Journal ArticleDOI
Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study
Jacob Horsager,Katrine B. Andersen,Karoline Knudsen,Casper Skjærbæk,Tatyana D. Fedorova,Niels Okkels,Eva Schaeffer,Sarah K Bonkat,Jacob Geday,Marit Otto,Michael Sommerauer,Erik H. Danielsen,Einar Bech,Jonas Kraft,Ole Lajord Munk,Sandra D Hansen,Nicola Pavese,Nicola Pavese,Robert Göder,David J. Brooks,David J. Brooks,Daniela Berg,Per Borghammer +22 more
TLDR
The existence of brain-first and body-first subtypes of Parkinson's disease is supported by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups using multimodal imaging.Abstract:
Parkinson's disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner However, it remains uncertain where the initial α-synuclein aggregates originate We have hypothesized that Parkinson's disease comprises two subtypes A brain-first (top-down) type, where α-synuclein pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system; and a body-first (bottom-up) type, where the pathology originates in the enteric or peripheral autonomic nervous system and then spreads to the brain We also hypothesized that isolated REM sleep behaviour disorder (iRBD) is a prodromal phenotype for the body-first type Using multimodal imaging, we tested the hypothesis by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups We included 37 consecutive de novo patients with Parkinson's disease into this case-control PET study Patients with Parkinson's disease were divided into 24 RBD-negative (PDRBD-) and 13 RBD-positive cases (PDRBD+) and a comparator group of 22 iRBD patients We used 11C-donepezil PET/CT to assess cholinergic (parasympathetic) innervation, 123I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure the integrity of locus coeruleus pigmented neurons, and 18F-dihydroxyphenylalanine (FDOPA) PET to assess putaminal dopamine storage capacity Colon volume and transit times were assessed with CT scans and radiopaque markers Imaging data from the three groups were interrogated with ANOVA and Kruskal-Wallis tests corrected for multiple comparisons The PDRBD- and PDRBD+ groups showed similar marked reductions in putaminal FDOPA-specific uptake, whereas two-thirds of iRBD patients had normal scans (P < 10-13, ANOVA) When compared to the PDRBD- patients, the PDRBD+ and iRBD patients showed reduced mean MIBG heart:mediastinum ratios (P < 10-5, ANOVA) and colon 11C-donepezil standard uptake values (P = 0008, ANOVA) The PDRBD+ group trended towards a reduced mean MRI locus coeruleus: pons ratio compared to PDRBD- (P = 007, t-test) In comparison to the other groups, the PDRBD+ group also had enlarged colon volumes (P < 0001, ANOVA) and delayed colonic transit times (P = 001, Kruskal-Wallis) The combined iRBD and PDRBD+ patient data were compatible with a body-first trajectory, characterized by initial loss of cardiac MIBG signal and 11C-colonic donepezil signal followed by loss of putaminal FDOPA uptake In contrast, the PDRBD- data were compatible with a brain-first trajectory, characterized by primary loss of putaminal FDOPA uptake followed by a secondary loss of cardiac MIBG signal and 11C-donepezil signal These findings support the existence of brain-first and body-first subtypes of Parkinson's diseaseread more
Citations
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Journal Article
MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)
Ronald B. Postuma,Daniela Berg +1 more
TL;DR: The International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease as discussed by the authors have been proposed for clinical diagnosis, which are intended for use in clinical research, but may also be used to guide clinical diagnosis.
Journal ArticleDOI
Gastrointestinal Dysfunction in Parkinson’s Disease
TL;DR: Bowel management for these people must remain empirical until well-designed controlled trials with adequate numbers and clinically relevant outcome measures become available, according to the conclusion from the latest Cochrane review on treatment of bowel dysfunction in central neurological diseases.
Journal ArticleDOI
Prodromal Parkinson disease subtypes - key to understanding heterogeneity.
Daniela Berg,Per Borghammer,Per Borghammer,Seyed-Mohammad Fereshtehnejad,Sebastian Heinzel,Jacob Horsager,Eva Schaeffer,Ronald B. Postuma,Ronald B. Postuma,Ronald B. Postuma +9 more
TL;DR: In this article, the authors classified clinical and prodromal PD into subtypes with different clinical manifestations, pathomechanisms and patterns of spatial and temporal progression in the CNS and PNS.
Journal ArticleDOI
Periphery and brain, innate and adaptive immunity in Parkinson's disease.
TL;DR: Parkinson's disease (PD) is a neurodegenerative disorder where alpha-synuclein plays a central role in the death and dysfunction of neurons, both, in central, as well as in the peripheral nervous system as discussed by the authors.
Journal ArticleDOI
The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson's Disease: Explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline.
TL;DR: The α-Synuclein Origin Site and Connectome (SOC) model proposed in this article is a new model of Parkinson's disease pathogenesis, incorporating two aspects of α-synuclein pathobiology that impact the disease course for each patient.
References
More filters
Journal ArticleDOI
Staging of brain pathology related to sporadic Parkinson’s disease
TL;DR: This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
Journal ArticleDOI
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium
Ian G. McKeith,Ian G. McKeith,Dennis W. Dickson,James Lowe,Murat Emre,John T. O'Brien,Howard Feldman,Jeffrey L. Cummings,John E. Duda,Carol F. Lippa,Elaine K. Perry,Dag Aarsland,Hiroyuki Arai,Clive Ballard,B. F. Boeve,David J. Burn,Durval C. Costa,T. Del Ser,Bruno Dubois,Douglas Galasko,Serge Gauthier,Christopher G. Goetz,Estrella Gómez-Tortosa,Glenda M. Halliday,L. A. Hansen,John Hardy,Takeshi Iwatsubo,Raj N. Kalaria,Daniel I. Kaufer,Rose Anne Kenny,Amos D. Korczyn,Kenji Kosaka,Virginia M.-Y. Lee,Andrew J. Lees,Irene Litvan,Elisabet Londos,Oscar L. Lopez,Satoshi Minoshima,Yoshikuni Mizuno,José Antonio Molina,Elizabeta B. Mukaetova-Ladinska,Florence Pasquier,Robert H. Perry,Jörg B. Schulz,John Q. Trojanowski,Masahito Yamada +45 more
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Journal ArticleDOI
MDS clinical diagnostic criteria for Parkinson's disease
Ronald B. Postuma,Daniela Berg,Matthew B. Stern,Werner Poewe,C. Warren Olanow,Wolfgang H. Oertel,Jose A. Obeso,Kenneth Marek,Irene Litvan,Anthony E. Lang,Glenda M. Halliday,Christopher G. Goetz,Thomas Gasser,Bruno Dubois,Piu Chan,Bastiaan R. Bloem,Charles H. Adler,Guenther Deuschl +17 more
TL;DR: The Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity, and two levels of certainty are delineated: clinically established PD and probable PD.
Journal ArticleDOI
‘Sniffin’ Sticks': Olfactory Performance Assessed by the Combined Testing of Odor Identification, Odor Discrimination and Olfactory Threshold
TL;DR: 'Sniffin'
Journal Article
MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)
Ronald B. Postuma,Daniela Berg +1 more
TL;DR: The International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease as discussed by the authors have been proposed for clinical diagnosis, which are intended for use in clinical research, but may also be used to guide clinical diagnosis.
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