Opsoclonus-myoclonus Syndrome Research Articles

Paraneoplastic Syndromes of the Nervous System in Patients Suffering from SCLC. A Review of the Recent Literature

Background. Paraneoplastic Neurological Syndromes (PNS) constitute a heterogeneous cluster of disease manifestations related to various cancers. Small Cell Lung Cancer (SCLC) is strongly related to PNS. This narrative review conducted a survey in the available PubMed literature to highlight the appearance of PNSs in SCLC cases and discuss published research highlights on the subject so that general practitioners can be acquainted with the medical phenomenon present in SCLC patients. Method. A narrative review of the medical literature was conducted as documentary informative research in the PubMed medical database, combined with a survey of the online e-library Google Books. The key words used were: “Paraneoplastic Neurological Syndromes” and “Small Cell Lung Cancer”. Results. Paraneoplastic syndromes are related to the presence of a malignancy and are not secondary to treatment. Paradoxally, both a malignancy and its therapeutic approach may cause a series of PNSs. Paraneoplastic cerebellar degeneration, motor neuron disorders, peripheral neuropathies, hyponatremia, and syndromes such as myasthenic Lambert-Eaton, ectopic Cushing’s, Stiffman, and Opsoclonus-myoclonus syndrome may also appear in SCLC cases. Diagnosis follows specific criteria, and they are caused by tumor-directed antibodies known as onconeural antibodies. Immunosuppressants, intravenous immunoglobulins, plasma exchange, rituximab, cyclophosphamide, azathioprine, and tocilizumab could be considered as treatment agents. Conclusions. Most patients demonstrate poor PNS treatment results with common relapse. The time for beginning treatment of PNS is discussed. A multidisciplinary team is needed for potentially earlier diagnosis and PNS improvement, better prognosis, and increased overall survival and quality of life.

Unveiling the Unconventional: Exploring Atypical Manifestations of Scrub Typhus

Scrub typhus is a rickettsial illness caused by Orientia tsutsugamushi. It is a common cause of undifferentiated febrile illness, especially in the Indian subcontinent, usually with multiorgan involvement, though central nervous involvement is rare. Here, we demonstrate a case of a young female who presented with fever, headache, vomiting, and seizures. Her examination was remarkable for generalized blanchable macular rash, opsoclonus–myoclonus along with neck rigidity and mild epigastric tenderness. Contrast-enhanced magnetic resonance imaging brain was suggestive of leptomeningitis. She also had mild pancreatitis, transaminitis, thrombocytopenia, and transaminitis. Given the ongoing tropical fever burden in Northern India, further workup was done and enzyme-linked immunosorbent assay anti-scrub typhus immunoglobulin M came as positive. Doxycycline along with supportive treatment was started, and all signs and symptoms improved gradually.

Kinsbourne syndrome: a case report

Introduction/Background: Kinsbourne syndrome or opsoclonus mioclonus ataxia is a rare syndrome, commonly post viral or paraneoplastic, characterized by opsoclonus, ataxia, myoclonic jerks of trunk and limbs and behavioral disturbances. Affects both adult and pediatric ages, with greater prevalence between one and three-year-old and equal gender prevalence. Neuroblastoma, hepatoblastoma and glangioneuromas are ordinarily associated with this syndrome. This paperwork aims to present a case report concerning Kinsbourne Syndrome and review literature about it. Case presentation: We report a case of a one-year-and-two-month-old male, with opsoclonus, gait disturbance and imbalance associated with a neuroblastoma, who has undergone therapy with prednisone 1mg/kg/day and surgical resection, evolving with complete resolution of symptoms after four years and a half of clinical following, presenting himself to the date without neurological deficits, contrary to literature statistics. Conclusion: KS is ordinarily a post-viral or paraneoplastic rare syndrome, with higher prevalence between 1 to 3-year-old infants, nevertheless also affecting adults. araneoplastic syndrome is majorly associated with NB

Decoding Multiple Antibody Positivity: Lessons from Paraneoplastic Sensory Ataxia.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert-Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Pediatric Autoimmune Neurologic Disorders.

