Search

Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neuroimmune disease with peak onset at 18 months, associated with neural crest tumors in 50% of patients. In part due to its rarity, misdiagnosis at onset is common, can delay treatment, and may contribute to adverse outcomes. Patient-reported registries may overcome some of these challenges in rare disease research. In this context, the OMSLife Foundation collaborated with the National Organization of Rare Diseases to create a patient-reported registry in OMAS., Methods: Retrospective analysis was performed of data entered by parents of patients with OMAS into nine online surveys assessing demographics, symptoms at onset, triggers, time of diagnosis, treatment, and additional therapies., Results: A total of 194 patients were enrolled. There was a female predominance (54%) and high rate of parental autoimmunity (31%). Age at onset peaked between 12 and 18 months overall. The age of onset was older in female patients (median [interquartile range]: females 22 [15 to 31] vs males 18 [14 to 23], P = 0.0223, P = 0.0223). Symptoms at onset most commonly included ataxia (84%) and were typically severe. Initial misdiagnosis occurred in nearly 50% and tumor discovery was delayed in 18 patients, but overall median time to correct diagnosis was 25 days. Most patients (56%) received combination immunomodulatory therapies, and nearly all underwent supportive therapies., Conclusions: Patient- and parent-powered research is feasible in OMAS and created the second largest published cohort of pediatric patients with OMAS. Results were similar to other large cohorts and also validated findings from prior case reports and smaller case series., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare autoimmune disorder of the nervous system presenting with abnormal eye and limb movements, altered gait, and increased irritability. Two to four percent of children diagnosed with neuroblastoma have neuroblastoma-associated OMAS (NA-OMAS). These children typically present with non-high-risk neuroblastoma that is cured with surgery, with or without chemotherapy. Despite excellent overall survival, patients with NA-OMAS can have significant persistent neurological and developmental issues., Objective: This study aimed to describe long-term neurocognitive and adaptive functioning of patients with NA-OMAS treated with multimodal therapy, including intravenous immunoglobulin (IVIG) on Children's Oncology Group (COG) protocol ANBL00P3., Methods: Of 53 children enrolled on ANBL00P3, 25 submitted evaluable neurocognitive data at diagnosis and at least one additional time point within 2 years and were included in the analyses. Adaptive development was assessed via the Vineland Adaptive Behavior Scale, and validated, age-appropriate measures of intellectual function were also administered., Results: Twenty-one of the 25 patients in this cohort ultimately received IVIG. Descriptive spaghetti plots suggest that this cohort demonstrated stable long-term cognitive functioning and adaptive development over time. This cohort also demonstrated decreased OMAS scores over time consistent with improved OMAS symptoms., Conclusions: While statistical significance is limited by small sample size and loss to follow-up over 10 years, findings suggest stable long-term cognitive and adaptive functioning over time in this treated cohort., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare disorder that causes significant neurodevelopmental sequelae in children. Approximately half of pediatric OMAS cases are paraneoplastic, typically associated with localized neuroblastic tumors. Since early persistence or relapse of OMAS symptoms is common even after tumor resection, OMAS relapses may not routinely prompt reevaluation for recurrent tumors. We report a 12-year-old girl with neuroblastic tumor recurrence associated with OMAS relapse a decade after initial treatment. Providers should be aware of tumor recurrence as a trigger for distant OMAS relapse, raising intriguing questions about the role of immune surveillance and control of neuroblastic tumors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Opsoclonus-myoclonus syndrome (OMS) is a rare, immune-mediated neurological disorder. In adults, the pathogenesis can be idiopathic, post-infectious or paraneoplastic, the latter etiology belonging to the ever-expanding group of defined paraneoplastic neurological syndromes (PNS). In contrast to other phenotypes of PNS, OMS cannot be ascribed to a single pathogenic autoantibody. Here, we report the first detailed case of paraneoplastic, antibody-negative OMS occurring in association with a pancreatic neuroendocrine tumor (pNET)., Case Presentation: A 33-year-old female presented with a two-week history of severe ataxia of stance and gait, dysarthria, head tremor, myoclonus of the extremities and opsoclonus. Her past medical history was notable for a metastatic pancreatic neuroendocrine tumor, and she was subsequently diagnosed with paraneoplastic opsoclonus-myoclonus syndrome. Further workup did not reveal a paraneoplastic autoantibody. She responded well to plasmapheresis, as she was refractory to the first-line therapy with corticosteroids., Conclusions: This case expands current knowledge on tumors associated with paraneoplastic opsoclonus-myoclonus syndrome and the age group in which it can occur. It further adds evidence to the effectiveness of plasmapheresis in severe cases of opsoclonus-myoclonus syndrome with a lack of response to first-line therapy., (© 2022. The Author(s).)

