Idiopathic intracranial hypertension (IIH; formerly known as pseudotumor cerebri or benign intracranial hypertension) is a syndrome of increased intracranial pressure of unclear etiology that most often occurs in obese women of childbearing age. Since IIH is a diagnosis of exclusion, other etiologies of increased intracranial pressure (table 5-1) must be ruled out. A number of diagnostic criteria for IIH have been proposed, but a diagnosis can usually be confidently made in accordance with the modified Dandy criteria: (1) awake and alert patient; (2) symptoms and signs of increased intracranial pressure; (3) absence of focal signs on neurologic examination (although sixth and seventh nerve palsies are permitted); (4) normal diagnostic studies (ie, neuroimaging and CSF evaluation), except for evidence of increased intracranial pressure (ie, a CSF opening pressure greater than 20 cm H2O with signs of increased intracranial pressure on neuroimaging); and (5) no other etiology for increased intracranial pressure identified.
The pathogenesis of IIH remains poorly understood and controversial. A variety of mechanisms have been proposed, including blockage of CSF absorption at the level of the arachnoid villi, perhaps as a consequence of or exacerbated by cerebral venous hypertension secondary to transverse venous sinus stenosis. Given the increased incidence in women and strong association with obesity, sex hormones (eg, androgens) and adipose tissue may play a role in the pathogenesis of IIH.
IIH most commonly occurs in obese women of childbearing age. The incidence of IIH is variable, being higher in geographic areas that have a higher prevalence of obesity. A study published in 1988 reported an annual incidence of IIH of about 1 per 100,000 in the general populations of Iowa and Louisiana. However, a study published in 2017 reported that the incidence of IIH had more than doubled from 1.0 per 100,000 (in 1990–2001) to 2.4 per 100,000 (in 2002–2014) in Minnesota. The incidence increased to 22 per 100,000 in obese women aged 15 to 44 years. Of note, this study reported a strong correlation between IIH incidence and obesity rates (R2 = 0.7). A high body mass index (BMI) was found to be associated with increased risk of IIH in a multicenter case-control study that compared women with newly diagnosed IIH to women with other neuro-ophthalmic disorders. This study found that greater levels of weight gain were associated with an increased risk of IIH, although an increased risk of IIH also existed in women who were not obese (BMI <30) in the setting of moderate weight gain.
IIH can also occur, albeit much less commonly, in men, children, and older adults. A 2017 study reported that the annual incidence of IIH in Minnesota was 0.3 per 100,000 in men compared to 3.3 per 100,000 in women. However, in the Idiopathic Intracranial Hypertension Treatment Trial, only four of the 165 participants (2.4%) were men; of note, patients who had diagnosed untreated obstructive sleep apnea were excluded, which may partly account for the low percentage of men recruited. The BMI of men with IIH is similar to that of women with IIH, although men tend to be older at the time of initial presentation. IIH also occurs in children but is not common. In a 2017 British study, the annual incidence of IIH in children and adolescents (aged 1 to 16 years) was 0.71 per 100,000. The incidence increased to 4.18 per 100,000 in obese males aged 12 to 15 years and 10.7 per 100,000 in obese females aged 12 to 15 years. Another large retrospective multicenter study confirmed a similar trend in children and adolescents, suggesting the presence of three distinct groups of patients in this population: a young group that is not overweight, an early adolescent group that is overweight or obese, and a late adolescent group that is mostly obese. Only a small percentage of patients present at an older age (ie, >50 years of age). Although older patients with IIH are usually obese, they tend to have a more benign clinical course compared to their younger counterparts.
Patients with IIH usually present with symptoms and signs of increased intracranial pressure. Common symptoms include headache, transient visual obscurations, and pulse-synchronous (pulsatile) tinnitus, whereas common signs include papilledema with or without associated retinal hemorrhages, folds, cotton wool spots, and exudates.
Headache is the most common symptom of IIH. In the Idiopathic Intracranial Hypertension Treatment Trial, 84% of participants had headache at presentation, although neck and back pain were often reported too. The headache of increased intracranial pressure is typically a global headache that is most severe in the morning and is often aggravated by maneuvers that increase the intracranial pressure (eg, Valsalva-like maneuvers), with associated nausea and vomiting. However, many patients with IIH have headaches with features of other headache disorders, such as migraine and tension headache. Some have a significant rebound component to their headache due to excessive use of simple analgesic medications. Although headache is often disabling and associated with poor quality of life, headache disability (based on the Headache Impact Test-6 score) is not correlated with CSF opening pressure. Furthermore, the headache may or may not improve with lowering of intracranial pressure.
Transient visual obscurations (TVOs) occur in about 68% of patients with IIH. TVOs are characterized by a partial or complete loss of vision that lasts for several seconds, followed by a rapid recovery of vision back to baseline. TVOs can occur many times per day and are often precipitated by postural changes or Valsalva-like maneuvers. TVOs are thought to result from transient ischemia of the edematous optic nerve head. They are associated with higher grades of papilledema and were found to be a predictor of treatment failure in the Idiopathic Intracranial Hypertension Treatment Trial.
Patients with IIH are less likely to report persisting visual symptoms than TVOs at initial presentation. Some have blurred vision due to hyperopic shift (from shortening of the globe due to increased intracranial pressure) or metamorphopsia (distortion of vision) due to retinal folds. While an observant patient might notice an enlarged blind spot, many do not notice visual field loss. Consequently, the visual field loss from papilledema can go unnoticed until it is severe and irreversible, underscoring the importance of perimetry (visual field testing) in the evaluation and monitoring of patients with IIH. Central vision (including visual acuity and color vision) is usually spared until late in the disease course, although a small percentage of patients have a central visual field defect at presentation, usually due to retinal pathology, such as retinal fluid or folds.
Pulse-synchronous (pulsatile) tinnitus occurs in about 52% to 60% of patients. It may not be spontaneously reported; therefore, patients must be specifically asked about its presence. Pulse-synchronous tinnitus can be unilateral or bilateral. While it is frequently intermittent, it can also be continuous. Since it can often be decreased with ipsilateral jugular compression and often resolves following stenting of transverse venous sinus stenoses, it likely arises because of turbulent blood flow across stenoses in the transverse venous sinuses.
