Pathophysiology Of Idiopathic Intracranial Hypertension Research Articles

Idiopathic Intracranial Hypertension with Disproportionately Enlarged Subarachnoid Space Hydrocephalus on Imaging: A Case Report.

The pathophysiology of idiopathic intracranial hypertension (IIH) and idiopathic normal-pressure hydrocephalus (iNPH) differs in terms of cerebrospinal fluid (CSF) pressure and imaging-related characteristics. A 51-year-old man presented with optic nerve papillary edema, visual disturbance, bilateral abducens nerve palsy, and a wide-based gait. Imaging showed characteristic findings of IIH and disproportionately enlarged subarachnoid space hydrocephalus (DESH)-characteristic of iNPH. A CSF examination revealed marked CSF hypertension. IIH with iNPH-like imaging features (DESH) was diagnosed, and ventriculoperitoneal shunt surgery was performed. Postoperatively, the visual acuity and visual field improved. This report also describes the distinct and overlapping pathophysiological mechanisms of IIH and iNPH.

Stenting for Venous Sinus Stenosis in Patients With Idiopathic Intracranial Hypertension: An Updated Systematic Review and Meta-Analysis of the Literature.

Although venous sinus stenting (VSS) improves cerebrospinal fluid reabsorption and decreases intracranial pressure in patients with idiopathic intracranial hypertension (IIH), the underlying pathophysiology of IIH is not well understood. We present a review and meta-analysis of the literature on VSS for IIH treatment, focusing on the rates of restenosis and symptom recurrence. We performed a systematic review of PubMed and Embase databases between January 1, 2011, and December 31, 2021. Articles including ≥5 patients with IIH and venous sinus stenosis treated with VSS and post-treatment rates of restenosis (de novo stenosis at a different anatomic location along the dural sinuses or restenosis within or adjacent to the stent) were selected. Demographic, procedural, and outcomes data were collected and analyzed. Mean values for variables collected were pooled, and a mean value was calculated with a 95% CI. Twenty-four articles were included, comprising 694 patients and 781 VSS cases. The mean age was 33.9 (CI, 31.5-36.2) years. The mean body mass index was 35.3 (CI, 32.9-37.7) kg/m 2 . Before VSS, 98.8% (CI, 96.8%-100.0%) of patients experienced headaches, 87.7% (CI, 80.6%-95.5%) had visual acuity issues, 78.7% (CI, 69.9%-88.5%) had papilledema, 58.3% (CI, 46.0%-73.9%) had tinnitus, and 98.8% (96.4%-100.0%) had symptoms refractory to previous therapies. After VSS, 77.7% (CI, 71.1%-84.95%) experienced symptom improvement and 22.3% (CI, 15.1%-29.0%) had persistent or worsened symptoms. Pooled restenosis rate was 17.7% (CI, 14.9%-20.9%). VSS is effective in alleviating IIH signs and symptoms, but the associated high rates of restenosis and persistent symptoms highlight the need for further investigation of this procedure and other adjunctive treatments for IIH.

Noninvasive, patient-specific computational fluid dynamics simulations of dural venous sinus pressures in idiopathic intracranial hypertension

BackgroundThe pathophysiology of Idiopathic Intracranial Hypertension (IIH) is poorly understood, making the disease difficult to properly diagnose and treat. Endovascular venous stenting has emerged as an effective non-invasive treatment option for a select cohort of IIH patients with venous sinus stenosis and elevated venous sinus pressure gradient. Unfortunately, current methods of determining patient eligibility for stenting treatment depend on highly invasive and insufficient measurement methods such as venous manometry, which can only measure pressure gradients and not other components of the complex 3D hemodynamic environment. Thus, there is a need for a non-invasive methodology for determining the 3D flow environment of the dural venous sinuses. ObjectiveTo develop a novel method of non-invasive, patient-specific computational fluid dynamic (CFD) simulation of venous sinus hemodynamics for evaluating stenting eligibility. MethodA patient with IIH and elevated sinus pressure gradient underwent MR venography, phase-contrast MR venography, and venous manometry. Patient-specific dural venous anatomy was segmented from the MR venography to construct 3D models of the venous sinuses. 3D transient patient-specific computational fluid dynamic simulations were conducted using flow velocities measured with phase-contrast MR venography as boundary conditions. ResultsSuccessful computational simulations were completed, allowing for the calculation of the spatio-temporal evolution of blood flow through the dural venous sinuses, and the quantitative examination of pressure gradients. Calculated pressure gradients from CFD were validated against venous manometry with an error of only ∼5%. ConclusionsWe have successfully developed time-resolved, patient-specific 3D computational simulations of the dural venous sinuses without assumptions at the boundary conditions for the first time. The methodology can accurately and non-invasively measure venous pressure gradients. This preliminary study serves as a proof of concept for our method to be used as a diagnostic tool for determining venous stenting eligibility, as well as a tool for advancing the general understanding of IIH pathophysiology. Statement of SignificanceThe pathophysiology of Idiopathic Intracranial Hypertension (IIH) is poorly understood making the disease difficult to properly diagnose and treat. Endovascular venous stenting has emerged as an effective non-invasive treatment option for a select cohort of IIH patients with venous sinus stenosis and elevated venous sinus pressure gradient. Our work provides a method for noninvasively determining eligibility for venous sinus stenting, avoiding costly and invasive venous manometry.

