Where does excessive beta in Parkinson's disease originate? Insights from a case of unilateral cortico-pallidal pathway dysfunction.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health consequences. Although initially recognized as a respiratory illness, it has become evident that COVID-19 also affects the vascular system, leading to endothelial dysfunction (ED) and ongoing inflammation with implications for various organs (; ; ). A subset of patients continues to experience persistent symptoms after recovering from the acute infection, a condition referred to as Post-COVID-19 syndrome (PCS) () or Long COVID (). Given the typical symptoms of fatigue, dyspnea, autonomic dysfunction, neurocognitive impairment, psychiatric disorders, arthralgia, myalgia, exertional malaise, and more, there is considerable overlap between PCS and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with some PCS patients meeting diagnostic criteria for ME/CFS, known as a sequela of other viral infections usually following pandemics (; ; ; ). Microvascular dysfunction has been proposed as a key factor in the development of these prolonged symptoms following SARS-CoV-2 infections (; ; ; ), with potential consequences for the retinal vasculature (). As a highly structured and accessible microvascular network, the retina provides a valuable model for investigating systemic vascular changes (). The retina is an ideal site for studying local microcirculatory dynamics due to its complex mechanisms of blood flow autoregulation involving a tightly coordinated neurovascular unit (). Optical coherence tomography angiography (OCTA) is a non-invasive imaging technique that enables detailed assessment of retinal capillary perfusion (). Previous studies have reported reduced vessel density following COVID-19, particularly in the superficial, intermediate, and deep capillary plexuses (; ; ; ; ; ). Additional findings include enlargement of the foveal avascular zone (FAZ), reduced foveal vascular density (VD), and reduced central macular thickness (CMT = retinal thickness measured at macula) suggesting persistent vascular damage. Conversely, transient thickening of the retinal nerve fiber layer (RNFL) has been interpreted as an early inflammatory response rather than permanent axonal loss (). Some of these changes were associated with the severity of the acute infection as well as with PCS symptom severity, indicating a potential role of SARS-CoV-2 in inducing long-term endothelial dysfunction (; ). Additional evidence of microcirculatory impairment in COVID-19 has been provided by other investigations, including a comprehensive review by Ackermann et al., which delineates widespread endothelial injury and microvascular dysfunction across multiple organ systems (). In a previous study by our group using static and dynamic retinal vessel analysis (RVA), we identified both structural and functional vascular abnormalities in PCS patients, compared to SARS-CoV-2 naïve participants (). According to our findings, Invernizzi et al. described dilated retinal veins in COVID-19 patients (). These findings support the hypothesis of an altered retinal microvasculature in PCS. Building on this observation, we aimed to investigate whether similar microvascular alterations can be detected using OCT and OCTA.