Abstracts

Rationale: To prospectively evaluate the etiology and yield of investigations in infants presenting with new-onset, infantile spasms. Methods: Twenty US pediatric epilepsy centers prospectively enrolled all infants presenting with newly diagnosed spasms, both due to new-onset epilepsy and evolved from other seizure types, in a central database. In addition to defining a specific cause, etiologies were classified into genetic, genetic-structural, congenital structural, acquired structural, metabolic, immune, infectious and unknown. Details of investigations to determine etiology were recorded. Results: From 06/2012-05/2014, 230 infants were enrolled. Mean age at spasm onset was 7.1±3.7 months and 56% were male. An underlying cause was identified in 152/230 (66.1%) cases and included genetic causes in 17.0% (Down syndrome - 12/39, CDKL5 - 3/39, STXBP1 - 2/39, ARX - 2/39, other -20/39), genetic-structural causes in 7.8% (tuberous sclerosis - 10/18, neurofibromatosis 1 - 1/18, other - 7/18), congenital structural causes in 11.3%, acquired structural causes in 22.2% (perinatal brain injury - 29/51, postnatal head trauma - 5/51, other - 17/51), metabolic causes in 5.6% (mitochondrial or lactic acidosis- 7/13), and infectious causes in 1.7% (4/4 - TORCH). Among those with a defined etiology, the cause was evident on initial clinical assessment (history and physical exam), or MRI in 119/152 (78.3%), whereas further genetic and metabolic studies were revealing in the remaining 21.7%. Of the 78 without known etiology, 45 (57.7%) had undergone genetic testing including chromosomal microarray in 30 (38.5%), single gene testing in 5 (6.4%), epilepsy panel in 15 (19.2%), whole exome/genome sequencing in 2 (2.6%) and mitochondrial genetic testing in 4 (5.1%). Additionally, 67/78 (85.9%) with unknown cause had undergone metabolic testing [blood - 64/78 (82.1%), urine - 55/78 (70.5%) and CSF 35/78 (44.9%)]. Of children without an evident cause after initial clinical evaluation and MRI, further genetic testing yielded an etiology in 20/65 (30.8%) and metabolic testing in 13/80 (16.3%). Conclusions: An underlying etiology for infantile spasms is discovered in nearly two thirds of cases. Most often, traditional clinical assessment and MRI provide the diagnosis. For those without an obvious cause of infantile spasms, genetic and metabolic testing yield a specific diagnosis in a significant minority of cases. PERC is supported by an American Epilepsy Society Infrastructure award