Relationships Among Hippocampal Volumetry, Proton Magnetic Resonance Spectroscopy, and Verbal Memory in Temporal Lobe Epilepsy Stephen M. Sawrie, Roy C. Martin, Robert Knowlton, Ed Faught, Frank Gilliam, and Ruben Kuzniecky Epilepsy Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A. Summary: Purpose: To examine the relationship between hippocampal volumes, 1 H magnetic resonance spectroscopy (MRS)-identified hippocampal metabolic function, and verbal memory in patients with unilateral mesial temporal lobe epi- lepsy (MTLE). Methods: Hippocampal volumes, 1 H MRS-derived hippo- campal creatine to N-acetylaspartate (Cr/NAA), and verbal memory assessment were obtained preoperatively in 22 pa- tients (six right, 16 left) with EEG-defined unilateral MTLE. Results: Left hippocampal volume correlated significantly with left hippocampal Cr/NAA (r  -0.549, p < 0.01), where- as right volume correlated significantly with right Cr/NAA (r  -0.478, p < 0.05). Verbal memory correlated significantly with left hippocampal Cr/NAA (r  -0.594, p < 0.01), but not with left hippocampal volume or right hippocampal measures. Conclusions: Hippocampal volumes and 1 H MRS-derived metabolite ratios are statistically related, but share only a small percentage of variance, suggesting separate but related patho- physiologic processes. Left hippocampal Cr/NAA appears to be more sensitive to verbal memory function than volumes. Key Words: Temporal lobe epilepsy—Epilepsy surgery—MRI— Volumetry—Proton magnetic resonance spectroscopy— Neuropsychology—Memory. Mesial temporal lobe epilepsy (MTLE) provides one of the better prototypes for the study of hippocampal pathology and memory function. Quantitative neuropa- thology studies of resected hippocampal tissue from pa- tients who have undergone surgery for MTLE have demonstrated a significant relationship between hippo- campal neuronal density and memory (1–3). The recent development of quantitative magnetic resonance (MR) techniques has allowed an in vivo examination of human hippocampus and memory. MRI hippocampal volumetry has demonstrated reliable correlations between hippo- campal structure and preoperative memory (4,5). The preoperative volume of the epileptogenic hippocampus is also a reliable predictor of postsurgical memory outcome (6,7). More recently, [ 1 H]-MR spectroscopy (MRS) has been used to study specific metabolites in the hippocam- pi of patients with MTLE, including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho). Levels of hip- pocampal NAA relative to Cr (NAA/Cr) have been found to correlate significantly with episodic memory function (8,9), semantic memory function (10), and in- telligence (11) in patients with MTLE. NAA is thought to reside almost exclusively in neurons (12), and it has therefore been interpreted as simply a marker for neuro- nal density (13,14). However, several recent studies have failed to find a significant association between degree of hippocampal atrophy and 1 H MRS-identified hippocam- pal metabolite ratios (15,16). Abnormal levels of hippo- campal NAA/Cr have been found in MRI-negative patients with TLE (17). Furthermore, abnormal preop- erative levels of NAA/Cr have been shown to normalize in the contralateral hippocampus after successful epi- lepsy surgery (18,19). These studies suggest that NAA may be a marker for neuronal function rather than structure. The lack of a strong correlation between MRI volum- etry and [ 1 H]-MRS suggests that the two technologies are measuring different pathophysiologic processes, yet both technologies yield meaningful information regard- ing cognitive function. Furthermore, both technologies appear to lateralize well, both independently and in combination (15,20). Thus the present study has two ob- jectives; (a) to examine the relationship between hippo- campal volumes and [ 1 H]-MRS-identified hippocampal Revision accepted July 10, 2001. Address correspondence and reprint requests to Dr. S.M. Sawrie at UAB Epilepsy Center, 1719 6 th Avenue South, CIRC 312, Birming- ham, AL 35294, U.S.A. E-mail: ssawrie@uab.edu Epilepsia, 42(11):1403–1407, 2001 Blackwell Science, Inc. © International League Against Epilepsy 1403