The Etiologic Trend of Infantile Seizures In Digital and Genomics Eras With Three Chronologic Periods: 1999-2009, 2010-2014, and 2015-2020

Objective. With the advent of new neuroradiologic modalities, genomics and metabolomics tests, more common definite etiologies are obtained in epileptic children. To evaluate the definite etiologic diagnosis in epileptic children with infantile seizures into three chronologic periods: 1999-2009, 2010-2014, and 2015-2020. Methods. A study cohort including 305 children with infantile seizures (range: 1-24 months) was conducted between 1999-2020. Inclusion criteria include 1.5 or 3 Tesla cranial magnetic resonance imaging (MRI), a full metabolic workup that includes a hemogram, blood chemistry, uric acid, lactate, pyruvate, ammonia, biotinidase, serum B12 levels, free and total carnitines, plasma acylcarnitine, urine organic acids, serum aminoacid profile, lysosomal storage disease panels, and aminoacids and neurotransmitter analysis in cerebrospinal fluid. The genetic tests, including chromosomal analysis, microarray, epileptic encephalopathy panels, and whole-exome sequencing, were also evaluated for etiologic diagnosis. Results. The following etiologic diagnosis was defined in the cohort according to the ILAE classification: structural (n=122, 40%); genetic (n=77, 25%), metabolic (n=36, 12%), immune- infectious (n=7, 2%), and unknown (n=63, 21%). We identified more definitive etiology in the genomic era (2010-2020). The etiologic trend was changed with a gradual decrease from structural and infectious-immune etiologies towards genetic etiology in the last decade (p=0.001): I (1999-2009); structural (n=37, 43.5%), infectious (n=5, 6%), and genetic (n=14, 16,5%), II (2010-2020); structural (n=85, 38.6%), infectious (n=2, 0.9%), and genetic (n=63, 30.3%). Conclusion. This cohort study showed a new etiological profile of epileptic seizures in infancy is changing with the extensive use of diagnostic tools in the digital and genomic era.