MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP–parkinsonism

Quattrone, Aldo; Morelli, Maurizio; Williams, David R.; Vescio, Basilio; Arabia, Gennarina; Nigro, S. Ló; Nicoletti, Giuseppe; Salsone, Maria; Novellino, Fabiana; Nisticò, Rita; Pucci, Franco; Chiriaco, Carmelina; Pugliese, Pierfrancesco; Bosco, Domenico; Caracciolo, Manuela

doi:10.1212/wnl.0000000000003125

Cited by 45 publications

(47 citation statements)

References 38 publications

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“…45 The pons/midbrain ratio, as calculated from conventional MRI, had high specificity and sensitivity for the diagnosis of pathologically confirmed PSP. 46 In studies of the early stages of PSP, 46 MRPI was also able to predict development of PSP-RS in unclassifiable parkinsonism and eye movement abnormalities in PSP-P. 45,47 …”

Section: Biomarkers (Table 1)mentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

347

359

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Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.

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Section: Biomarkers (Table 1)mentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

347

359

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“…Similarly, another autopsy study found that midbrain atrophy was present in only 86.4% of pathologically confirmed PSP, and the hummingbird sign was only present in 68.4%, even after a disease duration of 4.8 years . However, midbrain atrophy has been observed in speech and language disorders that are confirmed or suspected of having PSP pathology, as well as in PSP‐F and PSP‐P . Midbrain atrophy in vPSP is typically less severe than in PSP‐RS, although there is some suggestion that abnormalities on the MRPI could be an early feature in PSP‐P and have some value as a level 3 biomarker.…”

Section: Structural Mrimentioning

confidence: 99%

Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be?

et al. 2017

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PSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardson's syndrome and other variant PSP syndromes. A large body of neuroimaging research has been conducted over the past two decades, with many studies proposing different structural MRI and molecular PET/SPECT biomarkers for PSP. These include measures of brainstem, cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in striatal dopamine imaging and, most recently, PET imaging with ligands that bind to tau. Our aim was to critically evaluate the degree to which structural and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP. We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English over the past 20 years using postmortem diagnosis or the NINDS-SPSP criteria as the diagnostic standard from 1996 to 2016. We define a five-level theoretical construct for the utility of neuroimaging biomarkers in PSP, with level 1 representing group-level findings, level 2 representing biomarkers with demonstrable individual-level diagnostic utility, level 3 representing biomarkers for early disease, level 4 representing surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP biomarkers of PSP pathology. We discuss the degree to which each of the currently available biomarkers fit into this theoretical construct, consider the role of biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and autopsy confirmed PSP, and emphasize current shortfalls in the field.

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“…Magnetic resonance (MR) imaging measurements have been shown to be useful for diagnosing PSP . The MR Parkinsonism Index (MRPI) has proven to be an accurate biomarker for diagnosing patients with PSP and for predicting the clinical evolution toward PSP phenotypes of patients affected by undetermined parkinsonism or the appearance of vertical supranuclear gaze palsy (VSGP) in patients with PSP‐P . Overall, this biomarker is highly accurate in diagnosing PSP‐RS but shows a low sensitivity in distinguishing between patients with PSP‐P and those with PD .…”

mentioning

confidence: 99%

“…Magnetic resonance (MR) imaging measurements have been shown to be useful for diagnosing PSP. 12,13 The MR Parkinsonism Index (MRPI) has proven to be an accurate biomarker for diagnosing patients with PSP [14][15][16][17][18][19][20][21][22][23][24][25][26] and for predicting the clinical evolution toward PSP phenotypes of patients affected by undetermined parkinsonism 27,28 or the appearance of vertical supranuclear gaze palsy (VSGP) in patients with PSP-P. 29 Overall, this biomarker is highly accurate in diagnosing PSP-RS 12 but shows a low sensitivity in distinguishing between patients with PSP-P and those with PD. 18,26,30 Recently, we demonstrated that a new version of MRPI that included the measurement of third ventricle width (MRPI 2.0) was highly accurate in differentiating PSP-P patients from PD.…”

mentioning

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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MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP–parkinsonism

Cited by 45 publications

References 38 publications

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be?

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

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