DOI 10.1212/WNL.0000000000000699 published online July 3, 2014Neurology
Gary L. Bernardini and Christian StapfCavernoma today: Keep the surgeon away?
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EDITORIAL
Gary L. Bernardini, MD,PhD
Christian Stapf, MD
Correspondence toDr. Bernardini:[email protected]
Neurology® 2014;83:1–2
See page XXX
Cavernoma today:Keep the surgeon away?
Cerebral cavernous malformations (CCMs), or caver-nomas, are rounded or oval lesions in the CNS con-sisting of dilated vascular channels with single layerof endothelium, lacking muscular and elastic layers,without normal intervening brain parenchyma.Developmental venous anomalies may coexist withCCMs in up to 30% of cases, and along with capillarytelangiectasias and arteriovenous malformations,comprise 4 types of vascular malformations foundin CNS.
Cavernomas have certain clinical and imaging char-acteristics. They are found in patients in the secondthrough fifth decade of life, with an increasing numberof asymptomatic lesions found due to the increasingavailability of brain MRI. Symptomatic, affected pa-tients may present with seizures, intracranial hemor-rhage, or focal neurologic deficits, but up to 50%remain asymptomatic over a lifetime.1 Most CCMsare located supratentorially, but 20% occur in the pos-terior fossa. Rarely, CCMs can occur in the spinal cordor involve cranial nerves or the retina, often coexistingwith multiple brain CCMs. When seen on CT, CCMscan be mistaken for (sub)acute intracerebral hemor-rhage (ICH) or secondary brain lesions. On MRI,CCMs have a classic “popcorn” appearance on T2-weighted imaging, with surrounding hypointensityrepresenting a hemosiderin rim. CCMs always carryhemosiderin easily detected on gradient echo (T2*)or susceptibility-weighted images. Rarely, CCMs haveatypical radiographic features such as surrounding vaso-genic edema, mass effect, and fluid–fluid level.2 Thepresence of multiple CCMs in an individual or 2 ormore affected family members of an individual with asolitary CCM suggests an autosomal dominant familialform of CCM. To date, the 3 characterized autosomaldominant forms correspond to mutations in KRIT1(CCM1), MGC4607 (CCM2), and PDCD10(CCM3). Current treatment options for CCMs includeconservative management, microsurgical excision, orstereotactic radiosurgery. Untreated lesions seem tohave a low spontaneous bleeding risk, especially caver-nomas without prior symptomatic hemorrhage.3
In this issue ofNeurology®, Moultrie et al.4 presentresults on outcomes after surgical or conservativemanagement of CCMs. This prospectively designed,population-based study identified Scottish residentswith definite CCM diagnosis based on pathologicexamination after excision or brain MRI. Patientswere classified as managed conservatively if they didnot receive surgical or radiosurgical CCM treatmentwithin 5 years after initial presentation, or treated ifthey had undergone microsurgical excision or stereo-tactic radiosurgery of the CCM over this same timeperiod. The patients’ physicians made all treatmentdecisions. Of the 134 patients studied, 25 underwentmicrosurgery for excision of CCM a median of 10months after initial presentation. For the primaryanalysis, the investigators defined poor outcome asat least 2 successive ratings of Oxford Handicap Scale(OHS) score 2–6 (OHS derivative of modified Ran-kin Scale scoring system). The secondary analysesincluded a composite of symptomatic ICH or newfocal neurologic deficit (FND). The group undergo-ing CCM excision progressed to a poor outcometwice as frequently as the conservatively managedgroup (adjusted hazard ratio 2.2, 95% confidenceinterval 1.1–4.2). Similarly, the patients who under-went CCM excision endured a higher risk of experi-encing ICH or new FND. Sensitivity analysesexcluding events attributable primarily to the CCMshowed no change in the significance or magnitude ofthe association.
Overall, this study provides compelling evidencethat CCM excision may worsen short-term disabilityscores and increase the risk of symptomatic ICH andnew neurologic deficits. Contrary to prior conven-tional wisdom that selected symptomatic patientsshould undergo surgery, this study shows worsenedoutcomes in those who do so. The strengths of thestudy include the unbiased prospective population-based dataset, detailed case assessment, predefinedcontrol group, and near complete follow-up (97%),as well as independent neuroimaging review and out-come assessment.
From the Departments of Neurology and Neurosurgery (G.L.B.), Albany Medical Center, NY; and the Department of Neurology (C.S.), UniversitéDiderot–Sorbonne Paris Cité, APHP–Hôpital Lariboisière, France.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial.
© 2014 American Academy of Neurology 1
ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
Published Ahead of Print on July 3, 2014 as 10.1212/WNL.0000000000000699
The study has some limitations. This is not a ran-domized trial, and there were no predetermined selec-tion criteria for which patients had conservative vssurgical management. Therefore, systematic treatmentselection bias cannot be excluded, as sicker patients(ICH, FND) may have been preferentially selected formicrosurgical excision. Curiously, the patients progress-ing to primary outcome did so 1.5 years after treatment,suggesting other, as yet undetermined, confounding fac-tors that contributed to progressive worsening in surgi-cally treated patients. Also, the potential effect ofmultiple (i.e., genetically determined) CCMs on pro-gressive worsening remains unclear from the data.
These considerations aside, surgical cavernomaexcision cannot be routinely recommended, espe-cially for patients with asymptomatic CCM, basedon the risks documented in this study. These dataprovide ample justification for a randomized con-trolled trial evaluating patient management with orwithout surgical CCM excision. Similar concernsfor arteriovenous malformations have led to a ran-domized controlled trial that recently confirmedthe superiority of noninterventional managementover invasive management for the prevention ofdeath and symptomatic stroke for cases with
nonhemorrhagic lesions.5 The same may be truefor patients with CCM.
STUDY FUNDINGNo targeted funding reported.
DISCLOSUREThe authors report no disclosures relevant to the manuscript. Go to
Neurology.org for full disclosures.
REFERENCES1. Cortés Vela JJ, Concepción Aramendía L, Ballenilla
Marco F, Gallego León JI, González-Spinola San Gil J.
Cerebral cavernous malformations: spectrum of neuroradio-
logical findings. Radiologia 2012;54:401–409.
2. Rivera PP, Willinsky RA, Porter PJ. Intracranial cavernous
malformations. Neuroimaging Clin N Am 2003;13:27–40.
3. Schneble HM, Soumare A, Hervé D, et al. Antithrombotic
therapy and bleeding risk in a prospective cohort study of
patients with cerebral cavernous malformations. Stroke
2012;43:3196.
4. Moultrie F, Horne MA, Josephson CB, et al. Outcome after
surgical or conservative management of cerebral cavernous
malformations. Neurology 2014;83:xx–xx.
5. Mohr JP, Parides MK, Stapf C, et al. Medical management
with or without interventional therapy for unruptured brain
arteriovenous malformations (ARUBA): a multicentre, non-
blinded, randomised trial. Lancet 2014;383:614–621.
2 Neurology 83 August 12, 2014
ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
DOI 10.1212/WNL.0000000000000699 published online July 3, 2014Neurology
Gary L. Bernardini and Christian StapfCavernoma today: Keep the surgeon away?
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