scholarly journals Poor Bone Quality in Patients With Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Jordi Caplliure-Llopis ◽  
Dolores Escrivá ◽  
María Benlloch ◽  
José Enrique de la Rubia Ortí ◽  
José María Estrela ◽  
...  
Keyword(s):  
Vitamin D ◽  
Amyotrophic Lateral Sclerosis ◽  
Bone Health ◽  
Clinical Status ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Bone Parameters ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Tsh Levels

Objective: Musculoskeletal functional deterioration in Amyotrophic lateral sclerosis (ALS) is associated with an increase in bone fractures. The purpose of this study was to evaluate the influence of sex, ALS type, on bone quality in patients with ALS compared to healthy controls. The impact on bone health of the clinical status and some metabolic parameters was also analyzed in ALS patients.Methods: A series of 33 voluntary patients with ALS, and 66 healthy individuals matched in sex and age underwent assessment of bone mass quality using quantitative ultrasound (QUS) of the calcaneus. Ultrasonic broadband attenuation (BUA), the speed of sound (SOS), stiffness index and T-score were measured. Bone mineral density (BMD) was estimated using standard equations. Apart from fat and muscle mass percentage determinations, clinical baseline measures in ALS patients included ALSFRS-R score, Barthel index for activities of daily living, pulmonary function measured using FVC, and muscular strength assessed by a modified MRC grading scale. Laboratory tests included serum calcium, 25-HO-cholecalciferol (Vitamin D), alkaline phosphatase (ALP), T4 and TSH.Results: All bone parameters evaluated were statistically significant lower in ALS patients than in healthy controls. ALS females showed significantly lower bone parameters than healthy females. According to the estimated BMD, there were 25 ALS patients (75.8%) and 36 (54.5%) healthy individuals showing an osteoporotic profile (BMD <0.700 g/cm2). Only 16.7% of the ALS females had T-scores indicative of healthy bones. There was no correlation between any of the clinical parameters analyzed and the bone QUS measurements. Vitamin D and TSH levels positively correlated with all the bone parameters.Conclusions: This study confirms that ALS patients, particularly females, exhibited deteriorated bone health as compared to healthy individuals. These structural bone changes were independent of ALS subtype and clinical status. Bone health in ALS patients seems to be related to certain metabolic parameters such as Vitamin D and TSH levels.

scholarly journals Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lu Chen ◽  
Yong Chen ◽  
Mingming Zhao ◽  
Lemin Zheng ◽  
Dongsheng Fan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Gut Microbiota ◽  
Metabolic Pathway ◽  
Plasma Concentrations ◽  
Disease Onset ◽  
Healthy Controls ◽  
Age And Gender ◽  
And Gender ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract To compare the plasma concentrations of trimethylamine N-oxide (TMAO) and its precursors in amyotrophic lateral sclerosis (ALS) patients, their spouses and healthy controls and to find associations between gut microbiota metabolites and ALS. ALS patients were recruited at Peking University Third Hospital from January 2015 to December 2018. Information was collected from their spouses at the same time. Age and gender matched healthy controls were recruited from individuals who visited the physical examination center for health checkups. Blood samples were collected after at least 4 h of fasting. Concentrations of the metabolites were quantified using stable isotope dilution liquid chromatography–tandem mass spectrometry. Group differences were analyzed using parametric and nonparametric tests, as appropriate. In this study, 160 patients with ALS were recruited. In these patients, 63 were compared with their spouses, 148 were compared with age and gender matched controls, and 60 were compared with both their spouses and heathy controls in the same time. The carnitine concentration was significantly higher in patients than in their spouses, while there were no significant differences in the concentrations of other metabolites. The carnitine and betaine concentrations were higher, while the choline, TMAO and butyrobetaine concentrations were lower in ALS than in healthy controls. The concentrations of the metabolites in the spouses were more similar to the ALS patients rather than to the healthy controls. In the ALS group, the plasma concentrations of carnitine, betaine, choline and TMAO were inversely related to the severity of upper motor neuron impairment. The TMAO metabolic pathway of the gut microbiota is disturbed in both ALS patients and their spouses, which might suggest that the changes in the gut microbiota occurred before disease onset. The negative correlations between the involvement of UMNs and the concentrations of the metabolites might suggest that the inhibition of this metabolic pathway might lead to a better prognosis in ALS patients.

scholarly journals Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

2017 ◽  
Vol 75 (5) ◽  
pp. 272-276 ◽  
Author(s):  
Marcelo Chaves ◽  
Mariela Bettini ◽  
Maria Cecilia Fernandez ◽  
Maria Jose Garcia Basalo ◽  
Juan Ignacio Rojas ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Cognitive Profile ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Preliminary Study ◽  
Als Patients ◽  
Lateral Sclerosis

ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

scholarly journals Quantitative susceptibility-weighted imaging in amyotrophic lateral sclerosis with 3.0 T magnetic resonance imaging

