Idiopathic Intracranial Hypertension
- Author: Mark S Gans, MD; Chief Editor: Andrew G Lee, MD more...
Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology that predominantly affects obese women of childbearing age. The primary problem is chronically elevated intracranial pressure (ICP), and the most important neurologic manifestation is papilledema (see the image below), which may lead to secondary progressive optic atrophy, visual loss, and possible blindness. Although IIH, pseudotumor cerebri, and benign intracranial hypertension (BIH) are synonymous terms in the literature, IIH is the preferred term.
Signs and symptoms
Patients with IIH usually present with symptoms related to increased ICP and papilledema. Symptoms of increased ICP may include the following:
Headaches, typically nonspecific and varying in type, location, and frequency
Visual loss (typically visual field but rarely visual acuity loss)
Diplopia, usually horizontal (due to nonlocalizing sixth nerve palsy) but rarely vertical
Radicular pain, usually in the arms (uncommon symptom)
Rarely, patients presenting with increased ICP with related optic nerve edema may be asymptomatic.
Visual symptoms of papilledema may include the following:
Transient visual obscurations, often predominantly or uniformly orthostatic
Progressive loss of peripheral vision in one or both eyes (nerve fiber layer defects, enlargement of the blind spot)
Blurring and distortion (ie, metamorphopsia) of central vision due to macular edema or optic neuropathy
Sudden visual loss (eg, fulminant IIH)
Nonspecific symptoms of IIH may include dizziness, nausea, vomiting, photopsias, and retrobulbar pain.
The most significant physical finding is bilateral disc edema secondary to the increased ICP. Rarely, in more pronounced cases, macular involvement with subsequent edema and diminished central vision may be present. Sixth nerve palsy may occur as a nonlocalizing sign of increased ICP.
High-grade and atrophic papilledema in addition to subretinal hemorrhages are poor visual prognostic signs. Uncontrolled papilledema results in progressive peripheral visual field constriction or nerve fiber bundle defects.
Rarely, sudden loss of central vision results from an associated anterior ischemic optic neuropathy or a vascular occlusion.
Visual function tests are the most important parts of the neurologic examination for diagnosing and monitoring patients with IIH. Such tests include the following:
Ophthalmoscopy, optic nerve photography, and, in some cases, optical coherence tomography (OCT)
Formal visual field assessment
Ocular motility examination
See Clinical Presentation for more detail.
Typically, no laboratory testing is mandatory, but some authors have recommended blood tests, including the following:
Complete blood count
Full procoagulant profile (only in patients with a previous history of thrombosis or MRI evidence of a dural venous sinus occlusion on magnetic resonance venography [MRV])
Neuroimaging studies are essential to rule out the possibility of an intracranial lesion prior to performing a lumbar puncture. In addition, it is necessary to rule out the potential associated diagnosis of a dural sinus thrombosis. As a result, a combined MRI/MRV of the brain with gadolinium is the preferred study. At the very least, a CT of the brain to rule out an intracranial lesion can be performed if a MRI is not immediately available.
Once an intracranial mass lesion is ruled out, a lumbar puncture is usually indicated.
Cerebrospinal fluid studies may include the following:
White blood cell and differential counts
Red blood cell count
Quantitative protein electrophoresis
Aerobic bacterial culture and sensitivity
Acid-fast bacilli culture
Cryptococcal antigen (especially in patients with HIV)
Syphilis markers (eg, rapid plasma reagin [RPR])
Tumor markers and cytology (in patients with a history of cancer or with clinical features suggesting occult malignancy)
See Workup for more detail.
The goal is to preserve optic nerve function while managing increased ICP. Pharmacologic therapy may include the following:
Acetazolamide (the most effective agent for lowering ICP) and furosemide or, rarely, other diuretics
Primary headache prophylaxis with amitriptyline, propranolol, or other commonly prescribed migraine prophylaxis agents, or with topiramate
Corticosteroids (for lowering ICP in IIH of inflammatory etiology or for supplementing acetazolamide) (this should be used only on a short-term basis and only in patients who present with marked loss of visual function)
If visual function deteriorates while on maximal medical therapy, surgical interventions should be strongly considered. Such interventions include the following:
Optic nerve sheath fenestration (a protective measure to decompress the fluid surrounding the optic nerve)
Cerebrospinal fluid diversion (ie, via a lumboperitoneal or ventriculoperitoneal shunt)
Intracranial venous sinus stenting (in the presence of an area of evident focal stenosis of the dural sinus venous system)
Treatment of IIH with repeated lumbar punctures is considered to be of historic interest only, as the CSF volume reforms rapidly. However, serial lumbar punctures have been considered in some patients who refuse or cannot undergo conventional medical or surgical therapy (eg, pregnant patients).