This article discusses common principles in diagnosing and managing autoimmune neurologic conditions in children. The key to improving outcomes in all patients with autoimmune neurologic diseases is making an early diagnosis, promptly initiating treatment, and identifying patients who will benefit from long-term maintenance treatment. Some neuroinflammatory syndromes can be diagnosed with an antibody biomarker (eg, aquaporin-4 antibodies, N-methyl-d-aspartate [NMDA] receptor antibodies), whereas others require clinical diagnostic criteria (eg, multiple sclerosis, opsoclonus-myoclonus syndrome). A proportion of children will be labeled as seronegative, and further investigations for other inflammatory or monogenetic etiologies need to be carried out in parallel with treating the central nervous system inflammation. Time to treatment and treatment escalation were shown to correlate with outcomes in many patients with these disorders. The choice and duration of treatment should be evaluated considering side effects and risks in the short and long terms. The presence of a highly inflammatory disease process in children supports the use of highly effective disease-modifying therapies in pediatrics. The phenotypes of pediatric autoimmune neurologic conditions may change across different age groups, as the brain is still actively developing. In general, the presentation in children is more inflammatory, but overall disability is lower, likely because of better neuroplasticity and repair. Convincing evidence has increasingly emerged to support the biological rationale that effective immunosuppressive therapies used in adult neuroimmunology are equally effective in children.

Autoimmune Movement Disorders.

This article reviews the clinical and antibody spectrum of autoimmune cerebellar ataxia and other autoimmune movement disorders. It highlights characteristic phenotypes and red flags to the diagnosis and how these rare, but treatable, disorders are integrated into a differential diagnosis. An increasing number of neuronal antibodies have been identified in patients with cerebellar ataxia, for example, against Kelch-like protein 11 (KLHL11), seizure-related 6 homolog-like 2, septin-3 and septin-5, or tripartite motif containing protein 9 (TRIM9), TRIM46, and TRIM67. Ig-like cell adhesion molecule 5 (IgLON5) antibody-associated syndromes have emerged as an important alternative diagnostic consideration to various neurodegenerative diseases such as Huntington disease or atypical parkinsonism. Opsoclonus-myoclonus syndrome emerged as the most relevant parainfectious movement disorder related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune cerebellar ataxia and other autoimmune movement disorders encompass a broad spectrum of different clinical syndromes, antibodies, and immunopathophysiologic mechanisms. Clinical acumen is key to identifying the cases that should undergo testing for neuronal antibodies. Given the overlap between phenotypes and antibodies, panel testing in serum and CSF is recommended.

Paraneoplastic neurological syndromes of small cell lung cancer.

This article reviews the relevant literature on paraneoplastic neurological syndromes of small cell lung cancer and discusses the clinical presentation, pathophysiology, and diagnosis of these syndromes. It also includes a summary of the current treatment options for the management of them. Paraneoplastic syndromes are a group of signs and symptoms that develop due to cancer in a remote site, mainly triggered by an autoantibody produced by the tissues involved or lymphocytes during anti-cancer defense. Among the cancers associated with paraneoplastic syndromes, lung cancers are the most common type, with small cell lung cancer being the most common subtype. The most common antibody associated with paraneoplastic syndromes is anti-Hu. Neurological and neuroendocrine syndromes comprise the majority of small cell lung cancer-related paraneoplastic syndromes. Classical paraneoplastic neurological syndromes include inappropriate antidiuretic hormone secretion, Cushing's syndrome, myasthenia gravis, Lambert-Eaton myasthenic syndrome, limbic encephalitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus ataxia, sensory neuropathy, and chorea. Antibodies mediate paraneoplastic syndromes, and antibody detection is a crucial part of diagnosing these entities. Managing the underlying tumor is the best treatment approach for most paraneoplastic syndromes. Therefore, early diagnosis of small cell lung cancer may significantly improve the prognosis of paraneoplastic syndromes associated with it.

Paraneoplastic syndromes in childhood neuroblastoma

INTRODUCTION: Neuroblastoma is a malignant tumor primarily affecting infants. Originating from embryonic cells of the sympathetic nervous system, NB commonly arises in the adrenal glands, followed by the abdomen, mediastinum, head, and neck. Clinical presentation varies depending on the tumor's location. General symptoms, if present, include fatigue, weight loss, and fever. The paraneoplastic syndrome refers to symptoms and disorders associated with malignant tumors but not directly caused by the tumor itself or its metastases. Opsoclonus-myoclonus syndrome and diarrhea are the most common paraneoplastic syndromes linked to neuroblastoma. REVIEW METHODS: The article was conducted using PubMed and Google Scholar data concerning paraneoplastic syndromes associated with neuroblastoma. THE STATE OF KNOWLEDGE: Opsoclonus-myoclonus syndrome is a neurological paraneoplastic syndrome that presents itself with characteristic eye movement disorder, short, involuntary, irregular twitches or spasms occurring in a muscle, sleep disturbance, and changes in behavior. Diarrhea resulting in hypokalemia may be also present as a paraneoplastic syndrome associated with neuroblastoma. Cushing’s syndrome is a rare condition in childhood, but it also may be linked to neuroblastoma. CONCLUSIONS: Neuroblastoma is one of the most common childhood cancers, Paraneoplastic syndromes associated with neuroblastoma are rare conditions. Diagnosing chronic diarrhea, OMS, and Cushing's syndrome should always lead to the exclusion of neuroblastoma. Heightened awareness among pediatricians regarding PNS could result in faster diagnosis, timely treatment commencement, and ultimately enhance patient prognosis.

