James Goodwin, MD,
Associate Professor, Departments of Neurology
and Ophthalmology, University of Illinois College of
Medicine; Director, Neuro-Ophthalmology Service, University
of Illinois Eye and Ear Infirmary
Nothing to disclose.
Specialty Editor(s)
Eric R Eggenberger, DO, MS, FAAN,
Professor, Vice-Chairman, Department of
Neurology and Ophthalmology, Colleges of Osteopathic Medicine
and Human Medicine, Michigan State University; Director of
Michigan State University Ocular Motility Laboratory;
Director of National Multiple Sclerosis Society Clinic,
Michigan State University
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Senior Pharmacy Editor,
eMedicine
eMedicine Salary Employment
Robert A Egan, MD,
Director of Neuro-Ophthalmology, St Helena
Hospital
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Selim R Benbadis, MD,
Professor, Director of Comprehensive Epilepsy
Program, Departments of Neurology and Neurosurgery,
University of South Florida School of Medicine, Tampa General
Hospital
Robert A Egan, MD,
Director of Neuro-Ophthalmology, St Helena
Hospital
Nothing to disclose.
Background
Pseudotumor cerebri, also known as idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. It affects predominantly obese women of childbearing age.[1] 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.[1]
A dominant early theory concerning the pathogenesis of elevated ICP in these patients was cerebral edema. Against this is the fact that no altered level of alertness, cognitive impairment, or focal neurological findings are associated with the elevated ICP. In addition, no pathologic signs of cerebral edema have been 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 theories include increased resistance to cerebrospinal fluid (CSF) outflow at the arachnoid granulations that line the dural venous sinuses and through which CSF reabsorption is thought to occur by bulk flow. Alternatively, occult cerebral venous outflow abnormalities may produce IIH.
Farb and colleagues have demonstrated that, in a series of 29 patients with IIH, narrowing of the transverse dural venous sinus was demonstrable on MR venography, while none of the 59 control subjects had this finding.[2] These authors suggest that the narrowing is a consequence of elevated intracranial pressure, and, when the narrowing develops, it exacerbates the pressure elevation by increasing venous pressure in the superior sagittal sinus.
CSF production rate (mL/min) should be equal to the CSF reabsorption rate.
If production exceeds absorption, ICP rises until it exceeds mean arterial pressure, which, if sustained, would be fatal.
In IIH the production rate equals the reabsorption rate; however, a higher than normal pressure is required to achieve this owing to the increased resistance at the arachnoid granulations.
Bateman has shown that some patients with IIH with normal dural venous drainage have increased arterial inflow suggesting that collateral venous drainage occurs in addition to that provided by the superior sagittal sinus and transverse sinuses.[3] The same investigator measured MR venography and MR flow quantification in cerebral arteries and veins in a series of 40 patients with IIH, of which 21 patients had venous stenosis. The arterial inflow was 21% higher than normal and superior sagittal sinus outflow was normal, resulting in reduced percentage of venous outflow compared to inflow. The remainder of arterial inflow volume is presumed to have drained via collateral venous channels. With clinical remission of symptoms, the arterial inflow volumes returned to normal.[4]
More recently, Bateman et al proposed a mathematical model to account for collapsible dural venous sinuses in the pathogenesis of IIH since this has been shown to be an important factor in many cases. The model includes arterial inflow volume, venous outflow resistance, and CSF pressure. They 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 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 point in the normal range and the other in the range encountered in IIH patients. This accounts for the prolonged remission of symptoms that follows removal of CSF at lumbar puncture, presumably because this relieves the venous sinus stenosis. Without dural sinus collapse and stenosis, as is encountered in some patients with IIH, the model requires increased arterial inflow volume to account for the elevated intracranial pressure. Interestingly, the model did not require increased resistance to outflow of CSF across the arachnoid villi.[5]
Annual incidence of pseudotumor cerebri in Iowa and Louisiana[6]
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 ideal weight
19.3 cases per 100,000 in women 20% over ideal weight
Female-to-male ratio 8:1 for mean weight 38% over ideal weight for height
Annual incidence at Mayo Clinic (Rochester, MN) between 1976 and 1990[7]
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
International
Annual incidence of idiopathic intracranial hypertension in Benghazi, Libya, in a study conducted between 1982 and 1989 comprising 81 patients (76 females and 5 males) aged 8-55 years[8]
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
Mortality/Morbidity
IIH is associated with no known specific mortality risk. The increased mortality rate associated with morbid obesity has a selective expression in this group because of the strong predilection of the disease to affect obese females.