Background and Objectives: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder and myoclonus, in addition to ataxia, irritability, and sleep disturbance. There is good evidence that OMAS is an immune-mediated condition that may be paraneoplastic in the context of neuroblastoma. This syndrome may be associated with long-term cognitive impairment, yet it remains unclear how this is influenced by disease course and treatment. Treatment is largely predicated on immune suppression, but there is limited evidence to indicate an optimal regimen., Methods: Following an international multiprofessional workshop in 2004, a body of clinicians and scientists comprising the International OMS Study group continued to meet biennially in a joint professionals and family workshop focusing on pediatric OMAS. Seventeen years after publication of the first report, a writing group was convened to provide a clinical update on the definitions and clinical presentation of OMAS, biomarkers and the role of investigations in a child presenting with OMAS, treatment and management strategies including identification and support of long-term sequelae., Results: The clinical criteria for diagnosis were reviewed, with a proposed approach to laboratory and radiologic investigation of a child presenting with possible OMAS. The evidence for an upfront vs escalating treatment regimen was reviewed, and a treatment algorithm proposed to recognize both these approaches. Importantly, recommendations on monitoring of immunotherapy response and longer-term follow-up based on an expert consensus are provided., Discussion: OMAS is a rare neurologic condition that can be associated with poor cognitive outcomes. This report proposes an approach to investigation and treatment of children presenting with OMAS, based on expert international opinion recognizing the limited data available., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Opsoclonus-myoclonus-ataxia syndrome is a rare neuroimmunologic disorder typically presenting in previously healthy infants and toddlers. It is characterized by a clinical triad of (1) erratic saccadic intrusions; (2) myoclonus and/or ataxia; (3) behavioral features, typified by developmental plateauing, irritability and insomnia. About half of cases are associated with an underlying neuroblastoma and diagnostic imaging is essential once OMAS is suspected. A thorough workup, including serum, urine, and cerebrospinal fluid studies is critical to identify underlying biomarkers of OMAS itself or neuroblastoma. Historically, many children had relatively poor long-term outcomes, with residual neurologic and/or neuropsychiatry sequelae typical. More recent concepts have emphasized combined immunotherapy regimens that offer hope for better outcomes in children with this remarkable, challenging disease., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To determine predictors of full-scale IQ (FSIQ) in an international pediatric opsoclonus myoclonus syndrome (OMS) cohort., Method: In this retrospective and prospective cohort study at three academic medical centers (2006-2013), the primary outcome measure, FSIQ, was categorized based on z-score: above average (≥+1), average (+1 to -1), mildly impaired (-1 to -2), and impaired (<-2). Univariate analysis and multivariable linear regression modeling using stepwise selection with Akaike's information criterion was performed to understand the relationship between exposures and FSIQ., Results: Of 81 participants, 37 with sufficient data had mean FSIQ 84.38 (SD 20.55) and median 90 (40-114) at latest available evaluation (mean age 8y 5mo). Twenty (54%), nine (24.3%), and eight (21.6%) had normal, mildly impaired, and impaired FSIQ respectively. The final multivariable linear regression model included 34 participants with evaluable data: number of relapses occurring before neuropsychological testing (p<0.001) and OMS severity score at last follow-up (p<0.001) predicted FSIQ (adjusted R 2 =0.64). There was a mean decrease of 2.4 FSIQ points per OMS relapse., Interpretation: Number of relapses negatively correlates with FSIQ in pediatric OMS. Demographic and clinical measures available at OMS onset did not predict FSIQ. Strategies to reduce OMS relapses may improve intellectual outcomes., (© 2020 Mac Keith Press.)

Objective: To review the treatment and revaccination of neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome (OMAS) patients at Memorial Sloan Kettering Cancer Center (MSK)., Procedure: Institutional Review Board approval was obtained for this retrospective study of patients with neuroblastoma-associated OMAS followed at MSK from 2000 to 2016., Results: Fourteen patients (nine female) were 9-21 (median 17) months old at diagnosis of neuroblastoma and OMAS syndrome. They had stage 1 (n = 12), stage 2B, or intermediate-risk stage 4. Tumor histology was favorable in 11 patients, unfavorable in two, and unknown in one patient. No patient had amplified MYCN. All patients underwent tumor resection at diagnosis. Anti-neuroblastoma treatment was limited to chemotherapy in one patient. Overall survival is 100% at 3-16 (median 10) years. For OMAS, 13 patients received intravenous immune globulin (IVIg), adrenocorticotropic hormone (ACTH), and rituximab, and one received ACTH and IVIg. Seven patients experienced OMAS relapse. For these relapses, five patients received low-dose cyclophosphamide and two received rituximab. The mean total OMAS treatment was 20-96 (median 48) months. Seven patients started rituximab ≤3 months from diagnosis and did not relapse. The other six experienced OMAS relapse. To date, six patients have been revaccinated at a minimum of 2 years after completion of OMAS therapy without OMAS recurrence., Conclusions: Patients with neuroblastoma-associated OMAS had excellent overall survival. Early initiation of rituximab, IVIg, and ACTH may reduce risks of OMAS relapse. Revaccination can be resumed without exacerbation of OMAS. Further investigation with a larger cohort of patients is needed., (© 2020 Wiley Periodicals, Inc.)

Opsoclonus myoclonus syndrome (OMS) is a rare neurological syndrome caused by a paraneoplastic autoimmune process that affects children with neuroblastic tumors. Treatment includes corticosteroids, intravenous gamma globulin (IVIG), rituximab, and other immunosuppressive therapies. Here, we describe a patient diagnosed with OMS associated with a localized inflammatory myofibroblastic tumor. The patient has no evidence of tumor recurrence following surgical resection with 8-month follow-up. The neurologic symptoms resolved with corticosteroids and IVIG. This case demonstrates that in children, neoplasms other than neuroblastoma may be associated with this paraneoplastic syndrome, and highlights the importance of evaluating patients with OMS for underlying malignancies., (© 2020 Wiley Periodicals, Inc.)

Background: Treatment of opsoclonus-myoclonus syndrome (OMS) has historically involved corticosteroids and intravenous immunoglobulin (IVIG) for a duration of 6-12 months or longer. This study evaluated whether a brief upfront immunomodulatory therapy protocol with rituximab reduces the duration of OMS therapy without adversely affecting OMS outcomes., Procedure: Retrospective chart review was performed for consecutive children diagnosed with OMS from 2006 to 2019 at The Hospital for Sick Children (Toronto, Canada). Children treated within 3 months of diagnosis with a treatment protocol involving pulse methylprednisolone (3-5 days, followed by an oral steroid taper), IVIG and/or plasma exchange, and rituximab (protocol group, n = 7) were compared to a historical group treated primarily with prednisone and IVIG (n = 8)., Results: The duration of corticosteroid treatment was shorter in the protocol (median 4.5 [range 3-12] months) compared to that in the historical group (median 21.5 [range 6-70] months, P = .005), and subjects in the protocol group received fewer cycles of IVIG (median 1 [range 0-7] cycle vs 7 [range 1-70] cycles, P = .01). The proportion of children with OMS relapse was similar between the protocol and historic groups (2/6 vs 5/8, P = .59). OMS symptom rating scales at 12-month follow-up were similar in the protocol group (median 2.5, range 0-3) compared to that in the historical group (median 1, range 0-7; P = .66)., Conclusions: An upfront immunomodulatory therapy protocol with rituximab permits reduction in the duration of corticosteroid and IVIG therapy without a detrimental effect on OMS outcomes. Future studies with longer follow-up will have to determine whether neurocognitive and psychosocial outcomes are improved by this approach., (© 2019 Wiley Periodicals, Inc.)

