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.

Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study.

Background: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure occurring predominantly in women with obesity. The pathogenesis is not understood. We have applied untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry to characterize the cerebrospinal fluid (CSF) and serum in IIH compared to control subjects. Methods and findings: Samples were collected from IIH patients (n = 66) with active disease at baseline and again at 12 months following therapeutic weight loss. Control samples were collected from gender- and weight-matched healthy controls (n = 20). We identified annotated metabolites in CSF, formylpyruvate and maleylpyruvate/fumarylpyruvate, which were present at lower concentrations in IIH compared to control subjects and returned to values observed in controls following weight loss. These metabolites showed the opposite trend in serum at baseline. Multiple amino acid metabolic pathways and lipid classes were perturbed in serum and CSF in IIH alone. Serum lipid metabolite pathways were significantly increased in IIH. Conclusions: We observed a number of differential metabolic pathways related to amino acid, lipid, and acylpyruvate metabolism, in IIH compared to controls. These pathways were associated with clinical measures and normalized with disease remission. Perturbation of these metabolic pathways provides initial understanding of disease dysregulation in IIH.

Asymptomatic idiopathic intracranial hypertension: Prevalence and prognosis.

BACKGROUND: Little is known about the presentation and prognosis of asymptomatic idiopathic intracranial hypertension (IIH). Papilloedema can be found incidentally on routine fundus examination, with many of these patients actually having symptoms on direct questioning. The aim was to evaluate visual and headache outcomes in people with IIH who present with or without symptoms. METHODS: Prospective observational cohort study, between 2012 and 2021, 343 people with confirmed IIH diagnosis were enrolled in the IIH:Life database. Outcomes such as vision (LogMAR); Humphrey visual field perimetric mean deviation (PMD) and optical coherence tomography (OCT) and headache were evaluated using LOESS (locally weighted scatterplot smoothing) graphs and regression analysis. RESULTS: One hundred and twenty-one people had incidentally found papilloedema, with 36 people with completely asymptomatic presentations. Those with asymptomatic IIH at diagnosis had similar visual prognosis compared to those with symptomatic disease. Sixty-six percent of the asymptomatic cohort became symptomatic during follow-up, and of these the predominant symptom was headache (96%). Headache frequency during follow-up was lower in the asymptomatic cohort. CONCLUSIONS: The prognosis of those with IIH who present with or without symptoms is similar.

Co-morbid Polycystic Ovarian Syndrome with Idiopathic Intracranial Hypertension.

The link between polycystic ovarian syndrome (PCOS) and idiopathic intracranial hypertension (IIH) has long been debated. Historically, there is a wide range of reported occurrence of both conditions, being between 15% and 64%. Both conditions share a common phenotype. The awareness that in a new large data study that there is a 1.5-fold increased prevalence of diagnosed PCOS in participants with IIH as compared to the controls is important. Assessment for the potential of co-morbid PCOS in women with IIH is important as this may enable optimisation of weight and fertility management.

Different Characteristics of Pre-Pubertal and Post-Pubertal Idiopathic Intracranial Hypertension: A Narrative Review.

Idiopathic intracranial hypertension (IIH) affects both children and adults. There are currently no clinical trials in IIH for those who are adolescents or children. The aims of this narrative review were to characterise the differences between pre- and post-pubertal IIH and to highlight the need to be more inclusive in clinical trial planning and recruitment. A detailed search of the scientific literature was performed using the PubMed database, from inception until 30 May 2022 using keywords. This included English language papers only. The abstracts and full texts were reviewed by two independent assessors. The literature revealed that the pre-pubertal group had a more variable presentation. The presenting features in the post-pubertal paediatric group were more akin to adults with headache as the dominant feature. They were also more likely to be female and have an increased body mass index. A clear limitation of the literature was that a number of paediatric studies had variable inclusion criteria, including secondary causes of raised intracranial pressure. Pre-pubertal children do not display the same predilection towards the female sex and obesity as post-pubertal children, who have a similar phenotype to the adult cohort. Inclusion of adolescents in clinical trials should be considered given the similar phenotype to adults. There is a lack of consistency in the definition of puberty, making the IIH literature difficult to compare. Inclusion of secondary causes of raised intracranial pressure has the potential to confound the accuracy of analysis and interpretation of the results.

