目的:患有STXBP1致病变异的人在生命的第一年经常有癫痫发作,有多种癫痫发作类型,包括癫痫痉挛.然而,早发性癫痫发作和抗癫痫药物(ASM)对发生癫痫痉挛的风险和对其轨迹的影响知之甚少,限制知情和预期治疗,以及试验设计。
方法:我们以每周为间隔对STXBP1发育性脑病和癫痫性脑病(DEE)患者的癫痫发作和用药史进行回顾性重建,并定量分析纵向发作史和用药反应。
结果:我们纳入了61例早发性癫痫患者,其中29人患有癫痫性痉挛。新生儿癫痫发作的个体可能在新生儿期后持续癫痫发作(25/26)。新生儿癫痫发作或早期婴儿癫痫发作的个体发生癫痫痉挛的风险没有增加(21/41vs.8/16,比值比[OR]=1,95%置信区间[CI]=.3-3.9,p=1)。我们没有发现任何与癫痫发作后癫痫痉挛发展相关的ASM。既往有癫痫发作的个体(n=16/21,76%)发生难治性癫痫痉挛的风险较高(n=5/8,63%,OR=1.9,95%CI=2-14.6,p=.6)。与非难治性癫痫性痉挛患者相比,难治性癫痫性痉挛患者的癫痫性痉挛发作较晚(n=20,中位数=20周)(n=8,中位数=13周,p=.08)。
结论:我们对STXBP1-DEE中的早发性癫痫发作进行了全面评估,并表明在既往有早年癫痫发作史之后,癫痫性痉挛的风险并未增加,我们的研究为STXBP1-DEE早期癫痫发作的靶向治疗和预后提供了基线信息。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.