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Introduction: Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages., Methods: The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up., Results: Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0., Conclusions: Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3 rd V width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: MR planimetry of brainstem structures can be helpful for the discrimination of Parkinsonian syndromes. It has been suggested that ageing might influence brainstem MR measurements assessed by MR planimetry, while effects of gender and total intracranial volume (TIV) have not been assessed so far. The aim of this study was to evaluate age, gender and TIV effects on brainstem MR planimetric measures., Methods: Brainstem MR planimetric measures of diameters (midbrain, pons, middle and superior cerebellar peduncle) and areas (pons and midbrain), the derived ratios, and the magnetic resonance Parkinsonism index (MRPI) were assessed on 1.5-T MR images in a large cohort of 97 healthy controls and analysed for the influence of age, gender and TIV with univariate and multivariate linear models., Results: Neither gender nor age effects on planimetric measurements were observed in the population relevant for the differential diagnosis of neurodegenerative Parkinsonism, aged 50 to 80 years, except for single area-derived measurements, with gender effects on pontine area (p = 0.013) and age effects on midbrain area (p = 0.037). Results were similar upon inclusion of the TIV in the analyses., Conclusions: There is no need to correct for age, gender or TIV when using brainstem-derived MR planimetric measurements in the differential diagnosis of neurodegenerative Parkinsonism., Key Points: • There were no gender effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for pontine area). • There were no age effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for midbrain area). • There is no need for age- or gender-specific cut-offs for the relevant age group.

Background: The rate of clinical progression in patients with multiple system atrophy (MSA) varies between individuals and predictors for disease progression remain undefined. While the MSA-rasagiline study found no difference in the rates of clinical progression for patients treated with rasagiline versus placebo, it included a large, prospective magnetic resonance imaging (MRI) substudy that can provide new information on the underlying disease progression in patients with early MSA., Methods: This post-hoc analysis compared the rate of clinical progression in patients with MSA-specific structural changes at baseline (MRI-positive group) versus the rate of progression in patients without evidence of such changes at baseline (MRI-negative group) using a repeated measures ANCOVA. Clinical progression was assessed using the Unified MSA Rating Scale (UMSARS) and Clinical Global Impression of Improvement (CGI-I)., Results: Twenty-eight patients with early MSA of the parkinsonian subtype (MRI-positive n = 13; MRI-negative n = 15) who had complete baseline and follow-up UMSARS data were included in this analysis. Patients in the MRI-positive group had faster clinical progression from baseline to the end of the 48-week study compared with those in the MR-negative group as assessed by the UMSARS total (p = 0.028) and UMSARS motor (p = 0.008) scales. At week 48, MRI-positive patients also had a significantly worse health status vs. MRI-negative patients (p = 0.015)., Conclusions: This is the first study to demonstrate that MSA-specific abnormalities on structural MRI might represent a variant of MSA-P that is associated with more rapid progression and an overall worse prognosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: The hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism., Methods: Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up., Results: 481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement., Conclusion: Midbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Several previous studies examined different brainstem-derived MR planimetric measures with regards to their diagnostic accuracy in separating patients with neurodegenerative parkinsonian disorders and reported conflicting results. The current study aimed to compare their performance in a well-characterized sample of patients with neurodegenerative parkinsonian disorders., Methods: MR planimetric measurements were assessed in a large retrospective cohort of 55 progressive supranuclear palsy (PSP), 194 Parkinson's disease (PD) and 63 multiple system atrophy (MSA) patients. This cohort served as a training set used to build C4.5 decision tree models to discriminate PSP, PD and MSA. The models were validated in two independent test sets. The first test set comprised 84 patients with early, clinically unclassifiable parkinsonism (CUP). A prospective cohort of patients with PSP (n = 23), PD (n = 40) and MSA (n = 22) was exploited as a second test-set., Results: The pons-to-midbrain diameter ratio, the midbrain diameter, the middle cerebellar peduncle width and the pons area were identified as the most predictive parameters to separate PSP, MSA and PD in C4.5 decision tree models derived from the training set. Using these decision models, AUCs in discriminating PSP, MSA and PD were 0.90, 0.57 and 0.73 in the CUP-cohort and 0.95, 0.61 and 0.87 in the prospective cohort, respectively., Conclusion: We were able to demonstrate that brainstem-derived MR planimetric measures yield high diagnostic accuracy for the discrimination of PSP from related disorders when decision tree algorithms are applied, even at early, clinically uncertain stages. However, their diagnostic accuracy in discriminating PD and MSA was suboptimal., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Qualitative and quantitative structural magnetic resonance imaging offer objective measures of the underlying neurodegeneration in atypical parkinsonism. Regional changes in tissue volume, signal changes and increased deposition of iron as assessed with different structural MRI techniques are surrogate markers of underlying neurodegeneration and may reflect cell loss, microglial proliferation and astroglial activation. Structural MRI has been explored as a tool to enhance diagnostic accuracy in differentiating atypical parkinsonian disorders (APDs). Moreover, the longitudinal assessment of serial structural MRI-derived parameters offers the opportunity for robust inferences regarding the progression of APDs. This review summarizes recent research findings as (1) a diagnostic tool for APDs as well as (2) as a tool to assess longitudinal changes of serial MRI-derived parameters in the different APDs., (© 2018 Elsevier Inc. All rights reserved.)