Idiopathic intracranial hypertension: Evaluation of births and fertility through the Hospital Episode Statistics dataset.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) predominantly affects women of reproductive age with obesity, and these women have a distinct profile of hyperandrogenism and insulin resistance. Polycystic ovary syndrome (PCOS) has an established adverse fertility phenotype that typically affects obese women. As IIH may impact reproductive health, we sought to evaluate fertility, gestational complications and pregnancy outcome in IIH. DESIGN: Prospective cohort study from English Hospital Episode Statistics dataset. SETTING: English hospitals, UK. POPULATION: Women aged 18-45 years seen in English hospitals between 1 April 2002 and 31 March 2019. Patients were required to have an IIH diagnosis and were compared with those with PCOS and general population female controls. MAIN OUTCOME MEASURES: Pregnancies resulting in live births, complications of gestational diabetes and pre-eclampsia, and method of delivery. RESULTS: Data was collected from 17 587 IIH, 199633 PCOS and 10 947 012 women in the general population. The live birth rate, adjusted for age, was significantly lower among women with IIH (54.1%) than PCOS (67.9%), p < 0.0001 and the general population (57.7%), p < 0.0001. Pre-eclampsia and gestational diabetes risks were higher following a diagnosis of IIH (5.3-fold and 2.7-fold, respectively, p < 0.0001) compared with the general population controls. Following a diagnosis of IIH, elective caesarean section rates were more than twice that of general population (odds ratio [OR] 2.4) and prior to a diagnosis of IIH (OR 2.2). CONCLUSIONS: These data indicate there are lower age-adjusted total pregnancy rates, increased risk of pre-eclampsia and gestational diabetes, and a doubling of elective caesarean section rates in those with a diagnosis of IIH.

Cerebral lipiodol embolisation.

Cerebral lipiodol embolisation is a rare but serious complication of lymphangiography. A man in his seventies had undergone lymphangiography for a refractory chyle leak following oesophagectomy. The day after lymphangiography, his conscious level dropped with bilaterally miotic pupils, increased muscle tone and double incontinence. CT scan of the head showed patchy high density throughout basal ganglia, cortex and cerebellum but no infarct, in keeping with lipiodol embolisation. He was managed initially in intensive care and subsequently underwent thoracoscopy with clipping and suturing of the left thoracic duct, and later a talc pleurodesis. At 3 months, he had some cognitive limitations and was walking with a stick.

Managing idiopathic intracranial hypertension in pregnancy: practical advice.

Idiopathic intracranial hypertension (IIH) is more common in women of reproductive age who have obesity, yet there is little information on its management specifically in pregnancy. Women with IIH should plan their pregnancy including discussing contraception before pregnancy, recognising that hormonal contraceptives are not contraindicated. Potentially teratogenic medications including acetazolamide and topiramate are not recommended during pregnancy or in those with immediate plans to conceive; prescribing acetazolamide in pregnancy must only follow discussion with the patient and their obstetrician. Ideally, patients should aim to achieve disease remission or control before pregnancy, through optimising their weight. Although weight gain is expected in pregnancy, excessive weight gain may exacerbate IIH and increase maternal and fetal complications; evidence-based recommendations for non-IIH pregnancies may help in guiding optimal gestational weight gain. The vast majority of women with IIH can have a normal vaginal delivery, with spinal or epidural anaesthesia if needed, provided the papilloedema is stable or the IIH is in remission.

Inter-rater agreement of observable and elicitable neurological signs.

This paper reports on a study that aimed to assess the inter-rater agreement of observable neurological signs in the upper and lower limbs (eg inspection, gait, cerebellar tests and coordination) and elicitable signs (eg tone, strength, reflexes and sensation). Thirty patients were examined by two neurology doctors, at least one of whom was a consultant. The doctors' findings were recorded on a standardised pro forma. Inter-rater agreement was assessed using the kappa (κ) statistic, which is chance corrected. There was significantly better agreement between the two doctors for observable than for elicitable signs (mean ± standard deviation [SD] κ, 0.70 ± 0.17 vs 0.41 ± 0.22, p = 0.002). Almost perfect agreement was seen for cerebellar signs and inspection (a combination of speed of movement, muscle bulk, wasting and tremor); substantial agreement for strength, gait and coordination; moderate agreement for tone and reflexes; and only fair agreement for sensation. The inter-rater agreement is therefore better for observable neurological signs than for elicitable signs, which may be explained by the additional skill and cooperation required to elicit rather than just observe clinical signs. These findings have implications for clinical practice, particularly in telemedicine, and highlight the need for standardisation of the neurological examination.

