Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non‐familial disease

• Published in: European journal of neurology Vol. 29; no. 5; pp. 1427 - 1434
• Main Authors: Santos, Alejandro N., Rauschenbach, Laurèl, Saban, Dino, Chen, Bixia, Darkwah Oppong, Marvin, Herten, Annika, Gull, Hanah Hadice, Rieß, Christoph, Deuschl, Cornelius, Schmidt, Börge, Jabbarli, Ramazan, Wrede, Karsten H., Zhu, Yuan, Frank, Benedikt, Sure, Ulrich, Dammann, Philipp
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2022
• Subjects: cavernous angioma; CCM; Cerebral Hemorrhage - diagnostic imaging; Cerebral Hemorrhage - epidemiology; Cerebral Hemorrhage - etiology; Congenital defects; Diagnosis; familial; Hemangioma, Cavernous, Central Nervous System - complications; Hemangioma, Cavernous, Central Nervous System - diagnostic imaging; Hemangioma, Cavernous, Central Nervous System - genetics; Hemorrhage; Humans; Magnetic Resonance Imaging; multiple cerebral cavernous malformations; natural course; Patients; Regression analysis; Risk; risk factors; Statistical analysis; natural course; familial; risk factors; multiple cerebral cavernous malformations; cavernous angioma; CCM
• ISSN: 1351-5101; 1468-1331
• DOI: 10.1111/ene.15253

Background and Purpose Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non‐familial multiple cerebral cavernous malformation (CCM) disease over a 5‐year period. Methods Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow‐up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non‐familial multiple cavernous malformations. Kaplan–Meier and Cox regression analyses were performed to determine the cumulative 5‐year risk for hemorrhage and recurrent hemorrhage. Results A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non‐FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5‐year follow‐up (FU). The cumulative 5‐year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non‐FCCM cases. Conclusions FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5‐year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non‐FCCM patients showed an equal cumulative 5‐year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation. Kaplan–Meier curves of the complete cohort, stratified by presence. Bleeding as MOP (ICH as MOP = red), and confirmed‐FCCM (red) versus assumed‐FCCM (green) versus non‐FCCM (blue) are shown. ICH, intracerebral hemorrhage; FCCM, familial cerebral cavernous malformation.