Summary:Purpose: In some patients with temporal lobe epilepsy, histopathological evaluation of resected brain tissue after surgical treatment may reveal several features indicative of discrete cortical malformations. We sought to determine whether these histopathological features were accompanied by hippocampal changes detectable preoperatively by proton magnetic resonance (MR) spectroscopy and to evaluate their relationship with postoperative outcome.Methods: In 25 consecutive temporal lobe epilepsy patients who were scheduled for surgical treatment, MR spectroscopy was performed, and resected brain tissue was analyzed histopathologically for the presence of discrete cortical malformations (e.g., microdysgenesis). Outcome was assessed in all patients with an average postoperative period of 26 months.Results: In 13 patients, we found subtle, histopathologically detectable signs of cortical malformation: 6 of them with concomitant hippocampal sclerosis (dual pathology) and 7 without. The latter subgroup had a worse surgical outcome and showed enhanced bilateral and/or contralateral pathological changes in the hippocampal formation when investigated by MR spectroscopy.Conclusions: These data suggest that by showing contralaterally or bilaterally abnormal spectra, MR spectroscopy might be able to indicate pathological changes in subtle developmental disorders that are possibly more widespread over the brain. This observation may improve noninvasive diagnosis in presurgical evaluation and the neurobiological understanding of cortical malformations in pharmacoresistant temporal lobe epilepsy. Key Words: MR spectroscopy-Cortical malformations-Pharmacoresistant temporal lobe epilepsy-Neuropathology-Surgical outcome Histopathological analysis of resected brain tissue after surgical treatment can reveal different etiologies (1-3) in epilepsies that were considered "cryptogenic" before surgery, such as hippocampal sclerosis (HS) or cortical malformations (CMs). The diagnosis "cortical malformation" is often based on a high variety of subtle microscopic features, including heterotopic neurons or nodular heterotopia of neurons in the white matter, laminar disorganization, marked clustering of neurons (throughout layers II to VI), marked clustering of oligodendroglia in the white matter, glioneural hamartia, giant neurons, and balloon cell change. To elucidate the value and significance of these histopathological changes, Kasper et al. (4) compared brain tissue of surgically treated temporal lobe epilepsy patients with autopsy brains and demonstrated a higher prevalence of oligoclusters, hamartias, neurons in the white matter, and perivascular neurons in specimens from temporal lobe epilepsy patients. These changes can only be detected by precise histopathological analysis and then may be found as a single phenomenon in the temporal lobe or in combination with HS (dual pathology [DP]).Proton MR spectroscopy is reported to reveal histological abnormalities (particularly HS [5][6][7][8] but also CMs [9][10][11]) by obtaining s...