Objective: To assess longitudinal changes of serial neuroimaging-derived parameters in MSA.

Background: Different neuroimaging modalities hold potential as surrogate markers of neurodegeneration in multiple system atrophy(MSA). Serial neuroimaging is able to study lesion progression in vivo and seem to have lower progression rate variability than clinical assessments. We conducted a literature research and summarized the results in this review focusing on neuroimaging as a tool to measure disease progression in MSA.

Method: Studies were identified through a systematic literature research. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of patients with parkinsonian and cerebellar variant of MSA (MSA-P, MSA-C) and the performance of serial imaging. The coefficient of variation (COV) is given for each neuroimaging-derived progression rate.

Results: DAT binding decline in the anterior striatum (n=1) and microglial activation assessed with PK11195-PET (n=1) are both sensitive to change over time in MSA-P. MSA-C-specific progression pattern of cerebral glucose metabolism includes the cerebellum and different cortical areas (n=1). Regional atrophy rates of infratentorial structures (pons, cerebellum) are sensitive to change over time in MSA-P (n=1), while whole brain atrophy rate seems to be sensitive to change over time in earlier disease stages only (n=1). MSA-P-specific progression-pattern include different cortical and subcortical areas (n=1), while MSA-C-specific progression-pattern includes the cerebellum and different cortical areas (n=1). Moreover, abnormal putaminal diffusivity is sensitive to change over time in MSA (n=2). Number of patients needed to detect a drug effect with an anticipated ability to reduce the progression rate of neuroimaging marker by 30% over 1year with a power of 90% ranges between 80-283 depending on the imaging marker used compared to 171-391 patients needed using clinical markers.

Conclusion: Different modalities hold potential as surrogate markers of underlying neurodegeneration and may reflect cell loss, altered glucose metabolism, microglial proliferation, astroglial activation, and nigrostriatal denervation. Furthermore, serial neuroimaging is able to study lesion progression in vivo and seem to have lower variability of progression rates than clinical rating scales such as these markers might be more suitable especially in proof-of-concept phaseII trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/measuring-disease-progression-with-neuroimaging-in-msa-a-systematic-review/