Should Aquaporin-4 Antibody Test Be Performed in all Patients With Isolated Optic Neuritis?

BACKGROUND: Optic neuritis (ON) may be the initial manifestation of neuromyelitis optica spectrum disorder (NMOSD). Aquaporin-4 antibody (AQP4 Ab) is used to diagnose NMOSD. This has implications on prognosis and is important for optimal management. We aim to evaluate if clinical features can distinguish AQP4 Ab seropositive and seronegative ON patients. METHODS: We reviewed patients with first episode of isolated ON from Tan Tock Seng Hospital and Singapore National Eye Centre who tested for AQP4 Ab from 2008 to 2017. Demographic and clinical data were compared between seropositive and seronegative patients. RESULTS: Among 106 patients (120 eyes) with first episode of isolated ON, 23 (26 eyes; 22%) were AQP4 Ab positive and 83 (94 eyes; 78%) were AQP4 Ab negative. At presentation, AQP4 Ab positive patients had older mean onset age (47.9 ± 13.6 vs 36.8 ± 12.6 years, P < 0.001), worse nadir VA (OR 1.714; 95% CI, 1.36 to 2.16; P < 0.001), less optic disc swelling (OR 5.04; 95% CI, 1.682 to 15.073; p = 0.004), and higher proportions of concomitant anti-Ro antibody (17% vs 4%, p = 0.038) and anti-La antibody (17% vs 1%, p = 0.008). More AQP4 Ab positive patients received steroid-sparing immunosuppressants (74% vs 19%, p < 0.001) and plasma exchange (13% vs 0%, p = 0.009). AQP4 Ab positive patients had worse mean logMAR VA (visual acuity) at 12 months (0.70 ± 0.3 vs 0.29 ± 0.5, p = 0.051) and 36 months (0.37±0.4 vs 0.14 ± 0.2, p = 0.048) follow-up. CONCLUSION: Other than older onset age and retrobulbar optic neuritis, clinical features are non-discriminatory for NMOSD. We propose a low threshold for AQP4 Ab serology testing in inflammatory ON patients, particularly in high NMOSD prevalence populations, to minimize diagnostic and treatment delays.

Risk Factors and Clinical Prognosis Associated With RSV-ALRI Intensive Care Unit Admission in Children <2 Years of Age: A Multicenter Study.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) in children <2 years of age. Currently, there are limited data on risk factors for very severe RSV-ALRI requiring intensive care unit (ICU) admission. METHODS: We conducted a case-control study of children <2 years old admitted with RSV-ALRI to the Sydney Children's Hospital Network, comprising 2 large tertiary pediatric hospitals. Cases were children with laboratory-confirmed RSV-ALRI admitted to ICU, and controls were (1:2, matched on date of admission) children hospitalized with RSV-ALRI but not requiring ICU transfer. Data on risk factors were retrieved from the electronic medical record system. Adjusted odds ratios (aORs) with 95% confidence intervals (95% CI) associated with risk factors for ICU admission and the association with clinical and treatment factors were determined from logistic regression models. RESULTS: A total of 44 (44%) of 100 cases and 90 (48.1%) of 187 controls were male. Age <6 months and preterm births were associated with a 2.10-fold (95% CI: 1.14-3.79) and 2.35-fold (95% CI: 1.26-4.41) increased risk in ICU admissions, respectively. The presence of any chronic health condition was a significant risk factor for ICU admission. The clinical presentations on admission more commonly seen in cases were apnea (aOR: 5.01, 95% CI: 1.50-17.13) and respiratory distress (aOR: 15.91, 95% CI: 4.52-55.97). Cases were more likely to be hospitalized for longer duration and require respiratory support. CONCLUSIONS: Our results can be translated into a clinical risk algorithm to identify children at risk of very severe RSV disease.

