Pathogenesis Of Idiopathic Intracranial Hypertension Research Articles

Clinico demographic profile and short-term outcome of Pediatric Idiopathic Intracranial Hypertension in a tertiary care hospital of Bangladesh

Background: Diagnosis of IIH (idiopathic intracranial hypertension) in children is challenging. The pathogenesis of IIH is still largely unknown. The aim of this study to evaluate the clinico-demographic profile and short-term outcome of IIH among Bangladeshi children. Methodology: This observational cohort study was done in pediatric Neurology Department, National Institute of Neurosciences and Hospital Bangladesh from January 2018 to July 2019. Total 19 cases were enrolled who were clinically suspected and/or had normal CSF with opening pressure (OP) above 250 mmH2O. They were further categorized as “definite IIH”, definite IIH without papilledema, and “probable IIH”. Clinical, radiological profile and short-term outcome were analyzed by SPSS version 22. Result: Among them most were probable IIH (74%). Episodic (57.9%), moderate, diffuse headache was the predominant symptom along with vomiting, double vision, unilateral VI nerve palsy and papilledema. Obesity was found in 21% cases. Mean CSF pressure was 21.84+7.62cm H2O and found high in definite IIH. All the cases were treated with acetazolamide and serial LP was done in 4(15.8%) cases. Definite IIH requires longer hospital stay (6.42 ± 2.87days). Recurrence was observed in 10.5% cases and visual impairment was found in 15.8% cases. Conclusion: This study found wide range of diversity between clinical feature and CSF opening pressure in Pediatric IIH and diagnostic confirmation was challenging. Initial treatment response was satisfactory with a low recurrence rate. J Bangladesh Coll Phys Surg 2024; 42: 161-168

Recurrent reflex syncope in idiopathic intracranial hypertension patient resolved after lumbar puncture: pathogenetic implications

BackgroundIdiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the cerebrospinal fluid reabsorption rate, increasing cerebrospinal fluid volume and pressure at the expense of intracranial compliance and promoting further sinus compression. Intracranial compliance is the ability of the craniospinal space to accept small volumetric increases of one of its compartments without appreciable intracranial pressure rise. In idiopathic intracranial hypertension, a condition associated with a reduced rate of CSF reabsorption leading to its volumetric expansion, a pathologically reduced IC precedes and accompanies the rise of ICP. Syncope is defined as a transient loss of consciousness due to a transient cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. A transient global cerebral hypoperfusion represents the final mechanism of syncope determined by cardiac output and/or total peripheral resistance decrease. There are many causes determining low cardiac output including reflex bradycardia, arrhythmias, cardiac structural disease, inadequate venous return, and chronotropic and inotropic incompetence. Typically, syncopal transient loss of consciousness is mainly referred to an extracranial mechanism triggering a decrease in cardiac output and/or total peripheral resistance. Conversely, the association of syncope with a deranged control of intracranial compliance related to cerebral venous outflow disorders has been only anecdotally reported.Case PresentationWe report on a 57-year-old woman with daily recurrent orthostatic hypotension syncope and idiopathic intracranial hypertension-related headaches, which resolved after lumbar puncture with cerebrospinal fluid subtraction.ConclusionsA novel mechanism underlying the triggering of orthostatic syncope in the presence of intracranial hypertension-dependent reduced intracranial compliance is discussed.

Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.

The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change>1.5 or<0.67 and p-value<0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.

Elevated neurofilament light chain CSF/serum ratio indicates impaired CSF outflow in idiopathic intracranial hypertension

BackgroundImpaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.MethodsNfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.ResultsCSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = − 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.ConclusionsThe observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.

Sex hormones, CSF and serum leptin in patients with idiopathic intracranial hypertension

