Cavernoma

a.k.a. “cavernous (hem)angioma”, “cavernous malformation”

- First reported by H. Luschka in 1854.

- One of the four “classical” intracranial vascular malformations (cavernoma, AVM, venous malformation or anomaly, and capillary telangiectasia)

Pathology

- Vascular malformation composed of clusters of thin-walled immature veins.

- Large sinusoidal “caverns” with no intervening brain parenchyma – a characteristic feature on pathology.

- Red, purple, or blue; multilobulated; often compared to a “cluster of mulberries”.

- Inside the lesion:

- Blood, thrombus, hyalinization, calcification, cholesterol crystals, cystic changes

- Outside the lesion:

- Evidence of microhemorrage (Hemosiderin discolouration and hemosiderin-filled macrophages)

- Ferritin

- Gliomatous capsule

Cavernoma vs. AVM

Like an AVM:

- Usually a developmental abnormality of vascular bed

- Tends to bleed (unlike other two cerebral vascular malformations)

Unlike an AVM:

- No features of high flow.

- No important arterial feeders or large draining veins.

- No intervening brain parenchyma.

- seldom demonstrated on angiography

Epidemiology

- Prevalence has been rising as neuroimaging techniques improve:

0.02% – 0.53% prevalence on autopsy

0.45% - 0.90% prevalence on MRI

- Most commonly identified vascular abnormality on MRI

- May be found incidentally while AVMs usually are not

- 15-33% of patients have >1 lesion. (More likely familial if multiple)

- Incidence of first hemorrhage:

<2% per lesion per year.

- Gender: M = F

- Felt to be usually congenital lesions but can be acquired (eg after radiation)

- Occur at any age, but tend to become clinically significant in the 2^nd to 4^th decades of life.

Genetics

- Most cavernomas are sporadic. Many are familial, however (10-20% in white population). Usually seen in Hispanic population (in which up to 50% may be familial). Usually multiple in familial cases.

- Autosomal dominant inheritance.

CCM1 gene (Chr. 7q) à KRIT1 (40%)

CCM2 gene (Chr. 7p)à Malcavernin (20%)

CCM3 gene (Chr. 3q) à ??

Anatomy

- Cavernomas can occur anywhere in the brain.

- 64% - 84% are supratentorial.

- Pons (26%) and cerebellum (17%) are the most common infratentorial sites.

Within the pons:

50% close to the surface of the 4^th ventricle

30% extending into cerebellar peduncles

20% deep in the pons.

Clinical Behaviour

- Cavernomas have dynamic behaviour:

Intralesional hemorrhage

Perilesional hemorrhage

Fluctuations in size

- Symptoms may be aggressive or quiescent.

- Four main presentations:

1. Asymptomatic

2. Hemorrhage (gross or microhemorrage) (15%)

3. Focal neurological deficit (20%)

4. Seizures (40-50%)

- Symptoms may be stable for years, progress rapidly, or wax and wane.

Asymptomatic cavernomas

- Cavernomas are a frequent incidental finding on MRI.

- 25% of “asymptomatic” patients may have headaches.

- No data yet to suggest which cavernomas go on to become symptomatic.

Hemorrhage

- Microhemorrhages

- Universal, recurrent, usually subclinical.

- Blood extravasates through immature vessel walls and degrades in the nearby parenchyma.

- Gross hemorrhage

- Unlike AVM, rarely life-threatening. Initial bleeds are usually self-limited and recovery is usually good or fair. (but deficits can accumulate)

- Usually intraparenchymal. Sometimes IVH or SAH.

- May have H/A, change in LOC, neurological signs.

- Focal signs are more likely when bleed in the posterior fossa or brainstem.

- Recurrent bleeds can mimic MS.

- Recurrent bleeds lead to progressive neurological deficit.

- 20-80% chance of rebleeding from the same lesion over a range of weeks to years.

Focal Neurological Deficits

- Usually secondary to intralesional or perilesional hemorrhage or subsequent mass effect.

- Syndrome depends on lesion location and size.

- Deficits accumulate with repeated bleeds.

Seizure

- Most common presenting symptom of cavernoma, as cavernomas are primarily supratentorial and lobar.

- Blood degradation products (hemosiderin, iron) from perilesional microhemorrhages are irritating to the cortex and create seizure foci.

- Reactive gliosis ensues; calcification; further seizures.

Imaging

Angiography

- Lesions are very low-flow.

- Majority of patients have a negative angiogram.

CT

- 70-100% sensitivity.

- Well circumscribed, heterogeneous (hyperdense), nodular lesion.

- No mass effect, no surrounding edema. Commonly calcified

- Recent hemorrhage appears as a homogeneous hyperdense hematoma overlying the lesion.

MRI

- Most sensitive and specific test.

- Mixed signal within the lesion on T1 and T2, reflecting a heterogeneous composition. “Popcorn” appearance.

- Ring of low T2 signal surrounding the lesion.

- Gradient echo sequences the most useful for spotting blood degradation products surrounding small cavernomas.

- DDx: thrombosed AVMs, calcified or hemorrhagic neoplasms, infectious/inflammatory/granulomatous lesions, primary hemorrhages

Management of Cavernomas

- Not much data.

- Management approaches include:

Conservative

Medical

Surgical

Radiosurgical

Conservative Management

- Appropriate for asymptomatic patients, or patients with only vague complaints (e.g. headache).

- Low risk of a first debilitating hemorrhage (but increased after index bleed)

- Close follow-up with sequential MRIs is suggested.

- In the case of easily accessible cavernomas, elective surgical resection is an option.

Medical Management

- Anticonvulsant drugs to control seizures.

- Temporal lobe cavernomas are more likely to result in medically intractable epilepsy, requiring surgical excision.

Surgical Management

- Surgically accessible symptomatic cavernomas should be resected if possible. Outcomes are generally favourable.

- Intractable epilepsy: 50-91% seizure-free after resection.

- In the brainstem, excision of symptomatic cavernomas is controversial:

- 0-20% operative mortality risk.

- Lowest operative risk when cavernoma appears near the pial or ventricular surface.

- Mortality from symptomatic cavernoma unknown.

- Operate after first hemorrhage or wait for symptom progression? No consensus.

Radiosurgical Management

- An alternative to surgery for lesions in inaccessible or eloquent areas of the brain?

- Shown to be useful for AVMs, but cavernomas show poor clinical response and high rate of complications.

- Radiosurgery may be an option, but needs further study with regards to:

- Patient selection

- Dosing

- Short- and long-term risks

References:

Moriarty JL, et al. The natural history of cavernous malformations. Neurosurg Clin N Am 1999; 10(3): 411-7.

Maraire JN, Awad IA. Intracranial cavernous malformations: lesion behaviour and management strategies. Neurosurgery 1995; 37: 591-605.

Last update: August 2004

Reviewed by: pending review

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