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Myoclonus status revealing COVID 19 infection

Published:November 21, 2022DOI:https://doi.org/10.1016/j.seizure.2022.11.010

      Abstract

      Introduction

      At the beginning of the coronavirus virus (COVID-19) pandemic, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was thought to cause mainly respiratory symptoms, largely sparing the brain and the rest of the nervous system. However, as the knowledge about COVID-19 infection progresses and the number of COVID19-related neurological manifestations reports increases, neurotropism and neuroinvasion were finally recognized as major features of the SARS-CoV-2. Neurological manifestations involving the central nervous system are sparse, ranging from headaches, drowsiness, and neurovascular attacks to seizures and encephalitis [
      • Sharifian-Dorche M
      • Huot P
      • Osherov M
      • Wen D
      • Saveriano A
      • Giacomini PS
      • et al.
      Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic.
      ]. Thus far, several cases of non-epileptic myoclonus were reported in critical patients [
      • Przytuła F
      • Błądek S
      • Sławek J.
      Two COVID-19-related video-accompanied cases of the severe ataxia-myoclonus syndrome.
      ,
      • Rábano-Suárez P
      • Bermejo-Guerrero L
      • Méndez-Guerrero A
      • Parra-Serrano J
      • Toledo-Alfocea D
      • Sánchez-Tejerina D
      • et al.
      Generalized myoclonus in COVID-19.
      ]. Here, we report the first case of myoclonus status as the inaugural and sole symptom of COVID-19 in a conscious patient.

      Observation

      A 60-year-old man with unknown family history and no medical issues other than smoking one cigarette packet a day over the span of 25 years. The patient presented with 5 days of abnormal movements in bilateral arms following the COVID vaccination. They were described as brief, involuntary jerking, like in sleep starts, in the proximal part of their upper members, and his face with a regular tremor in his arms exacerbated by movements and emotion. His movement disorder worsened the second day, and he developed an abnormal gait with slurred speech, concomitantly with diarrhea. Seven days following the symptoms onset, the patient was alert. His neurological exam revealed multifocal myoclonic jerks affecting four limbs predominantly proximal, the face, and the trunk (video 1). The myoclonic jerks were sensitive to tactile and auditory stimuli, without enhanced startle response or hyperekplexia. His gait was unsteady due to severe myoclonus, without cerebellar ataxia (video 2) and he had mild dysarthria. No dysmetria at the finger-to-nose and heel-to-shin tests were found. Examination of eye movements revealed paralysis of Down-Gaze and no opsoclonus was detected. Physical exam was unremarkable, including lack of fever and meningitis signs. The electroencephalogram (EEG) did not show any abnormalities concomitant with myoclonic jerks (Fig.1). The cerebral Magnetic Resonance Imaging (MRI) was normal (Fig. 2). An extensive biological work-up including a complete blood count, a comprehensive metabolic panel, an arterial blood gas analysis, a urine drug screen, a thyroid function test, a vitamin B12, folate, and ammonia level, and HIV and syphilis serologies were inconclusive. Testing for autoimmune and paraneoplastic antineuronal antibodies including anti-NMDA-R was negative. The cerebrospinal fluid (CSF) study was unremarkable (0.3 g/l of proteinorachia, 1 white blood cell). Polymerase chain reaction (PCR) for herpes simplex virus, varicella-zoster virus, and SARS-CoV-2 in CSF was negative. However, the patient tested positive for COVID-19 through PCR for viral RNA from the nasopharyngeal swab. After the administration of 12mg/day of Dexamethasone for 3 days, along with clonazepam and levetiracetam, the patient's symptoms started improving on day 3 and he displayed a very slow but progressive recovery.