Idiopathic Intracranial Venous Hypertension: Toward a Better Understanding of Venous Stenosis and the Role of Stenting in Idiopathic Intracranial Hypertension.

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.

"Idiopathic" intracranial hypertension: An update from neurointerventional research for clinicians.

The recognition of venous sinus stenosis as a contributing factor in the majority of patients with idiopathic intracranial hypertension coupled with increasing cerebral venography and venous sinus stenting experience have dramatically improved our understanding of the pathophysiologic mechanisms driving this disease. There is now a dense, growing body of research in the neurointerventional literature detailing anatomical and physiological mechanisms of disease which has not been widely disseminated among clinicians. A literature search was conducted, covering the most recent neurointerventional literature on idiopathic intracranial hypertension, the pathophysiology of idiopathic intracranial hypertension, and management strategies (including venous sinus stenting), and subsequently summarized to provide a comprehensive review of the most recently published studies on idiopathic intracranial hypertension pathophysiology and management. Recent studies in the neurointerventional literature have greatly improved our understanding of the pathophysiologic mechanisms causing idiopathic intracranial hypertension and its associated conditions. The ability to make individualized, patient-specific treatment approaches has been made possible by advances in our understanding of how venous sinus stenosis and cerebral venous hypertension fundamentally contribute to idiopathic intracranial hypertension.

