LAUSR

Background: Cerebral cavernous angiomas with symptomatic hemorrhage (CASH) carry highest rebleed rates and are targeted for novel interventions. A multisite clinical trial readiness project (clinicaltrials.gov NCT03652181) aims to identify clinical and functional changes over time in trial eligible CASH patients. Methods: Adult patients from 5 high volume centers with a CASH in the prior year and no planned surgical intervention were enrolled. In addition to demographic, clinical, and imaging review, patients underwent baseline, 1 year and 2 year NIH-stroke scale (NIHSS), modified Rankin scale (mRS), Euro-QOL 5D-3L (EQ-5D-3L) and EQ VAS (visual analog score), and PROMIS 29 assessments. Recurrent symptomatic hemorrhages (SH) were verified. We assessed the hemorrhage rate, change in scores/scales over time, and determined which scales/scores were most affected in patients with SH. Results: 123 patients completed baseline assessments and were prospectively followed (60.9% female; mean age 44.1 years; 39.1% familial; 41.5% brainstem location). As of reporting date, 89 of 104 (86%) and 58 of 76 (76%) cases have completed assessments. There were 16 SHs during 147 patient-years of follow up (10.9% per patient year). At baseline, 111 (90.2%) of patients had NIHSS 0-2 and 77 (62.6%) patients had mRS baseline 0-1 which improved to 40 (95.2 %) and 43 (75.4%) at 2 years. At baseline, 54 (43.9%) of patients had at least one moderate to severely abnormal PROMIS-29 domain compared to 13 (26.5%) at 2 years. EQ-5D-3L baseline demonstrated a moderate proportion of patients reporting some difficulty with pain (48.8%), anxiety (41.5%), and activity (41.5%) which improved to 28%, 30%, and 34% respectively at 2 years. Patients with a prospective SH were more likely than those without recurrent SH at 2 years to display mild functional decline (0.5 SD) of most PROMIS-29 domains, a mRS of 2 or higher and an abnormal EQ- self-care (P<0.05). Other scales/scores were not significantly different between the groups. Conclusion: We report SH rate and functional outcome at baseline and rates of changes during 2 years in trial eligible CASH patients. The PROMIS-29, mRS, and EQ-self-care domains were most discriminative in patients with recurrent SH. No test was 100% specific.