Fatigue in Patients With Multiple System Atrophy

Neurology ◽  
2021 ◽  
Vol 98 (1) ◽  
pp. e73-e82
Author(s):  
Lingyu Zhang ◽  
Bei Cao ◽  
Yanbing Hou ◽  
Xiaojing Gu ◽  
Qian-Qian Wei ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Regression Model ◽  
Rating Scale ◽  
Early Stage ◽  
Progression Rate ◽  
Nonmotor Symptoms ◽  
Binary Logistic Regression Model ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background and ObjectivesNonmotor symptoms are common in patients with multiple system atrophy (MSA), but there is limited knowledge regarding fatigue in MSA. This study aimed to investigate the frequency and evolution of fatigue and the factors related to fatigue and its progression in patients with MSA at an early stage.MethodsPatients with probable MSA were comprehensively evaluated at both baseline and the 1-year follow-up, including their motor and nonmotor symptoms. Fatigue and anxiety were assessed using the Fatigue Severity Scale (FSS) and Hamilton Anxiety Rating Scale (HARS), respectively. Orthostatic hypotension (OH) was defined as a decrease in the systolic or diastolic blood pressure by at least 30 and 15 mm Hg, respectively. The binary logistic regression model and linear regression model were used to analyze the factors related to fatigue and its progression, respectively.ResultsThis study enrolled 146 patients with MSA. The frequency of fatigue was 60.3%, 55.1%, and 64.9% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. The frequency of fatigue and the FSS score in patients with MSA increased from baseline to the 1-year follow-up (p < 0.05). Young age (odds ratio [OR] 0.939, 95% confidence interval [CI] 0.894–0.987), OH (OR 2.806, 95% CI 1.253–6.286), and high HARS score (OR 1.014, 95% CI 1.035–1.177) were associated with fatigue in MSA. OH was associated with fatigue in MSA-P (OR 3.391, 95% CI 1.066–10.788), while high HARS score was associated with fatigue in MSA-C (OR 1.159, 95% CI 1.043–1.287). In addition, only low FSS scores at baseline were associated with the annual progression rate of FSS scores in MSA, MSA-P, and MSA-C (p < 0.05). Neurofilament light chain, α-synuclein, glial fibrillary acidic protein, brain-derived neurotrophic factor, and triggering receptor expressed on myeloid cell-2 were not significantly associated with fatigue and its progression in MSA.DiscussionFatigue was prevalent in early-stage MSA, and it increased and remained persistent over time. This study demonstrated that OH and anxiety were associated with fatigue in patients with MSA.

scholarly journals Serum neurofilament light chain in behavioral variant frontotemporal dementia

Neurology ◽  
2018 ◽  
Vol 91 (15) ◽  
pp. e1390-e1401 ◽  
Author(s):  
Petra Steinacker ◽  
Sarah Anderl-Straub ◽  
Janine Diehl-Schmid ◽  
Elisa Semler ◽  
Ingo Uttner ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Light Chain ◽  
Brain Atrophy ◽  
Rating Scale ◽  
Neurofilament Light Chain ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Neurofilament Light ◽  
Baseline Serum ◽  
Functional Scores

ObjectiveTo determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD).MethodsBlood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration–related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry.ResultsAt baseline, serum NfL level correlated with CSF NfL (bvFTDr= 0.706,p< 0.0001; AD/MCIr= 0.666,p= 0.0003). Highest serum levels were observed in bvFTD (p<0 0.0001 vs Con and MCI,p= 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p= 0.0039 andp= 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline]r= 0.4157,p= 0.0006; [follow-up]r= 0.5629,p< 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe:r= −0.5857,p< 0.0001; 95% confidence interval −0.7415 to −0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline]r= 0.6624,p< 0.0001; [follow-up]r= 0.5659,p= 0.0003) but not with regional brain volumes.ConclusionsAs serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials.Classification of evidenceThis study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.

