Papilledema and idiopathic intracranial hypertension.

Review Article

Papilledema and Idiopathic Intracranial Hypertension Deborah I. Friedman, MD, MPH, FAAN ABSTRACT Purpose of Review: Papilledema is one of the most concerning physical examination findings in neurology: it has a broad differential diagnosis of intracranial (and occasionally spinal) pathology associated with increased intracranial pressure. Papilledema impairs axoplasmic flow within the optic nerves and compresses the optic nerves externally; it may lead to profound visual loss. Thus, detection of papilledema and assessment of visual function are essential to patient management. This article reviews the treatment of papilledema-related visual loss in pseudotumor cerebri syndrome, one of the most common causes of papilledema encountered by neurologists. Recent Findings: Results from the Idiopathic Intracranial Hypertension Trial (IIHTT), the first randomized, double-masked, placebo-controlled trial for the treatment of patients with mild visual loss from idiopathic intracranial hypertension, were published in April 2014. The IIHTT provides the first evidence-based treatment recommendations, showing the benefit of acetazolamide and weight loss for improving visual status in patients with mild visual field loss from idiopathic intracranial hypertension. Summary: A detailed ophthalmic examination, including perimetry, is critical to the evaluation, treatment, and assessment of treatment response in patients with papilledema. Continuum (Minneap Minn) 2014;20(4):857–876.

INTRODUCTION Disc edema may accompany visual loss from disorders originating in the optic nerves and is sometimes accompanied by edema in the macular region and papillomacular bundle (eg, neuroretinitis). The term papilledema is reserved for optic nerve swelling caused by increased intracranial pressure. The dilemma facing the clinician is determining whether optic disc swelling results from an intracranial process or a local optic neuropathy. General features suggest one scenario or the other (Table 4-1), but the disc’s appearance is quite similar in both circumstances. Disorders producing papilledema often cause other neurologic symptoms external to the visual system. Optic disc elevation, retinal hemorrhages, Continuum (Minneap Minn) 2014;20(4):857–876

exudates, and macular edema may be present in disc edema due to either an intracranial process or a local optic neuropathy. Therefore, although neurologists may have clinical suspicions about the origin of optic disc swelling in a particular patient based on the patient’s history and examination, clinical evaluation alone is insufficient to distinguish (with certainty) papilledema from disc edema arising from a local optic neuropathy.

Address correspondence to Dr Deborah I. Friedman, Departments of Neurology and Neurotherapeutics and Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC 9036, Dallas, TX 75390, Deborah.Friedman@ utsouthwestern.edu. Relationship Disclosure: Dr Friedman’s institution receives grants from electroCore Medical LLC, Merck & Co, Inc, and the National Eye Institute, and her institution has received compensation for her speaking activities from Allergan, Inc. Dr Friedman has served as an expert witness regarding pseudotumor cerebri syndrome for various legal firms, on the board of the American Headache Society, on the editorial board of Neurology Reviews, and as a consultant for Zogenix, Inc. She has received personal compensation for the development of educational programs from the AAN and for manuscript preparation from MedLink Neurology. Unlabeled Use of Products/Investigational Use Disclosure: Dr Friedman discusses the unlabeled use of acetazolamide for the treatment of papilledema in idiopathic intracranial hypertension. * 2014, American Academy of Neurology.

DIAGNOSIS The ophthalmoscopic examination is key to diagnosing papilledema; neurologists generally use a handheld direct ophthalmoscope to examine a patient’s undilated pupil. To employ the technique successfully, the neurologist must have had www.ContinuumJournal.com

Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

857

Papilledema KEY POINTS

h The term papilledema refers to optic nerve head swelling from increased intracranial pressure. The term optic disc edema suggests other causes of optic disc swelling or uncertainty regarding the cause.

TABLE 4-1 Optic Disc Edema Versus Papilledema

h The keys to performing direct ophthalmoscopy are frequent practice and holding the ophthalmoscope close to the patient’s eye. The pupil is like a keyhole; the ophthalmoscope should be 0.5 inch to 1 inch away from the cornea.

h The temporal margin of the optic disc should normally be sharply demarcated from the surrounding retina.

Clinical Features

Optic Disc Edema

Papilledema

Laterality

Unilateral 9 bilateral

Usually bilateral but may be asymmetric

Early central visual loss (visual acuity impaired)

Common

Uncommon

Typical visual field defect

Central or paracentral scotoma, arcuate or altitudinal defect

Enlarged physiologic blind spot, arcuate defect, nasal step, inferotemporal loss, concentric constriction

Spontaneous venous pulsations

May be present

Absent

Afferent pupillary defect

Present if unilateral or asymmetric visual loss

Usually absent unless asymmetric visual loss

Disc leakage on fluorescein angiogram

May be present

Yes

Associated symptoms

Pain on eye movement, other symptoms specific to etiology (eg, giant cell arteritis)

Headache, diplopia, photophobia, nausea, vomiting, meningismus, and other neurologic symptoms if space occupying lesion is present; occasionally asymptomatic

considerable practice and the patient must be cooperative and able to steadily fixate his or her gaze. The most frequent cause of a poor view during ophthalmoscopy is too much distance between the examiner and the patient’s eye.1 Because the examiner sees the image in two dimensions, it may be difficult to appreciate the depth of a swollen optic nerve and subtle disc edema may be unapparent. Also, the limited field of view with direct ophthalmoscopy hinders the detection of macular edema, hemorrhages, and exudates in the posterior pole. Some examiners prefer the wide-angle handheld ophthalmoscope (PanOptic), which provides a wider field of view and greater magnification of the fundus than the standard direct ophthalmoscope. Because more retinal fibers enter the nerve on the nasal side (representing

858

the larger temporal visual field), the nasal aspect of the optic disc is physiologically elevated relative to the rest of the nerve. The temporal border of the optic nerve should always appear distinct and even with the surrounding retina. The color of the optic nerve varies from person to person; a reddish color may not indicate true hyperemia caused by increased vascularity of the nerve. Spontaneous retinal venous pulsations are caused by a pressure gradient along the retinal veins owing to a difference in the pulse pressure between the intraocular and intracranial spaces.2 They produce subtle narrowing and expansion of one or more retinal veins, are most optimally viewed through a dilated pupil and via a direct ophthalmoscope, and are seen over the disc near the exit of the retinal veins

www.ContinuumJournal.com


August 2014

from the eye. Spontaneous venous pulsations are present in about 90% of healthy individuals and indicate that the intracranial pressure is below about 190 mm CSF at the time of observation. Thus, their absence does not absolutely indicate increased intracranial pressure but their presence is generally reassuring. Ophthalmologists are better able to detect subtle papilledema with binocular viewing of the ocular fundus using an indirect ophthalmoscope or slit-lamp biomicroscopy because both methods allow depth perspective. Fluorescein angiography generally shows leakage of dye and early or late disc fluorescence when papilledema is present. Stereoscopic disc photographs are helpful in diagnosis as well as for monitoring of the disc appearance. Optical coherence tomography can reveal increased peripapillary and perimacular retinal nerve fiber layer thickness, but these retinal nerve fibers may also be abnormal with optic disc drusen.3 Assessment of the patient’s visual status is imperative.1 In emergent circumstances, neurologists are frequently relied upon to conduct visual examinations in the office or at the bedside. Visual acuity is recorded from each eye separately using the patient’s refractive correction (eg, contact lenses, eyeglasses). Distance acuity using a wall chart is preferred, but near acuity is acceptable if a distance chart is unavailable. The instructions on the near card should be followed, and the patient encouraged to read the smallest letters or numbers possible. Allowing the patient to ‘‘guess’’ often yields another line of acuity. Comparison of light brightness and red perception between the two eyes may provide additional evidence of an optic neuropathy. The pupils are often normal in papilledema, but an asymmetry in pupillary reactivity indicates an asymmetric optic neuropathy. Continuum (Minneap Minn) 2014;20(4):857–876

