Case Report

A Study of Vitamin D Deficiency in Patients of Epilepsy on Anti-Epileptic Drug

Dr. Anuya Chauhan mam, Dr.Gargi Pathak mam, Dr.Devhuti Godhani ,
Article Date Published : 9 August 2019 | Page No.: 4551-4553 | Google Scholar

Abstract

Medical literature has recently focused attention on the impact of vitamin D on various aspects of health. Besides its pivotal role in calcium homeostasis and bone mineral metabolism, it is now recognized to serve  a wide range of fundamental biological functions. The association between vitamin D, antiepileptic drugs , and bone health in individuals with epilepsy has been recognized for more than 30 years . Seizures themselves pose a risk for injury, including fractures; and the added co-morbidity of poor bone health increase this risk, especially in children with who suffer from seizures with motor manifestations, as well as those with impaired motor function and coordination. Many AEDs are inducers of hepatic cytochrome P450 metabolism. It has been postulated that these AEDs result in increased hepatic metabolism of vitamin D, leading to low vitamin D levels. However, non-enzyme inducing AEDs have also been associated with low vitamin D levels and in turn with poor bone health. Therefore, although the newer AEDs are less-potent enzyme inducers than older AED, they are not necessarily inert in bone metabolism. Studies have reported variable changes in vitamin D levels in children taking AEDs. We aimed to describe the prevalence of and risk factors for vitamin D deficiency among children with epilepsy on antiepileptic drugs.

Introduction :

Medical literature has recently focused attention on the impact of vitamin D on various aspects of health. Besides its pivotal role in calcium homeostasis and bone mineral metabolism, it is now recognized to serve a wide range of fundamental biological functions. The association between vitamin D, antiepileptic drugs , and bone health in individuals with epilepsy has been recognized for more than 30 years . Seizures themselves pose a risk for injury, including fractures; and the added co-morbidity of poor bone health increase this risk, especially in children with who suffer from seizures with motor manifestations, as well as those with impaired motor function and coordination. Many AEDs are inducers of hepatic cytochrome P450 metabolism. It has been postulated that these AEDs result in increased hepatic metabolism of vitamin D, leading to low vitamin D levels. However, non-enzyme inducing AEDs have also been associated with low vitamin D levels and in turn with poor bone health. Therefore, although the newer AEDs are less-potent enzyme inducers than older AED, they are not necessarily inert in bone metabolism. Studies have reported variable changes in vitamin D levels in children taking AEDs. We aimed to describe the prevalence of and risk factors for vitamin D deficiency among children with epilepsy on antiepileptic drugs.

Material And Methodology

-STUDY DESIGN : case control study

-STUDY SETTING : Pediatric OPD and epilepsy OPD of civil hospital Ahmedabad

-DURATION OF STUDY : January 2019 – March 2019

-A prospective study was done in pediatric OPD and epilepsy OPD on children <12 years age.

-Cases included those having epilepsy and having apparently normal physical and mental development, on antiepileptic monotherapy or polytherapy for atleast 6 month.

-Controls included age matched children who were not on any continous medication during the same period of study.

-Data including age, weight, height, type of epilepsy, drugs used for treatment of epilepsy, duration of epilepsy, frequency of seizures, duration of antiepileptic therapy were collected.

-Serum calcium, phosphate, alkaline phosphatase (ALP), urea, creatinine, proteins, aspartate amino transferase(AST) , alanine amino transferase(ALT) , 25 hydroxy vitamin D levels were assessed.

-Inclusion criteria :

-children with epilepsy aged <12 years

-Exclusion criteria :

-children with metabolic bone disease

-significant renal impairement, hepatic impairement, endocrine disorders

-children on vitamin D supplementation

-children on any other drug likely to affect bone metabolism

Aims And Objective :

-to study prevalence and incidence of vitamin D deficiency in children on antiepileptic drug

-to study effect of monotherapy and polytherapy of antiepileptic drug on severity of vitamin D deficiency

-to study variations in levels of bone markers in children on antiepileptic drug

Results :

Total 30 patients on monotherapy of AED , 30 patients on polytherapy of AED and 30 controls were included in the study.

Vit D deficiency was seen in 8 (26%) of patients on monotherapy , 13 (43%) of patients on polytherapy and 6 (20%) of controls.

Vit D deficiency Vit D normal Total
Pt on monotherapy AED 8 (26%) 22 30
Pt on polytherapy AED 13(43%) 17 30
Controls 6(20%) 24 30

Figure 1:

Age range was upto 12 years. There was equal distribution patients from infancy to adolescence.

Sex distribution was as follows in all :

Vit D deficiency in females Vit D deficiency in males Total
Pt on monotherapy AED 5 (62.5%) 3 (37.5%) 8
Pt on polytherapy AED 8 (61.5%) 5 (38.5%) 13
Controls 3 (50%) 3 (50%) 6
Total 16 (59.2%) 11 (40.8%) 27

This suggest preponderance of female (59.2%) as compared to male (40.8%).

