INTRODUCTION: Corticobasal syndrome (CBS) is a specific clinical manifestation shared by multiple pathologies. The exact mechanism of this phenomenon remains unclear. Differential diagnosis of CBS in everyday clinical practice is challenging, as this syndrome can overlap with other entities, especially progressive supranuclear palsy Richardson-Steele phenotype (PSP-RS). Several papers have suggested a possible role of vascular pathology as a linking factor in the pathogenesis of CBS based on different neuropathologies. This paper analyses differences in the occurrence of the most common vascular risk factors such as hypertension and lipid profile with respect to dietary habits among patients who fulfill the diagnostic criteria for probable/possible CBS and PSP-RS. MATERIAL AND METHODS: Seventy (70) patients in total were included in the study. Exclusion criteria comprised hydrocephalus, stroke in the past, the presence of marked vascular changes in white matter defined as the presence of vascular change ≥ 1 mm in 3T MRI, medical history of hyperlipidemia or the use of drugs that could impact upon lipid metabolism before the initiation of the neurodegenerative disease, and neoplastic focuses in the central nervous system. Patients with diabetes, or with BMI exceeding 18-25, or who were smokers, or who were affected by chronic stress were also excluded. Data was analysed statistically using the Shapiro-Wilk test, the U Mann-Whitney test for group comparison, and a Bonferroni correction to control the false discovery rate (FDR). RESULTS: Our obtained results indicated a statistically significantly higher level of total cholesterol in the CBS group (p = 0.0039) without a correlation with dietary habits. CONCLUSIONS AND CLINICAL IMPLICATIONS: The results obtained in our study may suggest a possible role of vascular pathology in CBS development. This issue requires further research.

• Klíčová slova
• CBS phenotype, corticobasal syndrome, hyperlipidemia, neurodegeneration, risk factor,
• MeSH
• hyperlipidemie * MeSH
• kortikobazální degenerace * MeSH
• lidé MeSH
• neurodegenerativní nemoci * etiologie   diagnóza   patologie   MeSH
• pilotní projekty MeSH
• progresivní supranukleární obrna * diagnóza   patologie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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).

• Klíčová slova
• 5-Hydroxyindoleacetic acid, Atypical parkinsonian syndromes, Cerebrospinal fluid, Parkinson’s disease,
• MeSH
• diferenciální diagnóza MeSH
• kyselina hydroxyindoloctová MeSH
• lidé MeSH
• multisystémová atrofie * diagnóza   MeSH
• Parkinsonova nemoc * diagnóza   MeSH
• parkinsonské poruchy * metabolismus   MeSH
• progresivní supranukleární obrna * MeSH
• tauopatie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyselina hydroxyindoloctová MeSH

OBJECTIVE: To investigate whether tau phosphorylated at Thr217 (p-tau T217) assay in CSF can distinguish patients with Alzheimer disease (AD) from patients with other dementias and healthy controls. METHODS: We developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from 3 cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy participants (n = 44). RESULTS: The p-tau T217 assay (cutoff 242 pg/mL) identified patients with AD with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, and 88% specificity, compared favorably with p-tau T181 ELISA (52 pg/mL), showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, and 97% sensitivity. The assay distinguished patients with AD from age-matched healthy controls (cutoff 163 pg/mL, 98% sensitivity, 93% specificity), similarly to p-tau T181 ELISA (cutoff 60 pg/mL, 96% sensitivity, 86% specificity). In patients with AD, we found a strong correlation between p-tau T217 and p-tau T181, total tau and β-amyloid 40, but not β-amyloid 42. CONCLUSIONS: This study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggest that the new p-tau T217 assay has potential as an AD diagnostic test in clinical evaluation. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes patients with AD from patients with other dementias and healthy controls.

• MeSH
• Alzheimerova nemoc mozkomíšní mok   diagnóza   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• diferenciální diagnóza MeSH
• frontotemporální demence mozkomíšní mok   diagnóza   MeSH
• imunoanalýza metody   normy   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurodegenerativní nemoci mozkomíšní mok   diagnóza   MeSH
• peptidové fragmenty mozkomíšní mok   MeSH
• prediktivní hodnota testů MeSH
• primární progresivní afázie mozkomíšní mok   diagnóza   MeSH
• progresivní supranukleární obrna mozkomíšní mok   diagnóza   MeSH
• proteiny tau mozkomíšní mok   MeSH
• reprodukovatelnost výsledků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• tauopatie mozkomíšní mok   diagnóza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amyloid beta-protein (1-40) MeSH Prohlížeč
• amyloid beta-protein (1-42) MeSH Prohlížeč
• amyloidní beta-protein MeSH
• MAPT protein, human MeSH Prohlížeč
• peptidové fragmenty MeSH
• proteiny tau MeSH