Automated perimetry, the preferred method for assessing the visual field, is very sensitive to early changes from papilledema and should be obtained whenever possible. The central visual field may be screened at the bedside using an Amsler grid, which looks like graph paper with a central fixation spot. The clinician asks the patient to look at the center dot with each eye and indicate whether he or she can see the entire grid, whether any parts are missing, and whether all the lines appear to be straight. Report of broken or wavy lines may indicate extension of severe papilledema into the macula. Confrontation visual fields are assessed on one eye at a time. Papilledema is one of the few causes of physiologic visual field constriction. Functional (ie, nonphysiologic) visual field loss occasionally occurs in patients with papilledema and produces visual field constriction.4 It is important to recognize functional visual loss to avoid unnecessary medication changes or surgery in such patients. Physiologic visual field loss produces a constricted field that expands at a distance. If the examiner backs up several feet and retests the peripheral field, it should enlarge. Patients with functional visual loss often frame the examiner’s face or report seeing the examiner’s hand only when it is directly in front of their own eye. The field does not expand at a distance; the frame still outlines the examiner’s face. Increased intracranial pressure may produce diplopia, most frequently from a unilateral or bilateral abducens palsy. Neuroimaging should be performed if a clinical suspicion of papilledema is present; in addition to pinpointing an obvious cause (eg, a mass producing hydrocephalus), neuroimaging should help to identify meningeal enhancement suggesting infection, inflammation, meningeal infiltration of tumor, or sarcoidosis.

KEY POINTS

h The absence of spontaneous venous pulsations in the fundus does not absolutely indicate increased intracranial pressure, but their presence is reassuring. They are best viewed over the disc, and it takes practice to see them.

h Allowing the patient to guess on the visual acuity chart often yields another line of acuity.

h Perimetry is the most important visual assessment in a patient with papilledema. Confrontation visual fields are insensitive for early visual field loss.

h It is important to recognize functional visual loss in patients with papilledema to avoid unnecessary medication changes or surgery.



859


h The subtle signs of pseudotumor cerebri syndrome include an empty sella, cerebellar tonsil ectopia, distended or tortuous optic sheath subarachnoid space, flattening of the posterior sclera, and protrusion of the optic nerve papilla into the vitreous. These signs tend to be underreported in clinical practice.

h An elevated lumbar puncture opening pressure is required for the diagnosis of pseudotumor cerebri syndrome; however, the syndrome is a constellation of symptoms and signs and is not solely based on the CSF opening pressure.

Thrombosis of the cerebral veins or internal jugular vein obstruction may also produce increased intracranial pressure and papilledema. Imaging findings in the absence of a mass or abnormal enhancement, such as in pseudotumor cerebri syndrome, include an empty sella, cerebellar tonsillar descent, flattening of the posterior sclerae, and distention of the perioptic subarachnoid space producing enlarged or tortuous optic nerves.5 Sometimes the papilledema is seen on the axial or sagittal images because the optic nerve papillae protrudes into the posterior vitreous. The confirmatory test is a lumbar puncture that should follow neuroimaging to avoid a situation that might produce herniation. Abnormal values are greater than 280 mm of CSF in children and greater than 250 mm of CSF in adults and in children of normal weight who are not sedated.6,7 Note that CSF pressure fluctuates constantly and false elevations or misleading normal values occasionally occur. The patient must be in the lateral decubitus position for the most accurate reading; if in the prone position, the base of the manometer must be aligned with the right atrium. Readings taken with the patient in the sitting position are invalid. Medications, Valsalva maneuvers, and conscious sedation with resulting hypoventilation and hypercapnia may all influence the opening pressure.8 Differential Diagnosis 1: Real Papilledema or Pseudopapilledema? Not all optic disc swelling is papilledema. Local optic neuropathies may produce optic disc edema. There are also conditions that simulate papilledema, which may present a diagnostic challenge to even the most experienced clinicians. Optic disc drusen are calcified deposits that often present in the second and

860

third decades.9 They are usually not associated with ophthalmic or systemic disease and are often discovered during a routine eye examination. Superficial drusen are generally round and yellowwhite in color, and cause an area of local elevation or a lumpy optic disc appearance (Figure 4-1). Deep or buried drusen are difficult to distinguish from true disc edema. Also, disc edema and drusen may coexist in the same patient. A study using optic disc photography found that superficial drusen are more likely than buried drusen to produce blurred edges, raised lesions, absent physiologic cup, altered optic disc contour, absent spontaneous venous pulsations, anomalous vascular branching pattern, cilioretinal vessels (arterioles arising from the temporal disc in a hooklike fashion and often coursing toward the macula), and peripapillary atrophy.9 Comparing eyes with papilledema to eyes with buried drusen, papilledema is more likely to produce blurred edges, disc elevation, lack of a physiologic cup, altered contour, and hemorrhages. The hemorrhages in papilledema generally follow the nerve fiber bundles and are flamelike, whereas drusen may produce

FIGURE 4-1

Optic disc drusen. Numerous superficial optic disc drusen causing a ‘‘lumpy-bumpy’’ optic nerve head. Courtesy of Wayne T. Cornblath, MD, FAAN.



August 2014

circumferential hemorrhage. Buried drusen are more likely than papilledema to cause an anomalous branching pattern and peripapillary atrophy. Autofluoresence (ie, a bright appearance when viewed with fundus camera settings used for fluorescein angiography prior to the administration of fluorescein dye) is frequently present with superficial drusen but often absent with buried drusen.10 Drusen can generally be confirmed with B-scan orbital ultrasonography or a CT scan of the orbits. A pediatric study found that only 25% of 12 children with pseudopapilledema had spontaneous venous pulsations compared with 75% of control subjects with normalappearing optic nerves.11 Fluorescein angiography demonstrates no early staining or early nodular staining with drusen, in contrast to early diffuse leakage with papilledema. Buried drusen often show late peripapillary staining that is either nodular or, most commonly, circumferential, or both. Papilledema produces early and late fluorescein leakage from the disc. Tilted optic discs are a congenital anatomic variant whereby the optic nerve enters the eye at an oblique angle and is rotated on the anterior-posterior axis (Figure 4-2).12 Tilted discs are frequently bilateral and appear as an exaggerated oval or D-shaped disc with one hemisphere of the disc more elevated than the contralateral half. The most common variant is an elevated superotemporal disc and flattened inferonasal disc, although the axis of tilt is variable. Peripapillary atrophy and situs inversus of the retinal vessels (vessels that exit nasally before turning temporally) are present in about 70% of tilted discs. Myopia, astigmatism, and visual field defects (particularly superotemporal visual field loss) are common. Infiltrative optic neuropathies from malignancy, infection, or inflammation Continuum (Minneap Minn) 2014;20(4):857–876

KEY POINT

h With tilted optic discs, myopia, astigmatism, and visual field defects (particularly superotemporal visual field loss) are common.