Other, less common, symptoms in IIH include diplopia due to unilateral or bilateral sixth nerve palsy, usually with moderate to severe disease. Occasional patients have facial weakness at presentation, although this is not common and should prompt a thorough workup for alternative diagnoses. Of note, up to 25% of patients are asymptomatic, with their papilledema being discovered during a routine eye examination.
Papilledema (optic disc edema secondary to increased intracranial pressure) is the most common and important sign in IIH. It is usually bilateral and symmetric, although occasional patients have highly asymmetric papilledema. Papilledema is a result of axoplasmic flow stasis secondary to increased intracranial pressure, producing edema of the retinal nerve fibers emanating from the optic disc. The threat of vision loss is correlated with the severity of papilledema. Thus, it is important to determine the severity of papilledema to help guide management. The severity of papilledema can be graded based on the appearance of the optic disc using the modified Frisén scale (figure 5-1): grade I (minimal papilledema) is characterized by a C-shaped halo with sparing of the temporal margin of the optic disc; grade II (mild papilledema) is characterized by a circumferential halo; grade III (moderate papilledema) is characterized by obscuration of at least one segment of a major blood vessel leaving the optic disc; grade IV (marked papilledema) is characterized by total obscuration of a segment of a major blood vessel on the optic disc; and grade V (severe papilledema) is characterized by total obscuration of all blood vessels on and leaving the optic disc.
Hemorrhages in the peripapillary retinal nerve fiber layer commonly occur in association with papilledema (figure 5-2a) and are correlated with the severity of papilledema. Subretinal hemorrhages can occur in association with papilledema (figure 5-2b). Since they can also occur with pseudopapilledema, they do not help to distinguish papilledema from pseudopapilledema (table 5-2). In rare cases, subretinal hemorrhage can result from peripapillary choroidal neovascularization (figure 5-2c). Retinal folds can often be detected with careful observation; the folds may be circumferential around the optic disc (Paton lines or peripapillary wrinkles [figure 5-3a]) or radial with extension into the macula (figure 5-3b). Cotton wool spots (ie, retinal nerve fiber layer infarcts) and retinal exudates can also be present, especially in patients with more severe grades of papilledema (figure 5-4a). Pseudodrusen are small white refractile deposits overlying the optic disc that can develop in patients with long-standing papilledema (figure 5-4b). Pseudodrusen must be distinguished from optic disc drusen, which are larger yellow refractile bodies arising from the substance of the optic disc.
If untreated, papilledema can result in progressive and irreversible vision loss with optic atrophy. Since the vision loss is typically slow and insidious, it may not be appreciated by the patient. However, it can be rapidly progressive in patients with a fulminant presentation, resulting in early and sometimes irreversible central vision loss.
Visual field defects are often difficult to exclude with confrontation visual field testing. Consequently, formal perimetry (visual field testing) is mandatory in the evaluation and monitoring of patients with IIH. Automated perimetry (eg, Humphrey visual field testing using the 24-2 or 30-2 SITA [Swedish Interactive Threshold Algorithm]-standard protocols) is usually adequate for patients who have minimal to moderate visual field loss. Automated perimetry is quantitative and compares the patient’s responses to those of age-matched controls. The sensitivities at each test location are expressed in decibels. The total deviation plot shows the difference (in decibels) between the patient’s sensitivities and those of age-matched controls at each test location, whereas the pattern deviation plot shows the patient’s sensitivities adjusted for generalized depression of the entire visual field (eg, due to refractive error or media opacities, such as cataract). The mean deviation is a measure (in decibels) of the average deviation of all test locations compared to age-matched controls. Patients with a normal visual field will usually have a mean deviation greater than –2 dB. Patients with mild papilledema (less than grade II) might have no visual field defects on automated perimetry (figure 5-5a). An enlarged physiologic blind spot is the first visual field defect to develop, producing a slight decrease in mean deviation (figure 5-5b). The enlarged blind spot is a refractive scotoma resulting from peripapillary hyperopia. With increasing severity and duration of papilledema, arcuate visual field defects can develop, initially in the inferonasal portion of the visual field (figure 5-5c). With more severe or long-standing papilledema, the visual field becomes progressively constricted, with sparing of the central visual field until late. Nonphysiologic visual field constriction can occur in patients with coexisting organic visual field loss; such constriction can also result from a poor performance in a patient having difficulty concentrating or staying awake during the test, giving a characteristic cloverleaf appearance on automated perimetry (figure 5-5d). Manual perimetry, such as kinetic perimetry using the Goldmann perimeter, may give more reliable results in patients who have severe visual field constriction or difficulties with performance on automated perimetry.
Other examination findings in IIH include unilateral or bilateral sixth nerve palsy causing an esotropia with limitation of abduction, although other ocular motility deficits (eg, third nerve palsy, fourth nerve palsy, and skew deviation) can rarely occur. Occasional patients have a facial nerve palsy at presentation.
Rare patients may have normal optic discs (ie, no papilledema) but have symptoms and imaging findings suggesting increased intracranial pressure as well as an increased CSF opening pressure; this controversial entity is known as IIH without papilledema. It has been proposed that papilledema might not develop in such cases because of anatomic compartmentalization of the subarachnoid space around the optic nerve stopping the CSF pressure gradient from reaching the retrolaminar portion of the optic nerve. Another possibility is that papilledema might not develop or could resolve because of the presence of a CSF leak (eg, causing CSF rhinorrhea or otorrhea) helping to decrease the intracranial pressure in a patient with IIH. When papilledema is absent and no damage to the optic nerve from resolved papilledema is evident (ie, no optic atrophy or evidence of structural damage to the optic nerve on the basis of optical coherence tomography [OCT]), visual function should be normal; the presence of visual field defects should raise concern for nonorganic vision loss.
