Authors :
Presenting Author: Megan Abbott, MD – University of Colorado
Peter Jacoby, PhD – The Kids Research Institute
Kaitlin Angione, MS – Children's Hospital Colorado
Megan Stringfellow, BS – Children's Hospital Colorado
Jacinta Saldaris, PhD – The University of Western Australia
Morgan Jolliffe, Psy.D. – Children's Hospital Colorado
Andrea Miele, PhD – Children's Hospital Colorado
Tim Benke, MD – Children’s Hospital Colorado
Jenny Downs, PhD – The Kids Research Institute Australia; Curtin School of Allied Health
Sarah Ruggiero, MS, CGC – Children's Hospital of Philadelphia
Zachary Grinspan, MD, MS – Cornell Weill Medicine
Hsiao-Tuan Chao, MD, PhD – Baylor College of Medicine
Danielle Takacs, MD – Baylor College of Medicine/Texas Children's Hospital
Alvina Zia, BS – Baylor College of Medicine
Elaine Seto, MD – Baylor College of Medicine/Texas Children's Hospital
Ekaterina Sanchez Romero, BS – Baylor College of Medicine
Kristen Fisher, DO – Baylor College of Medicine
Juliet Knowles, MD/PhD – Stanford University
Charlene Son Rigby, MBA – STXBP1 Foundation
James Goss, PhD – STXBP1 Foundation
Sarah Tefft, MSN, RN, CRNP – Children's Hospital of Philadelphia
Jillian McKee, MD, PhD – Children's Hospital of Philadelphia & University of Pennsylvania
Danielle deCampo, MD – Children's Hospital of Philadelphia
Kristin Cunningham, MS, OTR/L – Children's Hospital of Philadelphia
Samuel Pierce, PT, PhD – Children's Hospital of Philadelphia
Ingo Helbig, MD – Children's Hospital of Philadelphia
Scott Demarest, MD – Children's Hospital Colorado
Rationale:
STXBP1-related disorder is a severe developmental and epileptic encephalopathy (DEE) characterized by early-onset seizures and developmental challenges, with several disease-modifying trials on the horizon. Using a previously developed and validated clinician reported outcome measure for another severe DEE, CDKL5, the scale was modified and then piloted in STXBP1. The scale, now termed the STXBP1- Clinical Severity Assessment (S-CSA) was performed and psychometrically analyzed.
Methods:
The S-CSA is a newly modified clinician reported outcome measure (ClinRO) which includes items across motor, communication, and vision domains. It was modified from the CDKL5 Clinical Severity Assessment (CCSA) through expert consensus sessions with STXBP1 clinicians, which identified gaps and led to the addition of tremor and vision items. The new measure was then performed on 123 STXBP1 patients. Confirmatory factor analysis, internal consistency, average variance extracted, and divergent validity were evaluated and compared to predefined cut-offs.
Results:
Confirmatory factor analysis of 123 S-CSA datasets indicated that items loaded to three domains – Motor, Communication and Vision – with factor loadings >0.4. All domains showed strong reliability (Cronbach’s alpha >0.7; composite reliability >0.88). The fit statistics and average variance extracted by the factors were satisfactory, and the divergent validity criterion of the three factors was satisfied. The distribution of the overall score was appropriate with no ceiling/floor effect seen. Minimal skew was present in the motor and communication domains (0.34 and -0.16 respectively), with right positive skew (2.2) present in the Visual domain. This was improved by separating patients with and without CVI.
Conclusions: The S-CSA demonstrates strong psychometric properties in a cohort of 123 patients with
STXBP1-related disorder. This demonstrates the scale effectively measures a range of severity in
STXBP1. Validated now in two infantile-onset DEEs, this clinician-reported measure is likely to be valuable as an endpoint in clinical trial settings for
STXBP1 and potentially other severe DEEs.
Funding: This work was supported by funding from NIH/NINDS U01NS114312 and the
STXBP1 foundation.