Hanisch Frank, Müller Tobias, Muser Anett, Deschauer Marcus, Zierz Stephan
Klinik und Poliklinik für Neurologie, Martin-Luther-Universität, Halle-Wittenberg, Ernst-Grube Str. 40, 06097, Halle/Saale, Germany.
J Neurol. 2006 Apr;253(4):417-23. doi: 10.1007/s00415-006-0987-0. Epub 2006 Apr 20.
Mitochondrial disorders are characterized by an accumulation of lactate and an insufficient oxygen extraction from blood during exercise. Therefore, both parameters (lactate and oxygen saturation) can be used as screening tests in mitochondrial disorders. However, conflicting results regarding sensitivities and specifities of both tests have been reported.
We examined 27 patients with genetically defined mitochondrial disorders (single deletions n = 15, multiple deletions n = 5, A3243G mutation n = 7), patients with other neuromuscular disorders, and healthy controls. In the first test subjects performed intermittent isometric handgrip exercise (0.5 Hz) at 80% (3 minutes) and 30% (3 and 15 minutes) of maximal contraction force (MCF). Oxygen saturation and partial pressure in cubital venous blood from the exercising arm were measured. In the second test subjects underwent cycle ergometry at 30 W for 15 minutes. Venous lactate at rest, during and 15 minutes postexercise was determined.
Both tests showed specificities of 92-96%. Sensitivities for changes of venous oxygen partial pressure and oxygen saturation ranged from 21-26% at 80% MCF for 3 minutes to 47-58% at 30% MCF for 15 minutes. Sensitivities for venous resting, peak, and post-exercise lactate was 33%, 58%, and 67%, respectively. The degree of deoxygenation, however,was independent of the intensity and duration of the applied forces. Oxygen desaturation and lactate increase in patients with mitochondrial disorders were not different in patients with and without clinical symptoms of myopathy. There were significant correlations between the heteroplasmy and both the degree of oxygen desaturation and lactate increase in patients with single deletions. In patients who performed both protocols (n = 16) a combination of both tests increased sensitivity up to 87%.
Oxygen desaturation in forearm exercise tests and lactate increase in cycle ergometry tests show a high specifity but only moderate sensitivity. Combination of the two screening test clearly increases the sensitivity.
线粒体疾病的特征是乳酸堆积以及运动期间从血液中摄取氧气不足。因此，这两个参数（乳酸和血氧饱和度）均可用于线粒体疾病的筛查测试。然而，关于这两项测试的敏感性和特异性，已有相互矛盾的结果报道。
我们检查了27例经基因定义的线粒体疾病患者（单个缺失n = 15，多个缺失n = 5，A3243G突变n = 7）、其他神经肌肉疾病患者以及健康对照者。在第一项测试中，受试者以最大收缩力（MCF）的80%（3分钟）和30%（3分钟和15分钟）进行间歇性等长握力运动（0.5 Hz）。测量运动手臂肘静脉血中的血氧饱和度和分压。在第二项测试中，受试者以30 W进行15分钟的蹬车运动。测定静息、运动期间及运动后15分钟的静脉血乳酸水平。
两项测试的特异性均为92% - 96%。静脉血氧分压和血氧饱和度变化的敏感性在MCF为80%持续3分钟时为21% - 26%，在MCF为30%持续15分钟时为47% - 58%。静脉血静息、峰值及运动后乳酸的敏感性分别为33%、58%和67%。然而，脱氧程度与所施加力量的强度和持续时间无关。线粒体疾病患者的氧饱和度下降和乳酸增加在有和没有肌病临床症状的患者中并无差异。在单个缺失的患者中，异质性与氧饱和度下降程度和乳酸增加之间存在显著相关性。在进行了两项测试的患者（n = 16）中，两项测试相结合可将敏感性提高至87%。
前臂运动测试中的氧饱和度下降和蹬车运动测试中的乳酸增加显示出高特异性，但仅具有中等敏感性。两项筛查测试相结合明显提高了敏感性。
