Cavernous Malformations Management Strategies

Shikher ShresthaNINAS

Introduction

Vascular lesions compact bundle of dilated capillary like

channels lacking intervening neural parenchyma

Ranges from 1 mm to several centimeters

Found anywhere in CNS + in skin and eye

Histology: single layer of endothelial cellsLack structural elements like smooth muscle and elastin found in mature vesselsDiminished or absent astrocytic foot processes and pericytes found in BBB

Macroscopic:Reddish purple in appearanceMultilobulatedEncapsulated by a variable layer of fibrous adventitia – mulberry like

Types

Familial SporadicUsually multiple

Family history of neurological disease

Mutation in three genes CCM1, CCM2 and CCM3 in over 96% cases

De novo occurrence can occur and may impact long term outcome

Rarely have more than 2 lesions

Absent family history

Radiology

Radiographically best detected on MRI

Mixture of high and low T1 and T2 signal intensity surrounded by hemoglobin degradation products

Characteristics popcorn appearance – with surrounding hemosiderin ring due to chronic bleeds that appears hypointense both on T1 and T2 weighted images

Nonsepcific CT findings hence CT less useful

Angiographically occult

Developmental Venous anomalies (DVAs) can be detected on angiography should alert the presence of concomitant cavernoma

Epidemiology

Relatively common (1 in 200 individuals)

Accounts to 8-15% of all the CNS vascular malformations

63-90% in supratentorial compartment

7.8-35.8% in infratentorial location

9-35% of infratentorial lesions are located in the brainstem

3-5% - intramedullary spinal CCM

Mostly asymptomatic and discovered incidentally

20-30% symptomatic presenting in 3rd to 5th decades of life

Symptoms – headaches, seizures, and focal neurological deficits following lesion expansion due to thromboses and hemorrhages.

Since variability in symptomatology – choosing appropriate strategy a challenge

Natural History

Vary widely among patients

Once believed to be congenital; now recognized that it can occur de novo

Dynamic – expanding as lesions thrombose and hemorrhage and regressing as they recanalize and as blood products from hemorrhages are resorbed

Seizure – most common symptom; especially common with frontal and temporal locations

Surrounding area of reactive gliosis serve as an epileptogenic focus

Estimated annual risk of seizure is ~1-2%

Several seizure types reported – simple, complex partial, and generalized

Most severe presentation – gross apoplectic hemorrhages

Low flow, low- pressure lesions

Most bleeds relatively small; result from blood extravasation from leaky vascular channels

Larger bleeds can and do occur

Factors related to increased bleeding risks:

larger and deeper lesionsolder patientspregnancypatients who have suffered previous bleed

Asymptomatic patients or those presenting with seizures typically have the lowest risk (0.4 to 2% annually)

Symptoms of hemorrhage maximal at the time of bleed but gradually settles as the bleed organizes and resorbs

Repeat hemorrhage worsens deficits risk of permanent deficit

Hence, patient might present with progressive neurological deficit especially with infratentorial lesion with higher density of eloquent neural structures

Management Options

Expectant management

Medical management

Surgical resection

Stereotactic radiosurgery

Expectant Management

Regular radiographic follow up of lesions every 1 to 2 years

Each new MRI compared with prior ones to detect lesion changes over time

If signs of lesion expansion or hemorrhage then may need intervention esp. in high risk areas

Employed in patients who are not operative candidates or asymptomatic patients with lesion in eloquent areas

Medical Management

No medical cure; limited to providing symptomatic reliefanalgesics for headachesantiepileptic for seizure control

Surgery for patients with seizures refractory to medicines

Patients should be followed with regular MRIs

Recent in vitro and in vivo studies on animal models activation of Rho GTPases in CCM lesions; hence statin might have role which is known to inhibit signalling through these molecules

Surgical Resection

Can be fully curative if complete resection

Successful lesionectomy eliminates hemorrhage risk and achieves 80% seizure control

Invasive treatment method hence risks of permanent neurological deficits and death

Good outcomes if appropriate patients

Preoperative MRI is a prerequisite for understanding the anatomy and determining the approach

Preserving potential branches of a DVA which do not drain the lesion should be preserved

Intraoperative MRI with stereotactic images and neuronavigation are helpful for localization

Bipolar cauterization to shrink the lesion after entering into the lesion

Contracted cavernoma dissected from the surrounding neural tissue

Gliotic pseudocapsule around the lesion can provide a circumferential surgical plane

Following cavernoma excision, decision must be made regarding the pseudocapsule

Benefit vs risk of removing the pseudocapsule should be weighed

For infratentorial lesions, the pseudocapsule is generally left intact

Satellite lesions and cavernoma remnants should be looked for before closure; and removed to prevent lesion recurrence

Branches of DVAs should be preserved to prevent venous infarction

Criteria to operate on infratentorial lesion

Lesions that rise to the pial surface based on T1 weighted MRI

Lesions with repeated hemorrhages causing progressive neurological deficits

Lesions with acute hemorrhage extending outside the lesion capsule

Significant mass effect produced with a large intralesional hemorrhage

NB> Surgery is considered only when total resection can be achieved

Stereotactic Radiosurgery

Controversial

Current imaging techniques are unable to detect complete lesion occlusion

Efficacy must be based on postprocedural hemorrhage rates or histological results showing complete occlusion

Some studies report decreased hemorrhage rates following radiosurgery while others show increased complication like permanent neurological deficit

Histological studies of resected cavernoma from patients who had undergone radiosurgery anywhere from 1 to 10 years prior failed to show complete obliteration

In such cases – fibrinoid necrosis as main findings

Hence, not an effective treatment option and should be used only in highly selected cases

Spinal cavernomas

Lesions typically located in the thoracic cord

Cervical cavernomas are the second most common

Presents with slowly progressive myelopathy causing deficits in sensation, motor skills or both

Acute presentation of focal neurological deficits if hematomyelia, intralesional hemorrhage and cord compression

Symptoms from acute presentations often resolve spontaneously while those from chronic myelopathy do not improve after surgery

Out of 26 patients of spinal cavernoma12 (46%) improved in long term follow up12 (46%) remain unchanged and2 (8%) had worsened neurological conditions

Special considerations

Elderly and comorbid patients expectant and medical management

Multiple lesions Expectant with intervention reserved for clinically active specific lesion

Removal of cavernoma at the site of epileptogenic zone on EEG favors good chance of Engle class post operatively

Genetic screening NOT recommended even with family history because of myriad of associated genes in the development

To classify postoperative outcomes for epilepsy surgery, Jerome Engel proposed the following scheme,[1] the Engel Epilepsy Surgery Outcome Scale, which has become the de facto standard when reporting results in the medical literature:[2]

Class I: Free of disabling seizuresClass II: Rare disabling seizures ("almost seizure-free")Class III: Worthwhile improvementClass IV: No worthwhile improvement