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Opsoclonus

Opsoclonus is a rare, involuntary disorder of characterized by spontaneous bursts of rapid, chaotic, multidirectional conjugate saccades without intersaccadic intervals, often described as "." It serves as the hallmark ocular feature of opsoclonus-myoclonus-ataxia syndrome (OMAS), also known as opsoclonus-myoclonus syndrome (OMS) or dancing eyes-dancing feet syndrome, a severe neurological condition that typically emerges abruptly in children or adults. The syndrome, first described by Marcel Kinsbourne in 1962, has an estimated incidence of about 1 in 5 million people annually and affects approximately 1 in 1 million overall, with a peak onset in children aged 1 to 3 years—slightly more common in girls—and occurring in roughly 3% of pediatric neuroblastoma cases. In addition to opsoclonus, core symptoms include myoclonus (sudden, brief muscle jerks, particularly in the limbs and trunk), ataxia (impaired coordination leading to unsteady gait and falls), and behavioral or cognitive disturbances such as irritability, sleep dysregulation, anxiety, and developmental regression. Other associated features may encompass hypotonia, dysarthria, tremors, and encephalopathy, with symptoms often progressing over days to weeks and potentially persisting or relapsing in 30% to 50% of cases without prompt intervention. The underlying etiology of opsoclonus is predominantly autoimmune or inflammatory, frequently triggered as a paraneoplastic response where the mistakenly attacks neural tissue in reaction to an underlying tumor. In children, accounts for 50% to 80% of paraneoplastic cases, often occult and located in the chest or , while in adults, it is linked to small cell (20% to 40% of cases), , or ovarian . Non-paraneoplastic causes include post-infectious triggers such as Epstein-Barr virus, , or even , as well as idiopathic, toxic-metabolic, or other autoimmune mechanisms without identifiable tumors. Diagnosis relies on clinical recognition of the triad of opsoclonus, , and , supplemented by (MRI or to rule out structural lesions or detect tumors), cerebrospinal fluid analysis (often showing pleocytosis or ), and paraneoplastic antibody testing (e.g., anti-Hu or anti-Ri). In suspected paraneoplastic cases, comprehensive tumor screening—such as urine catecholamine levels, metaiodobenzylguanidine (MIBG) scans, or whole-body imaging—is essential, as early detection can significantly improve outcomes. Management focuses on to suppress the aberrant , including high-dose corticosteroids, intravenous immunoglobulin (IVIG), (ACTH), or rituximab, often continued for 1 to 2 years, alongside tumor resection if identified. Supportive therapies such as physical, occupational, and speech therapy address and developmental delays, while prognosis varies: early treatment in paraneoplastic cases yields better remission rates (up to 80%), but residual neurologic deficits like or motor issues persist in many survivors.

Clinical presentation

Ocular features

Opsoclonus is a rare oculomotor defined as involuntary, rapid, chaotic, multidirectional conjugate saccades occurring without intersaccadic intervals, involving horizontal, vertical, and torsional components. These erratic eye movements prevent sustained fixation or , resulting in profound visual disruption often described as "." The oscillations persist across various conditions, including attempts at , eyelid closure, darkness, and even sleep, leading to symptoms such as (the illusion of environmental motion) and . Clinically, opsoclonus manifests as unpredictable darting of the eyes in all directions, with bursts of saccades that are neither rhythmic nor coordinated, distinguishing it from other eye movement disorders. Episodes are typically intermittent, lasting from seconds to minutes, and may fluctuate in intensity over hours to days, often worsening with attempts at sustained gaze, visual stimuli such as light or threat, or factors like excitement and stress. Fatigue and gaze shifts can also exacerbate the movements, though the precise mechanisms remain linked to underlying central nervous system dysfunction. Historically termed "saccadomania" due to the frenzied saccadic activity, opsoclonus is differentiated from related conditions like ocular flutter, which involves purely horizontal oscillations, and , which features rhythmic, slow-fast phases rather than continuous chaotic saccades. It forms a core feature of opsoclonus-myoclonus-ataxia syndrome, a involving additional motor abnormalities.

