nach oben

Erschienen in:

04.03.2021 | Original work

Serum Biomarkers of Regeneration and Plasticity are Associated with Functional Outcome in Pediatric Neurocritical Illness: An Exploratory Study

verfasst von: Catherine Madurski, Jessica M. Jarvis, Sue R. Beers, Amy J. Houtrow, Amy K. Wagner, Anthony Fabio, Chunyan Wang, Craig M. Smith, Lesley Doughty, Keri Janesko-Feldman, Pamela Rubin, Dorothy Pollon, Amery Treble-Barna, Patrick M. Kochanek, Ericka L. Fink, for the PICU-Rehabilitation Study Group

Erschienen in: Neurocritical Care | Ausgabe 2/2021

Einloggen, um Zugang zu erhalten

Abstract

Background/Objective

Pediatric neurocritical care survivorship is frequently accompanied by functional impairments. Lack of prognostic biomarkers is a barrier to early identification and management of impairment. We explored the association between blood biomarkers and functional impairment in children with acute acquired brain injury.

Methods

This study is a secondary analysis of a randomized control trial evaluating early versus usual care rehabilitation in the pediatric intensive care unit (PICU). Forty-four children (17 [39%] female, median age 11 [interquartile range 6–13] years) with acute acquired brain injury admitted to the PICU were studied. A single center obtained serum samples on admission days 0, 1, 3, 5, and the day closest to hospital discharge. Biomarkers relevant to brain injury (neuron specific enolase [NSE], S100b), inflammation (interleukin [IL-6], C-reactive protein), and regeneration (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF]) were collected. Biomarkers were analyzed using a Luminex® bioassay. Functional status scale (FSS) scores were abstracted from the medical record. New functional impairment was defined as a (worse) FSS score at hospital discharge compared to pre-PICU (baseline). Individual biomarker fluorescence index (FI) values for each sample collection day were correlated with new functional impairment using Spearman rank correlation coefficient (ρ). Trends in repeated measures of biomarker FI over time were explored graphically, and the association between repeated measures of biomarker FI and new functional impairment was analyzed using covariate adjusted linear mixed-effect models.

Results

Functional impairment was inversely correlated with markers of regeneration and plasticity including BDNF at day 3 (ρ = − 0.404, p = .015), day 5 (ρ = − 0.549, p = 0.005) and hospital discharge (ρ = − 0.420, p = 0.026) and VEGF at day 1 (ρ = − 0.282, p = 0.008) and hospital discharge (ρ = − 0.378, p = 0.047), such that lower levels of both markers at each time point were associated with greater impairment. Similarly, repeated measures of BDNF and VEGF were inversely correlated with new functional impairment (B = − 0.001, p = 0.001 and B = − 0.001, p = 0.003, respectively). NSE, a biomarker of acute brain injury, showed a positive correlation between day 0 levels and new functional impairment (ρ = 0.320, p = 0.044).

Conclusions

Blood-based biomarkers of regeneration and plasticity may hold prognostic utility for functional impairment among pediatric patients with neurocritical illness and warrant further investigation.

Pollack MM, Holubkov R, Funai T, et al. Pediatric intensive care outcomes: development of new morbidities during pediatric critical care. Pediatr Crit Care Med. 2014;15(9):821–7.PubMedPubMedCentral

Fink EL, Kochanek PM, Tasker RC, et al. International survey of critically Ill children with acute neurologic insults: the PANGEA study to cite this version: HAL Id: hal-01717475 HHS public access. Pediatr Crit Care Med. 2017;4(18):330–42.

