Differentiation of atypical Parkinson syndromes

Höglinger, Günter U.; Kassubek, Jan; Csóti, Ilona; Ehret, R.; Herbst, Heinz; Wellach, Ingmar; Winkler, Jürgen; Jost, Wolfgang H.

doi:10.1007/s00702-017-1700-4

Cited by 32 publications

(21 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3 Given that DLB and PDD show overlapping clinical and pathological features, [4][5][6] it appears controversial whether they are different diseases or clinical manifestations of the same Lewy bodies disease spectrum. 3 Given that DLB and PDD show overlapping clinical and pathological features, [4][5][6] it appears controversial whether they are different diseases or clinical manifestations of the same Lewy bodies disease spectrum.…”

mentioning

confidence: 99%

Seeding variability of different alpha synuclein strains in synucleinopathies

Candelise

Schmitz

Llorens

et al. 2019

Annals of Neurology

View full text Add to dashboard Cite

Objectives: Currently, the exact reasons why different α-synucleinopathies exhibit variable pathologies and phenotypes are still unknown. A potential explanation may be the existence of distinctive α-synuclein conformers or strains. Here, we intend to analyze the seeding activity of dementia with Lewy bodies (DLB) and Parkinson's disease (PD) brain-derived α-synuclein seeds by real-time quaking-induced conversion (RT-QuIC) and to investigate the structure and morphology of the α-synuclein aggregates generated by RT-QuIC. Methods: A misfolded α-synuclein-enriched brain fraction from frontal cortex and substantia nigra pars compacta tissue, isolated by several filtration and centrifugation steps, was subjected to α-synuclein/RT-QuIC analysis. Our study included neuropathologically well-characterized cases with DLB, PD, and controls (Ctrl). Biochemical and morphological analyses of RT-QuIC products were conducted by western blot, dot blot analysis, Raman spectroscopy, atomic force microscopy, and transmission electron microscopy. Results: Independently from the brain region, we observed different seeding kinetics of α-synuclein in the RT-QuIC in patients with DLB compared to PD and Ctrl. Biochemical characterization of the RT-QuIC product indicated the generation of a proteinase K-resistant and fibrillary α-synuclein species in DLB-seeded reactions, whereas PD and control seeds failed in the conversion of wild-type α-synuclein substrate. Interpretation: Structural variances of α-synuclein seeding kinetics and products in DLB and PD indicated, for the first time, the existence of different α-synuclein strains in these groups. Therefore, our study contributes to a better understanding of the clinical heterogeneity among α-synucleinopathies, offers an opportunity for a specific diagnosis, and opens new avenues for the future development of strain-specific therapies. ANN NEUROL 2019;85:691-703 S ynucleinopathies, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), are a class of neurodegenerative diseases characterized by the presence of insoluble intraneural deposits consisting of fibrillary α-synuclein, 1,2 referred to as Lewy bodies. A PD with dementia (PDD) diagnosis is appropriate when the cognitive symptoms View this article online at wileyonlinelibrary.com.

show abstract

mentioning

confidence: 99%

Seeding variability of different alpha synuclein strains in synucleinopathies

Candelise

Schmitz

Llorens

et al. 2019

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…Further correlation analysis showed that the CBF of left IFG_Tri was positively correlated with the MMSE score and the CBF of the right cerebellum_crus2 was positively correlated with HAMA and HAMD scores in PPS patients. The association between the hypoperfusion in the cerebellum, thalamus, SMA and the damage in the extrapyramidal system has been described in PPS patients [41]. Thus, more widespread and severe impairment of CBF in PPS might re ect more severity of PPS or later stage of disease.…”

Section: Discussionmentioning

confidence: 94%

Discriminative Pattern of Reduced Cerebral Blood Flow in Parkinson's Disease and Parkinsonism-Plus Syndrome: an ASL-MRI study

Cheng

Guo

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Accurate identification of Parkinson's disease (PD) and Parkinsonism-Plus syndrome (PPS), especially in the early stage of the disease, is very important. The purpose of this study was to investigate the discriminative spatial pattern of cerebral blood flow (CBF) between patients with PD and PPS. Methods: Arterial spin labeling (ASL) perfusion-weighted imaging was performed in 20 patients with PD (mean age 56.35±7.56 years), 16 patients with PPS (mean age 59.62±6.89 years), and 17 healthy controls (HCs, mean age 54.17±6.58 years). Voxel-wise comparison of the CBF was performed among PD, PPS, and HC groups. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CBF in discriminating between PD and PPS. The relationship between CBF and non-motor neuropsychological scores was assessed by correlation analysis. Results: PD group showed a significantly decreased CBF in the right cerebelum_crus2, the left middle frontal gyrus (MFG), the triangle inferior frontal gyrus (IFG_Tri), the left frontal medial orbital gyrus (FG_Med_Orb) and the left caudate nucleus (CN) compared with the HC group (P < 0.05). Besides the above regions, the left supplementary motor area (SMA), the right thalamus had decreased CBF in the PPS group compared with the HC group (P < 0.05). PPS group had lower CBF value in the left MFG, the left IFG_Tri, the left CN, the left SMA, and the right thalamus compared with the PD group (P < 0.05). CBFs in left IFG_Tri, the left CN, the left SMA, and the right thalamus had moderate to high capacity in discriminating between PD and PPS patients (AUC 0.719-0.831). The CBF was positively correlated with MMSE and Montreal cognitive assessment (MoCA) scores in PD patients, while positively correlated with the Mini-mental State Examination (MMSE), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD) scores in PPS patients (P < 0.05). Conclusion: PD and PPS patients have certain discriminative patterns of reduced CBFs, which can be used as a surrogate marker for differential diagnosis.

show abstract

“…In addition, CBD can often present with complex cognitive difficulties and neuropsychiatric disturbances 4,5. Symptoms of depression, apathy, or agitation can be subtle and are often overlooked as reactions to receiving a new diagnosis of Parkinsonism 4–6. Here, we report a case of exacerbated depression with cognitive impairment that was later diagnosed as CBD.…”

Section: Introductionmentioning

confidence: 93%

Levodopa-responsive depression associated with corticobasal degeneration: a case report

Tarakita

Nishijima

Yasui‐Furukori

2017

NDT

View full text Add to dashboard Cite

A 60-year-old female was treated for depression with the antidepressant paroxetine for 13 years. The patient had experienced clumsiness and mild rigidity in the left hand, and had agraphia and mild subjective memory complaints for 3 years prior to admission in our hospital. She experienced exacerbated depression that included worsened depressive mood, lowered motivation, and suicidal ideation without precipitating stressful life events for 2 years prior to admission, and although she had continued taking the antidepressant, these symptoms were not ameliorated by increasing the dose of paroxetine. Following the development of myoclonus and pain in her left arm, we performed magnetic resonance imaging of her head, that revealed diffuse atrophy and right parietal lobe atrophy. The patient was ultimately diagnosed with corticobasal degeneration (CBD). Her left arm myoclonus and depression improved following levodopa administration. Therefore, we concluded that the recurrent depression may have been induced by CBD.

show abstract

Differentiation of atypical Parkinson syndromes

Cited by 32 publications

References 55 publications

Seeding variability of different alpha synuclein strains in synucleinopathies

Seeding variability of different alpha synuclein strains in synucleinopathies

Discriminative Pattern of Reduced Cerebral Blood Flow in Parkinson's Disease and Parkinsonism-Plus Syndrome: an ASL-MRI study

Levodopa-responsive depression associated with corticobasal degeneration: a case report

Contact Info

Product

Resources

About