Blood NfL

Neurology ◽  
2019 ◽  
Vol 93 (11) ◽  
pp. e1104-e1111 ◽  
Author(s):  
Chin-Hsien Lin ◽  
Cheng-Hsuan Li ◽  
Kai-Chien Yang ◽  
Fang-Ju Lin ◽  
Chau-Chung Wu ◽  
...  
Keyword(s):  
Rating Scale ◽  
Cox Regression ◽  
Cognitive Status ◽  
Class Iii ◽  
Neurofilament Light Chain ◽  
Yahr Stage ◽  
Neurofilament Light ◽  
Cox Regression Analysis ◽  
Updrs Part

ObjectiveTo examine whether plasma neurofilament light chain (NfL) levels were associated with motor and cognitive progression in Parkinson disease (PD).MethodsThis prospective follow-up study enrolled 178 participants, including 116 with PD, 22 with multiple system atrophy (MSA), and 40 healthy controls. We measured plasma NfL levels with electrochemiluminescence immunoassay. Patients with PD received evaluations of motor and cognition at baseline and at a mean follow-up interval of 3 years. Changes in the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score and Mini-Mental State Examination score were used to assess motor and cognition progression.ResultsPlasma NfL levels were significantly higher in the MSA group than in the PD and healthy groups (35.8 ± 6.2, 17.6 ± 2.8, and 10.6 ± 2.3 pg/mL, respectively, p < 0.001). In the PD group, NfL levels were significantly elevated in patients with advanced Hoehn-Yahr stage and patients with dementia (p < 0.001). NfL levels were modestly correlated with UPDRS part III scores (r = 0.42, 95% confidence interval 0.46–0.56, p < 0.001). After a mean follow-up of 3.4 ± 1.2 years, a Cox regression analysis adjusted for age, sex, disease duration, and baseline motor or cognitive status showed that higher baseline NfL levels were associated with higher risks for either motor or cognition progression (p = 0.029 and p = 0.015, respectively).ConclusionsPlasma NfL levels correlated with disease severity and progression in terms of both motor and cognitive functions in PD.Classification of evidenceThis study provides Class III evidence that plasma NfL level distinguishes PD from MSA and is a surrogate biomarker for PD progression.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012632
Author(s):  
Kjetil Bjornevik ◽  
Eilis J. O'Reilly ◽  
Samantha Molsberry ◽  
Laurence N. Kolonel ◽  
Loic Le Marchand ◽  
...  
Keyword(s):  
Light Chain ◽  
Conditional Logistic Regression ◽  
Disease Diagnosis ◽  
Health Study ◽  
Plasma Samples ◽  
Blood Draw ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Rate Ratios

Objective:To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations.Methods:We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels.Results:Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments.Conclusions:Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease.Classification of Evidence:This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

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.

Retinal Morphological Changes during the Two Years of Follow-Up in Parkinson's Disease

2020 ◽  
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryurek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Morphological Changes ◽  
Fiber Layer ◽  
Significant Difference ◽  
Yahr Scale ◽  
And Control

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

scholarly journals Correlational Analysis of ALS Progression and Serum NfL Measured by Simoa Assay in Chinese Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Kazuo Sugimoto ◽  
Yi Han ◽  
Yuebo Song ◽  
Ying Gao
Keyword(s):  
Disease Severity ◽  
Single Molecule ◽  
Clinical Relevance ◽  
Rating Scale ◽  
Diagnostic Delay ◽  
Chinese Patients ◽  
Progression Rate ◽  
Neurofilament Light Chain ◽  
Potential Biomarker ◽  
Als Patients

