Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress?

BACKGROUND: The exact cause of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress is one of the factors implicated in the etiology of ALS as well as in that of other neurodegenerative diseases. Uric acid is an important natural antioxidant that may reduce oxidative stress. The objective of this study was to prospectively determine the serum uric acid levels in ALS patients and allegedly healthy individuals and to correlate those values with measures of ALS disease progression among the patients. METHODS: The ALS patients and well-matched controls underwent blood tests for serum uric acid levels which were then correlated with the patients' disability status, as expressed by the ALS Functional Rating Scale (ALSFRS-R). RESULTS: Eighty-six ALS patients and 86 well-matched controls participated. The ALS patients' mean+/-SD uric acid level was significantly lower (4.78+/-1.3 mg/dl) than that of the controls (5.76+/-1.26 mg/dl) (p<0.0001). The findings were similar for a second examination performed after an interval of at least 6 months. There was a correlation between the relative decrease of serum uric acid levels among patients (the difference between the patients' level and the controls' level) and the rate of disease progression (ALSFRS-R decline) (p<0.0001, r=0.624). CONCLUSIONS: ALS patients had lower serum uric acid levels than healthy individuals. The decreased uric acid levels were correlated to the rate of disease progression (ALSFRS-R decline), further demonstrating the possible role of oxidative stress in the induction and propagation of the disease.

Low-grade systemic inflammation in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To prospectively determine the intensity of systemic low-grade inflammation in patients with amyotrophic lateral sclerosis (ALS). PATIENTS AND METHODS: Patients with ALS and matched healthy controls underwent blood tests for inflammation-sensitive biomarkers: erythrocyte sedimentation rate (ESR), quantitative fibrinogen, wide-range C-reactive protein (wrCRP) concentrations, leukocyte count and neutrophil-to-lymphocyte ratio (NLR). The correlation between these inflammatory biomarkers and disability status of the patients, expressed by the ALS Functional Rating Scale (ALSFRS-R), was evaluated. RESULTS: Eighty patients with ALS and 80 matched controls were included. wrCRP, fibrinogen, ESR and NLR values were significantly elevated in patients compared with controls. There was a significant correlation between the ALSFRS-R score and wrCRP, ESR and fibrinogen levels. This correlation persisted on sequential examinations. CONCLUSIONS: A systemic low-grade inflammation was detected in patients with ALS and correlated with their degree of disability. A heightened systemic inflammatory state is apparently associated with a negative prognosis in ALS.