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原发性胆汁性肝硬化的中枢神经系统功能障碍及其与症状的关系。

Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms.

机构信息

Institute of Cellular Medicine, Newcastle University, UK.

出版信息

J Hepatol. 2010 Dec;53(6):1095-100. doi: 10.1016/j.jhep.2010.05.036. Epub 2010 Aug 11.

Abstract

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is associated with fatigue, memory impairment, and sleep disturbances. These symptoms suggest the possibility of underlying central nervous system (CNS) dysfunction. During exercise, fatigue develops due to muscular processes (peripheral fatigue) and decreased neurological activation of the muscle (central fatigue). In this study we objectively quantify central and peripheral fatigue in PBC and investigate the integrity of cortical inhibitory and excitatory circuits. Finally, we determine the relationship of these indices to the symptoms of PBC.

METHODS

16 early-stage PBC patients, 8 post-liver transplant PBC patients, and 12 age-matched controls were studied at the Specialist PBC clinic and neuroscience research unit. In these patients, twitch interpolation was used to measure peripheral and central fatigue. Paired-pulse trans-cranial magnetic stimulation was used to assess intra-cortical inhibition (ICI) and facilitation (ICF).

RESULTS

PBC patients had a significantly lower central activation before fatiguing exercise (mean 86.6.8% (±12.75) vs. 95.2% (±7.4); p<0.05) and a greater response variability than controls. The decline in central activation during exercise and peripheral fatigue were normal. ICI was significantly reduced in PBC patients and daytime somnolence was greater in patients where net inhibition exceeded facilitation. Transplanted and non-transplanted patients had similar central activation, ICI, and ICF.

CONCLUSIONS

PBC patients have impaired central activation and abnormal ICI, suggesting CNS abnormalities beyond voluntary control. Transplanted and non-transplanted patients show similar abnormalities raising interesting questions about the mechanisms underpinning these changes and the permanence of neurological dysfunction in PBC. ICI and ICF and the balance between them are related to daytime somnolence (an important symptom in PBC).

摘要

背景与目的

原发性胆汁性肝硬化(PBC)与疲劳、记忆障碍和睡眠障碍有关。这些症状表明存在潜在的中枢神经系统(CNS)功能障碍。在运动过程中,由于肌肉过程(外周疲劳)和肌肉的神经激活减少(中枢疲劳)而导致疲劳。在这项研究中,我们客观地量化了 PBC 中的中枢和外周疲劳,并研究了皮质抑制和兴奋回路的完整性。最后,我们确定了这些指标与 PBC 症状的关系。

方法

在专门的 PBC 诊所和神经科学研究单位研究了 16 名早期 PBC 患者、8 名肝移植后 PBC 患者和 12 名年龄匹配的对照者。在这些患者中,使用抽搐插值法测量外周和中枢疲劳。使用成对脉冲经颅磁刺激评估皮质内抑制(ICI)和易化(ICF)。

结果

PBC 患者在疲劳运动前的中枢激活明显较低(平均值 86.6.8%(±12.75)比 95.2%(±7.4);p<0.05),并且比对照组的反应变异性更大。运动期间和外周疲劳时中枢激活的下降是正常的。ICI 在 PBC 患者中显著降低,并且在净抑制超过易化时,白天嗜睡更大。移植和未移植患者的中枢激活、ICI 和 ICF 相似。

结论

PBC 患者的中枢激活受损和 ICI 异常,表明 CNS 异常超出了自主控制。移植和未移植患者表现出相似的异常,这提出了关于这些变化背后的机制以及 PBC 中神经功能障碍的永久性的有趣问题。ICI 和 ICF 及其之间的平衡与白天嗜睡(PBC 的一个重要症状)有关。

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