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Objective Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure. Methods IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed. Results Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p Conclusions We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures. Trial registration This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486.

The understanding of raised intracranial pressure (ICP) is increasing with the directed use of intracranial telemetric ICP monitors. This case uniquely observed ICP changes by telemetric monitoring in a patient with idiopathic intracranial hypertension (IIH), who developed rapid sight-threatening disease. A lumbar drain was inserted, as a temporising measure, and was clamped prior to surgery. This resulted in a rapid rise in ICP, which normalised after insertion of a ventriculoperitoneal shunt. This case highlighted the utility of the ICP monitor and the lumbar drain as a temporising measure to control ICP prior to a definitive procedure as recommended by the IIH consensus guidelines.

There is increasing evidence and appreciation of idiopathic intracranial hypertension (IIH) in medicine. The pathological processes underlying raised intracranial pressure are being studied, with new insights found in both hormonal dysregulation and the metabolic neuroendocrine axis. These will potentially lead to novel therapeutic targets for IIH. The first consensus guidelines have been published on the investigation and management of adult IIH, and the International Headache Society criteria for headache attributable to IIH have been modified to reflect our evolving understanding of IIH. Randomized clinical trials have been published, and a number of studies in this disease area are ongoing.

With increasing incidence and prevalence of Idiopathic intracranial hypertension in the UK, the aim of this study was to explore emerging themes in Idiopathic intracranial hypertension using the Hospital Episode Statistics dataset and to quantify recent change in hospital admissions and surgeries performed within England. Methods: Hospital Episode Statistics national data was extracted between 1 April 2002 and 31 March 2019, and followed up until 31 March 2020. All those within England with a diagnosis of Idiopathic Intracranial Hypertension were included. Those with secondary causes of raised intracranial pressure such as tumors, hydrocephalus and cerebral venous sinus thrombosis were excluded. Results: 28,794 new IIH cases were diagnosed between 1 January 2002 and 31 December 2019. Incidence rose between 2002 to 2019 from 1.8 to 5.2 per 100,000 in the general population. Peak incidence occurred in females aged 25–29 years. Neurosurgical shunt was the commonest procedure performed (6.4%), followed by neovascular venous sinus stenting (1%), bariatric surgery (0.8%) and optic nerve sheath fenestration (0.5%). The portion of the total IIH population requiring a shunt fell from 10.8% in 2002/2003 to 2.46% in 2018/2019. The portion of the total IIH population requiring shunt revision also reduced over time from 4.84% in 2002/2003 to 0.44% in 2018/2019. The mean 30 days emergency readmissions for primary shunt, revision of shunt, bariatric surgery, neurovascular stent, and optic nerve sheath fenestration was 23.1%, 23.7%, 10.6%, 10.0% and 9.74%, respectively. There was a peak 30 days readmission rate following primary shunt in 2018/2019 of 41%. Recording of severe visual impairment fell to an all-time low of 1.38% in 2018/19. Conclusions: Increased awareness of the condition, specialist surgery and expert guidance may be changing admissions and surgical trends in IIH. The high 30 readmission following primary shunt surgery for IIH requires further investigation.

Background: The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) established the efficacy of bariatric surgery as compared to a community weight management intervention in reducing intracranial pressure in active IIH. The aim of this cost-effectiveness analysis was to evaluate the economic impact of these weight loss treatments for IIH. Methods: IIH:WT was a five-year randomised, controlled, parallel group, multicentre trial in the United Kingdom, where participants with active IIH and a body mass index ≥35 kg/m2 were randomly assigned (1:1) to receive access to bariatric surgery or a community weight management intervention. All clinical and quality of life data was recorded at baseline, 12 and 24 months. Economic evaluation was performed to assess health-care costs and cost-effectiveness. Evaluations were established on an intention to treat principle, followed by a sensitivity analysis using a per protocol analysis. Results: The mean total health care costs were GBP 1353 for the community weight management arm and GBP 5400 for the bariatric surgery arm over 24 months. The majority of costs for the bariatric surgery arm relate to the surgical procedure itself. The 85% who underwent bariatric surgery achieved a 12.5% reduction in intracranial pressure at 24 months as compared to 39% in the community weight management arm, a mean difference of 45% in favour of bariatric surgery. The cost effectiveness of bariatric surgery improved over time. Conclusions: The IIH:WT was the first to compare the efficacy and cost-effectiveness of bariatric surgery with community weight management interventions in the setting of a randomised control trial. The cost-effectiveness of bariatric surgery improved over time and therefore the incremental cost of surgery when offset against the incremental reduction of intracranial pressure improved after 24 months, as compared with 12 months follow up.

