COVID-19 Linked to Increased Risk for Parkinson's

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

One of the neurologic complications of COVID-19 may be the development of Parkinson's disease, new data suggest.

At least three case reports have been published of relatively young COVID-19 patients who developed clinical parkinsonism, either in isolation or with other neurologic deficits, within 2 to 5 weeks of contracting the disease. A fourth case has not yet been published.

The three published cases and possible mechanisms as to how COVID-19 could cause Parkinson's are discussed in an article entitled, "Is COVID-19 a Perfect Storm for Parkinson's Disease?," published online October 21 in Trends in Neurosciences.

"If this link is real, we might be in for an epidemic of Parkinson's disease in the future," the lead author of the article, Patrik Brundin, MD, told Medscape Medical News.

Brundin is director of the Center for Neurodegenerative Science at Van Andel Research Institute in Grand Rapids, Michigan. Coauthors of the article are Avindra Nath, MD, from the National Institute of Neurological Disorders and Stroke, and David Beckham, MD, associate professor of medicine–infectious disease at the University of Colorado Anschutz, in Aurora, Colorado.

They report that the three patients in the published cases were aged 35, 45, and 58 years. All had severe respiratory infection that required hospitalization. For two of three patients, symptoms of parkinsonism diminished upon administration of traditional dopaminergic medication. The third patient recovered spontaneously.

In all cases, brain imaging revealed reduced function of the nigrostriatal dopamine system, as is seen in Parkinson's disease. None of them had a family history of Parkinson's disease nor any history of signs of prodromal Parkinson's. One patient underwent genetic testing and was not found to carry any Parkinson's risk variants.

"These cases of acute Parkinson's in patents with COVID-19 are truly remarkable," Brundin said. "They occurred in relatively young people ― much younger than the average age of developing Parkinson's ― and none had a family history or early signs of Parkinson's prodrome. That is quite a stunning observation."

He added: "Parkinson's is normally a very slowly developing disease, but in these cases, something happened quickly."

Brundin believes that COVID-19 may predispose patients to develop Parkinson's disease either sooner or later. "It may be that a younger patient will recover from the infection but be left with neurological symptoms, such as brain fog and depression ― we know that this can happen in long-COVID. This is consistent with damage to the brain, and maybe Parkinson's disease will develop later."

He says that mounting evidence suggests that COVID-19 can cause long-term adverse effects, including neurologic problems, one of which could be Parkinson's disease.

"It does not appear to be just an acute condition which you survive or don't survive. There are many people for whom long-term outcomes may be affected," he commented.

If such serious conditions as Parkinson's are proven to be a complication of COVID-19, it is even more important for the population to avoid contracting the virus, he notes.

"This really should discourage the idea of trying to achieve herd immunity. It is a very bad idea to expose a large percentage of the population to a virus that we don't understand," Brundin stated. In the article, the authors say this could have "disastrous long-term implications."

Brundin also says the possibility of long-term neurologic sequelae strengthens the case for treating patients with COVID-19 as aggressively as possible. "If we can reduce the inflammatory response, that may be helpful in reducing neurological complications.'

The authors say that these cases do not prove a causal relationship between COVID-19 and the development of parkinsonism.

"Possibly, the reported patients were destined to develop Parkinson's disease, were on the cusp of losing the number of nigral dopamine neurons required for the emergence of motor symptoms, and the viral infection only accelerated an ongoing neurodegenerative process around a critical timepoint. However, the rapid onset of severe motor symptoms in close temporal proximity to the viral infection is still suggestive of a causal link," they write.

Although neuropathologic findings have not been described regarding patients who developed parkinsonism acutely following COVID-19, the authors note that there is a growing number of postmortem reports of patients who died from COVID-19. One such neuropathology study of 43 patients found evidence of microglial activation and invasion of cytotoxic T cells in the brainstem, which are neuropathologic signs associated with Parkinson's disease.

Three Possible Mechanisms: "A Perfect Storm"

The authors describe three possible mechanisms that could explain the link between COVID-19 and Parkinson's.

First, the virus may cause hypercoagulation. Small infarcts in multiple organs, including the brain, could trigger Parkinson's. Alternatively, the virus may a trigger defence response in nerve cells that leads to an increase in alpha-synuclein and its clumping ― a hallmark of Parkinson's. Finally, a massive systemic inflammation may trigger the condition.

These mechanisms together may produce "a perfect storm" for the development of Parkinson's, Brundin suggests.

He says he favors the latter two mechanisms.

"There is a growing body of evidence to suggest that alpha-synuclein is involved in the immune system and can be affected by viral infections," he explained. This includes studies showing that in mice infected with West Nile virus ― which causes encephalitis ― there is an increase in alpha-synuclein and clumping of alpha-synuclein.

"It would be interesting to find out if there are neuroinflammatory changes or increases in alpha-synuclein in the brains of patients who have died from COVID-19, but so far, there are few neuropathology reports available," Brundin added.

He points out that other viruses have been associated with Parkinson's. "Hepatitis C has been shown in several epidemiological studies to be associated with increased Parkinson's risk, and this is no longer seen when patients take modern antiviral therapies," he noted.

The authors call for long-term follow-up of large cohorts of patients affected by COVID-19, with monitoring for manifestations of Parkinson's. If patients who have had COVID-19 are found to have an increased risk for Parkinson's, and potentially other related neurodegenerative disorders, it would be critical to identify treatments that mitigate such an elevated risk, they say.

Brundin is supported by funding from the Van Andel Institute and the Farmer Family Foundation on projects related to infections and Parkinon's disease. He has received commercial support as a consultant or for research from Axial Biotherapeutics, Calico Life Sciences, CuraSen, Fujifilm-Cellular Dynamics International, Idorsia, IOS Press Partners, LifeSci Capital LLC, Lundbeck A/S, and Living Cell Technologies LTD, and Roche. He has ownership interests in Acousort AB and Axial Biotherapeutics and is on the steering committee of the NILO-PD trial.

Trends Neurosci. Published online October 21, 2020. Full text

For more Medscape Neurology news, join us on Facebook and Twitter.

Medscape Medical News © 2020 

Send news tips to news@medscape.net.

Cite this: COVID-19 Linked to Increased Risk for Parkinson's - Medscape - Nov 05, 2020.