Pathophysiology Of Idiopathic Intracranial Hypertension Research Articles

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...

The Potentially Modifiable Risk Factor in Idiopathic Intracranial Hypertension: Body Weight.

Idiopathic intracranial hypertension (IIH) prevalence increased in conjunction with rising obesity rates. Here, we highlight the importance of weight management in IIH and introduce glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) as potential treatment strategy for IIH. Weight gain is a risk factor for IIH, and weight loss (via any treatment strategy) plays a key role in IIH management. GLP-1 is an incretin secreted by the distal small intestine in response to a meal. GLP-1 RAs have been shown to improve glycaemic control (no hypoglycaemia) and lower body weight in patients with and without type 2 diabetes. The choroid plexus has been found to express GLP-1 receptors, and treatment with a GLP-1 RA significantly reduces CSF secretion in vitro and intracranial pressure (ICP) in rodents. New research evaluating the pathophysiology of IIH supports GLP-1 RA as a potential treatment for IIH via weight loss dependent and independent mechanism to directly reduce ICP.

Idiopathic Intracranial Hypertension: Glymphedema of the Brain.

During the last decade, our understanding of cerebrospinal fluid (CSF) physiology has dramatically improved, thanks to the discoveries of both the glymphatic system and lymphatic vessels lining the dura mater in human brains. We detail the recent basic science findings in the field of CSF physiology and connect them with our current understanding of the pathophysiology of idiopathic intracranial hypertension (IIH). Transverse sinus (TS) stenoses seem to play a major causative role in the symptoms of IIH, as a result of a decrease in the pressure gradient between the venous system and the subarachnoid space. However, the intracranial pressure can be highly variable among different patients, depending on the efficiency of the lymphatic system to resorb the CSF and on the severity of TS stenoses. It is likely that there is a subclinical form of IIH and that IIH without papilledema is probably under-diagnosed among patients with chronic migraines or isolated tinnitus. IIH can be summarized in the following pathological triad: restriction of the venous CSF outflow pathway-overflow of the lymphatic CSF outflow pathway-congestion of the glymphatic system. To better encompass all the stages of IIH, it is likely that the Dandy criteria need to be updated and that perhaps renaming IIH should be considered.

The Role of Arachnoid Granulations and the Glymphatic System in the Pathophysiology of Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder characterized by long-standing elevated intracranial pressure (ICP). As the name applies, no uniform cause has been identified. IIH is typically characterized by headaches, pulsatile tinnitus, and visual deterioration. Anomalies in cerebrospinal fluid (CSF) absorption are implicated in the pathophysiology of IIH. Non-invasive imaging of the brain parenchyma and the cerebral venous sinus has improved, and research has gained a better understanding of the role of cerebral venous sinus stenosis. Both have led to a better delineation of the role of arachnoid granulations (AG) and the glymphatic system in the development of IIH. IIH may occur as a result of restrictions of CSF absorption from the venous system, and or the congestion and overflow of the glymphatic system. Elucidating these mechanisms will lead to greater understanding of its underlying pathophysiologic mechanisms.

Migraine or idiopathic intracranial hypertension: Magnetic resonance venography and magnetic resonance imaging findings.

Idiopathic intracranial hypertension (IIH) is a disease characterised by increased cerebral pressure without a mass or hydrocephalus. We aimed to differentiate migraine and IIH patients based on imaging findings. Patients with IIH (n = 32), migraine patients (n = 34) and control subjects (n = 33) were evaluated. Routine magnetic resonance imaging, contrast-enhanced 3D magnetic resonance venography and/or T1-weighted 3D gradient-recalled echo were taken with a 1.5 T magnetic resonance scanner. Optic-nerve sheath distention, flattened posterior globe and the height of the pituitary gland were evaluated in the three groups. Transverse sinuses (TS) were evaluated with respect to score of attenuation/stenosis and distribution. Pearson chi-square, Fisher's exact test and chi-square trend statistical analyses were used for comparisons between the groups. A p-value of <0.05 was considered statistically significant. Decreased pituitary gland height, optic-nerve sheath distention and flattened posterior globe were found to be statistically significant (p < 0.001) in IIH patients. Bilateral TS stenosis was also more common in IIH patients than in the control group and migraine group (p = 0.02). Decreased pituitary gland height, optic-nerve sheath distention, flattened posterior globe, bilateral stenosis and discontinuity in TS are significant findings in differentiating IIH cases from healthy individuals and migraine patients. Bilateral TS stenosis may be the cause rather than the result of increased intracranial pressure. The increase in intracranial pressure, which is considered to be responsible for the pathophysiology of IIH, is not involved in the pathophysiology of migraine.

