Idiopathic intracranial hypertension in the pregnant patient: a narrative review on the management of visual disturbances

The Use of Acetazolamide in Idiopathic Intracranial Hypertension During Pregnancy

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Pseudotumor Cerebri (Benign Intracranial Hypertension): Etiopathogenesis, Diagnosis, And Management

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. 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. A detailed search of the scientific literature and narrative review was performed. 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. 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.

The purpose of this study was to analyse less known clinical scenarios associated with idiopathic intracranial hypertension. The study involved analysis of magnetic resonance imaging signs of idiopathic intracranial hypertension in patients with spontaneous rhinoliquorrhoea (n = 7), in patients with temporal lobe epilepsy and surgically treated antero-inferior temporal lobe meningo-encephaloceles (n = 15), and in patients who developed clinical signs of idiopathic intracranial hypertension following the treatment of spontaneous intracranial hypotension (n = 7). Three of six patients with spontaneous rhinoliquorrhoea and six of 15 operated patients with temporal lobe epilepsy due to temporal lobe meningo-encephaloceles showed magnetic resonance imaging signs of idiopathic intracranial hypertension and had a body mass index >30 kg/m2. Rebound high pressure headaches and sings of idiopathic intracranial hypertension occurred in seven of 44 surgically treated spontaneous intracranial hypotension patients. Magnetic resonance imaging findings should guide the clinician to consider (idiopathic) intracranial hypertension when patients develop spontaneous rhinoliquorrhoea, temporal lobe epilepsy secondary to temporal lobe meningoencephaloceles or high pressure headaches in spontaneous intracranial hypotension. Whether idiopathic intracranial hypertension must be regarded as a differential diagnosis or as a cause, or whether there are common pathophysiological pathways that lead to signs of idiopathic intracranial hypertension in this wider spectrum of disease is the focus of further study.

Venous sinus stenosis, typically at the junction of the transverse and sigmoid sinus, is increasingly recognized as a contributor to the pathophysiology of idiopathic intracranial hypertension (IIH), whether it be the intrinsic type that does not reverse with normalization of intracranial pressure or the extrinsic type, which does. Efforts to treat the stenosis and reduce the associated transstenotic gradient through placement of a stent at the site of stenosis have been studied over the past 2 decades, primarily through retrospective studies, with variable emphasis on formal visual testing and direct assessment of poststent opening pressure. Most studies have presented evidence for utilization of stenting as an alternative to cerebrospinal fluid shunting or optic nerve sheath fenestration in patients with IIH who harbor the stenosis and are refractory to or intolerant of intracranial pressure-lowering medications, but an assessment of the current data is needed to better understand the role of stenting for this patient population. A search in PubMed was made for "IIH," "papilledema," and "venous stenting." Data pre and post stenting, including symptoms attributable to IIH, intracranial pressure, papilledema, retinal nerve fiber layer thickening on optical coherence tomography, and visual field assessment (mean deviation), were collected. Need for retreatment and complications were assessed among all studies. Studies using stenting for special circumstances, such as cerebrospinal leaks or for stenosis along anomalous vessels, were reviewed. In total, 49 studies (45 retrospective and 4 prospective) and 18 case reports (with 3 or less patients) were found and included in the analysis, for a total of 1,626 patients. In 250 patients in whom poststent intracranial pressure was measured, the mean value was 19.7 cm H 2 O, reduced from a mean of 33 cm H 2 O. Transient visual obscurations resolved in 79.6% of 201 patients who complained of it, pulsatile tinnitus resolved in 84.7% of 515, diplopia resolved in 93% of 86 patients, and nonspecific visual symptoms such as "blurry vision" improved in 76.2% of 537 patients. Headaches resolved in 36% and improved in a further 40.7% of 1,105 patients in whom they were documented before stenting. Of 1,116 with papilledema, 40.8% demonstrated resolution and 38.2% improvement. The mean retinal nerve fiber layer thickness improved from 170.2 µm to 89.2 µm among 402 eyes in which optical coherence tomography was used to measure it. Among 135 eyes in which formal visual fields were performed pre and post stenting, the prestent average mean deviation of -7.35 dB improved to -4.72 dB after stenting. Complications associated with stenting included in-stent stenosis or thrombosis, subdural hematoma, intracerebral hematoma, cerebral edema, stent migration, and death. A recurrence of symptoms requiring a follow-up surgical intervention occurred in 9%. A growing body of evidence supports the use of venous sinus stenting as a viable option for medically refractory IIH, especially when papilledema threatens visual function. Complication and failure rates seem to be similar to alternative surgical approaches, although serious neurological sequalae can rarely occur. Emerging studies evaluating stent type, including novel stents designed for use in the venous system, may help improve ease of the procedure and long-term success rates. Prospective head-to-head studies are needed to better understand the performance of stenting compared with other interventions.

