Proinflammatory cytokines are elevated in serum of patients with multiple system atrophy.

Despite several lines of evidence from preclinical and post-mortem studies suggesting that inflammation is involved in Multiple System Atrophy (MSA), no previous studies have measured peripheral indices of inflammation in MSA patients

Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease

Objective: The purpose of this study was to investigate whether cerebrospinal fluid (CSF) levels of tau, phosphorylated tau, β‐amyloid42, α‐synuclein, neurofilament light, and YKL‐40 change over time and if changes correlate with motor progression and/or cognitive decline in patients with PD and controls. / Methods: We included 63 patients with PD (nondemented) and 21 neurologically healthy controls from the prospective and longitudinal Swedish BioFINDER study, all of whom had clinical assessments and lumbar punctures at baseline and after 2 years. / Results: CSF tau levels correlated strongly with α‐synuclein. The levels of CSF α‐synuclein, tau, phosphorylated tau, neurofilament light, and YKL‐40, but not β‐amyloid42, increased in CSF over 2 years in PD. No changes were seen in the control group. Studying patients with a short disease duration ( ≤ 5 years) and patients with a long disease duration ( > 5 years) separately, α‐synuclein and tau only increased in the PD group with long disease duration. In the PD group, an increase in phosphorylated tau over 2 years correlated with faster motor progression and faster cognitive decline. An increase in YKL‐40 over 2 years correlated with faster cognitive decline. / Conclusion: CSF biomarkers reflecting Lewy body pathology and neurodegeneration (α‐synuclein), neuronal degeneration (tau, phosphorylated tau, and neurofilament light), and inflammation (YKL‐40) increase significantly over 2 years in PD. CSF levels of α‐synuclein and tau correlate and remain stable in the early symptomatic phase of PD but increase in the later phase. We hypothesize that CSF α‐synuclein levels might increase as a result of more intense neurodegeneration in PD with long disease duration

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL.

Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF

Magnetic Resonance Imaging in Parkinsons's disease and related disoders

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

Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders

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 α-synuclein (α-syn), tau, tau phosphorylated at Thr181 (P-tau), Aβ42 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, α-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

CSF biomarkers and clinical progression of Parkinson disease.

To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease (PD)

Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease.

The purpose of this study was to investigate whether cerebrospinal fluid (CSF) levels of tau, phosphorylated tau, β-amyloid42 , α-synuclein, neurofilament light, and YKL-40 change over time and if changes correlate with motor progression and/or cognitive decline in patients with PD and controls

Non-motor symptoms in patients with Parkinson's disease - correlations with inflammatory cytokines in serum.

BACKGROUND: Parkinson's Disease (PD) is the second most common neurodegenerative disorder of the central nervous system. Motor symptoms are the focus of pharmacotherapy, yet non-motor features of the disease (e.g. fatigue, mood disturbances, sleep disturbances and symptoms of anxiety) are both common and disabling for the patient. The pathophysiological mechanisms behind the non-motor symptoms in PD are yet to be untangled. The main objective of this study was to investigate associations between pro-inflammatory substances and non-motor symptoms in patients with PD. METHODS AND MATERIALS: We measured C-reactive protein, interleukin (IL)-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor-α (TNF-α) in blood samples from PD patients (n=86) and healthy controls (n=40). Symptoms of fatigue, depression, anxiety and sleeping difficulties were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT), the Hospital Anxiety and Depression Scale (HAD), and the Scales for Outcome in PD-Sleep Scale respectively. RESULTS: IL-6 was significantly higher in PD patients than in healthy controls. Compared to healthy controls, PD patients displayed significantly higher mean scores on HAD and lower scores on FACIT, thus indicating more severe symptoms as measured with these scales. Within the PD sample, high levels of both sIL-2R and TNF-α were significantly associated with more severe symptoms assessed by means of FACIT and HAD (depression and anxiety subscales). SIL-2-R levels were able to significantly predict FACIT and HAD scores after the effects of age, gender, anti-parkinsonian medications, and severity of motor symptoms were controlled for. DISCUSSION: We suggest that non-motor symptoms in PD patients, such as fatigue and depressive symptoms, might be generated via inflammatory mechanisms. This knowledge might contribute to the development of novel treatment options in PD, specifically targeting non-motor symptoms

Cerebrospinal fluid inflammatory markers in Parkinson's disease - Associations with depression, fatigue, and cognitive impairment.

Neuroinflammation may be involved in the pathophysiology of Parkinson's disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation. We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N=87) and the reference group (N=33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively. There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p=0.032) and the reference group (p=0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p=0.010) and fatigue (p=0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p=0.032). Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers