Idiopathic intracranial hypertension: Imaging and clinical fundamentals

Abstract

Neuroimaging is a paramount element for the diagnosis of idiopathic intracranial hypertension, a condition characterized by signs and symptoms of raised intracranial pressure without the identification of a mass or hydrocephalus being recognized. The primary purpose of this review is to deliver an overview of the spectrum and the specific role of the various imaging findings associated with the condition while providing imaging examples and educational concepts. Clinical perspectives and insights into the disease, including treatment options, will also be discussed.

Key Words: Intracranial; Hypertension; Pseudotumor cerebri; Radiology; Neurology; Neuroimaging; STOP; Acronym; Imaging; Neuroradiology

Core Tip: Neuroimaging plays a crucial role in diagnosing idiopathic intracranial hypertension. This review provides a comprehensive synopsis of the various imaging findings associated with the disease, highlighting their diagnostic significance. Illustrative examples of neuroimaging findings, educational concepts and mnemonic tools are provided. Clinical perspectives, including treatment options and management strategies will also be discussed.

INTRODUCTION

Idiopathic intracranial hypertension (IIH), otherwise known as pseudotumor cerebri syndrome, is a complex condition characterized by elevated intracranial pressure (ICP) without a clear causal factor, ventriculomegaly or space-occupying lesions[1]. Historically, IIH was known as serious meningitis, but improvement of medical diagnostic methods allowed the exclusion of secondary causes and by 1950’s, the condition was named benign intracranial hypertension. Eventually, the term IIH emerged when the disorder was no longer considered benign[2]. The two primary symptoms of IIH are temporary visual disturbances with progressive vision loss due to papilledema (swelling of the optic disc) and chronic headache. Patients may also experience back and neck pain, pulsatile tinnitus, cranial nerve palsies, especially sixth cranial nerve palsy leading to double vision. Clinical presentation may vary leading to potential delays in reaching the diagnosis. If left untreated, the disorder can result in significant visual impairment and permanent vision loss[3].

Appropriate treatment generally prevents significant visual impairment. Most patients with IIH respond well to first-line medical therapy, which includes a weight loss program and acetazolamide[4], whereas surgical options are available for patients with severe or refractory symptoms[5]. Imaging has an imperative role in the diagnosis and management of IIH, aiding in excluding secondary causes of elevated ICP and assessing structural changes associated with the condition. Imaging analysis is needed to detect findings pointing towards the appropriate diagnosis. An in-depth imaging review is critical, as subtle imaging findings can impact both diagnosis and treatment decisions, emphasizing the need for familiarity with IIH-related imaging features. This review highlights the clinical importance of imaging in IIH.

EPIDEMIOLOGY

An obese female of reproductive age comprises the typical profile of a patient with IIH. The incidence of IIH in Western countries is estimated in the general adult population at 0.9/100000 people per year[6,7]. This increases to 3.5/100000 in females aged 15-44 and rises further to 19/100000 in females 20-44 years old, with a body mass index (BMI) 20% higher than normal[7]. According to two large cohort studies, a significant increase in IIH incidence has been shown, from 2.26 to 4.69 per 100000 between 2002 and 2016[8] and from 2.5 to 9.3 per 100000 between 2005 and 2017[9]. A probable direct link between the increasing IIH incidence and the obesity epidemic can be suggested[10]. The prevalence of IIH in men is 9%[11]. Men are diagnosed older compared to women, with a with a mean age of 37 vs 28 but have a double risk of severe visual loss. The syndrome has a bimodal distribution pattern in male patients, with a first peak at school age and a second one at middle age[11]. An annual incidence of 0.71 per 100000 is reported in the pediatric population, according to a United Kingdom study[12]. Patients were mostly female (67%), obese (65%), or overweight (11%). Age-specific incidences were 0.17 in children aged 1-6, 0.75 in the 7-11 age group, and up to 1.32 in children aged 12-16 years old. Interestingly, there is neither a gender difference nor an association with obesity in pre-pubertal age. Infantile IIH is extremely rare - only 27 cases have been described - of unknown etiology[13].

Geographic variation in IIH incidence has also been noted. A crude annual incidence of 2.2 per 100000 has been shown in Libya[14], 0.9-1.1 in the United States[7], and only 0.03 in Japan[15]. Despite the noteworthy lower obesity rates in Japan, which could explain the lower IIH incidence, data from two studies held in South Korea and Taiwan suggest that obesity may not play a pivotal role in the pathogenesis of the syndrome in Asians[16,17].

Financial burden on public health systems

The cost of IIH for public health systems has also been assessed. As a direct sequel to the increasing incidence, costs from increasing hospital admission rose from £9.2 million to £50 million per annum between 2002 and 2016 and are expected to rise to £462 million per annum by 2030, according to a United Kingdom study[8]. In the same study, 7.6% of patients had a cerebrospinal fluid (CSF) diversion procedure, 0.7% had bariatric surgery, and 0.1% underwent optic nerve sheath fenestration. The rate of elective caesarean sections was also higher among women with IIH compared to the general population (16% vs 9%). The total economic costs of IIH patients exceeded $444 million in the United States only in 2007, according to a United States study[18]. In a retrospective study of 450 patients, 197 of them African American, the risk of severe visual loss in at least one eye was proven to be higher in this population; the relative risk was 3.5 in at least one eye and 4.8 in both eyes compared to the non-African American patients[19]. It was shown that the difference in the disease burden was not related to diagnosis, treatment, or access to care.

PATHOGENESIS

The pathogenic mechanisms underlying the increase in ICP that leads to the clinical manifestations of IIH remain unclear with several factors having been proposed as underlying causes (Figure 1). Most of the theories proposed focus on the disturbance of CSF dynamics. Apart from the role of CSF dysregulation, which cannot fully explain the disease, accumulating data over the last decade has highlighted the systemic metabolic features of IIH.

Figure 1 Intracranial and metabolic mechanisms, considered to cause elevated intracranial pressure. CSF: Cerebrospinal fluid.

CSF dysregulation

The choroid plexus is the primary site of CSF production; approximately 2/3 of it comes from the choroid plexus epithelial cells, while the rest comes from the ependyma and possibly the blood-brain barrier[20]. The choroid plexus in patients with IIH does not show any macroscopic hypertrophy, distinguishing it from other pathological conditions such as choroid plexus papilloma[21]. CSF production is orchestrated by the globally expressed Na⁺/K⁺ ATPase, which creates an osmotic gradient across the epithelial cell membrane by actively transporting sodium ions and forcing water molecules to relocate[22]. Other channels and receptors, also playing a role in CSF production and expressed in the membrane of the choroid plexus epithelial cells, have been suggested as possible therapeutic targets, such as aquaporins, transient receptor potential vanilloid type 4, and the glucagon-like peptide-1 receptor (GLP-1R)[10].

Glymphatic system impairment

The glymphatic system, as a new pathway of CSF movement, was identified in 2012 using in vivo two-photon imaging[23]. CSF enters the brain interstitium via spaces around penetrating arteries and exits via paravenous drainage routes. It has been suggested that in patients with IIH, the impairment of the glymphatic venous outflow is related to increased cerebral venous sinus pressure, leading to increased ICP[24]. A dysfunctional aquaporin subtype could be responsible for the movement of water molecules from the paravenous space of a cortical vein to the dural sinus[25]. On a cellular level, pathological mitochondria in the perivascular astrocytic end-feet of IIH patients could be related to abnormal glymphatic flow[26]. Increased venous sinus pressure is considered a significant factor in the development of intracranial hypertension, although it is still unclear whether it is a primary cause or a secondary effect. Venous sinus stenosis, especially in transverse sinuses, is a commonly observed radiologic finding in patients with IIH[27].

Hormonal and metabolic factors

The strong correlation between IIH, obesity, and female gender has prompted theories suggesting that hormonal and metabolic factors may also be involved in the pathogenesis of IIH. Obesity is considered to increase ICP mainly through its physical effects of increased abdominal mass, which raises intrathoracic pressure and subsequently elevated venous pressure[28]. Inflammatory procedures, especially inflammatory mediators secreted by adipose tissue is an additional mechanism that may link obesity with IIH. Studies have demonstrated higher concentrations of C-C motif ligand 2, leptin and other inflammatory markers in the CSF of patients with IIH, compared to controls[29,30]. Leptin, a hormone involved in weight homeostasis and appetite regulation, enters the choroid plexus and has a prothrombotic effect leading to microthrombosis in the venous sinuses[31].

