Farqad Final.doc J Bagh College Dentistry Vol. 26(2), June 2014 Evaluation of oral Oral Diagnosis 69 Evaluation of oral health status in patients receiving antiepileptic medications Farqad Najm Abed, B.D.S. (1) Raja H. Al –Jubouri, B.D.S., M.Sc., Ph.D. (2) ABSTRACT Background: Epilepsy is a common neurological disorder of incidence rate 1-2%. Genetic, congenital, developmental, tumors, head trauma and central nervous system infections maybe the cause of epilepsy. This study aimed to determine the prevalence of stomatitis, xerostomia and taste disorder among patients taking carbamazepine or sodium valproate and to make salivary analysis for IgA, cystatin c and salivary flow rate. Material and method:This study performed in al- Yarmuk teaching hospital in Baghdad, Samples consist of (70) epileptics half of them treated with carbamazepine and other half treated with sodium valproate, and (18) healthy control group of both genders and with different ages to detect the prevalence of oral manifestations, salivary IgA and cystatin C changes. Results: Salivary IgA is significantly higher in epileptics than healthy group. DMFT is significantly lower in epileptics than in healthy control. GI is hardly affected by epilepsy. Salivary flow rate was significantly lower in epileptics than the healthy control group. On the other hand, cystatin C was obviously higher in epileptics but failed to reach the level of statistical significance. Mucositis in epileptics was significantly higher. Candidal infection and Dysguisia failed to reach the level of statistical difference. Conclusion: The most affected oral measurement by epilepsy was salivary IgA then salivary flow rate followed by DMFT. Cystatin C had a marginal contribution to the context of case –control discrimination.Sodium valproate is safer than carbamazepine when compared by its effects on the oral health. Mucositis, candida infection and dysguisia were lower in epileptics who were treated with Sodium valproate. Salivary flow rate was higher in Sodium valproate - treated group than in carbamazepine group. GI and DMFT were lower in sodium valproate treated group than the carbamazepine group. Keyword: Salivary IgA, cystatin C, antiepileptic medications (AEMs). (J Bagh Coll Dentistry 2014; 26(2): 69-73). :الخالصة . عصبي المركزي ھي من اھم اسباب الصرعاألورام الوراثیة والخلقیة والتنمویة، الصدمات النفسیة والتھابات الجھاز ال%. 2-1الصرع اضطراب عصبي شائع معدل االصابة یونو غلوبیولین أ، سیستاتین ج لتحدید مدى انتشار اضطراب التھاب الفم، وجفاف الفم، والذوق بین المرضى الذین یتناولون كاربامازبین أو الصودیوم فالبرویت وتحلیل ام: ھدف دراسة . ومعدل تدفق اللعاب مریض مصاب بالصرع یتم عالج نصفھم مع كاربامازبین، والنصف اآلخر مع ) 70(ھذه الدراسة أجریت في مستشفى الیرموك في بغداد، تتكون العینات من : المواد والطریقة نغلوبیف عن انتشار التغییرات الشفویة، امیونو من كال الجنسین ومع اإلعمار المختلفة للكش) 18(فالبرویت الصودیوم، وفریق مراقبة صحیة . مقیاس التھاب اللثة ال یكاد یتأثر بالصرع. أقل بكثیر في الصرع مما في مجموعة المراقبة مقیاس التسوس. امیونو غلوبیولین أ أعلى بكثیر في الصرع من مجموعة المراقبة: النتائج . في حین ان السیستاتین ج كان أعلى في الصرع ولكنھ فشل في الوصول إلى مستوى الداللة اإلحصائیة. جموعة المراقبة الصحیةوكان معدل تدفق اللعاب أقل بكثیر في الصرع من م . اإلصابة بالفطریات وتغییرات التذوق فشلتا في التوصل إلى مستوى الفرق اإلحصائي. التھاب الغشاء المخاطي في الصرع كان أعلى بكثیر وكان سیستاتین ج ذو مساھمة ھامشیة في سیاق التمییزبین . مقیاس التسوسالشفوي األكثر تأثرا بالصرع كان االمیونوغلوبیولین أ ثم معدل تدفق اللعاب تلیھا المقساس :االستنتاج الفطریات واضطرابات التذوق وب الغشاء المخاطي التھا. فالبرویت الصودیوم أكثر أمانًا من كاربامازبین إذا ما قورنت بإثارة على صحة الفم واألسنان. المصابین واالصحاء مجموعة كانتأقلفیمقیاس التسوسومقیاس التھاب اللثھ . فالبرویتالصودیومممافیمجموعةكاربامازبینمجموعة وكانمعدلتدفقاللعابأعلىفی. فالبرویتالصودیومیتم عالجھمبكانتأقلفیالصرعالذین .مازبینكارباالمجموعةمما ھي علیھ في فالبرویتالصودیوم .