Is pure autonomic failure an early marker for Parkinson disease, dementia with Lewy bodies, and multiple system atrophy? And other updates on recent autonomic research

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.

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Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies

Neurology ◽

10.1212/01.wnl.0000138500.73671.dc ◽

2004 ◽

Vol 63 (6) ◽

pp. 1093-1095 ◽

Cited By ~ 164

Author(s):

Horacio Kaufmann ◽

Kirsty Nahm ◽

Dushyant Purohit ◽

David Wolfe

Keyword(s):

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Autonomic Failure ◽

Lewy Bodies ◽

Initial Presentation

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Abstract P381: Understanding the Symptoms of Neurogenic Orthostatic Hypotension: Results From a Survey of Patients and Caregivers

Hypertension ◽

10.1161/hyp.70.suppl_1.p381 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Lawrence A Hewitt ◽

Charles H Adler ◽

Daniel O Claassen ◽

Christopher H Gibbons ◽

Satish R Raj

Keyword(s):

Multiple System Atrophy ◽

Parkinson Disease ◽

Orthostatic Hypotension ◽

Autonomic Failure ◽

Alpha Synuclein ◽

Pure Autonomic Failure ◽

Motor Symptoms ◽

Neurogenic Orthostatic Hypotension ◽

The Past ◽

Increased Risk

Objective: To understand the burden and impact of symptoms of neurogenic orthostatic hypotension (nOH) on patients Background: nOH and its symptoms such as dizziness/lightheadedness are common in patients with Parkinson disease (PD) and other forms of autonomic dysfunction. Methods: An author-designed, US-based survey was conducted by Harris Poll. Eligible participants were aged ≥18 years with PD, multiple system atrophy (MSA), or pure autonomic failure and ≥1 of the following: orthostatic hypotension, nOH, low BP, OH/nOH symptoms, or were caregivers of eligible patients. Results: Most patients (90%) had a diagnosis of PD, and most caregivers (88%) cared for a patient with PD (Table 1) . Patients (34%) and caregivers (49%) reported experiencing nOH symptoms before PD or MSA motor symptoms and >40% indicated that nOH symptoms were more troublesome than motor manifestations of PD or MSA. Less than a quarter (22%) of respondents suggested symptoms were most severe in the morning; more (30%) reported a consistent severity throughout the day. Patients (40%) and caregivers (63%) reported trouble managing symptoms during the day. In the past 12 months, a fall due to nOH symptoms was reported by 57% of patients and 80% of caregivers. Conclusions: These findings suggest that nOH symptoms may predate the onset of motor symptoms in neurodegenerative conditions linked to alpha-synuclein pathology. Many respondents report nOH symptoms are the same severity through the day. Patients with nOH may have trouble managing symptoms and note an increased risk for falls.

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Alpha-synuclein in the Cerebrospinal Fluid Differentiates Synucleinopathies (Parkinson Disease, Dementia With Lewy Bodies, Multiple System Atrophy) From Alzheimer Disease

Alzheimer Disease & Associated Disorders ◽

10.1097/wad.0b013e31823899cc ◽

2012 ◽

Vol 26 (3) ◽

pp. 213-216 ◽

Cited By ~ 77

Author(s):

Fuyuki Tateno ◽

Ryuji Sakakibara ◽

Takayuki Kawai ◽

Masahiko Kishi ◽

Takeyoshi Murano

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Multiple System Atrophy ◽

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Alpha Synuclein

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

PLoS ONE ◽

10.1371/journal.pone.0243454 ◽

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.

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Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease

Annals of Neurology ◽

10.1002/ana.24567 ◽

2015 ◽

Vol 79 (2) ◽

pp. 306-316 ◽

Cited By ~ 65

Author(s):

Vincenzo Donadio ◽

Alex Incensi ◽

Cristina Piccinini ◽

Pietro Cortelli ◽

Maria Pia Giannoccaro ◽

...

Keyword(s):

Parkinson Disease ◽

Autonomic Failure ◽

Pure Autonomic Failure

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Levodopa-induced dyskinesia in dementia with Lewy bodies and Parkinson disease with dementia

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000703 ◽

2019 ◽

Vol 10 (2) ◽

pp. 156-161

Author(s):

Pierpaolo Turcano ◽

Cole D. Stang ◽

James H. Bower ◽

J. Eric Ahlskog ◽

Bradley F. Boeve ◽

...

Keyword(s):

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Population Based ◽

Olmsted County ◽

Levodopa Dosage ◽

Younger Age ◽

Increased Risk ◽

Incident Cohort ◽

Median Interval

ObjectiveTo investigate the frequency of levodopa-induced dyskinesia in dementia with Lewy bodies (DLBs) and Parkinson disease with dementia (PDD) and compare these frequencies with patients with incident Parkinson disease (PD) through a population-based cohort study.MethodsWe identified all patients with DLB, PDD, and PD without dementia in a 1991–2010 population-based parkinsonism-incident cohort, in Olmsted County, Minnesota. We abstracted information about levodopa-induced dyskinesia. We compared patients with DLB and PDD with dyskinesia with patients with PD from the same cohort.ResultsLevodopa use and dyskinesia data were available for 141/143 (98.6%) patients with a diagnosis of either DLB or PDD; 87 (61.7%), treated with levodopa. Dyskinesia was documented in 12.6% (8 DLB and 3 PDD) of levodopa-treated patients. Among these patients, median parkinsonism diagnosis age was 74 years (range: 64–80 years); 63.6%, male. The median interval from levodopa initiation to dyskinesia onset was 2 years (range: 3 months–4 years); the median daily levodopa dosage was 600 mg (range: 50–1,600 mg). Dyskinesia severity led to levodopa adjustments in 5 patients, and all improved. Patients with dyskinesia were diagnosed with parkinsonism at a significantly younger age compared with patients without dyskinesia (p < 0.001). Levodopa dosage was unrelated to increased risk of dyskinesias among DLB and PDD. In contrast, 30.1% of levodopa-treated patients with PD developed dyskinesia. In age-, sex-, and levodopa dosage–adjusted models, Patients with DLB and PDD each had lower odds of developing dyskinesia than patients with PD (odds ratio = 0.42, 95% CI 0.21–0.88; p = 0.02).ConclusionsThe dyskinesia risk for levodopa-treated patients with DLB or PDD was substantially less than for levodopa-treated patients with PD.

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