Brainstem Biomarkers of Clinical Variant and Pathology in Progressive Supranuclear Palsy.

BACKGROUND: Magnetic resonance brainstem measurements are useful structural biomarkers in the Richardson's syndrome variant of progressive supranuclear palsy (PSP). However, it is unclear how these biomarkers differ across the phenotypic spectrum of PSP and how they relate to underlying pathology. OBJECTIVE: The aim of this study was to compare brainstem imaging measures across clinical variants of PSP and determine sensitivity and specificity based on pathologically diagnosed cases. METHODS: A total of 153 patients with PSP who represented eight clinical variants were recruited at Mayo Clinic (Rochester, MN, USA) and underwent structural magnetic resonance imaging (MRI). Midbrain and pons area and superior and middle cerebellar peduncle width measurements were performed, and midbrain/pons ratio and Magnetic Resonance Parkinsonism Index (MRPI) were calculated. Among the 43 patients who later died, PSP pathology was confirmed in 29, whereas 14 had other pathology. RESULTS: Brainstem measurements varied across PSP clinical variants and were most abnormal in PSP-Richardson's syndrome and frontal variants, followed by PSP-corticobasal, PSP-speech/language, and PSP-parkinsonism variants. All these variants showed abnormalities compared with controls. The PSP-gait freezing variant and patients with prominent corticospinal tract signs showed normal brainstem measures. Among cases with confirmed PSP pathology, the midbrain area, midbrain/pons ratio, and MRPI were all more abnormal compared to those with other pathologies, with best differentiation obtained with the MRPI (sensitivity = 83%; specificity = 85%). CONCLUSIONS: MRI brainstem measures show utility as diagnostic biomarkers across PSP clinical variants and have the potential to be useful in predicting underlying pathology. © 2021 International Parkinson and Movement Disorder Society.

A method for fast automated assessment of the magnetic resonance parkinsonism index.

In patients with parkinsonian syndromes, and particularly during the early stages of the clinical disease, differentiating between idiopathic Parkinson's disease and progressive supranuclear palsy is challenging. Imaging plays an important role in early diagnosis, and the magnetic resonance parkinsonism index was shown to reliably differentiate between the two entities. Calculation of the index is a time-consuming process. We developed an algorithm allowing its automatic calculation based on 3D T1-weighted images, producing additional color-coded images for verification.

The utility of quantitative MRI parameters in discriminating progressive supranuclear palsy from Parkinson's disease.

OBJECTIVE: We sought to re-evaluate the utility of all the quantitative neuroimaging parameters attributed to progressive supranuclear palsy (PSP) in discrimination between PSP and Parkinson' s disease (PD) subjects in our cohort. We aimed to propose some practical clinical remarks in this field. METHODS: In our retrospective study, 19 patients with 'probable' PSP and 37 patients with PD were enrolled. The radiological measurements of PSP, described in the previous reports, have been calculated in all subjects. The comparisons between the groups were performed and the measures regarding the accuracy of these parameters in the differentiation of PSP from PD subjects were analyzed. RESULTS: We found that the values of magnetic resonance parkinsonism index-2 (MRPI-2), pontine-to-midbrain area (P/M) ratio, P/M 2 ratio, and 3rdV/bifrontal width ratio had high AUC values and very good discriminative powers. The analyses revealed that; for the discrimination of PSP from PD subjects, a 3rdvent/bifrontal width cut-off value of 0.30 had 42.1 % sensitivity and 97.3 % specificity; a P/M cut-off value of 6.03 had a 52.6 % sensitivity and 97.3 % specificity; and an MRPI-2 cut-off value of 7.43 had 57.9 % sensitivity and 97.3 % specificity. Remarkably, we also found that the presence of high values for both P/M and 3rdV/bifrontal ventricle rate had a positive predictive value of 100% for the diagnosis of PSP. CONCLUSION: Our study results support the utility of previously defined neuroimaging parameters in distinguishing PSP and PD subjects. Besides, combined use of a high P/M ratio and 3rdV/bifrontal width may be practical and present strictly high evidence for the diagnosis of PSP.

Differentiating between common PSP phenotypes using structural MRI: a machine learning study.

