Clinical, neuroradiological and genetic findings in a cohort of patients with multiple Cerebral Cavernous Malformations

Cerebral cavernous malformations (CCM) consist of clusters of irregular dilated capillaries and represent the second most common type of vascular malformation affecting the central nervous system. CCM might be asymptomatic or cause cerebral hemorrhage, seizures, recurrent headaches and focal neurologic deficits. Causative mutations underlining CCM have been reported in three genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Therapeutic avenues are limited to surgery. Here we present clinical, neuroradiological and molecular findings in a cohort of familial and sporadic CCM patients. Thirty subjects underwent full clinical and radiological assessment. Molecular analysis was performed by direct sequencing and MLPA analysis. Twenty-eight of 30 subjects (93%) experienced one or more typical CCM disturbances with cerebral/spinal hemorrhage being the most common (43%) presenting symptom. A molecular diagnosis was achieved in 87% of cases, with three novel mutations identified. KRIT1/CCM1 patients displayed higher risk of de novo CCMs appearance and bleedings. Magnetic Resonance Imaging (MRI) showed that infratentorial region was more frequently affected in mutated subjects while brainstem was often spared in patients with negative genetic testing.

Automated summary

Cerebral cavernous malformations (CCM) can cause various symptoms including cerebral hemorrhage, seizures, headaches, and neurological deficits. Research has shown that patients with KRIT1/CCM1 mutations have a higher risk of developing new CCMs and experiencing bleedings. Magnetic Resonance Imaging (MRI) revealed that the infratentorial region is more frequently affected in mutated individuals, while the brainstem is often unaffected in patients with negative genetic testing.