scholarly journals Significance of Serological Markers in Neurological Function and Progression Rate of Amyotrophic Lateral Sclerosis

2021 ◽  
Author(s):  
Xiaowen Chen ◽  
Junrong Li ◽  
Yingying Lv ◽  
Wei Zhang ◽  
xiujian Xu ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Creatine Kinase ◽  
Uric Acid ◽  
Total Cholesterol ◽  
Cystatin C ◽  
Control Group ◽  
Progression Rate ◽  
Cholesterol Levels ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Objective The present study was to investigate the significance of creatinine, uric acid, creatine kinase, total cholesterol, triglyceride, HCY (Homocysteine), and cystatin C in neurological function and progression rate of amyotrophic lateral sclerosis. Methods According to the diagnostic criteria of EI-Escorial (2000), 103 patients with ALS were enrolled. All patients were given corresponding serological tests at the initial diagnosis. The Revised ALS Functional Rating Scale (ALSFRS-R) and Disease Progression Rate (DPR) were evaluated. The detected indexes in blood tests included creatinine, uric acid, creatine kinase, total cholesterol, triglycerides, homocysteine, and cystatin C. All data were input into the computer, and the data analysis was performed by SPSS22.0 statistical software.Results 1. There were significant differences in creatinine, uric acid, creatine kinase,
total cholesterol, HCY and cystatin C between the two groups (P<0.05). The levels of uric acid and creatinine of ALS group were lower than those of the control group, and the levels of creatine kinase, total cholesterol, triglyceride, HCY and cystatin C were higher than that in the control group.
2. The results from correlation analysis demonstrated that there was a significant correlation between ALSFRS-R and creatinine (P<0.01), the correlation coefficient was 0.567 (positive correlation); There was also a significant correlation between DPR and creatinine (P<0.01), and the correlation coefficient was -0.808 (negative correlation). The correlations of DPR with triglyceride and total cholesterol were significantly negative correlated (P<0.05), with -0.201 and -0.210 of correlation coefficients, respectively. The remaining indexes did not show any correlation with ALSFRS-R and DPR.
Conclusions 1. Uric acid and creatinine of ALS patients were lower than that in healthy people. Creatine kinase, triglyceride, total cholesterol, HCY, and cystatin C in ALS patients were higher than those in health controls. There were significant metabolic abnormalities in ALS patients.
2. Creatinine level is an independent risk factor affecting ALSFRS-R. The creatinine and total cholesterol levels are also the independent risk factors affecting DPR. Creatinine and total cholesterol levels could be used as reliable indicators to evaluate the ALSFRS-R and DPR of ALS patients.

scholarly journals Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1210
Author(s):  
Júlia Costa ◽  
Marta Gromicho ◽  
Ana Pronto-Laborinho ◽  
Conceição Almeida ◽  
Ricardo A. Gomes ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Motor Neurons ◽  
Neurological Diseases ◽  
Disease Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Progression Rate ◽  
Therapeutic Trials ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

scholarly journals Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan-ni Zhou ◽  
You-hong Chen ◽  
Si-qi Dong ◽  
Wen-bo Yang ◽  
Ting Qian ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Meta Analysis ◽  
Progression Rate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Risk Of Death ◽  
Disease Progression Rate ◽  
Als Patients ◽  
Lateral Sclerosis

Background: Neurofilaments in cerebrospinal fluid (CSF) and in blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased in patients with ALS. However, the roles of neurofilaments, especially blood neurofilaments, in the prognosis of ALS are inconsistent. We performed a meta-analysis to explore the prognostic roles of blood neurofilaments in ALS patients.Methods: We searched all relevant studies on the relationship between blood neurofilament levels and the prognosis of ALS patients in PubMed, Embase, Scopus, and Web of Science before February 2, 2021. The quality of the included articles was assessed using the Quality in Prognosis Studies (QUIPS) scale, and R (version 4.02) was used for statistical analysis.Results: Fourteen articles were selected, covering 1,619 ALS patients. The results showed that higher blood neurofilament light chain (NfL) levels in ALS patients were associated with a higher risk of death [medium vs. low NfL level: HR = 2.43, 95% CI (1.34–4.39), p &lt; 0.01; high vs. low NfL level: HR = 4.51, 95% CI (2.45–8.32), p &lt; 0.01]. There was a positive correlation between blood phosphorylated neurofilament heavy chain (pNfH) levels and risk of death in ALS patients [HR = 1.87, 95% CI (1.35–2.59), p &lt; 0.01]. The levels of NfL and pNfH in blood positively correlated with disease progression rate (DPR) of ALS patients [NfL: summary r = 0.53, 95% CI (0.45–0.60), p &lt; 0.01; pNfH: summary r = 0.51, 95% CI (0.24–0.71), p &lt; 0.01].Conclusion: The blood neurofilament levels can predict the prognosis of ALS patients; specifically, higher levels of blood neurofilaments are associated with a greater risk of death.