A case–control study is an observational epidemiologic study design that compares the prevalence of a risk factor or treatment exposure between 2 groups: those with a particular disease or condition of interest (cases), and a similar group that is at risk for this disease or condition but does not have it (controls). Because cases can be pooled across different centers and years of study, case–control studies are particularly well suited for studying rare diseases, which is frequently the case in neuro-ophthalmology. However, their inherently retrospective nature makes it challenging to establish temporality and to distinguish between association and causation. They are also susceptible to recall, selection, and confounding biases. It is therefore important for neuro-ophthalmologists to be familiar with the principles of case–control study design to critically appraise the neuro-ophthalmic epidemiologic literature. In this article, presented as a companion to Lin et al's "Idiopathic Intracranial Hypertension and Anemia: A Matched Case–Control Study" (1) and Rueløkke et al's "Optic Disc Drusen Associated Anterior Ischemic Optic Neuropathy: Prevalence of Comorbidities and Vascular Risk Factors" (2), we review the basics of case–control study design and highlight several common pitfalls in case–control studies for readers to consider when evaluating new studies. STUDY DESIGN Cohort and case–control studies both assess the association between an exposure (cause or risk factor, independent variable) and outcome (effect, dependent variable). In contrast to a prospective cohort study, where a large group of patients with heterogeneous exposures who have not yet experienced a particular outcome is followed over time to determine who develops the condition and who does not, case–control studies begin by identifying groups of patients with and without disease. In other words, cohort studies look forward in time, whereas case–control studies look backward in time. Identifying subjects based on outcome is ideal for studying rare diseases that have a low rate of incidence. A case–control study begins by defining the outcome and exposure of interest. The outcome refers to the disease or condition of interest (or if one is only studying patients with a particular disease, then a prespecified event or result associated with that disease). Study subjects who have the outcome of interest are known as cases, and subjects who are at risk for the outcome (i.e., who were capable of developing it) but do not have it are known as controls. In Lin et al's study of idiopathic intracranial hypertension (IIH) and anemia, the outcome was a diagnosis of IIH according to modified Dandy criteria: cases were IIH patients who were diagnosed at a single eye clinic over a 29-month period. Controls were patients seen at the same center and during the same period for conditions other than IIH. Note that controls are defined by the absence of an outcome rather than the presence of a different outcome: a study that compares the prevalence of risk factors between 2 different diseases (e.g., anemia in IIH vs anemia in NAION) would technically not be considered a case–control study. Exposure refers broadly to a patient-level or environmental-level characteristic or comorbidity, which can be anything from a genetic risk allele to a predisposing medical condition (in Lin et al's case, anemia), environmental exposure (e.g., smoking), or nonrandomized treatment. Case–control studies are classically retrospective in that assessment of the exposure occurs in hindsight, and the timing of the exposure is specified to occur before developing the outcome of interest. For example, in Rueløkke et al's study of ischemic optic neuropathy, patients were queried about whether they were diagnosed with sleep apnea or vascular risk factors before their diagnosis of ischemic optic neuropathy. However, this does not always occur in case–control studies. For example, Lin et al allowed for the assessment of anemia to occur at the time of IIH diagnosis or up to a year afterward, allowing for more of a cross-sectional design. Case–control studies can also use data from existing cohort studies to create a truly prospective study (these are termed nested case–control studies or case cohort studies and are beyond the scope of this review). Neuro-ophthalmologists are rare disease specialists. Even conditions such as IIH that are common in neuro-ophthalmic clinical practice are rare at the population level: the estimated incidence of IIH among overweight or obese women aged 20–44 years in the United States is less than 20 new cases per 100,000 individuals per year (3). Case–control designs are thus well suited to the study of neuro-ophthalmic disease. If Lin et al had wanted to use a prospective cohort study design to investigate the association between anemia and the risk of developing IIH in the future, they would have had to recruit over 200,000 new subjects, each with or without anemia, to identify 50 new IIH cases over a 2 year-period. A study of that magnitude would not be feasible because it would require hundreds of personnel and hundreds of millions of dollars. Instead, Lin et al were able to query their patient database and find 50 IIH patients and 50 patients without IIH, in whom they assessed for evidence of exposure to anemia. Because case–control studies are often used to study rare conditions, the availability of cases is typically the limiting factor in sample size determinations. STATISTICAL CONSIDERATIONS The standard measure of association between exposure and outcome in a case–control study is the odds ratio. An odds is a ratio of probabilities, specifically the probability of having the exposure and the probability of not having the exposure. An odds ratio, then, is a ratio of 2 odds (one for cases and one for controls). An odds ratio can best be illustrated using the classic two-by-two table—for example, using data from Table 1 in Lin et al's study, a 2-by-2 table can be created (Table 1).TABLE 1.: Odds ratio exampleFor IIH, the odds of anemia diagnosis is (9/50)/(41/50) = 0.22, and for controls, the odds of anemia is (6/50)/(44/50) = 0.14; so, the odds ratio is 0.22/0.14 = 1.57. Note that in calculating the odds separately for each group, the individual sample size cancels out, and the equation for odds ratio can be simplified to (a × d)/(b × c) as denoted by superscripts. If the odds ratio is greater than one, it indicates that cases have a greater odds of having the exposure, and if the odds ratio is less than one, it indicates the opposite. In this case, an odds ratio of 1.57 means that IIH patients are 57% more likely to have anemia than controls, and hypothesis testing (e.g., chi square test, Fisher exact test, logistic regression) is used to determine whether this is statistically significant (in this case, it was not). Continuous variables such as hemoglobin can be analyzed continuously using t-tests or linear regression (as in Lin et al's study) or categorically by defining categories for use in a 2-by-2 table. For example, the exposure of anemia could have been defined as hemoglobin <9 g/dL and compared to unexposed individuals with hemoglobin ≥9 g/dL. Selecting a cutpoint to define exposed and unexposed groups using a continuous variable depends on a number of factors including clinical definitions, sample size calculations, and underlying dose–response relationships. Note that the odds ratio is technically different from the relative risk that is reported in cohort studies. Relative risk is calculated from a prospective cohort study as the incidence of the outcome in the exposed group divided by the incidence of the outcome in the unexposed