Cerebral Cavernous Malformation (CCM).

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Synonyms Known also as : Cavernoma, cavernous angioma, cavernous hemangiomas, cerebral cavernous malformation (CCM).

Pathology:

CCM is a low pressure vascular lesion with inclination to bleed. It’s about discrete, lobulated,

"mulberry-like" mass of intermixed dilated thin-walled capillaries that are characterized by

multiple distended "caverns" of blood-filled vasculature through which the blood flows very

slowly. These internal cavities are of variable size containing blood products at different

stages of evolution. Complete hemosiderin rim surrounds lesion.

CMs size vary from microscopic to giant (> 6 cm). Majority are between 0.5 and 4 cm.

Vessels of a CM have a tendency to leak (bleed). This leakage is the underlying cause of clinical symptoms. CCM lesions are commonly intimately associated with developmental venous anomalies (DVA) wich are asymptomatic by their own. This association is uncommon in familial form.

Location Brain ( Supratentorial ( 80%) > brainstem, cerebellum) is the most common site of CM but they can also be found in the spinal cord ( rare, more common in patients with multiple CM

syndrome) , on the skin, and more rarely in the retina. CCMs are usually located in the white matter. They are usually solitary.

Epidemiology: - Benign - Majority of CCMs are solitary and sporadic. However, many of patients with sporadic

lesions have more than one.

- Multiple lesions may be familial and screening of family members may be indicated.

- CCMs, along with capillary telangiectasias, are commonly seen following cerebral radiotherapy . - CCMs are common cerebral vascular malformations. They account for a large proportion of all brain and spinal vascular malformations. - They are the most common "occult" vascular malformation of CNS. A lot of CCMs may remain asymptomatic and not diagnosed.

- Most are revealed between 40 and 60 years

- Frequency is equal between male and female.

Clinical Features - Typically: Asymptomatique----) Seizure----) Major Hemorrhage (2).

-The majority of lesions are asymptomatic and found incidentally.

- Presentation due to haemorrhage may cause a seizure or focal neurological deficit. The risk

of haemorrhage is 1% per year for familial cases and somewhat less for sporadic lesions (4).

- However, wide variety of symptoms are described: headaches or neurological deficits,

problems with memory or balance, or difficulties with vision or speech (3).

- Hemorrhagic stroke and seizures are the most severe symptoms.

- Broad range of dynamic behavior (1): De novo lesions may develop. Propensity for growth

via repeated intralesional hemorrhages. Some can regress. Familial CMs are at especially high

risk for hemorrhage and forming new lesions

CT Findings

NECT

Is frequently negative. When positive, it shows Hyperdense rounded lesion or somewhat

oval, often calcified.

There is no mass effect but when there is recent bleed it is more clearly visible and may be

surrounded by edema.

CECT: Weakly enhancement or no change by its own but when associated with DVA, the

enhancement take the pattern of this last abnormality.

CTA is usually unremarkable.

Magnetic resonance imaging (MRI) Is the gold standard for CCM diagnostic because it have a typical aspect on MRI. In fact, CCM is composed of several cavities or compartments of different size containing blood of different age. On MRI, the Classic and characteristic appearance is that of popcorn ball with locules of varied T1 and T2 signal depending on the age of degradation blood products. Fluid fluid levels may be observed in some locules. FLAIR: Peripheral edema may be present in recent intralesional hemorrhage T2*WI Sequences: This sequences (GRE T2) are the best to demarcate these lesion by producing a “ Blooming Artifact ” in form of high level of Hypointensity lesion.

In familial form this sequence reveal multiple Hypointense foci in form of black dots. It reveals lesions wich are not identified by conventional SE Sequences (T1 and T2). Susceptibility-Weighted Imaging Sequence maximes the sensibility to susceptibility effects by combining a long-TE high-resolution fully flow-compensated 3D GRE sequence with filtered phase information in each voxel (6). It was supposed that the fact that the SWI is a volumetric sequence with much fewer artifacts related to the bone-brain interface, might be responsible for the superiority of this sequence. In addition, the bloom effect, which is frequently seen on T2-weighted FSE and GRE sequences but not on SWI, results in blurring around the larger lesions and could obscure small CCM lesions. However results in comparison to T2*WI Sequences appear contradictory. In a study (6) including 15 patients with Familial CCM, the SWI showed 73% more lesions than T2-weighted GRE images. Authors emphasize, however, the need of further studies with pathologic correlation to clarify if the lesions seen on SWI might represent capillary telangiectasias or a CCM in an early stage. In a prospective study (7) including 23 consecutive cases SWI was more sensitive than T2*GRE in detecting CCM in multifocal/familial CCMs. Among cases classified as solitary/clustered with conventional imaging, including those associated with venous anomaly, the SWI did not impart additional sensitivity or reveal occult lesions not evident on T2*GRE sequence. No case was changed from the solitary/clustered to the multifocal clinical category because of SWI. Anyway, Perform T2* scan or SWI to look for additional lesions, especially in patients with

