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SFB-F44 - Cell signaling in chronic CNS disorders

Multiple system atrophy

Multiple system atrophy (MSA) belongs to a group of rare, sporadic, unrelenting, fatal, rapidly progressive degenerative neurological disorders. MSA is characterized by several clinical features of parkinsonism, cerebellar ataxia, autonomic dysfunction and corticospinal tract dysfunction, likely caused by cell loss or gliosis in specific brain structures, myelin pallor and α-synucleinopathy of unknown etiology. The prevalence of MSA is reported to be 4 cases per 100,000 people. In Austria currently 1,000 patients have been diagnosed.The average age of onset is 55-58 years and the average disease duration between 7 and 9 years. Men are more commonly affected by MSA than women. MSA progresses more quickly than Parkinson’s Disease (PD): a very high percentage of MSA patients are disabled within 5 years of their initial diagnosis.

The pathogenesis of the disease is still undetermined and no specific risk factor has been identified. Pathological changes in MSA include multisystem neuronal cell loss, gliosis, and α-synuclein-positive glial cytoplasmic inclusions in the brain and spinal cord. The term MSA was first proposed in 1969, recognizing the overlap of its three neuropathologies, i.e. striatonigral degeneration, olivopontocerebellar atrophy and central autonomic degeneration. More recently, MSA has been categorized into two clinical subtypes, MSA-P with predominant parkinsonism, and MSA-C with predominant cerebellar ataxia. Recent studies indicate that MSA-P is more common in Europe than MSA-C and the motor disorder is often mixed, with cerebellar features in MSA-P and parkinsonian symptoms in MSA-C. Autonomic failure is a characteristic feature of both MSA subtypes.

Diagnosis of MSA can be challenging because of the difficulty in differentiating the disease from other disorders, such as PD, pure autonomic failure or other rare movement disorders.  Certain MSA signs and symptoms also occur with them. Distinguishing MSA from other degenerative disorders crucially depends on the presence of early and severe cardiovascular autonomic failure (CAF). Combined with a lack of effective biomarkers, that implies a certain potential for clinical misdiagnosis, particularly in the early disease course. However, MSA pathology can be predicted in 90% of cases if the clinical diagnostic criteria for probable MSA are fulfilled. Only neuropathological confirmation can definitely validate the diagnosis of MSA.

A current multicenter study suggests that disease progression slows down in the second year of follow-up, and baseline parkinsonism and neurogenic bladder disturbance are linked to poor survival. Further, a shorter baseline symptom duration and absent levodopa response proved to be independent predictors of faster UMSARS progression (Unified Multiple System Atrophy Rating Scale). There is no remission of the disease and an effective treatment that can modify the MSA progression has not yet been established.

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