A meta-analysis comparing visual outcomes after these interventions reported the following findings :
252 optic nerve sheath decompressions: Visual defects improved or resolved in 80%
31 VP shunt placements: Visual defects improved or resolved in 38.7%
44 LP shunt placements: Visual defects improved or resolved in 44.6%
17 intracranial venous sinus stent placements: Visual defects improved or resolved in 47%
There are distinct risks and benefits associated with each of these interventions.
Weight loss is a cornerstone of long-term management of these patients. No activity restriction is required; in fact, exercise programs are strongly recommended in conjunction with the weight-reduction diet. Some patients with IIH have experienced dramatic improvement after bariatric surgery.
Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology that predominantly affects obese women of childbearing age. The primary problem is chronically elevated intracranial pressure (ICP), and the most important neurologic manifestation is papilledema, which may lead to progressive optic atrophy and blindness.
The presentation of a patient with symptoms of increased ICP and papilledema should be considered a clinical emergency until a neuroimaging study results confirm the presence or absence of an intracranial mass. A significant number of patients presenting in this manner whose neuroimaging study results do not reveal a mass lesion are diagnosed with IIH. Although IIH, pseudotumor cerebri, and benign intracranial hypertension (BIH) are synonymous and refer to the same diagnosis, IIH is the preferred term.
The diagnostic criteria for IIH, including those of the Dandy criteria as described by Dandy in 1937 and later modified by Smith in 1985, are as follows:
There are symptoms and signs of increased intracranial pressure
There are no localizing neurologic signs (with the exception of a unilateral or bilateral sixth nerve paresis)
Cerebrospinal fluid (CSF) may show increased pressure, but there are no cytologic or chemical abnormalities
Normal to small symmetric ventricles must be demonstrated
Subsequent additions to these criteria include the following[4, 5, 6] :
The diagnostic lumbar puncture should be performed with the patient in the lateral decubitus position
Magnetic resonance venography should be included to rule out intracranial venous sinus thromboses
Other causes of intracranial hypertension should be ruled out
The pathophysiology of IIH is unclear. A dominant early theory held that cerebral edema played a role in the pathogenesis of elevated ICP in these patients. Against this view was the observation that no altered levels of alertness, cognitive impairments, or focal neurologic findings were associated with the elevated ICP. In addition, no pathologic signs of cerebral edema were documented in these patients. Early reports describing edema were later considered to represent fixation artifact (ie, from tissue preparation) rather than in vivo edema.
Current hypotheses include the link between relatively obstructive segments in the distal transverse sinus and IIH and the presence of increased arterial inflow with an accompanying low-grade stenosis of the transverse sinus.[7, 2]
In a series reported by Farb et al, 29 patients with IIH showed demonstrable narrowing of the transverse dural venous sinus on magnetic resonance (MR) venography, whereas none of the 59 control subjects had this finding. The authors suggested that the narrowing is a consequence of elevated ICP and that when the narrowing develops, it exacerbates the pressure elevation by increasing venous pressure in the superior sagittal sinus. Their findings underscored the following points:
The CSF production rate (mL/min) should be equal to the CSF reabsorption rate
If production exceeds absorption, ICP rises until it exceeds the mean arterial pressure (MAP); if this rise should be sustained, it would be fatal
In IIH, the CSF production rate equals the CSF reabsorption rate; however, a higher than normal pressure is required to achieve this balance, owing to the increased resistance at the arachnoid granulations lining the dural venous sinuses
Bateman showed that some IIH patients with normal dural venous drainage have increased arterial inflow, which suggests that collateral venous drainage occurs in addition to the drainage provided by the superior sagittal sinus and transverse sinuses.
Bateman also used MR venography and MR flow quantification in cerebral arteries and veins in 40 IIH patients, 21 of whom had venous stenosis; arterial inflow was 21% higher than normal, and superior sagittal sinus outflow was normal, resulting in a reduced percentage of venous outflow as compared with inflow. The remainder of arterial inflow volume was presumed to have drained via collateral venous channels. With clinical remission of symptoms, arterial inflow volumes returned to normal.
Subsequently, Bateman et al proposed a mathematical model to address the role of collapsible dural venous sinuses in the pathogenesis of IIH; the model included arterial inflow volume, venous outflow resistance, and CSF pressure. The investigators used combined flow rates in the 2 carotid arteries and the basilar artery (as measured by MRI in individual patients) as the measure of inflow blood volume and used measured values from the literature for the pressure gradient from superior sagittal sinus to jugular bulb and venous outflow resistance.
The model predicts 2 CSF pressure equilibrium points for the collapsible dural sinus cases with greater than 40% stenosis (usually of the transverse sinus), one in the normal range and the other in the range encountered in IIH patients. This may account for the prolonged remission of symptoms that follows removal of CSF through lumbar puncture, presumably because this step relieves the venous sinus stenosis.
Without dural sinus collapse and stenosis, as is encountered in some patients with IIH, the model required increased arterial inflow volume to account for the elevated ICP; however, it did not require increased resistance to outflow of CSF across the arachnoid villi.
IIH commonly occurs in women who are overweight; however, the role obesity plays in this disorder is unclear. In some instances, obesity and IIH may be familial. It has been proposed that obesity increases intra-abdominal pressure and thereby raises cardiac filling pressures. These rises in pressure lead to impeded venous return from the brain (due to the valveless venous system that exists from the brain to the heart) with a subsequent elevation in intracranial venous pressure.
If this process is not treated appropriately, chronic interruption of the axoplasmic flow of the optic nerves with ensuing papilledema as a consequence of this pressure may lead to irreversible optic neuropathy.
Most cases of IIH occur in young women who are obese; a considerably smaller percentage occur in men who are otherwise healthy. Patients with higher body mass indexes (BMIs) and recent weight gain are at increased risk.[2, 12] If IIH presents in an individual who is not overweight, it is necessary to rule out associated risk factors, such as the following[6, 2] :
Exposure to or withdrawal from certain exogenous substances (eg, drugs)
Systemic diseases (including Lyme disease)
Disruption of cerebral venous flow
Certain endocrine or metabolic disorders
In 1994, Radhakrishnan et al reviewed the literature on IIH associated with other diseases and with drugs. They argued that for these diseases and drugs to be included in the list of causally related associations, the following criteria should be met :
At least 2 cases should have been described
The reported cases should have met all the criteria for the diagnosis of IIH
Intracranial dural sinus thrombosis should have been ruled out with reasonable certainty
The list of exogenous substances associated with IIH is extensive. Although the association between these substances and this disorder is generally considered well established, the exact causal relation has not been fully clarified in the literature.
Exogenous substances reportedly associated with IIH include amiodarone, antibiotics (eg, nalidixic acid, penicillin, and tetracycline), carbidopa, levodopa, chlordecone, corticosteroids (topical and systemic), cyclosporine, danazol, growth hormone, indomethacin, ketoprofen, lead, leuprolide acetate, levonorgestrel implants, lithium, oral contraceptives, oxytocin, perhexiline, phenytoin, and vitamin A (> 100,000 U/day)/retinoic acid.[6, 2]
According to the 1994 review by Radhakrishnan et al and numerous subsequent reports,[14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30] medication risk factors that meet minimal criteria but have not been confirmed in case-controlled studies include the following:
Cimetidine, corticosteroids, danazol, isotretinoin, levothyroxine, lithium,  minocycline, nalidixic acid, nitrofurantoin, tamoxifen, tetracycline, and trimethoprim-sulfamethoxazole
All- trans -retinoic acid (ATRA) used in the treatment of promyelocytic leukemia, cyclosporine, levonorgestrel implant, pancreatin
Recombinant human growth hormone/natural growth hormone (somatotropin)
Vitamin A in infants
In some instances, although a patient may present with IIH after exposure to a certain medication, the disorder can continue despite discontinuance of the presumed offending agent.
A myriad of illnesses are associated with IIH. Some of these disorders are known to result in increased viscosity of the CSF. In most of them, however, the causal link with Increased ICP is not clear. The following diseases have all been reportedly associated with IIH :
Chronic respiratory insufficiency
Familial Mediterranean fever
Polyangiitis overlap syndrome
Chronic renal disease
Disorders of cerebral venous drainage
Compression of cerebral veins by extravascular tumors, secondary thrombosis due to coagulopathy, or relative stenosis due to a venous flow anomaly can result in impaired absorption of CSF and, thus, IIH.[7, 33] Restriction of venous drainage from the head may be impaired with radical neck dissection, even if it is completed only on the right (drainage from the head takes place mainly via the right jugular vein). Spontaneous recanalization usually occurs, but if it is delayed, chronic papilledema may result.
The diagnosis of cerebral sinus thrombosis may be missed if only computed tomography (CT) is performed. Therefore, in patients who present atypically or in cases where management dilemmas arise, it is worthwhile to perform MRI or MR venography to rule out cerebral venous thrombosis.
Pregnancy is occasionally associated with IIH. The disorder can present at any stage of pregnancy. In view of the limitations of neuroimaging studies and the restrictions on medical treatment in pregnant patients, it is advisable that both diagnostic and therapeutic strategies be formulated on a case-by-case basis. Any neuroimaging studies or therapeutic interventions should be performed in conjunction with the patient’s obstetrician.
According to reports by Radhakrishnan and others,[14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30] endocrine risk factors that have been confirmed in epidemiologic studies include the following:
Reproductive age group
Recent weight gain
Endocrine risk factors that meet minimal criteria but have not been confirmed in case-controlled studies include the following:
Excessive thyroxine replacement in children (ie, low thyrotropin levels)
Other risk factors
Increased venous red blood cell (RBC) aggregation and relatively elevated fibrinogen concentrations have been demonstrated in patients with IIH as compared with matched control subjects.
The ratio of retinol to retinol-binding protein is elevated in the CSF of patients with IIH as compared with non-IIH neurologic control subjects and with normal control subjects.
Because IIH is concentrated in women between puberty and menopause, Fraser et al emphasized the potential role of sex hormones in the pathogenesis of IIH; they also pointed out that obstructive sleep apnea (OSA) has been proposed as a risk factor. Because women taking exogenous estrogen and pregnant women are not at particular risk for IIH, the investigators suggested that low levels of testosterone might be the important hormonal link in women with IIH.
Fraser et al administered 2 standardized questionnaires embedded in a telephone interview of 24 men with IIH and 48 control subjects matched for gender, age, race, and World Health Organization (WHO) BMI category. They found that the men with IIH were significantly more likely to have symptoms of testosterone deficiency and OSA than the control subjects were.
United States statistics
Studies of American-based populations have estimated that the incidence of IIH ranges from 0.9 to 1.0 per 100,000 in the general population, increasing to 1.6-3.5 per 100,000 in women and to 7.9-20 per 100,000 in women who are overweight.[4, 6, 2]
For example, annual figures for IIH in Iowa and Louisiana in the late 1980s were as follows :
0.9 case per 100,000 population
13 cases per 100,000 (Iowa) and 14.85 per 100,000 (Louisiana) in women aged 20-44 years and 10% over their ideal weight
19.3 cases per 100,000 in women 20% over their ideal weight
An 8:1 female-to-male ratio for a mean weight 38% over the ideal weight for height
Annual incidence figures for the Mayo Clinic (Rochester, MN) between 1976 and 1990 were as follows :
0.9 case per 100,000 population
1.6 cases per 100,000 women
3.3 cases per 100,000 females aged 15-44 years
7.9 cases per 100,000 obese women aged 15-44 years
The incidence of IIH varies from country to country. Because of the disease’s relation to body habitus, its occurrence varies according to the incidence of obesity in the respective region.
In a study conducted between 1982 and 1989 that comprised 81 patients (76 females and 5 males) aged 8-55 years, the annual incidence of IIH in Benghazi, Libya, was as follows :
2.2 cases per 100,000 population
4.3 cases per 100,000 women of all ages
12 cases per 100,000 women aged 15-44 years
21.4 cases per 100,000 obese women aged 15-44 years
Age-, sex-, and race-related demographics
Although IIH may affect individuals of any age, most patients with this disease present in the third decade of life. IIH can occur in the pediatric population ; these younger patients are often not obese.
IIH has a strong predilection for women. More than 90% of patients with IIH are women of childbearing age. However, men with IIH are twice as likely as women to lose visual function as a result of papilledema. Thus, the visual function of men with IIH must be followed more closely to avoid irreversible damage.
No evidence exists to suggest that IIH has a predilection for any particular racial or ethnic group over and above any variations in the prevalence of obesity that may be noted in the different groups.
IIH is not known to be associated with any specific mortality risk per se, but endovascular and surgical treatments (eg, venous sinus stenting or shunting) may cause morbidity and mortality. The increased mortality associated with morbid obesity has a selective expression in this group because of the strong predilection of the disease to affect obese females.
The morbidity of IIH is mainly related to the effects of papilledema on visual function. If left untreated, long-standing disc edema results in an irreversible optic neuropathy with accompanying constriction of the visual field and loss of color vision.[43, 44, 45] In end-stage papilledema, central visual acuity is also involved. With timely and appropriate treatment of IIH, the visual prognosis can be encouraging.
Unfortunately, the incidence of visual loss has been reported to be significant in some studies of this disease.
Since the increase in ICP tends to be chronic, all patients with IIH must be monitored for years after presentation. If necessary, medical treatment should be continued on a long-term basis.
The frequency and degree to which vision loss occurs in IIH is difficult to establish from the existing literature. Depending on the referral population and the rigor with which visual function is tested, the prognosis for vision loss in IIH has varied considerably in different series. Authors writing in the 1960s and 1970s indicated that fewer than 25% of these patients had functionally significant blindness; however, this figure has since been revised upward.
As outlined by Radhakrishnan et al in 1994, the reported incidence of vision impairment is much higher in series from referral centers (as many as 96% of cases with some degree of visual field loss) than in population-based series (eg, 22% in Iowa ). Two equally valid explanations for this discrepancy have been proposed:
The referral centers perform more extensive vision testing, including Goldmann and computerized automated threshold perimetry; thus, they discover visual deficits that are not tested for in the community-based studies
The worst cases are referred for tertiary care consultation; thus, the referral center series are biased toward more severe vision loss cases than the community-based studies are
In a major prospective study of visual function in IIH, Wall and George found that 96% of the 50 patients in a series had some degree of visual field loss on Goldmann-type perimetry, whereas 92% had abnormal findings on automated perimetry ; 50% had abnormal contrast sensitivity, and 22% had abnormal Snellen visual acuity. During follow-up (2-39 months; average, 12.4 months), visual fields improved in 60% of patients and deteriorated in 10%.
The University of Iowa observed 20 IIH patients for more than 10 years and found that whereas 11 of the 20 had followed a stable course without visual-field changes or papilledema, 9 had experienced deterioration after initially following a stable course for a time. In 6 of the 9, the deterioration occurred late (28-135 months after initial presentation), and in 3 of the 9, recurrences after resolution of papilledema developed 12-78 months after the initial resolution of IIH.
Informing patients who are overweight that weight control is a long-term factor in the management of IIH is important. Asking patients about their weight loss at the beginning of each visit reinforces this concept. In addition, it may be worthwhile to mention that the loss of as little as 6% of body weight may lead to the termination of this disorder and also may significantly diminish the risk of its recurrence. A recent clinical trial determined that acetazolamide and weight loss (compared with diet alone) was the preferred treatment in patients with mild visual loss (Idiopathic Intracranial Hypertension Treatment Trial at NORDIC Clinical Trials).
In particular, it is essential to educate patients regarding the potential for disabling blindness. The importance of weight loss as the only effective means of reducing the papilledema—and with it the threat of progressive blindness—cannot be overemphasized.[48, 49]
Patients should be urged to enroll in an aggressive weight-loss program, ideally one using a multidisciplinary approach that includes diet and exercise along with psychological and lifestyle counseling. Even when such a program is followed, many patients cannot sustain significant weight reduction and may require drastic steps such as gastric stapling or resection. These measures can be effective for patients who experience vision loss despite aggressive medical and surgical management.[50, 51]
Although IIH may appear to be self-limiting, it is considered to be a chronic disorder; therefore, once the medications given to treat it are tapered off, patients should be instructed to return to an ophthalmologist if symptoms of increased ICP recur. If a particular agent, such as tetracycline, is associated with the rise in ICP, the patient should be educated to avoid this agent.
Jindal M, Hiam L, Raman A, Rejali D. Idiopathic intracranial hypertension in otolaryngology. Eur Arch Otorhinolaryngol. 2009 Jun. 266(6):803-6. [Medline].
Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep. 2008 Mar. 8(2):87-93. [Medline].
Feldon SE. Visual outcomes comparing surgical techniques for management of severe idiopathic intracranial hypertension. Neurosurg Focus. 2007. 23(5):E6. [Medline].
Friedman DI, Jacobson DM. Idiopathic intracranial hypertension. J Neuroophthalmol. 2004 Jun. 24(2):138-45. [Medline].
Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology. 2002 Nov 26. 59(10):1492-5. [Medline].
Miller NR, Newman NJ. Pseudotumor cerebri (benign intracranial hypertension). In:. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. Vol 1. 5th ed. 1999:523-38.:
Bateman GA, Stevens SA, Stimpson J. A mathematical model of idiopathic intracranial hypertension incorporating increased arterial inflow and variable venous outflow collapsibility. J Neurosurg. 2009 Mar. 110(3):446-56. [Medline].
Farb RI, Vanek I, Scott JN, Mikulis DJ, Willinsky RA, Tomlinson G, et al. Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology. 2003 May 13. 60(9):1418-24. [Medline].
Bateman GA. Association between arterial inflow and venous outflow in idiopathic and secondary intracranial hypertension. J Clin Neurosci. 2006 Jun. 13(5):550-6; discussion 557. [Medline].
Bateman GA. Arterial inflow and venous outflow in idiopathic intracranial hypertension associated with venous outflow stenoses. J Clin Neurosci. 2008 Apr. 15(4):402-8. [Medline].
Corbett JJ. The first Jacobson Lecture. Familial idiopathic intracranial hypertension. J Neuroophthalmol. 2008 Dec. 28(4):337-47. [Medline].
Daniels AB, Liu GT, Volpe NJ, Galetta SL, Moster ML, Newman NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007 Apr. 143(4):635-41. [Medline].
Radhakrishnan K, Ahlskog JE, Garrity JA, Kurland LT. Idiopathic intracranial hypertension. Mayo Clin Proc. 1994 Feb. 69(2):169-80. [Medline].
Rogers AH, Rogers GL, Bremer DL, McGregor ML. Pseudotumor cerebri in children receiving recombinant human growth hormone. Ophthalmology. 1999 Jun. 106(6):1186-9; discussion 1189-90. [Medline].
Crock PA, McKenzie JD, Nicoll AM, Howard NJ, Cutfield W, Shield LK, et al. Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand. Acta Paediatr. 1998 Apr. 87(4):381-6. [Medline].
Williams JB. Adverse effects of thyroid hormones. Drugs Aging. 1997 Dec. 11(6):460-9. [Medline].
Raghavan S, DiMartino-Nardi J, Saenger P, Linder B. Pseudotumor cerebri in an infant after L-thyroxine therapy for transient neonatal hypothyroidism. J Pediatr. 1997 Mar. 130(3):478-80. [Medline].
Sacchi S, Russo D, Avvisati G, Dastoli G, Lazzarino M, Pelicci PG, et al. All-trans retinoic acid in hematological malignancies, an update. GER (Gruppo Ematologico Retinoidi). Haematologica. 1997 Jan-Feb. 82(1):106-21. [Medline].
Visani G, Bontempo G, Manfroi S, Pazzaglia A, D'Alessandro R, Tura S. All-trans-retinoic acid and pseudotumor cerebri in a young adult with acute promyelocytic leukemia: a possible disease association. Haematologica. 1996 Mar-Apr. 81(2):152-4. [Medline].
Selleri C, Pane F, Notaro R, Catalano L, Santoro LE, Luciano L, et al. All-trans-retinoic acid (ATRA) responsive skin relapses of acute promyelocytic leukaemia followed by ATRA-induced pseudotumour cerebri. Br J Haematol. 1996 Mar. 92(4):937-40. [Medline].
Ahmad S. Amiodarone and reversible benign intracranial hypertension. Cardiology. 1996 Jan-Feb. 87(1):90. [Medline].
Varadi G, Lossos A, Or R, Kapelushnik J, Nagler A. Successful allogeneic bone marrow transplantation in a patient with ATRA-induced pseudotumor cerebri. Am J Hematol. 1995 Oct. 50(2):147-8. [Medline].
Sivin I. Serious adverse events in Norplant users reported to the Food and Drug Administration's MedWatch Spontaneous Reporting System. Obstet Gynecol. 1995 Aug. 86(2):318-20. [Medline].
Baqui AH, de Francisco A, Arifeen SE, Siddique AK, Sack RB. Bulging fontanelle after supplementation with 25,000 IU of vitamin A in infancy using immunization contacts. Acta Paediatr. 1995 Aug. 84(8):863-6. [Medline].
Alder JB, Fraunfelder FT, Edwards R. Levonorgestrel implants and intracranial hypertension. N Engl J Med. 1995 Jun 22. 332(25):1720-1. [Medline].
Malozowski S, Tanner LA, Wysowski DK, Fleming GA, Stadel BV. Benign intracranial hypertension in children with growth hormone deficiency treated with growth hormone. J Pediatr. 1995 Jun. 126(6):996-9. [Medline].
Campos SP, Olitsky S. Idiopathic intracranial hypertension after L-thyroxine therapy for acquired primary hypothyroidism. Clin Pediatr (Phila). 1995 Jun. 34(6):334-7. [Medline].
Nasr SZ, Schaffert D. Symptomatic increase in intracranial pressure following pancreatic enzyme replacement therapy for cystic fibrosis. Pediatr Pulmonol. 1995 Jun. 19(6):396-7. [Medline].
Price DA, Clayton PE, Lloyd IC. Benign intracranial hypertension induced by growth hormone treatment. Lancet. 1995 Feb 18. 345(8947):458-9. [Medline].
Kelly SJ, O'Donnell T, Fleming JC, Einhaus S. Pseudotumor cerebri associated with lithium use in an 11-year-old boy. J AAPOS. 2009 Apr. 13(2):204-6. [Medline].
Mollan SP, Ball AK, Sinclair AJ, Madill SA, Clarke CE, Jacks AS, et al. Idiopathic intracranial hypertension associated with iron deficiency anaemia: a lesson for management. Eur Neurol. 2009. 62(2):105-8. [Medline].
Lin A, Foroozan R, Danesh-Meyer HV, De Salvo G, Savino PJ, Sergott RC. Occurrence of cerebral venous sinus thrombosis in patients with presumed idiopathic intracranial hypertension. Ophthalmology. 2006 Dec. 113(12):2281-4. [Medline].
Kesler A, Yatziv Y, Shapira I, Berliner S, Assayag EB. Increased red blood cell aggregation in patients with idiopathic intracranial hypertension. A hitherto unexplored pathophysiological pathway. Thromb Haemost. 2006 Oct. 96(4):483-7. [Medline].
Warner JE, Larson AJ, Bhosale P, Digre KB, Henley C, Alder SC, et al. Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension. J Neuroophthalmol. 2007 Dec. 27(4):258-62. [Medline].
Fraser JA, Bruce BB, Rucker J, Fraser LA, Atkins EJ, Newman NJ, et al. Risk factors for idiopathic intracranial hypertension in men: a case-control study. J Neurol Sci. 2010 Mar 15. 290(1-2):86-9. [Medline]. [Full Text].
Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988 Aug. 45(8):875-7. [Medline].
Radhakrishnan K, Ahlskog JE, Cross SA, Kurland LT, O'Fallon WM. Idiopathic intracranial hypertension (pseudotumor cerebri). Descriptive epidemiology in Rochester, Minn, 1976 to 1990. Arch Neurol. 1993 Jan. 50(1):78-80. [Medline].
Radhakrishnan K, Thacker AK, Bohlaga NH, Maloo JC, Gerryo SE. Epidemiology of idiopathic intracranial hypertension: a prospective and case-control study. J Neurol Sci. 1993 May. 116(1):18-28. [Medline].
Digre KB, Nakamoto BK, Warner JE, Langeberg WJ, Baggaley SK, Katz BJ. A comparison of idiopathic intracranial hypertension with and without papilledema. Headache. 2009 Feb. 49(2):185-93. [Medline].
Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS, 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 Aug. 39(8):461-74. [Medline].
Agostoni E, Aliprandi A. Alterations in the cerebral venous circulation as a cause of headache. Neurol Sci. 2009 May. 30 Suppl 1:S7-10. [Medline].
Ney JJ, Volpe NJ, Liu GT, Balcer LJ, Moster ML, Galetta SL. Functional visual loss in idiopathic intracranial hypertension. Ophthalmology. 2009 Sep. 116(9):1808-1813.e1. [Medline].
Wall M, George D. Visual loss in pseudotumor cerebri. Incidence and defects related to visual field strategy. Arch Neurol. 1987 Feb. 44(2):170-5. [Medline].
Shah VA, Kardon RH, Lee AG, Corbett JJ, Wall M. Long-term follow-up of idiopathic intracranial hypertension: the Iowa experience. Neurology. 2008 Feb 19. 70(8):634-40. [Medline].
Kupersmith MJ, Gamell L, Turbin R, Peck V, Spiegel P, Wall M. Effects of weight loss on the course of idiopathic intracranial hypertension in women. Neurology. 1998 Apr. 50(4):1094-8. [Medline].
Rowe FJ, Sarkies NJ. Assessment of visual function in idiopathic intracranial hypertension: a prospective study. Eye (Lond). 1998. 12 ( Pt 1):111-8. [Medline].
Sugerman HJ, Felton WL 3rd, Salvant JB Jr, Sismanis A, Kellum JM. Effects of surgically induced weight loss on idiopathic intracranial hypertension in morbid obesity. Neurology. 1995 Sep. 45(9):1655-9. [Medline].
Sugerman HJ, Felton WL 3rd, Sismanis A, Kellum JM, DeMaria EJ, Sugerman EL. Gastric surgery for pseudotumor cerebri associated with severe obesity. Ann Surg. 1999 May. 229(5):634-40; discussion 640-2. [Medline]. [Full Text].
González-Hernández A, Fabre-Pi O, Díaz-Nicolás S, López-Fernández JC, López-Veloso C, Jiménez-Mateos A. [Headache in idiopathic intracranial hypertension]. Rev Neurol. 2009 Jul 1-15. 49(1):17-20. [Medline].
Nampoory MR, Johny KV, Gupta RK, Constandi JN, Nair MP, al-Muzeiri I. Treatable intracranial hypertension in patients with lupus nephritis. Lupus. 1997. 6(7):597-602. [Medline].
Leker RR, Steiner I. Anticardiolipin antibodies are frequently present in patients with idiopathic intracranial hypertension. Arch Neurol. 1998 Jun. 55(6):817-20. [Medline].
Sussman J, Leach M, Greaves M, Malia R, Davies-Jones GA. Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension. J Neurol Neurosurg Psychiatry. 1997 Mar. 62(3):229-33. [Medline]. [Full Text].
Bachman DT, Srivastava G. Emergency department presentations of Lyme disease in children. Pediatr Emerg Care. 1998 Oct. 14(5):356-61. [Medline].
Agid R, Farb RI, Willinsky RA, Mikulis DJ, Tomlinson G. Idiopathic intracranial hypertension: the validity of cross-sectional neuroimaging signs. Neuroradiology. 2006 Aug. 48(8):521-7. [Medline].
Maralani PJ, Hassanlou M, Torres C, Chakraborty S, Kingstone M, Patel V, et al. Accuracy of brain imaging in the diagnosis of idiopathic intracranial hypertension. Clin Radiol. 2012 Jul. 67(7):656-63. [Medline].
Stone MB. Ultrasound diagnosis of papilledema and increased intracranial pressure in pseudotumor cerebri. Am J Emerg Med. 2009 Mar. 27(3):376.e1-376.e2. [Medline].
Digre KB, Varner MW, Corbett JJ. Pseudotumor cerebri and pregnancy. Neurology. 1984 Jun. 34(6):721-9. [Medline].
Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. Neurology. 1991 Feb. 41(2 ( Pt 1)):239-44. [Medline].
Hughes S. Drug Improves Vision in Idiopathic Intracranial Hypertension. Medscape Medical News. Available at http://www.medscape.com/viewarticle/824073. Accessed: April 29, 2014.
Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, 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 Apr 23-30. 311(16):1641-51. [Medline].
Goh KY, Schatz NJ, Glaser JS. Optic nerve sheath fenestration for pseudotumor cerebri. J Neuroophthalmol. 1997 Jun. 17(2):86-91. [Medline].
Brazis PW. Clinical review: the surgical treatment of idiopathic pseudotumour cerebri (idiopathic intracranial hypertension). Cephalalgia. 2008 Dec. 28(12):1361-73. [Medline].
Chandrasekaran S, McCluskey P, Minassian D, Assaad N. Visual outcomes for optic nerve sheath fenestration in pseudotumour cerebri and related conditions. Clin Experiment Ophthalmol. 2006 Sep-Oct. 34(7):661-5. [Medline].
Spoor TC, McHenry JG. Long-term effectiveness of optic nerve sheath decompression for pseudotumor cerebri. Arch Ophthalmol. 1993 May. 111(5):632-5. [Medline].
Nithyanandam S, Manayath GJ, Battu RR. Optic nerve sheath decompression for visual loss in intracranial hypertension: report from a tertiary care center in South India. Indian J Ophthalmol. 2008 Mar-Apr. 56(2):115-20. [Medline]. [Full Text].
Yadav YR, Parihar V, Agarwal M, Bhatele PR, Saxena N. Lumbar peritoneal shunt in idiopathic intracranial hypertension. Turk Neurosurg. 2012. 22(1):21-6. [Medline].
Burgett RA, Purvin VA, Kawasaki A. Lumboperitoneal shunting for pseudotumor cerebri. Neurology. 1997 Sep. 49(3):734-9. [Medline].
Woodworth GF, McGirt MJ, Elfert P, Sciubba DM, Rigamonti D. Frameless stereotactic ventricular shunt placement for idiopathic intracranial hypertension. Stereotact Funct Neurosurg. 2005. 83(1):12-6. [Medline].
Sinclair AJ, Kuruvath S, Sen D, Nightingale PG, Burdon MA, Flint G. Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review. Cephalalgia. 2011 Dec. 31(16):1627-33. [Medline].
Bussière M, Falero R, Nicolle D, Proulx A, Patel V, Pelz D. Unilateral transverse sinus stenting of patients with idiopathic intracranial hypertension. AJNR Am J Neuroradiol. 2010 Apr. 31(4):645-50. [Medline].
Arac A, Lee M, Steinberg GK, Marcellus M, Marks MP. Efficacy of endovascular stenting in dural venous sinus stenosis for the treatment of idiopathic intracranial hypertension. Neurosurg Focus. 2009 Nov. 27(5):E14. [Medline].
Fridley J, Foroozan R, Sherman V, Brandt ML, Yoshor D. Bariatric surgery for the treatment of idiopathic intracranial hypertension. J Neurosurg. 2011 Jan. 114(1):34-9. [Medline].
Johnson LN, Krohel GB, Madsen RW, March GA Jr. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology. 1998 Dec. 105(12):2313-7. [Medline].
Pollak L, Zohar E, Glovinsky Y, Huna-Baron R. Reevaluation of presentation and course of idiopathic intracranial hypertension - a large cohort comprehensive study. Acta Neurol Scand. 2012 Dec 31. [Medline].