Opsoclonus in Children: Diagnosis, Etiology and Ophthalmologic Assessment of Patients at a Tertiary Children’s Hospital

Opsoclonus in Children: Diagnosis, Etiology, and Ophthalmologic Assessment of Patients at a Tertiary Children's Hospital.

Magnetic resonance imaging findings in children with spasmus nutans

<h3>Objective:</h3> To describe peri-infectious opsoclonus myoclonus ataxia syndrome (OMAS) in the setting of COVID-19 infection in children. <h3>Background:</h3> OMAS is well described in pediatric patients with peripheral neuroblastic tumors and less defined in the setting of peri-infectious etiologies such as SARS-CoV-19 which is better appreciated in adults. <h3>Design/Methods:</h3> We describe two separate cases of peri-infectious COVID-19 OMAS in pediatric patients at a tertiary Children’s Hospital in 2022, both previously healthy female patients, 2 years and 18 months of age. <h3>Results:</h3> Patient A is a two year-old female who initially presented with ataxia in context of acute COVID-19 infection at 16 months of age and later developed abnormal eye movements, myoclonus and irritability with multiple relapses over a nine month period. Patient B is a 18 month-old female presenting with acute onset abnormal eye movements and ataxia at age 14 months and later developed myoclonic jerks and irritability with sleep disturbance, subsequently found to have COVID-19 antibodies, now with remission of symptoms. Both patients had comprehensive work up for malignancy, toxic-metabolic encephalopathy, structural central nervous system disease, infectious meningoencephalitis and genetic ataxia syndromes. Both were treated with IVIG and high dose steroids. Patient A had subsequent relapses and required escalation of treatment to ACTH. Patient A had a more complicated course which included treatment with acetazolamide and levetiracetam for myoclonus. Her myoclonic jerks demonstrated intermittent electrographic correlates on EEG. <h3>Conclusions:</h3> While OMAS associated with neuroblastic tumors is well described in the pediatric literature, it is less well known in relation to peri-infectious phenomena, particularly SARS-CoV-2 infection in children. Prior published reports of OMAS related to COVID-19 infection in adults indicated a favorable prognosis after initial treatment. However, we present a case with repeated relapses and the need for more aggressive treatment. The present report broadens the phenotypic spectrum for OMAS outside of paraneoplastic etiologies. <b>Disclosure:</b> Dr. Yakir has nothing to disclose. Dr. Most has nothing to disclose. Dr. Hermel has nothing to disclose. Dr. Zimbric has received personal compensation in the range of $0-$499 for serving as a Survey volunteer with Opinionsite. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as a Consultant for Sinopia Biosciences. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Pet Dx. Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology. Dr. Friedman has stock in Friedman Bioventure . Dr. Rho has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nutricia. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerecin. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. Dr. Rho has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. The institution of Dr. Rho has received research support from National Institutes of Health. Dr. Rho has received publishing royalties from a publication relating to health care.

A 35-Year-Old Patient With Midscapular Pain and Hypertension

Coronavirus disease 2019 (COVID-19) can have symptoms like many neurological diseases, and one of the rare forms of these presentations is opsoclonus-myoclonus ataxia syndrome (OMAS). The pathogenesis of OMAS in adults has not been clearly elucidated and OMAS can be fatal. We present a 71-year-old male patient who was admitted to the emergency department with complaints of involuntary tremor-like movements in his hands, feet and mouth, and speech impediment for three days, and was followed up with COVID-19. The patient was diagnosed with OMAS and clonazepam treatment was started. He died three days later due to respiratory arrest. Our case is the first case diagnosed with COVID-19-associated OMAS in Turkey. OMAS has no definitive treatment. Early diagnosis and initiation of corticosteroids and intravenous immunoglobulin (IVIG) therapy, if necessary, can be life-saving. In COVID-19 patients with unexplained clinical findings, awareness of different and rare diseases and a multidisciplinary approach has vital importance.