Paraneoplastic opsoclonus-myoclonus syndrome as a rare presentation of parotid adenocarcinoma

Paraneoplastic Opsoclonus-Myoclonus Ataxia Syndrome (POMA) is a rare neurological condition that affects approximately 1 in 10,000,000 people annually. This syndrome is poorly understood and can lead to long-term cognitive, behavioral, and motor complications. Opsoclonus is characterized by involuntary, rapid, repetitive, multi-vectorial oscillations of the eyes occurring in all directions of gaze. It is accompanied by diffuse or focal body myoclonus and may or may not include ataxia and other cerebellar signs. POMA is typically a paraneoplastic syndrome associated with neuroblastoma in childhood and breast carcinoma or small-cell lung carcinoma in adults. Additionally, viral or toxic agents are known to play a role in its etiology, and the immune system is involved in the pathogenesis. We report a case of a 41-year-old man with anti-Ri antibody opsoclonus-myoclonus syndrome and parotid adenocarcinoma involvement. After diagnosing opsoclonus-myoclonus syndrome, the patient underwent multimodal immunotherapy treatment, resulting in partial remission of the neurological symptoms.

Clinical Presentation, Management, and Diagnostic Performance of 2021 Criteria for Paraneoplastic Neurologic Syndromes in Childhood.

Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children. Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification. Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy). OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in pediatric opsoclonus myoclonus ataxia syndrome presenting with neuroblastoma.

Early precision diagnosis and effective treatment of opsoclonus myoclonus ataxia syndrome (OMAS) patients presenting with neuroblastoma can prevent serious neurological outcomes. To assess the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in pediatric OMAS with neuroblastoma. A retrospective evaluation of 45 patients diagnosed with OMAS who underwent 18F-FDG PET/CT was performed. A univariate analysis was performed to compare clinical characteristics between OMAS with and without neuroblastoma. Univariate and multivariate logistic regression analyses were applied to identify independent risk factors for OMAS with neuroblastoma and to develop the clinical model. Finally, independent risk factors and PET/CT were fitted to build the combined model for the diagnosis of OMAS with neuroblastoma and presented as a nomogram. Receiver operating characteristic curve, decision curve, and calibration curveanalyses were conducted to evaluate the performance of the models. Among 45 patients, 27 were PET/CT-positive, 23/27 lesions were neuroblastoma, and four were false positives. One of the false positive patients was confirmed to be adrenal reactive hyperplasia by postoperative pathology, and the symptoms of OMAS disappeared in the remaining three cases during clinical follow-up. The average maximal standardized uptake value of PET/CT-positive lesions was 2.6. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT were 100%, 81.8%, 85.2%, 100%, and 91.1%, respectively. Age at diagnosis, lactate dehydrogenase, and neuron-specific enolase showed statistically significant differences between OMAS with and without neuroblastoma. Lactate dehydrogenase was identified as the independent risk factor to develop the clinical model, and the clinical model demonstrated an area under the curve (AUC) of 0.82 for the diagnosis of OMAS with neuroblastoma, with an AUC as high as 0.91 when combined with PET/CT. The decision curve analysis and calibration curve demonstrated that the nomogram had good consistency and clinical usefulness. In patients with OMAS, 18F-FDG PET/CT has a high diagnostic accuracy in detecting tumors of the neuroblastoma, especially when combined with the independent risk factor serum lactate dehydrogenase.

Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia.

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann's syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms.