Tilted optic disc. The right optic disc is tilted such that the nasal disc is elevated relative to the temporal aspect of the disc, simulating nasal disc edema. The temporal optic disc appears truncated. Peripapillary atrophy temporally is present, giving the false impression that the disc is larger than it actually is.

FIGURE 4-2

may simulate true papilledema. Because malignant hypertension may produce bilateral optic disc edema that is often accompanied by vascular narrowing and other retinal abnormalities, such as nerve fiber layer hemorrhages, cottonwool spots, or macular edema, blood pressure should always be measured in patients with bilateral disc edema. Differential Diagnosis 2: Real Tumor or Pseudotumor? The most common initial symptoms of intracranial hypertension are headaches, nausea, vomiting, photophobia, and diplopia.13 Headache alone is an uncommon manifestation of a brain tumor.14 Mass lesions and tumors that are associated with hydrocephalus may also produce ataxia, focal neurologic deficits reflecting the location of the tumor, personality changes, and altered sensorium. There is no ventriculomegaly in the pseudotumor cerebri syndrome, which is often accompanied by transient visual obscurations, pulsatile tinnitus, neck or back pain, and radicular pain; the sensorium is normal. Visual loss may occur with either scenario. Superior sagittal sinus www.ContinuumJournal.com


861


h The preferred nonemergent neuroimaging test for patients with papilledema is MRI. A contrast-enhanced MRI and venous imaging may also be needed, depending on the clinical situation. Orbital imaging with contrast is helpful for suspected infectious or inflammatory (optic neuritis) conditions.

h Either papilledema or an abducens palsy is required for a definite diagnosis of the pseudotumor cerebri syndrome; an elevated lumbar puncture opening pressure alone is not adequate to make a definite diagnosis.

h The pseudotumor cerebri syndrome is one of just a few conditions causing true generalized visual field constriction resulting from retinal nerve fiber layer disruption.

h Nonphysiologic visual field loss may also occur in pseudotumor cerebri syndrome, causing an identical pattern of visual field loss. Consider a nonphysiologic component when other examination findings (eg, optic nerve appearance) are disproportionate to the degree of visual field loss claimed. Automated perimetry often shows square or cloverleaf patterns of preserved vision in such cases.

862

thrombosis may mimic the clinical presentation of pseudotumor cerebri syndrome, but extensive thrombosis typically produces seizures and focal neurologic deficits. Meningeal processes such as inflammatory conditions, infections, gliomatosis cerebri, and carcinomatosis are also in the differential diagnosis; systemic symptoms and signs, such as fever, weight loss, meningismus, cognitive dysfunction, and an altered sensorium, may be present in such cases. Evaluation of a patient with papilledema includes neuroimaging, preferably MRI of the brain. Contrast administration is needed to detect and define tumors and meningeal processes. Changes from venous sinus thrombosis are frequently seen on MRI, but magnetic resonance venography or CT venography demonstrate the location and extent of the thrombosis. If the patient is unable to have an MRI, contrast-enhanced CT should be performed. If no mass lesion or hydrocephalus is present, the next step in evaluation is a lumbar puncture with measurement of the opening pressure, glucose, protein, and cell count. Other spinal fluid studies need to be obtained depending on the clinical circumstance, such as appropriate tests for suspected infection or inflammatory conditions and cytology or tumor markers. Pseudotumor Cerebri Syndrome and Idiopathic Intracranial Hypertension Intracranial hypertension without ventriculomegaly, mass lesion, or evidence of infection characterize the pseudotumor cerebri syndrome.15 The diagnostic criteria for the pseudotumor cerebri syndrome are listed in Table 4-2 and require the presence of papilledema or an abducens palsy for a definite diagnosis.16 There are many conditions and medications associated with the pseudotumor cerebri syndrome, but the idiopathic form, idiopathic intracranial

hypertension, is most commonly encountered in practice. Idiopathic intracranial hypertension generally affects obese women of childbearing age. The visual manifestations of idiopathic intracranial hypertension and the pseudotumor cerebri syndrome from a secondary cause are similar. The earliest visual symptom of idiopathic intracranial hypertension is transient visual obscurations, which are episodes of visual blackout or dimming lasting seconds to minutes in one or both eyes. The episodes are characteristically provoked by arising after bending over or from eye movement; vision returns to baseline after each episode, and episodes may occur many times daily. They indicate the presence of papilledema and do not predict visual function. Although not exclusive to idiopathic intracranial hypertension or the pseudotumor cerebri syndrome, transient visual obscurations are rarely reported in patients with hydrocephalus or brain tumors, although they may occur with optic disc drusen. Patients with idiopathic intracranial hypertension sometimes become aware of their physiologic blind spot as it enlarges. As the blind spot, normally located 10 to 15 degrees temporal to fixation, enlarges toward fixation it obscures parts of text or images. Patients often report temporal expansion of the blind spot as seeing ‘‘something moving in my peripheral vision,’’ but redirection of the gaze toward the object reveals nothing amiss. The arcuate bundles of the retinal nerve fiber layer are often affected, causing peripheral field loss. Patients with progressive visual loss, secondary optic nerve ischemia, or fulminant idiopathic intracranial hypertension develop central visual loss early and report blurred, dim, or hazy vision. Binocular diplopia may also occur, usually with images displaced horizontally, reflecting a unilateral or bilateral abducens palsy. To assess binocular