Background: Rituximab (anti-CD20) has been used as B-cell-targeted intervention to treat opsoclonus-myoclonus syndrome. Due to isolated reports of chronic hypogammaglobulinemia and B lymphopenia following rituximab in several disorders, and rapid B-cell depletion after a few doses, we reduced the dosage 20% in our clinical practice., Methods: In this Institutional Review Board-approved retrospective study, 32 children with opsoclonus-myoclonus syndrome and cerebrospinal fluid B-cell expansion had received front-loaded adrenocorticotropic hormone, intravenous immunoglobulin, and rituximab combination immunotherapy for de novo opsoclonus-myoclonus syndrome. Parametric statistical analysis compared 10 children receiving 1200 mg/m 2 of rituximab (300 mg/m 2 × 4) and 22 receiving 1500 mg/m 2 (375 mg/m 2 × 4). Clinical response had been video documented and scored by a blinded observer., Results: In both groups, motor severity (total score) lessened by ≥76% and cerebrospinal fluid B cells were similarly depleted (≥95%) six months after treatment. None of the treated patients remained unable to walk independently. Serum IgM depletion was analogous in the 1200 mg/m 2 (-73%) and 1500 mg/m 2 group (-64%). The relapse frequency was similar in both groups. Side effects were principally steroidal, tolerable, and transient. Circulating B-cell repopulation was comparable., Conclusions: The reduced-dose of rituximab in rituximab combination immunotherapy was as effective and well tolerated as the standard dose, and provided rapid, early therapeutic intervention in opsoclonus-myoclonus syndrome. Pending a long-term prospective study, these are proof-of-concept data in support of challenging the dose of rituximab in various disorders, which may have different dose requirements., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Opsoclonus, myoclonus, ataxia syndrome (OMA) is a severe neurologic disorder often associated with neuroblastoma. It is challenging to treat and can have long-term neurologic sequelae. Current recommended therapies include intravenous immunoglobulin, corticosteroids, rituximab, and chemotherapy (cyclophosphamide). We present two cases who were refractory to conventional therapy and underwent autologous stem cell transplantation (ASCT). One patient had complete resolution of symptoms following ASCT and the other patient had minimal change in symptoms with this therapy. These findings support consideration of ASCT as a therapeutic option for patients with refractory OMA after failure of known effective therapies., (© 2018 Wiley Periodicals, Inc.)

Opsoclonus-myoclonus syndrome (OMS) is a neuroinflammatory disorder with pervasive morbidity that warrants better treatments. Twelve children with moderate/severe OMS (total score 23 ± 6) who did not remit to multiple immunotherapies were evaluated for neuroinflammation in a case-control study using cerebrospinal fluid (CSF) lymphocyte subset analysis by flow cytometry, chemokine/cytokine analysis by enzyme-linked immunoadsorption assay (ELISA), and oligoclonal bands by immunofixation with isoelectric focusing. Observations made on empirical treatment with rituximab, IVIg, and tetracosactide combination immunotherapy (coined "RITE-CI") were analyzed. All of the patients tested for multiple inflammatory markers were positive; 75% had ≥3 CSF markers. Fifty percent had CSF oligoclonal bands; 58%, B cell expansion; and 50 to 100%, elevated concentrations of multiple chemokines and neuronal/axonal marker neurofilament light chain. After RITE-CI, total score dropped significantly in the group (-85%, p  < 0.0001) from moderate to trace, and by 2 to 4 severity categories in each patient. The 24-week schedule was well tolerated and clinically effective for moderate or severe OMS, as were other schedules. RITE-CI is feasible and effective as rescue therapy and presents an initial option for children with moderate/severe OMS. Though preliminary, the schedule can be adjusted to patient severity, propensity for relapse, and other factors., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Opsoclonus myoclonus ataxia syndrome (OMAS) can be refractory to standard therapies and devastating. Alternative treatments are imperative. A 14-month-old male diagnosed with neuroblastoma and paraneoplastic OMAS achieved complete cancer remission with chemotherapy. The OMAS, however, persisted over the subsequent 4 years despite numerous immune-modulatory and immunosuppressive therapies. The patient ultimately achieved complete remission following therapeutic plasma exchange (TPE) combined with rituximab and intravenous immunoglobulin. After three asymptomatic years, he relapsed. Upon reintroducing TPE and rituximab plus oral prednisolone, the patient rapidly achieved a second complete remission. This case offers proof-of-principle for the potential efficacy of TPE for neuroblastoma-associated OMAS., (© 2017 Wiley Periodicals, Inc.)