Opsoclonus, an uncommon clinical sign, and is often described in the context of opsoclonus myoclonus ataxia syndrome (OMAS). OMAS may be paraneoplastic or postinfectious. However, opsoclonus with or without OMAS may occur in association with a wide gamut of infections. Infection-associated opsoclonus/OMAS (IAO) needs recognition as a separate entity, since it demands relatively brief immunosuppression, symptomatic treatment, and has a better outcome. Case records of children, who presented with opsoclonus to a tertiary-care teaching hospital of North India over a period of 1 year (2017-2018), were reviewed. Those with opsoclonus in the setting of an acute infection/febrile illness (symptomatic opsoclonus; IAO) were included. Of 15 children with opsoclonus, 6 children [median age: 42 months (range: 8 months to 7 years); 2 boys] had opsoclonus associated with an infective or febrile illness. Additional clinical findings in these children included myoclonus (n = 2), ataxia (n = 4) and behavioral abnormalities (n = 4). All these patients had an associated neurologic or nonneurologic illness- scrub typhus (n = 1), tuberculous meningitis (n = 1), mumps encephalitis (n = 1), brainstem encephalitis (n = 1), acute cerebellitis (n = 1), and subacute sclerosing panencephalitis (SSPE, n = 1). Children with acute cerebellitis, brainstem encephalitis, and mumps encephalitis were treated with steroids while those with scrub typhus, tuberculosis, and SSPE were treated with antibiotics, antitubercular therapy, and Isoprinosine, respectively. None of them needed long-term maintenance immunotherapy. The evaluation for tumor was negative in all. Three of the 6 children are functionally normal at the last follow-up. Acute neuro infections may trigger opsoclonus. A careful analysis of clinical data and suitable investigations can help differentiate these children from those with OMAS. This distinction may avoid unwarranted long-term immunosuppression.

Objective: Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neurological disorder characterized by acute/subacute onset multi-directional chaotic eye movements, accompanied by myoclonus and cerebellar ataxia; as well as sleep disturbance, cognitive dysfunction, and behavioral disturbance can be observed. Methods: We examined the information of eight patients (four females, four males) who applied to the hospital with OMAS between 2013 and 2020 from the medical records of the patients. Results: The median age of onset of the initial symptoms was 17.5 months (8-30 months). The most common initial complaints were abnormal eye movement and gait unsteadiness, respectively. Paraneoplastic OMAS was observed in three patients (37.5%), whereas idiopathic and infection-related OMAS was detected in three, and two patients, respectively. Conclusion: We emphasize that all symptoms of OMAS may not occur simultaneously, therefore comprehensive systemic investigations, and close observation should be made in patients with suspected OMAS.

Sirs, Neurological disorders are a well-known complication of human immunodeficiency virus (HIV) infection [7]. An incidence of 2–3% of clinically relevant movement disorders has been identified in patients with HIV infection seen at tertiary referral centers, and in several cases it may represent the initial manifestation of HIV infection [8]. Nevertheless, the incidence of movement disorders increases significantly, ranging between 5 and 44% in AIDS patients, with a large prevalence of tremor and Parkinsonism [2, 8]. Opsoclonus–myoclonus–ataxia syndrome (OMAS) is a rare neurological disorder associated with many clinical settings [11]. Although the pathophysiology of opsoclonus is still undefined, a dysfunction at the pontine paramedian reticular formation (PPRF) and the cerebellum secondary to a dysregulation of the humoral and cell mediated immune mechanisms is postulated [11]. To our knowledge, OMAS has been previously reported in only two HIV patients [5, 9] but not at the time of seroconversion. We report a 44-year-old white man who was admitted 24 h after the onset of acute opsoclonus, truncal ataxia and orthostatic myoclonus that led to postural instability. His personal and family medical history was unremarkable, with the exception of a mild congenital right brachial paresis. Physical examination revealed involuntary, multidirectional, high-amplitude, conjugate saccadic eye movements. Gait was moderately unsteady, due to involuntary jerking of lower extremities and wide-base standing. The remainder of the neurological and systemic examinations were normal. The routine blood chemistry tests, including thyroid function, were normal but the liver chemistry tests showed elevated s-GOT (74 units/l) and s-GPT (185 units/ l). Serology for Epstein Barr virus, CMV, hepatitis A, B and C virus and VDRL were negative. An HIV antibody test performed 2 months before the onset of symptoms was negative, but two new HIV ELISA and a Western blot (IgG) tests performed 24 h and 48 h after admission showed positive, with a CD4 count of 511 cells/ml (17%) and a viral load of 1.5 9 10 (6.17 log) (NASBA methods). The CSF constituents, a brain MRI and EEG were normal. The patient’s symptoms improved with lorazepam 1 mg/ day and resolved completely after 1 week, but he refused antiretroviral therapy. Two additional viral load assessments and CD4 counts were obtained 1 month and 1 year later, respectively (Fig. 1). This case fulfills the clinical diagnostic criteria of OMAS. Its temporal occurrence and evolution suggest that this syndrome might be not only a random association but the clinical expression of the HIV seroconversion. The HIV seroconversion in this patient was supported by a negative HIV antibody test performed 2 months before the onset of OMAS, followed by a new HIV positive test at time of admission. In accordance with A. Ayarza V. Parisi D. Visconti G. Persi C. A. Rugilo E. M. Gatto Department of Neurology, Sanatorio de la Trinidad Mitre, Bartolome Mitre 2553, CP 1039, Buenos Aires, Argentina

OMAS is rare affecting 1 in 10 million people per year. Symptoms include rapid, involuntary, multidirectional conjugate eye movements, brief involuntary movements of muscles and truncal/appendicular cerebellar ataxia. The combination...

