The Utility of Genetic Testing in Infantile Epileptic Spasms Syndrome: A Step-Based Approach in the Next-Generation Sequencing Era.

BACKGROUND: To evaluate the utility of genetic testing for etiology-specific diagnosis (ESD) in infantile epileptic spasms syndrome (IESS) with a step-based diagnostic approach in the next-generation sequencing (NGS) era. METHODS: The study cohort consisted of 314 patients with IESS, followed by the Pediatric Neurology Division of Ege University Hospital between 2005 and 2021. The ESD was evaluated using a step-based approach: step I (clinical phenomenology), step II (neuroimaging), step III (metabolic screening), and step IV (genetic testing). The diagnostic utility of genetic testing was evaluated to compare the early-NGS period (2005 to 2013, n = 183) and the NGS era (2014 to 2021, n = 131). RESULTS: An ESD was established in 221 of 314 (70.4%) infants with IESS: structural, 40.8%; genetic, 17.2%; metabolic, 8.3%; immune-infectious, 4.1%. The diagnostic yield of genetic testing increased from 8.9% to 41.7% in the cohort during the four follow-up periods. The rate of unknown etiology decreased from 34.9% to 22.1% during the follow-up periods. The genetic ESD was established as 27.4% with genetic testing in the NGS era. The genetic testing in the NGS era increased dramatically in subgroups with unknown and structural etiologies. The diagnostic yields of the epilepsy panels increased from 7.6% to 19.2%. However, the diagnostic yield of whole exome sequencing remained at similar levels during the early-NGS period at 54.5% and in the NGS era at 59%. CONCLUSIONS: The more genetic ESD (27.4%) was defined for IESS in the NGS era with the implication of precision therapy (37.7%).

Assessment of Prognostic Factors and Validity of Scoring Models in Childhood Autoimmune Encephalitis.

OBJECTIVE: The aim of this study is to evaluate the prognostic factors in a single-center pediatric cohort with autoimmune encephalitis. MATERIALS AND METHODS: The study group consisted of 23 pediatric autoimmune encephalitis patients (seropositive autoimmune encephalitis: 15, seronegative autoimmune encephalitis: 8). Five group prognostic parameters were evaluated: clinical manifestations, elect roenc ephal ograp hy features, magnetic resonance imaging characteristics, biomarkers, and treatment modalities. Three scoring models were applied: the Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy for predicting autoimmune-related epilepsy in the whole cohort and the anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score for overall outcome in patients with anti-N-methyl-d-aspartate receptor encephalitis. RESULTS: The initial clinical spectrum of the disease was similar in the seronegative and seropositive groups. Almost half of the patients (48%) recovered without any complications with first-line immunotherapy. The patients with movement disorders in the acute phase of the disease needed more likely second-line immunotherapy (P = .039). The presence of status epilepticus at admission was significantly associated with adverse outcomes and the development of autoimmune-related epilepsy (P = .019). Autoimmune-related epilepsy was defined in an equal proportion of patients (91.5%) with 2 immune epilepsy scores (Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy). The N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score and the modified Rankin score assessed for the first-year prognosis were strongly correlated among the patients with anti-N-methyl-d-aspartate receptor encephalitis (P = .03, Spearmen's rho = 0.751). CONCLUSIONS: The presence of status epilepticus was the most important prognostic factor in the patients with the adverse outcome. The studied scoring models (Anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status, Antibody Prevalence in Epilepsy, and Response to Immunotherapy in Epilepsy) have also been proven to be applicable to the pediatric age group for predicting overall outcome and autoimmune-related epilepsy.