Subcortical Myoclonus in Coronavirus Disease 2019: Comprehensive Evaluation of a Patient

Abstract

Myoclonus has been reported as a possible manifestation of coronavirus disease 2019 (COVID-19), yet its neurophysiology and pathogenesis were poorly investigated. 1-4 We describe a middleaged man with COVID-19 who underwent extensive examinations for his disabling myoclonus. CASE REPORT A 58-year-old hypertensive man with a 1-week history of fever and cough presented to the emergency department with dyspnea. A nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was admitted to the intensive care unit after 1 week and placed on invasive mechanical ventilation as a result of respiratory distress. He was treated with hydroxychloroquine, tocilizumab, and remdesivir. Respiratory status quickly improved, thus he was extubated after 5 days, and oxygen therapy was progressively weaned off. Two days after discharge from the intensive care unit, he became markedly agitated. His mental status normalized in 48 hours; however, at this point he developed multifocal myoclonus elicited by action and tactile stimuli, predominant in the right proximal inferior limb muscles, preventing his ability to stand (Video SS1). Cognitive deficits were not observed. Electrolytes and renal and liver function tests were unremarkable. Cerebrospinal fluid (CSF) analysis, performed 8 days after myoclonus onset, demonstrated 5 leukocytes/μL, elevated protein levels (75 mg/dL) and CSF/serum albumin ratio (13.1), and negative SARS-CoV-2 reverse-transcription polymerase chain reaction. Cytokine analyses revealed interleukin-6 at 11.6 pg/mL in CSF (29.3 pg/mL in serum, reference < 5.9) and interleukin-8 at 38 pg/ mL in CSF (11 pg/mL in serum, reference < 70). A serologic panel

Myoclonus and cerebellar ataxia associated with COVID-19: a case report and systematic review

“…Duration consistent with cortical-subcortical myoclonus, long loop C-reflex consistent with cortical myoclonus Not reported Not reported Post-infectious, metabolic, hypoxic Khoo et al 2020 [ 19 ] 65 F 7 days Face, tongue, upper extremities, lower extremities Tactile stimuli, visual stimuli, auditory stimuli Confusion, ocular flutter, convergence spasm with miosis, expressive aphasia, perseveration, echopraxia, visual hallucinations MRI: Unremarkable N/A Levetiracetam 750 mg BID and clonazepam 0.25 mg BID; methylprednisolone 1000 mg IV daily for 3 days (day 14–16 after symptom onset), then prednisone 1 mg/kg PO daily Partially improved after levetiracetam and clonazepam. Progressively improved after corticosteroids, discharged 10 days after Post-infectious Méndez-Guerro et al 2020 [ 20 ] 58 M 34 days Upper extremities Action Postural tremor upper extremities, decreased consciousness, opsoclonus, upgaze restriction, round the house vertical saccades, impaired smooth pursuit, tetraparesis, right-sided hypokinetic-rigid syndrome, hypomimia, decreased blinking, glabellar tap CT/CTA: Unremarkable MRI: Normal DaTSPECT: Bilateral decrease in presynaptic dopamine uptake in putamen EEG: Unremarkable EMG: 7 Hz rest tremor (completed after myoclonus resolved) None Spontaneously resolved Post-infectious Muccioli et al 2020 [ 21 ] 58 M At least 23 days Multifocal Action, tactile stimuli None MRI: Cerebral small-vessel disease EEG: Unremarkable EMG: Myoclonus with 140–220 ms duration. Duration consistent with subcortical myoclonus Clonazepam and levetiracetam …”

Myoclonus and COVID‐19: A Challenge for the Present, a Lesson for the Future

“…4 A postinfectious possibility is supported in the remaining 3 cases by the lack of other potential causes identified and the improvement after immunotherapy. [5][6][7] Interestingly, analysis of cerebrospinal fluid (CSF) revealed no pleocytosis and no SARS-CoV-2 RNA in these cases, suggesting an immunemediated pathogenesis. In 1 case there were signs of blood-brain barrier disruption together with elevated CSF interleukin-6 levels and increased interleukin-8 CSF/blood ratio involved in COVID-19 secondary hyperinflammation syndrome.…”

“…3 cases [4][5][6] and sensitive to touch in 2 cases 5,7 and to auditory stimuli in 1 case. 7 Although in 2 cases myoclonus was isolated, 4,5 in the other 2 cases it was accompanied by cerebellar signs (such as saccadic intrusions, hypermetric saccades and ocular flutter on eye movement assessment, and ataxia) 6,7 ; 1 patient also had cognitive dysfunction. 7 Electrophysiological testing was performed in 1 case 5 and revealed a combination of long-duration electromyographic bursts with no sign of cortical discharges time locked to individual myoclonic jerks, consistent with a subcortical origin of the myoclonus.…”

“…7 Although in 2 cases myoclonus was isolated, 4,5 in the other 2 cases it was accompanied by cerebellar signs (such as saccadic intrusions, hypermetric saccades and ocular flutter on eye movement assessment, and ataxia) 6,7 ; 1 patient also had cognitive dysfunction. 7 Electrophysiological testing was performed in 1 case 5 and revealed a combination of long-duration electromyographic bursts with no sign of cortical discharges time locked to individual myoclonic jerks, consistent with a subcortical origin of the myoclonus. In 3 patients, myoclonus improved following treatment with clonazepam or levetiracetam, drugs that are typically effective in cortical myoclonus rather than subcortical or spinal myoclonus.…”

“…In 3 patients, myoclonus improved following treatment with clonazepam or levetiracetam, drugs that are typically effective in cortical myoclonus rather than subcortical or spinal myoclonus. [4][5][6] In 1 case, the authors suspected a postinfectious etiology and started treatment with steroids followed by immunoglobulin infusion with a good response 7 ; however, whether the improvement was related to a natural and self-limited evolution of the disease is not known.…”