Surgical removal of accessible lesions is the only direct therapeutic approach for cerebral cavernous malformations (CCMs). The approach should be carefully evaluated according to clinical, anatomical, and neuroradiological assessment in order to both select the patient and avoid complications. In selected cases, a quantitative anatomical study with a preoperative simulation of surgery could be used to plan the operation. Neuronavigation, ultrasound, and neurophysiologic monitoring are generally required respectively to locate the CCMs and to avoid critical areas. The chapter describes all the possible surgical approaches for supratentorial, infratentorial, deep seated and brain stem CCMs. In any case before performing surgery, the physicians should always consider the benign nature of the lesions and the absolute necessity to avoid not only neurological deficits, but also a neuropsychological impairment that could affect the quality of life of the patients.Cavernous cerebral malformations (CCMs) can show typical and characteristic findings at neuroradiology, above all at magnetic resonance imaging, but differential diagnosis with other lesions of similar appearance can be challenging and should be taken into consideration. Management of CCMs can be conservative in most cases, and thus appropriate follow-up timing and modality is required. Growing input from neurologists, neurosurgeons, neuroradiologists, and patients recommend to offer a standard neuroradiological report, to enhance interpretation and comparability in daily clinical practice. The purpose of this chapter is to present differential diagnosis, follow-up, and reporting of CCMs by neuroradiology.This is a review of imaging techniques used to evaluate cerebral cavernous malformations (CCMs) and imaging findings associated with CCMs. This chapter includes discussion of computed tomography and magnetic resonance imaging sequences, appearance of CCMs and associated hemorrhage and key features to evaluate on imaging studies.Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by brain lesions that can cause hemorrhagic strokes, seizures, and neurological deficits. Carriers of the same genetic mutation can present with variable symptoms and severity of disease, suggesting the influence of modifier factors. Genetic modifiers of CCM1 disease severity have been recently identified and included common genetic variants in inflammatory, immune response, and oxidative stress genes and pathways. Here, we describe the genotyping of CCM1 patients with the same gene mutation (Q455X) using a high-throughput genotyping array optimized for individuals of Hispanic/Latino ancestry. We then review the quality control steps following the genome-wide genotyping. Genome-wide genotyping of larger cohorts of CCM1 patients might reveal additional genetic variants contributing to the disease severity of CCM1.The application of next generation sequencing (NGS) technique has a great impact on complex disease studies. Indeed, genetic heterogeneity, phenotypic variability, and disease rarity are all factors that make the traditional diagnostic approach to genetic disorders, whereby a specific gene is selected for sequencing based on the clinical phenotype, very challenging and obsolete.Exome sequencing, which sequences the protein-coding region of the genome, has been rapidly applied to variant discovery in research settings. Recent coverage and accuracy improvements have accelerated the development of clinical exome sequencing (CES) platforms targeting disease-related genes and enabling variant identification in patients with suspected genetic diseases. Nowadays, CES is rapidly becoming the diagnostic test of choice in patients with suspected Mendelian diseases, especially for those with heterogeneous etiology and clinical presentation. Reporting large CES series can improve guidelines on best practices for test utilization, and a better variant interpretation through clinically oriented data sharing.Herein, we suggest a feasible CES procedure for the genetic testing of Cerebral Cavernous Malformation (CCM) disease, including proband identification, library preparation, data analysis, and variant interpretation.Cerebral Cavernous Malformations (CCMs) are vascular lesions which can occur as a sporadic (80% of the cases) or a familial autosomal dominant disease (20%), the latter being characterized by the presence of multiple lesions. Three CCM genes have been identified in the last 10 years. More than 95% of familial cases and 60% of sporadic cases with multiple lesions harbor a germline heterozygous loss of function mutation in one of these 3 genes. Most mutations lead to a premature stop codon whatever the mechanism, including nonsense mutations, deletions, insertions and intronic mutations leading to abnormal splicing and frameshift. A combination of analyses, including sequencing and copy number analysis of germline DNA extracted from blood and cDNA analysis, are therefore required to ensure the best diagnostic sensitivity. Additional causative rare structural CCM gene anomalies have been identified in a research context, as well as rare causative missense mutations. These mutations are rarely searched for in a diagnostic context and explain part of the negative cases, in addition to germline mosaicism which occurs in some sporadic cases with multiple lesions. On top of germline mutations, somatic mutations occur on the wild-type allele in endothelial cells lining CCM lesions. BMS-777607 cell line These data established both the role of a double hit in the pathophysiology of CCM lesions and the heterogeneity of endothelial cells lining these lesions.We describe Natural history, clinical and surgical management of cavernous malformation of the brain and spinal cord. Decision-making for treatment of cavernous malformations cannot ignore their natural history and risk of bleeding, which is different depending on the location. Surgical morbidity also depends on the position of the lesion. We performed a review of hemorrhage risk and clinical assessment of superficial and deep supratentorial, brainstem and intramedullary cavernous malformations.