When evaluating a patient with presumed IIH, further investigations are obtained for two broad purposes. First, neuroimaging and CSF evaluation are required to exclude other etiologies of increased intracranial pressure (table 5-1). Second, ophthalmic investigations should be obtained to determine the severity of vision loss and papilledema to help guide management. However, before further investigations are obtained, other etiologies of optic disc edema and conditions that mimic optic disc edema (eg, optic disc drusen) should be considered. Differentiation of papilledema from pseudopapilledema can be challenging; a distinction can usually be made based on clinical and investigation findings (table 5-2). However, it is important to keep in mind that occasional patients have papilledema that is superimposed on pseudopapilledema. Consultation with an ophthalmologist or neuro-ophthalmologist is suggested for patients with equivocal papilledema or pseudopapilledema, or when another etiology for optic disc edema is suspected. Specialized ophthalmic investigations (eg, fundus autofluorescence, ultrasonography, and OCT) are often needed for definitive diagnosis of optic disc drusen (figure 5-6).
Neuroimaging is the first step in the evaluation of a patient with increased intracranial pressure. Most structural causes of increased intracranial pressure can be identified on MRI of the brain with contrast. However, magnetic resonance venography (MRV) of the head with contrast should also be obtained to ensure that cerebral venous sinus thrombosis is excluded, especially in patients with an atypical or fulminant presentation for IIH (case 5-1).
Several somewhat subtle findings on neuroimaging can suggest increased intracranial pressure. An empty sella turcica is a common finding (figure 5-7a) but can also be present in the absence of increased intracranial pressure. Dilation and increased tortuosity of the optic nerve sheaths may be seen as well as posterior globe flattening (figure 5-7b). Occasionally, the swollen optic discs may be visible and enhancing (figure 5-7c). In some patients, acquired cerebellar tonsillar descent below the level of the foramen magnum is seen; this can be mistaken for a (congenital) Chiari malformation (figure 5-7a).
MRV of the head often shows smoothly tapered stenoses in the transverse venous sinuses (figure 5-8). These are thought to result from mechanical compression of the venous sinus in the setting of increased intracranial pressure. Less commonly, stenoses can result from intrinsic factors, such as arachnoid granulations, septations, and organized thrombus. Catheter venography with manometry often shows a pressure gradient across these stenoses, with increased venous pressures in the superior sagittal sinus and transverse venous sinuses proximal to the stenoses. The stenoses might play a role in the pathogenesis of IIH or exacerbate it. Thus, transverse venous sinus stenting has been proposed as a potential surgical treatment for the disease.
The lumbar puncture has a dual role in the diagnosis of IIH. First, it is obtained to confirm the presence of an increased CSF opening pressure. Second, evaluation of the CSF constituents is required to exclude other etiologies of increased intracranial pressure (eg, infectious, inflammatory, or neoplastic meningitis).
Ideally, the lumbar puncture should be obtained with the patient positioned in the left lateral recumbent position. The CSF opening pressure should be measured with the legs extended, head in a neutral position, and the patient breathing normally. The normal CSF opening pressure in adults is 10 cm H2O to 20 cm H2O. A CSF opening pressure of greater than 25 cm H2O is considered high, whereas a pressure of 20 cm H2O to 25 cm H2O is considered borderline, although probably abnormal in a patient who has symptoms, signs, and neuroimaging findings suggesting increased intracranial pressure. Recent studies have found that the normal range for CSF opening pressure in children is higher than in adults; less than 28 cm H2O is considered normal in children. The CSF opening pressure can be influenced by a number of factors, such as incorrect positioning of the patient or manometer during the opening pressure measurement and use of sedation during the procedure; in children who receive minimal or no sedation, less than 25 cm H2O is considered normal.
The CSF constituents should be normal (ie, normal white cell count with normal protein and glucose concentrations) in patients with IIH. The presence of an increased white cell count or protein concentration should raise concern for another etiology of increased intracranial pressure.
Formal perimetry is mandatory for evaluation and monitoring of patients with IIH (as discussed earlier). Other investigations, such as fundus autofluorescence and ultrasonography, can be helpful in the evaluation of suspected pseudopapilledema. OCT may have a role in quantifying the severity of papilledema (figure 5-9); the retinal nerve fiber layer thickness correlates well with papilledema severity based on the modified Frisén scale, especially for lower grades of papilledema. However, OCT measures of retinal nerve fiber layer thickness must be interpreted with caution, since combined retinal nerve fiber layer edema and atrophy might give a retinal nerve fiber layer thickness that appears to be close to normal despite significant visual field loss from optic nerve damage. In such cases, OCT might show thinning of the retinal ganglion cell and inner plexiform layer complex (containing the cell bodies for retinal nerve fibers), which correlates well with the severity of vision loss secondary to optic nerve damage. Finally, high-resolution raster scans obtained through the optic nerve head using OCT can demonstrate biomechanical changes that correlate well with increased intracranial pressure; an inward deflection of the peripapillary retinal pigment epithelium and Bruch membrane complex toward the vitreous of the eye (figure 5-10) appears to reverse with a decrease in intracranial pressure.
Several etiologies of increased intracranial pressure can mimic IIH and, therefore, must be specifically considered. Several medications are associated with a clinical syndrome that mimics IIH, although they might also precipitate or worsen preexisting IIH. These medications include the tetracycline antibiotics (eg, minocycline), retinoids (eg, vitamin A derivatives and all-trans retinoic acid), and lithium. Corticosteroid withdrawal has also been reported to cause rebound intracranial hypertension. Thus, a thorough review of medication use is mandatory in the evaluation of a patient with suspected IIH (case 5-2).
Cerebral venous hypertension due to cerebral venous sinus thrombosis, extrinsic venous sinus compression (eg, by a meningioma), or arterialization of the sinus by a dural arteriovenous fistula can cause a clinical syndrome that mimics IIH. Features suggesting cerebral venous sinus thrombosis are listed in table 5-3. When cerebral venous sinus thrombosis is suspected, MRV of the head with contrast should be obtained (case 5-1).
The two main goals of treatment are to preserve visual function and alleviate symptoms. Many treatment approaches have been proposed for IIH, including lifestyle interventions (weight loss), medical therapies, and surgical interventions.
