Abstract: Background Cognitive deficits considerably contribute to the patient's burden in Parkinson's disease (PD). While cognitive decline is linked to neuronal dysfunction, the additional role of white matter lesions (WML) is discussed controversially. Objective To investigate the influence of WML, in comparison to neuronal dysfunction, on cognitive deficits in PD. Methods We prospectively recruited patients with PD who underwent neuropsychological assessment using the Mattis Dementia Rating Scale 2 (DRS-2) or Parkinson Neuropsychometric Dementia Assessment (PANDA) and both MRI and PET with [18F]fluorodeoxyglucose (FDG). WML-load and PD cognition-related covariance pattern (PDCP) as a measure of neuronal dysfunction were read out. Relationship between cognitive performance and rank-transformed WML was analyzed with linear regression, controlling for the patients' age. PDCP subject scores were investigated likewise and in a second step adjusting for age and WML load. Results Inclusion criteria were met by 76 patients with a mean (± SD) age of 63.5 ± 9.0 years and disease duration of 10.7 ± 5.4 years. Neuropsychological testing revealed front executive and parietal deficits and a median DRS-2 score of 137 (range 119-144)/144 and PANDA score of 22 (range 3-30)/30. No association between WML and cognition was observed, whereas PDCP subject scores showed a trend-level negative correlation with the DRS-2 (P = 0.060) as well as a negative correlation with PANDA (P = 0.049) which persisted also after additional correction for WML (P = 0.039). Conclusion The present study indicates that microangiopathic WML do not have a relevant impact on neurocognitive performance in PD whereas neuronal dysfunction does

Abstract: Identification of patients with idiopathic normal pressure hydrocephalus (iNPH) in a collective with suspected neurodegenerative disease is essential. This study aimed to determine the metabolic spatial covariance pattern of iNPH on FDG PET using an established technique based on scaled subprofile model principal components analysis (SSM-PCA). We identified 11 patients with definite iNPH. By applying SSM-PCA to the FDG PET data, they were compared to 48 age-matched healthy controls to determine the whole-brain voxel-wise metabolic spatial covariance pattern of definite iNPH (iNPH-related pattern, iNPHRP). The iNPHRP score was compared between groups of patients with definite iNPH, possible iNPH (N = 34), Alzheimer's (AD, N = 38), and Parkinson's disease (PD, N = 35) applying pairwise Mann-Whitney U tests and correction for multiple comparisons. SSM-PCA of FDG PET revealed an iNPHRP that is characterized by relative negative voxel weights at the vicinity of the lateral ventricles and relative positive weights in the paracentral midline region. The iNPHRP scores of patients with definite iNPH were substantially higher than in patients with AD and PD (both p 0.05) and non-significantly higher than those of patients with possible iNPH. Subject scores of the iNPHRP discriminated definite iNPH from AD and PD with 96% and 100% accuracy and possible iNPH from AD and PD with 83% and 86% accuracy.br

Abstract: [18F]fluorodeoxyglucose (FDG) PET and [123I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 ± 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred

Abstract: This image depicts [18F] FDG and [18F]PM-PBB3 uptake surface projections of two male patients with complex movement disturbances. They were referred for PET imaging with the suspected diagnosis of a 4-repeat (4R)-tauopathy Figure 1. Patient #1 (79 years) presented with an aggressive, non-levodopa responsive hypokinetic-rigid syndrome with early falls and a vertical supranuclear gaze palsy. Patient #2 (68 years) presented with unusually rapidly progressive dystonia, right-sided rigor, bradykinesia, alien limb phenomenon and action myoclonus of the right arm, likewise without response to levodopa. Disease duration was 11 and 5 months, respectively. CSF levels of tau and amyloid in either patient were not indicative for Alzheimer's disease. In both, [18F] FDG-PET revealed a corticobasal degeneration-like bilateral reduction of cerebral glucose metabolism in frontoparietal cortical areas (arrowheads) and in the thalamus.1 A clear asymmetry to the detriment of the right hemisphere was observed in #1, whereas hypometabolism of the left hemisphere was only slightly pronounced in #2. Subsequent imaging with tau ligand [18F]PM-PBB32 showed elevated binding (arrowheads, asterisks indicate unspecific uptake of the choroid plexus) suggestive for pathological tau aggregates in frontal and parietal areas of #1, supporting the diagnosis of a 4R-tauopathy.2 In contrast, the lack of specific [18F]PM-PBB3 binding in patient #2 questioned the diagnosis of a 4R-tau related corticobasal syndrome (CBS; eg, progressive supranuclear palsy--CBS). Diagnosis of Creutzfeld-Jakob disease in this patient was made via 14-3-3 and PrPSc aggregation assays. In conclusion, [18F]PM-PBB3-PET reveals clinical and [18F] FDG-PET mimics of 4R-tau CBS caused by Creutzfeld-Jakob disease

