Neurofilaments as biomarkers in neurological disorders — towards clinical application

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(5), P. 269 - 287

Published: April 12, 2024

Language: Английский

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Coma Prognostication After Acute Brain Injury

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(4), P. 405 - 405

Published: March 4, 2024

Importance Among the most impactful neurologic assessments is that of neuroprognostication, defined here as prediction recovery from disorders consciousness caused by severe, acute brain injury. Across a range injury etiologies, these determinations often dictate whether life-sustaining treatment continued or withdrawn; thus, they have major implications for morbidity, mortality, and health care costs. Neuroprognostication relies on diverse array tests, including behavioral, radiologic, physiological, serologic markers, evaluate brain’s functional structural integrity. Observations Prognostic such examination, electroencephalography, conventional computed tomography magnetic resonance imaging (MRI), been foundational in assessing patient’s current level capacity recovery. Emerging techniques, MRI, diffusion advanced forms provide new ways evaluating brain, leading to evolving schemes characterizing function novel methods predicting Conclusions Relevance Neuroprognostic markers are rapidly integrity after discovered. Many techniques remain development, further research needed optimize their prognostic utility. However, even efforts underway, series promising findings coupled with imperfect predictive value high stakes prompted clinical guidelines endorse emerging neuroprognostication. Thus, clinicians thrust into an uncertain predicament which not yet perfected but too ignore. This review illustrates current, likely future, landscapes markers. No matter how much evolve improve, must be approached humility individualized reflect each values.

Language: Английский

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Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial

Intensive Care Medicine, Journal Year: 2023, Volume and Issue: 49(12), P. 1467 - 1478

Published: Nov. 9, 2023

Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) still at a high risk of neurological damage and death. Inflammation brain injury components the post-cardiac syndrome, can be assessed by systemic interleukin 6 (IL-6) neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose could reduce IL-6 NSE in comatose OHCA patients. The STEROHCA trial was randomized, blinded, placebo-controlled, phase II performed two centers Denmark. Resuscitated patients suspected etiology were randomly assigned 1:1 single intravenous injection 250 mg or placebo. co-primary outcome reduction NSE-blood levels measured daily for 72 h from admission. main secondary survival 180 days follow-up. We randomized 137 (n = 68) placebo 69). found reduced (p < 0.0001) intervention group, median (interquartile range, IQR) 24 2.1 pg/ml (1.0; 7.1) 30.7 (14.2; 59) group. observed no difference between groups 0.22), 48 18.8 ug/L (14.4; 24.6) 14.8 (11.2; 19.4) respectively. In 51 (75%) survived 44 (64%) Prehospital patients, resulted after h, but did not levels.

Language: Английский

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Intimate Partner Violence-Related Brain Injury: Unmasking and Addressing the Gaps

Journal of Neurotrauma, Journal Year: 2024, Volume and Issue: 41(19-20), P. 2219 - 2237

Published: Feb. 7, 2024

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV tend to experience severe injuries. There has been growing concern about the of exposure IPV-related head trauma, resulting in brain injury (IPV-BI), its consequences. Past work suggests that significant proportion women exposed IPV-BI, likely representing distinct phenotype compared BI other etiologies. An IPV-BI often co-occurs psychological trauma mental complaints, leading unique issues related identifying, prognosticating, managing outcomes. The goal this review identify important gaps research clinical practice suggest potential solutions address them. We summarize five key priority areas: (1) considerations study design; (2) understanding non-fatal strangulation as form BI; (3) identifying objective biomarkers IPV-BI; (4) consideration chronicity, cumulative late effects (5) factor engagement. Our concludes call action help investigators develop ecologically valid studies addressing identified clinical-research knowledge strategies improve care IPV-BI. By reducing current answering these calls action, we will approach trauma-informed manner, ultimately improving outcomes quality life those impacted by

Language: Английский

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The 2022 Lady Estelle Wolfson lectureship on neurofilaments

Journal of Neurochemistry, Journal Year: 2022, Volume and Issue: 163(3), P. 179 - 219

Published: Aug. 11, 2022

Neurofilament proteins (Nf) have been validated and established as a reliable body fluid biomarker for neurodegenerative pathology. This review covers seven Nf isoforms, light (NfL), two splicing variants of medium (NfM), heavy (NfH),

Language: Английский

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Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic–ischaemic brain injury after cardiac arrest

Intensive Care Medicine, Journal Year: 2023, Volume and Issue: 49(9), P. 1062 - 1078