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.

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.

Disease Course and Long-term Outcomes in Pregnant Women With Idiopathic Intracranial Hypertension: The IIH Prospective Maternal Health Study.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) most typically occurs in women of childbearing age with increased weight as a key risk factor for development or exacerbation of the disease. Pregnancy is common in this group of patients. The longer-term effect of pregnancy on IIH has not been established and was the aim of this study. METHODS: A prospective cohort study (IIH Life) recruited consecutive patients with IIH between 2012 and 2021 and evaluated outcomes including vision (logarithm of the minimum angle of resolution visual acuity, Humphrey visual field perimetric mean deviation, and optical coherence tomography [OCT] imaging) and headache. Four cohorts were evaluated: those with IIH diagnosed for the first time while pregnant, those with established IIH who became pregnant, those with a pregnancy prior to their diagnosis of IIH, and those with IIH who never became pregnant. RESULTS: Three hundred seventy-seven people with IIH agreed to participate in the IIH Life maternal health study. Mean follow-up was 17.5 months (SD 20.5). IIH diagnosed in pregnancy was rare. Patients diagnosed with IIH while pregnant had greater papilledema (mean OCT total retinal thickness +11.59 µm/mo [95% CI 1.25-21.93]), although they had comparable visual field and acuity measures compared with those with established IIH who became pregnant during their disease course (-1.2 µm/mo [95% CI -2.6 to 0.21]). In those with established IIH, pregnancy did not adversely affect visual or headache outcomes over time, and the trajectory was akin to those with IIH who never had a pregnancy. Headache outcomes showed variability reflecting the IIH cohort as a whole. DISCUSSION: A diagnosis of IIH while pregnant was rare but associated with more severe papilledema. Long-term visual outcomes in IIH were analogous irrespective of the timing of the pregnancy. These data are reassuring; however, close vigilance of IIH clinical features during pregnancy is recommended.

Current and emerging diagnostic and management approaches for idiopathic intracranial hypertension.

INTRODUCTION: Idiopathic intracranial hypertension is characterized by raised intracranial pressure that triggers disabling headaches and can cause permanent visual loss. There is an increased incidence and prevalence of the condition linked to location-specific obesity rates. There are no licensed treatments for the condition. The majority of approaches to managing the disease prioritize resolution of papilledema. However, evidence is emerging that idiopathic intracranial hypertension is a systemic metabolic disease. AREAS COVERED: The aim of this review is to present the emerging pathophysiology evidence which is leading to novel targeted therapeutics. The diagnostic pathway is outlined. The current and potential management approaches for idiopathic intracranial hypertension are also discussed. EXPERT OPINION: Idiopathic intracranial hypertension is a condition with metabolic dysregulation with systemic manifestations that are present over and above what can be expl.ained by obesity alone. While most of the current management of this condition focuses on the eyes, future management needs to address the disabling headaches and the systemic risks of preeclampsia, gestational diabetes, and major cardiovascular events.

Longitudinal prospective cohort study evaluating prognosis in idiopathic intracranial hypertension patients with and without comorbid polycystic ovarian syndrome.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) and polycystic ovary syndrome (PCOS) are hyperandrogenic metabolic disorders that affect women of reproductive age living with obesity. The previously reported prevalence of comorbid PCOS in IIH patients is highly variable and the longitudinal impact on visual and headache outcomes are unknown. METHODS: In this prospective longitudinal cohort study patients were identified from the IIH: Life database over a nine-year period (2012-2021). Data collected included demographics and PCOS questionnaire data. Key visual and detailed headache outcomes were recorded. We analysed the key variables for influential outcomes of vision and headache. Logistical regression methods were used to model long term visual and headache outcomes. RESULTS: Overall 398 women with IIH and documented PCOS questionnaires were followed up for a median of 10 months (range 0-87). Prevalence of PCOS in IIH was 20% (78/398) diagnosed by the Rotterdam criteria. Patients with IIH and comorbid PCOS reported higher self-reported fertility problems (3.2-fold increased risk) and increased need for medical help in becoming pregnant (4.4-fold increased risk). Comorbid PCOS in IIH patients does not adversely impact long-term vision or headache outcomes. The headache burden was high in both cohorts studied. CONCLUSIONS: The study demonstrated that comorbid PCOS in IIH is common (20%). Diagnosing comorbid PCOS is important as it can impact on fertility and is known to have long-term adverse cardiovascular risks. Our data suggest that a diagnosis of PCOS in those with IIH does not significantly exacerbate long-term vision or headache prognosis.

