scholarly journals Serial assessment of iron in the motor cortex in limb-onset Amyotrophic Lateral Sclerosis using Quantitative Susceptibility Mapping

2019 ◽  
Author(s):  
Anjan Bhattarai ◽  
Zhaolin Chen ◽  
Phillip G. D. Ward ◽  
Paul Talman ◽  
Susan Mathers ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Iron Concentration ◽  
Motor Area ◽  
Healthy Controls ◽  
Quantitative Susceptibility Mapping ◽  
Iron Dysregulation ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Limb Onset

ABSTRACTObjectiveDysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with Amyotrophic Lateral Sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based Quantitative Susceptibility Mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a six-month period.MethodsIron concentration was investigated using magnetic resonance based -QSM in the primary motor cortex and the pre-motor area in thirteen limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and eleven age and sex-matched healthy controls. Nine ALS patients underwent follow-up scans at six months.ResultsSignificantly increased QSM was observed in the left posterior primary motor area (p = 0.02, Cohen’s d = 0.9) and right anterior primary motor area (p = 0.02, Cohen’s d = 0.92) in all individuals with limb-onset ALS compared to healthy controls. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to healthy controls. No significant change in QSM was observed at the six-month follow-up scans in the ALS patients.ConclusionsThe findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a radiological indicator in disease diagnosis, and in clinical trials in limb-onset ALS and its subtypes.HighlightsSerial measurement of QSM in the motor cortex in limb-onset ALS was performedQSM changes in the motor cortex in ALS sub-groups were investigatedHigher QSM was observed in the motor cortex in Lumbar ALS relative to controlsQSM is sensitive to iron dysregulation in the motor cortex in limb-onset ALS

scholarly journals The Profile of Amyotrophic Lateral Sclerosis in Natives of Western Himalayas: Hospital-Based Cohort Study

2018 ◽  
Vol 09 (03) ◽  
pp. 305-311
Author(s):  
Sachin Sondhi ◽  
Sudhir Sharma ◽  
S. S. Kaushal ◽  
Ayushi Mehta ◽  
Vikas Banayal
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Clinical Characteristics ◽  
Western Himalayas ◽  
Duration Of Symptoms ◽  
Female Ratio ◽  
Bulbar Onset ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Limb Onset

ABSTRACT Background: Despite the disabling nature of amyotrophic lateral sclerosis (ALS), there are no contemporary data on clinical characteristics available from rural hilly states from India. Thus, the present study aimed at reporting clinical profile in ALS patients from natives of Western Himalayas. Materials and Methods: A total of 32 patients of ALS were enrolled over a period of 1 year (2013–2014) in the present study. The demographic profile, clinical characteristics, and risk factors were systematically recorded, and these patients were followed for 1 year. Results: The mean age of ALS patients was 53 ± 15.88 (23–90 years). Maximum number of patients of both limb onset and bulbar onset were in the age group of 40–49 years Figure 1. Male to female ratio was 1.46. Limb-onset was seen in 23 (72%) and bulbar-onset in 9 (28%) of patients. Bulbar-onset was more common in females as compared to males. Mean duration of symptoms were 19.06 ± 24 months (range 4–120 months). None of the studied risk factor showed statistically significant association with outcome of the disease. No familial association was found. The most common site of weakness was upper limb distal weakness. Definite ALS was seen in 13 (40.6%) patients. Mean ALS functional rating scale (ALSFRS) at presentation is 35.7 ± 7.9. All patients were started on riluzole. Mean ALSFRS at 9-month follow-up was 32.9 ± 7.4. After 1 year of follow up, 5 out of 32 patients died and among them, 4 were of limb onset and 1 was of bulbar onset ALS. Mean age at death in males was 66 ± 16 years and in females was 56.33 ± 24.8 years; mean survival in these patients was 25 months. Conclusion: This present study highlights following findings: (1) Male preponderance is less common in our patients as compared to earlier reports from India. Bulbar onset is more common in elderly (age >60 years) females. (2) As per previous reports from India, when compared to Western population present study supports the fact of the younger age of onset and longer duration of symptoms and slow course of disease in Indian patients.

