Project description:Background and purposePatients with COVID-19 can have central or peripheral neurological manifestations.MethodsThe cases of two patients with acute cerebellar ataxia and myoclonus associated with COVID-19 are reported (with Video S1) and five previously reported patients are discussed.ResultsAcute cerebellar ataxia and myoclonus started between 10 days and 6 weeks after the first manifestations of COVID-19. Opsoclonus or ocular flutter was present in four patients. Patients were treated with intravenous immunoglobulins and/or steroids except for one patient, resulting in a striking improvement within a week.ConclusionAcute cerebellar ataxia and myoclonus with or without opsoclonus belongs to the wide spectrum of neurological manifestations associated with COVID-19. It is important to recognize this possible manifestation since early treatment allows for rapid recovery.
Project description:A patient presented with an opsoclonus-myoclonus-ataxia syndrome after a 2-week period of fever. In her work as an assistant nurse, she had been exposed to patients infected with severe acute respiratory syndrome coronavirus-2. Laboratory investigations showed that the patient had positive IgG antibodies against this pathogen, and a chest CT showed changes compatible with this infection. Other known causes for this syndrome were excluded. Our case shows that the opsoclonus-myoclonus-ataxia syndrome can occur as a post-/para-infectious manifestation in patients infected with severe acute respiratory syndrome coronavirus-2.
Project description:ObjectiveTo identify neuronal surface antibodies in opsoclonus myoclonus ataxia syndrome (OMAS) using contemporary antigen discovery methodology.MethodsOMAS patient serum immunoglobulin G immunohistochemistry using age-equivalent rat cerebellar tissue was followed by immunoprecipitation, gel electrophoresis, and mass spectrometry. Data are available via ProteomeXchange (identifier PXD009578). This generated a list of potential neuronal surface cerebellar autoantigens. Live cell-based assays were used to confirm membrane-surface antigens and adsorb antigen-specific immunoglobulin Gs. The serologic results were compared to the clinical data.ResultsFour of the 6 OMAS sera tested bound rat cerebellar sections. Two of these sera with similar immunoreactivities were used in immunoprecipitation experiments using cerebellum from postnatal rat pups (P18). Mass spectrometry identified 12 cell-surface proteins, of which glutamate receptor δ2 (GluD2), a predominately cerebellar-expressed protein, was found at a 3-fold-higher concentration than the other 11 proteins. Antibodies to GluD2 were identified in 14/16 (87%) OMAS samples, compared with 5/139 (5%) pediatric and 1/38 (2.6%) adult serum controls (p < 0.0001), and in 2/4 sera from patients with neuroblastoma without neurologic features. Adsorption of positive OMAS sera against GluD2-transfected cells substantially reduced but did not eliminate reactivity toward cerebellar sections.ConclusionAutoantibodies to GluD2 are common in patients with OMAS, bind to surface determinants, and are potentially pathogenic.
Project description:Opsoclonus myoclonus ataxia syndrome (OMAS) is an autoimmune disorder characterized by rapid, random, conjugate eye movements (opsoclonus), myoclonus, and ataxia. Given these symptoms, autoantibodies targeting the cerebellum or brainstem could mediate the disease or be markers of autoimmunity. In a subset of patients with OMAS, we identified such autoantibodies, which bind to non-synaptic puncta on the surface of live cultured cerebellar and brainstem neuronal dendrites. These findings implicate autoimmunity to a neuronal surface antigen in the pathophysiology of OMAS. Identification of the targeted antigen(s) could elucidate the mechanisms underlying OMAS and provide a biomarker for diagnosis and response to therapy.
Project description:Opsoclonus-myoclonus ataxia (OMA) syndrome is rare in children, mostly caused by neuroblastoma. Here, we present two very rare cases presenting with OMA due to falciparum malaria. Both of them responded to a high dose of adrenocorticotrophin hormone and intravenous immunoglobulin without recurrence and complication.
Project description:Opsoclonus-myoclonus-ataxia syndrome (OMAS) in children is most often of paraneoplastic origin, but it can also result from infectious processes, toxic and metabolic disorders, and organic events that cause damage to the brainstem or cerebellum. Post-vaccination OMAS has also been reported. We report the case of a 15-year-old girl who developed OMAS 24 hours after her first dose of mRNA COVID-19 (BioNTech) vaccine.
Project description: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. 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. 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. 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.