title: Elimination Rate of Serum Lactate is Correlated with Amyotrophic Lateral Sclerosis Progression.
abstract: 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.
  
  
  CONCLUSIONS
  There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.
authors.forename: Yuan-Jin
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Fan
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D000704:Analysis of Variance; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D019344:Lactic Acid