BackgroundIdiopathic intracranial hypertension (IIH) is typically seen in females of childbearing period; therefore, it is possible that female sex hormones have a pathogenic role in IIH. Obesity is considered as a strong risk factor for IIH, Leptin levels in the serum and CSF were found to be positively correlated with anthropological measures of obesity. The role of leptin and sex hormones in the pathogenesis of idiopathic intracranial hypertension is not fully understood. The aim of this work was to assess CSF leptin, serum leptin, estradiol, testosterone, Dehydroepiandrosterone sulfate (DHEAS) levels in idiopathic intracranial hypertension (IIH) patients.ResultsThis is a case control study which was conducted on 38 IIH female patients and 38 females as controls. IIH patients had significantly higher levels of serum Leptin, CSF Leptin, serum estradiol and serum testosterone than controls (P value < 0.001, < 0.001, 0.005 and < 0.001, respectively), whereas there was no statistically significant difference between IIH patients and controls in serum DHEAS (P value = 0.142). IIH patients with body mass index (BMI) ≥ 30 kg/m2 had significantly higher levels of serum Leptin, CSF Leptin, serum estradiol, serum testosterone, and serum DHEAS than IIH patients with BMI < 30 kg/m2 (P value < 0.001, < 0.001, 0.009, < 0.001, and < 0.001, respectively).ConclusionsPatients with IIH express a characteristic elevation in CSF leptin, serum leptin, estradiol and testosterone levels. These hormones are significantly elevated in patients with high BMI.

Advances in the Understanding of the Complex Role of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up‐to‐date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis.Level of Evidence1Technical Efficacy Stage2

Prediction of the trans-stenotic pressure gradient with arteriography-derived hemodynamic features in patients with idiopathic intracranial hypertension

The pathogenesis of idiopathic intracranial hypertension (IIH) is attributed to segmental stenosis of the venous sinus. The current treatment paradigm requires a trans-stenotic pressure gradient of ≥8 mmHg or ≥6 mmHg threshold. This study aimed to develop a machine learning screening method to identify patients with IIH using hemodynamic features. A total of 204 venous manometry instances (n = 142, training and validation; n = 62, test) from 135 patients were included. Radiomic features extracted from five arteriography perfusion parameter maps were selected using least absolute shrinkage and selection operator and then entered into support vector machine (SVM) classifiers. The Thr8-23-SVM classifier was created with 23 radiomic features to predict if the pressure gradient was ≥8 mmHg. On an independent test dataset, prediction sensitivity, specificity, accuracy, and AUC were 0.972, 0.846, 0.919, and 0.980, respectively (95% confidence interval: 0.980–1.000). For the 6 mmHg threshold, thr6-28-SVM incorporated 28 features, and its sensitivity, specificity, accuracy, and AUC were 0.923, 0.956, 0.935, and 0.969, respectively (95% confidence interval: 0.927–1.000). The trans-stenotic pressure gradient result was associated with perfusion pattern changes, and SVM classifiers trained with arteriography perfusion map-derived radiomic features could predict the 8 mmHg and 6 mmHg dichotomized trans-stenotic pressure gradients with favorable accuracy.

Хроническая церебральная венозная дисфункция: взгляд на проблему

В статье представлен аналитический обзор результатов отечественных и зарубежных исследований по проблеме хронических нарушений мозгового венозного кровообращения, которым уделяют меньше внимания в сравнении с патологией артериальной системы из-за нечеткости проявлений, особенно ранних, анатомической изменчивости венозного русла даже у здоровых, сложности верификации диагноза и т.д. Когда баланс артериального притока и венозного оттока нарушается и это нарушение прогрессирует, развиваются необратимые изменения в других структурах полости черепа — в первую очередь страдает головной мозг (что согласуется с концепцией Монро — Келли). Хронические нарушения церебрального венозного кровообращения могут иметь разные причины и разную степень выраженности. Синдром хронической церебральной венозной дисфункции, терминологически принятый у нас, в некоторых странах рассматривается как хроническая венозная цереброспинальная недостаточность, что подчеркивает патогенетическую связь нарушений церебрального венозного кровотока с внечерепными венами, что, на наш взгляд, является логичным и обоснованным. Признание хронической цереброспинальной венозной недостаточности вызвало значительный интерес к изучению роли внечерепной венозной патологии и вариантов ее развития. Несмотря на то, что диагноз изначально был основан на допплерографической сонографии, пока не установлено диагностических способов визуализации, неинвазивных или инвазивных, которые могут служить золотым стандартом для выявления венозных отклонений, свидетельствующих о хронической цереброспинальной венозной недостаточности. Обсуждаются результаты ряда исследований, в частности, гипотезы о роли хронической цереброспинальной венозной недостаточности в патогенезе рассеянного склероза и многих сопутствующих клинических проявлений. Анализируется общность по патогенезу идиопатической внутричерепной гипертензии, болезни Меньера, синдрома спондилогенной вертебрально-базилярной недостаточности. Акцентируется внимание и на другом мнении ученых, которые повышение венозного кровенаполнения головного мозга и других образований полости головы при определенных условиях рассматривают как компенсаторную реакцию. Рассматриваются анатомо-физиологические особенности венозной системы черепной полости, обосновывающие клинические проявления венозной дисфункции, способы диагностики и лечения патологии. Обобщая вышесказанное отметим, что хроническое нарушение циркуляции венозной крови в полости черепа в значительной степени связано с проблемами внечерепного венозного кровотока и не только само по себе является достаточно характерным синдромокомплексом, который негативно влияет не только на неврологические функции за счет гипоксии мозга и метаболических изменений, ухудшает качество жизни, но и на течение или имеет патогенетическую связь с другими заболеваниями, в частности, может сопровождаться различным уровнем артериального давления.

