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 characterised by raised intracranial pressure. Weight loss leads to 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 was the focus for this study.Meal stimulation tests (fasted plasma sample, then samples at 15, 30, 60, 90 and 120 minutes following a standardised 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.18 idiopathic intracranial hypertension patients were included (Roux-En-Y gastric bypass n=7, gastric banding n=6, or sleeve gastrectomy n=5). At 2 weeks post-bariatric surgery, despite similar weight loss, Roux-En-Y gastric bypass had a two-fold (50%) greater reduction in intracranial pressure compared to sleeve. Increased meal stimulated glucagon-like peptide-1 secretion was observed after Roux-En-Y gastric bypass (+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 Roux-En-Y gastric bypass 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. Roux-En-Y gastric bypass 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 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

The effect of GLP-1RA exenatide on idiopathic intracranial hypertension:a randomized clinical trial

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure &gt;25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.</p

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

Implementing a COVID-19 vaccination outreach service for people experiencing homelessness

Issue addressed: In 2021, the Australian government implemented a population wide COVID-19 vaccination program. People experiencing homelessness faced challenges accessing vaccines and many were not being reached. By reorienting vaccination services to include assertive outreach strategies, a Brisbane-based nonprofit healthcare team successfully administered 2065 COVID-19 vaccinations to homeless and precariously housed people. This study examines insights from stakeholders delivering the service and perspectives of clients who received a vaccine. Methods: Semi-structured interviews with five stakeholders and a survey of 63 clients involved in the Micah Projects COVID-19 vaccination program are reported. Client survey questions covered demographic characteristics, and motivations and hesitancies around vaccination. Stakeholder interviews were inductively analysed and quantitative survey data were exported into SPSS (IBM V27) and analysed using descriptive statistics. Results: The Micah Projects team initiated 220 pop-up vaccination clinics and worked closely with Aboriginal and Torres Strait Islander communities. Downsizing and mobilising the service engaged greater numbers of people sleeping rough and Aboriginal and Torres Strait Islander people. Clients’ decisions to vaccinate were often spontaneous, driven by immediate availability and motivated by a desire to stay healthy and protect the community. Conclusions: Tailoring vaccination programs to include assertive outreach strategies effectively reduces barriers for people experiencing homelessness. Community embeddedness, trust, flexibility and cultural safety are critical elements for success

Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: A narrative review.

OBJECTIVE Headache is a near-universal sequela of idiopathic intracranial hypertension (IIH). The aim of this paper is to report current knowledge of headache in IIH and to identify therapeutic options. BACKGROUND Disability in IIH is predominantly driven by headache; thus, headache management is an urgent and unmet clinical need. At present, there is currently no scientific evidence for the directed use of abortive or preventative headache therapy. METHODS A detailed search of the scientific literature and narrative review was performed. RESULTS Headache in IIH is driven by raised intracranial pressure (ICP) and reduction of ICP has been reported in some studies to reduce headache. Despite resolution of papilledema and normalization of raised ICP, a majority suffer persistent post-IIH headache. The lack of evidence-based management approaches leaves many untreated. Where clinicians attempt to manage IIH headache, they use off-label therapies to target the prevailing headache phenotype. A recent prospective open-label study demonstrated the effective use of a calcitonin gene-related peptide monoclonal antibody therapy in IIH for persistent post-IIH headache. CONCLUSIONS There is overwhelming evidence of the headache burden in IIH. Studies are required to investigate the biological foundations of headache related to ICP and to develop treatments specifically directed to manage headache in IIH

New horizons for idiopathic intracranial hypertension: advances and challenges.

INTRODUCTION Idiopathic intracranial hypertension (IIH) is becoming a recognized condition due to the increasing incidence linked to a global obesity epidemic. SOURCES OF DATA All English papers on PubMed, Cochrane and Scholar between inception until 1 March 2020 were considered. AREAS OF AGREEMENT Studies suggest central adiposity has a pathogenic role. Recent weight gain is a risk factor and weight loss has a key role in management. AREAS OF CONTROVERSY Interpretation of abnormal lumbar puncture opening pressure is debated. There is an increasing recognition of obesity stigma and how this should be approached. GROWING POINTS Further evidence is required for the choice of surgical intervention for fulminant IIH. Education regarding IIH should be evidence based. AREAS TIMELY FOR DEVELOPING RESEARCH Novel research of the pathology of IIH is influencing development of therapies such as glucagon-like peptide-1 receptor agonists and targeting unique androgen signatures. The newly discovered cardiovascular risk requires further attention

Optimizing Access to the COVID-19 Vaccination for People Experiencing Homelessness

The success of the Australian COVID-19 vaccination strategy rested on access to primary healthcare. People experiencing or at risk of homelessness are less likely to access primary healthcare services. Therefore, leaders in homeless health service delivery in Sydney identified the need to develop a vaccine hub specifically for this vulnerable population. The aim of this study was to develop an evidenced based model of care to underpin the Vaccine Hub and optimize access to vaccination for people experiencing or at risk of homelessness. A mixed methods study was conducted that included interviews with key stakeholders involved in establishing and delivering the Inner City COVID-19 Vaccine Hub, and a survey with people receiving COVID-19 vaccination. Over the 6-month period of this study, 4305 COVID-19 vaccinations were administered. Partici-pants receiving vaccination reported feeling safe in the Vaccine Hub and would recommend it to others. Stakeholders paid tribute to the collective teamwork of the Vaccine Hub, the collaboration between services, the ‘no wrong door’ approach to increasing access and the joy of being able to support such a vulnerable population in challenging times. The study findings have been popu-lated into a Vaccination Hub Blueprint document that can be used as a template for others to improve access to vaccinations for vulnerable populations

Current Perspectives on Idiopathic Intracranial Hypertension without Papilloedema.

The pseudotumor cerebri syndrome embraces disorders characterised by raised intracranial pressure, where the commonest symptom is headache (90%). Idiopathic intracranial hypertension without papilloedema (IIHWOP) is increasingly recognised as a source of refractory headache symptoms and resultant neurological disability. Although the majority of patients with IIHWOP are phenotypically similar to those with idiopathic intracranial hypertension (IIH), it remains uncertain as to whether IIHWOP is nosologically distinct from IIH. The incidence, prevalence, and the degree of association with the world-wide obesity epidemic is unknown. Establishing a diagnosis of IIHWOP can be challenging, as often lumbar puncture is not routinely part of the work-up for refractory headaches. There are published diagnostic criteria for IIHWOP; however, some report uncertainty regarding a pathologically acceptable cut off for a raised lumbar puncture opening pressure, which is a key criterion. The literature provides little information to help guide clinicians in managing patients with IIHWOP. Further research is therefore needed to better understand the mechanisms that drive the development of chronic daily headaches and a relationship to intracranial pressure; and indeed, whether such patients would benefit from therapies to lower intracranial pressure. The aim of this narrative review was to perform a detailed search of the scientific literature and provide a summary of historic and current opinion regarding IIHWOP