A rare case of opsoclonus myoclonus syndrome following COVID-19 illness

A rare case of opsoclonus myoclonus syndrome following COVID-19 illness

The current state of the paraneoplastic neurological syndromes problem

Paraneoplastic syndromes (PS) are immune-mediated manifestations of a distant oncological process, which is a reaction of autoantibodies against antigens expressed by the tumor. These syndromes are divided into neurological, endocrine, hematological, and dermatological. PS can be diagnosed before or in parallel with tumor detection and often masquerade as neurological or psychiatric disorders. The review discusses the updated 2021 diagnostic criteria, which include revisions to diagnostic levels since 2004, as well as new classifications of antibodies based on the pathogenetic mechanisms of nerve cell damage and their frequency of detection in patients. The phenotypes of high-, medium-, and low-risk paraneoplastic neurological syndromes (PNS) are highlighted, with a special emphasis on the clinical features of high-risk phenotypes. Particular attention is paid to limbic encephalitis, its clinical signs, specific antibodies, instrumental and laboratory studies, and associated oncological diseases. Encephalomyelitis and subacute cerebellar degeneration are also discussed, detailing pathological changes, key antibodies and neoplasia, emphasizing the need for differential diagnosis and immunosuppressive treatment. General features about opsoclonus myoclonus syndrome, its clinical manifestations and causes, as well as Lambert—Eaton myasthenic syndrome are provided, in particular, its association with small cell lung cancer is emphasized, and the features of diagnosis, differential diagnosis with myasthenia gravis and treatment are highlighted. Based on the updated diagnostic criteria, the data analysis will provide clinicians with guidelines for identifying specific phenotypes of PNS and associated antibodies, which are key to improving diagnostic processes and selecting an effective treatment strategy.

Review of Opsoclonus-Myoclonus Ataxia Syndrome in Pediatric Patients.

Opsoclonus-myoclonus ataxia syndrome (OMAS), also known as Kinsbourne syndrome, is a rare disorder that presents with myoclonus, ataxia, abnormal eye movements, irritability, and sleep disruptions, often in young children. We report a case of an infant barely 6 months old, with no significant past medical history, who presented to the emergency department with tremors, jerking motions of the head and arms, and rapid eye movements. After an extensive workup, she was found to have a neuroblastoma, which was subsequently surgically removed via thoracotomy. Despite an initial improvement in symptoms post-resection, the patient's symptoms recurred. She was subsequently treated with dexamethasone, intravenous immunoglobulin (IVIG), and rituximab. After treatment, the patient was noted to have mild global developmental delays but was otherwise well. This case report highlights the rare occurrence of OMAS in an infant barely 6 months old at diagnosis. Using the PubMed database, a systematic review was conducted to highlight the clinical presentation, diagnosis, and management of OMAS.

Brain Volumes in Opsoclonus-Myoclonus Ataxia Syndrome: A Longitudinal Study.

Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain volumes in pediatric opsoclonus-myoclonus ataxia syndrome patients compared with age- and sex-matched healthy children. This longitudinal case-control study included brain magnetic resonance imaging (MRI) scans from consecutive pediatric opsoclonus-myoclonus ataxia syndrome patients (2009-2020) and age- and sex-matched healthy control children. FreeSurfer analysis provided automatic volumetry of the brain. Paired t tests were performed on the curvature of growth trajectories, with Bonferroni correction. A total of 14 opsoclonus-myoclonus ataxia syndrome patients (12 female) and 474 healthy control children (406 female) were included. Curvature of the growth trajectories of the cerebral white and gray matter, cerebellar white and gray matter, and brainstem differed significantly between opsoclonus-myoclonus ataxia syndrome patients and healthy control children (cerebral white matter, P = .01; cerebral gray matter, P = .01; cerebellar white matter, P < .001; cerebellar gray matter, P = .049; brainstem, P < .01). We found abnormal brain maturation in the supratentorial brain, brainstem, and cerebellum in children with opsoclonus-myoclonus ataxia syndrome.

The case of Kinsburn’s Encephalopathy in a child with neuroblastoma of posterior mediastinum