Vision loss[9, 10]
The only permanent morbidity in IIH is vision loss from decompensation of papilledema with progressive optic atrophy. The frequency and degree to which visual loss occurs in this disease is difficult to establish from the existing literature.
As outlined by Radhakrishnan et al in 1994[11] , the reported incidence of vision impairment is much higher in series published from referral centers (as many as 96% of cases with some degree of visual field loss) compared to population-based series (eg, 22% in Iowa[6] ).
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, and thus discovered visual deficits that were not tested for in the community-based studies.
The worst cases are referred for tertiary care consultation and thus the referral center series are biased toward more severe vision loss cases than the community-based studies.
Race
No evidence exists to suggest predilection for any particular racial or ethnic group apart from variation in the prevalence of obesity in the different groups.
Sex
Obese females of childbearing age are affected selectively by IIH.[1]
Specific numbers are available from the epidemiological studies.
Durcan et al[6] - Female-to-male ratio 8:1
Radhakrishnan[7] - Female-to-male ratio 8:1 (N = 9)
Radhakrishnan[7] - Female-to-male ratio 8:1 (N = 76)
Age
Please refer to the incidence statistics in Frequency. The highest incidence is among obese women of childbearing age. For most of the epidemiological series, this was women aged 15-44 years.
Headache that is nonspecific and varies in type, location, and frequency
Pulsatile tinnitus - A rhythmic sound, heard in one or both ears, with pulsing synchronous rhythm that may be exacerbated by the supine or bending position
Horizontal diplopia - A symptom of a false-localizing sixth cranial nerve palsy
Radicular pain (usually in the arms) - An uncommon symptom
Symptoms of papilledema
Transient visual obscurations (eg, dimming or blackout of vision in one or both eyes lasting for a few seconds) may be present. They may be predominantly or uniformly orthostatic (ie, after bending over).
Progressive loss of peripheral vision in one or both of the eyes may be noted, most often starting in the nasal inferior quadrant, followed by loss of central visual field (possibly affecting visual acuity) and, lastly, loss of color vision.
Blurring and distortion (ie, metamorphopsia) of central vision is caused by macular wrinkling and subretinal fluid spreading from the swollen optic disc.
Sudden visual loss is due to intraocular hemorrhage secondary to peripapillary subretinal neovascularization related to chronic papilledema.
Visual function testing, in particular, visual field, funduscopy, and ocular motility examination, are the most important parts of the neurologic examination for diagnosing and monitoring patients with idiopathic intracranial hypertension (IIH).
Papilledema
Peripapillary flame hemorrhages, venous engorgement, and hard exudates are features consistent with acute papilledema.
Telangiectatic vessels on the disc surface, optociliary shunt veins (which exit the disc at its margin), and optic disc pallor are associated with chronic papilledema, shown below.
View Image
Left optic disc with moderate chronic papilledema in a patient with pseudotumor cerebri. Paton lines (arc-shaped retinal wrinkles concentric with disc....
Visual fields
The first sign of incipient postpapilledema optic atrophy is constriction of the inferior nasal quadrant of the visual field with a border respecting the nasal horizontal midline (nasal step). This starts in the most peripheral points in the visual field (ie, 50 degrees from fixation) and progresses inward, depicted below.
View Image
Right optic disc with postpapilledema optic atrophy in a patient with pseudotumor cerebri. Diffuse pallor of the disc and absence of small arterial ve....
Goldmann-type dynamic perimetry is the best test, since it provides reliable information concerning the most peripheral parts of the visual field.
Computerized automated Humphrey-type static perimetry is generally unreliable beyond 30 degrees eccentricity and may not be as sensitive as dynamic perimetry for this problem.
Visual acuity: This is usually normal until significant peripheral visual field loss with progressive postpapilledema optic atrophy has occurred.
Color vision: This usually is tested in the office with color-confusion type plates, most commonly the Ishihara or Hardy-Rand-Rittler (HRR). Unlike visual acuity testing, it is not sensitive in picking up early postpapilledema optic atrophy, since color perception is concentrated in the central visual field.
Ocular motility
Occasionally limited abduction of one or both of the eyes results from increased ICP. This is termed false-localizing sixth cranial nerve palsy.
