Authors :
Presenting Author: Kim Marie Thalwitzer, N/A – Children's Hospital of Philadelphia
Julie Xian, N/A – Children's Hospital of Philadelphia; Katie Rose Sullivan, MS, LCGC – Children's Hospital of Philadelphia; Danielle DeCampo, MD, PhD – Children's Hospital of Philadelphia; Jan Magielski, N/A – Children's Hospital of Philadelphia; James Goss, PhD – STXBP1 Foundation; Charlene Son Rigby, MBA – STXBP1 Foundation; Michael Boland, PhD – University of Pennsylvania; Ben Prosser, PhD – University of Pennsylvania; Steffen Syrbe, MD, PhD – Heidelberg University Hospital; Sarah Ruggiero, MS, LCGC – Children's Hospital of Philadelphia; Ingo Helbig, MD, PhD – Children's Hospital of Philadelphia
Rationale:
STXBP1
-related disorders are one of the most common genetic neurodevelopmental and epileptic encephalopathies. Most individuals have epilepsy onset in the first year of life, presenting with a variety of seizure types, including epileptic spasms. However, the impact of early-onset seizures, anti-seizure medications (ASMs), and genetic alterations on the prevalence and trajectories of epileptic spasms is poorly understood, limiting targeted counseling of families and design of clinical trials.Methods:
We retrospectively reconstructed seizure and medication histories in weekly intervals across all individuals with
STXBP1-related disorders with epilepsy onset in the first year of life at a major
STXBP1 specialty clinic.
Results:
Twenty-nine out of 61 individuals with
STXBP1-related seizures in the first year of life had epileptic spams. Out of the individuals with epileptic spasms, 21 (72%) had seizures before the onset of epileptic spasms including neonatal seizures in 14 individuals (48%), and only 8 individuals had epileptic spasms as their first seizure type. Most individuals with neonatal seizures had ongoing seizures beyond the neonatal period (n=25/26). However, the risk of developing epileptic spasms was not increased in individuals with neonatal seizures or early infantile seizures (21/41 vs. 8/16; OR 1, 95% CI 0.3-3.9,
p = 1). We did not find any ASM that increases or decreases the risk to develop epileptic spasms following prior seizures. However, individuals with prior seizures (n = 16/21, 76%) had a higher risk to develop refractory epileptic spasms (n = 5/8, 63%, OR =1.9, 95% CI 0.2-14.6,
p = 0.6). Individuals with refractory epileptic spasms had a later onset of epileptic spasms (n = 20, median 20 weeks) compared to individuals with non-refractory epileptic spasms (n = 8, median 13 weeks;
p = 0.08). We did not find an association between variant subtypes and the risk of refractory epileptic spasms. When assessing treatment response, we found that no ASM was favorable in reducing the frequency of epileptic spasms, but clonazepam (n = 3, OR 12.6, 95% CI 2.2-509.4;
p < 0.01), clobazam (n=7, OR 3, 95% CI 1.6-6.2;
p < 0.01), topiramate (n=9, OR 2.3, 95% CI 1.4-3.9;
p < 0.01), and levetiracetam (n=16, OR 1.7, 95% CI 1.2-2.4;
p < 0.01) were more likely to reduce seizure frequency and/or to maintain seizure freedom than all other medications.