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. 2022 Dec 15;47(1):1–6. doi: 10.1080/01658107.2022.2128378

Opsoclonus Myoclonus Ataxia Syndrome Due to SARS-CoV-2

Josef Finsterer a,✉, Fulvio A Scorza b
PMCID: PMC9928447  PMID: 36798867

ABSTRACT

Opsoclonus myoclonus syndrome (OMS)/opsoclonus myoclonus ataxia syndrome (OMAS), also known as Kinsbourne’s syndrome or ‘dancing eyes-dancing feet’ syndrome, is a rare central nervous system manifestation of COVID-19 but an increasing number of articles have reported patients in whom COVID-19 was complicated by OMS/OMAS. This narrative review aims at summarising and discussing current knowledge about the clinical presentation, diagnosis, treatment and outcome of SARS-CoV-2 associated OMS/OMAS. Altogether, 29 articles reporting 45 patients with SARS-CoV-2 associated OMS/OMAS were retrieved. Their ages ranged from 2 to 88 years. Three patients were children and the remainder adults. Gender was male in 32 patients and female in 13 patients. Opsoclonus was described in 29 patients, which was associated with myoclonus in 28 cases. Myoclonus was described in 43 patients, which was associated with opsoclonus and ataxia in 18 patients. Cerebral magnetic resonance imaging and cerebrospinal fluid investigations were not informative in the majority of the cases. OMS/OMAS was treated with steroids in 28 patients and with intravenous immunoglobulin (IVIG) in 15 patients. Clonazepam was given to 18 patients, levetiracetam to 13 patients, and sodium valproate to eight patients. Complete recovery was achieved in 12 cases and incomplete recovery in 22 cases. Diagnosing SARS-CoV-2 associated OMS/OMAS requires extensive neurological work up and exclusion of various differentials. SARS-CoV-2 associated OMS/OMAS may not always present with the full spectrum of manifestations but as an abortive syndrome. OMS/OMAS should not be missed as it usually responds favourably to steroids or IVIG.

KEYWORDS: SARS-CoV-2, COVID-19, neuro-COVID, complications, myoclonus, opsoclonus

Introduction

There is ample evidence that infections with SARS-CoV-2 not only manifest clinically in the lungs but also in extra-pulmonary organs.1 The organs most commonly affected after the lungs are the central nervous system (CNS) and the peripheral nervous system, which is termed neuro-COVID.2 Manifestations of neuro-COVID include ischaemic stroke, encephalopathy, acute disseminated encephalomyelitis, acute, haemorrhagic leucoencephalitis, Guillain-Barré syndrome, seizures, cerebral vasculitis, immune encephalitis, hypophysitis, cerebellitis, ventriculitis, intracerebral bleeding, subarachnoid bleeding, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome, multiple sclerosis, neuromyelitis optica spectrum disorder, pontine myelinolysis, venous sinus thrombosis, Wernicke’s encephalopathy, pseudotumour cerebri, headache, impaired consciousness, delirium, and transverse myelitis.3,4 The most common CNS manifestations of SARS-CoV-2 infections include headache, cerebrovascular disease, and demyelinating disorders.3

A rare CNS manifestation of neuro-COVID is opsoclonus myoclonus syndrome (OMS)/opsoclonus myoclonus ataxia syndrome (OMAS), also known as Kinsbourne’s syndrome or ‘dancing eyes-dancing feet’ syndrome. However, an increasing number of articles have reported patients in whom COVID-19 was complicated by OMS/OMAS.5 According to a stimulation model of macro-saccadic oscillations OMA/OMAS is attributed to combined pathology of the brainstem and cerebellum with increased gamma-aminobutyric acid-A receptor sensitivity.

This narrative review aims at summarising and discussing current knowledge about the clinical presentation, pathophysiology, diagnosis, treatment and outcome of SARS-CoV-2 associated OMS/OMAS.

Methods

Data for this review were identified by searches of MEDLINE, Current Contents, EMBASE, Web of Science, Web of Knowledge, LILACS, SCOPUS, and Google Scholar for references of relevant articles. Terms applied for searching these databases were ‘SARS-CoV-2’, ‘COVD-19’, and ‘coronavirus’ combined with ‘opsoclonus’, ‘myoclonus’, and ‘myocloni’. Results of the search were screened for potentially relevant studies. Reference lists of retrieved studies were checked for additional articles.

