Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
Department of Neurosurgery, Washoukai Sadamoto Hospital, 1-6-1 Takehara, Matsuyama, Ehime, 790-0052, Japan.
Acta Neurochir (Wien). 2022 Dec;164(12):3253-3266. doi: 10.1007/s00701-022-05363-y. Epub 2022 Sep 15.
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).
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.
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.
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.
已知细胞外谷氨酸水平升高会导致胶质母细胞瘤（GBM）患者发生癫痫发作。然而，预测癫痫是否会成为难治性的则较为困难。本研究通过磁共振波谱（MRS）定量测量代谢物浓度，探讨评估包括谷氨酸在内的各种代谢物水平是否可以预测 GBM 患者难治性癫痫的发生。
2017 年 4 月至 2021 年 7 月，在爱媛大学医院，按照相同的原发性 GBM 治疗方案对 40 名患者进行治疗。其中 23 名患者接受 MRS 检查，通过 LC-Model 测定肿瘤周边谷氨酸、N-乙酰天冬氨酸、肌酸和乳酸等代谢物的浓度。每种代谢物的浓度均表示为与肌酸浓度的比值。将患者分为三组：A 型，无癫痫发作；B 型，经治疗后癫痫发作消失；C 型，经治疗后癫痫仍未缓解或发作（难治性癫痫）。分析代谢物浓度与癫痫发作类型之间的关系。
在 23 例 GBM 中，11 例患者出现癫痫发作，其中 B 型 4 例，C 型 7 例。癫痫发作患者（B 型或 C 型）的谷氨酸和 N-乙酰天冬氨酸值明显高于非癫痫发作患者（A 型）（p<0.05）。B 型和 C 型患者的谷氨酸或 N-乙酰天冬氨酸水平无显著差异。相反，C 型患者的乳酸浓度明显高于 B 型（p=0.001）。乳酸/肌酸、谷氨酸/肌酸和 N-乙酰天冬氨酸/肌酸比值的截值分别为>1.25、>1.09 和>0.88，用于预测难治性癫痫发作。
难治性癫痫发作的 GBM 患者肿瘤周边细胞外谷氨酸、N-乙酰天冬氨酸和乳酸浓度显著升高。MRS 测量这些代谢物可能有助于预测此类患者的难治性癫痫，并可能成为继续使用抗癫痫药物的指标。
