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Percorrer por autor "Bentes, C."

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  • Circulating miR-146a and mir-134 as potential therapeutic biomarkers in refractory status epilepticus: an exploratory study
    Publication . Palhete-Ferreira, Lígia; Leal, B.; Santos, C.; Franco, S.; Parreira, S.; Peralta, A. R.; Moniz, I.; Gaibino, N.; Teixeira, A.; Mateus, C.; Santos, R.; Bentes, C.
    Purpose: Refractory Status Epilepticus (RSE) is defined by persisting electroclinical/electrographic seizures despite intravenous therapy with two anti-seizure medication (ASM), including a benzodiazepine. The therapeutic approach includes underlying cause treatment, other ASMs and intravenous anesthetic therapy (IVAT). In clinical practice, biomarkers for RSE treatment are needed, aiming for its effective reversal and diligent IVAT reduction. MicroRNAs (miR) have been identified in epileptogenesis, including refractory epilepsies, with promising roles as diagnostic, prognostic and therapeutic response biomarkers. Previous studies, animal model of RSE and SE patients, reported miR upregulation. However, serum miR in RSE clinical model have not been studied. We aim to evaluate circulating levels of miR-146a and mir-134 in patients under IVAT for RSE treatment. Method: MiR-146a and miR-134 were quantified by real-time PCR in serum of adult patients with optimized IVAT for RSE treatment (EEG validated) and healthy individuals. Anoxic etiology was excluded. Relative expression values were calculated using 2-ΔΔCT method and compared with controls (Mann-Whitney and T-Student, p<0.05). Results: MiR circulating levels were quantified in 19 patients (8.53±15.70 years), 84,21% with electroclinical status epilepticus and 15,79% with electrographic status epilepticus, and 10 healthy individuals (27.60±12.00 years). RSE patients with optimized IVAT dose presented downregulated serum levels of miR-146a (20-fold lower (p<0,001) and miR-134 (3-fold lower,p<0,001). Conclusion: In this work, a significant downregulation in serum levels of miR-146a and miR-134 was demonstrated in optimized IVAT for RSE treatment, contradicting miR upregulation stated in SE, both in animal and human models. We postulate that our results are due to the therapy established for RSE, reflecting the importance of intervention models in mechanisms of neuroinflammation, neuronal excitability and dendritic spine morphology. Future work should analyze the role of miRs as RSE therapeutical response biomarkers.
    2025-09Póster em conferência Desconhecido Ver mais
  • Refractory status epilepticus outcome: a retrospective study from a Portuguese hospital
    Publication . Palhete-Ferreira, Lígia; Dias, J.; Peralta, A. R.; Bentes, C.
    Purpose: Refractory Status Epilepticus (RSE) is a severe neurological emergency characterized by refractoriness to initial anti-seizure medications (ASM) and often requiring intravenous anesthetics therapy (IVAT) in an intensive care unit (ICU) setting. Despite previous efforts, biomarkers of successful RSE reversal are still lacking. Aim: study clinical predictors of successful IVAT weaning off and outcome in patients with RSE under IVAT. Method: Retrospective study including RSE adult patients, under optimized IVAT for at least 72h, between November 2017 and December 2018. Clinical and functional outcome (mRS) data were collected at ICU discharge and at the last follow-up time. The association between clinical variables, successful IVAT weaning-off, and functional outcome was analyzed using statistical methods. Results: 32 patients (mean age 67.6 years; mean time follow-up 17months) were included, and 58 IVAT weaning-off attempts were analyzed, of which 41,3% were successful. All patients with a previous epilepsy diagnosis had a successful IVAT weaning-off attempt (p=0,022). However, no clinical factor was found to be an independent predictor of successful IVAT weaning-off in our binary-logistic regression model. At ICU discharge, 96,6% patients had mRS >2, 36,2% had died, and there was a positive association between mRS score and age (p=0,000), RSE type (p=0,004; mostly focal-motor RSE) and etiology (p=0,006), number of ASMs (p=0,004), treatment with LCS (p=0,000) and VPA (p=0,004) and STESS score (p=0,000). At last follow-up, 90,9% patients had mRS >2, 86,4% had died, and there was an association between mRS score and RSE etiology (p=0,049; mostly acute-symptomatic) and CNS infection (p=0,022). Conclusion: This study shows a negative outcome associated with RSE. Successful IVAT weaning-off was more frequent in epilepsy patients. RSE patients’ functional outcome was associated with multiple clinical factors, although identification of independent predictors was not possible. Larger, prospective, and multimodal studies are needed to better understand refractory forms of RSE and outcome predictors.
    2025-09Póster em conferência Acesso aberto Ver mais