Çocukluk Çağı Epilepsisinde Valproat Tedavisi Beslenme Durumunu ve Biyokimyasal Parametreleri Etkiler mi?
Abstract
Amaç: Valproik asit, çeşitli nörolojik ve nöropsikiyatrik bozuklukların tedavisi için yaygın olarak reçete edilmektedir. Bu çalışmada epilepsili çocuklarda ağırlık artışına etkisi olduğu düşünülen valproik asit tedavisinin beslenme durumu ve bazı biyokimyasal faktörler üzerine etkisinin belirlenmesi amaçlanmıştır.
Gereç ve Yöntemler: Çalışmaya epilepsi tanısı ile valproik asit monoterapisi alan 30 çocuk ve ergen dahil edildi. VPA tedavisinden önce ve 12 ay sonra seçilen biyokimyasal parametreler hasta dosyalarından geriye dönük olarak kaydedildi. Etken madde dozu 11-40 mg/kg/gün arasında değişmektedir. Valproik asit plazma seviyeleri, çalışma boyunca terapötik sınırlar içinde tutulmuştur. Hastaların antropometrik ölçümleri 1-5 yaş arası çocuklar için WHO Anthro programına ve 5-18 yaş arası çocuklar için WHO Anthro-Plus programı ile hesaplanmıştır.
Bulgular: Hastaların epilepsi yaşı 48,85±38,16 ay olarak belirlenmiş olup hastalar ortalama 18,95±6,02 aydır 25,00±10,75 mg/kg/gün valproik asit tedavisi almaktadırlar. Tedavi öncesi ve sonrası açlık VAS skorları açısından fark bulunmazken, iştah VAS skoru artmış, tokluk VAS skoru ise azalmıştır (p<0.05). Tedavi sonrası hastaların yaşa göre BKİ z skorları, açlık insülini, HDL kolesterol ve trigliserit seviyelerinin arttığı saptanmıştır (p<0.05).
Sonuç: VPA tedavisi alan çocuklarda büyüme ve ağırlık takibi için multidisipliner ekipte bir diyetisyenin bulunmasının önemli olduğu düşünülmüştür.
Keywords
Supporting Institution
Başkent Üniversitesi
Project Number
KA16/120
Thanks
Gülhane Eğitim Araştırma Hastanesi Çocuk Nöroloji ve Endokrinoloji Bölüm Doktorları ve Değerli Hasta ve Aileleri
References
- 1. Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020;54:185-91.
- 2. Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet 2019;393: 689-701.
- 3. Zhang H, Lu P, Tang HL, Yan HJ, Jiang W, Shi H, et al. Valproate induced epigenetic upregulation of hypothalamic fto expression potentially linked with weight gain. Cell Mol Neurobiol 2021;41:1257-69.
- 4. Dimitrijević A, Stojanović R, Bogićević D, Mitić V, Nikolić DM. Influence of sodium valproate treatment on body mass and insulin resistance parameters in children with epilepsy. Serbian Archive of Medicine 2021;149:53-58.
- 5. Bai X, Xu C, Wen D, Chen Y, Li H, Wang X, et al. Polymorphisms of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36) associated with valproate-induced obesity in epileptic patients. Psychopharmacology 2018;235:2665-73.
- 6. Carmona-Vazquez CR, Ruiz-Garcia M, Pena-Landin DM, Diaz-Garcia L, Greenawalt SR. The prevalence of obesity and metabolic syndrome in paediatric patients with epilepsy treated in monotherapy with valproic acid. Rev Neurol 2015;61:193-201.
- 7. Rehman T, Sachan D, Chitkara A. Serum insulin and leptin levels in children with epilepsy on valproate-associated obesity. J Pediatr Neurosci 2017;12(2):135-7.
- 8. Çiçek NF, Kamaşak T, Serin M, Okten A, Alver A, Cansu A. The effects of valproate and topiramate use on serum insulin, leptin,neuropeptide Y and ghrelin levels in epileptic children. Seizure 2018;58:90-95.
- 9. Tokgoz H, Aydin K, Oran B, Kiyici A. Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate. Childs Nerv Syst 2012;28:1049-53.
- 10. World Health Organization BMI for age (5-19 years). Erişim tarihi: 25 Kasım 2021. Available from: https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators/bmi-for-age
- 11. Noai M, Soraoka H, Kajiwara A, Tanamachi Y, Oniki K, Nakagawa K, et al. Cytochrome P450 2C19 polymorphisms and valproic acid-induced weight gain. Acta Neurol Scand. 2016;133(3):216-23.
- 12. Matsushita Y, Sakai Y, Torio M, Inoue H, Ochiai M, Yasuoka K, et al. Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan. J Perinatol 2019;39:1472-9.
- 13. Ghosh S, Philip J, Patel N, Munoz-Pareja J, Lopez-Colon D, Bleiweis M, et al. Risk factors for seizures and epilepsy in children with congenital heart disease. JCN 2020;35(7):442-7.
- 14. Martin CK, Han H, Anton SD, Greenway FL, Smith SR. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol 2009;23(7):814-25.
- 15. Pylvanen V, Knip M, Pakarinen, A, Kotila M, Turkka J, Isojarvi JI Serum insulin and leptin levels in valproate-associated obesity. Epilepsia 2002;43:514-17.
- 16. Luef GJ, Lechleitner M, Bauer G, Trinka E, Hengster P. Valproic acid modulates islet cell insulin secretion: a possiblemechanism of weight gain in epilepsy patients. Epilepsy Res 2003;5(1-2):53-8.
- 17. Gungor S, Yücel G, Akinci A, Tabel Y, Ozerol IH, Yologlu S. The role of ghrelin in weight gain and growth in epileptic children using valproate. J Child Neurol 2007;22(12):1384-8.
- 18. Masuccio F, Verrotti A, Chiavaroli V, de Giorgis T, Giannini C, Chiarelli F, et al. Weight gain and insulin resistance in children treated with valproate: The influence of time. J Child Neurol 2010;25(8):941-7.
- 19. Wirrell EC. Valproic acid-associated weight gain in older children and teens with epilepsy. Pediatr Neurol 2003;28(2):126-9.
- 20. Belcastro V, D’Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproicacid chronic treatment. Epilepsy Res 2013;107:1-8.
- 21. Grosso S, Mostardini R, Piccini B, Balestri P. Body mass index and serum lipid changes during treatment with valproic acid in children with epilepsy. Ann Pharmacother 2009;43:45-50.
- 22. Abaci A, Saygi M, Yis U, Demir K, Dirik E, Bober E. Metabolic alterations during valproic acid treatment: a prospective study. Pediatr Neurol 2009;41:435-439.
- 23. Verrotti A, Basciani F, Morresi S, de Martino M, Morgese G, Chiarelli F. Serum leptin changes in epileptic patientswho gain weight after therapy with valproic acid. Neurology 1999;53:230-232.
- 24. Kılıc H, Demirel A, Uysal S. The effects of valproate on serum leptin, insulin, and lipid levels in epileptic children. Pediatr Int 2021;63(11):1351-6.
- 25. Sidhu HS, Srinivas R, Sadhotra A. Evaluate the effects of long-term valproic acid treatment on metabolicprofiles in newly diagnosed or untreated female epileptic patients: A prospective study. Seizure 2017;48:15-21.
- 26. Nikolaos T, Stylianos G, Chryssoula N, Irini P, Christos M, Dimitrios T. The effect of long-term antiepileptic treatment on serum cholesterol (TC, HDL, LDL) and triglycerid elevelsin adult epileptic patients on monotherapy. Med Sci Monit 2004;10:50-52.
- 27. Chuang YC, Chuang HY, Lin TK, Chang CC, Lu CH, Chang, WN, et al. Effects of long-term antiepilepticdrug monotherapy on vascular risk factors and atherosclerosis. Epilepsia 2012;53:120-8.
Does Valproate Treatment in Childhood Epilepsy Affect Nutritional Status and Biochemical Parameters?
Abstract
Objective: Valproic acid is widely prescribed for the treatment of various neurological and neuropsychiatric disorders. This study aimed to determine the effect of valproic acid therapy, which is thought to have weight gain effect on nutritional status and some biochemical factors in children with epilepsy.
Material and Methods: The study included 30 children and adolescents who received valproic acid monotherapy because of the diagnosis of epilepsy. Selected biochemical parameters before and 12 months after treatment were recorded retrospectively from the patient files. Valproic acid doses ranged from 11-40 mg/kg/day and plasma levels were maintained within the therapeutic limits throughout the study. The anthropometric measurements of the patients were recorded in the WHO Anthro program for children aged 1-5 years and the WHO Anthro-Plus program for children aged 5-18 years.
Results: The epilepsy age of the patients was determined as 48.85±38.16 months; and they have been receiving valproic acid therapy at a dose of 25.00±10.75 mg/kg/day for 18.95±6.02 months. While no difference was found in terms of hunger VAS scores before and after treatment, VAS scores of appetite increased and satiety decreased (p<0.05). BMI-SDs, fasting insulin, HDL cholesterol and triglyceride levels increased after treatment (p<0.05).
Conclusion: For this reason, it was thought that it is important to include a dietitian in multidisiplinary team for growth and weight monitoring in children receiving VPA therapy.
Keywords
Project Number
KA16/120
References
- 1. Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020;54:185-91.
- 2. Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet 2019;393: 689-701.
- 3. Zhang H, Lu P, Tang HL, Yan HJ, Jiang W, Shi H, et al. Valproate induced epigenetic upregulation of hypothalamic fto expression potentially linked with weight gain. Cell Mol Neurobiol 2021;41:1257-69.
- 4. Dimitrijević A, Stojanović R, Bogićević D, Mitić V, Nikolić DM. Influence of sodium valproate treatment on body mass and insulin resistance parameters in children with epilepsy. Serbian Archive of Medicine 2021;149:53-58.
