Abstract：
OBJECTIVE: We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders.
METHODS: A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree.
RESULTS: Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients.
CONCLUSIONS: This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.
METHODS: A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree.
RESULTS: Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients.
CONCLUSIONS: This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.
摘要：
目的：我们旨在就SCN8A相关疾病的诊断/治疗达成共识。利用修改后的Delphi过程，一个由经验丰富的临床医生和护理人员组成的全球队列提供了诊断输入，表型，治疗,和SCN8A相关疾病的管理。
方法：核心小组(13名临床医生，一名研究员,六名护理人员)，分为三个亚组(诊断/表型，治疗,合并症/预后)，进行了文献综述，并提出了改进的德尔菲过程的问题。28位临床专家,一名研究员,来自16个国家的13名护理人员参加了随后的三轮调查。我们将共识定义为：强烈共识，≥80%完全同意；中等共识，≥80%完全/部分同意，<10%不同意；和适度的共识，67%-79%完全/部分同意，10%不同意。
结果：早期诊断对于SCN8A相关疾病的长期临床结局很重要。有五种表型：三种具有早期癫痫发作（严重发育性和癫痫性脑病[DEE]，轻度/中度DEE,自限性（家族性）婴儿癫痫[SeL（F）IE]）和两个发作较晚/无癫痫发作（神经发育迟缓伴广泛性癫痫[NDDwGE]，无癫痫的NDD[NDDwoE])。看护者代表六名严重DEE患者，五个轻度/中度DEE，一个NDDwGE,还有一个NDDwoe.癫痫发作/发育延迟发作时的表型因年龄而异，癫痫发作类型,脑电图/磁共振成像发现,一线治疗。功能增益(GOF)与功能丧失(LOF)对于告知治疗是有价值的。钠通道阻滞剂是GOF的最佳一线治疗方法，严重的DEE,轻度/中度DEE,和SeL（F）IE；左乙拉西坦在GOF患者中相对禁忌。NDDwGE的一线治疗是丙戊酸盐，乙苏肟,或拉莫三嗪；钠通道阻滞剂在LOF患者中相对禁忌。
结论：这是关于SCN8A相关疾病的诊断和治疗的首次全球共识。这种共识将减少疾病识别的知识差距，并为这种异质性疾病的首选治疗提供信息。这种共识允许更多的临床医生提供循证护理，并使SCN8A家庭能够为他们的孩子辩护。
方法：核心小组(13名临床医生，一名研究员,六名护理人员)，分为三个亚组(诊断/表型，治疗,合并症/预后)，进行了文献综述，并提出了改进的德尔菲过程的问题。28位临床专家,一名研究员,来自16个国家的13名护理人员参加了随后的三轮调查。我们将共识定义为：强烈共识，≥80%完全同意；中等共识，≥80%完全/部分同意，<10%不同意；和适度的共识，67%-79%完全/部分同意，10%不同意。
结果：早期诊断对于SCN8A相关疾病的长期临床结局很重要。有五种表型：三种具有早期癫痫发作（严重发育性和癫痫性脑病[DEE]，轻度/中度DEE,自限性（家族性）婴儿癫痫[SeL（F）IE]）和两个发作较晚/无癫痫发作（神经发育迟缓伴广泛性癫痫[NDDwGE]，无癫痫的NDD[NDDwoE])。看护者代表六名严重DEE患者，五个轻度/中度DEE，一个NDDwGE,还有一个NDDwoe.癫痫发作/发育延迟发作时的表型因年龄而异，癫痫发作类型,脑电图/磁共振成像发现,一线治疗。功能增益(GOF)与功能丧失(LOF)对于告知治疗是有价值的。钠通道阻滞剂是GOF的最佳一线治疗方法，严重的DEE,轻度/中度DEE,和SeL（F）IE；左乙拉西坦在GOF患者中相对禁忌。NDDwGE的一线治疗是丙戊酸盐，乙苏肟,或拉莫三嗪；钠通道阻滞剂在LOF患者中相对禁忌。
结论：这是关于SCN8A相关疾病的诊断和治疗的首次全球共识。这种共识将减少疾病识别的知识差距，并为这种异质性疾病的首选治疗提供信息。这种共识允许更多的临床医生提供循证护理，并使SCN8A家庭能够为他们的孩子辩护。
