Long-term regional atrophy and association with clinical outcome following severe traumatic brain injury: A tensor based morphometry study

NeuroImage ◽  
2009 ◽  
Vol 47 ◽  
pp. S68
Author(s):  
A Skimminge ◽  
K Sidaros ◽  
M Liptrot ◽  
AW Engberg ◽  
M Herning ◽  
...  
2021 ◽  
Author(s):  
Caroline Lindblad ◽  
Elisa Pin ◽  
David Just ◽  
Faiez Al Nimer ◽  
Peter Nilsson ◽  
...  

Abstract Background: Severe traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. Methods: We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6-12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (QA), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort.Results: TBI patients had an upregulation of structural and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with QA, among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained ~10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, DR2 = 7.4%) and complement factor B in serum (p = 0.003, DR2 = 9.2%) were independent outcome predictors also following step-down modelling. Conclusions: This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Caroline Lindblad ◽  
Elisa Pin ◽  
David Just ◽  
Faiez Al Nimer ◽  
Peter Nilsson ◽  
...  

Abstract Background Severe traumatic brain injury (TBI) is associated with blood–brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. Methods We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6–12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (QA), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort. Results TBI patients had an upregulation of structural CNS and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with QA, among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained ~ 10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, ΔR2 = 7.4%) and complement factor B in serum (p = 0.003, ΔR2 = 9.2%) were independent outcome predictors also following step-down modelling. Conclusions This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.


2020 ◽  
Author(s):  
Caroline Lindblad ◽  
Elisa Pin ◽  
David Just ◽  
Faiez Al Nimer ◽  
Peter Nilsson ◽  
...  

Abstract Background: Severe traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. Methods: We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Scale, was collected after 6-12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (QA), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses.Results: TBI patients had an upregulation of structural and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with QA, among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained ~10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, ΔR2 = 7.4%) and complement factor B in serum (p = 0.003, ΔR2 = 9.2%) were independent outcome predictors also following step-down modelling. Conclusions: This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.


2002 ◽  
Vol 32 (4) ◽  
pp. 639-647 ◽  
Author(s):  
Kevin W Greve ◽  
Jeff Love ◽  
Elisabeth Sherwin ◽  
Matthew S Stanford ◽  
Charles Mathias ◽  
...  

2021 ◽  
Author(s):  
Alex Vicino ◽  
Philippe Vuadens ◽  
Bertrand Léger ◽  
Charles Benaim

Abstract PurposeDecompressive craniectomy (DC) can rapidly reduce intracranial pressure and save lives in the acute phase of severe traumatic brain injury (TBI) or stroke, but little is known about the long-term outcome after DC. We evaluated quality of life (QoL) a few years after DC for severe TBI/stroke.MethodsThe following data were collected for stroke/TBI patients hospitalized for neurorehabilitation after DC: 1) at discharge, motor and cognitive sub-scores of the Functional Independence Measure (motor-FIM [score 13-91] and cognitive-FIM [score 5-35]) and 2) more than 4 years after discharge, the QOLIBRI health-related QoL (HR-QoL) score (0-100; <60 representing low or impaired QoL) and the return to work (RTW: 0%, partial, 100%)ResultsWe included 88 patients (66 males, median age 38 [interquartile range 26.3-51.0], 65 with TBI/23 stroke); 46 responded to the HR-QoL questionnaire. Responders and non-responders had similar characteristics (age, sex, functional levels upon discharge). Median motor-FIM and cognitive-FIM scores were 85/91 and 27/35, with no significant difference between TBI and stroke patients. Long-term QoL was borderline low for TBI patients and within normal values for stroke patients (score 58.0[42.0-69.0] vs. 67.0[54.0-81.5], p=0.052). RTW was comparable between the groups (62% full time).ConclusionWe already knew that DC can save the lives of TBI or stroke patients in the acute phase and this study suggests that their long-term quality of life is generally quite acceptable.


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