August 2014

a TABLE 4-2 Diagnostic Criteria for Pseudotumor Cerebri Syndrome

A diagnosis of pseudotumor cerebri syndrome is ‘‘definite’’ if the patient fulfills criteria AYE. The diagnosis is considered ‘‘probable’’ if criteria AYD are met but the measured CSF pressure is lower than specified for a ‘‘definite’’ diagnosis. b Required for diagnosis of pseudotumor cerebri syndrome A. Papilledema B. Normal neurologic examination except for cranial nerve abnormalities C. Neuroimaging: Normal brain parenchyma without evidence of hydrocephalus, mass, or structural lesion and no abnormal meningeal enhancement on MRI, with and without gadolinium, for typical patients (female and obese), and MRI, with and without gadolinium, and MR venography for others. If MRI is unavailable or contraindicated, contrast-enhanced CT may be used. D. Normal CSF composition E. Elevated lumbar puncture opening pressure (Q250 mm CSF in adults and Q280 mm CSF in children [250 mm CSF if the child is not sedated and not obese]) in a properly performed lumbar puncture. b Diagnosis of pseudotumor cerebri syndrome without papilledema In the absence of papilledema, a diagnosis of ‘‘probable’’ pseudotumor cerebri syndrome can be made if BYE from above are satisfied and, in addition, the patient has a unilateral or bilateral abducens nerve palsy. In the absence of papilledema or sixth nerve palsy, a diagnosis of pseudotumor cerebri syndrome can be ‘‘suggested,’’ but not made, if BYE from above are satisfied and, in addition, at least three of the following neuroimaging criteria are satisfied. Empty sella Flattening of the posterior aspect of the globe Distention of the perioptic subarachnoid space with or without a tortuous optic nerve Transverse venous sinus stenosis CSF = cerebrospinal fluid; MRI = magnetic resonance imaging; MR = magnetic resonance; CT = computed tomography. a Reprinted with permission from Friedman DI et al, Neurology.16 B 2013 American Academy of Neurology. www.neurology.org/ content/81/13/1159.abstract?sid=640c2896-fc9a-4419-a0b3-68c323d41750.

diplopia, the clinician can ask a patient what happens to his or her double vision when either eye is covered.17 True binocular diplopia, resulting from ocular misalignment, resolves if either eye is covered. Diplopia from an abducens palsy is worse at distance than at near; an observant patient may note that the images are uncrossed (ie, the right eye sees the image on the right and the left eye see the image on the left). Vertical diplopia occasionally occurs. Photosensitivity is common, perhaps a manifestation of the headache. Massive papilledema produces retinal edema and may lead to central vision loss or metamorphopsia (distorted images) if the macula is involved. Many patients, particularly those with headache, report Continuum (Minneap Minn) 2014;20(4):857–876

ocular, periocular, or retroocular pain, and, occasionally, pain with eye movement. Pulsatile tinnitus occurs in about 50% of patients. The examination reveals normal or near-normal visual acuity in many cases; the expected normal Snellen acuity should be 20/15 to 20/20 in the patient cohort that is typically affected by idiopathic intracranial hypertension. Decreased central acuity represents optic neuropathy, macular edema, or a combination of both. The pupils are equal in size. Idiopathic intracranial hypertension usually affects both optic nerves fairly symmetrically, so the finding of a relative afferent pupillary defect generally indicates that there has been substantial visual loss in the ipsilateral eye www.ContinuumJournal.com


863

Papilledema KEY POINT

h The most important features of papilledema on direct ophthalmoscopy are a peripapillary halo, elevation of the disc, and lack of continuity of the vessels over the disc and crossing the disc margin. Hemorrhages and exudates, although dramatic in appearance, are not helpful in grading the severity of papilledema. Subtle or early papilledema is best viewed stereoscopically.

that may require surgical intervention. Patients with marked bilateral visual loss exhibit large, poorly reactive pupils. Perimetry reveals enlargement of the blind spot, indicative of an enlarged optic nerve head from the papilledema (Figure 4-3). Other common visual field defects include a generalized reduction in retinal sensitivity, arcuate defects, nasal step, paracentral scotomata, generalized field constriction, and central scotomata (Figure 4-4, Figure 4-5, and Figure 4-6). Some of these defects can be detected at the bedside, but the importance of quantitative visual field assessment cannot be overemphasized. Ocular motility examination may reveal an esotropia with a unilateral or bilateral abducens nerve palsy. Involvement of the oculomotor or trochlear nerves is unusual. Generalized ophthalmoplegia suggests a secondary cause of pseudotumor cerebri syndrome or ´ syndrome. coexisting Guillain-Barre Papilledema is graded using the ń scale (Table 4-3).18 Signs of early Frise

FIGURE 4-3

864

(grade 1 to 2) papilledema include an incomplete, dark peripapillary halo and elevation of the optic disc. Moderate (grade 3) papilledema results in a complete peripapillary halo, obscuration of major vessels crossing the disc, and diffuse nerve head elevation. With severe papilledema (grades 4 to 5), two or more major vessels crossing the disc are obscured, vessels on the optic nerve head are not visible beneath the swollen retinal nerve fiber layer, and the optic cup is obliterated (Figure 4-7). Hemorrhages, exudates, and retinal edema may be present in acute to subacute papilledema but are not factors that determine severity. Retinal edema produces a ‘‘high water mark’’ of circumferential choroidal folds (Figure 4-8). Chronic papilledema is generally devoid of hemorrhages or exudates (Figure 4-9). Resolution of papilledema occurs in one of two circumstances: either the process has truly improved or the optic nerve axons have been damaged, preventing axoplasmic flow.

Automated perimetry of the central 24 degrees of visual field in the right eye. A, The gray tone depiction of the visual field shows enlargement of the physiologic blind spot. B, The pattern deviation plot, which compares the patient’s responses to aged-matched normal values, confirms the high probability that the blind spot is enlarged. The blind spot is depicted as a blank area and the dark boxes surrounding that area are abnormal.



August 2014

FIGURE 4-4

Inferior nasal step in the left eye. A, The gray tone depiction of the visual field shows enlargement of the physiologic blind spot and an inferonasal step, respecting the nasal horizontal meridian. B, The dark boxes on the pattern deviation plot confirm the defect. The step corresponds to the horizontal raphe of the retina that separates the fibers from the superior and inferior nerve fiber bundles.

Thus, ‘‘improvement’’ of papilledema is not always a good sign. Atrophic optic nerves do not swell, even in the face of recurrent intracranial hypertension. Conversely, loss of normal nerve fiber layer elasticity with scarring may prevent

FIGURE 4-5

resolution of papilledema with correction of the intracranial hypertension and should not be confused with persistent disease. Postpapilledema atrophy produces ‘‘dirty’’ or ‘‘secondary’’ optic atrophy with an indistinct appearance of the

Superior arcuate defect in the left eye. A, The gray tone depiction of the visual field shows enlargement of the physiologic blind spot and superior arcuate, extending from the physiologic blind spot to the nasal horizontal meridian. B, The pattern deviation plot confirms the arcuate nature of the defect that represents interruption of axons in the inferior retinal nerve fiber bundle.

Continuum (Minneap Minn) 2014;20(4):857–876



865

Papilledema

FIGURE 4-6

Diffuse depression. The gray scale (B) looks normal, but the total deviation plot (A) reveals a generalized reduction in retinal sensitivity. All but a few of the abnormal points resolve on pattern deviation plot (C). This type of abnormality may occur with diffuse retinal and optic nerve problems, as well as uncorrected refractive errors.

a TABLE 4-3 Friseń Papilledema Grading Scale

Stage

Severity

Description

0

Normal

Blurring of nasal and temporal disc borders by overlying nerve fiber bundles in inverse proportion to the disc diameter.

1

Early

Excessive blurring of the nasal disc border relative to the disc diameter, normal temporal margin, subtle circumferential grayish halo with a temporal gap.

2

Early

Elevation of the nasal circumference and blurring of the temporal margin with a complete circumferential halo. Choroidal folds may be present.