Defining the Phenotype and Prognosis of People With Idiopathic Intracranial Hypertension After Cerebrospinal Fluid Diversion Surgery.

PURPOSE: To characterize the phenotype of patients with idiopathic intracranial hypertension (IIH) who received cerebrospinal (CSF) diversion surgery and to detail the trajectory of recovery. DESIGN: Prospective cohort registry study. METHODS: Patients with IIH with sight-threatening papilledema presenting to a single United Kingdom neuroscience center between 2019 and 2021 were included. Outcomes consisted of perimetric mean deviation (PMD) and optical coherence tomography measures of papilledema (retinal nerve fiber layer [RNFL]) and macular ganglion cell layer (GCL) in both eyes. Headache outcomes included monthly headache days (MHD). Logistic regression methods were used to model long-term outcomes. RESULTS: Fifty-one patients without previous surgical interventions were included (92% female, mean age 28.1 years [SD 8.4], body mass index 37.4 kg/m2 [SD 9.7], mean days of follow-up 330 [SD 209]). Measurements before surgery showed mean PMD -11.4 dB (SD 9.7), RNFL 364 µm (SD 128), Frisén grade papilledema 4.3 (SD 0.9). and MHD 23 (SD 10.6). At 1 month postoperatively, RNFL and PMD had improved by 38% and 4%, respectively. At 4 months postoperatively, papilledema had resolved. GCL declined by 13% over 12 months. MHD reduced by 75% 3 months postoperatively before returning to baseline levels by 12 months. Five patients (9.8%) required revision surgeries. CONCLUSIONS: Detailed characteristics of patients with sight-threatening IIH who received CSF diversion surgery and their typical postoperative recovery are presented. These parameters should guide physicians as to when patients with IIH may require surgery and enable the early identification of outliers who fail to respond. Papilledema and PMD recovered but GCL atrophy continued for 12 months. The implication of this delayed atrophy is unknown.

The idiopathic intracranial hypertension prospective cohort study: evaluation of prognostic factors and outcomes.

BACKGROUND: There are limited longitudinal data evaluating outcomes in idiopathic intracranial hypertension (IIH). We aimed to evaluate the long-term outcomes in a real-world cohort of patients with IIH and sought to establish the prognostic factors. METHODS: A longitudinal prospective cohort study was conducted over 9 years (2012-2021). Data included demographics and disease status. All consenting patients with IIH were recruited. Visual outcomes included visual acuity, Humphrey visual field and optical coherence tomography (OCT) imaging measurements. Headache frequency, severity, and impact were noted. We analysed the key variables impacting visual and headache outcomes. RESULTS: The cohort contained 490 patients with a confirmed IIH diagnosis. 98% were female with a mean body mass index (BMI) of 38 kg/m2. Those with the highest OCT retinal nerve fibre layer had the worst visual outcomes. We noted a delayed decline, in the visual field and OCT ganglion cell layer after 12 months. In the medically managed cohort (n = 426), we found that disease duration and change in BMI had the greatest influence on visual outcomes. There was a high burden of headache, with a daily headache at presentation and prior migraine history influencing long-term headache prognosis. CONCLUSIONS: There is a delayed decline in visual outcomes in those with the most severe papilloedema. Disease duration and change in BMI were the key visual prognostic factors, therefore those with the more acute disease may require closer monitoring. Improving prognosis in IIH should focus on the potentially modifiable factor of weight management.

Multiple lumbar punctures aiming to relieve headache results in iatrogenic spinal hematoma: a case report.

