Epilepsia Open最新文献

Pathogenic variants in SLC6A1 cause a neurodevelopmental disorder characterized by developmental delay with behavioral disturbances, seizures, often pharmacoresistant, and a spectrum of movement disorders such as ataxia. A similar triad is observed in other monogenic conditions, such as SLC2A1, CHD2, and CACNA1A-related disorders, where acetazolamide (ACZ) has shown beneficial effects. We assessed the efficacy of ACZ as an adjunctive treatment in patients with SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) and drug-resistant seizures. We recruited patients with genetically confirmed pathogenic SLC6A1 variants and drug-resistant seizures treated with add-on ACZ. The medical records were reviewed to evaluate changes in seizure frequency and severity, and to document adverse events. Improvements in ataxia and social interaction were determined by clinical judgment together with caregiver reports. Six patients with a mean age of 7 years were included. The mean dose of ACZ was 16.2 mg/kg/day, and the mean treatment duration was 30 months. Three (50%) patients achieved full seizure remission, and the remaining three patients had a reduction in seizure frequency ranging from 50 to 90%. Except for weight loss in one patient, no serious adverse effects were reported. Three out of four patients with baseline ataxia showed improvement. Caregivers noted improvement in social interaction and school engagement in five out of six patients. ACZ may offer a promising therapeutic option for drug-resistant SLC6A1-related seizures. Prospective studies with larger cohorts and standardized outcome measures are necessary to confirm the efficacy and long-term safety of ACZ in this population.

Plain Language Summary

Pathogenic SLC6A1 variants in children cause developmental delay with behavioral issues, seizures, and often ataxia. In six children with drug-resistant seizures, adjunctive acetazolamide (ACZ) led to seizure freedom in three and a 50–90% reduction in the others. Improvement in ataxia and behavior, with better social and school performances, was reported. One child had mild weight loss. These early findings suggest ACZ may be a safe, effective, and affordable option for SLC6A1-related neurodevelopmental disorder when standard treatments fail, warranting further study.

Epilepsy surgery, particularly dominant temporal lobe resection, poses a significant risk of post-surgical language decline. There is considerable heterogeneity in the language assessment protocols employed across epilepsy surgery centers. This in turn is reflected in the observed variability in the incidence of language decline reported in the literature. We systematically surveyed cognitive outcome literature to critically appraise the nature and frequency of language assessment in order to establish the parameters of the existing evidence base. We found that confrontation naming was the most frequently used paradigm to assess language function (96%), followed by verbal fluency (47%) and language comprehension (13%). Over 75% of studies reported outcomes within the first two years of surgery, and close to 50% used reliable change index (RCI) to measure pre–post change in function, which is considered to be the gold standard. The evidence base is currently saturated with short-term post-surgical language outcomes assessed at single-word level. Future studies employing comprehensive language assessment, longer follow-up intervals, and designs comparing different metrics of pre–post change in function are needed.

Plain Language Summary

Driving is consistently reported as an important goal for people with epilepsy. We sought to determine the proportion of people with drug-resistant epilepsy (DRE) who became medically fit to drive after treatment with vagus nerve stimulation (VNS). We conducted a retrospective observational study of consecutive patients treated with VNS attending our neuromodulation clinic. We classified patients as either “VNS responders without additional intervention” or “VNS responders with additional intervention” and determined if patients were eligible to drive Group 1 vehicles (cars, motorcycles, and light work vehicles) under Irish Medical Fitness to Drive regulations. Among 87 patients treated with VNS for ≥12 months, 15 became medically eligible to drive: five were current drivers, three were learner drivers, and seven were eligible to drive based on their seizure control but were not driving for various reasons. Eleven were seizure-free, three had nondisabling focal seizures with preserved consciousness, and one had exclusive sleep-related seizures. Eleven were “VNS responders without additional intervention,” while four achieved eligibility after adding ASM or following subsequent epilepsy surgery, while VNS was still active. No patients reported driving-related accidents. ASM burden remained unchanged post-VNS. VNS was well tolerated, and no patients discontinued treatment. In this cohort, 17.2% of patients treated with VNS became eligible to drive, despite it being considered a palliative treatment. These findings highlight the potential role of neuromodulation in improving seizure control and promoting patient autonomy and independence.

Plain Language Summary

This study investigated whether people with refractory epilepsy in Ireland could become eligible to drive after VNS treatment. In our single-center cohort, 17.2% of patients treated with VNS for at least 12 months were eligible to drive at last follow-up. Most achieved this without increasing their medication after VNS implantation. These findings suggest that VNS, often considered a palliative treatment, can help some patients regain independence through improved seizure control.

Epilepsy is primarily defined by the repetitive occurrence of seizures, but the full impact of seizures extends beyond these episodic events. Seizures themselves cause changes at the cellular, network, and systemic levels in individual patients with epilepsy and may contribute to the progressive nature of the disease in some patients. Seizures may have an impact on brain structure and function over time. There is also a high societal and economic burden associated with persistent seizures, including major impacts on quality of life, activities of daily living, and productivity. Therefore, seizure freedom with no or minimal side effects should be the key goal in the treatment of epilepsy, with the potential to reduce both disease progression and the societal and economic impacts of the disease. Physicians have a responsibility to address the key obstacles to early seizure freedom, including optimizing initial treatment strategies, minimizing treatment delays, overcoming therapeutic nihilism, and improving medication adherence.

Plain Language Summary

Epilepsy involves repeated seizures which can cause changes in the brain over time and affect memory, thoughts, and everyday activities. Repeated seizures place a heavy burden on individuals, families, and society, affecting their quality of life, independence, and work. The main goal of epilepsy treatment should be the elimination of all seizures with few or no side effects. To achieve this, doctors should act quickly, choose the right treatments early, avoid treatment delays, and support patients in taking their medications.