scholarly journals Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis

2021 ◽  
Author(s):  
Xintong Guo ◽  
Xiaoxuan Liu ◽  
Shan Ye ◽  
Xiangyi Liu ◽  
Xu Yang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Eye Movement ◽  
Smooth Pursuit ◽  
Oculomotor System ◽  
Control Group ◽  
Clinical Markers ◽  
Square Wave ◽  
Movement Parameters ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Background and Purpose It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and the corresponding pattern has not yet been established. Furthermore, bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. Methods Patients with clinically definite, probable or laboratory-supported probable ALS (n=60) and a control group composed of their caregivers (n=30) underwent clinical assessments and standardized evaluations of the oculomotor system using videonystagmography. The gaze test, reflexive saccade test and smooth pursuit test were administered to all subjects. Results Eye movement abnormalities such as square-wave jerks, abnormal cogwheeling during smooth pursuit, and saccade hypometria were observed in ALS patients. Square-wave jerks (p<0.001) and abnormal cogwheeling during smooth pursuit (p=0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (p=0.004) and abnormal cogwheeling during smooth pursuit (p=0.031) were found to be more common in ALS patients with bulbar involvement (n=44) than in those without bulbar involvement (n=16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n=12) and spinal-onset patients (n=48). Conclusion ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. These abnormalities were observed more common in the ALS patients with bulbar involvement. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS.

scholarly journals Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Massimo Tortarolo ◽  
Daniele Lo Coco ◽  
Pietro Veglianese ◽  
Antonio Vallarola ◽  
Maria Teresa Giordana ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune System ◽  
Disease Progression ◽  
Protective Role ◽  
Progression Rate ◽  
Neuron Death ◽  
Multisystem Disease ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFαis one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFαlevels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFαtoxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg) whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFαis considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFαin ALS in the light of its multisystem nature.

scholarly journals Association of serum uric acid, homocystine and ferritin among amyotrophic lateral sclerosis patients

2021 ◽  
Vol 8 (2) ◽  
pp. 158
Author(s):  
M. Raknuzzaman ◽  
Tasnim Jannaty ◽  
Abu Shams M. Hasan Ali Masum ◽  
Golam Sagir ◽  
M. Wahiduzzaman ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Serum Ferritin ◽  
Rating Scale ◽  
Inverse Correlation ◽  
Control Group ◽  
Group I ◽  
Annual Decline ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) disease which is also known as motor neuron disease (MND) or Lou Gehrig's disease, is causes the death of neurons controlling voluntary muscles. There may have association of serum uric acid, homocystine and ferritin with amyotrophic lateral sclerosis. But we have not enough data regarding these issues. The aim of this study was to evaluate the association of serum uric acid, homocystine and ferritin with amyotrophic lateral sclerosis.Methods: It was a case-control study conducted in the department of neurology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2010 to December 2011. Finalized 76 study people were divided into two equal groups containing 38 participants in each. In group I (case group) there were 38 patients with ALS and in group II (control group) there were 38 healthy people. The correlation of annual decline of ALS Functional Rating Scale-Revised (ALS-FRS) and forced vital capacity (FVC) were analyzed. Data were collected through pre-designed questioners and processed and analyzed by using SPSS version 11.5.Results: In this study the inverse correlation between serum uric acid and the annual decline of ALS-FRS in male, spearman rho correlation was -0.37 (p<0.01) and in female it was -0.78 (p<0.001). The inverse correlation between serum uric acid and the annual decline of FVC were in male, spearman rho correlation was -0.33 (p<0.05) and in female it was -0.39 (p<0.05). Inverse correlation between homocystine and the annual decline of ALS-FRS in male, spearman rho correlation was -0.42 (p<0.02) and in female, it was -0.64 (p<0.001). The inverse correlation between homocystine and the annual decline of FVC in male, spearman rho correlation was -0.41 (p<0.04) and in female, spearman rho correlation was -0.37 (p<0.05). The inverse correlation between serum ferritin and the annual decline of ALS-FRS in male, spearman rho correlation was 0.47 (p<0.01) and in female, spearman rho correlation was 0.76 (p<0.001). The inverse correlation between serum ferritin and the annual decline of FVC in male, spearman rho correlation was 0.49 (p<0.001) and in female, it was 0.71 (p<0.001).Conclusions: In most of the cases we found significant correlation of serum uric acid, serum homocystine and serum ferritin with amyotrophic lateral sclerosis (ALS). So all these components would be considered as some potential indicators or bio-markers of amyotrophic lateral sclerosis (ALS).