Cancer and autoimmunity come together in paraneoplastic syndromes (PNS), which reflect the remote, not direct, effects of cancer. In the pediatric population, a variety of PNS have been described, but the most common of these rare disorders are instigated by neuroblastic tumors, such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. The main pediatric-onset neurological PNS are ROHHAD syndrome, anti-ANNA1 (anti-Hu), and opsoclonus-myoclonus syndrome. They manifest distinctive neurological features, which aid the diagnosis, though under-recognition still poses serious challenges and risks. In each clinical syndrome, a large subgroup of patients had no demonstrated tumor. Most neurological PNS are immunologically mediated, and CSF neuroimmunological studies show common elements of immune involvement in PNS as well as important differences. Future immunotherapy strategies may be able to take advantage of these abnormalities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Opsoclonus-myoclonus syndrome (OMS) is a rare and primarily immune-mediated disease in children and adults. The main symptoms include opsoclonus, myoclonus and ataxia. In children, the symptoms also include irritability, and, over a long-term course, learning and behavioural disturbances. OMS can be idiopathic, parainfectious or occur as a paraneoplastic (tumour-associated) syndrome. Paraneoplastic OMS in children is almost exclusively associated with neuroblastoma, whereas in adults, small cell lung cancer and breast cancer are the main underlying tumours. An autoimmune pathophysiology is suspected because childhood OMS patients have functionally active autoantibodies, proinflammatory changes in the cytokine network and immunotherapy responses. Children appear to respond regularly to immunosuppressive treatment. However, although the neurological symptoms show a good response, most children continue to show neuropsychological disturbances.

Background: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease characterized by opsoclonus, myoclonus, ataxia, and behavioral changes. The aim of our study was to investigate the epidemiological characteristics of OMS in Japan and to clarify the association between therapy and prognosis., Methods: We retrospectively collected the data from 626 Japanese medical institutions from 2005 to 2010, and analyzed the clinical features of pediatric patients with OMS based on the data., Results: In this survey, there were 23 patients (10 males and 13 females). The median ages at the disease onset and the time of study were 16.5 months (range: 11-152 months) and 54 months (range: 24-160 months), respectively. The principal symptoms were opsoclonus (23 patients, 100%), myoclonus (21 patients, 91.3%), and ataxia (23 patients, 100%). The related factors were neuroblastoma (10, 43.5%), infection (9, 39.1%), and immunization (2, 8.7%). The treatments for OMS were included intravenous immunoglobulin (17, 73.9%), methylprednisolone pulse (13, 56.5%), oral prednisolone (12 patients, 52.2%), and chemotherapy and/or operation for the underlying tumors (6, 26.1%), and rituximab (2, 8.7%). Complete remissions were obtained in 35.3%, 23.1%, 33.3%, 66.7%, and 100% of these treatments, respectively. At the latest follow-up period, 8 (34.8%) and 17 patients (73.9%) showed neurological sequelae of motor and intellectual functions, respectively. Patients whose treatment was started more than 30 weeks after the disease onset suffered from the severest neurological sequelae (OMS severity 4) more frequently than those less than 30 weeks (p=0.022)., Conclusion: The annual incidence of OMS was estimated to be 0.27-0.40 cases per million in Japanese children. More than 70% of OMS patients had neurological sequelae, especially intellectual function. Early effective treatments within 30 weeks after the onset may be required to prevent the serious neurological outcome., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Opsoclonus myoclonus syndrome (OMS) produces long-term cognitive, behavioral, and motor deficits. Objective was to see if more aggressive treatment improved outcome. Assessment included opsoclonus myoclonus syndrome rating, developmental/cognitive and motor assessment, and adaptive behavior. Fourteen subjects completed testing. Nine had neuroblastoma. Onset was at 10 to 35 months; onset to diagnosis: 2 days to 14 months, and onset to first treatment: 5 days to 15 months. Initial treatment was corticotropin (12), oral steroids (3), plus intravenous immunoglobulin in all. Ten received rituximab, 5 cyclophosphamide. Age at testing ranged from 2.5 to 10.3 years. Adaptive Behavior Score (11 subjects), mean 93.5; estimated Intelligence Quotient/Developmental Quotient mean 93.5; Motor: mean 92.8. Residual opsoclonus myoclonus syndrome symptoms at the time of the evaluation were generally minor; opsoclonus myoclonus syndrome scores ranged from 0 to 6. Comparison to previously reported opsoclonus myoclonus syndrome subjects showed improved outcomes: Adaptive behavior, cognitive and motor scores were significantly higher (P < .001) in new subjects. Outcomes have improved with more aggressive immunosuppression, with most opsoclonus myoclonus syndrome survivors now functioning at or near normal., (© The Author(s) 2014.)

Opsoclonus-myoclonus syndrome (OMS) is a rare neurologic disorder characterized by opsoclonus, myoclonus, ataxia and behavioral disturbance. In the pathogenesis, an autoimmune process with infectious or paraneoplastic trigger has been suggested. We describe the case of a 22-month-old girl with OMS following rotavirus gastroenteritis. Rotavirus should be considered in the differential diagnosis of OMS in children., (© 2014 Japan Pediatric Society.)

Objective: To investigate the efficacy of combined modality therapy for neuroblastoma in children associated with opsoclonus-myoclonus syndrome (OMS-NB)., Method: From May 2011 to December 2013, 6 consecutive patients (4 boys and 2 girls) diagnosed as OMS-NB underwent surgery and chemotherapy in the First Hospital, Peking University. The median age of onset was 19.5 months (range 13-24 months) and misdiagnosis occurred 7.5 months (range 2-14 months) ago. A retrospective analysis for the location, stage, pathological type, treatment way and outcome of neuroblastoma was done., Result: (1) All patients were misdiagnosed as simply opsoclonus-myoclonus syndrome (OMS) at the time of onset. They had been receiving treatment with adrenocorticotropic hormone and intravenous immunoglobulin within 1-13 months.OMS-NB was diagnosed by means of enhanced abdominal CT image which was delayed to be given after the poor efficacy or relapse. (2) The primary tumors were almost all small, stage I-II, located in adrenal, retroperitoneal or pelvis. The pathology of tumors included ganglioneuroblastoma (5/6) and neuroblastoma (1/6). (3) All these cases underwent surgery, 4/6 cases with complete tumor resection, 2/6 cases with tumor around the aorta and induced local residue. Preoperative and postoperative chemotherapy was given to 2 and 5 cases, respectively. (4) The patients were followed up for 3-31 months, except 1 patient lost, the other 5 are currently surviving disease-free (3 having been at the end of chemotherapy, 1 still in chemotherapy, and another had local recurrence and is receiving radiotherapy and chemotherapy after the second operation and now also stopped taking the medicine). The symptoms of nervous system have been significantly improved during postoperative chemotherapy., Conclusion: To reduce the misdiagnosis, regular CT imaging of the abdomen or pelvic should be ordered for all cases with OMS. The children with OMS-NB need to be actively treated with the combined modality therapy including surgery, chemotherapy or radiotherapy, to reduce recurrence and reduce the symptoms of nervous system.

