Faculty Bibliography

This Viewpoint discusses insights from basic science and clinical perspectives on coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in the brain, with a particular focus on Parkinson's disease. Major points include that neuropathology studies have not answered the central issue of whether the virus enters central nervous system neurons, astrocytes or microglia, and the brain vascular cell types that express virus have not yet been identified. Currently, there is no clear evidence for human neuronal or astrocyte expression of angiotensin-converting enzyme 2 (ACE2), the major receptor for viral entry, but ACE2 expression may be activated by inflammation, and a comparison of healthy and infected brains is important. In contrast to the 1918 influenza pandemic and avian flu, reports of encephalopathy in COVID-19 have been slow to emerge, and there are so far no documented reports of parkinsonism apart from a single case report. We recommend consensus guidelines for the clinical treatment of Parkinson's patients with COVID-19. While a role for the virus in causing or exacerbating Parkinson's disease appears unlikely at this time, aggravation of specific motor and non-motor symptoms has been reported, and it will be important to monitor subjects after recovery, particularly for those with persisting hyposmia.

Patients with severe mental illnesses may present extrapyramidal symptoms as part of a concomitant neurological disorder or secondary to medications. Extrapyramidal symptoms are frequently unrecognized, have negative consequences for adherence to treatment, negatively affect quality of life and can induce stigma. We estimated and correlated with demographic and clinical variables prevalence of extrapyramidal symptoms in in-patients with severe mental illnesses. Additionally we evaluated ¹²³I-FP-CIT SPECT binding to striatal dopamine transporter in subjects with clinical manifestations suggestive of Parkinson's Disease and recorded therapeutic management and clinical evolution for 6-months. Extrapyramidal symptoms were present in 144 out of 285 patients (50.5%), mainly tremor (94 patients, 33%). There were 38 patients (13.3%) with parkinsonism and they had older age, more medical comorbidities and medical treatments. In 15/38 patients striatal dopamine transporter binding was abnormal resulting in dose reduction or change of psychotropic drugs as well as combination with antiparkinson therapy. Our study confirmed the clinical and epidemiological relevance of extrapyramidal symptoms among inpatients with severe mental illnesses. A small percentage of patients with extrapyramidal symptoms had features compatible with possible diagnosis of Parkinson's Disease. ¹²³I-FP-CIT SPECT was useful to identify dopaminergic dysfunction and initiate dopamine replacement therapy.

The presence of an extra copy of human chromosome 21 (Hsa21) leads to a constellation of phenotypic manifestations in Down syndrome (DS), including prominent effects on the brain and immune system. Intensive efforts to unravel the molecular mechanisms underlying these phenotypes may help developing effective therapies, both in DS and in the general population. Here we review recent progress in genetic and epigenetic analysis of trisomy 21 (Ts21). New mouse models of DS based on syntenic conservation of segments of the mouse and human chromosomes are starting to clarify the contributions of chromosomal subregions and orthologous genes to specific phenotypes in DS. The expression of genes on Hsa21 is regulated by epigenetic mechanisms, and with recent findings of highly recurrent gene-specific changes in DNA methylation patterns in brain and immune system cells with Ts21, the epigenomics of DS has become an active research area. Here we highlight the value of combining human studies with mouse models for defining DS critical genes and understanding the trans-acting effects of a simple chromosomal aneuploidy on genome-wide epigenetic patterning. These genetic and epigenetic studies are starting to uncover fundamental biological mechanisms, leading to insights that may soon become therapeutically relevant.