INTRACEREBRAL HEMORRHAGE / VASCULAR MALFORMATIONS

Cerebral cavernous malformation

Created 20/04/2021, last revision 29/04/2023

cerebral cavernous malformation (CCM) is a well-circumscribed accumulation of dilated, thin-walled vessels affecting the brain
- only a layer of endothelium and subendothelial stroma is present; smooth muscle cells and elastic fibers are absent
- the pathogenesis of CM remains unclear
forms:
- sporadic
  - incidence in the population 0.4-0.9% [Sage, 1993]
  - accounts for 8-15% of all vascular malformations
  - usually one lesion (in about 70% of cases)
- familial
  - a genetically linked multiple cavernomatosis (AD)
  - often symptomatic
  - possible de novo CM formation
can be localized anywhere (approximately 80% are supratentorial)
CM-associated anomalies:
- café au lait spots
- DVA (venous angioma)

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erythrocyte diapedesis through the pathological cavernoma wall
- hemoglobin degradation products lead to pathological excitability, oxidative damage, and gliosis ⇒ epilepsy
bleeding into the cavernoma ⇒ ↑ malformation volume
bleeding into the surrounding area

asymptomatic in up to 44% of cases
epileptic seizures (45-70%) [Májovský, 2014] [Sage, 1993]
- mainly in lesions localized in the frontal and temporal lobes
- cavernous malformations are the cause of approximately 4% of refractory epilepsies
bleeding
- low risk (0.25-0.7% per year), increased with previous bleeding (⇒ 4.5% / year)
- higher risk with infratentorial lesions
- hemorrhages are not fatal due to low pressure within the malformation; repeated hemorrhages, however, may ultimately lead to severe deficit
headache (20-30%)
focal neurological deficit (e.g., in case of cerebellar or brainstem lesion)
risk factors for adverse outcome
- multiple lesions
- CCM3 genotype
- early clinical presentation
- infratentorial localization
- diameter >1 cm
- associated venous anomaly (DVA)

CT
- usually poorly visible lesion (negative CT in up to 50% of cases)
- cavernous malformation may be slightly hyperdense, with small calcifications
- none or only minimal postcontrast enhancement
- no mass effect, no collateral edema
- recent bleeding may be detected
MRI (sensitivity 100%)
- popcorn appearance
- heterogeneous lesion with hemosiderin rim (T2-hypointense)
- prominent finding on GRE – “blooming artifact”
- slight enhancement is possible [Pinker, 2006]
DSA is normal

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the Zabramski MRI classification has been proposed as a way to classify cerebral cavernous malformations
useful rather for scientific purposes

type I: subacute hemorrhage
- T1: hyperintense
- T2: hypo-/hyperintense
type II: classic “popcorn” lesion
- T1 and T2: mixed-signal intensity centrally
- T2*/GRE/SWI: hypointense rim with blooming
type III: chronic hemorrhage
- T1: hypointense/isointense centrally
- T2: hypointense centrally
- T2*/GRE/SWI: hypointense rim with blooming
type IV: multiple punctate microhemorrhages
- GRE/SWI: “black dots” with blooming
- difficult to distinguish from small capillary telangiectasias

microsurgical resection
- relatively safe surgical procedure with low morbidity and mortality [Májovský, 2014]
- proven indications:
  - refractory epilepsy (up to 90% of patients are seizure free after the surgery)
  - recurrent bleeding
- in infratentorial CMs, surgery is preferred in cerebellar lesions and hemorrhagic lesions localized near the ventricle or cistern [Amato, 2013]
stereotactic radiosurgery (SRS) may be considered for inoperable lesions [Liščák, 2013] [Liščák, 2000]
- indications and therapy results are controversial
- in contrast to AVMs, the direct effect of therapy cannot be observed; the long-term clinical course may change compared to untreated lesions

follow-up MRI every 1-2 years in asymptomatic lesions
keep blood pressure in the normal range
beta-blockers may reduce the risk of intracranial hemorrhage or persistent/progressive focal neurological deficit in patients with CCM (Zuurbier, 2022)