Acute parkinsonism can follow COVID-19 infection, according to the authors of a new review, although other experts say the jury is still out. "We should not think of COVID-19 as a respiratory disorder, if there is anyone out there that still does that!" Dr. Patrik Brundin of the Center for Neurodegenerative Science at Van Andel Institute, in Grand Rapids, Michigan, told Reuters Health by email. "This is a systemic disease, and the brain is not spared." In light of at least three published single-case reports of clinical parkinsonism that developed within two to five weeks after contracting SARS-CoV-2, Dr. Brundin and colleagues discuss the potential link between COVID-19 and Parkinson's disease in a report in Trends in Neurosciences. Two of these three patients responded to traditional dopaminergic medication with reduced parkinsonian symptoms, and the third patient recovered spontaneously. Brain imaging in all cases revealed reduced function of the nigrostriatal dopamine system. Besides these case reports, one neuropathology study of 43 patients described evidence of microglial activation and invasion of cytotoxic T cells in the brainstem, which are similar to signs associated with Parkinson disease (PD). The authors propose three potential mechanisms for the rapid development of parkinsonism following SARS-CoV-2 infection. First, vascular insults, which have been reported in severe COVID-19 in conjunction with a hypercoagulable state, could directly damage the nigrostriatal system, similar to what is seen in vascular parkinsonism. Second, the marked systemic inflammation caused by severe COVID-19 could contribute to the destruction of nigral dopamine neurons, which are thought to be particularly susceptible to systemic inflammation. And finally, SARS-CoV-2 might be a neurotropic virus: viral RNA has been detected in postmortem brains of some COVID-19 patients, and neuroinvasion of SARS-CoV-2 could result in upregulation of neuronal alpha-synuclein, which could lead to the formation of aggregates similar to those seen in the PD brain. If this latter mechanism is correct, the authors suggest, SARS-CoV-2 could predispose to the development of PD later in life. "I think one has to be vigilant and start following large cohorts of post-COVID-19 people," Dr. Brundin said. "Ideally, monitoring them for signs of prodromal PD (hyposmia, constipation, anxiety, depression, REM sleep behavior disorder, and constipation) should be done. If there is an overrepresentation of these signs, a subgroup should be imaged with dopamine transporter (DAT) scans or PET scans to visualize if there is loss of dopamine in the nigrostriatal pathway." "It will be very important to develop therapies that reduce the duration and the severity (perhaps assessed as inflammatory response) of COVID-19," he said. "At this point, we do not know how the brain changes develop, but it is likely that reducing the viral load and reducing the inflammation might be important." Dr. Brundin added, "This also means that we have to be very careful when we say that children and young people do well. We really do not know this for sure yet." "We know so little about SARS-CoV-2 at this point, except that it can be a very nasty virus," he said. "Taking a cautious route seems wise." Dr. K. Ray Chaudhuri of King's College London, editor-in-chief of npj Parkinson's Disease, told Reuters Health by email, "Of the three cases quoted, none really have typical PD (spontaneous remission does not occur in PD and one case is described as an akinetic rigid syndrome) and could have occurred because of secondary vascular events and hypoxia in the brain, as they were all ill and had significant respiratory disease." "There is no robust evidence of direct neurotropism of SARS-CoV-2 apart from the occurrence of hyposmia, but this needs more work," he said. "The message as in this paper may spread worry and alarm among many who have had COVID-19 pneumonia or were hospitalized and recovered," Dr. Chaudhuri said. "As outlined in the paper by Sulzer et al. (https://go.nature.com/37J0ftS), there is no convincing arguments that COVID-19 may cause parkinsonism and only time will tell, and it is, in my view, better to observe and critically analyze data we have rather than jumping into prediction at this stage." —Will Boggs MD Source
