OBJECTIVE: Differentiating Parkinson's disease (PD) from atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it remains unknown which PIGD test - or combination of tests - can best distinguish PD from APD. We evaluated the discriminative value of several widely-used PIGD tests, and aimed to develop a short PIGD evaluation that can discriminate parkinsonian disorders. METHODS: In this multicentre cohort study patients were recruited by 11 European MSA Study sites. Patients were diagnosed using standardized criteria. Postural instability and gait disability was evaluated using interviews and several clinical tests. RESULTS: Nineteen PD, 21 MSA-p and 25 PSP-RS patients were recruited. PIGD was more common in APD compared to PD. There was no significant difference in axial symptoms between PSP-RS and MSA-p, except for self-reported falls (more frequent in PSP-RS patients). The test with the greatest discriminative power to distinguish APD from PD was the ability to perform tandem gait (AUC 0.83; 95% CI 71-94; p < 0.001), followed by the retropulsion test (AUC 0.8; 95% CI 0.69-0.91; p < 0.001) and timed-up-and-go test (TUG) (AUC 0.77; 95% CI 0.64-0.9; p = 0.001). The combination of these three tests yielded highest diagnostic accuracy (AUC 0.96; 95% CI 0.92-1.0; p < 0.001). CONCLUSIONS: Our study suggests that simple "bedside" PIGD tests - particularly the combination of tandem gait performance, TUG and retropulsion test - can discriminate APD from PD.

• Klíčová slova
• Atypical parkinsonian disorders, Multiple system atrophy, Parkinson's disease, Parkinsonian type, Postural instability and gait disability, Progressive supranuclear palsy,
• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurologické poruchy chůze diagnóza   epidemiologie   patofyziologie   MeSH
• Parkinsonova nemoc diagnóza   epidemiologie   patofyziologie   MeSH
• parkinsonské poruchy diagnóza   epidemiologie   patofyziologie   MeSH
• posturální rovnováha fyziologie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   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

• 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

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

The term 'endemic parkinsonism' refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region; one in the Caribbean islands of Guadeloupe and Martinique; and four in Europe. Some of these disease entities seem to be disappearing over time and therefore are probably triggered by unique environmental factors. By contrast, other types persist because they are exclusively genetically determined. Given the geographical clustering and potential overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism. Knowledge obtained from the study of these disease entities supports the hypothesis that both genetic and environmental factors contribute to the development of neurodegenerative diseases, not only in endemic parkinsonism but also in general. At the same time, this understanding suggests useful directions for further research in this area.

• MeSH
• biologie MeSH
• fenotyp MeSH
• lidé MeSH
• parkinsonské poruchy * epidemiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH
• Guadeloupe epidemiologie   MeSH

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disease which causes health problem that affects more patients in the past few years. To be able to offer appropriate care, epidemiological analyses are crucial at the national level and its comparison with the international situation. AIM: The demographic description of reported patients with parkinsonism (including Parkinson's disease and atypical parkinsonian syndromes) according to the International Classification of Diseases (ICD-10) from the national health registries. METHODS: Retrospective analysis of data available from the National Health Information System-NHIS and the National Registry of Reimbursed Health Services (NRRHS). Analyzed epidemiological data are intending to determine the regional and specific prevalence of Parkinsonism in the Czech Republic. The International Classification of Diseases diagnoses (ICD-10) of G20 (Parkinson's disease-PD) and G23.1, G23.2, G23.3 (other degenerative disorders of basal ganglia), and G31.8 (another degenerative disease of basal ganglia) from the period of 2012 to 2018 were included into the analysis. RESULTS: We identified 78 453 unique patients from national registries in the period 2012 to 2018. Diagnoses of G20, G23.1, G23.2, and G31.8 were registered as the principal diagnoses in 76.6% of all individual patients. CONCLUSION: We have found a growing number of patients coded with ICD-10 of dg. G20, G23.1, G23.2, G23.3, or G31.8 (N = 27 891 in 2012, and N = 30 612 in 2018). We have proven regional differences in the prevalence of Parkinson´s diagnoses. Therefore we assume most likely also differences in the care of patients with PD based on the availability of specialty care centers.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurodegenerativní nemoci epidemiologie   MeSH
• Parkinsonova nemoc diagnóza   epidemiologie   MeSH
• parkinsonské poruchy diagnóza   epidemiologie   MeSH
• prevalence MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Gait festination is one of the most characteristic gait disturbances in patients with Parkinson's disease or atypical parkinsonism. Although festination is common and disabling, it has received little attention in the literature, and different definitions exist. Here, we argue that there are actually two phenotypes of festination. The first phenotype entails a primary locomotion disturbance, due to the so-called sequence effect: a progressive shortening of step length, accompanied by a compensatory increase in cadence. This phenotype strongly relates to freezing of gait with alternating trembling of the leg. The second phenotype results from a postural control problem (forward leaning of the trunk) combined with a balance control deficit (inappropriately small balance-correcting steps). In this viewpoint, we elaborate on the possible pathophysiological substrate of these two phenotypes of festination and discuss their management in daily clinical practice.

• Klíčová slova
• Balance, Festination, Freezing of gait, Gait, Parkinson’s disease,
• MeSH
• fenotyp MeSH
• lidé MeSH
• neurologické poruchy chůze klasifikace   etiologie   patofyziologie   terapie   MeSH
• parkinsonské poruchy komplikace   patofyziologie   terapie   MeSH
• posturální rovnováha fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). OBJECTIVE: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. METHODS: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. RESULTS: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. CONCLUSION: Our results do not support a major role for variants in these genes in the risk of iRBD. © 2020 International Parkinson and Movement Disorder Society.

• Klíčová slova
• REM sleep behavior disorder; genetic analysis; Parkinson's disease,
• MeSH
• heterozygot MeSH
• lidé MeSH
• Parkinsonova nemoc * genetika   MeSH
• parkinsonské poruchy * genetika   MeSH
• porucha chování v REM spánku * genetika   MeSH
• spánek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

An increased prevalence of familial neurodegenerative parkinsonism or cognitive deterioration was recently found in a small region of southeastern Moravia.The aim of the study was to assess the genetic background of this familial disease.Variants in the ADH1C, EIF4G1, FBXO7, GBA + GBAP1, GIGYF2, HTRA2, LRRK2, MAPT, PRKN, DJ-1, PINK1, PLA2G6, SNCA, UCHL1, VPS35 genes were examined in 12 clinically positive probands of the pedigree in which familial atypical neurodegenerative parkinsonism was identified in previous epidemiological studies. Libraries were sequenced by massive parallel sequencing (MPS) on the Personal Genome Machine (PGM; Ion Torrent). Data were analyzed using Torrent Suite and IonReporter software. All variants were then verified and confirmed by Sanger sequencing.We identified 31 rare heterozygous variants: 11 missense variants, 3 synonymous variants, 8 variants in the UTR region, and 9 intronic variants. Six variants (rs1801334, rs33995883, rs35507033, rs781737269, rs779760087, and rs63750072) were evaluated as pathogenic by at least one in-silico predictor.No single "founder" pathogenic variant associated with parkinsonism has been found in any of the probands from researched pedigree. It may rather be assumed that the familial occurrence of this disease is caused by the combined influence of several "small-effect" genetic variants that accumulate in the population with long-lasting inbreeding behavior.

• MeSH
• elektroencefalografie MeSH
• elektromyografie MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• motorické evokované potenciály MeSH
• neuropsychologické testy MeSH
• Parkinsonova nemoc etnologie   genetika   MeSH
• rodokmen * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Parkinson's disease and parkinsonism are relatively common neurodegenerative disorders. This study aimed to assess potential genetic risk factors of haplotypes in genes associated with parkinsonism in a population in which endemic parkinsonism and atypical parkinsonism have recently been found. The genes ADH1C, EIF4G1, FBXO7, GBA, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1 PLA2G6, SNCA, UCHL1, and VPS35 were analyzed in 62 patients (P) and 69 age-matched controls from the researched area (C1). Variants were acquired by high-throughput sequencing using Ion Torrent workflow. As another set of controls, the whole genome sequencing data from 100 healthy non-related individuals from the Czech population were used (C2); the results were also compared with the Genome Project data (C3). We observed shared findings of four intron (rs11564187, rs36220738, rs200829235, and rs3789329) and one exon variant (rs33995883) in the LRRK2 gene in six patients. A comparison of the C1-C3 groups revealed significant differences in haplotype frequencies between ratio of 2.09 for C1, 1.65 for C2, and 6.3 for C3, and odds ratios of 13.15 for C1, 2.58 for C2, and 7.6 for C3 were estimated. The co-occurrence of five variants in the LRRK2 gene (very probably in haplotype) could be an important potential risk factor for the development of parkinsonism, even outside the recently described pedigrees in the researched area where endemic parkinsonism is present.

• Klíčová slova
• LRRK2 gene, Parkinson’s disease, atypical Parkinson syndrome, haplotype, high-throughput sequencing,
• Publikační typ
• časopisecké články MeSH