Abstract 188: Clinical Factors Associated with Lesion Count in Familial Cerebral Cavernous Malformation Type 1 Patients with the Common Hispanic Mutation

Introduction: Cerebral Cavernous Malformations (CCMs) are clusters of abnormally enlarged, capillary cavities that can lead to hemorrhages, seizures, neurological deficits and death. Familial CCM type 1 (CCM1) is caused by mutations in KRIT1 and is characterized by multiple lesions that vary widely among patients. The factors that influence variability in lesion count within patients with the same gene mutation are not known. The purpose of this study was to identify clinical factors associated with lesion count among familial CCM1 patients who all carry the common Hispanic mutation (CCM1-CHM). Methods: As a part of the Brain Vascular Malformation Consortium (BVMC) study, we reviewed detailed clinical and neuroimaging data on 137 CCM1-CHM patients from 34 families with at least two members and 35 singletons. We performed a cross-sectional analysis of clinical factors and lesion count using linear regression analysis, adjusting for covariates and standard errors for clustering within families. Results: Sixty-three percent of patients were symptomatic at presentation with a mean age ± standard deviation (SD) at CCM diagnosis of 30.8 ± 18.7 years (range: 0.32-70.9). The main clinical symptom leading to diagnosis was hemorrhage (24%); others included seizure (21%), headache (24%), and focal neurologic deficit (4%). Lesion count (range: 0-713; mean ± SD: 63.7 ± 124.4) was highly variable among CCM1-CHM patients and positively correlated with increasing age (P Conclusions: Hispanic familial CCM1-CHM patients present with a wide range in lesion count. Older age, male gender and absence of obesity may be predictors of higher lesion count. Further work is needed to elucidate how these factors influence lesion burden and determine associations with clinical outcomes.