In a large population-based matched controlled cohort study in the United Kingdom, the incidence rate ratio for IIH was 3.76 for female patients with a BMI of 25-30 kg/m² and 17.55 for those with a BMI > 30 kg/m², compared to control patients with a BMI less than 25 kg/m²[9]. The role of obesity in IIH development is emphasized by the remission of the disease in weight loss of 6%-10%[31] and worse visual outcomes, especially in patients with a BMI > 40 kg/m²[32]. Bariatric surgery has proven effective in reducing ICP; the greater the weight loss, the more profound the reduction in ICP[33]. In particular, the centripetal adipose tissue has been linked with the metabolic profile of IIH since its reduction by weight loss reduces ICP[34]. The first metabolic phenotype of IIH was based on the analysis of omental and subcutaneous adipose cells and had some striking results[34]. Patients with IIH showed insulin resistance and hyperleptinemia. Moreover, their subcutaneous adipose cells were transcriptionally primed for greater calorie intake and lipogenesis[34]. In total agreement with these results, women with IIH have demonstrated a higher absolute risk compared with control patients for type 2 diabetes, hypertension, and ischemic heart disease[9].

GLP-1 is secreted in the small intestine in response to food intake, leading to glucose-dependent insulin secretion[35]. GLP-1 is also expressed in neurons of the nucleus tractus solitarii in the medulla oblongata and co-regulates satiety and weight loss[36,37]. Moreover, GLP-1 acts in the renal proximal tubule by activating GLP-1R, which in turn stimulates the cyclic adenosine monophosphate-driven inhibition of the Na⁺/H⁺ exchanger, and eventually reduces Na⁺ absorption into the bloodstream[38]. GLP-1R agonists have already been used in managing diabetes mellitus type 2 and obesity[39]. Interestingly, GLP-1R is also expressed in the choroid plexus, and interaction with its agonist, exendin-4, reduces Na⁺/K⁺ ATPase activity[40]. Administration of exendin-4 to female rats with raised ICP caused a GLP-1R-dependent reduction in ICP[40]. The effects of exenatide (a synthetic exendin-4) on 15 adult women with raised ICP (> 25 cm CSF) and papilledema were assessed in a randomized, controlled, double-blind trial[41]. Exenatide significantly reduced ICP at 2.5 hours, 24 hours, and 12 weeks post-administration[41]. Bariatric surgery, and especially Roux-en-Y gastric bypass surgery, increased meal-stimulated GLP-1 levels and decreased ICP, outlining the co-relation of weight loss, GLP-1 blood levels, and ICP[42].

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to active cortisol and is widely expressed, including the adipose tissue and choroid plexus[43,44]. Weight loss is associated with a reduction both in global 11β-HSD1 activity and ICP, suggesting the therapeutic potential of enzyme inhibition[43]. A small cohort of 31 women aged 18-55 years old with active IIH was recruited in a multicenter, phase II, double-blind randomized controlled trial to evaluate the effect of the 11β-HSD1 inhibitor AZD4017[45]. AZD4017 reduced serum cortisol and ICP. Furthermore, the 11β-HSD1 inhibitor reduced risk factors linked with IIH by improving the lipid profile of the subjects and increasing lean muscle mass[46]. The dysfunctional metabolic profile of patients with IIH is further highlighted by a study showing higher than obesity activity of systemic and adipose 11β-HSD1 and 5α-reductase activity, another enzyme involved in steroid metabolism[47].

Since the vast majority of IIH patients are women, a probable role of sex hormones in the pathogenesis of the disease may be suggested. Female rats treated with subcutaneous testosterone injections showed elevated ICP and increased CSF secretion[48]. Using liquid chromatography-tandem mass spectrometry, the serum concentration of testosterone in female patients with IIH proved significantly higher than in controls with non-IIH obesity or polycystic ovary syndrome[49]. CSF testosterone levels were also higher in IIH patients than in females with simple obesity or a normal BMI[49]. Moreover, it was shown that the androgen receptor is expressed in the human choroid plexus, which also possesses the enzymes that activate androstenedione to testosterone[49]. The role of androgen excess in IIH is further supported by the appearance of IIH symptoms and signs in patients undergoing female-to-male gender reassignment after commencing testosterone therapy[50,51]. Understandably, IIH likely results from multiple interacting factors. CSF dysregulation and glymphatic system impairment are key mechanisms, yet they cannot fully explain IIH. High venous sinus pressure and venous sinus stenosis are often observed in patients. Additionally, metabolic and hormonal factors such as obesity, insulin resistance, and elevated testosterone contribute to IIH pathogenesis, with weight loss shown to reduce ICP.

CLINICAL PRESENTATION, FINDINGS & DIAGNOSIS

Clinical presentation

The clinical presentation of IIH varies. Although patients with IIH may be asymptomatic, they usually present with symptoms related to raised ICP, which can be either systemic or visual[52]. Headache is the most common symptom of the disease, affecting approximately 75%-94% of patients[52,53] and presenting with high variability[54]. Headaches are often described as pressure-like, holocranial, frontal, or retro-orbital, aggravating in supine position or by Valsalva maneuvers, and improving with CSF removal. Migraine-like features may also be reported, such as unilateral or focal throbbing headache, along with nausea, photophobia, and phonophobia[55].

As for the visual symptoms, they are commonly not present in mildly elevated ICP or in the early stages of IIH. In more advanced stages of established papilledema or higher ICP, the patients frequently encounter episodes of temporary visual loss, which last up to 60 seconds and are commonly triggered by changes in the patient’s posture or by Valsalva manoeuvres[3]. The cause has been suggested to be raised ICP at the optic nerve, causing transient ischemia of the optic nerve head[56]. As for the visual acuity, although it is generally normal or minimally affected, it can be diminished in mild cases; however, in fulminant or advanced stages of IIH[57], it is severely decreased. Regarding visual field disturbances, they are common findings in IIH. An enlarged blind spot is a typical early visual field defect in raised ICP[58]. The visual field abnormalities also include nasal and arcuate defects, while a severe visual field constriction may also occur[3].

Cranial nerve examination is usually unremarkable, except for sixth cranial nerve palsy that causes binocular horizontal diplopia. The length and the ascending path of the sixth cranial nerve through Dorello’s canal are considered factors contributing to dysfunction in cases of increased ICP[3]. Concerning the third and fourth cranial nerve palsies, they are significantly rarer causes of diplopia in cases of IIH[3]. Other symptoms reported by patients with IIH are pulsatile tinnitus, believed to be caused by flow turbulence within the transverse venous sinus, as well as back and neck pain[52,53].

Clinical findings

Optic disc swelling, which is known as papilledema, is the hallmark sign of IIH[3]. It results from orthograde axoplasmic flow stasis at the optic nerve head, leading to edema development due to increased ICP pressing the nerve posteriorly to the eye. Although typically bilateral and symmetric, unilateral and/or asymmetrical cases may also be present[3]. If left untreated, it may progress to optic disc atrophy and even blindness[3]. Upon fundus examination, variable signs are detected, depending on the severity of the situation. Regarding the optic nerve head, it may be hyperemic with elevated margins, while the retinal nerve fibres can be opacified and the optic cup obliterated[59]. Further findings include the presence of venous dilation, vascular tortuosity, hemorrhages, cotton wool spots, and exudates[59]. Additional characteristic findings that accompany papilledema are the Paton’s striae, which are retinal peripapillary circumferential folds, as well as the choroidal folds (Figure 2)[60].

Figure 2 Photos of the A: right and B: left optic nerve heads of a patient suffering from papilledema due to idiopathic intracranial hypertension. A: Photos of the right optic nerve heads; B: Photos of the left optic nerve heads. Elevation of the disc borders is noted (black arrowheads) as well as obscuration of the nasal optic disc border (black arrow). A circumferential halo is also present in both eyes. A diagnosis of early papilledema was set.

In chronic papilledema, apart from the previously mentioned signs, optic disc pallor may be noted, which is accompanied by little or no optic disc swelling due to loss of axons. Moreover, optociliary shunts and refractile bodies may be identified[3]. The “Frisén scale” is the most frequently used grading system to describe the severity of papilledema from “Stage 0” to “Stage 5” (Table 1)[59,61].

Table 1 Frisén Scale - papilledema grading system.

