Multiple System Atrophy – Cerebellar Type: Clinical Picture and Treatment of an Often-Overlooked Disorder

Ortíz, Juan Fernando; Betté, Sagari; Tambo, Willians; Tao, Feiyang; Cozar, Jazmin Carolina; Isaacson, Stuart

doi:10.7759/cureus.10741

Cited by 8 publications

(4 citation statements)

References 42 publications

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“…The only features that were significantly different in MSA-P and MSA-C groups were slowness of movements, masking of the face, and bradykinesia, which were more frequent among MSA-P patients and gait ataxia, which was more common in MSA-C patients, and these findings were consistent with the earlier knowledge. [ 30 ] Although not the primary aim of this study, we found that cerebellar atrophy was the most frequent imaging finding in our MSA patients, the others being pontine atrophy, putaminal atrophy, and middle cerebellar peduncular atrophy. According to past research, putaminal atrophy, hyperintense rim, cerebellar atrophy, the “hot cross bun” sign, and middle cerebellar peduncle hyperintensity are frequent in MSA.…”

Section: Discussionmentioning

confidence: 84%

Nature of Parkinsonian features in multiple system atrophy

Pradhan,

Tandon

2023

JNRP

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Objectives: For this observational study, we evaluated the clinical profile of Parkinsonian features in multiple system atrophy (MSA), as there is no clarity about the specifics of these features in this disease compared to progressive supranuclear palsy (PSP) and Parkinson’s disease (PD). Materials and Methods: Here, we selected 57 patients with MSA based on standard criteria and grouped them into two categories – Parkinsonian variant of MSA (MSA-P) and cerebellar variant of MSA (MSA-C). However, researchers did not distinguish among patients based on the nature of extrapyramidal syndrome or levodopa responsiveness. Then, we examined the patients at the time of their first visit to outpatient clinics or indoor wards and recorded and analyzed the specific extrapyramidal features or their variations. Results: The extrapyramidal features including levodopa responsiveness were highly variable among MSA-C as well as MSA-P patients. A subset of patients presented with features resembling PSP (symmetry [56.1%], axial rigidity [52.6%], backward falls [28.1%], and down-gaze restriction [17.5%]), while others presented with features resembling PD (asymmetry [43.9%], tremors [71.9%], and peripheral rigidity [40.4%]). After grouping patients based on predominant extrapyramidal features, 36.8% of patients had PD-like, 19.3% had PSP-like, and 43.9 % had mixed presentation. Moreover, 86% of patients had a perceptible levodopa response, including a sustained response for more than six months in 64% of patients. Conclusion: Extrapyramidal features in MSA patients may be PD-like, PSP-like, or mixed. Moreover, an initial presentation resembling PSP or PD may be deceptive and one must follow it up for MSA.

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Section: Discussionmentioning

confidence: 84%

Nature of Parkinsonian features in multiple system atrophy

Pradhan,

Tandon

2023

JNRP

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“…On the basis of clinical features, MSA is divided into two main types: the parkinsonian type (MSA-P) with poor levodopa responsive parkinsonian syndrome and cerebellar type (MSA-C) with cerebellar ataxia syndrome (Ortiz et al, 2020). In MSA-C, the degree of morphological changes in cerebellum is more pronounced than MSA-P (Rusholt et al, 2020) as well as the purkinje neuron dysfunctions include the increase of torpedoes in purkinje axonal morphology and reduction in dendritic spines of purkinje dendritic arbor have implicated cerebellar dysfunction (Kuo et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Epsin2, a novel target for multiple system atrophy therapy via α-synuclein/FABP7 propagation

