Brain arteriovenous malformations. New perspectives on aetiology, prognosis, and treatment

Abstract

Brain arteriovenous malformations (BAVMs) consist of direct connections between arteries and veins. BAVMs most frequently present with intracranial haemorrhage. BAVMs can be obliterated using microsurgery, radiosurgery, embolisation alone or combined to prevent haemorrhage. Twenty-five families comprising 53 BAVM patients were diagnosed at a younger age than patients with sporadic BAVMs. The child’s age at diagnosis was younger than the parent’s age when BAVMs occurred in successive generations, suggesting anticipation. These families may indicate familial occurrence of BAVMs. Questionnaires to retrieve information about the occurrence of BAVMs among first-degree relatives were returned by 460 (67%) BAVM patients. We identified two families with two BAVM patients each yielding a prevalence of 2per 2,992 first-degree relatives compared to 93 per 628,788 adults from a Scottish study (prevalence ratio 4.5, CI 1.1-18) indicating an increased risk in first-degree relatives. However the absolute risk is very low. The utility of radiological investigations to determine the cause(s) of intracerebral haemorrhage (ICH) was explored by reviewing the literature and performing a survey investigating the daily practice in three European countries. The shortage of studies may contribute to the variation in practice. Younger age had the largest impact on the decision to further investigate ICH. Case-fatality after spontaneous ICH (sICH) is higher than after BAVM-ICH when comparing patients from two population-based cohorts [61% versus 12% at 1 year), as was death or dependence (83% versus 40%). Independent predictors of death were sICH and increasing ICH volume, and sICH and GCS on admission predicted death or dependence. Women with BAVM haemorrhage at fertile age from four Dutch university hospitals and a Scottish prospective, population-based cohort are analysed to estimate the relative BAVM haemorrhage rate during pregnancy, delivery and puerperium. The relative BAVM haemorrhage rate during pregnancy was 4.1 (CI 2.4-6.9) using case-crossover method, and 4.7 (CI 2.4-7.9) using self-controlled case-series method, suggesting an increased risk of BAVM haemorrhage during pregnancy. Case-fatality, long-term haemorrhage, complications, and obliteration rates after BAVM treatment are presented. The meta-analysis of 137 observational studies revealed that larger proportions of males, small BAVMs and BAVMs with strictly deep venous drainage were associated with both lower case-fatality and lower haemorrhage rate. Younger age and BAVMs with Spetzler-Martin grades (SMGs) I-III were associated with lower case-fatality, whereas fewer eloquent BAVMs and higher proportions of obliterated BAVMs were associated with lower haemorrhage rate. Treated and untreated patients with unruptured BAVMs did not differ in progression to Oxford Handicap Scale of 2-6 or 3-6 in survival analysis, but treated patients were younger, more likely to present with seizure(s), and had fewer comorbidities than those who were not treated. In multivariable analyses, the risk of poor outcome was greater in treated patients, and in patients with a larger BAVM nidus. The BAVM treatment varies in a Scottish population-based cohort. Treated adults were younger, more frequently presented with haemorrhage, and had smaller BAVMs than adults who were not treated. The centres differed in the SMG of the BAVMs they treated. The two largest centres differed in the use of microsurgery or radiosurgery.