Associated neurological symptoms

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterized by a triad of hallmark chaotic eye movements known as opsoclonus, alongside prominent motor disturbances including and . These neurological symptoms typically manifest acutely or subacutely, progressing over days to weeks, with opsoclonus often appearing first or concurrently with the motor features. Myoclonus in OMAS consists of brief, shock-like, involuntary muscle jerks that are arrhythmic and non-rhythmic, affecting the limbs, trunk, and sometimes the face. These jerks are often stimulus-sensitive or action-related, leading to significant functional impairment such as disrupted posture, gait, and fine motor control. In reported cases, can involve the hands, legs, and voice, with diffuse or focal distribution contributing to overall motor instability. Ataxia accompanies myoclonus as a cerebellar-type disorder, featuring truncal unsteadiness, wide-based gait, intention tremor, dysmetria, and hypotonia. This results in staggering, falling, and loss of balance, often rendering patients unable to sit, stand, or walk independently, particularly in pediatric cases where it is more pronounced. The severity of these symptoms varies by age and individual factors. In children, who comprise the majority of cases with onset typically around , profound can produce a "ragdoll" appearance, exacerbating and leading to severe . In adults, where OMAS is rarer, symptoms tend to involve more focal limb and milder , though cases can still be debilitating. Long-term motor deficits, such as persistent coordination issues, affect 20% to 60% of pediatric patients.

Behavioral and cognitive effects

In children with opsoclonus-myoclonus syndrome (OMS), behavioral changes such as irritability and anxiety are common, affecting up to 88.9% of cases during the acute phase. Sleep disturbances, including insomnia and night terrors, occur in approximately 55.6% of pediatric patients, while temper tantrums and hyperactivity contribute to overall behavioral dysregulation in about 33.3%. These manifestations often emerge early in the disease course, sometimes preceding overt motor symptoms, and are linked to underlying encephalopathic processes. Cognitive deficits in pediatric OMS frequently include impairments and poor concentration, observed in the majority of affected children, alongside and affective dysregulation. Speech delays and language disorders are prevalent, impacting 88.9% of cases with features like deficits, while learning disabilities and developmental regression affect up to 53% long-term, leading to low-average intelligence quotients (e.g., full-scale IQ around 81). These issues can evolve over years, with visuospatial and adaptive functioning deficits persisting even after neurological stabilization, as seen in serial assessments showing declines in verbal and performance IQ scores. In adults with OMS, behavioral effects often manifest as mood disturbances including , , and , which may persist beyond acute symptoms and exacerbate underlying cognitive challenges. Cognitive impairments in this population typically involve mild inattention, disorientation, and encephalopathy-related deficits, occurring in about 35% of cases and contributing to affective dysregulation or anxiety. Overall, neuropsychiatric features in OMS highlight the syndrome's impact on development, with cognitive and behavioral impairments predominating long-term in up to 87.5% of pediatric survivors despite motor recovery.

Etiology

Paraneoplastic causes

Paraneoplastic opsoclonus-myoclonus syndrome (OMS) accounts for approximately 50% of cases in children, with the majority linked to underlying , typically low-stage tumors located in the or . In pediatric paraneoplastic OMS, over 90% of cases are associated with , a neural crest-derived that often presents with favorable and spontaneous regression potential. In adults, paraneoplastic OMS is less common overall but frequently tied to malignancies such as small cell lung cancer (SCLC), , and ovarian tumors. Anti-neuronal antibodies, including anti-Hu and anti-Ri, are identified in 20-40% of adult paraneoplastic cases, supporting an autoimmune basis. The underlying mechanism involves an to tumor antigens that cross-reacts with neural tissues, resulting in autoimmune-mediated damage to the , , and other structures. Symptom onset typically precedes tumor by several months, prompting urgent for occult malignancies. In children with neuroblastoma-associated OMS, early tumor resection can lead to symptom alleviation in some instances and is associated with improved overall prognosis when combined with .

