Cavernous Malformations Management Strategies Shikher Shrestha NINAS
Jan 15, 2017
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