BACKGROUND: Multiple lumbar punctures have historically been a strategy to relieve headaches associated with idiopathic intracranial hypertension despite limited clinical evidence of long-term efficacy. Lumbar puncture is typically a straightforward procedure with minimal complications reported, however, serious complications can occur. Lumbar-puncture-related spinal hematomas are rare but can lead to irreversible paralysis. CASE PRESENTATION: We report a case of a 28-year-old Caucasian woman who was treated with multiple lumbar punctures to manage headache, thought to be attributed to idiopathic intracranial hypertension. The patient developed a lumbosacral epidural hematoma following a lumbar puncture, which led to incomplete cauda equina syndrome. Multiple lumbar punctures had been the long-term management for the patient's chronic headaches associated with her diagnosis of idiopathic intracranial hypertension. She had no risks of an underlying coagulopathy. Following a lumbar puncture, she re-presented with lower back pain and bilateral paresthesia. Over the subsequent 48 hours, this progressed to urinary incontinence and saddle paresthesia. Imaging revealed an epidural hematoma, which was conservatively managed. She continued to report saddle paresthesia and urinary incontinence 7 months following the lumbar puncture. Between 1974 to 2022, our literature search found 41 case reports detailing lumbar-puncture-related spinal hematomas. It is an established but rare complication of lumbar puncture and there are limited studies looking at the incidence of its occurrence. Whilst coagulopathy has been found to be a risk factor, it is unclear if the gauge of the needle is relevant. Case evidence suggests there may be no significant difference in outcomes between surgical and conservative management of spinal hematomas. This case highlights that lumbar punctures can be invasive, with potentially serious complications. A lumbar puncture should therefore only be performed when clinically justified. CONCLUSIONS: This case highlights a rare complication of lumbar puncture and emphasizes the importance of a risk-benefit discussion for each procedure. Spinal hematoma following lumbar puncture is a rare complication but with potentially devastating consequences. Within the setting of idiopathic intracranial hypertension, the evidence base for the long-term benefit of headache relief by repeat lumbar puncture is low.

Evaluation of diurnal and postural intracranial pressure employing telemetric monitoring in idiopathic intracranial hypertension.

OBJECTIVES: Intracranial pressure (ICP) has been thought to vary diurnally. This study evaluates diurnal ICP measurements and quantifies changes in ICP occurring with changes in body posture in active idiopathic intracranial hypertension (IIH). METHODS: This prospective observational study utilized telemetric ICP monitoring in people with active IIH. Participants had the Raumedic p-Tel ICP intraparenchymal device (Raumedic, Hembrechts, Germany) surgically inserted. Changes in ICP in the supine position were evaluated. Then, the ICP was measured in the standing, sitting, supine, left lateral decubitus positions and with coughing and bending. Ultimately, changes in ICP over the course of 24 h were recorded. ISRCTN registration number 12678718. RESULTS: 15 women were included, mean (standard deviation) age 29.5 (9.5) years, body mass index 38.1 (6.2) kg/m2, and baseline mean ICP of 21.2 (4.8) mmHg (equivalent to 28.8 (6.5) cmCSF). Mean ICP rose with the duration in the supine position 1.2 (3.3) mmHg over 5-minutes (p = 0.175), 3.5 (2.8) mmHg over 30-minutes (p = 0.0002) and by a further 2.1 (2.2) mmHg over 3 h (p = 0.042). Mean ICP decreased by 51% when moving from the supine position to standing (21.2 (4.8) mmHg to 10.3 (3.7) mmHg respectively, p = 0.0001). Mean ICP increased by 13% moving from supine to the left lateral decubitus position (21.2 (4.8) mmHg to 24.0 (3.8) mmHg, p = 0.028). There was no significant difference in ICP measurements at any point during the daytime, or between 5-minute standing or supine recordings and prolonged ambulatory daytime and end of night supine recordings respectively. ICP, following an initial drop, increased progressively in conjunction with lying supine position from 23:00 h to 07:00 h by 34% (5.2 (1.9) mmHg, p = 0.026). CONCLUSION: This analysis demonstrated that ICP does not appear to have a diurnal variation in IIH, but varies by position and duration in the supine position. ICP rose at night whilst the patient was continuously supine. Furthermore, brief standing and supine ICP measures in the day predicted daytime prolonged ambulatory measures and end of night peak ICP respectively. This knowledge gives reassurance that ICP can be accurately measured and compared at any time of day in an ambulant IIH patient. These are useful findings to inform clinical measurements and in the interpretation of ICP analyses in IIH. TRIAL REGISTRATION: ISTCRN (12678718).