Infectious and post-infectious triggers

Opsoclonus-myoclonus syndrome (OMS) can be triggered by various infectious agents, with viral and bacterial pathogens implicated in initiating an immune-mediated response leading to the disorder. Common pathogens associated with OMS include Epstein-Barr virus (EBV), which has been linked to cases through molecular mimicry in the , varicella-zoster virus, often following acute varicella infection, and , a frequent cause of post-infectious neurological complications in children. The post-infectious pattern of OMS typically involves symptom onset 1 to 4 weeks after the resolution of the acute , distinguishing it from direct encephalitic effects. Cerebrospinal fluid (CSF) examination in these cases reveals no evidence of active replication or persistent , supporting an autoimmune driven by cross-reactive antibodies or T-cell responses against neural tissues. Post-infectious OMS represents a substantial portion of non-paraneoplastic cases, accounting for approximately 40% to 50% of pediatric presentations where no tumor is identified, often classified within the broader idiopathic category. This form of OMS shows a marked predominance in pediatric populations, particularly children under 5 years of age, with a peak incidence around 12 to 24 months. It frequently follows common childhood illnesses such as upper respiratory tract infections or gastroenteritis, where the preceding symptoms resolve prior to neurological involvement. Recent case reports up to 2025 have highlighted SARS-CoV-2 (COVID-19) as an emerging post-infectious trigger for OMS, with symptoms appearing in the convalescent phase of the illness. These associations are thought to involve dysregulated immune responses, including cytokine storms characteristic of severe COVID-19, which may amplify neuroinflammation and autoimmunity.

Other causes

In approximately 60-80% of adult cases of opsoclonus-myoclonus syndrome (OMS), no underlying trigger is identified, classifying them as idiopathic; these may involve subtle autoimmune processes without detectable antibodies or tumors. Toxic-metabolic etiologies are uncommon but well-documented, often leading to transient opsoclonus that resolves with removal of the offending agent. , particularly in patients treated for , has been associated with opsoclonus through disruption of glycinergic and pathways. use can induce opsoclonus via serotoninergic, , and noradrenergic effects, with symptoms improving over months after cessation. Metabolic encephalopathies, such as those from hepatic failure, , or , may also precipitate opsoclonus by altering neurotransmitter balance. Structural lesions affecting the or can cause opsoclonus by directly impairing oculomotor control pathways. infarcts have been reported to produce opsoclonus as part of acute vascular disruption. Demyelinating conditions like can lead to opsoclonus through plaque formation in the , compressing or inflaming critical neural circuits. Rare associations include , such as , where opsoclonus-myoclonus may manifest as part of the broader syndrome, though it is not the primary feature. Genetic disorders, including ataxia-telangiectasia and , have been linked to opsoclonus in isolated cases, but these are not considered primary causes.

Pathophysiology

Immune-mediated mechanisms

Opsoclonus is primarily driven by autoimmune processes, with autoantibodies playing a central role in both paraneoplastic and idiopathic forms. In paraneoplastic cases, onconeural antibodies such as anti-Hu (ANNA-1) and anti-Ri (ANNA-2) have been detected in (CSF) and , contributing to neuronal dysfunction through cross-reactivity with antigens. Intrathecal synthesis of , indicative of local B-cell activation, occurs in approximately 58% of untreated pediatric opsoclonus-myoclonus syndrome (OMS) cases, correlating with disease severity and supporting an intrathecal . Cytokine dysregulation further amplifies the autoimmune cascade in opsoclonus. Elevated interleukin-6 (IL-6) levels in the CSF of untreated OMS patients, approximately 2.3-fold above controls, promote B-cell proliferation and differentiation while inducing neuronal hyperexcitability via microglial activation. Similarly, tumor necrosis factor-alpha (TNF-α), though not consistently elevated in CSF, is upregulated in microglial responses triggered by OMS patient-derived IgG, exacerbating inflammation and synaptic disruption. These proinflammatory cytokines foster a permissive environment for autoantibody production and immune cell recruitment within the central nervous system. T-cell mediated immunity contributes significantly to the , particularly in paraneoplastic opsoclonus associated with . + cytotoxic T cells infiltrate the and , where they target Purkinje cells and omnipause neurons through recognition of shared tumor-neuronal antigens, leading to cytotoxic damage via and perforin release. This infiltration, often accompanied by macrophages and activated , forms inflammatory nodules that perpetuate neuronal hyperexcitability and opsoclonus. Recent studies as of 2025 highlight the role of broader neuroinflammatory pathways in opsoclonus, with immune infiltration landscapes in neuroblastoma-associated OMS revealing upregulated genes involved in T-cell and metabolic responses that sustain chronic inflammation. These findings underscore the interplay between humoral and cellular immunity, often triggered by neuroblastoma antigens that mimic neuronal proteins.

