The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium

Abstract

Summary Objective The multicenter National Infantile Spasms Consortium prospective cohort was used to compare outcomes and phenotypic features of patients with infantile spasms with and without hypsarrhythmia. Methods Patients aged 2 months to 2 years were enrolled prospectively with new-onset infantile spasms. Treatment choice and categorization of hypsarrhythmia were determined clinically at each site. Response to therapy was defined as resolution of clinical spasms (and hypsarrhythmia if present) without relapse 3 months after initiation. Results Eighty-two percent of patients had hypsarrhythmia, but this was not associated with gender, mean age, preexisting developmental delay or epilepsy, etiology, or response to first-line therapy. Infants with hypsarrhythmia were more likely to receive standard treatment (adrenocorticotropic hormone, prednisolone, or vigabatrin [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–4.7] and preexisting epilepsy reduced the likelihood of standard treatment (OR 3.2, 95% CI 1.9–5.4). Hypsarrhythmia was not a determinant of response to treatment. A logistic regression model demonstrated that later age of onset (OR 1.09 per month, 95% CI 1.03–1.15) and absence of preexisting epilepsy (OR 1.7, 95% CI 1.06–2.81) had a small impact on the likelihood of responding to the first-line treatment. However, receiving standard first-line treatment increased the likelihood of responding dramatically: vigabatrin (OR 5.2, 95% CI 2–13.7), prednisolone (OR 8, 95% CI 3.1–20.6), and adrenocorticotropic hormone (ACTH; OR 10.2, 95% CI 4.1–25.8). Significance First-line treatment with standard therapy was by far the most important variable in determining likelihood of response to treatment of infantile spasms with or without hypsarrhythmia.

CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development

“…In broader populations of patients with infantile spasms, >80% of patients have hypsarrhythmia, whereas only 47% of patients in our CDD cohort who had infantile spasms also had evidence of hypsarrhythmia. Prior reports have also supported that patients can have normal EEGs early in infancy despite having severe epilepsy, although this can be variable.…”

Treatment of infantile spasms

“…However, it is important to note that although hypsarrhythmia is seemingly obvious in some cases, there are also many instances in which hypsarrhythmia is difficult to identify. The demonstration that interrater reliability for identification of hypsarrhythmia is poor betrays the conventional notion that hypsarrhythmia is an obvious present‐or‐absent phenomenon and illustrates hypsarrhythmia's many “shades of gray.” With this limitation in mind, it comes as little surprise that the presence of hypsarrhythmia does not predict response to initial therapy . Despite these limitations, the gold standard measure of short‐term response to therapy is freedom from ES and hypsarrhythmia, usually after a treatment interval of not more than 2 weeks, and without relapse of ES or hypsarrhythmia over a prespecified interval such as 1–3 months.…”

“…With this limitation in mind, it comes as little surprise that the presence of hypsarrhythmia does not predict response to initial therapy. 11 Despite these limitations, the gold standard measure of short-term response to therapy is freedom from ES and hypsarrhythmia, usually after a treatment interval of not more than 2 weeks, and without relapse of ES or hypsarrhythmia over a prespecified interval such as 1-3 months. This outcome measure requires the implementation of extended video-EEG to verify resolution of spasms and exclude the possibility of persistent or intermittent hypsarrhythmia.…”

Infantile Spasms: Opportunities to Improve Care

“…Most, but not all, children with ES have hypsarrhythmia; studies report 52% 18 to 100%. 8,[19][20][21] This variation is primarily due to inclusion of variants of hypsarrhythmia. 22 When hypsarrhythmia is not present, the EEG pattern is still markedly abnormal.…”