Elimination Rate of Serum Lactate is Correlated with Amyotrophic Lateral Sclerosis Progression

• Main Authors: Yuan-Jin Zhang, Dong-Sheng Fan
• Format: Article
• Language: English
• Published: Wolters Kluwer 2016-01-01
• Series: Chinese Medical Journal
• Subjects: Advanced Phase; Amyotrophic Lateral Sclerosis; Early Phase; Elimination Rate of Serum Lactate
• Online Access: http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=1;spage=28;epage=32;aulast=Zhang
• ISSN: 0366-6999

Background: Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to examine the relationship between mitochondrial dysfunction with motor deterioration. Methods: We enrolled 116 patients and observed clinical variables, including the survival state. Results: Patients with a rapid slope of revised ALS functional rating scales (ALSFRS-r) (>20 U/year) exhibited the slowest elimination rate (median −4.67 × 10−3 mmol·L−1·min−1 , coefficient of variation, 590.15%), the shortest duration (0.63 ± 0.28 years) and the worst ALSFRS-r (32.59 ± 4.93). Patients with a moderate slope of ALSFRS-r (10-20 U/year) showed a moderate elimination rate (median −11.33 × 10−3 mmol·L−1·min−1 , coefficient of variation, 309.89%), duration (1.16 ± 0.45 years), and ALSFRS-r (34.83 ± 6.11). The slower progressing (<10 U/year group) patients exhibited a rapid elimination rate (median: −12.00 × 10−3 mmol·L−1·min−1 , coefficient of variation: 143.08%), longer duration (median: 3 years, coefficient of variation: 193.33%), and adequate ALSFRS-r values (39.58 ± 9.44). Advanced-phase ALS patients also showed slower elimination rate (ER, quartiles −17.33, −5.67, 4.00) and worse ALSFRS-r (34.88 ± 9.27), while early-phase patients showed a more rapid ER (quartiles −25.17, −11.33, −3.50) and better ALSFRS-r (39.28 ± 7.59). These differences were statistically significant. Multiple linear regression analysis revealed strong direct associations among ER, ALSFRS-r slope (standard beta = 0.33, P = 0.007), and forced vital capacity (predict %) (standard beta = −0.458, P = 0.006, adjusted for ALSFRS-r, course and onset region). However, the data obtained from 3 years of follow-up showed no statistically significant difference in the survival rates between the most rapid and slowest ER groups. Conclusion: There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.