Blinkenberg Morten, Mathiesen Henrik K, Tscherning Thomas, Jønsson Agnete, Svarer Claus, Holm Søren, Sellebjerg Finn, Paulson Olaf B, Hanson Lars G, Sorensen Per S
Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
Neurol Res. 2012 Jan;34(1):52-8. doi: 10.1179/1743132811Y.0000000059.
Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction and neurological disability.
We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically tested and a cognitive dysfunction factor (CDF) was calculated.
Cortical CMRglc correlated with cortical NAA/Cr (r = 0.45; P < 0.05), but there were no correlation between CMRglc and other NAA/Cr measurements, conventional magnetic resonance imaging measurements, or CDF. Stepwise regression analysis showed association between cortical NAA/Cr and CMRglc of the left ventrolateral prefrontal cortex (P < 0.001), left putamen (P = 0.010), and left hippocampus (P = 0.011). Furthermore, CDF was related to CMRglc in the left cerebellum (P = 0.001) and the left caudate nucleus (P = 0.013). The results of the statistical analysis should be regarded as exploratory, since we did not correct for multiple comparisons.
Our findings suggest that reductions in cortical CMRglc are associated with reductions in cortical NAA/Cr in early MS. These changes affect cortical and subcortical neural circuits of importance to cognitive function.
正电子发射断层扫描（PET）研究表明，多发性硬化症（MS）患者大脑皮质葡萄糖代谢率（CMRglc）降低。以肌酸为标准的N-乙酰天门冬氨酸（NAA）定量磁共振波谱（MRS）测量可评估神经元退变情况，多项研究显示MS患者的该指标降低。此外，PET和MRS测量结果的降低均与MS患者的认知功能障碍相关。我们的目的是确定早期MS患者大脑皮质CMRglc的变化是否与神经元退变的NAA/Cr测量值、认知功能障碍及神经功能残疾相关。
我们研究了20例近期诊断为临床确诊复发缓解型MS的患者。使用18-F-脱氧葡萄糖PET估算全脑和大脑皮质CMRglc，并使用多层回波平面波谱成像测量NAA/Cr比值。所有受试者均接受神经心理学测试，并计算认知功能障碍因子（CDF）。
大脑皮质CMRglc与大脑皮质NAA/Cr相关（r = 0.45；P < 0.05），但CMRglc与其他NAA/Cr测量值、传统磁共振成像测量值或CDF之间无相关性。逐步回归分析显示，左侧腹外侧前额叶皮质（P < 0.001）、左侧壳核（P = 0.010）和左侧海马体（P = 0.011）的大脑皮质NAA/Cr与CMRglc之间存在关联。此外，CDF与左侧小脑（P = 0.001）和左侧尾状核（P = 0.013）的CMRglc相关。由于未对多重比较进行校正，统计分析结果应视为探索性的。
我们的研究结果表明，早期MS患者大脑皮质CMRglc降低与大脑皮质NAA/Cr降低相关。这些变化影响对认知功能至关重要的大脑皮质和皮质下神经回路。
