Hubungan Rasio GABA/Glutamate pada Magnetic Resonance Spectroscopy dengan Gambaran Lesi pada Epilepsi

Authors

  • Rachmi Fauziah Rahayu Rumah Sakit Umum Daerah Dr. Moewardi
  • Sulistyani Kusumaningrum Rumah Sakit Umum Daerah Dr. Moewardi
  • Maryama Aisyah Pribadi Rumah Sakit Umum Daerah Dr. Moewardi

DOI:

https://doi.org/10.58344/locus.v5i8.6131

Keywords:

Epilepsi, GABA, Glutamat, Magnetic Resonance Spectroscopy, Lesi Otak, Biomarker

Abstract

Epilepsi merupakan gangguan neurologis kronis yang ditandai oleh ketidakseimbangan neurotransmiter eksitatori dan inhibitor, terutama glutamat dan gamma-aminobutyric acid (GABA), yang berperan dalam proses epileptogenesis dan kekambuhan kejang. Pemeriksaan Magnetic Resonance Imaging (MRI) konvensional belum selalu mampu mendeteksi seluruh lesi struktural sehingga diperlukan biomarker tambahan yang dapat menggambarkan perubahan metabolik jaringan otak epileptogenik. Penelitian ini bertujuan menganalisis hubungan antara rasio GABA/glutamat yang diukur menggunakan Magnetic Resonance Spectroscopy (MRS) dengan gambaran lesi pada pasien epilepsi. Penelitian menggunakan desain cross-sectional prospektif terhadap 52 pasien epilepsi yang menjalani pemeriksaan MRS di Instalasi Radiologi RSUD Dr. Moewardi Surakarta dengan teknik consecutive sampling. Analisis data meliputi statistik deskriptif, uji normalitas Shapiro–Wilk, uji Fisher's Exact, serta analisis akurasi diagnostik. Hasil penelitian menunjukkan bahwa 94,2% pasien memiliki rasio GABA/glutamat yang tidak normal, mencerminkan adanya ketidakseimbangan neurokimia yang dominan. Tidak ditemukan hubungan yang bermakna antara rasio GABA/glutamat dengan lokasi lesi (p = 0,660) maupun jenis lesi (p = 0,723). Analisis diagnostik menunjukkan sensitivitas sebesar 95,0%, spesifisitas 10,0%, nilai prediksi positif 81,6%, dan nilai prediksi negatif 33,3%. Disimpulkan bahwa rasio GABA/glutamat lebih merefleksikan aktivitas metabolik epileptogenik dibandingkan karakteristik lesi struktural serta berpotensi menjadi biomarker pelengkap MRI dalam evaluasi klinis pasien epilepsi.

References

Akyuz, E., Polat, A. K., Eroglu, E., Kullu, I., Angelopoulou, E., & Paudel, Y. N. (2021). Revisiting the role of neurotransmitters in epilepsy: An updated review. Life Sciences, 265, 118826.

Ali, W. E., Eezz, A. A. E.-B. A., Shafey, R. A. El, & Teama, A. H. (2022). Role of Magnetic Resonance Spectroscopy in Diagnosis of Developmental Delay in Children. Journal of Advances in Medicine and Medical Research, 34(13 SE-Original Research Article), 86–92. https://doi.org/10.9734/jammr/2022/v34i1331382

Baldini, S., Pittau, F., Birot, G., Rochas, V., Tomescu, M. I., Vulliemoz, S., & Seeck, M. (2020). Detection of Epileptic Activity in Presumably Normal EEG. Brain Communications, 2(2), 1–10. https://doi.org/10.1093/braincomms/fcaa104

Beghi, E. (2020). The Epidemiology of Epilepsy. Neuroepidemiology, 54(2), 185–191. https://doi.org/10.1159/000503831

Bryson, A., Reid, C., & Petrou, S. (2023). Fundamental Neurochemistry Review: GABA Receptor Neurotransmission and Epilepsy: Principles, Disease Mechanisms and Pharmacotherapy. Journal of Neurochemistry, 165(1), 6–28. https://doi.org/https://doi.org/10.1111/jnc.15769

Chen, T. S., Huang, T. H., Lai, M. C., & Huang, C. W. (2023). The Role of Glutamate Receptors in Epilepsy. Biomedicines, 11(3). https://doi.org/10.3390/biomedicines11030783

Duncan, J. S. (2019). Brain Imaging in Epilepsy. Practical Neurology, 19(5), 438 LP – 443. https://doi.org/10.1136/practneurol-2018-002180

Fisher, R. S., Cross, J. H., Souza, C. D., French, J. A., Haut, S. R., Higurashi, N., Hirsch, E., Jansen, F. E., Lagae, L., Mosh, S. L., Peltola, J., Perez, E. R., Scheffer, I. E., & Schulze-bonhage, A. (2017). Instruction manual for the ILAE 2017 operational classification of seizure types. 531–542. https://doi.org/10.1111/epi.13671

Ford, T. C., Nibbs, R., & Crewther, D. P. (2017). Glutamate/GABA+ Ratio is Associated with the Psychosocial Domain of Autistic and Schizotypal Traits. PloS One, 12(7), e0181961. https://doi.org/10.1371/journal.pone.0181961

