“GINGIVAL ENLARGEMENT & SERUM FOLIC ACID LEVELS IN PATIENTS ON ANTIEPILEPTIC DRUGS”
BRIEF RESUME OF THE INTENDED WORK:
6.1 Need for the study:
Epilepsy is a condition in which a patient has recurrent seizures due to a chronic underlying process.1 A recent meta-analysis of published and unpublished studies puts the overall prevalence rate of epilepsy in India at 5.59 per 1,000 populations, with no statistically different rates between men and women or urban and rural residences.2 Among these patients, about 50% patients taking phenytoin, one of the widely used drugs in anti-epileptic therapy, have been seen with some degree of gingival enlargement.3 Several drugs have been tried with varying success rates and adverse effects in the management of epileptic patients, however, phenytoin is chiefly responsible for this drug induced gingival enlargement whereas other anti-epileptic drugs have not been shown to bring such severe gingival enlargements.1,4 Many studies report folic acid as an adjuvant to anti-epileptic drugs to prevent gingival enlargements5,6,7 However, some studies have, also, shown no improvement in prevention of these gingival enlargements even on supplementation with folic acid.7
The exact etio-pathogenesis of this drug induced gingival enlargement remains unknown, however, it is hypothesized to be multi-factorial in origin1,7,8 including the involvement of bacterial plaque9 and anti-epileptic drugs induced folic acid deficiency5,6,7. The precise mechanism by which this gingival enlargement occurs, is still not completely understood, although a number of hypotheses have suggested phenytoin probably interacting with a sub-type of susceptible fibroblasts (termed responders) resulting in gingival enlargement.1,8 There have been studies with varying reports in recognition of the incidence of gingival enlargement related to the dosage, duration of the drug and with the oral hygiene status.
Gingival enlargement, recognized since long as a deleterious side effect of chronic phenytoin therapy, whenever occur, lasts throughout the period of drug therapy7.And sometimes, it is associated with difficulty in mastication, speech and causes considerable cosmetic disfigurement7,8.
Hence, the present study is planned to evaluate the gingival enlargements and
serum folic acid levels in patients on anti-epileptic therapy.
6.2 Review of literature:
In a study conducted in the year 2000, on the factors influencing phenytoin induced gingival enlargements, it was found that the bacterial plaque was the single most important determinant of phenytoin induced gingival enlargement9.
A study conducted in 2004 at Chandigarh, India reported 60% incidence of drug induced gingival enlargement in patients without folic acid supplements while 50% in patients who were given adjuvant folate supplements and concluded that systemic folic acid supplementation with anti-epileptic therapy was beneficial in delaying the onset and severity of gingival enlargement and also, proposed various mechanisms of gingival enlargement other than poor oral hygiene and folic acid deficiency7.
In a study conducted in the year 2005, it was shown that there was an increase in the connective tissue extra cellular matrix along with genetic heterogeneity as the determinant factors behind drug induced gingival enlargements.11
In a review reported in the same year , it has been focused that drug induced gingival enlargement is characterized by the accumulation of extra cellular matrix in gingival connective tissue with various degrees of inflammation due to disruption of homeostasis of collagen synthesis and degradation induced by these drugs by some unknown mechanism10.
In a recent study conducted in 2007,it was concluded that neurologists shall be aware of the potential etiologic agents of anti-epileptic drug induced gingival enlargement and its characteristic features in order to prevent, diagnose and successfully manage it.8
6.3 Objectives of the Study:
1. To study the incidence and assess the scores of gingival enlargement in epileptic
patients before and with anti-epileptic therapy periodically up to 6 months;
2. To assess the serum folic acid levels in epileptic patients before and after 6 months
of anti-epileptic therapy and to co-relate with the drug induced gingival enlargements;
3. To assess the scores of gingival enlargement and co-relate with serum folic acid levels
and the dosage and duration of the anti epileptic drugs.
MATERIALS AND METHODS: 7.1 Source Of Data:
100 patients of epilepsy visiting the Department of Neurology, Victoria Hospital, Bangalore and Department of Oral Medicine and Radiology, Government Dental College and Research Institute, Bangalore will be selected before therapy based on the inclusion and exclusion criteria.
7.2 Method Of Collection Of Data: Patients who are selected for the study are subjected to a detailed history and a thorough clinical examination. Patients who are selected based on the inclusion/ exclusion criteria are explained in detail about the study and a written consent is obtained.
Patients are initially subjected to a through oral prophylaxis, routine hematological examination and serum folic acid level assessments. In the subsequent appointment after a gap of 1 week , these patients are thoroughly examined and their gingival status are assessed with GO Index (Miller and Damm) and MB Index (Miranda et al)7.
Further,patients are asked to take anti-epileptic regime as prescribed by Neurologist. After an initial period of 2 months, patients are reviewed with history and clinical examination and gingival scores are recorded with same criteria .The same procedure will be periodically repeated with an interval of one month up-to 6 months and at the end of 6 months of anti-epileptic therapy, serum folic acid levels are estimated. Results are tabulated and statistically analyzed.
Epileptic patients in the age group of 20-40 years;
Patients who will be started with phenytoin and other anti-epileptic drugs;
Patients with full complement of the teeth without any carious or periodontal involvement or any other pathological process in the teeth and jaws.
Patients with any systemic condition other than epilepsy;
Patients on multi-vitamin therapy for any reasons;
Patients on folate antagonists as anti-neoplastic drugs as methotrexate;
Patients with pre-existing gingival enlargements due to any reasons as-idiopathic, inflammatory, neoplastic, endocrinal, chronic vitamin C deficiency, mouth breathing or pregnancy;
Patients who had dental treatment and trauma to teeth earlier.
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly. Yes , the study requires-
Assessment of serum folic acid levels before and after 6 months of anti-epileptic
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
LIST OF REFERENCES:
Brunet L, Miranda J, Roset P, Berini L, .Farre M, Mendieta C. Prevalence and risk of gingival enlargement in patients treated with anticonvulsant drugs, European Journal of Clinical Investigation 2001;31:781-788.
Bharucha N.E. Epidemiology of epilepsy in India, Epilepsia, 44(Suppl.1):9-11, 2003, Blackwell Publishing, Inc.