To assess the level of cytokines and chemokines in patients of idiopathic intracranial hypertension (IIH)

Background: Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure(ICP) without an identifiable etiology. While, Headache, double vision and subsequently visual loss are the common symptoms, it is probably the commonest neurological cause of reversible blindness. The pathogenesis of idiopathic intracranial hypertension(IIH) remains unclear and as such it remains a diagnosis of exclusion. Aim: To measure the levels of pro and anti- inflammatory cytokines in serum and CSF of patients with IIH and study the association between inflammatory cytokines with neurological, ophthalmological and radiological profile 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.

An Unusual Cause of Irritability in a Single Ventricle Patient after Bidirectional Glenn Shunt

The differential diagnosis for irritability in children is broad. In patients with congenital heart disease, one must strongly consider cardiac etiologies such as low cardiac output or elevated central venous pressure (CVP). In patients with single-ventricle physiology, the second stage of palliation includes bidirectional Glenn, which involves anastomosis of the superior vena cava to the pulmonary artery resulting in volume offloading of the single systemic ventricle. Typically, early in the post-operative period, patients may experience a headache due to the acute increase in CVP, and symptoms improve over time. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a rare neurologic disorder in children, characterized by raised intracranial pressure (ICP) in the absence of brain parenchymal lesions or cerebrospinal fluid (CSF) abnormalities. While the pathogenesis of IIH is unknown, early recognition and treatment of IIH are important to prevent permanent vision loss. There are only rare reports of IIH in patients with Fontan circulation. To our knowledge, we report the first case of IIH in a 2-year-old female after bidirectional Glenn.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammation markers in patients with papilledema due to idiopathic intracranial hypertension.

Purpose:The aim of this study was to investigate the role of inflammation in the pathogenesis of idiopathic intracranial hypertension (IIH) using the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as inflammation markers.Methods:The files of 33 IIH patients and 33 controls were screened for this retrospective study. For each patient, the NLR and PLR values were calculated using a single fasting blood sample. For both eyes, papilledema (PE) grades, best-corrected visual acuity (BCVA), retinal nerve fiber layer thickness (RNFLT), and ganglion cell layer thickness (GCLT) measurements were recorded along with the demographic data, including body mass index (BMI), and complete neurological and ophthalmological findings. Comparisons between the two groups and between the IIH patients with and without PE were made. The associations of NLR and PLR with all other parameters were analyzed independently from age, gender, and BMI.Results:NLR and PLR were higher in patients with IIH than controls (P < 0.05). They were also higher in patients with PE (P < 0.05) in the IIH group. NLR and PLR were found to be associated with BCVA (P < 0.001 and P = 0.023, respectively), global RNFLT (P = 0.004 and 0.012, respectively), RNFLT of the temporal quadrant (P < 0.001 and P = 0.042, respectively) and PE grade (P < 0.001 and P = 0.035, respectively).Conclusion:The NLR and PLR values and their associations with BCVA, RNFLT, and PE support the hypothesis that inflammation is a very important component of the pathogenesis of IIH.

Serum glial fibrillary acidic protein (GFAP)-antibody in idiopathic intracranial hypertension

Aim Idiopathic intracranial hypertension (IIH), a disease of obscure origin, is characterized by headache and visual disturbances due to increased intracranial pressure. Recent line of evidence has suggested involvement of inflammation in IIH pathogenesis thus bringing forward anti-glial autoimmunity as a potential contributor of IIH. Glial fibrillary acidic protein (GFAP) is a major astrocytic autoantigen associated with a specific form of meningoencephalitis. Materials and methods In this study, we investigated the presence of GFAP-antibody in 65 sera (49 obtained during active disease and 16 during remission) and in 15 cerebrospinal fluid (CSF) samples of 58 consecutively recruited IIH patients using cell based assay and indirect immunohistochemistry. Results GFAP-antibody was found in active period sera of 2 IIH patients with classical symptoms and good treatment response. Two remission period sera obtained at different time points from one of these cases showed lower titers of GFAP-antibody positivity. IgG from positive samples yielded an astrocytic immunoreactivity pattern. None of the CSF samples showed GFAP-antibodies. Conclusions These results suggest that anti-astrocyte autoimmunity might be present in a fraction of IIH patients. Exact pathogenic significance of this association needs to be further studied.

Metabolic Concepts in Idiopathic Intracranial Hypertension and Their Potential for Therapeutic Intervention.

Background:Traditional risk factors associated with idiopathic intracranial hypertension (IIH) include obesity, weight gain, and female sex. The incidence of IIH is increasing and yet the underlying trigger and the fueling pathological mechanisms are still poorly understood.Evidence Acquisition:Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, and neurosurgery literature was made.Results:The facts that implicate sex and obesity in IIH and headache are examined. The role of fat distribution in IIH is questioned, and the concept of adipose tissue functioning as an endocrine organ driving IIH is discussed. The impact of androgen metabolism in IIH is reviewed as is the emerging role of glucagon-like-peptide-1 analogues in modulating intracranial pressure. This introduces the concept of developing targeted disease-modifying therapeutic strategies for IIH.Conclusions:This review will discuss the possible role of the adipose/gut/brain metabolism axis in IIH and speculate how this may impact the pathogenesis of IIH and therapeutic opportunities.

Fluid-structure Interaction in the Cerebral Venous Transverse Sinus.

The biomechanics of the cerebral venous system plays an important role in determining blood flow to the brain. Computational approaches to help elucidate the role of the cerebral venous system in health and disease have largely focused on lumped-parameter models and one-dimensional computational fluid dynamics simulations. To expand upon the prior work, and to investigate the possible role of cerebral venous collapse in normal physiology and pathological conditions, we developed a fluid-structure interaction (FSI) model of the cerebral venous transverse sinus (TS), coupled to a lumpedparameter representation of the upstream cerebral circulation to provide boundary conditions for the FSI simulation. We simulated the effects of local venous hemodynamics on the TS distention and investigated TS vascular collapse under increased intracranial pressure, as has been hypothesized in the pathogenesis of idiopathic intracranial hypertension. Our baseline simulations reproduced pressures and flows in the cerebral venous system that compared favorably with what has been reported in the literature. The FSI simulations under increased intracranial pressure showed a decreased venous flow through and progressive collapse of the TS veins. Our simulations captured the dynamic behavior of the vascular collapse and may help shed light on the interactions between the cerebrovascular and cerebrospinal fluid spaces in health and disease.

Is cerebral edema effective in idiopathic intracranial hypertension pathogenesis?: Diffusion weighted MR imaging study

The aim of this study is to research whether cerebral edema is effective in the pathogenesis of patients with idiopathic intracranial hypertension (IIH) by using diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) measurements. Was changed into thirty-six IHH patients who received DWI and 36 age- and sex-matched healthy control group were assessed retrospectively. ADCmin, ADCmean, and ADCmax values were measured from different regions of the brain for both IHH patients and the control group. The StudentÂ’s t-test was used to compare the ADCmin, ADCmax, ADCmean values acquired from distinct parts of the brain parenchyma of IIH patients with the values of control group. No significant difference was found between ADCmin, ADCmax, and ADCmean values of IIH and control group in bilateral frontal, parietal temporal and occipital lobe cortical and subcortical white matter, caudate nucleus head, putamen, thalamus, corpus callosum splenium and genu (P>0.05). This study showed that cerebral edema cannot be a significant mechanism in the pathogenesis of IIH.

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.

Population-based incidence and clinical characteristics of idiopathic intracranial hypertension.

To validate the diagnosis of idiopathic intracranial hypertension (IIH) from the Swedish National Patient Register (NPR) and investigate the incidence of IIH, as well as co-morbidities and medication use in a large Swedish population-based sample. We searched the NPR to find all patients ≥18years old with the ICD-10 diagnosis code (G93.2) for IIH in Stockholm County from Jan 1, 2006, to Dec 31, 2013. All medical records were reviewed to validate the diagnosis and to collect additional information. We included 207 patients with an IIH diagnosis, of which 135 (65%) were correctly diagnosed when validated by charts review. Eighty-three patients had disease onset during the study period. This gave a yearly incidence of 0.65/100000. Female-to-male ratio was 6.1:1. Females, mean age 31.0 (CI 28.8-33.1), were younger at time of diagnosis compared to males, mean age 42.9 (CI 36.4-49.5), P<.001. The most common co-morbidities were obesity (92%), hormonal conditions (21%) and recent infections preceding the diagnosis (21%). Prior treatment with tetracycline derivatives were seen in 9%. The incidence of IIH in Stockholm is in the lower range of previously reported rates, possibly due to a lower prevalence of obesity. A substantial proportion of patients (35%) did not fulfill diagnostic criteria. Disease onset occurs at younger age in females. Co-morbidities were mainly associated with diseases affecting hormonal balance or causing inflammatory activation. These findings raise new hypothetical theories regarding mechanisms involved in IIH pathogenesis.

Starling resistors, autoregulation of cerebral perfusion and the pathogenesis of idiopathic intracranial hypertension.

Two critical functions for the control of intracranial fluids dynamics are carried on the venous side of the perfusion circuit: the first is the avoidance of cortical veins collapse during the physiological increases of cerebrospinal fluid (CSF) pressure in which they are immersed. The second, is the generation of an abrupt venous pressure drop at the confluence of the cortical veins with the dural sinuses that is required to allow a CSF outflow rate balanced with its production. There is evidence that both of these effects are ensured by a Starling resistor mechanism (a fluid dynamic construct that governs the flow in collapsible tubes exposed to variable external pressure) acting at the confluence of cortical veins in the dural sinus. This implies that, in normal circumstances of perfusion balance, a certain degree of venous collapse physiologically occurs at the distal end of the cortical vein. This is passively modulated by the transmural pressure of the venous wall (i.e. the difference between internal blood pressure and external CSF pressure). The mechanism provides that the blood pressure of the cortical vein upstream the collapsed segment is dynamically maintained a few mmHg higher than the CSF pressure, so as to prevent their collapse during the large physiological fluctuations of the intracranial pressure. Moreover, the partial collapse of the vein confluence also generates a sharp pressure drop of the blood entering into the sinus. The CSF is drained in dural sinus through arachnoid villi proportionally to its pressure gradient with the sinus blood. The venous pressure drop between cortical veins and dural sinus is therefore needed to ensure that the CSF can leave the cranio-spinal space with the same speed with which it is produced, without having to reach a too high pressure, which would compress the cortical veins. Notably, the mechanism requires that the walls of the dural sinuses are rigid enough to avoid the collapse under the external cerebrospinal fluid pressure, and predicts that in the presence of excessively flexible dural sinuses, the system admits a second point of balance between cerebral fluid pressure and dural sinus pressure, at higher values. The second balance state is due to the triggering of a self-limiting venous collapse feedback loop between the CSF pressure, that compresses the sinus, and the subsequent increase of the dural sinus pressure, that further raises the intracranial pressure. The loop may stabilize only when the maximum stretching allowed by the venous wall is reached. Then, a new relatively stable and self-sustaining balance state is achieved, at the price of a higher CSF and dural sinus pressure values. We propose that this model is crucially involved in Idiopatic Intracranial Hypertension pathogenesis with and without papilledema, a condition that could be described as a pathological new balance state, relatively stable, between intracranial and dural venous pressure, at higher absolute values.

Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension.

BackgroundTransorbital sonography (TOS) has been proven to be able to non-invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH.MethodsTwenty-one patients with newly diagnosed IIH or secondary IH were prospectively evaluated and compared with 21 age, gender and BMI-matched controls. Experienced vascular sonographers used B-mode TOS to evaluate ONSD, optic nerve diameter (OND) and IJVVI. CSF opening pressures were also measured.ResultsONSD values were significantly higher in patients (6.50 ± 0.67) than controls (5.73 ± 0.66; p < 0.0001). No differences were found in OND values between patients (2.99 ± 0.26) and controls (2.93 ± 0.41; p = 0.574). No correlation was demonstrated between ONSD and CSF opening pressure (r = 0,086) (p = 0.73). No difference in frequency of IJVVI between patients (11/42 valves, 26 %) and controls (9/42, 21 %) was observed (p = 0.777).ConclusionsIncreased ONSD values detected by TOS support the diagnosis of IH. Our results do not support the hypothesis of a venous congestion as a potential factor contributing to the pathogenesis of IIH.Trial registrationNot applicable. Observational, non-interventional study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0594-3) contains supplementary material, which is available to authorized users.