Frisén Scale - papilledema grading system
Stage 0: Normal optic disc	Retinal NFL prominence at the nasal, superior, and inferior poles in an inverted proportion to disc diameter
	Radial NFL striations - no tortuosity
	Rarely obscuration of a major blood vessel, usually on the upper pole
Stage 1: Very early papilledema - minimal degree of edema	No elevation of the disc borders
	Obscuration of the nasal border of the disc
	Normal temporal disc margin
	Disruption of the normal radial NFL arrangement striations
	Subtle and grayish halo (C-shaped) with temporal gap; underlying retinal details obscured
	Concentric or radial choroidal folds
Stage 2: Early papilledema - low degree of edema	Obscuration of all borders
	Circumferential halo
	Elevation of the nasal border
	No obscuration of any major vessel
Stage 3: Moderate papilledema - moderate degree of edema	Obscurations of all borders
	Circumferential halo
	Obscuration of one or more segments of major blood vessels leaving the disc
	Elevation of all borders
	Peripapillary halo-irregular outer fringe with finger-like extensions
Stage 4: Marked papilledema - marked degree of edema	Total obscuration of a segment of a major blood vessel on the disc
	Elevation of the entire nerve head, including the cup
	Obscuration of all borders
	Complete peripapillary halo
Stage 5: Severe papilledema - severe degree of edema	Dome-shaped protrusions representing anterior expansion of the optic nerve head
	Peripapillary halo is narrow and smoothly demarcated
	Partial obscuration of all vessels and total obscuration of at least one major blood vessel on optic disc
	Obliteration of the optic cup

Adapted from Scott et al[59]. NFL: Nerve fiber layer.

Diagnosis

Historically, the first diagnostic criteria for IIH, the Dandy criteria, were published in 1937. In 1987, the modified Dandy criteria included brain imaging with computed tomography (CT) brain and in 2001, CT or magnetic resonance imaging (MRI), particularly venography, were recommended to be performed in order to exclude secondary causes of raised ICP, such as venous sinus thrombosis[62]. In 2013, the updated modified Dandy criteria were published, highlighting the presence of papilledema as a requirement for a confident diagnosis of IIH, in addition to unremarkable neurological examination except sixth cranial nerve palsy, normal brain parenchyma and meningeal imaging, exclusion of venous sinus thrombosis and lumbar puncture with normal CSF components and elevated opening pressure (≥ 250 mm CSF in adults)[1]. These revised criteria (Table 2) are useful for a safe and prompt diagnosis of IIH in order to initiate timely the appropriate treatment and thus prevent a permanent visual loss[1].

Table 2 Diagnostic criteria for idiopathic intracranial hypertension.

	Diagnostic criteria for idiopathic intracranial hypertension1
I	Papilledema
II	Normal neurologic examination excepting abnormalities of the cranial nerves (VIth or VIIth nerve dysfunction)
III	Neuroimaging: Normal brain parenchyma without signs of hydrocephalus, mass, structural lesions, or abnormal meningeal enhancement on MRI (performed with and without gadolinium) for typical patients (female and obese), and on MRI (performed with and without gadolinium) along with MRV for other patients; if MRI is unavailable or contraindicated, a contrast-enhanced CT may serve as an alternative
IV	Normal CSF composition
V	Increase LP opening pressure [≥ 250 mm CSF in adults and ≥ 280 mm CSF in children (250 mm CSF if the child is not sedated and not obese)] in an appropriately performed LP
Neuroimaging criteria	A: Empty sella
	B: Posterior globe flattening
	C: Optic nerve sheath distention (with or without optic nerve tortuosity)
	D: Transverse venous sinus stenosis

¹Criteria: (1) An idiopathic intracranial hypertension (IIH) diagnosis is confirmed if criteria I-V are met; (2) If only criteria I-IV are met, then IIH diagnosis is probable; (3) If criteria I (papilledema) is not met, an IIH diagnosis can be made if criteria II–V are met, and the patient demonstrates a unilateral or bilateral abducens nerve palsy; and (4) If criteria I (papilledema) is not met and there is no abducens nerve palsy, an IIH diagnosis can be suggested (but not made) if criteria II-V are met, and also at least 3 of the 4 neuroimaging criteria (A-D) are met.

Adapted from Friedman et al[1]. MRI: Magnetic resonance imaging; MRV: Magnetic resonance venography; CT: Computed tomography; LP: Lumbar puncture; CSF: Cerebrospinal fluid.

In cases of papilledema, the initial approach is an immediate blood pressure assessment to rule out malignant hypertension[1]. Moreover, an urgent neurological examination and imaging by CT or MRI are required to exclude the possibility of a space occupying lesion[1]. In order to dismiss the presence of venous sinus thrombosis, MRI and MR venography (MRV) with contrast are needed[1]. A lumbar puncture is performed to measure the opening pressure in order to set a definite diagnosis, while CSF is obtained and sent for composition evaluation to confirm the diagnosis of elevated ICP and to assess for other possible underlying causes of high ICP[1].

The ophthalmologist’s role is usually restricted initially to the diagnosis of IIH and in the long term in the monitoring of the optic nerve appearance changes and the assessment of visual function, by the evaluation of visual acuity and visual fields. Besides fundus examinations, further ophthalmological exams are useful for the diagnosis of IIH. They include B-scan ultrasonography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography (OCT) of the optic nerve head. Fluorescein angiography can differentiate true papilledema from pseudo-papilledema since these conditions are characterized by dye leakage and staining, respectively. Fundus autofluorescence, B-scan ultrasonography, and enhanced depth imaging OCT of the optic nerve head may also identify causes of pseudo-papilledema, such as optic nerve head drusen. Furthermore, OCT of the optic disc can detect cases of subtle papilledema while also allowing its monitoring[63].

IMAGING FINDINGS & THE ROLE OF IMAGING

Neuroimaging studies are crucial for patients suspected of having IIH. Initially, performing neuroimaging studies is necessary in order to rule out increased ICP pressure caused by other conditions (i.e., masses or structural lesions, hydrocephalus, abnormal meningeal enhancement, dural venous sinus thrombosis, etc.). If there is no obvious relevant pathology identified for the increased ICP, then several imaging characteristics can suggest a diagnosis of IIH. Therefore, the role of radiologists entails ruling out obvious pathology and thoroughly assessing the presence of imaging signs that may support IIH diagnosis. Below, we present the relevant neuroimaging findings associated with IIH. Although CT is faster to perform and is characterized by its wide availability, MRI is the preferred imaging method to diagnose IIH, as it can discern the intracranial structures with better accuracy and detail compared to CT (i.e., meningeal infiltration and various tumors are better identified with MRI). MRI studies are more likely to detect various signs related to IIH (discussed below) than CT studies. In addition, compared to other methods such as CT, MRI does not involve radiation exposure and has a lower risk of contrast-induced allergic reactions. Therefore, examples of these signs will be mostly depicted below on MRI. Following their analytical description, conclusive educational concepts will be provided as rough guides for everyday clinical practice.

Empty or partially empty sella turcica

The neuroimaging term “empty sella” refers to the appearance of sella turcica, the midline structure of the sphenoid bone, filled with CSF compressing the pituitary gland housed in the fossa. The upper margin of the pituitary gland appears concave, and the infundibulum is elongated[64]. Although partially (< 50% of sella) or fully (> 50%) CSF-filled sellar space is commonly an incidental finding, it is strongly associated with IIH[65,66]. An at least partially empty sella has been shown to have a sensitivity from as low as 26.7%[67] to as high as 92%[68] and a specificity from as low as 74%[68] to as high as 100%[69]. Importantly, however, a normal appearing sella does not exclude the diagnosis of IIH[70]. Primary empty sella (PES) cannot be attributed to any obvious pathology of the pituitary gland, such as in the case of IIH. In contrast, secondary empty sella arises after surgery, trauma, radiotherapy, the development of a pituitary tumor, spontaneous regression, or Sheehan syndrome[71]. A PES in IIH results from pituitary gland compression by herniation of the subarachnoid space and CSF protrusion into the sella due to intracranial hypertension. It has also been suggested that chronic ICP can remodel the thin bone floor of the sella turcica, leading to a larger and seemingly emptier sella[72,73]. In a retrospective study of 48 female patients with IIH, the mean sellar area was 38% larger in patients than in controls[73]. In the same study, there was only a slight reduction in pituitary gland size, implying that the empty sella is related to the enlargement of the pituitary fossa[73]. With an 82% sensitivity and 67% specificity, a pituitary/sella height ratio < 0.5 is related to increased ICP[74]. The empty sella in IIH patients treated with acetazolamide or lumboperitoneal shunting can be resolved after successful therapy, depending on the chronicity of increased ICP and the extent of bone remodelling[75]. Figure 3 illustrates partially empty, and empty sella examples.