Symptom: Runny Nose Six Years After Acoustic Neuroma Surgery

A 58-year-old woman presented with a history of right-sided hearing loss and synkinesis following her vestibular schwannoma resection in 2016 elsewhere. She showed some improvement in synkinesis after botulinum toxin treatment. However, on questioning the patient notes that she experienced persistent, clear water-like nasal drainage while bending over, exercising, or doing household work. In 2019, she underwent a right trans-canal cerebrospinal fluid leakage repair with the closure of the Eustachian tube at an outside facility. Eight months later, the symptoms recurred. Her examination showed an obese female (body mass index of 35.1) with clear external auditory canal with tissue behind the tympanic membrane on the right. Nasal exam was normal with no evidence of allergic rhinitis.Figure 1: Axial (horizontal) T1 FLAIR non-enhanced MRI showing the Eustachian tube packing is still in place. Clinical Consultation, runny nose, acoustic neuroma surgery, cerebrospinal fluid leak.Figure 2: Axial (horizontal) CT of temporal bones after contrast injection into the CSF space showing the contrast in the CSF. Clinical Consultation, runny nose, acoustic neuroma surgery, cerebrospinal fluid leak.Figure 3: Coronal (parallel to the face) CT of temporal bones after contrast injection into the CSF space showing no gross contrast in the middle ear indicating not a fast flow leak. Clinical Consultation, runny nose, acoustic neuroma surgery, cerebrospinal fluid leak.Figure 4: Axial (horizontal) T2 MRI demonstrating ischemic changes in middle cerebellar peduncle and cerebellum on left side of image (patient’s right side) from the surgical resection. Clinical Consultation, runny nose, acoustic neuroma surgery, cerebrospinal fluid leak.Figure 5: Coronal (parallel to the face) T2 demonstrating the anatomy in the coronal plane. Clinical Consultation, runny nose, acoustic neuroma surgery, cerebrospinal fluid leak.DIAGNOSIS: CEREBROSPINAL FLUID LEAK Negaar Aryan, MD; Karen Tawk, MD; Mehdi Abouzari, MD, PhD; and Hamid R. Djalilian, MD Clear fluid coming from the nose after a skull base surgery should alarm the clinician of a possible -cerebrospinal fluid (CSF) leak. CSF is a colorless liquid that provides nutrients, hormones, and signaling molecules. It maintains a constant intracranial pressure through production or reabsorption, and clears out unnecessary or toxic metabolic byproducts from the brain. On average, humans have 150 cc of CSF but 450 cc of CSF is produced daily and 450 cc of CSF has to be absorbed. Any imbalances in this equilibrium will lead to excess production of fluid, causing an elevation in intracranial pressure, implicated in idiopathic intracranial hypertension (IIH), hydrocephalus, brain trauma, brain tumors, and stroke. 1,2 CSF leak is a rare but severe condition with serious and potentially fatal outcomes. They are classified into two groups, traumatic and spontaneous. The traumatic group is divided into iatrogenic (related to nasal, ear, or cranial surgery) and non-iatrogenic (related to blunt or penetrating trauma) subgroups. The spontaneous group is further divided into high-pressure and low-pressure subgroups (according to CSF pressure). 3 Idiopathic intracranial hypertension is defined as an increase of CSF pressure inside the skull without any identifier cause. The vast majority of patients (about 90%) are obese women. The pathophysiology of IIH is still unclear, but cerebral venous hypertension is known as the primary underlying cause, which leads to dysfunctional arachnoid granulation, reduced CSF resorption, and elevated intracranial pressure. Patients mostly present with headaches (usually daily, mostly upon waking), vision loss (brief episodic blurring or loss of peripheral vision), and bilateral papilledema. Pulsatile tinnitus and dizziness may also become chief complaints of undiagnosed patients. On the other hand, in patients who have undergone brain surgery, the arachnoid villi (which facilitate reabsorption of CSF) may get clogged up with blood during the surgery, and this may lead to communicating hydrocephalus or decreased absorption, which in the presence of IIH can exacerbate symptoms. Diagnosis of CSF leaks is still a challenge. Diagnosis of post-traumatic leaks is immediate, whereas in spontaneous leaks it is more difficult since they are characterized by intermittent symptoms, and are dependent on disease etiology, leading to delayed diagnosis. The diagnostic algorithm includes clinical otolaryngology assessment with neurosurgical and ophthalmological consultation, radiological imaging, and laboratory findings of the nasal liquid. In clinical evaluations, performing some maneuvers (e.g., occluding the jugular vein, the Valsalva maneuver or having the patient bend over for a few minutes) can increase the intracranial pressure and reveal the leak. Nasal endoscopy is used to detect bone defects, meningoceles, or meningoencephaloceles in the nose. Neuro-ophthalmologists have an important in the diagnosis of intracranial hypertension. They use fundoscopy and visual field testing to evaluate the retina and optic nerve head and papilledema, and use optical coherence tomography to check the optic nerve changes. Neuro-ophthalmologists are the primary clinicians who treat IIH. Neuroradiological evaluations, including fine cut CT scan and magnetic resonance imaging (MRI), are important for suspected or diagnosed CSF leaks. 