Restless legs syndrome in Parkinson's disease: relationship with quality of life and medication.

OBJECTIVES: We aimed to disclose the relationship between restless leg syndrome (RLS) and antiparkinsonian treatment, and its effect on quality of life (QoL) in patients with Parkinson's disease (PD). BACKGROUND: Previous studies documented the prevalence of RLS among patients with PD to be higher than in the general population, but conclusions regarding the aetiology and impact were contradictory. METHODS: We examined 101 patients with idiopathic PD. All participants completed the five-dimension/five-level-EuroQoL questionnaire (EQ-5D-5L) and the International Restless-Legs-syndrome-study-group rating Scale (IRLS). RESULTS: The prevalence of RLS was 22.77 %. There were no statistically significant differences in levodopa or dopamine agonists (DA) doses between RLS-positive and negative participants. However, the use of levodopa as the last night-time medication was connected with a higher risk of RLS (OR=2.049, p=0.041). There was significantly lower prevalence of RLS in patients after surgical treatment for PD (p=0.024). Participants with RLS were at a greater risk for sleep disturbances (OR=3.866, p=0.023) and excessive daytime sleepiness (OR=7.202, p<0.001). Greater RLS symptoms were associated with worse QoL (higher IRLS score predicted higher EQ5D5L score, p=0.023). CONCLUSION: RLS is prevalent among PD patients and night-time dopaminergic over-excitation with levodopa plays an important role in its pathogenesis. Since the symptoms of RLS are associated with decreased QoL, early accurate diagnosis and appropriate adjustment of dopaminergic therapy can lead to immediate relief from RLS symptoms and to QoL improvement (Tab. 4, Fig. 1, Ref. 34).

Decreased plasma levels of 25(OH)D in multiple sclerosis patients. Correlation with disease severity expressed by EDSS, MSSS, progression index and Herbert´s scale severity grade.

OBJECTIVES: Multiple sclerosis is a chronic inflammatory and autoimmune demyelinating disease of the brain and spinal cord. Vitamin D has anti-inflammatory and anti-Th1, Th17 activities, activates the function of regulatory T cells, shifts the immune response towards Th2, so it might be favorable for downregulation of the disease pathogenesis, and if inflammation and Th1 and Th17 immunity are hyperactivated. The aim of our study was to highlight the role of vitamin D in multiple sclerosis pathogenesis. METHODS: We investigated 178 patients with multiple sclerosis. Plasma levels of 25(OH)D and HMGB1 were investigated. RESULTS: Despite a regular use of VD by patients, the plasma levels of 25(0H)D were significantly decreased in 57% of them, 14.1% had VD deficiency (level of 25(OH)D < 20 ng/mL) and more than 6 % of patients had VD severe deficiency with the plasma level of 25(OH)D < 12 ng/mL. The level of 25(OH)D negatively correlated with the severity of the disease (EDSS, index of progression, duration of the disease) and negative association was found also with Herbert´s six severity grades. HMGB1 levels were higher in patients (p < 0.0001). CONCLUSION: Our result showed that vitamin D deficiency plays a role in multiple sclerosis pathogenesis. We believe that administration of vitamin D to patients at a sufficient dose providing a physiological level of vitamin D could have a positive effect on the course of the disease. However, regular monitoring of vitamin D levels is required, which should be at least within 30-75 ng/mL, and even more, but below the toxicity limit (Tab. 6, Ref. 66).

DNA versus RNA oxidation in Parkinson's disease: Which is more important?

BACKROUND: 8-hydroxy-2 deoxyguanosine (8-OHdG) and the 8-hydroxyguanosine (8-OHG) are the most widely used biomarkers of nucleoside oxidation affecting DNA and RNA and are considered reliable markers of oxidative stress. Increased levels of these markers are found in the various biological fluids of patients with neurodegenerative disorders. OBJECTIVE: The primary aim of our study was to assess the differences of investigated markers between patient groups and subsequently study the influence of clinical factors that might modify the levels of investigated markers during the disease progression. METHODS: In this study, we analysed the 8-OHdG and 8-OHG levels in the cerebrospinal fluid (CSF) and serum from 44 patients with Parkinson's disease (PD) and 32 controls using an ELISA. RESULTS: There were significantly higher CSF levels of both investigated markers in Parkinson's disease patients as compared to controls (p=0.02 and p=0.04). Significantly higher CSF values of 8-OHdG were found in PD patients without dementia (p=0.05), whereas patients with dementia recorded lower 8-OHG CSF levels compared to controls (p=0.04). The disease duration and age influenced the levels of both markers within investigated groups. CONCLUSION: Oxidative DNA damage plays an important role in the early stages of PD, whereas during the progression of the disease the process is more complex, and other mechanisms are in the foreground. The measurement of 8-OHdG might be used as an "early-stage marker", whereas the decrease of 8-OHG in CSF might reflect the degree of neurodegeneration during the disease progression, suggesting its utility as a prognostic marker of advanced PD stages.

Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid ß1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. METHODS: The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. RESULTS: Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype. PRNP codon 129 genotype, PrP(sc) isotype, disease duration and clinical stage influenced the test sensitivity in all proteins. CONCLUSIONS: Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known.

8-OHdG in cerebrospinal fluid as a marker of oxidative stress in various neurodegenerative diseases.

BACKGROUND: The 8-hydroxy-2 deoxyguanosine (8-OHdG) is a product of nucleoside oxidation of DNA and a reliable marker of oxidative stress markers. Increased levels of oxidative stress have been reported in the cerebrospinal fluid (CSF) of patients with various neurodegenerative disorders. OBJECTIVE: In search of a biochemical indicator of Parkinson's disease (PD), we analyzed the levels 8-OHdG in the CSF of 99 patients, using ELISA to assess the differences between various neurodegenerative disorders. RESULTS: Statistically significant higher CSF levels (p = 0.022) of 8-OHdG in non-demented PD patients as compared to the control group were observed. No differences between CSF 8-OHdG levels and age at the time of lumbar puncture, presence or severity of dementia, or gender were found. CONCLUSIONS: 8-OHdG levels could be potentially useful in the neurochemically supported diagnosis of PD.

Different head morphology of full-term gypsy and non-gypsy newborns from Slovak Republic.

BACKGROUND: Early detection of cranial growth defects in childhood is extremely important for subsequent growth, development of head and could be a screening aid for early detection of growth deviations. METHODS: Seven head dimensions and two indexes of 90 Gypsy and 99 non-Gypsy newborns from Slovakia were examined to asses the potential differences between the groups. RESULTS: Gypsy newborns had significantly lower head circumference, lower head length, lower width of head basis and facial width compared to non-Gypsy newborns. Gypsy newborns have shown significantly higher value of the index cephalicus while in non-Gypsy newborns mesocephalic values have been detected. Moreover, Gypsy newborns had significantly higher cranium as compared to non-Gypsy. CONCLUSIONS: Gypsy subpopulation has a different head morphology compared to the majority of the population. Knowledge about the different head morphology between these ethnic groups could give us clues about the genetic influences determining head morphology in the prenatal development and therefore might be a helpful diagnostic tool in neonatology (Tab. 1, Ref. 14).

14-3-3 CSF levels in sporadic Creutzfeldt-Jakob disease differ across molecular subtypes.

BACKGROUND: The 14-3-3 protein is a physiological cellular protein expressed in various tissues, and its release to CSF reflects extensive neuronal damage as in Creutzfeldt-Jakob disease (CJD), but also in other neurological diseases. 14-3-3 protein in CSF in the proper clinical context is a reliable diagnostic tool for sporadic CJD. However, the sensitivity varies across molecular CJD subtypes. OBJECTIVE: We determined the level of the 14-3-3 protein in CSF from 70 sporadic CJD patients with distinct molecular subtypes using an improved enzyme-linked immunosorbent assay (ELISA) protocol technique. RESULTS: The 14-3-3 levels varied markedly across various molecular subtypes. The most elevated levels of 14-3-3 protein were observed in the frequently occurring and classical subtypes, whereas the levels were significantly lower in the subtypes with long disease duration and atypical clinical presentation. PRNP codon 129 genotype, PrP(sc) isotype, disease stage and clinical subtype influenced the 14-3-3 level and the test sensitivity. CONCLUSIONS: The 14-3-3 protein levels differ across molecular subtypes and might be used for their early pre-mortem identification when the codon 129 genotype is known, especially for the less common molecular subtypes such as MV2 and MM2.