Bilateral optic neuritis as a first presentation of lymph node tuberculosis.

Tuberculosis (TB) may affect the nervous system in many ways. We describe an immunocompetent teenage girl with lymph node TB who had first presented with bilateral optic neuritis. Detailed history identified features inconsistent with immune-mediated optic neuritis. Several unusual features prompted further investigation, including transient visual obscurations without raised intracranial pressure, prominent disc swelling and absence of laboratory findings to support an immune-mediated cause. Whole body PET/MR imaging identified widespread mediastinal and supraclavicular lymphadenopathy. Despite no known TB contacts, a negative interferon gamma release assay and a normal chest X-ray, a targeted lymph node biopsy confirmed TB.

Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system.

Sarcoidosis and neuromyelitis optica in a patient with optic neuritis - a case report.

We present a case of atypical recurrent optic neuritis. A man in his 50s presented with right optic neuritis and profound visual loss, associated with elevated inflammatory markers. Lymph-node biopsy was consistent with sarcoidosis. Aquaporin-4 antibodies were also present. Three months following corticosteroid treatment, his right optic neuritis relapsed, again with raised inflammatory markers. He was started on azathioprine and prednisolone with good effect. A dual diagnosis of sarcoidosis and neuromyelitis optica with aquaporin-4 antibodies is very rare. Long-term immunosuppression is required. The case highlights the importance of identifying the features and cause of atypical optic neuritis.

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.

Purpose: The purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants. Methods: Patients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospective clinical data were collected from the medical records. Haplotype reconstruction was performed in families harboring the same missense variant. Results: Ten individuals from 8 unrelated families with biallelic candidate variants in FDXR were identified. In addition to bilateral optic atrophy and variable extra-ocular findings, 7 of 10 individuals manifested retinal dystrophy comprising dysfunction and degeneration of both rod and cone photoreceptors. Five of 10 subjects had sensorineural hearing loss. The previously unreported missense variant (c.1115C > A, p.(Pro372His)) was found in 5 of 8 (62.5%) study families. Haplotype reconstruction using WGS data demonstrated a likely ancestral haplotype. Conclusions: FDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort. In addition, we hypothesize that a number of factors are likely to drive the pathogenesis of optic atrophy, retinal degeneration, and perhaps the associated systemic manifestations.

Evidence of cultural group selection in territorial lobstering in Maine.

Relatively little is known about how resource conservation practices and institutions emerge. We examine the historical emergence of territoriality and conservation rules in Maine's lobstering industry, using a cultural evolutionary perspective. Cultural evolution suggests that cultural adaptations such as practices and institutions arise as a result of evolutionary selection pressure. The cultural multilevel selection framework of Waring et al. (Ecol Soc, 2015) further proposes that group cultural adaptations tend to emerge at a level of social organization corresponding to the underlying dilemma. Drawing on detailed history and ethnography, we conduct a retrospective assessment to determine which levels of social organization experienced selection pressures that might explain the emergence of lobstering territoriality and conservation practices we observe in history. The evidence strongly suggests that informal territoriality evolved by selection on harbor gang behavior, while some conservation practices spread via selection at other levels from individuals to regional lobstering zones. We identify two apparent historical shifts in the dominant level of selection for these practices over the history of the industry and discuss the implications of this trajectory for the evolution of lobster management in the Gulf of Maine.

Moving beyond panaceas in fisheries governance.

In fisheries management-as in environmental governance more generally-regulatory arrangements that are thought to be helpful in some contexts frequently become panaceas or, in other words, simple formulaic policy prescriptions believed to solve a given problem in a wide range of contexts, regardless of their actual consequences. When this happens, management is likely to fail, and negative side effects are common. We focus on the case of individual transferable quotas to explore the panacea mindset, a set of factors that promote the spread and persistence of panaceas. These include conceptual narratives that make easy answers like panaceas seem plausible, power disconnects that create vested interests in panaceas, and heuristics and biases that prevent people from accurately assessing panaceas. Analysts have suggested many approaches to avoiding panaceas, but most fail to conquer the underlying panacea mindset. Here, we suggest the codevelopment of an institutional diagnostics toolkit to distill the vast amount of information on fisheries governance into an easily accessible, open, on-line database of checklists, case studies, and related resources. Toolkits like this could be used in many governance settings to challenge users' understandings of a policy's impacts and help them develop solutions better tailored to their particular context. They would not replace the more comprehensive approaches found in the literature but would rather be an intermediate step away from the problem of panaceas.