5,6 Findings on CT scans, such as bony defect of the skull base (dehiscence in the anterior skull base or and temporal bone) can be helpful in the diagnosis. MRIs can show the presence of meningoceles (dura and CSF outpouching), meningoencephaloceles (brain, dura, and CSF outpouching), and inflammation of the dura in the area in question on post-contrast imaging. MRI also plays an important role in the diagnosis of spontaneous CSF leak in IIH by demonstrating noteworthy signs including an empty sella, flattening of the posterior globes, optic nerve head protrusions, distention of the optic nerve sheaths, tortuosity of the optic nerve, cerebellar tonsillar herniation, meningoceles, CSF leaks, and transverse venous sinus stenosis. The most sensitive and specific laboratory tests for CSF leak diagnosis are beta2-transferrin and beta trace protein which are used on collected nasal secretions. Nasal endoscopy with intrathecal 5% fluorescein is indicated when no signs of leak are found on nasal endoscopy or imaging and when beta2-transferrin and beta trace protein are inconclusive or unavailable. If no CSF leak is found, pseudo-CSF leak diagnosis is made and an intranasal ipratropium trial is indicated. Finally, if the patient shows no improvement, then surgical exploration and treatment are indicated. In addition, screening for medication that can exacerbate IIH, including doxycycline, carbidopa, levodopa, cyclosporine, danazol, lithium, phenytoin, vitamin A, and some contraceptive drugs is also necessary. 3,4 This patient’s imaging showed no leak at the site of the previous craniotomy. Her MRI showed the Eustachian tube packing is still in place (Figures 1 and 2). In addition, contrast concentration (per pixel) in bilateral acoustic meatus or paranasal sinuses measured on radionuclide cisternography did not reveal any rapid or high-flow leak (Figure 3). These findings might be attributable to a very slow-flow and intermittent CSF leakage that cannot be identified using standard imaging—as in this case, the tracer did not have the time to egress the subarachnoid space. Treatment includes conservative and surgical therapies. Conservative therapy is the first choice in patients without an immediate need for intervention. It is recommended for patients to be on bed rest with the head raised by 30 degrees for 1-2 weeks. Medications include antitussives, antiemetics, corticosteroids, and stool softeners. Diuretics such as acetazolamide, reduce the CSF production at the choroid plexus, resulting in lower intracranial (IC) pressure. Lumbar puncture with opening pressure is recommended in patients with high IC pressure. Surgical strategies include wound exploration, mastoid obliteration, Eustachian tube occlusion, and lumboperitoneal shunts placement. Since late-onset CSF leak following a vestibular schwannoma resection can be due to increased intracranial pressure, patient’s evaluation is completed by a referral to a neuro-ophthalmologist. Since patient workup (nasal endoscopy, CT scan, MRI, radionuclide cisternography) (Figures 4 and 5) showed no sign of CSF leak, an intranasal ipratropium trial (0.03%, twice a day for two weeks) was initiated. In addition, the patient was advised to see a neuro-ophthalmologist for further evaluation of intracranial hypertension. The patient came back after two weeks with no improvement, and therefore, our next step was to discuss surgical options. The two main options included exploration of the previous craniotomy wound versus left-sided transcanal and transnasal endoscopic (transtympanic) CSF leakage control with blockage of the Eustachian tube given the history of multiple late leaks in this patient. Patients with CSF leaks need to be evaluated by a neuro-ophthalmologist after closure of the leak as the closure of the leak can lead to increased intracranial pressure again. The CSF leak creates a pressure valve that will decrease the intracranial pressure while open. However, when the leak is closed, the intracranial pressure can start increasing. BONUS ONLINE VIDEOS: VISUAL DIAGNOSIS Read this month’s Clinical Consultation case, then watch the accompanying videos from Hamid R. Djalilian, MD, to review the patient’s imaging for yourself. Video 1. Axial (horizontal) T1 FLAIR non-enhanced MRI showing the Eustachian tube packing is still in place. Video 2. Axial (horizontal) CT of temporal bones after contrast injection into the CSF space showing the contrast in the CSF. Video 3. Coronal (parallel to the face) CT of temporal bones after contrast injection into the CSF space showing no gross contrast in the middle ear indicating not a fast flow leak. Video 4. Axial (horizontal) T2 MRI demonstrating ischemic changes in middle cerebellar peduncle and cerebellum on left side of image (patient’s right side). Video 5. Axial (horizontal) CISS MRI showing the different density in the mastoid and middle ear representing scar, fat, and fluid. Video 6. Coronal (parallel to the face) T1 FLAIR demonstrating the anatomy in the coronal plane. Watch the patient videos online at thehearingjournal.com.