االدویة المضادة للصرع, سیستاتین ج,امیونوغلوبیولین أ: مفاتیح البحث INTRODUCTION Epilepsy is defined as a neurological condition characterized by recurrent epileptic seizures unprovoked by any immediately identifiable cause. An epileptic seizure is the clinical manifestation of an abnormal and excessive discharge of a set of neurons in the brain (1). Epilepsy should be viewed as a symptom of an underlying neurological disorder and not as a single disease entity. The clinical presentation of epilepsy depends on a number of factors, chiefly: the parts of the brain affected the pattern of spread of epileptic discharges through the brain, the cause of the epilepsy and the age of the individual (2). (1) M.Sc. Student, Department of Oral Diagnosis, College of Dentistry, University of Baghdad. (2) Professor, Department of Oral Diagnosis, College of Dentistry, University of Baghdad. The classification of the epilepsies is controversial and has tended to focus on both the clinical presentation (type of epileptic seizure) and on the underlying neurological disorder (3). Epilepsy is primarily a clinical diagnosis based on a detailed description of the events before, during and after a seizure given by the person and/or witness. Electroencephalogram (EEG), magnetic resonance imaging (MRI) and computed tomography (CT) are used to investigate individuals with known and suspected epilepsy (4). The UK National General Practice Study of Epilepsy found that 60% of people with epilepsy have convulsive seizures, of which two thirds have focal epilepsies and secondarily generalized seizures and the other third have generalized tonic-clonic seizures. They also found that the majority (60%) of people with newly diagnosed or suspected epileptic seizures had epilepsy with no J Bagh College Dentistry Vol. 26(2), June 2014 Evaluation of oral Oral Diagnosis 70 identifiable etiology. Vascular disease was the etiology in 15% and tumor in 6%. Among older subjects the proportion with an identifiable cause was much higher: 49% were due to vascular disease and 11% to tumors (5). The mainstay of treatment for epilepsy is antiepileptic medications (AEMs) taken daily to prevent the recurrence of epileptic seizures. Since the development of MRI there has been an increase in the number of people identified with epilepsy who could benefit from surgery. There is also a need to ensure provision of appropriate information to people with epilepsy and their carries (6). It is a general impression that patients with epilepsy tend to have poorer oral health and receive less adequate dental treatment in comparison with the general (nonepilepsy) population (7). A survey of oral health and dental status of patients with epilepsy in comparison with the non-epilepsy population had been taken. Only one such survey has been published (8), which was, however, uncontrolled. Others concentrated on only the periodontal status in relation to antiepileptic medication (AEMs) (9).The aim was to test statistically whether these patients did indeed have poorer oral health compared with that of the nonepilepsy population, and if so, to cast light on the possible reasons and measures to be taken to avoid it. Oral health is an important aspect of quality of life, and every effort should therefore be made to improve oral health, especially in a group of people already disadvantageously affected by their disease. Since no extensive study was conducted in Iraq on the effect of epilepsy and AEMs on the oral health (Carbamazepine and sodium valproate), therefore this study was to detect the relationship between epilepsy and oral health status in relation to salivary IgA, Cystatin C and salivary flow rate were determined. MATERIALS AND METHODS The study sample consisted of (70) patients complaining from epilepsy, 50 % of them (35) patients were taking carbamazepine; the other 50% (35) patients were taking sodium valproate (patients were on medication for minimal 6 months) and the control group is (18) apparently healthy