{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:45:49Z","timestamp":1782276349180,"version":"3.54.5"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.03) and 100% (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.123.044068","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T19:00:45Z","timestamp":1703271645000},"page":"22-30","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome"],"prefix":"10.1161","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6021-1190","authenticated-orcid":true,"given":"Kelly D.","family":"Flemming","sequence":"first","affiliation":[{"name":"Department of Neurology (K.D.F.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-354X","authenticated-orcid":true,"given":"Helen","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Cerebrovascular Research, Department of Anesthesiology and Perioperative Care (H.K.), University of California San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8168-4621","authenticated-orcid":true,"given":"Stephanie","family":"Hage","sequence":"additional","affiliation":[{"name":"Neurovascular Surgery Program, Department of Neurological Surgery, University of Chicago Medicine and Biological Sciences, IL (S.H., S.K., R.G., J.L., A.S., R.J.A.-F., R.S., I.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Mandrekar","sequence":"additional","affiliation":[{"name":"Department of Biostatistics (J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Kinkade","sequence":"additional","affiliation":[{"name":"Neurovascular Surgery Program, Department of Neurological Surgery, University of Chicago Medicine and Biological Sciences, IL (S.H., S.K., R.G., J.L., A.S., R.J.A.-F., R.S., I.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romuald","family":"Girard","sequence":"additional","affiliation":[{"name":"Neurovascular Surgery Program, Department of Neurological Surgery, University of Chicago Medicine and Biological Sciences, IL (S.H., S.K., R.G., J.L., A.S., R.J.A.-F., R.S., I.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-9683","authenticated-orcid":true,"given":"Michel","family":"Torbey","sequence":"additional","affiliation":[{"name":"Department of Neurology (M.T.), University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-1935","authenticated-orcid":true,"given":"Judy","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery (J. Huang, J.F.), Johns Hopkins University Medical Institutions, Baltimore, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-9460","authenticated-orcid":true,"suffix":"III","given":"John","family":"Huston","sequence":"additional","affiliation":[{"name":"Department of Radiology (J. Huston, Y.S.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-9088","authenticated-orcid":true,"given":"Yunhong","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Radiology (J. 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