Anatomical and physiological basis

Opsoclonus results from disruptions in the neural circuitry governing saccadic eye movements, primarily involving the and . Central to this are the omnipause neurons (OPNs) situated in the nucleus raphe interpositus within the (PPRF). These glycinergic neurons normally inhibit burst neurons in the PPRF and rostral interstitial nucleus of the (riMLF) during fixation, preventing unwanted saccades. Dysfunction of OPNs, whether through direct damage or impaired signaling, fails to maintain this inhibition, allowing continuous activation of burst neurons and leading to bursts of multidirectional saccades without intersaccadic intervals. The contributes significantly through the , particularly its caudal oculomotor region, which modulates accuracy, velocity, and coordination with postural adjustments. s in the oculomotor vermis provide inhibitory input to the ; loss of this inhibition—often due to dysfunction—results in overactivation of fastigial output to saccadic generators, exacerbating chaotic eye movements and integrating ataxia-like features. Functional MRI studies in patients with opsoclonus demonstrate hyperactivation of the bilateral fastigial nuclei during symptomatic periods, supporting this disinhibitory mechanism. Neural pathways linking these structures include projections from the , which triggers initiation, to the PPRF and riMLF, as well as connections from that stabilize gaze and generate quick phases during vestibular responses. Disruptions in these pathways, often at the cerebellar- interface, propagate uncontrolled signals, producing the physiological hallmark of opsoclonus: absent pauses between saccades due to unchecked burst neuron firing. In a subset of cases, T2-weighted or FLAIR MRI reveals hyperintensities in the or , reflecting underlying inflammatory or structural changes. Experimental models corroborate these findings. Computational simulations of overactivation further replicate the multidirectional, high-frequency saccades, highlighting the nucleus's role in timing and gating ocular motor commands.

Clinical assessment

The clinical of opsoclonus-myoclonus-ataxia (OMAS) commences with a thorough to capture the acute onset of abnormal eye movements, often within days to weeks, alongside recent infections that may serve as post-infectious triggers. Inquiry should include symptoms suggestive of an underlying tumor, such as unexplained , and family of autoimmune disorders, which is reported in up to 38% of pediatric cases and may indicate a predisposing genetic factor. In children, the predominant demographic affected, parents frequently describe accompanying irritability, sleep disturbances, and developmental regression, which can precede or coincide with motor symptoms. Physical examination emphasizes direct observation of spontaneous opsoclonus, characterized by chaotic, multidirectional, high-amplitude saccades without intersaccadic intervals, typically evident during rest or routine without the need for provocation. To further evaluate saccadic dysfunction, optokinetic testing may be employed, revealing absent or irregular responses that distinguish opsoclonus from other ocular oscillations. Fundoscopy is routinely performed to exclude pathology, such as or congenital anomalies, that could contribute to or mimic the disorder. appears as sudden, arrhythmic jerks of the limbs or trunk, while manifests as gait instability and truncal titubation, often briefly referenced in the context of the broader presentation. Diagnosis of OMAS requires at least three of the following four features: opsoclonus, and/or , behavioral changes and/or sleep disturbances, and . In paraneoplastic cases, confirmation of fulfills one diagnostic feature and necessitates tumor screening regardless of other findings. In pediatric patients, standardized behavioral screening using tools like the (CBCL) is essential to quantify , attention deficits, and , which affect over half of cases and may persist beyond acute motor symptoms. Red flags during assessment include asymmetric eye movements or progressive worsening of symptoms, which deviate from the typical bilateral, subacute pattern and raise concern for a structural central nervous system lesion.

