The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

Ch, Hulme; Sj, Brown; Fuller, Heidi R.; Riddell, John S.; Osman, Aheed; Chowdhury, Joy; Kumar, Naveen; We, Johnson; Kt, Wright

doi:10.1038/sc.2016.174

Cited by 58 publications

(53 citation statements)

References 87 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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“…Candidate markers for traumatic SCI include glial fibrillary acidic protein (GFAP), neurofilaments, cleaved tau, myelin basic protein, neuronspecific enolase, S100b, and soluble CD95 ligand. 4,17,41 To date, S100b-a calcium-binding protein in astroglial and Schwann cells-is the most studied, showing elevations after traumatic SCI or vertebral fractures. Serum S100b and neuron-specific enolase have been shown to increase after polytrauma, hemolysis, and/or inadequate resuscitation.…”

Section: Biomarkers For Early Diagnosismentioning

confidence: 99%

Update on critical care for acute spinal cord injury in the setting of polytrauma

Yue

Winkler

Rick

et al. 2017

Neurosurgical Focus

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Traumatic spinal cord injury (SCI) often occurs in patients with concurrent traumatic injuries in other body systems. These patients with polytrauma pose unique challenges to clinicians. The current review evaluates existing guidelines and updates the evidence for prehospital transport, immobilization, initial resuscitation, critical care, hemodynamic stability, diagnostic imaging, surgical techniques, and timing appropriate for the patient with SCI who has multisystem trauma. Initial management should be systematic, with focus on spinal immobilization, timely transport, and optimizing perfusion to the spinal cord. There is general evidence for the maintenance of mean arterial pressure of > 85 mm Hg during immediate and acute care to optimize neurological outcome; however, the selection of vasopressor type and duration should be judicious, with considerations for level of injury and risks of increased cardiogenic complications in the elderly. Level II recommendations exist for early decompression, and additional time points of neurological assessment within the first 24 hours and during acute care are warranted to determine the temporality of benefits attributable to early surgery. Venous thromboembolism prophylaxis using low-molecular-weight heparin is recommended by current guidelines for SCI. For these patients, titration of tidal volumes is important to balance the association of earlier weaning off the ventilator, with its risk of atelectasis, against the risk for lung damage from mechanical overinflation that can occur with prolonged ventilation. Careful evaluation of infection risk is a priority following multisystem trauma for patients with relative immunosuppression or compromise. Although patients with polytrauma may experience longer rehabilitation courses, long-term neurological recovery is generally comparable to that in patients with isolated SCI after controlling for demographics. Bowel and bladder disorders are common following SCI, significantly reduce quality of life, and constitute a focus of targeted therapies. Emerging biomarkers including glial fibrillary acidic protein, S100β, and microRNAs for traumatic SCIs are presented. Systematic management approaches to minimize sources of secondary injury are discussed, and areas requiring further research, implementation, and validation are identified.

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“…Some of those biomarkers derived from proteins are neurofilament proteins, glial fibrillary acidic protein (GFAP), tau, neuron-specific enolase, and S100 calcium-binding protein β (S100β), being part of the components of neurons, oligodendrocytes, and reactive astrocytes. A more detailed list can be found in the works of Lubieniecka et al and the Hulme et al review [21,22].…”

Section: Proteins As Target Of Oxidationmentioning

confidence: 99%

Current Developments in Antioxidant Therapies for Spinal Cord Injury

Villa¹,

Villamar²,

Zapien³

et al. 2019

Spinal Cord Injury Therapy [Working Title]

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When spinal cord injury (SCI) occurs, numerous sources of reactive oxygen species and nitrogen species may be active within first minutes or hours and even reactivate few days later. Free radical formation and lipid peroxidation (LP) have been described as an important mechanism in the beginning and accelerated progress in the development of diverse pathologies, importantly in those related to central nervous system. The compromise of molecules and cellular structures due to the oxidative state of microenvironment in SCI may determinate survival or apoptosis of resident and infiltrating cells and polarization toward an inflammatory response, which lead to an extension of damaged tissue and loss of neuronal function, or a regulatory/regenerative response. The investigation of new antioxidant agents and their action at a molecular level begins to reveal mechanisms that, if correctly modulated, promise an improvement in recovery of functions with respect to conventional pharmacological therapies. In this chapter, we will review the general mechanisms of oxidative stress and lipid peroxidation, those antioxidant treatments in experimental development and clinical phase, as well as their achievements and limitations.

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The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

Cited by 58 publications

References 87 publications

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy

Update on critical care for acute spinal cord injury in the setting of polytrauma

Current Developments in Antioxidant Therapies for Spinal Cord Injury

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