Levels of phosphorylated axonal neurofilament subunit H (pNfH) are increased in acute ischemic stroke

Singh, Pradeep K.; Yan, Jun; Hull, Renee; Read, Stephen; O’Sullivan, John D.; Henderson, R.D.; Rose, Stephen; Greer, Judith M.; McCombe, Pamela A.

doi:10.1016/j.jns.2011.01.025

Cited by 59 publications

(59 citation statements)

References 41 publications

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“…Second, we found that sNfL levels were independently associated with stroke severity as measured by the NIHSS. This finding supports the presence of a relationship between the severity of symptoms and the extent of neuronal damage as measured by sNfL and refines previous research showing an association between serum NfH levels, stroke severity and infarct volume [16] .…”

Section: Discussionsupporting

confidence: 91%

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Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection

et al. 2015

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Background: Serum neurofilament light chain (sNfL) levels represent a promising marker of neuroaxonal injury. They are elevated in several neurological conditions, but their importance in cerebrovascular diseases remains unclear. In a proof of concept study, we compared sNfL levels with clinical characteristics and outcome in patients with cervical artery dissection (CeAD). Methods: A total of 49 non-traumatic CeAD patients were included. sNfL levels were measured by high-sensitivity electrochemiluminescence immunoassay. Levels were compared with regard to (i) type of presenting symptoms (local symptoms only (n = 8), transient ischemic attack (TIA; n = 10) or ischemic stroke (n = 31)), (ii) stroke severity quantified by National Institute of Health Stroke Scale (NIHSS), (iii) time interval between onset of symptoms and blood sampling and (iv) 3-month outcome as measured by the modified Rankin Scale score. Analyses were performed using univariate and multivariate linear and ordinal regression models. Results: CeAD patients presenting with stroke had significantly higher sNfL levels (median 108.9 pg/ml, interquartile range (37.8-427.7)) than patients with TIA (16.4 pg/ml (8.7-36.3), p = 0.002) or local symptoms (23.4 pg/ml (17.8-30.8), p = 0.0007). Among stroke patients, sNfL levels were positively associated with both NIHSS (p = 0.0002) and time between stroke onset and serum sampling (p = 1.9 × 10^-6). Higher sNfL levels were associated with unfavorable outcome at 3 months (OR 4.67, 95% CI 1.69-12.95, p = 0.003). However, this association lost significance after adjustment for NIHSS. The highest sNfL level was observed in a TIA patient who had ischemic stroke 1 day after serum sampling for sNfL measurement. Conclusion: sNfL levels were increased in CeAD patients presenting with stroke, correlated with clinical severity and were influenced by the time point of blood sampling. The prognostic meaning of sNfL in CeAD deserves further testing.

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Section: Discussionsupporting

confidence: 91%

“…A time-dependent increase after stroke has also been shown for serum NfH levels [16] . Similarly, our studies on sNfL in traumatic spinal cord injury have shown a progressive increase over 8 days after symptom onset [6] .…”

Section: Discussionmentioning

confidence: 74%

Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection

et al. 2015

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“…Singh et al did not find significantly increased NfH values on day 1 compared to controls [11], but did not report hourly timing from stroke onset and their samples may have been taken later than in the present study. Additionally, methodological differences may apply as the analytical sensitivity in not known.…”

Section: Discussioncontrasting

confidence: 79%

“…So far, quantification from serum is possible for NfH only. Significant positive associations were found for blood NfH levels and clinical severity, volume of the ischaemic territory and outcome when assessed 3 weeks after symptom onset [11]. There is no linear correlation for CSF and serum concentration.…”

Section: Introductionmentioning

confidence: 85%

Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

et al. 2011

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Serological biomarkers which enable quick and reliable diagnosis or measurement of the extent of irreversible brain injury early in the course of stroke are eagerly awaited. Neurofilaments (Nf) are a group of proteins integrated into the scaffolding of the neuronal and axonal cytoskeleton and an established biomarker of neuroaxonal damage. The Nf heavy chain (NfH SMI35 ) was assessed together with brain-specific astroglial proteins GFAP and S100B in hyperacute stroke (6 and 24 h from symptom onset) and daily for up to 6 days. Twenty-two patients with suspected stroke (median NIHSS 8) were recruited in a prospective observational study. Evidence for an ischaemic or haemorrhagic lesion on neuroimaging was found in 18 (ischaemia n = 16, intracerebral haemorrhage n = 2). Serum NfH SMI35 levels became detectable within 24 h post-stroke (P \ 0.0001) and elevated levels persisted over the study course. While GFAP was not detectable during the entire course, S100B levels peaked at the end of the observation period. The data indicate that significant in vivo information on the pathophysiology of stroke may be obtained by the determination of NfH SMI35 . Further studies are required to evaluate whether NfH SMI35 in hyperacute stroke reflects the extent of focal ischaemic injury seen on neuroimaging or is a consequence of more diffuse neuroaxonal damage.

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“…In this thesis a meta-analysis of the use of neurofilaments as a biomarker in ALS was performed. [186] Alzheimer's disease Gaiottino et al [178] Creutzfeldt-Jakob disease Steinacker et al [342] Peripheral neuropathy in type 2 diabetes Qiao et al [343] Frontotemporal dementia Meeter et al [344] Spinal cord injury Kuhle et al [345] Hypoxic-Ischemic Encephalopathy Douglas et al [346] Traumatic brain injury Shahim et al [347] Stroke Singh et al [348] One of the limitations of the systematic review and meta-analysis of neurofilaments in ALS is that there was no standardization of the timing of the blood or CSF sampling after the onset of the disease. It is known that there is an average one year diagnostic delay after onset of symptoms [349] .…”

Section: Neurofilamentsmentioning

confidence: 99%

Clinical and laboratory features of ALS

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Levels of phosphorylated axonal neurofilament subunit H (pNfH) are increased in acute ischemic stroke

Cited by 59 publications

References 41 publications

Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection

Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection

Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

Clinical and laboratory features of ALS

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