Validation of the MDS clinical diagnostic criteria for Parkinson's disease

Postuma, Ronald B.; Poewe, Werner; Litvan, Irene; Lewis, Simon J.G.; Lang, Anthony E.; Halliday, Glenda M.; Goetz, Christopher G.; Chan, Piu; Slow, Elizabeth; Seppi, Klaus; Schäffer, Eva; Ríos‐Romenets, Silvia; Mi, Taomian; Maetzler, Corina; Li, Yuan; Heim, Beatrice; Bledsoe, Ian O.; Berg, Daniela

doi:10.1002/mds.27362

Cited by 203 publications

(125 citation statements)

References 17 publications

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“…This is consistent with age being the greatest risk factor for Parkinson's disease and the idea that Parkinson's is a disease of accelerated ageing (83). Finally, there is a need for a Parkinson's biomarker (84,85). Measuring translation from peripheral cells could potentially lead to a biomarker readout.…”

Section: Discussionsupporting

confidence: 58%

Protein synthesis is suppressed in sporadic and familial Parkinson’s Disease by LRRK2

Deshpande

Flinkman

Yun

et al. 2020

Preprint

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Gain of function LRRK2-G2019S is the most common mutation associated with both familial and sporadic Parkinson's disease. It is expected therefore that understanding the cellular function of LRRK2 will provide much needed insight on the pathological mechanism of sporadic Parkinson's, which is the most common form. Here we show that constitutive LRRK2 activity represses nascent protein synthesis in rodent neurons. Specifically, enzymatic inhibition of LRRK2, gene silencing or gene knockout of Lrrk2 increase translation. In the rotenone model of Parkinson's, LRRK2 activity increases, leading to repression of translation and dopaminergic neuron atrophy both of which are prevented by LRRK2 inhibition. This is accompanied by altered phosphorylation of eIF2a-S52(↑), eIF2s2-S2(↓) and eEF2-T57(↑) in striatum/substantia nigra in a direction that signifies inhibition of protein synthesis. Significantly, LRRK2 is activated and translation is 40% reduced in Parkinson's patient fibroblasts (G2019S and sporadic) and LRRK2 inhibition restores normal translation. In contrast, translation is unchanged in cells from multiple system atrophy patients, implying disease specificity. These findings suggest that LRRK2-dependent repression of translation may be a proximal function of LRRK2 in Parkinson's pathology. Words: 178Table 1. Demographic and clinical characteristics of patients and healthy controls -The source of material either Turku University Hospital (TUH), Telethon network of genetic biobanks (TNGB) or NINDS Coriell repository (NINDS) is indicated. *Unified Parkinson's Disease rating scale (UPDRS). Gender male (m)and female (f), and age in years when the biopsy was taken, are indicated. Estimated age of onset refers to the age when motor symptoms were first reported. For patients where the relevant information was not available, a hyphen is shown.

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Section: Discussionsupporting

confidence: 58%

Protein synthesis is suppressed in sporadic and familial Parkinson’s Disease by LRRK2

Deshpande

Flinkman

Yun

et al. 2020

Preprint

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“…Overall, the MDS‐PSP criteria perform very favorably compared with other criteria for clinical diagnosis of other neurodegenerative disorders. For comparison, a recent study of the PD criteria found an 11.5% false‐positive rate, sensitivity of 94.5%, and specificity of 88.5% . Sensitivity of the clinical diagnosis of Alzheimer's disease (AD) ranges from 70.9% to 87.3% and specificity from 44.3% to 70.8% .…”