Gong, C., Liu, A., Lian, B., Wu, X., Zeng, P., Hao, C., Wang, B., Jiang, Z., Pang, W., Guo, J., & Zhou, S. (2023). Prevalence and Related Factors of Epilepsy in Children and Adolescents with Cerebral Palsy: A Systematic Review and Meta-analysis. Frontiers in Pediatrics, 11(July). https://doi.org/10.3389/fped.2023.1189648

Goodman, A. M., & Szaflarski, J. P. (2021). Recent Advances in Neuroimaging of Epilepsy. Neurotherapeutics, 18(2), 811–826. https://doi.org/https://doi.org/10.1007/s13311-021-01049-y

Grent-’t-Jong, T., Gajwani, R., Gross, J., Gumley, A. I., Lawrie, S. M., Schwannauer, M., Schultze-Lutter, F., Williams, S. R., & Uhlhaas, P. J. (2022). MR-Spectroscopy of GABA and Glutamate/Glutamine Concentrations in Auditory Cortex in Clinical High-Risk for Psychosis Individuals. Frontiers in Psychiatry, 13(March), 1–10. https://doi.org/10.3389/fpsyt.2022.859322

Ip, I. B., & Bridge, H. (2022). Investigating the Neurochemistry of the Human Visual System Using Magnetic Resonance Spectroscopy. Brain Structure and Function, 227(4), 1491–1505. https://doi.org/10.1007/s00429-021-02273-0

Jamalipour Soufi, G., Hekmat Nia, A., Hajalikhani, P., Mehvari-Habibabadi, J., & Chit Saz, N. (2024). Correlation of Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging with Findings of Electroencephalography in Patients with Temporal Lobe Epilepsy. Journal of Medical Radiation Sciences, 71(1), 51–56. https://doi.org/10.1002/jmrs.718

Kanagasabai, K., Palaniyappan, L., & Théberge, J. (2024). Precision of Metabolite-Selective MRS Measurements of Glutamate, GABA and Glutathione: A review of Human Brain Studies. NMR in Biomedicine, 37(3), e5071. https://doi.org/https://doi.org/10.1002/nbm.5071

Kentab, A. Y., Al Bulayhi, S., Hamad, M. H., Al Wadei, A., & Bashiri, F. A. (2022). Pattern and Etiology of Early Childhood Epilepsy: An Experience at a Tertiary Care University Center. Neurosciences, 27(4), 244–250. https://doi.org/10.17712/nsj.2022.4.20220001

Kiemes, A., Davies, C., Kempton, M. J., Lukow, P. B., Bennallick, C., Stone, J. M., & Modinos, G. (2021). GABA, Glutamate and Neural Activity: A Systematic Review with Meta Analysis of Multimodal (1) H-MRS-fMRI Studies. Frontiers in Psychiatry, 12, 644315. https://doi.org/10.3389/fpsyt.2021.644315

Lee, Y. J., Jo, Y. H., Choi, S. H., Yoo, H. W., Jo, H. Y., Park, S. J., Park, K. H., Kong, J. H., Lee, Y. J., Nam, S. O., & Kim, Y. M. (2024). Is Electroencephalography Useful in Children with Developmental Delays but without Overt Seizures? Annals of Child Neurology, 32(2), 105–114. https://doi.org/10.26815/acn.2024.00444

Lowenstein, D. H. (2018). Seizures and Epilepsy. In J. L. Jameson, A. S. Fauci, D. L. Kasper, S. L. Hauser, D. L. Longo, & J. Loscalzo (Eds.), Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill Education. http://accessmedicine.mhmedical.com/content.aspx?aid=1187887265

Mandei, J. M., & Salendu, P. M. (2022). Tatalaksana Status Epileptikus Terkini pada Anak. E-CliniC, 11(1 SE-Articles), 146–156. https://doi.org/10.35790/ecl.v11i1.44460

Mastrangelo, M. (2021). Epilepsy in Inherited Neurotransmitter Disorders: Spotlights on Pathophysiology and Clinical Management. Metabolic Brain Disease, 36(1), 29–43. https://doi.org/10.1007/s11011-020-00635-x

Mastrangelo, M., & Esposito, D. (2022). Paediatric Sudden Unexpected Death in Epilepsy: From Pathophysiology to Prevention. Seizure, 101(May), 83–95. https://doi.org/10.1016/j.seizure.2022.07.020

Mikkelsen, M., Barker, P. B., Bhattacharyya, P. K., Brix, M. K., Buur, P. F., Cecil, K. M., Chan, K. L., Chen, D. Y.-T., Craven, A. R., Cuypers, K., Dacko, M., Duncan, N. W., Dydak, U., Edmondson, D. A., Ende, G., Ersland, L., Gao, F., Greenhouse, I., Harris, A. D., … Edden, R. A. E. (2017). Big GABA: Edited MR spectroscopy at 24 research sites. NeuroImage, 159, 32–45. https://doi.org/10.1016/j.neuroimage.2017.07.021