3

Moderate

Increased optic nerve head diameter. Elevated borders totally obscure one or more segments of the major retinal vessels. Circumferential halo has an irregular outer fringe with fingerlike extension.

4

Severe

Elevation of the entire nerve head with obliteration of the optic cup, compression of the cup to a slit, or total obscuration of a segment of the central retinal artery or vein.

5

Severe

Dome-shaped protrusion of the nerve with a narrow and smoothly demarcated halo. Major retinal vessels climb steeply over the domed surface, and segments of these vessels may or may not be totally obscured by overlying swollen tissue.

a

866

Reprinted with permission from Frisen L, J Neurol Neurosurg Psychiatry.18 B 1982 BMJ Publishing Group. jnnp.bmj.com/ content/45/1/13.abstract?sid=453dc7e7-1b20-4cd5-98d8-7dc9d209b7b7.



August 2014

KEY POINT

h Treatment of the

Severe (Friseń Grade 4) papilledema. The entire optic nerve head is elevated with total obscuration of portions of the central retinal artery inferiorly. A partial macular star is present, an indication of extension of the disc edema in the papillomacular bundle and macula.

FIGURE 4-7

optic nerve borders because of overlying nerve fiber layer gliosis. TREATMENT Treatments of papilledema in idiopathic intracranial hypertension include weight loss, acetazolamide, and surgical options. The goal of treatment is to improve or maintain visual function. Surgery is employed to improve visual acuity and lessen visual field impairment, but not to treat papilledema per se. The management strategy is similar in children, adolescents, and adults.19

FIGURE 4-8

Choroidal folds (dark stripes between arrows) temporal to the optic disc with a diagonal orientation. Courtesy of Janet C. Rucker, MD.


Chronic papilledema. The optic nerve is elevated, but there is mild disc pallor. The disc margins are not distinct because of nerve fiber layer gliosis.

FIGURE 4-9

Weight Loss Several studies have demonstrated improvement in papilledema grade with weight loss. The initial report of dietary intervention in 1974 by Newborg, an internist, described nine patients who were treated with a low sodium (100 mg/d), low calorie (400 cal/d to 1000 cal/d) diet consisting of rice, fruits, vegetables, and small amounts of meat.20 Papilledema improved in all patients with follow-up periods ranging from 2 to 15 months. Subsequent studies have investigated weight loss in combination with acetazolamide therapy. A retrospective study analyzed papilledema, visual acuity, and visual field status in 58 women with idiopathic intracranial hypertension who were treated medically.21 Patients who lost at least 2.5 kg (5.5 lb) in any 3-month interval had more rapid improvement of one papilledema grade (4.0 versus 6.7 months) and visual field (4.6 versus 12.2 months) than those who lost less than 2.5 kg (5.5 lb). Papilledema resolved in 28 of 38 patients with weight loss compared with 8 of 20 patients without weight loss. There was no difference in the final visual acuity or visual field between groups. Another retrospective study of 15 patients with idiopathic intracranial

pseudotumor cerebri syndrome is directed at preserving vision and is stratified based on the degree of visual loss. Mild visual loss is generally managed medically, while surgery is employed for more severe or progressive visual loss. Additional medical management of headaches beyond the measures used to lower the intracranial pressure is frequently needed. Treatment strategies are similar in children and adults.



867


h Two studies showed a relationship between weight loss and improvement of papilledema grade; loss of approximately 6% of body weight was associated with resolution of marked papilledema.

h The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) studied 165 patients with mild visual loss from idiopathic intracranial hypertension who were randomized to a supervised dietary program and either acetazolamide or matching placebo.

hypertension who were treated with acetazolamide showed improvement in 10 patients after 24 weeks.22 There was a relationship between weight loss and improvement of papilledema grade, with approximately 6% of body weight loss being associated with resolution of marked papilledema. A prospective cohort study from the United Kingdom of women with active or chronic (greater than 3 months) papilledema assessed them for 3 months with no change in intervention, then incorporated a nutritionally complete, very low calorie diet (425 cal/d) for 3 months and a 3-month follow-up period.23 After the dietary intervention, mean weight loss was 15.7 kg (34.61 lb). There was improvement in optic disc elevation using ultrasonography and retinal nerve fiber layer thickness as measured by optical coherence tomography. Visual acuity and visual field did not change significantly. The IIHTT studied 165 patients with mild visual loss from idiopathic intracranial hypertension who were randomized to a supervised dietary program and either acetazolamide or matching placebo. There was a modest but statistically significant improvement in perimetric mean deviation (a global measurement of visual field loss) at 6 months in participants who received acetazolamide therapy. The improvement was independent of weight loss. Acetazolamide treatment was also associated

with a greater amount of weight loss, improvement in papilledema grade, and improved quality life measures compared to placebo.24 Weight loss is not recommended as the sole therapy for treatment of visual loss in the acute stages because the effect is delayed, but it is a helpful adjunctive therapy over the long term. Carbonic Anhydrase Inhibitors Acetazolamide, the most widely used carbonic anhydrase inhibitor, has been used as a treatment for idiopathic intracranial hypertension and secondary causes of pseudotumor cerebri syndrome since the 1970s. The proposed rationale for its use is an inhibitory effect on CSF production by the choroid plexus. Studies suggest that a dose of 4 g/d is required to achieve this effect,25,26 but there is a paucity of data currently available substantiating its use. The IIHTT is the first randomized trial testing its effectiveness when combined with a supervised weight loss diet. The most common practice is starting with 1 g/d in divided doses, gradually increasing the dose as needed or tolerated to a maximum of 4 g/d. Counseling patients about expected side effects, such as paresthesia, gastrointestinal symptoms, and fatigue, often improves adherence to the regimen. Acetazolamide (category C) may be used during pregnancy after the first trimester (Case 4-1). Hypokalemia rarely occurs if no other diuretics are

Case 4-1 A 27-year-old right-handed woman began developing headaches in her 15th week of pregnancy. She had had minor headaches in the past but nothing as severe. She described these new headaches as tension in her neck with pain radiating to the front of her head. The pain was throbbing and pressurelike and associated with photophobia, nausea, and vomiting. She saw light flashes and spots during the headache. There was no phonophobia or osmophobia. Her headaches occurred daily for 1 month, were severe intermittently, and were generally worse in the evening. Her headaches worsened with bending over, sometimes awakened her from sleep, and could last for hours. There were no transient obscurations of vision, but she had muffled hearing and pulsatile tinnitus. A few

