Continuum (Minneap Minn). Author manuscript; available in PMC 2020 Dec 17. Published in final edited form as: Continuum (Minneap Minn). 2020 Feb; 26(1): 72–92. doi: 10.1212/CON.0000000000000819
PMCID: PMC7745651 NIHMSID: NIHMS1649538 PMID: 31996623
Synucleinopathies
Elizabeth A. Coon, MD and Wolfgang Singer, MD Author information Copyright and License information PMC Disclaimer The publisher's final edited version of this article is available at Continuum (Minneap Minn)
Abstract
PURPOSE OF REVIEW:
This article reviews the α-synucleinopathies pure autonomic failure, multiple system atrophy, dementia with Lewy bodies, and Parkinson disease with respect to autonomic failure.
RECENT FINDINGS:
The pattern and severity of autonomic involvement in the synucleinopathies is related to differences in cellular deposition and neuronal populations affected by α-synuclein aggregation, which influences the degree and manifestation of autonomic failure. Clinical and laboratory autonomic features distinguish the different synucleinopathies based on pattern and severity. These features also determine which patients are at risk for evolution from pure autonomic failure to the synucleinopathies with prominent motor involvement, such as multiple system atrophy, dementia with Lewy bodies, or Parkinson disease.
SUMMARY:
Autonomic failure is a key feature of the synucleinopathies, with varying type and degree of dysfunction from predominantly peripheral involvement in the Lewy body disorders to central involvement in multiple system atrophy.
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CONCLUSION
Autonomic failure is a key feature of the synucleinopathies of pure autonomic failure, MSA, DLB, and Parkinson disease. Involvement of the autonomic nervous system varies from predominantly peripheral involvement in the Lewy body disorders to predominantly central involvement in MSA. The severity of autonomic dysfunction also varies, with the most severe involvement in MSA, moderate involvement in DLB, and less severe impairment classically seen in Parkinson disease. Patients with pure autonomic failure typically manifest a severe degree of autonomic failure, and certain clinical and laboratory features may predict evolution into other synucleinopathies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745651/
Synucleinopathies
K.A. Jellinger
https://doi.org/10.1016/B978-0-12-374105-9.00291-4
Synucleinopathies, a group of disorders featured by progressive aggregation of insoluble fibrillary α-synuclein (αSyn) in neurons and glia, associated with multisystem neurodegeneration, underlies a wide spectrum of clinical syndromes, movement disorders/parkinsonism (Parkinson's disease, pantothenate kinase-associated neurodegeneration), dementia (Parkinson's disease dementia, dementia with Lewy body), and autonomic dysfunction (pure autonomic failure, multiple system atrophy). Pathogenetically, they arise from disturbances in the metabolism of αSyn (increased synthesis, oligomer formation due to insufficient degradation). The pathophysiology, epidemiology, clinical features and diagnostic criteria, differential diagnosis, biological/surrogate markers, and current/future treatment options with variable impact on their natural history are summarized.
https://www.sciencedirect.com/science/article/abs/pii/B9780123741059002914
Neurological Review
February 2001
Synucleinopathies
Clinical and Pathological Implications
James E. Galvin, MD, MSc; Virginia M.-Y. Lee, PhD; John Q. Trojanowski, MD, PhD
Author Affiliations Article Information
Arch Neurol. 2001;58(2):186-190. doi:10.1001/archneur.58.2.186
Abstract
The synucleinopathies are a diverse group of neurodegenerative disorders that share a common pathologic lesion composed of aggregates of insoluble α-synuclein protein in selectively vulnerable populations of neurons and glia. Growing evidence links the formation of abnormal filamentous aggregates to the onset and progression of clinical symptoms and the degeneration of affected brain regions in neurodegenerative disorders. These disorders may share an enigmatic symmetry, ie, missense mutations in the gene encoding for the disease protein (α-synuclein) cause familial variants of Parkinson disease as well as its hallmark brain lesions, but the same brain lesions also form from the corresponding wild-type brain protein in the more common sporadic varieties of Parkinson disease. It is likely that clarification of this enigmatic symmetry in 1 form of synucleinopathy will have a profound impact on understanding the mechanisms underlying all these disorders. Furthermore, these efforts will likely lead to novel diagnostic and therapeutic strategies in regard to the synucleinopathies.
https://jamanetwork.com/journals/jamaneurology/fullarticle/778475
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