Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis-A Review.

ABSTRACT: Our understanding of demyelinating optic neuritis has substantially evolved over the past 2 decades. With advancements in serological testing, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been recently discovered in a distinct subset of demyelinating neuroinflammatory disease. Although MOG-immunoglobulin G (IgG)-associated disorder (MOGAD) has previously been seen as a component of neuromyelitis optica spectrum disorder (NMOSD), evidence increasingly suggests that it should be distinguished as a separate condition. The distinction of MOGAD from aquaporin-4 IgG NMOSD is imperative as treatment plans need to be tailored to its unique disease course and prognosis. The purpose of this review is to explore the nature and outcomes of MOGAD optic neuritis to help guide acute and long-term immunosuppressive treatment decisions.

Impact of the eye clinic liaison officer at an NHS foundation trust: a retrospective study.

OBJECTIVE: Vision loss has a significant impact on physical, mental and social well-being. Eye clinic liaison officers (ECLOs) have a crucial role in providing holistic care for patients with visual impairment. The aim of this study was to review the work of an ECLO over a period of 1 year at an NHS Trust to determine the volume of work and the areas of support provided by the ECLO. METHODS AND ANALYSIS: A secondary data analysis of the ECLO case notes for all patients reviewed by the ECLO at University Hospitals Birmingham (UHB) NHS Trust during the year 2019, was performed. Demographic data and certification of visual impairment (CVI) status were noted. The main outcome variable recorded was the categories of support provided by the ECLO. Case vignettes were chosen to illustrate the variety of support offered to individual patients. RESULTS: A total of 1127 consecutive participants were reviewed by the ECLO at University Hospitals Birmingham (UHB) NHS Trust during the year 2019. Areas of support most commonly provided by the ECLO included aiding the process of registration for CVI, and assistance in accessing benefits, social support and low vision support. Severely sight impaired patients required significantly more areas of support than sight impaired patients (Χ2=52.7, p=2.16×10-6). Three case vignettes, chosen by the ECLO, highlighted the positive impact of the ECLO with respect to emotional support, practical advice and as a point of contact ensuring continuity of care, also during the COVID-19 pandemic. CONCLUSIONS: The ECLO at UHB NHS Trust provides a core patient service within the ophthalmology department by being a key source of practical and emotional support and the crucial link between healthcare, social care and voluntary services.

Idiopathic intracranial hypertension: consensus guidelines on management.

The aim was to capture interdisciplinary expertise from a large group of clinicians, reflecting practice from across the UK and further, to inform subsequent development of a national consensus guidance for optimal management of idiopathic intracranial hypertension (IIH). METHODS: Between September 2015 and October 2017, a specialist interest group including neurology, neurosurgery, neuroradiology, ophthalmology, nursing, primary care doctors and patient representatives met. An initial UK survey of attitudes and practice in IIH was sent to a wide group of physicians and surgeons who investigate and manage IIH regularly. A comprehensive systematic literature review was performed to assemble the foundations of the statements. An international panel along with four national professional bodies, namely the Association of British Neurologists, British Association for the Study of Headache, the Society of British Neurological Surgeons and the Royal College of Ophthalmologists critically reviewed the statements. RESULTS: Over 20 questions were constructed: one based on the diagnostic principles for optimal investigation of papilloedema and 21 for the management of IIH. Three main principles were identified: (1) to treat the underlying disease; (2) to protect the vision; and (3) to minimise the headache morbidity. Statements presented provide insight to uncertainties in IIH where research opportunities exist. CONCLUSIONS: In collaboration with many different specialists, professions and patient representatives, we have developed guidance statements for the investigation and management of adult IIH.

Development and validation of a questionnaire assessing the quality of life impact of Colour Blindness (CBQoL).