group. In other words, relative risk compares the frequency of an outcome between groups according to exposure, and odds ratio compares the frequency of an exposure between groups according to outcome. Relative risk is interpreted as the extent to which a particular exposure increases the risk of developing a particular disease or outcome relative to the baseline population risk; for example, if Lin et al had conducted a prospective cohort study of anemia and IIH and found a relative risk of 1.57, it would mean that patients with anemia are 57% more likely to develop IIH than patients without anemia. In a case–control study, one cannot know the true baseline population risk (i.e., the risk of developing IIH in people without anemia) because the study is being conducted after patients have already developed or not developed the outcome. However, as long as the disease of interest is rare, the odds ratio from a case–control study will approximate the relative risk from a prospective cohort study. SOURCES OF BIAS In a case–control study, cases and controls are not randomized to having the exposure, and there is the potential for other differences between groups to confound the association between exposure and outcome, resulting in a significant association between the exposure and outcome that may in reality be due to other confounding variables associated with both the exposure and outcome. There are a number of statistical methods that can be used to adjust for potential confounding. One method that is highlighted in Lin et al's study is matching, whereby the case and control groups are balanced according to a particular characteristic, thereby removing it as a potential confounder. In this case, Lin et al matched cases to controls by sex and age to account for the fact that young women are more likely to have anemia and are also the demographic at greatest risk for developing IIH. Paired statistical tests (e.g., paired t test, matched chi-square test, conditional logistic regression) must be used to account for the matched structure of the data. Although confounding is a potential weakness in any observational epidemiologic study, there are several methodologic issues that are of particular concern in case–control studies. One important type of bias is recall bias, which refers to the fact that knowing whether a patient has a disease of interest affects their ability to recall whether they had a previous exposure or not. Recall bias can occur in any retrospective study where the exposure is ascertained after the outcome is already known, and it is most problematic when the exposure is self-reported. For example, Rueløkke et al compared patients with anterior ischemic optic neuropathy who had optic disc drusen (ODD) to those who did not (NA-AION). Patients with NA-AION are often counseled at the time of their diagnosis on the relationship between vascular risk factors such as diabetes, hypertension, hyperlipidemia, smoking, and obstructive sleep apnea and NA-AION, and the theoretical possibility that better control of these risk factors could reduce their risk of fellow eye involvement. If this experience makes it more likely for patients to recall their previous diagnoses of diabetes or other vascular risk factors, there could be greater recall among those patients, and any difference in the prevalence of vascular risk factors in the NA-AION group relative to the ODD group could be exaggerated. In Lin et al's study of anemia and IIH, anemia was measured using a complete blood count (CBC) rather than self-report. Because patient recollection is not involved, recall bias is minimized. Information Bias Information bias can result from limited availability of data. This is a consideration in Lin et al's retrospective study, where measuring the exposure depends on the availability of data that have been collected for routine clinical purposes rather than research. Of an initial sample of 95 IIH patients, 45 (47.3%) were excluded due to a lack of available CBC. If these excluded subjects all had undiagnosed anemia, the prevalence of anemia in IIH would actually be 57% (54/95 × 100) instead of 18% (9/50 × 100), and a true association between anemia and IIH would be missed. Selection Bias Selection bias can occur as a result of how cases and controls are defined. For cases, rigorous diagnostic criteria (e.g., modified Dandy criteria for IIH in Lin et al's study) are used to ensure that cases have an accurate clinical diagnosis. Inclusion criteria for controls are frequently less clearly defined but are equally important. Specifically, it is important for controls to be representative of the general population of interest, and the method in which controls are identified should not be associated with exposure because this would result in selection bias. A famous example of selection bias comes from a case–control study of coffee consumption and pancreatic cancer (4). In this study (published in the New England Journal of Medicine), cases (pancreatic cancer patients) and controls (patients without pancreatic cancer) were asked about their coffee consumption, and cases were 2.7 times more likely to report drinking 3 or more cups of coffee daily. This led to widespread fear that coffee caused pancreatic cancer. However, one must ask an important question: from what population was the control group selected? In this case, controls were recruited from gastroenterology clinics, where the same providers were also seeing pancreatic cancer patients, and most control patients had gastroesophageal reflux disease, peptic ulcer disease, and other conditions that could potentially cause them to reduce their coffee consumption to reduce their symptoms. Thus, the prevalence of coffee consumption in the control group was lower than the population of patients with pancreatic cancer, resulting in a spurious association between coffee consumption and pancreatic cancer that subsequent studies have failed to confirm. In Lin et al's study of IIH and anemia, control subjects were selected from patients who were seen at the same eye center for reasons other than IIH and had a CBC collected. If their reasons for seeking ophthalmic care (e.g., dry eye, uveitis) were associated with anemia, then the prevalence of anemia in the control group would not reflect the prevalence of anemia in the general population, and this could cause selection bias. Specifically, if both the IIH and control groups have a significantly increased prevalence of anemia relative to the general population, comparing IIH to controls would fail to demonstrate a significant difference (bias toward the null). Knowing that these conditions are not associated with anemia is reassuring, although the precise indications for checking a CBC in this group remain unclear. The potential for bias limits the generalizability of case–control study results. Prospective cohort studies protect against information and recall biases, and randomized controlled trials provide ideal control for confounding, so the findings of a case–control study would ideally be confirmed in a prospective observational or interventional study before being implemented into clinical practice, but this is not always feasible. CONCLUSION In summary, case–control studies are a popular epidemiologic study design, and because they are ideal for studying rare diseases, they have widespread applications in neuro-ophthalmology. However, it is important for readers to understand how case–control studies are conducted and the potentials for confounding, information, recall, and selection biases to judge the extent to which a study's findings affect true causal relationships that are relevant to the care of their patients.