Obstructive Sleep Apnea in Men With Idiopathic Intracranial Hypertension: A Prospective Case-Control Study.

Idiopathic intracranial hypertension (IIH) is uncommon in men. Previous studies reported on high frequency of obstructive sleep apnea (OSA) in men with IIH, but the pathophysiology of this association remains unclear. One possible culprit for increased intracranial pressure in patients with OSA is hypercapnia. The purpose of this study was to compare the rate of hypercapnia during polysomnography (PSG) study in men with and without IIH and to report on the rate and severity of OSA in men with IIH compared with control subjects of similar age and body mass index (BMI). Prospective case-control study of male patients diagnosed with IIH underwent PSG with continuous oxygen and carbon dioxide monitoring overnight. Healthy control subjects with similar age and BMI also underwent PSG. The incidence of OSA diagnosis, rate of hypercapnia and hypoxia, and apnea hypopnea index (AHI) were compared between 2 groups. Eleven subjects with IIH and 10 controls underwent PSG. Both groups were similar regarding age and BMI on the Mann-Whitney U test ( P = 0.072 for age, P = 0.251 for BMI). Subjects for whom carbon dioxide data were not available for more than 50% of total sleep time were excluded from hypercapnia analysis. The mean age was 41.9 years, and the mean BMI was 33.8 kg/m 2 in subjects and controls. OSA was diagnosed in 9 of 11 men with IIH and 4 of 10 controls. There was no statistically significant difference in the rate of hypercapnia and hypoxia between 2 groups for whom the data were available. All patients with BMI over 30 kg/m 2 (7 of 7) and 50% (2 of 4) controls with BMI over 30 kg/m 2 were diagnosed with OSA compared with 50% (2 of 4) of cases and 33% (2 of 6) of controls with BMI less than 30 kg/m 2 . BMI was a significant predictor of total AHI ( P = 0.042) and OSA severity ( P = 0.023), but IIH diagnosis was not ( P > 0.05). There was no difference in hypercapnia rate between men with IIH and controls; thus, hypercapnia is an unlikely causative factor in pathophysiology of IIH. OSA on PSG was almost 2 times as prevalent in patients with IIH compared with controls; however, BMI was the strongest predictor of OSA diagnosis, and most patients (9 of 11) with BMI over 30 kg/m 2 had OSA on PSG. In men with BMI less than 30, the rate of OSA on PSG study was higher in men with IIH. Based on these data, we recommend that all men with the diagnosis of IIH should undergo PSG study.

Idiopathic intracranial hypertension: an illustrated guide for the trainee radiologist.

Idiopathic intracranial hypertension is characterized by increased intracranial pressure, headache, and visual perturbations. Although the pathophysiology of idiopathic intracranial hypertension is obscure, several mechanisms have been proposed, such as increased cerebral blood volume, excessive cerebrospinal fluid volume (due to high production or impaired resorption), and inflammatory mechanisms as a likely cause of or contributor to impaired cerebrospinal fluid circulation. It predominantly affects women of reproductive age who are overweight or obese. The most common symptoms are daily headache, synchronous pulsatile tinnitus, transient visual perturbations, and papilledema with visual loss. The main neuroimaging findings are a partially empty sella turcica; flattening of the posterior sclera; transverse sinus stenosis (bilateral or in the dominant sinus); a prominent perioptic subarachnoid space, with or without optic nerve tortuosity; and intraocular protrusion of the optic nerve head. The main complication of idiopathic intracranial hypertension is visual loss. Within this context, neuroimaging is a crucial diagnostic tool, because the pathology can be reversed if properly recognized and treated early.

Cerebrospinal fluid levels of sortilin-1, lipocalin-2, autotaxin, decorin and interleukin-33 in patients with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure of unknown cause. It has been suggested that the inflammatory process plays a role in the pathophysiology of the disease. Sortilin-1, lipocalin-2, autotaxin, decorin, and interleukin-33 (IL-33) are among the factors involved in inflammatory processes. To investigate the CSF levels of sortilin-1, lipocalin-2, autotaxin, decorin, and IL-33 in patients with IIH. A total of 24 IIH patients and 21 healthy controls were included in the study. Demographic characteristics of the patients and of the control group as well as CSF pressures were evaluated. Sortilin-1, lipocalin-2, autotaxin, decorin and IL-33 levels in the CSF were measured. The CSF levels lipocalin-2, sortilin-1, autotaxin, IL-33 and CSF pressure were significantly higher in the patients group compared with the control group (p < 0.001). Decorin levels were reduced in patients (p < 0.05). There was no correlation between the autotaxin and IL-33 levels and age, gender, CSF pressure, and body mass index. The results of our study showed that inflammatory activation plays an important role in the development of the pathophysiology of IIH. In addition, the fact that the markers used in our study have never been studied in the etiopathogenesis of IIH is important in explaining the molecular mechanism of this disease. Studies are needed to evaluate the role of these cytokines in the pathophysiology of the disease. It is necessary to evaluate the effects of these molecules on this process.

A New Perspective on the Pathophysiology of Idiopathic Intracranial Hypertension: Role of the Glia-Neuro-Vascular Interface.

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.

Intracranial computed tomography histogram analysis detects changes in the setting of elevated intracranial pressure and normal imaging.

