Pengaruh durasi pemberian fenitoin terhadap gangguan fungsi eksekutif pada pasien epilepsi tonik klonik
https://doi.org/10.22146/bns.v19i2.69199 Kinanti Sekarsari(1*), Astuti Astuti(2), Ismail Setyopranoto(3)
(1) KSM Saraf, RS Universitas Islam Indonesia, Yogyakarta
(2) Departemen Neurologi Fakultas Kedokteran, Kesehatan Masyarakat, dan Keperawatan, Universitas Gadjah Mada, Yogyakarta
(3) Departemen Neurologi Fakultas Kedokteran, Kesehatan Masyarakat, dan Keperawatan, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author
Abstract
One comorbid in epilepsy patients is impaired executive function caused by antiepileptic drugs. Phenytoin is a widely used antiepileptic drug especially for generalized tonic clonic epilepsy therapy which cause cognitive impairment if given in long-term duration. This study aims to determine the relationship between duration of phenytoin monotherapy use and the decrease of the specific domain of cognitive executive function of mental flexibility, planning, verbal fluency, and working memory in adult generalized tonic clonic epileptic patient. Retrospective cohort studies were performed by conducting executive function assessments with Trail Making Test B, Clock Drawing Test, Digit Span Test, and Animal Verbal Fluency Test at the time of study, then the duration of phenytoin use was taken from the patient’s medical records during the first phenytoin therapy. Of the 102 subjects, bivariate analysis results showed a significant correlation between the duration of phenytoin therapy and executive function in mental flexibility domain (p
=0.001; RR =1.88), verbal fluency domain (p =0.002; RR =3.24), planning domain (p =0.008; RR =7.46), and on domain working memory (p =0.000; RR =6.16). In a multivariate analysis logistic regression showed that the executive domain function of working memory disorder was an independent factor due to phenytoin >1 year in patients with generalized tonic clonic epileptic seizures (p =0.005).
ABSTRAK
Salah satu komorbid pada pasien epilepsi adalah gangguan fungsi eksekutif yang disebabkan oleh pemakaian obat antiepilepsi. Fenitoin adalah obat antiepilepsi yang banyak digunakan terutama untuk terapi epilepsi dengan bangkitan umum tonik klonik yang memiliki efek menyebabkan gangguan kognitif jika diberikan dalam durasi jangka panjang. Penelitian ini bertujuan mengetahui adanya hubungan antara durasi penggunaan monoterapi fenitoin dengan penurunan domain kognitif spesifik fungsi eksekutif yaitu mental flexibility, planning, verbal fluency, dan working memory pada pasien epilepsi dewasa bangkitan umum tonik klonik. Penelitian kohort retrospektif dilakukan dengan melakukan asesmen fungsi eksekutif dengan tools Trail Making Test B, Clock Drawing Test, Digit Span Test, dan Animal Verbal Fluency Test pada saat studi, kemudian durasi pemakaian fenitoin diambil dari catatan medis pasien saat dilakukan terapi fenitoin yang pertama kali. Dari 102 subjek, hasil analisis bivariat terdapat korelasi yang bermakna durasi penggunaan terapi fenitoin dengan gangguan fungsi eksekutif pada domain mental flexibility (p =0,001; RR =1,88), pada domain planning (p =0,008; RR =7,46), domain verbal fluency (p =0,002; RR =3,24) dan pada domain working memory (p =0,000; RR =6,16). Pada analisis multivariat regresi logistik menunjukkan bahwa gangguan domain fungsi eksekutif working memory merupakan faktor independen akibat pemberian fenitoin >1 tahun pada pasien epilepsi bangkitan umum tonik klonik (p =0,005).
Keywords
Full Text:
PDFReferences
1. Shehata GA, Bateh AEM, Hamed SA. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy. Neuropsychiatric Disease and Treatment. 2009;5:527-533.
