scholarly journals Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?

2021 ◽  
Author(s):  
Silvia Bozzetti ◽  
Sergio Ferrari ◽  
Serena Zanzoni ◽  
Daniela Alberti ◽  
Michele Braggio ◽  
...  
Keyword(s):  
Axonal Damage ◽  
Neurological Symptoms ◽  
University Hospital ◽  
Normal Range ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Medical Unit ◽  
Impaired Memory ◽  
The Common

AbstractThe persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4–62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.

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.

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 Association of intrathecal pleocytosis and IgG synthesis with axonal damage in early MS

2020 ◽  
Vol 7 (3) ◽  
pp. e679 ◽  
Author(s):  
Sinah Engel ◽  
Falk Steffen ◽  
Timo Uphaus ◽  
Peter Scholz-Kreisel ◽  
Frauke Zipp ◽  
...  
Keyword(s):  
Single Molecule ◽  
Leukocyte Count ◽  
Cross Sectional Study ◽  
Axonal Damage ◽  
Oligoclonal Bands ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Igg Synthesis ◽  
Healthy Donors

ObjectiveTo investigate the association of serum neurofilament light chain (sNfL) levels with CSF parameters in clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS), taking into account radiologic and clinical parameters of disease activity.MethodsSimultaneously collected serum and CSF samples of 112 untreated patients newly diagnosed with CIS or RRMS were included in this cross-sectional study. CSF parameters were obtained as part of routine diagnostic tests. sNfL levels of patients and of 62 healthy donors were measured by highly sensitive single molecule array (SiMoA) immunoassay.ResultsPatients with RRMS (n = 91, median 10.13 pg/mL, interquartile range [IQR] 6.67–17.77 pg/mL) had higher sNfL levels than healthy donors (n = 62, median 5.25 pg/mL, IQR 4.05–6.81 pg/mL, p < 0.001) and patients with CIS (n = 21, median 5.69 pg/mL, IQR 4.73–9.07 pg/mL, p < 0.001). Patients positive for oligoclonal bands (OCBs) (n = 101, median 9.19 pg/mL, IQR 6.34–16.38 pg/mL) had higher sNfL levels than OCB-negative patients (n = 11, median 5.93 pg/mL, IQR 2.93–8.56 pg/mL, p = 0.001). sNfL levels correlated with CSF immunoglobulin G (IgG) levels (r = 0.317, p = 0.002), IgG ratio (QIgG) (r = 0.344, p < 0.001), and CSF leukocyte count (r = 0.288, p = 0.002). In linear regression modeling, the CSF leukocyte count combined with the number of contrast-enhancing lesions in MRI predicted sNfL levels best.ConclusionsIn active MS, sNfL levels correlate with intrathecal pleocytosis and IgG synthesis, indicating that axonal damage is associated with both acute and chronic CNS-intrinsic inflammation.

scholarly journals Serum Neurofilament Light Chain in NMOSD and Related Disorders: Comparison According to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies Status

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774309 ◽  
Author(s):  
Mariotto S ◽  
Farinazzo A ◽  
Monaco S ◽  
Gajofatto A ◽  
Zanusso G ◽  
...  
Keyword(s):  
Light Chain ◽  
Malignant Disease ◽  
Serum Levels ◽  
Axonal Damage ◽  
Aquaporin 4 ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Spectrum Disorders ◽  
Multiple Sclerosis Patients ◽  
Demyelinating Disorders

Background Neurofilament light chain (NF-L) levels reflect axonal damage in different conditions, including demyelinating disorders. Objectives We aimed to compare serum NF-L levels in patients with aquaporin-4 antibodies (AQP4-Ab), myelin oligodendrocyte antibodies (MOG-Ab) and seronegative cases with neuromyelitis optica spectrum disorders and related disorders. Methods We analysed AQP4-Ab and MOG-Ab with cell-based assay and NF-L with ultrasensitive electrochemiluminescence immunoassay. Results Median NF-L levels were increased in 25 AQP4-Ab-positive patients (59 pg/ml) as compared with 22 MOG-Ab-positive cases (25 pg/ml), 52 seronegative patients (18 pg/ml), 25 multiple sclerosis patients (12 pg/ml) and 14 healthy controls (12 pg/ml). Conclusions Increased serum levels of NF-L in patients with AQP4-Ab or MOG-Ab might reflect an ongoing axonal damage and a more malignant disease course.

