Tento projekt je zaměřen na zkoumání klinických, neuroradiologických a biochemických biomarkerů Parkinsonovy nemoci (PN), parkinsonských syndromů a Wilsonovy nemoci (WN). Všechni pacienti budou vyšetřeni před nasazením terapie pomocí klinických škál, neuropsychologické baterie, zobrazení mozku magnetickou rezonancí (MRI mozku), transkraniální sonografie (TCS) a analýzy krve/mozkomíšního moku. Prediktivní hodnota těchto biomarkerů bude zhodnocena vzhledem ke klinickému stavu pacientů 9 měsíců, 3 roky a 5 let po zahájení léčby. Dále bude stanovena senzitivita a specificita MRI, TCS a biochemických biomarkerů v diferenciální diagnostice PN. U dlouhodobě léčených pacientů s WN budeme zkoumat vztah mezi typem ATP7B mutace, enzymatickou aktivitou ceruloplasminu, stupněm jaterní léze a způsobem léčby a tíží reziduálních neurologických příznaků a neuroradiologickými nálezy. Pomocí MRI-histopatologické korelační studie plánujeme potvrdit validitu MRI ve stanovení koncentrace kovů v bazálních gangliích a kvantifikaci stupně neurodegenerace v substantia nigra pars compacta.; This project is aimed at examining clinical, neuroradiological and biochemical biomarkers of Parkinson’s disease (PD), other parkinsonian syndromes and Wilson’s disease (WD). All patients will be examined using clinical scales, cognitive battery, brain magnetic resonance imaging (MRI), transcranial sonography (TCS) and blood/cerebrospinal fluid (CSF) analysis before treatment initiation. Predicitive values of these biomarkers will be assesed with regards to clinical outcome at 9 months, 3 years and 5 years after treatment initiation. We will also examine the sensitivity/specificity of MRI, TCS and blood/CSF biomarkers in the differential diagnosis of PD. In chronically treated WD patients we will examine whether the type of ATP7B mutation, ceruloplasmin activity, hepatic dysfunction or mode of treatment will predict clinical outcome and neuroradiological parameters. Post-mortem MRI-histopathology correlation study will be performed to validate MRI data in measuring metal concentration in basal ganglia as well as in quantification of neuronal loss in substantia nigra pars compacta.

• MeSH
• biologické markery MeSH
• hepatolentikulární degenerace diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• neurodegenerativní nemoci diagnostické zobrazování   MeSH
• parkinsonské poruchy diagnostické zobrazování   MeSH
• progrese nemoci MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.

• MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• hepatolentikulární degenerace * patologie   diagnostické zobrazování   MeSH
• játra patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: In Wilson's disease (WD), demyelination, rarefaction, gliosis, and iron accumulation in the deep gray matter cause opposing effects on T2 -weighted MR signal. However, the degree and interplay of these changes in chronically treated WD patients has not been quantitatively studied. PURPOSE: To compare differences in brain multiparametric mapping between controls and chronically treated WD patients with neurological (neuro-WD) and hepatic (hep-WD) forms to infer the nature of residual WD neuropathology. STUDY TYPE: Cross-sectional. POPULATION/SUBJECTS: Thirty-eight WD patients (28 neuro-WD, 10 hep-WD); 26 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0T: susceptibility, T2 *, T2 , T1 relaxometry; 1.5T: T2 , T1 relaxometry. ASSESSMENT: The following 3D regions of interest (ROIs) were manually segmented: globus pallidus, putamen, caudate nucleus, and thalamus. Mean bulk magnetic susceptibility, T2 *, T2 , and T1 relaxation times were calculated for each ROI. STATISTICAL TESTS: The effect of group (neuro-WD, hep-WD, controls) and age was assessed using a generalized least squares model with different variance for each ROI and quantitative parameter. A general linear hypothesis test with Tukey adjustment was used for post-hoc between-group analysis; P < 0.05 was considered significant. RESULTS: Susceptibility values were higher in all ROIs in neuro-WD compared to controls and hep-WD (P < 0.001). In basal ganglia, lower T2 and T2 * were found in neuro-WD compared to controls (P < 0.01) and hep-WD (P < 0.05) at 3.0T. Much smaller intergroup differences for T2 in basal ganglia were observed at 1.5T compared to 3.0T. In the thalamus, increased susceptibility in neuro-WD was accompanied by increased T1 at both field strengths (P < 0.001 to both groups), and an increased T2 at 1.5T only (P < 0.001 to both groups). DATA CONCLUSION: We observed significant residual brain MRI abnormalities in neuro-WD but not in hep-WD patients on chronic anticopper treatment. Patterns of changes were suggestive of iron accumulation in the basal ganglia and demyelination in the thalamus; 3.0T was more sensitive for detection of the former and 1.5T of the latter abnormality. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1829-1835.

• MeSH
• hepatolentikulární degenerace * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek diagnostické zobrazování   MeSH
• průřezové studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia. OBJECTIVES: The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using 1 H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers. METHODS: We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single-volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN. RESULTS AND CONCLUSION: In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. © 2019 International Parkinson and Movement Disorder Society.

• MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• membránové proteiny genetika   MeSH
• mitochondriální membrány metabolismus   MeSH
• mitochondriální proteiny genetika   MeSH
• mitochondrie metabolismus   MeSH
• mozek metabolismus   patologie   MeSH
• mutace genetika   MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Idiopathic rapid eye movement sleep behaviour (iRBD) is considered as a risk factor for Parkinson's disease (PD) development. Evaluation of repetitive movements with finger tapping, which serves as a principal task to measure the extent of bradykinesia in PD, may undercover potential PD patients. The aim of this study was to explore whether finger tapping abnormalities, evaluated with a 3D motion capture system, are already present in RBD patients. METHODS: Finger tapping data was acquired using a contactless 3D motion capture system from 40 RBD subjects and compared to 25 de-novo PD patients and 25 healthy controls. Objective assessment of amplitude decrement, maximum opening velocity and their combination representing finger tapping decrement was performed in the sequence of the first ten tapping movements. The association between instrumental finger tapping data and semi-quantitative clinical evaluation was analyzed. RESULTS: While significant differences between PD and controls were found for all investigated finger tapping measures (p < 0.002), RBD differed from controls in finger tapping amplitude (p = 0.004) and velocity (p = 0.007) decrement but not in maximal opening velocity. A significant relationship between the motor score from the Movement Disorders Society - Unified Parkinson's Disease Rating Scale and finger tapping decrement was shown for both patient groups, ie RBD (r = 0.36, p = 0.02) and PD (r = 0.60, p = 0.002). CONCLUSIONS: In our group of RBD patients we demonstrated amplitude decrement of repetitive movements, which may correspond with prodromal bradykinesia. Our findings suggest instrumental analysis of finger tapping abnormalities as a potential novel clinical marker reflecting subclinical motor disturbances in RBD.

• MeSH
• biologické markery MeSH
• hypokineze diagnóza   MeSH
• lidé MeSH
• Parkinsonova nemoc * komplikace   diagnóza   MeSH
• parkinsonské poruchy * MeSH
• pohyb MeSH
• porucha chování v REM spánku * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are often presenting with overlapping symptoms. The aim of this study was to determine whether and how NMO and MS differ regarding cerebral iron deposits in deep gray matter (DGM) and the correlation between iron deposition and clinical severity as well as to regional atrophy of the DGM. Methods: We analyzed 20 patients with NMO, 40 patients with a relapsing-remitting (RR) form of MS, and 20 healthy controls with 1.5T MRI. Quantitative susceptibility mapping (QSM) was performed to estimate iron concentration in the DGM. Results: Patients with NMO have higher magnetic susceptibility values in the substantia nigra compared to healthy controls. RRMS patients have lower magnetic susceptibility values in the thalamus compared to healthy controls and NMO patients. Atrophy of the thalamus, pulvinar, and putamen is significant both in RRMS compared to NMO patients and healthy controls. A correlation was found between the disability score (EDSS) and magnetic susceptibility in the putamen in RRMS. Conclusions: This study confirms that a disturbed cerebral iron homeostasis in patients with NMO occurs in different structures than in patients with RRMS. Increased magnetic susceptibility in substantia nigra in NMO and decreased magnetic susceptibility within the thalamus in RRMS were the only significant differences in the study sample. We could confirm that iron concentration in the thalami is decreased in RRMS compared to that in the HC group. Positive association was found between putaminal iron and EDSS in RRMS.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek * diagnostické zobrazování   metabolismus   patologie   MeSH
• neuromyelitis optica * metabolismus   patologie   MeSH
• průřezové studie MeSH
• relabující-remitující roztroušená skleróza * metabolismus   patologie   MeSH
• šedá hmota chemie   MeSH
• železo analýza   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: MRI is a sensitive method for the assessment of brain abnormalities in Wilson disease, that is, T2 hyperintensities, T2 hypointensities, and atrophy, but a validated scoring system for the classification of radiological severity is lacking. The objective of this study was to develop and validate a brain MRI visual rating scale for Wilson disease. METHODS: The proposed Wilson disease brain MRI severity scale consists of acute toxicity and chronic damage subscores from predefined structures. The former, calculated by summing scores of T2 hyperintensities (excluding cavitation), is likely to be partially reversible with treatment. The latter, representing the sum of scores of T2 hypointensities and brain atrophy, reflects pathology that is not readily reversible. Validation was performed on MRI scans acquired using 1.5T system from 39 Wilson disease patients examined at baseline and after 24 months on anticopper treatment. Intraclass correlation coefficients of 5 ratings from 3 raters were calculated. Temporal evolution of the MRI severity score and its association with clinical severity, assessed using the Unified Wilson Disease Rating Scale part III, was calculated. RESULTS: Intrarater and interrater agreement were good (r > 0.93; P < 0.001; and r > 0.74; P < 0.001, respectively). In neurologic Wilson disease patients, the total MRI severity score improved over 2 years (P = 0.032), mainly because of reduced acute toxicity (P = 0.0015), whereas the chronic damage score deteriorated (P = 0.035). Unified Wilson Disease Rating Scale part III score was positively associated with chronic damage and total score at baseline (P = 0.005 and P = 0.003, respectively) and in month 24 (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: The Wilson disease brain MRI severity scale is a simple, reliable, and valid instrument that allows semiquantitative assessment of radiological Wilson disease severity. © 2020 International Parkinson and Movement Disorder Society.

