Cerebrospinal Fluid Levels of 5-Hydroxyindoleacetic Acid in Parkinson's Disease and Atypical Parkinsonian Syndromes.

BACKGROUND: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. METHODS: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal syndrome (CBS) patients, and 31 controls. We also compared the values in depressed and nondepressed patients. RESULTS: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/L, in MSA 13.6 µg/L vs. 24.3 µg/L in controls; p = 0.0008 in PD, p = 0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBS compared to the control group (median in PSP 22.7 µg/L, in CBS 18.7 µg/L vs. 24.3 µg/L in controls; p = 1 in both PSP and CBS). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, p < 0.0001). CONCLUSIONS: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD; however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD and MSA) than in tauopathies (PSP and CBS).

Premotor Parkinson's disease: Overview of clinical symptoms and current diagnostic methods.

Parkinson's disease (PD) is characterized by typical motor symptoms. However, recent studies show several non-motor features that may precede the development of the motor symptoms of PD. The best known premotor symptoms include hyposmia, REM sleep behavior disorder (RBD), constipation, and depression; other symptoms are excessive daytime somnolence, orthostatic hypotension and symptomatic hypotension, erectile or urinary dysfunction, musculoskeletal symptoms, pain, and global cognitive deficit. In this review, we summarize currently available diagnostic methods for these symptoms. We also briefly summarize neuroimaging, polyneuropathy, peripheral markers, and cerebrospinal fluid biomarkers that may be used in the early diagnosis of PD.

Cerebrospinal Fluid Levels of Chromogranin A in Parkinson's Disease and Multiple System Atrophy.

BACKGROUND: Chromogranin A (CgA) and other peptides from the chromogranin-secretogranin family have been recently studied as potential biomarkers of various neurodegenerative diseases, including Parkinson's disease (PD). METHODS: We measured CgA in the cerebrospinal fluid (CSF) of 119 PD patients, 18 multiple system atrophy (MSA) patients, and 31 age-matched controls. We also correlated the values with disease duration and levodopa dose equivalent. RESULTS: In the PD patients, CSF CgA tended to be lower than the control group (median 124.5 vs. 185.2 µg/L; p = 0.057); however, the results did not reach statistical significance. CSF CgA levels in MSA were significantly lower compared to the control group (median 104.4 vs. 185.2; p = 0.014). There was no significant difference in CSF CgA between PD and MSA patients (p = 0.372). There was no association between CSF CgA and disease duration or levodopa dose equivalent in PD or in MSA. CONCLUSIONS: We observed a tendency toward lower CSF CgA levels in both PD and MSA compared to the control group; however, the difference reached statistical significance only in MSA. Based on these results, CgA may have potential as a biomarker in PD and MSA, but further studies on larger numbers of patients are needed to draw conclusions.

Stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan-related neuroactive substances in human serum and cerebrospinal fluid.

Many compounds related to L-tryptophan (L-TRP) have interesting biological or pharmacological activity, and their abnormal neurotransmission seems to be linked to a wide range of neurodegenerative and psychiatric diseases. A high-throughput method based on ultra-high performance liquid chromatography connected to electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS) was developed for the quantitative analysis of L-TRP and 16 of its metabolites in human serum and cerebrospinal fluid (CSF), representing both major and minor routes of L-TRP catabolism. The combination of a fast LC gradient with selective tandem mass spectrometry enabled accurate analysis of almost 100 samples in 24h. The standard isotope dilution method was used for quantitative determination. The method's lower limits of quantification for serum and cerebrospinal fluid ranged from 0.05 to 15nmol/L and 0.3 to 45nmol/L, respectively. Analytical recoveries ranged from 10.4 to 218.1% for serum and 22.1 to 370.0% for CSF. The method's accuracy ranged from 82.4 to 128.5% for serum matrix and 90.7 to 127.7% for CSF matrix. All intra- and inter-day coefficients of variation were below 15%. These results demonstrate that the new method is capable of quantifying endogenous serum and CSF levels of a heterogeneous group of compounds spanning a wide range of concentrations. The method was used to determine the physiological levels of target analytes in serum and CSF samples from 18 individuals, demonstrating its reliability and potential usefulness in large-scale epidemiological studies.

