A Case of Adult-Onset Postviral Opsoclonus–Myoclonus Syndrome

Case Presentation
OQ, aged mid-20s, who was previously healthy, presented with a 2-week history of jerky movements of the trunk and upper limbs, head tremors, eye jerking, vertigo, and gait disturbance, co-occurring with nausea, vomiting, and diarrhea. These symptoms had developed 3 days after upper respiratory infection symptoms, which had resolved. OQ was initially treated with meclizine and ondansetron by the primary care provider. They were then referred to the otolaryngology department, where they were diagnosed with viral otitis and treated with methylprednisolone. However, OQ’s symptoms worsened.

OQ presented to an emergency department for evaluation and was admitted overnight. Labyrinthitis was diagnosed and a 2-week course of high-dose prednisone prescribed. Despite treatment, the symptoms persisted and worsened to the point where OQ could not walk, largely affecting their ability to perform daily activities. OQ then presented to the emergency department of a different hospital. 

Diagnostic Process
On neurologic examination at the time of this second hospital presentation, mental status, sensory, and reflex examinations had normal results. Cranial nerve examination had normal results except for conjugate, multidirectional rapid eye movements (opsoclonus; see the Video available at www.practicalneurology.com), which persisted with tracking and interrupted pursuits, despite full versions being present. Oscillatory head titubation (tremor) and low-amplitude, high-frequency postural tremor in the upper extremities and trunk, which improved at rest, were also present. OQ had a wide-based, cautious gait, but dysmetria testing was affected by the adventitious movements.

Laboratory testing results were largely unremarkable. Electrolyte levels and renal function markers were within reference limits, and aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin levels were normal. Nutritional laboratory studies, including vitamin B12 and copper levels, were within normal limits. The autoimmune panel showed a positive antinuclear antibody titer of 1:640 (speckled pattern), but other specific autoantibodies (anti-DNA, anti-SM, and anti-RNP) were negative. Testing for human immunodeficiency virus (HIV), hepatitis B virus, and encephalitis pathogens also had negative results. Initial mild leukocytosis (16.7x10⁹/L) and polycythemia (hemoglobin 19.0 g/dL, hematocrit 53.0%) were present, both of which resolved without intervention. Cerebrospinal fluid analysis was unremarkable, with normal protein (30 mg/dL) and glucose (68 mg/dL) levels, no pleocytosis, and a negative encephalitis panel. Imaging, including MRI of the brain, CT chest/abdomen/pelvis, and testicular ultrasound, showed no abnormalities. 

Case Resolution
Given the patent history and persistent abnormal eye and head movements, OQ was diagnosed with postviral opsoclonus-myoclonus syndrome (OMS). A 5-day course of intravenous immunoglobulin (IVIG) at 400 mg/kg/d was administered concurrently with intravenous methylprednisolone at 1 g/d. OQ had considerable symptomatic improvement and was discharged on a steroid taper, after which the improvement in symptoms continued. At a follow-up visit with the neurology department 1 week later, residual ocular flutter (transient periods of ocular instability with small, rapid, horizontal oscillations) and myoclonic movements were noted on physical examination. Additional IVIG cycles were recommended in addition to clonazepam 0.5 mg 3 times daily as needed for symptoms, and OQ was referred to physical therapy. OQ was unable to schedule additional appointments for IVIG administration, but continued to improve without further intervention. Six weeks later, OQ reported having almost returned to their baseline level of health. OQ continued to demonstrate an exaggerated startle response, which was improving in severity, and mild neck musculature shaking when stretching. IVIG therapy was discontinued and OQ was able to return to work. The Table outlines the sequence of events in the disease course and episodes of care. 

Discussion
OMS is primarily seen in children, with an annual incidence in children of 0.2 per million.¹ Adult-onset OMS, especially postviral OMS, is rare, contributing to the limited literature on diagnosis and management. This case highlights diagnostic challenges, differential diagnosis, and appropriate treatment in a case of adult OMS with a presumed parainfectious source. This case expands the current understanding of OMS presentations in adults and underlines the necessity of detailed history and comprehensive neurologic examination to differentiate OMS from other neurologic or vestibular disorders.

OMS is thought to arise from immune-mediated disruption of cerebellar and brainstem circuits—specifically the cerebellar vermis, fastigial nuclei, and brainstem omnipause neurons—that regulate saccadic eye movements.² Etiologies of OMS can be classified as paraneoplastic or parainfectious.² Paraneoplastic OMS is uncommon in people aged <40 years,³ except with ovarian teratomas associated with anti-Ri and anti-NMDAR antibodies.⁴ Paraneoplastic OMS is linked to encephalopathy and worse outcomes, including more relapses, compared with idiopathic OMS.^5,6 In this case, a thorough investigation of paraneoplastic causes and occult cancer was unremarkable. 

