MRS Measurements of GABA in Temporal Lobe Epilepsy

描述(申请人提供)：作为哺乳动物大脑中主要的抑制性神经递质，GABA及其含量和受体系统是许多抗癫痫药物的靶点。尽管Petroff和他的同事已经研究了各种抗癫痫药物对枕叶(远离致痫区域的部位)大脑GABA水平的影响，但到目前为止，关于颞叶癫痫患者致痫区域的GABA水平的信息很少。这些数据在很大程度上表明，与健康对照组相比，控制不良的患者大脑GABA水平降低，并且对各种抗癫痫药物有反应。相反，最近的初步微透析研究表明，与非硬化症患者相比，硬化症患者的ECF GABA水平更高(6)。此外，我们的初步数据显示，与ECF GABA的相关性类似，与海马NAA水平呈负相关(即，NAA水平较低的患者ECF GABA水平较高。致痫区域的总GABA与对照组相比有多大程度的增加或减少还不得而知。同样，致痫的平行GABA水平是否远离癫痫灶的总GABA水平也是未知的。显然，这些问题可能会对我们理解导致癫痫灶致痫活动的因素产生重大影响，并可能为癫痫患者的治疗提供帮助。因此，开发可靠的方法来测量颞叶癫痫患者的颞叶GABA将是非常有益的。

DESCRIPTION (provided by applicant): As the primary inhibitory neurotransmitter in mammalian brain, GABA, its content and its receptor systems are the targets of a number of anti-epileptic drugs. Although Petroff and colleagues have studied the effects of various anti-epileptics on brain GABA levels in the occipital lobe, a site distant from the epileptogenic region, to date little information exists regarding GABA levels in the epileptogenic region of patients with temporal lobe epilepsy. This data has largely shown that brain GABA levels are decreased in patients with poor control in comparison to healthy controls and are responsive to a variety of anti-epileptic medications. Conversely, recent preliminary microdialysis studies have shown that ECF GABA is higher in patients with sclerosis as opposed to those without sclerosis (6). Additionally our preliminary data has shown a similar correlation with ECF GABA inversely correlated with hippocampal NAA levels (i.e higher ECF GABA levels are seen in patients with lower NAA levels. To what extent total GABA in the epileptogenic region is increased or decreased relative to control is unknown. Similarly it is unknown if total GABA levels in the epileptogenic parallel GABA levels distant from the seizure focus. Clearly these questions may have significant impact on our understanding of the factors leading to epileptogenic activity in the seizure focus and also provide measures that may aid in the therapeutic management of epilepsy patients. Therefore the development of robust methods for measuring GABA from the temporal lobe in patients with temporal lobe epilepsy would be of significant benefit.