The First Consensus Diagnosis & Treatment for SCN8A
Publications coming soon!
We must often fight to see our children get the best possible care. The International SCN8A Alliance is working to find treatments that improve quality of life for this devastating disorder
With a rare disorder like SCN8A, only discovered to cause epilepsy in the last decade, there are many more questions than 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 comorbidities?
This is due, in part, to substantial scientific uncertainties – but also because of the absence of evidentiary-based consensus treatments.
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 treatments – 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 consensus diagnosis & treatment which will then be evaluated by an even larger panel of experts and families to build global consensus 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 a consensus standard of care for other rare, heterogeneous disorders.
The Process
Using a scientific methodology, called modified-Delphi, we set out to develop consensus for diagnosis/management of SCN8A-related disorders. To do this, we recruited a Core Panel (13 clinicians, 1 researcher, 6 caregivers) to work collaboratively to build the basis for the consensus process. The core panel was divided into three subgroups—diagnosis/phenotypes, treatment and comorbidities/prognosis)—who then performed a comprehensive literature review, and developed questions for the first round of the modified-Delphi consensus. A larger group of global experts, including 28 clinicians, 1 researcher, and 13 caregivers from 16 countries participated in the subsequent 3 survey rounds, which each refine what we agreed was possible to conclude about SCN8A (see Methods graphic below). 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.
Authors of this work include:
Gabrielle Conecker1,18, Maya Y Xia1,2,18, JayEtta Hecker1,18, Christelle Achkar3, Cristine Cukiert4, Seth Devries5, Elizabeth Donner6, Mark Fitzgerald7, Elena Gardella8, Michael Hammer1,9, Anaita Hegde10, Chunhui Hu11, Mitsuhiro Kato12, Tian Luo11, John M. Schreiber13, Yi Wang11, Tammy Kooistra14, Madeleine Oudin1,14,15, Kayla Waldrop14,
J. Tyler Youngquist14, Dennis Zhang14, Elaine Wirrell16, M. Scott Perry17
Affiliations:
1 International SCN8A Alliance, Washington, DC, USA.
2 COMBINEDBrain, Brentwood, TN, USA.
3 Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children’s Hospital, Boston, MA, USA.
4 Department of Neurology and Neurosurgery, Cukiert Clinic, São Paulo, São Paulo, Brazil.
5 Pediatric Neurology, Helen DeVos Children’s Hospital, Grand Rapids, Michigan 49503, USA.
6 Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
7 Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
8 Department of Epilepsy Genetics and Personalized Treatment, The Danish Epilepsy Center, 4293 Dianalund, Denmark.
9 Department of Neurology and Bio5 Institute, University of Arizona, Tucson, Arizona.
10 Department of Pediatric Neurosciences, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India.
11 Department of Neurology, Children’s Hospital of Fudan University, Shanghai, 201102 China.
12 Department of Pediatrics, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
13 Department of Neurology, Children’s National Hospital, Washington, DC.
14 International SCN8A Alliance Caregiver Representative
15 Department of Biomedical Engineering, Tufts University, Medford, MA
16 Divisions of Child and Adolescent Neurology and Epilepsy, Mayo Clinic, Rochester, Minnesota
17 Jane and John Justin Institute for Mind Health, Neurosciences Center, Cook Children’s Medical Center, Ft Worth, Texas.
18 Denotes equal contribution
Leading this process are
Dr. Scott Perry, Co-chair of the Consensus Diagnosis & Treatment for SCN8A project. A prominent SCN8A clinician and Neurosciences Medical Director at Cook Children’s in Fort Worth Texas.
Gabi Conecker, MPH – Executive Director 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 Consensus Diagnosis & Treatment for SCN8A project.
We are thrilled to have Dr. Elaine Wirrell, Director of Pediatric Epilepsy at the Mayo Clinic in Minnesota. She’s an expert with procedural direction and support, and importantly brings expertise in applying the modified Delphi process, which were foundational for the development of Consensus Diagnosis & Treatment for SCN8A.
JayEtta Hecker, Co-Founder of the International SCN8A Alliance, is serving as the process guide for the Consensus Diagnosis & Treatment for SCN8A Project .
Maya Xia is part of the Consensus Diagnosis & Treatment for SCN8A Project 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.
Thank you to our partners at SCN8A Italia, SCN8A Nederland & SCN8A UK & Ireland for supporting the work of the Consensus Diagnosis and Treatment for SCN8A!
Together, we are working to assure our children receive the best care as soon as possible!
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.
