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Acta Neuropathologica

, Volume 128, Issue 1, pp 55–65 | Cite as

Cerebral cavernous malformations in the setting of focal epilepsies: pathological findings, clinical characteristics, and surgical treatment principles

  • Lara E. JehiEmail author
  • Andre Palmini
  • Usha Aryal
  • Roland Coras
  • Eliseu Paglioli
Review

Abstract

Cavernous cerebral malformations (CCMs) are a well-defined epilepsy-associated pathology. They represent lesions/conglomerates of abnormally configured vessels leading to seizures either as a result of physiological changes affecting the cerebral cortex immediately surrounding the CCM (an epileptogenic mechanism that is relevant for both temporal and extratemporal lesions), or as a result of promoting epileptogenicity in remote but anatomo-functionally connected brain regions (a mechanism that is particularly relevant for temporal lobe lesions). This review details the pathological findings in CCMs and discusses the mechanisms of epileptogenicity in this context. The bulk of the review will focus on therapeutic strategies. Medical therapy using antiepileptic drugs is recommended as a first-line therapy, but surgical removal of the CCM with the surrounding cortex should be pursued if seizures prove to be drug resistant. Early timing of the resection and complete removal of any associated epileptic pathology are critical for best outcomes. In addition to reviewing the available data from prior series, we present original research from two specialized epilepsy centers targeted at answering particularly pressing clinical questions mainly related to the ideal timing and extent of surgery. Further research is needed to define the best surgical strategies in patients with temporal lobe CCMs and structurally normal hippocampi.

Keywords

Cerebral cavernous malformation CCM Seizure outcome Lesionectomy Lobectomy Epilepsy surgery 