individual of both genders; they were examined from the period (Jan-2013 to May - 2013) in Al-Yarmouk Teaching Hospital in Baghdad, to detect the oral manifestations related to these antiepileptic medications and IgA and Cystatin C were measured in the saliva of both groups. Approval was obtained from Ministry of Health for patient’s examination and collection of saliva and laboratory work. Exclusion criteria: Patients with other chronic diseases such as: metabolic, liver disease, severe inflammation, malignancy or children under the age of 6 or individuals above 60 years. Instruments used for oral examination of patients - Diagnostic instruments - Disposable gloves. - Periodontal probes. - Antiseptic solution (Hipitane 5%). - Dental Chair Oral Examination All the patients examined by a single examiner, under standardized conditions; the oral cavity examined by diagnostic instrument. The procedure of examination of oral soft tissue was done in sequence according to directions suggested by the WHO(1987), the examination begun with the lip, upper and lower sulcus, retro-molar area, upper and lower labial mucosa, buccal mucosa, then the hard and soft palate, dorsal, margins and inferior surface of tongue, floor of the mouth were also examined. In case of oral mucosal lesion, the duration, size, clinical description, location of lesion, and finally the clinical diagnosis were stated. Oral Manifestations Dry Mouth (Salivary flow rate) Dry mouth is a common symptom most often caused by a decrease in the amount of saliva or a change in the quality of saliva. (10). In this study dry mouth and salivary flow rate were diagnosed according to the anamenesis below: Does your mouth feel dry? Do you experience any difficulties in chewing dry foods? Do you experience any difficulties in swallowing dry foods? Are you aware of any recent increase in the frequency of liquid intake? (11) Salivary flow rate measurement The average salivary flow rate was obtained from the total volume collected in the study time (12) and salivary flow rate was calculated as ml/min. Mucositis Oral mucositis is inflammation of the mucosa of the mouth which ranges from redness to severe ulceration. Symptoms of mucositis vary from pain J Bagh College Dentistry Vol. 26(2), June 2014 Evaluation of oral Oral Diagnosis 71 and discomfort to an inability to tolerate food or fluids Candidal infection It was determined clinically. Dysguisia Taste alteration can be diagnosed in this study according to the criteria taken from the European Organization for Research and Treatment of Cancer (EORTC): Have you had problems with your sense of taste? and did food and drink taste different from usual? The abnormal taste may appear bizarre or limited to a part of the mouth. (13). Caries presentation DMFT index (14) : Decayed-Missing-Filled Index (DMF) which was introduced by Klein, Palmer and Knutson in 1938 and modified by WHO: DMF teeth index (DMFT) which measures the prevalence of dental caries/Teeth. Gingival overgrowth and bleeding(Gingival Index) (15). Indices used for gingival disease assessment: *Gingival Index (GI).... which was introduced by Loe and Silness in 1963 Immunological analysis Saliva collection: the method of Wu-Wang was used for saliva collection (16). To avoid circadian variation, saliva samples were collected between 9 a.m. and 1 p.m. In order to obtain a sample of total saliva, the patients were instructed not to eat or drink (except water) for 1 hour (17). Mouth washing with pure water was carried out right before sampling. All participants were instructed to collect saliva in their mouths for 5 minutes and to spit into a clean plastic container (plain tube). Saliva samples were kept in ice during the collection. In order to reduce bubble and foam, samples were centrifuged, pipetted into two androff tubes one for IgA and the other for Cystatin C analysis and stored at 70 oC freezer until immunological analysis (18). Finally