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Case Report
Myoclonus-Ataxia Syndrome Associated with COVID-19 -
Kuldeep Shetty1
, Atul Manchakrao Jadhav1, Ranjith Jayanthakumar2, Seema Jamwal1, Tejaswini Shanubhogue1, Mallepalli Prabhakar Reddy1, Gopal Krishna Dash1, Radhika Manohar1, Vivek Jacob Philip1, Vikram Huded1 -
Journal of Movement Disorders 2021;14(2):153-156.
DOI: https://doi.org/10.14802/jmd.20106
Published online: April 6, 2021
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1Department of Neurology, Mazumdar Shaw Medical Center, Narayana Hrudayalaya Hospital, Bangalore, India
2Department of Pulmonology, Mazumdar Shaw Medical Center, Narayana Hrudayalaya Hospital, Bangalore, India
- Corresponding author: Kuldeep Shetty, MD, DM Department of Neurology, Mazumdar Shaw Medical Center, Narayana Hrudayalaya Hospital, No 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore 560099, India / Tel: +91-80-71222585 / Fax: +91-80-27832648 / E-mail: kuldeepsshetty@yahoo.com
• Received: September 9, 2020 • Revised: November 10, 2020 • Accepted: December 24, 2020
Copyright © 2021 The Korean Movement Disorder Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
- Neurological manifestations of coronavirus disease (COVID-19) have increasingly been reported since the onset of the pandemic. Herein, we report a relatively new presentation. A patient in the convalescence period following a febrile illness with lower respiratory tract infection (fever, myalgia, nonproductive cough) presented with generalized disabling myoclonus, which is phenotypically suggestive of brainstem origin, along with additional truncal cerebellar ataxia. His neurology work-ups, such as brain MRI, electroencephalography, serum autoimmune and paraneoplastic antibody testing, were normal. His CT chest scan revealed right lower lung infiltrates, and serological and other laboratory testing did not show evidence of active infection. COVID-19 titers turned out to be strongly positive, suggestive of post-COVID-19 lung sequelae. He responded partially to antimyoclonic drugs and fully to a course of steroids, suggesting a para- or postinfectious immune-mediated pathophysiology. Myoclonusataxia syndrome appears to be a neurological manifestation of COVID-19 infection, and knowledge regarding this phenomenon should be increased among clinicians for better patient care in a pandemic situation.
- A 41-year-old male from Tamil Nadu state, India, had a history of febrile illness with myalgia and dry cough for approximately 1 week; he was nonalcoholic. He was treated only with oral paracetamol for fever at a local hospital [he had no history of using any drugs causing myoclonus at presentation or in the recent past (e.g., quinolones, cephalosporins, antiviral agents such as lopinavir or ritonavir, tramadol, antidepressants)]. Upon resolution of the abovementioned symptoms by approximately day 10, he noted subtle jerky involuntary movements of the limb along with difficulty while walking. His symptoms peaked over the next 10 days when he had severe limb and truncal jerking at rest that worsened upon action. He could not walk without support. He did not complain of any headache, cognitive symptoms, speech problems or any other neurological symptoms.
- On examination at presentation (20 days post fever, 10 days post onset of neurological symptoms), the patient was alert and oriented; his score on the Mini-Mental Status Examination (MMSE) was 29/30. The patient predominantly had generalized myoclonus (mostly synchronous, both positive and negative) that was most prominent in the proximal upper and lower limbs and trunk, with auditory and mantle area tactile stimulus sensitivity. Clinically, myoclonus appeared to be a subcortical-brainstem origin phenotype. The patient had gait ataxia with normal upper and lower limb coordination, motor power, deep tendon reflexes and sensory examination, as well as possible gait disturbance due to myoclonus involving the proximal lower limb and trunk (Supplementary Video 1 in the online-only Data Supplement). The rest of the examination, including smell, speech, and eye movements, was within normal limits.
- At this juncture, the likely pathophysiologies considered were brainstem encephalitis (in view of a predominant brainstem myoclonus-ataxia clinical syndrome) of direct viral, para/postinfectious or a primary autoimmune cause, as there was no history suggestive of other etiologies, such as drugs or hypoxic insult. Contrast MRI of the brain (Supplementary Figure 1 in the online-only Data Supplement), cerebrospinal fluid biochemistry and cytology were normal. Somatosensory evoked potentials (SSEPs) did not show any giant potential, and EEG did not reveal any epileptiform discharges. Detailed neuropsychology evaluation showed mild frontal dysfunction. In view of the current pandemic and a suspicious recent febrile history, a CT scan was performed on the chest, which showed right lower lobe ground glass opacities and associated interstitial thickening suggestive of a resolved viral lung infection (Figure 1). Reverse transcriptase polymerase chain reaction test for COVID-19 was predictably negative due to late presentation. His other serum markers, including D-dimer, ferritin, lactate dehydrogenase, and C-reactive protein, were within normal limits. An anti-COVID-19 antibody test was performed to rule out a recent COVID-19 infection. The IgG titer was 45.2, which was strongly positive (reference > 1 implies positive for COVID-19 infection), supporting the diagnosis of a recent COVID-19 infection. In view of the latent period of approximately 10 days for the onset of the neurological symptoms following the onset of fever, the likelihood of para/post infectious brainstem encephalitis-related myoclonus-ataxia syndrome was considered [1].
