Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis

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dc.contributor.advisorFigaji, Anthonyen_ZA
dc.contributor.authorRohlwink, Ursula Karinen_ZA
dc.date.accessioned2014-11-11T06:52:19Z
dc.date.available2014-11-11T06:52:19Z
dc.date.issued2014en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstract[Background] Tuberculous meningitis (TBM) in children has high mortality and neurological morbidity rates. The assessment of disease severity and prognostication are difficult because several factors influence initial presentation, and advanced tools for these are lacking. Biomarkers of neurological injury could help to assess severity and to prognosticate, but have not been assessed in paediatric TBM. This study examined serum and cerebrospinal fluid (CSF) biomarkers of neurological injury in paediatric TBM in association with clinical and physiological data, radiology, inflammatory markers, and outcome. [ Methods ] Serum and CSF (ventricular and lumbar) samples were taken on admission and over 3 weeks in children with probable TBM and hydrocephalus. These were analysed with ELISA for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and with Luminex multianalyte array assay for a panel of inflammatory markers. Results were compared with 2 controls groups. Computerized tomography was done on admission and magnetic resonance imaging (brain, spine and magnetic resonance angiography) at 3 weeks. Brain oxygenation was monitored invasively and non-invasively in selected patients. Clinical and neurodevelopmental outcomes were assessed at 6 months. Data were analysed with various statistical tools, including principal component analysis. [ Results ] Data were collected from 44 children. Of these, 16% died and 36% had disability (25% mildmoderate, 11% severe). S100B, NSE, GFAP and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Elevated neuromarkers were significantly associated with poor outcome and increased over time in patients who died, although combined inflammatory biomarkers decreased. Cerebral infarcts occurred in 66% of patients and were associated with neuromarker elevation. Novel findings on spinal MRI were the high frequency of asymptomatic disease. Cerebral vascular pathology was documented frequently on imaging but did not predict infarcts. Low brain oxygenation was common and in keeping with physiological events and outcome. [ Conclusion ] CSF neuro- and inflammatory markers are elevated in TBM. Neuromarkers were prognostic of clinical and radiological outcome and an increasing trend suggested ongoing injury. This does not appear to be related to ongoing inflammation as measured by cytokines but may reflect the ongoing secondary injury processes initiated by inflammation.en_ZA
dc.identifier.apacitationRohlwink, U. K. (2014). <i>Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Neurosurgery. Retrieved from http://hdl.handle.net/11427/9524en_ZA
dc.identifier.chicagocitationRohlwink, Ursula Karin. <i>"Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Neurosurgery, 2014. http://hdl.handle.net/11427/9524en_ZA
dc.identifier.citationRohlwink, U. 2014. Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Rohlwink, Ursula Karin AB - [Background] Tuberculous meningitis (TBM) in children has high mortality and neurological morbidity rates. The assessment of disease severity and prognostication are difficult because several factors influence initial presentation, and advanced tools for these are lacking. Biomarkers of neurological injury could help to assess severity and to prognosticate, but have not been assessed in paediatric TBM. This study examined serum and cerebrospinal fluid (CSF) biomarkers of neurological injury in paediatric TBM in association with clinical and physiological data, radiology, inflammatory markers, and outcome. [ Methods ] Serum and CSF (ventricular and lumbar) samples were taken on admission and over 3 weeks in children with probable TBM and hydrocephalus. These were analysed with ELISA for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and with Luminex multianalyte array assay for a panel of inflammatory markers. Results were compared with 2 controls groups. Computerized tomography was done on admission and magnetic resonance imaging (brain, spine and magnetic resonance angiography) at 3 weeks. Brain oxygenation was monitored invasively and non-invasively in selected patients. Clinical and neurodevelopmental outcomes were assessed at 6 months. Data were analysed with various statistical tools, including principal component analysis. [ Results ] Data were collected from 44 children. Of these, 16% died and 36% had disability (25% mildmoderate, 11% severe). S100B, NSE, GFAP and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Elevated neuromarkers were significantly associated with poor outcome and increased over time in patients who died, although combined inflammatory biomarkers decreased. Cerebral infarcts occurred in 66% of patients and were associated with neuromarker elevation. Novel findings on spinal MRI were the high frequency of asymptomatic disease. Cerebral vascular pathology was documented frequently on imaging but did not predict infarcts. Low brain oxygenation was common and in keeping with physiological events and outcome. [ Conclusion ] CSF neuro- and inflammatory markers are elevated in TBM. Neuromarkers were prognostic of clinical and radiological outcome and an increasing trend suggested ongoing injury. This does not appear to be related to ongoing inflammation as measured by cytokines but may reflect the ongoing secondary injury processes initiated by inflammation. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis TI - Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis UR - http://hdl.handle.net/11427/9524 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/9524
dc.identifier.vancouvercitationRohlwink UK. Biomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitis. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Neurosurgery, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/9524en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Neurosurgeryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.titleBiomarkers of neurological tissue injury and inflammation in paediatric tuberculous meningitisen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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