Selvarajah Arunan, Sabo Andrea, Gorodetsky Carolina, Marques Paula T, Chandran Ilakkiah, Thompson Miles, Zulfiqar Ali Quratulain, McAndrews Mary Pat, Tartaglia Maria Carmela, Lira Victor S T, Huh Linda, Connolly Mary, Rezazadeh Arezoo, Qaiser Farah, Fantaneanu Tadeu A, Duong Monica, Barboza Karen, Lomax Lysa Boissé, Inuzuka Nakaharada Luciana, Valente Kette, Arbinuch Jack, Espindola Mariana, Garzon Eliana, Sorrento Gianluca, Meskis Mary Anne, Villas Nicole, Hood Veronica, Gonzalez Marta, Cardenal-Muñoz Elena, Aiba Jose Angel, McKenna Lauraine, Linehan Christine, Hohn Sophine, Auvin Stéphane, Devinsky Orrin, Yuen Ryan, Berg Anne T, Taati Babak, Fasano Alfonso, Andrade Danielle M
Adult Genetic Epilepsy Program, Division of Neurology, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
Kite Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Epilepsia. 2025 Jun;66(6):1975-1987. doi: 10.1111/epi.18329. Epub 2025 Mar 4.
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency in the majority of cases. Caregivers of adults with DS often complain about the loss of previously acquired skills. We set out to explore these perceptions and determine whether abnormalities reported were detectable in validated tests. We also investigated possible correlations between symptoms, age, and exposure to sodium channel blockers (SCBs).
This cross-sectional, multicenter study used the Vineland Adaptive Behavior Scales, 3rd edition (raw scores) for behavior analyses and Moss-Psychiatric Assessment Schedules checklist to screen for psychiatric symptoms. The Social Communication Questionnaire screened for social communication deficits. Parkinsonian features were evaluated with the modified Unified Parkinson's Disease Rating Scale. For gait evaluation, we validated the use of home videos, using instrumental gait analysis in a subgroup of patients, and then used the home videos for the remainder.
A total of 92 patients were enrolled (age range = 18-51 years, mean = 27.93 ± 8.59 years). Sixty percent of caregivers observed a decline in previously acquired skills, including intelligence, speech, interaction with others, ability to climb stairs and walk without support, and hand coordination. Adaptive skills, parkinsonian symptoms, and gait were worse in older patients and those exposed to SCBs for longer periods of time. Fourteen percent of patients screened positive for affective disorders, 11.6% for dementia, and 10.5% for a psychotic disorder. Fifty-three percent screened positive for social communication deficits.
This is the largest group of adults with DS to be systematically evaluated. They had severe nonseizure symptoms. Older age and longer use of SCBs were associated with worse adaptive skills, gait, and parkinsonism. Some older adults screened positive for depression and dementia. Caregivers identified functional decline in activities of daily living (ADLs). Taken together, the risk of dementia, parkinsonian gait, and decline in ability to perform previously mastered ADLs support that some adults with DS may be developing a neurodegenerative disorder.
多数情况下，德拉韦综合征（DS）是一种由SCN1A单倍体不足引起的严重发育性和癫痫性脑病。成年DS患者的照料者常常抱怨患者先前已掌握的技能丧失。我们着手探究这些认知情况，并确定在经过验证的测试中是否能检测到所报告的异常情况。我们还研究了症状、年龄与钠通道阻滞剂（SCB）暴露之间可能存在的相关性。
这项横断面多中心研究使用第三版文兰适应行为量表（原始分数）进行行为分析，并使用莫斯精神病学评估量表清单筛查精神症状。社交沟通问卷用于筛查社交沟通缺陷。采用改良的统一帕金森病评定量表评估帕金森病特征。对于步态评估，我们在部分患者亚组中使用仪器步态分析验证了家庭视频的使用，然后对其余患者使用家庭视频进行评估。
共纳入92例患者（年龄范围为18至51岁，平均年龄为27.93±8.59岁）。60%的照料者观察到患者先前已掌握的技能出现下降，包括智力、言语、与他人互动、独立爬楼梯和行走的能力以及手部协调性。年龄较大的患者以及暴露于SCB时间较长的患者，其适应技能、帕金森病症状和步态更差。14%的患者情感障碍筛查呈阳性，11.6%的患者痴呆筛查呈阳性，10.5%的患者精神病性障碍筛查呈阳性。53%的患者社交沟通缺陷筛查呈阳性。
这是对成年DS患者进行系统评估的最大样本组。他们存在严重的非癫痫性症状。年龄较大和使用SCB时间较长与较差的适应技能、步态和帕金森病相关。一些老年患者抑郁和痴呆筛查呈阳性。照料者发现患者日常生活活动（ADL）功能下降。综合来看，痴呆、帕金森病步态以及先前掌握的ADL执行能力下降的风险表明，一些成年DS患者可能正在发展为神经退行性疾病。
