Important notes:

1. This background is “as is” from the First HHT Guidelines. To access references or the complete manuscript, refer to the First Guidelines. 
2. The term Cerebral Vascular Malformations was used in the was used in the First Guidelines (instead of the term Brain VM’s used in the Second Guidelines).

Definition

The term CVM refers to a variety of vascular abnormalities, classified on the basis of morphology, including: 

1. arteriovenous malformations (CAVMs) (including microAVMs measuring <1 cm in size); 
2. cavernous malformations; 
3. venous angiomas/developmental venous anomalies (DVAs); 
4. capillary telangiectasias, enlarged capillary-sized vessels; 
5. vein of Galen malformations; 
6. high-flow pial fistulae (arterivenous fistulae (AVFs)); and 
7. mixed malformations (46).  All of these types of CVMs can be found in HHTpatients, although typically HHT is associated with CAVMs, AVFs, micro AVMs and telangiectasias (47).

Background

Approximately 23% of HHT patients will harbour a CVM (48-50).  The rationale for screening for CVMs in HHT is that screening will detect a treatable CVM before the development of a life threatening or debilitating complication. We therefore reviewed the evidence regarding complications of CVMs, the performance of screening tests, and the effectiveness of treatment for CVMs. Given the rarity of HHT-related CVMs, most of the evidence reviewed relates to the more common sporadic CVMs. 

The bleeding risk of CVMs in HHT has been estimated retrospectively at ~0.5% per year (51) although there are no prospective natural history studies. In larger series of sporadic CAVMs (52) the annual rate of rupture is 2-4%/year (52). On the basis of case series, CAVMs and AVFs appear to have a more aggressive natural history,while cavernous malformations(CM), capillary telangiectasias and DVAs, also reported to occur in HHT (49) appear to have a more benign natural history (12,48, 51, 53, 54). There are several case series and reports of catastrophic haemorrhagic sequelae of CVMs and spinal AVFs occurring during childhood (50, 55-58). Rarely, spontaneous resolution of CVMs has been reported (59,60). 

The typical imaging features of HHT CVMs include the presence of either multiple, cortical, micro AVMs or AVFs harbouring single feeding arteries and single draining veins (12, 53-54). Catheter angiography remains the ‘gold standard’ for diagnosis of most types of CVMs, but carries a 0.5% risk of permanent stroke (61).  MRI is considered to be safe, non-invasive modality to screen for CVMs, but unfortunately there are no screening studies assessing its performance in HHT. MRI screening studies for non-HHT CVMs have been limited by small size, retrospective design and lack of blinding to clinical status, but suggest sensitivity of 80-95% for medium to large sized CVMs (62-64) MRI is less sensitive for the detection of micro AVMs (64) but the addition of contrast enhancement (gadolinium for patients >2 years of age) to MRI sequences increases the sensitivity for microAVMs. The inclusion of sequences designed to detect blood products (currently gradient echo sequences) also increases the sensitivity of MRI for microAVMs and signs of asymptomatic haemorrhage (55). ‘False-positive’ results may occur when other types of CVMs are encountered including telangiectasias which have a favourable natural history (49) and for which no further invasive imaging is required. Transcranial Doppler ultrasonography (US) has also been used to screen for CVMs (65-66) with reported sensitivity of ~80% for medium to large-sized CVMs, but studies are limited by sample size and design. No evidence exists for follow up screening after initial negative study, as there is no evidence to suggest that adult patients with HHT develop new CVMs. 

MRI provides a relatively safe, sensitive testing modality to identify CVMs in children (67).  While MRI itself poses little risk, the expert panel acknowledges the risk related to sedation/ anaesthesia of children for diagnostic procedures. Of greatest concern is the risk of respiratory depression, but this should be minimised with appropriate cardiorespiratory monitoring. No evidence exists at this time to recommend follow-up screening after an initial negative study during childhood, but consideration should be given to one adulthood MRI following initial negative childhood MRI. 

The expert panel agreed that CVM obliteration is required to effectively eliminate the future risk of haemorrhage. Although treatment may provide a large relative risk (RR) reduction for cerebral bleeding, procedural risks are significant. There are no published studies of the efficacy or safety of any form of treatment of CVMs in HHT patients. However, several large case series (>200 patients, mostly single-centre) of embolisation, microsurgery and stereotactic radiation in non-HHT CAVMs show widely ranging effectiveness for each modality (49, 54, 56, 68-78). On the basis of this, as well as expert experience, the expert panel agreed that effective treatment strategies include embolisation, microsurgery and stereotactic radiation, or combinations of these. With the rarity of CVMs and the associated risks of treatment, the expert panel agreed that each case should be managed in an individualised manner and decisions about invasive testing and therapy should occur at centres with significant experience and expertise in all treatment modalities. Although there is no evidence regarding differences in outcomes according to expertise in management of these cases, the expert panel agreed that centres with experience in HHT-related CVMs will be more aware of important issues related to the care of HHT patients and likely to have better outcomes of surgical and other procedures. 

CVMs occur in infants and children with HHT (12, 47, 50, 57, 79-80). Before the age of 6 these malformations tendtobehigh-flowpial fistulae (cerebral or spinal cord AVFs) (47). Expert opinion is that these malformations have amor aggressive natural history than nidus-type CAVMs, including presenting events such as intracerebral haemorrhage, cognitive deficit, cardiac insufficiency, epilepsy and hydrocephalus (12, 47, 79, 80).  Embolisation or microsurgical obliteration of these high-flow pial fistulae in children may therefore be of significant benefit when performed by a neurovascular centre with expertise in these techniques in children. 

There is no evidence to guide the management of CVMs during pregnancy and delivery, as there is no good evidence regarding the risk of CVM complications or treatment during pregnancy and delivery.

Important notes: 

1. This background is “as is” from the First HHT Guidelines. To access references or the complete manuscript, refer to the First Guidelines.
2. The term Cerebral Vascular Malformations was used in the was used in the First Guidelines (instead of the term Brain VM’s used in the Second Guidelines).