Aim: To correlate cerebral cavernous malformations (CCMs) disease aggressiveness with peripheral blood biomarkers hypothesized mechanistically. Patients & methods: A prospective case–control study enrolled 43 CCM patients, where 25-(OH) vitamin D, HDL and non-HDL cholesterol, CRP plasma levels and leukocyte ROCK activity were correlated with parameters of disease aggressiveness reflecting chronic and acute domains. Results: Patients with one or more features of chronically aggressive disease (early age at symptom onset, two or more symptomatic bleeds, high lesion burden) had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels in comparison to patients without these features. Conclusion: Validation of these biomarkers and their potential treatment modulation may influence the clinical care of patients with CCM disease.
The level of evidence on which to base surgical decision making related to cholesteatomatous labyrinthine fistula is poor, and the data do not demonstrate significant differences in hearing outcomes based on surgical technique.
Introduction and Hypothesis: Cerebral cavernous malformations (CCMs) are common cerebrovascular anomalies with highly variable but potentially disabling disease behavior disease behavior. Factors portending an aggressive clinical course are not known. An association of disease severity with vitamin D has been suggested in preclinical studies, and other evidence supports a role of inflammation in the pathobiology of CCM. Methods: A prospective case-controlled study enrolled 43 consecutive patients with CCM disease (20 sporadic/solitary and 23 multifocal/familial). Non-fasting peripheral venous blood samples were analyzed for plasma levels of 25-(OH) vitamin D, high-density lipoprotein (HDL) and non-HDL cholesterol, C-reactive protein (CRP), and for leukocyte Rho-kinase (ROCK) activity. We correlated these biomarkers with prospectively defined parameters of chronic (a history of multiple adjudicated clinically overt hemorrhages, early age of clinical onset or high lesion burden in familial cases) and recent (lesional growth or hemorrhage in the preceding year, or new lesion formation in familial cases) disease aggressiveness. Results: Patients with historically aggressive CCM disease had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels. Neither was predictive of recent disease activity. HDL cholesterol, CRP levels and ROCK activity did not correlate with historical or recent disease severity. Receiver operating characteristic curves for 25-(OH) vitamin D or non-HDL cholesterol showed ‘fair’ accuracy: Area under curve (AUC)= 0.73 (p=0.01) and 0.74 (p=0.007), respectively. Combination of the two parameters improved the accuracy to AUC=0.80 (p<0.001). Conclusions: This is the first evidence of correlation of peripheral blood biomarkers with the severity of human CCM disease. Validation of these biomarkers and their potential modification may influence the clinical care of CCM.
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