Laboratory and imaging investigations

Laboratory investigations for opsoclonus begin with cerebrospinal fluid (CSF) analysis, which often reveals mild lymphocytic pleocytosis (typically 10-50 cells/μL), elevated protein levels (usually 50-100 mg/dL), and oligoclonal bands in approximately 60% of cases, supporting an inflammatory or autoimmune process. Urine catecholamine metabolites, such as vanillylmandelic acid (VMA) and homovanillic acid (HVA), are measured to screen for underlying neuroblastoma, with elevations above the upper limit of normal observed in about 50-70% of paraneoplastic cases associated with this tumor, though normal levels do not exclude the diagnosis. Serologic testing includes panels for paraneoplastic antibodies like anti-Hu, anti-Ri, and anti-Yo, which are detected in approximately 10-20% of adult cases and guide the search for occult malignancies such as breast or lung cancer. Infectious etiologies are evaluated through serology and polymerase chain reaction (PCR) for viruses including Epstein-Barr virus (EBV) and cytomegalovirus (CMV), particularly in post-infectious presentations where IgM or IgG titers may indicate recent exposure. Imaging studies are essential to identify structural lesions or underlying tumors. Brain magnetic resonance imaging (MRI) using T2-weighted and (FLAIR) sequences is the initial modality to assess for or cerebellar abnormalities, though findings are often normal or show nonspecific hyperintensities in inflammatory cases. For suspected paraneoplastic opsoclonus in children, computed (CT) or MRI of the abdomen and thorax targets neuroblastoma detection, with metaiodobenzylguanidine (MIBG) offering a of approximately 90% for identifying primary tumors and metastases due to its specificity for neural crest-derived cells. In adults, whole-body -computed (PET-CT) with 18F-fluorodeoxyglucose (FDG) is increasingly utilized as of 2025 to detect occult tumors, demonstrating high (up to 95%) for malignancies like that may underlie the syndrome. (EEG) is performed to exclude seizures mimicking myoclonic jerks, typically showing no epileptiform activity in true opsoclonus-myoclonus syndrome.

Management

Immunosuppressive therapy

Immunosuppressive therapy forms the cornerstone of management for opsoclonus-myoclonus (OMS), targeting its presumed autoimmune to modulate aberrant immune responses against neural tissues. First-line treatments typically involve high-dose corticosteroids, such as intravenous at 30 mg/kg/day for 5 days, followed by an oral taper, or (ACTH) in pediatric cases, with ACTH often demonstrating superior efficacy over corticosteroids alone in achieving symptom remission. Corticosteroids, often in combination with other agents, yield improvement in approximately 40% of cases in some studies, while ACTH achieves higher remission rates, particularly in children, though long-term remains a concern. Intravenous immunoglobulin (IVIG) is frequently administered as an adjunct or early second-line therapy, dosed at 2 g/kg over 2-5 days initially, followed by 1-2 g/kg monthly for up to a year, enhancing response rates to 81% when combined with corticosteroids and reducing risk. For refractory cases, rituximab, a monoclonal , is employed at 375 mg/m² weekly for 4 doses, promoting B-cell depletion and sustained neurological improvement in pediatric patients unresponsive to initial therapies. serves as another option for treatment-resistant OMS, often in low doses combined with corticosteroids or IVIG, leading to complete symptom resolution in select pediatric cohorts. In acute exacerbations or refractory scenarios, therapeutic plasma exchange (TPE) has shown efficacy, with a standard course of 5-6 exchanges over alternating days facilitating remission when integrated with rituximab and IVIG. Emerging approaches, such as combining pulsed intravenous dexamethasone, IVIG, and rituximab, have demonstrated reduced relapses and neurological sequelae in recent evaluations as of 2025. There is currently no consensus for OMS . These therapies are often used alongside tumor resection in paraneoplastic cases to optimize outcomes. Response to immunosuppressive is monitored using validated scales, such as the Opsoclonus- (OMS) severity score, which assesses domains including opsoclonus, , , and behavior, with improvement defined as a reduction in total score by at least 2 points or stabilization below moderate severity. Tapering is guided by clinical stability, typically over 12-24 months, with vigilant surveillance for relapse given the condition's relapsing-remitting nature.

