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Natural history of incidentally diagnosed brainstem cavernous malformations in a prospective observational cohort

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Abstract

There was a lack of natural history of incidental brainstem cavernous malformations (CMs), hemorrhage of which would lead to severe neuropathies. The study aimed to evaluate the prospective hemorrhage rate and neurological outcome of the disease. This prospective cohort included patients with incidental brainstem CMs referred to our institute from 2009 to 2015. The diagnosis was confirmed based on the patients’ complain, physical examination, and radiographic evidence. Clinical data were collected, scheduled follow-up was performed, and the independent risk factors were identified by multivariate analysis. This cohort included 48 patients (22 female, 45.8%). The median follow-up duration was 60.7 months, and 13 prospective hemorrhages occurred within 244.0 patient-years yielding an annual hemorrhage rate of 5.3%. The hemorrhage-free survival at 1 and 5 years was 91.6% and 80.6%. Age ≥ 55 years (hazard ratio (HR) = 8.59, p = 0.003), lesion size (per 1-mm increase) (HR = 3.55, p = 0.041), developmental venous anomaly (HR = 10.28, p = 0.017), and perilesional edema (HR = 4.90, p = 0.043) were independent risk factors for hemorrhage. Seven patients (14.6%) received surgical resection, and the other 41 patients remained under observation. Neurological function was improved in 22 patients (45.8%), unchanged in 19 (39.6%), and worsened in 7 (14.6%). Prospective hemorrhage (odds ratio = 14.95, p = 0.037) was the only independent risk factor for worsened outcomes. The natural history of incidental brainstem CMs seemed to be acceptable with improved/unchanged outcomes in most patients (85.4%). These results improved our understanding of the disease, and the future study of a large cohort was required to verify our findings.

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References

  1. Abla AA, Lekovic GP, Garrett M, Wilson DA, Nakaji P, Bristol R, Spetzler RF (2010) Cavernous malformations of the brainstem presenting in childhood: surgical experience in 40 patients. Neurosurgery 67:1589–1598; discussion 1598-1589. https://doi.org/10.1227/NEU.0b013e3181f8d1b2

    Article  PubMed  Google Scholar 

  2. Abla AA, Lekovic GP, Turner JD, de Oliveira JG, Porter R, Spetzler RF (2011) Advances in the treatment and outcome of brainstem cavernous malformation surgery: a single-center case series of 300 surgically treated patients. Neurosurgery 68:403–414; discussion 414-405. https://doi.org/10.1227/NEU.0b013e3181ff9cde

    Article  PubMed  Google Scholar 

  3. Aiba T, Tanaka R, Koike T, Kameyama S, Takeda N, Komata T (1995) Natural history of intracranial cavernous malformations. J Neurosurg 83:56–59. https://doi.org/10.3171/jns.1995.83.1.0056

    Article  CAS  PubMed  Google Scholar 

  4. Akers A, Al-Shahi Salman R, Awad IA, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K (2017) 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. Neurosurgery 80:665–680. https://doi.org/10.1093/neuros/nyx091

    Article  PubMed  PubMed Central  Google Scholar 

  5. Al-Holou WN, O’Lynnger TM, Pandey AS, Gemmete JJ, Thompson BG, Muraszko KM, Garton HJ, Maher CO (2012) Natural history and imaging prevalence of cavernous malformations in children and young adults. J Neurosurg Pediatr 9:198–205. https://doi.org/10.3171/2011.11.PEDS11390

    Article  PubMed  Google Scholar 

  6. Al-Shahi Salman R, Berg MJ, Morrison L, Awad IA, Angioma Alliance Scientific Advisory B (2008) Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board. Stroke 39:3222–3230. https://doi.org/10.1161/STROKEAHA.108.515544

    Article  PubMed  Google Scholar 

  7. Al-Shahi Salman R, Hall JM, Horne MA, Moultrie F, Josephson CB, Bhattacharya JJ, Counsell CE, Murray GD, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP, Scottish Audit of Intracranial Vascular Malformations c (2012) Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. Lancet Neurol 11:217–224. https://doi.org/10.1016/S1474-4422(12)70004-2

    Article  PubMed  Google Scholar 

  8. Barker FG 2nd, Amin-Hanjani S, Butler WE, Lyons S, Ojemann RG, Chapman PH, Ogilvy CS (2001) Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery 49:15–24 discussion 24-15

