| 1. |
- Dickens, Alex Mountfort, et al.
(author)
-
Serum Metabolites Associated with Computed TomographyFindings after Traumatic Brain Injury
- 2018
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:22, s. 2673-2683
-
Journal article (peer-reviewed)abstract
- There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC=0.77 in Turku patients and AUC=0.73 in Cambridge patients). Furthermore, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC=0.87 in Turku patients and AUC=0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.
|
|
| 2. |
- Hossain, Iftakher, et al.
(author)
-
Early Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein in Predicting the Outcome of Mild Traumatic Brain Injury
- 2019
-
In: Journal of neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 36:10, s. 1551-1560
-
Journal article (peer-reviewed)abstract
- To correlate the early levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) with outcome in patients with mild traumatic brain injury (mTBI). 107 patients with mTBI [Glasgow Coma Scale (GCS) ≥13] having the blood samples for GFAP and NF-L available within 24 hrs from arrival were included. Patients with mTBI were divided into computed tomography (CT)-positive and CT-negative groups. Glasgow Outcome Scale extended (GOSE) was used to assess the outcome. Outcomes were defined as complete (GOSE 8) vs. incomplete (GOSE <8), and favorable (GOSE 5-8) vs. unfavorable (GOSE 1-4). GFAP and NF-L concentrations in blood were measured using ultrasensitive single molecule array technology. Patients with incomplete recovery had significantly higher levels of NF-L compared to those with complete recovery (p=0.005). The levels of GFAP and NF-L were significantly higher in patients with unfavorable outcome than in patients with favorable outcome (p=0.002 for GFAP and p <0.001 for NF-L). For predicting favorable outcome, the area under the ROC curve for GFAP and NF-L was 0.755 and 0.826, respectively. In a multivariate logistic regression model, the level of NF-L was still a significant predictor for complete recovery (OR=1.008, 95%CI, 1.000-1.016). Moreover, the level of NF-L was a significant predictor for complete recovery in CT-positive patients (OR=1.009, 95%CI, 1.001-1.016). The early levels of GFAP and NF-L are significantly correlated with the outcome in patients with mTBI. The level of NF-L within 24 hrs from arrival has a significant predictive value in mTBI also in a multivariate model.
|
|
| 3. |
- Oresic, Matej, 1967-, et al.
(author)
-
Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury
- 2016
-
In: EBioMedicine. - : Elsevier. - 2352-3964. ; 12, s. 118-126
-
Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale. The control group (n=28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n=23), moTBI (n=7), mTBI (n=37) patients and controls (n=27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC=0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified 'TBI metabotype' in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new venue for the development of diagnostic and prognostic markers of broad spectrum of TBIs. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
|
|
| 4. |
- Posti, Jussi P., et al.
(author)
-
SERUM METABOLITES ASSOCIATE WITH HEAD COMPUTED TOMOGRAPHY FINDINGS FOLLOWING TRAUMATIC BRAIN INJURY
- 2018
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:16, s. A67-A67
-
Journal article (other academic/artistic)abstract
- There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of bio-markers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminalhydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein bio-markers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, thre esugar derivatives and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC=0.77 in Turku patients and AUC=0.73 in Cambridge patients). Furthermore, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC=0.87 in Turku patients and AUC=0.68 in Cambridge pa-tients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.
|
|
| 5. |
- Koivisto, Mika, et al.
(author)
-
TMS-EEG reveals hemispheric asymmetries in top-down influences of posterior intraparietal cortex on behavior and visual event-related potentials
- 2017
-
In: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 107, s. 94-101
-
Journal article (peer-reviewed)abstract
- Clinical data and behavioral studies using transcranial magnetic stimulation (TMS) suggest right-hemisphere dominance for top-down modulation of visual processing in humans. We used concurrent TMS-EEG to directly test for hemispheric differences in causal influences of the right and left intraparietal cortex on visual event-related potentials (ERPs). We stimulated the left and right posterior part of intraparietal sulcus (IPS1) while the participants were viewing and rating the visibility of bilaterally presented Gabor patches. Subjective visibility ratings showed that TMS of right IPS shifted the visibility toward the right hemifield, while TMS of left IPS did not have any behavioral effect. TMS of right IPS, but not left one, reduced the amplitude of posterior N1 potential, 180–220 ms after stimulus-onset. The attenuation of N1 occurred bilaterally over the posterior areas of both hemispheres. Consistent with previous TMS-fMRI studies, this finding suggests that the right IPS has top-down control on the neural processing in visual cortex. As N1 most probably reflects reactivation of early visual areas, the current findings support the view that the posterior parietal cortex in the right hemisphere amplifies recurrent interactions in ventral visual areas during the time-window that is critical for conscious perception.
|
|
