Multimodal Hippocampal Spectroscopy and Cognitive Profile in Mesial Temporal Lobe Epilepsy: A Case–Control Study

Abstract. Introduction. Mesial temporal lobe epilepsy (MTLE) is a frequent focal epilepsy and a significant cause of pharmacoresistance. Hippocampal magnetic resonance spectroscopy (MRS) and multimodal cognitive evaluation allow examination of its metabolic and functional correlates. Objective. To determine whether hippocampal MRS abnormalities differentiate MTLE from healthy controls and to describe the resulting cognitive profile using the NEUROPSI battery. Materials and Methods. Retrospective case–control study, N = 175 (85 MTLE, 90 controls). Structural MRI, hippocampal MRS, interictal single-photon emission computed tomography (SPECT), EEG/video-EEG, and age- and education-adjusted NEUROPSI were applied. Mixed-effects models, logistic regression, ANCOVA with covariates (age, sex, education), and false-discovery-rate correction were used. Results. Hippocampal N-acetylaspartate-to-creatine (NAA/Cr) and N-acetylaspartate-to-choline (NAA/Cho) ratios were lower in MTLE than in controls (NAA/Cr: t(173) = 13.8, p < .001; NAA/Cho: t(173) = 11.5, p < .001). A significant group × hemisphere interaction was observed (F(1, 173) = 18.4, p < .001) with left-sided predominance. Logistic regression for abnormal spectroscopy yielded adjusted OR = 8.70, 95% CI [4.00, 18.80], p < .001; AUC = 0.91. NEUROPSI revealed the largest group effect in visuospatial skills (F(1, 171) = 45.2, p < .001, partial η² = 0.21), followed by attention/concentration and executive functions. Conclusions. Hippocampal MRS identifies a distinctive metabolic pattern in MTLE and is associated with a selective cognitive profile involving visuospatial, attentional, and executive domains, supporting its incorporation into multimodal neuropsychiatric assessment.