Figure 3 Partially empty sella and empty sella. The figure displays T2-weighted sagittal images from magnetic resonance scans of different patients. A: A normal pituitary gland with normal height and a convex upper border is presented for reference (dashed circle); B: A pituitary gland with partial height loss, indicating a partially empty sella; C: An almost complete height loss of the pituitary gland, indicating an empty sella, are shown in patients with idiopathic intracranial hypertension (dashed circle). Note how the increased intracranial pressure forces appear to stretch the pituitary gland onto the sella turcica (arrows).

Posterior displacement of pituitary stalk

Herniation of the subarachnoid space and CSF protrusion under chronic increased ICP have another effect apart from the “empty sella” turcica appearance. A gradually increasing volume of CSF leads to the formation of a diverticulum, which displaces the pituitary stalk from its typical mid-cavity position[76]. Along with the compression of the pituitary gland, the infundibulum is initially moved mildly posteriorly. Over time and because of remodelling, the cavity floor expands, and the stalk is displaced even more posteriorly[76]. Posterior displacement of the pituitary stalk was observed in 17/40 patients with a clinical diagnosis of IIH (i.e., 43%) with herniation located predominantly anterior to the stalk[76]. In another retrospective study of 43 patients with IIH and 43 control subjects, posterior displacement of the pituitary stalk was observed in 39.5% of them with a specificity of 90.7%[70]. The low incidence of stalk displacement in patients with acute disorders affecting the sellar or hypersellar region, such as a subarachnoid hemorrhage, underlines the role of chronicity in the development of pituitary stalk displacement[76]. Figure 4 illustrates an example of posterior displacement of the pituitary stalk.

Figure 4 Posterior displacement of the pituitary stalk. A and B: Sagittal T2-weighted (A) and contrast-enhanced T1-weighted (B) magnetic resonance images display a pituitary gland of normal dimensions and shape (dashed circle) and a pituitary stalk with normal positioning (arrow); C and D: Sagittal T2-weighted (C) and contrast-enhanced T1-weighted (D) magnetic resonance images of a patient with idiopathic intracranial hypertension display an empty sella (dashed circle) and posterior displacement of the pituitary stalk (arrow), which appears to be pressed against the dorsum sellae as a result of the increased intracranial pressure forces.

Meningoceles

Meningoceles are protrusions of the meninges through a weak or defective point, usually in the skull base, and are categorized into congenital, spontaneous, or iatrogenic (e.g., post-craniotomy). In conditions of ICP such as in IIH, the development of meningoceles through these points of structural vulnerability is often observed[77,78]. In a retrospective case-control study of 79 IIH patients and 76 control subjects between 2000 and 2011, meningoceles were noted in 11% of patients and 0% of controls (P < 0.003)[79]. All meningoceles were positioned in the temporal bone, either Meckel’s cave or petrous apex. The authors suggest that the formation of meningoceles in patients with increased ICP expands the subarachnoid space aiming thus to regulate the high ICP[79]. Additionally, meningoceles could represent sites of CSF micro-leaks to reduce ICP, leading to the clinical manifestations of rhinorrhea or otorrhea in IIH patients[79,80].

Apart from the temporal bone, meningoceles or meningoencephaloceles can appear in other, atypical positions. A rare case of a clival meningocele in a patient with known IIH and a worsening headache has been reported; communication of the clival cavity with the prepontine cistern was noted[81]. Bilateral facial canal meningoceles have also been reported in the context of IIH[82]. Zhang et al[83] reported a case of a 54-year-old woman who had had repeated hospitalizations within 10 years due to meningitis without CSF leak. The patient’s symptoms and radiologic findings were compatible with the diagnosis of IIH. A meningoencephalocele of the right temporal lobe was also observed. Strikingly, treatment with oral acetazolamide for 6 months after discharge protected the patient from recurrent meningitis[83]. The authors conclude that a temporal anteromedial meningoencephalocele enables bacteria to travel intracranially from the nasal cavity to the meninges and ventricles[83]. The patient had been previously treated for various pathogens, but the causative pathology for relapsing meningitis had not been identified. Notably, meningoceles and encephaloceles have been implicated as epileptogenic foci in patients with seizures as the initial presenting feature of IIH[84,85]. Figure 5 illustrates different examples of meningoceles.

Figure 5 Meningoceles. A: Coronal T2-weighted magnetic resonance image is shown displaying a normal temporal bone; B and C: A coronal T2-weighted image (B) and corresponding coronal computed tomography (CT) image (C) of a patient with idiopathic intracranial hypertension demonstrates meningeal protrusions in the sphenoid wings, bilaterally (dashed circles), consistent with meningoceles; D and E: An axial T2-weighted image (D) and corresponding axial CT image (E) of a different patient with idiopathic intracranial hypertension also demonstrate meningeal protrusions (dashed circles), most evidently on the right sphenoid wing than on the left, findings that are consistent with meningoceles.

Meckel’s cave enlargement

Meckel’s cave, a CSF-filled cavity in the medial portion of the middle cranial fossa containing the trigeminal nerve ganglion and proximal rootlets (cranial nerve V), is located posterolaterally to the cavernous sinus on either side of the sphenoid bone and connects the sinus to the prepontine cistern[86]. In a retrospective case-control study of 79 patients with IIH, enlarged Meckel’s caves were found in 9% of patients and 0% of controls (P < 0.003) showing the specificity of the MRI sign for IIH[79]. In a morphometric analysis of 25 patients with IIH and 25 BMI-, sex-, and age-matched control subjects, Meckel’s cave was found bilaterally longer in IIH patients; left side 13812.22 mm and right side 13282.38 mm vs controls (11341.97 mm, P < 0.001; 11361.74 mm, P < 0.01, respectively)[87].

Aaron et al[88] measured Meckel’s cave dimensions in 63 patients with spontaneous CSF leaks - linked with raised ICP - and 91 control subjects. In axial MRI T2-weighted slices, patients with spontaneous CSF leaks showed a statistically significantly longer (14.7 ± 2.8 mm vs 11.55 ± 1.9 mm) and wider Meckel’s cave (6.3 ± 1.8 mm vs 5.1 ± 0.9 mm)[88]. As expected, the area measured was also higher in the CSF leak cohort; 0.81 ± 0.35 cm²vs 0.52 ± 0.15 cm²[88]. Kamali et al[68] evaluated the size and shape of Meckel’s caves in 75 patients with IIH and 75 age- and sex-matched control subjects. The mean diameters of Meckel’s caves were measured on the coronal T2 plane and found larger in IIH patients; 5.21 ± 1.22 mm on the right side and 5.16 ± 0.90 mm on the left side, vs 3.89 ± 0.62 mm and 4.09 ± 0.68 mm, respectively, in the control cohort (P < 0.001)[68]. Coronal T2-weighted measurements showed higher sensitivity and specificity than the axial T2 measurements; 80% sensitivity and 89.3% specificity vs 75% sensitivity and 66% specificity, respectively[68]. In addition, 76% of patients with IIH had a bilobed Meckel’s cave with a notch in the middle of the cavity vs 28% in the control subject[68]. The distorted shape probably results from the increased ICP that pushes the cistern towards the osseous opening. In a case-control study of 48 patients with IIH matched with 192 controls, a high lumbar puncture opening pressure was directly related to a wide Meckel’s cave diameter[89]. Furthermore, according to receiver operator curve analysis, a cut-off value of 4.5 mm with sensitivity of 60% and specificity of 59% was suggested[89]. Figure 6 illustrates different examples displaying Meckel’s cave enlargement.

Figure 6 Meckel’s cave enlargement. A: An axial T2-weighted magnetic resonance image demonstrating Meckel’s caves of normal caliber (dashed circles) is provided for reference; B: Axial; C: Coronal T2-weighted magnetic resonance images displaying bilaterally enlarged Meckel’s caves in different patients with idiopathic intracranial hypertension (dashed circles) are provided.

Optic nerve tortuosity

The tortuosity of the optic nerve results from the combined effects of increased CSF pressure and the anchoring of the optic nerve sheath at both distal and proximal points. Optic nerve tortuosity could be depicted in either the vertical or horizontal planes also influenced by the section thickness used during imaging[64]. Vertical tortuosity is frequently associated with a “smear sign”, where the central portion of the optic nerve is obscured by a “smear” of orbital fat[90]. Axial MRI can detect even slight horizontal tortuosity of the optic nerve, though this finding is not highly specific. Conversely, vertical tortuosity, which requires a more pronounced curvature of the optic nerve, exhibits higher specificity[90]. The sensitivity of this finding for IIH can reach up to 60% and the specificity up to 95%[70]. Figure 7 illustrates an example displaying optic nerve tortuosity.

