Magnetic Resonance Spectroscopy and Metabolic MRI in Epilepsy: A Systematic Review and Quantitative Synthesis of Neurochemical Biomarkers and Clinical Applications

Abstract Background: Since the introduction of proton magnetic resonance spectroscopy (¹H-MRS) in epilepsy research in the 1980s, metabolic MRI has provided unique insights into the neurochemical alterations underlying epilepsy. However, evidence has remained fragmented across imaging modalities, epilepsy syndromes, and clinical applications. We systematically reviewed the literature to define the metabolic phenotype of epilepsy and evaluate the evolving role of metabolic MRI in epilepsy research and clinical practice. Methods: Following PRISMA 2020 guidelines, PubMed and Scopus were systematically searched through April 2026 for original human studies investigating metabolic MRI in epilepsy. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were synthesized through structured qualitative evidence, supported by integrated methodological, scientometric, tabular, and visual analyses. Results: A total of 298 studies were included. Focal epilepsy demonstrated widespread alterations involving N-acetyl aspartate, glutamate, Gamma-aminobutyric acid, choline-containing compounds, myo-inositol, lactate, and other metabolites across epileptogenic and brain networks. Generalized epilepsy was characterized by predominantly bilateral and thalamo-cortical metabolic abnormalities, whereas tumor-associated epilepsy showed distinct metabolic alterations within tumors and the peritumoral zone. Treatment and prognostic studies demonstrated metabolite-specific changes following pharmacological and surgical interventions, and emerging metabolic MRI techniques provided complementary information on bioenergetics, ionic homeostasis, glutamatergic cycling, and metabolic flux. Conclusions: The available evidence supports epilepsy as a disorder of distributed metabolic networks that share a common signature of neuronal dysfunction while exhibiting syndrome-specific alterations in neurotransmission, gliosis, and energy metabolism. Complementary metabolic MRI techniques provide distinct biological information, but their clinical translation will require methodological harmonization and multimodal integration.