Clear speech refers to intentionally modifying conversational speech to maximise intelligibility. This study aimed to compare the speech behaviour of patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and Parkinson's disease (PD) under conversational and clear speech conditions to gain greater pathophysiological insight. A total of 68 participants including 17 PD, 17 MSA, 17 PSP and 17 healthy controls (HC) performed two readings of the same standardized passage. During the first reading, participants were instructed to read the text in an ordinary way, while during the second reading to read the text as clearly as possible. Acoustic analyses were based upon measurements of mean loudness, loudness variability, pitch variability, vowel articulation, articulation rate and speech severity. During clear speech production, PD patients were able to achieve improvements mainly in loudness (p < 0.05) and pitch variability (p < 0.001), leading to a reduction in overall speech severity (p < 0.001), whereas PSP and MSA patients were able to modulate only articulation rate (p < 0.05). Contrary to HC and PD groups, which slowed or maintained articulation rate, PSP and MSA groups employed a markedly faster articulation rate under the clear speech condition indicating an opposing approach to speech adaptation. Patients with atypical Parkinsonism showed a different strategy to intentionally improve their speech performance following a simple request to produce speech more clearly compared to PD, suggesting important therapeutic implications for speech rehabilitation management.

• Klíčová slova
• Acoustic analysis, Atypical parkinsonian syndromes, Clear speech, Dysarthria, Parkinson's disease, Speech impairment,
• MeSH
• dysartrie etiologie   MeSH
• lidé MeSH
• multisystémová atrofie * komplikace   MeSH
• Parkinsonova nemoc * komplikace   MeSH
• progresivní supranukleární obrna * komplikace   MeSH
• řeč MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: We aimed to produce a detailed neuropathological analysis of pyramidal motor system pathology and provide its clinical pathological correlation in cases with definite progressive supranuclear palsy (PSP). METHODS: Pyramidal motor system pathologies were analyzed in 18 cases with neuropathologically confirmed PSP. Based on a retrospective clinical analysis, cases were subtyped according to Movement Disorder Society criteria for clinical diagnosis of PSP as probable, possible or suggestive of PSP with Richardson's syndrome (n = 10), PSP with predominant corticobasal syndrome (n = 3), PSP with predominant parkinsonism (n = 3), PSP with predominant speech/language disorder (n = 1), and PSP with progressive gait freezing (n = 1). Clinical manifestations of motor neuron involvement (pseudobulbar or bulbar signs and spasticity) were retrospectively assessed semiquantitatively. Neuropathologically, hyperphosphorylated tau-related pyramidal motor system neuronal, neuritic, and glial pathology using anti-tau AT8 clone immunohistochemistry, was also evaluated. RESULTS: Clinical manifestations of pyramidal motor system involvement were found in patients with different PSP subtypes. A statistically significant higher load of tau pathology was found in the pyramidal system in PSP-Richardson's syndrome compared to other PSP subtypes (p = 0.016); however, there was no significant correlation between pyramidal system tau pathology and related motor clinical symptoms. CONCLUSIONS: Tau pathology in the spinal cord and pyramidal motor system structures is very common in progressive supranuclear palsy and may neuropathologically supplement the distinction between classic Richardson's syndrome from other progressive supranuclear palsy subtypes.

• Klíčová slova
• Atypical parkinsonism, Progressive supranuclear palsy, Spinal cord, Tauopathies,
• MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozková kůra patologie   MeSH
• parkinsonské poruchy diagnóza   patologie   MeSH
• pohybové poruchy diagnóza   patologie   MeSH
• progresivní supranukleární obrna diagnóza   patologie   MeSH
• proteiny tau metabolismus   MeSH
• pyramidové dráhy patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• MAPT protein, human MeSH Prohlížeč
• proteiny tau MeSH

• MeSH
• F-box proteiny genetika   MeSH
• fenotyp MeSH
• Lewyho tělíska patologie   MeSH
• lidé MeSH
• parkinsonské poruchy diagnóza   genetika   patologie   MeSH
• progresivní supranukleární obrna diagnóza   genetika   patologie   MeSH
• senioři nad 80 let MeSH
• vezikulární transportní proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• F-box proteiny MeSH
• FBXO7 protein, human MeSH Prohlížeč
• vezikulární transportní proteiny MeSH
• VPS35 protein, human MeSH Prohlížeč

Disturbances of the gamma-aminobutyric-acid (GABA) system have been suspected of contributing to the pathophysiology of progressive supranuclear palsy (PSP). The ability to rapidly resolve competitive action decisions, such as shifting the gaze to one particular stimulus rather than another, can be predicted by the concentration of GABA in the region of the frontal cortex relevant to eye movements. For this reason, our study measured GABA levels in seven PSP patients and eight healthy controls, using proton magnetic resonance spectroscopy, and assessed the relationship of these measurements to the remote distractor effect (RDE), an eye-movement paradigm investigating competitive action decisions. No significant differences were found in either frontal-eye-field GABA levels or RDE between PSP patients and controls.