- The patient was treated with clonazepam and levetiracetam with mild improvement in symptoms over the first 3 days of treatment with significant residual disability. He was subsequently treated with 1 g intravenous methylprednisolone (IVMP) for 5 days with significant improvement in symptoms. At discharge on day 10 of admission, the patient could walk easily without support (Supplementary Video 2 in the online-only Data Supplement). At the last outpatient follow-up at 6 weeks, the patient had complete resolution of ataxia and near total resolution of myoclonus while on 0.5 mg per day of clonazepam alone (levetiracetam was tapered off following discharge), with normal scores on the MMSE and Frontal Assessment Battery. Detailed neuropsychology evaluations could not be repeated.
CASE REPORT
- As COVID-19 infection has been shown to have multisystemic manifestations, awareness among neurologists/general physicians/intensivists about the neurological manifestations of COVID-19 should be increased. The well-known COVID-19-related neurological syndromes described by various groups include encephalitis, meningitis, anosmia, GBS, ADEM, and acute cerebrovascular events [1-3]. Myoclonus-ataxia spectrum syndrome following COVID-19 infection appears to be another neurological manifestation, as observed in a few recent case reports that had similar phenotypes, as listed in Table 1 [4-6]. Our patient also presented with this phenomenon of myoclonus-ataxia syndrome with onset approximately 10 days following a probable COVID-19 infection (supported by history of a recent febrile illness with cough, predominant right lung infiltrates on CT chest and strongly positive anti-COVID-19 IgG titer). In the context of the recent probable COVID-19-related febrile illness followed by a neurological syndrome within 6 weeks, the diagnosis of COVID19-related myoclonus-ataxia syndrome is very likely in the absence of any hypoxic injury, absence of exposure to culpable drugs, and an unrevealing detailed work-up [7].
- The anatomical substrate of myoclonus is likely to be subcortical in our case, as he predominantly had generalized myoclonus, mostly synchronous, both positive and negative, most prominent in the proximal upper and lower limbs and trunk, with auditory and mantle area tactile stimulus sensitivity with normal brain imaging, SSEP and EEG [8].
- In recent similar case reports (detailed in Table 1), myoclonus has also been generalized, which affects proximal muscles of the limb and trunk with auditory and tactile stimulus sensitivity in most cases, suggestive of brainstem origin. One group showed an absence of jerk-locked cortical potential on backaveraging, supporting the anatomical localization of myoclonus to subcortical origin [5].
- Our patient additionally had probable pure truncal ataxia, which could be related to vermian involvement, although gait issues could also be additionally attributable to truncal and proximal lower limb myoclonus. This is not surprising, as the neurological spectrum of COVID-19 infection is very vast and ever expanding. There has been a recent case report of opsoclonus myoclonus ataxia syndrome following COVID-19 [9].
- Our case did not present with any symptoms suggestive of encephalopathy, although detailed neuropsychology evaluation showed mild frontal dysfunction. The possibilities include COVID-19-related subtle cognitive dysfunction, but there were confounding factors in terms of medications, including clonazepam, levetiracetam and high-dose steroids. Encephalitis has been very well described in COVID-19, and thus, a subtle degree of cognitive dysfunction is not surprising in our case [1].
- Our patient showed a subacute temporal evolution with severe disability towards the peak of syndrome, and he could not walk without support due to severe jerking. The disease severity has been variable in the cases reported until now. Our patient improved significantly (> 75%) with antimyoclonic drugs and a 5-day course of IVMP. Although all reported cases have significantly improved, the speed of recovery has been variable. There also has been variable response to available medications—some have responded very well to only anti-myoclonic medication, whereas some had to escalate the therapy to plasma exchange due to lack of benefit with anti-myoclonic and steroid medications [4-6].