Continued on page 869

868



August 2014

Continued from page 868 weeks after headache onset, she experienced blurred vision for a few days followed by horizontal, constant binocular diplopia. Her left eye seemed to turn inward. There was no eye pain or ptosis. She initially saw her obstetrician for the headaches, who prescribed a butalbital and acetaminophen product that helped the headaches but not the neck pain. The double vision did not improve. Her obstetrician later prescribed hydrocodone, which helped the neck pain but not the headaches. An optometrist and ophthalmologist found papilledema and a brain MRI and magnetic resonance venogram were performed and reported as normal. She was admitted to the hospital and underwent a lumbar puncture that showed an opening pressure of 360 mm of CSF with normal CSF contents. The spinal tap immediately relieved her headache, and the double vision started improving. She started taking 500 mg of acetazolamide 2 times a day and was referred for neuro-ophthalmologic consultation during her 21st week of pregnancy. On neuro-ophthalmic examination, her best corrected visual acuity was 20/20 in both eyes. Color vision, Amsler grid, pupils, external examination, and ocular motility were normal. Automated perimetry showed a slightly enlarged blind spot in the right eye and no specific defect in the left eye (Figure 4-10). There was Friseń grade 3 disc edema in the right eye and Friseń grade 2 edema in the left eye (Figure 4-11). Her brain MRI, magnetic resonance venography, and magnetic resonance angiography were reviewed and showed dilation of the perioptic nerve sheath, flattening of the posterior sclerae, and protrusion of the optic papillae into the globe. There was no Chiari malformation or empty sella. The brain was otherwise normal. The acetazolamide was changed to 500 mg of extended-release 3 times a day with improvement in her diplopia. She continued taking acetazolamide throughout her pregnancy with no adverse effects. She developed diet-controlled gestational diabetes mellitus, and the papilledema resolved in the third trimester with concomitant normalization of her physiologic blind spot on perimetry. After delivery, she forgot to take the acetazolamide and noticed that her headaches were better without the medication, so it was discontinued. Topiramate was initiated for headache prevention, but she experienced cognitive side effects at a low dose. She continued to have two to three headaches per week and was started on zonisamide.

FIGURE 4-10

Visual fields. Automated perimetry revealed a normal left eye (A) and enlargement of the physiologic blind spot in the right eye (B).

Continued on page 870 Continuum (Minneap Minn) 2014;20(4):857–876



869

Papilledema

Continued from page 869

FIGURE 4-11

A Friseń grade 3 disc edema in the right eye (on left) with a complete peripapillary halo. The peripapillary halo is incomplete in the left eye (on right) with relative preservation of the temporal disc margin, typical of Friseń grade 2 disc edema.

Comment. Idiopathic intracranial hypertension may develop during pregnancy, although the incidence in pregnancy is no higher than in age-matched control subjects.27 Acetazolamide (category C) may be used after the first trimester of pregnancy; this patient had mild papilledema and good visual function, so she was treated with acetazolamide and followed closely throughout her pregnancy. The papilledema resolved with acetazolamide but it did not alleviate her headaches. Headaches frequently persist as a sequela of idiopathic intracranial hypertension and are treated medically. As with other headache disorders, trials of several preventive medications may be needed before finding one that is effective, is well tolerated, and does not adversely affect other medical problems. Headache prevention medications associated with weight gain are best avoided. Symptomatic headache treatment is monitored closely to avoid medication-overuse headaches.

used concurrently. Renal stones and elevated transaminase levels occur uncommonly. The sulfa moiety in acetazolamide is different from the sulfa component in antibiotics, so an allergy to sulfa antibiotics does not preclude a trial of acetazolamide. Carbonic anhydrase inhibitors as the sole treatment are unlikely to reverse severe visual loss. Therapeutic Lumbar Puncture Patients occasionally have relief of symptoms after a diagnostic lumbar puncture. Therapeutic lumbar puncture may be useful during pregnancy to buy time while awaiting a surgical intervention, or for patients who have occasional symptom flare-ups.

870

Optic Nerve Sheath Fenestration Optic nerve sheath fenestration (ONSF), performed with a medial or lateral orbitotomy or a superior lid crease approach, involves cutting a slit, series of slits, or window in the fibrous dural sheath around the edematous optic nerve (Case 4-2). It is performed under general anesthesia and may be done on an outpatient basis. Because the procedure is done by orbital surgeons, the data on visual outcomes are more detailed for ONSF than for shunting procedures. Numerous retrospective case series report that visual acuity and visual fields improve in most cases following ONSF 28; some patients experience bilateral improvement after a unilateral procedure. A meta-analysis



August 2014

of ONSF showed worsening of visual acuity or visual field in 11% of eyes with a mean follow-up at 21 months.29 The mechanism of effectiveness is

uncertain. The pressure in the optic nerve sheath is immediately lowered as CSF egresses from the incision site, but the long-term effectiveness declines

Case 4-2 A 22-year-old woman described symptoms of blurred vision in either eye for 1 to 2 months. Words blurred out while reading, and she had occasional episodes of foggy vision lasting 2 to 3 minutes. There was no diplopia. Within the few weeks before presentation she experienced stabbing pain around her right eye that radiated to her right ear or to her upper neck on the right side. The pain occurred 2 to 3 times weekly and lasted 2 to 3 hours or sometimes all day. She experienced photophobia in her right eye, phonophobia at times, and worsening of headache with activity. She sometimes closed her eyes because of the ocular discomfort. There was no nausea, vomiting, or anorexia. Sometimes ibuprofen helped, and she also used cold compresses. She heard beeping in her ears and occasionally heard her heartbeat; these symptoms were long-standing. The patient was referred by an optometrist who had found visual acuities of 20/25 in her right eye and 20/20 in her left eye with bilateral papilledema. There was no known weight change or use of vitamin A or antibiotics. Her body mass index was 47.75 kg/m2. The patient’s visual acuity with best correction was 20/20-2 in her right eye and 20/20-1 in her left eye, and she correctly identified 12 of 13 Ishihara color plates with her right eye and all 13 plates with her left eye. Amsler grid testing showed metamorphopsia temporal to fixation in her right eye and the area appeared faded; Amsler grid testing was normal in her left eye. Light brightness in her right eye was 50% of the light brightness in her left eye; her pupils measured 3 mm in the light and 5 mm in the dark, with a brisk light reaction and a trace right relative afferent pupillary defect. Tangent screen visual field testing using a 3 mm target at 1 meter showed a constricted field to about 15 degrees in the right eye; static testing was normal within this area. The blind spot broke out into the periphery. There was physiologic expansion using the examiner’s hand as the test target. In the left eye, the field was full with an enlarged blind spot and normal static testing. The external examination and intraocular pressures were normal. The extraocular movements were full with normal pursuits and saccades and no nystagmus. The dilated fundus examination showed bilateral chronic Friseń grade 3 disc edema, with optic disc drusen in the right eye (Figure 4-12). The vessels, macula, and periphery were normal in both eyes, and spontaneous venous pulsations were absent bilaterally.

FIGURE 4-12

Friseń grade 3 papilledema in both optic nerves (A, right eye; B, left eye). A peripapillary halo and all vessels are seen clearly as they traverse the disc margin. Prominent optic disc drusen are present in the right eye.

Continued on page 872 Continuum (Minneap Minn) 2014;20(4):857–876



871

Papilledema

Continued from page 871 Automated perimetry showed a marked generalized reduction in sensitivity with relative temporal and superior arcuate field loss. In the left eye, there was a generalized reduction in sensitivity, enlargement of the blind spot, and a superior nasal step (Figure 4-13).