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199222
Author(s):  
Meng-Yu Liu ◽  
Zhi-Ye Chen ◽  
Jin-Feng Li ◽  
Hua-Feng Xiao ◽  
Lin Ma
Keyword(s):  
Magnetic Resonance Imaging ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Shift ◽  
Susceptibility Weighted Imaging ◽  
Precentral Gyrus ◽  
Healthy Controls ◽  
Resonance Imaging ◽  
3.0 T ◽  
Als Patients ◽  
Lateral Sclerosis

Objective To evaluate alterations in phase-shift values in the gray matter of patients with amyotrophic lateral sclerosis (ALS) using susceptibility-weighted imaging (SWI). Methods Twenty patients with definite or probable ALS and 19 age- and sex-matched healthy controls were enrolled. SWI was performed using a 3.0 T magnetic resonance imaging scanner. Phase-shift values were measured in corrected phase images using regions of interest, which were placed on the bilateral precentral gyrus, frontal cortex, caudate nucleus, globus pallidus, and putamen. Results Phase-shift values of the precentral gyrus were significantly lower in ALS patients (−0.176 ± 0.050) than in the control group (−0.119 ± 0.016) on SWI. The average phase-shift values of the frontal cortex, caudate nucleus, globus pallidus, and putamen in ALS patients (−0.089 ± 0.023, −0.065 ± 0.016, −0.336 ± 0.191, and −0.227 ± 0.101, respectively) were not significantly different from those in the healthy controls (−0.885 ± 0.015, −0.079 ± 0.018, −0.329 ± 0.136, and −0.229 ± 0.083, respectively). Conclusions Compared with healthy controls, ALS patients had a lower phase-shift value in the precentral gyrus, which may be related to abnormal iron overload. Thus, SWI is a potential method for identifying ALS patients.

scholarly journals Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

2021 ◽  
Vol 15 ◽  
Author(s):  
Haining Li ◽  
Qiuli Zhang ◽  
Qianqian Duan ◽  
Jiaoting Jin ◽  
Fangfang Hu ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Correlation Analysis ◽  
Disease Severity ◽  
Structural Changes ◽  
Diffusion Tensor ◽  
Healthy Controls ◽  
Significant Difference ◽  
Als Patients ◽  
And Diffusion ◽  
Lateral Sclerosis

IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

scholarly journals Nine Hole Peg Test and Transcranial Magnetic Stimulation: Useful to Evaluate Dexterity of the Hand and Disease Progression in Amyotrophic Lateral Sclerosis

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
David Czell ◽  
Christoph Neuwirth ◽  
Markus Weber ◽  
Sabine Sartoretti-Schefer ◽  
Andreas Gutzeit ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Progression ◽  
Motor Neurons ◽  
Fine Motor ◽  
Healthy Controls ◽  
Good Tool ◽  
Resting Motor Threshold ◽  
Als Patients ◽  
Nine Hole Peg Test ◽  
Lateral Sclerosis

Objective. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with involvement of the upper and lower motor neurons. Since the loss of fine motor skills is one of the earliest signs of ALS, the hypothesis was tested if the nine hole PEG test (NHPT) and transcranial magnet stimulation (TMS) with resting-motor threshold (RMT) could be useful in monitoring disease progression. Methods. We examined 28 ALS patients and 27 age-matched healthy controls. ALS patients and healthy controls underwent the nine hole peg test (NHPT) and TMS with RMT. Measurements in patients were repeated after three and six months. Results. At baseline, the median NHPT durations were 1,4-fold longer (p<0.001), and TMS scores showed a significant 0.8-fold smaller score in ALS patients compared with healthy controls (p<0.001). The comparison of three and six months versus baseline revealed significant differences for NHPT durations and ALSFRS-R in patients, whereas TMS scores did not significantly differ in the patients. Conclusion. NHPT seems to be a good tool to evaluate dexterity of the hand and the progression of the disease in ALS patients. TMS RMT to the hand muscles seems to be poorly qualified to evaluate the dexterity of the hand function and the course of the disease.

scholarly journals Cortical Thinning of Motor and Non-Motor Brain Regions Enables Diagnosis of Amyotrophic Lateral Sclerosis and Supports Distinction between Upper- and Lower-Motoneuron Phenotypes

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1195
Author(s):  
Stefano Ferrea ◽  
Frederick Junker ◽  
Mira Korth ◽  
Kai Gruhn ◽  
Torsten Grehl ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Temporal Lobe ◽  
Cortical Thickness ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Precentral Gyrus ◽  
Healthy Controls ◽  
Cortical Thinning ◽  
Als Patients ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. In addition to the classical ALS affecting both the upper and lower motoneurons (UMN and LMN), other subtypes with the predominant (or even exclusive) affection of the UMN or LMN have been identified. This work sought to detect specific patterns of cortical brain atrophy in the UMN and LMN phenotypes to distinguish these two forms from the healthy state. Methods: Using high-resolution structural MRI and cortical thickness analysis, 38 patients with a diagnosis of ALS and predominance of either the UMN (n = 20) or the LMN (n = 18) phenotype were investigated. Results: Significant cortical thinning in the temporal lobe was found in both the ALS groups. Additionally, UMN patients displayed a significant thinning of the cortical thickness in the pre- and postcentral gyrus, as well as the paracentral lobule. By applying multivariate analyses based on the cortical thicknesses of 34 brain regions, ALS patients with either a predominant UMN or LMN phenotype were distinguished from healthy controls with an accuracy of 94% and UMN from LMN patients with an accuracy of 75%. Conclusions: These findings support previous hypothesis that neural degeneration in ALS is not confined to the sole motor regions. In addition, the amount of cortical thinning in the temporal lobe helps to distinguish ALS patients from healthy controls, that is, to support or discourage the diagnosis of ALS, while the cortical thickness of the precentral gyrus specifically helps to distinguish the UMN from the LMN phenotype.