Studies suggest that weight loss of about 6% to 10% of initial body weight is adequate to induce remission in most patients with IIH. In a 2010 prospective cohort study, a low-calorie diet resulted in a significant reduction in CSF opening pressure, papilledema, and headache disability based on the Headache Impact Test-6 score; participants lost an average of about 15.5 kg (34 lb). While effective in the long term, weight loss is not a practical or effective treatment in the short term; other treatments must be initiated in parallel for most patients with IIH. Of note, bariatric surgery is an option for patients who are morbidly obese whose weight loss attempts have been unsuccessful, although visual outcomes from bariatric surgery have not been studied in detail.
Carbonic anhydrase inhibitors, such as acetazolamide and methazolamide, are the mainstay of medical therapy for IIH. These drugs are thought to decrease CSF production, although they do have a mild diuretic effect. The 2014 Idiopathic Intracranial Hypertension Treatment Trial was a double-masked randomized controlled trial of diet plus placebo versus diet plus maximally tolerated acetazolamide in patients with newly diagnosed IIH and mild vision loss (mean deviation of –2 dB to –7 dB). The acetazolamide dose was titrated up, as tolerated, to a maximum of 2000 mg 2 times a day. The primary outcome measure was change in mean deviation (from Humphrey 24-2 SITA-standard perimetry). Secondary outcome measures included changes in papilledema grade, symptoms, quality of life, and weight. Treatment with acetazolamide was associated with statistically significant improvements in mean deviation, papilledema grade, symptoms, and quality of life. Of note, participants in the acetazolamide group lost more weight than those in the placebo group. Acetazolamide was well tolerated by most participants, although common side effects included paresthesia, dysgeusia, nausea, vomiting, and diarrhea. The risk factors for treatment failure included male sex, higher papilledema grade (ie, grades III–V), decreased visual acuity at presentation, greater than 30 transient visual obscurations per month, and peripapillary retinal nerve fiber layer hemorrhages at presentation, suggesting that such patients require closer monitoring and may need more aggressive treatment. While the acetazolamide dose was increased to a maximum of 2000 mg 2 times a day, most patients with IIH and mild vision loss seem to respond well to doses of 500 mg to 1000 mg 2 times a day. The optimum acetazolamide dose for patients with moderate to severe vision loss at presentation remains unclear, although many clinicians rapidly titrate up to high doses (eg, 1500 mg to 2000 mg 2 times a day), as tolerated, before considering surgical interventions.
Topiramate is often used for treatment of primary headache disorders, such as migraine. It is also a weak carbonic anhydrase inhibitor that seems to have similar efficacy to acetazolamide in treating patients with mild to moderate IIH. Since topiramate often causes some weight loss, it can be considered when acetazolamide cannot be tolerated or when headache is prominent. The dose of topiramate required for a therapeutic response has not been specifically studied. However, many patients appear to respond to low doses of 25 mg/d to 50 mg/d, although the dose can be titrated up to 100 mg 2 times a day for improved symptom control. Topiramate seems to be better tolerated than acetazolamide, although common side effects include mental slowing, lethargy, paresthesia, and decreased appetite. Other important, but less common, side effects include renal stones and acute angle-closure glaucoma.
Other diuretics, such as furosemide, can be administered alone or in combination with other medications for a synergistic effect. However, monitoring of electrolytes and potassium supplementation is required when furosemide is used. Corticosteroids were used for treatment in the past but produce undesirable long-term complications, such as weight gain. Furthermore, corticosteroid withdrawal can result in a rebound increase in intracranial pressure. High-dose IV corticosteroids are sometimes used for the short-term treatment of patients who have a fulminant presentation while awaiting definitive surgical intervention (eg, CSF shunting).
Surgical intervention is often required for patients with a fulminant presentation of IIH but may also be needed in those who fail to improve or worsen despite maximally tolerated medical therapy. The three most commonly used interventions are CSF shunting, optic nerve sheath fenestration, and transverse venous sinus stenting.
CSF shunting is very effective for rapidly reducing intracranial pressure and papilledema. Stereotactic ventriculoperitoneal shunting is preferred over lumboperitoneal shunting because of its lower complication rate. Incorporation of an adjustable valve into the shunt apparatus allows the CSF flow rate to be adjusted according to symptoms and signs. Unfortunately, shunting has a significant complication rate, including infection, obstruction, and migration of shunt tubing. Consequently, shunt revisions are often needed. Given the potential for complications and need for revision, CSF shunting should not be considered for the management of isolated intractable headache unless the headache is known to respond to decreases in intracranial pressure (eg, following a lumbar puncture) and noninvasive management options have been ineffective. One large retrospective study found that headache initially improved in most patients with IIH following CSF shunting, but almost 50% had recurrent headaches at 36 months following CSF shunting.
Optic nerve sheath fenestration is an effective intervention to consider when vision is threatened. A superior or medial orbital approach is used to create slits or a window in the retrolaminar optic nerve sheath, thereby creating a fistula between the subarachnoid space and orbital cavity. The resultant decrease in pressure on the optic nerve results in reduced papilledema with improved visual function. In some patients, unilateral optic nerve sheath fenestration improves the papilledema and visual function on the contralateral side, but many patients will require bilateral sequential optic nerve sheath fenestrations. Complications of optic nerve sheath fenestration include transient or persistent vision loss (eg, from optic nerve trauma), tonic pupil (eg, from damage to the ciliary ganglion or postganglionic parasympathetic fibers), and diplopia.
Transverse venous sinus stenting is a surgical intervention to consider in patients who have transverse venous sinus stenoses with pressure gradients (>8 mm Hg) across the stenoses and increased venous pressures in the superior sagittal sinus and venous sinuses proximal to the stenoses. It has been proposed that stenting will reduce cerebral venous hypertension, resulting in increased CSF absorption, reduced intracranial hypertension, and, thus, improved symptoms and signs. Accordingly, several retrospective and prospective studies have reported improvement in symptoms, signs, visual function, and intracranial pressure. Potential complications of transverse venous sinus stenting include in-stent thrombosis and subdural hemorrhage as well as development of recurrent stenoses immediately proximal to the stent.
