scholarly journals Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

2020 ◽  
Vol 8 (1) ◽  
pp. e001516 ◽  
Author(s):  
Frederic Sampedro ◽  
Nicole Stantonyonge ◽  
Saül Martínez-Horta ◽  
Daniel Alcolea ◽  
Alberto Lleó ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gray Matter ◽  
Light Chain ◽  
Healthy Controls ◽  
Cerebral Damage ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Impaired Awareness

IntroductionImpaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH.Research design and methods54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI.ResultsWe found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH.ConclusionOverall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials.

scholarly journals Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

2021 ◽  
Vol 11 (2) ◽  
pp. 238
Author(s):  
Keld-Erik Byg ◽  
Helle H. Nielsen ◽  
Tobias Sejbaek ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chain ◽  
Plasma Levels ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Fluid Levels

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

scholarly journals Neurofilament Light Chain (NfL) as a Potential Biomarker of Treatment Response in Hereditary TransthyretinMediated (hATTR) Amyloidosis: Patisiran Global OLE Study

2021 ◽  
Author(s):  
Fernanda Reis de Azevedo ◽  
Michael Polydefkis ◽  
Simina Ticau ◽  
David Erbe ◽  
Anastasia McManus ◽  
...  
Keyword(s):  
Placebo Group ◽  
Treatment Response ◽  
Light Chain ◽  
Open Label ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Term Change ◽  
Potential Biomarker ◽  
Open Label Extension

Introduction: Patisiran is approved for the treatment of hATTR amyloidosis with polyneuropathy and its long-term efficacy/safety is being studied in a Global OLE. Plasma biomarkers are being investigated for utility in facilitating earlier diagnosis and monitoring disease /treatment response. Objective: Evaluate long-term change in neurofilament light chain (NfL) levels in response to patisiran in patients enrolled in the Global Open-Label Extension (OLE) study. Methods: NfL plasma levels were measured in duplicate in healthy controls and patients with ATTRv amyloidosis with polyneuropathy using the Quanterix Simoa platform. Patient samples were analyzed from the APOLLO study at baseline and 18 months, and also measured at 12 and 24 months following APOLLO in patients who rolled into the Global OLE. Results: NfL levels at APOLLO baseline were 63.2 (placebo) and 72.1 pg/ mL (patisiran). NfL increased during APOLLO in the placebo group (99.5 pg/mL), whereas a significant decrease was observed at 18 months following patisiran (48.8 pg/mL). Reduced NfL levels were maintained in the APOLLO-patisiran group through 24 months of additional patisiran treatment in the Global OLE (44.0 pg/mL), consistent with maintained improvement in mNIS+7. Upon initiation of patisiran in the Global OLE, the APOLLO-placebo group experienced a reduction in NfL levels through 24 months (44.2 pg/mL), reaching a similar level to the APOLLO-patisiran group. Conclusions: NfL may serve as a biomarker of active nerve damage and polyneuropathy, making it useful as a potential biomarker of disease progression, treatment response and for earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and monitoring disease.

scholarly journals Neurofilament Light Chain as A Biomarker for Brain Metastases

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2852 ◽  
Author(s):  
Anne Winther-Larsen ◽  
Claus Vinter Bødker Hviid ◽  
Peter Meldgaard ◽  
Boe Sandahl Sorensen ◽  
Birgitte Sandfeld-Paulsen
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Single Molecule ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Lung Cancer Patients ◽  
Potential Biomarker

Background: Brain metastases are feared complications in cancer. Treatment by neurosurgical resection and stereotactic radiosurgery are only available when metastatic lesions are limited and early detection is warranted. The neurofilament light chain (NfL) is a sensitive neuron-specific biomarker released following neuronal decay. We explored serum NfL as a biomarker of brain metastases. Methods: Serum was collected from 43 stage IV lung cancer patients with brain metastases and 25 stage I lung cancer patients. Serum was collected at time of cancer diagnosis and at time of brain metastasis diagnosis. In nine patients with brain metastases, additional samples were available between the two time points. NfL was quantified by Single Molecule Array (Simoa)™. Results: The median NfL level was significantly higher in patients with brain metastases than in patients without (35 versus 16 pg/mL, p = 0.001) and separated patients with an area under the curve of 0.77 (0.66–0.89). An increase in NfL could be measured median 3 months (range: 1–5) before the brain metastasis diagnosis. Further, a high level of NfL at time of brain metastasis diagnosis correlated with an inferior survival (hazard ratio: 2.10 (95% confidence interval: 1.11–3.98)). Conclusions: This study implies that NfL could be a potential biomarker of brain metastases.

