COVID-19 and Parkinson’s disease: a casual association or a possible second hit in neurodegeneration?

Cavallieri, Francesco; Fioravanti, Valentina; Toschi, Giulia; Grisanti, S.; Napoli, Manuela; Moratti, Claudio; Pascarella, Rosario; Versari, Annibale; Fraternali, Alessandro; Casali, Massimiliano; Paul, Jefri J.; Moro, Elena; Bauer, Péter; Zedde, Marialuisa; Valzania, Franco

doi:10.1007/s00415-021-10694-4

Cited by 23 publications

(33 citation statements)

References 7 publications

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“…On the contrary, the second scenario (unmasking of underlying still non-symptomatic PD) might be more intriguing and more interesting. Indeed, in this setting, if we consider COVID-19 infection as a second hit that has unmasked PD in predisposed patients [ 8 , 9 , 21 ], it would appear extremely appealing to investigate why these subjects were predisposed to developing PD. If this predisposition has a genetic basis, it would be interesting to analyze these subjects for the presence of variants in the main genes involved in the genetic form of PD [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, myoclonus and ataxia are the most frequently identified movement disorders in COVID-19 infection [ 6 ]. A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome [ 8 , 9 , 10 , 11 , 12 ]. This hypothesis has been supported by: the well-known ability of coronaviruses to enter the central nervous system (CNS) through the olfactory system with subsequent neuronal death [ 10 , 11 , 12 ]; the presence of higher levels of antibodies against coronaviruses in the cerebrospinal fluid (CSF) of PD patients compared to healthy controls suggesting a possible involvement of viral infection in the pathogenesis of PD [ 9 , 10 , 11 , 12 ]; the negative immediate and lasting effects of a COVID-19-related cytokine storm on the CNS with brain cell damage [ 11 ], and the possible hypoxic or vascular damage to the basal ganglia caused by COVID-19 infection [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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COVID-19 and Parkinsonism: A Critical Appraisal

et al. 2022

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A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this review is to summarize the clinical, biological, and neuroimaging features of published cases describing COVID-19-related parkinsonism and to discuss the possible pathophysiological mechanisms. A comprehensive literature search was performed using NCBI’s PubMed database and standardized search terms. Thirteen cases of COVID-19-related parkinsonism were included (7 males; mean age: 51 years ± 14.51, range 31–73). Patients were classified based on the possible mechanisms of post-COVID-19 parkinsonism: extensive inflammation or hypoxic brain injury within the context of encephalopathy (n = 5); unmasking of underlying still non-symptomatic Parkinson’s Disease (PD) (n = 5), and structural and functional basal ganglia damage (n = 3). The various clinical scenarios show different outcomes and responses to dopaminergic treatment. Different mechanisms may play a role, including vascular damage, neuroinflammation, SARS-CoV-2 neuroinvasive potential, and the impact of SARS-CoV-2 on α-synuclein. Our results confirm that the appearance of parkinsonism during or immediately after COVID-19 infection represents a very rare event. Future long-term observational studies are needed to evaluate the possible role of SARS-CoV-2 infection as a trigger for the development of PD in the long term.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

COVID-19 and Parkinsonism: A Critical Appraisal

et al. 2022

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“…A total of 16 papers were included, describing 20 cases that met our criteria (Table 2). [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] In 13 patients, SARS-CoV-2 infection was confirmed with a nasopharyngeal swab, found positive for SARS-CoV-2 in a real time reverse-transcription polymerase chain reaction (RT-PCR) assay. For the residual seven cases reported to have been diagnosed with 8,10,11,15,16,20) the diagnostic means of confirmation were not provided.…”

Section: Resultsmentioning

confidence: 99%

“…Αll seven patients who underwent functional nigrostriatal imaging showed a decreased dopamine uptake in the striatum, revealing a deficit in the dopaminergic nigrostriatal pathway, which, although suggestive of a parkinsonian syndrome, is not diagnostic of PD. Although such findings in nuclear imaging usually refer to an older, possibly ongoing, brain lesion, 35 there have been reports of decreased nigrostriatal uptake developing acutely or sub‐acutely. 62 , 63 These latter lesions are usually accompanied by abnormal findings in the brain MRI scan as well, which was not the case in these seven patients.…”

Section: Discussionmentioning

confidence: 99%

Coronavirus Disease 2019 and Related Parkinsonism: The Clinical Evidence Thus Far

Boura

2022

Movement Disord Clin Pract

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Background The Coronavirus disease 2019 (Covid‐19) pandemic has fueled both research and speculation, as to whether it could be a “perfect storm” for a post‐Covid emergence of parkinsonism in some susceptible individuals, analogous to the post‐encephalitic parkinsonism reported after the 1918 influenza epidemic. This theory is further augmented by reports of a pathogenic effect of the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) on the central nervous system with specific impact on the dopaminergic pathway, as well as the possibility of the virus to selectively bind to Angiotensin‐Converting Enzyme‐2 (ACE‐2); these molecules are expressed abundantly in the midbrain dopamine neurons and, are likely involved in several cellular mechanisms cited in Parkinson's Disease (PD) pathophysiology. Objectives—Methods Therefore, we performed a review of the literature up to February 2022 to explore the current landscape considering published cases of new‐onset parkinsonism after a SARS‐CoV‐2 infection in otherwise healthy individuals. We summarized their clinical features, diagnostic and treatment approaches, discussing potential underlying mechanisms in light of PD pathogenesis theories. Results Twenty cases that developed parkinsonian features simultaneously or shortly after a reported SARS‐CoV‐2 infection were reviewed. In 11 of them, parkinsonism appeared in the context of encephalopathy, while four patients developed post‐infectious parkinsonism without encephalopathy, and four bore similarities to idiopathic PD. Nine patients exhibited a good response to dopaminergic therapy, while four responded to immunomodulatory treatment. Conclusions Available data does not yet justify a clear association between the Covid‐19 pandemic and a parkinsonism wave. However, vigilance is necessary, as long‐term effects might have not been revealed.

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“…A few cases of parkinsonism after COVID-19 have been reported so far. Although the possibility of post-infectious parkinsonism cannot be excluded, these cases probably suggest that COVID-19 may unmask an underlying Parkinson’s disease, which was previously in a preclinical stage ( Cavallieri et al, 2021 ; Makhoul and Jankovic, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report

et al. 2021

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Cognitive symptoms after COVID-19 have been increasingly recognized several months after the acute infection and have been designated as “brain fog.” We report a patient with cognitive symptoms that started immediately after COVID-19, in which cerebrospinal fluid biomarkers were highly suggestive of Alzheimer’s disease. Our case highlights the need to examine patients with cognitive symptoms following COVID-19 comprehensively. A detailed assessment combining clinical, cognitive, and biomarker studies may help disentangle the underlying mechanisms associated with cognitive dysfunction in each case. The investigation of neurodegenerative processes in an early stage, especially in older patients, is probably warranted.

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COVID-19 and Parkinson’s disease: a casual association or a possible second hit in neurodegeneration?

Cited by 23 publications

References 7 publications

COVID-19 and Parkinsonism: A Critical Appraisal

COVID-19 and Parkinsonism: A Critical Appraisal

Coronavirus Disease 2019 and Related Parkinsonism: The Clinical Evidence Thus Far

“Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report

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