Neurological symptoms and blood neurofilament light levels

Barro, Christian; Zetterberg, Henrik

doi:10.1111/ane.13415

Cited by 18 publications

(17 citation statements)

References 54 publications

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“…It would have been beneficial if the baseline examination had been completed even earlier in the course of the infection to give a better picture of the acute findings following mild disease. However, the delay in sampling serum for NfL analysis might give a more trustworthy picture, as the rise in serum values following neuronal damage will peak weeks to months after the event ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults

et al. 2022

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IntroductionCoronavirus disease 2019 (COVID-19) is prevalent among young people, and neurological involvement has been reported. We investigated neurological symptoms, cognitive test results, and biomarkers of brain injury, as well as associations between these variables in non-hospitalized adolescents and young adults with COVID-19.MethodsThis study reports baseline findings from an ongoing observational cohort study of COVID-19 cases and non-COVID controls aged 12–25 years (Clinical Trials ID: NCT04686734). Symptoms were charted using a standardized questionnaire. Cognitive performance was evaluated by applying tests of working memory, verbal learning, delayed recall, and recognition. The brain injury biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp), were assayed in serum samples using ultrasensitive immunoassays.ResultsA total of 405 COVID-19 cases and 111 non-COVID cases were prospectively included. Serum Nfl and GFAp concentrations were significantly elevated in COVID-19 cases as compared with non-COVID controls (p = 0.050 and p = 0.014, respectively). The COVID-19 cases reported more fatigue (p < 0.001) and post-exertional malaise (PEM) (p = 0.001) compared to non-COVID-19 controls. Cognitive test performance and clinical neurological examination did not differ across the two groups. Within the COVID-19 group, there were no associations between symptoms, cognitive test results, and NfL or GFAp levels. However, fatigue and PEM were strongly associated with older age and female sex.ConclusionsNon-hospitalized adolescents and young adults with COVID-19 reported more fatigue and PEM and had slightly elevated levels of brain injury markers, but showed normal cognitive performance. No associations were found between symptoms, brain injury markers, and cognitive test results, but fatigue and PEM were strongly related to female sex and older age.

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Section: Discussionmentioning

confidence: 99%

Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults

et al. 2022

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“…Recently, we determined that blood NFL concentrations are associated with radiographic markers of brain tissue damage, as well as indicators of neurological, functional, and cognitive status in patients with ischemic or hemorrhagic stroke (19). On the basis of these findings and others (20) establishing NFL as a marker of axonal injury, we investigated whether serum NFL was elevated in hospitalized patients with COVID-19 and whether it correlated with clinical outcomes and disease severity.…”

Section: Introductionmentioning

confidence: 99%

Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19

et al. 2021

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Brain imaging studies of patients with COVID-19 show evidence of macro- and micro-hemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In one hundred hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

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“…In addition, inflammatory brain TNF-α expression was significantly elevated following SE, without peripheral changes in protein levels. A striking effect was observed in the serum concentration of neurofilaments, which are novel markers of brain damage (Lambertsen et al, 2020 ; Yuan and Nixon, 2021 ) and neuronal damage (Gaetani et al, 2019 ; Barro and Zetterberg, 2021 ). Through these experiments, we have shown that in an animal model of SE, neurofilaments’ concentration increases in a relatively short time frame.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Thrombin Pathway Restores LTP in a Pilocarpine Mice Model of Status Epilepticus

Shavit‐Stein

Berkowitz

Davidy

et al. 2022

Front. Cell. Neurosci.

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BackgroundStatus epilepticus (SE) leads to memory impairment following a seizure, attributed to long-term potentiation (LTP) reduction. Thrombin, a coagulation factor that activates protease-activated receptor 1 (PAR1) is involved in cognitive impairment following traumatic brain injury by reducing hippocampal LTP and in seizures as seen in a SE pilocarpine-induced mice model. Thrombin pathway inhibition prevents this cognitive impairment. We evaluated the effect of thrombin pathway inhibition in the pilocarpine-induced SE mice model, on LTP, hippocampal, and serum markers for inflammation, the PAR1 pathway, and neuronal cell damage.MethodsSE was induced by injecting C57BL/6J mice with pilocarpine. Before pilocarpine injection, mice were injected with either the specific thrombin inhibitor α-NAPAP [Nα-(2-naphthalene-sulfonylglycyl)-4-amidino-DL-phenylalaninepiperidide], the PAR1 antagonist SCH79797, or vehicle-only solution. Recordings of excitatory postsynaptic potentials (EPSP) were conducted from hippocampal slices 24 h following pilocarpine injection. Hippocampal real-time PCR for the quantification of the PAR1, prothrombin, and tumor necrosis factor α (TNF-α) mRNA expression levels was conducted. Serum levels of neurofilament light chain (NfL) and TNF-α were measured by a single molecule array assay.ResultsThe EPSP was reduced in the pilocarpine-induced SE mice (p < 0.001). This reduction was prevented by both NAPAP and SCH79797 treatments (p < 0.001 for both treatments). Hippocampal expression of TNF-α was elevated in the pilocarpine-induced SE group compared to the control (p < 0.01), however, serum levels of TNF-α were not changed. NfL levels were elevated in the pilocarpine-induced SE group (p = 0.04) but not in the treated groups.ConclusionsPilocarpine-induced SE reduces LTP, in a thrombin PAR1-related mechanism. Elevation of serum NfL supports neuronal damage accompanying this functional abnormality which may be prevented by PAR1 pathway modulation.

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Neurological symptoms and blood neurofilament light levels

Cited by 18 publications

References 54 publications

Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults

Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults

Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19

Modulation of the Thrombin Pathway Restores LTP in a Pilocarpine Mice Model of Status Epilepticus

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