Helen Kim1,2, Kelly D Flemming3, Jeffrey A Nelson1, Avery Lui1, Jennifer J Majersik4, Michael Dela Cruz4, Joseph Zabramski5, Odilette Trevizo5, Giuseppe Lanzino6, Atif Zafar7, Michel Torbey8, Marc C Mabray9, Myranda Robinson10, Jared Narvid11, Janine Lupo11, Richard E Thompson12, Daniel F Hanley13, Nichol McBee13, Kevin Treine13, Noeleen Ostapkovich13, Agnieszka Stadnik14, Kristina Piedad14, Nicholas Hobson14, Timothy Carroll15, Abdallah Shkoukani14, Julián Carrión-Penagos14, Carolina Mendoza-Puccini16, James I Koenig17, Issam Awad14. 1. Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care (H.K., J.A.N., A.L.), University of California, San Francisco. 2. Department of Epidemiology and Biostatistics (H.K.), University of California, San Francisco. 3. Department of Neurology (K.D.F.), Mayo Clinic, Rochester, MN. 4. Department of Neurology, University of Utah, Salt Lake City (J.J.M., M.D.C.). 5. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ (J.Z., O.T.). 6. Department of Neurosurgery (G.L.), Mayo Clinic, Rochester, MN. 7. Department of Neurology, University of Toronto, Canada (A.Z.). 8. Department of Neurology (M.T.), University of New Mexico, Albuquerque. 9. Department of Radiology (M.C.M.), University of New Mexico, Albuquerque. 10. Department of Neurosurgery (M.R.), University of New Mexico, Albuquerque. 11. Department of Radiology and Biomedical Imaging (J.N., J.L.), University of California, San Francisco. 12. Department of Biostatistics (R.E.T.), Johns Hopkins University, Baltimore, MD. 13. Brain Injury Outcomes, Department of Neurology (D.F.H., N.M., K.T., N.O.), Johns Hopkins University, Baltimore, MD. 14. Department of Neurosurgery (A. Stadnik, K.P., N.H., A. Shkoukani, J.C.-P., I.A.), University of Chicago, IL. 15. Department of Diagnostic Radiology (T.C.), University of Chicago, IL. 16. Division of Clinical Research (C.M.-P.), National Institute of Neurological Disorders and Stroke, Bethesda, MD. 17. Division of Neuroscience (J.I.K.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
Abstract
BACKGROUND AND PURPOSE: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. METHODS: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. RESULTS: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. CONCLUSIONS: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.
BACKGROUND AND PURPOSE: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. METHODS: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. RESULTS: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. CONCLUSIONS: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.
Entities:
Keywords:
biomarkers; clinical trial; intracranial hemorrhage; magnetic resonance imaging; quality of life; vascular malformations
Authors: Sean P Polster; Ying Cao; Timothy Carroll; Kelly Flemming; Romuald Girard; Daniel Hanley; Nicholas Hobson; Helen Kim; James Koenig; Janne Koskimäki; Karen Lane; Jennifer J Majersik; Nichol McBee; Leslie Morrison; Robert Shenkar; Agnieszka Stadnik; Richard E Thompson; Joseph Zabramski; Hussein A Zeineddine; Issam A Awad Journal: Neurosurgery Date: 2019-04-01 Impact factor: 4.654
Authors: Rustam Al-Shahi Salman; Julie M Hall; Margaret A Horne; Fiona Moultrie; Colin B Josephson; Jo J Bhattacharya; Carl E Counsell; Gordon D Murray; Vakis Papanastassiou; Vaughn Ritchie; Richard C Roberts; Robin J Sellar; Charles P Warlow Journal: Lancet Neurol Date: 2012-01-31 Impact factor: 44.182
Authors: Margaret A Horne; Kelly D Flemming; I-Chang Su; Christian Stapf; Jin Pyeong Jeon; Da Li; Susanne S Maxwell; Philip White; Teresa J Christianson; Ronit Agid; Won-Sang Cho; Chang Wan Oh; Zhen Wu; Jun-Ting Zhang; Jeong Eun Kim; Karel Ter Brugge; Robert Willinsky; Robert D Brown; Gordon D Murray; Rustam Al-Shahi Salman Journal: Lancet Neurol Date: 2015-12-02 Impact factor: 44.182