Striosomes and matrix are two compartments that comprise the striatum, each having its own distinct immunohistochemical properties, function, and connectivity. It is currently not clear whether prodromal or early manifest Parkinson's disease (PD) is associated with any striatal matrix or striosomal abnormality. Recently, a method of striatal parcellation using probabilistic tractography has been described and validated, using the distinct connectivity of these two compartments to identify voxels with striosome- and matrix-like connectivity. The goal of this study was to use this approach in tandem with DAT-SPECT, a method used to quantify the level of nigrostriatal denervation, to analyze the striatum in populations of de novo diagnosed, treatment-naïve patients with PD, isolated REM behavioral disorder (iRBD) patients, and healthy controls. We discovered a shift in striatal connectivity, which showed correlation with nigrostriatal denervation. Patients with PD exhibited a significantly higher matrix-like volume and associated connectivity than healthy controls and higher matrix-associated connectivity than iRBD patients. In contrast, the side with less pronounced nigrostriatal denervation in PD and iRBD patients showed a decrease in striosome-like volume and associated connectivity indices. These findings could point to a compensatory neuroplastic mechanism in the context of nigrostriatal denervation and open a new avenue in the investigation of the pathophysiology of Parkinson's disease.

• Publikační typ
• časopisecké články MeSH

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

• Klíčová slova
• Parkinson disease, QSM, REM sleep behavioral disorder, iron, whole brain,
• MeSH
• lidé MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• Parkinsonova nemoc * komplikace   MeSH
• porucha chování v REM spánku * diagnostické zobrazování   MeSH
• substantia nigra diagnostické zobrazování   patologie   MeSH
• synukleinopatie * komplikace   patologie   MeSH
• železo MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• železo MeSH

REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.

• Publikační typ
• časopisecké články MeSH

Oxidative stress supposedly plays a role in the pathogenesis of Parkinson's disease (PD). Uric acid (UA), a powerful antioxidant, is lowered in PD while allantoin, the oxidation product of UA and known biomarker of oxidative stress, was not systematically studied in PD. We aim to compare serum and cerebrospinal fluid (CSF) levels of UA, allantoin, and allantoin/UA ratio in de novo PD patients and controls, and evaluate their associations with clinical severity and the degree of substantia nigra degeneration in PD. We measured serum and CSF levels of UA, allantoin, and allantoin/UA ratio in 86 PD patients (33 females, mean age 57.9 (SD 12.6) years; CSF levels were assessed in 51 patients) and in 40 controls (19 females, 56.7 (14.1) years). PD patients were examined using Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson Disease-Autonomic (SCOPA-AUT), the University of Pennsylvania Smell Identification Test (UPSIT), one-night video-polysomnography, and dopamine transporter single-photon emission computed tomography (DAT-SPECT). Serum allantoin and allantoin/UA ratio were significantly increased in the PD group compared to controls (p < 0.001 and p = 0.002, respectively). Allantoin/UA ratios in serum and CSF were positively associated with the SCOPA-AUT score (p = 0.005 and 0.031, respectively) and RBD presence (p = 0.044 and 0.028, respectively). In conclusion, serum allantoin and allantoin/UA ratio are elevated in patients with de novo PD. Allantoin/UA ratio in serum and CSF is associated with autonomic dysfunction and RBD presence, indicating that higher systemic oxidative stress occurs in PD patients with more diffuse neurodegenerative changes.

• Publikační typ
• časopisecké články MeSH

Imprecise vowels represent a common deficit associated with hypokinetic dysarthria resulting from a reduced articulatory range of motion in Parkinson's disease (PD). It is not yet unknown whether the vowel articulation impairment is already evident in the prodromal stages of synucleinopathy. We aimed to assess whether vowel articulation abnormalities are present in isolated rapid eye movement sleep behaviour disorder (iRBD) and early-stage PD. A total of 180 male participants, including 60 iRBD, 60 de-novo PD and 60 age-matched healthy controls performed reading of a standardized passage. The first and second formant frequencies of the corner vowels /a/, /i/, and /u/ extracted from predefined words, were utilized to construct articulatory-acoustic measures of Vowel Space Area (VSA) and Vowel Articulation Index (VAI). Compared to controls, VSA was smaller in both iRBD (p = 0.01) and PD (p = 0.001) while VAI was lower only in PD (p = 0.002). iRBD subgroup with abnormal olfactory function had smaller VSA compared to iRBD subgroup with preserved olfactory function (p = 0.02). In PD patients, the extent of bradykinesia and rigidity correlated with VSA (r = -0.33, p = 0.01), while no correlation between axial gait symptoms or tremor and vowel articulation was detected. Vowel articulation impairment represents an early prodromal symptom in the disease process of synucleinopathy. Acoustic assessment of vowel articulation may provide a surrogate marker of synucleinopathy in scenarios where a single robust feature to monitor the dysarthria progression is needed.