- 5. Bai X, Xu C, Wen D, Chen Y, Li H, Wang X, et al. Polymorphisms of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36) associated with valproate-induced obesity in epileptic patients. Psychopharmacology 2018;235:2665-73.
- 6. Carmona-Vazquez CR, Ruiz-Garcia M, Pena-Landin DM, Diaz-Garcia L, Greenawalt SR. The prevalence of obesity and metabolic syndrome in paediatric patients with epilepsy treated in monotherapy with valproic acid. Rev Neurol 2015;61:193-201.
- 7. Rehman T, Sachan D, Chitkara A. Serum insulin and leptin levels in children with epilepsy on valproate-associated obesity. J Pediatr Neurosci 2017;12(2):135-7.
- 8. Çiçek NF, Kamaşak T, Serin M, Okten A, Alver A, Cansu A. The effects of valproate and topiramate use on serum insulin, leptin,neuropeptide Y and ghrelin levels in epileptic children. Seizure 2018;58:90-95.
- 9. Tokgoz H, Aydin K, Oran B, Kiyici A. Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate. Childs Nerv Syst 2012;28:1049-53.
- 10. World Health Organization BMI for age (5-19 years). Erişim tarihi: 25 Kasım 2021. Available from: https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators/bmi-for-age
- 11. Noai M, Soraoka H, Kajiwara A, Tanamachi Y, Oniki K, Nakagawa K, et al. Cytochrome P450 2C19 polymorphisms and valproic acid-induced weight gain. Acta Neurol Scand. 2016;133(3):216-23.
- 12. Matsushita Y, Sakai Y, Torio M, Inoue H, Ochiai M, Yasuoka K, et al. Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan. J Perinatol 2019;39:1472-9.
- 13. Ghosh S, Philip J, Patel N, Munoz-Pareja J, Lopez-Colon D, Bleiweis M, et al. Risk factors for seizures and epilepsy in children with congenital heart disease. JCN 2020;35(7):442-7.
- 14. Martin CK, Han H, Anton SD, Greenway FL, Smith SR. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol 2009;23(7):814-25.
- 15. Pylvanen V, Knip M, Pakarinen, A, Kotila M, Turkka J, Isojarvi JI Serum insulin and leptin levels in valproate-associated obesity. Epilepsia 2002;43:514-17.
- 16. Luef GJ, Lechleitner M, Bauer G, Trinka E, Hengster P. Valproic acid modulates islet cell insulin secretion: a possiblemechanism of weight gain in epilepsy patients. Epilepsy Res 2003;5(1-2):53-8.
- 17. Gungor S, Yücel G, Akinci A, Tabel Y, Ozerol IH, Yologlu S. The role of ghrelin in weight gain and growth in epileptic children using valproate. J Child Neurol 2007;22(12):1384-8.
- 18. Masuccio F, Verrotti A, Chiavaroli V, de Giorgis T, Giannini C, Chiarelli F, et al. Weight gain and insulin resistance in children treated with valproate: The influence of time. J Child Neurol 2010;25(8):941-7.
- 19. Wirrell EC. Valproic acid-associated weight gain in older children and teens with epilepsy. Pediatr Neurol 2003;28(2):126-9.
- 20. Belcastro V, D’Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproicacid chronic treatment. Epilepsy Res 2013;107:1-8.
- 21. Grosso S, Mostardini R, Piccini B, Balestri P. Body mass index and serum lipid changes during treatment with valproic acid in children with epilepsy. Ann Pharmacother 2009;43:45-50.
- 22. Abaci A, Saygi M, Yis U, Demir K, Dirik E, Bober E. Metabolic alterations during valproic acid treatment: a prospective study. Pediatr Neurol 2009;41:435-439.
- 23. Verrotti A, Basciani F, Morresi S, de Martino M, Morgese G, Chiarelli F. Serum leptin changes in epileptic patientswho gain weight after therapy with valproic acid. Neurology 1999;53:230-232.
- 24. Kılıc H, Demirel A, Uysal S. The effects of valproate on serum leptin, insulin, and lipid levels in epileptic children. Pediatr Int 2021;63(11):1351-6.
- 25. Sidhu HS, Srinivas R, Sadhotra A. Evaluate the effects of long-term valproic acid treatment on metabolicprofiles in newly diagnosed or untreated female epileptic patients: A prospective study. Seizure 2017;48:15-21.
- 26. Nikolaos T, Stylianos G, Chryssoula N, Irini P, Christos M, Dimitrios T. The effect of long-term antiepileptic treatment on serum cholesterol (TC, HDL, LDL) and triglycerid elevelsin adult epileptic patients on monotherapy. Med Sci Monit 2004;10:50-52.
- 27. Chuang YC, Chuang HY, Lin TK, Chang CC, Lu CH, Chang, WN, et al. Effects of long-term antiepilepticdrug monotherapy on vascular risk factors and atherosclerosis. Epilepsia 2012;53:120-8.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Project Number | KA16/120 |
| Publication Date | May 30, 2022 |
| Submission Date | November 26, 2021 |
| Published in Issue | Year 2022 Volume: 16 Issue: 3 |
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