Optic pathway gliomas (OPGs) are low-grade neoplasms that may be associated with profound vision loss, endocrinologic deficits, and neurologic dysfunction. OPGs occur sporadically or in association with the neurocutaneous disorder neurofibromatosis type 1 (NF1). There is ample debate regarding the most effective way for ophthalmologists to screen patients with NF1 for the presence of these tumors. Furthermore, the decision to treat and the criteria that serve as a basis for this treatment remain topics of significant discussion amongst the multidisciplinary team managing these patients including pediatric ophthalmologists, neuro-ophthalmologists, neuro-oncologists, neurosurgeons, and geneticists. Prospective natural history data are needed to develop consensus recommendations for a screening protocol for OPGs, the criteria for treatment of OPGs, and risk factors for poor visual outcomes.

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neuroinflammatory disorder that is typically associated with paraneoplastic and postinfectious processes. Opsoclonus myoclonus ataxia syndrome has not been previously reported in association with tuberculous meningitis (TBM). This report presents a unique case in which TBM manifested as OMAS, highlighting the complex interplay between tuberculosis and autoimmune neurological conditions. A 1.5-year-old previously healthy girl, presented with acute-onset jerky movements, opsoclonus, irritability, and reduced sleep over 4 weeks. A neurological examination revealed opsoclonus, irritability, generalized tremulousness, and fragmentary myoclonus. Neuroimaging was suggestive of TBM. A cerebrospinal fluid (CSF) analysis indicated lymphocytic pleocytosis with positive CSF cartridge-based nucleic acid amplification test results for tuberculosis. The patient was treated with methylprednisolone pulse therapy, intravenous immunoglobulins, and anti-tuberculous therapy (ATT). Significant symptom improvement was observed within 2 weeks. This case underscores a rare association between OMAS and TBM, demonstrating that tuberculosis can trigger OMAS through autoimmune mechanisms. A timely diagnosis and treatment with ATT and immunotherapy can lead to substantial recovery.

Narcolepsy, a neurologic disorder that leads to excessive daytime sleepiness, may represent a rare consequence of neoplastic lesions involving the sellar/parasellar and hypothalamic regions, the anatomical areas responsible for wakefulness. Optic pathway gliomas represent the most common neoplasm of these regions and present an excellent overall survival, while long-term neurologic impairments, such as visual loss, endocrinopathies, or sleep disorders, are the principal causes of morbidity. In this case report, we describe a non-NF1 patient suffering from a very extensive optical pathway glioma, who several years after the diagnosis in a radiological condition of stable disease, presented with severe narcolepsy, a rare complication, that led to the death of the patient.

To compare visual function assessment, optic disc evaluation by indirect ophthalmoscopy, and retinal nerve fiber layer analysis by optical coherence tomography (OCT) for the screening of optic pathway gliomas in pediatric patients (2-15 years old) affected by neurofibromatosis type 1. Fifty-seven consecutive patients with neurofibromatosis type 1 with recent (<6 months) orbital/brain magnetic resonance images (MRI) were included. Patients underwent visual function assessment (Hyvarinen symbols chart and/or Snellen charts) and optic disc evaluation by indirect ophthalmoscopy performed by experienced, masked pediatric ophthalmologists. Spectral domain OCT was performed to assess retinal nerve fiber layer. Fifteen of 57 enrolled patients (26%) were affected by MRI-proven optic pathway gliomas. Visual function assessment, optic disc evaluation, and retinal nerve fiber layer analysis by OCT were feasible in 84%, 95%, and 88% of patients, respectively. Visual function assessment, retinal nerve fiber layer analysis, and optic disc evaluation results correlated with the presence of optic pathway gliomas (P = 0.007, P < 0.0001, and P = 0.03, respectively). Specificity and negative predictive value of each test were statistically significant in detecting optic pathway glioma (P < 0.0001), whereas only retinal nerve fiber layers analysis reached statistically significant sensitivity and positive predictive value (P = 0.0386). Retinal nerve fiber layer analysis assessment using spectral domain OCT is superior to visual function assessment and optic disc evaluation as a clinical screening tool for optic pathway gliomas.

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Optic pathway gliomas (OPGs) are the most common brain tumor that pediatric ophthalmologists and neuro-ophthalmologists care for. These low-grade gliomas are found along the anterior portion of the visual pathway and demonstrate unique features in their growth, impact on visual function and response to treatment. The standardized approach to the ophthalmologic evaluation and testing positions the ophthalmologist to play a vital role in the care of these unique tumors. This review will cover the epidemiology, clinical evaluation, treatment and outcomes of OPGs.