Dados do Trabalho

Título

Investigation of plasma biomarkers in cases of cavernoma-related epilepsy.

Resumo

Cerebral cavernous malformations (CCM) are a type vascular disease found in the central nervous system. CCM are triggered by mutations in different genes, called CCM1, CCM2 and CCM3, whose loss of function modifies the endothelial cytoskeleton and results in lesion. Although most cases are asymptomatic, the increased vascular permeability and fragility at the site can trigger cavernoma-related epilepsy (CRE). Currently, there are not clinically established or user-friendly biomarkers to determine the likelihood of this complication. Furthermore, most available studies have used symptomatic hemorrhages in cavernous angioma (CASH ) as the only primary endpoint, with CRE being considered a minor comorbity for CCM patients. In this context, from a cohort of 128 patients with CCM, we tried to identify possible plasma biomarkers for CRE. The disease was classified as familial or sporadic according to the distribution of lesions in SWI sequence, with familial being synonymous to the presentation of multiple lesions in this method. From this, the division between the groups was made using clinical history and complementary exams. CRE was defined with documented epileptic syndrome arising in CCM topography. We selected and obtained plasma samples from 20 patients (8 asymptomatic and 12 with CRE diagnosis). Vascular Endothelial Growth Fator (VEGF) and Thrombomodulin proteins, linked to vasculogenesis and coagulation, respectively, were selected for analysis from a pre-designed panel of molecules of interest. Both proteins were measured in our samples by ELISA assays. Patients diagnosed with asymptomatic CCM had a mean level of 49.45 pg/mL for VEGF and 482.88 pg/mL for thrombomodulin, while patients diagnosed with CRE had 24.45pg/mL and 441.57 pg/mL for VEGF and thrombomodulin, respectively. A decrease in VEGF was observed in patients with CRE when compared to asymptomatic patients, with statistical significance (P<0.05). Disruption of VEGF expression has been widely studied in CCM disease and models. Low levels of this molecule are known to alter blood-brain barrier permeability and induce progression of CCM lesions. Interestingly, decreased plasma VEGF has been described as a predictor of disease severity. This pilot study opens a path for VEGF as potential target in future studies on CCM biomarkers and justifies the understanding of CRE as a distinguishable clinical entity, while larger samples for a more meaningful analysis are still needed.

Palavras Chave

Epilepsy; cavernous angioma; CCM; VEGF