Colonfinch3403

Intragenic mutations in FGF12 are associated with intractable seizures, developmental regression, intellectual disability, ataxia, hypotonia, and feeding difficulties. FGF12 duplications are rarely reported, but it was suggested that those might have a similar gain-of-function effect and lead to a more or less comparable phenotype. A favorable response to the sodium blocker phenytoin was reported in several cases, both in patients with an intragenic mutation and in patients with a duplication of FGF12. We report three individuals from two families with FGF12 duplications. The duplications are flanked and probably mediated by two long interspersed nuclear elements (LINEs). The duplication cases show phenotypic overlap with the cases with intragenic mutations. Though the onset of epilepsy might be later, after the onset of seizures both groups show developmental stagnation and regression in several cases. This illustrates and further confirms that chromosomal FGF12 duplications and intragenic gain-of-function mutations yield overlapping phenotypes.Ring chromosome 20 syndrome (r(20)) is an ultra-rare disease characterized by drug-refractory epilepsy, cognitive impairment, and behavioral problems. Nonpharmacological treatments alongside antiepileptic drugs early after diagnosis may help reduce seizure frequency and preserve cognition. Ketogenic dietary therapy (KDT) has benefitted children with complex, refractory epilepsies, but its efficacy in r(20) is unknown. We assessed clinical prescription, implementation, and patient experience of KDT in r(20) through online surveys and a workshop. Forty-two patients, families, carers, and 23 healthcare professionals completed the surveys. While nearly all patients were familiar with KDT, only half had tried it. Significant improvement in seizure activity, cognition, and alertness was reported; side effects were typically mild but with one report of increased seizure frequency. A high rate of co-morbidity, older age at presentation, behavioral problems, and cognitive impairment can make implementing KDT in r(20) challenging. In the UK, NHS KDT services are predominantly available to pediatric patients, with very limited adult access. A health economic analysis illustrating reduced acute care costs or improved quality of life may support more widespread KDT implementation. Growing evidence supports KDT as an effective and safe intervention, but further research is needed to understand the mechanisms of r(20) and its interaction with ketosis.Objective Epilepsy is one of the most common neurological disorders . Many individuals continue to have seizures despite medical and surgical treatments, suggesting adjunctive management strategies are required. Promising effects of daily listening to Mozart on reducing seizure frequency in individuals with epilepsy have been demonstrated over the last 20 years, but not in a rigorously controlled manner. In this study, we compared the effect on seizure frequency of daily listening to either Mozart K.448 or a spectrally similar, yet non-rhythmic control piece. We hypothesized that there would be no difference in seizure counts when participants listened to Mozart K.448 vs when they listened to the control piece. Methods We employed a randomized crossover design, in which each participant was exposed to both three months of daily listening to the first six minutes of Sonata for two pianos in D major by Mozart (Mozart K.448; treatment period) and three months of daily listening to phase-scrambled version (control period). There was a three-month baseline and a three-month follow-up period before and after the six-month listening period, respectively. Change in seizure counts obtained from the seizure diaries was considered as the main study outcome. Results Using three methodologies to investigate the existence of the treatment effect (paired t test, estimation statistics and plots, and Cohen's d), our results revealed a reduction in seizure counts during the treatment period, which was not observed for the control period (P-value less then .001). Significance Using a spectrally similar control piece, our study advances previous reports that were limited by a "no music" control condition. Daily listening to Mozart K.448 was associated with reducing seizure frequency in adult individuals with epilepsy. These results suggest that daily Mozart listening may be considered as an adjunctive therapeutic option to reduce seizure burden in individuals with epilepsy.Objective Our study assessed perampanel monotherapy in patients (aged ≥12 years) with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures (FBTCS) in Japan and South Korea. Methods Study 342 (NCT03201900; FREEDOM) is a single-arm, open-label, Phase III study. Patients initially received perampanel in a 32-week 4-mg/d Treatment Phase (6-week Titration; 26-week Maintenance Periods). If they experienced a seizure during the 4-mg/d Maintenance Period, they could be up-titrated to 8 mg/d across an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance Periods). Primary endpoint was the seizure-freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Vactosertib cost Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment-emergent adverse events (TEAEs) were monitored. Results At data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4-mg/d Titration Period, meaning 73 patients entered the 4-mg/d Maintenance Period and were included in the primary analysis set for efficacy. Seizure-freedom rate in the 26-week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI] 50.9-74.0) at 4 mg/d and 54/73 (74.0%; 95% CI 62.4-83.5) at 4 or 8 mg/d. Cumulative probability of seizure-onset and withdrawal rates during Maintenance was 30.8% (95% CI 21.5-43.0) and 23.7% (95% CI 15.4-35.3) at 4 mg/d, and 18.2% (95% CI 11.0-29.3) and 23.3% (95% CI 15.2-34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness. Significance Perampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.