This usually can be observed as the patient follows the examiner's hand to the right and the left with both eyes. The involved eye does not move fully outward (ie, abduction), leaving some white sclera showing lateral to the cornea on the involved side compared to the other side. Speed of the abducting movement in the paretic eye also usually is slower than in the normal eye.
Some patients with full abduction still show some sclera; therefore, when using this sign demonstrating asymmetry between the eyes in abduction is important.
Diplopia testing is another way to detect even a low-grade sixth nerve paresis.
The patient is told to look at a focal light source (eg, penlight, Finnoff head), preferably placed more than 10 ft away. Either a red glass or a Maddox rod is placed in front of the patient's right eye. The Maddox rod creates an image of a vertical red line when the patient views a focal light source through it.
In a positive test for limited abduction, the red image (focal light or line) is displaced to the right of the light (homonymous or uncrossed diplopia) in the patient's view. This indicates that the visual axes are convergent with respect to one another (ie, esotropia, relative weakness of the lateral rectus muscle or muscles, sixth cranial nerve palsy).
Alternate cover testing also may reveal a slight corrective saccade when the other eye is covered in patients with sixth nerve palsies.
In 1994, Radhakrishnan et al reviewed the literature on IIH associated with other diseases and with drugs. These authors insisted that, to be included in the list of causally related associations, the following criteria should be met:[11]
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 following data were obtained from this 1994 study and subsequent case reports. The authors' organization of categories is preserved here.
Endocrine risk factors confirmed in epidemiological studies
Female sex
Reproductive age group
Menstrual irregularity
Obesity
Recent weight gain
Endocrine risk factors that meet minimal criteria, unconfirmed in case-controlled studies
Adrenal insufficiency
Cushing disease
Hypoparathyroidism
Hypothyroidism
Excessive thyroxine replacement in children (ie, low thyrotrophin levels)
Medication risk factors that meet minimal criteria, unconfirmed in case-controlled studies
All-trans -retinoic acid (ATRA) used in the treatment of promyelocytic leukemia, cyclosporine, levonorgestrel implant (Norplant; 39 women reported to US Food and Drug Administration [FDA] from February 1991-December 1993), pancreatin (pancreatic enzyme replacement for cystic fibrosis patients)
Recombinant human growth hormone (7 children in 3 papers)/natural growth hormone (somatotropin)
Vitamin A in infants
Miscellaneous risk factors that meet minimal criteria, unconfirmed in case-controlled studies
Chronic renal failure
Systemic lupus erythematosus
References cited for additions since 1994 include Rogers, 1999[13] ; Howell, 1998[14] ; Crock, 1998[15] ; Williams, 1997[16] ; Raghavan, 1997[17] ; Sacchi, 1997[18] ; Tanaka, 1997; Visani, 1996; Cruz, 1996; Querfeld, 1996; Blethen, 1996; Visani and Bontempo, 1996[19] ; Selleri, 1996[20] ; Ahmad, 1996[21] ; Varadi, 1995[22] ; Sivin, 1995[23] ; Baqui, 1995[24] ; Alder, 1995[25] ; Malozowski, 1995[26] ; Campos and Olitsky, 1995[27] ; Nasr and Schaffert, 1995[28] ; Wysowski and Green, 1995; and Price, 1995[29] .
Increased venous red blood cell aggregation and relatively elevated fibrinogen concentration were demonstrated in patients with IIH compared with matched controls.[30]
The retinol/retinol-binding protein ratio is elevated in the CSF of patients with IIH compared with non-IIH neurologic controls and with normal controls.[31]
Because IIH is concentrated in women between puberty and menopause, Fraser and colleagues emphasized the potential role of sex hormones in the pathogenesis of IIH. They also point out that obstructive sleep apnea has been proposed as a risk factor. Since women taking exogenous estrogen and pregnant women are not at particular risk for IIH, they suggest that low levels of testosterone may be the important hormonal link in women with IIH. The authors administered 2 standardized questionnaires embedded in a telephone interview of 24 men with IIH and 48 controls matched for gender, age, race and WHO BMI category. The questionnaires were 1) Androgen Deficiency in Aging Males (ADAM) and 2) Obstructive Sleep Apnea (OSA). They found that the men with IIH were significantly more likely than controls to have symptoms of testosterone deficiency and obstructive sleep apnea.[32]
Rule out systemic lupus erythematosus or other collagen-vascular disease, since these have been reported as underlying conditions in some patients who present with idiopathic intracranial hypertension (IIH).[33]
An increased incidence of anti-cardiolipin antibodies has been reported in patients with IIH. Some authors advocate anti-cardiolipin antibody assessment in IIH patients regardless of prior history of thrombosis.[34] Some authors advocate screening for anti-cardiolipin antibodies and other procoagulant states in all patients with IIH who are either male or nonobese.[35]
Cases of IIH associated with Lyme disease have been reported.[36]
Most patients with typical history, gender, and body habitus need only routine blood work, if any.