scholarly journals Combination of serum and CSF neurofilament-light and neuroinflammatory biomarkers to evaluate ALS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandre Brodovitch ◽  
José Boucraut ◽  
Emilien Delmont ◽  
Amandine Parlanti ◽  
Aude-Marie Grapperon ◽  
...  
Keyword(s):  
Serum Levels ◽  
Healthy Controls ◽  
Peripheral Neuropathies ◽  
Neurofilament Light ◽  
Cutoff Value ◽  
Csf Analysis ◽  
Diagnostic Potential ◽  
Ifn Γ ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractThis monocentric prospective study of patient suffering from Amyotrophic lateral sclerosis (ALS) aims to evaluate the prognosis and diagnostic potential of both Neurofilament-Light (Nf-L) and neuroinflammatory biomarkers in serum and CSF. Candidate markers levels were measured using multiplex method in serum of 60 ALS patients, 94 healthy controls of 43 patients suffering from Inflammatory Peripheral Neuropathies (IPN). A comparative CSF analysis was performed for 20 ALS and 17 IPN patients. Among the altered biomarkers, CSF Nf-L level remains the best marker of ALS severity, while serum levels correlate strongly with disease progression. The combination of Nf-L and ICAM-1 concentrations in the CSF and IFN-γ concentration in the serum differentiate ALS patients from IPN patients with improved sensibility and specificity relative to individual biomarkers. A cutoff value of 0.49 for the fitted values of these 3 biomarkers discriminate ALS from IPN patients with a specificity of 100% (78.20–100%) and a sensibility of 85.71% (57.19–98.22%) with an AUC of 0.99 ± 0.01. The measure of Nf-L and neuroinflammatory biomarkers in CSF and serum can be useful biomarkers panel in the differential diagnosis of ALS.

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 Longitudinal dentate nuclei iron concentration and atrophy in Friedreich ataxia: IMAGE-FRDA

2018 ◽  
Author(s):  
Phillip G. D. Ward ◽  
Ian H Harding ◽  
Thomas G. Close ◽  
Louise A Corben ◽  
Martin B Delatycki ◽  
...  
Keyword(s):  
Iron Concentration ◽  
Friedreich Ataxia ◽  
Susceptibility Mapping ◽  
Disease Stage ◽  
Healthy Controls ◽  
Quantitative Susceptibility Mapping ◽  
Rates Of Change ◽  
Longitudinal Biomarker ◽  
Baseline Disease Severity

AbstractBackgroundFriedreich ataxia is a recessively inherited, progressive neurological disease characterised by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of pathology in these structures.MethodsUsing in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n=20) and healthy controls (n=18) over a two-year period.ResultsThe longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Moreover, atrophy was maximal in individuals early in the disease course, while the rate of iron concentration increased with disease progression.ConclusionsProgressive dentate nuclei pathology is evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a two-year period highlights the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool.

scholarly journals Orbitofrontal-hypothalamic projections are disrupted in hypermetabolic murine ALS model and human patients

2020 ◽  
Author(s):  
David Bayer ◽  
Stefano Antonucci ◽  
Hans-Peter Müller ◽  
Luc Dupuis ◽  
Tobias Boeckers ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Mouse Model ◽  
Lateral Hypothalamus ◽  
Large Scale ◽  
Energy Homeostasis ◽  
Metabolic Phenotype ◽  
Metabolic Disturbances ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractIncreased catabolism is a new clinical manifestation of Amyotrophic Lateral Sclerosis. A dysfunction of lateral hypothalamus may drive hypermetabolism in ALS; however, Its causes and anatomical substrates are unknown. We hypothesize that disruption cortico-hypothalamic circuits may impair energy homeostasis in ALS. We used rAAV2 for large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik to quantify projections from the forebrain to the latera hypothalamus of the SOD1(G93A) ALS mouse model as well as of the FusΔNLS ALS mouse model. Expanded projections from agranular Insula, ventrolateral orbitofrontal and secondary motor cortex to lateral hypothalamus were found in two independent cohorts of the hypermetabolic SOD1(G93A) ALS model. The non-hypermetabolic FusΔNLS ALS mouse model display a loss of projections from motor cortex but no change in projections from insula and orbitofronal cortex. 3T DTI-MRI data on 83 ALS patients and 65 controls confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients. Converging murine and human data demonstrate the selective disruption of hypothalamic inputs in ALS as a factor contributing to the origin of hypermetabolism.Significance statementWe provide a circuit perspective of the recently identified and medically relevant hyper-metabolic phenotype of Amyotrophic Lateral Sclerosis. We demonstrate the selective involvement of orbitofrontal, insular and motor cortex projections to hypothalamus in murine ALS models and in human patients. The enhanced pipeline for large-scale registration, segmentation projections mapping, the identification of new circuits target of neurodegeneration, and the relevance of these circuits in metabolic disturbances make this work relevant not only for the investigation of ALS but also for other neurodegenerative disease as well as for all conditions characterized by systemic energy imbalances.

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 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.

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