The New England Journal of MedicineCavernous Malformations of the Central Nervous System

Unveiling the Complex Origins of Cerebral Cavernous Malformations: Implications for Diagnosis and Treatment

Cerebral cavernous malformations (CCMs) are vascular anomalies within the central nervous system that pose significant diagnostic and therapeutic challenges for physicians. Characterized by their distinctive appearance on MRI and potential for neurological complications, CCMs present a unique interplay of genetic and possibly environmental factors influencing their pathogenesis and clinical management. This article delves into the intricate nature of CCMs, offering key insights into their epidemiology, genetic underpinnings, clinical presentations, and evolving treatment strategies, thereby equipping healthcare professionals with crucial knowledge to enhance patient care.

Key Points:

• CCMs, occurring in approximately 0.5% of the population, are primarily diagnosed based on characteristic MRI findings and may present with headaches, seizures, or focal neurologic deficits.
• The majority of CCMs are sporadic, single lesions, with about 15% being familial, showing associations with mutations in the CCM1, CCM2, or CCM3 genes, which influence cellular signaling and vascular integrity.
• MRI techniques, particularly susceptibility-weighted and T2-weighted imaging, are essential for detecting and assessing CCMs, with specific imaging features guiding diagnosis and management.
• Clinical management varies, ranging from observation to surgical excision or stereotactic irradiation, especially for symptomatic lesions or those associated with seizures.
• Genetic and environmental factors, including potential influences from the gut microbiome, are being explored as contributors to CCM pathogenesis, with implications for future therapeutic strategies.
• Advances in molecular genetics have delineated distinct pathways involved in CCM development, offering potential targets for novel therapeutic interventions.
• Patients with CCMs generally do not have increased bleeding risks with routine physical activities, but certain factors, like poorly controlled diabetes or low vitamin D levels, may warrant further investigation for their possible impact on hemorrhage risk.
• Ongoing and future research focuses on repurposing existing drugs and developing new treatments targeting specific molecular pathways involved in CCM pathogenesis, aiming to provide non-surgical management options.

In a 2017 study, researchers found an overall CCM population prevalence of 0.46% (95% CI, 0.09-0.81) in participants between 50 and 89 years of age.

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