Tumor treatment

In paraneoplastic opsoclonus associated with , particularly in pediatric patients with low- or intermediate-risk tumors (stages 1-2), surgical resection remains the cornerstone of oncological management, often leading to rapid resolution of neurological symptoms such as opsoclonus and in the majority of cases shortly after complete tumor removal. Complete resection is feasible in over 85% of these early-stage tumors, which are typically localized and favorable, contributing to excellent overall survival rates exceeding 95% without the need for additional in low-risk cases. For advanced or cases involving incomplete resection, chemotherapy regimens such as , , , and are employed, often improving neurological outcomes by addressing residual disease and reducing symptom persistence. In adults with opsoclonus linked to small cell lung cancer (SCLC), standard treatment includes platinum-based (e.g., or combined with ), frequently augmented by radiotherapy for limited-stage disease, which has been associated with substantial neurological improvement and tumor response in reported cases. A multidisciplinary approach involving tumor board reviews by pediatric oncologists, neurosurgeons, and neurologists is essential to optimize treatment planning, including postoperative surveillance imaging (e.g., MRI or MIBG scans) every 3-6 months to detect relapse early and prevent neurological exacerbation. Early oncological intervention, ideally within one month of symptom onset, significantly lowers the risk of long-term neurological sequelae, reducing incidence from nearly 100% in delayed cases to approximately 42% with prompt action. Adjunctive immunotherapy may complement tumor-directed therapies in select cases to further support symptom control.

Supportive care

Supportive care for opsoclonus-myoclonus- syndrome (OMAS) focuses on alleviating symptoms and enhancing functional abilities through targeted pharmacological interventions and rehabilitative strategies, complementing disease-modifying immunotherapies. In acute presentations, hospitalization is often necessary to stabilize patients, particularly children who exhibit severe leading to frequent falls; fall precautions, such as bed alarms, padded side rails, and supervised ambulation, are essential to prevent injuries during episodes of staggering or imbalance. Pharmacological management targets prominent motor symptoms without addressing the underlying immune pathology. For , is commonly administered at doses of 0.01-0.03 mg/kg/day, divided into multiple doses, to reduce involuntary jerks and improve , with careful monitoring for . serves as an alternative for refractory , typically starting at 20-40 mg/kg/day in pediatric cases, providing symptomatic relief by modulating synaptic transmission. Ataxia-related , which can exacerbate and discomfort, is managed with antiemetics such as , administered at 0.15 mg/kg intravenously or orally as needed, to support tolerance of oral intake during acute phases. Rehabilitation plays a central role in restoring mobility and communication skills. Physical and occupational therapies emphasize training through exercises, such as supported walking on uneven surfaces or use of assistive devices, to mitigate and enhance coordination; these interventions, often initiated early, can significantly improve functional independence. Speech therapy addresses by focusing on exercises and communication strategies, helping patients regain verbal expression amid slurred speech and language disruptions. Behavioral interventions, including structured routines and cognitive-behavioral techniques, target and common in pediatric OMAS, reducing episodes and promoting emotional . A multidisciplinary approach ensures holistic support, addressing secondary complications. Nutrition support is crucial due to hypotonia-induced feeding difficulties, involving high-calorie supplements or enteral feeding if oral intake is inadequate, to prevent weight loss and support muscle recovery. Sleep hygiene practices, such as consistent bedtime routines and minimizing stimulants, help manage insomnia and fragmented sleep patterns that worsen behavioral symptoms. Psychological counseling for families provides coping strategies for the emotional toll of caregiving, including support groups to address anxiety and adjustment challenges during the child's recovery.

