OBJECTIVE: The purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease. METHODS: One hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board-approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed. RESULTS: There were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC. CONCLUSIONS: Rates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.
OBJECTIVE: The purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease. METHODS: One hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board-approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed. RESULTS: There were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC. CONCLUSIONS: Rates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.
Authors: Nicolas Menjot de Champfleur; Christophe Langlois; William J Ankenbrandt; Emmanuelle Le Bars; Marie Anne Leroy; Hugues Duffau; Alain Bonafé; Jennifer Jaffe; Issam A Awad; Pierre Labauge Journal: Neurosurgery Date: 2011-03 Impact factor: 4.654
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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
Authors: Robert Shenkar; Changbin Shi; Douglas A Marchuk; Issam A Awad; Tania Rebeiz; Rebecca A Stockton; David A McDonald; Abdul Ghani Mikati; Lingjiao Zhang; Cecilia Austin; Amy L Akers; Carol J Gallione; Autumn Rorrer; Murat Gunel; Wang Min; Jorge Marcondes De Souza; Connie Lee Journal: Genet Med Date: 2014-08-14 Impact factor: 8.822