Figure 2:

The distribution of levels of vit D deficiency was as follows :

Total Vit D deficiency Severe Vit D deficiency
Pt on monotherapy AED 8 2 (25%)
Pt on polytherapy AED 13 4 (30.7%)
Controls 6 1 (16.6%)

This shows severe vitamin D deficiency is seen more in patients on polytherapy of AED.

Figure 3:

The levels of serum calcium,phosphate and alkaline phosphate in all 3 groups were noted as follows :

Low S.calcium Low S.phosphate Raised ALP
Pt on monotherapy AED (30) 4 (13.3%) 4 (13.3%) 6 (20%)
Pt on polytherapy AED (30) 8 (26.6%) 8 (26.6%) 11 (36.6%)
Controls (30) 5 (16.6%) 5 (16.6%) 2 (6.6%)

Manifestations of vitamin D deficiency either clinically or on X ray were seen as follows :

Manifestations of vit D defi
Pt on monotherapy AED (30) 3 (10%)
Pt on polytherapy AED (30) 8 (26.6%)
Controls (30) 2 (6.6%)

Thus,clinical manifestions Of vitamin D deficiency are more frequently seen in patient taking anti epileptic drugs as compared to control group.

Discussion :

Vitamin D is an essential nutrient that maintains the homeostasis of calcium and phosphorous in the body. The importance of vitamin D was recently emphasized when it was reported that it has several non-skeletal physiological functions too. Many AEDs are inducers of hepatic cytochrome P450 metabolism. It has been postulated that these AEDs result in increased hepatic metabolism of vitamin D, leading to low vitamin D levels. However, non-enzyme inducing AEDs have also been associated with low vitamin D levels and in turn with poor bone health. Therefore, although the newer AEDs are less-potent enzyme inducers than older AED, they are not necessarily inert in bone metabolism.Research has shown that adult epilepsy patients on AEDs can exhibit deficiency of vitamin D. In pediatric patients, however, controversies still remain regarding the effect of AEDs on vitamin D levels.

This study showed that the serum levels were significantly lower in patients on anti epileptic drugs .

Vit D deficiency showed preponderence to females as compared to males.

Chances of vit D deficiency increases with increase in duration of AED and number of AED.

One limitation of this study was that vit D levels were not assessed before AED use

One previous study showed that patients who took anticonvulsants for more than 2 years had normal vitamin D levels, although BMD was found to be decreased; these authors mentioned the possibility of high vitamin D intake among the experimental group. However, we ruled out any vitamin supplementation in our study

Conclusion :

We found vitamin D deficiency to be highly prevalent among children with epilepsy on AED. The high prevalence of hypovitaminosis D suggests that, almost all children with epilepsy are at risk. Increased duration of AED therapy was associated with increased risk of vitamin D deficiency. Increased attention on the part of both pediatric neurologists and pediatricians to vitamin D status among children with epilepsy is warranted as vitamin D has a vast impact on health of children other than bone health such as reducing the frequency of seizures, immunity, autoimmune disease and malignancy to mention a few.

Thus,this study suggest that patient on Anti-epileptic drug should be Monitored for Vit-D deficiency at regular interval. Vit-D supplements and Calcium should be given to all patients on Anti-epileptic Drugs.

References

  1. Holick MF, Chen TC. Vitamin D deficiency: A worldwide problem with health consequences. Am J Clin Nutr 2008;87(4):1080S-6.

  2. Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 2009;94(1):26-34.

  3. Sheth RD, Gidal BE, Hermann BP. Pathological fractures in epilepsy. Epilepsy Behav 2006;9(4):601-5.

  4. Souverein PC, Webb DJ, Weil JG, Van Staa TP, Egberts AC. Use of antiepileptic drugs and risk of fractures: Case-control study among patients with epilepsy. Neurology 2006;66(9):1318-24.

  5. Vestergaard P. Epilepsy, osteoporosis and fracture risk - A metaanalysis. Acta Neurol Scand 2005;112(9):277-86.

  6. Erbayat Altay E, Serdaroglu A, Tümer L, Gücüyener K, Hasanoglu A. Evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid. J Pediatr Endocrinol Metab 2000;13(7):933-9.

  7. Holick MF. The use and interpretation of assays for vitamin D and its metabolites. J Nutr 1990;120 Suppl 11:1464-9.

  8. Nicolaidou P, Georgouli H, Kotsalis H, Matsinos Y, Papadopoulou A, Fretzayas A, et al. Effects of anticonvulsant therapy on vitamin D status in children: Prospective monitoring study. J Child Neurol 2006;21(3):205-9.

  9. Siegel A, Malkowitz L, Moskovits MJ, Christakos S. Administration of 1,25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats. Brain Res 1984;298(1):125-9.

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Article Details


Issue: Vol 6 No 08 (2019)
Page No.: 4551-4553
Section: Case Report
DOI: https://doi.org/10.18535/ijmsci/v6i8.05

How to Cite

Chauhan mam, D. A., Pathak mam, D., & Godhani , D. (2019). A Study of Vitamin D Deficiency in Patients of Epilepsy on Anti-Epileptic Drug. International Journal of Medical Science and Clinical Invention, 6(08), 4551-4553. https://doi.org/10.18535/ijmsci/v6i8.05

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