Manning JC, Pinto NP, Rennick JE, Colville G, Curley MAQ. Conceptualizing post intensive care syndrome in children—the PICS-p framework. Pediatr Crit Care Med. 2018;19(4):298–300.PubMed

Bone MF, Feinglass JM, Goodman DM. Risk factors for acquiring functional and cognitive disabilities during admission to a PICU*. Pediatr Crit Care Med. 2014;15(7):640–8.PubMed

Choong K, Fraser D, Al-Harbi S, et al. Functional recovery in critically ill children, the “WeeCover” multicenter study. Pediatr Crit Care Med. 2018;19(2):145–54.PubMed

Bedell GM. Functional outcomes of school-age children with acquired brain injuries at discharge from inpatient rehabilitation. Brain Inj. 2008;22(4):313–24.PubMed

Fink EL, Beers SR, Houtrow AJ, et al. Early protocolized versus usual care rehabilitation for pediatric neurocritical care patients: a randomized controlled trial. Pediatr Crit Care Med. 2019;20(6):540–50.PubMedPubMedCentral

Tepas JJ, Leaphart CL, Pieper P, et al. The effect of delay in rehabilitation on outcome of severe traumatic brain injury. J Pediatr Surg. 2009;44(2):368–72.PubMed

Lone NI, Seretny M, Wild SH, Rowan KM, Murray GD, Walsh TS. Surviving intensive care: a systematic review of healthcare resource use after hospital discharge. Crit Care Med. 2013;41(8):1832–43.PubMed

10.

Moreau JF, Fink EL, Hartman ME, et al. Hospitalizations of children with neurologic disorders in the United States. Pediatr Crit Care Med. 2013;14(8):801–10.PubMedPubMedCentral

11.

Walker T, Kudchadkar SR. Early mobility in the pediatric intensive care unit: can we move on? J Pediatr. 2018;203:1–3.

12.

Failla MD, Juengst SB, Arenth PM, Wagner AK. Preliminary associations between brain-derived neurotrophic factor, memory impairment, functional cognition, and depressive symptoms following severe TBI. Neurorehabil Neural Repair. 2016;30(5):419–30.PubMed

13.

Yende S, D’Angelo G, Kellum JA, et al. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med. 2008;177(11):1242–7.PubMedPubMedCentral

14.

Griffith DM, Lewis S, Rossi AG, et al. Systemic inflammation after critical illness: relationship with physical recovery and exploration of potential mechanisms. Thorax. 2016;71(9):820–9.PubMed

15.

Korley FK, Diaz-Arrastia R, Wu AHB, et al. Circulating brain-derived neurotrophic factor has diagnostic and prognostic value in traumatic brain injury. J Neurotrauma. 2016;33(2):215–25.PubMedPubMedCentral

16.

Au AK, Bell MJ, Fink EL, Aneja RK, Kochanek PM, Clark RSB. Brain-specific serum biomarkers predict neurological morbidity in diagnostically diverse pediatric intensive care unit patients. Neurocrit Care. 2017;28:1–9.

17.

Fink EL, Berger RP, Clark RSB, et al. Serum biomarkers of brain injury to classify outcome after pediatric cardiac arrest. Crit Care Med. 2014;42(3):664–74.PubMedPubMedCentral

18.

Topjian AA, Lin R, Morris MC, et al. Neuron-specific enolase and S-100B are associated with neurologic outcome after pediatric cardiac arrest. Pediatr Crit Care Med. 2009;10(4):479–90.PubMed

19.

Park SH, Hwang SK. Prognostic value of serum levels of S100 calcium-binding protein B, neuron-specific enolase, and interleukin-6 in pediatric patients with traumatic brain injury. World Neurosurg. 2018;118:e534–42.PubMed

20.

Bembea MM, Rizkalla N, Freedy J, et al. Plasma biomarkers of brain injury as diagnostic tools and outcome predictors after extracorporeal membrane oxygenation. Crit Care Med. 2015;43(10):2202–11.PubMed

21.

Daoud H, Alharfi I, Alhelali I, Charyk Stewart T, Qasem H, Fraser DD. Brain injury biomarkers as outcome predictors in pediatric severe traumatic brain injury. Neurocrit Care. 2014;20(3):427–35.PubMed

22.

Berger RP, Adelson PD, Richichi R, Kochanek PM. Serum biomarkers after traumatic and hypoxemic brain injuries: Insight into the biochemical response of the pediatric brain to inflicted brain injury. Dev Neurosci. 2006;28(4–5):327–35.PubMed

23.

Spadaro S, Park M, Turrini C, et al. Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine. J Inflamm (U K). 2019;16(1):1–11.

24.

Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA J Am Med Assoc. 2019;321:15261.

