Chronic Traumatic Encephalopathy, Neurodegenerative Diseases, Traumatic Brain Injury
Conditions
Keywords
Fluid biomarkers, Neuroinflammatory process, Auto-immunity, Structural imaging, Clinical assessment, Long-term follow-up
Brief summary
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).
Interventions
DIAGNOSTIC_TESTMagnetic Resonance Imaging (MRI) (including functional MRI)
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.
DIAGNOSTIC_TESTBlood sampling (serum/plasma preparation)
Blood will be screened for genetic modifications. Serum will be analyzed for auto-antibodies and other inflammatory and neurodegenerative biomarkers.
DIAGNOSTIC_TESTCerebrospinal fluid (CSF)
CSF will be analyzed for inflammatory and neurodegenerative biomarkers.
DIAGNOSTIC_TESTClinical assessments / questionnaires
* 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.
Sponsors
Karolinska Institutet
Karolinska University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Having suffered a traumatic brain injury and being treated at the Karolinska University Hospital between 2007 and 2015. * Age \>18 years of age
Exclusion criteria
\- Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Structural outcome vs auto-antibodies in serum | Assessed at the chronic time-point (10-15 years after injury). | 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) |
| MADRS vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | 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). |
| Structural outcome vs proteomic markers in serum | Assessed at the chronic time-point (10-15 years after injury). | 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)). |
| Structural outcome vs proteomic markers in cerebrospinal fluid | Assessed at the chronic time-point (10-15 years after injury). | 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)). |
| GOSE vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | Glasgow Outcome Score extended (1-8) will be associated alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels). |
| Barthel Index vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | Barthel Index (0-100) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels). |
| Fatigue Severity Scale vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | Fatigue Severity Scale (9-63) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels). |
| MOCA vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | 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). |
| SF-36 vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | 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). |
| EQ-5D vs structural outcome | Assessed at the chronic time-point (10-15 years after injury). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute vs chronic comparisons of proteomic markers in CSF | From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury) | 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). |
| Acute vs chronic comparisons of autoantibodies | From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury) | A panel of auto-antibodies targeting central nervous system antigens will be compared between the acute and chronic phase (comparison of antibody titers) |
| Acute vs chronic comparisons of proteomic markers in serum | From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury) | 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). |
Countries
Sweden
Contacts
Primary ContactEric P Thelin, MD, PhD
Backup ContactSusanna Friberg, MD
Outcome results
None listed