Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

Fink, Ericka L.; Kochanek, Patrick M.; Panigrahy, Ashok; Beers, Sue R.; Berger, Rachel P.; Bayır, Hülya; Pineda, José; Newth, Christopher J. L.; Topjian, Alexis; Press, Craig A.; Maddux, Aline B; Willyerd, Frederick; Hunt, Elizabeth A.; Siems, Ashley; Chung, Melissa G.; Smith, Lincoln; Wenger, Jesse; Doughty, Lesley; Diddle, J. Wesley; Patregnani, Jason; Piantino, Juan; Walson, Karen; Balakrishnan, Binod; Meyer, Michael T.; Friess, Stuart H.; Maloney, David G.; Rubin, P.; Haller, Tamara; Treble‐Barna, Amery; Wang, Chunyan; Clark, Robert; Fabio, Anthony; Desai, Beena; Richardson, Maureen G.; Bates, Cynthia Helen; Parikh, Darshana; Prodell, Janice L.; Winters, Maddie; Smith, Katherine; Kwok, Jeni; Cabrales, A.; Adewale, Ronke; Melvin, Pam; Shad, Sadaf; Siegel, Katherine; Murkowski, Katherine; Kasch, Mary C.; Hensley, Josey; Steele, Lisa; Brown, Danielle D.; Burrows, B. L.; Hlivka, Lauren; Rich, Deana; Tutundzic, Amila; Day, Tina; Barganier, Lori; Wolfe, Ashley; Little, M Bryan; Tomanio, Elyse; Patel, Neha; Hession, Diane; Sierra, Yamila; Jones, Rhonda; Benken, Laura; Elmer, Jonathan; Subramanian, Subramanian; Narayanan, Srikala; Toney, Nicole; Wallace, Julia; Robinson, Tami Echavarria; Frank, Andrew U.; Blüml, Stefan; Wisnowski, Jessica L.; Feldman, Keri; Vemulapalli, Avinash; Ryan, Linda; Szypulski, Scott; Keys, Christopher B.

doi:10.1001/jamanetworkopen.2022.30518

Cited by 23 publications

(18 citation statements)

References 44 publications

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“…Our pilot work confirmed these findings in the basal ganglia and thalamus . Our results in POCCA strengthen the potential utility for MRS as an objective prognostic biomarker in pediatric cardiac arrest. Still, more work is needed to demonstrate that MRS improves the diagnostic accuracy of clinical variables and conventional MRI.…”

Section: Discussionsupporting

confidence: 83%

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Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest

et al. 2023

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ImportanceMorbidity and mortality after pediatric cardiac arrest are chiefly due to hypoxic-ischemic brain injury. Brain features seen on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) after arrest may identify injury and aid in outcome assessments.ObjectiveTo analyze the association of brain lesions seen on T2-weighted MRI and diffusion-weighted imaging and N-acetylaspartate (NAA) and lactate concentrations seen on MRS with 1-year outcomes after pediatric cardiac arrest.Design, Setting, and ParticipantsThis multicenter cohort study took place in pediatric intensive care units at 14 US hospitals between May 16, 2017, and August 19, 2020. Children aged 48 hours to 17 years who were resuscitated from in-hospital or out-of-hospital cardiac arrest and who had a clinical brain MRI or MRS performed within 14 days postarrest were included in the study. Data were analyzed from January 2022 to February 2023.ExposureBrain MRI or MRS.Main Outcomes and MeasuresThe primary outcome was an unfavorable outcome (either death or survival with a Vineland Adaptive Behavior Scales, Third Edition, score of &lt;70) at 1 year after cardiac arrest. MRI brain lesions were scored according to region and severity (0 = none, 1 = mild, 2 = moderate, 3 = severe) by 2 blinded pediatric neuroradiologists. MRI Injury Score was a sum of T2-weighted and diffusion-weighted imaging lesions in gray and white matter (maximum score, 34). MRS lactate and NAA concentrations in the basal ganglia, thalamus, and occipital-parietal white and gray matter were quantified. Logistic regression was performed to determine the association of MRI and MRS features with patient outcomes.ResultsA total of 98 children, including 66 children who underwent brain MRI (median [IQR] age, 1.0 [0.0-3.0] years; 28 girls [42.4%]; 46 White children [69.7%]) and 32 children who underwent brain MRS (median [IQR] age, 1.0 [0.0-9.5] years; 13 girls [40.6%]; 21 White children [65.6%]) were included in the study. In the MRI group, 23 children (34.8%) had an unfavorable outcome, and in the MRS group, 12 children (37.5%) had an unfavorable outcome. MRI Injury Scores were higher among children with an unfavorable outcome (median [IQR] score, 22 [7-32]) than children with a favorable outcome (median [IQR] score, 1 [0-8]). Increased lactate and decreased NAA in all 4 regions of interest were associated with an unfavorable outcome. In a multivariable logistic regression adjusted for clinical characteristics, increased MRI Injury Score (odds ratio, 1.12; 95% CI, 1.04-1.20) was associated with an unfavorable outcome.Conclusions and RelevanceIn this cohort study of children with cardiac arrest, brain features seen on MRI and MRS performed within 2 weeks after arrest were associated with 1-year outcomes, suggesting the utility of these imaging modalities to identify injury and assess outcomes.