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is an autoimmune rare disease of the central nervous system with lesion of the cerebellum and its ligaments. Purpose - to present a case of the rare Kinsburn’s Encephalopathy - OMAS and to attract the attention to its timely diagnosis. Clinical case. A child at the age of 1 year and 9 months was observed in the neurological department of the National Children’s Specialized Hospital “OKHMATDYT”. Neurological status: eyes opsoclonus, truncal tremor, ataxia of the cerebellum. There were also changes in behavior and a sleep disorder. She became sick in 1 month after acute respiratory infection. True diagnosis was made: Kinsburn’s Encephalopathy - opsoclonus-myoclonus syndrome. A study of the child’s immune status was made and, most importantly, computerized tomography (CT) of the whole body. Mediastinal neuroblastoma was diagnosed. In addition to the diagnosis, the child receive adequate therapy - intravenous immunoglobulin at a dose of 2 g/kg for a 5-day course. On the background of the received therapy, the child was marked with positive dynamics, she began to walk by herself, the atactic syndrome diminished, opsoclonus remained unchanged. Consequently, the main cause of autoimmune defeat of the nervous system was detected and the child was directed to the further examination and treatment to the Cancer Institute of the National Academy of Medical Science of Ukraine. Radical removal of the left hemopleura neuroblastoma was made. According to the results of morphological and immunohistochemistry tests, the phenotype obtained in the material of the operation is characteristic of the neuroblastoma (ICD-O code 9500/3), pT1bpN0M0, negative form. In the future, the child continued to receive courses of immunosuppressive therapy. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

NOVA1 acts as an oncogenic RNA-binding protein to regulate cholesterol homeostasis in human glioblastoma cells

NOVA1 is a neuronal RNA-binding protein identified as the target antigen of a rare autoimmune disorder associated with cancer and neurological symptoms, termed paraneoplastic opsoclonus-myoclonus ataxia. Despite the strong association between NOVA1 and cancer, it has been unclear how NOVA1 function might contribute to cancer biology. In this study, we find that NOVA1 acts as an oncogenic factor in a GBM (glioblastoma multiforme) cell line established from a patient. Interestingly, NOVA1 and Argonaute (AGO) CLIP identified common 3' untranslated region (UTR) targets, which were down-regulated in NOVA1 knockdown GBM cells, indicating a transcriptome-wide intersection of NOVA1 and AGO-microRNA (miRNA) targets regulation. NOVA1 binding to 3'UTR targets stabilized transcripts including those encoding cholesterol homeostasis related proteins. Selective inhibition of NOVA1-RNA interactions with antisense oligonucleotides disrupted GBM cancer cell fitness. The precision of our GBM CLIP studies point to both mechanism and precise RNA sequence sites to selectively inhibit oncogenic NOVA1-RNA interactions. Taken together, we find that NOVA1 is commonly overexpressed in GBM, where it can antagonize AGO2-miRNA actions and consequently up-regulates cholesterol synthesis, promoting cell viability.

Characteristics of Opsoclonus-Myoclonus Syndrome in Patients of the Largest Pediatric Hospital in Latin America

BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare neuroinflammatory disorder characterized by ataxia, opsoclonus, and myoclonus. Clinical diagnosis of OMS has been challenging; therefore, we sought to determine the clinical and treatment profiles of patients with OMS at the largest pediatric hospital in Latin America. MethodsWe analyzed the data of patients diagnosed with OMS between 2010 and 2020 at Pequeno Principe Hospital (Brazil) to determine the corresponding clinical profile more accurately. ResultsOf the approximately 50,000 visitors to our pediatric neurology department from 2010 to 2020, 10 patients with OMS were observed. Five nontumor cases included three parainfectious and two idiopathic cases. The median time from symptom onset to diagnosis was 34 days. All patients with diagnostic OMS criteria in the idiopathic, nontumor group underwent whole-exome sequencing, with potentially pathogenic mutations identified in two cases. Nine patients were treated with methylprednisolone pulse, followed by oral steroids; eight received one or more intravenous immunoglobulin treatments; and six received azathioprine and cyclophosphamide. Complete symptomatic recovery was observed in only one patient. ConclusionsOMS diagnosis remains challenging. Diagnostic suspicion is necessary to improve the management of these patients and allow early immunosuppressive treatment. Paraneoplastic etiology is the most prevalent. In idiopathic patients who do not respond to immunosuppressive treatment, tests, such as whole-exome sequencing, may reveal a differential diagnosis. Genetic alterations that increase the risk of tumors may be an important clue to the pathophysiology of OMS.

Opsoclonus-Myoclonus Syndrome in a Child with Birth Asphyxia

A case of Opsoclonus Myoclonus Syndrome associated with birth asphyxia presented with antiseizure treatment started soon after birth and continued after discharge. The child presented at two years of age and had jerky movements in the limbs and eyes. The eye movements promptly responded to phenobarbital, and the limb movements appreciably diminished after adding clonazepam. The practice of continuing antiseizure treatment post-discharge in asphyxiated babies is questionable. No asphyxiated baby is reported in the literature to have OMS.