Cohort Study in Parkinsonism: Delayed Transit, Accelerated Gastric Emptying, and Prodromal Dysmotility

2020 ◽  
pp. 10.1212/CPJ.0000000000001003
Author(s):  
Katayoun Khoshbin ◽  
Anhar Hassan ◽  
Michael Camilleri
Keyword(s):  
Gastric Emptying ◽  
Multiple System Atrophy ◽  
Parkinson Disease ◽  
Disease Duration ◽  
Lewy Bodies ◽  
Colonic Transit ◽  
Parkinsonian Syndrome ◽  
Record Review ◽  
Motor Onset ◽  
Levodopa Equivalent Daily Dose

ABSTRACTObjectives:To evaluate gastric emptying and colonic transit in a cohort of patients with Parkinson disease and other parkinsonism disorders, and to determine whether abnormal gut transit precedes motor-onset of parkinsonism.Methods:Medical record review of 84 patients with parkinsonism who underwent clinically-indicated transit studies at Mayo Clinic (2001-2019); and 11 patients with transit studies who subsequently developed parkinsonism. Data are summarized as median (IQR).Results:The 84 patients (52% female) with parkinsonism were aged 72 (66, 76) years with a disease duration of 5 (2, 8) years: Parkinson disease=70, multiple system atrophy=7, dementia with Lewy bodies=4, progressive supranuclear palsy=2, parkinsonian syndrome=1. Ten had delayed GE, 10 slow colonic transit, 16 accelerated GE (14 Parkinson disease, 1 multiple system atrophy, 1 parkinsonian syndrome), and 49 normal transit. One parkinsonian syndrome patient had both slow colonic and accelerated gastric transit. Longer disease duration and higher levodopa equivalent daily dose were observed for Parkinson disease compared to other parkinsonisms and with slow compared to normal colonic transit. Of 11 patients (5 female) with transit studies who later developed motor parkinsonism after 4 (3, 5) years: 1 had accelerated GE, 1 had delayed GE, and 1 had both delayed GE and colonic transit.Conclusions:Accelerated GE was newly identified in patients with parkinsonism, in addition to delayed GE or colonic transit. Furthermore, gut dysmotility was objectively identified to precede the motor-onset of parkinsonism.

Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease

Neurology ◽  
2018 ◽  
Vol 90 (12) ◽  
pp. e1029-e1037 ◽  
Author(s):  
Andrea Pilotto ◽  
Enrico Premi ◽  
Silvia Paola Caminiti ◽  
Luca Presotto ◽  
Rosanna Turrone ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Fdg Pet ◽  
Cognitive Assessment ◽  
Disease Duration ◽  
Age At Onset ◽  
Statistical Parametric Mapping ◽  
Lewy Bodies ◽  
Single Subject ◽  
Incident Dementia

ObjectiveTo evaluate the statistical parametric mapping (SPM) procedure for fluorodeoxyglucose (FDG)-PET imaging as a possible single-subject marker of progression to dementia in Parkinson disease (PD).MethodsFifty-four consecutive patients with PD without dementia (age at onset of 59.9 ± 10.1 years, disease duration of 5.3 ± 3.4 years) entered the study. The patients underwent an extensive motor and cognitive assessment and a single-subject FDG-PET SPM evaluation at baseline. A 4-year follow-up provided disease progression and dementia diagnosis.ResultsThe FDG-PET SPM was evaluated by 2 expert raters allowing the identification of a “typical PD pattern” in 29 patients, whereas 25 patients presented with “atypical patterns,” namely, dementia with Lewy bodies (DLB)-like (n = 12), Alzheimer disease (AD)-like (n = 6), corticobasal syndrome (CBS)-like (n = 5), and frontotemporal dementia (FTD)-like (n = 2). At 4-year follow-up, 13 patients, all showing atypical brain metabolic patterns at baseline, progressed to dementia (PD dementia). The DLB- and AD-like SPM patterns were the best predictor for incident dementia (p < 0.005, sensitivity 85%, specificity 88%), independently from demographics or cognitive baseline classification.ConclusionsThis study suggests that FDG-PET SPM at the single-subject level might help in identifying patients with PD at risk of developing dementia.

scholarly journals Slow Progressive Accumulation of Oligodendroglial Alpha-Synuclein (α-Syn) Pathology in Synthetic α-Syn Fibril-Induced Mouse Models of Synucleinopathy

