Serum neurofilament light is sensitive to active cerebral small vessel disease

Gattringer, Thomas; Pinter, Daniela; Enzinger, Christian; Seifert-Held, Thomas; Kneihsl, Markus; Fandler, Simon; Pichler, Alexander; Barro, Christian; Gröbke, Svenya; Voortman, Margarete; Pirpamer, Lukas; Hofer, Edith; Ropele, Stefan; Schmidt, Reinhold; Kuhle, Jens; Fazekas, Franz; Khalil, Michael

doi:10.1212/wnl.0000000000004645

Cited by 152 publications

(180 citation statements)

References 29 publications

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“…We found a correlation between sNfL levels and axonal damage assessed with NCS in CIDP patients starting IT (Figure ) in line with previous findings of sNfL levels being a reflection of neuro‐axonal damage . The correlation in our study was, however, no longer significant when corrected for age, which may be explained by the relatively small number of NCS.…”

Section: Discussionsupporting

confidence: 91%

“…We found a correlation between sNfL levels and axonal damage assessed with NCS in CIDP patients starting IT (Figure 2) in line with previous findings of sNfL levels being a reflection of neuro-axonal damage. 10,[16][17][18][19][20][21] The correlation in our study was, however, no longer significant when corrected for age, which may be explained by the relatively small number of NCS. We used the electrophysiological data from NCS performed in our center to exclude variation in CMAP measurements due to local differences in measurement protocols and equipment, which limited the number of patients available for this analysis.…”

Section: Snfl As a Biomarker For Axonal Damagecontrasting

confidence: 88%

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Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy

Lieverloo

Wieske

Verhamme

et al. 2019

J Peripheral Nervous Sys

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Axonal damage in chronic inflammatory demyelinating polyneuropathy (CIDP) is the main predictor of poor outcome. We hypothesized that serum neurofilament light chain (sNfL) reflects disease activity by detecting ongoing neuro‐axonal damage in CIDP. Three prospective cohorts of CIDP patients were studied: (a) patients starting induction treatment (IT cohort, N = 29) measured at baseline and 6 months after starting treatment; (b) patients on maintenance treatment (MT) starting intravenous immunoglobuline (IVIg) withdrawal (MT cohort, N = 24) measured at baseline and 6 months after IVIg withdrawal or at time of relapse; and (c) patients in long‐term remission without treatment (N = 27). A single molecule array assay was used to measure sNfL. Age‐matched healthy controls (N = 30) and age‐specific reference values were used for comparison. At baseline, sNfL was higher in patients starting IT compared to healthy controls. Ten out of 29 IT (34%) patients have sNfL levels above the 95th percentile of age‐specific cut‐off values. In the MT and remission cohort, elevated sNfL levels were infrequent and not different from healthy controls. sNfL levels were correlated with electrophysiological markers of axonal damage. At follow‐up assessment, patients with active disease (non‐responders and patients who relapsed after IVIg withdrawal) had higher sNfL levels compared with patients with stable disease (responders and patients who were successfully withdrawn from IVIg treatment). sNfL levels were increased in a third of CIDP patients starting IT and reflected axonal damage. sNfL levels might be usable as biomarker of disease activity in a subset of CIDP patients.

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Section: Discussionsupporting

confidence: 91%

Section: Snfl As a Biomarker For Axonal Damagecontrasting

confidence: 88%

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy

Lieverloo

Wieske

Verhamme

et al. 2019

J Peripheral Nervous Sys

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“…Direct systematic comparisons of CSF biomarkers between DPA and CAA are still missing. While already established as a CSF biomarker in certain neurodegenerative diseases , with the exception of one study neurofilament light chain indicating axonal damage and myelin breakdown has thus far, however, not been taken into account in CSVD.…”