NICE The National Institute for Health and Care Excellence. (2019). Epilepsies in Children, Young People and Adults. Nice.Org.Uk, March 2019, 1–11. https://www.nice.org.uk/guidance/indevelopment/gid-ng10112

Rideaux, R., Ehrhardt, S. E., Wards, Y., Filmer, H. L., Jin, J., Deelchand, D. K., Marja?ska, M., Mattingley, J. B., & Dux, P. E. (2022). On the Relationship between GABA+ and Glutamate Across the Brain. NeuroImage, 257. https://doi.org/10.1016/j.neuroimage.2022.119273

Saleh, M. G., Prescot, A., Chang, L., Cloak, C., Cunningham, E., Subramaniam, P., Renshaw, P. F., Yurgelun-Todd, D., Zöllner, H. J., Roberts, T. P. L., Edden, R. A. E., & Ernst, T. (2024). Glutamate Measurements Using Edited MRS. Magnetic Resonance in Medicine, 91(4), 1314–1322. https://doi.org/https://doi.org/10.1002/mrm.29929

Sanaei Nezhad, F., Anton, A., Michou, E., Jung, J., Parkes, L. M., & Williams, S. R. (2018). Quantification of GABA, glutamate and glutamine in a single measurement at 3 T using GABA-edited MEGA-PRESS. NMR in Biomedicine, 31(1), e3847. https://doi.org/https://doi.org/10.1002/nbm.3847

Sarlo, G. L., & Holton, K. F. (2021). Brain Concentrations of Glutamate and GABA in Human Epilepsy: A Review. Seizure, 91(January), 213–227. https://doi.org/10.1016/j.seizure.2021.06.028

Sarmast, S. T., Abdullahi, A. M., & Jahan, N. (2020). Current Classification of Seizures and Epilepsies: Scope, Limitations and Recommendations for Future Action. Cureus, 12(9), e10549. https://doi.org/10.7759/cureus.10549

Savic, I. (2020). MRS Shows Regionally Increased Glutamate Levels among Patients with Exhaustion Syndrome Due to Occupational Stress. Cerebral Cortex, 30(6), 3759–3770. https://doi.org/10.1093/cercor/bhz340

Schubert, K. M., Schmick, A., Stattmann, M., & Galovic, M. (2025). Prognostic Models for Seizures and Epilepsy after Stroke, Tumors and Traumatic Brain Injury. Clinical Neurophysiology Practice, 10(February), 116–128. https://doi.org/10.1016/j.cnp.2025.02.008

Shrikrishana, S. A., & Sachan, A. (2022). Study on MRI Evaluation of Various Etiologies of Seizures. International Journal of Health Sciences, 6(S4 SE-Peer Review Articles), 3970–3977. https://doi.org/10.53730/ijhs.v6nS4.10422

Sone, D. (2021). Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy. Frontiers in Neuroscience, Volume 15. https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.699176

Sumadewi, K. T., Harkitasari, S., & Tjandra, D. C. (2023). Biomolecular Mechanisms of Epileptic Seizures and Epilepsy: A Review. Acta Epileptologica, 5(1). https://doi.org/10.1186/s42494-023-00137-0

Takado, Y., Takuwa, H., Sampei, K., Urushihata, T., Takahashi, M., Shimojo, M., Uchida, S., Nitta, N., Shibata, S., Nagashima, K., Ochi, Y., Ono, M., Maeda, J., Tomita, Y., Sahara, N., Near, J., Aoki, I., Shibata, K., & Higuchi, M. (2022). MRS-measured Glutamate Versus GABA Reflects Excitatory Versus Inhibitory Neural Activities in Awake Mice. Journal of Cerebral Blood Flow and Metabolism, 42(1), 197–212. https://doi.org/10.1177/0271678X211045449

Velde Andersen, J., & Schousboe, A. (2022). Glial Glutamine Homeostasis in Health and Disease. Neurochemical Research, 48, 1–29. https://doi.org/10.1007/s11064-022-03771-1

Vera-González, A. (2022). Pathophysiological Mechanisms Underlying the Etiologies of Seizures and Epilepsy. In Epilepsy. https://doi.org/10.36255/exon-publications-epilepsy-pathopysiology

Wang, Q. (2023). ? -Aminobutyric acid as a biomarker of the lateralizing and monitoring drug effect in patients with magnetic resonance imaging-negative temporal lobe epilepsy. May, 1–13. https://doi.org/10.3389/fnins.2023.1184440

Wijaya, J. S., Saing, J. H., & Destariani, C. P. (2020). Politerapi Antiepilepsi pada Penderita Epilepsi Anak. Cermin Dunia Kedokteran, 47(3 SE-Articles), 191–194. https://doi.org/10.55175/cdk.v47i3.350

Youssf, A. F., Shwaky, K. M., El Ghaiaty, H. A., & Soliman, F. I. (2021). Role of MRI in the Diagnosis of Epilepsy in Children. Benha Journal of Applied Sciences, 6(6), 155–159. https://doi.org/10.21608/bjas.2021.214404

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Published

2026-08-10