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Systemic and CNS manifestations of inherited cerebrovascular malformations

      Highlights

      • Radiologists improve diagnosis and assessment of these diseases by recognizing systemic manifestations.
      • Features suspicious for CCM or HHT in the CNS or elsewhere in the body should lead to optimized imaging for each.
      • Understanding genetic and molecular mechanisms underlying these diseases will likely lead to new treatment options.
      • Molecular mechanisms in these diseases may be relevant to sporadic vascular malformations involving somatic mutations.

      Abstract

      Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a genetic basis. Genetic diseases such as familial cerebral cavernous malformations and hereditary hemorrhagic telangiectasia often have manifestations in bone, skin, eyes, and visceral organs, which should be recognized. Genetic and molecular mechanisms underlying the inherited disorders are becoming better understood, and treatments are likely to follow. An interaction between the intestinal microbiome and formation of cerebral cavernous malformations has emerged, with possible treatment implications. Two-hit mechanisms are involved in these disorders, and additional triggering mechanisms are part of the development of malformations. Hereditary hemorrhagic telangiectasia encompasses a variety of vascular malformations, with widely varying risks, and a more recently recognized association with cortical malformations. Somatic mutations are implicated in the genesis of some sporadic malformations, which means that discoveries related to inherited disorders may aid treatment of sporadic cases. This paper summarizes the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.

      Keywords

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