To the Editors: The COVID-19 pandemic represents an unprecedented international crisis with significant health, economic, and social consequences. This scenario has forced the medical community to face new practical and ethical challenges that require rapid responses. Early data show a variety of neurological manifestations in a significant proportion of patients with SARS-CoV-2 infection,1,2 although there is little documentation of the effects on people with epilepsy.2,3 In this study, we assess the impact of the COVID-19 pandemic in a particularly vulnerable population: individuals with genetic developmental and epileptic encephalopathies (DEEs) and their caregivers. Although children appear to present milder COVID-19 manifestations,4 patients with DEEs present an increased susceptibility to certain triggers related to viral infections and respiratory comorbidities, are at risk of missing medical follow-up and emergency assistance due to health care resource allocation focus on COVID-19 patients, and are exposed to broader sociopsychological impact related to lockdown. Therefore, this study evaluates the impact of the pandemic on patients with genetic DEEs and their caregivers in Spain, one of the current hotspots of the pandemic. This study was a cross-sectional survey open between April 7 and April 11, 2020, 23-27 days after national lockdown was established in Spain. Participants were caregivers of DEE patients with proven or suspected genetic origin, recruited through patient advocacy groups, using internet-based sources. They were asked to fill out a structured questionnaire. Informed written consent was obtained from each caregiver. This methodology, previously used for Dravet syndrome and other neurodevelopmental diseases,5 permits collecting larger samples for rare conditions. Statistical analysis was performed with R v3.6.2. A total of 277 responses from caregivers were collected, covering several different conditions. The most frequent genetic diagnoses were as follows: SCN1A, CDKL5, STXBP1, KCNQ2, PCDH19, and SYNGAP1 (see Table 1). DEEs of suspected genetic origin with negative genetic findings were reported by 36.8%. Mean age was 12.4 years; 58.1% were female. Fifteen patients (5.5%) were reported to present typical COVID-19 symptoms. Only seven of them were tested with SARS-CoV-2 polymerase chain reaction, with a positive result in three cases. The type of DEE of these three patients was Dravet syndrome, STXBP1 encephalopathy, and DEE without genetic diagnosis. All of them had mild symptoms, and none needed hospitalization or showed either seizure or behavioral worsening. Because of the high rate of mild or asymptomatic cases in pediatric populations, we also asked whether there had been confirmed COVID-19 cases in people with close contact with the patient. That was the case in 30 (10.8%). Overall, 39 (14.1%) and 87 (30.3%) cases reported seizure frequency increase or behavioral deterioration during the lockdown, respectively. In addition, there was one case of status epilepticus and nine patients who experienced some degree of neurological regression. Caregivers reported a series of partly overlapping factors that could contribute to seizure or behavioral deterioration: (1) new onset symptoms of anxiety (68.6%) or depression (69.7%) in caregivers, (2) inability to reach their neurologist using telemedicine resources (62.8%), (3) living in homes without a terrace or yard (62.8%), (4) economic problems (62.4%), (5) loss of regular stimulation and physical therapies (51.8%), (6) avoidance of seeking medical advice for serious health issues in the emergency department due to fear of COVID-19 (20.6%), (7) cancelation of essential medical appointments (18.5%), and (8) difficulties finding their antiseizure medication (ASM) at a pharmacy (8.3%). Some of these factors might be affected by the oversaturated health care system, mainly in the Spanish regions with the highest incidence of COVID-19 (Madrid or Catalonia), where 55.5% of the survey responders live.6 To explore the association between these factors and epilepsy or behavior worsening we performed bivariate (see Table 1) and multivariate analysis. Multivariate logistic regression showed that the main variables associated with seizure increase were age (P = .034) and difficulties finding ASM (P = .05), whereas the main variables associated with behavioral deterioration were type of epilepsy (P = .015), living in a home without a terrace or yard (P = .009), and caregivers’ anxiety (P < .001).

