Jabbarli, Ramazan

Cerebral Cavernous Malformations (CCMs) are low-flow vascular lesions located within the central nervous system, with a reported prevalence in the general population of 0.16–0.5%. Patients with CCMs may remain asymptomatic or present new onset symptoms such as seizures or focal neurological deficits often related to the occurrence of intracerebral hemorrhage. CCM may appear sporadic or as part of familial forms linked to mutations in the CCM-gene cluster, affecting endothelial cell integrity and triggering molecular cascades, including the MEKK3/KLF2/4 signaling pathway. Recent studies have highlighted the roles of inflammatory, angiogenic, and coagulation pathways alongside the emerging evidence of a gut–brain axis influencing microbiome-driven TLR4 signaling. This systematic review aims to describe molecular biomarkers associated with CCM pathophysiology, emphasizing their potential use as diagnostic and prognostic tools. Circulating plasma biomarkers such as CRP, vitamin D, and interleukins may reflect ongoing inflammatory and endothelial processes, while some imaging biomarkers like Quantitative Susceptibility Mapping (QSM) have shown a correlation with iron deposition and vascular leakage. Leveraging both circulating and imaging biomarkers may improve the therapeutic decision-making process. Further studies are encouraged to validate these findings and to facilitate the development of personalized, evidence-based strategies for the management of CCM.

BACKGROUND AND OBJECTIVES: Brainstem cavernous malformations (BSCM) can result in spontaneous intracerebral hemorrhage (ICH), often resulting in significant morbidity. We aimed to assess the functional outcome and identify predictors of functional neurological outcome after single and multiple symptomatic hemorrhages. METHODS: As part of an international multicenter collaboration, institutional databases from 3 different tertiary referral centers included BSCM patients with complete baseline characteristics, MRI Data set, ≥1 ICH, and ≥1 follow-up examination followed at our institutions between 2003 and 2023. Functional neurological outcome was obtained using the modified Rankin Scale at diagnosis, before and after each ICH, and last follow-up. Patients were excluded after surgical removal of the lesion and/or loss of follow-up. RESULTS: A total of 383 patients (41.47 ± 15.51 age; 220 [57.4%] female) were included and followed for an average of 63.16 ± 85.75 months. Functional neurological outcome deteriorated in 47.2% ( P = .010) after the second ICH and in 46.5% ( P = .007) after the third ICH. Moreover, the functional neurological status was impaired in 22.3% ( P < .001) of patients at last available follow-up compared with the time of BSCM diagnosis. CONCLUSION: In our study, we observed that the chance of full recovery might decrease with each ICH. We observed a significantly associated neurological deterioration after each ICH compared with initial ICH.