    PubMed  Google Scholar 

  9. Batra S, Lin D, Recinos PF, Zhang J, Rigamonti D (2009) Cavernous malformations: natural history, diagnosis and treatment. Nat Rev Neurol 5:659–670. https://doi.org/10.1038/nrneurol.2009.177

    Article  PubMed  Google Scholar 

  10. Bertalanffy H, Benes L, Miyazawa T, Alberti O, Siegel AM, Sure U (2002) Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients. Neurosurg Rev 25:1–53; discussion 54-55

  11. Cantu C, Murillo-Bonilla L, Arauz A, Higuera J, Padilla J, Barinagarrementeria F (2005) Predictive factors for intracerebral hemorrhage in patients with cavernous angiomas. Neurol Res 27:314–318. https://doi.org/10.1179/016164105X39914

    Article  PubMed  Google Scholar 

  12. Chen L, Zhao Y, Zhou L, Zhu W, Pan Z, Mao Y (2011) Surgical strategies in treating brainstem cavernous malformations. Neurosurgery 68:609–620; discussion 620-601. https://doi.org/10.1227/NEU.0b013e3182077531

    Article  PubMed  Google Scholar 

  13. Dalyai RT, Ghobrial G, Awad I, Tjoumakaris S, Gonzalez LF, Dumont AS, Chalouhi N, Randazzo C, Rosenwasser R, Jabbour P (2011) Management of incidental cavernous malformations: a review. Neurosurg Focus 31:E5. https://doi.org/10.3171/2011.9.FOCUS11211

    Article  PubMed  Google Scholar 

  14. Del Curling O Jr, Kelly DL Jr, Elster AD, Craven TE (1991) An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702–708. https://doi.org/10.3171/jns.1991.75.5.0702

    Article  PubMed  Google Scholar 

  15. Flemming KD, Link MJ, Christianson TJ, Brown RD Jr (2012) Prospective hemorrhage risk of intracerebral cavernous malformations. Neurology 78:632–636. https://doi.org/10.1212/WNL.0b013e318248de9b

    Article  CAS  PubMed  Google Scholar 

  16. Fritschi JA, Reulen HJ, Spetzler RF, Zabramski JM (1994) Cavernous malformations of the brain stem. A review of 139 cases. Acta Neurochir 130:35–46

    Article  CAS  Google Scholar 

  17. Garcia RM, Ivan ME, Lawton MT (2015) Brainstem cavernous malformations: surgical results in 104 patients and a proposed grading system to predict neurological outcomes. Neurosurgery 76:265–277; discussion 277-268. https://doi.org/10.1227/NEU.0000000000000602

    Article  PubMed  Google Scholar 

  18. Gross BA, Batjer HH, Awad IA, Bendok BR (2009) Brainstem cavernous malformations. Neurosurgery 64:E805–E818; discussion E818. https://doi.org/10.1227/01.NEU.0000343668.44288.18

    Article  PubMed  Google Scholar 

  19. Gross BA, Du R (2017) Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis. J Neurosurg 126:1079–1087. https://doi.org/10.3171/2016.3.jns152419

    Article  PubMed  Google Scholar 

  20. Gross BA, Du R, Orbach DB, Scott RM, Smith ER (2016) The natural history of cerebral cavernous malformations in children. J Neurosurg Pediatr 17:123–128. https://doi.org/10.3171/2015.2.PEDS14541

    Article  PubMed  Google Scholar 

  21. Horne MA, Flemming KD, Su IC, Stapf C, Jeon JP, Li D, Maxwell SS, White P, Christianson TJ, Agid R, Cho WS, Oh CW, Wu Z, Zhang JT, Kim JE, Ter Brugge K, Willinsky R, Brown RD Jr, Murray GD, Salman RA, Cerebral Cavernous Malformations Individual Patient Data Meta-analysis C (2016) Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data. Lancet Neurol 15:166–173. https://doi.org/10.1016/S1474-4422(15)00303-8

    Article  PubMed  PubMed Central  Google Scholar 

  22. Jeon JS, Kim JE, Chung YS, Oh S, Ahn JH, Cho WS, Son YJ, Bang JS, Kang HS, Sohn CH, Oh CW (2014) A risk factor analysis of prospective symptomatic haemorrhage in adult patients with cerebral cavernous malformation. J Neurol Neurosurg Psychiatry 85:1366–1370. https://doi.org/10.1136/jnnp-2013-306844

    Article  PubMed  Google Scholar 

  23. Kim DS, Park YG, Choi JU, Chung SS, Lee KC (1997) An analysis of the natural history of cavernous malformations. Surg Neurol 48:9–17 discussion 17-18