BACKGROUND: Differentiating Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) from PSP-Parkinsonism (PSP-P) may be extremely challenging. In this study, we aimed to distinguish these two PSP phenotypes using MRI structural data. METHODS: Sixty-two PSP-RS, 40 PSP-P patients and 33 control subjects were enrolled. All patients underwent brain 3 T-MRI; cortical thickness and cortical/subcortical volumes were extracted using Freesurfer on T1-weighted images. We calculated the automated MR Parkinsonism Index (MRPI) and its second version including also the third ventricle width (MRPI 2.0) and tested their classification performance. We also employed a Machine learning (ML) classification approach using two decision tree-based algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) with different combinations of structural MRI data in differentiating between PSP phenotypes. RESULTS: MRPI and MRPI 2.0 had AUC of 0.88 and 0.81, respectively, in differentiating PSP-RS from PSP-P. ML models demonstrated that the combination of MRPI and volumetric/thickness data was more powerful than each feature alone. The two ML algorithms showed comparable results, and the best ML model in differentiating between PSP phenotypes used XGBoost with a combination of MRPI, cortical thickness and subcortical volumes (AUC 0.93 ± 0.04). Similar performance (AUC 0.93 ± 0.06) was also obtained in a sub-cohort of 59 early PSP patients. CONCLUSION: The combined use of MRPI and volumetric/thickness data was more accurate than each MRI feature alone in differentiating between PSP-RS and PSP-P. Our study supports the use of structural MRI to improve the early differential diagnosis between common PSP phenotypes, which may be relevant for prognostic implications and patient inclusion in clinical trials.

Imaging Criteria for the Diagnosis of Progressive Supranuclear Palsy: Supportive or Mandatory?

We present the case of a 54-year-old male, without any significant medical history, who insidiously developed speech disturbances and walking difficulties, accompanied by backward falls. The symptoms progressively worsened over time. The patient was initially diagnosed with Parkinson's disease; however, he failed to respond to standard therapy with Levodopa. He came to our attention for worsening postural instability and binocular diplopia. A neurological exam was highly suggestive of a Parkinson-plus disease, most likely progressive supranuclear gaze palsy. Brain MRI was performed and revealed moderate midbrain atrophy with the characteristic "hummingbird" and "Mickey mouse" signs. An increased MR parkinsonism index was also noted. Based on all clinical and paraclinical data, a diagnosis of probable progressive supranuclear palsy was established. We review the main imaging features of this disease and their current role in diagnosis.

Magnetic Resonance Planimetry in the Differential Diagnosis between Parkinson's Disease and Progressive Supranuclear Palsy.

The clinical differential diagnosis between Parkinson's disease (PD) and progressive supranuclear palsy (PSP) is often challenging. The description of milder PSP phenotypes strongly resembling PD, such as PSP-Parkinsonism, further increased the diagnostic challenge and the need for reliable neuroimaging biomarkers to enhance the diagnostic certainty. This review aims to summarize the contribution of a relatively simple and widely available imaging technique such as MR planimetry in the differential diagnosis between PD and PSP, focusing on the recent advancements in this field. The development of accurate MR planimetric biomarkers, together with the implementation of automated algorithms, led to robust and objective measures for the differential diagnosis of PSP and PD at the individual level. Evidence from longitudinal studies also suggests a role of MR planimetry in predicting the development of the PSP clinical signs, allowing to identify PSP patients before they meet diagnostic criteria when their clinical phenotype can be indistinguishable from PD. Finally, promising evidence exists on the possible association between MR planimetric measures and the underlying pathology, with important implications for trials with new disease-modifying target therapies.

Is MRPI 2.0 More Useful than MRPI and M/P Ratio in Differential Diagnosis of PSP-P with Other Atypical Parkinsonisms?

Differential diagnosis of progressive supranuclear palsy remains difficult, especially when it comes to the parkinsonism predominant type (PSP-P), which has a more favorable clinical course. In this entity, especially during the advanced stages, significant clinical overlaps with other tauopathic parkinsonian syndromes and multiple system atrophy (MSA) can be observed. Among the available additional diagnostic methods in every-day use, magnetic resonance imaging (MRI) focused specifically on the evaluation of the mesencephalon seems to be crucial as it is described as a parameter associated with PSP. There is growing interest in relation to more advanced mesencephalic parameters, such as the magnetic resonance parkinsonism index (MRPI) and MRPI 2.0. Based on the evaluation of 74 patients, we demonstrate that only the mesencephalon/pons ratio and MRPI show a significant difference between PSP-P and MSA-parkinsonian type (MSA-P). Interestingly, this differential feature was not maintained by MRPI 2.0. The mesencephalon to pons ratio (M/P), MRPI and MRPI 2.0 were not found to be feasible for the differentiation of PSP-P from other atypical tauopathic syndromes.