A novel intronic variant in ROBO3 associated with horizontal gaze palsy with progressive scoliosis: case report and literature review.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessive inherited disorder caused by mutations in ROBO3 gene. The clinical features of HGPPS include horizontal gaze palsy, progressive scoliosis, other oculomotor abnormalities such as strabismus and nystagmus. Whole-exome sequencing (WES) is used to diagnose rare Mendelian disorders, when routine standard tests have failed to make a formal pathological diagnosis. However, WES may identify variants of uncertain significance (VUS) that may add further ambiguity to the diagnosis. We report the case of a 4-year-old boy with horizontal gaze palsy, progressive scoliosis, microcephaly, and mild developmental delay. WES identified an intronic VUS in ROBO3 gene. We performed minigene splicing functional analysis to confirm the pathogenicity of this VUS. This report illustrates that WES data analysis with supportive functional analysis provides an effective approach to improve the diagnostic yield for unsolved clinical cases. This case also highlights the phenotypic heterogeneity in patients with HGPPS.

Classification of Temporal Bone Pneumatization on High-Resolution Computed Tomography: Prevalence Patterns and Implications.

Objective The degree of pneumatization of the temporal bone has implications in the pathophysiology and surgical considerations of many temporal bone disorders. This study aims to identify common pneumatization patterns in the petrous apex, mastoid, and infralabyrinthine compartments of the temporal bone. Variables associated with temporal bone pneumatization were also identified. Study Design Case series with chart review. Setting Single tertiary hospital. Subjects and Methods In total, 299 high-resolution computed tomography scans of the temporal bone performed on patients between 2013 and 2016 were reviewed. Only normal temporal bone scans in patients aged 13 years and older were included. Previously published grading systems were used to classify pneumatization patterns in the petrous apex, mastoid, and infralabyrinthine region. Results The most common pneumatization pattern in the petrous apex was group 2 (less than half of the petrous apex medial to the labyrinth is pneumatized), that in the mastoid was group 4 (hyperpneumatization), and that in the infralabyrinthine region was type B (limited pneumatization), at 54.8%, 55.4%, and 76.0% of patients, respectively. Patients with increased pneumatization of 1 temporal bone compartment tended to have increased pneumatization of the same compartment on the contralateral side and the other compartments on the ipsilateral side ( P < .05). Younger age ( P < .001) and male sex ( P = .001) were associated with increased pneumatization in the petrous apex and infralabyrinthine compartments. Conclusion The degree of temporal bone pneumatization varies among the different compartments. Age and sex have a significant association with the degree of pneumatization of the petrous apex and infralabyrinthine compartment.

Ethambutol-associated optic neuropathy.

INTRODUCTION: Ethambutol is used in the treatment of tuberculosis, which is still prevalent in Southeast Asia, and can be associated with permanent visual loss. We report 3 cases which presented with bitemporal hemianopia. CLINICAL PICTURE: Three patients with ethambutol-associated toxic optic neuropathy are described. All 3 patients had loss of central visual acuity, colour vision (Ishihara) and visual field. The visual field loss had a bitemporal flavour, suggesting involvement of the optic chiasm. TREATMENT: Despite stopping ethambutol on diagnosis, visual function continued to deteriorate for a few months. Subsequent improvement was mild in 2 cases. In the third case, visual acuity and colour vision normalised but the optic discs were pale. OUTCOME: All 3 patients had some permanent loss of visual function. CONCLUSIONS: Ethambutol usage is associated with permanent visual loss and should be avoided if possible or used with caution and proper ophthalmological follow-up. The author postulates that in cases of ethambutol associated chiasmopathy, ethambutol may initially affect the optic nerves and subsequently progress to involve the optic chiasm.

Guiding follow-up of paediatric idiopathic intracranial hypertension with optical coherence tomography.

Idiopathic intracranial hypertension (IIH) is uncommon in the paediatric population. Papilloedema is the hallmark sign and patients can suffer permanent vision loss as a consequence. We describe the role of optical coherence tomography (OCT) in the follow-up of two paediatric patients with newly diagnosed IIH. Patient A presented with vomiting and examination showed ophthalmoplaegia and papilloedema. She was treated with acetazolamide, furosemide and therapeutic lumbar punctures. Patient B presented with incidental papilloedema and was treated with acetazolamide and she reported intermittent headache during follow-up. Fundoscopic examinations for both patients showed persistent blurred disc margins but OCT examinations documented improvement of average retinal nerve fibre layers. OCT may be of value in monitoring for recurrence in paediatric IIH.