FIGURE 4-13

Initial visual fields. A, Automated perimetry shows superior and inferior arcuate defects in the left eye. B, A dense superior arcuate defect with an enlarged blind spot and an incomplete inferior arcuate defect in the right eye are present.

MRI showed a partially empty sella and cerebellar tonsillar descent and was otherwise normal (Figure 4-14). A lumbar puncture revealed an opening pressure of 370 mm CSF with normal CSF contents, so 500 mg of acetazolamide 2 times a day was prescribed. Two weeks later her symptoms were improved, but there was slight worsening of the visual field in both eyes, so the acetazolamide dose was doubled and a right optic nerve sheath fenestration was performed within a week. Her visual acuity and visual fields improved following surgery (Figure 4-15). Comments. Often the exact time of onset of idiopathic intracranial hypertension is unknown. Some patients develop symptoms prior to diagnosis, while others are asymptomatic and diagnosed during a routine eye examination. This patient had symptoms for a few months. Her visual symptoms were vague, and the episodes of transient visual blurring were longer than usually reported with papilledema. The appearance of her optic nerve on her initial examination suggested that she had had increased CSF pressure for several weeks to months. There was FIGURE 4-14 Sagittal MRI reveals tonsillar descent and a evidence of asymmetric optic neuropathy. Central herniation partially empty sella. after lumbar puncture is rare in the presence of a Chiari I malformation but lumbar puncture is best avoided with a large Chiari I malformation.

Continued on page 873

872



August 2014

Continued from page 872

FIGURE 4-15

Postoperative visual fields. Following right optic nerve sheath fenestration, there is marked improvement in the visual field of both eyes (A, left eye; B, right eye). There is residual enlargement of the blind spot in both eyes with subtle arcuate defects.

over time, with about one-third of patients experiencing visual deterioration over 3 to 5 years after an initially successful procedure.30 Headaches may improve after ONSF, although the procedure is not indicated for the treatment of headache alone. A major advantage of ONSF over shunting is the lack of implanted hardware. Postoperative diplopia is usually transient. The risk of worsening of vision from surgical complications (eg, nerve sheath hemorrhage) is low when the procedure is performed by an experienced surgeon. Trends. A lateral orbitotomy involves fracturing the lateral orbital wall. Most orbital surgeons prefer the medial approach, but the superior eyelid-crease approach provides a good visualization of the optic nerve and avoids the postoperative complications of conjunctival injection, irritation from conjunctival sutures, and diplopia. Shunting Various types of shunts have been used to treat the pseudotumor cerebri syndrome, including ventriculoContinuum (Minneap Minn) 2014;20(4):857–876

peritoneal, lumboperitoneal, ventriculoatrial, and ventriculopleural shunts; ventriculoperitoneal and lumboperitoneal shunts are more frequently employed. No randomized studies have been conducted comparing the two types of shunts, but small series suggest that they have equal efficacy with regard to headache and visual outcomes.28,31 A retrospective analysis of 6-month outcomes in 44 patients followed for nearly 5 years after lumboperitoneal shunting showed improvement of papilledema in 15.9%, resolution of papilledema in 22.7%, improvement of headache in 27.3%, resolution of headache in 18.2%, and visual worsening in 4.5%.29 A similar analysis of 31 patients after ventriculoperitoneal shunting showed visual improvement in 38.7%, no change in 61.3%, and resolution of papilledema in all 17 patients in whom it was reported.29 A report of a 30-year experience of shunting for headaches at a single institution described 115 procedures in 42 patients32: The initial effectiveness (95%) for headache immediately after the shunts were www.ContinuumJournal.com


873

Papilledema KEY POINT

h The headaches of idiopathic intracranial hypertension do not correlate with the lumbar opening pressure, degree of papilledema, or amount of visual loss. They are best managed medically.

inserted declined by half in 3 years, and 75% of all shunts failed at 2 years. Lumboperitoneal shunts failed at twice the rate of ventriculoperitoneal shunts. Programmable valves have a lower failure rate and may be used with ventriculoperitoneal shunts. Complications of shunting procedures include infection, migration of the distal catheter, and valve malfunction or obstruction. Complications unique to lumboperitoneal shunts are tonsillar descent, low-pressure headaches, and radiculopathy.33 No data exist comparing surgical procedures for treatment of the pseudotumor cerebri syndromeYrelated visual loss; the procedure performed is often determined by the local available resources. Any of the procedures may fail over time and occasionally shunting and ONSF are needed. Trends. Because of the small ventricular size in pseudotumor cerebri syndrome, lumboperitoneal shunting was the shunting procedure of choice for many years. This trend seems to be reversing with the use of stereotactic techniques and the development of programmable valves, which are designed to be used with ventriculoperitoneal shunts. Cerebral Venous Sinus Stenting The finding of narrowed transverse sinuses and associated pressure gradients across the transverse sinuses in patients with idiopathic intracranial hypertension has prompted treatment using endovascular stenting. In most cases, the stenosis seems to be the result of intracranial hypertension rather than the cause of it,34 but it is possible the stenotic sinus compounds the situation by further reducing CSF absorption in a feed-forward situation. The criteria for stenting vary between centers with regard to the visual status, presence of a pressure gradient, and failure of other

874

treatments prior to stenting. Some patients have been successfully treated, with improvement in their vision, headaches, and papilledema, whereas others have not benefitted from the procedure.30,35 Complications, while uncommon, are severe, including one death, and lifethreatening cerebral hematomas. Shunt patency over the long term is generally favorable.36 One study of 51 patients showed no correlation between the degree of venous sinus stenosis and the clinical course, visual status, or lumbar puncture opening pressure in idiopathic intracranial hypertension.37 Trends. Stenting for idiopathic intracranial hypertension is currently one of the most controversial topics in neuroophthalmology. While the venous sinuses are undoubtedly involved in idiopathic intracranial hypertension, the safety, efficacy, and indications for stenting remain uncertain. At this point, most neuroophthalmologists would not consider stenting a first-line procedure. Treatment of Headaches Headaches associated with idiopathic intracranial hypertension do not correlate with the lumbar opening pressure, degree of papilledema, or amount of visual loss. They are best managed medically with standard headache preventive medications (as per the headache phenotype) and symptomatic treatments that do not produce medication-overuse headache. Avoid barbiturates, opioids, frequent use of acetaminophen, and preventive medications that are known to produce weight gain. Surgery is not recommended for the treatment of headache alone. REFERENCES 1. Friedman DI, Digre KB. Headache medicine meets neuro-ophthalmology: exam techniques and challenging cases. Headache 2013;53(4): 703Y716. 2. Jacks AS, Miller NR. Spontaneous retinal venous pulsation: aetiology and significance. J Neurol Neurosurg Psychology 2003;74(1):7Y9.



