Beyond Seizures as an Outcome Measure: A Global Severity Scoring System for CDKL5 Deficiency Disorder

Area of Science:

• Neurology
• Genetics
• Clinical Research

Background:

• CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE).
• CDD presents with multiple impairments and comorbidities.
• Validated outcome measures are crucial for disease-modifying clinical trials in DEEs, capturing caregiver priorities.

Purpose of the Study:

• To develop and validate a global severity score for CDKL5 deficiency disorder (CDD).
• To assess the suitability of this score as an outcome measure for clinical trials in DEEs.

Main Methods:

• An observational study using data from the International CDKL5 Clinical Research Network.
• Structural Equation Modeling was used to calculate a global severity score from various clinical assessments.
• Quantitative EEG power and Quality of Life Inventory-Disability were used for external validation.

Main Results:

• Models achieved acceptable fit statistics with data from 206 subjects.
• Motor and communication measures were key contributors to the global severity score.
• The global severity score showed good correlation with EEG biomarkers and quality of life measures.

Conclusions:

• The developed global severity score reliably captures the diverse severity spectrum in CDD.
• The score and its underlying network of relationships are suitable for clinical trials in CDD and other DEEs.
• This provides a validated outcome measure for therapeutic development in rare neurological disorders.