The choice of surgical intervention remains controversial and often varies depending on local resources or practices. However, the patient’s symptoms and signs should be considered in the decision-making process. For example, a patient who has papilledema and vision loss without other symptoms and signs of increased intracranial pressure might be best treated with an optic nerve sheath fenestration, whereas a patient with severe symptoms (eg, headache), papilledema with vision loss, and other signs (eg, sixth nerve palsy) might be best treated with CSF shunting. Given the controversy with regard to choice and timing of surgical intervention for IIH, the National Eye Institute of the National Institutes of Health (NIH) has sponsored a multicenter, randomized, single-masked clinical trial comparing maximal medical therapy versus maximal medical therapy plus optic nerve sheath fenestration versus maximal medical therapy plus CSF shunting for management of patients with IIH and moderate to severe vision loss at initial presentation. This trial, called the SIGHT (Surgical Idiopathic Intracranial Hypertension Treatment) trial, will evaluate short- and long-term outcomes of these therapies, with the primary outcome being change in mean deviation on automated perimetry. Other outcomes will include time to treatment failure and change in CSF opening pressure, papilledema grade, quality of life, and headache disability.
Summary of Management Approach
The management approach for individual patients with IIH depends on the severity of their vision loss based on formal perimetry, severity of papilledema based on Frisén grade, severity of symptoms, response to medical therapy, and ability to tolerate medical therapy. Patients with minimal vision loss (mean deviation better than –3 dB) can often be managed with weight loss alone (low-calorie and low-sodium diet plus exercise), although medical therapy can be added depending on the severity of symptoms and response to weight-loss attempts. Patients with mild vision loss (mean deviation of –3 dB to –7 dB) can usually be managed with weight loss plus medical therapy. Patients with moderate vision loss (mean deviation of –7 dB to –15 dB) can often be managed with weight loss plus more aggressive medical therapy, although surgical intervention could be considered depending on the response to weight loss and medical therapy. Patients with severe vision loss (mean deviation worse than –15 dB) often require a combination of weight loss plus aggressive medical therapy plus surgical intervention, although the timing and choice of surgical intervention remains controversial.
Patients with IIH require long-term monitoring, since this is a chronic disease prone to relapses in association with weight gain. The severity of vision loss, papilledema, and symptoms influence treatment decisions. Comanagement with an ophthalmologist or neuro-ophthalmologist is crucial, with the timing of follow-up tailored according to the severity of symptoms and signs at presentation, response to treatment, and subsequent clinical course.
IIH is a syndrome of increased intracranial pressure of unclear etiology that most often occurs in obese women of childbearing age. Recent studies have found that the annual incidence of IIH is increasing in parallel with obesity rates. Common symptoms of IIH include headache, transient visual obscurations, and pulse-synchronous (pulsatile) tinnitus. Papilledema is the most common and important clinical sign. If untreated, it can result in progressive and irreversible vision loss with optic atrophy, underscoring the importance of funduscopic examination and formal visual field testing (perimetry) for the monitoring of IIH. Management options include weight loss, medical therapy (eg, acetazolamide or topiramate), and surgical interventions (eg, CSF shunting, optic nerve sheath fenestration, or transverse venous sinus stenting). The management approach should be tailored for each patient according to the severity of vision loss, severity of papilledema, severity of symptoms, response to medical therapy, and ability to tolerate medical therapy.
- Idiopathic intracranial hypertension is a syndrome of increased intracranial pressure that usually occurs in obese women of childbearing age.
- Idiopathic intracranial hypertension is a diagnosis of exclusion. Therefore, other etiologies of increased intracranial pressure must be ruled out based on clinical history, neuroimaging, and CSF examination.
- The incidence of idiopathic intracranial hypertension appears to be increasing and is strongly correlated with obesity rates.
- Greater levels of weight gain are associated with increased risk of idiopathic intracranial hypertension, although the condition can also develop in the setting of moderate weight gain in patients who are not obese.
- Headache is the most common symptom of idiopathic intracranial hypertension. However, many patients have headaches that have features of other primary headache disorders, such as migraine and tension headache.
- Headache in idiopathic intracranial hypertension is often disabling and associated with poorer quality of life but is not correlated with intracranial pressure and, thus, may not improve with lowering of intracranial pressure.
- Transient visual obscurations are the second most common symptom of idiopathic intracranial hypertension. They are thought to result from transient ischemia of the optic nerve head and are associated with higher grades of papilledema.
- Progressive visual field loss may not be appreciated by patients, underscoring the importance of formal perimetry (visual field testing) in the evaluation and monitoring of idiopathic intracranial hypertension.
- Pulse-synchronous (pulsatile) tinnitus occurs in about half of patients with idiopathic intracranial hypertension and is thought to arise because of turbulent blood flow across transverse venous sinus stenoses.
- Papilledema is the most common and important sign in idiopathic intracranial hypertension. It is usually bilateral and symmetric. The threat of vision loss is correlated with its severity.
- If untreated, papilledema can result in progressive and irreversible vision loss with optic atrophy.
- Visual field loss is difficult to exclude with confrontation visual field testing. Consequently, formal perimetry is mandatory in the evaluation and monitoring of idiopathic intracranial hypertension.
- An enlarged physiologic blind spot is the first visual field defect to develop in idiopathic intracranial hypertension, followed by arcuate visual field defects (initially in the inferonasal visual field) and, subsequently, progressive constriction with sparing of central vision until late.
- Sixth and seventh nerve palsies can occur as false localizing signs in patients with idiopathic intracranial hypertension.
- Ophthalmic investigations are necessary to determine the severity of vision loss and papilledema. In patients with equivocal papilledema or possible pseudopapilledema, consultation with an ophthalmologist or, ideally, a neuro-ophthalmologist is suggested.
- In patients with an atypical or fulminant presentation of idiopathic intracranial hypertension, magnetic resonance venography of the head with contrast should be obtained to exclude cerebral venous sinus thrombosis.
- Common imaging findings in idiopathic intracranial hypertension include an empty sella turcica, increased optic nerve sheath dilation and tortuosity, posterior globe flattening, optic disc elevation and enhancement, inferior cerebellar tonsillar descent, and transverse venous sinus stenosis.