Guide to preclinical models used to study the pathophysiology of idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and papilloedema in the absence of an identifiable secondary cause typically occurring in young women with obesity. The impact is considerable with the potential for blindness, chronic disabling headaches, future risk of cardiovascular disease and marked healthcare utilisation. There have been marked advances in our understanding the pathophysiology of IIH including the role of androgen excess. Insight into pathophysiological underpinnings has arisen from astute clinical observations, studies, and an array of preclinical models. This article summarises the current literature pertaining to the pathophysiology of IIH. The current preclinical models relevant to gaining mechanistic insights into IIH are then discussed. In vitro and in vivo models which study CSF secretion and the effect of potentially pathogenic molecules have started to glean important mechanistic insights. These models are also useful to evaluate novel therapeutic targets to abrogate CSF secretion. Importantly, in vitro CSF secretion assays translate into relevant changes in ICP in vivo. Models of CSF absorption pertinent to IIH, are less well established but highly relevant and of future interest. There is no fully developed in vivo model of IIH but this remains an area of importance. Progress is being made to improve our understanding of the underlying aetiology in IIH including the characterisation of disease biomarkers and their mechanistic role in driving disease pathology. Preclinical models, used to evaluate IIH mechanisms are yielding important mechanistic insights. Further work to refine these techniques will provide translatable insights into disease aetiology.

Exploring The Current Management Idiopathic Intracranial Hypertension, And Understanding The Role Of Dural Venous Sinus Stenting.

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

The Association of Optical Coherence Tomography Results With Neuroimaging Signs and Some Clinical Parameters in Idiopathic Intracranial Hypertension

Background: Recently, optical coherence tomography (OCT) has enhanced our understanding of visual disturbances in idiopathic intracranial hypertension (IIH). Its importance in the evaluation process of IIH has been established; however, there are many unknown aspects regarding the relationship of OCT measurements with several clinical features of IIH. Herein, we aimed to investigate the associations of OCT measurements with neuroimaging findings and some clinical parameters in our cohort with IIH. Methods: Patients over 18 years of age presenting to the neurology and neuro-ophthalmology outpatient clinics, between 2017 and 2019, who were diagnosed with IIH were included in the study. Cranial magnetic resonance imaging (MRI) recordings were retrospectively evaluated for the presence of neuroimaging signs of intracranial hypertension. Peripapillary retinal nerve fiber layer (RNFL) measurements and other clinical parameters were retrospectively evaluated from the hospital recoding system. SPSS Statistics (version 20) were used for statistical analyses. Results: We have included 18 patients of IIH with a mean age of 38.6 years (range: 19 - 69 years) and female/male ratio was 17:1. Mean body mass index (BMI) of the patients was 30.5 ± 5.7 and mean lumbar puncture (LP) opening pressure was 313.8 ± 66.6 mm H 2 O. Correlation analyses between LP opening pressure and average RNFL thickness of the right eye revealed a significant positive correlation. The results of the other correlation analyses were unremarkable. Conclusions: We have found a significant correlation between LP opening pressure and RNFL thickness of the right eye. No association between RNFL measurement and MRI signs of intracranial hypertension was found. Investigating the possible associations between RNFL measurements and the clinical and neuroimaging signs in future studies may provide crucial contributions regarding the unknown aspects of IIH pathophysiology. J Neurol Res. 2019;9(4-5):65-71 doi: https://doi.org/10.14740/jnr550

Endovascular Stenting in a Transgender Patient With Idiopathic Intracranial Hypertension

Endovascular Stenting in a Transgender Patient With Idiopathic Intracranial Hypertension

Diagnosis and Management of Cerebral Venous Diseases in Neuro-Ophthalmology: Ongoing Controversies.