Section: Interaction Between Dpa and Caa – Pathophysiological Considementioning

confidence: 99%

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

Schreiber

Wilisch‐Neumann

Schreiber

et al. 2019

Neuropathology Appl Neurobio

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Invited Review: The spectrum of age-related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathiesDeep perforator arteriopathy (DPA) and cerebral amyloid angiopathy (CAA) are the commonest known cerebral small vessel diseases (CSVD), which cause ischaemic stroke, intracebral haemorrhage (ICH) and vascular cognitive impairment (VCI). While thus far mainly considered as separate entities, we here propose that DPA and CAA share similarities, overlap and interact, so that 'pure' DPA or CAA are extremes along a continuum of age-related small vessel pathologies. We suggest blood-brain barrier (BBB) breakdown, endothelial damage and impaired perivascular b-amyloid (Ab) drainage are hallmark common mechanisms connecting DPA and CAA. We also suggest a need for new biomarkers (e.g. high-resolution imaging) to deepen understanding of the complex relationships between DPA and CAA.

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“…For example, plasma glial fibrillary acidic protein shows > 90% specificity as a biomarker for haemorrhagic stroke, and concentrations are positively correlated with the risk of subsequent clinical deterioration [64]. Neurofilaments are released during neuroaxonal injury [68], including following traumatic brain injury [69], but are also elevated in active cerebral small vessel disease [70] and acute ischaemic stroke [71], particularly in those with higher severity of primary injury [72] and recurrent ischaemic lesions [71]. These markers may prove a valuable avenue of investigation for further studies of END.…”

Section: Recommendationsmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

Martin

Price

2018

Cerebrovasc Dis

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Background: Early neurological deterioration (END) following acute stroke is associated with poorer long-term outcomes. Identification of patients at risk could assist early monitoring and treatment decisions. This review summarised the evidence describing non-radiological biomarkers for END. Summary: Electronic searches from January 1990 to March 2017 identified studies reporting a blood/cerebrospinal fluid (CSF)/urine biomarker measurement within 24 h of acute stroke and at least 2 serial assessments of clinical neurological status (< 24 h and < 7 days). Out of 12,895 citations, 82 studies were included, mostly focusing on ischaemic stroke. Using higher neurological thresholds, the n-weighted END incidence for ischaemic stroke was 11.9% (95% CI 11.4–12.4%) and 18.6% (17.9–19.2%) for lower thresholds. Incidence decreased with advancing study publication year (Pearson r-squared 0.23 and 0.15 for higher and lower threshold studies). After classification into 3 broad categories, meta-analysis showed that biomarkers associated with increased END risk (n; fixed-effects mean difference; 95% CI) were “metabolic” (glucose [n = 9,481; 0.90 mmol/L; 0.74–1.06], glycosylated haemoglobin [n = 3,146; 0.33%; 0.19–0.46], low-density lipoprotein [n = 4,839; 0.13 mmol/L; 0.06–0.21], total cholesterol [n = 4,762; 0.21 mmol/L; 0.11–0.31], triglycerides [n = 4,820; 0.11 mmol/L; 0.06–0.17], urea [n = 1,351; 0.55 mmol/L; 0.14–0.96], decreasing albumin [n = 513; 0.33 g/dL; 0.05–0.61]); “inflammatory and excitotoxic” (plasma glutamate [n = 688; 60.13 µmol/L; 50.04–70.22], CSF glutamate [n = 369; 7.50 µmol/L; 6.76–8.23], homocysteine [n = 824; 2.15 µmol/L; 0.68–3.61], leucocytes [n = 3,766; 0.54 × 10⁹/L; 0.34–0.74], high-sensitivity C-reactive protein [n = 1,707; 3.79 mg/L; 1.23–6.35]); and “coagulation/haematological” (fibrinogen [n = 3,132; 0.32 g/L; 0.25–0.40]; decreasing haemoglobin [n = 3,586; 2.38 g/L; 0.15–4.60]). Key Messages: Declining incidence of END may represent improving care standards; however, it remains a frequent occurrence. Although statistical associations exist between biomarkers and an increased risk of END, the most promising still need prospective evaluation to determine their additional value relative to baseline radiological and clinical characteristics.

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Serum neurofilament light is sensitive to active cerebral small vessel disease

Abstract: Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

Cited by 152 publications

References 29 publications

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

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