Patients with idiopathic intracranial hypertension (IIH) have elevated intracranial pressure (ICP) of unclear etiology. This study evaluated the ability of quantitative intracranial Hounsfield unit (HU) histogram analysis to detect pathophysiological changes from elevated ICP in the setting of a normal head CT. Retrospective analysis of non-contrast-enhanced head CT images of IIH patients and matched controls. Following skull stripping, total intracranial CT voxels within the range of 0-70 HU were divided into seven 10 HU bins. A measurement of total intracranial HU was also calculated for each patient. Imaging studies for IIH patients were reviewed for features of IIH including transverse sinus stenosis (TSS). Histogram measures were compared between IIH and control groups and correlated with imaging and clinical data. Fourteen IIH patients with CSF opening pressure ≥25cm water, and 31 age-, sex-, and ethnicity-matched controls were included. Compared to controls, IIH patients had a significantly greater proportion of voxels in the 40-50, 50-60, and 60-70 HU bins (p = 0.003, 0.001, and 0.003, respectively) but similar proportion in the 0-10 HU range. Severity of TSS significantly correlated with total intracranial HU measures. 50-60 HU and 60-70 HU bins demonstrated high AUCs of 0.81 and 0.80, respectively, in differentiating IIH from normal status. Idiopathic intracranial hypertension patients have a greater proportion of high intracranial HU voxels representing blood volume, which may be explained by TSS causing venous congestion. The pattern provides further insights into the pathophysiology of IIH and may be useful for detecting elevated ICP in the setting of normal head CT imaging.

Update on Idiopathic Intracranial Hypertension Management.

Idiopathic Intracranial Hypertension (IIH) is a secondary headache with a steadily growing incidence. Currently, there is little evidence to guide the treatment of IIH. To review the pathophysiology of IIH, with focus on the role of obesity as a risk factor, and the implications for new therapeutic perspectives. in this narrative review, we summarized the current knowledge on treatment options highlighting available evidence for managing intracranial hypertension, obesity, and headache. Clinical Presentation: headache is the most common symptom and a significant cause of quality-of-life impairment. Visual loss is common in the diagnosis. Pathophysiology: there is no unified theory able to explain all symptoms and the evolution of the disease. There is growing data pointing to metabolic changes and obesity with a central role in IIH pathophysiology. Treatment: most published data on IIH treatment is related to pressure control and protection from visual loss. Acetazolamide and cerebrospinal fluid diversion are the best options available. Optic nerve sheath fenestration might be useful to temporally control the pressure over the optic nerve and thus protect from visual deterioration. Recently, venous sinus stenting has proven to be a safe option in selected cases. Finally, bariatric surgery has proven to effectively control elevated intracranial pressure. IIH is a potential cause of high disability. Early recognition is important, and treatment should be tailored to the needs of each case. There is a lack of research on headache management, which might persist after ICP control.

[Diagnosis and Therapy for Idiopathic Intracranial Hypertension].

Idiopathic intracranial hypertension is a pathological state of increased intracranial pressure without intracranial mass lesion, vascular lesion, or hydrocephalus. For the diagnosis of this pathology, various secondary and primary headaches, such as migraine and medication overuse headaches should be excluded. Radiological imaging, including diffusion tensor imaging may show secondary findings of intracranial hypertension. These imaging techniques may be useful to diagnose intracranial hypertension, because at present there is no reliable non-invasive method to measure intracranial pressure. The pathophysiology of idiopathic intracranial hypertension has not been revealed; however there are some theories include, the disorder of cerebrospinal fluid circulation, disturbance of intracranial venous circulation, and metabolic disorders. Headache, nausea, and optic disc edema are frequently observed. The disease is frequently seen in obese females of childbearing age. Several therapies, including weight reduction, medication, and surgery have been studied; however the level of evidence for these therapies remains low.

Benign Intracranial Hypertension Due to Hypoparathyroidism: A Case Report.

