Efficacy and safety of Perampanel in the treatment of post stroke epilepsy: A multicenter, real-world study.

Background: Since 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023. Method: This study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment. Results: The study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61-70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05). Conclusion: PER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti-GABABR encephalitis.

OBJECTIVE: To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. METHODS: We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. RESULTS: Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrin releasing peptide (ProGRP) levels were found in 70% of patients with a median value of 490.10 pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p > .05). The value between SCLC and non-SCLC subgroup was significantly different (p < .05). Ten patients received immunotherapy (three patients refused treatment). After immunotherapy, the frequency of seizures was significantly reduced. There was a significant difference in mRS between admission and after treatment (p < .05). The average survival time after onset was 27.7 months. CONCLUSIONS: Epilepsy is the most common clinical manifestation of Anti-GABABR encephalitis. The prognosis of anti-GABABR encephalitis is poor. Section of anti-GABABR encephalitis patients have higher level of serum ProGRP and positive GSF oligoclonal bands. Elevated ProGRP or positive CSF oligoclonal bands with classic clinical features can potentially help to improve early recognition of anti-GABABR encephalitis.

The finding of a new heterozygous mutation site of the SCN2A gene in a monozygotic twin family carrying and exhibiting genetic epilepsy with febrile seizures plus (GEFS+) using targeted next-generation sequencing.

OBJECTIVES: Generalized epilepsy with febrile seizures plus (GEFS+) is a new epilepsy syndrome named by the International League Against Epilepsy (ILAE) in 2001. The SCN2A gene encoding α2 subunit of the neuronal sodium channel has been reported to be associated with BFNIS, GFES+, Dravet syndrome and some intractable childhood epilepsies. This study aimed to develop an approach based on next-generation sequencing to determine the genetic defects in a monozygotic twin family with GEFS+. PATIENTS AND METHODS: We collected a twin family with GEFS+. The DNA of the twin patients was extracted from their peripheral venous whole blood. A total of 308 known genes related to epilepsies were selected for deep exon resequencing. The patients family's DNA was sequenced through Sanger's sequencing for expanded validation. Through systematic data analysis using established bioinformatics pipeline and segregation analysis techniques, a number of genetic variants were released. RESULTS: Through detailed data analysis, we found a new heterozygous mutation c.1399G > A on exon11 of SCN2A (Nav1.2) which has not been reported in the HGMD (Human Gene Mutation Database), in the twin patients. Then we tested and verified the presence of the same mutation site in all individuals of the family. Asymptomatic individuals of this family didn't show this mutation. CONCLUSION: The methodology provides a reliable strategy for routine gene diagnosis of GEFS+. This observation of a potentially pathogenic mutation of SCN2A (Nav1.2) indicates that this gene should be further evaluated in order to determine possible routes of causation of GEFS+.

Features of a Chinese family with cerebral cavernous malformation induced by a novel CCM1 gene mutation.

BACKGROUND: Familial cerebral cavernous malformations (CCMs), characterized by hemorrhagic stroke, recurrent headache and epilepsy, are congenital vascular anomalies of the central nervous system. Familial CCMs is an autosomal dominant inherited disorder and three CCM genes have been identified. We report a Chinese family with CCMs and intend to explore clinical, pathological, magnetic resonance imaging (MRI) features and pathogenic gene mutation of this family. METHODS: Totally 25 family members underwent brain MRI examination and clinical check. Two patients with surgical indications had surgical treatment and the specimens were subjected to histopathological and microstructural examination. In addition, polymerase chain reaction (PCR) and direct sequencing were performed with genomic DNA extracted from 25 family members' blood samples for mutation detection. RESULTS: Brain MRI identified abnormal results in seven family members. All of them had multiple intracranial lesions and four cases had skin cavernous hemangioma. T2-weighted sequence showed that the lesions were typically characterized by an area of mixed signal intensity. Gradient-echo (GRE) sequence was more sensitive to find micro-cavernous hemangiomas. There was a wide range in the clinical manifestations as well as the age of onset in the family. The youngest patient was an 8-year-old boy with least intracranial lesions. Histopathological and microstructural examination showed that CCMs were typically discrete multi-sublobes of berry-like lesions, with hemorrhage in various stages of illness evolution. They were formed by abnormally enlarged sinusoids and the thin basement membranes. A novel T deletion mutation in exon 14 of CCM1 gene was identified by mutation detection in the seven patients. But unaffected members and healthy controls did not carry this mutation. CONCLUSIONS: The clinical manifestations were heterogenic within this family. We identified a novel mutation (c.1396delT) was the disease-causing mutation for this family and extended the mutational spectrum of CCMs.