Reply to Letter to Editor: Is SARS-CoV-2 responsible for relapses of Parkinson’s disease?

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. To the Editor We read with interest the comments made by Scorza and colleagues [1] on our article regarding worsening of parkinsonian symptoms in a patient with advanced Parkinson’s disease (PD) as the sole initial presentation of COVID-19 infection [2]. Herein, we would like to respond to some points that were raised as concerns and comments. In our case, we ruled out various possible causes for clinical deterioration, as previously mentioned in our case description, along with normal initial computed tomography (CT) of the brain on presentation. We agree that cerebrospinal fluid (CSF) examination would be helpful in such cases; however, the lack of fever, signs of meningeal irritation on presentation, in addition to the overall outcome, ruled out CNS infection. As regards to not performing dopamine transporter (DAT) scan, our patient had a typical history of PD, with good response to dopaminergic therapy, and a dopamine transporter (DAT) scan is not mandatory for either diagnosis or follow-up. The authors postulated that confusion in our patient could be related to mismanagement of his medications; however, there was no history of any change in his usual doses, even when the family noticed the unusual worsening of his symptoms on his current regimen, which did not contain dopamine agonists. Moreover, no adjustment of his L-dopa dose was needed following admission, as the patient needed ventilatory support that required a small dose of propofol to relax his muscles. The authors suggested that respiratory distress could be related to a central etiology, which is unlikely in our case, in the context of severe COVID-19 infection. Moreover, Guillain–Barre syndrome (GBS) was not considered, as deep tendon reflexes were present, with the absence of any obvious weakness, as we recently reported such a case [3]. Although we have no evidence that the virus had entered the brain, worsening of PD symptoms is a known complication of any systemic infection without direct invasion to CSF. That was partly explained by Brugger and colleagues [4], through different mechanisms, including enhanced neurodegeneration by peripheral inflammation, downregulation of dopaminergic receptors, altered transport of dopaminergic drugs through the blood–brain barrier, altered presynaptic reuptake of L-dopa and dopamine, respectively, and impaired packaging of neurotransmitters into vesicles, among other explanations. Central dopaminergic hypoactivity associated with PD has been related to an increased risk of inflammation. Furthermore, recently it was shown that dopamine inhibits TRAF6-mediated NF-κB activation and inflammation via the D5 dopamine receptor in macrophages, and mutations in the LRRK2 gene are also found in some bacterial infections and autoimmune disorders [5, 6]. Supporting our claim, a genome-wide association study [7] reported that LRRK2 mutations, as the most common genetic cause of both familial and sporadic PD, has a role in regulating inflammatory responses systemically and in the brain, and are associated with autoimmune diseases [8]. Since no other apparent explanation of PD deterioration was determined, in addition to the improvement of the condition after stabilizing COVID-19 infection, we could suggest a probable association between Open Access The Egyptian Journal of Neurology, Psychiatry and Neurosurgery


To the Editor
We read with interest the comments made by Scorza and colleagues [1] on our article regarding worsening of parkinsonian symptoms in a patient with advanced Parkinson's disease (PD) as the sole initial presentation of COVID-19 infection [2]. Herein, we would like to respond to some points that were raised as concerns and comments. In our case, we ruled out various possible causes for clinical deterioration, as previously mentioned in our case description, along with normal initial computed tomography (CT) of the brain on presentation. We agree that cerebrospinal fluid (CSF) examination would be helpful in such cases; however, the lack of fever, signs of meningeal irritation on presentation, in addition to the overall outcome, ruled out CNS infection.
As regards to not performing dopamine transporter (DAT) scan, our patient had a typical history of PD, with good response to dopaminergic therapy, and a dopamine transporter (DAT) scan is not mandatory for either diagnosis or follow-up. The authors postulated that confusion in our patient could be related to mismanagement of his medications; however, there was no history of any change in his usual doses, even when the family noticed the unusual worsening of his symptoms on his current regimen, which did not contain dopamine agonists. Moreover, no adjustment of his L-dopa dose was needed following admission, as the patient needed ventilatory support that required a small dose of propofol to relax his muscles.
The authors suggested that respiratory distress could be related to a central etiology, which is unlikely in our case, in the context of severe COVID-19 infection. Moreover, Guillain-Barre syndrome (GBS) was not considered, as deep tendon reflexes were present, with the absence of any obvious weakness, as we recently reported such a case [3]. Although we have no evidence that the virus had entered the brain, worsening of PD symptoms is a known complication of any systemic infection without direct invasion to CSF. That was partly explained by Brugger and colleagues [4], through different mechanisms, including enhanced neurodegeneration by peripheral inflammation, downregulation of dopaminergic receptors, altered transport of dopaminergic drugs through the blood-brain barrier, altered presynaptic reuptake of L-dopa and dopamine, respectively, and impaired packaging of neurotransmitters into vesicles, among other explanations. Central dopaminergic hypoactivity associated with PD has been related to an increased risk of inflammation. Furthermore, recently it was shown that dopamine inhibits TRAF6-mediated NF-κB activation and inflammation via the D5 dopamine receptor in macrophages, and mutations in the LRRK2 gene are also found in some bacterial infections and autoimmune disorders [5,6]. Supporting our claim, a genome-wide association study [7] reported that LRRK2 mutations, as the most common genetic cause of both familial and sporadic PD, has a role in regulating inflammatory responses systemically and in the brain, and are associated with autoimmune diseases [8].
Since no other apparent explanation of PD deterioration was determined, in addition to the improvement of the condition after stabilizing COVID-19 infection, we could suggest a probable association between

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The Egyptian Journal of Neurology, Psychiatry and Neurosurgery