scholarly journals CSF Neurofilament light chain level predicts axonal damage in cerebral vasculitis

2019 ◽  
Vol 6 (6) ◽  
pp. 1134-1137 ◽  
Author(s):  
Marc Pawlitzki ◽  
Michaela Butryn ◽  
Florian Kirchner ◽  
Jacqueline Färber ◽  
Oliver Beuing ◽  
...  
Keyword(s):  
Light Chain ◽  
Cerebral Vasculitis ◽  
Axonal Damage ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Chain Level

Validation of CA-125 concentration nadir within the normal range following primary treatment as a predictor of survival for epithelial ovarian cancer (EOC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16007-16007
Author(s):  
A. Prat ◽  
J. Del Campo ◽  
S. Peralta ◽  
S. Cedres ◽  
A. Perez ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Model ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Stage Iii ◽  
Ca 125 ◽  
Rank Test ◽  
Normal Range

16007 Background: Recent studies suggest that the CA-125 nadir within the normal range after surgery and chemotherapy treatment is a predictor of survival (Crawford, ASCO 2004; Crawford, Ann Oncol 2005) and relapse (Markman, J Clin Oncol 2006). In order to validate these previous findings, we have conducted a retrospective analysis of patients (pts) treated in our institution for EOC. Methods: Between March 1, 1997, and October 30, 2005, all pts treated for EOC at Vall d'Hebron University Hospital were identified from the tumor registry database and screened retrospectively for their standard prognostic factors (age at diagnosis (=65 vs. >65), stage (III-IV vs. IC-II), and suboptimal vs. optimal cytorreduction). Inclusion criteria: an elevated CA-125 at time of diagnosis (>35 U/mL); primary treatment (PT) that consisted in surgery and intravenous carboplatin/paclitaxel for a maximum of 6–9 cycles; complete clinical and radiological response to initial treatment with normalization of CA-125 (=35 U/mL); and disease status at the time of last follow-up. Standard Kaplan-Meier methods were used to plot the progression-free survival (PFS) of members of each of the nadir groups. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: 123 pts were identified: 64 Group A (=10 U/mL), 42 Group B (11–20 U/mL), 17 Group C (21–35 U/mL). Median age: 56. Stage IC 25%, II 13%, III 52%, IV 10%. Median follow-up 39.2 months (m). Median PFS was 69.7 m, 27.7 m, and 15.8 m for A, B and C, respectively (p< .0001, log-rank test). The Cox model showed a highly-significant impact on PFS in relation to CA-125 nadir levels, residual tumor after surgery and stage. Hazard ratios (HR) for PFS (95% CI) of B vs. A, C vs. B, and C vs. A were 1.98 (p= .034), 2.35 (p= .02), and 4.67 (p< .001), respectively. HR for PFS (95% CI) of suboptimal vs. optimal cytorreduction and stage III-IV vs. IC-II were 1.84 (p= .058) and 3.2 (p= .002), respectively. Conclusions: The CA-125 nadir in the normal range following PT for EOC is a reproducible predictor of PFS in stage IC-IV. Prospective studies of maintenance-consolidation therapies or different approaches in selected pts based on CA-125 nadir seem warranted. No significant financial relationships to disclose.

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.

scholarly journals CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

2020 ◽  
Vol 7 (6) ◽  
pp. e880 ◽  
Author(s):  
Saúl Reyes ◽  
Ide Smets ◽  
David Holden ◽  
Karina Carrillo-Loza ◽  
Tatiana Christmas ◽  
...  
Keyword(s):  
Disease Activity ◽  
Light Chain ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Oral Disease ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Treatment Escalation

ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

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