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Erschienen in: Indian Journal of Pediatrics 7/2018

25.01.2018 | Original Article

Effect of Folic Acid Supplementation on Seizure Control in Epileptic Children Receiving Long Term Antiepileptic Therapy

verfasst von: Bindu Deopa, Manish Parakh, Pawan Dara, Vikas Payal, Kapil Chordiya, Ankit Panday, Sumeet Singh, Devesh Parashar

Erschienen in: Indian Journal of Pediatrics | Ausgabe 7/2018

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Abstract

Objective

To evaluate the effect of folic acid supplementation on seizure control in folate deficient children receiving long term antiepileptic therapy.

Methods

In a prospective interventional study, 140 children between age group 6 mo to 180 mo fulfilling the inclusion criteria were enrolled in study group, from October 2015 through November 2016. On the basis of serum folate, study group was divided into two subgroups by non randomization: Group A (<10 ng/ml) given folic acid supplementation for 3 mo and Group B (>10 ng/ml) was not supplemented. Response to folic acid supplementation in group A was compared with group B in terms of change in blood folate levels, frequency and duration of seizures after three months.

Results

Mean age of study group was 73.58 ± 46.89 mo (72.14% boys and 27.85% girls). 67.85% children were in group A and 32.14% in group B. On 3 mo follow up, children supplemented with folic acid (Group A) had significant fall in mean seizure frequency while in non-supplemented children (Group B), no significant change was seen (p value <0.05). Similar reduction in duration of seizure episode was seen in group A as compared to group B. Serum and RBC folate levels improved from baseline in group A, while in group B there was significant fall in folate levels.

