Abstract DP373: Patient-Reported Quality of Life and Symptom Associations in Pediatric Familial Cerebral Cavernous Malformation

Background: Familial cerebral cavernous malformation (fCCM) is an autosomal dominant neurovascular disorder characterized by multiple lesions that increase risk of intracranial hemorrhage (ICH), seizures, and headaches. The impact of these symptoms on physical, mental, and social quality of life (QoL) in children with fCCM is unknown. We aimed to assess QoL domains and their associations with clinical symptoms and functional status at baseline and longitudinally in pediatric fCCM. Methods: Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were completed by children or parent proxy for 66 pediatric fCCM participants (ages 5–17) enrolled in the Brain Vascular Malformation Consortium CCM study (2019–2025). Domain scores were converted to T-scores standardized to a U.S. pediatric reference population (mean=50, SD=10); higher scores reflect worse QoL. One-sample t-tests compared domain scores to population norms. Multivariable regression assessed associations between baseline PROMIS scores and prior ICH, seizures, headaches, or modified Rankin Scale (mRS) scores, adjusting for age, sex, and respondent type. Longitudinal analyses evaluated whether new symptom onset was associated with changes in PROMIS scores over time. Results: Among 66 participants (mean age 11.6±4.5), <50% reported prior ICH, seizures, or headaches; 93.3% had mRS scores of 0–1. PROMIS scores in anxiety (45.59 [95% CI: 42.51–48.67], p=0.006), depression (43.89 [41.63–46.14], p<0.001), fatigue (41.7 [39.03–44.37], p<0.001), and pain (43.29 [40.84–45.74], p<0.001) were significantly better than population norms. No significant baseline symptom-domain associations were observed, though moderate effect sizes were noted for prior ICH and worse fatigue (+3.83), mobility (+3.01), and sleep disturbance (+4.34); and for prior headache and fatigue (+3.64). Longitudinally, new headache onset was associated with increasing fatigue (+5.59 [0.046–11.13], p=0.048), with trends for worsening anxiety, pain, and sleep. Higher mRS scores correlated with worse pain (p=0.001), mobility (p=0.004), and sleep (p=0.011). Conclusions: PROMIS surveys captured QoL variation in pediatric fCCM, with moderate symptom-domain associations and significant correlations with mRS scores. Longitudinal changes in PROMIS scores tracked evolving symptom burden, particularly with new onset headaches and fatigue. Larger studies are needed to confirm PROMIS validity and refine its clinical utility in pediatric fCCM.