References

  1. 1.
    Amin-Hanjani S, Robertson R, Arginteanu MS, Scott RM (1998) Familial intracranial arteriovenous malformations. Case report and review of the literature. Pediatr Neurosurg 29:208–213PubMedCrossRefGoogle Scholar
  2. 2.
    Awad I, Jabbour P (2006) Cerebral cavernous malformations and epilepsy. Neurosurg Focus 21:e7PubMedGoogle Scholar
  3. 3.
    Bacigaluppi S, Retta SF, Pileggi S, Fontanella M, Goitre L, Tassi L, La Camera A, Citterio A, Patrosso MC, Tredici G, Penco S (2013) Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management. Clin Genet 83:7–14. doi: 10.1111/j.1399-0004.2012.01892.x PubMedCrossRefGoogle Scholar
  4. 4.
    Baumann CR, Schuknecht B, Lo Russo G, Cossu M, Citterio A, Andermann F, Siegel AM (2006) Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed. Epilepsia 47:563–566. doi: 10.1111/j.1528-1167.2006.00468.x PubMedCrossRefGoogle Scholar
  5. 5.
    Baumann CR, Acciarri N, Bertalanffy H, Devinsky O, Elger CE, Lo Russo G, Cossu M, Sure U, Singh A, Stefan H, Hammen T, Georgiadis D, Baumgartner RW, Andermann F, Siegel AM (2007) Seizure outcome after resection of supratentorial cavernous malformations: a study of 168 patients. Epilepsia 48:559–563. doi: 10.1111/j.1528-1167.2006.00941.x PubMedCrossRefGoogle Scholar
  6. 6.
    Ben-Ari Y, Dudek FE (2010) Primary and secondary mechanisms of epileptogenesis in the temporal lobe: there is a before and an after. Epilepsy Curr 10:118–125. doi: 10.1111/j.1535-7511.2010.01376.x PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Blumcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, Jacques TS, Avanzini G, Barkovich AJ, Battaglia G, Becker A, Cepeda C, Cendes F, Colombo N, Crino P, Cross JH, Delalande O, Dubeau F, Duncan J, Guerrini R, Kahane P, Mathern G, Najm I, Ozkara C, Raybaud C, Represa A, Roper SN, Salamon N, Schulze-Bonhage A, Tassi L, Vezzani A, Spreafico R (2011) The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia 52:158–174. doi: 10.1111/j.1528-1167.2010.02777.x PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Cappabianca P, Alfieri A, Maiuri F, Mariniello G, Cirillo S, de Divitiis E (1997) Supratentorial cavernous malformations and epilepsy: seizure outcome after lesionectomy on a series of 35 patients. Clin Neurol Neurosurg 99:179–183PubMedCrossRefGoogle Scholar
  9. 9.
    Chassoux F, Landre E, Mellerio C, Laschet J, Devaux B, Daumas-Duport C (2013) Dysembryoplastic neuroepithelial tumors: epileptogenicity related to histologic subtypes. Clin Neurophysiol 124:1068–1078. doi: 10.1016/j.clinph.2012.11.015 PubMedCrossRefGoogle Scholar
  10. 10.
    Churchyard A, Khangure M, Grainger K (1992) Cerebral cavernous angioma: a potentially benign condition? Successful treatment in 16 cases. J Neurol Neurosurg Psychiatry 55:1040–1045PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Cohen DS, Zubay GP, Goodman RR (1995) Seizure outcome after lesionectomy for cavernous malformations. J Neurosurg 83:237–242. doi: 10.3171/jns.1995.83.2.0237 PubMedCrossRefGoogle Scholar
  12. 12.
    Del Curling O, Kelly DL Jr, Elster AD, Craven TE (1991) An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702–708. doi: 10.3171/jns.1991.75.5.0702 PubMedCrossRefGoogle Scholar
  13. 13.
    Dube C, da Silva Fernandes MJ, Nehlig A (2001) Age-dependent consequences of seizures and the development of temporal lobe epilepsy in the rat. Dev Neurosci 23:219–223 Doi:46147PubMedCrossRefGoogle Scholar
  14. 14.
    Englot DJ, Han SJ, Lawton MT, Chang EF (2011) Predictors of seizure freedom in the surgical treatment of supratentorial cavernous malformations. J Neurosurg 115:1169–1174. doi: 10.3171/2011.7.JNS11536 PubMedCrossRefGoogle Scholar
  15. 15.
    Fauser S, Schulze-Bonhage A (2006) Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings. Brain 129:82–95 awh687 [pii]PubMedCrossRefGoogle Scholar
  16. 16.
    Fernandez S, Miro J, Falip M, Coello A, Plans G, Castaner S, Acebes JJ (2012) Surgical versus conservative treatment in patients with cerebral cavernomas and non refractory epilepsy. Seizure 21:785–788. doi: 10.1016/j.seizure.2012.09.004 PubMedCrossRefGoogle Scholar
  17. 17.
    Ferrer I, Ferrer I, Kaste M, Kalimo H (2008) Vascular diseases. In: Love S, Louis DN, Ellison DW (eds) Greenfield’s Neuropathology, vol 1. Edward Arnold, London, pp 121–240Google Scholar
  18. 18.
    Ferrier CH, Aronica E, Leijten FS, Spliet WG, Boer K, van Rijen PC, van Huffelen AC (2007) Electrocorticography discharge patterns in patients with a cavernous hemangioma and pharmacoresistent epilepsy. J Neurosurg 107:495–503. doi: 10.3171/JNS-07/09/0495 PubMedCrossRefGoogle Scholar
  19. 19.
    Ferroli P, Casazza M, Marras C, Mendola C, Franzini A, Broggi G (2006) Cerebral cavernomas and seizures: a retrospective study on 163 patients who underwent pure lesionectomy. Neurol Sci 26:390–394. doi: 10.1007/s10072-006-0521-2 PubMedCrossRefGoogle Scholar
  20. 20.
    Hammen T, Romstock J, Dorfler A, Kerling F, Buchfelder M, Stefan H (2007) Prediction of postoperative outcome with special respect to removal of hemosiderin fringe: a study in patients with cavernous haemangiomas associated with symptomatic epilepsy. Seizure 16:248–253. doi: 10.1016/j.seizure.2007.01.001 PubMedCrossRefGoogle Scholar
  21. 21.
    Hauser WA, Mohr JP (2011) Seizures, epilepsy, and vascular malformations. Neurology 76:1540–1541. doi: 10.1212/WNL.0b013e318219fb97 PubMedCrossRefGoogle Scholar
  22. 22.
    Janszky J, Janszky I, Schulz R, Hoppe M, Behne F, Pannek HW, Ebner A (2005) Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome. Brain 128:395–404. doi: 10.1093/brain/awh358 PubMedCrossRefGoogle Scholar