Active surveillance of choroidal neovascularisation in children: incidence, aetiology and management findings from a national study in the UK.

BACKGROUND/AIMS: To determine the UK incidence, demographics, aetiology, management and visual outcome for children developing choroidal neovascularisation (CNV). METHODS: A prospective population-based observational study of routine practice via the British Ophthalmological Surveillance Unit between January 2012 and December 2013 with subsequent 1-year follow-up in children under 16 years old with newly diagnosed CNV. RESULTS: Twenty-seven children with CNV were reported. The UK estimated annual incidence for those aged 16 and under was 0.21 per 100 000 (95% CI 0.133 to 0.299). The mean age was 11.1 years (SD 3.9, range 4-16). Fourteen were female. Seventy-seven per cent (22 patients) were Caucasian British. Twenty-three children (85%) had unilateral disease. The most common aetiology included inflammatory retinochoroidopathy (n=9), optic disc abnormalities (n=9) and idiopathic (n=5). Optical coherence tomography was performed in all cases and fundus fluorescein angiography in 61%. Management included observation only (n=10), anti-vascular endothelial growth factor (anti-VEGF) injection of bevacizumab (n=14) or ranibizumab (n=2), or both (n=1), and additional use of oral (n=1) and local (periocular n=2 and intravitreal n=2) steroids in five children with inflammatory retinochoroidopathy. The mean number of anti-VEGF injections was 2±1, with eight patients receiving only one injection. The mean (SD) best corrected visual acuity in LogMAR was 0.91 (0.53) at presentation and 0.74 (0.53) at 1-year follow-up (p=0.09). CONCLUSION: This is the first population-based prospective study of CNV in children. This is a rare disorder with a poor visual prognosis irrespective of CNV location and the use of anti-VEGF therapy.

Detecting optic nerve head swelling on ultrasound and optical coherence tomography in children and young people: an observational study.

BACKGROUND: Following high-profile cases, referrals for evaluation of 'suspicious optic discs' to eye clinics in the UK have sharply increased, asking ophthalmologists to reliably distinguish between true and pseudopapilloedema. Optic nerve sheath dilatation (ONSD) on ocular ultrasound (US) is considered a reliable sign of true papilloedema, but this test is not widely available. Recently, anterior bowing of Bruch's membrane (BM) and increased retinal nerve fibre layer thickness on optical coherence tomography (OCT) have emerged as indicators of intracranial hypertension, and OCT is widely available. We aimed to evaluate safety and efficacy of the diagnostic workup in our service, with particular emphasis of diagnostic reliability of US and OCT. METHODS: Retrospective service evaluation/cohort study of children and young people younger than 16 years investigated for 'suspicious discs' over a 7-month period in 2016 at a single eye care provider in London, UK. 61 children and young people underwent clinical assessment, US scan and OCT. RESULTS: Of 61 cases, 3 had intracranial pathology. At presentation, only one had ONSD on US and anterior bowing of BM on OCT. Increased nerve fibre layer thickness in at least one of three relevant sectors was observed in two cases. All three cases of intracranial pathology, however, had significant points in their presenting or medical history. CONCLUSION: Ophthalmologists and optometrists must not rely on funduscopy and ocular imaging when assessing a child for possible intracranial disease; history and basic neurological assessment are critical in the diagnostic workup.

Artificial vision: principles and prospects.

PURPOSE OF REVIEW: The aim of this article is to give an overview of the strategies and technologies currently under development to return vision to blind patients and will answer the question: What options exist for artificial vision in patients blind from retinal disease; how close are these to clinical practice? RECENT FINDINGS: Retinal approaches will be the focus of this review as they are most advanced in terms not only of development, but entry into the imagination of the general public; they are technologies patients ask about, but may be less familiar to practicing neurologists.The prerequisites for retinal survivor cell stimulation are discussed, followed by consideration of the state of the art of four promising methods making use of this principle: electronic prostheses, stem cells, gene therapy and the developing field of ophthalmic optogenetics. SUMMARY: Human applications of artificial vision by survivor cell stimulation are certainly with us in the research clinic and very close to commercialization and general use. This, together with their place in the public consciousness, makes the overview provided by this review particularly helpful to practicing neurologists.