2019 ◽  
Vol 78 (10) ◽  
pp. 877-890 ◽  
Author(s):  
Norihito Uemura ◽  
Maiko T Uemura ◽  
Angela Lo ◽  
Fares Bassil ◽  
Bin Zhang ◽  
...  
Keyword(s):  
White Matter ◽  
Multiple System Atrophy ◽  
Parkinson Disease ◽  
Mouse Models ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Wild Type ◽  
Time Points ◽  
Progressive Accumulation

Abstract Synucleinopathies are composed of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Alpha-synuclein (α-Syn) forms aggregates mainly in neurons in PD and DLB, while oligodendroglial α-Syn aggregates are characteristic of MSA. Recent studies have demonstrated that injections of synthetic α-Syn preformed fibrils (PFFs) into the brains of wild-type (WT) animals induce intraneuronal α-Syn aggregates and the subsequent interneuronal transmission of α-Syn aggregates. However, injections of α-Syn PFFs or even brain lysates of patients with MSA have not been reported to induce oligodendroglial α-Syn aggregates, raising questions about the pathogenesis of oligodendroglial α-Syn aggregates in MSA. Here, we report that WT mice injected with mouse α-Syn (m-α-Syn) PFFs develop neuronal α-Syn pathology after short postinjection (PI) intervals on the scale of weeks, while oligodendroglial α-Syn pathology emerges after longer PI intervals of several months. Abundant oligodendroglial α-Syn pathology in white matter at later time points is reminiscent of MSA. Furthermore, comparison between young and aged mice injected with m-α-Syn PFFs revealed that PI intervals rather than aging correlate with oligodendroglial α-Syn aggregation. These results provide novel insights into the pathological mechanisms of oligodendroglial α-Syn aggregation in MSA.

scholarly journals Serotonin Transporter Availability in Early Stage Parkinson’s Disease and Multiple System Atrophy

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
S. R. Suwijn ◽  
H. W. Berendse ◽  
C. V. M. Verschuur ◽  
R. M. A. de Bie ◽  
J. Booij
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Dopamine Transporter ◽  
Serotonin Transporter ◽  
Disease Duration ◽  
Early Stage ◽  
Spect Imaging ◽  
Parkinsonian Syndrome ◽  
Atypical Parkinsonian Syndrome

Background. Differentiating Parkinson’s disease (PD) from multiple system atrophy (MSA) can be challenging especially early in the course of the disease. Previous studies have shown that midbrain serotonin transporter (SERT) availability in patients with established MSA was significantly lower compared to PD. It is unknown if this is also true for early-stage patients. Methods. 77 early-stage, untreated PD patients were recruited between 1995 and 1998, underwent [123I]β-CIT SPECT imaging, and were followed for at least five years. 16 patients were lost to followup, and in 4 the diagnosis was changed to another atypical parkinsonian syndrome, but not in MSA. In 50 patients, the PD diagnosis was unchanged at followup. In seven patients, the diagnosis was changed to MSA at followup. We retrospectively assessed baseline midbrain SERT availability as well as midbrain SERT-to-striatal dopamine transporter (DAT) ratios. Results. No difference in baseline [123I]β-CIT SERT availability was found. The midbrain SERT-to-striatal DAT ratio for whole striatum was significantly lower in patients with PD compared to MSA (P=0.049). However, when adjusting for the disease duration at imaging this difference is not significant (P=0.070). Conclusion. Midbrain SERT availability is not different between early-stage PD and MSA. Therefore, SERT imaging is not useful to differentiate between early PD and MSA.

Gastric emptying after semi–solid food in multiple system atrophy and Parkinson disease

2005 ◽  
Vol 252 (9) ◽  
pp. 1055-1059 ◽  
Author(s):  
T. Thomaides ◽  
T. Karapanayiotides ◽  
Y. Zoukos ◽  
C. Haeropoulos ◽  
E. Kerezoudi ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Multiple System Atrophy ◽  
Parkinson Disease ◽  
Solid Food ◽  
Semi Solid

scholarly journals REM sleep behavior in Parkinson disease: Frequent, particularly with higher age

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243454
Author(s):  
Heide Baumann-Vogel ◽  
Hyun Hor ◽  
Rositsa Poryazova ◽  
Philipp Valko ◽  
Esther Werth ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Parkinson Disease ◽  
Progressive Supranuclear Palsy ◽  
Rem Sleep ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Corticobasal Degeneration ◽  
Sleep Behavior

This retrospective single-center polysomnography-based study was designed to assess the frequency of REM sleep behavior disorder (RBD) in consecutive patients with Parkinsonism, including Parkinson disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. We observed RBD in 77% of 540 Parkinson patients, with rising frequency at higher age and regardless of sex, in >89% of 89 patients with dementia with Lewy bodies or multiple system atrophy, and in <15% of 42 patients with progressive supranuclear palsy or corticobasal degeneration. Thus, the prevalence of RBD in sporadic Parkinson disease might be higher than previously assumed, particularly in elderly patients.

