gms | German Medical Science

Objective: Multiple cerebral cavernous malformations are rare lesions that occur in sporadic or familial form. Depending on the disease form, the natural history and treatment of the lesions vary strongly. Molecular analysis of an underlying germ-line mutation (CCM1-3) is the most sensitive screening method for distinguishing between sporadic and familial cases. However, based on the different patho-mechanisms supposed to be involved in either form, significant distinctions in the CCM-associated cerebral venous angioarchitecture should be detectable. This has not been systematically studied, yet.

Method: A consecutive series of 28 patients with multiple CCMs (633) diagnosed on 1.5 T MRI underwent genetic screening for CCM1-3 mutations and high-resolution susceptibility weighted imaging (SWI) of the cerebral venous angioarchitecture at 7T MRI. Imaging data was analysed to examine the venous angioarchitecture associated with the CCM. Results were correlated with findings of molecular analysis for CCM1-3 mutations.

Results: Two main different SWI patterns (sporadic = cluster-type and familial = scattered type) were found. The presence of associated developmental venous anomalies and focal cavernomatosis (n=11, sporadic cases) correlated with a negative screening for germ-line mutations in all cases. On the other hand, all patients with confirmed familial disease showed normal underlying venous angioarchitecture and multifocal cavernomatosis. Additionally, two very unusual cases (cavernomatosis exclusively localized to one hemisphere) of a probable somatic mutation are presented.

Conclusions: SWI of the venous angioarchitecture of multiple CCM correlates with sporadic or familial disease. Our results are consistent with the theory that venous anomalies are due to the sporadic form of multiple CCMs. These, of course, preliminary results may be very helpful on the counselling of patients with multiple CCM.