Figure 7 Optic nerve tortuosity. A: An axial T2-weighted magnetic resonance image at the level of the globe and optic nerve in a patient with no intracranial hypertension signs or symptoms is provided for reference. Note the course of this normal-appearing optic nerve (arrows); B: An axial T2-weighted magnetic resonance image at the level of the globe and optic nerve in a patient with signs and symptoms of idiopathic intracranial hypertension demonstrates obvious tortuosity of the optic nerves in their intraorbital segments (arrows). Also note an empty sella appearance (*) and optic nerve sheath distension, representing additional signs supporting this diagnosis.

Optic nerve sheath distension

The diameter of the optic nerve sheath changes with fluctuations in CSF pressure as the subarachnoid space between the nerve and its sheath expands when ICP rises. The optic nerve sheath diameter is typically measured at a distance of 3 mm from the posterior globe margin, as this location is considered to reflect the maximum pressure changes along the optic nerve’s long axis[91]. Normal values of nerve sheath diameter differ across the literature. The upper limit for the maximum optic nerve sheath diameter ranges between 4.8 and 6.2 mm[92]. In IIH, optic nerve sheath distention is a prevalent and specific finding, with sensitivity rates reported up to 84%[68] and specificity rates up to 100%[69]. Nonetheless, the clinical correlation is limited, as no significant association with clinical symptoms has been established[93,94]. Reversibility is achievable with appropriate treatment[95]. Recent studies highlighted the use of 3D DRIVE sequences for the accurate measurement of optic nerve sheath distention, achieving excellent sensitivity and specificity compared to conventional imaging[96]. Figure 8 illustrates examples displaying optic nerve sheath distension.

Figure 8 Optic nerve sheath distension. A and B: Axial (A) and coronal T2-weighted magnetic resonance images (B) at the level of the globes and optic nerves in a patient with no idiopathic intracranial hypertension signs or symptoms are provided for reference. Note the normal caliber and diameter of the optic nerve sheaths (arrows); C and D: Axial (C) and coronal T2-weighted magnetic resonance images (D) at the level of the globes and optic nerves in a patient with signs and symptoms of idiopathic intracranial hypertension demonstrate increased caliber of the optic nerve sheaths (arrows) (diameter > 8-9 mm) as a result of cerebrospinal fluid distension.

Optic nerve enhancement

The prevalence of optic nerve head enhancement has been reported to demonstrate a sensitivity from as low as 6.7%[67] to as high as 50%[97] in individuals with IIH and a specificity up to 98.2% and 100% in the corresponding studies[67,97]. In a recent study, Golden et al[98] demonstrated the first application of contrast-enhanced 3D-fluid-attenuated inversion recovery (FLAIR) sequences to detect this finding as an indication of papilledema in clinically diagnosed IIH patients and confirmed it to be a sensitive and specific sign for this subgroup of patients.

In the current literature abnormal optic nerve sheath enhancement is considered a rare finding. Optic nerve enhancement is attributed to the disruption of the blood-brain barrier, resulting in contrast overflow due to increased ICP which induces alterations in the osmotic pressure gradient and propagates venous stasis[99]. This finding has not shown correlation with demographic characteristics, clinical symptoms, degree of visual impairment, papilledema, or clinical outcomes. However, the presence of optic nerve enhancement could potentially indicate a prolonged course of the disease[99]. Figure 9 illustrates different examples displaying optic nerve head enhancement in contrast-enhanced FLAIR sequences and black blood imaging techniques.

Figure 9 Optic nerve head enhancement. A: An axial fluid-attenuated inversion recovery image at the level of the orbits from a patient without idiopathic intracranial hypertension (IIH) signs or symptoms is provided for reference. Note the absence of signal intensity in the posterior aspect of both globes in the expected location of the optic nerve heads (ONHs) (dashed circles), corresponding to the expected normal appearance; B: An axial fluid-attenuated inversion recovery image, following intravenous gadolinium injection (C+), at the level of the orbits in a patient with IIH is provided. Note the signal hyperintensity in the posterior aspect of both globes in the expected location of the ONHs, compatible with ONH enhancement (arrows within dashed circles), which is more evident on the right than on the left ONH; C: An axial black blood image, following intravenous gadolinium injection (C+), at the level of the orbits from a normal patient is provided for reference. Observe the absence of signal intensity in the posterior aspect of the globe in the expected location of the ONH (dashed circle); D: An axial black blood image, following intravenous gadolinium injection (C+), at the level of the orbits from a patient with IIH is provided. Note the signal hyperintensity in the posterior aspect of the globe in the expected location of the ONH, compatible with ONH enhancement (arrow within the dashed circle). BB: Black blood; Flair: Fluid-attenuated inversion recovery.

Posterior globe flattening

Posterior globe flattening, indicated by loss of the normal curvature of the posterior sclera at the optic nerve insertion point, constitutes a sensitive and a specific marker suggestive of IIH. Brodsky and Vaphiades[97] highlighted the significance of this finding, encountered in up to 80% of patients with IIH, while specificity of this sign has been described to reach up to 100%[67,68]. Although flattening of the posterior globe and optic nerve sheath distension are common findings in IIH, these features do not significantly correlate with visual prognosis or outcomes[93].

Elevated CSF pressure due to elevated ICP propagates through the subarachnoid space of the optic nerve extending into the posterior globe, affecting the balance between intracranial and intraocular pressure[100]. This phenomenon could lead to the formation of chorioretinal folds and acquired hyperopia[90], often encountered in patients suffering from IIH. Posterior globe flattening constitutes an objective imaging finding, mainly assessed on axial T1 and T2 weighted images. However, recent studies introduced the use of a 2D map for quantitative measurement of posterior globe deformation, increasing diagnostic accuracy[101]. Following appropriate treatment this marker is reversible in up to 50% of the patients[95]. Figure 10 illustrates an example displaying posterior globe flattening as well as optic nerve head protrusion, which is explained below.

Figure 10  Posterior globe flattening and optic nerve head protrusion. A: An axial T2-weighted magnetic resonance image at the level of the globe and optic nerve in a normal patient is provided for reference. Note the normal, expected curvature of the posterior aspect of the globe; B: An axial T2-weighted magnetic resonance image at the level of the globes and optic nerves in a patient with signs and symptoms of idiopathic intracranial hypertension demonstrates loss of the expected curvature of the posterior aspect of the globes with flattening (dashed straight lines). There is also a slight emergence of right optic nerve head protrusion, evident by a “smear” of signal loss at the level of the posterior globe-optic nerve junction (arrow); C: An even more apparent example of optic nerve head protrusion is provided (arrow).

Optic nerve head protrusion

The protrusion of the optic nerve head is the imaging representation of papilledema, resulting from the distension of the optic nerve sheath caused by elevated CSF pressure[64]. In the study of Agid et al[67] optic nerve head protrusion and posterior globe flattening emerged as the most specific signs of IIH. Protrusion of the optic nerve head is usually evaluated as hypointense relative to the vitreous fluid of the globe in T2-weighted images and hyperintense in the region of the papilla on T1-weighted images after intravenous contrast enhancement. Enhancement of the optic nerve head is mainly attributed to flow disruption in the optic prelaminar capillaries[90,97]. Optic nerve head protrusion has been significantly correlated with the papilledema grade and demonstrated the highest sensitivity for the assessment of treatment efficacy in IIH[101]. The same authors reported that nerve protrusion constitutes a more specific sign compared to posterior globe flattening[101]. Similar results were reported by Wong et al[102], who highlighted the association between optic nerve protrusion and the severity of papilledema. Figure 10 illustrates an example displaying posterior globe flattening and optic nerve head protrusion, both of which are mentioned above.

Diffusion weighted image bright spot at fundus

Abnormal hyperintensity at the optic nerve head encountered on diffusion weighted images (DWI) has been recently reported as a marker of papilledema. One of the initial studies available was the study of Viets et al[103], who demonstrated a significant association between the hyperintensity of the optic nerve head on DWI and the presence of papilledema (P = 0.001). The finding demonstrated high specificity (100%) but low sensitivity. Additionally, Morris et al[104] found comparable outcomes, showing a sensitivity of 9.5% and a specificity of 99%.