• MeSH
• hepatolentikulární degenerace * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• nemoci mozku * MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Transcranial sonography (TCS) can reveal pathology in brain structures including insula. This study compared insula echogenicity among 22 patients with Wilson's disease (WD), 21 patients with early-onset Parkinson's disease (EO-PD) and 24 healthy patients. Echogenicity of predefined brain structures (insula, lentiform nucleus, caudate nucleus, substantia nigra and raphe nuclei) was evaluated using digitized analysis of TCS fusion imaging with magnetic resonance. Cortical, subcortical and cerebellar atrophy and ventricle diameters were determined from magnetic resonance images. The mean echogenicity index of insula did not differ between males and females (p = 0.92), but the echogenicity of insula was higher in patients with WD than in patients with EO-PD and healthy patients (p < 0.05). The substantia nigra echogenicity was higher in patients with EO-PD, and lentiform nucleus echogenicity was higher in patients with WD (p < 0.05). The echogenicity of insula correlated with lentiform nucleus echogenicity (r = 0.75) but not with age (r = -0.14), disease duration (r = -0.36), symptom severity (r = 0.28), cortical (r = 0.11) nor subcortical (r = 0.05) atrophy.

• MeSH
• dospělí MeSH
• hepatolentikulární degenerace diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   MeSH
• mozková kůra diagnostické zobrazování   MeSH
• multimodální zobrazování MeSH
• Parkinsonova nemoc diagnostické zobrazování   MeSH
• ultrasonografie dopplerovská transkraniální * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUNDS: This study aims to characterize eye movement abnormalities in Wilson disease and examine their association with the degree of brainstem atrophy. METHODS: Twenty patients (10 males, mean age 46.8, SD 8.9 years) with genetically confirmed neurological WD on stable anti-copper treatment and 20 age- and sex-matched healthy subjects were examined. Eye movements, including prosaccade and antisaccade tasks, were evaluated using infrared videooculography. MRI was performed using 1.5 T system, and T2-weighted images were used for the measurement of midbrain and pontine area on mid-sagittal slices. Clinical severity was assessed using the Unified Wilson's Disease Rating Scale (UWDRS). RESULTS: Compared to healthy controls, WD patients showed prolonged latencies of horizontal prosaccades and hypometry of both horizontal (p = 0.04) and vertical (p = 0.0046) prosaccades. In the antisaccade task, WD patients showed prolonged latency of both horizontal (p = 0.04) and vertical antisaccades (p = 0.047) and increased error rate of vertical antisaccades (p = 0.04). There is a significant association between midbrain area and horizontal latencies (r = -0.53; p = 0.02) and vertical maximum speed in prosaccades (r = 0.47; p = 0.04). The pons area inversely correlated with horizontal prosaccade and antisaccade latencies (p = 0.007). CONCLUSIONS: We showed impairments of ocular saccades such as prolonged latencies, hypometry, and increased error rate in antisaccades. The strong association between prolonged latencies of prosaccades and the brainstem atrophy suggests that VOG might serve as a sensitive electrophysiological marker of brainstem dysfunction in WD.

• MeSH
• atrofie MeSH
• dospělí MeSH
• hepatolentikulární degenerace komplikace   patologie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• měření pohybů očí MeSH
• mozkový kmen diagnostické zobrazování   patologie   patofyziologie   MeSH
• poruchy hybnosti oka komplikace   patologie   patofyziologie   MeSH
• sakadické oční pohyby fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Neuromelanin (NM) is a black pigment located in the brain in substantia nigra pars compacta (SN) and locus coeruleus. Its loss is directly connected to the loss of nerve cells in this part of the brain, which plays a role in Parkinson's Disease. Magnetic resonance imaging (MRI) is an ideal tool to monitor the amount of NM in the brain in vivo. The aim of the study was the development of tools and methodology for the quantification of NM in a special neuromelanin-sensitive MRI images. The first approach was done by creating regions of interest, corresponding to the anatomical position of SN based on an anatomical atlas and determining signal intensity threshold. By linking the anatomical and signal intensity information, we were able to segment the SN. As a second approach, the neural network U-Net was used for the segmentation of SN. Subsequently, the volume characterizing the amount of NM in the SN region was calculated. To verify the method and the assumptions, data available from various patient groups were correlated. The main benefit of this approach is the observer-independency of quantification and facilitation of the image processing process and subsequent quantification compared to the manual approach. It is ideal for automatic processing many image sets in one batch.

• MeSH
• deep learning * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• melaniny analýza   MeSH
• počítačové zpracování obrazu MeSH
• prodromální symptomy MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• substantia nigra diagnostické zobrazování   MeSH
• synukleinopatie diagnostické zobrazování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH