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Background In 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times. Methods Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cutoff. Results A total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes. Conclusion The International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society.

We studied the association of three personality traits related to neuroticism with the subsequent risk of Parkinson's disease (PD) using a historical cohort study. We included 7,216 subjects who resided within the 120-mile radius centered in Rochester, MN, at the time they completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 to 1965. We considered three MMPI personality scales (pessimistic, anxious, and depressive traits). A total of 6,822 subjects (94.5%) were followed over four decades either actively or passively. During follow-up, 227 subjects developed parkinsonism (156 developed PD). An anxious personality was associated with an increased risk of PD [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.16-2.27]. A pessimistic personality trait was also associated with an increased risk of PD but only in men (HR = 1.92; 95% CI = 1.20-3.07). By contrast, a depressive trait was not associated with increased risk. Analyses combining scores from the three personality scales into a composite neuroticism score showed an association of neuroticism with PD (HR = 1.54; 95% CI = 1.10-2.16). The association with neuroticism remained significant even when the MMPI was administered early in life (ages 20-39 years). By contrast, none of the three personality traits was associated with the risk of non-PD types of parkinsonism grouped together. Our long-term historical cohort study suggests that an anxious personality trait may predict an increased risk of PD developing many years later.

Rare mutations in PARK loci genes cause Parkinson’s disease (PD) in some families and isolated populations. We investigated the association of common variants in PARK loci and related genes with PD susceptibility and age at onset in an outbred population. 1,103 PD cases from the upper Midwest, USA were individually matched to unaffected siblings (n = 654) or unrelated controls (n = 449) from the same region. Using a sequencing approach in 25 cases and 25 controls, single nucleotide polymorphisms (SNPs) in species-conserved regions of PARK loci and related genes were detected. We selected additional tag SNPs from the HapMap. We genotyped a total of 235 SNPs and two variable number tandem repeats (VNTRs) in the ATP13A2, DJ1, LRRK1, LRRK2, MAPT, Omi/HtrA2, PARK2, PINK1, SNCA, SNCB, SNCG, SPR, and UCHL1 genes in all 2,206 subjects. Case-control analyses were performed to study association with PD susceptibility, while cases-only analyses were used to study association with age at onset. Only MAPT SNP rs2435200 was associated with PD susceptibility after correction for multiple testing (OR = 0.74, 95% CI = 0.64 – 0.86, uncorrected P < 0.0001, log additive model); however, 16 additional MAPT variants, seven SNCA variants, and one LRRK2, PARK2, and UCHL1 variants each had significant uncorrected P-values. There were no significant associations for age at onset after correction for multiple testing. Our results confirm the association of MAPT and SNCA genes with PD susceptibility, but show limited association of other PARK loci and related genes with PD.

We investigated the association of Bell's palsy (BP) with the subsequent risk of Parkinson's disease (PD) using a case-control study design. We matched 196 incident cases of PD in Olmsted County, MN, to 196 general population controls with same age (+/-1 year) and sex, and we reviewed the complete medical records of cases and controls in a medical records-linkage system to detect BP. Six of the 196 patients with PD and none of the 196 controls were diagnosed with BP before PD (exact binomial probability, P = 0.02). The median age at occurrence of BP was 49.5 years (range, 15-84 years) and the median time between BP and the onset of PD was 27.5 years (range, 2-54 years). The findings were similar using a standardized incidence ratio (SIR) approach, but were not statistically significant. This initial association between BP and PD awaits replication.

Parkinson's disease (PD) occurs worldwide, but little is known about PD in Africa. We systematically reviewed publications on PD in Africa, with emphasis on epidemiologic and genetic studies. Articles published between 1944 and December 2004 were identified using several strategies. The studies emanated from 13 African countries (Kenya, Uganda, Tanzania, Ethiopia, Nigeria, Senegal, Ghana, Togo, Libya, Tunisia, Algeria, Zimbabwe, and South Africa). The publications fell into four categories: clinical series (n = 17), prevalence studies (n = 7), incidence studies (n = 1), and genetic studies (n = 3). The clinical series documented the occurrence of PD in Africa and described its clinical characteristics. The prevalence studies suggested some intracontinental geographic variation in PD prevalence. Overall, the prevalence figures and the incidence rates of PD in Africa appeared lower than those reported for European and North American populations. Few genetic studies of PD have been reported from Africa, and none in blacks. There are no case-control or cohort studies of PD reported from Africa. This review provides a summary of PD research in Africa over the past 60 years and highlights the information gaps and potential areas for future research.

The objective was to provide population-based estimates of incremental medical costs associated with Parkinson's disease (PD) from onset forward. All Olmsted County, Minnesota, residents with confirmed PD onset from 1987 through 1995 (n = 92) and one age- and sex-matched non-PD referent subject per case were identified with retrospective record review and followed in provider-linked billing data for direct medical costs (excluding outpatient pharmaceutical costs) from 1 year before index (i.e., year of symptom onset) through 10 years after index. Costs for each referent subject were subtracted from those for his/her matched case. Tests for statistical significance used Wilcoxon signed ranks. Preindex costs were similar [median difference in annual costs (MD) = -3 dollars; P = 0.59]. One year post index, PD subjects exhibited borderline significantly higher costs compared to referent subjects (MD = 581 dollars; P = 0.052); the difference diminished over 5 years (MD = 118 dollars; P = 0.82). By 5 to 10 years, however, PD subjects exhibited significantly higher costs (MD = 1,146 dollars; P = 0.01). Over the full 10 years, excess costs were concentrated among PD subjects without rest tremor (MD = 2,261 dollars, P < 0.01, for those without tremor and -229 dollars, P = 0.99, for those with tremor). These population-based estimates of PD-associated direct medical costs from onset forward can uniquely inform policy decisions and cost-effectiveness research.

The burden of comorbidity in Parkinson's disease (PD) remains unclear. All Olmsted County, Minnesota, residents with incident PD in 1976-1995 (n = 197) plus one age- and sex-matched non-PD referent subject per case were followed for all clinical diagnoses from 5 years before through 15 years after index (i.e., year of PD onset for each case and same year for the referent subject). Both members of a case-referent pair were censored at death or emigration of either member to ensure equivalent follow-up. Cases and referent subjects were compared for summary comorbidity (Charlson index) and for the likelihood of having one or more diagnoses within each International Classification of Diseases chapter/subchapter. Before index, the groups were similar for all comparisons. After index, cases had a higher likelihood of diagnoses within the chapters "Mental Disorders" and "Diseases of the Genitourinary System," and within the subchapters "Organic Psychotic Conditions," "Other Psychoses," "Neurotic/Personality/Other Nonpsychotic Disorders," "Hereditary/Degenerative Diseases of Central Nervous System," "Symptoms," "Other Diseases of Digestive System," "Other Diseases of Urinary System," "Diseases of Veins/Lymphatics/Other Circulatory System Diseases," "Fractures of Lower Limb," "Other Diseases of Skin/Subcutaneous Tissue," "Osteopathies/Chrondropathies/Acquired Musculoskeletal Deformities," and "Pneumonia and Influenza." The excess morbidity and mortality observed for persons with PD are consistent with recognized PD sequelae.

We conducted a case-control study of the α-synuclein–interacting protein gene (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319 PD cases and 195 controls were genotyped for four SNCAIP variants, including a microsatellite repeat in intron 4 and three restriction fragment length polymorphisms (RFLP) proximal to the 5′ terminal of exons 1, 4, and 6. None of the variants were found associated with PD overall. Global score statistics were not significant for four, three, and two loci haplotypes. All four loci were in linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the α-synuclein gene (SNCA) or the parkin (PARK2) gene. © 2003 Movement Disorder Society

A lower prevalence of Parkinson's disease (PD) has been reported for Chinese populations, but it is unclear whether this observation reflects a lower disease risk or is an artifact of case finding. We ascertained the prevalence of PD in elderly residents of an area that was a composite of 27 urban and rural communities of Greater Beijing, China. A team of university neurologists went door-to-door throughout the study area, examining 5,743 residents (at age 55 years or older) and made preliminary determinations of which residents had PD or other types of parkinsonism. Final determinations were made after follow-up and reevaluation of those persons who were either deemed to have parkinsonism or were suspected of having the condition (n = 144; median follow-up = 40 months). Based on stringent diagnostic criteria, 110 persons were identified to have parkinsonism, of whom 64 (58%) had PD. The prevalence of PD increased with advancing age and was about 1% overall and for each gender. In rural communities, 22 persons had PD, but 20 persons (91%) were first diagnosed for this condition by the study neurologists. The prevalence figures obtained in this study are similar to some of the highest prevalence figures reported in the West.

The identification of pathogenic mutations in the three genes α-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). In addition, polymorphisms of these three genes have been shown to be independently associated with PD. In a sample of 298 unrelated PD cases and 185 controls, we applied a two-phased approach of recursive partitioning and logistic regression analyses to explore complex interactions. For women only, we observed an epistatic interaction of UCHL1 and α-synuclein genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS. © 2003 Movement Disorder Society

The clinical features of familial Parkinson's disease (PD) were investigated by examining the families of 20 British probands who were selected on the basis of having clinically typical PD and at least one affected relative. Forty-nine secondary cases were identified. These subjects were clinically indistinguishable from sporadic cases of idiopathic PD. If it is assumed that familial PD has a genetic basis, pedigree and segregation analysis suggested autosomal dominant inheritance of a gene or genes with reduced penetrance as the most likely explanation. The data did not support the possibilities of either mitochondrial or polygenic inheritance, although the latter cannot be excluded. The role of genetic factors in sporadic cases of PD remains unclear.

A 17-year-old boy is described who experienced circling behavior interrupting his gait and complex stereotyped movements of the hands after a complicated repair of an aortic coarctation. An MRI scan showed a right putaminal infarct. The boy's behavior and stereotypies bear a close resemblance to those found in autism.