Published: July 28, 2023

The cerebral oxygen cascade includes three key stages: (a) convective delivery representing the bulk flow of to vascular bed; (b) diffusion from blood into brain tissue; and (c) cellular utilisation for aerobic metabolism. All stages may become dysfunctional after resuscitation cardiac arrest contribute hypoxic–ischaemic injury (HIBI). Improving by optimising has been widely investigated as a strategy mitigate HIBI. However, clinical trials aimed at have yielded neutral results. Advances in understanding HIBI pathophysiology suggest that impairments pertaining should also be considered identifying therapeutic strategies management patients. Culprit mechanisms these include widening barrier due peri-vascular oedema mitochondrial dysfunction. An integrated approach encompassing both intra-parenchymal non-invasive neuromonitoring techniques aid detecting pathophysiologic changes enable patient-specific reducing severity

Language: Английский

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Neurofilaments contribution in clinic: state of the art

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Nov. 1, 2022

Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response treatment. This field of neurology has evolved considerably in recent years with the improvement analytical methods, allowing detection not only cerebrospinal fluid (CSF) but also less invasive fluids like blood. These advances greatly facilitate repeated quantification biomarkers, including at asymptomatic stages disease. Among various informative neurological disorders, neurofilaments (NfL) have proven particular interest many contexts, such neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies potential value NfL assay management patients, both diagnosis prognosis. We describe added compared other currently monitor diseases described this review.

Language: Английский

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Hypoxic-Ischemic Brain Injury in ECMO: Pathophysiology, Neuromonitoring, and Therapeutic Opportunities

Cells, Journal Year: 2023, Volume and Issue: 12(11), P. 1546 - 1546

Published: June 5, 2023

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic (HIBI) is one the most common types ABI ECMO patients. Various factors, such as history hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early pulse pressure, have been associated development HIBI The pathogenic mechanisms are complex multifactorial, attributing to underlying pathology requiring initiation itself. likely occur or peri-decannulation time secondary refractory cardiopulmonary failure before after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia ischemia, by employing targeted temperature management case extracorporeal resuscitation (eCPR), optimizing O2 saturations perfusion. This review describes pathophysiology, neuromonitoring, therapeutic techniques improve neurological outcomes patients order prevent minimize morbidity HIBI. Further studies aimed at standardizing relevant neuromonitoring techniques, perfusion, minimizing severity once it occurs will long-term

Language: Английский

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Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation – A sub-analysis of Prague-OHCA study

Resuscitation, Journal Year: 2024, Volume and Issue: 199, P. 110219 - 110219

Published: April 21, 2024

Language: Английский

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Characterizing the Relationship Between Arterial Carbon Dioxide Trajectory and Serial Brain Biomarkers with Central Nervous System Injury During Veno-Venous Extracorporeal Membrane Oxygenation: A Prospective Cohort Study

Neurocritical Care, Journal Year: 2024, Volume and Issue: 41(1), P. 20 - 28

Published: Feb. 1, 2024

Abstract Background Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in partial pressure arterial carbon dioxide (PaCO 2 ) VV-ECMO has been suggested as an etiological factor, but the challenges diagnosing CNS injuries made discerning a relationship between PaCO and difficult. Methods We conducted prospective cohort study adult patients undergoing for respiratory failure. Arterial blood gas measurements were obtained prior to VV-ECMO, at every 2–4 h first 24 h. Neuroimaging was within 7–14 days who suspected having neurological or unable be examined because sedation. collected biospecimens measure brain biomarkers [neurofilament light (NF-L); glial fibrillary acidic protein (GFAP); phosphorylated-tau 181] 7 VV-ECMO. assessed both over with using mixed methods linear regression. Finally, we explored effects absolute change on serum levels by separate regression each biomarker three exposures hypothesized result injury. Results In our cohort, 12 59 (20%) had overt identified head computed tomography. The steeper developed (− 0.32%, 95% confidence interval − 0.25 0.39) compared those without 0.18%, 0.14 0.21, P interaction < 0.001). mean concentration NF-L increased time higher (464 [739]) (127 [257]; = GFAP (4278 [11,653] pg/ml) (116 [108] pg/ml; NF-L, GFAP, tau stratified thresholds showed no differences significant time. Conclusions Although rapid decreases slightly greater versus without, data overlap absence relationships suggests other pathophysiologic variables are likely play.

Language: Английский

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