Objective: The objective of this study is to present the rare case of a young girl with idiopathic intracranial hypertension secondary to hypoparathyroidism.Background: Idiopathic intracranial hypertension is a neurological syndrome characterized by elevated intracranial pressure (> 25 cmH2O) in the absence of intracerebral abnormalities or hydrocephalus. The pathophysiology of idiopathic intracranial hypertension is unknown, and rare cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. It is supposed that hypocalcemia causes decrease in the absorption of cerebrospinal fluid in arachnoidal granulations.Methods: The workup of the girl with idiopathic intracranial hypertension and hypoparathyroidism included physical examination, blood tests, diagnostic imaging, and lumbar puncture.Results: We present a 9-year-old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent an ophthalmologic examination that revealed papilledema. Lumbar puncture revealed an opening pressure of 65 cm H2O; cerebrospinal fluid analysis and brain computed tomography scan were normal. The patient started taking acetazolamide. Blood tests revealed hypocalcemia associated with high phosphorus level and undetectable PTH hormone, which led us to suspect hypoparathyroidism. She had never had cramps, paraesthesias, or tetany. Chvostek's and Trousseau's signs were positive. In the neck ultrasonography, parathyroids were not visible. Oral supplementation with calcitriol and calcium was started. Headache, nausea, and vomiting immediately disappeared after the lumbar puncture, and the papilledema improved gradually.Conclusions: Several anecdotal cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. However, our case report is of particular interest, since the child did not present with typical neurological hypoparathyroidism symptoms. Therefore, we recommend that hypoparathyroidism should be included in diagnostic investigations on children with clinical findings of idiopathic intracranial hypertension, because clinical manifestations of hypoparathyroidism are variable and may involve almost all organ systems.

Morphological alterations of the hypothalamus in idiopathic intracranial hypertension.

The pathophysiology of idiopathic intracranial hypertension (IIH), a condition characterized by raised intracranial pressure, is not well understood. We hypothesized that the hypothalamus might exhibit alterations in patients with IIH, based on its established association with obesity and the potential role of hormonal and metabolic factors in IIH. Retrospective single-center cohort study. Thirty-three individuals with IIH and 40 matched healthy individuals were studied, including levels of the hormones and proteins leptin, adiponectin, ghrelin, insulin, growth/differentiation factor 15 (GDF15), somatostatin, and melatonin. In vivo high-resolution T1-weighted magnetic resonance imaging (MRI) data were analyzed by quantification of hypothalamic volumes using a well-established segmentation method, separate for the anterior and the posterior hypothalamic subvolumes. An additional analysis was performed using age, gender, and BMI-matched subgroups of 20 IIH patients and 20 controls. The analysis of laboratory values showed significantly increased insulin, leptin, and melatonin levels for IIH patients in comparison to controls, while adiponectin levels were decreased in IIH; however, only melatonin level differences could be confirmed in the analysis with BMI matching. There was no statistical difference in total hypothalamus volumes between IIH and controls, but the hypothalamic morphology was altered in IIH patients with a lower volume of the anterior part of the hypothalamus and a higher volume of the posterior part; these results were identical in the analysis of the BMI-matched groups. The correlation analyses between hormonal changes and hypothalamic morphology did not achieve significant results. In this exploratory study, morphological abnormalities of the hypothalamus were observed to be associated with the IIH complex, although the mechanism remains to be unraveled. These findings expand the metabolic phenotype of IIH, but further functional studies are necessary to corroborate these data.

Idiopathic Intracranial Hypertension is Associated with a Higher Burden of Visible Cerebral Perivascular Spaces: The Glymphatic Connection.

Research suggests a connection between idiopathic intracranial hypertension and the cerebral glymphatic system. We hypothesized that visible dilated perivascular spaces, possible glymphatic pathways, would be more prevalent in patients with idiopathic intracranial hypertension. This prevalence could provide a biomarker and add evidence to the glymphatic connection in the pathogenesis of idiopathic intracranial hypertension. We evaluated 36 adult (older than 21 years of age) patients with idiopathic intracranial hypertension and 19 controls, 21-69 years of age, who underwent a standardized MR imaging protocol that included high-resolution precontrast T2- and T1-weighted images. All patients had complete neuro-ophthalmic examinations for papilledema. The number of visible perivascular spaces was evaluated using a comprehensive 4-point qualitative rating scale, which graded the number of visible perivascular spaces in the centrum semiovale and basal ganglia; a 2-point scale was used for the midbrain. Readers were blinded to patient diagnoses. Continuous variables were compared using a Student t test. The mean number of visible perivascular spaces overall was greater in the idiopathic intracranial hypertension group than in controls (4.5 [SD, 1.9] versus 2.9 [SD, 1.9], respectively; P = .004). This finding was significant for centrum semiovale idiopathic intracranial hypertension (2.3 [SD, 1.4] versus controls, 1.3 [SD, 1.1], P = .003) and basal ganglia idiopathic intracranial hypertension (1.7 [SD, 0.6] versus controls, 1.2 [SD, 0.7], P = .009). There was no significant difference in midbrain idiopathic intracranial hypertension (0.5 [SD, 0.5] versus controls, 0.4 [SD, 0.5], P = .47). Idiopathic intracranial hypertension is associated with an increased number of visible intracranial perivascular spaces. This finding provides insight into the pathophysiology of idiopathic intracranial hypertension, suggesting a possible relationship between idiopathic intracranial hypertension and glymphatic dysfunction and providing another useful biomarker for the disease.