25.

Wilkinson AA, Dennis M, Simic N, et al. Brain biomarkers and pre-injury cognition are associated with long-term cognitive outcome in children with traumatic brain injury. BMC Pediatr. 2017;17(1):1–11.

26.

Fiser DH. Assessing the outcome of pediatric intensive care. J Pediatr. 1992;121(1):68–74.PubMed

27.

Pollack MM, Holubkov R, Glass P, et al. Functional status scale: new pediatric outcome measure. Pediatrics. 2009;124(1):e18-28.PubMed

28.

Holden JE, Kelley K, Agarwal R. Analyzing change: a primer on multilevel models with applications to nephrology. Am J Nephrol. 2008;28(5):792–801.PubMedPubMedCentral

29.

Ross KA, Dorris L, Mcmillan T. A systematic review of psychological interventions to alleviate cognitive and psychosocial problems in children with acquired brain injury. Dev Med Child Neurol. 2011;53(8):692–701.PubMed

30.

Berger RP, Dulani T, Adelson PD, Leventhal JM, Richichi R, Kochanek PM. Identification of inflicted traumatic brain injury in well-appearing infants using serum and cerebrospinal markers: a possible screening tool. Pediatrics. 2006;117(2):325–32.PubMed

31.

Berger RP, Adelson PD, Pierce MC, Dulani T, Cassidy LD, Kochanek PM. Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurg. 2005;103(Suppl. 1):61–8.PubMed

32.

Bechtel K, Frasure S, Marshall C, Dziura J, Simpson C. Relationship of serum S100B levels and intracranial injury in children with closed head trauma. Pediatrics. 2009;124(4):e697–704.PubMed

33.

Müller K, Townend W, Biasca N, et al. S100B serum level predicts computed tomography findings after minor head injury. J Trauma Inj Infect Crit Care. 2007;62(6):1452–6.

34.

Thelin EP, Nelson DW, Bellander BM. A review of the clinical utility of serum S100B protein levels in the assessment of traumatic brain injury. Acta Neurochir (Wien). 2017;159(2):209–25.

35.

Ghanem G, Loir B, Morandini R, Sales F, Lienard D, Eggermont A, Lejeune F. On the release and half-life of S100B protein in the peripheral. Int J Cancer. 2001;94:586–90.PubMed

36.

Berger RP, Bazaco MC, Wagner AK, Kochanek PM, Fabio A. Trajectory analysis of serum biomarker concentrations facilitates outcome prediction after pediatric traumatic and hypoxemic brain injury. Dev Neurosci. 2011;32(5–6):396–405.

37.

Mehta T, Fayyaz M, Giler GE, et al. Current trends in biomarkers for traumatic brain injury. Open Access J Neurol Neurosurg. 2020;12(4):86–94.PubMedPubMedCentral

38.

Bell MJ, Kochanek PM, Doughty LA, et al. Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children. J Neurotrauma. 2009;14:451–7.

39.

Muszynski JA, Thakkar R, Hall MW. Inflammation and innate immune function in critical illness. Curr Opin Pediatr. 2016;28(3):267–73.PubMed

40.

Peberdy MA, Andersen LW, Abbate A, et al. Inflammatory markers following resuscitation from out-of-hospital cardiac arrest—a prospective multicenter observational study. Resuscitation. 2016;103:117–24.PubMed

41.

Buerki SE, Grandgirard D, Datta AN, et al. Inflammatory markers in pediatric stroke: an attempt to better understanding the pathophysiology. Eur J Paediatr Neurol. 2016;20(2):252–60. https://doi.org/10.1016/j.ejpn.2015.12.006.CrossRefPubMed

42.

Chiaretti A, Genovese O, Aloe L, et al. Interleukin 1β and interleukin 6 relationship with paediatric head trauma severity and outcome. Child’s Nerv Syst. 2005;21(3):185–93.

43.

Ferreira LCB, Regner A, Miotto KDL, et al. Increased levels of interleukin-6, -8 and -10 are associated with fatal outcome following severe traumatic brain injury. Brain Inj. 2014;28(10):1311–6.PubMed

44.

