Platelet serotonin level predicts survival in amyotrophic lateral sclerosis.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a life-threatening neurodegenerative disease involving upper and lower motor neurons loss. Clinical features are highly variable among patients and there are currently few known disease-modifying factors underlying this heterogeneity. Serotonin is involved in a range of functions altered in ALS, including motor neuron excitability and energy metabolism. However, whether serotoninergic activity represents a disease modifier of ALS natural history remains unknown.


METHODS
Platelet and plasma unconjugated concentrations of serotonin and plasma 5-HIAA, the major serotonin metabolite, levels were measured using HPLC with coulometric detection in a cohort of 85 patients with ALS all followed-up until death and compared to a control group of 29 subjects.


RESULTS
Platelet serotonin levels were significantly decreased in ALS patients. Platelet serotonin levels did not correlate with disease duration but were positively correlated with survival of the patients. Univariate Cox model analysis showed a 57% decreased risk of death for patients with platelet serotonin levels in the normal range relative to patients with abnormally low platelet serotonin (p = 0.0195). This protective effect remained significant after adjustment with age, gender or site of onset in multivariate analysis. Plasma unconjugated serotonin and 5-HIAA levels were unchanged in ALS patients compared to controls and did not correlate with clinical parameters.


CONCLUSIONS
The positive correlation between platelet serotonin levels and survival strongly suggests that serotonin influences the course of ALS disease.
INSERM U692, Strasbourg, France. ldupuis@unistra.fr
Luc
L
Dupuis
Odile
O
Spreux-Varoquaux
Gilbert
G
Bensimon
Philippe
P
Jullien
Lucette
L
Lacomblez
François
F
Salachas
Gaëlle
G
Bruneteau
Pierre-François
PF
Pradat
Jean-Philippe
JP
Loeffler
Vincent
V
Meininger
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D012701:Serotonin / Q000097:blood*; D016019:Survival Analysis
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid