Supplementary MaterialsSupplement: eTable 1. profile, serum neurofilament light string level, genetic, and volumetric magnetic resonance imaging measures helped to distinguish the clinical subtypes of progressive supranuclear palsy and corticobasal syndrome; clinical trajectory and serum neurofilament light chain levels distinguished Parkinson disease from progressive supranuclear palsy and corticobasal syndrome. Meaning This study suggests that subtypes of progressive supranuclear palsy and corticobasal syndrome have distinct characteristics that may enhance their early diagnosis. Abstract Importance Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are Rabbit Polyclonal to Neuro D often misdiagnosed (E)-2-Decenoic acid as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. Objective To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD. Design, Setting, Participants This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBSCAlzheimer disease (CBS-AD), and CBSCnon-AD. Data were analyzed from February 1, through May 1, 2019. Primary Outcomes and Procedures Baseline group evaluations used (1) scientific trajectory; (2) cognitive verification scales; (3) serum neurofilament light string (NF-L) amounts; (4) genotypes; and (5) volumetric magnetic resonance imaging procedures. Results A complete of 222 sufferers with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) had been recruited (129 [58.1%] man; mean [SD] age group at recruitment, 68.3 [8.7] years). Age-matched control individuals (n?=?76) and sufferers with PD (n?=?1967) were included for evaluation. Concordance between your antemortem scientific and pathologic diagnoses was attained in 12 of 13 sufferers with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Culture PSP diagnostic requirements almost doubled the amount of patients identified as having PSP from 58 to 101. Forty-nine of 101 sufferers with reclassified PSP (48.5%) didn’t have the basic PSP-RS subtype. Sufferers in the (E)-2-Decenoic acid PSP-subcortical group got an extended diagnostic latency and a far more benign scientific trajectory than those in PSP-RS and PSP-cortical groupings. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging steps (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher (OMIM 157140) H1/H1, (OMIM 107741) 4 allele, and (OMIM 607868) rs564309 minor allele group frequencies. Neuroimaging A subset of PROSPECT participants attended 3 scanning centers (UCL, Cambridge, and Oxford) and underwent baseline volumetric T1-weighted magnetic resonance imaging (MRI) on 3T scanners (Siemens, Prisma, or TRIO) (eMethods in the Supplement). We combined the basal ganglia (caudate, putamen, and pallidum), accumbens, and thalamus as central structures for summarizing groupwise subcortical atrophy. Imaging data from Tracking Parkinsons participants were not available. MSA Group Data We have included cases with MSA in the description of our PROSPECT study cohort and baseline clinical features. However, the statistical analyses described below and comparisons with PD data have been restricted to PSP, CBS, and IDT cases because these cases were reclassified under the MDS PSP diagnostic criteria. The analysis of associated MSA group data will be published separately. Statistical Analysis Data were analyzed from February 1 through May 1, 2019, using Plink, version 1.9 (Harvard University), GraphPad, version 8 (Prism), and Stata, version 15 (StataCorp LLC). For missing data in clinical scales, an adjusted mean score was used if at least 80% of the assessment was complete. Group comparisons of clinical, cognitive, and biomarker steps were made using logistic regression analyses with sex, age at symptom onset, and disease duration at testing as covariates. We calculated the clinical disease trajectory by dividing PSP Rating Level and MDS (E)-2-Decenoic acid Unified Parkinsons Disease Rating Level parts II and III scores at baseline by the number of.