scholarly journals Texture Analysis to Detect Cerebral Degeneration in Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 45 (5) ◽  
pp. 533-539 ◽  
Author(s):  
Abdullah Ishaque ◽  
Rouzbeh Maani ◽  
Jerome Satkunam ◽  
Peter Seres ◽  
Dennell Mah ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Texture Analysis ◽  
Brain Mri ◽  
Texture Features ◽  
Visual Assessment ◽  
Image Resolution ◽  
Healthy Controls ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Cerebral Degeneration

AbstractBackgroundEvidence of cerebral degeneration is not apparent on routine brain MRI in amyotrophic lateral sclerosis (ALS). Texture analysis can detect change in images based on the statistical properties of voxel intensities. Our objective was to test the utility of texture analysis in detecting cerebral degeneration in ALS. A secondary objective was to determine whether the performance of texture analysis is dependent on image resolution.MethodsHigh-resolution (0.5×0.5 mm2 in-plane) coronal T2-weighted MRI of the brain were acquired from 12 patients with ALS and 19 healthy controls on a 4.7 Tesla MRI system. Image data sets at lower resolutions were created by down-sampling to 1×1, 2×2, 3×3, and 4×4 mm2. Texture features were extracted from a slice encompassing the corticospinal tract at the different resolutions and tested for their discriminatory power and correlations with clinical measures. Subjects were also classified by visual assessment by expert reviewers.ResultsTexture features were different between ALS patients and healthy controls at 1×1, 2×2, and 3×3 mm2 resolutions. Texture features correlated with measures of upper motor neuron function and disability. Optimal classification performance was achieved when best-performing texture features were combined with visual assessment at 2×2 mm2 resolution (0.851 area under the curve, 83% sensitivity, 79% specificity).ConclusionsTexture analysis can detect subtle abnormalities in MRI of ALS patients. The clinical yield of the method is dependent on image resolution. Texture analysis holds promise as a potential source of neuroimaging biomarkers in ALS.

scholarly journals Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elisa Conti ◽  
Gessica Sala ◽  
Susanna Diamanti ◽  
Marco Casati ◽  
Christian Lunetta ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Serum Levels ◽  
The Other ◽  
Diagnostic Process ◽  
Healthy Controls ◽  
Naturally Occurring ◽  
Als Patients ◽  
First Time ◽  
Lateral Sclerosis

AbstractAmyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer’s disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.

scholarly journals Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways

2011 ◽  
Vol 208 (12) ◽  
pp. 2429-2447 ◽  
Author(s):  
Vivek Swarup ◽  
Daniel Phaneuf ◽  
Nicolas Dupré ◽  
Susanne Petri ◽  
Michael Strong ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Messenger Rna ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Healthy Individuals ◽  
Wild Type ◽  
Disease Symptoms ◽  
Als Patients ◽  
Lateral Sclerosis

TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-κB activation and that NF-κB may constitute a therapeutic target for the disease.

scholarly journals TDP-43 and HERV-K Envelope-Specific Immunogenic Epitopes Are Recognized in ALS Patients

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2301
Author(s):  
Elena Rita Simula ◽  
Giannina Arru ◽  
Ignazio Roberto Zarbo ◽  
Paolo Solla ◽  
Leonardo A. Sechi
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Humoral Response ◽  
Dna Binding Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Als Patients ◽  
Circulating Levels ◽  
Lateral Sclerosis

The human endogenous retrovirus-K (HERV-K) and TAR DNA-binding protein 43 (TDP-43) have been associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the humoral response against HERV-K envelope surface (env-su) glycoprotein antigens and TDP-43 in the plasma of ALS patients and healthy controls (HCs). The measured levels of Abs against the different epitopes’ fragments were significantly elevated in ALS patients, both in long-survivor (LS) and newly diagnosed (ND) patients, compared to HCs. We observed a positive correlation between HERV-K and TDP-43 antibodies (Abs) levels, which seemed to strengthen with disease progression, that was not found in HCs. The TDP-43 and HERV-K epitopes identified in this study are highly immunogenic and recognized by the humoral response of ALS patients. Increased circulating levels of Abs directed against specific HERV-K- and TDP-43-derived epitopes could serve as possible biomarkers.

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