• Publikační typ
• časopisecké články MeSH

Even though hypomimia is a hallmark of Parkinson's disease (PD), objective and easily interpretable tools to capture the disruption of spontaneous and deliberate facial movements are lacking. This study aimed to develop a fully automatic video-based hypomimia assessment tool and estimate the prevalence and characteristics of hypomimia in de-novo PD patients with relation to clinical and dopamine transporter imaging markers. For this cross-sectional study, video samples of spontaneous speech were collected from 91 de-novo, drug-naïve PD participants and 75 age and sex-matched healthy controls. Twelve facial markers covering areas of forehead, nose root, eyebrows, eyes, lateral canthal areas, cheeks, mouth, and jaw were used to quantitatively describe facial dynamics. All patients were evaluated using Movement Disorder Society-Unified PD Rating Scale and Dopamine Transporter Single-Photon Emission Computed Tomography. Newly developed automated facial analysis tool enabled high-accuracy discrimination between PD and controls with area under the curve of 0.87. The prevalence of hypomimia in de-novo PD cohort was 57%, mainly associated with dysfunction of mouth and jaw movements, and decreased variability in forehead and nose root wrinkles (p < 0.001). Strongest correlation was found between reduction of lower lip movements and nigro-putaminal dopaminergic loss (r = 0.32, p = 0.002) as well as limb bradykinesia/rigidity scores (r = -0.37 p < 0.001). Hypomimia represents a frequent, early marker of motor impairment in PD that can be robustly assessed via automatic video-based analysis. Our results support an association between striatal dopaminergic deficit and hypomimia in PD.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Sialic acid-protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration. OBJECTIVES: We evaluate the differences in serum transferrin sialylation in prodromal and early-stage Parkinson's disease (PD), its relation to substantia nigra degeneration, and the risk of phenoconversion to manifest disease. METHODS: Sixty treatment-naive PD patients; 72 polysomnography-confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, that is, patients with prodromal synucleinopathy; and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month were included. The proportion of serum low-sialylated, carbohydrate-deficient transferrin (CDT) isoforms was assessed using high-performance liquid chromatography, and the values were adjusted for alcohol intake (CDTadj ). Dopamine transporter single-photon emission computed tomography (DaT-SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT-SPECT and CDTadj was evaluated using Cox regression adjusted for age and sex. RESULTS: Median CDTadj was lower in PD (1.1 [interquartile range: 1.0-1.3]%) compared to controls (1.2 [1.1-1.6]%) (P = 0.001). In iRBD, median CDTadj was lower in subjects with abnormal (1.1 [0.9-1.3]%) than normal (1.3 [1.2-1.6]%) DaT-SPECT (P = 0.005). After a median 44-month follow-up, 20% of iRBD patients progressed to a manifest disease. Although iRBD converters and nonconverters did not significantly differ in CDTadj levels (P = 0.189), low CDTadj increased the risk of phenoconversion with hazard ratio 3.2 (P = 0.045) but did not refine the phenoconversion risk associated with abnormal DaT-SPECT yielding hazard ratio 15.8 (P < 0.001). CONCLUSIONS: Decreased serum CDTadj is associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDTadj are more likely to phenoconvert to manifest disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

• Klíčová slova
• Parkinson's disease, phenoconversion, rapid eye movement sleep behavior disorder, sialylation, transferrin,
• MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• lidé MeSH
• Parkinsonova nemoc * komplikace   diagnostické zobrazování   MeSH
• porucha chování v REM spánku * komplikace   diagnostické zobrazování   MeSH
• synukleinopatie * MeSH
• transferin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• transferin MeSH

Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

• MeSH
• alfa-synuklein MeSH
• biologické markery * MeSH
• lidé MeSH
• porucha chování v REM spánku komplikace   diagnóza   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• synukleinopatie diagnóza   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• alfa-synuklein MeSH
• biologické markery * MeSH