Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.

2022

08/2022

1526-632X

BACKGROUND AND OBJECTIVE: Standard therapies (ACTH, oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of non-responders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response.

METHODS: The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (adrenocorticotropic hormone (ACTH), oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks post-treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response.

RESULTS: Among 395 infants, clinical infantile spasms remission occurred in 43% (n=171) within the first two weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range (IQR) 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pre-treatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% confidence interval 1.39-3.57). No other clinical factors predicted early responders to therapy.

CONCLUSIONS: Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.

10.1212/WNL.0000000000201232

Neurology

36038267

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

2021

2766-2777

2021 11

1528-1167

<p><strong>OBJECTIVE: </strong>This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE).</p>

<p><strong>METHODS: </strong>This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45&nbsp;min from seizure onset and before escalating to non-BZD ASM.</p>

<p><strong>RESULTS: </strong>We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR]&nbsp;=&nbsp;.998, 95% confidence interval [CI] = .997-.999 per minute, p&nbsp;=&nbsp;.01). Patients received BZDs beyond 30 and 45&nbsp;min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30&nbsp;min (IRR&nbsp;=&nbsp;2.43, 95% CI = 1.73-3.46, p&nbsp;&lt;&nbsp;.0001) and beyond 45&nbsp;min (IRR&nbsp;=&nbsp;3.75, 95% CI&nbsp;=&nbsp;2.40-6.03, p&nbsp;&lt;&nbsp;.0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45&nbsp;min compared to continuous SE (IRR&nbsp;=&nbsp;1.44, 95% CI = 1.01-2.06, p&nbsp;=&nbsp;.04). Forty-seven percent of patients (n&nbsp;=&nbsp;94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n&nbsp;=&nbsp;54), 48.1% received additional BZDs at hospital arrival.</p>

<p><strong>SIGNIFICANCE: </strong>Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.</p>

10.1111/epi.17043

Epilepsia

34418087