Prognosis and complications

Acute outcomes

Immunotherapy, typically involving corticosteroids, intravenous immunoglobulin (IVIG), and rituximab, yields partial symptom improvement in 70-90% of pediatric opsoclonus-myoclonus syndrome (OMS) cases within 1-3 months of initiation, with response rates reaching 81% when IVIG is added to conventional regimens like prednisolone and . In paraneoplastic OMS linked to , tumor resection combined with contributes to symptom improvement in many cases during the post-treatment phase. Relapses occur in 30-50% of OMS patients within the first year after initial , frequently triggered by or reduction in immunosuppressive therapy. Relapse rates tend to be higher in idiopathic OMS (around 40-100% in reported series) compared to paraneoplastic cases (0-25%), though overall frequencies vary by study cohort and intensity. Early and initiation within 2 months of symptom onset correlate with superior acute control, including reduced severity and faster stabilization of motor symptoms. Pediatric OMS cases generally exhibit faster resolution of acute symptoms than adult-onset cases, with children achieving better short-term motor recovery due to less severe and more responsive . Data from a 2025 clinical study on multimodal (intravenous dexamethasone, IVIG, and rituximab) in a small (n=6) reported an acute rate of 17%, lower than historical benchmarks of 30-50%, supporting a transition to ongoing monitoring for sustained remission.

Long-term sequelae

Long-term sequelae of (OMS) primarily manifest as enduring neurological, cognitive, and behavioral impairments that persist years after the acute phase, affecting a majority of patients despite . Neurological residuals are common, with 20% to 60% of children experiencing persistent , subtle , or coordination deficits, though overt opsoclonus rarely recurs fully. Patients may also retain , contributing to ongoing visual instability and balance issues. In adults, these residuals can include motor impairments, though data are limited due to the rarity of adult-onset OMS. Cognitive outcomes are particularly challenging, especially in pediatric cases, where 50% to 80% of children with OMS demonstrate declines in full-scale IQ, often by 10 to 30 points from baseline, alongside visuospatial, language, and processing speed deficits. Attention-deficit/hyperactivity disorder (ADHD) and learning disorders, such as or difficulties with reading and writing, affect up to 50% of survivors, leading to academic underperformance even in those with normal-range IQ scores. Adults face risks of chronic fatigue and subtle cognitive lingering effects, exacerbating daily functioning. Quality of life remains impacted long-term, with many patients requiring ongoing multidisciplinary , including speech, occupational, and behavioral interventions, to address adaptive and social deficits. In children, approximately 50% have learning disabilities that may require support, while early aggressive has been shown to improve outcomes in recent longitudinal analyses. Mortality is low at 5% to 10%, predominantly attributable to progression of the underlying associated tumor, such as , rather than the syndrome itself.

Epidemiology

Incidence and prevalence

Opsoclonus-myoclonus (OMS) is an exceedingly rare , with an estimated annual incidence of approximately 1 in 5 million individuals worldwide. Prevalence estimates are approximately 1 per million globally, though the condition is likely underdiagnosed, particularly in adults where cases are less frequently reported and recognized compared to pediatric presentations. In the United States, this translates to roughly 40-50 new pediatric cases annually, reflecting the disorder's concentration in young children. The incidence in children specifically is estimated at 0.18 to 0.6 cases per million per year. Overall incidence trends remain stable over time, with no significant shifts reported in recent epidemiological data. Geographic variations show higher reporting rates in developed countries, attributable to advanced diagnostic capabilities and systems, while underreporting is probable in regions with limited access to specialized care. OMS is associated with in about 50% of pediatric cases, aligning with the tumor's own incidence patterns in children.