    Article  CAS  Google Scholar 

  24. Kondziolka D, Lunsford LD, Kestle JR (1995) The natural history of cerebral cavernous malformations. J Neurosurg 83:820–824. https://doi.org/10.3171/jns.1995.83.5.0820

    Article  CAS  PubMed  Google Scholar 

  25. Kupersmith MJ, Kalish H, Epstein F, Yu G, Berenstein A, Woo H, Jafar J, Mandel G, De Lara F (2001) Natural history of brainstem cavernous malformations. Neurosurgery 48:47–53 discussion 53-44

    CAS  PubMed  Google Scholar 

  26. Labauge P, Brunereau L, Laberge S, Houtteville JP (2001) Prospective follow-up of 33 asymptomatic patients with familial cerebral cavernous malformations. Neurology 57:1825–1828

    Article  CAS  Google Scholar 

  27. Labauge P, Brunereau L, Levy C, Laberge S, Houtteville JP (2000) The natural history of familial cerebral cavernomas: a retrospective MRI study of 40 patients. Neuroradiology 42:327–332

    Article  CAS  Google Scholar 

  28. Li D, Hao SY, Jia GJ, Wu Z, Zhang LW, Zhang JT (2014) Hemorrhage risks and functional outcomes of untreated brainstem cavernous malformations. J Neurosurg 121:32–41. https://doi.org/10.3171/2014.3.JNS132537

    Article  PubMed  Google Scholar 

  29. Li D, Hao SY, Tang J, Xiao XR, Jia GJ, Wu Z, Zhang LW, Zhang JT (2014) Clinical course of untreated pediatric brainstem cavernous malformations: hemorrhage risk and functional recovery. J Neurosurg Pediatr 13:471–483. https://doi.org/10.3171/2014.2.PEDS13487

    Article  PubMed  Google Scholar 

  30. Li D, Hao SY, Tang J, Xiao XR, Jia GJ, Wu Z, Zhang LW, Zhang JT (2014) Surgical management of pediatric brainstem cavernous malformations. J Neurosurg Pediatr 13:484–502. https://doi.org/10.3171/2014.2.PEDS13536

    Article  PubMed  Google Scholar 

  31. Li D, Jiao YM, Wang L, Lin FX, Wu J, Tong XZ, Wang S, Cao Y (2018) Surgical outcome of motor deficits and neurological status in brainstem cavernous malformations based on preoperative diffusion tensor imaging: a prospective randomized clinical trial. J Neurosurg 130:286–301. https://doi.org/10.3171/2017.8.JNS17854

    Article  PubMed  Google Scholar 

  32. Li D, Yang Y, Hao SY, Wang L, Tang J, Xiao XR, Zhou H, Jia GJ, Wu Z, Zhang LW, Zhang JT (2013) Hemorrhage risk, surgical management, and functional outcome of brainstem cavernous malformations. J Neurosurg 119:996–1008. https://doi.org/10.3171/2013.7.JNS13462

    Article  PubMed  Google Scholar 

  33. Moore SA, Brown RD Jr, Christianson TJ, Flemming KD (2014) Long-term natural history of incidentally discovered cavernous malformations in a single-center cohort. J Neurosurg 120:1188–1192. https://doi.org/10.3171/2014.1.JNS131619

    Article  PubMed  Google Scholar 

  34. Moriarity JL, Wetzel M, Clatterbuck RE, Javedan S, Sheppard JM, Hoenig-Rigamonti K, Crone NE, Breiter SN, Lee RR, Rigamonti D (1999) The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 44:1166–1171 discussion 1172-1163

    CAS  PubMed  Google Scholar 

  35. Pandey P, Westbroek EM, Gooderham PA, Steinberg GK (2013) Cavernous malformation of brainstem, thalamus, and basal ganglia: a series of 176 patients. Neurosurgery 72:573–589; discussion 588-579. doi:https://doi.org/10.1227/NEU.0b013e318283c9c2

  36. Porter PJ, Willinsky RA, Harper W, Wallace MC (1997) Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190–197. https://doi.org/10.3171/jns.1997.87.2.0190

    Article  CAS  PubMed  Google Scholar 

  37. Porter RW, Detwiler PW, Spetzler RF, Lawton MT, Baskin JJ, Derksen PT, Zabramski JM (1999) Cavernous malformations of the brainstem: experience with 100 patients. J Neurosurg 90:50–58. https://doi.org/10.3171/jns.1999.90.1.0050

