EUNOS 2023 Practical Neuro-Ophthalmology Course: Groningen, The Netherlands, June 1st-2nd, 2023.

The European Neuro-Ophthalmology Society (EUNOS) practical neuro-ophthalmology course, henceforth referred to as the EUNOS course, took place in 2023 in Groningen, the Netherlands. This two-day international event featured a blend of plenary lecture sessions, workshops, and case reports, providing a practical update on fundamental neuro-ophthalmology topics for residents and young specialists in both neurology and ophthalmology.

The Pressure of Headache at the United Kingdom CSF Disorders Day 2023.

Headache in intracranial disorders drives significant disability in our patients. Management principles for secondary headaches require a multidisciplinary approach with expertise from the neurological, neuro-ophthalmological, neuroradiological, and neurosurgical specialities. The Pressure of Headache was the theme of the annual United Kingdom CSF Disorders Day and saw speakers and panellists from Australia, Europe, and the United States. Among the topics presented were the newest concepts underpinning idiopathic intracranial hypertension management and spontaneous intracranial hypotension. Advances in our knowledge of cerebrospinal fluid secretion and the visual snow syndrome debate were particular highlights. This review provides a summary of the research on headache disorders that overlap the neuro-ophthalmological axis of care for patients.

Managing idiopathic intracranial hypertension in the eye clinic.

Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological condition characterised by a raised intracranial pressure and papilloedema that causes disabling headaches. The main risk factors of female sex and living with obesity have been known for some time, however the knowledge of the underlying pathophysiology is evolving. Papilloedema can impact the visual function, and the majority of people are offered acetazolamide. Those with sight threatening disease need urgent management, though there is little high quality evidence to recommend any particular surgical intervention. Headache treatment is an unmet clinical need and simple medication overuse advice has the potential to reduce the chronification of migraine-like headaches. IIH is emerging as a systemic metabolic disease distinct from people living with obesity alone. While weight loss is the main stay of disease modifying therapy this is challenging to access and many healthcare professionals that manage the condition have no formal training or accessible pathways for weight management. The aim of this "how to do it" article is to present the latest advances in knowledge of IIH that we pragmatically included in routine clinical care for people living with the condition.

Risk factors and disease associations in people living with idiopathic intracranial hypertension.

INTRODUCTION: Idiopathic intracranial hypertension is a neurological condition characterized by a raised intracranial pressure and papilledema, leading to chronic headaches and visual disturbances. By recognizing modifiable risk factors and deploying evidence-based interventions, healthcare providers have the potential to mitigate the burden of the disease and improve patient outcomes. AREAS COVERED: It is well known that the condition occurs in predominantly pre-menopausal females who live with obesity particularly in the context of recent weight gain. This review discusses what risk factors may contribute to the metabolic underpinnings of cerebrospinal fluid dysregulation. There are a number of disease associations that are important to screen for as they can alter management. EXPERT OPINION: There is emerging evidence to suggest that idiopathic intracranial hypertension is a systemic metabolic disease and it is unknown what are all the risk factors are that precipitate the condition. Targeting certain hardwired risk factors is unachievable. However, as recent weight gain has been identified as a predominant risk factor for the development of the disease and relapse, modification of body weight should be the primary aim of management. Insightful research into the involvement of the neuroendocrine axis driving cerebrospinal fluid dysregulation now has the potential for the development of therapeutic targets.

Cranial involvement in giant cell arteritis.

Since its first clinical description in 1890, extensive research has advanced our understanding of giant cell arteritis, leading to improvements in both diagnosis and management for affected patients. Imaging studies have shown that the disease frequently extends beyond the typical cranial arteries, also affecting large vessels such as the aorta and its proximal branches. Meanwhile, advances in comprehending the underlying pathophysiology of giant cell arteritis have given rise to numerous potential therapeutic agents, which aim to minimise the need for glucocorticoid treatment and prevent flares. Classification criteria for giant cell arteritis, as well as recommendations for management, imaging, and treat-to-target have been developed or updated in the last 5 years, and current research encompasses a broad spectrum covering basic, translational, and clinical research. In this Series paper, we aim to discuss the current understanding of giant cell arteritis with cranial manifestations, describe the clinical approach to this condition, and explore future directions in research and patient care.