      Discussion

      Our patient presented with acute isolated multifocal myoclonus status without cognitive impairment. These movements were prominent, spontaneous, worsened by action, and sensitive to touch and sound. The anatomical source of this myoclonus could be cortical or subcortical despite the absence of evident EEG discharges. Several diseases can cause acute myoclonus such as severe hypoxia, metabolic disturbances, and paraneoplastic syndromes. these diagnoses were ruled out in our patient. Post-vaccinal origin was also suggested, but its accountability was not proven. Thus, the two hypothetic etiologies raised were either para-infectious or infectious mechanisms in relation to SARS-Cov 2 infection. HIV, VZV, HSV, and syphilis infections were eliminated and the patient tested positive for SARS-Cov2 infection. In the literature, COVID-19-related myoclonus was reported as a complication of an already-known SARS-CoV-2 infection in about 50 patients so far. It generally occurs between 6 days and 26 days following the SARS-CoV-2 infection [
      • Przytuła F
      • Błądek S
      • Sławek J.
      Two COVID-19-related video-accompanied cases of the severe ataxia-myoclonus syndrome.
      ,
      • Rábano-Suárez P
      • Bermejo-Guerrero L
      • Méndez-Guerrero A
      • Parra-Serrano J
      • Toledo-Alfocea D
      • Sánchez-Tejerina D
      • et al.
      Generalized myoclonus in COVID-19.
      ,
      • Grieb A
      • Seitz T
      • Kitzberger R
      • Schmidbauer M
      • Hoepler W
      • Baumgartner S
      • et al.
      COVID-19-associated myoclonus in a series of five critically ill patients.
      ,
      • Foucard C
      • San-Galli A
      • Tarrano C
      • Chaumont H
      • Lannuzel A
      • Roze E
      Acute cerebellar ataxia and myoclonus with or without opsoclonus: a para-infectious syndrome associated with COVID-19.
      ], and affects critical illness patients with cognitive decline, mainly from the intensive care unit [
      • Rábano-Suárez P
      • Bermejo-Guerrero L
      • Méndez-Guerrero A
      • Parra-Serrano J
      • Toledo-Alfocea D
      • Sánchez-Tejerina D
      • et al.
      Generalized myoclonus in COVID-19.
      ,
      • Grieb A
      • Seitz T
      • Kitzberger R
      • Schmidbauer M
      • Hoepler W
      • Baumgartner S
      • et al.
      COVID-19-associated myoclonus in a series of five critically ill patients.
      ]. Yet, our patient did not display any symptoms of COVID-19 infection before the occurrence of these abnormal movements. Furthermore, he had a relatively good general condition and no cognitive impairment. Several pathophysiological mechanisms were suggested regarding the COVID-19-related myoclonus. Either central nervous invasion by SARS-Cov 2 after transneuronal spread and/or auto-immune cross-reactivity reaction, are likely incriminated in the pathophysiology of most of the cases [
      • Chan JL
      • Murphy KA
      • Sarna JR.
      Myoclonus and cerebellar ataxia associated with COVID‑19: a case report and systematic review.
      ]. We believe that there is an inflammatory process involved with increased levels of proinflammatory cytokines and systemic inflammation, including cytokine storm or cytokine release syndrome targeting the brain and more specifically the cortex and basal ganglia [
      • Chan JL
      • Murphy KA
      • Sarna JR.
      Myoclonus and cerebellar ataxia associated with COVID‑19: a case report and systematic review.
      ]. Data collection in clinical registries is needed to increase our knowledge of the prevalence of neurological symptoms in patients with COVID-19 and will hopefully clarify the causal relationship between SARS-CoV-2 infection and post-COVID-19 myoclonic syndrome.

      Keywords

      Standard protocol approvals, registrations, and patient consent

      Written informed consent was obtained from the patient (consent for research) (Figs. 1 and 2).
      Fig 1:
      Fig. 1Bipolar transverse electroencephalogram showing no abnormalities concomitant with myoclonic jerks.
      Fig 2:
      Fig. 2Brain MRI: Axial T1 (A-1 and A-2), T2 (B-1 and B-2) and T2 FLAIR images (C-1 and C-2) showing no abnormalities.

      Disclosure

      The authors report no disclosures relevant to the manuscript.

      Declaration

      Funding info

      there are no funders to report for this submission.

      Ethical approval information

      The authors attest that the ethical consent for publication of this article was obtained from all the patients.

      Consent to participate

      The authors give consent to participate in the preparation and the submission of this manuscript

      Consent for publication

      The authors declare that they take fully responsibility over decisions to submit the manuscript for publication.

      Availability of data and material

      The authors attest that they had full access to all case data, take fully responsibility for the accuracy of the data analysis, have authority over manuscript preparation and that all data used in this case are available.

      Code availability

      Not applicable.

      Video legend

      Video 1: A recording of the patient having spontaneous multifocal myoclonus over the limbs, head, and trunk, the myoclonus worsened by action but he had no cerebellar dysmetria.
      Video 2: A recording of the patient's gait showing an unsteady walk due to severe myoclonus with no cerebellar ataxia.

      Declaration of competing interest

      We, Dina Ben Mohamed, Rania Zouari, Jihen Ketata, Fatma Nabli, Samir Blel and Samia Ben Sassi, authors of the article “Myoclonus Status revealing COVID 19 infection” attest that we had full access to all study data, take fully responsibility for the accuracy of the data analysis, and have authority over manuscript preparation and decisions to submit the manuscript for publication. None declared under financial, general and institutional competing interests.

      Acknowledgements

      One. This includes no finding organization, no awards and no grant recipient.

      Appendix. Supplementary materials

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