scholarly journals Prognosis of amyotrophic lateral sclerosis with cognitive and behavioural changes based on a sixty-month longitudinal follow-up

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0253279
Author(s):  
Shan Ye ◽  
Pingping Jin ◽  
Lu Chen ◽  
Nan Zhang ◽  
Dongsheng Fan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Survival Time ◽  
Progression Rate ◽  
Behavioural Changes ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Behaviour Changes ◽  
Als Patients ◽  
Lateral Sclerosis

Objective Approximately 50% of amyotrophic lateral sclerosis (ALS) patients have cognitive and behavioural dysfunction in varying degrees and forms. Previous studies have shown that cognitive and behavioural changes may indicate a poor prognosis, and cognitive function gradually deteriorates over the course of disease, but the results of different studies have been inconsistent. In addition, there are relatively limited long-term follow-up studies tracking death as an endpoint. The purpose of this study was to investigate the clinical prognostic characteristics of ALS patients with cognitive behavioural changes through long-term follow-up in a cohort. Methods A total of 87 ALS patients from 2014 to 2015 in the Third Hospital of Peking University were selected and divided into a pure ALS group, an ALS with behavioural variant of frontotemporal dementia (ALS-bvFTD) group, and an ALS with cognitive and behaviour changes group. All patients were followed up for 60 months. The main end point was death and tracheotomy. Results There was no significant difference in survival curve between pure ALS and ALS with cognitive and behavioural change group, but the survival time of ALS-bvFTD group was significantly lower than the other two groups (P < 0.001). For those who was followed up to the endpoint, the survival time of the ALS-bvFTD group was significantly shorter than that of the pure ALS group (t = 5.33, p < 0.001) or the ALS with cognitive and behaviour changes group (t = 4.25, p < 0.001). The progression rate of ALS Functional Rating Scale–Revised (FRS-R) scores from recruitment to endpoint was significantly faster in the ALS-bvFTD group than in the pure ALS group (z = 2.68, p = 0.01) or the ALS with cognitive and behavioural changes group (z = 2.75, p = 0.01). There was no significant difference in survival time (t = 0.52, P = 0.60) or FRS-R score progression rate (z = 0.31, p = 0.76) between the pure ALS group and the ALS with cognitive and behavioural changes group. The total Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) score was positively correlated with survival time (r = 0.38, p = 0.01). Conclusion ALS-bvFTD patients have shorter survival time. The total ECAS score may be correlated with survival time.

scholarly journals Creatine Kinase and Progression Rate in Amyotrophic Lateral Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1174 ◽  
Author(s):  
Marco Ceccanti ◽  
Valeria Pozzilli ◽  
Chiara Cambieri ◽  
Laura Libonati ◽  
Emanuela Onesti ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rating Scale ◽  
Axonal Damage ◽  
Mouse Strains ◽  
Disease Rate ◽  
Progression Rate ◽  
Predisposing Factor ◽  
Slow Progressors ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no recognized clinical prognostic factor. Creatinine kinase (CK) increase in these patients is already described with conflicting results on prognosis and survival. In 126 ALS patients who were fast or slow disease progressors, CK levels were assayed for 16 months every 4 months in an observational case-control cohort study with prospective data collection conducted in Italy. CK was also measured at baseline in 88 CIDP patients with secondary axonal damage and in two mouse strains (129SvHSD and C57-BL) carrying the same SOD1G93A transgene expression but showing a fast (129Sv-SOD1G93A) and slow (C57-SOD1G93A) ALS progression rate. Higher CK was found in ALS slow progressors compared to fast progressors in T1, T2, T3, and T4, with a correlation with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores. Higher CK was found in spinal compared to bulbar-onset patients. Transgenic and non-transgenic C57BL mice showed higher CK levels compared to 129SvHSD strain. At baseline mean CK was higher in ALS compared to CIDP. CK can predict the disease progression, with slow progressors associated with higher levels and fast progressors to lower levels, in both ALS patients and mice. CK is higher in ALS patients compared to patients with CIDP with secondary axonal damage; the higher levels of CK in slow progressors patients, but also in C57BL transgenic and non-transgenic mice designs CK as a predisposing factor for disease rate progression.

