Opsoclonus myoclonus ataxia syndrome following COVID-19 infection.

Introduction

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neuroinflammatory disease of paraneoplastic, parainfectious, toxic/metabolic or idiopathic etiology, characterized by subacute onset of opsoclonus, myoclonus, ataxia, behavioral and sleep disturbance [1]. The most common underlying malignancy associated with OMAS in children is neuroblastoma, and a thorough diagnostic workup, including imaging, serum, urine, and cerebrospinal fluid studies, is essential in all cases [2].

Post-infectious or para-infectious OMAS can develop after various viral, bacterial, and parasitic infections. Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the declaration of coronavirus disease 2019 (COVID‐19) pandemic, a variety of neurological disorders have been reported in association with this infection, including OMAS [3]. Herein, we present a case of OMAS following COVID-19 infection in pediatric age group.

Case report

A 5-year-old Egyptian boy with normal developmental milestones and no relevant medical history presented with subacute onset of ataxia and abnormal eye movements. His symptoms began one month following mild COVID-19 infection with fever and cough, and confirmed with positive nasopharyngeal swab reverse transcription- polymerase chain reaction (RT-PCR) for SARS-CoV-2.

On examination, he had chaotic, involuntary, saccadic, multidirectional conjugate eye movements in the horizontal and vertical planes (opsoclonus), marked limb and truncal ataxia, in addition to myoclonic jerks (Video S1). The patient was unable to stand or walk without support due to ataxia. Other findings of his neurological examination were normal. He had no sleep or behavioral disturbances.

His baseline investigations including complete blood count, urine routine examination, thyroid profile were within normal limits. Magnetic resonance imaging of the brain, computed tomography of chest, abdomen, and pelvis was negative. Positron emission tomography (PET) scan of the whole body was also negative. Cerebrospinal fluid tests for cells, protein, and glucose were normal. PCR screening for neurotropic viruses (HSV, VZV, EBV, CMV, and EV) was negative. Testing for SARS-CoV-2 in CSF was not performed due to delayed presentation of the patient. A comprehensive work-up for vasculitis [erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor (RF), antinuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA), extractable nuclear antigen (ENA) and antineutrophil cytoplasmic antibodies (ANCA), complement level, protein electrophoresis, immunoglobulin essay], and auto-immune encephalitis [anti-N-methyl-D-aspartate (NMDA) receptor, α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, voltage-gated potassium channels (VGKC), leucine-rich glioma-inactivated-1 (LGI-1), contactin-associated protein-like 2 (CASPR2), gamma-aminobutyric acid-B (GABA-B), glutamic acid decarboxylase (GAD), antithyroid autoantibodies] was negative. Serology testing for viruses (HSV, CMV, EBV, VZV, EV, HIV, HBV, and HCV) was negative. A repeat nasopharyngeal COVID-19 swab was negative, and COVID-19 IgG antibody test was positive. He was treated with intravenous immunoglobulins (IVIg); 2 gm/kg body weight in five divided doses, following 5 days of intravenous methylprednisolone (30 mg/kg/dose as a single dose), with full resolution of the symptoms within 4 weeks.

Discussion

Herein, we report a case of OMAS in the setting of COVID-19 infection in a child. OMAS in children is commonly seen as a paraneoplastic phenomenon following neuroblastoma, followed by post-infectious etiology. Following SARS-CoV-2 infection, several cases of OMAS have been reported, mostly in adults. A 2021 systematic review [4] reported 51 cases of myoclonus or ataxia associated with COVID-19, with most cases being males (79.4%) with a mean age of 59.6 years. Myoclonus occurred in isolation (46.7%), with ataxia (40.0%) or with cognitive changes (30.0%), within 1 month of COVID-19 symptoms. Interestingly, most of the cases followed mild/moderate COVID-19 infection, with a favorable prognosis in the majority within 2 months, either spontaneously or with treatment with immunotherapy and/or anti-epileptic medications [4]. The prognosis of OMAS depends on the cause, being worse with paraneoplastic etiology, and favorable in para/post infectious or idiopathic OMAS, with good response to immunotherapy (mainly IVIg or corticosteroids) [5].

The pathophysiology of OMAS is still poorly understood; however, an autoimmune etiology has been proposed in such patients [6]. Autoantibodies are produced against cerebellar neurons and Purkinje cells due to molecular mimicry between tumors or infectious agents and the brain cells. The finding of oligoclonal bands, BAFF (B-cell activating factor), quantitative abnormalities of IgG, and altered cytokine profile in CSF are all suggestive of autoimmunity [7]. Furthermore, mild cellular loss along with inflammatory changes in Purkinje cell layer, inferior olives, and brainstem have been described in the literature [8].

Conclusions

Our case expands the list of novel and rare neurologic manifestations in association with COVID-19 infection. Although causality cannot readily be inferred, our case might suggest a probable causal relationship between the development of OMAS and mild SARS-CoV-2 infection in children. Further research is needed to better understand the underlying pathophysiological mechanisms in association with COVID-19-induced neurological disorders.

Below is the link to the electronic supplementary material.

Video S1 This video is showing an involuntary repetitive chaotic saccadic multidirectional conjugate eye movement during fixation and more during pursuit movement (opsoclonus). In the second part of the video, ataxia is evident in the form of neck and trunk titubation, in addition to myoclonic jerks that are more evident in lower limbs. Finger-to-finger test is abnormal in both sides, although it is only shown in the left side in this video. (MP4 30354 kb)