Clusterin CSF levels in differential diagnosis of neurodegenerative disorders.

INTRODUCTION: Clusterin, a heterodimeric glycoprotein, is thought to be involved in many cellular functions, including cell-cell interaction, cell survival and apoptosis. In the brain, post-mortem analysis has found increased clusterin associated with the pathology of many other neurodegenerative diseases (ND) such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and multiple system atrophy (MSA). In vivo cerebrospinal fluid (CSF) levels of clusterin in ND diseases may reflect differences in the pathology and thus aid in the differential diagnosis. METHODS: CSF levels of clusterin were assessed in 102 patients with clinical manifestations of neurodegenerative diseases (23 patients with PD, 18 with PDD, 15 with DLB, 18 with AD, 16 with PSP, 12 with MSA) and 21 subjects as a control group (CG). RESULTS: Significantly higher CSF clusterin levels were found in PD compared to CG (median 6884 vs. 4484; p=0.012), DLB (median 6884 vs. 4192; p=0.023), MSA (median 6884 vs. 3606; p=0.001) and PSP (median 6884 vs. 4193; p=0.014). Significantly higher CSF clusterin levels were found in PDD compared to CG (median 8617 vs. 4484; p=0.045), DLB (median 8617 vs. 4192; p=0.025) and MSA (median 8617 vs. 3606; p=0.004). CONCLUSION: The results of the presented "feasibility" study support the role of clusterin in PD/PDD pathogenesis. Clusterin CSF levels could serve as a potential marker for PDD and DLB differentiation.

Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD.

Tau protein, beta-amyloid1₋42 and clusterin CSF levels in the differential diagnosis of Parkinsonian syndrome with dementia.

BACKGROUND: Parkinson's disease (PD), PD with dementia (PDD) and Lewy body dementia (DLB) are synucleinopathies. PDD and DLB are sometimes considered a transition between PD and Alzheimer dementia (AD). Finding in vivo markers or their combination could help in the differential diagnosis of these neurodegenerative (ND) diseases. OBJECTIVE: The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau protein, betaamyloid1-42 and clusterin and to compare these levels among patients with probable PD, PDD, DLB and AD. METHODS: CSF levels of ND markers were assessed in 96 patients (27 patients with PD, 14 with PDD, 14 with DLB, 17 with AD and 24 subjects as a control group). RESULTS: In all of the groups of patients, beta-amyloid1-42 levels were decreasing in the order PD>PDD>DLB>AD, whereas tau protein and the tau protein/beta-amyloid1-42 index were increasing in the same order (PD

Cerebrospinal fluid levels of chromogranin A in the treatment-naïve early stage Parkinson's disease: a pilot study.

Chromogranin A (CgA) levels in cerebrospinal fluid (CSF) have been reported to be significantly reduced in the later stages of Parkinson's disease (PD). There are only limited data regarding its levels in the early stages, so its significance as a potential biomarker in the diagnosis of PD cannot be established. The aim of our study was to establish the level of CgA in a cohort of treatment-naïve patients with early stage PD. Ten patients (4 males, 6 females) and 10 gender- and age-matched controls were examined for CgA levels in the CSF. Control subjects were patients with low-back pain or tension-type headache. The mean CSF CgA level in PD patients was 74.8 (41.9-123.8) µg/l; in the control group it was 143.9 (116-181.3) µg/l. Statistical analysis showed a difference at the significance level P ≤ 0.05. Our pilot study shows that CSF CgA levels are reduced in the early stages of PD. CgA could therefore be a potential biomarker helpful in the diagnosis of PD.

