Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 2;14(17):e035926.
doi: 10.1161/JAHA.124.035926. Epub 2025 Aug 29.

Association of Quality of Life Domains and Clinical Symptoms in Patients With Familial Cerebral Cavernous Malformation

Cynthia Tsang  1 , Jeffrey Nelson  1 , Rachel Vassar  2 , Nerissa U Ko  2 , Charles McCulloch  3 , Edward R Smith  4 , Sudhakar Vadivelu  5 , Amy Akers  6 , Cornelia Lee  6 , Joseph Zabramski  7 , Michel T Torbey  8 , Issam A Awad  9 , Helen Kim  1   3 ; Brain Vascular Malformation Consortium CCM Investigators
Collaborators, Affiliations

Association of Quality of Life Domains and Clinical Symptoms in Patients With Familial Cerebral Cavernous Malformation

Cynthia Tsang et al. J Am Heart Assoc. .

Abstract

Background: Familial cerebral cavernous malformation (fCCM) is characterized by multiple brain lesions affecting quality of life. PROMIS-29 (Patient-Reported Outcomes Measurement Information System 29) is a quality of life survey validated in some neurological diseases but not in fCCM. We assessed the reliability, validity, and association of PROMIS-29 in fCCM with clinical symptoms and with the modified Rankin Scale.

Methods: PROMIS-29 surveys assessing 7 quality of life domains were completed by 198 patients with fCCM ≥18 years old in the Brain Vascular Malformation Consortium cerebral cavernous malformation study. Raw domain scores were converted to T scores standardized to a reference population (mean 50±10) and tested using intercept-only regression (P≤0.05). Linear mixed models tested whether domain scores were associated with age, sex, clinical symptoms at time of first survey, or with modified Rankin Scale score.

Results: PROMIS domains had high reliability (Cronbach α >0.85). Patients with fCCM reported significantly worse anxiety (52.71 [95% CI, 51.23-54.20]), pain (52.50 [95% CI, 50.93-54.07]), and physical functioning (52.96 [95% CI, 51.40-54.52]), but better social participation (46.95 [95% CI, 45.35-48.54]) versus reference. Prior intracranial hemorrhage was associated with worse anxiety (+3.11 [95% CI, 0.10-6.12]), fatigue (+3.68 [95% CI, 0.61-6.76]), physical functioning (+3.79 [95% CI, 0.74-6.84]), and social participation (+4.42 [95% CI, 1.28-7.56]). Headaches were associated with worse depression (+3.17 [95% CI, 0.18-6.17]), fatigue (+4.14 [95% CI, 0.70-7.59]), pain (+3.88 [95% CI, 0.40-7.37]), and sleep disturbance (+2.94 [95% CI, 0.03-5.85]). Modified Rankin Scale score was weakly to moderately and positively associated with all domains except sleep disturbance (0.01≤R2≤0.55).

Conclusions: PROMIS domains were reliable and correlated with modified Rankin Scale score and symptoms in fCCM, identifying affected domains beyond physical functioning. Future studies should determine whether changes in health domains are associated with fCCM disease severity and further evaluate clinical usefulness of PROMIS.

Keywords: cerebral cavernous malformations; cerebrovascular disorders; cohort studies; familial; intracerebral hemorrhage; outcome; quality of life.

PubMed Disclaimer

Supplementary concepts