Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Epilepsia. 2024 Mar;65(3):805-816. doi: 10.1111/epi.17886. Epub 2024 Jan 27.
Individuals with disease-causing variants in STXBP1 frequently have epilepsy onset in the first year of life with a variety of seizure types, including epileptic spasms. However, the impact of early onset seizures and antiseizure medication (ASM) on the risk of developing epileptic spasms and impact on their trajectory are poorly understood, limiting informed and anticipatory treatment, as well as trial design.
We retrospectively reconstructed seizure and medication histories in weekly intervals for individuals with STXBP1 developmental and epileptic encephalopathy (DEE) with epilepsy onset in the first year of life and quantitatively analyzed longitudinal seizure histories and medication response.
We included 61 individuals with early onset seizures, 29 of whom had epileptic spasms. Individuals with neonatal seizures were likely to have continued seizures after the neonatal period (25/26). The risk of developing epileptic spasms was not increased in individuals with neonatal seizures or early infantile seizures (21/41 vs. 8/16, odds ratio [OR] = 1, 95% confidence interval [CI] = .3-3.9, p = 1). We did not find any ASM associated with the development of epileptic spasms following prior seizures. Individuals with prior seizures (n = 16/21, 76%) had a higher risk of developing refractory epileptic spasms (n = 5/8, 63%, OR = 1.9, 95% CI = .2-14.6, p = .6). Individuals with refractory epileptic spasms had a later onset of epileptic spasms (n = 20, median = 20 weeks) compared to individuals with nonrefractory epileptic spasms (n = 8, median = 13 weeks, p = .08).
We provide a comprehensive assessment of early onset seizures in STXBP1-DEE and show that the risk of epileptic spasms is not increased following a prior history of early life seizures, nor by certain ASMs. Our study provides baseline information for targeted treatment and prognostication in early life seizures in STXBP1-DEE.
携带 STXBP1 致病变异的个体通常在生命的第一年出现癫痫发作，伴有多种发作类型，包括癫痫性痉挛。然而，早期发作和抗癫痫药物（ASM）对发展为癫痫性痉挛的风险以及对其轨迹的影响知之甚少，这限制了知情和预期治疗以及试验设计。
我们以每周为间隔，回顾性地重建了 STXBP1 发育性和癫痫性脑病（DEE）患者的癫痫发作和药物使用史，对纵向癫痫发作史和药物反应进行了定量分析。
我们纳入了 61 名早期发作的患者，其中 29 名有癫痫性痉挛。新生儿期发作的患者在新生儿期后仍可能持续发作（25/26）。新生儿期发作或婴儿早期发作的患者发展为癫痫性痉挛的风险并未增加（21/41 比 8/16，优势比[OR] = 1，95%置信区间[CI] =.3-3.9，p = 1）。我们没有发现任何 ASM 与之前的发作后癫痫性痉挛的发展有关。有先前发作的患者（n = 16/21，76%）发展为难治性癫痫性痉挛的风险更高（n = 5/8，63%，OR = 1.9，95% CI =.2-14.6，p =.6）。难治性癫痫性痉挛患者的癫痫性痉挛发作时间较晚（n = 20，中位数 = 20 周），而非难治性癫痫性痉挛患者（n = 8，中位数 = 13 周，p =.08）。
我们对 STXBP1-DEE 的早期发作进行了全面评估，结果表明，早期生命发作史或某些 ASM 均不会增加癫痫性痉挛的风险。我们的研究为 STXBP1-DEE 早期生命发作的靶向治疗和预后提供了基线信息。