Pseudo-Foster Kennedy syndrome due to idiopathic intracranial hypertension

The role of aquaporin-1 in idiopathic and drug-induced intracranial hypertension

Idiopathic intracranial hypertension (IIH) is a syndrome of increased intracranial pressure without hydrocephalus or mass lesion with elevated cerebrospinal fluid (CSF) pressure but otherwise normal CSF composition. It has been found that pregnancy occurs in IIH patients at about the same rate as in the general population, that IIH can occur in any trimester of pregnancy, that patients have the same spontaneous abortion rate as the general population, and that the visual outcome is the same as for nonpregnant patients with IIH. Although it is also stated that pregnant patients with IIH should be managed and treated the same way as any other patient with IIH, the use of imaging and drug contraindications do make a difference between the two groups. The treatment has two major goals, which are to preserve vision and to improve symptoms. The medical therapy includes weight control, nonketotic diet, serial lumbar punctures, diuretics, steroids, and certain analgesics. When medical therapy fails, surgical procedures should be considered. The two main procedures are optic nerve sheath fenestration and lumboperitoneal shunt. Anesthetic considerations in the pregnant patient are an additional factor when surgeries are contemplated. It is also noted that therapeutic abortion to limit progression of disease is not indicated and that subsequent pregnancies do not increase the risk of recurrence.