Cheng

Wang

Sekimori

et al. 2022

Preprint

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Background: Multiple system atrophy (MSA) is an adult-onset, fatal neurodegenerative disease featured by propagation of misfolded α-synuclein and dysregulation of myelin integrity in central nervous systems (CNS). In our previous study, we identified that fatty acid binding protein 7 (FABP7), one glial protein regulated α-synuclein (α-syn) toxicity and closely related to oligodendrocyte loss. Here, we investigated how FABP7 works in MSA pathological process. Methods: The mouse model of MSA: PLP-hαSyn transgenic mice (PLP-hαSyn mice) were used for understanding the underling role of FABP7 in α-syn aggregation. In vitro, FABP7/α-syn hetero-aggregates were constructed by recombinant human-α-syn and 6X His-tag human-FABP7. By immunohistochemical analyze of brain tissue from PLP-hαSyn mice and aggregates injection mice, we identified the toxicity of aggregates and the region or cell type in brain which aggregates prefer to propagate. Furthermore, through the bioinformatics analysis of MSA patient blood, PLP mouse brain tissue we found candidate proteins related to α-syn propagation. Then, the hypothesis was verified by adeno-associated virus (AAV) knockdown in aggregates injection mice. Findings: In PLP-hαSyn mice, FABP7 also forms hetero-aggregates with α-syn and the FABP7/α-syn hetero-aggregates exhibited higher molecular weight and stronger toxicity than α-syn aggregates both in vitro and in vivo. The same with PLP-hαSyn mice, in the FABP7/α-syn hetero-aggregates injected mice, aggregates prefer to accumulate in oligodendrocyte and purkinje neurons. By bioinformatics analysis we found the protein epsin-2 as a potential receptor which regulate FABP7/α-syn hetero-aggregates propagate to oligodendrocytes and purkinje neurons. In AAV-dependent epsin-2 knock down mice we observed decreased levels of FABP7/α-syn hetero-aggregates in purkinje neurons and oligodendrocytes. Conclusions: These data suggest that epsin-2 is an important potential therapeutic target for MSA via regulating FABP7/α-syn hetero-aggregates propagation. It is very meaningful for further investigation and developing specific inhibitors. Funding: This work was supported by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development (JP17dm0107071, JP18dm0107071, JP19dm0107071, and JP20dm0107071).

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“…There have been three clinical trials involving riluzole in the treatment of hereditary ataxia in the following conditions: Friedreich’s ataxia (FRDA), spinocerebellar ataxia (SCA), multiple system atrophy (MSA), and GAD-related neurological syndrome. Table 1 shows the main features of these hereditary ataxias [ 4 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Use of Riluzole for the Treatment of Hereditary Ataxias: A Systematic Review

et al. 2022

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Ataxia is a constellation of symptoms that involves a lack of coordination, imbalance, and difficulty walking. Hereditary ataxia occurs when a person is born with defective genes, and this degenerative disorder may progress for several years. There is no effective cure for ataxia, so we need to search for new treatments. Recently, interest in riluzole in the treatment of ataxia has emerged. We conducted this systematic review to analyze the safety and efficacy of riluzole for treating hereditary ataxia in recent clinical trials. We conducted a systematic review using PubMed and Google Scholar as databases in search of this relationship. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocols to conduct this study. For inclusion criteria, we included full-text clinical trials on humans written in English and found three clinical trials. We excluded case reports, literature reviews, systematic reviews, and meta-analyses for this analysis. We aimed to evaluate the Scale for the Assessment and Rating of Ataxia (SARA) score, the International Cooperative Ataxia Rating Scale (ICARS) score, and the safety of the medication. Two out of the three clinical trials showed statistically significant clinical improvement in the ICARS and SARA scores, while the other trial did not show improvement in the clinical or radiological outcomes. The drug was safe in all clinical trials. Overall, the results of this analysis of riluzole for the treatment of hereditary ataxia are encouraging. Further clinical trials are needed to investigate the efficacy of riluzole on hereditary ataxia.

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Multiple System Atrophy – Cerebellar Type: Clinical Picture and Treatment of an Often-Overlooked Disorder

Cited by 8 publications

References 42 publications

Nature of Parkinsonian features in multiple system atrophy

Nature of Parkinsonian features in multiple system atrophy

Epsin2, a novel target for multiple system atrophy therapy via α-synuclein/FABP7 propagation

Use of Riluzole for the Treatment of Hereditary Ataxias: A Systematic Review

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