CSF neurotoxic metals/metalloids levels in amyotrophic lateral sclerosis patients: comparison between bulbar and spinal onset.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system (CNS) that causes progressive and irreversible damage in motor neurons. Different causal hypotheses include genetic, viral, traumatic and environmental mechanisms, such as exposure to heavy metals. The aim of this study was to compare metal/metalloid levels in cerebro-spinal fluid of ALS subtypes (spinal vs bulbar clinical onset). MATERIAL AND METHODS: This observational study consecutively screened all ALS patients referring to the Neurology Clinic of the University of Catania (Italy). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify magnesium (Mg), cuprum (Cu), selenium (Se), iron (Fe), manganese (Mn), vanadium (V), zinc (Zn), alluminium (Al), arsenic (As), cobalt (Co), nickel (Ni), mercury (Hg), lead (Pb), cadmium (Cd) and palladium (Pd) levels. RESULTS: Thirty-seven patients were enrolled (62.2% females), median age of 65 years (IQR: 59-71 years). Thirty-one (83.8%) patients had a spinal onset and 6 (16.2%) a bulbar onset. Se and As levels were higher compared to the reference values (RV) both in spinal and bulbar onset, while Cu was higher than RV only in bulbar onset. Moreover, Cu (129.8 µg/L vs 29.8 µg/L), Fe (54.5 µg/L vs 33.3 µg/L), Mn (3.4 µg/L vs 1.8 µg/L), Zn (46.1 µg/L vs 35.7 µg/L), Al (12.2 µg/L vs 6.7 µg/L), Ni (2.80 µg/L vs 1.40 µg/L), and Pb (0.60 µg/L vs 0.30 µg/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 µg/L vs 1.10 µg/L). Overall, Cu (129 µg/L vs 31 µg/L), Fe (92.2 µg/L vs 32.9 µg/L), Mn (3.35 µg/L vs 1.80 µg/L), Zn (56.5 µg/L vs 35.2 µg/L), Al (14.45 µg/L vs 6.70 µg/L), and Cd (0.40 µg/L vs 0.08 µg/L) levels were higher in patients with disease duration less than 19 months. CONCLUSION: Our results supported the hypothesis that metals/metalloids with neurotoxic effects could be involved in the etiology of ALS, showing higher levels of Cu, Se and As. Relevant differences in Cu and Mn levels were found between bulbar and spinal onset patients.

A retrospective study of the clinical phenotype and predictors of survival in non-Caucasian Hispanic patients with amyotrophic lateral sclerosis.

BACKGROUND: Little is known about the clinical phenotype of amyotrophic lateral sclerosis (ALS) in non-Caucasian populations. Here, we aimed to describe the clinical characteristics, prognostic factors and survival of Mexican patients with ALS. METHODS: We conducted a retrospective study by reviewing the medical records of patients with ALS that attended and were regularly followed at a third level hospital in Mexico City from 2000 to 2015. We calculated absolute and relative frequencies of the clinical characteristics from all the participants. We also estimated correlation coefficients between clinical features and overall survival. Additionally, survival rates were compared for all participants grouped according to different clinical features using the Kaplan-Meier method and the log-rank test. RESULTS: We enrolled 45 ALS patients, 53.33% had spinal-onset ALS and 46.66% presented bulbar ALS. The male/female ratio was 0.8. The mean age at onset of symptoms was 58.11 years. Mean survival time from onset was 64.73 ± 34.83 months. Cumulative survival rate after 5 years of disease onset was 44.44%. Age at onset and age at diagnosis inversely correlated with overall survival time. Also, we found that bulbar-onset, short diagnostic delay, percutaneous endoscopic gastrostomy, mechanical ventilation, and lower total cholesterol serum levels were associated with short survival. CONCLUSIONS: The clinical characteristics of Mexican ALS patients differ from the disease phenotype observed in Caucasians. Nonetheless, the predictive value of certain well-recognized prognostic factors remains consistent in our population. The current study provides relevant information for a better understanding of prognostic factors in ALS patients from Mexico and other Latin American countries.

Muscle Function Differences between Patients with Bulbar and Spinal Onset Amyotrophic Lateral Sclerosis. Does It Depend on Peripheral Glucose?

BACKGROUND: One of the pathogenic mechanisms of ALS disease is perturbed energy metabolism particularly glucose metabolism. Given the substantial difference in the severity and the prognosis of the disease, depending on whether it has a bulbar or spinal onset, the aim of the study was to determine metabolic differences between both types of ALS, as well as the possible relationship with muscle function. MATERIALS AND METHODS: A descriptive, analytical, quantitative, and transversal study was carried out in hospitals and Primary Care centers in the region of Valencia, Spain. Fasting glucose and alkaline phosphatase (AP) levels in venous blood, muscle percentage, fat percentage, muscle strength (MRC scale), and functional capacity (Barthel Index) were measured in 31 patients diagnosed with ALS (20 with spinal onset ALS and 11 with bulbar onset ALS). A healthy control of 29 people was included. RESULTS: No significant differences were observed in blood AP and glucose levels between spinal onset and bulbar onset ALS patients. However, a significant positive correlation was observed between the mean values of both substances in patients with spinal onset ALS. Moreover, a lower percentage of muscle mass and a higher percentage of fat mass were also seen in spinal ALS patients, who also presented lower muscle strength and lower functional capacity. CONCLUSION: The results of this study seem to point to a possible difference in the peripheral use of glucose between patients with bulbar onset ALS and spinal onset ALS, who appear to have possible insulin resistance. These metabolic differences could explain the lower muscle percentage and lower muscular function in spinal onset ALS patients, although further studies are required.