Objective: There is paucity of data concerning the impact of bariatric surgery on idiopathic intracranial hypertension (IIH). We therefore present the clinical course of two cases that were managed at our centre, which is a regional referral centre for bariatric surgery and present a literature review of patients with IIH who underwent bariatric surgery for the treatment of obesity.Method: Two patients were referred for bariatric surgery who were both morbidly obese and were diagnosed with IIH. One patient underwent bariatric surgery; the other patient’s weight was managed conservatively. We followed up both patients for 2 years. PubMed was searched for published studies of patients with IIH undergoing bariatric surgery.Results: The patient that underwent weight loss surgery achieved sustained weight loss from 108kg to 87kg and gross resolution of their symptoms. The patient whose weight was managed conservatively lost weight initially and then put the weight back on. Her IIH symptoms persisted despite CSF shunt therapy. The literature review identified 12 original studies, containing 51 patients. Weight loss after bariatric surgery was reported for 84% of patients and improvement or resolution of IIH symptoms was reported for 84% of patients.Conclusion: In light of the literature review and our experience, bariatric surgery appears to be a potential treatment option for IIH alongside the comorbidities associated with obesity. However, more robust studies are needed.

A 6-year-old girl complained of diplopia and headache over a 2-week period after sustaining a minor head injury. Her neurological examinations were normal, but visual examination identified bilateral papilledema. Magnetic resonance imaging of the brain revealed a protruding nodular lesion causing compression within the anterior superior sagittal sinus in the midline, showing high signal intensity on T2-weighted imaging (T2WI) and low signal intensity on T1WI, similar to that of cerebrospinal fluid. Enhanced T1WI showed irregular narrowing of the anterior superior sagittal sinus adjacent to this lesion. The cortical vein drained to the frontal pole of the arachnoid granulation lesion and into the superior sagittal sinus. No other parenchymal abnormality was noted. A lumbar puncture showed increased opening pressure (30mmHg), and the laboratory findings were normal. Based on the imaging and clinical findings, benign intracranial venous hypertension with giant arachnoid granulation was diagnosed. The patient's symptoms were reduced satisfactorily following daily treatment with 750mg acetazolamide. We report a case of giant arachnoid granulation involving the anterior superior sagittal sinus in a 6-year-old girl who presented with benign intracranial hypertension. Clinicians should be aware of this rare anatomic variant to avoid unnecessary invasive procedures or examinations in children with benign intracranial hypertension.

HighlightsWhat are the main findings?The increasing incidence of IIH in children and adolescents is strongly linked to the global obesity epidemic.Weight loss (6–10%) remains the cornerstone of treatment, with bariatric surgery and new anti-obesity medications (GLP-1 agonists) emerging as highly effective options for long-term IIH remission.What is the implication of the main finding?The complex pathophysiology—linking obesity, hormones, and CNS pressure—mandates a multidisciplinary team (Neuro-Ophthalmology, Pediatric Endocrinology, Nutrition) for optimal patient prognosis.Since weight loss is the only etiological treatment, therapeutic strategies must prioritize prompt, effective weight reduction, incorporating newer anti-obesity agents and surgical options in refractory adolescent cases to prevent permanent vision loss.Background: Idiopathic intracranial hypertension (IIH), also known as primary pseudotumor cerebri, is characterized by increased intracranial pressure (ICP) without an identifiable cause. It can lead to significant morbidity, including permanent vision loss, especially in younger children. The exact cause of IIH is still unclear, but excess adiposity seems to be a key risk factor. Current treatment options are unsatisfactory, but research is exploring novel therapies targeting obesity-related mechanisms. Methods: Narrative review of the literature aimed at summarizing current knowledge regarding the epidemiology, pathophysiology, clinical features, treatment options and long-term outcomes for pediatric IIH, with a particular focus on the link with obesity. Results: The incidence of IIH is rising, mirroring the obesity epidemic. Excess adiposity, predominantly visceral, might cause IIH through several factors such as decreased venous return, hormone dysregulation, inflammation, obstructive sleep apnea, and dysfunction of the glymphatic system. The extent of weight loss required and the most appropriate strategy to achieve it are still uncertain. Given the difficulty in achieving and maintaining weight loss with dietary strategies, bariatric surgery and weight loss medications are emerging as effective options for long-term remission of both obesity and IIH. Conclusions: IIH is a rare and poorly understood disease. At present, weight loss represents the only treatment that addresses the pathophysiology of IIH. The role and potential as standalone or synergistic therapies of weight loss drugs and bariatric surgery for IIH in adolescents require future research.