Demographic patterns

Opsoclonus-myoclonus syndrome (OMS) exhibits a bimodal age distribution, with the majority of cases occurring in young children and a smaller proportion in adults. In pediatric populations, approximately 80% of OMS cases present between 1 and 4 years of age, with a onset around 18 months; the condition is rare in infants under 6 months (about 2% of cases) and uncommon in children over 6 years. In adults, onset typically occurs between 40 and 60 years, with a median age of around 47 years, and it is infrequent in the elderly beyond 80 years. Regarding sex differences, OMS affects males and females equally in children, though some studies report a slight female predominance with a of 1.2:1. In adults, there is a more pronounced female predominance, with ratios ranging from 1.5:1 to nearly 2:1, potentially linked to associations with as an underlying paraneoplastic cause. No strong genetic risk factors have been identified for OMS, though familial autoimmune diseases are more prevalent in affected pediatric families compared to the general population. Associations with Epstein-Barr virus (EBV) have been documented in both children and adults, suggesting a possible role in para-infectious cases, particularly in regions with high EBV seroprevalence. Pediatric OMS is more frequently reported among Caucasians, comprising about 70% of cases in large cohorts.

History

Initial descriptions

The term "opsoclonus" was coined in 1913 by Polish neurologist Kazimierz Orzechowski to describe rapid, irregular, conjugate eye movements resembling jerks in a 21-year-old pregnant woman with a cerebellar tumor and encephalitis-like symptoms. Orzechowski's description emphasized the chaotic, multidirectional saccades without intersaccadic intervals, distinguishing it from other forms, and he expanded on its linkage to and myoclonus in a 1927 report. Pediatric cases gained prominence in the mid-20th century, with early reports framing the syndrome as "" due to the prominent ocular component in infants and young children, often following viral infections such as those causing coryza or fever. In 1956, Dunn and colleagues described infantile polymyoclonus with erratic eye movements in affected children, underscoring the post-infectious etiology prevalent in initial observations. The full pediatric syndrome, now known as opsoclonus-myoclonus syndrome (OMS), was systematically outlined in 1962 by Marcel Kinsbourne, who reported six cases of with , , and " and feet," formalizing its recognition beyond isolated adult . An important early association with underlying emerged in 1968 when and Chutorian reported a case of occult accompanied by opsoclonus, marking the first link to neuroblastoma in children, though most pre-1970s cases were attributed to infectious triggers rather than tumors. Prior to the 1970s, diagnostic challenges were significant, with opsoclonus often misattributed to psychogenic causes like or epileptic phenomena due to the absence of focal lesions on early and the dramatic, fluctuating nature of symptoms. This led to delayed recognition and inappropriate treatments, such as anticonvulsants or , before the paraneoplastic and post-infectious patterns became clearer.

Advances in understanding

In the and , solidified the paraneoplastic link between opsoclonus-myoclonus syndrome (OMS) and , establishing that approximately 50% of pediatric OMS cases were associated with this tumor, often with favorable neuroblastoma prognosis despite neurological persistence. Initial approaches emerged during this era, with early trials of corticosteroids demonstrating partial symptom control in acute OMS, though long-term outcomes remained variable. The 1990s brought key etiological insights through the discovery of anti-Ri antibodies in OMS patients, particularly in paraneoplastic adult cases linked to or other tumors, as reported in a 1993 study of a steroid-responsive . By the , international efforts advanced understanding via OMS registries; a landmark cross-sectional analysis by Pranzatelli et al. in 2017 examined 389 children, revealing demographic patterns, immunologic markers like elevated B-cell activity, and triggers in over half of cases. During the 2010s, therapeutic breakthroughs included demonstrations of rituximab's efficacy in refractory OMS, with 2012 case reports showing sustained clinical and immunologic responses in neuroblastoma-associated pediatric patients through B-cell depletion. Etiological research also tied post-infectious OMS to Epstein-Barr virus (EBV) using detection of viral DNA in , supporting immune-mediated mechanisms in non-paraneoplastic cases. In the 2020s, studies identified as a rare trigger for OMS, with multiple 2022 reports documenting onset within one month of infection, often presenting with and in isolation or combination. Advances in biologics included exploratory trials of for modulation in refractory cases, alongside multimodal regimens reducing relapse rates. Genetic investigations, such as a 2024 whole-genome sequencing study of 42 children, ruled out strong heritability by identifying only rare polygenic variants in 23.8% of cases, implicating environmental triggers over . As of 2025, ongoing research continues to explore novel immunotherapies and genetic modifiers in OMS cohorts.