Results

Altogether, 29 articles reporting 45 patients with SARS-CoV-2 associated OMS/OMAS were retrieved (Table 1). Their ages ranged from 2 to 88 years (Table 1). Three patients were paediatric patients and the remainder adults. Gender was male in 32 patients and female in 13 patients. Opsoclonus alone or with other features was described in 30 patients. Myoclonus alone or together with other features was described in 43 patients. Opsoclonus was associated with myoclonus in 28 cases. Eighteen patients presented with opsoclonus, myoclonus, and ataxia; 11 patients with myoclonus and ataxia; ten patients with opsoclonus and myoclonus; and one patient with opsoclonus and ataxia (Table 1). Isolated myoclonus was described in four cases (Table 1), while isolated opsoclonus was reported in a single patient (Table 1). In 11 patients the OMS/OMAS was associated with cognitive impairment. One patient was extensively tested by means of the Wechsler Intelligence Scale for Children – Fourth Edition (WISC-IV) test, showing an inhomogeneous cognitive profile (verbal comprehension index 95, perceptional reasoning 56, working memory index 70, processing speed index: 47) resulting in an intelligence quotient of 58 (Table 1).

Table 1.

Patients in whom opsoclonus myoclonus syndrome/opsoclonus myoclonus ataxia syndrome has been reported as a manifestation of neuro-COVID.

