Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.
CCM
SCM
cavernous angioma
cerebral cavernous malformations
intracerebral hemorrhage
natural course
risk factors
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
09
09
2022
received:
09
08
2022
accepted:
12
09
2022
pubmed:
2
10
2022
medline:
17
12
2022
entrez:
1
10
2022
Statut:
ppublish
Résumé
The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.
Sections du résumé
BACKGROUND AND PURPOSE
The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system.
METHODS
Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage.
RESULTS
Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease.
CONCLUSIONS
During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-149Informations de copyright
© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Références
Horne MA, Flemming KD, Su IC, et al. Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data. Lancet Neurol. 2016;15:166-173.
Taslimi S, Modabbernia A, Amin-Hanjani S, Barker FG, Macdonald RL. Natural history of cavernous malformation. Neurology. 2016;86:1984-1991.
Robinson JR, Awad IA, Little JR. Natural history of the cavernous angioma. J Neurosurg. 1991;75:709-714.
Goyal A, Rinaldo L, Alkhataybeh R, et al. Clinical presentation, natural history and outcomes of intramedullary spinal cord cavernous malformations. J Neurol Neurosurg Psychiatry. 2019;90:695-703.
Santos AN, Rauschenbach L, Darkwah Oppong M, et al. Natural course of untreated spinal cord cavernous malformations: a follow-up study within the initial 5 years after diagnosis. J Neurosurg Spine. 2021;36:1-5.
Moore SA, Brown RD, Christianson TJH, Flemming KD. Long-term natural history of incidentally discovered cavernous malformations in a single-center cohort: clinical article. J Neurosurg. 2014;120:1188-1192.
Flemming KD, Link MJ, Christianson TJH, Brown RD. Prospective hemorrhage risk of intracerebral cavernous malformations. Neurology. 2012;78:632-636.
Santos AN, Rauschenbach L, Saban D, et al. Natural course of cerebral cavernous malformations in children: a five-year follow-up study. Stroke. 2022;53:817-824.
Kharkar S, Shuck J, Conway J, Rigamonti D. The natural history of conservatively managed symptomatic intramedullary spinal cord cavernomas. Neurosurgery. 2007;60:865-871.
Moultrie F, Horne MA, Josephson CB, et al. Outcome after surgical or conservative management of cerebral cavernous malformations. Neurology. 2014;83:582-589.
Salman RAS, Berg MJ, Morrison L, Awad IA. Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Stroke. 2008;39:3222-3230.
Akers A, Al-Shahi Salman R, Awad IA, et al. Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the Angioma Alliance Scientific Advisory Board Clinical Experts panel. Clin Neurosurg. 2017;80:665-680.
Arauz A, Patiño-Rodriguez HM, Chavarria-Medina M, Becerril M, Longo GM, Nathal E. Rebleeding and outcome in patients with symptomatic brain stem cavernomas. Cerebrovasc Dis. 2017;43:283-289.
Li D, Wu Z-Y, Liu P-P, et al. Natural history of brainstem cavernous malformations: prospective hemorrhage rate and adverse factors in a consecutive prospective cohort. J Neurosurg. 2020;134:917-928.
Liang JT, Bao YH, Zhang HQ, Huo LR, Wang ZY, Ling F. Management and prognosis of symptomatic patients with intramedullary spinal cord cavernoma: clinical article. J Neurosurg Spine. 2011;15:447-456.
Salman RAS, Hall JM, Horne MA, et al. Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. Lancet Neurol. 2012;11:217-224.
Chen B, Herten A, Saban D, et al. Hemorrhage from cerebral cavernous malformations: the role of associated developmental venous anomalies. Neurology. 2020;95:89-96.
Chen B, Saban D, Rauscher S, et al. Modifiable cardiovascular risk factors in patients with sporadic cerebral cavernous malformations: obesity matters. Stroke. 2021;52:1259-1264.
Santos AN, Rauschenbach L, Darkwah Oppong M, et al. Assessment and validation of proposed classification tools for brainstem cavernous malformations. J Neurosurg. 2020;135:1-7.
Flemming KD, Kumar S, Brown RD, Lanzino G. Predictors of initial presentation with hemorrhage in patients with cavernous malformations. World Neurosurg. 2020;133:e767-e773. doi:10.1016/j.wneu.2019.09.161
Denier C, Labauge P, Bergametti F, et al. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol. 2006;60:550-556.
Dammann P, Wrede K, Zhu Y, et al. Correlation of the venous angioarchitecture of multiple cerebral cavernous malformations with familial or sporadic disease: a susceptibility-weighted imaging study with 7-Tesla MRI. J Neurosurg. 2017;126:570-577.
Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81:515-526. doi:10.1093/biomet/81.3.515
Badhiwala JH, Farrokhyar F, Alhazzani W, et al. Surgical outcomes and natural history of intramedullary spinal cord cavernous malformations: a single-center series and meta-analysis of individual patient data. J Neurosurg Spine. 2014;21:662-676.
Dammann P, Wrede K, Jabbarli R, et al. Outcome after conservative management or surgical treatment for new-onset epilepsy in cerebral cavernous malformation. J Neurosurg. 2017;126:1303-1311.
Bubenikova A, Skalicky P, Benes VJ, Benes VS, Bradac O. Overview of cerebral cavernous malformations: comparison of treatment approaches. J Neurol Neurosurg Psychiatry. 2022;93:475-480.
Zhang L, Yang W, Jia W, et al. Comparison of outcome between surgical and conservative management of symptomatic spinal cord cavernous malformations. Neurosurgery. 2016;78:552-561.
Ohnishi Y, Nakajima N, Takenaka T, et al. Conservative and surgical management of spinal cord cavernous malformations. World Neurosurg X. 2020;5:100066. doi:10.1016/j.wnsx.2019.100066
Sandalcioglu IE, Wiedemayer H, Gasser T, Asgari S, Engelhorn T, Stolke D. Intramedullary spinal cord cavernous malformations: clinical features and risk of hemorrhage. Neurosurg Rev. 2003;26:253-256.
Jeon JS, Kim JE, Chung YS, et al. A risk factor analysis of prospective symptomatic haemorrhage in adult patients with cerebral cavernous malformation. J Neurol Neurosurg Psychiatry. 2014;85:1366-1370.