perampanel and Autism-Spectrum-Disorder

This study reported the first case of Kohlschütter-Tönz syndrome (KTS) in China and reviewed the literature of the reported cases.. This patient was registered at the Children's Hospital of Chongqing Medical University. The patient's symptoms and treatments were recorded in detail, and the patient was monitored for six years. We employed a combination of the following search terms and Boolean operators in our search strategy: Kohlschütter-Tönz syndrome, KTS, and ROGDI. These terms were carefully selected to capture a broad range of relevant publications in PubMed, Web of Science, WHO Global Health Library, and China National Knowledge Infrastructure, including synonyms, variations, and specific terms related to KTS. The pathogenicity of the variants was predicted using SpliceAI and MutationTaster, and the structures of the ROGDI mutations were constructed using I-TASSER.. This is the first case report of KTS in China. Our patient presented with epilepsy, global developmental delay, and amelogenesis imperfecta. A trio-WES revealed homozygous mutations in ROGDI (c.46-37_46-30del). The brain magnetic resonance imaging (MRI) and video electroencephalogram (VEEG) were normal. The efficacy of perampanel (PMP) in treating seizures and intellectual disability was apparent. Furthermore, 43 cases of ROGDI-related KTS were retrieved. 100% exhibited epilepsy, global developmental delay, and amelogenesis imperfecta. 17.2% received a diagnosis of attention deficit hyperactivity disorder (ADHD), and 3.4% were under suspicion of autism spectrum disorder (ASD). Language disorders were observed in all patients. Emotional disorders, notably self-harm behaviors (9.1%), were also reported.. ROGDI-related KTS is a rare neurodegenerative disorder, characterized by three classic clinical manifestations: epilepsy, global developmental delay, and amelogenesis imperfecta. Moreover, patients could present comorbidities, including ADHD, ASD, emotional disorders, and language disorders. PMP may be a potential drug with relatively good efficacy, but long-term clinical trials are still needed.

Topics: Amelogenesis Imperfecta; Autism Spectrum Disorder; Child; Epilepsy; Humans; Language Disorders; Membrane Proteins; Nuclear Proteins

The aim of this study was to assess the usefulness of perampanel (PER), and to identify the relationship between behavioral impairments and electroencephalogram (EEG) findings in epilepsy patients with autism spectrum disorder (ASD).. Participants were ASD patients with epilepsy recruited between June 1, 2016 and June 30, 2018. Inclusion criteria were: seizures refractory to two appropriate antiseizure medications (ASMs); presence of neuropsychological impairments; and ≥12 months of monitoring. PER was administered once daily, starting at a dose of 2 mg/day, increased to 12 mg/day. Seizure/EEG responders were identified as participants showing a >50 % reduction in seizure/interictal epileptiform discharge (IED) frequency (indicated as complete disappearance and response). Behavioral responders were identified as participants with a ≥50 % reduction in scores of the Japanese manuals for the Aberrant Behavior Checklist (ABC-J).. Eleven (64.7 %) of 17 patients were considered to be both seizure and EEG responders. Five (45.5 %) of these 11 patients with seizure/EEG response were considered as behavioral responders. Mean ABC-J scores were significantly decreased at 12 months after PER administration (p = 0.0002). A correlation between decreased IED frequency and ABC-J score was evident in frontal IEDs, but not in non-frontal IEDs. Participants presenting with frontal IEDs showed a significantly higher correlation between seizures/EEG and behavioral improvements (p = 0.023). Moreover, 2 of 6 patients without seizure/EEG improvement were considered as behavioral responders. No patients discontinued PER.. The results from this study suggest the utility of PER treatment in reducing clinical seizures and IEDs for ASD patients with intractable epilepsy, at least in some patients. Moreover, the present results also indicate the usefulness of PER in improving neuropsychiatric impairments, including behavioral disturbances in ASD related to improvement of clinical seizures/frontal IEDs, but also unrelated to seizure/EEG improvement in at least some ASD patients.

Topics: Autism Spectrum Disorder; Electroencephalography; Epilepsy; Humans; Nitriles; Pyridones; Seizures