Christoph Mueller

Dorsolateral nigral hyperintensity on 3.0T susceptibility‐weighted imaging in neurodegenerative Parkinsonism

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 Parkinsons disease (PD).

Potential of Diffusion Tensor Imaging and Relaxometry for the Detection of Specific Pathological Alterations in Parkinson's Disease (PD)

The purpose of the present study was to evaluate the potential of multimodal MR imaging including mean diffusivity (MD), fractional anisotropy (FA), relaxation rates R2 and R2* to detect disease specific alterations in Parkinsons Disease (PD). We enrolled 82 PD patients (PD-all) with varying disease durations (≤5 years: PD≤5, n = 43; >5 years: PD>5, n = 39) and 38 matched healthy controls (HC), receiving diffusion tensor imaging as well as R2 and R2* relaxometry calculated from multi-echo T2*-weighted and dual-echo TSE imaging, respectively. ROIs were drawn to delineate caudate nucleus (CN), putamen (PU), globus pallidus (GP) and substantia nigra (SN) on the co-registered maps. The SN was divided in 3 descending levels (SL 1–3). The most significant parameters were used for a flexible discrimination analysis (FDA) in a training collective consisting of 25 randomized subjects from each group in order to predict the classification of remaining subjects. PD-all showed significant increases in MD, R2 and R2* within SN and its subregions as well as in MD and R2* within different basal ganglia regions. Compared to the HC group, the PD≤5 and the PD>5 group showed significant MD increases within the SN and its lower two subregions, while the PD≤5 group exhibited significant increases in R2 and R2* within SN and its subregions, and tended to elevation within the basal ganglia. The PD>5 group had significantly increased MD in PU and GP, whereas the PD≤5 group presented normal MD within the basal ganglia. FDA achieved right classification in 84% of study participants. Micro-structural damage affects primarily the SN of PD patients and in later disease stages the basal ganglia. Iron contents of PU, GP and SN are increased at early disease stages of PD.

Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study

Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was to evaluate changes in the substantia nigra using single‐ and bi‐tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP.

Differences in MDS‐UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration

The Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinsons disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD.

Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients

BACKGROUND The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients. METHODS We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items. RESULTS A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue. CONCLUSIONS This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.

The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism

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 Parkinsons 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.

Diagnostic potential of dentatorubrothalamic tract analysis in progressive supranuclear palsy

BACKGROUND The differentiation of progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinsons disease (PD) remains a major clinical challenge. OBJECTIVES To evaluate the diagnostic potential of observer-independent assessments of microstructural integrity within infratentorial brain regions to differentiate PSP-Richardsons syndrome (PSP-RS), PSP-P and PD. METHODS 3T MRI parameters of mean diffusivity, fractional anisotropy, grey and white matter volumes from patients with PSP-RS (n = 12), PSP-P (n = 12) and mean disease duration of 2.4 ± 1.7 years were compared with PD patients (n = 20) and healthy controls (n = 23) by using statistical parametric mapping and the spatially unbiased infratentorial template. Subsequently MRI measurements of the dentatorubrothalamic tract were determined observer-independently by a validated probabilistic infratentorial atlas. The impairment of gait and postural stability was evaluated by a sum-score derived from the Unified Parkinson Disease Rating Scale. RESULTS Significant mean diffusivity increases, fractional anisotropy decreases and corresponding volume loss were localized in mesencephalic tegmentum, superior cerebellar peduncle, decussation of superior cerebellar peduncle and dentate nucleus in PSP-RS and PSP-P compared to PD and healthy controls. Altered microstructural integrity of the dentatorubrothalamic tract in PSP-RS was significantly more pronounced compared to PSP-P and correlated significantly with the gait and postural stability sum-score. Linear discriminant analysis identified diffusion tensor imaging measures of the dentatorubrothalamic tract and the gait and postural stability sum-score to classify correctly 95.5% of PRP-RS, PSP-P and PD patients. CONCLUSIONS Observer-independent analysis of microstructural integrity within the dentatorubrothalamic tract in combination with assessments of gait and postural stability differentiate PSP-P from PSP-RS and PD in early to moderately advanced stages.

Clinical Heterogeneity in Cerebral Hemiatrophy Syndromes

Cerebral hemiatrophy syndromes can present with variable neurological symptoms. In childhood epilepsy, mental retardation and neuropsychiatric disorders are common while in adults movement disorders, such as highly asymmetric parkinsonism or hemidystonia as well as neuropsychiatric problems have been reported.

Structural MRI in Idiopathic Parkinson Disease and Parkinsonism

Parkinsonian disorders are characterized by both motor and nonmotor symptoms with varying degrees of treatment response and disability. While current conventional magnetic resonance imaging (MRI) methods are unable to confirm a diagnosis of idiopathic Parkinson disease, they may provide a means for identifying other atypical parkinsonian syndromes. This chapter will review the state of current structural MRI modalities, the structural imaging findings in various parkinsonian disorders and disease mimics, and the use of structural MRI as a biomarker of neurodegeneration. The discussion will also provide insights into the integration of high-field MRI and multimodal imaging to future clinical practice.