Hyperintensity of the optic nerve head has been significantly associated with the clinical grade of papilledema in patients with IIH[105]. Moreover, in a prospective study by Ray et al[106], the authors noted that the ADC value of the optic nerve head could serve as a non-invasive quantitative indicator of elevated ICP under appropriate clinical circumstances. The authors outlined a mean cutoff ADC value for the optic nerve head (1844.5 × 10^-6 mm²/second)[106]. The underlying mechanism of this phenomenon is still not yet completely understood, though it’s thought to be associated with ischemic events in the pathogenesis of papilledema[106]. Figure 11 illustrates various examples exhibiting DWI signal hyperintensity at the level of the optic nerve heads.

Figure 11  Diffusion-weighted imaging bright spot at fundus. A: For reference, we provide an axial image of a diffusion-weighted imaging (DWI) magnetic resonance sequence from a normal patient. Note the absence of signal intensity in the posterior aspect of both globes in the expected location of the optic nerve heads (dashed circles), which corresponds to the expected normal appearance; B and C: Display axial DWI images in different patients with idiopathic intracranial hypertension. Note the obvious abnormal DWI signal hyperintensity in the optic nerve heads (arrows in dashed circles). DWI: Diffusion-weighted imaging.

Transverse sinus stenosis

Transverse sinus stenosis (TSS) is the observed narrowing of the transverse sinuses. Bilateral TSS has been reported as a very sensitive marker, present in up to 94% of IIH cases[104]. To date, the etiology and pathophysiology of TSS in IIH remains controversial. Some authors suggest that TSS can cause an increase in ICP by inducing an increase in venous pressure and impairing CSF clearance, while others suggest that TSS is the result of increased ICP[64,107,108]. Studies have demonstrated a reduction in intrasinus pressures after treating IIH with CSF withdrawal[109,110]. Reversibility of TSS after normalization of venous pressure suggests that raised sinus pressure is secondary to IIH[104].

Neuroimaging has been an essential part of the diagnostic workup of patients suspected of IIH and its main role is to exclude other causes of increased ICP[1]. MRV and CT venography are utilized to exclude sinus thrombosis or other vascular anomalies (giant arachnoid granulations, congenital stenosis, webs or small bony grooves), mostly in patients that do not belong to the typical group (female of childbearing age and elevated BMI)[104,111]. Unfortunately, dedicated venography is not part of typical diagnostic workup, unless IIH is suspected beforehand, therefore TSS can be missed.

Evaluating the transverse sinuses can be challenging, as there are many variations in their appearance and distinguishing between anatomical variants and disease can be difficult[108,112]. The following imaging findings are proposed to accurately diagnose sinus stenosis: Signs of sinus collapse compared to more posterior segments, signs of herniated brain parenchyma into the sinuses or absence of a sinus on > 1 section[104]. Unilateral hypoplasia or agenesis is considered a normal variant[1,113]. To accurately diagnose hypoplasia, the diameter at the mid-lateral portion of the sinus in question should be less than 50% of the diameter of the contralateral sinus[114].

In 2003, Farb et al[107] proposed a grading scale to assess the degree of TSS, termed “the combined venous conduit score”. They evaluated each side separately and graded the transverse-sigmoid conduit according to the highest degree of stenosis, assigning a number from 0 to 4 (0: Discontinuity/aplastic segment, 1: Hypoplasia/severe stenosis, 2: Moderate stenosis, 3: Mild stenosis, and 4: No stenosis). A conduit score < 4 is very specific for IIH[70]. Carvalho et al[113] utilized a different scaling system to classify TSS, scoring from 0 to 4 (0: Normal, 1: Stenosis < 33%, 2: Stenosis 33%-66%, 3: Stenosis > 66%, 4: Hypoplasia or agenesis). The degree of stenosis was calculated by comparing the stenotic with the immediate pre-stenotic segment. The product of the degree of stenosis of each sinus can be utilized as an index to identify patients with IIH, which is termed “index of transverse sinus stenosis”[112,113]. The cutoff value is 2, while patients with IIH demonstrate ≥ 2[112].

In the future, TSS degree could potentially be utilized to monitor treatment effects. To date, Chan et al[115] failed to demonstrate a change in sinus morphology after medical treatment of IIH. Understandably, given the strong association between IIH and venous sinus abnormalities, high-resolution MRV images are vital to ensure a more precise assessment of these structures, improving detection of stenosis and other subtle abnormalities, thus aiding in diagnosis, treatment planning, and optimal monitoring. Figure 12 illustrates the appearances of transverse sinus stenosis.

Figure 12  Transverse sinus stenosis. A: For reference, a maximum-intensity-projection axial reconstruction of a 3D phase contrast magnetic resonance venography examination of the brain in a normal patient is provided. Note that the caliber of the transverse sinus bilaterally is within expected-normal limits (arrows); B and C: Display axial maximum-intensity-projection 3D phase contrast magnetic resonance venography reconstructions in different patients with signs and symptoms of increased intracranial pressure, demonstrating significant bilateral transverse sinus stenosis (arrows).

Slit-like ventricles

The term “slit-like ventricles” describes the narrowing or collapse of the walls of the lateral ventricles, a finding that would be unexpected in adults[78]. It stood as one of the earliest described imaging findings in patients with IIH, before the age of modern imaging modalities such as MRI, when intracranial pathologies were evaluated with skull radiographs (pneumoencephalograms and ventriculograms)[116]. Recent studies have demonstrated slit-like ventricles to not represent a sensitive finding (sensitivity as low as 3.3%)[67]. Currently, slit-like ventricles are of historical, rather than clinical, value. Figure 13 illustrates the appearance of slit-like ventricles and tight subarachnoid spaces, which is explained below.

Figure 13  Slit-like ventricles and tight subarachnoid spaces. A: For reference, a coronal contrast-enhanced T1-weighted magnetic resonance image is provided, displaying normal-sized ventricles (arrows) and normally expanded subarachnoid spaces (dashed ovals); B: Coronal contrast-enhanced T1-weighted magnetic resonance image displays the presence of slit-like ventricles (arrows) and tight subarachnoid spaces (dashed ovals).

Tight subarachnoid spaces

The subarachnoid spaces are considered tight when there are very small sulci and cisterns that would not typically be expected in the normal adult population. This finding is also characterized by its very low sensitivity thus rendering it of limited clinical value[67,69]. Figure 13 illustrates the appearance of slit-like ventricles and tight subarachnoid spaces, both of which are mentioned above.

Inferior position of cerebellar tonsils

A change in normal position of the cerebellar tonsils is defined as displacement of the tonsils through the foramen magnum into the upper portion of the spinal canal[78]. It is a finding typically encountered in Chiari 1 malformation (CM1) but is not explicit of it[117]. Up to 15% of healthy population have a small degree of tonsillar herniation, > 2 mm and < 5 mm, called tonsillar ectopia[118]. If the displacement is ≥ 5 mm, the term herniation can be used instead.

As this finding is encountered in other types of pathology (CM1, low ICP), this sign is not specific to IIH[1]. In CM1 the herniation is typically more pronounced[119]. Recently it has been reported that patients with CM1 also display imaging findings of IIH and patients with diagnosed IIH show a degree of tonsillar ectopia or herniation[120,121]. It remains unclear whether there is a causative relationship between these two diseases. Nonetheless, in IIH patients, this sign demonstrates a pooled sensitivity and a pooled specificity of 16% and 95%, respectively[78]. Figure 14 illustrates the appearance of inferior position of cerebellar tonsils.

Figure 14  Inferior position of cerebellar tonsils. A: For reference, a coronal fluid-attenuated inversion recovery image is provided, which displays normally positioned cerebellar tonsils above the level of the foramen magnum (*), as indicated by the dashed line; B: Coronal fluid-attenuated inversion recovery image demonstrates only mild ectopic localization of the inferior part of the cerebellar tonsils, just below their expected level (dashed line) and through the foramen magnum (*).

Overall, the neuroimaging signs indicated above may exhibit varying sensitivities and specificities across different studies, which can be attributed to differences in methodology and statistical analysis. Nevertheless, Table 3 features the sensitivities and specificities of these findings from several studies with the purpose of serving as a rough guide.

Table 3 Magnetic resonance imaging signs for the diagnosis of idiopathic intracranial hypertension.

