Israeli researchers note possible link between Parkinson's and COVID-19

"We diagnosed parkinsonism, meeting the Movement Disorders Society Unified Parkinson's Disease Rating Scale criteria for the diagnosis of probable Parkinson's disease," researchers explained.

By JERUSALEM POST STAFF
Updated: OCTOBER 4, 2020 10:55
An image of the human brain (photo credit: REUTERS)
An image of the human brain
(photo credit: REUTERS)
Israeli researchers have noted a possible connection between a novel coronavirus infection and the early onset of Parkinson's disease, based off the data of a Ashkenazi-Jewish man who was hospitalized at Samson Assuta Ashdod University Hospital in Ashdod.
The 45-year-old man was initially hospitalized with a dry cough and muscle pain - the patient also reported a loss of smell. He was admitted two days after returning from Israel after being abroad in the USA. The patient believes he contracted the virus on the plane as he reported a passenger coughing repeatedly behind him.
Via PCR testing he was found positive for SARS-CoV-2, the scientific term for the novel coronavirus - he had two underlying conditions: hypertension and asthma.
He was treated for three days at the hospital, mainly for his asthma with salbutamol inhalations with no need for invasive treatments such as oxygen assistance via a ventilator or oxygen supplementation. His only other symptoms were fatigue, shortness of breath and chest pain; no fever.
The patient was then released into isolation following his three-day stint in the hospital.
During his three-week isolation, the patient "noticed that his handwriting had changed and become smaller and less readable than previously. He started having difficulties speaking and writing text messages on his mobile phone. He also had episodes of tremor in his right hand," the researchers said.
Two months following his initial positive coronavirus diagnosis, the patient was admitted to the Department of Neurology at Shaare Zedek Medical Center after his Parkinson's-like symptoms failed to subside.
"On examination, the patient had hypomimia and hypophonic fluent speech. He had moderate cogwheel rigidity in the neck and in the right arm, mild cogwheel rigidity in the left arm, moderate bradykinesia in the right extremities, mild bradykinesia in the left extremities, and no tremor," the researchers said. "His gait was slightly slow, with no right arm swing, and the elbow appeared to be in flexion during walking but with normal step length and height.
"No retropulsion was found on a pull test. He did not have cognitive decline, shown by a Montreal Cognitive Assessment score of 28 of 30, but his subjective impression was that his cognitive performance was lower than usual."
As far as his blood tests went, the results were "unremarkable" showing mainly normal readings across the board. CT, MRI and EEG tests also came back normal. The researchers were beginning to think the cognitive decline was subjective, meaning its quite possible the difficulties could be all in his head.

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"But a 18F-fluorodopa (18F-FDOPA) PET scan showed decreased 18F-FDOPA uptake in both putamens, more apparent on the left side. Additionally, mild decreased uptake in the left caudate was also suspected," the researchers said.
The researchers then performed genetic testing for mutations of the LRRK2 gene and other GBA variants. They also ran Next Generation Sequencing to screen for other genes related to Parkinson's. Some 62 genetic analyses total, all came back negative. However, the researchers still diagnosed the patient with Parkinson's, based off the PET scan.
"We diagnosed parkinsonism, meeting the Movement Disorders Society Unified Parkinson's Disease Rating Scale criteria for the diagnosis of probable Parkinson's disease," they explained. "We initiated treatment with 0·375 mg extended release pramipexole, once daily, which resulted in a quick improvement according to the patient's subjective impression, as well as in clinical signs."
"During his 9 days of hospitalization, the patient started complaining of tremor in both legs, more on the right side than the left, and of increased urinary frequency. On discharge, he still had unreadable handwriting, hypomimia, bradykinesia, and cogwheel rigidity, mostly on the right side," the researchers noted. "He was empirically treated with a course of 5 days intravenous high-dose methylprednisolone, without any consistent effect. Because of the worsening of tremor in his right extremities, in a follow-up visit on June 29, biperiden was added at a dose of 2 mg daily, and increased to 4 mg daily after 1 week, which resulted in improvement of the tremor."
The researchers believe the genetic makeup of the patient left him susceptible to immunologically mediated mitochondrial injury and neuronal oxidative stress, adding that the viral infection could have contributed to protein aggregation and neurodegeneration.
"However, the short time interval between the acute infection and the parkinsonian symptoms makes this hypothesis unlikely," the researchers said, noting that the viral infection did not specifically cause Parkinson's within the patient, but that the way it interacted with the body could have brought on early symptoms of Parkinson's.
"Other researchers have proposed the so-called multiple hit hypothesis, by which the combination of toxic stress and an inhibition of neuroprotective responses can lead to neuronal death," they added.
Considering Parkinson's disease is normally proceeded by loss of smell - as has been reported in COVID-19 patients -  "immune activation in the olfactory system might eventually lead to the misfolding of α-synuclein and the development of Parkinson's disease" which is "supported by post-mortem studies, showing increased levels of TNF."
"Moreover, patients with Parkinson's disease had an elevated CSF antibody response to seasonal coronaviruses, compared with age-matched healthy controls," they added, explaining that "in Ashkenazi-Jewish people with Parkinson's disease, about a third are carriers of either a GBA or a LRRK2 mutation."
"We cannot exclude an interaction between other, less frequent mutations and SARS-CoV-2. The temporal association between the episode of SARS-CoV-2 infection and parkinsonian symptoms, which appeared during the acute infection, is intriguing. Before his admission to the Department of Neurology, the patient had tested negative for SARS-CoV-2 on real-time RT-PCR on two occasions," the researchers concluded. "However, he was then found positive for anti-SARS-CoV-2 IgG antibodies in serum, but negative for these antibodies in CSF.
"Nonetheless, we cannot exclude the possibility that SARS-CoV-2 entered the CNS, particularly in view of the olfactory involvement and borderline pleocytosis," causing the cognitive degeneration in the patient.
The researchers published their findings the peer-reviewed scientific journal Lancet. The researchers were part of teams from Shaare Zedek Medical Center and the Hebrew University of Jerusalem.


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