Kumar RG, Diamond ML, Boles JA, et al. Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome. Brain Behav Immun. 2015;2015(45):253–62. https://doi.org/10.1016/j.bbi.2014.12.021.CrossRef

45.

Wurzelmann M, Romeika J, Sun D. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury. Neural Regen Res. 2017;12(1):7–12.PubMedPubMedCentral

46.

Wong AW, Xiao J, Kemper D, Kilpatrick TJ, Murray SS. Oligodendroglial expression of TrkB independently regulates myelination and progenitor cell proliferation. J Neurosci. 2013;33(11):4947–57.PubMedPubMedCentral

47.

Erickson KI, Prakash RS, Voss MW, et al. Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. J Neurosci. 2010;30(15):5368–75.PubMedPubMedCentral

48.

Chiaretti A, Piastra M, Polidori G, et al. Correlation between neurotrophic factor expression and outcome of children with severe traumatic brain injury. Intensive Care Med. 2003;29(8):1329–38.PubMed

49.

Stanne TM, Aberg ND, Nilsson S, et al. Low circulating acute brain-derived neurotrophic factor levels are associated with poor long-term functional outcome after ischemic stroke. Stroke. 2016;47(7):1943–5.PubMed

50.

Hashimoto K. Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatry Clin Neurosci. 2010;64(4):341–57.PubMed

51.

Xu J, Roberts RE. The power of positive emotions: it’s a matter of life or death–subjective well-being and longevity over 28 years in a general population. Health Psychol. 2010;29(1):9–19.PubMed

52.

Seale GS, Berges I-M, Ottenbacher K, Ostir GV. Change in positive emotion and recovery of functional status following stroke. Rehabil Psychol. 2010;55(1):33–9.PubMedPubMedCentral

53.

Jarvis JM, Downer B, Baillargeon J, Khetani M, Ottenbacher KJ, Graham JE. The modifying effect of positive emotion on the relationship between cognitive impairment and disability among older Mexican Americans: a cohort study. Disabil Rehabil. 2018;41(13):1–8.

54.

Rosenstein JM, Krum JM, Ruhrberg C. VEGF in the nervous system. Organogensis. 2010;6(2):107–14.

55.

Taylor JM, Montgomery MH, Gregory EJ, Berman NEJ. Exercise preconditioning improves traumatic brain injury outcomes. Brain Res. 2015;1622:414–29. https://doi.org/10.1016/j.brainres.2015.07.009.CrossRefPubMedPubMedCentral

56.

Zhou S, Yin DP, Wang Y, Tian Y, Wang ZG, Zhang JN. Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury. Neural Regen Res. 2018;13(12):2134–40.PubMedPubMedCentral

57.

Voss MW, Erickson KI, Prakash RS, et al. Neurobiological markers of exercise-related brain plasticity in older adults. Brain Behav Immun. 2013;28:90–9.PubMed

58.

El-Tamawy MS, Abd-Allah F, Ahmed SM, Darwish MH, Khalifa HA. Aerobic exercises enhance cognitive functions and brain derived neurotrophic factor in ischemic stroke patients. NeuroRehabilitation. 2014;34(1):209–13.PubMed

59.

Coelho FM, Pereira DS, Lustosa LP, et al. Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women. Arch Gerontol Geriatr. 2012;54(3):415–20.PubMed

60.

Rahmani F, Saghazadeh A, Rahmani M, et al. Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: a systematic review and meta-analysis. Brain Res. 2018;2019(1704):127–36.

61.

Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity—exercise-induced response of peripheral brain-derived neurotrophic factor. Sport Med. 2010;40(9):765–801.

62.

Choong K, Awladthani S, Khawaji A, et al. Early exercise in critically ill youth and children, a preliminary evaluation: the wEECYCLE pilot trial. Pediatr Crit Care Med. 2017;18(11):e546–54.PubMed

63.

Kudchadkar SR, Nelliot A, Awojoodu R, et al. Physical rehabilitation in critically Ill Children: a multicenter point prevalence study in the United States. Crit Care Med. 2020;48(5):634–44.PubMedPubMedCentral

64.