Reference Age (years) Sex Presentation Cognitive impairment Magnetic resonance imaging Cerebrospinal fluid findings Treatment Outcome
(follow-up latency reported)
Children
Della Corte et al.6 12 Male Myoclonus Yes* Normal Normal, PCR -ve Methylprednisolone (10 mg/kg/day), clonazepam (0.02 mg/kg/day), IVIG Complete recovery
Wiegand et al.7 2 Female Opsoclonus, myoclonus # NR Normal NR Steroids, IVIG Complete recovery (6 months)
Heald et al.8 0.3 Female Opsoclonus NR Normal Normal Steroids, IVIG Complete recovery
Adults
Nelson et al.9 NR Female Opsoclonus, myoclonus, ataxia No Normal ↑NSE Steroids, clonazepam, rituximab Partial recovery
Smyth et al.10 ∮ 50 Male Opsoclonus, myoclonus Yes Stroke Normal, PCR -ve Steroids, clonazepam, levetiracetam Partial recovery
Paterson et al.11 45 Female Opsoclonus, myoclonus Yes Normal Normal Steroids, clonazepam, levetiracetam Partial recovery
  65 Female Opsoclonus, myoclonus Yes Normal Normal Not reported Not reported
Sanguinetti et al.12 57 Male Opsoclonus, myoclonus No Normal NR Methylprednisolone (80 mg/day), IVIG, clonazepam Partial recovery
Ishaq et al.13 63 Male Opsoclonus, myoclonus, ataxia Yes Normal Normal IVIG Complete recovery
Saha et al.14 78 Female Opsoclonus, myoclonus, ataxia No Normal Normal Methylprednisolone (1 g/day), levetiracetam (1 g/day), IVIG Partial recovery
Fernandes et al.15 58 Female Opsoclonus, myoclonus, ataxia No Normal PCR -ve Clonazepam, IVIG Not reported
Urrea-Mendoza et al.16 32 Male Opsoclonus, myoclonus, ataxia No Normal NR Methylprednisolone (40 mg/day), clonazepam (3 mg/day), divalproex (3 g/day) Partial recovery (24 days)
Foucard et al.17 83 Male Opsoclonus, myoclonus, ataxia Yes Normal Normal Steroids (1 g/day), IVIG, diazepam Not reported
  63 Male Myoclonus, ataxia No Normal Normal IVIG Not reported
  NR Male Opsoclonus, myoclonus, ataxia No Normal Normal Steroids (1 g/d), clonazepam (2 mg/day), levetiracetam (2 g/day), sodium valproate (20 mg/kg/day) Not reported
  44 Male Opsoclonus, myoclonus, ataxia Yes Normal Normal Steroids (1 g/day), IVIG Not reported
  57 Male Opsoclonus, myoclonus, ataxia No Normal NR Steroids (80 mg/day), clonazepam, IVIG Not reported
  72 Male Myoclonus, ataxia No Normal ↑Protein Steroids (1 g/day), IVIG Not reported (49 days)
  48 Male Myoclonus, ataxia No Normal Normal Levetiracetam Partial recovery
Emamikhah et al.5 51 Male Opsoclonus, myoclonus, ataxia No NR NR Clonazepam (2 mg/day), levetiracetam (1 g/day), IVIG Complete recovery
  54 Male Opsoclonus, myoclonus, ataxia No Normal Normal Levetiracetam (2 g/day), sodium valproate (1 g/day) Partial recovery
  52 Male Opsoclonus, myoclonus, ataxia No Normal NR Clonazepam (4 mg/day), sodium valproate (1 g/day) Partial recovery (2 months)
  42 Female Opsoclonus, myoclonus, ataxia No Normal NR Clonazepam, sodium valproate Not reported
  44 Male Opsoclonus, myoclonus, ataxia No Normal Normal, PCR -ve Clonazepam, sodium valproate Complete recovery (2 months)
  52 Male Opsoclonus, myoclonus, ataxia No NR Normal Clonazepam, IVIG Partial recovery
  39 Male Opsoclonus, myoclonus, ataxia No NR NR Steroids, clonazepam, levetiracetam, sodium valproate, IVIG Not reported
Mendez-Guerrero et al.18 58 Male Opsoclonus, myoclonus No Normal Normal Levetiracetam, apomorphine Partial recovery
Wright et al.19 79 Male Opsoclonus, ataxia Yes Normal NR Not reported Partial recovery
Rabano-Suarez et al.20 64 Male Myoclonus No Normal Normal Methylprednisolone (1 g/day), propofol, PLEX Partial recovery
  88 Female Myoclonus No NR NR Methylprednisolone (250 mg/day) Complete recovery
  76 Male Myoclonus No Normal NR Methylprednisolone (250 mg/day), clonazepam, levetiracetam Partial recovery
Guerra et al.21 50 Male Myoclonus, ataxia No NR NR Methylprednisolone (250 mg/day) Complete recovery
  80 Male Myoclonus, ataxia No NR NR Methylprednisolone (120 mg/day) Partial recovery
Shah et al.22 NR Male Opsoclonus, myoclonus, ataxia No Normal Normal Methylprednisolone (1 g/day), clonazepam (2 mg/day), levetiracetam (2 g/day), sodium valproate (20 mg/kg/day) Complete recovery
Kaur et al.23 55 Female Opsoclonus, myoclonus No NR Normal Not reported Not reported
Kini et al.24 39 Female Opsoclonus, myoclonus No Normal NR Sodium valproate Partial recovery
Przytula et al.25 49 Male Myoclonus, ataxia No Normal Normal Methylprednisolone (1 g/day) Partial recovery
  62 Male Opsoclonus, myoclonus, ataxia No Normal Normal Methylprednisolone (1 g/day), IVIG Partial recovery
Dijkstra et al.26 44 Male Myoclonus, ataxia Yes NR Normal, PCR -ve Methylprednisolone (1 g/day), IVIG Complete recovery
Schellekens et al.27 48 Male Myoclonus, ataxia No Normal Normal, PCR -ve Levetiracetam Partial recovery
Grimaldi et al.28 72 Male Myoclonus, ataxia No Normal Normal, PCR -ve Methylprednisolone (1 g/day), IVIG Complete recovery
Osawa et al.29 52 Male Myoclonus, ataxia No Normal Normal, PCR -ve Methylprednisolone (1 g/day) Complete recovery (3 months)
Chacko et al.30 53 Female Opsoclonus, myoclonus Yes Stroke Normal Methylprednisolone (0.5 g/day), PLEX, rituximab (500 mg), levetirazetam Partial recovery
Shetty et al.31 41 Male Myoclonus, ataxia No Normal Normal Methylprednisolone (1 g/day), clonazepam (0.5 mg/day), levetiracetam Complete recovery (6 weeks)
Salgado et al.32 61 Female Opsoclonus, myoclonus Yes NR NR IVIG Partial recovery
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* Extensive neuropsychological testing performed.

# History of opsoclonus due to a neuroblastoma.

∮ Serum leucine-rich glioma-inactivated 1 antibody positive.

-ve = negative; ↑ = raised; IVIG = intravenous immunoglobulins; NR = not reported; NSE = neuron specific enolase; PCR = polymerase chain reaction; PLEX = plasmapheresis.

Cerebral magnetic resonance imaging (MRI) was carried out in 36 patients and was not informative in 34 cases. In two patients a subacute ischaemic stroke was seen (Table 1). Cerebrospinal fluid (CSF) investigations were carried out in 30 patients and were not informative in 28 cases (Table 1). Elevated protein was seen in one patient and the neuron-specific enolase was elevated in another (Table 1). The polymerase chain reaction (PCR) status for SARS-CoV-2 in the CSF was determined in eight patients and was negative in all of them (Table 1).

