Authors :
Presenting Author: Daniel Shrey, MD – Children's Hospital of Orange County
Renée Shellhaas, MD, MS – Washington University in St Louis; Zachary Grinspan, MD, MS – Weill Cornell Medicine; Sonam Bhalla, MD – Children's Healthcare of Atlanta; Sonal Bhatia, MD – Medical University of South Carolina; Peter Chang, MD – UC Irvine; Wei-Liang Chen, MD – Children's National Hospital; Michael Ciliberto, MD – University of Iowa; Jason Coryell, MD, MS – Oregon Health & Sciences University; Chellamani Harini, MD – Harvard University; Ann Hyslop, MD – Stanford University; Cynthia Keator, MD – Cook Children's; Hollie Lai, MD – Children's Hospital of Orange County; Beth Lopour, PhD – UC Irvine; Jennifer Madan Cohen, MD – Connecticut Children's; Venus Mostaghimi, MS – UC Irvine; John Mytinger, MD – Nationwide Children's Hospital; Sunil Naik, MD – Penn State Children's Hospital; Kerri Neville, MD – University of Michigan; Adam Numis, MD – UC San Francisco; Archana Pasupuleti, MD – Children's National Hospital; Debopam Samanta, MD – Arkansas Children's/University of Arkansas for Medical Sciences; Amanda Sandoval Karamian, MD – University of Utah; Rani Singh, MD – Atrium Health; Deepa Sirsi, MD – University of Texas Southwestern Medical Center; Emily Spelbrink, MD, PhD – Stanford University; Carl Stafstrom, MD, PhD – Johns Hopkins University; Danielle Takacs, MD – Baylor College of Medicine; Tyler Terrill, MD – University of Texas Southwestern Medical Center; Linh Tran, DO, MS – Cook Children's; Elissa Yozawitz, MD – Montefiore Medical Center; Christopher Yuskaitis, MD, PhD – Harvard University; Kelly Knupp, MD – University of Colorado, Anschutz Medical Campus; Shaun Hussain, MD – University of California, Los Angeles
Rationale:
Treatment regimens and diagnostic technologies for infantile epileptic spasms syndrome (IESS) have evolved over the past decade, including identification of three standard therapies (ACTH, prednisolone, vigabatrin), use of dual therapy (hormonal treatment concurrent with vigabatrin), and advancement of genetic testing. The impact of these changes on the real-world management of IESS is unknown. We conducted a large multicenter retrospective study of contemporary US practice trends. In this initial analysis, we focus on the diagnostic evaluation, epidemiology, and first-line treatment of IESS.Methods:
Clinical and demographic data were abstracted retrospectively from the electronic medical records of 567 children with IESS from 20 centers in the US, diagnosed between January 1, 2016 and December 31, 2020 as part of the National Investigation of Multi-modal Biomarkers for Infantile Spasms (NIMBIS) Study. A total of 450 children had sufficient data to robustly characterize these five year trends. All were diagnosed with new-onset IESS before 12 months of age. Salient variables were collected, including the latency from spasm onset to diagnosis and treatment, MRI field strength and yield, genetic testing, etiologic classification, and first treatment regimen. Trends were analyzed using non-parametric Spearman rank correlation coefficients.Results:
From 2016 to 2020, the median latency from epileptic spasm onset to IESS diagnosis was seven days (IQR 3-21 days), with no significant change over time. Latency from onset to treatment had a median duration of 10.5 days (IQR 5-28 days) also without significant change over time. Selection of treatment changed during this period. There was a significant increase in the use of prednisolone (p=0.005) and vigabatrin (p=0.02) and a decrease in regimens containing ACTH (p=0.008). The use of dual therapy also increased during this period (p=0.003). The use of non-standard therapies did not change significantly.
Over five years, the percentage of three Tesla vs. 1.5 Tesla MRI scans did not change, nor did the percentage of MRI scans yielding pathologic abnormalities. Epilepsy gene panels and exome/genome sequencing increased over time. There was a non-significant trend towards a decrease in the portion of subjects with no known cause of their IESS. There were no significant changes in the portion of other etiological classifications.
Conclusions:
The diagnosis and management of IESS changed significantly during the five year interval from 2016 to 2020: (1) The use of prednisolone and dual therapy as first treatments increased, while (2) the use of ACTH-containing regimens declined. (3) The use of next-generation genetic testing increased, and (4) there was a non-significant trend towards a decrease in the portion of subjects with no known cause of their spasms. Notably, the COVID-19 pandemic undoubtedly played a role in the increased use of prednisolone and decreased use of ACTH in 2020. These practice changes were likely driven by many factors, and their impacts on the outcomes of children with IESS warrant careful investigation.Funding:
This study was accomplished with support from the Pediatric Epilepsy Research Foundation® and a CHOC CSO Award.