Functional visual loss in adults and children patient characteristics, management, and outcomes.

OBJECTIVE: To compare the characteristics of functional visual loss (FVL) in adults and children. DESIGN: Retrospective chart review. PARTICIPANTS: One hundred forty patients diagnosed with FVL over a 5-year period. METHODS: Medical records of these patients were reviewed and data analyzed using statistical software. OUTCOME: Demographics, underlying organic and psychiatric disease, concomitant psychosocial events, and resolution rates were studied. RESULTS: Functional visual loss, with or without functional overlay, was initially diagnosed in 140 patients and was, in retrospect, a correct diagnosis in 138. There were 56 (40.6%) children and 82 (59.4%) adults (mean age, 13.4 and 40.0 years). The gender ratio, incidence of concomitant psychosocial events, incidence of functional overlay, prevalence of migraine or facial pain, and proportion referred for counseling were similar in the 2 groups. Concomitant psychosocial events were primarily social in children and related to trauma in adults. Thirty-two (39.0%) adults had a history of psychiatric illness, versus 10 (17.9%) children (P = 0.008). Symptoms were bilateral in 65.0% of cases. Functional visual loss manifested as visual acuity (VA) loss only occurred in 26.1% of patients, FVL manifested as visual field (VF) loss only was present in 28.3% of patients, and FVL with loss of both VA and VF occurred in 45.6% of patients. There was no significant difference in children versus adults in the proportion of VA, VF, or both being affected. Functional visual loss with coexistent organic disease (functional overlay) was present in 16.7% of patients. Follow-up information was available for 26.1% of patients. Normalization of any one parameter occurred in 58.3% of patients and was more likely in children. Three patients (2.2%) originally felt to have solely functional disease were subsequently diagnosed with organic disease. CONCLUSION: Functional visual loss is most common in teenagers, is typically bilateral, and involves both VA and VF. Normal VA was proven half the time at initial consultation. At all ages, patients were predominantly female, and one fifth had migraine, facial pain, or coexistent organic pathology. Concomitant psychosocial events were mainly social in children and related to trauma in adults. Psychiatric disease was twice as likely in adults. Normalization of visual function occurred in a majority of patients. Early-onset macular dystrophies and hereditary optic neuropathies may be misdiagnosed as FVL.

Severe optic neuritis in a patient with combined neuromyelitis optica spectrum disease and primary Sjögren's syndrome: a case report.

INTRODUCTION: Optic neuritis, although uncommon, can be the initial presentation of Sjögren's syndrome. Coexisting Sjögren's syndrome has also been reported with neuromyelitis optica spectrum disorder. This case report highlights the association between the two diseases and the importance of rheumatological and neurological evaluations in patients with such diagnoses. Distinction of neuromyelitis optica with coexisting connective tissue disease has both prognostic and therapeutic significance for the patient. CASE PRESENTATION: We report a case of a 56-year-old Chinese woman who presented with bilateral asymmetric visual loss secondary to optic neuritis. She was subsequently found to be seropositive for neuromyelitis optica immunoglobulin G (NMO-IgG) (anti-aquaporin-4 antibody) and was diagnosed with neuromyelitis optica spectrum disorder. She also fulfilled the international criteria for Sjögren's syndrome. Despite initial high dose immunosuppressive therapy, she failed to regain vision in one eye. CONCLUSION: Patients presenting with optic neuritis and severe visual loss should be screened for neuromyelitis optica and treated appropriately. Neuromyelitis optica has been associated with systemic autoimmune diseases, in particular Sjögren's syndrome, and current evidence indicates that they are two distinct entities. We recommend that both diagnoses be considered in cases of optic neuritis with severe visual loss.

Magnetic resonance imaging in acute optic neuritis in Singapore.