Background: Neurofilament light chain (NFL) was believed to be a promising biomarker for the diagnosis of Amyotrophic lateral sclerosis (ALS) and disease burden evaluation.Objective: To determine the serum NFL level and its clinical relevance, including its association with disease severity [evaluated by the ALS Functional Rating Scale–revised (ALSFRS-r) score and King's College staging system] and progression (evaluated by the disease progression rate (DPR) and diagnostic delay), in ALS patients in China.Method: Serum NFL levels were detected using the Single Molecule Array (Simoa) technology in 30 ALS patients and 20 healthy controls (HCs).Results: There were significantly elevated levels of serum NFL in patients with ALS than in the HCs (P &lt; 0.001). The serum NFL levels were significantly higher in rapidly progressive ALS and patients in Stage 3 than in slowly progressive ALS and patients in Stage 2 (PDPR &lt; 0.001, PDiagnosticdelay = 0.019; Pstage= 0.033). Furthermore, the serum NFL levels negatively correlated with the diagnostic delay (R2 = 0.23, P = 0.016), the ALSFRS-r score (R2 = 0.15, P = 0.047) and disease duration (R2 = 0.15, P = 0.034), and positively correlated with the DPR (R2 = 0.42, P &lt; 0.001).Conclusions: The present study preliminarily investigated the diagnostic value of serum NFL and its clinical relevance in the Chinese ALS population using the ultrasensitive Simoa technology. The results demonstrated that the level of serum NFL may become a potential biomarker for ALS diagnosis and indicate disease severity and progression.

Predictors of Mortality in Nondemented Patients With Parkinson Disease: Motor Symptoms Versus Nonmotor Symptoms

2017 ◽  
Vol 31 (1) ◽  
pp. 19-26 ◽  
Author(s):  
D. Santos-García ◽  
E. Suárez-Castro ◽  
J. Ernandez ◽  
I. Expósito-Ruiz ◽  
C. Tuñas-Gesto ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Rating Scale ◽  
Evaluation Study ◽  
Motor Symptoms ◽  
Motor Complications ◽  
Nonmotor Symptoms ◽  
Predictors Of Mortality ◽  
Hazard Ratios ◽  
Long Term Follow Up

Background and Objective: The aim of this study is to identify risk factors for mortality in a community-based cohort of nondemented patients with Parkinson disease (PD) during prospective long-term follow-up, while also comparing the effect of motor complications to nonmotor symptoms (NMS) on risk of mortality. Methods: One hundred forty seven nondemented patients with PD (57.1% males; 70.9 ± 8.6 years old) were included in this 48 month follow-up, longitudinal, single, evaluation study. Motor and therapy-related complications were assessed using the Unified Parkinson’s Disease Rating Scale/part-IV (UPDRS-IV). Non-Motor Symptoms Scale (NMSS) total score was used to assess NMS burden. Cox proportional hazard models were applied to identify independent predictors of mortality during follow-up. Results: Twenty-two patients of 146 (15.1%) died (1 case without information). Both UPDRS-IV and NMSS total scores were higher at baseline in patients with PD who died (3.5 ± 3.1 vs 2.4 ± 2.4, P = .049 and 96.9 ± 58.6 vs 61.9 ± 51.0, P = .004, respectively). Unadjusted hazard ratios (HRs) associated with UPDRS-IV and NMSS total scores among those who died during follow-up were 1.171 (95% confidence interval [CI]: 1.012-1.357; P = .035) and 1.008 (95% CI: 1.002-1.013; P = .006), respectively. Independent predictors of mortality during follow-up after adjusting for other covariates were UPDRS-IV (HR: 1.224; 95% CI: 1.002-1.494; P = .047), age (HR: 1.231; 95% CI: 1104-1.374; P < .0001), and comorbidity (Charlson Index; HR: 1.429; 95% CI: 1.023-1.994; P = .036), but not NMSS total score (HR: 1.005; 95% CI: 0.996-1.014; P = .263). Conclusions: Both motor complications (UPDRS-IV) and NMS (NMSS) were associated with mortality at 4 years, being motor complications an independent predictor of it.

scholarly journals Linking Neuroinflammation and Extracellular Free Water in HIV Infection: A Longitudinal Study