BACKGROUND: Congenital colour vision deficiency (CVD), commonly called 'colour blindness', affects around 8% of men and 0.4% of women. Although many aspects of health (e.g. change in colour of urine) and healthcare (e.g. coloured medication, colour-coded diagnostic tests), and modern life depend upon colour coding (e.g. graphs, maps, signals), the impact of colour blindness on everyday life is not generally considered a topic of importance. This study is the first to create and validate a questionnaire measuring the quality of life (QoL) impact of being colour blind. METHODS: This study consisted of two phases. Firstly, the questionnaire design and development phase was led by an expert panel and piloted on a focus group. Secondly, an online sample of 128 men and 291 women filled in the questionnaire, and the psychometric properties of the questionnaire were analysed using principal components analysis (PCA). The scores of colour blind (CB) participants and normal-sighted controls, controlling for age and sex, were compared using matched t-tests. RESULTS: The PCA resulted in a questionnaire with three domains (or subscales): QoL for Health & Lifestyle, QoL for Work, and QoL for Emotions. Controlling for age, there was a significantly greater negative impact on QoL for CB people than normal-sighted controls in regards to confusion over colour in various aspects of their health (p = 5 × 10-7), work (p = 1.3 × 10-7), and emotional life (p = 6 × 10-5). CONCLUSION: Colour blindness can significantly impact quality of life for health, emotions, and especially careers. The tool developed here could be useful in future clinical studies to measure changes in CBQoL in response to therapy in conditions where colour vision is affected. We also discuss ways in which everyday problems related to colour vision might be reduced, for example, workplaces could avoid colour coding where a non-colour alternative is possible.

A practical approach to, diagnosis, assessment and management of idiopathic intracranial hypertension.

Adult patients who present with papilloedema and symptoms of raised intracranial pressure need urgent multidisciplinary assessment including neuroimaging, to exclude life-threatening causes. Where there is no apparent underlying cause for the raised intracranial pressure, patients are considered to have idiopathic intracranial hypertension (IIH). The incidence of IIH is increasing in line with the global epidemic of obesity. There are controversial issues in its diagnosis and management. This paper gives a practical approach to assessing patients with papilloedema, its investigation and the subsequent management of patients with IIH.

Detection of branch retinal artery occlusions in Susac's syndrome.

BACKGROUND: We report an interesting case of asymptomatic retinal involvement in an encephalopathic patient enabling early identification of Susac's syndrome. CASE PRESENTATION: A 39-year-old Caucasian lady with hearing loss and encephalopathy was referred for ophthalmic assessment, including screening for branch retinal artery occlusions characteristic of Susac's syndrome. Clinical features included severe headaches, right-sided hypoacusis, dysphasia and poor memory. Routine blood tests were normal. MRI brain showed numerous hyperintense lesions mainly in corpus callosum. Although she was visually asymptomatic, dilated funduscopy detected bilateral multiple peripheral branch retinal artery occlusions which were confirmed on fluorescein angiography. She was subsequently started on intravenous steroids and pulsed cyclophosphamide which improved her symptoms within 48 hours. Full recovery was made with no new arterial occlusions on four months follow-up. CONCLUSION: The case further establishes the crucial role of a detailed ophthalmic examination supported by fluorescein angiography in the assessment of these patients, who are at risk of being misdiagnosed and undertreated.

Rating papilloedema: an evaluation of the Frisén classification in idiopathic intracranial hypertension.

The appearance of the optic disc is a key measure of disease status in idiopathic intracranial hypertension (IIH). The Frisén classification describes stages of optic disc swelling (grades 0-5). It is the only classification of papilloedema, and is used internationally in clinical and research practice. Despite this, there has been very limited evaluation of the scale. We assessed the inter-rater reproducibility and ability to discriminate optic disc changes over time using the Frisén classification compared with a system of ranking papilloedema severity in patients with IIH. Paired disc photographs (before and after treatment) were obtained from 47 patients with IIH (25 acute and 22 chronic). Six neuro-ophthalmologists blinded to patient identity, clinical information and chronology of the photographs reviewed the discs and allocated a Frisén grade and ranked the paired discs in order of papilloedema severity (disc ranking). A total of 188 optic disc photographs were reviewed. All six reviewers agreed in only three comparisons (1.6%) when using the Frisén classification, compared with 42 comparisons (45.2%) when using disc ranking. The probability of agreement between any two reviewers was 36.1% for Frisén grade and 70.0% for disc ranking. Disc ranking had significantly greater sensitivity for finding differences in degree of disc oedema, identifying a difference in 75.3% of paired photographs compared to 53.2% detected using the Frisén classification (p < 0.001). This study demonstrated the limited reproducibility and discriminative ability of the Frisén classification in identifying changes in serial optic disc photographs in IIH. Simple optic disc ranking appears to be a more sensitive and reliable tool to monitor changes in optic disc appearance. The use of disc ranking in clinical practice and research studies is recommended to monitor alterations in optic disc appearance until alternative schemes, specific to IIH, have been developed.

Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review.

BACKGROUND: The role of cerebrospinal fluid (CSF) diversion in treating idiopathic intracranial hypertension (IIH) is disputed. METHOD: We conducted a 10-year, retrospective case note review to evaluate the effects of CSF diversion in IIH. Symptoms, signs and details of shunt type, complications and revisions were documented at baseline, 6, 12 and 24 months post-operatively. RESULTS: Fifty-three IIH patients were shunted [predominantly lumboperitoneal (92%)]. The most common symptom pre-surgery was headache (96%). Post-operatively, significantly fewer patients experienced declining vision and visual acuity improved at 6 (p = 0.001) and 12 months (p = 0.016). Headache continued in 68% at 6 months, 77% at 12 months and 79% at 2 years post-operatively. Additionally, post-operative low-pressure headache occurred in 28%. Shunt revision occurred in 51% of patients, with 30% requiring multiple revisions. CONCLUSION: We conclude that CSF diversion reduces visual decline and improves visual acuity. Unfortunately, headache remained in the majority of patients and low-pressure headache frequently complicated surgery. Over half of the patients required shunt revision with the majority of these requiring multiple revisions. We suggest that CSF shunting should be conducted as a last resort in those with otherwise untreatable, rapidly declining vision. Alternative treatments, such as weight reduction, may be more effective with less associated morbidity.

A randomised controlled trial of treatment for idiopathic intracranial hypertension.

The cause of idiopathic intracranial hypertension (IIH) remains unknown, and no consensus exists on how patients should be monitored and treated. Acetazolamide is a common treatment but has never been examined in a randomised controlled trial. The objectives of this pilot trial are to prospectively evaluate the use of acetazolamide, to explore various outcome measures and to inform the design of a definitive trial in IIH. Fifty patients were recruited from six centres over 23 months and randomised to receive acetazolamide (n = 25) or no acetazolamide (n = 25). Symptoms, body weight, visual function and health-related quality-of-life measures were recorded over a 12-month period. Recruited patients had typical features of mild IIH and most showed improvement, with 44% judged to have IIH in remission at the end of the trial. Difficulties with recruitment were highlighted as well as poor compliance with acetazolamide therapy (12 patients). A composite measure of IIH status was tested, and the strongest concordance with final disease status was seen with perimetry (Somers' D = 0.66) and optic disc appearance (D = 0.59). Based on the study data, a sample size of 320 would be required to demonstrate a 20% treatment effect in a substantive trial. Clinical trials in IIH require pragmatic design to involve sufficiently large numbers of patients. Future studies should incorporate weighted composite scores to reflect the relative importance of common outcome measures in IIH.

Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients with idiopathic intracranial hypertension: a link between 11beta-HSD1 and intracranial pressure regulation?

CONTEXT: The etiology of idiopathic intracranial hypertension (IIH) is unknown. We hypothesized that obesity and elevated intracranial pressure may be linked through increased 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity. OBJECTIVE: The aim was to characterize 11ß-HSD1 in human cerebrospinal fluid (CSF) secretory [choroid plexus (CP)] and drainage [arachnoid granulation tissue (AGT)] structures, and to evaluate 11ß-HSD1 activity after therapeutic weight loss in IIH. DESIGN AND SETTING: We conducted in vitro analysis of CP and AGT and a prospective in vivo cohort study set in two tertiary care centers. PATIENTS OR OTHER PARTICIPANTS: Twenty-five obese adult female patients with active IIH were studied, and 22 completed the study. INTERVENTION: Fasted serum, CSF, and 24-h urine samples were collected at baseline, after 3-month observation, and after a 3-month diet. MAIN OUTCOME MEASURES: Changes in urine, serum, and CSF glucocorticoids (measured by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry) after weight loss were measured. RESULTS: 11ß-HSD1 and key elements of the glucocorticoid signaling pathway were expressed in CP and AGT. After weight loss (14.2±7.8 kg; P<0.001), global 11ß-HSD1 activity decreased (P=0.001) and correlated with reduction in intracranial pressure (r=0.504; P=0.028). CSF and serum glucocorticoids remained stable, although the change in CSF cortisone levels correlated with weight loss (r=-0.512; P=0.018). CONCLUSIONS: Therapeutic weight loss in IIH is associated with a reduction in global 11ß-HSD1 activity. Elevated 11ß-HSD1 may represent a pathogenic mechanism in IIH, potentially via manipulation of CSF dynamics at the CP and AGT. Although further clarification of the functional role of 11ß-HSD1 in IIH is needed, our results suggest that 11ß-HSD1 inhibition may have therapeutic potential in IIH.

Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study.

OBJECTIVE: To observe intracranial pressure in women with idiopathic intracranial hypertension who follow a low energy diet. DESIGN: Prospective cohort study. SETTING: Outpatient department and the clinical research facility based at two separate hospitals within the United Kingdom. PARTICIPANTS: 25 women with body mass index (BMI) >25, with active (papilloedema and intracranial pressure >25 cm H(2)O), chronic (over three months) idiopathic intracranial hypertension. Women who had undergone surgery to treat idiopathic intracranial hypertension were excluded. INTERVENTION: Stage 1: no new intervention; stage 2: nutritionally complete low energy (calorie) diet (1777 kJ/day (425 kcal/day)); stage 3: follow-up period after the diet. Each stage lasted three months. MAIN OUTCOME MEASURE: The primary outcome was reduction in intracranial pressure after the diet. Secondary measures included score on headache impact test-6, papilloedema (as measured by ultrasonography of the elevation of the optic disc and diameter of the nerve sheath, together with thickness of the peripapillary retina measured by optical coherence tomography), mean deviation of Humphrey visual field, LogMAR visual acuity, and symptoms. Outcome measures were assessed at baseline and three, six, and nine months. Lumbar puncture, to quantify intracranial pressure, was measured at baseline and three and six months. RESULTS: All variables remained stable over stage 1. During stage 2, there were significant reductions in weight (mean 15.7 (SD 8.0) kg, P<0.001), intracranial pressure (mean 8.0 (SD 4.2) cm H(2)O, P<0.001), score on headache impact test (7.6 (SD 10.1), P=0.004), and papilloedema (optic disc elevation (mean 0.15 (SD 0.23) mm, P=0.002), diameter of the nerve sheath (mean 0.7 (SD 0.8) mm, P=0.004), and thickness of the peripapillary retina (mean 25.7 (SD 36.1) micro, P=0.001)). Mean deviation of the Humphrey visual field remained stable, and in only five patients, the LogMAR visual acuity improved by one line. Fewer women reported symptoms including tinnitus, diplopia, and obscurations (10 v 4, P=0.004; 7 v 0, P=0.008; and 4 v 0, P=0.025, respectively). Re-evaluation at three months after the diet showed no significant change in weight (0.21 (SD 6.8) kg), and all outcome measures were maintained. CONCLUSION: Women with idiopathic intracranial hypertension who followed a low energy diet for three months had significantly reduced intracranial pressure compared with pressure measured in the three months before the diet, as well as improved symptoms and reduced papilloedema. These reductions persisted for three months after they stopped the diet.

NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases--a diagnostic tool?

We sought to evaluate the diagnostic accuracy of metabolomic biomarker profiles in neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) compared to controls with either no neurological disease or mixed neurological diseases). Spectra of CSF (n = 87) and serum (n = 72) were acquired using (1)H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease-specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a second cohort of patients (n = 25). CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity:specificity of 63:75% and 67:75%, respectively). These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease-unique metabolites may also impart information on disease pathology.

Exploring the pathogenesis of IIH: an inflammatory perspective.

Idiopathic intracranial hypertension (IIH) is a common blinding condition amongst the young obese female population (20 per 100,000) characterised by elevated intracranial pressure (ICP). The aetiology of IIH is not known. In this review we explore the literature investigating the pathogenesis of IIH and suggest additional hypotheses. Chronic inflammation is emerging as an aetiological factor in the pathogenesis of obesity and we propose that this may be a feature of IIH. Obesity is also related to dysregulation of cortisol production by the pre-receptor enzyme, 11beta-hydroxysteroid dehydrogenase, and we speculate that this may have a role in the pathogenesis of obesity and raised ICP seen in IIH.