Fatigue in multiple sclerosis: Mechanisms and management
Fatigue in multiple sclerosis: Mechanisms and management
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多发性硬化症中的疲劳：机制和治疗
DOI：
10.1016/j.clinph.2009.12.013
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发表时间：
2010
影响因子：
4.7
通讯作者：
M. Kiernan
中科院分区：
文献类型：
--
作者：
S. Vucic;D. Burke;M. Kiernan
多发性硬化症 [MS] 是一种慢性免疫介导的中枢神经系统 [CNS] 疾病。疲劳可能是多发性硬化症患者的一种使人衰弱的症状，对他们的生活质量产生不利影响。临床上，疲劳可能表现为精疲力竭、精力不足、嗜睡加剧或多发性硬化症症状恶化。活动和高温通常会加剧疲劳症状。现在有强有力的证据表明，疲劳是由于中枢机制对肌肉的自主激活减少造成的。鉴于轴突脱髓鞘是多发性硬化症的病理标志，活动依赖性传导阻滞 [ADCB] 被认为是多发性硬化症疲劳的潜在机制。这种 ADCB 是由 Na+/K+ 电泵介导的轴突膜超极化引起的，脱髓鞘的轴突会导致传导失败，脉冲传输的安全系数降低。此外，如多发性硬化症中报道的，Na+/K+泵功能障碍可能会诱发与Na+通道失活相关的去极化传导阻滞。这些过程可能会引起继发效应，包括通过 Na+–Ca2+ 交换器的反向操作导致细胞内 Ca2+ 水平升高而引发的轴突变性。使用选择性通道阻滞剂恢复脱髓鞘轴突的正常传导可以改善疲劳，并且可能被证明可以作为一种神经保护策略，预防继发性轴突变性和随之而来的功能障碍。
Multiple sclerosis [MS] is a chronic immune-mediated disorder of the central nervous system [CNS]. Fatigue may be a debilitating symptom in MS patients, adversely impacting on their quality of life. Clinically, fatigue may manifest as exhaustion, lack of energy, increased somnolence, or worsening of MS symptoms. Activity and heat typically serve to exacerbate symptoms of fatigue. There is now strong evidence to suggest that fatigue results from reduced voluntary activation of muscles by means of central mechanisms. Given that axonal demyelination is a pathological hallmark of MS, activity-dependent conduction block [ADCB] has been proposed as a mechanism underlying fatigue in MS. This ADCB results from axonal membrane hyperpolarization, mediated by the Na+/K+electrogenic pump, with conduction failure precipitated in demyelinated axons with a reduced safety factor of impulse transmission. In addition, Na+/K+pump dysfunction, as reported in MS, may induce a depolarizing conduction block associated with inactivation of Na+channels. These processes may induce secondary effects including axonal degeneration triggered by raised levels of intracellular Ca2+through reverse operation of the Na+–Ca2+exchanger. Restoration of normal conduction in demyelinated axons with selective channel blockers improves fatigue and may yet prove useful as a neuroprotective strategy, in preventing secondary axonal degeneration and consequent functional impairment.
金刚烷胺、疲劳和多发性硬化症。
影响因子：
--
作者：
Rosenberg,GA;Appenzeller,O
通讯作者：
Appenzeller,O
DOI：
10.1073/pnas.090034797
发表时间：
2000-05-09
影响因子：
11.1
作者：
Caldwell, JH;Schaller, KL;Levinson, SR
通讯作者：
Levinson, SR
影响因子：
--
作者：
Inglese, Matilde;Park, Sun-Jung;Grossman, Robert I.
通讯作者：
Grossman, Robert I.