Investigating potential cerebrospinal fluid (CSF) shunt malfunction can be a challenge. Optical coherence tomography (OCT), a non-invasive imaging technique, is used to monitor changes at the optic nerve head in papilloedema. Conventional teaching suggests that in the presence of optic atrophy the optic nerve head may not re-swell in response to a relapse in raised intracranial pressure (ICP).A retrospective case series of three patients who had prior CSF diversion surgery for idiopathic intracranial cranial hypertension (IIH) is presented demonstrating the benefit of non-invasive OCT imaging confirming raised ICP.Recurrence of raised ICP, due to malfunctioning CSF shunt, was diagnosed in three patients requiring further surgical intervention. All re-presented acutely with headache and visual disturbances. All had a prior diagnosis of optic atrophy. In all patients, OCT peripapillary retinal nerve fibre layer qualitative image analysis and quantified progression analysis permitted easy detection of the recurrence of papilloedema.OCT imaging supports clinical decision making in shunt malfunction, even in the presence of established optic atrophy secondary to IIH.

Idiopathic Intracranial Hypertension (IIH) is a debilitating disorder characterised by raised intracranial pressure (ICP), papilloedema with the potential risk of permanent visual loss, and headaches that are profoundly disabling and reduce the quality of life. The first consensus guidelines have been published on investigation and management of adult IIH and one key area of uncertainty is the utility of dural venous sinus stenting for the management of headache and visual loss. There are an increasing number of series published and to help understand the successes and complications. During a patient physician priority setting, the understanding of the best type of intervention to treat IIH was assigned to the top 10 of most desired research questions for the disease. Ultimately randomised clinical trials (RCTs) in neurovascular stenting for IIH would be instructive, as the literature to date may suffer from publication bias. Due to the increasing incidence of IIH, there is no better time to systematically investigate interventions that may reverse the disease process and achieve remission. In this review we discuss the pathophysiology of IIH in relation to venous sinus stenosis, the role of venous sinus stenting with a review of the relevant literature, the advantages and disadvantages of stenting compared with other surgical interventions, and the future of stenting in the treatment of IIH.

The landscape of the investigation and management of giant cell arteritis (GCA) is advancing. In this review we will outline the recent advances by searching the current English literature for relevant articles using key words of giant cell arteritis, temporal arteritis, Horton's disease, investigation, and treatment. Delay in diagnosis, diagnostic uncertainty and glucocorticoid (GC) morbidity are among the highest concerns of clinicians and patients in this disease area. The positive news is that fast track pathways, imaging techniques and new therapies are emerging for routine management of GCA. Future directions for intervention in the treatment paradigm will be discussed.摘要: 巨细胞动脉炎 (GCA) 的诊疗发生了很大进展。在这篇综述中, 我们通过关键词搜索目前相关的英文文献, 以总结和回顾巨细胞动脉炎的最新进展。所使用的关键词为巨细胞动脉炎; 颞动脉炎; 霍顿病;观察;治疗等。在GCA疾病领域内, 临床医生和患者们最关注的问题是诊断延迟, 诊断不确定性和糖皮质激素 (GC) 的使用情况。好消息是诊疗快速通道的建立, 成像技术以及新治疗的日新月异已经应用于GCA的常规管理。在本文中我们也会探讨治疗、干预策略的新方向。.

IntroductionAtraumatic needles are associated with a decreased incidence of postdural-puncture headache. They also reduce the need for additional treatment and have similar efficacy to conventional needles. The aim of this Quality Improvement Project (QIP) was to encourage the use of atraumatic needles in Neurology ambulatory care by developing a sustainable Lumbar Puncture (LP) training method.MethodsA specialised atraumatic needle training video was guru.kumar@nhs.net created for junior doctors starting in Neurology. This accompanied further teaching and opportunities to practice LPs on a simulation mannequin under supervision. Atraumatic needles were added to standard stock and supply was ensured.Two audit cycles recorded the number of LPs performed using an atraumatic needle. Patient age, body mass index, length of stay, pain experienced and any need for image guidance were also recoded. Junior doctor confidence was measured before and after training.Results81 LPs were performed in the first cycle, 83 in the second. Atraumatic needle use increased from 26% to 50% between cycles. Junior doctor confidence increased with training from 2/10 to 8/10 (p=0.02).ConclusionsDedicated induction teaching and observed simulation practice increased junior doctors’ confidence in, and frequency of, the use of atraumatic needles.

Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% (p = 0.0009) and 21% (p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% (p = 0.018), compared to 5% reduction with acetazolamide (p = >0.999). Conclusion Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.

There is increasing interest in using neurostimulation to treat headache disorders. There are now several non-invasive and invasive stimulation devices available with some open-label series and small controlled trial studies that support their use. Non-invasive stimulation options include supraorbital stimulation (Cefaly), vagus nerve stimulation (gammaCore) and single-pulse transcranial magnetic stimulation (SpringTMS). Invasive procedures include occipital nerve stimulation, sphenopalatine ganglion stimulation and ventral tegmental area deep brain stimulation. These stimulation devices may find a place in the treatment pathway of headache disorders. Here, we explore the basic principles of neurostimulation for headache and overview the available methods of neurostimulation.

Background Management of Idiopathic Intracranial Hypertension (IIH) aims to reduce intracranial pressure (ICP). Acetazolamide is the most commonly used drug, with class 1 evidence demonstrating modest improvement in patients with mild visual loss. Other drugs used include Topiramate, Furosemide, Amiloride and Octreotide, despite little mechanistic or clinical evidence to support their use. The aim of this study was to ascertain which of these drugs has the greatest effect on lowering ICP in-vivo. Methods Using a validated epidural ICP recording method we measured changes in ICP in conscious female rodents after subcutaneous administration of these drugs at clinically equivalent and supra-clinical doses over 2 hours (peak plasma concentrations). Results At clinical doses, Topiramate lowered ICP by 32% (p=0.0009) compared to a 25% reduction for Acetazolamide (p=0.0081). Post-hoc analysis showed no significant difference between the two (p=0.85). Furosemide, Amiloride and Octreotide had no significant effect. Conclusion Our in-vivo studies have demonstrated that, at clinically equivalent doses, Topiramate significantly lowers ICP and is as effective as acetazolamide. Topiramate may have additional advantages in IIH, including its migraine prevention properties and weight loss effects. These findings support the need for future randomised controlled trials evaluating the therapeutic efficacy of topiramate in IIH.

While developing a synthesis towards tagged dizocilpine (MK-801) analogues, we observed highly restricted inversion of a nitrogen centre in a number hydroxylamines obtained as key intermediates. These compounds are shown to possess some of the structural elements which are expected to significantly hinder the nitrogen inversion, potentially leading to hydroxylamines with a chiral nitrogen centre. Free energy barriers (DG6¼) of the nitrogen inversion were estimated to be ca. 22 kcal molS1 at temperatures near 420 K using variable temperature NMR measurements in DMSO-d6. Further density functional studies of a number model systems were undertaken in order to better rationalize the measured inversion barriers and follow the role of various structural factors in raising the barrier height of the nitrogen inversion process.

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.

Current therapies for reducing raised intracranial pressure (ICP) in conditions such as idiopathic intracranial hypertension (IIH) have limited efficacy and tolerability; therefore there is an urgent need to develop novel therapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used therapeutically to treat diabetes and promote weight loss but have also been shown to affect fluid homeostasis in the kidney. The GLP-1R is also present in the choroid plexus, therefore we investigated whether Exendin-4, a GLP-1R agonist, is able to modulate cerebrospinal fluid (CSF) secretion at the choroid plexus and subsequently reduce ICP. We used in vitro models of the choroid plexus to demonstrate the presence of the GLP-1R and, after Exendin-4 treatment, showed a two fold increase in cAMP, a downstream signaling molecule. We also determine that treatment with Exendin-4 reduces Na+ K+ ATPase activity, a key regulator of CSF secretion. Finally, we demonstrate that administration of Exendin-4 in normal and raised ICP (hydrocephalic) rats significantly reduces ICP. These findings provide the first proof of concept that GLP-1R agonists can affect CSF secretion and ICP. Repurposing existing GLP-1 drugs may represent a novel therapeutic strategy for conditions of raised ICP including IIH, hydrocephalus and traumatic brain injury.

Dystonia complicating homocystinuria is extremely rare in the absence of thromboembolic disease. We report a unique case of recurrent dystonia in a patient with homocystinuria secondary to pyridoxine-unresponsive cystathionine β-synthase deficiency. Brain MRI was normal. Two biochemical markers for homocystinuria, homocystine and methionine, were markedly elevated during periods when our patient manifested dystonia. These findings suggest that accumulation of sulfur-containing amino acids may contribute to the pathophysiology of dystonia in patients with homocystinuria. © 2006 Movement Disorder Society