- The pathophysiology of neurological findings, in the current case and similar recently reported cases, is more likely to be paraor postinfectious in view of the onset of neurological symptoms in the 2nd or 3rd week from the onset of febrile illness, with a monophasic course and resolution of the symptoms in the subsequent weeks. It is difficult to conclude whether the improvement occurred as a part of the natural course of disease or due to medications. Alternate pathophysiology could be direct transneural spread of the virus to the central nervous system through the olfactory tract, especially in view of hyposmia at the onset of viral fever. Other pathophysiologies, such as hypoxia-related or any culpable drug, were ruled out in the abovementioned cases. As noted in our case, this syndrome does not appear to have any consistent correlation with the severity of COVID-19 infection or the presence of cytokine release syndrome or any specific laboratory parameter derangement [enlisted in Supplementary Table 1 (in the online-only Data Supplement)] [10].
- Brainstem myoclonus-ataxia syndrome appears to be another addition to the spectrum of COVID-19-related neurological manifestations. Its pathophysiology is mostly para/post infectious phenomenon. Although the response to medications seems to be variable, the overall prognosis appears to be fair.
DISCUSSION
Supplementary Material
Video 1.
Video 2.
Supplementary Figure 1.
Supplementary Table 1.
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Ethics Statement
Informed consent was obtained from patient for using his video (without masking) for publication purpose.
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Conflicts of Interest
The authors have no financial conflicts of interest.
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Author Contributions
Conceptualization: Kuldeep Shetty, Atul Manchakrao Jadhav, Ranjith Jayanthakumar. Data curation: all authors. Formal analysis: all authors. Funding acquisition: Kuldeep Shetty, Atul Manchakrao Jadhav, Ranjith Jayanthakumar, Gopal Krishna Dash, Radhika Manohar, Vivek Jacob Philip, Vikram Huded. Investigation: all authors. Methodology: all authors. Project administration: Kuldeep Shetty, Atul Manchakrao Jadhav, Ranjith Jayanthakumar. Resources: all authors. Software: Kuldeep Shetty, Atul Manchakrao Jadhav, Ranjith Jayanthakumar. Supervision: Kuldeep Shetty, Atul Manchakrao Jadhav, Ranjith Jayanthakumar. Validation: all authors. Visualization: all authors. Writing—original draft: all authors. Writing—review & editing: all authors.
Notes
- None.
Acknowledgments
Table 1.Literature review of clinical manifestations of reported cases of COVID-19 related generalised myoclonus
| Study | Cases (age in years, sex) | Lung involvement | Latency to onset of neurological symptoms from onset of systemic symptoms related to COVID-19 | Neurological features | Treatment and response |
|---|---|---|---|---|---|
| Rábano-Suárez et al. [4] | Case 1: 63, M | Case 1: Bilateral pneumonia, mechanically ventilated | Case 1: 9 days | Case 1: anosmia; myoclonic storm, more involving upper half of body; auditory and tactile stimulus sensitive; somnolence | Case 1: LEV, CLN, IVMP 1g/day for 5 days. PLEX × 5 cycles. Patient had sustained improvement only after PLEX. |
| Case 2: 88, F | Case 2: Bilateral pneumonia | Case 2: 3 weeks | Case 2: anosmia, mild myoclonus, mild hypersomnia | Case 2: resolved with IVMP 250 mg/day for 3 days | |
| Case 3: 76, M | Case 3: Bilateral pneumonia | Case 3: 11 days | Case 3: anosmia, mild myoclonus | Case 3: LEV, CLN, IVMP 250 mg/day for 3 days. Patient had delayed improvement after 2 weeks. | |
| CSF: done for case 1 and 3, normal | |||||
| Muccioli et al. [5] | 58, M | Respiratory distress, mechanically ventilated | 3 weeks | Brief agitation for 2 days-self resolved followed by multifocal myoclonus: action and tactile stimulus sensitive; diffuse, but more prominent in right proximal lower limb - causing marked disablility to stand | Symptoms resolved completely with symptomatic treatment with CLN and LEV in 5 days. |
| HCQ, tocilizumab remdesivir given | |||||
| Khoo et al. [6] | 65, F | Bilateral lung infiltrates seen | 7 days | Patient had baseline Alzheimer’s disease | IVMP 1 g /day for 3 days followed by oral steroid taper with prednisolone |
| Unilateral onset of myoclonus generalised within 2 days, stimulus sensitive, with hyperkplexia to tactile, visual and auditory stimulus | Patient had significant improvement in cognition and myoclonus. Cognition improved to baseline. Myoclonus had not completely resolved at discharge (follow up till day 10 from start of steroids) | ||||
| Noted cognitive decline: language difficulties, visual hallucination | |||||
| This study | 41, M | Predominant right lower lung infiltrates | 10 days | Generalised severe myoclonus predominantly proximal, involving limbs and trunk, present at rest and on action, auditory and tactile stimulus sensitivity present, truncal ataxia noted | Noted moderate benefit with LEV and CLN |
| Mild frontal dysfunction noted on detailed neuropsychology evaluation | IVMP 1 g/day given for 5 days -continued to improve |
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