Parkinson's disease diagnosed after SARS-CoV-2

As the COVID-19 pandemic continues to spread, new and unusual chronic sequelae of the disease are cropping up in many medical practices. Now, a new case paper published in The Lancet in September 2020 describes a case of new-onset Parkinson's disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Parkinson's disease is a recognized sequel of several viral infections, including influenza A, varicella-zoster, hepatitis C virus, HIV, Japanese encephalitis virus, or West Nile virus. In the current report, the authors describe the onset of severe acute COVID-19 in an Ashkenazi Jewish 45-year old male in Israel. Admitted to hospital with a dry cough, muscle pain, and anosmia.

History of Parkinsonism in the Patient

The infection may have been contracted on a visit to the US or on the flight back, where a passenger behind his row of seats was heard to be repeatedly coughing. The symptoms were noted two days later.

With a medical history of hypertension and asthma, he tested positive by real-time RT-PCR testing of a nasopharyngeal swab and was promptly admitted. During hospitalization, he experienced dyspnea and fatigue, as well as chest pain. He was treated for mild asthma symptoms but did not progress to severe COVID-19, not requiring either oxygen supplementation or mechanical ventilation.

Following three days of inpatient treatment, he underwent isolation in a COVID-19 center for three weeks. During this period, he found his handwriting was becoming cramped. He also found it hard to speak normally, and texting on his phone became a challenge. Another new symptom was a tremor of the right hand.

Eventually, he was discharged home, but because these symptoms persisted, he visited a neurological facility and was admitted at about two months from the initial positive PCR. At this point, there was reduced facial expression and soft speech but without a loss of fluency.

He also displayed characteristic cogwheel rigidity in the neck and in the right arm to a moderate degree, with a slow movement of the right limbs, but no tremor. They found his gait had become a little slower, right arm swing was absent, and the right elbow was flexed during walking. His step remained as long and high as before, however.

Cognitive decline was objectively absent, but he felt that he was not performing normally in this area. He had no family history of Parkinson's disease. He had not been exposed to any neurological toxins or recreational drugs.

Image Credit: Kateryna Kon / Shutterstock
Image Credit: Kateryna Kon / Shutterstock

Normal Laboratory Investigations

There were no alterations in the blood tests, either during the acute SARS-CoV-2 infection or during the current episode. He was seropositive for anti-SARS-CoV-2 IgG in blood but not in cerebrospinal fluid (CSF), which was also negative for the virus by real-time RT PCR.

No sign of autoimmune antibodies to neural tissue was found in serum or in CSF. Brain CT, MRI, and EEG were all normal. However, a specialized 18F-fluorodopa (18F-FDOPA) PET scan indicated that the uptake of the isotope was reduced in the putamen on both sides but more on the left.

They ruled out mutations in LRRK2 gene loci and in the GBA gene sequences, which are present in a third of Ashkenazi-Jewish people with Parkinson's disease. Other genes related to Parkinson's were examined by next-generation sequencing without any abnormality being turned up. Other unrecognized mutations might have been present, of course.

Diagnosis and Management

The neurological diagnosis was finally Parkinsonism, probably Parkinson's disease. The patient was put on pramipexole and experienced rapid symptomatic improvement and a reduction in the severity of clinical signs. However, during the rest of his 9 days of hospitalization, he developed a tremor in both legs, more on the right side, increased frequency of urination and complained of the persistence of the earlier symptoms that had brought him to the center.

Treatment with intravenous high-dose corticosteroids was ineffective, while tremor in the right extremities continued to worsen. The addition of biperiden resulted in a reduction of tremors.

Mechanism of Parkinsonism in this Patient

The researchers speculate that the nigrostriatal dopaminergic nerve terminals degenerated due to an unknown process, perhaps coupling genetic predisposition with immune injury to the mitochondria triggered by SARS-CoV-2 infection. The resulting oxidative stress on the nerve cells might have caused the injury.

An alternative is that virally-mediated activation of the brain microglia led to inflammation, causing neural proteins to aggregate and causing degeneration of the brain cells. This is unlikely, say the researchers, because of the insufficient interval between the acute infection and the onset of Parkinsonism.

A third possible mechanism is the multiple hit theory, where toxins interact with impaired neuroprotective responses to kill the brain cells.

Supporting Findings and Implications

Some crucial findings here are the presence of anosmia, often found in COVID-19 but also the period preceding Parkinson's disease. The researchers postulate that infection of the olfactory epithelium could have triggered the local immune response, leading to misfolding of the α-synuclein protein over time, leading to eventual Parkinson's disease. This might also indicate that the virus did enter the brain even though antibodies were absent from the CSF.

Post-mortem studies show that high levels of TNF, IL1, and IL6 are present in these patients. Parkinson's disease is also linked to higher levels of CSF antibody production in response to seasonal coronaviruses, relative to age-matched controls without the disease.

The study thus reports the development of Parkinsonism, probably Parkinson's disease, following acute SARS-CoV-2 infection, which may increase the awareness of this condition among healthcare professionals.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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