Iwona Żarnowska1, Dominika Wróbel-Dudzińska2, Maria Tulidowicz-Bielak3, Tomasz Kocki4, Krystyna Mitosek-Szewczyk5, Maciej Gasior6, Waldemar Andrzej Turski7. 1. Department of Child Neurology, Medical University, Lublin, Poland. Electronic address: zarnowskai@gmail.com. 2. Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland. Electronic address: doolores@interia.pl. 3. Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland. Electronic address: mtulidowiczbielak@gmail.com. 4. Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland. Electronic address: tomasz.kocki@umlub.pl. 5. Department of Child Neurology, Medical University, Lublin, Poland. Electronic address: krystyna.mitosek@gmail.com. 6. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: NextPharma@gmail.com. 7. Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland. Electronic address: waldemar.turski@umlub.pl.
Abstract
PURPOSE: There is growing evidence to support the role of the kynurenine pathway in the anticonvulsant efficacy of ketogenic diets (KDs) in refractory epilepsy. The aim of the present study was to measure blood levels of tryptophan (TRP) and its kynurenine derivatives and correlate them with seizure reduction after starting the KD in children with refractory epilepsy. METHODS: Sixteen children (9 F/7 M; 7.1 ± 5.1 years) with refractory epilepsy were treated with the KDs. Clinical efficacy and metabolic ketosis were monitored throughout the study; blood levels of TRP, kynurenine (KYN), kynurenic acid (KYNA), and 3-OH-kynurenine (3-OH-KYN) were measured at 3, 6, and 12 months on the diet and compared to the pre-KD levels. RESULTS: Out of 16 children, 14 attained a ≥50% reduction (responders) in seizure frequency 3 months after starting the KD. In the 14 responders, TRP levels decreased numerically (18-25%) but not significantly (P = 0.077) compared to the pre-KD control values. KYN levels decreased significantly (30-57%; P = 0.001) compared to the pre-KD control levels while KYNA levels significantly increased (38-96%; P < 0.001). KYNA/KYN ratios significantly increased (100-323%; P = 0.003) while 3-OH-KYN levels (P = 0.680) and KYN/TRP ratios (P = 0.385) remained unchanged. Higher concentrations of KYNA and lower concentrations of KYN (P < 0.05) were found in patients who attained a higher reduction in seizure frequencies on the KD. CONCLUSIONS: We report a pattern of changes in the blood level of kynurenines in patients with refractory epilepsy who started the KD. The results of this study further support the role of specific kynurenines (e.g. KYNA) in the efficacy of the KD in refractory epilepsy.
PURPOSE: There is growing evidence to support the role of the kynurenine pathway in the anticonvulsant efficacy of ketogenic diets (KDs) in refractory epilepsy. The aim of the present study was to measure blood levels of tryptophan (TRP) and its kynurenine derivatives and correlate them with seizure reduction after starting the KD in children with refractory epilepsy. METHODS: Sixteen children (9 F/7 M; 7.1 ± 5.1 years) with refractory epilepsy were treated with the KDs. Clinical efficacy and metabolic ketosis were monitored throughout the study; blood levels of TRP, kynurenine (KYN), kynurenic acid (KYNA), and 3-OH-kynurenine (3-OH-KYN) were measured at 3, 6, and 12 months on the diet and compared to the pre-KD levels. RESULTS: Out of 16 children, 14 attained a ≥50% reduction (responders) in seizure frequency 3 months after starting the KD. In the 14 responders, TRP levels decreased numerically (18-25%) but not significantly (P = 0.077) compared to the pre-KD control values. KYN levels decreased significantly (30-57%; P = 0.001) compared to the pre-KD control levels while KYNA levels significantly increased (38-96%; P < 0.001). KYNA/KYN ratios significantly increased (100-323%; P = 0.003) while 3-OH-KYN levels (P = 0.680) and KYN/TRP ratios (P = 0.385) remained unchanged. Higher concentrations of KYNA and lower concentrations of KYN (P < 0.05) were found in patients who attained a higher reduction in seizure frequencies on the KD. CONCLUSIONS: We report a pattern of changes in the blood level of kynurenines in patients with refractory epilepsy who started the KD. The results of this study further support the role of specific kynurenines (e.g. KYNA) in the efficacy of the KD in refractory epilepsy.
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