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

Abstract

Background 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. Objectives 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. Methods 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. Results 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. Conclusions 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.

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

“…Neurofilament light chain (NfL) level in CSF >1400 pg/mL detected by enzyme‐linked immunosorbent assay (ELISA) yielded 97% sensitivity and 90% specificity to distinguish MSA from LBD. Moverover, CSF NfL correlates with plasma NfL concentrations 36,78 . In patients who progressed from isolated autonomic failure to MSA, CSF NfL level was increased already at the stage of isolated autonomic failure, in contrast to the patients who did not phenoconvert 80 …”

A case of Lewy body disease and anaplastic astrocytoma presenting with atypical parkinsonism

“… 16 In retrospect, the abnormal olfactory test supported a diagnosis of PD, as olfaction is typically preserved in MSA. 17 The visuo‐spatial dysfunction and cognitive decline also supported a cortical LBD. Olfactory testing could be more widely applied to clinical practice to help with differential diagnosis.…”

“…Autonomic failure in PD, including postural hypotension meeting criteria for MSA, is increasingly recognized and is associated with more rapid progression and reduced survival 16 . In retrospect, the abnormal olfactory test supported a diagnosis of PD, as olfaction is typically preserved in MSA 17 . The visuo‐spatial dysfunction and cognitive decline also supported a cortical LBD.…”

Multiple system atrophy

“…The only tests needed to fulfil core clinical criteria are a postvoid bladder residual volume and a lying and standing blood pressure. However, if uncertainty remains, other investigations can help to prove autonomic involvement, for example formal urodynamics showing detrusor sphincter dyssynergia15 or external anal sphincter electromyography showing chronic reinnervation changes in Onuf’s nucleus (however, this finding is not specific to MSA, and occurs in long-standing Parkinson’s disease, progressive supranuclear palsy and after pelvic surgery) 16…”