The opsoclonus-myoclonus syndrome is a distinct disorder characterized by opsoclonus, myoclonus, and ataxia, along with marked irritability and behavioral changes. Worldwide, data on its epidemiology, clinical features, and outcome are scarce. The aim of the study was to determine the clinical profile and outcome of children with this disorder. A retrospective study of all children admitted with a diagnosis of opsoclonus-myoclonus from 2000 to 2012 was done. Outcome was assessed on follow-up by direct assessment and by telephonic interview. Eleven patients with a diagnosis of opsoclonus-myoclonus were admitted over a 12-year period. Of the 11, 4 had paraneoplastic etiology. Children with paraneoplastic opsoclonus had more relapses and a poor outcome as compared to an idiopathic group. Paraneoplastic opsoclonus had a poor outcome in our experience.

Opsoclonus myoclonus syndrome (dancing eye syndrome) is a rare paraneoplastic syndrome characterized by opsoclonus, myoclonus, and ataxia, usually accompanied by behavioral abnormalities. In adults, opsoclonus myoclonus syndrome has been reported in association with different types of cancer; whereas in children, the syndrome may be associated with neuroblastic tumors. Although a direct proof is lacking, the syndrome is assumed to be of autoimmune origin. The treatment is corticosteroid based with the addition of other immunosuppressive or immunomodulating drugs if intensification seems necessary. Because of the rarity of the disease, international collaborations as well on research as on therapeutic strategies are urgently needed. A European consortium just started a trial for this rare condition., (Georg Thieme Verlag KG Stuttgart · New York.)

Opsoclonus-myoclonus syndrome (OMS) is a neuroinflammatory disorder associated with remote cancer. To understand more clearly the role of inflammatory mediators, the concentration of CXCR3 ligands CXCL10, CXCL9 and CXCL11 was measured in 245 children with OMS and 81 paediatric controls using enzyme-linked immunosorbent assay (ELISA), and CXCR3 expression on CD4(+) T cells was measured by flow cytometry. Mean cerebrospinal fluid (CSF) CXCL10 was 2·7-fold higher in untreated OMS than controls. Intrathecal production was demonstrated by significantly different CXCL10 CSF : serum ratios. The dichotomized 'high' CSF CXCL10 group had higher CSF leucocyte count (P = 0·0007) and B cell activating factor (BAFF) and CXCL13 concentrations (P < 0·0001). CSF CXCL10 did not correlate with clinical severity or relapse using grouped data, although it did in some patients. Among seven types of immunotherapy, including rituximab or chemotherapy, only adrenocorticotrophic hormone (ACTH) monotherapy showed reduced CSF CXCL10, but prospective longitudinal studies of ACTH combination therapies indicated no reduction in CXCL10 despite clinical improvement (P < 0·0001). CXCL10 concentrations were 11-fold higher in CSF and twofold higher in serum by multiplexed fluorescent bead-based immunoassay than enzyme-linked immunosorbent assay, but the two correlated (r = 0·7 and 0·83). In serum, no group differences for CXCL9 or CXCL11 were found. CXCR3 expression on CD4(+) T cells was fivefold higher in those from CSF than blood, but was not increased in OMS or altered by conventional immunotherapy. These data suggest alternative roles for CXCL10 in OMS. Over-expression of CXCL10 was not reduced by clinical immunotherapies as a whole, indicating the need for better therapeutic approaches., (© 2013 British Society for Immunology.)

Background: B-cell dysregulation has been implicated but not fully characterized in pediatric opsoclonus-myoclonus syndrome (OMS), a neuroblastoma-associated neuroinflammatory disorder., Objective: To assess the role of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two critical B cell-modulating cytokines, as potential biomarkers of disease activity and treatment biomarkers in OMS., Methods: Soluble BAFF and APRIL were measured in cerebrospinal fluid (CSF) and serum by ELISA in 433 children (296 OMS, 109 controls, 28 other inflammatory neurological disorders (OIND)). BAFF-R receptors on circulating CD19+ B cells were measured by flow cytometry. A blinded scorer rated motor severity on the OMS Evaluation Scale. Immunotherapies were evaluated cross-sectionally and longitudinally., Results: The mean CSF BAFF concentration, which was elevated in untreated OMS and OIND, correlated with OMS severity category (P = 0.006), and reduction by adrenocorticotropic hormone or corticotropin (ACTH) (-61%) or corticosteroids (-38%) was seen at each level of severity. In contrast, CSF APRIL was normal in OMS and OIND and unaffected by immunotherapy. When the entire OMS dataset was dichotomized into 'high' versus 'normal' CSF BAFF concentration, the phenotype of the high group included greater motor severity and number of CSF oligoclonal bands, and a higher concentration of inflammatory chemokines CXCL13 and CXCL10 in CSF and CXCL9 and CCL21 in serum. Serum APRIL was 6.7-fold higher in the intravenous immunoglobulins (IVIg) group, whereas serum BAFF was 2.6-fold higher in the rituximab group. The frequency of B cell BAFF-R expression was similar in untreated and treated OMS. Longitudinal studies of CSF BAFF revealed a significant decline in ACTH-treated patients (with or without rituximab) (P < 0.0001). Longitudinal studies of serum APRIL showed a 2.9-fold increase after 1 to 2 g/kg IVIg monotherapy (P = 0.0003)., Conclusions: Striking distinctions in BAFF/APRIL signaling were found. OMS displayed heterogeneity in CSF BAFF expression, which met many but not all criteria as a potential biomarker of disease activity. We speculate that CSF BAFF may have more utility in a biomarker panel than as a stand-alone biomarker, and that the selective upregulation of both serum APRIL by IVIg and BAFF by rituximab, as well as downregulation of CSF BAFF by ACTH/steroids, may have utility as treatment biomarkers.

Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.

Objective: To investigate the basic clinical characteristics of paraneoplastic neurological syndrome (PNS) in children., Method: To retrospectively analyze the clinical data of 12 PNS children who were hospitalized in neurology department in Beijing Children's Hospital from 2010 to 2011. Some patients were followed up after surgery., Result: In 12 patients with PNS, 11 were male and 1 was female. The mean onset age were (30.5 ± 15.3) months. The mean duration from neurological symptom onset to finding out of tumor was (112.7 ± 154.4) days. The onset of the disease in 2 patients was acute, in 3 was subacute and in the other 7 was chronic (2 of 7 had 2 to 3 relapses). Of 12 patients, 11 had symptoms of ataxia (3 patients also had opsoclonus and myoclonus, OMS), 1 had weakness of limbs at onset and then had ataxia. Nine of 12 patients had surgery, and pathologic diagnosis was neuroblastoma and ganglioneuroma. Six patients were followed-up for 8 to 21 months. One patient had a little improvement and 5 almost recovered., Conclusion: The PNS children can have neurological symptoms only at the onset and there were no particular evidence of tumor. It is prone to misdiagnosis. The prognosis of PNS in children was poor.

Objective: Opsoclonus-myoclonus syndrome (OMS) is a serious and often chronically disabling neurologic illness with onset in early childhood. Our aim was to identify long-term neurologic sequelae of OMS and predictors for disease outcome., Methods: We retrospectively assessed the case records of 101 patients diagnosed with OMS over a 53-year period. Clinical data were obtained from medical record review; we documented age at onset, severity of symptoms, response to treatment, and neurocognitive sequelae., Results: Overall, 21% of the patients had a neuroblastoma detected; however, in those born after 1990, this figure rose to 40%. Sixty-one percent of the patients had a chronic-relapsing course, 32% experienced several acute exacerbations, and 7% had a monophasic course. At the most recent review, 60% had residual motor problems, 66% speech abnormalities, 51% learning disability, and 46% behavior problems. One-third of the patients had normal intellectual outcome and cessation of symptoms. A severe initial presentation predicted a chronic disease course (odds ratio [OR]: 2.77 [95% confidence interval (CI): 1.47-5.23]; P = .002) and later learning disability (OR: 2.03 [95% CI: 1.08-3.79]; P = .026). Those with cognitive impairment were younger at disease onset (15.0 vs 19.5 months; P = .029). A chronic-relapsing disease course was associated with motor (P < .001), speech (P = .001), cognitive (P < .001), and behavior (P = .006) problems., Conclusions: OMS is a chronic and debilitating illness; those with severe initial symptoms and those who are very young at disease onset are at increased risk of developing long-term sequelae. It is important for affected children to be identified early, because they might benefit from targeted immunomodulating therapy in specialist centers.

Objectives: To report the clinical, laboratory, and radiographic features and the response to plasmapheresis in a patient with encephalopathy, opsoclonus, and myoclonus whose cerebrospinal fluid was positive for N-methyl-D-aspartate receptor-IgG., Design: Case report., Setting: St Marys Hospital, Rochester, Minnesota., Patient: A 27-year-old woman with a history of episodic migraine developed subacute progressive myoclonus, opsoclonus, and encephalopathy., Results: Magnetic resonance imaging demonstrated nodular leptomeningeal enhancement in the superior cerebellar folia and subsequent T2 hyperintensities in the periventricular regions and amygdala. A positron emission tomographic scan of the head demonstrated predominantly frontotemporoparietal cortical hypometabolism with sparing of the primary sensory and motor cortices. Cerebrospinal fluid examination revealed a lymphocytic pleocytosis, mildly elevated protein level, elevated IgG index, and positive oligoclonal banding. Autoimmune cerebrospinal fluid screening revealed a neural-specific IgG that bound to synapse-rich regions of mouse hippocampus and cerebellar granular layer; the neural-specific IgG was confirmed to be N-methyl-D-aspartate receptor specific. No neoplasm was detected by physical examination or by whole-body computed tomography and positron emission tomography. A 5-day course of high-dose intravenous methylprednisolone sodium succinate yielded limited improvement, and the patient subsequently required intensive care unit admission following a pulseless electrical activity arrest associated with pulmonary embolism. The encephalopathy improved dramatically after plasmapheresis., Conclusions: This case highlights opsoclonus and myoclonus as manifestations of autoimmune N-methyl-D-aspartate receptor encephalitis in the setting of a novel appearance on positron emission tomography, and it shows a remarkable clinical response to plasmapheresis.

Opsoclonus myoclonus ataxia (OMA) is a rare neurological disorder (incidence = approximately 1/5 million) primarily associated with involuntary conjugate saccadic eye movements, involuntary muscle jerks, cerebellar ataxia, and neuropsychological impairments. Unfortunately, there is limited published data regarding the nature and course of neuropsychological impairments following OMA diagnosis and treatment. This study presents neuropsychological data obtained at 1, 4, and 18 months post-diagnosis of a 52-year-old male with OMA. The patient initially demonstrated significant global neurocognitive, psychomotor, and psychological difficulties with substantial improvement over time. Treatment included medication management, physical rehabilitation, and psychological intervention.