levels of salivary IgA and Cystatin C were determined by ELISA. Immunological analysis (Salivary IgA) Determination of salivary IgA is done by Enzyme Link Immunosorbent Assay ELISA (19). Immunological analysis (Cystatin C) This assay employs the quantitative sandwich enzyme immunoassay technique. Antibody specific for Cys-C has been pre-coated onto a micro plate. Standards and samples are pipetted into the wells and any Cys-C present is bound by the immobilized antibody. After removing any unbound substances, a biotin-conjugated antibody specific for Cys-C is added to the wells. After washing, avidin conjugated Horseradish Peroxidase (HRP) is added to the wells. Following a wash to remove any unbound avidin- enzyme reagent, a substrate solution is added to the wells and color develops in proportion to the amount of Cys-C bound in the initial step. The color development is stopped and the intensity of the color is measured. RESULTS The mean age range of sodium valproate group was significantly lower than carbamazepine group. As shown in Table 1. Table 1: The difference between Carbamazepine and sodium valproate treatment for epilepsy on mean of age range Carbamazepine sodium valproate P Age (years) <0.001 Range (6 - 60) (6 - 60) Mean 31.5 20.4 SD 13.9 11 SE 2.36 1.87 N 35 35 Table 2: The difference between Carbamazepine and sodium valproate treatment for epilepsy on mean of salivary IgA, DMFT and GI. Carbamazepine Sodium valproate P Salivary IgA 0.74[NS] Range (59 - 369) (80 - 379) Mean 237.8 244.5 SD 91.7 75.9 SE 15.5 12.83 N 35 35 DMFT 0.02 Range (1 - 20) (0 - 20) Mean 7.9 5.5 SD 3.9 4.4 SE 0.65 0.74 N 35 35 Gingival Index 0.008 Range (0.12 - 1.43) (0.04 - 1.25) Mean 0.63 0.43 SD 0.31 0.29 SE 0.052 0.049 N 35 35 J Bagh College Dentistry Vol. 26(2), June 2014 Evaluation of oral Oral Diagnosis 72 Both DMFT and GI were significantly lower in sodium valproate group than carbamazepine group. While IgA was higher in valproate group but failed to reach the statistical significance (Table 2). Salivary flow rate was higher in sodium valproate group and cystatin C was lower in the same group than in carbamazepine group, even though both differences were not significant. (Table 3). Table 3: The difference between Carbamazepine and sodium valproate treatment for epilepsy on median of salivary flow rate and Cystatin C. Carbamazepine Sodium valproate P Salivary Flow Rate 0.2 [NS] Range (0.01 - 1.2) (0.02 - 1.3) Median 0.2 0.33 Inter- quartile range (0.05 - 0.56) (0.1 - 0.52) N 35 35 Mean rank 32.4 38.6 Salivary Cystatin C 0.51 [NS] Range (20.5 - 450) (17 - 320) Median 80 72 Inter- quartile range (60 - 135) (45 - 150) N 35 35 Mean rank 37.1 33.9 In figure (1) it is shown that mucositis was significantly higher in carbamazepine group than valproate group. Both candida infection and dysguisia were higher in carbamazepine group but fail to reach statistical significance. DISCUSSION Salivary IgA is the prominent immunoglobulin and is considered to be the main specific defense mechanism in oral cavity (8). The variations in the immunoglobulin level in different studies are related to the source, method of collection, measurement as well as number of other variable, the salivary secretion rates may inversely influence the IgA concentration in saliva (20). IgA was higher in valproate -group, this may be due to the effect of the drug on the immune system. DMFT and GI were lower in valproate group as they have higher IgA The present study shows that the mucositis is significantly lower in patient on sodium valproate treatment as compared to the carbamazepine group this may be due to higher salivary flow rate and higher IgA. Figure 1: Bar chart showing Carbamazepine - sodium valproate difference in positivity rate of selected clinical features. Tegretol and depakene are the trade names for carbamazepine and sodium valproate respectively. REFERENCES 1. 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