Full procoagulant profile including protein S, protein C, homocysteine levels, antithrombin III, factor V Leiden variant, anti-phospholipid/anti-cardiolipin antibodies, lupus anticoagulant, and platelet aggregation studies (in patients with previous history of thrombosis or MRI evidence of dural venous sinus occlusion)
Lyme screening test (enzyme-linked immunosorbent assay [ELISA]) in patients who have a history of exposure to Lyme in areas of endemic disease
CSF studies
Opening pressure
White blood cell and differential counts
Red blood cell count
Total protein
Quantitative protein electrophoresis
Glucose
Aerobic bacterial culture and sensitivity
Acid-fast bacilli (AFB) 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)
Most patients with typical history, gender, and body habitus need only routine CSF tests. However, extra fluid should be frozen in case the preliminary workup reveals unexpected abnormalities, such as pleocytosis or elevated gamma globulin, indicating that more complete investigation for autoimmune, infectious, or neoplastic conditions is warranted.
MRI: Brain MRI with gadolinium enhancement is probably the study of choice for all patients with IIH since it provides sensitive screening for hydrocephalus, intracerebral masses, meningeal infiltrative or inflammatory disease, and dural venous sinus thrombosis. In a retrospective study of imaging features that have been suggested as typical for patients with IIH, only flattening of the posterior globe was found statistically to be a reliable indicator of IIH, with a specificity of 100% and a sensitivity of 43.5%.[37]
MR venography: MR venography can be useful for patients who are at greater risk for dural venous sinus thrombosis, such as those with suspected thrombosis on MRI, nonobese or male individuals, or those with a documented procoagulant state. Sagittal T1-weighted images often provide excellent views of the superior sagittal sinus, and these typically are included in routine MRI. Extraluminal narrowing of the transverse sinuses may be a typical feature of IIH as reported by Farb and coworkers.[2]
CT scan: Brain CT scan is less expensive than MRI and is adequate to rule out larger tumors or lesions, but it is not as sensitive as MRI for meningeal infiltration and/or dural venous sinus thrombosis.
Ultrasonography: In the emergency department, bedside ultrasonography has been used to identify intracranial hypertension by measuring the diameter of the optic nerve sheath.[38]
Lumbar puncture ideally is carried out with the patient in the lateral decubitus position. Because finding landmarks is difficult in obese patients, the tap frequently is performed with the patient seated.
Remember that the normal CSF pressure at the foramen magnum in the seated position is nearly 500 mm water from the lumbar entry point in persons of average height.
Therefore, note that an opening pressure of 500 mm water is extremely high in the lateral decubitus position, but is normal for the sitting position. If possible, the patient should be moved to lateral decubitus position before measuring the pressure.
Another approach to lumbar puncture in obese patients utilizes fluoroscopic guidance in the radiology department. The prone positioning on the x-ray table and the increased abdominal pressure in this position may elevate the CSF pressure falsely.
If the pressure is normal with the patient in the prone position, then the measurement is probably accurate. However, if it is high, the patient must be rolled into lateral decubitus position and allowed to relax before a reliable pressure reading can be completed.
Obviously, such maneuvers carry a risk of displacing the needle from the thecal space. However, no alternative method exists for obtaining an accurate pressure reading.
Patients without visual loss most often are treated with a carbonic anhydrase inhibitor (eg, acetazolamide) to lower the intracranial pressure (ICP). The starting dose is typically brand name Diamox at 500 mg bid. Some authors believe digoxin has the same effect and is associated with fewer adverse effects.
In patients with severe symptoms, early visual field loss, or poor response to standard medical therapy, some clinicians utilize a short course of high-dose corticosteroids (eg, prednisone).
When new visual field loss is documented, medical management should be coupled with plans for emergency surgical intervention if the visual function continues to deteriorate or does not improve immediately with corticosteroid treatment.
For patients with idiopathic intracranial hypertension (IIH) who have progressive visual field loss, currently 2 general surgical approaches can be considered: CSF shunting procedures or optic nerve sheath fenestration.