The treatment and disposition of patients with neurological disorders is commonplace in the emergency setting, but atypical and uncommon presentations can prove to be especially challenging. In this article we discuss the case of a 31-year-old woman who presented with a rare disorder known as opsoclonus myoclonus syndrome (OMS). OMS is characterized by involuntary, multidirectional movement of the eyes, myoclonus, and truncal ataxia. The etiology is thought to be autoimmune, and is most commonly associated with encephalitis or paraneoplastic syndrome. After an 8-day hospital course, which included several different treatment modalities including plasmapheresis, the patient was discharged after making a complete recovery. Unusual presentations such as the one described in this article illustrate the point that it is crucial to have a systematic approach that can be applied to identify and treat potentially life-threatening neurological conditions., (Published by Elsevier Inc.)

The aim of this article is to review the paraneoplastic opsoclonus-myoclonus syndrome (POMS). Opsoclonus is characterized by involuntary, arrhythmic, chaotic, multi-directional saccades with horizontal, vertical and torsional components, and it is commonly accompanied by cerebellar ataxia and myoclonic jerks in the trunk and limbs. Parainfectious brainstem encephalitis, toxic-metabolic disturbances and others condition should be considered as potential causes of these symptoms. In adults, POMS is most commonly associated with small-cell lung cancer, breast cancer, and ovarian cancer. In children, a neuroblastoma is detected in approximately 50% of cases. Many autoantibodies have been detected in patients with POMS: this finding suggests the involvement of a humoral immune mechanism. However, most patients are seronegative for these autoantibodies. This implies that a cell-mediated immune mechanism may also be involved in the pathogenesis of opsoclonus. Although the exact pathophysiology mechanism of opsoclonus remains unclear, recent reports suggest that disinhibition of the fastigial nucleus of the cerebellum is involved. In children, the immunotherapy with corticosteroids, intravenous immunoglobulin, adrenocorticotropic hormone, plasma exchange, cyclophosphamide, or rituximab is used. Although opsoclonus is often responsive to therapy, the high incidence of sequelae related to motor function, speech, behavior, and sleep is an important problem. In adults, POMS is less responsive to immunotherapy and improves only with tumor resection. In order to develop novel and effective therapeutic strategies, further studies on the immunopathogenesis and pathophysiology of POMS are required.

The incidence, mode of presentation and management of Dancing Eye Syndrome/Opsoclonus-Myoclonus Syndrome (DES/OMS) was prospectively evaluated in 20 United Kingdom (UK) paediatric neurology centres by questionnaire over a 24-month period between 2003 and 2005. Nineteen children were notified, giving an incidence of 0.18 cases per million total population per year. Mean age at presentation was 18 months (range 3-42 months). Fifteen families consented to participate in the study. Atypical features were present in 6/15 cases including very delayed presentation of opsoclonus, dysphagia, and rapid spontaneous improvement without treatment. Only 4/15 cases were associated with neuroblastoma (NB) but current practice in excluding this is diverse and a standardised approach is suggested., (2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Twelve immunotherapy-naïve children with opsoclonus-myoclonus syndrome and CSF B cell expansion received rituximab, adrenocorticotropic hormone (ACTH), and IVIg. Motor severity lessened 73% by 6 mo and 81% at 1 yr (P < 0.0001). Opsoclonus and action myoclonus disappeared rapidly, whereas gait ataxia and some other motor components improved more slowly. ACTH dose was tapered by 87%. Reduction in total CSF B cells was profound at 6 mo (-93%). By study end, peripheral B cells returned to 53% of baseline and serum IgM levels to 63%. Overall clinical response trailed peripheral B cell and IgM depletion, but improvement continued after their levels recovered. All but one non-ambulatory subject became ambulatory without additional chemotherapy; two relapsed and remitted; four had rituximab-related or possibly related adverse events; and two had low-titer human anti-chimeric antibody. Combination of rituximab with conventional agents as initial therapy was effective and safe. A controlled trial with long-term safety monitoring is indicated., ((c) 2009 Movement Disorder Society.)

Background: Opsoclonus-myoclonus-ataxia (OMS) is a rare, autoimmune, neurobehavioral syndrome that presents with a movement disorder, developmental regression, behavior disorder and cognitive decline. The syndrome is more prevalent in the first two years of life but can also affect adults. The diagnosis is based on the combination of clinical signs and assessment of the cerebrospinal fluid (CSF) for subtypes of T and B lymphocytes. Since it is a paraneoplastic disorder in 50% of cases, it is imperative to search for a neural crest tumor. The treatment is complex and prolonged and the prognosis depends on early diagnosis and full treatment., Aims: Description of the experience of the Pediatric Movement Disorder Service at Wolfson Medical Center in the diagnosis and treatment of opsoclonus-myoclonus-ataxia syndrome., Methods: The files of all the patients who were evaluated for OMS in the last 4 years were reviewed. Five of ten patients were diagnosed and treated., Results: The age at presentation was 5 to 20 months. In 4 children the diagnosis was delayed beyond 3 months. All the patients were males. A neuroblastoma was found in one patient. Four children had behavioral and sleep disturbances which necessitated treatment. All the children were treated with adrenocorticotropic hormone (ACTH) and immunoglobulins. CSF lymphocyte immunophenotyping was pathologic in 4 patients and they were treated with rituximab. All the children showed developmental delay and received rehabilitation. Two children completed the treatment. The child who received early treatment shows normal development. The other has language delay., Conclusions: Although opsoclonus-myoclonus-ataxia is a rare disorder, it is necessary to increase the physicians' awareness of this syndrome in order to enable early diagnosis and treatment.

