Cerebral metabolism in fatal familial insomnia: Relation to duration, neuropathology, and distribution of protease-resistent prion protein
Cerebral metabolism in fatal familial insomnia: Relation to duration, neuropathology, and distribution of protease-resistent prion protein
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DOI：
10.1212/wnl.49.1.126
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发表时间：
1997-07-01
期刊：
影响因子：
9.9
通讯作者：
Fazio, F
中科院分区：
文献类型：
--
作者：
Cortelli, P;Perani, D;Fazio, F
我们使用[F-18]-2-氟-2-脱氧-D-葡萄糖（FDG）和PET研究了7例致命性家族性失眠症（FFI）患者的局部脑葡萄糖利用率，FFI是一种遗传性朊病毒疾病，朊病毒蛋白基因的密码子178处发生突变。4名患者为密码子129处的甲硫氨酸/甲硫氨酸纯合子（症状持续时间，8.5 +/-1个月），3名为甲硫氨酸/缬氨酸（MET/瓦尔（129））杂合子（症状持续时间，35 +/-11个月）。在所有FFI患者中发现丘脑葡萄糖利用率严重降低和扣带回皮质轻度代谢减退。在6名受试者中，大脑代谢低下还影响了基底和外侧额叶皮质、尾状核以及中颞叶皮质和下颞叶皮质。在密码子129处纯合子或杂合子患者之间的比较显示，代谢低下在MET/瓦尔（129）组中更普遍，在[F-18] FDG PET研究时其症状持续时间显著更长。6例患者的神经病理和[F-18] FDG PET结果之间的比较显示，神经元丢失的区域也是低代谢的。然而，脑代谢低下比组织病理学变化更广泛，并与蛋白酶抗性朊蛋白（PrPres）的存在显着相关。我们的研究结果表明，丘脑和扣带回皮质的代谢低下是FFI的标志，而其他大脑区域的参与取决于症状的持续时间和一些未知的因素，具体到每个病人。目前的数据也支持的概念，PrPres的形成是朊病毒疾病的神经元功能障碍的原因。
We used [F-18]-2-fluoro-2-deoxy-D-glucose (FDG) and PET to study regional cerebral glucose utilization in seven patients with fatal familial insomnia (FFI), an inherited prion disease with a mutation at codon 178 of the prion protein gene. Four patients were methionine/methionine homozygotes at codon 129 (symptom duration, 8.5 +/- 1 months) and three were methionine/valine (MET/VAL(129)) heterozygotes (symptom duration, 35 +/- 11 months). A severely reduced glucose utilization of the thalamus and a mild hypometabolism of the cingulate cortex were found in all FFI patients. In six subjects the brain hypometabolism also affected the basal and lateral frontal cortex, the caudate nucleus, and the middle and inferior temporal cortex. Comparison between homozygous or heterozygous patients at codon 129 showed that the hypometabolism was more widespread in the MET/VAL(129) group, which had a significantly longer symptom duration at the time of [F-18] FDG PET study. Comparison between neuropathologic and [F-18] FDG PET findings in six patients showed that areas with neuronal loss were also hypometabolic. However, cerebral hypometabolism was more widespread than the histopathologic changes and significantly correlated with the presence of protease-resistent prion protein (PrPres). Our findings indicate that hypometabolism of the thalamus and cingulate cortex is the hallmark of FFI, while the involvement of other brain regions depends on the duration of symptoms and some unknown factors specific to each patient. The present data also support the notion that PrPres formation is the cause of neuronal dysfunction in prion diseases.