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Shefaye Khatam 2018, 6 - The Summer Supplement of Shefaye Khatam 2 -: 29-29 Back to browse issues page
P2: Bumetanide as an Effective Adjunct Therapy in Intractable Epilepsy
Mahmoud Reza Hadjighassem, Maryam Gharaylou, Abbas Tafakhori *
Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran , abbas.tafakhori@gmail.com
Abstract:   (1071 Views)
Introduction: Reduced KCC2 expression and increased NKCC1 expression can shift Gamma-aminobutyric acid (GABA) responses toward excitation and generate seizures. Previous studies suggested that bumetanide, an inhibitor of NKCC1, might have antiepileptic effects. Here, for the first time, we assessed NKCC1 and KCC2 dysregulation and possible modifying role of bumetanide in living human subjects with drug-resistant TLE. Materials and Methods: Eligible patients with drug-resistant TLE were included. Peripheral blood mononuclear cells (PBMCs) were isolated from collected blood samples and used for polymerase chain reaction (PCR) and western blot analyses. Bumetanide treatment was initiated with the dose of 0.5 mg/day and then was weakly increased by 0.5 mg until a target dose of 2mg/day was achieved. Then, seizure frequency and drug safety were assessed at each monthly visit. Results: A total of 39 patients were evaluated and 27 patients were included. Overall, 70.4% were responders. The median seizure frequency reduced significantly from 9 (7-15) at baseline to 4 (2-11.67) at first three months (P<0.001), 2.67 (1-5.33) at last three months (P<0.001), and 3.33 (1.33-7.17) during the six months of treatment (P<0.001). The forward logistic regression showed eGFR (OR: 0.953, 95% CI: 0.912-0.996, P=0.033) as the only significant predictor of drug response. The level of NKCC1 and KCC2 gene transcripts and KCC2 protein did not significantly alter following treatment (P>0.05). However, we observed a significant reduction in NKCC1 protein levels after bumetanide treatment (P=0.0156). Conclusion: Altogether, it seems that bumetanide is an effective and relatively tolerable drug in patients with drug-resistant TLE. We confirm that KCC2 is significantly downregulated while NKCC1 is markedly upregulated in TLE patients. Bumetanide treatment led to a significant reduction of NKCC1 protein expression which we believe is the underlying reason for its antiepileptic efficiency.
Keywords: Adjunct Therapy, Epilepsy, Expression
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Type of Study: Research --- Open Access, CC-BY-NC | Subject: Basic research in Neuroscience

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Hadjighassem M R, Gharaylou M, Tafakhori A. P2: Bumetanide as an Effective Adjunct Therapy in Intractable Epilepsy. Shefaye Khatam. 2018; 6 (S2) :29-29
URL: http://shefayekhatam.ir/article-1-1789-en.html

Volume 6 - The Summer Supplement of Shefaye Khatam 2 - Back to browse issues page
مجله علوم اعصاب شفای خاتم The Neuroscience Journal of Shefaye Khatam
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