  23. 23.
    Jeong SW, Lee SK, Hong KS, Kim KK, Chung CK, Kim H (2005) Prognostic factors for the surgery for mesial temporal lobe epilepsy: longitudinal analysis. Epilepsia 46:1273–1279. doi: 10.1111/j.1528-1167.2005.33504.x PubMedCrossRefGoogle Scholar
  24. 24.
    Josephson CB, Leach JP, Duncan R, Roberts RC, Counsell CE, Al-Shahi Salman R, Scottish Audit of Intracranial Vascular Malformations (SAIVMs) Steering Committee and Collaborators (2011) Seizure risk from cavernous or arteriovenous malformations: prospective population-based study. Neurology 76:1548–1554. doi: 10.1212/WNL.0b013e3182190f37 PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Luders HO (2001) Clinical evidence for secondary epileptogenesis. Int Rev Neurobiol 45:469–480PubMedCrossRefGoogle Scholar
  26. 26.
    McIntosh AM, Kalnins RM, Mitchell LA, Fabinyi GC, Briellmann RS, Berkovic SF (2004) Temporal lobectomy: long-term seizure outcome, late recurrence and risks for seizure recurrence. Brain 127:2018–2030. doi: 10.1093/brain/awh221 PubMedCrossRefGoogle Scholar
  27. 27.
    Menzler K, Chen X, Thiel P, Iwinska-Zelder J, Miller D, Reuss A, Hamer HM, Reis J, Pagenstecher A, Knake S, Bertalanffy H, Rosenow F, Sure U (2010) Epileptogenicity of cavernomas depends on (archi-) cortical localization. Neurosurgery 67:918–924. doi: 10.1227/NEU.0b013e3181eb5032 PubMedCrossRefGoogle Scholar
  28. 28.
    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 1172-3PubMedGoogle Scholar
  29. 29.
    Morrell F (1989) Varieties of human secondary epileptogenesis. J Clin Neurophysiol 6:227–275PubMedCrossRefGoogle Scholar
  30. 30.
    Morrell F (1985) Secondary epileptogenesis in man. Arch Neurol 42:318–335PubMedCrossRefGoogle Scholar
  31. 31.
    Morrell F, deToledo-Morrell L (1999) From mirror focus to secondary epileptogenesis in man: an historical review. Adv Neurol 81:11–23PubMedGoogle Scholar
  32. 32.
    Riant F, Bergametti F, Ayrignac X, Boulday G, Tournier-Lasserve E (2010) Recent insights into cerebral cavernous malformations: the molecular genetics of CCM. FEBS J 277:1070–1075. doi: 10.1111/j.1742-4658.2009.07535.x PubMedCrossRefGoogle Scholar
  33. 33.
    Rosenow F, Alonso-Vanegas MA, Baumgartner C, Blumcke I, Carreno M, Gizewski ER, Hamer HM, Knake S, Kahane P, Luders HO, Mathern GW, Menzler K, Miller J, Otsuki T, Ozkara C, Pitkanen A, Roper SN, Sakamoto AC, Sure U, Walker MC, Steinhoff BJ, Surgical Task Force, Commission on Therapeutic Strategies of the ILAE (2013) Cavernoma-related epilepsy: review and recommendations for management––report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 54:2025–2035. doi: 10.1111/epi.12402 PubMedCrossRefGoogle Scholar
  34. 34.
    Simasathien T, Vadera S, Najm I, Gupta A, Bingaman W, Jehi L (2013) Improved outcomes with earlier surgery for intractable frontal lobe epilepsy. Ann Neurol 73:646–654. doi: 10.1002/ana.23862 PubMedCrossRefGoogle Scholar
  35. 35.
    Sommer B, Kasper BS, Coras R, Blumcke I, Hamer HM, Buchfelder M, Roessler K (2013) Surgical management of epilepsy due to cerebral cavernomas using neuronavigation and intraoperative MR imaging. Neurol Res 35:1076–1083. doi: 10.1179/016164113X13801151880551 PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Stavrou I, Baumgartner C, Frischer JM, Trattnig S, Knosp E (2008) Long-term seizure control after resection of supratentorial cavernomas: a retrospective single-center study in 53 patients. Neurosurgery 63:888–896. doi: 10.1227/01.NEU.0000327881.72964.6E discussion 897PubMedCrossRefGoogle Scholar
  37. 37.
    Surges R, Schulze-Bonhage A, Altenmuller DM (2008) Hippocampal involvement in secondarily generalised seizures of extrahippocampal origin. J Neurol Neurosurg Psychiatry 79:924–929 (pii): jnnp.2007.129387PubMedCrossRefGoogle Scholar
  38. 38.
    von der Brelie C, Schramm J (2011) Cerebral cavernous malformations and intractable epilepsy: the limited usefulness of current literature. Acta Neurochir (Wien) 153:249–259. doi: 10.1007/s00701-010-0915-z CrossRefGoogle Scholar
  39. 39.
    von der Brelie C, Malter MP, Niehusmann P, Elger CE, von Lehe M, Schramm J (2013) Surgical management and long-term seizure outcome after epilepsy surgery for different types of epilepsy associated with cerebral cavernous malformations. Epilepsia 54:1699–1706. doi: 10.1111/epi.12327 PubMedCrossRefGoogle Scholar
  40. 40.
    Williamson A, Patrylo PR, Lee S, Spencer DD (2003) Physiology of human cortical neurons adjacent to cavernous malformations and tumors. Epilepsia 44:1413–1419PubMedCrossRefGoogle Scholar
  41. 41.
    Yeon JY, Kim JS, Choi SJ, Seo DW, Hong SB, Hong SC (2009) Supratentorial cavernous angiomas presenting with seizures: surgical outcomes in 60 consecutive patients. Seizure 18:14–20. doi: 10.1016/j.seizure.2008.05.010 PubMedCrossRefGoogle Scholar
  42. 42.
    Zevgaridis D, van Velthoven V, Ebeling U, Reulen HJ (1996) Seizure control following surgery in supratentorial cavernous malformations: a retrospective study in 77 patients. Acta Neurochir (Wien) 138:672–677CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Lara E. Jehi
    • 1
    Email author
  • Andre Palmini
    • 2
  • Usha Aryal
    • 1
  • Roland Coras
    • 3
  • Eliseu Paglioli
    • 2
  1. 1.Epilepsy CenterCleveland Clinic Neurological InstituteClevelandUSA
  2. 2.Faculty of Medicine, Pontificia Universidade Catolica Do Rio Grande do Sul (PUCRS)Porto Alegre Epilepsy Surgery Program, Hospital Sao Lucas (PUCRS)Porto AlegreBrazil
  3. 3.Department of NeuropathologyUniversity Hospital ErlangenErlangenGermany

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