• cerebral cavernous malformation (CCM) is a well-circumscribed accumulation of dilated, thin-walled vessels that affect 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)  Multiple cerebral cavernomatosis (SWI)
      • often symptomatic
      • possible de novo CM formation
  • can be localized anywhere (approximately 80% are supratentorial)
  • CM-associated anomalies:
MRI 0.25-0.7%
rebleeding 4.5%
MRI, DSA 0.2-0.4%
DSA, CTA 2-4 %
rebleeding 6-18%
MRI very low
type I – very low
type II, III – up to 8%
Carotido-cavernous fistula (CCF) DSA, MRA very low
Vascular malformations
  • familial cases of CCM have autosomal dominant (AD) inheritance with incomplete penetrance
  • account for 10–50% of all cases
  • mutations have been identified in three genes:
    • KRIT1 (Krev interaction trapped 1) on 7q21-q22 (CCM1)
    • MGC4067 (Malcavernin) on 7p13 (CCM2)
    • PDCD10 (programmed cell death 10) on 3q26-q27 (CCM3)
  • genotype–phenotype correlations between the three forms are emerging
    • CCM1 mutation carriers appear to have a milder hemorrhage phenotype but may present with more seizures and extraneurologic manifestations
    • CCM3 patients may have a more aggressive clinical course with an earlier age of onset of symptoms and greater risk of ICH
Cavernous malformation


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

Clinical presentation

  • asymptomatic in up to 44% of cases
  • epileptic seizures (45-70%) [Májovský, 2014] [Sage, 1993]
    • mostly associated with lesions localized in the frontal and temporal lobes
    • cavernous malformations account for approximately 4% of refractory epilepsy
  • bleeding
    • low risk (0.25-0.7% per year), increased after prior bleeding episodes  (⇒ 4.5% / year)
    • higher risk with infratentorial lesions
    • hemorrhages are generally non-fatal due to low pressure within the malformation; however, repeated hemorrhages may ultimately lead to severe neurological deficit
  • headache (20-30%)
  • focal neurological deficit (e.g., in case of cerebellar or brainstem lesion)
  • risk factors for adverse outcome
    • multiple lesions
    • presence of CCM3 genotype
    • early clinical presentation
    • infratentorial localization
    • lesion diameter >1 cm
    • associated developmental venous anomaly (DVA)

Diagnostic evaluation

  • CT
    • lesion is typically poorly visible (negative CT in up to 50% of cases)
    • cavernous malformation may appear slightly hyperdense, with small calcifications   Slightly hyperdense cavernous malformation on NCCT   Cavernous malformation
    • minimal or absent postcontrast enhancement Cavernous malformation with a subtle enhancement on contrast-enhanced CT
    • no mass effect or collateral edema
    • recent bleeding may be detected
  • MRI (sensitivity 100%) Cavernous malformation  
    • characteristic popcorn appearance   Cavernous malformation with a characteristic popcorn appearance
    • heterogeneous lesion with a hemosiderin rim (T2-hypointense) Large cavernous malformation with hemosiderin rim 
    • prominent finding on GRE – “blooming artifact”
    • slight enhancement is possible  [Pinker, 2006]
  • DSA is normal
Cavernous malformation (FLAIR)

Appearance of the cavernous malformation on different imaging modalities
Cavernous malformation
Multiple cavernous malformations (MRI SWAN)
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  • the Zabramski MRI classification has been proposed for the classification of cerebral cavernous malformations
  • primarily useful for scientific purposes
  • type I: subacute hemorrhage
    • T1: hyperintense
    • T2: hypo-/hyperintense
  • type II:  classic “popcorn” lesion  Cavernous malformation - popcorn appearance
    • 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


Surgery and radiotherapy

  • microsurgical resection
    • relatively safe 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]
    • markers associated with the unfavorable outcomes of surgery: a preoperative motor deficit, recurrent hemorrhage, and large cavernomas crossing the axial midpoint (Li, 2024)
  • 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 is not immediately observable; the long-term clinical course may differ from that of untreated lesions

Conservative therapy and follow-up

  • follow-up MRI is recommended every 1-2 years for 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)
Size (mm) Points #hemorrhgaic event (HE) Points
 ≤ 10 0 0 0
 > 10, ≤ 20 1 1 1
 > 20, ≤ 30 2 0 2
 > 30 3  ≥ 3 3
mRS (0–5) Points Age (years) Points
0 0  > 60 0
1 1  ≤ 60 1
2 2 Crossing midline Points
3 3 Yes 0
4-5 4 No 1

The crossover point between surgery and non-surgery recommendations lay between grades V and VI, while surgical treatment was found in favor at grades VII–X (Yang, 2021)

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Cerebral cavernous malformation