Comorbid pathologies and their impact on multiple system atrophy: current view

A combination of pathological alterations such as vascular lesions and multiple protein depositions is common in most neurodegenerative diseases, however, the frequency of comorbid pathologies in multiple system atrophy (MSA) and their clinical relevance are poorly understood. Recent studies reported that up to 40% of MSA patients have significant co-existing pathologies, the number of which shows positive correlations with age at onset or death, while according to others, up to 65% of MSA patients suffer from multimorbidities. Co-existent pathologies include progressive supranuclear palsy, Alzheimer-related neuropathological changes (ADNC), including β-amyloid predominant forms, cerebral amyloid angiopathy, Lewy body disorders, and TDP-43 pathology, while clinical studies emphasized the burden of genitourinary and other comorbidities. Although MSA is considered a sporadic disorder, pedigrees with neuropathologically confirmed combinations of MSA and Parkinson disease have been described, the genetic risk factors of which warrant further elucidation. While some described minimal clinical impact of comorbid pathologies in MSA, according to others, comorbidities represent a substantial burden for patients and caregivers. Emerging biomarkers in clinical practice will allow the recognition of these comorbidities, potentially leading to a differential therapeutic response.