• Klíčová slova
• Distraction, Eye movements, GABA, Magnetic resonance, Progressive supranuclear palsy, Spectroscopy,
• MeSH
• GABA metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• magnetická rezonanční tomografie MeSH
• okulomotorické svaly diagnostické zobrazování   patofyziologie   MeSH
• pilotní projekty MeSH
• pohyby očí MeSH
• prefrontální mozková kůra diagnostické zobrazování   metabolismus   MeSH
• progresivní supranukleární obrna diagnostické zobrazování   metabolismus   psychologie   MeSH
• sakadické oční pohyby MeSH
• senioři MeSH
• světelná stimulace MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• zraková pole MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• GABA MeSH

Frontotemporal lobar degeneration with transactive response DNA-binding protein 43 (FTLD-TDP) and progressive supranuclear palsy (PSP) are distinct neurodegenerations with different clinical presentations. We report two cases with FTLD-TDP and PSP in comorbidity: a patient with amnestic dementia developing frontal lobe dementia, Parkinsonism and supranuclear gaze palsy and a patient with cerebellar ataxia and nystagmus developing akinesia, rigidity, and subcortical dementia. Neuropathological examination revealed neuronal and glial tau pathology together with ubiquitin, and phospho-TDP-43-immunoreactivities in the hippocampus, striatum, mesencephalon, and frontal and temporal cortices. Clinical and neuropathological correlations in atypical neurodegenerations are crucial to describe new entities of overlapping syndromes.

• Klíčová slova
• Progressive supranuclear palsy, TDP-43 inclusions, dementia, frontotemporal lobar degeneration, tauopathy,
• MeSH
• DNA vazebné proteiny metabolismus   MeSH
• frontotemporální demence komplikace   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   metabolismus   MeSH
• neuropsychologické testy MeSH
• progresivní supranukleární obrna komplikace   diagnostické zobrazování   patologie   MeSH
• ubikvitin metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• TARDBP protein, human MeSH Prohlížeč
• ubikvitin MeSH

Distinct speech characteristics that may aid in differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) remain tremendously under-explored. Here, the patterns and degree of consonant articulation deficits across voiced and voiceless stop plosives in 16 PD, 16 PSP, 16 MSA and 16 healthy control speakers were evaluated using acoustic and perceptual methods. Imprecise consonant articulation was observed across all Parkinsonian groups. Voice onset time of voiceless plosives was more prolonged in both PSP and MSA compared to PD, presumably due to greater severity of dysarthria and slower articulation rate. Voice onset time of voiced plosives was significantly shorter only in MSA, likely as a consequence of damage to cerebellar structures. In agreement with the reduction of pre-voicing, MSA manifested increased number of voiced plosives misclassified as voiceless at perceptual evaluation. Timing of articulatory movements may provide important clues about the pathophysiology of underlying disease.

• Klíčová slova
• Acoustic analysis *, Atypical Parkinsonian syndromes *, Dysarthria *, Parkinson’s disease *, Perceptual assessment *, Speech disorders *, Voice onset time *,
• MeSH
• dysartrie patofyziologie   MeSH
• hlas MeSH
• lidé středního věku MeSH
• lidé MeSH
• lingvistika * MeSH
• mozeček patofyziologie   MeSH
• multisystémová atrofie patofyziologie   MeSH
• Parkinsonova nemoc patofyziologie   MeSH
• progresivní supranukleární obrna patofyziologie   MeSH
• řeč * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A higher prevalence of parkinsonism was recently identified in southeastern Moravia (Czech Republic). Further research confirmed 3 large pedigrees with familial autosomal-dominant parkinsonism spanning 5 generations. METHODS: This case report concerns a patient belonging to one of these 3 pedigrees, in whom motor and oculomotor symptoms were accompanied by frontal-type dementia, who finally developed a clinical phenotype of progressive supranuclear palsy. Molecular genetic examinations were performed due to the positive family history. RESULTS: No previously described causal mutation was found. After filtering against common variants (minor allele frequency (MAF) < 0.01), 2 noncoding and 1 synonymous rare mutation potentially associable with parkinsonism were identified: GIGYF2-GRB10 Interacting GYF Protein 2, PARK11 (c.*2030G > A, rs115669549); VPS35 gene-vacuolar protein sorting 35, PARK17 (c.102 + 33G > A, rs192115886); and FBXO7-F-box only protein 7 gene, PARK15 (c.540A > G, rs41311141). CONCLUSION: As to the changes in the FBXO7 and VPS35 genes (despite phylogenetic conservation in primates), probably neither the FBXO7 nor the VPS35 variants will be direct causal mutations. Both described variants, and possibly the influence of their combination, could increase the risk of the disease.

• MeSH
• F-box proteiny genetika   MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   MeSH
• mutace MeSH
• parkinsonské poruchy * komplikace   diagnóza   genetika   MeSH
• progresivní supranukleární obrna * diagnóza   etiologie   patofyziologie   MeSH
• rodokmen MeSH
• senioři nad 80 let MeSH
• vezikulární transportní proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• F-box proteiny MeSH
• FBXO7 protein, human MeSH Prohlížeč
• vezikulární transportní proteiny MeSH
• VPS35 protein, human MeSH Prohlížeč