Cavernous Malformation

Cavernous malformations (cavernomas, cavernous angiomas) are clusters of dilated, endothelium-lined caverns without intervening brain parenchyma. They are low-pressure lesions that enlarge through repeated small haemorrhages, thrombosis and organisation, which produces the characteristic layered blood products. Lesions occur sporadically, often next to a developmental venous anomaly, or in a familial form caused by loss-of-function mutations in CCM1 (KRIT1), CCM2 or CCM3 (PDCD10), in which multiple lesions develop and new ones appear over time^[1]. Cranial radiotherapy is a recognised cause of de novo lesions.

An individual patient data meta-analysis of untreated cavernomas found that the strongest predictors of a future symptomatic haemorrhage are a prior haemorrhage at presentation and brainstem location^[2]. Patients with neither had a low five-year risk, whereas brainstem lesions that had already bled carried a five-year risk of roughly one in three. Re-haemorrhage risk is highest in the first years after a bleed and declines afterwards (temporal clustering), which matters when interpreting surgical series.

The Zabramski MRI classification, developed in a prospective familial cohort, describes lesions by their blood products: type I subacute haemorrhage, type II the classic mixed-signal “popcorn” lesion, type III chronic haemorrhage, and type IV punctate lesions visible only on gradient-echo imaging^[3].

Supratentorial lesions most often present with seizures, followed by headache and focal deficits. Brainstem and deep (thalamic, basal ganglia) lesions present with acute or stepwise cranial-nerve and long-tract deficits after haemorrhage, frequently with partial recovery between events. Many lesions are found incidentally.

MRI is diagnostic: a reticulated core of mixed signal with a complete T2-hypointense haemosiderin rim, and blooming on gradient-echo or susceptibility-weighted imaging (SWI). SWI also reveals additional small lesions that suggest the familial form. Catheter angiography is normal and is not needed unless another vascular lesion is suspected; contrast-enhanced MRI shows any associated DVA, which must be preserved at surgery. Genetic counselling and testing are recommended for patients with multiple lesions or a family history^[1]. For epilepsy surgery, EEG and seizure semiology are correlated with the lesion.

Consensus guidelines support resection for accessible lesions causing epilepsy (especially drug-resistant seizures) and for symptomatic lesions that have bled when the surgical risk is acceptable; asymptomatic lesions and those in eloquent, deep locations without a surface presentation are usually observed^[1]. For brainstem cavernomas, surgery is generally offered after a second symptomatic haemorrhage, or after a single haemorrhage with significant deficit, when the lesion abuts the pial or ependymal surface. Timing in the subacute window, after the haematoma has begun to liquefy but before dense gliosis forms, eases dissection.

The Lawton–Garcia grading system for brainstem cavernomas predicts outcome from lesion size, crossing of the axial midpoint, an associated DVA, patient age and the timing of surgery after the last haemorrhage^[4]. Stereotactic radiosurgery has a limited and debated role, mostly for high-risk deep lesions that cannot be resected.

• Use neuronavigation, and for brainstem lesions neurophysiological monitoring (motor and somatosensory evoked potentials, cranial-nerve and corticobulbar monitoring).
• Choose the approach so that the lesion is reached where it comes closest to the surface (the two-point method), and enter the brainstem through an anatomically defined safe entry zone if it does not reach the surface^[5].
• Debulk the lesion from inside and then dissect it from the surrounding gliotic plane with minimal traction; avoid bipolar coagulation on the brainstem floor.
• Preserve any developmental venous anomaly; sacrificing it risks venous infarction.
• For epilepsy, removal of the haemosiderin-stained cortex improves seizure outcome in non-eloquent cortex; in the brainstem the rim is left.

After supratentorial resection most patients achieve good seizure control, particularly when surgery is performed early in the course of epilepsy. Brainstem surgery carries a substantial risk of new or worsened deficits immediately after surgery, many of which improve; long-term outcome is related to the preoperative status and the Lawton–Garcia grade^[4]. Residual cavernoma carries a high risk of further haemorrhage, so complete removal is the goal whenever surgery is undertaken.