Neurosurgical operations
Lumboperitoneal shunt is the traditional method for providing prompt reduction of ICP in patients with IIH.[39] However, this procedure has a high 1-year failure rate.
Some neurosurgeons prefer ventriculoperitoneal or ventriculoatrial shunts over lumboperitoneal shunting.
The reason for this preference is that ventricular shunts can be monitored for function using an extracranial subcutaneous compressible bulb and one-way valve (intracranial to abdominal flow) in series with the intracranial and abdominal ends of the shunt.
The bulb will resist digital compression if the distal (abdominal or atrial) end is obstructed.
The bulb will collapse under digital pressure but will fail to re-inflate if the intracranial end is obstructed.
Many neurosurgeons have been reluctant to place ventricular shunts in patients with IIH because the ventricles are small and difficult to cannulate without radiographic guidance. There are also a significant number of complications including infection, stroke, seizures, and shunt failure.
However, Woodworth and colleagues have recently shown that, using a stereotactic frame, they were uniformly able to place ventricular shunts even in slit ventricles in patients with IIH using a single pass in all patients, with good long-term viability.[40]
The ophthalmic surgical approach to managing patients with progressive vision loss and papilledema involves cutting slits or rectangular patches in the dura surrounding the optic nerve immediately behind the globe.[41]
This allows egress of CSF directly into the orbital fat where it is absorbed into the venous circulation.
Lumbar puncture following this procedure does not consistently show significant reduction of CSF pressure, and headache is not reliably relieved by this approach.
Despite general lack of an ICP-lowering effect, papilledema in both eyes may regress following fenestration of one optic nerve.
Visual function stabilizes or improves following optic nerve sheath decompression in most cases in the short run[42] , but in at least a third of cases, secondary visual decline may occur within 3-5 years and may require repeat surgery or an alternative treatment.[43]
A study of optic nerve sheath fenestration on 41 eyes from 21 patients with vision loss from either IIH or intracranial hypertension from cerebral venous thrombosis found best-corrected visual acuity and visual field stabilization or improvement in 32 of 34 eyes (94%) over a 3-month follow-up interval. Transient benign complications were apparent in 4 eyes. Only marginal improvement was shown in 4 eyes with no light perception vision; these were not analyzed with the remainder of the group.[44]
Comparison of shunt vs optic nerve sheath fenestration
Feldon[45] performed a meta-analysis of existing literature comparing visual outcomes after the following:
Visual worsening was rare for all procedures. The author concluded that visual outcome was best documented for optic nerve sheath fenestration and appeared to be the best surgical procedure for vision loss in IIH
Dural venous sinus stent
Following up on the work of Farb et al, Bussiere and coworkers studied 13 patients with IIH that was refractory to medical management who were found to have stenosis of 1 or both transverse dural sinuses on time-of-flight MR venography. Ten of these also had increased pressure gradient across the stenotic dural venous sinus (>10 mm Hg) and these underwent stent placement without significant complications. All 10 of these patients had complete headache resolution or significant improvement, and papilledema resolved completely or almost completely in 8 of them. The authors suggest only that a randomized controlled study of transverse dural venous sinus stenting in the management of IIH is needed to establish the safety and efficacy of the procedure in this setting.[46]
Arac and colleagues reported 1 case of endovascular stenting for IIH and reviewed the same published series as did Bussière et al, arriving at essentially the same conclusions. They also discuss Bateman’s recently proposed mathematical model of the relationship among intracranial arterial inflow, CSF pressure, and venous outflow.[47] (See Bateman above.)
Bariatric surgery for obesity in IIHP: Fridley et al reviewed the literature on bariatric surgery for obese patients with IIH. They found a total of 62 patients, of which 52 (92%) had resolution of the presenting symptoms. Of 35 patients who had postoperative fundoscopy, 34 had resolution of papilledema. Of 12 patients who had pre- and postoperative visual field examinations, 11 had resolution of visual field defects. Among 13 patients with pre- and postoperative cerebrospinal fluid pressure measurements, there was an average postoperative decrease of 254 mm H2 O. The authors call for prospective controlled studies to confirm the effectiveness of this surgery for IIH patients in long-term follow-up.[48]
Diagnosis and long-term management of patients with IIH requires the performance of lumbar puncture, typically performed by neurologists or internists, and careful monitoring of visual status (most importantly peripheral visual field and fundus photography). Vision examination and fundus photography are in the domain of ophthalmologists, and neuro-ophthalmologists are especially expert in examining visual fields. A team approach is, therefore, needed for most, if not all, patients.