Diseases of the cerebral venous system frequently lead to neuro-ophthalmic complications. Cortical venous sinus thrombosis and dural arteriovenous fistulas may be complicated by elevation of intracranial pressure, with secondary papilledema or abducens palsies. There is increasing recognition that stenosis at the transverse sinus-sigmoid sinus junction plays a role in the pathophysiology of idiopathic intracranial hypertension and offers a new avenue of treatment in patients who fail medical therapy. Diseases of the cavernous sinus manifest with their own set of neuro-ophthalmic symptoms, reflecting the presence of all 3 ocular motor nerves and the oculosympathetic fibers within its walls, along with its role as the primary drainage pool of the globe and orbit. Numerous questions and controversies remain regarding the diagnosis and optimal treatment of cerebral venous disease, including the role of venous stenting in idiopathic intracranial hypertension, the role of anticoagulation in cavernous sinus thrombosis, and the risks and benefits of embolization of mild indirect cavernous carotid fistulas.

Endovascular Treatment of Idiopathic Intracranial Hypertension with Stenting of the Transverse Sinus Stenosis.

For many years, the pathophysiology of idiopathic intracranial hypertension (IIH) was interpreted as “secondary intracranial hypertension,” and IIH was considered to be caused by brain edema due to obstructive sleep apnea. Another theory proposed cerebrospinal fluid (CSF) absorption impairment due to excessive medication with vitamin A derivatives. Other reports pointed out the importance of obesity, which may cause an impairment of intracranial venous drainage due to elevated right atrial pressure. Patients with medically refractory IIH have traditionally undergone a CSF diversion. Venous outlet impairment on IIH has recently been reported as a causative or contributory cause, and thus focused venoplasty of the stenotic sinus with a stent has emerged as a new treatment strategy. We report the cases of two patients who presented with headache and papilledema with IIH. They successfully underwent stent placement at the stenosis of the transverse sinus and experienced complete resolution of symptoms.

Idiopathic intracranial hypertension: adult versus pediatric patients

Idiopathic intracranial hypertension (IIH), also known as benign intracranial hypertension or pseudotumor cerebri, is characterized by increased intracranial pressure secondary to unknown causes. IIH affects both adults and children but predominately young obese females of child-bearing age. IIH gives rise to headache, visual disturbances, and symptoms of raised intracranial pressure. The pathophysiology of IIH remains elusive; postulations include obesity-related hormonal changes, obstruction of the central venous sinus, and hereditary causes. Diagnosing IIH is based on modified Dandy criteria. Diagnosis in children is challenging as symptoms and presentations vary; atypical and delayed presentations are not uncommon. Treatment for IIH includes oral acetazolamide or lumbar puncture; surgical treatment with shunts and optic nerve sheath fenestration is reserved for complicated and recurring cases. Treatment options for children are limited and associated with considerable risks and side effects. Vision loss is debilitating and occurs in 10% of IIH patients. A thorough and collaborative approach in managing IIH is needed. This study reviews the epidemiology, clinical presentation, diagnosis, and management of IIH in adults and pediatric patients.

Understanding the complex pathophysiology of idiopathic intracranial hypertension and the evolving role of venous sinus stenting: a comprehensive review of the literature.

Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure without established etiology. Although there is now consensus on the definition of the disorder, its complex pathophysiology remains elusive. The most common clinical symptoms of IIH include headache and visual complaints. Many current theories regarding the etiology of IIH focus on increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it has been postulated that obesity plays a role, given its prevalence in this population of patients. Several treatments, including optic nerve sheath fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts, and more recently venous sinus stenting, have been described for medically refractory IIH. Despite the availability of these treatments, no guidelines or standard management algorithms exist for the treatment of this disorder. In this paper, the authors provide a review of the literature on IIH, its clinical presentation, pathophysiology, and evidence supporting treatment strategies, with a specific focus on the role of venous sinus stenting.

CSF Pressure Change in Relation to Opening Pressure and CSF Volume Removed.