scholarly journals Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis

2020 ◽  
Vol 7 (4) ◽  
pp. e749 ◽  
Author(s):  
Marie-Christine Reinert ◽  
Pascal Benkert ◽  
Jens Wuerfel ◽  
Zuzanna Michalak ◽  
Esther Ruberte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Single Molecule ◽  
Light Chain ◽  
Interferon Beta ◽  
Class Iii ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker

ObjectiveTo investigate serum neurofilament light chain (sNfL) as a potential biomarker for disease activity and treatment response in pediatric patients with multiple sclerosis (MS).MethodsIn this retrospective cohort study, sNfL levels were measured in a pediatric MS cohort (n = 55, follow-up 12–105 months) and in a non-neurologic pediatric control cohort (n = 301) using a high-sensitivity single-molecule array assay. Association of sNfL levels and treatment and clinical and MRI parameters were calculated.ResultsUntreated patients had higher sNfL levels than controls (median 19.0 vs 4.6 pg/mL; CI [4.732, 6.911]), p < 0.001). sNfL levels were significantly associated with MRI activity (+9.1% per contrast-enhancing lesion, CI [1.045, 1.138], p < 0.001; +0.6% per T2-weighted lesion, CI [1.001, 1.010], p = 0.015). Higher values were associated with a relapse <90 days ago (+51.1%; CI [1.184, 1.929], p < 0.001) and a higher Expanded Disability Status Scale score (CI [1.001, 1.240], p = 0.048). In patients treated with interferon beta-1a/b (n = 27), sNfL levels declined from 14.7 to 7.9 pg/mL after 6 ± 2 months (CI [0.339, 0.603], p < 0.001). Patients with insufficient control of clinical or MRI disease activity under treatment with interferon beta-1a/b or glatiramer acetate who switched to fingolimod (n = 18) showed a reduction of sNfL levels from 16.5 to 10.0 pg/mL 6 ± 2 months after switch (CI [0.481, 0.701], p < 0.001).ConclusionssNfL is a useful biomarker for monitoring disease activity and treatment response in pediatric MS. It is most likely helpful to predict disease severity and to guide treatment decisions in patients with pediatric MS. This study provides Class III evidence that sNfL levels are associated with disease activity in pediatric MS.

Absence of attack-independent neuroaxonal injury in MOG antibody-associated disease: Longitudinal assessment of serum neurofilament light chain

2021 ◽  
pp. 135245852110637
Author(s):  
Jae-Won Hyun ◽  
So Yeon Kim ◽  
Yeseul Kim ◽  
Na Young Park ◽  
Ki Hoon Kim ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Single Molecule ◽  
Light Chain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Acidic Protein ◽  
Healthy Controls ◽  
Longitudinal Assessment ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD.

scholarly journals Neurofilament light chain (NfL) as a biomarker of hereditary transthyretin-mediated amyloidosis

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011090
Author(s):  
Simina Ticau ◽  
Gautham V. Sridharan ◽  
Shira Tsour ◽  
William L. Cantley ◽  
Amy Chan ◽  
...  
Keyword(s):  
Disease Progression ◽  
Light Chain ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Controlled Study ◽  
Healthy Controls ◽  
Class Iii ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Impact

ObjectiveTo identify changes in the proteome associated with onset and progression of ATTRv amyloidosis, we performed an observational, case-controlled study which compared proteomes of patients with ATTRv amyloidosis and healthy controls.MethodsPlasma levels of >1,000 proteins were measured in patients with ATTRv amyloidosis with polyneuropathy who received either placebo or patisiran in the APOLLO study and in healthy controls. The impact of patisiran on the time profile of each protein was determined by linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) was further assessed using an orthogonal quantitative approach.ResultsLevels of 66 proteins were significantly changed with patisiran vs placebo, with NfL change most significant (p < 10−20). Analysis of changes in protein levels demonstrated that the proteome of patisiran-treated patients trended toward healthy controls at 18 months. Healthy controls' NfL levels were 4-fold lower than in patients with ATTRv amyloidosis with polyneuropathy (16.3 vs 69.4 pg/mL, effect: −53.1 pg/mL, 95% CI [–60.5 to −45.9]). NfL levels at 18 months increased with placebo (99.5 vs 63.2 pg/mL, 36.3 pg/mL, [16.5–56.1]) and decreased with patisiran treatment (48.8 vs 72.1 pg/mL, −23.3 pg/mL, [–33.4 to −13.1]) from baseline. At 18 months, improvement in modified Neuropathy Impairment Score +7 following patisiran significantly correlated with reduced NfL (R = 0.43, [0.29–0.55]).ConclusionsFindings suggest NfL may serve as a biomarker of nerve damage and polyneuropathy in ATTRv amyloidosis, may enable earlier diagnosis of patients with ATTRv amyloidosis, and facilitate monitoring of disease progression.Classification of evidenceThis study provides Class III evidence that NfL levels may enable earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and facilitate monitoring of disease progression.

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