Abstract：
OBJECTIVE: We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A-related disorders.
METHODS: A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%-79% fully or partially agree, <10% disagree.
RESULTS: Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE.
CONCLUSIONS: Significant comorbidities are present in most phenotypes of SCN8A-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of SCN8A-related disorders. Identifying the prognosis of patients with SCN8A-related disorders will also improve care and quality-of-life for patients and their caregivers.
METHODS: A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%-79% fully or partially agree, <10% disagree.
RESULTS: Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE.
CONCLUSIONS: Significant comorbidities are present in most phenotypes of SCN8A-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of SCN8A-related disorders. Identifying the prognosis of patients with SCN8A-related disorders will also improve care and quality-of-life for patients and their caregivers.
摘要：
目标：我们旨在就合并症达成共识（频率，严重程度,和预后）和癫痫的总体结局，发展,以及对SCN8A相关疾病的五种表型的认知。
方法：由13名临床医生组成的核心小组，1名研究员,并成立了6名护理人员，分为三个工作组。一组侧重于合并症和预后。所有小组都进行了文献综述，并提出了用于改良Delphi过程的问题。28名临床医生,一名研究员,来自16个国家的13名护理人员参加了三轮改良德尔菲程序.共识定义如下：强烈共识≥80％完全同意；中等共识≥80％完全或部分同意，<10%不同意；适度共识67%-79%完全或部分同意，10%不同意。
结果：关于严重发育性和癫痫性脑病（严重DEE）患者存在14种合并症，包括非癫痫性神经系统疾病和其他器官系统；影响大多严重，不太可能改善或解决。在轻度/中度发育性和癫痫性脑病（轻度/中度DEE）中，神经发育迟缓伴广泛性癫痫（NDDwGE），和NDD无癫痫（NDDwoE）表型，与重度DEE相比,可能存在认知和睡眠相关的合并症以及精细和粗大运动延迟,但不那么严重,更有可能改善.关于SeL（F）IE表型的合并症尚无共识，但强烈的结论是癫痫发作将在很大程度上解决。重度DEE患者很少出现癫痫发作自由，但在一些轻度/中度DEE和NDDwGE患者中可能会出现。
结论：在SCN8A相关疾病的大多数表型中存在显著的合并症，但在严重DEE表型中最为严重和普遍。我们希望这项工作能提高认可度，早期干预,以及这些合并症患者的长期管理，并为未来关于SCN8A相关疾病的最佳治疗的循证研究提供基础。确定SCN8A相关疾病患者的预后也将改善患者及其护理人员的护理和生活质量。
方法：由13名临床医生组成的核心小组，1名研究员,并成立了6名护理人员，分为三个工作组。一组侧重于合并症和预后。所有小组都进行了文献综述，并提出了用于改良Delphi过程的问题。28名临床医生,一名研究员,来自16个国家的13名护理人员参加了三轮改良德尔菲程序.共识定义如下：强烈共识≥80％完全同意；中等共识≥80％完全或部分同意，<10%不同意；适度共识67%-79%完全或部分同意，10%不同意。
结果：关于严重发育性和癫痫性脑病（严重DEE）患者存在14种合并症，包括非癫痫性神经系统疾病和其他器官系统；影响大多严重，不太可能改善或解决。在轻度/中度发育性和癫痫性脑病（轻度/中度DEE）中，神经发育迟缓伴广泛性癫痫（NDDwGE），和NDD无癫痫（NDDwoE）表型，与重度DEE相比,可能存在认知和睡眠相关的合并症以及精细和粗大运动延迟,但不那么严重,更有可能改善.关于SeL（F）IE表型的合并症尚无共识，但强烈的结论是癫痫发作将在很大程度上解决。重度DEE患者很少出现癫痫发作自由，但在一些轻度/中度DEE和NDDwGE患者中可能会出现。
结论：在SCN8A相关疾病的大多数表型中存在显著的合并症，但在严重DEE表型中最为严重和普遍。我们希望这项工作能提高认可度，早期干预,以及这些合并症患者的长期管理，并为未来关于SCN8A相关疾病的最佳治疗的循证研究提供基础。确定SCN8A相关疾病患者的预后也将改善患者及其护理人员的护理和生活质量。
