Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Abstract

Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06–0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12–78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52–4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90–127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = − 2.42, 95% CI [− 3.93, − 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02–1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.

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

“…In turn, in the study by Pradat et al, 2010, abnormal glucose tolerance was seen in non-diabetic ALS patients when compared to healthy patients, which was accompanied by higher levels of free fatty acids in the blood that indicate insulin resistance [14]. These results seem to be in line with the conclusions recently published by Cheng et al, which show fasting glucose levels are higher in patients with ALS compared to healthy people [42]. However, neither of the two studies made a distinction between patients with bulbar or spinal onset ALS.…”

Neutrophils-to-Lymphocyte Ratio Is Associated with Progression and Overall Survival in Amyotrophic Lateral Sclerosis

“…Prediction of disease progression and survival has so far mainly been based upon clinical features, including age, El-Escorial diagnostic category at diagnosis, forced vital capacity (FVC), site of onset, phenotype, BMI, and diagnostic delay [ 2 , 3 ]. Given the urgent need to find sensitive, reliable, and easy-to-obtain biomarkers for monitoring disease progression and predict prognosis, attention has been recently turned to body fluid biomarkers, such as serum albumin, C-reactive protein [ 4 ], ferritin [ 5 ], creatinine [ 6 ], uric acid, hemoglobin, potassium, sodium, calcium, and glucose [ 7 , 8 , 9 ]. Moreover, given the growing evidence from human and animal studies of the involvement of both inflammation (local, innate immunity) and immune response (peripheral adaptive response) in ALS, markers of inflammation have also been evaluated.…”

Alterations of the serum and CSF ferritin levels and the diagnosis and prognosis of amyotrophic lateral sclerosis

“…On the other hand, another recent work suggested significantly increased CSF ferritin levels in ALS patients compared to controls, while among the serum markers, the only significant result was regarding the heightened serum transferrin levels in ALS patients [ 4 ]. A very recent meta-analysis concluded significantly increased serum ferritin levels in ALS patients compared to controls [ 17 ], even though, according to this work, results regarding alterations of the CSF ferritin levels in the ALS patients remain a subject to debate [ 18 ].…”

“…Former works have confirmed this result; that is, increased serum ferritin level is associated with a higher progression rate [ 19 ] and a shorter disease duration [ 9 ]. Also, pooled hazard ratios of a noteworthy recent meta-analysis in this regard has indicated significantly reduced survival associated with heightened serum ferritin levels [ 17 ]. Altogether, these results indicate an association between elevated serum ferritin levels and a more aggressive manifestation of ALS, which might as well justify its negative correlation with the disease duration.…”