| 1. |
- Hall, Sara, et al.
(författare)
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Cerebrospinal fluid concentrations of inflammatory markers in Parkinson's disease and atypical parkinsonian disorders
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation has been implicated in the pathogenesis of Parkinson's disease (PD). We here investigate levels of inflammatory biomarkers in cerebrospinal fluid (CSF) in PD and atypical parkinsonian disorders (APD) compared with neurologically healthy controls. We included 131 patients with PD and 27 PD with dementia (PDD), 24 with multiple system atrophy (MSA), 14 with progressive supranuclear palsy (PSP) and 50 controls, all part of the Swedish BioFINDER study. CSF was analyzed for CRP, SAA, IL-6, IL-8, YKL-40 and MCP-1 (CCL2) as well as alpha-synuclein (alpha-syn), tau, tau phosphorylated at Thr181 (P-tau), A beta(42) and NfL. In this exploratory study, we found higher levels of the inflammatory biomarker SAA in PDD and MSA compared with controls and PD and higher levels of CRP in PDD and MSA compared with PD. YKL-40 was lower in PD compared with controls. There were multiple positive correlations between the inflammatory markers, a-syn and markers of neuroaxonal injury (NfL and tau). In PD, higher levels of inflammatory biomarkers correlated with worse motor function and cognitive impairment. Thus, inflammatory biomarkers were increased in PDD and MSA. Furthermore, inflammatory biomarkers correlated with more severe disease regarding motor symptoms and cognitive impairment in PD, indicating an association between inflammation and more aggressive disease course. However, the results need confirmation in follow-up studies.
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| 2. |
- Surova, Yulia, et al.
(författare)
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Alteration of putaminal fractional anisotropy in Parkinson’s disease : a longitudinal diffusion kurtosis imaging study
- 2018
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 60:3, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In Parkinson’s disease (PD), pathological microstructural changes occur that may be detected using diffusion magnetic resonance imaging (dMRI). However, there are few longitudinal studies that explore the effect of disease progression on diffusion indices. Methods: We prospectively included 76 patients with PD and 38 healthy controls (HC), all of whom underwent diffusion kurtosis imaging (DKI) as part of the prospective Swedish BioFINDER study at baseline and 2 years later. Annualized rates of change in DKI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK), were estimated in the gray matter (GM) by placing regions of interest (ROIs) in the basal ganglia and the thalamus, and in the white matter (WM) by tract-based spatial statistics (TBSS) analysis. Results: When adjusting for potential confounding factors (age, gender, baseline-follow-up interval, and software upgrade of MRI scanner), only a decrease in FA in the putamen of PD patients (β = − 0.248, P < .01) over 2 years was significantly different from the changes observed in HC over the same time period. This 2-year decrease in FA in the putamen in PD correlated with higher l-dopa equivalent dose at baseline (Spearman’s rho = .399, P < .0001). Conclusion: The study indicates that in PD microstructural changes in the putamen occur selectively over a 2-year period and can be detected with DKI.
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| 3. |
- Surova, Yulia
(författare)
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Magnetic Resonance Imaging in Parkinsons's disease and related disoders
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To identify diagnostic and prognostic biomarkers in the cerebral white (WM) and the deep grey matter (GM) in patients with Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS) using magnetic resonance imaging (MRI). Methods: Patients with a clinical diagnosis of PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) were included in the study. Patients and controls underwent standardized clinical assessment and testing regarding motor and cognitive function. All patients underwent MRI, including Diffusion tensor imaging (DTI), Diffusion tensor tractography (DTT), Diffusion kurtosis imaging (DKI), Neurite density Imaging (NDI), morphometric analyses and Susceptibility weighted imaging (SWI).Results: In paper I we assessed both global and regional changes in larger cerebral WM tracts of patients with PD, MSA-P, and PSP, employing DTT. We found that the anterior portion of the corpus callosum is a promising region for detection of neurodegenerative changes in patients with PSP, as well as for differential diagnosis between PSP and PD.In paper II we investigated the disease specific changes in the basal ganglia, the thalamus, the pons, the midbrain, and the dentato-rubro-thalamic tract (DRTT) of patients with PD, MSA-P, and PSP, using DTI and morphometric analyses. We found that patients with PSP, but not PD or MSA-P, exhibit signs of structural abnormalities in the thalamus and in the DRTT. We also found that these disease-specific changes are associated with disease stage and impaired motor function.In paper III we investigated if changes in subcortical nuclei, brainsteam and WM tracts measured by DKI and NDI could differentiate between PD and controls, and between phenotypes, such as postural instability gait difficulty (PIGD) and tremor dominant (TD) PD. We found that patients with PD exhibit diffusion MRI (dMRI) changes in the putamen, the thalamus, and the superior longitudinal fasciculus associated with worse disease severity. However, the dMRI changes were not sufficiently specific to improve the diagnostic work-up of PD.In paper IV we investigated longitudinal dMRI measures over a two year period in PD. The study indicates that in PD microstructural changes in the putamen occur selectively over a two-year period and can be detected with DKI.In paper V we evaluated the use of quantitative susceptibility mapping (QSM) for clinical diagnostics in PD, PSP and MSA. PSP showed higher susceptibility in the globus pallidus, substantia nigra, red nucleus and dentate nucleus compared to all other groups, and higher putaminal susceptibility compared to PD and controls. MSA showed higher putaminal susceptibility compared to PD and controls, and higher susceptibility in the substantia nigra and dentate nucleus compared to PD. Discriminant analysis between PSP and all other groups combined, a sensitivity of 91% and specificity of 97% was achieved. Using all regions to separate MSA from all other groups combined, a sensitivity of 70% and specificity of 93% was noted. We also found correlations between disease severity measured by motor part of unified PD raiting scale (UPDRS-III) and putaminal susceptibility in PD.
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