Abstract: Objectives The precise segmentation of atrophic structures remains challenging in neurodegenerative diseases. We determined the performance of a Deep Neural Patchwork (DNP) in comparison to established segmentation algorithms regarding the ability to delineate the putamen in multiple system atrophy (MSA), Parkinson's disease (PD), and healthy controls. Methods We retrospectively included patients with MSA and PD as well as healthy controls. A DNP was trained on manual segmentations of the putamen as ground truth. For this, the cohort was randomly split into a training (N = 131) and test set (N = 120). The DNP's performance was compared with putaminal segmentations as derived by Automatic Anatomic Labelling, Freesurfer and Fastsurfer. For validation, we assessed the diagnostic accuracy of the resulting segmentations in the delineation of MSA vs. PD and healthy controls. Results A total of 251 subjects (61 patients with MSA, 158 patients with PD, and 32 healthy controls; mean age of 61.5 ± 8.8 years) were included. Compared to the dice-coefficient of the DNP (0.96), we noted significantly weaker performance for AAL3 (0.72; p .001), Freesurfer (0.82; p .001), and Fastsurfer (0.84, p .001). This was corroborated by the superior diagnostic performance of MSA vs. PD and HC of the DNP (AUC 0.93) versus the AUC of 0.88 for AAL3 (p = 0.02), 0.86 for Freesurfer (p = 0.048), and 0.85 for Fastsurfer (p = 0.04).brbrConclusionbrBy utilization of a DNP, accurate segmentations of the putamen can be obtained even if substantial atrophy is present. This allows for more precise extraction of imaging parameters or shape features from the putamen in relevant patient cohorts.

Abstract: The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists. Five different topics with several clinical symptom items were discussed and consensus criteria were tested. This resulted in distinct symptom patterns for each atypical Parkinsonian syndrome showing the multitude of clinical involvement in each neurodegenerative disease. Strongly discriminating clinical signs were few and levels of indication were variable. A prospective validation of the assessments made is needed. This demonstrates that both clinical evaluation and elaborate additional diagnostic procedures are needed to achieve a high diagnostic standard

Abstract: Grammar provides the framework for understanding and producing language. In aphasia, an acquired language disorder, grammatical deficits are diversified and widespread. However, the few assessments for testing grammar in the German language do not consider current linguistic, psycholinguistic, and functional imaging data, which have been shown to be crucial for effective treatment. This study developed German language versions of the Northwestern Assessment of Verbs and Sentences (NAVS-G) and the Northwestern Anagram Test (NAT-G) to examine comprehension and production of verbs, controlling for the number and optionality of verb arguments, and sentences with increasing syntactic complexity. The NAVS-G and NAT-G were tested in 27 healthy participants, 15 right hemispheric stroke patients without aphasia, and 15 stroke patients with mild to residual aphasia. Participants without aphasia showed near-perfect performance, with the exception of (object) relative sentences, where accuracy was associated with educational level. In each patient with aphasia, deficits in more than one subtest were observed. The within and between population-groups logistic mixed regression analyses identified significant impairments in processing syntactic complexity at the verb and sentence levels. These findings indicate that the NAVS-G and NAT-G have potential for testing grammatical competence in (German) stroke patients