Parainfectious or idiopathic etiologies, which are more common in younger adults, include HIV infection,⁷ immune reconstitution with antiretroviral therapy initiation,⁸ herpes simplex virus, and SARS-CoV-2.⁹ Infectious workup was largely unremarkable in OQ, who had leukocytosis and polycythemia that resolved without intervention during hospitalization. Although certain antibodies (eg, anti-Ri and glycine receptor antibodies) have been linked to some paraneoplastic OMS cases, no specific or reproduceable epitope or biomarkers of the disease have been identified.^2,3,10,11 Further investigation is needed to elucidate whether molecular mimicry or antigenic targets predispose the cerebellar vermis and brainstem saccadic control centers to autoimmune attack after infection.¹² OMS also can result from structural, metabolic, or, rarely, toxic causes, such as organophosphate poisoning or cocaine use.¹³

OMS can be confused with cerebellar ataxia, especially in atypical cases or when opsoclonus is absent. OQ exhibited opsoclonus, myoclonus, and head titubation, but no ataxia. Diagnosis of OMS is based on the presence of clinical features, including opsoclonus (back-to-back multidirectional conjugate saccades without intersaccadic interval), myoclonus associated with ataxia, and other neurologic signs.^1,2 Misdiagnosis or delayed diagnosis, especially >2 months beyond initial symptom onset, can lead to worsened neurologic and behavioral outcomes.^1,2 Long-term neurologic sequelae in adults with OMS include gait ataxia and dysarthria. Relapses can occur in the setting of infection or treatment reduction, although the prognosis for idiopathic OMS is often self-limiting and generally more favorable than for paraneoplastic OMS.^1,14

Because OMS is an autoimmune process, the standard treatment is a combination of corticosteroids or adrenocorticotropic hormone with IVIg.¹ Immunomodulatory medications such as rituximab, cyclophosphamide, and methotrexate can be used in refractory cases.^1,2 If an underlying infection or cancer is identified, appropriate treatment with pharmacotherapy, radiation, or surgery is indicated. Clonazepam, baclofen, and levetiracetam can provide symptomatic relief for myoclonus and sleep disturbances.¹⁵ In this case, treatment with corticosteroids and IVIG resulted in improvement of symptoms. 

This case contributes to the limited literature on adult-onset OMS with atypical presentation in a young adult, which may aid in the recognition of similar cases. Adult-onset OMS attributed to an assumed parainfectious cause but without confirmed infectious agent is exceedingly rare. Most cases of adult OMS are paraneoplastic, and in the largest review, the majority of parainfectious cases were associated with HIV infection, with many cases not associated with HIV infection presenting with another confirmed infectious trigger.^3,6 Idiopathic or parainfectious OMS is more common in adults aged <40 years, and is less likely to present with encephalopathy or other major neurologic deficits at onset, as in OQ. The atypical presentation of OMS following a mild upper respiratory illness in a young, immunocompetent individual who experienced multiple misdiagnoses (viral otitis and labyrinthitis) highlights the diagnostic complexity of the case. Whereas overlapping features of peripheral vestibular pathology and OMS at onset have been documented, the sequence of misdiagnoses in this young, otherwise healthy adult augments the existing literature.^3,6

Awareness of cases like the one presented here can facilitate the clinical suspicion necessary for timely diagnosis and inpatient intervention, which requires interdisciplinary collaboration. OQ’s OMS was idiopathic and presumed parainfectious due to the timing of postinfectious symptoms and favorable response to immunotherapy. The case highlights the challenge of distinguishing OMS from other neurologic and vestibular conditions, encouraging consideration of OMS when presented with unusual eye and limb movements after infection. 

Conclusion
OMS is rare in adults, but can occur in paraneoplastic and parainfectious settings. It is crucial to recognize postviral OMS as a distinct clinical entity in young adults even without a definitive parainfectious source in the appropriate clinical context. Younger age, lack of oncologic risk factors, and the presence of postinfectious symptoms can aid diagnosis of parainfectious OMS. Thorough evaluation to rule out potential paraneoplastic, structural, toxic, and metabolic causes is important. Physical examination can help distinguish OMS from other neurologic and vestibular disorders, such as cerebellar ataxia and labyrinthitis. In this case, timely diagnosis and intervention resulted in marked symptomatic improvement and a favorable outcome. 

Patient Perspective
OQ initially experienced poor mental health due to their persistent symptoms. The motor symptoms and inability to walk were “debilitating and limiting,” leading to feelings of hopelessness and depression. Receiving the diagnosis of OMS provided relief, although OQ remained uncertain about the prognosis. OQ tolerated the IVIG treatments well. At the first follow-up with neurology, OQ expressed concerned about residual symptoms. However, steady improvement continued in the following weeks, and OQ returned to baseline and resumed their full-time job.