Neurosurgical consultation is required for ventriculoperitoneal shunting when patients are losing visual field and medical management does not arrest or reverse the process promptly (within hours to days). Consultation with an Orbit/Plastic surgeon is required for optic nerve sheath fenestration for the same clinical indications.
On initial diagnosis, a weight-reduction diet coupled with an exercise program should be strongly advised to all patients with IIH. Some recent evidence suggests that weight loss is associated with improvement of papilledema in these patients.[49, 50] Often, a formal weight-loss program is required.
Specific therapy for idiopathic intracranial hypertension (IIH) is aimed at lowering intracranial pressure (ICP) pharmacologically. Carbonic anhydrase inhibitors and other diuretics are thought to have their effect on ICP by reducing cerebral spinal fluid (CSF) production at the choroid plexus. Cardiac glycosides have a similar effect. Corticosteroids are effective in reducing ICP. However, the mechanism of action is unknown. Corticosteroids are often used as maximum medical management when rapid lowering of ICP is required.
Clinical Context:
Reduces CSF production by about 50% (Maren, 1972; McCarthy and Reed, 1974) and lowers ICP. Commonly achieves long-lasting control of transient visual obscurations (TVO), headache, and diplopia, all of which are manifestations of intracranial hypertension, even though papilledema does not resolve completely. Effect on ICP has been shown to be unsustained (Plum and Siesio, 1975), and many patients develop adverse effects severe enough to hinder compliance.
Some clinicians prefer Sequels formulation of Diamox, which may be better tolerated than standard version.
Few patients tolerate more than 2 g/d, but 4 g/d may be required to produce measurable pressure-lowering effect (Gucer and Viernstein, 1978); treatment usually initiated at 1 g/d and increased to 2 g/d if symptoms are not controlled and adverse effects are not severe; treatment with Diamox alone not appropriate for patients who are experiencing progressive visual field loss.
Clinical Context:
Present in high concentration in choroid plexuses of patients taking standard cardiac doses (Bertler, 1973), has been shown to reduce CSF production by as much as 78% in humans (Neblett, 1972), probably by inhibiting Na-K-ATPase pump (Vates, 1963). Only one report in which a patient with IIH was treated with digoxin, but patient was asymptomatic, so not known whether symptoms would have been controlled (Schott and Holt, 1974).
Clinical Context:
Mechanism of action by which corticosteroids lower CSF pressure unknown. Some believe that may facilitate outflow at arachnoid granulations.
Even for initial diagnosis, most patients do not require inpatient care, as lumbar puncture usually is performed in the ambulatory care setting.
An occasional patient may develop intractable low-tension headache following lumbar puncture and may require a short hospital stay for intravenous (IV) hydration and analgesic management.
A blood patch (by an anesthesiologist) sometimes is indicated if the post-lumbar puncture headache does not subside spontaneously within a few days.
Admission for surgical management of increased ICP
Patients who complain of progressive visual loss (typically constriction of peripheral vision and/or dimming of vision in one or both eyes) and have documented new visual field loss may respond to high-dose corticosteroids; they should be admitted to the hospital with daily monitoring of visual function.
If the visual field worsens or does not recover promptly (ie, within 24-48 h) with corticosteroids, then emergency CSF shunting (lumboperitoneal or ventriculoperitoneal/atrial) or optic nerve sheath fenestration should be carried out.
If any delay in implementing surgical decompression of the failing optic nerve is anticipated, then the patient should be moved to the ICU or a "step-down" unit for lumbar CSF drainage until the definitive procedure can be performed. Another short-term treatment option is IV mannitol, but definitive pressure-lowering surgery must be done within 2-3 days.
A very small number of patients with normal visual fields may require surgical relief of CSF pressure because of intractable headache. Optic nerve sheath fenestration does not provide reliable CSF pressure normalization or headache relief, and thus these patients require one of the shunting procedures outlined in Surgical Care. Since patients with pseudotumor cerebri frequently have other types of headaches, the decision to choose ventriculoperitoneal shunting over optic nerve sheath fenestration should not be made on the basis of headache alone.
Patients with normal visual field or stable minor field loss (inferonasal step with little concentric constriction of isopters) can be managed with office visits approximately every 3 months.
