抗- γ氨基丁酸B自身免疫性脑炎在印度儿童早发性癫痫发作,神经退行性变,脑钙化由于NRROS变异:全球首例报道病例

IF 0.2 Q4 PEDIATRICS Journal of Pediatric Epilepsy Pub Date : 2022-08-04 DOI:10.1055/s-0042-1758147
Aritra Kapat, A. Pandit, Suman Das, D. Paul, A. K. Mandal, A. Bala
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引用次数: 0

摘要

摘要1例1.5岁男童,6个月前生长发育参数正常。然而,在7个月大时,他出现了多种类型的癫痫发作,最初是复杂的发热性癫痫发作,随后是发热性癫痫发作。多灶性阵挛、全身性强直阵挛和肌阵挛(多灶性和全身性)是不断发展的发作类型。他有躯干张力过低,但在接下来的几个月里,他的阑尾张力过低发展为张力过高,并进一步发展为去皮状体位。脑磁共振成像(MRI)显示广泛性萎缩,以额颞叶为主,未见局灶性信号异常或对比增强。计算机断层扫描显示皮层下白质有斑点状钙化。脑电图显示双侧额颞叶癫痫样放电伴继发性泛化。脑脊液细胞学和生化结果正常,但抗-氨基丁酸B抗体阳性。全外显子组测序显示,3号染色体上的NRROS基因可能存在致病性的新型常染色体隐性纯合变异[c]。1487G > A (p.Trp496Ter)],其损害抗炎细胞因子转化生长因子β的功能,导致中枢神经系统内的促炎状态,从而促进自身免疫性脑炎。父母桑格测序证实了他父母的变异。患者接受甲强的松龙脉冲治疗(30 mg/kg/天,连用5天)和静脉注射免疫球蛋白(2 g/kg),随后逐渐减少口服强的松龙和每月静脉注射免疫球蛋白(1 g/kg)。癫痫发作频率显著降低,脑电图上癫痫样放电消失。然而,运动和认知方面的改善并没有发生,在最后一次随访时,他出现了小头畸形和生长衰竭。这是第11例与NRROS基因变异相关的神经退行性变报告,但第一例由儿童变异引发的自身免疫性脑炎报告。
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Anti–Gamma Aminobutyric Acid B Autoimmune Encephalitis in an Indian Child with Early-Onset Seizures, Neurodegeneration, and Brain Calcification due to NRROS Variation: The First Reported Case Worldwide
Abstract A 1.5-year-old boy presented to us with a history of normal growth and developmental parameters until 6 months of age. However, at 7 months of age, he developed multiple types of seizures consisting initially of complex febrile seizures, followed by afebrile seizures. Multifocal clonic, generalized tonic–clonic, and myoclonic (multifocal and generalized) were the evolving seizure types. He had truncal hypotonia, but his appendicular hypotonia progressed to hypertonia over the next few months and further to decorticate posturing. Brain magnetic resonance imaging (MRI) showed generalized atrophy, predominantly frontotemporal, without any focal signal abnormalities or contrast enhancement. Computed tomography (CT) showed speckled calcification in subcortical white matter. Electroencephalogram showed bilateral frontotemporal epileptiform discharges with secondary generalization. His cerebrospinal fluid had normal cytology and biochemical results but was positive for anti–gamma aminobutyric acid B antibodies. Whole exome sequencing showed likely pathogenic, novel autosomal recessive homozygous variation of NRROS gene on chromosome 3 [c.1487G > A (p.Trp496Ter)], which impairs the functioning of anti-inflammatory cytokine transforming growth factor beta, resulting in a proinflammatory state within the central nervous system and thereby promoting autoimmune encephalitis. Parental Sanger sequencing validated the variation in both his parents. He was treated with both pulse methylprednisolone (30 mg/kg/day for 5 days) and intravenous immunoglobulin (2 g/kg), followed by slowly tapering of oral prednisolone and monthly intravenous immunoglobulin infusion (1 g/kg). There was significant reduction in seizure frequency and disappearance of epileptiform discharges from the electroencephalogram. However, the motor and cognitive improvement did not occur, and he had microcephaly and growth failure at the last follow-up. This is the 11th case report of neurodegeneration associated with NRROS gene variations, but the first report of autoimmune encephalitis being triggered by the variation in a child.
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期刊介绍: The Journal of Pediatric Epilepsy is an English multidisciplinary peer-reviewed international journal publishing articles on all topics related to epilepsy and seizure disorders, epilepsy surgery, neurology, neurosurgery, and neuropsychology in childhood. These topics include the basic sciences related to the condition itself, the differential diagnosis, natural history, and epidemiology of seizures, and the investigation and practical management of epilepsy (including drug treatment, neurosurgery and non-medical and behavioral treatments). Use of model organisms and in vitro techniques relevant to epilepsy are also acceptable. Journal of Pediatric Epilepsy provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis and treatment of childhood epilepsy.
期刊最新文献
New-Onset Status Epilepticus in an 11-year-old Patient with Thyroid Autoimmune Dysfunction: A Case Report of Pediatric Hashimoto Encephalopathy Variable Phenotypes in the Same Patient with PRRT2-Associated Disorders Minor Neurological Dysfunction: A Comparative Study in Pediatrics with Different Types of Focal Epilepsy Challenges in the Treatment of Juvenile Myoclonic Epilepsy in Female Patients Standardizing the Treatment for Pediatric Status Epilepticus: A Quality Improvement Study
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