Section: Discussionmentioning

confidence: 99%

“…For comparison, a recent study of the PD criteria found an 11.5% false-positive rate, sensitivity of 94.5%, and specificity of 88.5%. 24 Sensitivity of the clinical diagnosis of Alzheimer's disease (AD) ranges from 70.9% to 87.3% and specificity from 44.3% to 70.8%. 25 Similarly, criteria for "possible bvFTD" have sensitivity of 95% and specificity of 82%, whereas "probable bvFTD" has a sensitivity of 85% and specificity of 95%.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity and Specificity of Diagnostic Criteria for Progressive Supranuclear Palsy

et al. 2019

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Background: In 2017, the Movement Disorders Society put forward new clinical criteria for the diagnosis of PSP recognizing diverse PSP phenotypes. Objectives: In this study, we compare the sensitivity and specificity of the new criteria to the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy (NINDS-SPSP) criteria at different time points. Methods: Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP were identified from the Society for Progressive Supranuclear Palsy (SPSP) brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at one of the three Mayo Clinic sites located in Florida, Arizona and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether or not patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cut off. Results: A total of 129 patients were included of which 66 (51%) had PSP pathology. The remainder had other neurodegenerative diseases. The overall sensitivity of the Movement Disorders Society criteria was 87.9% compared to 45.5% for National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the Movement Disorders Society criteria probable PSP criteria was 85.7% and 90.5% for National Institutes of Neurological Disease criteria. Individual patients were noted to have features of multiple PSP phenotypes. Conclusion: The Movement Disorders Society criteria recognize several phenotypes of PSP and hence have a higher sensitivity than the previous criteria.

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“…who had more than 10 years of experience in the diagnosis of movement disorders. Although new clinical diagnostic criteria for PD have been recently proposed 43 and very recently validated, 44 these criteria have not been used in our patients because the patient recruitment ended before the publication of the new diagnostic criteria. Second, the abnormalities of vertical saccades may occasionally be present both in aging and in vascular parkinsonism.…”

Section: Discussionmentioning

confidence: 99%

Refining initial diagnosis of Parkinson's disease after follow‐up: A 4‐year prospective clinical and magnetic resonance imaging study

Quattrone

Morelli

Vescio³

et al. 2019

Movement Disorders

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Background No prospective study of patients with Parkinson's disease (PD) has investigated the appearance of vertical gaze abnormalities, a feature suggestive of progressive supranuclear palsy (PSP). Objective To identify, within a cohort of patients with an initial diagnosis of PD, those who developed vertical gaze abnormalities during a 4‐year follow‐up, and to investigate the performance of new imaging biomarkers in predicting vertical gaze abnormalities. Methods A total of 110 patients initially classified as PD and 74 controls were enrolled. All patients underwent clinical assessment at baseline and every year up to the end of the follow‐up. The pons/midbrain area ratio 2.0 and the Magnetic Resonance Parkinsonism Index 2.0 were calculated. Results After 4‐year follow‐up, 100 of 110 patients maintained the diagnosis of PD, whereas 10 PD patients (9.1%) developed vertical gaze abnormalities, suggesting an alternative diagnosis of PSP‐parkinsonism. At baseline, the Magnetic Resonance Parkinsonism Index 2.0 was the most accurate biomarker in differentiating PD patients who developed vertical gaze abnormalities from those who maintained an initial diagnosis of PD. At the end of follow‐up, both of these biomarkers accurately distinguished PSP‐parkinsonism from PD. Conclusions Our results demonstrate that a number of patients with an initial diagnosis of PD developed vertical gaze abnormalities during a 4‐year follow‐up, and the diagnosis was changed from PD to PSP‐parkinsonism. In PD patients, baseline Magnetic Resonance Parkinsonism Index 2.0 showed the best performance in predicting the clinical evolution toward a PSP‐parkinsonism phenotype, enabling PSP‐parkinsonism patients to be identified at the earliest stage of the disease for promising disease‐modifying therapies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Validation of the MDS clinical diagnostic criteria for Parkinson's disease

Cited by 203 publications

References 17 publications

Protein synthesis is suppressed in sporadic and familial Parkinson’s Disease by LRRK2

Protein synthesis is suppressed in sporadic and familial Parkinson’s Disease by LRRK2

Sensitivity and Specificity of Diagnostic Criteria for Progressive Supranuclear Palsy

Refining initial diagnosis of Parkinson's disease after follow‐up: A 4‐year prospective clinical and magnetic resonance imaging study

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