The interval between visits should be shortened if the patient has any questionable symptoms of vision worsening or if visual field examination reveals a minor or questionably significant new deficit.
Acetazolamide: Most patients have adequate relief of symptoms, typically headache, using this first-line agent. Patients typically respond and tolerate brand name Diamox better than the generic form, acetazolamide. Please note that many physicians start patients on 250 mg bid, which is considered too small of a dose — 500 mg bid is the beginning dosage in this condition in adults.
Headache prophylaxis
For patients with stable visual function but inadequate headache relief with first-line pressure-lowering drugs, treatment with primary headache prophylaxis should be considered.
Patients with IIH and headaches with many features of migraine have been encountered. Headaches often can be controlled with amitriptyline, propranolol (Inderal), or any of the other commonly prescribed migraine prophylaxis agents. Topiramate is also an excellent choice since one of its side effects is weight loss, a common association in pseudotumor cerebri, which can help put the disease in remission.
Corticosteroids/digoxin/furosemide
Patients experiencing progressive loss of visual field in one or both eyes should be placed immediately on a high dose (60-100 mg/d) of oral prednisone (or equivalent corticosteroid treatment). Digoxin and furosemide (Lasix) have been advocated by some investigators, but these are on the same effectiveness level as acetazolamide and are not appropriate as sole therapy for patients who are losing vision.
If a moderately severe new visual field loss is detected on a routine office visit and the patient is not experiencing progressive symptoms, outpatient management can continue. However, visual fields should be measured every few days or at 1- to 2-week intervals depending on the magnitude and progression of the defect. If the visual field continues to worsen on corticosteroid treatment, the patient should be admitted for immediate surgical management.
If the patient presents with symptomatic deterioration of vision, and the examination documents worsening of visual field despite adequate standard medical therapy, the patient should be started immediately on corticosteroids as previously outlined.
The patient also should be admitted to the hospital for consideration of emergency surgical decompression.
Visual field examination should be performed daily, and surgical decompression should be carried out if no improvement or further worsening is noted in the subsequent 24-48 hours.
The only severe and permanent complication of IIH is progressive blindness from postpapilledema optic atrophy.
As optic nerve axons die, the apparent degree of papilledema may diminish, giving a false sense of improvement. For this reason (and others), the patients must be monitored with frequent visual field examinations.
The earliest visual loss is in the peripheral fields (outside 30 degrees) and thus Goldmann-type dynamic perimetry is preferred over computerized, automated visual fields.
For reasons that are not clear, the earliest field loss tends to be in the inferior nasal quadrant.
Visual acuity and color vision are not affected until late in the disease, when the peripheral visual field isopters are quite contracted.
Depending on the referral population and the rigor with which visual function is tested, the prognosis for visual 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, more recently that figure has been revised upward.
In a unique 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, while 92% had abnormal findings on automated perimetry; 50% had abnormal contrast sensitivity and 22% abnormal Snellen visual acuity. During follow-up (2-39 mo, average 12.4 mo), visual fields improved in 60% of patients and deteriorated in 10%.[51]
The University of Iowa observed 20 patients with IIH for more than 10 years. Their studies indicated that 11 had followed a stable course without change in visual field or papilledema and 9 worsened after a stable course for an interval. In 6 out of the 9, the worsening occurred late (28-135 mo after initial presentation) and 3 of the 9 had recurrence after resolution of papilledema that occurred from 12-78 months after initial resolution of papilledema.[52]
Left optic disc with moderate chronic papilledema in a patient with pseudotumor cerebri. Paton lines (arc-shaped retinal wrinkles concentric with disc margin) are seen along the temporal side of the inferior pole of the disc.
Right optic disc with postpapilledema optic atrophy in a patient with pseudotumor cerebri. Diffuse pallor of the disc and absence of small arterial vessels on the surface are noted, with very little disc elevation. The disc margin at the upper and lower poles and nasally is obscured by some residual edema in the nerve fiber layer and gliosis that often persists even after all the edema has resolved.
The most common early visual field defect in papilledema as the optic nerve develops optic atrophy is an inferior nasal defect as shown in the left eye field chart (left side of figure). The shaded area indicates the defective portion of the field. Note the sharp line of demarcation between defective lower nasal quadrant and normal upper nasal quadrant along the horizontal midline. This is characteristic of early papilledema optic atrophy and is called a nasal step or inferonasal step.
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