中文翻译：

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遗传性癫痫和 COVID-19 大流行：从照顾者的角度来看的教训

致编辑：COVID-19 大流行代表了一场史无前例的国际危机，对健康、经济和社会造成了重大影响。这种情况迫使医学界面临新的实践和伦理挑战，需要迅速做出反应。早期数据显示，很大比例的 SARS-CoV-2 感染患者存在多种神经系统表现，1,2 尽管几乎没有文献证明对癫痫患者的影响。2,3 在本研究中，我们评估了COVID-19 大流行在特别脆弱的人群中：患有遗传发育性和癫痫性脑病 (DEE) 的个体及其护理人员。尽管儿童的 COVID-19 表现似乎较温和，4 名 DEE 患者对与病毒感染和呼吸道合并症相关的某些触发因素的易感性增加，由于医疗资源分配侧重于 COVID-19 患者，因此面临错过医疗随访和紧急援助的风险，并暴露于更广泛的社会心理与锁定有关的影响。因此，本研究评估了大流行对西班牙遗传性 DEE 患者及其护理人员的影响，西班牙是当前大流行的热点之一。这项研究是一项横断面调查，于 2020 年 4 月 7 日至 4 月 11 日期间，即西班牙实行国家封锁后 23 至 27 天开放。参与者是经证实或疑似遗传来源的 DEE 患者的照护者，通过患者倡导团体招募，使用基于互联网的资源。他们被要求填写一份结构化的问卷。从每位护理人员那里获得了知情的书面同意。这种方法以前用于 Dravet 综合征和其他神经发育疾病 5，允许为罕见疾病收集更大的样本。使用 R v3.6.2 进行统计分析。总共收集了来自护理人员的 277 份回复，涵盖了几种不同的情况。最常见的基因诊断如下：SCN1A、CDKL5、STXBP1、KCNQ2、PCDH19 和 SYNGAP1（见表 1）。36.8% 报告了疑似遗传起源且遗传结果为阴性的 DEE。平均年龄为 12.4 岁；58.1% 是女性。据报道，15 名患者 (5.5%) 出现典型的 COVID-19 症状。其中只有 7 人接受了 SARS-CoV-2 聚合酶链反应检测，其中 3 人呈阳性。这三名患者的 DEE 类型为 Dravet 综合征、STXBP1 脑病和未进行基因诊断的 DEE。他们都有轻微的症状，没有人需要住院，也没有人出现癫痫发作或行为恶化。由于儿科人群中轻度或无症状病例的比例很高，我们还询问与患者密切接触的人中是否有确诊的 COVID-19 病例。30 个 (10.8%) 就是这种情况。总体而言，分别有 39 例（14.1%）和 87 例（30.3%）病例报告在锁定期间癫痫发作频率增加或行为恶化。此外，还有 1 例癫痫持续状态和 9 例患者出现某种程度的神经功能退化。护理人员报告了一系列可能导致癫痫发作或行为恶化的部分重叠因素：(1) 护理人员出现焦虑 (68.6%) 或抑郁 (69.7%) 的新症状，(2) 无法使用远程医疗资源联系到他们的神经科医生 (62.8%)，(3) 住在没有露台或院子的家中 (62.8 %), (4) 经济问题 (62.4%), (5) 失去定期刺激和物理治疗 (51.8%), (6) 由于害怕 COVID- 19 (20.6%)，(7) 取消基本医疗预约 (18.5%)，以及 (8) 在药房难以找到抗癫痫药物 (ASM) (8.3%)。其中一些因素可能会受到过度饱和的医疗保健系统的影响，主要是在 COVID-19 发病率最高的西班牙地区（马德里或加泰罗尼亚），55.5% 的调查响应者居住在这些地区。6 为了探索这些因素与癫痫或行为恶化之间的关联，我们进行了双变量（见表 1）和多变量分析。多变量逻辑回归显示，与癫痫发作增加相关的主要变量是年龄 (P = .034) 和难以发现 ASM (P = .05)，而与行为恶化相关的主要变量是癫痫类型 (P = .015)，住在没有露台或院子的家中 (P = .009)，以及看护者的焦虑 (P < .001)。