Conclusions

Folate deficiency is common in epileptic children on long term antiepileptic drugs (AEDs), contributes to poor seizure control and should be considered in the etiologic differentials of drug resistant epilepsy. Folate supplementation improves seizure control in these children.
Literatur
1.
2.
Zurück zum Zitat French JA, Gazzola DM. New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety? Ther Adv Drug Saf. 2011;2:141–58.CrossRefPubMedPubMedCentral French JA, Gazzola DM. New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety? Ther Adv Drug Saf. 2011;2:141–58.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Attilakos A, Papakonstantinou E, Schulpis K, et al. Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res. 2006;71:229–32.CrossRefPubMed Attilakos A, Papakonstantinou E, Schulpis K, et al. Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res. 2006;71:229–32.CrossRefPubMed
5.
Zurück zum Zitat Nayyar AS, Nataraju B, Subhas GT. Phenytoin-folate interactions : how far is safe folate supplementation in phenytoin treated epileptic patients? J Appl Pharm Sci. 2012;02:230–5. Nayyar AS, Nataraju B, Subhas GT. Phenytoin-folate interactions : how far is safe folate supplementation in phenytoin treated epileptic patients? J Appl Pharm Sci. 2012;02:230–5.
7.
Zurück zum Zitat Maxwell JD, Hunter J, Stewart DA, Ardeman S, Williams R. Folate deficiency after anticonvulsant drugs: an effect of hepatic enzyme induction? Br Med J. 1972;1:297–9.CrossRefPubMedPubMedCentral Maxwell JD, Hunter J, Stewart DA, Ardeman S, Williams R. Folate deficiency after anticonvulsant drugs: an effect of hepatic enzyme induction? Br Med J. 1972;1:297–9.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Mangold S, Blau N, Opladen T, et al. Cerebral folate deficiency: a neurometabolic syndrome? Mol Genet Metabol. 2011;104:369–72.CrossRef Mangold S, Blau N, Opladen T, et al. Cerebral folate deficiency: a neurometabolic syndrome? Mol Genet Metabol. 2011;104:369–72.CrossRef
9.
Zurück zum Zitat Ramaekers VT, Sequeira JM, Blau N, Quadros EV. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. 2008;50:346–52. Ramaekers VT, Sequeira JM, Blau N, Quadros EV. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. 2008;50:346–52.
10.
Zurück zum Zitat Al-Baradie RS, Chudary MW. Diagnosis and management of cerebral folate deficiency: a form of folinic acid-responsive seizures. Neurosciences. 2014;19:312–6.PubMedPubMedCentral Al-Baradie RS, Chudary MW. Diagnosis and management of cerebral folate deficiency: a form of folinic acid-responsive seizures. Neurosciences. 2014;19:312–6.PubMedPubMedCentral
12.
Zurück zum Zitat Ormazabal A, García-Cazorla A, Pérez-Dueñas B, et al. Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: reference values for a paediatric population. Clin Chim Acta. 2006;371:159–62.CrossRefPubMed Ormazabal A, García-Cazorla A, Pérez-Dueñas B, et al. Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: reference values for a paediatric population. Clin Chim Acta. 2006;371:159–62.CrossRefPubMed
13.
14.
Zurück zum Zitat Karabiber H, Sonmezgoz E, Ozerol E, Yakinci C, Otlu B, Yologlu S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev. 2003;25:113–5. Karabiber H, Sonmezgoz E, Ozerol E, Yakinci C, Otlu B, Yologlu S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev. 2003;25:113–5.
15.
Zurück zum Zitat Mohamad A. Mikati, Hani AJ. Seizure in childhood, 1st South Asia ed. South Asia: Reed Elsevier India Pvt. Ltd.; 2016. Mohamad A. Mikati, Hani AJ. Seizure in childhood, 1st South Asia ed. South Asia: Reed Elsevier India Pvt. Ltd.; 2016.
16.
Zurück zum Zitat Pérez-Dueñas B, Ormazábal A, Toma C, et al. Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol. 2011;68:615–21. Pérez-Dueñas B, Ormazábal A, Toma C, et al. Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol. 2011;68:615–21.
17.
Zurück zum Zitat Opladen T, Blau N, Ramaekers VT. Effect of antiepileptic drugs and reactive oxygen species on folate receptor 1 (FOLR1)-dependent 5-methyltetrahydrofolate transport. Mol Genet Metabol. 2010;101:48–54. Opladen T, Blau N, Ramaekers VT. Effect of antiepileptic drugs and reactive oxygen species on folate receptor 1 (FOLR1)-dependent 5-methyltetrahydrofolate transport. Mol Genet Metabol. 2010;101:48–54.
18.
Zurück zum Zitat Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M. Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6. Seizure. 2006;15:79–85.CrossRefPubMed Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M. Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6. Seizure. 2006;15:79–85.CrossRefPubMed
19.
Zurück zum Zitat Eldeen ON, Eldayem SMA, Shatla RH, Omara NA, Elgammal SS. Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children. Egyptian J Med Hum Genet. 2012;13:275–80. Eldeen ON, Eldayem SMA, Shatla RH, Omara NA, Elgammal SS. Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children. Egyptian J Med Hum Genet. 2012;13:275–80.
20.
Zurück zum Zitat Geda G, Caksen H, Icagasioglu D. Serum lipids, vitamin B12 and folic acid levels in children receiving long-term valproate therapy. Acta Neurol Belg. 2002;102:122–6. Geda G, Caksen H, Icagasioglu D. Serum lipids, vitamin B12 and folic acid levels in children receiving long-term valproate therapy. Acta Neurol Belg. 2002;102:122–6.
21.
Zurück zum Zitat Huemer M, Ausserer B, Graninger G, et al. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Epilepsia. 2005;46:1677-83. Huemer M, Ausserer B, Graninger G, et al. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Epilepsia. 2005;46:1677-83.
22.
Zurück zum Zitat Kurul S, Ünalp A, Yiş U. Homocysteine levels in epileptic children receiving antiepileptic drugs. J Child Neurol. 2007;22:1389–92.CrossRefPubMed Kurul S, Ünalp A, Yiş U. Homocysteine levels in epileptic children receiving antiepileptic drugs. J Child Neurol. 2007;22:1389–92.CrossRefPubMed
23.
Zurück zum Zitat Vilaseca MA, Monrós E, Artuch R, et al. Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C→ T mutation of the methylenetetrahydrofolate reductase gene. Eur J Paediatr Neurol. 2000;4:269–77.CrossRefPubMed Vilaseca MA, Monrós E, Artuch R, et al. Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C→ T mutation of the methylenetetrahydrofolate reductase gene. Eur J Paediatr Neurol. 2000;4:269–77.CrossRefPubMed
24.
Zurück zum Zitat Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res. 2001;47:27–35.CrossRefPubMed Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res. 2001;47:27–35.CrossRefPubMed
25.
Zurück zum Zitat Kishi T, Fujita N, Eguchi TA, Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci. 1997;145:109–12.CrossRefPubMed Kishi T, Fujita N, Eguchi TA, Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci. 1997;145:109–12.CrossRefPubMed
26.
Zurück zum Zitat Linnebank M, Moskau S, Semmler A, et al. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol. 2011;69:352–9.CrossRefPubMed Linnebank M, Moskau S, Semmler A, et al. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol. 2011;69:352–9.CrossRefPubMed
27.
Zurück zum Zitat Reynolds EH. Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients. Lancet. 1967;289:1086–8.CrossRef Reynolds EH. Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients. Lancet. 1967;289:1086–8.CrossRef
29.
Zurück zum Zitat Ralston AJ, Snaith RP, Hinley JB. Effects of folic acid on fit-frequency and behaviour in epileptics on anticonvulsants. Lancet. 1970;295:867–8.CrossRef Ralston AJ, Snaith RP, Hinley JB. Effects of folic acid on fit-frequency and behaviour in epileptics on anticonvulsants. Lancet. 1970;295:867–8.CrossRef
30.
Zurück zum Zitat Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol. 1981;19:57–60.CrossRefPubMed Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol. 1981;19:57–60.CrossRefPubMed
Metadaten
Titel
Effect of Folic Acid Supplementation on Seizure Control in Epileptic Children Receiving Long Term Antiepileptic Therapy
verfasst von
Bindu Deopa
Manish Parakh
Pawan Dara
Vikas Payal
Kapil Chordiya
Ankit Panday
Sumeet Singh
Devesh Parashar
Publikationsdatum
25.01.2018
Verlag
Springer India
Erschienen in
Indian Journal of Pediatrics / Ausgabe 7/2018
Print ISSN: 0019-5456
Elektronische ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-018-2608-1

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