AUTHOR=Goswami Ipsita , Maguire Bryan , Chau Vann , Tam Emily W. , Pinchefsky Elana , Whitney Robyn , Wilson Diane , Miller Steven P. , Cortez Miguel A. 

TITLE=Early transient dysautonomia predicts the risk of infantile epileptic spasm syndrome onset: A prospective cohort study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1090155

DOI=10.3389/fneur.2022.1090155

ISSN=1664-2295

ABSTRACT=Background Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS.
Methods: Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram and electrocardiogram recording for 60 mins at every 2-month interval. HRV metrics were calculated from 5 minutes time-epoch during sleep included frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic (CSI) index, and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric.
Results: IESS were diagnosed in 20/60 (33%) of the cohort by 12 months follow up and 3 (5%) were lost to follow up. Median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at initial presentation. The infants with high CSI (hazard ratio 2.5,95% CI 1.2-5.2, P=0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P=0.04) at 2 months were more likely to develop hypsarrhythmia by first year of life. There was a trend towards decreasing CSI and DFA α1 and increasing CVI in the first 8 months of life. 
Conclusion: Our data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympatho-vagal balance per se would provide clinical benefit must be addressed by future studies.