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Neurofilament Light Chain in the Blood As Biochemical Markers in the Critically Ill

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Biomarkers in Trauma, Injury and Critical Care

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Abstract

Neurofilament light chain (NfL) is a protein of the neuronal cytoskeleton and a biochemical marker specific for neuroaxonal damage when released and detected in the blood of critically ill patients. As serum NfL (sNfL) is not disease-specific one must consider the natural history of diseases and the temporal evolution of sNfL concentrations when interpreting sNfL for diagnosis and prognostication in clinical practice. The interpretation is further challenged by many interfering and confounding factors that need to be considered, such as increasing age, preexisting neurological comorbidities, altered renal function that decreases the clearance of sNfL from the blood, and non-neurological comorbidities that may damage the nervous system, including cardiovascular diseases and neurotoxic side effects of treatment measures. With increasing availability of sNfL test kits, analyses of sNfL concentrations have been on the forefront when it comes to new and promising diagnosis and prognosis. Their diagnostic and prognostic yields have been evaluated and validated in many (neuro-)critical illnesses and neurologic emergencies encountered and treated in intensive care units (ICU). Among these are ischemic and hemorrhagic strokes, subarachnoid hemorrhages, traumatic brain injuries, epilepsies, Guillain-Barré syndrome, hypoxic-ischemic encephalopathies, delirium, postoperative states, sepsis, and coronavirus infectious disease (COVID)-19. The several studies that have shown the great potential of sNfL as a promising diagnostic and prognostic marker that may also optimize current clinical risk scores call for a careful consideration and critical interpretation of the data.

The aim of this chapter is to elucidate the current evidence of the diagnostic and prognostic yield of sNfL and to discuss interfering factors and potential interferences and confounders in (neuro-)critically ill patients.

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Abbreviations

ADEM:

Acute Disseminated Encephalomyelitis

ARDS:

Acute Respiratory Distress Syndrome

BBB:

Blood-Brain Barrier

BMI:

Body Mass Index

CA:

Cardiac Arrest

CAA:

Cerebral Amyloidangiopathy

CAHP:

Cardiac Arrest Hospital Prognosis (Score)

COVID-19:

Coronavirus Infectious Disease

cMRI:

Cerebral Magnetic Resonance Imaging

CNS:

Central Nervous System

CSF:

Cerebrospinal Fluid

DAI:

Diffuse Axonal Injury

DTI:

Diffusion Tensor Imaging

ECMO:

Extracorporeal Membrane Oxygenation

EEG:

Electroencephalography

ICH:

Intracerebral Hemorrhage

ICU:

Intensive Care Unit

MRI:

Magnetic Resonance Imaging

NfL:

Neurofilament Light Chain

NIHSS:

National Institute of Health Stroke Scale

NSE:

Neuron-Specific Enolase

OHCA:

Out-of-Hospital Cardiac Arrest (Score)

PNS:

Peripheral Nervous System

ROSC:

Return of Spontaneous Circulation

SAE:

Sepsis-Associated Encephalopathy

SAH:

Subarachnoid Hemorrhage

SARS-CoV:

Severe Acute Respiratory Syndrome-associated CoronaVirus

SE:

Status Epilepticus

sNfL:

Serum Neurofilament Light chain

SSEP:

Somatosensory Evoked Potentials

TBI:

Traumatic Brain Injury

TIA:

Transient Ischemic Attack

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Authors and Affiliations

  1. Department of Intensive Care, University Hospital of Basel, Basel, Switzerland

    Lisa Hert & Raoul Sutter

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  1. Lisa Hert
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  2. Raoul Sutter
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Correspondence to Lisa Hert .

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Editors and Affiliations

  1. College of Medicine, King Saud bin Abdulaziz University of Health Sciences, Riyadh, Saudi Arabia

    Rajkumar Rajendram

  2. School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

  3. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

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Hert, L., Sutter, R. (2023). Neurofilament Light Chain in the Blood As Biochemical Markers in the Critically Ill. In: Rajendram, R., Preedy, V.R., Patel, V.B. (eds) Biomarkers in Trauma, Injury and Critical Care. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-07395-3_38

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