Neurologic paraneoplastic syndromes (NPSs) result from damage to the nervous system due to the remote effects of cancer not related to metastasis, infection, or metabolic derangements. NPSs are rare, affecting 1 in 10,000 patients with cancer. Pathogenesis is likely related to the immune mechanisms: normal neural tissue is mistakenly attacked due to the similarity in the onconeural antigens expressed by the tumor cells. Among the various "classic" and other NPSs, this review focuses on paraneoplastic movement disorders, including ataxia due to cerebellar degeneration, stiff-person syndrome, opsoclonus-myoclonus syndrome, chorea, parkinsonism, and tremor. The recently described syndrome of paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis is also included, given that these patients have complex movements such as stereotypies and dyskinesias in addition to psychiatric symptoms, altered sensorium, and other neurologic signs. Although variable, treatment and prognosis of NPSs rely heavily on treatment of the underlying malignancy and immunotherapy.

Opsoclonus myoclonus ataxia syndrome (OMAS) is a very infrequent paraneoplastic or postinfectious movement disorder, which may occur at any age, most commonly between 6 and 36 months of age. In four days, a previously healthy 30-month-old girl progressively developed gait instability, intention tremor, dysarthric speech, irritability and altered sleep. Physical and neurological examination did not reveal additional deficits. She had had a transient exanthema without fever three weeks before. Basic blood analysis, serologies, cultures, urine toxin detection, EEG and cerebral CT were normal. Lumbar puncture showed minimal lymphocytosis. On the fifth day following the onset of symptoms, the ataxia worsened, precluding sitting, and the tremor was aggravated by intentional myoclonus. Chaotic saccadic, large amplitude multidirectional but conjugated eye movements appeared. An opsoclonus was suspected and a chest X-ray and CT revealed a paravertebral thoracic mass. Surgery confirmed a localized ganglioneuroblastoma. Blood neuron-specific enolase and urine catecholamine levels were normal. Opsoclonus disappeared with high doses of prednisone and following surgery. Ataxia improved but the patient still required low daily doses of steroids for one year.

The opsoclonus-myoclonus syndrome in children is a rare entity which is characterized by irritability, chaotic ocular movements with vertical, horizontal, rotatory components (opsoclonus) along with myoclonus and ataxia. In a high proportion of cases, it is associated with neuroblastoma although other etiologies involving infectious or toxic agents have been reported. An autoimmune mechanism would be responsible for the dysfunction of structures in brain stem and cerebellum thus explaining some of the cardinal symptoms such as opsoclonus, myoclonus and ataxia. However, encephalopathic symptoms and the high percentage of patients with neurocognitive and psychiatric sequels are in favor of a wider dysfunction. Treatment with steroids, ACTH, immunomodulatory or immunosuppressive drugs is being used although prospective studies are needed to determine whether the prolonged use of these drugs influences favorably the evolution of these patients.

Objective: Clinical manifestations of opsoclonus-myoclonus syndrome (OMS) in children were summarized and analyzed and the clinical features and therapeutic approaches to OMS were investigated in order to improve its diagnosis and management., Methods: Clinical information on features and management of 6 cases with OMS inpatients being followed up from 2006 to 2007 were collected and analyzed., Results: Among the 6 cases, one was male and the other five were female. The age at the onset ranged from 12 to 26 months (average 21.0 months). Four of them had history of prior infection. The symptoms were opsoclonus, myoclonus, ataxia, sleep disturbances and behavioural problems in the 6 cases. Urinary DL-3-methoxy-4-hydroxy-acid amygdalin (VMA) was positive in 1 case. Abdominal B-mode ultrasound showed a mild hepatomegaly in 4 cases. The EEG showed abnormal findings such as slow background activity in 3 cases. Epileptiform discharges were found in none of the patients. MRI showed a high signal in medial longitudinal fasciculus and tectospinal tract on T2-weighted image in 1 case. Computerized tomography found L3-4 arachnoid cysts in 1 case and was normal in the others. Adrenocorticotropic hormone (ACTH) was given to all these patients and was effective in all during acute stage. In 2 cases the disease relapsed during follow-up stage., Conclusion: OMS is a rare neurological condition with opsoclonus, myoclonus, ataxia, sleep disturbances and behavioral problems, which might relapse easily and is associated with adverse neurological outcome. ACTH therapy is effective in management of OMS.

Paraneoplastic opsoclonus-myoclonus syndrome (OMS) is associated with small cell lung cancer (SCLC) in adults. Without appropriate treatment for SCLC, all reported patients with SCLC and OMS have died of complications of OMS within 3 months of diagnosis. With appropriate treatment, about half of reported patients have had improvement in neurologic function, and several have become long-term survivors (6-84 months). We report a patient with SCLC who presented with OMS and was refractory to immunosuppressive therapy but responded rapidly to antineoplastic therapy and remains alive with no sign of SCLC recurrence and minimal residual neurologic deficits 30 months after diagnosis. In patients presenting with OMS, early recognition and treatment of the underlying malignancy probably improve the chances for recovery from the OMS with minimal deficit and ultimate survival.

Opsoclonus-myoclonus syndrome (OMS) is a rare paraneoplastic syndrome that occurs in 2%-3% of patients with neuroblastoma. The cause of this syndrome is believed to be immune mediated, but the exact mechanism still remains unclear. There is an urgent need to improve our current strategies for treating patients with OMS, as many patients have significant long-term neurologic deficits and behavior disorders with current treatment approaches. Therapies that have shown to improve symptoms in these patients have ranged from ACTH and corticosteroids, to intravenous gammaglobulin and plasmapheresis. We report our experience with Rituximab in a patient with neuroblastoma and OMS., ((c) 2007 Wiley-Liss, Inc.)