The underlying pathophysiology following traumatic brain injury (TBI) in how different neurodegenerative conditions are developed are still unknown. Different neuroinflammatory and neurodegenerative pathways have been suggested. The goal of this study is to follow-up patients that have been treated for TBI at the neurosurgical department about 10-15 years after their initial injury, in order to analyze fluid biomarkers of inflammation, injury and degeneration and associate these with structural imaging and long-term functional outcome. The investigators aim to invite about 100 patients back and perform advanced magnetic resonance imaging protocols, sample cerebrospinal fluid and blood for different bio- and inflammatory markers, study genetic modifications and associate it with outcomes being assessed through questionnaires. The investigators' hypothesis is that patients with ongoing inflammatory processes will present with more fluid biomarkers of neurodegeneration, worse clinical presentation and also more structural/atrophic signs on imaging. This will result in an increased understanding of the interplay between neuroinflammation and neurodegeneration in chronic TBI, as well as a panel of tentative biomarkers that could be used to assess level of disability following TBI and chronic traumatic encephalopathy (CTE).
Study Type
OBSERVATIONAL
Enrollment
100
Patients will undergo magnetic resonance imaging including the following protocols: * 3D T1w MPRAGE * 3D T2w FLAIR SPACE * 3D T2w SPACE * 3D T1w PSIR (cortical visualization) * 2D synthetic MRI (quantitative T1, T2, PD and myelin quantification) * Resting-state fMRI (6 min, human connectome protocol, 2 mm iso) * 3D SWI * DWI b1000 32 directions and b3000 64 directions.
Blood will be screened for genetic modifications. Serum will be analyzed for auto-antibodies and other inflammatory and neurodegenerative biomarkers.
CSF will be analyzed for inflammatory and neurodegenerative biomarkers.
* Glasgow Outcome Scale Extended (functional outcome) * Short-Form 36 (quality of life), * EQ-5D (quality of life), * Mini-Mental State Extended (MMSE) (mental state assessment). * Barthel Index (daily living disabilities), * Montgomery-Åsberg Depression Score (MADRS-S) (level of depression) * Fatigue Severity Scale (FSS) (level of fatigue) Other than that, neurological assessments focusing on the Unified Parkinson's Disease Rating Scale (UPDRS) will be performed.
Karolinska University Hospital
Stockholm, Sweden
RECRUITINGGOSE vs structural outcome
Glasgow Outcome Score extended (1-8) will be associated alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
Barthel Index vs structural outcome
Barthel Index (0-100) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
Fatigue Severity Scale vs structural outcome
Fatigue Severity Scale (9-63) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
MOCA vs structural outcome
Montreal Cognitive Assessment (MoCA) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (MOCA score vs affected voxels).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
SF-36 vs structural outcome
Short-Form 36 will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (SF-36 score vs affected voxels on MRI).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
EQ-5D vs structural outcome
Health-related quality of life (EQ-5D) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (EQ5D score vs affected voxels on MRI).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
MADRS vs structural outcome
Montgomery-Åsberg depression rating scale (MADRS) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (MADRS score vs affected voxels).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
Structural outcome vs proteomic markers in serum
Alterations at axonal and myelin integrity as assessed by magnetic resonance imaging will be associated with a proteomic profiling using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin (affected voxels vs mean fluorescent intensities (MFI)).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
Structural outcome vs proteomic markers in cerebrospinal fluid
Alterations at axonal and myelin integrity as assessed by magnetic resonance imaging will be associated with a proteomic profiling of cerebrospinal fluid using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin (affected voxels vs mean fluorescent intensities (MFI)).
Time frame: Assessed at the chronic time-point (10-15 years after injury).
Structural outcome vs auto-antibodies in serum
Alterations at axonal and myelin integrity as assessed by magnetic resonance imaging will be associated with a panel of auto-antibodies targeting central nervous system antigens ((affected voxels vs antibody titers)
Time frame: Assessed at the chronic time-point (10-15 years after injury).
Acute vs chronic comparisons of proteomic markers in serum
Proteomic profiling using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin will be compared in a subset of patients between the acute and chronic stage comparing mean flourescent intensities (MFI).
Time frame: From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)
Acute vs chronic comparisons of proteomic markers in CSF
Proteomic profiling using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin in CSF will be compared in a subset of patients between the acute and chronic stage comparing mean flourescent intensities (MFI).
Time frame: From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)
Acute vs chronic comparisons of autoantibodies
A panel of auto-antibodies targeting central nervous system antigens will be compared between the acute and chronic phase (comparison of antibody titers)
Time frame: From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)
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