The Impact of Valsalva Manoeuvres and Exercise on Intracranial Pressure and Cerebrovascular Dynamics in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disease characterised by elevated intracranial pressure (ICP). The impact of straining and exercise on ICP regulation is poorly understood yet clinically relevant to IIH patient care. We sought to investigate the impact of Valsalva manoeuvres (VMs) and exercise on ICP and cerebrovascular haemodynamics in IIH. People with IIH were prospectively enrolled and had an intraparenchymal telemetric ICP sensor inserted. Three participants (age [mean ± standard deviation]: 40.3 ± 13.9 years) underwent continuous real-time ICP monitoring coupled with cerebrovascular haemodynamic assessments during VMs and moderate exercise. Participants had IIH with supine ICP measuring 15.3 ± 8.7 mmHg (20.8 ± 11.8 cm cerebrospinal fluid (CSF)) and sitting ICP measuring -4.2 ± 7.9 mmHg (-5.7 ± 10.7 cmCSF). During phase I of a VM ICP increased by 29.4 ± 13.5 mmHg (40.0 ± 18.4 cmCSF) but returned to baseline within 16 seconds from VM onset. The pattern of ICP changes during the VM phases was associated to that of changes in blood pressure, the middle cerebral artery blood velocity and prefrontal cortex haemodynamics. Exercise led to minimal effects on ICP. In conclusion, VM-induced changes in ICP were coupled to cerebrovascular haemodynamics and showed no sustained impact on ICP. Exercise did not lead to prolonged elevation of ICP. Those with IIH experiencing VMs (for example, during exercise and labour) may be reassured at the brief nature of the changes. Future research must look to corroborate the findings in a larger IIH cohort.

A systematic review of optical coherence tomography findings in adults with mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is common with many patients suffering disabling long-term sequelae, with visual symptoms frequently reported. There are no objective biomarkers of mTBI that are routinely used in clinical practice. Optical coherence tomography (OCT) has been used in mTBI research, as it enables visualisation of the neuroretina, allowing measurement of the retinal nerve fibre layer and ganglion cell layer. This systematic review aims to appraise the available literature and assess whether there are significant changes within the retinal nerve fibre layer and ganglion cell layer in subjects after mTBI. A systematic review was carried out in accordance with PRISMA guidelines and registered with PROSPERO (Number: CRD42022360498). Four databases were searched for relevant literature published from inception until 1 September 2022. Abstracts and full texts were screened by three independent reviewers. Initial screening of databases yielded 341 publications, of these, three fulfilled all the criteria for inclusion. All three studies showed thinning of the retinal nerve fibre layer, whereas there were no significant changes in the ganglion cell layer. This systematic review demonstrated that thinning of the retinal nerve fibre layer (but not of the ganglion cell layer) is associated with mTBI. It provides preliminary evidence for the use of the retinal nerve fibre layer as a potential biomarker of damage to the visual system in mTBI. Further prospective longitudinal studies ensuring uniform diagnosis and accurate phenotyping of mTBI are needed to understand the effects on the visual system and potential of OCT as a prognostic biomarker.

Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension.

BACKGROUND: Cognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH. METHODS: This was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks. RESULTS: Cognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315). CONCLUSIONS: In patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Common Design and Data Elements Reported on Idiopathic Intracranial Hypertension Trials: A Systematic Review.

BACKGROUND: There are an increasing number of controlled clinical trials and prospective studies, ongoing and recently completed, regarding management options for idiopathic intracranial hypertension (IIH). We present a Common Design and Data Element (CDDE) analysis of controlled and prospective IIH studies with the aim of aligning essential design and recommending data elements in future trials and enhancing data synthesis potential in IIH trials. METHODS: We used PubMed and ClinicalTrials.gov to screen for ongoing and published trials assessing treatment modalities in people with IIH. After our search, we used the Nested Knowledge AutoLit platform to extract pertinent information regarding each study. We examined outputs from each study and synthesized the data elements to determine the degree of homogeneity between studies. RESULTS: The most CDDE for inclusion criteria was the modified Dandy criteria for diagnosis of IIH, used in 9/14 studies (64%). The most CDDE for outcomes was change in visual function, reported in 12/14 studies (86%). Evaluation of surgical procedures (venous sinus stenting, cerebrospinal fluid shunt placement, and others) was more common, seen in 9/14 studies (64%) as compared with interventions with medical therapy 6/14 (43%). CONCLUSIONS: Although all studies have similar focus to improve patient care, there was a high degree of inconsistency among studies regarding inclusion criteria, exclusion criteria, and outcomes measures. Furthermore, studies used different time frames to assess outcome data elements. This heterogeneity will make it difficult to achieve a consistent standard, and thus, making secondary analyses and meta-analyses less effective in the future. Consensus on design of trials is an unmet research need for IIH.

Weight management communications in idiopathic intracranial hypertension: challenges and recommendations from the patients' perspective.

Background: Idiopathic intracranial hypertension (IIH) is a neurometabolic condition severely impacting the quality of life of people living with IIH (PwIIH). Most PwIIH are overweight or live with obesity, and weight loss is recommended by healthcare professionals (HCPs) as it is central to disease management. There is currently no research evaluating patient-clinician interactions when discussing weight management in IIH. The aim of this study was to evaluate the patient experience of communication with HCPs regarding weight management from the perspective of PwIIH. Methods: A cross-sectional online survey was developed and distributed by the IIH UK charity via their mailing list and social media network. Eligible participants were adults with IIH who have been recommended to lose weight by their HCP. Descriptive statistics were used to summarise quantitative responses and content analysis was used to inductively draw out themes from open-ended free-text responses. Results: There were 625 respondents. One-fifth of PwIIH (n=127/603, 21%) felt that HCPs were supportive and empathetic about weight management. Five themes were identified on how experiences regarding weight management for IIH can be improved, with PwIIH recommending for HCPs to: (1) detail the relationship between IIH and weight, (2) individualise care, (3) give advice, (4) provide support and (5) adapt communication. Conclusion: The majority of PwIIH recalled a poor experience and negative emotions when engaged in discussions regarding weight management with their HCPs. Further research should explore the HCPs perspective and evaluate interventions aiming to improve the quality of patient-HCPs communication in IIH.

Experimental drugs for the treatment of idiopathic intracranial hypertension (IIH): shedding light on phase I and II trials.

INTRODUCTION: Idiopathic intracranial hypertension is a neurological condition characterized by a raised intracranial pressure and papilledema that causes debilitating headaches. While the extent of the pathophysiology is being discovered, the condition is emerging as a systemic metabolic disease distinct to people living with obesity alone. Idiopathic intracranial hypertension is becoming more common and therefore establishing licensed therapeutics is a key priority. AREA COVERED: The translation of preclinical work in idiopathic intracranial hypertension is evident by the two early phase trials evaluating 11-ß-hydroxysteroid dehydrogenase inhibitor, AZD4017, and a glucagon like peptide-1 receptor agonist, Exenatide. This review summarizes these two early phase trials evaluating targeted medicines for the treatment of intracranial pressure. The modulation of these two distinct mechanisms have potential for therapeutic intervention in people living with idiopathic intracranial hypertension. EXPERT OPINION: The clinical trial landscape in idiopathic intracranial hypertension is a challenge due to the rarity of the disease and the lack of agreed meaningful trial outcomes. Further preclinical work to fully understand the pathogenesis is required to enable personalized targeted drug treatment.

Idiopathic intracranial hypertension: a step change in understanding the disease mechanisms.

