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Laboratory-Supported Multiple System Atrophy beyond Autonomic Function Testing and Imaging: A Systematic Review by the MoDiMSA Study Group.

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Neuroimaging has been used to support a diagnosis of possible multiple system atrophy (MSA). Only blood pressure changes upon standing are included in the second consensus criteria but other autonomic function tests (AFT) are also useful to diagnose widespread and progressive autonomic failure typical of MSA. Additional diagnostic tools are of interest to improve accuracy of MSA diagnosis.


To assess the utility of diagnostic tools beyond brain imaging and AFT in enhancing a laboratory-supported diagnosis of MSA to support the upcoming revision of the consensus criteria.


The International Parkinson and Movement Disorders Society MSA Study Group (MoDiMSA) performed a systematic review of original papers on biomarkers, sleep studies, genetic, neuroendocrine, neurophysiological, neuropsychological and other tests including olfactory testing and acute levodopa challenge test published before August 2019.


Evaluation of history of levodopa responsiveness and olfaction is useful in patients in whom MSA-parkinsonian subtype is suspected. Neuropsychological testing is useful to exclude dementia at time of diagnosis. Applicability of sphincter EMG is limited. When MSA-cerebellar subtype is suspected, a screening for the common causes of adult-onset progressive ataxia is useful, including spinocerebellar ataxias in selected patients. Diagnosing stridor and REM sleep behavior disorder is useful in both MSA subtypes. However, none of these tools are validated in large longitudinal cohorts of postmortem confirmed MSA cases.


Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy.

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