A case of multiple system atrophy

Multiple system atrophy (MSA) is the most rapidly progressive neurodegenerative disorder among the various types of synucleinopathies. The cause of MSA remains unknown, but it can involve the extrapyramidal system, the pyramidal system, the autonomic nerves and the cerebellum. The main clinical manifestations are Parkinson's symptoms, cerebellar ataxia, pyramidal tract signs and autonomic nervous system disorders. Depending on the initial predominant motor deficits, MSA is subclassified into either Parkinsonian type (MSA-P) or cerebellar type (MSA-C). MSA is rare in the Zunyi area of Guizhou Province, so when it is observed for the first time it often results in a convoluted diagnosis and treatment process, which takes a lot of time, money, manpower and material resources, which can also have a psychological impact on the patient. This report describes the case of a 60-year-old woman who presented with syncope for 1 year combined with dizziness for 1 day. She had been diagnosed twice with transient ischaemic attack in the previous 6 months. Cranial magnetic resonance imaging suggested widening of the cerebellar sulcus and mild cerebellar atrophy. Based on the patient’s medical history, physical signs and auxiliary examinations, she was diagnosed with MSA-C.

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Dynamic Cerebrospinal Fluid Flow on MRI in Cortical Cerebellar Atrophy and Multiple System Atrophy-cerebellar Type

Internal Medicine ◽

10.2169/internalmedicine.54.4747 ◽

2015 ◽

Vol 54 (14) ◽

pp. 1717-1723 ◽

Cited By ~ 1

Author(s):

Yusuke Fukui ◽

Nozomi Hishikawa ◽

Kota Sato ◽

Syoichiro Kono ◽

Kosuke Matsuzono ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Flow ◽

Multiple System Atrophy ◽

Cerebellar Atrophy ◽

Cerebrospinal Fluid Flow ◽

Cerebellar Type ◽

Cortical Cerebellar Atrophy

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Cerebellar Atrophy in Multiple System Atrophy (Cerebellar Type) and Its Implication for Network Connectivity

The Cerebellum ◽

10.1007/s12311-020-01144-4 ◽

2020 ◽

Vol 19 (5) ◽

pp. 636-644

Author(s):

Hao Zhang ◽

Shaozhen Ji ◽

Shan Ren ◽

Ming Liu ◽

Weizheng Ran ◽

...

Keyword(s):

Multiple System Atrophy ◽

Cerebellar Atrophy ◽

Network Connectivity ◽

Cerebellar Type

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Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1609291113 ◽

2016 ◽

Vol 113 (34) ◽

pp. 9593-9598 ◽

Cited By ~ 50

Author(s):

Fares Bassil ◽

Pierre-Olivier Fernagut ◽

Erwan Bezard ◽

Alain Pruvost ◽

Thierry Leste-Lasserre ◽

...

Keyword(s):

Multiple System Atrophy ◽

Neurodegenerative Disorder ◽

Disease Onset ◽

Neuronal Cell ◽

Alpha Synuclein ◽

Motor Deficits ◽

Neuroprotective Effects ◽

Caspase 1

Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation.

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Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type (MSA-C) using three-dimensional gyrification index analysis

NeuroImage ◽

10.1016/j.neuroimage.2012.02.057 ◽

2012 ◽

Vol 61 (1) ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Yu-Te Wu ◽

Kuo-Kai Shyu ◽

Chii-Wen Jao ◽

Yuan-Lin Liao ◽

Tzu-Yun Wang ◽

...

Keyword(s):

Multiple System Atrophy ◽

Three Dimensional ◽

Cerebellar Atrophy ◽

Index Analysis ◽

Gyrification Index ◽

Cerebellar Type

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W246G Mutant ELOVL4 Impairs Synaptic Plasticity in Parallel and Climbing Fibers and Causes Motor Defects in a Rat Model of SCA34

Molecular Neurobiology ◽

10.1007/s12035-021-02439-1 ◽

2021 ◽

Author(s):

Raghavendra Y. Nagaraja ◽

David M. Sherry ◽

Jennifer L. Fessler ◽

Megan A. Stiles ◽

Feng Li ◽

...