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

OBJECTIVE: Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy. METHODS: Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom. RESULTS: The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient -0.16, p=0.004) and presence of intellectual disability (coefficient -4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model. CONCLUSIONS: Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings.

Effect of Developmental Binocular Vision Abnormalities on Visual Vertigo Symptoms and Treatment Outcome.

BACKGROUND AND PURPOSE: Customized vestibular rehabilitation incorporating optokinetic (OK) stimulation improves visual vertigo (VV) symptoms; however, the degree of improvement varies among individuals. Binocular vision abnormalities (misalignment of ocular axis, ie, strabismus) may be a potential risk factor. This study aimed to investigate the influence of binocular vision abnormalities on VV symptoms and treatment outcome. METHODS: Sixty subjects with refractory peripheral vestibular symptoms underwent an orthoptic assessment after being recruited for participation in an 8-week customized program incorporating OK training via a full-field visual environment rotator or video display, supervised or unsupervised. Treatment response was assessed at baseline and at 8 weeks with dynamic posturography, Functional Gait Assessment (FGA), and questionnaires for symptoms, symptom triggers, and psychological state. As no significant effect of OK training type was noted for any variables, data were combined and new groups identified on the basis of the absence or presence of a binocular vision abnormality. RESULTS: A total of 34 among 60 subjects consented to the orthoptic assessment, of whom 8 of the 34 had binocular vision abnormalities and 30 of the 34 subjects completed both the binocular function assessment and vestibular rehabilitation program. No significant between-group differences were noted at baseline. The only significant between-group difference was observed for pre-/post-VV symptom change (P = 0.01), with significant improvements noted only for the group without binocular vision abnormalities (P < 0.0005). Common vestibular symptoms, posturography, and the FGA improved significantly for both groups (P < 0.05). DISCUSSION AND CONCLUSIONS: Binocular vision abnormalities may affect VV symptom improvement. These findings may have important implications for the management of subjects with refractory vestibular symptoms.Video Abstract available for insights from the authors regarding clinical implication of the study findings (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A115).

Multiphasic presentation of Rasmussen's encephalitis.

Rasmussen's encephalitis is a rare, chronic inflammatory disorder of unknown cause, characterised by drug-resistant focal epilepsy that may rarely present in adolescence or adulthood. We present a case of Rasmussen's encephalitis with prominent recurrent fluctuation in symptoms and well-documented fluctuating changes on MRI, adding to the spectrum of diversity of Rasmussen's encephalitis.

Evolution of visual field loss over ten years in individuals taking vigabatrin.

PURPOSE: Vigabatrin-associated visual field loss (VAVFL) occurs in around 45% of exposed people. It is generally accepted that, once established, VAVFL is stable and does not progress with continued VGB use. Most studies have, however, only followed people for short periods. We assessed the evolution of VAVFL over a ten-year period of continued VGB use. METHODS: From a group of 201 vigabatrin-exposed individuals with epilepsy, fourteen individuals were identified who were currently taking vigabatrin. All individuals had at least ten years exposure to vigabatrin. Individuals underwent several visual field examinations using Goldmann perimetry between Test 1 (first recorded examination) and Test 2 (most recent examination). All visual field results were analysed and quantified retrospectively by one investigator. RESULTS: 174 visual fields from the fourteen participants were available. The average follow-up period was 128 months. The prevalence of VAVFL increased from 64% at Test 1 to 93% at Test 2. The visual field size was significantly smaller at Test 2 compared to Test 1. All subjects showed a trend for decreasing visual field size with increasing cumulative vigabatrin exposure, when all fields for an individual were taken into account. There was a high degree of variability in visual field size between successive test sessions. CONCLUSIONS: VAVFL progresses with continued vigabatrin exposure over a ten-year period. Progression may be slow and difficult to detect because of the high degree of variability in visual field size between successive test sessions. New techniques are needed to monitor the effects of vigabatrin retinotoxicity in people who continue vigabatrin therapy.

Management options for visual pathway compression from optic gliomas.

Optic pathway gliomas (OPGs) manifest with neuro-ophthalmic symptoms and signs; however, presentation can vary as their location and growth patterns are highly variable. An exophytic expansion of an OPG within the intracranial cavity can cause compression on neurological structures, warranting intervention. However, management guidelines are limited and the treatment itself may also cause neuro-ophthalmic complications. Therefore, clinical decision-making must include input from a multidisciplinary team that includes ophthalmology, neurosurgery, radiation oncology and neuroradiology.