BackgroundElevated intracranial pressure (ICP) is observed in association with a range of brain disorders. One of these challenging disorders is idiopathic intracranial hypertension (IIH), characterized by raised ICP of unknown cause with significant morbidity and limited therapeutic options. In this review, special focus is put on the preclinical research performed in order to understand the pathophysiology behind ICP regulation and IIH. This includes cerebrospinal fluid dynamics, molecular mechanisms underlying disturbances in brain fluids leading to elevated ICP, role of obesity in IIH, development of an IIH model and ICP measurements in rodents. The review also discusses existing and new drug targets for IIH that have been evaluated in vivo.ConclusionsICP monitoring in rodents is challenging and different methods have been applied. Some of these methods are invasive, depend on use of anesthesia and only allow short-term monitoring. Long-term ICP recordings are needed to study IIH but existing methods are hampered by several limitations. As obesity is one of the most common risk factors for IIH, a rodent obese model has been developed that mimics some key aspects of IIH. The most commonly used drugs for IIH have been evaluated in vivo for their efficacy at lowering ICP in the existing animal models. These studies suggest these drugs, including acetazolamide, might have limited or no reducing effect on ICP. Two drug targets that can impact ICP in healthy rodents are topiramate and a glucagon-like peptide-1 receptor (GLP-1R) agonist. However, it remains to evaluate their effect in an IIH model with more precise and valid ICP monitoring system. Therefore, continued evaluation in the preclinical research with refined tools is of great importance to further understand the pathophysiology behind disorders with raised ICP and to explore new drug targets.

Idiopathic intracranial hypertension (IIH) is a neurological disease characterized by symptoms and signs of increased intracranial pressure (ICP) of unknown cause. Most attention has been given to the role of cerebrospinal fluid (CSF) disturbance and intracranial venous hypertension caused by sinus vein stenosis. We previously proposed that key pathophysiological processes take place within the brain at the glia-neuro-vascular interface. However, the relative importance of the proposed mechanisms in IIH disease remains unknown. Modern treatment regimens aim to reduce intracranial CSF and venous pressures, but a substantial proportion of patients experience lasting complaints. In 2010, the first author established a database for the prospective collection of information from individuals being assessed for IIH. The database incorporates clinical, imaging, physiological, and biological data, and information about treatment/outcome. This study retrieved information from the database, asking the following research questions: In IIH subjects responding to shunt surgery, what is the occurrence of signs of CSF disturbance, sinus vein stenosis, intracranial hypertension, and microscopic evidence of structural abnormalities at the glia-neuro-vascular interface? Secondarily, do semi-quantitative measures of abnormal ultrastructure at the glia-neurovascular differ between subjects with definite IIH and non-IIH (reference) subjects? The study included 13 patients with IIH who fulfilled the diagnostic criteria and who improved following shunt surgery, i.e., patients with definite IIH. Comparisons were done regarding magnetic resonance imaging (MRI) findings, pulsatile and static ICP scores, and immune-histochemistry microscopy. Among these 13 IIH subjects, 6/13 (46%) of patients presented with magnetic resonance imaging (MRI) signs of CSF disturbance (empty sella and/or distended perioptic subarachnoid spaces), 0/13 (0%) of patients with IIH had MRI signs of sinus vein stenosis, 13/13 (100%) of patients with IIH presented with abnormal preoperative pulsatile ICP [overnight mean ICP wave amplitude (MWA) above thresholds], 3/13 (23%) patients showed abnormal static ICP (overnight mean ICP above threshold), and 12/13 (92%) of patients with IIH showed abnormal structural changes at the glia-neuro-vascular interface. Comparisons of semi-quantitative structural variables between IIH and aged- and gender-matched reference (REF) subjects showed IIH abnormalities in glial cells, neurons, and capillaries. The present data suggest a key role of disease processes affecting the glia-neuro-vascular interface.