INTRODUCTION: The Optic Neuritis Treatment Trial (ONTT) has established that the magnetic resonance imaging (MRI) findings at the time of presentation of optic neuritis (ON) is the strongest indicator of the development of multiple sclerosis (MS). Reports from Singapore as well as other Asian countries have indicated that these abnormalities are less frequently encountered compared to that reported by the ONTT. This paper aims to describe systematically the brain MRI as well as the optic nerve abnormalities in patients after an episode of acute optic neuritis. MATERIALS AND METHODS: Patients who presented with acute optic neuritis were retrieved from our prospective optic neuritis study and their MRI scans were reviewed and graded in accordance with the standardised classification employed in the ONTT. RESULTS: Fifteen of 24 patients had MRI brain and optic nerves performed during the acute episode. In the evaluation of brain abnormalities, 40% were classified as grade 0, 20% grade I, 20% grade II, 6.7% grade III and 13.3% grade IV. Optic nerve abnormalities were observed in 80% of cases. At study entry, 10 patients had idiopathic (monosymptomatic) ON, 3 had multiple sclerosis (MS), one each with infective and autoimmune optic neuritis, respectively. The single patient who developed MS at study completion presented with grade II brain abnormalities at the initial MRI. For those with idiopathic ON, our study revealed a higher percentage of grade 0-I brain changes as well as a lower lesion load compared to the ONTT.Lesion Load and grade was also lower in anterior optic neuritis compared with retrobulbar disease. CONCLUSION: Our study revealed a lower percentage of grade II-IV brain MRI abnormalities as well as less lesion load in idiopathic ON compared to the ONTT. This may be related to the lower prevalence of MS in our predominantly Asian population. As diagnostic tests and understanding of neuromyelitis optica or Devic's disease improves, we may see more patients being diagnosed with this condition, which may also explain our findings. Our data also showed that MRI grade and lesion load in cases of anterior ON was lower than for retrobulbar disease. MRI in ON has an essential role in characterising the disease, evaluating for associated brain lesions, and assessing prognosis in retrobulbar disease but may be less useful in anterior disease.

The incidence of neuro-ophthalmic diseases in Singapore: a prospective study in public hospitals.

PURPOSE: To describe the incidence of neuro-ophthalmic diseases in a multi-ethnic Asian population in Singapore. METHODS: Prospective study in public hospitals in Singapore. All neuro-ophthalmic cases seen in four public sector hospitals over a 22-month period (September 2002 to June 2004) were identified using a standardized protocol. The 2004 Singapore population was used as a denominator to estimate annual incidence. The prevalence of ischemic risk factors (hypertension, diabetes, and hypercholesterolemia) among cases was compared to population data. RESULTS: A total of 1,356 patients with neuro-ophthalmic diseases were seen during the study period, of which 627 were new incident cases. The overall annual incidence of neuro-ophthalmic diseases was 9.81 per 100,000 (95% confidence interval, 8.80-10.90). The incidence increased with age. After controlling for age, the annual incidence was similar between men (10.75 per 100,000) and women (9.00 per 100,000), but was higher in Chinese (10.33 per 100,000) and Indians (9.34 per 100,000) than in Malays (6.62 per 100,000). The three commonest specific neuro-ophthalmic conditions were abducens nerve palsy (1.27 per 100,000), anterior ischemic optic neuropathy (1.08 per 100,000) and oculomotor nerve palsy (0.91 per 100,000). The incidence of optic neuritis was 0.83 per 100,000. Compared with the Singapore general population, the prevalence of diabetes was significantly higher in people aged 40-59, while the prevalence of hypercholesterolemia was significantly higher in 60-69 year age group. CONCLUSION: In this study of public hospitals in Singapore, the incidence of neuro-ophthalmic diseases was higher in Chinese and Indians compared to Malays.

Pediatric neuro-ophthalmology.

PURPOSE OF REVIEW: This review will update the ophthalmologist on recent developments in pediatric neuro-ophthalmology. RECENT FINDINGS: Research into the genetics of congenital strabismus syndromes has brought new insights into the development of the ocular motor system. There is also new literature on childhood ocular myasthenia gravis and childhood neurosarcoidosis. The results of three different surgical treatments for congenital nystagmus are described. Reviews on cortical visual impairment, dyslexia, Aicardi syndrome, and neuronal ceroid lipofuscinosis are presented. SUMMARY: Pediatric neuro-ophthalmology is a diverse and challenging field. As we strive to provide excellent care to these patients, we will use the results of basic science, genetic, and neurobiological research.