The understanding of idiopathic intracranial hypertension (IIH) has evolved over the past few years. Previously, IIH was considered a disease exclusively affecting the neuro-ophthalmic axis, characterized by raised intracranial pressure, headache and papilloedema, and resulting in the risk of severe and permanent visual loss and life-changing disabling headaches. Recent advances have begun to redefine IIH as a probable metabolic disease involving a range of systemic manifestations. More than 95% of individuals affected by the disease are women of reproductive age with obesity. The incidence is rapidly rising and parallels the escalating worldwide obesity rates. Contemporary insights identify associations with insulin resistance, type 2 diabetes and a twofold increased risk of cardiovascular disease in excess of that driven by obesity alone. Adipose distribution in people with IIH, like that in other metabolic diseases, is preferentially centripetal and is associated with changes in intracranial pressure. Evidence now demonstrates adipose tissue dysfunction in people with IIH, involving transcriptional and metabolic priming for lipogenesis and weight gain. Hormonal perturbations are also observed, including a unique phenotype of androgen excess that promotes cerebrospinal fluid secretion. Knowledge of these additional disease features is driving research into novel therapeutic targets and altering the approach to multidisciplinary care.

Determining the role of novel metabolic pathways in driving intracranial pressure reduction after weight loss.

Idiopathic intracranial hypertension, a disease classically occurring in women with obesity, is characterized by raised intracranial pressure. Weight loss leads to the reduction in intracranial pressure. Additionally, pharmacological glucagon-like peptide-1 agonism reduces cerebrospinal fluid secretion and intracranial pressure. The potential mechanisms by which weight loss reduces intracranial pressure are unknown and were the focus of this study. Meal stimulation tests (fasted plasma sample, then samples at 15, 30, 60, 90 and 120 min following a standardized meal) were conducted pre- and post-bariatric surgery [early (2 weeks) and late (12 months)] in patients with active idiopathic intracranial hypertension. Dynamic changes in gut neuropeptides (glucagon-like peptide-1, gastric inhibitory polypeptide and ghrelin) and metabolites (untargeted ultra-high performance liquid chromatography-mass spectrometry) were evaluated. We determined the relationship between gut neuropeptides, metabolites and intracranial pressure. Eighteen idiopathic intracranial hypertension patients were included [Roux-en-Y gastric bypass (RYGB) n = 7, gastric banding n = 6 or sleeve gastrectomy n = 5]. At 2 weeks post-bariatric surgery, despite similar weight loss, RYGB had a 2-fold (50%) greater reduction in intracranial pressure compared to sleeve. Increased meal-stimulated glucagon-like peptide-1 secretion was observed after RYGB (+600%) compared to sleeve (+319%). There was no change in gastric inhibitory polypeptide and ghrelin. Dynamic changes in meal-stimulated metabolites after bariatric surgery consistently identified changes in lipid metabolites, predominantly ceramides, glycerophospholipids and lysoglycerophospholipids, which correlated with intracranial pressure. A greater number of differential lipid metabolites were observed in the RYGB cohort at 2 weeks, and these also correlated with intracranial pressure. In idiopathic intracranial hypertension, we identified novel changes in lipid metabolites and meal-stimulated glucagon-like peptide-1 levels following bariatric surgery which were associated with changes in intracranial pressure. RYGB was most effective at reducing intracranial pressure despite analogous weight loss to gastric sleeve at 2 weeks post-surgery and was associated with more pronounced changes in these metabolite pathways. We suggest that these novel perturbations in lipid metabolism and glucagon-like peptide-1 secretion are mechanistically important in driving a reduction in intracranial pressure following weight loss in patients with idiopathic intracranial hypertension. Therapeutic targeting of these pathways, for example with glucagon-like peptide-1 agonist infusion, could represent a therapeutic strategy.

A Neuro-Ophthalmologist's Guide to Advances in Intracranial Pressure Measurements.

Cerebrospinal fluid disorders have a wide-ranging impact on vision, headache, cognition and a person's quality of life. Due to advances in technology and accessibility, intracranial pressure measurement and monitoring, usually managed by neurosurgeons, are being employed more widely in clinical practice. These developments are of direct importance for Ophthalmologists and Neurologists because the ability to readily measure intracranial pressure can aide management decisions. The aim of this review is to present the emerging evidence for intracranial pressure measurement methods and interpretation that is relevant to Neuro-ophthalmologists.