2020 ◽  
Author(s):  
Md Nasir Uddin ◽  
Abrar Faiyaz ◽  
Lu Wang ◽  
Yuchuan Zhuang ◽  
Kyle D Murray ◽  
...  
Keyword(s):  
White Matter ◽  
Hiv Infection ◽  
Cognitive Performance ◽  
Brain Mri ◽  
Free Water ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Linear Mixed Effects ◽  
Neuropsychological Assessments

Abstract Background Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. However, no studies to date have investigated the FW in HIV infection, its temporal evolution, nor its association with brain-derived blood markers. Methods Ninety-six age-matched participants underwent brain MRI and clinical and neuropsychological assessments at baseline. HIV- participants underwent follow-up evaluation annually for two years while HIV + participants were seen 12 weeks after initiating cART and annually thereafter. Whole brain grey and white matter FW measures were compared between groups and correlated with clinical characteristics and cognitive scores. In addition, several pre-specified subcortical grey and white matter regions-of-interest (ROIs) were explored. Results At baseline, FW was significantly elevated in grey and white matter in cART-naïve HIV + participants compared to HIV- participants. Similarly, at baseline, HIV + participants had increased neurofilament light chain (NfL) values that correlated with FW and CD4 count, and decreased cognitive performance compared to HIV- participants. FW decreased in grey and white matter in HIV + participants after 12 weeks of cART treatment. 12-week cART treatment was also associated with a decrease in NfL and improvement in cognitive performance. Linear mixed effects regression models also revealed that FW was significantly reduced in most ROIs after 12 weeks of cART treatment. No significant FW differences were noted between the HIV + and HIV- participants at 1 and 2-year follow-up. Conclusions FW elevation in cART-naïve HIV + participants is likely due to neuroinflammation. The correlation between FW and NfL and the improvement in both FW and NfL after 12 weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2 years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.

Serum NFL discriminates Parkinson disease from atypical parkinsonisms

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1479-e1486 ◽  
Author(s):  
Tainá M. Marques ◽  
Anouke van Rumund ◽  
Patrick Oeckl ◽  
H. Bea Kuiperij ◽  
Rianne A.J. Esselink ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Single Molecule ◽  
Predictive Value ◽  
Clinical Symptoms ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Clinical Diagnoses

ObjectiveTo investigate the diagnostic value of serum neurofilament light chain (NFL) in patients with clear signs of parkinsonism but whose specific diagnosis was yet uncertain.MethodsSerum samples were collected from patients with clear signs of parkinsonism but with uncertain diagnosis at the inclusion. Clinical diagnoses of Parkinson disease (PD) and atypical parkinsonism disorders (APDs) were established after 3 years of follow-up and updated again after a maximum of 12 years in case longer follow-up data were available. Serum NFL was quantified by single molecule array in patients with PD (n = 55) and APD (n = 29, multiple system atrophy = 22, progressive supranuclear palsy = 7) and 53 nonneurologic controls.ResultsSerum NFL levels were elevated and differentiated the APD group (mean 23.8 ± 10.3 ng/L) from PD (mean 10.4 ± 4.9 ng/L) and controls (mean 11.5 ± 6.5 ng/L, p < 0.0001) with accuracy levels up to 91% (sensitivity = 86% and specificity = 85%). Serum NFL strongly correlated with CSF NFL levels (r = 0.72, p < 0.0001) in all groups and with age in PD (r = 0.78, p < 0.0001) and controls (r = 0.66, p < 0.0001). In our cohort, the probability of having APD was 76% (positive predictive value) and of having PD 92% (negative predictive value).ConclusionSerum NFL levels are markedly elevated in APD compared to PD and discriminate APDs from PD with high accuracy. Serum NFL may be a useful clinical biomarker to identify APD, even at stages when clinical symptoms are not yet conclusive.Classification of evidenceThis study provides Class II evidence that serum NFL levels accurately discriminate APDs from PD.

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