- In adults, a CSF opening pressure of greater than 25 cm H2O is high, while an opening pressure of 20 cm H2O to 25 cm H2O is probably abnormal if symptoms, signs, and imaging findings are consistent with increased intracranial pressure. In children, recent studies suggest that a CSF opening pressure of greater than 28 cm H2O is high.
- Retinal nerve fiber layer thickness from optical coherence tomography correlates with papilledema severity. However, retinal nerve fiber layer thickness measurements must be interpreted with caution in patients who could have combined optic disc edema and atrophy.
- Raster scans obtained through the optic nerve head with optical coherence tomography may show biomechanical changes that correlate with increased intracranial pressure and might be useful for monitoring response to treatment.
- Several medications (eg, tetracycline antibiotics, retinoids, and lithium) and cerebral venous outflow obstruction (eg, due to cerebral venous sinus thrombosis) can cause a clinical syndrome that mimics idiopathic intracranial hypertension.
- Weight loss of 6% to 10% of initial body weight can be effective in inducing a remission of idiopathic intracranial hypertension. Bariatric surgery can be effective in patients who are morbidly obese and struggle to lose weight.
- Treatment of idiopathic intracranial hypertension with acetazolamide produces improvement in visual field loss, papilledema, symptoms, and quality of life. Common side effects of acetazolamide therapy include paresthesia, dysgeusia, nausea, vomiting, and diarrhea.
- Topiramate is effective in treatment of mild to moderate idiopathic intracranial hypertension and can be considered in patients who are unable to tolerate acetazolamide or when headache is prominent. Common side effects of topiramate therapy include mental slowing, lethargy, paresthesia, and loss of appetite.
- Surgical therapies are usually reserved for patients with idiopathic intracranial hypertension who have a fulminant presentation and for patients who fail to improve or worsen despite maximally tolerated medical therapy.
- CSF shunting is effective for rapidly reducing intracranial pressure. Complications can include infection, obstruction, and migration of shunt tubing; shunt revision is often needed.
- Optic nerve sheath fenestration is effective in relieving pressure on the optic nerve, thereby reducing papilledema and improving visual function. Complications can include vision loss, tonic pupil, and diplopia.
- Transverse venous sinus stenting has been reported to improve symptoms, signs, visual function, and intracranial pressure. Complications can include in-stent thrombosis, subdural hemorrhage, and development of new stenoses proximal to the stent.
- The indications for surgical intervention in idiopathic intracranial hypertension, the timing and choice of surgical intervention, and long-term outcomes remain unclear.
- The main goals of treatment of idiopathic intracranial hypertension are to preserve vision and alleviate symptoms. Thus, the management is tailored depending on the severity of vision loss, papilledema, and symptoms as well as the patient’s response to medical therapy and ability to tolerate medical therapy.
- Patients with idiopathic intracranial hypertension with minimal to mild vision loss can usually be managed with weight loss and medical therapy, whereas patients with moderate to severe vision loss often need a combination of weight loss, aggressive medical therapy, and, occasionally, surgical intervention.
- Patients with idiopathic intracranial hypertension should be managed in coordination with an ophthalmologist or neuro-ophthalmologist, since formal perimetry and monitoring of papilledema severity is needed to guide management.
1. Thurtell MJ, Tomsak RL. What do I do now? Neuro-ophthalmology. 2nd ed. New York, NY: Oxford University Press, 2019.
2. Smith JL. Whence pseudotumor cerebri? J Clin Neuroophthalmol 1985;5(1):55–56.
3. Markey KA, Mollan SP, Jensen RH, Sinclair AJ. Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. Lancet Neurol 2016;15(1):78–91. doi:10.1016/S1474-4422(15)00298-7.
4. Hornby C, Mollan SP, Botfield H, et al. Metabolic concepts in idiopathic intracranial hypertension and their potential for therapeutic intervention. J Neuroophthalmol 2018;38(4):522–530. doi:10.1097/WNO.0000000000000684.
5. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol 1988;45(8):875–877. doi:10.1001/archneur.1988.00520320065016.
6. Kilgore KP, Lee MS, Leavitt JA, et al. Re-evaluating the incidence of idiopathic intracranial hypertension in an era of increasing obesity. Ophthalmology 2017;124(5):697–700. doi:10.1016/j.ophtha.2017.01.006.
7. Daniels AB, Liu GT, Volpe NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol 2007;143(4):635–641. doi:10.1016/j.ajo.2006.12.040.
8. Wall M, Kupersmith MJ, Kieburtz KD, et al. The idiopathic intracranial hypertension treatment trial: clinical profile at baseline. JAMA Neurol 2014;71(6):693–701. doi:10.1001/jamaneurol.2014.133.
9. Bruce BB, Kedar S, Van Stavern GP, et al. Idiopathic intracranial hypertension in men. Neurology 2009;72(4):304–309. doi:10.1212/01.wnl.0000333254.84120.f5.
10. Matthews YY, Dean F, Lim MJ, et al. Pseudotumor cerebri syndrome in childhood: incidence, clinical profile and risk factors in a national prospective population-based cohort study. Arch Dis Child 2017;102(8):715–721. doi:10.1136/archdischild-2016-312238.
11. Sheldon CA, Paley GL, Xiao R, et al. Pediatric idiopathic intracranial hypertension: age, gender, and anthropometric features at diagnosis in a large, retrospective, multisite cohort. Ophthalmology 2016;123(11):2424–2431. doi:10.1016/j.ophtha.2016.08.004.
12. Bruce BB, Kedar S, Van Stavern GP, et al. Atypical idiopathic intracranial hypertension: normal BMI and older patients. Neurology 2010;74(22):1827–1832. doi:10.1212/WNL.0b013e3181e0f838.
13. Friedman DI, Rausch EA. Headache diagnoses in patients with treated idiopathic intracranial hypertension. Neurology 2002;58(10):1551–1553. doi:10.1212/WNL.58.10.1551.
14. Friedman DI, Quiros PA, Subramanian PS, et al. Headache in idiopathic intracranial hypertension: findings from the idiopathic intracranial hypertension treatment trial. Headache 2017;57(8):1195–1205. doi:10.1111/head.13153.
15. Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. Neurology 1991;41(2 pt 1):239–244. doi:10.1212/WNL.41.2_Part_1.239.
16. Wall M, Falardeau J, Fletcher WA, et al. Risk factors for poor visual outcome in patients with idiopathic intracranial hypertension. Neurology 2015;85(9):799–805. doi:10.1212/WNL.0000000000001896.
17. Wall M, George D. Idiopathic intracranial hypertension. A prospective study of 50 patients. Brain 1991;114(pt 1A):155–180. doi:10.1093/oxfordjournals.brain.a101855.
18. Warner JE, Katz BJ. Metamorphopsia as an initial complaint of idiopathic intracranial hypertension. Arch Ophthalmol 2005;123(7):1003–1006. doi:10.1001/archopht.123.7.1003.
19. Corbett JJ, Savino PJ, Thompson HS, et al. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol 1982;39:461–474. doi:10.1001/archneur.1982.00510200003001.
20. Chen JJ, Thurtell MJ, Longmuir RA, et al. Causes and prognosis of visual acuity loss at the time of initial presentation in idiopathic intracranial hypertension. Invest Ophthalmol Vis Sci 2015;56(6):3850–3859. doi:10.1167/iovs.15-16450.
21. Sismanis A. Otologic manifestations of benign intracranial hypertension syndrome: diagnosis and management. Laryngoscope 1987;97(8 pt 2 suppl 42):1–17. doi:10.1288/00005537-198708001-00001.
22. Dinkin MJ, Patsalides A. Venous sinus stenting in idiopathic intracranial hypertension: results of a prospective trial. J Neuroophthalmol 2017;37(2):113–121. doi:10.1097/WNO.0000000000000426.
23. Boddu S, Dinkin M, Suurna M, et al. Resolution of pulsatile tinnitus after venous sinus stenting in patients with idiopathic intracranial hypertension. PLoS One 2016;11(10):e0164466. doi:10.1371/journal.pone.0164466.
24. Capobianco DJ, Brazis PW, Cheshire WP. Idiopathic intracranial hypertension and seventh nerve palsy. Headache 1997;37(5):286–288. doi:10.1046/j.1526-4610.1997.3705286.x.
25. Galvin JA, Van Stavern GP. Clinical characterization of idiopathic intracranial hypertension at the Detroit Medical Center. J Neurol Sci 2004;223(2):157–160. doi:10.1016/j.jns.2004.05.009.
26. Wall M, White WN 2nd. Asymmetric papilledema in idiopathic intracranial hypertension: prospective interocular comparison of sensory visual function. Invest Ophthalmol Vis Sci 1998;39(1):134–142.
27. Bidot S, Bruce BB, Saindane AM, et al. Asymmetric papilledema in idiopathic intracranial hypertension. J Neuroophthalmol 2015;35(1):31–36. doi:10.1097/WNO.0000000000000205.
28. Frisén L. Swelling of the optic nerve head: a staging scheme. J Neurol Neurosurg Psychiatry 1982;45(1):13–18. doi:10.1136/jnnp.45.1.13.
29. Scott CJ, Kardon RH, Lee AG, et al. Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch Ophthalmol 2010;128(6):705–711. doi:10.1001/archophthalmol.2010.94.
30. Wall M, Thurtell MJ, NORDIC Idiopathic Intracranial Hypertension Study Group. Optic disc haemorrhages at baseline as a risk factor for poor outcome in the idiopathic intracranial hypertension treatment trial. Br J Ophthalmol 2017;101(9):1256–1260. doi:10.1136/bjophthalmol-2016-309852.
31. McCasland BJ, Mendicino ME, Newman NJ. Subretinal haemorrhage in idiopathic intracranial hypertension. Br J Ophthalmol 1999;83(7):883–884. doi:10.1136/bjo.83.7.878g.
32. Sathornsumetee B, Webb A, Hill DL, et al. Subretinal hemorrhage from a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension. J Neuroophthalmol 2006;26(3):197–199. doi:10.1097/01.wno.0000235583.10546.0a.
33. Sibony PA, Kupersmith MJ, Feldon SE, et al. Retinal and choroidal folds in papilledema. Invest Ophthalmol Vis Sci 2015;56(10):5670–5680. doi:10.1167/iovs.15-17459.
34. Okun E. Chronic papilledema simulating hyaline bodies of the optic disc. A case report. Am J Ophthalmol 1962;53:922–927. doi:10.1016/0002-9394(62)93012-X.
35. Thambisetty M, Lavin PJ, Newman NJ, Biousse V. Fulminant idiopathic intracranial hypertension. Neurology 2007;68(3):229–232. doi:10.1212/01.wnl.0000251312.19452.ec.
36. Corbett JJ, Jacobson DM, Mauer RC, Thompson HS. Enlargement of the blind spot caused by papilledema. Am J Ophthalmol 1988;105(3):261–265. doi:10.1016/0002-9394(88)90007-4.
37. Wall M, George D. Visual loss in pseudotumor cerebri. Incidence and defects related to visual field strategy. Arch Neurol 1987;44(2):170–175. doi:10.1001/archneur.1987.00520140040015.
38. Ney JJ, Volpe NJ, Liu GT, et al. Functional visual loss in idiopathic intracranial hypertension. Ophthalmology 2009;116(9):1808–1813. doi:10.1016/j.ophtha.2009.03.056.
39. Friedman DI, Forman S, Levi L, et al. Unusual ocular motility disturbances with increased intracranial pressure. Neurology 1998;50(6):1893–1896. doi:10.1212/WNL.50.6.1893.
40. Bruce BB, Newman NJ, Biousse V. Ophthalmoparesis in idiopathic intracranial hypertension. Am J Ophthalmol 2006;142(5):878–880. doi:10.1016/j.ajo.2006.06.007.
41. Marcelis J, Silberstein SD. Idiopathic intracranial hypertension without papilledema. Arch Neurol 1991;48(4):392–399. doi:10.1001/archneur.1991.00530160060014.
42. Digre KB, Nakamoto BK, Warner JE, et al. A comparison of idiopathic intracranial hypertension with and without papilledema. Headache 2009;49(2):185–193. doi:10.1111/j.1526-4610.2008.01324.x.
43. Killer HE, Laeng HR, Flammer J, Groscurth P. Architecture of arachnoid trabeculae, pillars, and septa in the subarachnoid space of the human optic nerve: anatomy and clinical considerations. Br J Ophthalmol 2003;87(6):777–781. doi:10.1136/bjo.87.6.777.
44. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology 1999;53(7):1537–1542. doi:10.1212/WNL.53.7.1537.
45. Agid R, Farb RI, Willinsky RA, et al. Idiopathic intracranial hypertension: the validity of cross-sectional neuroimaging signs. Neuroradiology 2006;48(8):521–527. doi:10.1007/s00234-006-0095-y.
46. Banik R, Lin D, Miller NR. Prevalence of Chiari I malformation and cerebellar ectopia in patients with pseudotumor cerebri. J Neurol Sci 2006;247(1):71–75. doi:10.1016/j.jns.2006.03.016.
47. Farb RI, Vanek I, Scott JN, et al. Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology 2003;60(9):1418–1424. doi:10.1212/01.WNL.0000066683.34093.E2.
48. King JO, Mitchell PJ, Thomson KR, Tress BM. Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology 2002;58(1):26–30. doi:10.1212/WNL.58.1.26.
49. King JO, Mitchell PJ, Thomson KR, Tress BM. Cerebral venography and manometry in idiopathic intracranial hypertension. Neurology 1995;45(12):2224–2228. doi:10.1212/WNL.45.12.2224.
50. Ahmed RM, Wilkinson M, Parker GD, et al. Transverse sinus stenting for idiopathic intracranial hypertension: a review of 52 patients and of model predictions. AJNR Am J Neuroradiol 2011;32(8):1408–1414. doi:10.3174/ajnr.A2575.
51. Avery RA, Shah SS, Licht DJ, et al. Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med 2010;363(9):891–893. doi:10.1056/NEJMc1004957.
52. Sibony P, Kupersmith MJ, Honkanen R, et al. Effects of lowering cerebrospinal fluid pressure on the shape of the peripapillary retina in intracranial hypertension. Invest Ophthalmol Vis Sci 2014;55(12):8223–8231. doi:10.1167/iovs.14-15298.
53. Wang JK, Kardon RH, Ledolter J, et al. Peripapillary retinal pigment epithelium layer shape changes from acetazolamide treatment in the idiopathic intracranial hypertension treatment trial. Invest Ophthalmol Vis Sci 2017;58(5):2554–2565. doi:10.1167/iovs.16-21089.
54. Chausson N, Bocquet J, Aveillan M, et al. Intracranial hypertension caused by a meningioma compressing the transverse sinus. J Clin Neurosci 2010;17(12):1589–1592. doi:10.1016/j.jocn.2010.03.039.
55. Spitze A, Gersztenkorn D, Al-Zubidi N, et al. Transverse and sigmoid sinus dural arteriovenous fistula mimicking idiopathic intracranial hypertension and carotid cavernous fistula. Neuroophthalmology 2014;38(1):29–35. doi:10.3109/01658107.2013.830628.
56. Sinclair AJ, Burdon MA, Nightingale PG, et al. Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study. BMJ 2010;341:c2701. doi:10.1136/bmj.c2701.
57. Handley JD, Baruah BP, Williams DM, et al. Bariatric surgery as a treatment for idiopathic intracranial hypertension: a systematic review. Surg Obes Relat Dis 2015;11(6):1396–1403. doi:10.1016/j.soard.2015.08.497.
58. NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee, Wall M, McDermott MP, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA 2014;311(16):1641–1651. doi:10.1001/jama.2014.3312.
59. ten Hove MW, Friedman DI, Patel AD, et al. Safety and tolerability of acetazolamide in the idiopathic intracranial hypertension treatment trial. J Neuroophthalmol 2016;36(1):13–19. doi:10.1097/WNO.0000000000000322.
60. Celebisoy N, Gökçay F, Sirin H, Akyürekli O. Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study. Acta Neurol Scand 2007;116(5):322–327. doi:10.1111/j.1600-0404.2007.00905.x.
61. Schoeman JF. Childhood pseudotumor cerebri: clinical and intracranial pressure response to acetazolamide and furosemide treatment in a case series. J Child Neurol 1994;9(2):130–134. doi:10.1177/088307389400900205.
62. Liu GT, Glaser JS, Schatz NJ. High-dose methylprednisolone and acetazolamide for visual loss in pseudotumor cerebri. Am J Ophthalmol 1994;118(1):88–96. doi:10.1016/S0002-9394(14)72847-8.
63. Kalyvas AV, Hughes M, Koutsarnakis C, et al. Efficacy, complications and cost of surgical interventions for idiopathic intracranial hypertension: a systematic review of the literature. Acta Neurochir (Wien) 2017;159(1):33–49. doi:10.1007/s00701-016-3010-2.
64. Menger RP, Connor DE Jr, Thakur JD, et al. A comparison of lumboperitoneal and ventriculoperitoneal shunting for idiopathic intracranial hypertension: an analysis of economic impact and complications using the Nationwide Inpatient Sample. Neurosurg Focus 2014;37:E4. doi:10.3171/2014.8.FOCUS14436.
65. McGirt MJ, Woodworth G, Thomas G, et al. Cerebrospinal fluid shunt placement for pseudotumor cerebri-associated intractable headache: predictors of treatment response and an analysis of long-term outcomes. J Neurosurg 2004;101(4):627–632. doi:10.3171/jns.2004.101.4.0627.
66. Patsalides A, Oliveira C, Wilcox J, et al. Venous sinus stenting lowers the intracranial pressure in patients with idiopathic intracranial hypertension. J Neurointerv Surg 2019;11(2):175–178. doi:10.1136/neurintsurg-2018-014032.
. Surgical Idiopathic Intracranial Hypertension Treatment Trial (SIGHT). clinicaltrials.gov/ct2/show/NCT03501966
. Accessed July 26, 2019.