MRI finding	Sensitivity	Specificity	Ref.
Empty sella turcica	53.9%	94.3%	[104]
	26.7%	94.6%	[67]
	70%	95%	[97]
Partially empty sella	92%	74%	[68]
	43%	100%	[69]
	65.1%	95.3%	[70]
	53.3%	75%	[67]
	80%	92%	[76]
Posterior displacement of pituitary stalk	39.5%	90.7%	[70]
	42.7%	97.9%	[76]
Meningoceles	11%	100%	[79]
Meckel’s cave enlargement	60%	59%	[89]
	75%	86%	[68]
	9%	100%	[79]
Optic nerve tortuosity	60%	95%	[69]
	34.9%	86%	[70]
	40%	91.1%	[67]
	40%	95%	[97]
Optic nerve sheath distension	77%	85%	[89]
	84%	84%	[68]
	46%	100%	[69]
	66.7%	82.1%	[67]
	45%	95%	[97]
Optic nerve head enhancement	6.7%	98.2%	[67]
	50%	100%	[97]
Posterior globe flattening	55%	100%	[68]
	64%	100%	[69]
	43.3%	100%	[67]
	80%	95%	[97]
Optic nerve head protrusion	32%	100%	[69]
	37.2%	100%	[70]
	3.3%	100%	[67]
	30%	95%	[97]
DWI bright spot at fundus	9.5%	99%	[104]
	26.3%	100%	[103] (reader 1)
	42.1%	100%	[103] (reader 1)
Transverse sinus stenosis	73%	92%	[68]
	93%	93%	[107]
	94%	97%	[104]
	62.8%	100%	[70] (combined stenosis score)
Slit-like ventricles	3%	100%	[69]
	3.3%	100%	[67]
	39.5%	79.1%	[70]
Tight subarachnoid spaces	3%	100%	[69]
	0%	0%	[67]
Inferior position of cerebellar tonsils	16%1	95%1	[78]

¹Pooled data.

MRI: Magnetic resonance imaging; DWI: Diffusion-weighted imaging.

Recommended imaging protocol: Considering the above, in suspected IIH cases, we recommend a full routine brain MRI study including T2-weigthed, FLAIR, and T1 weighted pre- and post-intravenous gadolinium injection sequences, which, if possible, should be obtained with 3D data sets, as well as DWI and susceptibility-weighted imaging sequences. This will allow for the accurate assessment of imaging signs indicative of intracranial hypertension and exclude alternative diagnoses and confounding pathologies (thus attributing those signs to idiopathic causes). Furthermore, we recommend MRV to rule out venous sinus thrombosis and evaluate the presence of venous sinus stenosis. According to the literature, MRV, in addition to MRI pre- and post-intravenous gadolinium injection, is suggested for patients without the typical phenotype usually presenting with this condition (female and obese)[1]. On the occasion that an MRI is unavailable or contraindicated, contrast-enhanced CT may be used[1].

Digital subtraction angiography: As previously mentioned, according to current diagnostic criteria, MR and CT are the preferred imaging modalities for suspected IIH cases, as they are essential to exclude other conditions that can cause a secondary increase in ICP[1]. Digital subtraction angiography (DSA) is generally not required in the diagnostic evaluation of suspected cases and its main role is in IIH management. Intracranial venography with DSA can be utilized supplementary to MRV/CT venography to assess intracranial venous sinuses, in case of suspected stenosis[122]. Evaluating the transverse sinus junctions can be difficult, as DSA is performed in static planes. To accurately perform DSA venography, large quantities of contrast media are required to fully fill the sinuses and avoid filling artifacts[107]. Another indication for performing angiography during diagnostic work up is to measure the venous pressure gradient of a stenotic segment (proximal-to-distal) with manometry, to assess candidacy for stenting[122]. This will be discussed further in the treatment section of this review.

EDUCATIONAL CONCEPTS

IIH illustrative guide

The several aforementioned neuroimaging markers of IIH that one should look out for when considering this diagnosis can be effortlessly recalled and sought out on MRI studies if one considers them to reflect the consequences of elevated ICP seeking pathways to be alleviated by pushing outwards against the margins of the cranial cavity that is trying to contain it. Figure 15 provides an illustration of this concept with the mere purpose of serving as an imaging guide that will assist in memorizing the relevant signs to look out for.

Figure 15  Idiopathic intracranial hypertension illustration. A: In this illustration, the red dot in all panels represents an assumption of the supposed reference point from where the increased intracranial forces arise, while all the red arrows represent the outward direction of this force, which is attempting to release itself. As a result of intracranial hypertension, the force (red dot) is directed (red arrows) towards the optic nerves and their sheaths, causing their distension and tortuosity (panel a1), flattening of the posterior aspect of the globes (panel a2), and protrusion of the optic nerve head within the globe (panel a3); B: In a similar manner, the Meckel’s caves may be distended in an attempt to accommodate the excess cerebrospinal fluid pressure (panel b1), and meningoceles may also be created, mainly in the sphenoid bone wings and temporal bones, through bony clefts (panel b2); C: The pituitary gland may be stretched downwards against the expanded sella turcica (panel C), thus creating the empty or partially empty sella appearance; D: Compression of the transverse venous sinuses against the cranial bony cavity can result in stenosis of these veins (panel D) (although stenosis may preexist, causing an increase in intracranial pressure secondarily). This illustration/mechanism is only hypothetical and solely described in a rudimentary way for educational purposes to assist in memorizing the neuroimaging finding’s end results; besides, as previously mentioned, the exact pathogenesis of idiopathic intracranial hypertension (IIH) is complex and multifactorial. Neuroimaging findings may be promising clues for IIH diagnosis, although their absence does not rule it out. Various combinations of the related neuroimaging findings described may be encountered in IIH cases, and the radiologists should be aware of them to assist in the proper and timely diagnosis of the condition. Nonetheless, the role of the radiologists will primarily entail the exclusion of other intracranial pathologies hindering alternative diagnosis.

IIH checklist

We believe that a systematic assessment of neuroimaging findings in IIH cases would be necessary to enhance the radiologists’ ability to diagnose this condition accurately and promptly, reducing the likelihood of diagnostic errors. For this purpose, we have fabricated Table 4, which provides a summary of what the radiologists should evaluate when assessing a possible IIH case in the form of a simplistic yet helpful checklist.

Table 4 A step-by-step checklist for the radiologist to enable the systematic assessment of suspected idiopathic intracranial hypertension cases.

Step-by-step checklist
Step 1: Exclude the presence of an alternative and obvious cause of increased intracranial pressure. Note: This is a vital step required for IIH diagnosis, according to the revised criteria[1]	Normal brain parenchyma without findings suggesting the presence of: (1) Hydrocephalus; (2) Masses or structural lesions; (3) Abnormal meningeal enhancement (caution should be exercised as diffuse dural enhancement may be encountered following a lumbar puncture); and (4) Venous sinus thrombosis
Step 2: Assess the presence of neuroimaging findings commonly encountered in IIH patients. Note: These findings demonstrate varying sensitivities and specificities. Various combinations of the related neuroimaging findings may be encountered, although their absence does not rule out the diagnosis. The radiologists should be aware of these signs to assist in the proper and timely diagnosis of the condition and/or to advocate for equivocal cases	Primary neuroimaging signs1. Note: These signs are very important to be assessed and mentioned in the report, as the presence of 3 out of 4 of them may suggest (but not verify) the probability of IIH diagnosis in specific clinical scenarios according to the revised IIH criteria[1]: (1) Empty sella turcica (Figure 3) (CSF-filled sella turcica, compressing the pituitary gland housed within it); (2) Posterior globe flattening (Figure 10) (loss of the normal posterior sclera curvature at the optic nerve insertion point); (3) Optic nerve sheath distension (Figure 8) (increased diameter of the optic nerve sheath with CSF filling of the subarachnoid space between the nerve and its expanded sheath; typically measured at 3 mm from the posterior globe margin; whether optic nerve tortuosity is synchronously present will not alter the evaluation of the presence of this sign as positive or negative); and (4) Transverse venous sinus stenosis (Figure 12) [most commonly occurs at the lateral aspect (transverse-sigmoid sinus junction) and may be caused by intrinsic or extrinsic processes. Assess using the combined venous conduit score or the index of transverse sinus stenosis]
	Other neuroimaging signs. Note: Although not part of the revised criteria for the diagnosis of IIH[1], these are signs useful to assess and mention in the report as, nonetheless, they may be encountered in IIH cases: (1) Optic nerve tortuosity (Figure 7) (optic nerve tortuosity depicted in the horizontal, or preferably, the vertical planes); (2) Optic nerve head protrusion (Figure 10) (the imaging representation of papilledema; usually evaluated as hypointense relative to the vitreous fluid of the globe in T2-weighted images); (3) Optic nerve head enhancement (Figure 9) (contrast-enhanced optic nerve head within the posterior aspect of the globe); (4) Posterior displacement of the pituitary stalk (Figure 4) (besides pituitary gland compression, the pituitary stalk is posteriorly displaced); (5) Meningoceles (Figure 5) (meningeal protrusions through weak or defective points, usually in the skull base, usually in sphenoid bone wings); (6) Meckel’s cave enlargement (Figure 6) (CSF-filled enlargement of Meckel’s caves); (7) DWI bright spot at fundus (Figure 11) (abnormal hyperintensity at the optic nerve head encountered on DWI; recently reported as a marker of papilledema); (8) Slit-like ventricles (Figure 13) (narrowing/collapse of the lateral ventricle walls); (9) Tight subarachnoid spaces (Figure 13) (very small sulci and cisterns not typically expected in the normal adult population); and (10) Inferior position of cerebellar tonsils (Figure 14) (cerebellar tonsillar displacement through the foramen magnum into the upper portion of the spinal canal)
Step 3: Correlate with the clinical presentation and clinical findings. Note: Close communication and collaboration with referring physicians are important both for patient care and for the advancement of medical knowledge. Correlating the various findings encountered on imaging studies by the radiologist with the level of clinical suspicion and the other IIH diagnostic criteria, as communicated by the referring physicians, enables the radiologist to acknowledge which of them are usually most relevant and to what extent