spontaneous intracranial hemorrhage +++.

T1WI C+ Minimal or no enhancement. May show associated venous malformation. MRA Normal (unless mixed malformation present) Zabramski classification of CMs (2) Type 1 = subacute hemorrhage (hyperintense on T1WI; hyper- or hypointense on T2WI). Large

acute hemorrhage may obscure underlying CM.

Type 2 = mixed signal intensity on T1, T2WI with degrading hemorrhage of various ages (classic

"popcorn ball" lesion)

Type 3 = chronic hemorrhage (hypo- to isointense on T1, T2WI) Type 4 = punctate microhemorrhages (blooming "black spots" on T2* or on SWI), poorly seen on others sequences.

DSA Usually normal unless mixed with DVA

Molecular genetic testing for mutations is available to confirm the diagnosis:

individuals with a family history and/or multiple CCM lesions.

Differential 1- "Giant" CMs can mimic neoplasm ++++ 2- "Popcorn Ball" Lesion: AVM, Hemorrhagic neoplasm, Calcified neoplasm. 3- Multiple "Black Dots" : Old Diffuse Axonal Injury, Hypertensive microbleeds, Amyloid angiopathy, Capillary telangiectasias.

Treatment Most cavernous malformations are initially observed by clinical and MRI follow-up due to the risk of growth and hemorrhage. Choices of therapy should take into account age, location of the lesion, effects on seizures, and risk factors for severe, potentially life-threatening hemorrhage. Medications for seizures and headaches Surgery (Total removal via microsurgical resection) is typically assessed on a patient-by-patient basis and may be advocated for cavernous malformations with recent hemorrhage, and/or those that are causing seizures. If CCM is associated with DVA, venous drainage must be preserved because disturbing the DVA during surgery could cause dangerous bleeding. Radiosurgery, is controversial: has been used on cavernous malformations that are too dangerous to reach through traditional surgery. Not recommended for individuals with familial CCM and/or multiple lesions.

BIBLIOGRAPHY

1-Anne G. Osborn: Cavernous Malformation , website article in Statdx.com, (Brain > Diagnosis > Pathology-based Diagnoses > Vascular Malformations > CVMs Without AV Shunting) https://my.statdx.com/document/cavernous-malformation/08bdea5f-e1a4-4f77-9624-d597aa030062. Viewed on 10/17/2016. 2- Cavernous Malformation, http://headneckbrainspine.com/Case-1-discussion.php

3- Cavernous Malformation, Website article in NORD ( National Organization of Rare Disease) website. https://rarediseases.org/rare-diseases/cavernous-malformation/

4- Dr Yuranga Weerakkody and Dr Donna D'Souza et al., Cerebral cavernous venous malformation, Website article in Radiopaedia https://radiopaedia.org/articles/cerebral-cavernous-venous-malformation

5- A.Prof Frank Gaillard and Dr Craig Hacking et al., Zabramski classification of cerebral cavernous malformations, website article in Radiopaedia https://radiopaedia.org/articles/zabramski-classification-of-cerebral-cavernous-malformations

6-J.M. de Souza & co, Susceptibility-Weighted Imaging for the Evaluation of Patients with Familial Cerebral Cavernous Malformations: A Comparison with T2-Weighted Fast Spin-Echo and Gradient-Echo Sequences, AJNR January 2008 29: 154-158. Published online before print October 18, 2007, doi: 10.3174/ajnr.A0748 http://www.ajnr.org/content/29/1/154.full

7-Magnetic resonance imaging evaluation of cerebral cavernous malformations with susceptibility-weighted imaging. Neurosurgery. 2011 Mar;68(3):641-7; discussion 647-8. doi: 10.1227/NEU.0b013e31820773cf. https://www.ncbi.nlm.nih.gov/pubmed/21164377