Wagner AK, Sowa G. Rehabilomics research: a model for translational rehabilitation and comparative effectiveness rehabilitation research. Am J Phys Med Rehabil. 2014;93(10):913–6.PubMed

65.

The World Health Organization. International Classification of Functioning, Disability, and Health: Children & Youth Version: ICF-CY. 2007.

66.

Wagner AK. TBI translational rehabilitation research in the 21st Century: exploring a rehabilomics research model. Eur J Phys Rehabil Med. 2010;46(4):549–55.PubMed

67.

Wagner AK. TBI rehabilomics research: an exemplar of a biomarker-based approach to precision care for populations with disability. Curr Neurol Neurosci Rep. 2017;17(11):1–8.

68.

Särkämö T, Tervaniemi M, Laitinen S, et al. Music listening enhances cognitive recovery and mood after middle cerebral artery stroke. Brain. 2008;131(Pt 3):866–76.PubMed

69.

Jarvis JM, Gurga A, Lim H, et al. Caregiver strategy use to promote children’s home participation after pediatric critical illness. Arch Phys Med Rehabil. 2019;100(11):2144–50. https://doi.org/10.1016/j.apmr.2019.05.034.CrossRefPubMed

70.

Jarvis JM, Choong K, Khetani MA. Associations of participation-focused strategies and rehabilitation service use with caregiver stress after pediatric critical illness. Arch Phys Med Rehabil. 2019;100(4):703–10.PubMed

71.

Thomaz A, Jaeger M, Buendia M, et al. BDNF/TrkB signaling as a potential novel target in pediatric brain tumors: anticancer activity of selective TrkB inhibition in medulloblastoma cells. J Mol Neurosci. 2016;59(3):326–33.PubMed

72.

Fink EL, Jarvis JM, Maddux AB, et al. Development of a core outcome set for pediatric critical care outcomes research. Contemp Clin Trials. 2020;91(March):105968. https://doi.org/10.1016/j.cct.2020.105968.CrossRefPubMedPubMedCentral

73.

Maddux AB, Pinto N, Fink EL, et al. Postdischarge outcome domains in pediatric critical care and the instruments used to evaluate them: a scoping review. Crit Care Med. 2020;48(12):e1313–21.PubMed

74.

Jarvis JM, Kaelin V, Anaby D, Teplicky R, Khetani M. Electronic participation-focused care planning support for families: a pilot study. Dev Med Child Neurol. 2020;62:954–61.PubMedPubMedCentral

75.

Fink EL, Maddux AB, Pinto N, et al. A core outcome set for pediatric critical care. Crit Care Med. 2020;48(12):1819–28.

Titel: Serum Biomarkers of Regeneration and Plasticity are Associated with Functional Outcome in Pediatric Neurocritical Illness: An Exploratory Study
verfasst von: Catherine Madurski
Jessica M. Jarvis
Sue R. Beers
Amy J. Houtrow
Amy K. Wagner
Anthony Fabio
Chunyan Wang
Craig M. Smith
Lesley Doughty
Keri Janesko-Feldman
Pamela Rubin
Dorothy Pollon
Amery Treble-Barna
Patrick M. Kochanek
Ericka L. Fink
for the PICU-Rehabilitation Study Group
Publikationsdatum: 04.03.2021
Verlag: Springer US
Erschienen in: Neurocritical Care / Ausgabe 2/2021
Print ISSN: 1541-6933
Elektronische ISSN: 1556-0961
DOI: https://doi.org/10.1007/s12028-021-01199-z

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Background/Objective

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2021

Electroencephalography, Hospital Complications, and Longitudinal Outcomes After Subarachnoid Hemorrhage

Proceedings of the Second Regional Neurocritical Care Meeting in the Middle East and Africa in conjunction with the 17th Emirates Critical Care Conference (ECCC)

Pathophysiology of Brain Injury and Neurological Outcome in Acute Respiratory Distress Syndrome: A Scoping Review of Preclinical to Clinical Studies

Not Always a Nail in the Coffin! Brainstem Lesions After Traumatic Brain Injury

The Association Between Functional Status and Health-Related Quality of Life Following Discharge from the Pediatric Intensive Care Unit