Retrospective Study of Multi-site CADASIL: Implications for Clinical and Research Practice
Michael Geschwind1, Jennifer Zitser-Koren1, Fanny Elahi2, Ihab Hajjar3, Jose Gutierrez4, Iman Fathali1, Daven Crossland1, Michael Terranova1, Theresa Driscoll1, Henry Bockholt5, Jane Paulsen6, Mirjana Djakovic7, Michael Schneck7, Jose Biller7
1UCSF, 2Icahn School of Medicine at Mount Sinai, 3UT Southwestern Medical Center, 4Columbia University, 5GSU, 6University of Wisconsin, Madison, 7Loyola University Chicago, Stritch School of Medicine
Objective:
To present data on 4 USA CADASIL cohorts.
Background:
CADASIL is the most common monogenic cause of vascular cognitive impairment and dementia (VCID). Persons with
NOTCH3 pathogenic variants causing CADASIL can be evaluated from presymptomatic to symptomatic phases of VCID. An NIH-funded multi-site natural history study of 400 CADASIL patients and 100 non-carrier family members (www.cadasil-consortium.org) has begun
to characterize cross-sectional and longitudinal VCID, detect the earliest changes in biomarkers, and document the phenotype of CADASIL in North America. Here we present background data obtained from four US institutions.
Design/Methods:
By requesting research collaboration via email, we quickly received more than 60 responses. Following one in-person meeting and more than 30 teleconferences, a grant was submitted for a multi-site CADASIL study. In preparation, several neurologists with active cohorts submitted retrospective clinical data. Phenotype data were harmonized and analyzed at UCSF.
Results:
110 subjects with clinical data were identified at four US sites: UCSF (n=58), Loyola University Medical Center (n= 32), Emory University (n= 11) and Columbia University (n=9). Median age of onset not including migraine was 47 years but including migraine was 28. Anterior temporal pole white matter involvement on brain MRI was noted in 89%. 25% had microbleeds. 56% had migraine of any type, with 49% having migraine with aura; nearly one-third had headache not otherwise specified. 24% had seizures noted in their records. 91% were considered symptomatic based on their clinical history, neurological exam and/or cognitive performance. Half had MCI and 29% had dementia. Mean MMSE was 27.0 ± 4.5 (range 8, 30) and mean MoCA was 24.7 ± 4.6 (range 5, 30).
Conclusions:
Although most findings were consistent with reports from European and Asian cohorts, notable differences exist and will be presented. This retrospective data supported our recently NIH-funded multi-site CADASIL natural history study.