¹These neuroimaging signs are included in the “STOP” acronym for idiopathic intracranial hypertension, which will be explained below in the manuscript.

IIH: Idiopathic intracranial hypertension; CSF: Cerebrospinal fluid; DWI: Diffusion-weighted imaging.

IIH acronym

To help memorize the primary neuroimaging findings discussed in Table 4, we have created an easy-to-remember acronym. This acronym, the “STOP” acronym for the primary IIH neuroimaging findings, which is illustrated in Figure 16, has the principal purpose of aiding in recalling these not-to-be-missed key findings more effectively, thus reducing the chances of any of them being overlooked.

Figure 16  The “STOP” acronym for idiopathic intracranial hypertension. We have fabricated the “STOP” acronym for idiopathic intracranial hypertension (IIH) merely as a mnemonic tool. Although there are several signs that may be encountered in IIH cases, the presence of 3 out of 4 of these signs mentioned above may suggest (but not verify) the probability of IIH diagnosis in specific clinical scenarios according to the revised IIH criteria (Friedman et al[1], 2013). Therefore, specifically assessing these neuroimaging signs and addressing their presence or absence in the radiological report may be of increased value for the referring physician.

TREATMENT OPTIONS & PATIENT MANAGEMENT

The main principles of IIH treatment are to prevent permanent vision loss and alleviate symptoms, particularly headaches[4,123]. Weight loss and pharmacological treatment tend to be effective for the majority of patients[29], whereas several interventional options are also available for patients with fulminant or medically refractory IIH[4].

Weight loss

Weight reduction is integral to the management of IIH and is considered as a first-line treatment[4]. Clinical trials have demonstrated the significance of dietary intervention[124], or even bariatric surgery for selected patients, in clinical improvement of patients with IIH[125].

Pharmacological treatment

Acetazolamide is commonly recommended in treating IIH due to its effect on altering CSF secretion at the choroid plexus, by inhibiting carbonic anhydrase. This leads to a decrease in the movement of ions and water across the choroid plexus, subsequently lowering CSF secretion[126]. The Idiopathic Intracranial Hypertension Treatment Trial was a randomized, multicenter, double-blinded trial aimed at evaluating the efficacy of acetazolamide (up to 4 g) compared to placebo in IIH patients with mild visual loss, additionally with a low-sodium weight reduction diet. This pivotal study remains the only randomized controlled trial for the pharmacological treatment of IIH[52]. Topiramate, an antiepileptic and migraine prophylactic, is gaining popularity as a treatment choice for IIH. This medication offers several benefits, such as mild inhibition of carbonic anhydrase, effectiveness in migraine prevention, and a side effect of appetite suppression[127]. Furosemide is occasionally used to treat IIH, although limited clinical data support its use. In a case series of pediatric patients, combination of acetazolamide and furosemide showed promising outcomes. However, additional evidence is necessary before furosemide can be recommended as a standard management option[128]. In patients with rapidly progressive vision loss (fulminant IIH), those that do not demonstrate clinical improvement, patients with moderate or severe visual symptoms, or patients with medically refractory IIH, interventional therapies are considered the next line of management in order to preserve vision[4].

Interventional treatment

Interventional treatment options include optic nerve sheath fenestration, CSF shunting, bariatric surgery, and venous sinus stenting (VSS) procedures[129]. To our knowledge, there are no randomized controlled studies that directly compare the different techniques. The treatment offered is usually dependent on local availability[3]. To date, CSF diversion procedures are the most commonly performed techniques[130].

Regarding interventional radiology treatment options, VSS was first described by Higgins et al[131], who used a self-expanding stent across the stenosis which immediately reduced the pressure gradient and led to clinical improvement. There is a growing body of literature supporting its role as a treatment option for IIH[122,130,132]. A recent meta-analysis by Satti et al[133] demonstrated its efficacy, safety and cost-effectiveness, advocating for its consideration as a first-line therapy. Overall complication rate is estimated at 1.4%-7.4%, with the most severe complications reported being subdural hematoma and subarachnoid hemorrhage[122,133]. Around 9%-12% of patients who underwent VSS required an additional procedure due to treatment failure[132,133]. Long term data are currently lacking[4,123]. VSS is recommended for selected patients with clear evidence of an elevated pressure gradient across a stenosis[3]. Most studies suggest a pressure gradient > 8 mmHg to consider VSS, with higher gradients showing more favorable outcomes[133-136].

FUTURE PROSPECTS

Despite significant advancements, the precise etiology of IIH remains unclear, posing challenges for diagnosis and management. Future research should focus on enhancing diagnostic accuracy and understanding the underlying mechanisms of the disease. Currently, the diagnosis is based on a combination of clinical symptoms and physical and neuroimaging findings. However, the symptoms and signs can be subtle or overlap with other conditions, leading to diagnostic uncertainty. Developing a comprehensive clinical and radiological scoring system to improve the diagnosis of IIH could represent a promising future research avenue. This proposed scoring system could integrate multiple diagnostic criteria into a unified framework, providing a standardized method for assessing the likelihood of IIH. This scoring system might include weighted scores for the various clinical and specific neuroimaging findings. By assigning scores to these elements, clinicians could quantify the probability of IIH, thus facilitating a timelier and more accurate diagnosis. Moreover, such a scoring system could be valuable in differentiating IIH from other disease mimickers, which can present similarly but require different treatments. Additionally, future research also bears the weight of exploring the complex pathophysiological mechanisms underlying IIH. Although valuable insights are already within our reach, pinpointing exact mechanisms may provide new data to prevent disease occurrence and progression and also provide effective treatment. For instance, the role of obesity and its related metabolic abnormalities represent key areas of focus, potentially leading to targeted therapies that modify these risk factors.

On the other hand, in the future, novel and advanced MRI techniques may enhance diagnostic precision in IIH. For example, black-blood imaging, a novel MRI technique where blood signal is suppressed, offers improved visualization of vascular structures and surrounding tissues, which can be especially beneficial in IIH, where vascular abnormalities, such as venous sinus stenosis, are commonly implicated. With its high contrast resolution, black-blood imaging can highlight vessel wall abnormalities and thrombus formation[137], aiding in distinguishing IIH from conditions with similar presentations. Its ability to detail the anatomy of the cerebral venous sinuses provides clinicians with more nuanced information, which may support more accurate diagnosis and better-targeted treatments for IIH. Moreover, a recent study employing MR elastography found that brain stiffness was greater in IIH patients than controls[138]. This suggests that MR elastography may serve as a promising novel indicator for monitoring disease status and treatment response in IIH.

CONCLUSION

IIH presents a significant clinical challenge due to its variable symptoms and the complexity of its diagnosis. Although the condition’s exact etiology remains elusive, advancements in imaging and treatment strategies have improved patient outcomes. Early and accurate diagnosis is crucial to prevent irreversible visual impairment and manage symptoms effectively. Current diagnostic practices rely heavily on clinical presentation and neuroimaging studies, specifically contrast-enhanced MRI and MV venography, which are primarily essential to exclude underlying pathology and secondarily valuable in detecting commonly encountered imaging findings attributable to intracranial hypertension. Amongst others, future research endeavors could entail the development of a comprehensive clinical and radiological scoring system that could greatly enhance diagnostic precision, offering a structured approach to evaluating IIH likelihood.