Patterns of peripapillary retinal nerve fiber layer thinning in vigabatrin-exposed individuals.

PURPOSE: To explore the relationship of peripapillary retinal nerve fiber layer (ppRNFL) thinning in individuals exposed to the antiepileptic drug vigabatrin with respect to 2 separate variables: cumulative vigabatrin exposure and severity of vigabatrin-associated visual field loss (VAVFL). DESIGN: Cross-sectional observational study. PARTICIPANTS: Subjects were older than 18 years, 129 with vigabatrin-treated epilepsy (vigabatrin-exposed group) and 87 individuals with epilepsy never treated with vigabatrin (nonexposed group). METHODS: All subjects underwent ppRNFL imaging using spectral-domain optical coherence tomography. Eighty-four vigabatrin-exposed individuals underwent Goldmann kinetic perimetry. The visual field examined from the right eye was categorized as normal (n = 47), mildly abnormal (n = 18), or moderately to severely abnormal (n = 19). In 91 vigabatrin-exposed individuals, the cumulative vigabatrin exposure could be ascertained: 41 subjects received 1000 g or less, 23 subjects received more than 1000 g but equal to or less than 2500 g, 16 subjects received more than 2500 g but equal to or less than 5000 g or less, and 11 subjects received more than 5000 g. MAIN OUTCOME MEASURES: Differences in ppRNFL thickness across the twelve 30° sectors: (1) among all nonexposed individuals and all vigabatrin-exposed individuals, (2) between each vigabatrin-exposed group, according to cumulative vigabatrin exposure, and the nonexposed group, (3) among different vigabatrin-exposed subjects grouped according to cumulative vigabatrin exposure, and (4) among vigabatrin-exposed subjects grouped according to severity of VAVFL. RESULTS: The ppRNFL was significantly thinner in vigabatrin-exposed compared with nonexposed individuals in most 30° sectors (P<0.004). The temporal, temporal superior, and temporal inferior 30° sectors, as well as the nasal 30° sector, were not affected. There was a trend for increasing ppRNFL thinning with increasing cumulative vigabatrin exposure. The nasal-superior 30° sector was significantly thinner in group 1 (≤1000 g) compared with nonexposed individuals (P<0.05) and in vigabatrin-exposed individuals with normal visual fields compared with nonexposed individuals (P<0.05). CONCLUSIONS: After vigabatrin exposure in individuals receiving cumulative doses of 1000 g or less or in the presence of normal visual fields, ppRNFL thinning in the nasal superior 30° sector may occur. With higher cumulative doses of vigabatrin exposure, additional ppRNFL thinning was observed. The temporal aspects of the ppRNFL are spared, even in individuals with large cumulative vigabatrin exposures and moderate or severe VAVFL.

A 'web app' for diagnosing hemianopia.

BACKGROUND: Hemianopia commonly complicates stroke and, less frequently, head injury and brain tumours. Patients' activities of daily living are often affected although these can be ameliorated by appropriate behavioural therapy. Identifying a field defect is the first step in the rehabilitation process. An online visual field test (an 'app') was developed as part of a free to use web based therapy site for patients with hemianopic alexia, called Read-Right (http://www.readright.ucl.ac.uk). This study is an attempt to validate this test by comparing with a clinical 'gold standard'-the Humphrey automated visual field analyser. METHODS: 22 patients had their visual fields assessed with both techniques on the same day. The criterion validity of the Read-Right was examined by comparing it with Humphrey 10-2 and 24-2 perimetry using the following measures: (1) sensitivity and specificity; (2) κ statistics; and (3) intraclass correlation. RESULTS: Read-Right demonstrated high sensitivity and specificity, particularly for the undamaged field. In the damaged field, κ values were highly significant, especially for points along the horizontal meridian. The intraclass correlation score for the damaged field indicated excellent correlation between the two tests. Read-Right perimetry performed well on all measures. It had a tendency to under call damaged points offset from the horizontal meridian, and this and other aspects of the test will be revamped. CONCLUSION: Read-Right is not designed to replace standardised visual perimetry; it does, however, offer a quick and easy assessment that can be used to screen patients. The test is available as part of two free to use web based therapy applications.