Abstract
The aim of this study was to evaluate the kynurenine pathway (KP) and amino acids profile, using mass spectrometry, in the cerebrospinal fluid (CSF) of 42 amyotrophic lateral sclerosis (ALS) patients at the diagnosis and 40 controls to detect early disorders of these pathways. Diagnostic and predictive ability (based on weight loss, forced vital capacity, ALS Functional Rating Scale—Revised evolution over 12 months, and survival time) of these metabolites were evaluated using univariate followed by supervised multivariate analysis. The multivariate model between ALS and controls was not significant but highlighted some KP metabolites (kynurenine (KYN), kynurenic acid (KYNA), 3-Hydroxynurenine (3-HK)/KYNA ratio), and amino acids (Lysine, asparagine) as involved in the discrimination between groups (accuracy 62%). It revealed a probable KP impairment toward neurotoxicity in ALS patients and in bulbar forms. Regarding the prognostic effect of metabolites, 12 were commonly discriminant for at least 3 of 4 disease evolution criteria. This investigation was crucial as it did not show significant changes in CSF concentrations of amino acids and KP intermediates in early ALS evolution. However, trends of KP modifications suggest further exploration. The unclear kinetics of neuroinflammation linked to KP support the interest in exploring these pathways during disease evolution through a longitudinal strategy.
Highlights
Introduction iationsAmyotrophic lateral sclerosis (ALS), the most common form of motor neuron disorder in adults, is characterized by degeneration of both upper and lower motor neurons in bulbar and spinal territories
Eighty-two patients were included in this study, comprising 40 amyotrophic lateral sclerosis (ALS) patients and 42 control subjects matched by age and sex
We did not highlight any early modifications of amino acids or the kynurenine pathway in ALS patients in our population
Summary
Amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disorder in adults, is characterized by degeneration of both upper and lower motor neurons in bulbar and spinal territories. Initial presentation of ALS may vary between patients, most presenting a spinal-onset disease, though bulbar or respiratory onset can be observed. As no effective treatment is available, disease evolution is rapid, and death typically occurs after 3 to 5 years of evolution due to respiratory paralysis [1]. Diagnosis of ALS relies on the Airlie House criteria [2]. Diagnosis according to these criteria requires elimination of other neurological diseases and relies primarily on clinical criteria and progression of motor weakness. To date there is no diagnostic or prognostic biomarker available in clinical practice.
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