Developing the First Diagnosis and Treatment Guidelines for SCN8A
Working to assure our children receive the best care as soon as possible
The pain of learning our children have a devastating disorder is only made worse by how we must often fight to see our children get the best possible care.
With a rare disorder like SCN8A, only discovered to cause epilepsy in the last decade, there are many more questions that answers at this stage.
– How do the many different mutations affect our children?
– What is the progression of the disease and prognosis?
– And most importantly, how do we best treat the often evolving seizures and many comoribidities?
This is due, in part, to substantial scientific uncertainties – but also because of the absence of evidentiary-based consensus treatment guidelines.
Late in 2020, the International SCN8A Alliance convened the inaugural gathering of an SCN8A Clinician’s Network with over twenty pediatric neurologists. At this meeting, we presented feedback from a family survey on the issues of most concern to SCN8A families. Based on these community concerns, the clinicians agreed that the most urgent order of business was to develop standards of care to improve the treatment of SCN8A.
In early 2021, we officially launched the first step of the process to develop consensus treatment guidelines – completing a thorough and structured review of the published literature and development of a draft disease concept model for SCN8A.
In November 2021, we held the first meeting of the core panel of leading clinicians and families representing a diverse range of exerts from across 5 continents. With their expertise and drawing from all available data, they are working to develop draft treatment guidelines which will then be evaluated by an even larger panel of experts and families to build global consensus on guidelines to diagnose and treat those with SCN8A.
First Global Consensus for the Diagnosis and Treatment of SCN8A-Related Disorders
In 2022, after round 1 of 3, a consensus was achieved across various areas relating to phenotype, diagnosis, and treatments. 95% of clinicians and caregivers fully or partially agree that there are 5 distinct phenotypes in SCN8A-related disorders. Age of seizure/developmental delay onset, seizure types, and non-seizure issues are distinct across phenotypes. Following rounds will focus on defining the multitude of comorbid conditions associated with these disorders, while refining preferred methods of diagnosis and treatment. Further work will continue to elucidate the possible alignment of function of variant with seizure types, optimal treatments, prognosis, and phenotypes. Longitudinal SCN8A Registry data will be useful for providing supplemental data to support final recommendations. Given the heterogeneity of SCN8A-related disorders, this process may be useful in adapting the Delphi model to develop standard of care guidelines for other rare, heterogeneous disorders.
This initial consensus was shared at the American Epilepsy Society conference in December 2022.
Here is a further breakdown of the findings to date:
- There was a high consensus (over 80%) that the first symptom of Severe DEE is seizures with or without developmental delay and the first symptom of Mixed Epilepsy is seizures.
- There was a high consensus that the age of seizure onset for Severe DEE is 0-6 months, for Mixed Epilepsy is 4-18 months, and for Generalized Epilepsy is 24-48 months.
- There was a high consensus that the age of developmental delay onset for Severe DEE is 0-12 months, for Mixed Epilepsy is 5-36 months, for Generalized Epilepsy is 12-60 months, and for NDD/ID is 6-48 months.
- There was a high consensus (over 80%) that Levetiracetam (Keppra) was poorly tolerated in SCN8A patients and that physicians should be cautious of prescribing it for SCN8A gain of function.
- There was a high consensus that Carbamazepine and Oxcarbazepine were optimal first-line treatments for SCN8A gain of function.
- There was a high consensus that physicians should be cautious of prescribing sodium channel blockers for SCN8A loss of function.
It’s an incredibly rigorous and time-consuming process. At the end, there will still be many more questions than answers but it will nonetheless represent the first major step by the community of experts—leading SCN8A clinicians, prominent researchers, and engaged families—in codifying the best available evidence on treatment protocols for our children.
This has the potential to be the single most critical component to improving quality of care for our children with recognized and institutionalized guidelines to treat those with SCN8A. Once published, this effort has the potential to improve care whether your child is seen in a major university-based pediatric epilepsy center, a general neurologist or even a pediatrician in a remote setting anywhere around the globe. We believe it will provide a foundation for more structured and continuous rapid learning about what works or does not for specific and well-defined subgroups of our children with SCN8A.
We are incredibly grateful to this amazing group of leaders—caregivers and clinicians—who are giving their time and energy to this critical project.
Leading this process are:
The SCN8A Treatment Guideline Project is Co-chaired by Dr. Scott Perry, a prominent SCN8A clinician and Neurosciences Medical Director at Cook Children’s in Fort Worth Texas.
Gabi Conecker, President and Co-founder of the International SCN8A Alliance and mother to Elliott, a 10 yo with a severe form of SCN8A, is Co-chair the Treatment Guidelines process.
We are thrilled to have expert procedural direction and support from Dr. Elaine Wirrell, Director of Pediatric Epilepsy at the Mayo Clinic in Minnesota, who brings expertise in applying the modified Delphi process for the development of consensus treatment guidelines.
JayEtta Hecker, Co-Founder of the International SCN8A Alliance, is serving as the process guide for the Diagnosis & Treatment Guidelines process.
Maya Xia is part of the Diagnosis & Treatment Guidelines analysis team. She graduated from Vanderbilt University in May 2021 with a bachelor’s degree in Neuroscience. As a student at Vanderbilt, she took a course on Neurodevelopmental Disorders taught by Dr. Terry Jo Bichell, which inspired her to begin working with COMBINEDBrain and the International SCN8A Alliance to connect her basic science background with the lived experiences and needs of patients. Alongside this work, she is also doing full-time research at the NIH on mechanisms underlying PTSD. Next fall, she will begin her studies at an MD/PhD program.
For a detailed discussion of the process and outcome of efforts to develop a standard of care for the Dravet Syndrome, see this article.
We will keep the community informed as the work progresses – and as opportunities arise for specific input and/or questions.