Near-Infrared Spectroscopy Screening to Allow Detection of Pathogenic Mitochondrial DNA Variants in Individuals with Unexplained Abnormal Fatigue: A Preliminary Study.

Unexplained abnormal fatigue is characterized by chronic fatigue persisting for at least six months and not sufficiently explained by any recognized medical condition. In this pilot study, twelve individuals with abnormal fatigue remaining unexplained after thorough screening were investigated using a near-infrared (NIR) spectroscopy handgrip test. Four of them were found to have an abnormal oxygen extraction pattern similar to participants with documented mitochondrial myopathy. In three of the four individuals, diverse mitochondrial abnormalities were documented by spectrophotometric, immunocytological, fluorescent, and morphological analyses performed in skeletal muscle and in cultured skin fibroblasts. Three of the four participants with decreased muscular oxygen extraction were each shown to harbor a different homoplasmic pathogenic mitochondrial DNA point mutation (m.961T > C, m.1555A > G, m.14484T > C). In the fourth participant, the presence of multiple large mitochondrial DNA deletions was suspected in muscle tissue. In contrast, none of the eight abnormally fatigued participants with normal NIR spectroscopy results harbored either a pathogenic mitochondrial DNA point mutation or large deletions ( P < 0.001). This pilot study shows that NIR spectroscopy may serve as a noninvasive screening tool to delineate a subgroup (of participants) with mitochondrial dysfunction among the large group of individuals with unexplained abnormal fatigue.

Possible Influences on the Interpretation of Functional Domain (FD) Near-Infrared Spectroscopy (NIRS): An Explorative Study.

The influence of subcutaneous adipose tissue (ATT) and oxygen (O2) delivery has been poorly defined in frequency domain (FD) near-infrared spectroscopy (NIRS). Therefore, the aim of this study was to investigate the possible influence of these variables on all FD NIRS responses using a reliable protocol. Moreover, these influences were also investigated when using relative oxy- and deoxyhemoglobin and -myoglobin (oxy[Hb + Mb] and deoxy[Hb + Mb]) values (in %). A regression analysis was carried out for ATT and maximal-minimum oxy[Hb + Mb], deoxy[Hb + Mb], oxygen saturation (SmO2), and total hemoglobin (totHb) amplitudes during an incremental cyclic contraction protocol (ICCP) in a group of 45 participants. Moreover, the same analysis was carried out between subcutaneous ATT and the relative oxy- and deoxy[Hb + Mb] values (in %). In the second part of this study, a regression analysis was performed for peak forearm blood flow (FBF) during ICCP and the absolute and relative NIRS values in a group of 37 participants. Significant exponential correlation coefficients were found between ATT and deoxy[Hb + Mb] (r = 0.53; P < 0.001), oxy[Hb + Mb] (r = 0.57; P < 0.001), and SmO2 amplitudes (r = 0.57; P < 0.001). No significant relations were found between ATT and relative oxy[Hb + Mb] (r = 0.37; P = 0.07) and deoxy[Hb + Mb] (r = 0.09; P = 0.82). Significant positive correlation coefficients were found between force at exhaustion and maximal FBF (r = 0.66; P < 0.001), maximal differences in deoxy[Hb + Mb] (r = 0.353; P = 0.032) and totHb (r = 0.512; P = 0.002) while no significant correlation coefficients were found between these maximal force values and maximal differences in oxy[Hb + Mb] (r = -0.267; P = 0.111) and SmO2 (r = -0.267; P = 0.111). Significant linear correlation coefficients were found between FBF and deoxy[Hb + Mb] (r = 0.51; P = 0.001), oxy[Hb + Mb] (r = -0.50; P = 0.001), SmO2 (r = -0.54; P = 0.001), and totHb amplitude (r = 0.61; P < 0.001). No significant correlations were found when using relative oxy[Hb + Mb] (r = -0.01; P = 0.957) and deoxy[Hb + Mb] (r = -0.02; P = 0.895). Based on these findings, caution is advised when using NIRS values, as subcutaneous ATT and O2 delivery significantly influence NIRS measurements. To eliminate these influences, use of relative deoxy[Hb + Mb] is advised, especially in clinical settings or in people with a higher subcutaneous ATT layer.

Forearm deoxyhemoglobin and deoxymyoglobin (deoxy[Hb + Mb]) measured by near-infrared spectroscopy (NIRS) using a handgrip test in mitochondrial myopathy.

The purpose of this paper is to test whether peripheral oxygenation responses measured with near-infrared spectroscopy (NIRS) would differ between patients suffering from mitochondrial myopathy (MM) and healthy controls during an incremental handgrip exercise test. Two groups of subjects were studied: 11 patients with MM and 11 age- and gender-matched untrained healthy controls. A handgrip exercise until exhaustion protocol was used consisting of 2 min periods of work (½ Hz) at different intensities, separated by a 60 s rest period. The changes in deoxyhemoglobin and deoxymyoglobin (deoxy[Hb + Mb]) during each work step were expressed in percent to the maximum deoxy[Hb + Mb]-value measured during arterial occlusion in forearm muscles. A repeated measures analysis of variance was used to compare the increase in deoxy[Hb + Mb] between MM patients and controls with increasing intensity. Statistical analysis revealed a significant difference between both populations (P < 0.001) indicating that the increase in deoxy[Hb + Mb] showed a significantly different pattern in the two populations. In the post hoc analysis significant lower deoxy[Hb + Mb] -values were found for MM patients at every intensity. The results of this paper show significantly different skeletal muscle oxygenation responses, measured with an optical method as NIRS, between MM patients and age- and gender-matched healthy subjects at submaximal and maximal level during an incremental handgrip exercise. This optical method is thus a valuable tool to assess differences in peripheral oxygenation. Moreover, this method could be used as an evaluation tool for follow up in interventional pharmacological studies and rehabilitation programs.