Frontrunner in Translation: Progressive Supranuclear Palsy

Shoeibi, Ali; Olfati, Nahid; Litvan, Irene

doi:10.3389/fneur.2019.01125

Cited by 20 publications

(32 citation statements)

References 241 publications

(255 reference statements)

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“…PSP-RS is the most recognized phenotype (1,5); however, up to half of PSP patients may initially display less specific or well-recognized features of the disease, such as PSP-parkinsonism predominant (PSP-P) (2,14), and the most common diagnosis at initial assessment is Parkinson's disease (12). Although no diseasemodifying treatments are currently available (9,(15)(16)(17), a better understanding of the natural history, including comorbidities and early features of PSP is key to patient management.…”

Section: Introductionmentioning

confidence: 99%

Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database

et al. 2021

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Background: Progressive supranuclear palsy is a rare neurodegenerative movement disorder and little is known about its epidemiology.Objective: Estimate age-adjusted prevalence of progressive supranuclear palsy and describe antecedent diagnoses and progressive supranuclear palsy patient features in the 5 years before first diagnostic code.Methods: In a nested case-control study in the IBM MarketScan Commercial and Medicare Supplemental Databases, a large set of US insurance databases containing medical service and prescription drug claims from employer-based commercial and Medicare supplemental health insurance plans, progressive supranuclear palsy cases (identified via International Statistical Classification of Diseases 9th/10th revision codes) and controls were included if enrollment was ≥1 month in the study period (October 1, 2015–October 31, 2017). Two controls with no diagnosis codes for PSP were matched to cases on birth year, sex, enrollment time in the database, and pharmacy benefit eligibility. Controls were assigned a randomly selected index date from their eligibility period. Prevalence of progressive supranuclear palsy was estimated in 2016 among patients with ≥1 month of continuous enrollment in that year. Prevalence ratios for comorbidities (claim/diagnosis codes) were examined in the ≤ 5 years before index date (first progressive supranuclear palsy claim date).Results: Age-adjusted progressive supranuclear palsy prevalence was 2.95/100,000 in 2016. The most common diagnosis codes in cases vs. controls in the 5 years pre-index were gait abnormalities (79.3 vs. 21.8%), pain in joint (54.9 vs. 36.0%), Parkinson's disease (54.6 vs. 1.0%), fatigue (49.8 vs. 21.6%), and cerebrovascular disease (45.6 vs. 16.4%).Conclusions: In this large database analysis, based on preliminary analyses, the prevalence of diagnosed progressive supranuclear palsy was 2.95/100,000, which is lower than many prior studies. Typical symptoms suggestive of progressive supranuclear palsy were present before index date, indicating a potential delay in time to diagnosis. The identification of diagnostic codes for clinical features of progressive supranuclear palsy that occurred before index date may be used to develop predictive models to identify potential progressive supranuclear palsy patients earlier in their disease course.

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Section: Introductionmentioning

confidence: 99%

Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database

et al. 2021

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“…(1) In human studies, high levels of iron have been reported to co-localize with hyperphosphorylated tau aggregates 19 . Tau-containing globose neurofibrillary tangles are prevalent in the PSP midbrain, including in the oculomotor nerve complex 20 . (2) Anatomically, the fibers of the oculomotor nerve fascicles from the nucleus pass by the RN and SN, and these two structures contain a high level of iron concentration 17 .…”

Section: Discussionmentioning

confidence: 99%

Iron accumulation in the oculomotor nerve of the progressive supranuclear palsy brain

Lee

Kim

et al. 2021

Sci Rep

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Abnormal iron accumulation around the substantia nigra (SN) is a diagnostic indicator of Parkinsonism. This study aimed to identify iron-related microarchitectural changes around the SN of brains with progressive supranuclear palsy (PSP) via postmortem validations and in vivo magnetic resonance imaging (MRI). 7 T high-resolution MRI was applied to two postmortem brain tissues, from one normal brain and one PSP brain. Histopathological examinations were performed to demonstrate the molecular origin of the high-resolution postmortem MRI findings, by using ferric iron staining, myelin staining, and two-dimensional laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging. In vivo iron-related MRI was performed on five healthy controls, five patients with Parkinson’s disease (PD), and five patients with PSP. In the postmortem examination, excessive iron deposition along the myelinated fiber at the anterior SN and third cranial nerve (oculomotor nerve) fascicles of the PSP brain was verified by LA-ICP-MS. This region corresponded to those with high R2* values and positive susceptibility from quantitative susceptibility mapping (QSM), but was less sensitive in Perls’ Prussian blue staining. In in vivo susceptibility-weighted imaging, hypointense pixels were observed in the region between the SN and red nucleus (RN) in patients with PSP, but not in healthy controls and patients with PD. R2* and QSM values of such region were significantly higher in patients with PSP compared to those in healthy controls and patients with PD as well (vs. healthy control: p = 0.008; vs. PD: p = 0.008). Thus, excessive iron accumulation along the myelinated fibers at the anterior SN and oculomotor nerve fascicles may be a pathological characteristic and crucial MR biomarker in a brain with PSP.

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“…Tau in PSP has a shifted ratio of 4R:3R tau. 4R-tau assembles into 13–14 nm straight filaments that aggregate to form NFT in neurons and tufted astrocytes in glial cells [ 150 ]. In CBD, aggregates are formed from 4-repeat tau alone.…”

Section: Protein Pathology In Various Forms Of Parkinsonismmentioning

confidence: 99%

“…Astrocytic plaques are the typical lesions because the aggregated tau is mainly located in cell processes. In contrast, PSP’s tufted astrocytes are laden with tau fibrillary deposits at the soma, with propagation to the cell processes [ 150 ]. Despite the identical composition of the tau isoforms in both diseases, post-mortem studies indicate different proteolytic processing of abnormal tau in CBD and PSP cases [ 151 ].…”

Section: Protein Pathology In Various Forms Of Parkinsonismmentioning

confidence: 99%

Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences

Koziorowski

Figura

Milanowski

et al. 2021

Cells

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Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

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Frontrunner in Translation: Progressive Supranuclear Palsy

Cited by 20 publications

References 241 publications

Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database

Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database

Iron accumulation in the oculomotor nerve of the progressive supranuclear palsy brain

Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences

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