key: cord-0828848-fnh5flwc authors: Rita Lo Monaco, Maria; Rita Bentivoglio, Anna; Fusco, Domenico; Calabresi, Paolo; Piano, Carla title: Subacute onset dystonia in a woman affected by Parkinson’s disease following SARS-COV-2 infection date: 2020-11-27 journal: Clin Park Relat Disord DOI: 10.1016/j.prdoa.2020.100082 sha: b192f2299e7fd2c56fac7f8d008baaf59347ad5b doc_id: 828848 cord_uid: fnh5flwc nan In this letter, we reported the case of a woman affected by Parkinson's Disease who developed transient generalized dystonia during SARS-COV-2 infection with a mild course. We have revised the manuscript according to the reviewers' comments and also provided a point to point reply listed below. All authors approved the revised version of the manuscript. Looking forward to your reply. Minor revision 1."Within a few years, the motor disorder progressed towards a complete parkinsonian syndrome." --It could be better to describe the patient's conditions and neurological examination results before the COVID-19 infection. We thank the reviewer for the comment and we provide clarifications about the patient's condition neurological examination results before the COVID-19 infection. 2."Here we describe the case of a woman affected by Parkinson's disease who presented severe generalized dystonia, heralding SARS-CoV-2 infection. --PD patients with a combination of subacute onset dystonia cannot directly deduce the SARS-CoV-2 infection. This sentence may be misguiding. We changed the text to be more precise, in agreement with the comment of the reviewer. 3."The clinical suspect of COVID-19 was confirmed by the positive nasopharyngeal swab test." --Confirmed by two consecutive positive RT-PCR results or more? We pointed out that the clinical suspicion was confirmed by two positive nasopharyngeal swab. The third swab done was negative. 4. Did the therapy for PD symptoms change after COVID-19 infection? --This could also be one of the reasons for the dystonia and needs to be clarified or to be added as a limitation. We clarified in the text that within three weeks, the therapy regimen returned to the previous one. This is an interesting case report. I only have few minor comments: 1. Is there any video of the patient? We agree that it would have been a very interesting track but unfortunately, we could not collect any video of the presentation and course of this clinical case 2. Was the previous regimen of L-dopa therapy reinstalled after COVID-19 resolved? Within three weeks, the therapy regimen returned to the previous one. We highlighted in the text. 3. Was this case already reported in the MDS online repository? Other similar cases needing an increase of L-dopa therapy have been reported and perhaps Authors might quote them too. 4. An alternative explanation is just a generic worsening of the disease, as seen during other viral illnesses. Among the phenotypic spectrum of Parkinson's disease (PD), dystonia is common, especially in juvenile forms. Dystonic spasms are also observed in patients under dopaminergic treatment or in the case of fever, trauma, surgery, and infections; in a minority of cases dystonia may progress to a severe condition such as status dystonicus 1 . Here we describe the case of a woman affected by Parkinson's disease who presented severe generalized dystonia, developing in a short amount of time after SARS-CoV-2 infection. In April 2020, in the middle of the COVID-19 pandemic in Italy, we evaluated a 58-year-old woman with idiopathic PD, diagnosed when she was 50 years old. The patient, at the onset of the disease, began experiencing a mild tremor in his right hand and left shoulder rigidity which became progressively worse. In about two years the patient was diagnosed with PD alter the tremor had advanced in severity and his left shoulder was becoming increasingly rigid. The patient then began taking dopamine agonists suffered from an important constellation of side effects and then levodopa with good control of tremor and rigidity. At the time of evaluation, when "on" she started to experience "mild" dyskinesias initiated by levodopa dosing and worsening akinetic symptoms while "off". The dyskinetic and akinetic symptoms were not so severe and she could work and live an almost normal life. In the following years, she was treated with different combinations of drugs and clozapine was introduced to control levodopa-induced hallucinations. Recently, antiparkinsonian treatment consisted of levodopa/benserazide and clozapine administration. On April 12, we were contacted by the patient's husband as her temperature had risen slightly (37.2 ∞C), and she showed slurred speech and confusion. In the following hours, the patient presented severe spasms of arms and legs. Considering the high risk of contagion, and according to national guidelines, we arranged a session of telemedicine consulting. The patient was sleepy but quickly awakened. Her speech was slurred but intelligible without evidence of dysarthria or aphasia. She was not in respiratory distress (no dyspnea or cough). Blood pressure, heart, and respiratory frequency were within the range of normality. Percutaneous oxygen saturation was 97% in room air. She showed sustained dystonic spasms of the four limbs, reported as persistent in the "off" and the "on" med condition. No other focal neurological deficits were present when compared to the last neurologic examination of two months before. She was advised to increase the daily dose of levodopa (from 400 to 600) and clozapine (from 25 to 50 mg). Two positive nasopharyngeal swab test confirmed the clinical suspect of COVID-19. The infection had a mild course with fever never exceeding 37.5 °C and temperature dropping after a few days. She never presented respiratory distress or other complications. No therapy for viral infection was prescribed; neurological conditions rapidly improved. At the end of the quarantine, she was evaluated at the Movement Disorder Clinic. Thoracic findings, temperature and oxygen saturation were normal. Neurological examination revealed global bradykinesia, resting tremor of the right hand, and mild upper limbs rigidity. The UPDRS III score in on status was 32/108, and no dystonic spasms of the limbs were present. Within three weeks, the therapy regimen returned to the previous one. Neurological manifestations in patients infected with SARS-CoV-2 have been reported, and severe respiratory distress seems to predispose to neurological disorders. Moreover, patients with advanced PD and longer disease duration are more sensitive to COVID-19 disease 2 . To our knowledge, no case of worsening of dystonic symptoms in Sars-Cov2 infection of PD has been described in the literature. Furthermore, in this case, the severity of the infectious disease was mild, but neurological manifestation was important. Various mechanisms may explain the CNS involvement by SARS-CoV-2 infection. Encephalopathy may be a consequence of CNS metabolic distress due to fever or hypoxia, in other cases, autoimmune vasculitis or a cytokine storm in the brain or viral direct damage 3 have been pointed out. In our patient, the short duration of symptoms, their limited clinical relevance and duration may suggest a different origin of transient dystonia. Indeed, an interference of the infection with the levodopa metabolism that spoils its bioavailability within the CNS may be hypothesized. The cell receptor for SARS coronaviruses angiotensin-converting enzyme 2 (ACE2) 4 and the dopamine decarboxylase have been reported to be co-expressed and co-regulated in nonneuronal cell types. As such, the involvement of the synthetic dopamine pathway in the pathophysiology of COVID-19 can be hypothesized 5 . In line with this hypothesis is the observation of improved dystonia with increasing levodopa dosage. Clozapine has also been reported to improve hyperkinetic movement disorders, including tardive dystonia. We prescribed a higher dose of this drug to avoid re-emergence of psychosis, but clozapine may have also played a role in the rapid resolution of subacute limbs dystonia. This case report provides further evidence that the neurological manifestations of COVID-19 not being fully framed. Hence, case reports may be relevant for a better and more comprehensive understanding of the interaction between the virus and CNS. Management of status dystonicus: Our experience and review of the literature Outcome of Parkinson's Disease patients affected by COVID-19 The neuroinvasive potential of SARSCoV2 may be at least partially responsible for the respiratory failureof COVID-19 patients Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19