Weight Management Interventions for Adults With Idiopathic Intracranial Hypertension: A Systematic Review and Practice Recommendations.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this systematic review was to evaluate weight loss interventions in people with IIH to determine which intervention is superior in terms of weight loss, reduction in intracranial pressure (ICP), benefit to visual and headache outcomes, quality of life, and mental health. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42023339569). MEDLINE and CINAHL were searched for relevant literature published from inception until December 15, 2022. Screening and quality appraisal was conducted by 2 independent reviewers. Recommendations were graded using Scottish Intercollegiate Guidelines Network methodology. RESULTS: A total of 17 studies were included. Bariatric surgery resulted in 27.2-27.8 kg weight loss at 24 months (Level 1- to 1++). Lifestyle weight management interventions resulted in between 1.4 and 15.7 kg weight loss (Level 2+ to 1++). Bariatric surgery resulted in the greatest mean reduction in ICP (-11.9 cm H2O) at 24 months (Level 1++), followed by multicomponent lifestyle intervention + acetazolamide (-11.2 cm H2O) at 6 months (Level 1+) and then a very low-energy diet intervention (-8.0 cm H2O) at 3 months (Level 2++). The least ICP reduction was shown at 24 months after completing a 12-month multicomponent lifestyle intervention (-3.5 cm H2O) (Level 1++). Reduction in body weight was shown to be highly correlated with reduction in ICP (Level 2++ to 1++). DISCUSSION: Bariatric surgery should be considered for women with IIH and a body mass index (BMI) ≥35 kg/m2 since this had the most robust evidence for sustained weight management (grade A). A multicomponent lifestyle intervention (diet + physical activity + behavior) had the most robust evidence for modest weight loss with a BMI <35 kg/m2 (grade B). Longer-term outcomes for weight management interventions in people with IIH are required to determine whether there is a superior weight loss intervention for IIH.

Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

A Datasheet for the INSIGHT University Hospitals Birmingham Retinal Vein Occlusion Data Set.

Purpose: Retinal vein occlusion (RVO) is the second leading cause of visual loss due to retinal disease. Retinal vein occlusion increases the risk of cardiovascular mortality and the risk of stroke. This article describes the data contained within the INSIGHT eye health data set for RVO and cardiovascular disease. Design: Data set descriptor for routinely collected eye and systemic disease data. Participants: All people who had suffered an RVO aged ≥ 18 years old, attending the Ophthalmology Clinic at Queen Elizabeth Hospital, University Hospitals Birmingham (UHB) National Health Service (NHS) Trust were included. Methods: The INSIGHT Health Data Research Hub for Eye Health is an NHS-led ophthalmic bioresource. It provides researchers with safe access to anonymized routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT UHB RVO and major adverse cardiovascular events data set, a data set of ophthalmology and systemic data derived from the United Kingdom's largest acute care trust. Main Outcome Measures: This data set consists of routinely collected data from the hospital's electronic patient records. The data set primarily includes structured data (relating to their hospital eye care and any cardiovascular data held for the individual) and OCT ocular images. Further details regarding the available data points are available in the supplementary information. Results: At the time point of this analysis (September 30, 2022) the data set was composed of clinical data from 1521 patients, from Medisoft records inception. The data set includes 2196 occurrences of RVO affecting 2026 eyes, longitudinal eye follow-up clinical parameters, over 6217 eye-related procedures, and 982 encountered complications. The data set contains information on 2534 major adverse cardiovascular event occurrences, their subtype, number experienced per patient, and chronological relation to RVO event. Longitudinal follow-up data including laboratory results, regular medications, and all-cause mortality are also available within the data set. Conclusions: This data set descriptor article summarizes the data set contents, the process of its curation, and potential uses. The data set is available through the structured application process that ensures research studies are for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.