Thalwitzer Kim M, Xian Julie, deCampo Danielle, Parthasarathy Shridhar, Magielski Jan, Sullivan Katie Rose, Goss James, Rigby Charlene Son, Boland Michael, Prosser Ben, Ruggiero Sarah M, Syrbe Steffen, Helbig Ingo
Division of Neurology, Children's Hospital of Philadelphia, USA.
The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, USA.
medRxiv. 2023 Jun 28:2023.06.26.23291892. doi: 10.1101/2023.06.26.23291892.
Individuals with disease-causing variants in 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 anti-seizure medication (ASM) on the risk of developing epileptic spasms and impact on their trajectory is 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 -related disorders 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; OR 1, 95% CI 0.3-3.9, = 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 to develop refractory epileptic spasms (n = 5/8, 63%, OR =1.9, 95% CI 0.2-14.6, = 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; = 0.08). When assessing treatment response, we found that clonazepam (n = 3, OR 12.6, 95% CI 2.2-509.4; < 0.01), clobazam (n=7, OR 3, 95% CI 1.6-6.2; < 0.01), topiramate (n=9, OR 2.3, 95% CI 1.4-3.9; < 0.01), and levetiracetam (n=16, OR 1.7, 95% CI 1.2-2.4; < 0.01) were more likely to reduce seizure frequency and/or to maintain seizure freedom with regards to epileptic spasms than other medications.
We provide a comprehensive assessment of early-onset seizures in -related disorders and show that the risk of epileptic spasms is not increased following a prior history of early-life seizures, nor by certain ASM. Our study provides baseline information for targeted treatment and prognostication in early-life seizures in -related disorders.
患有[相关疾病名称]致病变体的个体通常在生命的第一年出现癫痫发作，发作类型多样，包括癫痫性痉挛。然而，早发性癫痫发作和抗癫痫药物（ASM）对癫痫性痉挛发生风险的影响以及对其病程的影响尚不清楚，这限制了明智且具有前瞻性的治疗以及试验设计。
我们回顾性地按周重建了在生命第一年出现癫痫发作的[相关疾病名称]相关疾病个体的癫痫发作和用药史，并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例早发性癫痫发作个体，其中29例有癫痫性痉挛。新生儿期癫痫发作的个体在新生儿期后很可能继续发作（25/26）。新生儿期癫痫发作或早期婴儿期癫痫发作的个体发生癫痫性痉挛的风险并未增加（21/41对8/16；比值比1，95%置信区间0.3 - 3.9，P = 1）。我们未发现任何与先前癫痫发作后癫痫性痉挛发生相关的抗癫痫药物。先前有癫痫发作的个体（n = 16/21，76%）发生难治性癫痫性痉挛的风险更高（n = 5/8，63%，比值比 = 1.9，95%置信区间0.2 - 14.6，P = 0.6）。与非难治性癫痫性痉挛个体相比，难治性癫痫性痉挛个体的癫痫性痉挛发作时间更晚（n = 20，中位数20周）（n = 8，中位数13周；P = 0.08）。在评估治疗反应时，我们发现氯硝西泮（n = 3，比值比12.6，95%置信区间2.2 - 509.4；P < 0.01）、氯巴占（n = 7，比值比3，95%置信区间1.6 - 6.2；P < 0.01）、托吡酯（n = 9，比值比2.3，95%置信区间1.4 - 3.9；P < 0.01）和左乙拉西坦（n = 16，比值比1.7，95%置信区间1.2 - 2.4；P < 0.01）相较于其他药物，更有可能降低癫痫性痉挛的发作频率和/或维持无癫痫发作状态。
我们对[相关疾病名称]相关疾病中的早发性癫痫发作进行了全面评估，结果表明，既往有早发性癫痫发作史或使用某些抗癫痫药物并不会增加癫痫性痉挛的风险。我们的研究为[相关疾病名称]相关疾病早发性癫痫发作的靶向治疗和预后提供了基线信息。
