seizure activity, highlighting its potential as a therapeutic target. Furthermore, miRNA134 holds promise as a biomarker for epilepsy diagnosis and prognosis, offering opportunities for personalized treatment approaches. However, further research is warranted to elucidate the precise mechanisms underlying miRNA134\'s effects and to translate these findings into clinical applications.