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【Epilepsy】癫痫患者海马萎缩伴有细胞外谷氨酸增
*†Idil Cavus, ‡Jullie W. Pan, †Hoby P. Hetherington, *Walid Abi-Saab, ‡Hitten P. Zaveri, †Kenneth P. Vives, *John H. Krystal, †‡Susan S. Spencer, and †Dennis D. Spencer
Departments of *Psychiatry , †Neurosurgery , and ‡Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
Address correspondence to Idil Cavus, M.D., Ph.D., Yale University, Department of Psychiatry, 300 George St., 9th Floor, Room 27, New Haven, CT 06511, U.S.A. E-mail: idil.cavus@yale.edu
Walid Abi-Saab is currently in Abbott Laboratories.
Copyright © 2008 by the International League Against Epilepsy
KEYWORDS
Hippocampal volume • Glutamate • GABA • Microdialysis • MRI • Epilepsy • TLE
ABSTRACT
Purpose: Temporal lobe epilepsy (TLE) is associated with smaller hippocampal volume and with elevated extracellular (EC) glutamate levels. We investigated the relationship between the hippocampal volume and glutamate in refractory TLE patients.
Methods: We used quantitative MRI volumetrics to measure the hippocampal volume and zero-flow microdialysis to measure the interictal glutamate, glutamine, and GABA levels in the epileptogenic hippocampus of 17 patients with medication-resistant epilepsy undergoing intracranial EEG evaluation. The relationships between hippocampal volume, neurochemical levels, and relevant clinical factors were examined.
Results: Increased EC glutamate in the epileptogenic hippocampus was significantly related to smaller ipsilateral (R2= 0.75, p < 0.0001), but not contralateral hippocampal volume when controlled for glutamine and GABA levels, and for clinical factors known to influence hippocampal volume. Glutamate in the atrophic hippocampus was significantly higher (p = 0.008, n = 9), with the threshold for hippocampal atrophy estimated as 5 μM. GABA and glutamine levels in the atrophic and nonatrophic hippocampus were comparable. Decreased hippocampal volume was related to higher seizure frequency (p = 0.008), but not to disease duration or febrile seizure history. None of these clinical factors were related to the neurochemical levels.
Conclusions: We provide evidence for a significant association between increased EC glutamate and decreased ipsilateral epileptogenic hippocampal volume in TLE. Future work will be needed to determine whether the increase in glutamate has a causal relationship with hippocampal atrophy, or whether another, yet unknown factor results in both. This work has implications for the understanding and treatment of epilepsy as well as other neurodegenerative disorders associated with hippocampal atrophy.
http://www3.interscience.wiley.com/journal/120120294/abstract 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients
癫痫患者MRI海马容积减少与细胞外谷氨酸水平增加有关
ABSTRACT
Purpose: Temporal lobe epilepsy (TLE) is associated with smaller hippocampal volume and with elevated extracellular (EC) glutamate levels. We investigated the relationship between the hippocampal volume and glutamate in refractory TLE patients.
研究目的：颞叶癫痫（TLE）与海马容积减小以及细胞外谷氨酸水平上升有关。我们对难治性TLE患者海马容积与谷氨酸之间的关联性进行分析。
Methods: We used quantitative MRI volumetrics to measure the hippocampal volume and zero-flow microdialysis to measure the interictal glutamate, glutamine, and GABA levels in the epileptogenic hippocampus of 17 patients with medication-resistant epilepsy undergoing intracranial EEG evaluation. The relationships between hippocampal volume, neurochemical levels, and relevant clinical factors were examined.
研究方法：我们利用MRI定量容积测量技术测量17例经颅内EEG评估确定的药物抵抗癫痫患者海马容积，并利用零流量微量分析技术测量其致痫区海马发作间的谷氨酸、谷胺酰胺和GABA浓度。分析海马容积，上述神经化学物质浓度以及临床因素之间的关系。
Results: Increased EC glutamate in the epileptogenic hippocampus was significantly related to smaller ipsilateral (R2= 0.75, p < 0.0001), but not contralateral hippocampal volume when controlled for glutamine and GABA levels, and for clinical factors known to influence hippocampal volume. Glutamate in the atrophic hippocampus was significantly higher (p = 0.008, n = 9), with the threshold for hippocampal atrophy estimated as 5 μM. GABA and glutamine levels in the atrophic and nonatrophic hippocampus were comparable. Decreased hippocampal volume was related to higher seizure frequency (p = 0.008), but not to disease duration or febrile seizure history. None of these clinical factors were related to the neurochemical levels.
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作者:admin@医学,生命科学 2011-05-29 05:14
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