    Article  CAS  PubMed  Google Scholar 

  38. Rigamonti D, Drayer BP, Johnson PC, Hadley MN, Zabramski J, Spetzler RF (1987) The MRI appearance of cavernous malformations (angiomas). J Neurosurg 67:518–524. https://doi.org/10.3171/jns.1987.67.4.0518

    Article  CAS  PubMed  Google Scholar 

  39. Robinson JR, Awad IA, Little JR (1991) Natural history of the cavernous angioma. J Neurosurg 75:709–714. https://doi.org/10.3171/jns.1991.75.5.0709

    Article  CAS  PubMed  Google Scholar 

  40. Schneble HM, Soumare A, Herve D, Bresson D, Guichard JP, Riant F, Tournier-Lasserve E, Tzourio C, Chabriat H, Stapf C (2012) Antithrombotic therapy and bleeding risk in a prospective cohort study of patients with cerebral cavernous malformations. Stroke 43:3196–3199. https://doi.org/10.1161/STROKEAHA.112.668533

    Article  CAS  PubMed  Google Scholar 

  41. Tarnaris A, Fernandes RP, Kitchen ND (2008) Does conservative management for brain stem cavernomas have better long-term outcome? Br J Neurosurg 22:748–757. https://doi.org/10.1080/02688690802354210

    Article  CAS  PubMed  Google Scholar 

  42. Taslimi S, Modabbernia A, Amin-Hanjani S, Barker FG 2nd, Macdonald RL (2016) Natural history of cavernous malformation: systematic review and meta-analysis of 25 studies. Neurology 86:1984–1991. https://doi.org/10.1212/WNL.0000000000002701

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tian KB, Zheng JJ, Ma JP, Hao SY, Wang L, Zhang LW, Wu Z, Zhang JT, Li D (2017) Clinical course of untreated thalamic cavernous malformations: hemorrhage risk and neurological outcomes. J Neurosurg 127:480–491. https://doi.org/10.3171/2016.8.jns16934

    Article  PubMed  Google Scholar 

  44. Velz J, Stienen MN, Neidert MC, Yang Y, Regli L, Bozinov O (2018) Routinely performed serial follow-up imaging in asymptomatic patients with multiple cerebral cavernous malformations has no influence on surgical decision making. Front Neurol 9:848. https://doi.org/10.3389/fneur.2018.00848

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wang CC, Liu A, Zhang JT, Sun B, Zhao YL (2003) Surgical management of brain-stem cavernous malformations: report of 137 cases. Surg Neurol 59:444–454; discussion 454

  46. Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, Brown B, Rigamonti D, Brown G (1994) The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80:422–432. https://doi.org/10.3171/jns.1994.80.3.0422

    Article  CAS  PubMed  Google Scholar 

  47. Zaidi HA, Mooney MA, Levitt MR, Dru AB, Abla AA, Spetzler RF (2017) Impact of timing of intervention among 397 consecutively treated brainstem cavernous malformations. Neurosurgery 81:620–626. https://doi.org/10.1093/neuros/nyw139

    Article  PubMed  Google Scholar 

  48. Zuurbier SM, Hickman CR, Tolias CS, Rinkel LA, Leyrer R, Flemming KD, Bervini D, Lanzino G, Wityk RJ, Schneble HM, Sure U, Al-Shahi Salman R, Scottish Audit of Intracranial Vascular Malformations Steering C (2019) Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis. Lancet Neurol 18:935–941. https://doi.org/10.1016/S1474-4422(19)30231-5

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The study was supported by Beijing Municipal Science & Technology Commission (No. Z171100001017067) and Capital’s Funds for Health Improvement and Research (No. CFH 2018-2-2043).

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  1. Jing-Jie Zheng and Pan-Pan Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

    Jing-Jie Zheng & Yu-Mei Wu

  2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nansihuan Xilu 119, Fengtai District, Beijing, People’s Republic of China

    Pan-Pan Liu, Liang Wang, Li-Wei Zhang, Jun-Ting Zhang, Da Li & Zhen Wu

  3. Department of Neurosurgery, The Municipal Hospital of Weihai, No. 70 Heping Road, Huancui District, Weihai, People’s Republic of China

    Pan-Pan Liu

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Correspondence to Da Li, Zhen Wu or Yu-Mei Wu.

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Zheng, JJ., Liu, PP., Wang, L. et al. Natural history of incidentally diagnosed brainstem cavernous malformations in a prospective observational cohort. Neurosurg Rev 44, 1151–1164 (2021). https://doi.org/10.1007/s10143-020-01308-0

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