Yawara Nakamura1, Akihiro Inoue2, Masahiro Nishikawa1, Takanori Ohnishi3, Hajime Yano4, Yonehiro Kanemura5,6, Yoshihiro Ohtsuka1, Saya Ozaki1, Kosuke Kusakabe1, Satoshi Suehiro1, Daisuke Yamashita1, Seiji Shigekawa1, Hideaki Watanabe1, Riko Kitazawa7, Junya Tanaka4, Takeharu Kunieda1. 1. Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan. 2. Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan. iakihiro3@gmail.com. 3. Department of Neurosurgery, Washoukai Sadamoto Hospital, 1-6-1 Takehara, Matsuyama, Ehime, 790-0052, Japan. 4. Department of Molecular and Cellular Physiology, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan. 5. Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Osaka, 540-0006, Japan. 6. Department of Neurosurgery, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Osaka, 540-0006, Japan. 7. Division of Diagnostic Pathology, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
Abstract
BACKGROUND: Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS). METHODS: Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated. RESULTS: In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively. CONCLUSIONS: Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.
BACKGROUND: Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS). METHODS: Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated. RESULTS: In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively. CONCLUSIONS: Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.
Authors: Michael C Dewan; Reid C Thompson; Steven N Kalkanis; Fred G Barker; Constantinos G Hadjipanayis Journal: J Neurosurg Date: 2016-06-24 Impact factor: 5.115
Authors: Changho Choi; Sandeep K Ganji; Ralph J DeBerardinis; Kimmo J Hatanpaa; Dinesh Rakheja; Zoltan Kovacs; Xiao-Li Yang; Tomoyuki Mashimo; Jack M Raisanen; Isaac Marin-Valencia; Juan M Pascual; Christopher J Madden; Bruce E Mickey; Craig R Malloy; Robert M Bachoo; Elizabeth A Maher Journal: Nat Med Date: 2012-01-26 Impact factor: 53.440
Authors: Jacqueline A French; Gregory L Krauss; Robert T Wechsler; Xue-Feng Wang; Bree DiVentura; Christian Brandt; Eugen Trinka; Terence J O'Brien; Antonio Laurenza; Anna Patten; Francesco Bibbiani Journal: Neurology Date: 2015-09-15 Impact factor: 9.910