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Section: Discussionsupporting

confidence: 83%

“…The primary outcome was the association of brain MRI Injury Score and MRS features with an unfavorable outcome (either death or survival with a Vineland Adaptive Behavior Scales, Third Edition [VABS-3] score <70) at 1 year. Patient follow-up was standardized and performed at each center as per the parent study …”

Section: Methodsmentioning

confidence: 99%

Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest

et al. 2023

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“…25,36,46 A recent US-based retrospective report of paediatric brain injury from cardiac arrest identified early elevated NfL levels as mostly strongly associated with unfavourable neurodevelopmental outcomes evaluated 1 year later. 28 More research is needed to assess the value of prospective NfL levels in identifying children with SCA cerebrovascular injury and whether the extent of elevation has prognostic relevance.…”

Section: Discussionmentioning

confidence: 99%

“…40 Like GFAP, UCH-L1 was elevated in non-SCA paediatric ICU-associated brain injury, including infarcts, seizures or brain oedema. 28 The multiplex analysis included assay in duplicate for each sample, per the package insert instructions, along with calibrators and positive and negative controls for each biomarker. Laboratory coefficients of variance within-and between-run for plasma samples are 4%-6%.…”

Section: Glial Fibrillary Acidic Protein (Gfap) Is a Cytoskeletal Pro-mentioning

confidence: 99%

“…Blood-based biomarkers, including NfL, have been tested in children without SCA and can remain elevated following brain injury. 28 Prolonged biomarker elevation would be a key feature for potential use in screening for non-incident cerebral infarcts. Bloodbased brain biomarkers have not been previously reported in childhood SCA except for a 2011 report of elevated glial fibrillary acid protein (GFAP) in children with SCA compared to controls.…”

Section: Introductionmentioning

confidence: 99%

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Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

et al. 2023

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SummaryCerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI‐MRA) in sub‐Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood‐based brain biomarkers of cerebral infarcts have been identified in non‐SCA adults. Using plasma samples from a well‐characterized cross‐sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI‐detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4‐plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron‐specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non‐SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI‐detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI‐detected infarcts after adjusting for sex and age. All non‐SCA controls and SCA participants lacking MRI‐detected infarcts had low NfL levels. These data suggest potential utility of plasma‐based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.

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Neuromonitoring after Pediatric Cardiac Arrest: Cerebral Physiology and Injury Stratification

et al. 2023

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Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

Cited by 23 publications

References 44 publications

Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest

Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

Neuromonitoring after Pediatric Cardiac Arrest: Cerebral Physiology and Injury Stratification

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