The link between inflammation and autonomic dysfunction in alpha-synucleinopathies - narrative review

Alpha-synucleinopathies are a group of disorders characterized by the accumulation of the pathological form of alpha-synuclein. This group comprises Parkinson's disease, Parkinson's disease dementia, multiple system atrophy, dementia with Lewy bodies, pure autonomic failure, and idiopathic REM sleep behavior disorder. Despite sharing a similar molecular basis, these disorders differ in their clinical presentation. Characteristic manifestations include signs of autonomic failure such as orthostatic hypotension, postural orthostatic tachycardia syndrome, constipation, gastroparesis, urinary incontinence, and erectile dysfunction, among others. These symptoms significantly impair patients' daily functioning and are also negative prognostic factors.

Currently, research is investigating the link between inflammation and dysautonomic symptoms. Elevated levels of pro-inflammatory cytokines, such as IFN-γ, TNF-α, IL-6, IL-1β, and IFN-α, have been found to accompany these symptoms. Notably, in other diseases characterized by chronic inflammation, autonomic dysfunction is also common.

In two human studies of dysautonomic symptoms in other conditions, intravenous immunoglobulin therapy was shown to improve these symptoms. Animal studies have shown that other immunomodulatory agents reduce symptom severity.

Modulation of inflammation, dietary modification, the use of probiotics and prebiotics, and fecal microbiota transplantation are potential therapeutic approaches for these diseases. These approaches offer hope for improving the quality of life of patients with alpha-synucleinopathies. Further research in this area is needed.