Methods and utility of quantitative brainstem measurements in progressive supranuclear palsy versus Parkinson's disease in a routine clinical setting.

BACKGROUND AND PURPOSE: The clinical diagnosis of progressive supranuclear palsy can be challenging, as the clinical presentation overlaps with that of Parkinson's disease and multiple system atrophy. We sought to examine the practical utility of radiologic markers of progressive supranuclear palsy by investigating whether these markers could distinguish between patients with progressive supranuclear palsy-Richardson syndrome (PSP-RS) and those with Parkinson's disease based on imaging obtained in a typical clinical setting, not in a prospective research environment. MATERIALS AND METHODS: This retrospective study included 13 patients with PSP-RS and 13 patients with Parkinson's disease who were followed for either condition at our institution at the time of the study and who had MRI records available. Patients were selected without regard to type of imaging obtained. All diagnoses were confirmed by a trained movement disorders specialist using validated diagnostic criteria. Groups were matched for age and disease duration at the time of scanning. MRI records were retrospectively obtained, and image analysis was performed by investigators blinded to disease classification. Midbrain area, midbrain to pons area ratio, midbrain anterior-posterior diameter, and MR parkinsonism index were calculated for each patient. RESULTS: All established measures of identifying progressive supranuclear palsy (midbrain area, midbrain to pons area ratio, midbrain anterior-posterior diameter, and MR parkinsonism index) were significantly different between patients with PSP-RS and those with Parkinson's disease. CONCLUSION: Previously established radiographic markers distinguishing between PSP-RS and Parkinson's disease have practical utility in the clinical setting and not just in well-designed prospective analyses.

Diagnostic validity of magnetic resonance parkinsonism index in differentiating patients with progressive supranuclear palsy from patients with Parkinson's disease.

BACKGROUND: Progressive supranuclear palsy is a neuropathologically defined disease, and many studies worked on detecting the diagnostic use of Magnetic resonance imaging. This article purposed to detect the diagnostic performance of Magnetic resonance parkinsonism index (MRPI). METHODS: We systematically searched electronic database PubMed for articles published since 1996 using the National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria as the diagnostic standard. Methodological quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and software Review Manager 5.3, software STATA 14.0 and meta-disc were applied in statistics analysis. RESULTS: Totally 14 articles were included in this article. MRPI is proved to have pooled sensitivity of 0.98, pooled specificity of 0.99 in differentiating patients with Progressive supranuclear palsy (PSP) from patients with Parkinson's disease (PD) and the area under the Receiver operating characteristic curve value was 1.00. CONCLUSION: MRPI shows excellent performance in differentiating patients with PSP from patients with PD, the clinical usage of MRPI in auxiliary diagnosis of PSP is recommended.

Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease.

BACKGROUND: Advanced brain MR techniques are useful tools for differentiating Progressive Supranuclear Palsy from Parkinson's disease, although time-consuming and unlikely to be used all together in routine clinical work. We aimed to compare the diagnostic accuracy of quantitative morphometric, volumetric and DTI metrics for differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease. METHODS: 23 Progressive Supranuclear Palsy-Richardson's Syndrome and 42 Parkinson's disease patients underwent a standardized 1.5T brain MR protocol comprising high-resolution T1W1 and DTI sequences. Brainstem and cerebellar peduncles morphometry, automated volumetric analysis of brain deep gray matter and DTI metric analyses of specific brain structures were carried out. We determined diagnostic accuracy, sensitivity and specificity of MR-markers with respect to the clinical diagnosis by using univariate receiver operating characteristics curve analyses. Age-adjusted multivariate receiver operating characteristics analyses were then conducted including only MR-markers with a sensitivity and specificity exceeding 80%. RESULTS: Morphometric markers (midbrain area, pons to midbrain area ratio and MR Parkinsonism Index), DTI parameters (infratentorial structures) and volumetric analysis (thalamus, putamen and pallidus nuclei) presented moderate to high diagnostic accuracy in discriminating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, with midbrain area showing the highest diagnostic accuracy (99%) (mean ± standard deviation: 75.87 ± 16.95 mm(2) vs 132.45 ± 20.94 mm(2), respectively; p < 0.001). CONCLUSION: Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.