Evaulating peripapillary vessel density ın regressed papilledema ın ıdiopathic ıntracranial hypertension patients

PurposeTo evaluate the retinal nerve fiber layer (RNFL) thickness, the ganglion cell complex (GCC) and vessel density of the radial peripapillary capillary (RPC) plexus of eyes with regressed papilledema in idiopathic intracranial hypertension (IIH) patients using optical coherence tomography angiography (OCT-A) and comparing the results with healthy controls. Materials and methodsFifty-one eyes of 31 patients diagnosed with IIH and 52 eyes of 52 healthy subjects were enrolled in this study. All patients underwent a complete ophthalmological examination and a 4.5 × 4.5 mm peripapillary OCT-A scanning. The quantitative results of the peripapillary RNFL and GCC thicknesses and vessel density of the RPC were analyzed. ResultsThe vessel density in the inferior, superior nasal, and inferior nasal sectors of the patients with IIH significantly exceeded the vessel density of the healthy controls (P = 0.008, P = 0.008, and P = 0.000, respectively). The RNFL and GCC thickness measurements were comparable in both groups. ConclusionsPatients with IIH show vascular abnormalities in the inferior nasal region, which can be detected with OCT-A. As a noninvasive imaging modality, OCT-A could provide a new perspective for understanding the pathophysiology of IIH and could also be useful in the follow-up of these patients.

Role of tumor necrosis factor-alpha in the pathophysiology of idiopathic intracranial hypertension.

Although the pathogenesis of idiopathic intracranial hypertension (IIH) is still poorly understood, the contribution of inflammatory mechanisms has been proposed in its pathophysiology. This study aimed to measure serum tumor necrosis factor-α (TNF-α) levels in patients with IIH and to examine its relationship with clinical and ophthalmological parameters and cerebrospinal fluid (CSF) opening pressure. Thirty-six IIH patients and 30healthy subjects were enrolled in the study. Patients were subjected to complete neurological, general, and ophthalmological assessments. Serum TNF-α levels were measured for patients and controls using the enzyme-linked immunosorbent assay. Serum TNF-α levels were significantly higher in IIH patients compared to healthy controls (p value <.001). Serum TNF-α level was significantly negatively correlated with grade of perimetry and CSF opening pressure (r=-.36, p value=.02), (r=-.37, p value=.02) respectively. However, serum TNF-α was not significantly correlated either with age at onset, disease duration, BMI, headache severity, relapse rate, visual acuity, or papilloedema grade. Serum TNF-α was found to be a significant predictor of the severity of the visual field affection in IIH patients, as one-grade increase of the perimetric grading was associated with a decrease in serum TNF-α by 13.96ng/ml. Altered serum TNF-α levels may suggest the potential involvement of pro-inflammatory mechanisms in the pathogenesis of IIH. Serum TNF-α level may be an indicator of the severity of the visual field affection in IIH.

Intracranial Venous Hypertension and Venous Sinus Stenting in the Modern Management of Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is a debilitating condition that has traditionally been difficult to treat. In recent years, there has been increasing focus on the role of intracranial venous hypertension in the pathophysiology of IIH. Based on increased understanding of this pathophysiology, venous sinus stenting (VSS) has emerged as a safe and reliable treatment for a certain population of patients with IIH. Stratifying patients with IIH based on the status of their venous outflow can provide insight into which patients may enjoy reduction in their symptoms after VSS and provides information regarding why some patients may have symptom recurrence. The traditional view of IIH as a disease due to obesity in young women has been cast into doubt as the understanding of the role of intracranial venous hypertension has improved.

Correlation between intracranial pressure and venous sinus pressures in patients undergoing cerebral venography and manometry

BackgroundThe pathophysiology of idiopathic intracranial hypertension (IIH) is complex but is directly related to cerebral venous hypertension. Few studies have simultaneously recorded venous sinus pressures and lumbar puncture (LP) opening...