Keyword(s):

Fatty Acids ◽

Synaptic Plasticity ◽

Rat Model ◽

Neurodegenerative Disorder ◽

Cerebellar Atrophy ◽

Long Term Potentiation ◽

Motor Deficits ◽

Fatty Acid Elongase ◽

Long Chain

AbstractSpinocerebellar ataxia (SCA) is a neurodegenerative disorder characterized by ataxia and cerebellar atrophy. A number of different mutations gives rise to different types of SCA with characteristic ages of onset, symptomatology, and rates of progression. SCA type 34 (SCA34) is caused by mutations in ELOVL4 (ELOngation of Very Long-chain fatty acids 4), a fatty acid elongase essential for biosynthesis of Very Long Chain Saturated and Polyunsaturated Fatty Acids (VLC-SFA and VLC-PUFA, resp., ≥28 carbons), which have important functions in the brain, skin, retina, Meibomian glands, testes, and sperm. We generated a rat model of SCA34 by knock-in of the SCA34-causing 736T>G (p.W246G) ELOVL4 mutation. Rats carrying the mutation developed impaired motor deficits by 2 months of age. To understand the mechanism of these motor deficits, we performed electrophysiological studies using cerebellar slices from rats homozygous for W246G mutant ELOVL4 and found marked reduction of long-term potentiation at parallel fiber synapses and long-term depression at climbing fiber synapses onto Purkinje cells. Neuroanatomical analysis of the cerebellum showed normal cytoarchitectural organization with no evidence of degeneration out to 6 months of age. These results point to ELOVL4 as essential for motor function and cerebellar synaptic plasticity. The results further suggest that ataxia in SCA34 patients may arise from a primary impairment of synaptic plasticity and cerebellar network desynchronization before onset of neurodegeneration and progression of the disease at a later age.

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Amelioration of motor and nonmotor symptoms in cortical cerebellar atrophy and multiple system atrophy-cerebellar type by inpatient rehabilitation

International Journal of Rehabilitation Research ◽

10.1097/mrr.0000000000000455 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Yuma Sonoda ◽

Yuya Yamanaka ◽

Shinichiro Sawano ◽

Ryo Komada ◽

Masato Kugo ◽

...

Keyword(s):

Multiple System Atrophy ◽

Cerebellar Atrophy ◽

Inpatient Rehabilitation ◽

Nonmotor Symptoms ◽

Cerebellar Type ◽

Cortical Cerebellar Atrophy

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Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

BMC Medical Genomics ◽

10.1186/s12920-021-00944-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xi Luo ◽

Xiang-mei Zhang ◽

Liu-song Wu ◽

Jindong Chen ◽

Yan Chen

Keyword(s):

Genetic Counseling ◽

Peripheral Blood ◽

Clinical Phenotype ◽

Globin Gene ◽

Clinical Manifestations ◽

Gene Mutations ◽

Guizhou Province ◽

Globin Genes ◽

Phenotype Correlation ◽

Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

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Multiple-System Atrophy in Long-Term Professional Painter: A Case Report

Case Reports in Pathology ◽

10.1155/2012/613180 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5

Author(s):

Yusa Nagai ◽

Riko Kitazawa ◽

Miku Nakagawa ◽

Munenori Komoda ◽

Takeshi Kondo ◽

...

Keyword(s):

Multiple System Atrophy ◽

Medulla Oblongata ◽

Neurodegenerative Disorder ◽

Histopathological Examination ◽

Neuronal Loss ◽

Cytoplasmic Inclusion ◽

Multiple Organ ◽

Old Japanese ◽

History Of

Introduction. Multiple system atrophy (MSA) is a rare and severe adult-onset, sporadic, and progressive neurodegenerative disorder. Here, we describe an autopsy case of MSA in a long-term professional painter. Although typical glial cytoplasmic inclusion (GCI) was not observed in a routine histological examination, strong α-synuclein immunostaining in the nucleus confirmed the diagnosis of MSA.Case Presentation. A 48-year-old Japanese man with a long occupational history of professional painter was sent to the emergency room, where he died of multiple organ failure. The patient had suffered tremors and inarticulateness at age 28, developed diabetes at 42 and was diagnosed with spinocerebellar degeneration at 46. A histopathological examination showed severe neuronal loss, gliosis, and tissue rarefaction in the paleostriatum, striate body of the substantia nigra, the pons, and the olivary nucleus of the upper medulla oblongata, intermediolateral of the spinal gray matter (sacral region). α-synuclein-positive GCI in oligodendroglia was occurred in the cerebral cortex, the midbrain, the medulla oblongata, and the spinal cord. These findings confirmed the presence of multiple-system atrophy (OPCA+SDS).Conclusion. Although the pathogenesis of MSA is still unclear, prolonged, and extensive exposure to organic solvents, together with a hyperglycemic morbidity attributed to diabetes, may have contributed to the onset and clinical course of the present case.

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