Tau protein and beta-amyloid(1-42) CSF levels in different phenotypes of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder with highly heterogeneous clinical manifestations. This fact has prompted many attempts to divide PD patients into clinical subgroups. This could lead to a better recognition of pathogenesis, improving targeted treatment and the prognosis of PD patients. The aim of the present study was to obtain cerebrospinal fluid (CSF) samples in PD patients and to search for a relationship between neurodegenerative CSF markers (tau protein, beta-amyloid(1-42) and index tau protein/beta-amyloid(1-42)) and the clinical subtypes. PD patients were divided into three subgroups: early disease onset (EDO), tremor-dominant PD (TD-PD), and non-tremor dominant PD (NT-PD) according to the previously published classification. Neurodegenerative markers in the CSF were assessed in these three groups of patients suffering from PD (EDO-17, TD-15, NT-16 patients) and in a control group (CG) of 19 patients suffering from non-degenerative neurological diseases and 18 patients with Alzheimer's disease (AD). The NT-PD patients were found to have significantly higher levels of CSF tau protein and index tau/beta than the control subjects and other Parkinsonian subgroups, but no significant differences in these markers were found between AD and NT-PD patients. In the context of more rapid clinical progression and more pronounced neuropathological changes in the NT-PD patient group, our results corroborate the opinion that CSF level of tau protein may be regarded as a potential laboratory marker of the presence and severity of neurodegeneration.

CSF markers of neurodegeneration in Parkinson's disease.

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disease with a multifactorial etiology. Protein accumulation is speculated by some to play a prominent role in the pathogenesis of PD. The severity of neurodegeneration should correlate with cerebrospinal fluid (CSF) levels of these neurodegenerative markers (NDMs). The aims of the study were to assess the CSF levels of tau protein, beta-amyloid (1-42), cystatin C, and clusterin in patients suffering from PD and in a control group, to compare the CSF levels between the two groups and to correlate them to PD duration. NDMs in the CSF were assessed in 32 patients suffering from PD and in a control group (CG) of 30 patients. The following statistically significant differences in the CSF were found: higher tau protein (p = 0.045) and clusterin levels (p = 0.004) in PD patients versus CG; higher tau protein levels (p = 0.033), tau protein/beta-amyloid (1-42) ratio (p = 0.011), and clusterin (p = 0.044) in patients suffering from PD for <2 years versus patients suffering PD for more than 2 years. No differences between beta-amyloid (1-42) and cystatin C CSF levels were found in the CG and PD patients groups. Significantly higher tau protein and clusterin CSF levels in the group of PD patients with disease duration of <2 years probably reflect the fact that most neurodegenerative changes in PD patients occur in the initial stage of disease.

Effect of entacapone on plasma homocysteine levels in Parkinson's disease patients.

Peripheral metabolism of L-DOPA via enzyme catechol-O-methyltransferase (COMT) is one of the possible sources of homocysteine (HCY). The aim of this study was to assess plasma HCY levels in L-DOPA-treated Parkinson's disease (PD) patients and its influence by adding the inhibitor COMT (entacapone). Patients were divided into two groups: (1) patients long term treated with L-DOPA but were naïve to entacapone, (2) L-DOPA naïve patients, in whom a combined treatment with L-DOPA and entacapone was started. The HCY levels were higher in Group 1 than in Group 2. No statistically significant changes of HCY concentrations were found in both patient groups after adding entacapone to their L-DOPA treatments. Results of this study confirm that patients treated with L-DOPA for a long term have increased plasma HCY concentrations. We believe combined L-DOPA and entacapone therapy could be a possible protective mechanism against hyperhomocysteinemia in early PD.

Identification of viscoelastic parameters of skin with a scar in vivo, influence of soft tissue technique on changes of skin parameters.

The goal of the experiment was to develop an identification method capable of objective detection of changes of viscoelastic properties of skin with a scar remaining after a modified radical mastectomy. We compared the intact skin and the skin with a scar, a scar before and after physiotherapy. We used two methods. The first one is based on measurements of the local dynamic deformation response of the skin and the second one is the matrix identification of static deformation that identifies properties of the whole tested region of the explored tissues. We identified the skin stretchability, shiftability against deeper layers and deeply analysed both the methods. In some patients, we found statistically proven difference. In all these cases the measurement methods have detected changes of the observed tissue condition. We found both methods to be potentially applicable after further improvements as a diagnostic tool, which can contribute to the improvement of postoperative care of patients.