scholarly journals Gastroparesis in Parkinson Disease: Pathophysiology, and Clinical Management

2021 ◽  
Vol 11 (7) ◽  
pp. 831
Author(s):  
Heithem Soliman ◽  
Benoit Coffin ◽  
Guillaume Gourcerol
Keyword(s):  
Gastric Emptying ◽  
Parkinson Disease ◽  
Delayed Gastric Emptying ◽  
Gastrointestinal Symptoms ◽  
Lewy Bodies ◽  
Motor Symptoms ◽  
Prodromal Phase ◽  
Postprandial Fullness ◽  
Gastric Scintigraphy ◽  
Cardinal Symptoms

Patients with Parkinson disease (PD) experience a range of non-motor symptoms, including gastrointestinal symptoms. These symptoms can be present in the prodromal phase of the disease. Recent advances in pathophysiology reveal that α-synuclein aggregates that form Lewy bodies and neurites, the hallmark of PD, are present in the enteric nervous system and may precede motor symptoms. Gastroparesis is one of the gastrointestinal involvements of PD and is characterized by delayed gastric emptying of solid food in the absence of mechanical obstruction. Gastroparesis has been reported in nearly 45% of PD. The cardinal symptoms include early satiety, postprandial fullness, nausea, and vomiting. The diagnosis requires an appropriate test to confirm delayed gastric emptying, such as gastric scintigraphy, or breath test. Gastroparesis can lead to malnutrition and impairment of quality of life. Moreover, it might interfere with the absorption of antiparkinsonian drugs. The treatment includes dietary modifications, and pharmacologic agents both to accelerate gastric emptying and relieve symptoms. Alternative treatments have been recently developed in the management of gastroparesis, and their use in patients with PD will be reported in this review.

scholarly journals Multiple system atrophy-associated oligodendroglial protein p25α stimulates formation of novel α-synuclein strain with enhanced neurodegenerative potential

2021 ◽  
Author(s):  
Nelson Ferreira ◽  
Hjalte Gram ◽  
Zachary A. Sorrentino ◽  
Emil Gregersen ◽  
Sissel Ida Schmidt ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Protein Misfolding ◽  
Resonance Energy Transfer ◽  
Lewy Bodies ◽  
Resonance Energy ◽  
Alpha Synuclein ◽  
Striatal Neurons ◽  
End Stage ◽  
Intracellular Aggregates

AbstractPathology consisting of intracellular aggregates of alpha-Synuclein (α-Syn) spread through the nervous system in a variety of neurodegenerative disorders including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. The discovery of structurally distinct α-Syn polymorphs, so-called strains, supports a hypothesis where strain-specific structures are templated into aggregates formed by native α-Syn. These distinct strains are hypothesised to dictate the spreading of pathology in the tissue and the cellular impact of the aggregates, thereby contributing to the variety of clinical phenotypes. Here, we present evidence of a novel α-Syn strain induced by the multiple system atrophy-associated oligodendroglial protein p25α. Using an array of biophysical, biochemical, cellular, and in vivo analyses, we demonstrate that compared to α-Syn alone, a substoichiometric concentration of p25α redirects α-Syn aggregation into a unique α-Syn/p25α strain with a different structure and enhanced in vivo prodegenerative properties. The α-Syn/p25α strain induced larger inclusions in human dopaminergic neurons. In vivo, intramuscular injection of preformed fibrils (PFF) of the α-Syn/p25α strain compared to α-Syn PFF resulted in a shortened life span and a distinct anatomical distribution of inclusion pathology in the brain of a human A53T transgenic (line M83) mouse. Investigation of α-Syn aggregates in brain stem extracts of end-stage mice demonstrated that the more aggressive phenotype of the α-Syn/p25α strain was associated with an increased load of α-Syn aggregates based on a Förster resonance energy transfer immunoassay and a reduced α-Syn aggregate seeding activity based on a protein misfolding cyclic amplification assay. When injected unilaterally into the striata of wild-type mice, the α-Syn/p25α strain resulted in a more-pronounced motoric phenotype than α-Syn PFF and exhibited a “tropism” for nigro-striatal neurons compared to α-Syn PFF. Overall, our data support a hypothesis whereby oligodendroglial p25α is responsible for generating a highly prodegenerative α-Syn strain in multiple system atrophy.

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