Idiopathic intracranial hypertension is a complex neurologic disorder resulting from increased intracranial pressure. Our aim was to determine whether a correlation exists between the CSF pressure-volume relationship, specifically the craniospinal elastance and pressure-volume index, in patients with idiopathic intracranial hypertension and whether opening pressure affects this relationship. Lumbar punctures performed for suspected idiopathic intracranial hypertension from 2006 to 2017 were identified. Opening and closing pressures, CSF volume removed, and clinical diagnosis of idiopathic intracranial hypertension were obtained from the medical records. The craniospinal elastance (pressure change per milliliter of CSF removed) and pressure-volume index were calculated, and the Pearson correlation coefficients between both the craniospinal elastance and pressure-volume index and opening pressure were determined. Linear regression models of craniospinal elastance and the pressure-volume index and interaction terms with opening pressure were assessed for covariate influence on this association. One hundred sixteen patients were included in the final analysis. The mean craniospinal elastance according to opening pressure group was 0.52 ± 0.18 for <20 cm H2O, 0.57 ± 0.20 for 20-29 cm H2O, 0.91 ± 0.28 for 30-39 cm H2O, and 1.20 ± 0.25 for ≥40 cm H2O. There was a positive linear association between opening pressure and craniospinal elastance with a 0.28 cm H2O/mL increase in craniospinal elastance (standard error = 0.03, P < .001) for every 10 cm H2O increase in opening pressure. Of the covariables analyzed, only age older than 50 years and total volume of CSF removed affected this association. As opening pressure increases, the craniospinal elastance increases in a linear fashion while the pressure-volume index decreases. Further studies are needed to determine whether these changes relate to the underlying pathophysiology of idiopathic intracranial hypertension or simply represent established CSF volume pressure dynamics.

Pseudotumor Cerebri and Glymphatic Dysfunction.

In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer’s disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.

Cerebrospinal fluid total protein in idiopathic intracranial hypertension

ObjectiveTo evaluate the relationship between CSF total protein concentration (CSF protein) and CSF opening pressure in idiopathic intracranial hypertension (IIH), and to explore the association of age, gender, race, BMI, and Humphrey visual field mean deviation (HVF MD) with CSF total protein. MethodsThe medical records of all IIH patients seen between 1989 and 2016 at one institution were systematically reviewed for demographics, CSF opening pressure, CSF contents, and HVF MD (at initial evaluation and most recent follow-up). Linear regression of CSF protein on CSF opening pressure was performed also considering BMI, age, gender, race, HVF MD, and year of lumbar puncture. ResultsWe included 266 IIH patients (13 pre-pubertal children, 35 post-pubertal children, 218 adults). There was a negative linear association between CSF opening pressure and CSF protein: CSF protein decreased by 0.18mg/dL for each 1cm H2O increase in CSF opening pressure (p<0.001). After controlling for CSF opening pressure, mean CSF protein was 4.1mg/dL higher in white patients than in black patients (p<0.001). Multivariable analysis found that CSF opening pressure (p=0.007), white race (p<0.001), and HVF MD (most recent follow-up, worst eye, p=0.05) remained independently associated with CSF protein controlling for year of lumbar puncture and age. ConclusionsThere was a negative association between CSF protein and CSF opening pressure. After controlling for CSF opening pressure, CSF protein was higher in white patients and unaffected by age, gender, or BMI. Our findings help clarify inconsistent results of prior studies, but do not really help clarify IIH pathophysiology.

Glial and neuronal antibodies in patients with idiopathic intracranial hypertension.

Headache and visual disturbances are the main presenting symptoms of idiopathic intracranial hypertension (IIH) characterized by increased intracranial pressure (ICP) with an unknown cause. We aimed to investigate the antibodies against optic neuritis-associated glial antigens, aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) and uncharacterized neuronal membrane antigens in IIH patients. Consecutive patients diagnosed according to Friedman revised diagnostic criteria and control subjects were included after their consent. All serum samples were analyzed for antibodies against AQP4 and MOG using cell-based immunofluorescent assays and for uncharacterized neuronal membrane antigens by indirect immunocytochemistry utilizing live neurons. Sera of 34 patients with IIH and 40 control subjects were investigated but none of the patients showed AQP4 and MOG antibodies. However, serum IgG of five IIH patients showed reactivity against membrane antigens of rat hippocampal and cortical neurons. Interestingly, three out of these five patients had nonspecific white matter lesions on MRI, whereas only four of all other patients had these lesions (p=0.048). AQP4 and MOG antibodies do not seem to have a role in the pathophysiology of IIH. However, association of immunocytochemistry findings with the presence of white matter lesions may suggest that immunological factors contribute to the pathogenesis of IIH in at least some of the patients.