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

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.

We enrolled 116 patients and observed clinical variables, including the survival state.

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.

There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.