OMS/OMAS was treated with steroids in 28 patients, with intravenous immunoglobulin (IVIG) in 15 patients, with rituximab in two patients and with plasmapheresis in two patients. Clonazepam was given to 18 patients, levetiracetam to 13 patients, sodium valproate to eight patients, and diazepam to a single patient. Steroids were combined with IVIG in 13 patients. Myoclonus responded favourably to clonazepam, levetiracetam or sodium valproate. The outcome was reported in 34 cases. Follow-up latency was reported in seven patients and ranged from 24 days to 6 months (Table 1). Complete recovery was achieved in 12 cases and incomplete recovery in 22 cases.

Discussion

This review shows that OMS/OMAS is not an infrequent complication of SARS-CoV-2 infections. It also shows that male patients and adults are more frequently affected than females and children, respectively. The review provides evidence that cerebral imaging and CSF investigations are frequently normal including negative PCR tests for SARS-CoV-2. Steroids or IVIG can be beneficial for opsoclonus and clonazepam or levetiracetam for myoclonus.

OMAS, also known as Kinsbourne’s syndrome or ‘dancing eyes-dancing feet’ syndrome, is a rare neurological syndrome clinically characterised by either opsoclonus together with myoclonus, or the triad of opsoclonus, myoclonus, and ataxia.33 There are abortive forms of OMS/OMAS, which manifest without myoclonus.21 There are even cases which only manifest with myoclonus.34 In addition to the cardinal manifestations OMS/OMAS patients can present with a number of other neurological abnormalities, most frequently with cognitive impairment. Opsoclonus is defined as back-to-back multidirectional conjugate saccades without an inter-saccadic interval.33 Myoclonus is defined as a sudden, brief, ‘shock-like’, non-epileptic involuntary movement.35 Myoclonus is the most frequent movement disorder reported in COVID-19 patients.36

OMS/OMAS can have several underlying aetiologies.15 It can be paraneoplastic, para-infectious, toxic-metabolic, or idiopathic.33 Infectious agents causing OMS/OMAS include herpes viruses, arbovirus, and several parasitic infections, including malaria.16 Since the occurrence of the SARS-CoV-2 pandemic, several patients with OMS/OMAS have been described in association with SARS-CoV-2 infection. The exact pathophysiological mechanism behind SARS-CoV-2 associated OMS/OMAS is unknown but there are cases in which SARS-CoV-2 associated autoimmune encephalitis manifested with OMS/OMAS.10,34 SARS-CoV-2 associated OMS/OMAS is most likely immune-mediated since steroids, IVIG, and rituximab can be highly effective, CSF investigations are frequently normal including negative PCR testing for SARS-CoV-2, the frequency of auto-antibodies is high in the CSF of patients with neuro-COVID,37 and that OMS/OMAS has been reported in associated with immunological diseases.38

The cause of the male preponderance in SARS-CoV-2 associated OMS/OMAS remains elusive but it can be speculated that endocrine parameters (pituitary hormones) contribute to the development of OMS/OMAS. The finding that adults more frequently develop OMS/OMAS may possibly be due to the lower prevalence of SARS-CoV-2 infections in children as compared with adults. Only 28 patients presented with complete features of OMS. In the remainder, abortive forms of OMS/OMAS were diagnosed. In some of the abortive forms without opsoclonus, horizontal saccadic intrusions and transient ocular flutter have been reported.16 Some patients with OMS/OMS present additionally with extra-pyramidal manifestations.17

In conclusion, diagnosing SARS-CoV-2 associated OMS/OMAS requires extensive neurological work up by clinical neurological examination, cerebral imaging with contrast medium, CSF investigations, and exclusion of differential causes. SARS-CoV-2 associated OMS/OMAS may not always present with the entire spectrum of manifestations but also as an abortive syndrome OMS/OMAS should not be overlooked as it usually responds favourably to steroids or IVIG. Since the exact pathophysiological background of SARS-CoV-2 associated OMS/OMAS is still not fully elucidated, further studies on underlying mechanisms and the most effective therapy are warranted.

Funding Statement

The authors reported there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

JF: design, literature search, discussion, first draft, critical comments, final approval, FS: literature search, discussion, critical comments, final approval.

Data availability statement

All data are available from the corresponding author.

Ethics approval

Ethics approval was in accordance with ethical guidelines. The study was approved by the institutional review board.

Consent to participate

Consent to participate was obtained from the patient.

Consent for publication

No original data were inlcuded.

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