2. Baker GA, Hothersal AJ, Mallow JE. Memory. Epilepsy Action. 2008;10:1-6.
3. Desai JD. Epilepsy and cognition. Journal of Pediatric Neurosciences. 2008;3(1):16-27.
4. Bender HA, Auciello D, Morrison CE, MacAllister WS, Zaroff CM. Comparing the convergent validity and clinical utility of the Behavior Assessment System for Children-Parent Rating Scales and Child Behavior Checklist in children with epilepsy. Epilepsy & Behavior. 2008;13(1):237-242.
5. Faria C de A, Alves HVD, Charchat-Fichman H. The most frequently used tests for assessing executive functions in aging. Dementia & Neuropsychologia. 2015;9(2):149–155.
6. Manford M. Practical guide to epilepsy. Burlington, MA: Butterworth-Heinemann; 2003.
7. Ames BN, Shigenaga MK, Gold LS. DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis. Environmental Health Perspectives. 1993;101(suppl 5):35-44.
8. Sherman EM, Slick DJ, Eyrl KL. Executive dysfunction is a significant predictor of poor quality of life in children with epilepsy. Epilepsia. 2006;47(11):1936-1942.
9. Aldenkamp AP, Krom MD, Reijs R. Newer antiepileptic drugs and cognitive issues. Epilepsia. 2003;44:21-29.
10. Kim EH, Ko TS. Cognitive impairment in childhood onset epilepsy: up-to-date information about its causes. Korean Journal of Pediatrics. 2016;59(4):155.
11. Loring DW, Meador KJ. Cognitive and behavioural effects of epilepsy treatment. Epilepsia. 2001;42:24-32.
12. Sudha S, Lakshmana MK, Pradhan N. Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels. Pharmacology Biochemistry and Behavior. 1995;52(1):119-124.
13. McQueen CA, Reilly C, editors. Respiratory toxicology. Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo: Elsevier; 2018.
14. Schlienger RG, Shear NH. Antiepileptic drug hypersensitivity syndrome. Epilepsia. 1998;39:S3–S7.
15. Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002;58:S9–S20.
16. Farwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures—effects on intelligence and on seizure recurrence. New England Journal of Medicine. 1990;322(6):364-369.
17. Ortinski P, Meador KJ. Cognitive side effects of antiepileptic drugs. Epilepsy & Behavior. 2004;5:60-65.
18. Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs. Epilepsy research. 2002;51(3):237-247.
19. Tassino M, Campos TF, Guerra RO. Homocysteine (Hcy) and cognitive performance in a population sample of elderly Brazilians. Archives of Gerontology and Geriatrics. 2009;48(2):142-145.
20. Sullivan PM, Han B, Liu F, Mace BE, Ervin JF, Wu S, Koger D, Paul S, Bales KR. Reduced levels of human apoE4 protein in an animal model of cognitive impairment. Neurobiology of Aging. 2011;32(5):791-801.
21. 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(2):79-85.
22. Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Research. 2001;47(1-2):27–35.
23. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dementia and Geriatric Cognitive Disorders.1999;10(1):12–20.
24. Lin SK, Kao JT, Tsai SM, Tsai LY, Lin MN, Lai CJ, et al. Association of apolipoprotein E genotypes with serum lipid profiles in a healthy population of Taiwan. Annals of Clinical & Laboratory Science. 2004;34(4):443-448.
25. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. New England Journal of Medicine. 200;346(7):476-483.
26. Altenburg MK, Malloy SI, Knouff C, Parks JS, Maeda N. ApoE4 trapping by the low density lipoprotein receptor. International Congress Series. 2004;1262:388–391.
27. Eggers C, Herholz K, Kalbe E, Heiss WD. Cortical acetylcholine esterase activity and ApoE4-genotype in Alzheimer disease. Neuroscience Letters. 2006;408(1):46-50.
DOI: https://doi.org/10.22146/bns.v19i2.69199
Article Metrics
Abstract views : 1420
| 
views : 12232
Refbacks
- There are currently no refbacks.
Copyright (c) 2021 Berkala NeuroSains
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.