Abstract
BackgroundAmyotrophic 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.MethodologyPlatelet 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.Principal FindingsPlatelet 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/SignificanceThe positive correlation between platelet serotonin levels and survival strongly suggests that serotonin influences the course of ALS disease.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both lower motor neurons (LMN) and upper motor neurons (UMN), and leads to death within 2 to 5 years of onset
Energy metabolism abnormalities have been shown in ALS patients [2,3,4,5] and their potential contribution to the course of the disease has been stressed [6], but little is known about the factors triggering these abnormalities
Decreased platelet serotonin levels in ALS patients The demographic data of ALS patients (Table 1) are in close accordance with previous reports showing that the patients included in the present study are representative of the ALS population
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both lower motor neurons (LMN) and upper motor neurons (UMN), and leads to death within 2 to 5 years of onset. Energy metabolism abnormalities have been shown in ALS patients [2,3,4,5] and their potential contribution to the course of the disease has been stressed [6], but little is known about the factors triggering these abnormalities. The neurotransmitter serotonin is involved in a range of functions altered in ALS, including motor neuron excitability and energy metabolism (reviewed in [7,8,9]). 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 diseasemodifying factors underlying this heterogeneity. Serotonin is involved in a range of functions altered in ALS, including motor neuron excitability and energy metabolism. Whether serotoninergic activity represents a disease modifier of ALS natural history remains unknown
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