Locus Coeruleus Degeneration Correlated with Levodopa Resistance in Parkinson's Disease: A Retrospective Analysis.
Locus Coeruleus Degeneration Correlated with Levodopa Resistance in Parkinson's Disease: A Retrospective Analysis.
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DOI：
10.3233/jpd-212720
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
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作者：
Zhou C;Guo T;Wu J;Wang L;Bai X;Gao T;Guan X;Gu L;Huang P;Xuan M;Gu Q;Xu X;Zhang B;Cheng W;Feng J;Zhang M
帕金森病（PD）患者对左旋多巴的广泛反应性是一个重要的临床问题，因为它关系到生活质量和疾病预后。初步的动物实验表明，蓝斑变性（LC）减弱了左旋多巴治疗的效果。探讨PD患者LC变性与左旋多巴反应性的关系。对57例PD患者进行了神经黑色素敏感磁共振成像（NM-MRI）和左旋多巴激发试验，这是LC和黑质（SN）变性的良好指标。通过统一帕金森病评定量表第III部分评分的变化率和静息状态功能MRI计算的体运动网络同步度来评估左旋多巴的反应性。接下来，我们评估了LC的对比噪声比（CNRLC）与左旋多巴反应性之间的关系。采用多元线性回归分析，排除SN变性对左旋多巴反应性的潜在影响。左旋多巴后CNRLC与运动改善呈显著正相关（R = 0.421, p = 0.004）。CNRLC还与躯体运动网络同步改善相关（R = -0.323, p = 0.029）。此外，CNRLC与左旋多巴反应的关系与SN变性无关。LC变性可能是左旋多巴耐药的重要因素。使用纳米核磁共振成像进行LC评估可能是预测左旋多巴反应性的一种替代工具，有助于将患者分层到旨在提高左旋多巴疗效的临床试验中。
The widely divergent responsiveness of Parkinson’s disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment. To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of the Unified Parkinson’s Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness. A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = –0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration. LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa.