AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The presentation of a patient with symptoms of increased intracranial pressure and papilledema is a clinical emergency. Although this scenario may be the harbinger of a brain mass, other clinical entities should be considered. A significant number of patients presenting in the above fashion are diagnosed with idiopathic intracranial hypertension.

Although idiopathic intracranial hypertension, pseudotumor cerebri, and benign intracranial hypertension are synonymous with this diagnosis, the preferred term is idiopathic intracranial hypertension.

The diagnostic criteria include the following: symptoms and signs restricted to those of elevated intracranial pressure; normal findings on neuroimaging studies, excluding nonspecific findings of raised intracranial pressure; and increased cerebrospinal fluid pressure with a normal composition.

Pathophysiology

The pathophysiology of this disorder is unclear. A relative resistance to the absorption of cerebrospinal fluid across the arachnoid villi is widely presumed to be present. Other theories support an abnormality in the cerebral circulation with a resulting increase in the brain's water content. The subsequent increase in the intracranial pressure is transmitted to the structures within the intracranial cavity, including the optic nerves. Unfortunately, due to the difficulty in applying animal models of cerebrospinal fluid dynamics to humans, the underlying pathophysiology in idiopathic intracranial hypertension remains unclear. A recent mathematical model suggested that individuals with a compressible, as opposed to rigid, transverse sinus results in a relative stenosis and, thus, an elevated intracranial pressure.

The disease commonly occurs in women who are overweight. The role of obesity in this disorder is unclear. Obesity has been proposed to increase intra-abdominal pressure, which, in turn, raises cardiac filling pressures. This rise in pressure leads 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 not treated appropriately, chronic interruption of the axoplasmic flow of the optic nerves with ensuing papilledema due to this pressure may lead to irreversible optic neuropathy.

Frequency

United States

Studies of American-based populations have estimated that the incidence of idiopathic intracranial hypertension ranges from 0.9-1.0 per 100,000 in the general population. This incidence rate increases to 1.6-3.5 per 100,000 in women, and 7.9-19 per 100,000 in women who are overweight.

International

The incidence of idiopathic intracranial hypertension is variable from country to country. Because of the relation of the disease to body habitus, its occurrence varies according to the incidence of obesity in the respective region. A study performed in Libya demonstrated an incidence of 2.2 per 100,000 in the general population, 4.3 per 100,000 in women, and 21.4 per 100,000 in women who are overweight.

Mortality/Morbidity

• The morbidity of this disorder is mainly related to the effects of papilledema.
• 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.
• In end-stage papilledema, central visual acuity is also involved.

Sex

A strong predilection of this disease exists for women. In the literature, the female-to-male ratio ranges from 2:1 to 10:1.

Age

Although idiopathic intracranial hypertension may affect individuals of any age, most patients with this disease present in the third decade of life.

Idiopathic intracranial hypertension does occur in the pediatric population; these younger patients are often not obese.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients usually present with symptoms related to increased intracranial pressure. These symptoms include headache, transient visual obscurations, and diplopia due to unilateral or bilateral sixth nerve palsy. Rarely, patients presenting with increased intracranial pressure with related optic nerve edema may be asymptomatic.
• Nonspecific symptoms may include dizziness, nausea, vomiting, and tinnitus.
• Headaches
• • Headaches are recorded in 99% of patients presenting to neurologists and slightly less in patients presenting to ophthalmologists.
  • The pain is generally described as being diffuse, which worsens in the morning and is exacerbated by the Valsalva maneuver.
• Transient visual obscurations: This visual symptom occurs in most patients. The disturbance usually lasts 1-5 seconds and is described as a graying out of vision. Orthostatic changes, such as standing up or bending over, induce this symptom.
• Diplopia: Patients who present with double vision most frequently complain of horizontal displacement of the images. Vertical diplopia is rare, but it has been reported.

Physical

• The most significant finding in patients with this disease is bilateral disc edema secondary to the increased intracranial pressure.
• This papilledema varies from patient to patient and is indistinguishable from optic nerve swelling caused by intracranial space-occupying lesions. In more pronounced cases of disc swelling, macular involvement with subsequent edema and diminished central vision may be present. High-grade and atrophic papilledema in addition to subretinal hemorrhages are poor visual prognostic signs.
• In some instances, the disc swelling is asymmetric, or, rarely, the appearance of the optic nerve may be relatively normal.
• If left untreated, chronic disc swelling eventually leads to clinically significant visual loss. Although all patients present with enlarged blind spots during their initial perimetry, uncontrolled papilledema results in progressive peripheral visual field constriction or nerve fiber bundle defects (eg, nasal depression, nasal steps, arcuate scotomas).
• The central visual field is affected in end-stage chronic papilledema.
• Sudden loss of central vision may result from an associated anterior ischemic optic neuropathy, a vascular occlusion, or an associated subretinal neovascular membrane.
• The diplopia noted in patients with idiopathic intracranial hypertension is invariably due to unilateral or bilateral sixth nerve palsy. These cranial nerve palsies diminish with the lowering of the intracranial pressure.
• Occasionally, patients with diplopia present with oculomotor or trochlear nerve palsy.
• In rare instances, vertical diplopia is due to a skew deviation.

Causes

• Most cases of idiopathic intracranial hypertension occur in young women who are obese and, less frequently, in men who are otherwise healthy. Patients with higher body mass indexes and recent weight gain are at an increased risk for this disorder.¹
• If this disorder presents in an individual who is not overweight, ruling out associated risk factors is necessary. These risk factors include systemic diseases (including Lyme disease), disruption of cerebral venous flow, certain endocrine or metabolic disorders, and exposure to or withdrawal from certain exogenous substances.
• Risk factors
• • Exogenous substances
  • • The list of exogenous substances associated with idiopathic intracranial hypertension is extensive. Although an association exists between these substances and this disorder, the exact causal relationship is somewhat lacking in the literature.
    • Exogenous substances associated with idiopathic intracranial hypertension include amiodarone, antibiotics (eg, nalidixic acid, penicillin, tetracycline), carbidopa, levodopa, chlordecone, corticosteroids (eg, topical, systemic), cyclosporine, danazol, growth hormone, indomethacin, ketoprofen, lead, leuprolide acetate, levonorgestrel implants, lithium, oral contraceptives, oxytocin, perhexiline, phenytoin, and vitamin A (>100,000 U/d)/retinoic acid.
    • In some instances, although a patient may present with idiopathic intracranial hypertension following exposure to a certain medication, the disorder can continue despite the cessation of the presumed offending agent.
    • Ironically, withdrawal from corticosteroids may result in idiopathic intracranial hypertension.
  • Systemic diseases
  • • A myriad of illnesses are associated with idiopathic intracranial hypertension. Some of these disorders result in an increased viscosity of the cerebrospinal fluid. However, in most of the listed entities, the causal link with raised intracranial pressure is not clear.
    • The following diseases have been associated with idiopathic intracranial hypertension: anemia, chronic respiratory insufficiency, familial Mediterranean fever, hypertension, multiple sclerosis, polyangiitis overlap syndrome, psittacosis, renal disease, Reye syndrome, sarcoidosis, systemic lupus erythematosus, and thrombocytopenic purpura.
  • Disorders of cerebral venous drainage
  • • Cerebral venous compression by extravascular tumors or secondary thrombosis results in impaired absorption of the cerebrospinal fluid and, thus, idiopathic intracranial hypertension. Restriction of venous drainage from the head may be impaired with radical neck dissection, even if completed only on the right side (predominant drainage from the head is via the right jugular vein). Spontaneous recanalization usually occurs, but, if delayed, chronic papilledema may result.
    • The diagnosis of cerebral sinus thrombosis may be missed with the exclusive use of computed tomography (CT). Therefore, either in patients who present atypically or in management dilemmas, ruling out cerebral venous thrombosis with the use of magnetic resonance imaging (MRI)/venography is worthwhile.
  • Endocrine disturbances: Pregnancy is occasionally associated with idiopathic intracranial hypertension. This disorder can present at any stage of pregnancy. Given the limitations of neuroimaging studies and of medically treating patients who are pregnant, both the diagnosis and the management of these patients are determined on a case-by-case basis. Any neuroimaging studies or therapeutics should be performed in conjunction with the patient's obstetrician.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Bilateral optic nerve head edema is presumably due to increased intracranial pressure secondary to an intracranial tumor until proven otherwise. Ruling out malignant hypertension prior to pursuing the diagnostic trail of idiopathic intracranial hypertension is always worthwhile.

If the patient's blood pressure is normal or minimally to moderately elevated, obtaining urgent neuroimaging studies to rule out a space-occupying lesion or a dural sinus thrombosis is essential. If the neuroimaging study does not demonstrate any pathology and if a lumbar puncture demonstrates a raised opening pressure, then one of the above-mentioned causes of increased intracranial pressure must be considered (see Risk Factors).

In the absence of a specific offending agent, the diagnosis of the patient is presumably idiopathic intracranial hypertension.

Other causes of bilateral raised discs include the following:

• Pseudopapilledema
• Drusen of the optic nerve heads
• Malignant hypertension
• Bilateral infiltrative/infectious/inflammatory optic neuropathy
• Bilateral anterior ischemic optic neuropathy
• Bilateral optic nerve papillitis
• Bilateral optic nerve tumors (eg, glioma, meningioma)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Imaging Studies

• Neuroimaging
• • A patient with bilateral disc swelling should undergo urgent neuroimaging studies to rule out an intracranial mass or a dural sinus thrombosis.
  • Although CT is certainly adequate in most instances, MRI and magnetic resonance venography are effective in ruling out both a mass lesion and a potential dural sinus thrombosis.
  • In the setting of idiopathic intracranial hypertension, the findings on neuroimaging studies either are normal or demonstrate small slitlike ventricles, enlarged optic nerve sheaths, and occasionally an empty sella.
• Ultrasonography
• • Standardized A-scan orbital ultrasonography precisely measures the diameter of the optic nerve sheath.
  • If this diameter increases in primary gaze and diminishes by 25% in eccentric gaze (30° test), then increased subarachnoid fluid surrounding the optic nerve is presumably present. This finding is consistent with papilledema if it is bilateral.
  • The drawback of this noninvasive technique is that it requires a highly skilled clinician to obtain reproducible results.

Procedures

• Lumbar puncture
• • Once an intracranial mass lesion is ruled out, a lumbar puncture is indicated. The opening pressure should be measured with the patient relaxed to avoid a falsely elevated pressure reading.
  • The clinician performing the procedure must indicate to the ophthalmologist if any specific difficulty was encountered that may have falsely elevated the pressure reading.
  • Unfortunately, some patients demonstrate a transiently normal pressure despite their harboring idiopathic intracranial hypertension. Confirming the disease in these patients is difficult.
  • Besides the value of the opening pressure, the clarity and the color of the cerebrospinal fluid should be noted. In addition, the cerebrospinal fluid should be forwarded for assessment of the cell count, cytology, culture, glucose, protein, and electrolyte concentration. All of these findings are normal in patients with idiopathic intracranial hypertension.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The treatment goal for patients is to preserve optic nerve function while managing their increased intracranial pressure.

• Optic nerve function should be carefully monitored with an assessment of visual acuity, color vision, optic nerve head observation, and perimetry.
• The medical management is multifaceted and consists of the following:
• • Weight control for patients who are overweight
    • Most patients with this disorder are females who are overweight. Weight loss is a cornerstone in the management of these patients. Unfortunately, weight reduction generally proves to be a difficult task for these patients.
    • As little as a 6% weight loss has been demonstrated to result in a reduction of the intracranial pressure with the accompanying resolution of papilledema.
    • To formalize the process of weight reduction, referral to a dietitian may be appropriate.
  • Treatment of related underlying diseases (see Causes)
  • Cessation of exogenous agents related to increased intracranial pressure
  • Use of diuretics to control the intracranial pressure
    • To protect the optic nerve function, the intracranial pressure must be lowered.
    • Acetazolamide appears to be the most effective diuretic in lowering the intracranial pressure. The initial dose should be 1 g/d. Although for compliance purposes, the 500 mg sequel taken orally twice a day is preferred; some insurers only cover an oral dose of 250 mg taken 4 times per day. This dose can be increased to 2 g/d, although most patients do not tolerate the troubling adverse effects (eg, extremity paresthesias, fatigue, metallic taste when drinking carbonated beverages, decreased libido) of this medication at this high dose.
    • In the event of intolerance to acetazolamide, furosemide may be used as a replacement diuretic in this group. Unfortunately, furosemide does not appear to be as effective as acetazolamide.
  • Corticosteroids
  • • Corticosteroids are effective in lowering the intracranial pressure in those patients with an inflammatory etiology for their idiopathic intracranial hypertension.
    • In addition, steroids may be used as a supplement to acetazolamide to hasten recovery in patients who present with severe papilledema.
    • Because of the significant adverse effects, corticosteroids should not be considered as a long-term solution for these patients.

Surgical Care

Patients with idiopathic intracranial hypertension should be closely monitored while on medical treatment. The frequency of visits is determined by the initial state of the patient's visual function and the response to medical treatment. Despite close follow-up care and maximum medical treatment, some patients experience deterioration of their visual function. In this situation, surgical intervention should be considered. Two procedures that can be performed are optic nerve sheath fenestration or a cerebrospinal fluid diversion procedure (ie, lumboperitoneal shunt, ventriculoperitoneal shunt). Treatment of this disorder by repeated lumbar punctures is considered to be of historic interest.

• Optic nerve sheath fenestration
• • Optic nerve sheath fenestration has been demonstrated to result in the reversal of optic nerve edema with some recovery of optic nerve function. The approach to the optic nerve may be from the medial or lateral aspect of the orbit; each technique has its benefits and drawbacks.
  • Occasionally, a bilateral curative effect of the papilledema occurs from unilateral surgery. However, if this is not the case, then the opposite nerve must undergo the same procedure.
  • Although the intracranial pressure remains elevated in these patients postoperatively, the local filtering effect of the fenestration acts as a safety valve and eliminates the pressure from being transmitted to the optic nerve.
  • Complications related to this procedure include diplopia, optic nerve injury, vascular occlusion, a tonic pupil, and the inherent risk of hemorrhage and infection with intraconal surgery.
  • Unfortunately, Spoor has demonstrated that the long-term success rate of this operation may be only 16%.²
• Cerebrospinal fluid diversion procedures (ie, lumboperitoneal shunt, ventriculoperitoneal shunt)
• • These two neurosurgical interventions are highly effective in lowering the intracranial pressure. In some facilities, they remain the procedures of choice for treating patients with idiopathic intracranial hypertension who do not respond to maximum medical treatment.
  • Shunts are also indicated in the following: patients with intractable headaches, regions where no access is available to a surgeon who is comfortable with optic nerve sheath fenestration, and patients with a failed optic nerve sheath fenestration.

Diet

• Weight reduction has been clearly demonstrated to be an important factor in the long-term management of these patients.
• As little as a 6% decrease in the total body weight can result in the resolution of papilledema. Unfortunately, weight loss in patients who are obese is difficult.
• A referral to a dietitian is worthwhile in patients who are motivated to lose weight.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The medications used in this disorder are directed at lowering intracranial pressure. The diuretic acetazolamide is the most effective drug for this task. Furosemide may be used as a replacement, although it is not as potent as acetazolamide. Corticosteroids are indicated on a short-term basis in patients who present with severe papilledema and compromise of their visual function.

Drug Category: Carbonic anhydrase inhibitors

Carbonic anhydrase (CA) is an enzyme found in many tissues. Catalyzes a reversible reaction where carbon dioxide becomes hydrated and carbonic acid becomes dehydrated. These changes may result in a decrease in cerebrospinal fluid by the choroid plexus.

Drug Category: Loop diuretics

These agents inhibit reabsorption of sodium in the ascending limb of Henle loop and have a weak inhibitory action on carbonic anhydrase.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• The frequency of the follow-up visits is determined by a number of factors, to include the following:
• • Initial visual function of the patient
  • Underlying disease causing increased intracranial pressure
  • Perceived compliance of the patient with respect to medical therapy
• Once the initial diagnosis has been established, investigations have been performed, and the therapy has been initiated, the patient can be observed every 3-4 weeks. However, patients who present with a significant visual function deficit or marked papilledema should be monitored daily for a week until they demonstrate some improvement and subsequent stability in their visual function. The clinician should be prepared to titrate the patient's treatment to the status of the visual function and should not hesitate to refer the patient for surgical treatment (optic nerve sheath fenestration or a neurosurgical shunting procedure) in the absence of stabilization of the visual function. 
• During follow-up visits, the best-corrected visual acuity for distant and near vision, color vision (using pseudoisochromatic plates), static perimetry, and optic nerve appearance (including the status of spontaneous venous pulsations) should be recorded. Patients who do not perform well on static perimetry testing may be better followed with kinetic perimetry testing. The spontaneous pulsation of large retinal veins generally indicates a normal intracranial pressure. If the patient continues to remark on the persistence of a significant headache despite the presence of spontaneous venous pulsations, evaluating a source other than idiopathic intracranial hypertension for the headache is important.
• When a patient appears to have stabilized with respect to visual function and treatment, follow-up visits can extend to once every 2-4 months.

Complications

• The main complication of this disorder is progressive optic neuropathy. Despite timely treatment, some patients develop an optic neuropathy related to the optic nerve edema.
• Generally, this dysfunction presents in a progressive fashion with constriction of the peripheral visual field; worsening nerve fiber bundle visual field defects; a decrease of color vision; and, in end-stage disease, a drop in the central visual function.
• Occasionally, a patient may develop an acute loss of vision due to ischemic optic neuropathy or a retinal vascular occlusion associated with the papilledema.

Prognosis

• The visual prognosis in timely and appropriately treated patients can be encouraging in cases of idiopathic intracranial hypertension.
• Unfortunately, the incidence of visual loss has been reported to be significant in some studies of this disease. Corbett et al documented visual dysfunction in close to one half of patients with idiopathic intracranial hypertension.³
• Since the increase in intracranial pressure tends to be chronic in nature, all patients with this disorder must be monitored for years after presentation. If necessary, medical treatment should be continued on a long-term basis.

Patient Education

• Informing patients who are overweight that weight control is a long-term factor in idiopathic intracranial hypertension 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.
• Although the disease may appear to be self-limiting, it is considered to be a chronic disorder; therefore, once the medication is tapered off, patients should be alerted to return to an ophthalmologist if symptoms of increased intracranial pressure recur.
• If a particular agent, such as tetracycline, is associated with the rise in intracranial pressure, the patient should be educated to avoid this agent.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Although idiopathic intracranial hypertension typically develops in young females who are overweight, the disease does occur in males and in patients who are not overweight.  To complicate matters, some patients may present with idiopathic intracranial hypertension who have either asymmetric optic nerve swelling or the absence of optic nerve edema in either eye.
• When a patient presents with bilateral disc edema, the diagnosis is presumably an intracranial mass until proven otherwise. A lumbar puncture should not be performed until the findings on neuroimaging studies have eliminated the possibility of a space-occupying lesion. A lumbar puncture performed in the presence of an intracranial mass may result in the fatal occurrence of herniation of the temporal lobe or the cerebellum. Thus, reviewing the images prior to performing a lumbar puncture is essential to avoid this outcome.
• In addition to ruling out a mass lesion, ensuring that patients with papilledema do not have a dural sinus thrombosis is important. Although a high-quality CT scan or MRI with infusion may eliminate this possibility, magnetic resonance venography is preferable.⁴ 
• If the findings on neuroimaging studies are normal and a lumbar puncture indicates increased intracranial pressure in a patient with papilledema, long-term monitoring for progressive optic neuropathy is indicated.
• Although the disease may appear to be self-limiting, it may recur and subsequently result in severe visual loss.
• Patients who are administered acetazolamide should be aware of both the precautions and the adverse reactions listed in Medication.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. 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. Apr 2007;143(4):635-41. [Medline].
2. Spoor TC, McHenry JG. Long-term effectiveness of optic nerve sheath decompression for pseudotumor cerebri. Arch Ophthalmol. May 1993;111(5):632-5. [Medline].
3. 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. Aug 1982;39(8):461-74. [Medline].
4. 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. Dec 2006;113(12):2281-4. [Medline].
5. Brazis PW, Lee AG. Elevated intracranial pressure and pseudotumor cerebri. Curr Opin Ophthalmol. Dec 1998;9(6):27-32. [Medline].
6. Canadian Pharmacists Association. Diamox - acetazolamide; carbonic anhydrase inhibitor. Compendium of Pharmaceuticals and Specialties. 1998;33:474-5.
7. Corbett JJ. Increased intracranial pressure: idiopathic and otherwise. J Neuroophthalmol. Jun 2004;24(2):103-5. [Medline].
8. Friedman DI, Jacobson DM. Idiopathic intracranial hypertension. J Neuroophthalmol. Jun 2004;24(2):138-45. [Medline].
9. 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. Dec 1998;105(12):2313-7. [Medline].
10. Miller NR, Newman NJ. Pseudotumor cerebri (benign intracranial hypertension). In: Walsh and Hoyt's Clinical Neuro-Ophthalmology. Vol 1. 5^th ed. 1999:523-38.
11. Skau M, Brennum J, Gjerris F, Jensen R. What is new about idiopathic intracranial hypertension? An updated review of mechanism and treatment. Cephalalgia. Apr 2006;26(4):384-99. [Medline].

Article Last Updated: Nov 6, 2007