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 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 Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

2021 ◽  
Author(s):  
Fabiola De Marchi ◽  
◽  
Claudia Carrarini ◽  
Antonio De Martino ◽  
Luca Diamanti ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Time Course ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Multisystem Disorder ◽  
Behavioral Impairment ◽  
Behavioral Impairments ◽  
Als Patients ◽  
Disease Stages ◽  
Lateral Sclerosis

Abstract Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

scholarly journals Common and rare variant association analyses in Amyotrophic Lateral Sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

2021 ◽  
Author(s):  
Wouter van Rheenen ◽  
Rick A.A. van der Spek ◽  
Mark K. Bakker ◽  
Joke J.F.A. van Vugt ◽  
Paul J. Hop ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rare Variants ◽  
Unmet Need ◽  
Life Time ◽  
Cell Types ◽  
Brain Regions ◽  
Multiple Traits ◽  
Association Analyses ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Across environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.

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 Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis

2020 ◽  
Author(s):  
Cezar Thomas Suratos ◽  
Naoko Takamatsu ◽  
Hiroki Yamazaki ◽  
Yusuke Osaki ◽  
Tatsuya Fukumoto ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Phrenic Nerve ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Pulmonary Function Tests ◽  
Cross Sectional ◽  
The Right ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons causing progressive weakness. It eventually involves the diaphragm which leads to respiratory paralysis and subsequently death. Phrenic nerve (PN) conduction studies and diaphragm ultrasound has been studied and correlated with pulmonary function tests in ALS patients. However, PN ultrasonography has not been employed in ALS. This study aims to sonographically evaluate the morphologic appearance of the PN of ALS patients. Thirty-eight ALS patients and 28 normal controls referred to the neurophysiology laboratory of two institutions were retrospectively included in the study. Baseline demographic and clinical variables such as disease duration, ALS Functional Rating Scale-Revised score, and ALS region of onset were collected. Ultrasound was used to evaluate the PN cross-sectional area (CSA) of ALS and control subjects. The mean PN CSA of ALS patients were 1.08 ± 0.39 mm on the right and 1.02 ± 0.34 mm on the left. The PN CSA of ALS patients were significantly decreased compared to controls (p value < 0.00001). The PN CSA of ALS patients was not correlated to any of the demographic and clinical parameters tested. This study demonstrates that ALS patients have a smaller PN size compared to controls using ultrasonography.

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 &lt;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 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 Pain in Amyotrophic Lateral Sclerosis: A Neglected Aspect of Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Chalonda R. Handy ◽  
Christina Krudy ◽  
Nicholas Boulis ◽  
Thais Federici
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Viral Vectors ◽  
Neurodegenerative Disorder ◽  
Respiratory Dysfunction ◽  
Clostridial Neurotoxins ◽  
Reduction Of Pain ◽  
Als Patients ◽  
Number Of Individuals ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive loss of motor neurons, muscle wasting, and respiratory dysfunction. With disease progression, secondary symptoms arise creating new problematic conditions for ALS patients. Amongst these is pain. Although not a primary consequence of disease, pain occurs in a substantial number of individuals. Yet, studies investigating its pathomechanistic properties in the ALS patient are lacking. Therefore, more exploratory efforts into its scope, severity, impact, and treatment should be initiated. Several studies investigating the use of Clostridial neurotoxins for the reduction of pain in ALS patients suggest the potential for a neural specific approach involving focal drug delivery. Gene therapy represents a way to accomplish this. Therefore, the use of viral vectors to express transgenes that modulate the nociceptive cascade could prove to be an effective way to achieve meaningful benefit in conditions of pain in ALS.

Progesterone and cortisol levels in sporadic amyotrophic lateral sclerosis (sALS): correlation with prognostic factors

2011 ◽  
Vol 6 (1) ◽  
Author(s):  
Gisella Gargiulo Monachelli ◽  
Maria Meyer ◽  
Gabriel Rodríguez ◽  
Laura Garay ◽  
Roberto E. Sica ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Prognostic Factors ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Sporadic Als ◽  
Bulbar Onset ◽  
Als Patients ◽  
Short Time ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Worse prognostic factors in ALS are: (a) advanced age, (b) bulbar onset, and (c) short time between onset and diagnosis. Progesterone (PROG) has been associated with neuroprotective and promyelinating activities in injury, ischemia and degeneration of the central and peripheral nervous system. Cortisol is connected to the response to stress situations and could contribute to neuronal damage. The goals of this study were: (i) to investigate whether PROG levels are modified by ALS prognostic factors and (ii) to determine whether cortisol follows the same pattern. We determined serum steroid levels in 27 patients with sporadic ALS (sALS) and 21 controls. Both steroid hormones showed significantly increased levels in ALS patients versus controls (mean±SEM: PROG ALS vs. control: 0.54±0.05 vs. 0.39±0.04 ng/mL, p<0.05; cortisol ALS vs. control: 17.02±1.60 vs. 11.83±1.38 μg/dL, p<0.05).

scholarly journals Magnetic resonance metrics to evaluate the effect of therapy in amyotrophic lateral sclerosis: the experience with edaravone

2021 ◽  
Author(s):  
Eugenio Distaso ◽  
Giammarco Milella ◽  
Domenico Maria Mezzapesa ◽  
Alessandro Introna ◽  
Eustachio D’Errico ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Magnetic Resonance ◽  
Brain Mri ◽  
Prognostic Indicators ◽  
Precentral Gyrus ◽  
Longitudinal Mri ◽  
Effect Of Therapy ◽  
New Treatment ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Background Edaravone was approved as a new treatment for amyotrophic lateral sclerosis (ALS), although there are different opinions on its effectiveness. Magnetic resonance (MRI) measures appear promising as diagnostic and prognostic indicators of disease. However, published studies on MRI using to monitor treatment efficacy in ALS are lacking. Purpose The objective of this study was to investigate changes in brain MRI measures in patients treated with edaravone. Methods Thirteen ALS patients assuming edaravone (ALS-EDA) underwent MRI at baseline (T0) and after 6 months (T6) to measure cortical thickness (CT) and fractional anisotropy (FA) of white matter (WM) tracts. MRI data of ALS-EDA were compared at T0 with those of 12 control subjects (CS), and at T6 with those of 11 ALS patients assuming only riluzole (ALS-RIL), extracted from our ALS cohort using a propensity-score-matching. A longitudinal MRI analysis was performed in ALS-EDA between T6 and T0. Results At T0, ALS-EDA showed a cortical widespread thinning in both hemispheres, particularly in the bilateral precentral gyrus, and a reduction of FA in bilateral corticospinal tracts, in comparison to CS. Thinning in bilateral precentral cortex and significant widespread reduction of FA in several WM tracts were observed in ALS-EDA at T6 compared to T0. At T6, no significant differences in MRI measures of ALS-EDA versus ALS-RIL were found. Conclusions Patients treated with edaravone showed progression of damage in the motor cortex and several WM tracts, at a six-month follow-up. Moreover, this study showed no evidence of a difference between edaravone and riluzole.

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