013 Lipid metabolism and body composition in frontotemporal dementia-amyotrophic lateral sclerosis spectrum: effect on survival and disease progression

2018 ◽  
Vol 89 (6) ◽  
pp. A6.3-A7
Author(s):  
Rebekah M Ahmed ◽  
Elizabeth Highton-Williamson ◽  
Jashelle Caga ◽  
Nicollette Thornton ◽  
Eleanor Ramsey ◽  
...  
Keyword(s):  
Body Composition ◽  
Lipid Metabolism ◽  
Total Cholesterol ◽  
Eating Behaviour ◽  
Density Lipoprotein ◽  
Cognitive Change ◽  
Fat Intake ◽  
Cholesterol Levels ◽  
Als Patients ◽  
Lateral Sclerosis

IntroductionPatients with Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) exhibit changes in eating behaviour that could potentially affect lipid levels and body composition. This study aimed to document changes in lipid metabolism and body composition across the ALS-FTD spectrum to identify potential relationships to eating behaviour (including fat intake), cognitive change, body mass index (BMI) and effect on survival.MethodsOne hundred and twenty eight participants were recruited: 37 ALS patients, 15 ALS patients with cognitive and behavioural change (ALS-Plus), and 13 ALS-FTD, 31 behavioural variant FTD, and 32 healthy controls. Fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride levels were measured and correlated to eating behaviour (caloric, fat intake), cognitive change, and BMI; effect on survival was examined using cox regression analyses. In a cohort of 60 patients, changes in body composition and fat deposition was examined using Dual energy X-ray absorptiometry scans (DEXA), a technique used in obesity research.ResultsThere was a spectrum of lipid changes from ALS to FTD with increased triglyceride (p<0.001), total cholesterol/HDL ratio (p<0.001), and lower HDL levels (p=0.001) in all patient groups compared to controls. Whilst there was no increase in total cholesterol levels, a higher cholesterol level was found to correlate with 3.25 times improved survival (p=0.031). Triglyceride and HDL cholesterol correlated to fat intake, BMI, and measures of cognition andConclusionA spectrum of changes in lipid metabolism and body composition has been identified in ALS-FTD, with total cholesterol levels found to potentially impact on survival. These changes were mediated by changes in fat intake, and BMI, and may also be mediated by the neurodegenerative process, offering the potential to modify these factors to slow disease progression and improve survival.

scholarly journals Side of Limb-Onset Predicts Laterality of Gray Matter Loss in Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Qiuli Zhang ◽  
Cuiping Mao ◽  
Jiaoting Jin ◽  
Chen Niu ◽  
Lijun Bai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Onset ◽  
Progression Rate ◽  
Imaging Evaluation ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Limb Onset

Conflicting findings have been reported regarding the lateralized brain abnormality in patients with amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the probable lateralization of gray matter (GM) atrophy in ALS patients. We focused on the relationship between the asymmetry in decreased GM volume and the side of disease onset in patients with limb-onset. Structural imaging evaluation of normalized atrophy (SIENAX) and voxel-based morphometry (VBM) were used to assess differences in global and local brain regions in patients with heterogeneous body onset and subgroups with different side of limb-onset. We found global brain atrophy and GM losses in the frontal and parietal areas in each patient group as well as left predominant GM losses in the total cohort. The intriguing findings in subgroup analyses demonstrated that the motor cortex in the contralateral hemisphere of the initially involved limb was most affected. We also found that regional brain atrophy was related to disease progression rate. Our observations suggested that side of limb-onset can predict laterality of GM loss in ALS patients and disease progression correlates with the extent of cortical abnormality.

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