August 2014

3. Marzoli SB, Ciasca P, Curone M, et al. Quantitative analysis of optic nerve damage in idiopathic intracranial hypertension (IIH) at diagnosis. Neurol Sci 2013;34(suppl 1): S143YS145. 4. Ney JJ, Volpe NJ, Liu GT, et al. Functional visual loss in idiopathic intracranial hypertension. Ophthalmology 2009;116(9):1801Y1803. 5. Butros SR, Goncalves LF, Thompson D, et al. Imaging features of idiopathic intracranial hypertension, including a new finding: widening of the foramen ovale. Acta Radiol 2012;53(6):682Y688. 6. Avery RA, Shah SS, Licht DJ, et al. Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med 2010; 363(9):891Y893. 7. Avery RA, Licht DJ, Shah SS, et al. CSF opening pressure in children with optic nerve head edema. Neurology 2012;76(19):1658Y1661. 8. Neville L, Egan RA. Frequency and amplitude of elevation of cerebrospinal fluid resting pressure by the Valsalva maneuver. Can J Ophthalmol 2005;40(6):775Y777. 9. Flores-Rodrı´guez, Gili P, Martıń-Rıós MD. Ophthalmic features of optic disc drusen. Ophthalmologica 2012;228(1):59Y66. 10. Pinelas SL, Arnold AC. Fluorescein angiographic identification of optic disc drusen with and without optic disc edema. J Neuroophthalmol 2012;32(1):17Y22. 11. Ekdawi NS, Brodsky MC. Absence of spontaneous venous pulsations in children with pseudopapilledema. Br J Ophthalmol 2011; 95(11):1615Y1616. 12. Witmer MT, Margo CE, Drucker M. Tilted optic disks. Surv Ophthalmol 2010;55(5):403Y428. 13. Pollak L, Zohar E, Glovinsky Y, Huna-Baron R. Reevaluation of presentation and course of idiopathic intracranial hypertensionVa large cohort comprehensive study. Acta Neurol Scand 2013;127(6):406Y412. 14. Boiardi A, Salmaggi A, Eoli M, et al. Headache in brain tumours: a symptom to reappraise critically. Neuro Sci 2004;25(suppl 3):S143YS147. 15. Friedman DI. Pseudotumor cerebri presenting as headache. Exp Rev Neurotherapeutics 2008;8(3):397Y407. 16. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 2013;81(13): 1159Y1165.

19. Ko MW, Liu GT. Pediatric idiopathic intracranial hypertension (pseudotumor cerebri). Horm Res Paediatr 2010;74(6):381Y389. 20. Newborg B. Pseudotumor cerebri treated by rice reduction diet. Arch Intern Med 1974; 133(5):802Y807. 21. Kupersmith MJ, Gamell L, Turbin R, et al. Effects of weight loss on the course of idiopathic intracranial hypertension in women. Neurology 1998;50(4):1094Y1098. 22. 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;105(12):2313Y2317. 23. Ball AK, Howman A, Wheatley K, et al. A randomised controlled trial of treatment for idiopathic intracranial hypertension. J Neurol 2011;258(5):874Y881. 24. Wall M, McDermott MP, Kieburtz KD, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss. JAMA Neurol 2014; 13(16):1641Y1651. 25. Gu¨cer G, Viernstein L. Long-term intracranial pressure recording in the management of pseudotumor cerebri. J Neurosurg 1978; 49(2):256Y263. 26. Tomsak RL, Niffenegger AS, Remler BF. Treatment of pseudotumor cerebri with Diamox (acetazolamide). J Clin Neuro-Ophthalamol. 1988;8:93Y98. 27. Digre KB, Varner MW, Corbett JJ. Pseudotumor cerebri and pregnancy. Neurology 1984;34(6): 721Y729. 28. Uretsky S. Surgical interventions for idiopathic intracranial hypertension. Curr Opin Ophthalmol 2009;20(6):451Y455. 29. Feldon SE. Visual outcomes comparing surgical techniques for management of severe idiopathic intracranial hypertension. Neurosurg Focus 2007;23(5):E6. 30. Brazis P. Clinical review: the surgical treatment of idiopathic pseudotumor cerebri (idiopathic intracranial hypertension). Cephalalgia 2009;28(12):1361Y1373.

17. Friedman DI. Pearls: diplopia. Semin Neurol 2010;30(1):54Y65.

31. Tarnaris A, Toma AK, Watkins LD, Kitchen ND. Is there a difference in outcomes of patients with idiopathic intracranial hypertension with the choice of cerebrospinal fluid diversion site: a single centre experience. Clin Neurol Neurosurg 2011;113(6):477Y479.

18. Friseń L. Swelling of the optic nerve head: a staging scheme. J Neurol Neurosurg Psychiatry 1982;45(1):13Y18.

32. McGirt MJ, Woodworth G, Thomas G, et al. Cerebrospinal fluid shunt placement for pseudotumor cerebri-associated




875

Papilledema

intractable headache: predictors of treatment response and analysis of long term outcomes. J Neurosurg 2004;101(4): 627Y632.

876

35. Puffer RC, Mustafa W, Lanzino G. Venous sinus stenting for idiopathic intracranial hypertension: a review of the literature. J Neurointerv Surg 2013;5(5):483Y486.

33. Sinclair AJ, Kuruvath S, Sen D, et al. Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review. Cephalalgia 2011;31(16): 1627Y1633.

36. Ducruet AF, Crowley RW, McDougall CG, Albuquerque FC. Long-term patency of venous sinus stents for idiopathic intracranial hypertension. J Neurointerv Surg 2013;[Epub ahead of print].

34. King JO, Mitchell PJ, Thomson KR, Tress BM. Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology 2002;58(1):26Y30.

37. Riggeal BD, Bruce BB, Saindane AM, et al. Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis. Neurology 2013;80(3):289Y295.



August 2014

Idiopathic intracranial hypertension without papilledema.

Intracranial Hypertension in Children without Papilledema.

Intracranial Hypertension Without Papilledema in Children.

Correlation between papilledema grade and diffusion-weighted magnetic resonance imaging in idiopathic intracranial hypertension.

Idiopathic Intracranial Hypertension in a Prepubertal Pediatric Japanese Patient Complicated by Severe Papilledema.

Axonal damage in papilledema linked to idiopathic intracranial hypertension as revealed by multifocal visual evoked potentials.

P027. Idiopathic intracranial hypertension without papilledema in refractory chronic daily headache.

Treating idiopathic intracranial hypertension.

Idiopathic intracranial hypertension.

Idiopathic intracranial hypertension--reply.

Idiopathic intracranial hypertension.

Idiopathic intracranial hypertension and obesity.

[Bilateral papilledema secondary to intracranial hypertension in an adolescent girl].

Idiopathic intracranial hypertension: pseudotumor cerebri.

Overdiagnosis of idiopathic intracranial hypertension.

Treating idiopathic intracranial hypertension--reply.

Patient-controlled intracranial pressure for managing idiopathic intracranial hypertension.

Imaging the eye in idiopathic intracranial hypertension.

A review of pediatric idiopathic intracranial hypertension.

Available tests for idiopathic intracranial hypertension.

Headache management in idiopathic intracranial hypertension.

Pediatric pseudotumor cerebri (idiopathic intracranial hypertension).

The headache profile of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension: report of seven cases.