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology and error rates in the clinical diagnosis can be high even at specialized centres. Despite several limitations, magnetic resonance imaging (MRI) has undoubtedly enhanced the diagnostic accuracy in the differential diagnosis of neurodegenerative parkinsonism over the last three decades. This review aims to summarize research findings regarding the value of the different MRI techniques, including advanced sequences at high- and ultra-high-field MRI and modern image analysis algorithms, in the diagnostic work-up of Parkinson's disease. This includes not only the exclusion of alternative diagnoses for Parkinson's disease such as symptomatic parkinsonism and atypical parkinsonism, but also the diagnosis of early, new onset, and even prodromal Parkinson's disease.

Background: Dorsolateral nigral hyperintensity on iron-sensitive magnetic resonance imaging (MRI) sequences seems to be a typical finding in Parkinson's disease (PD), but most studies have involved small samples and have had heterogeneous control populations., Objectives: The objective of this study was to perform a meta-analysis on dorsolateral nigral hyperintensity as an imaging marker for PD., Methods: The methods included a systematic literature search and a hierarchical summary receiver operating characteristics curve approach., Results: Of the 16 identified studies, 10 were suitable for analysis, including 364 PD and 231 control cases. The meta-analysis showed an overall sensitivity and specificity of the absence of dorsolateral nigral hyperintensity for PD versus controls of 97.7% and 94.6% (3 and 7 Tesla) and of 94.6% and 94.4% (3 Tesla only). Descriptive analysis among the 4 studies including patients with non-PD parkinsonism showed that dorsolateral nigral hyperintensity was absent in 89.4% of cases with atypical parkinsonian disorders (n = 74), but only in 21.7% of cases with non-neurodegenerative parkinsonism (n = 69). Moreover, in 2 of these studies, the absence of dorsolateral nigral hyperintensity predicted ipsilateral dopamine-transporter deficiency with 87.5% sensitivity and 83.6% specificity., Conclusions: Visual assessment of dorsolateral nigral hyperintensity on iron-sensitive MRI sequences provides excellent diagnostic accuracy for PD versus controls. Moreover, its loss appears to be a marker of nigral pathology and holds the potential for the differentiation of neurodegenerative from non-neurodegenerative parkinsonian disorders. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Background: Absence of a hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense pars compacta of the substantia nigra (referred to as dorsolateral nigral hyperintensity) on iron-sensitive high-field magnetic resonance imaging sequences seems to be a typical finding for patients with Parkinson's disease (PD)., Objective: This study was undertaken to evaluate the diagnostic value of the dorsolateral nigral hyperintensity in a cohort of patients with neurodegenerative parkinsonism including PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) as well as healthy controls using high-field susceptibility-weighted imaging (SWI) at 3.0 Tesla (T)., Methods: Absence of dorsolateral nigral hyperintensity was assessed on visual inspection of anonymized 3.0T SWI scans in a case-control study including 148 patients with neurodegenerative parkinsonism (PD: n = 104; MSA: n = 22; PSP: n = 22) and 42 healthy controls., Results: Dorsolateral nigral hyperintensity was absent unilaterally in all patients with MSA or PSP, in 83 of 90 patients with PD, but only in one of the healthy controls resulting in an overall correct classification of 95.2% in discriminating neurodegenerative parkinsonism from controls in the per-protocol analysis. Overall correct classification was 93.2% in the intent-to-diagnose analysis, including also SWI scans with poor quality (12.1% of all scans) for nigral evaluation., Conclusion: Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for neurodegenerative parkinsonian disorders., (© 2015 International Parkinson and Movement Disorder Society.)