This chapter reviews the distinction between papilledema (disc swelling secondary to increased intracranial pressure), disc swelling associated with optic neuropathy, and disc elevation due to pseudopapilledema. The fundus appearance of papilledema, the associated visual loss and its mechanisms, and the differential diagnosis in and evaluation of patients with papilledema are discussed. In addition, conditions associated with papilledema are covered, with the greatest emphasis placed on diagnosis and management of a relatively common nontumor cause of papilledema, pseudotumor cerebri syndrome.
Distinction of Papilledema from Optic Neuropathy, Pseudopapilledema, and Other Causes of Disc Swelling
Table 6.1 outlines the differential diagnosis of a swollen disc. The term papilledema refers to optic disc swelling due to increased intracranial pressure, and the two conditions most commonly mistaken for it are disc swelling due to optic neuropathy and pseudopapilledema (disc elevation without nerve fiber layer edema). The distinction between these three major causes of disc swelling is aided by review of the history, evaluation of visual function, ophthalmoscopic appearance of the disc, and ancillary testing. At times the diagnosis may be difficult, but there are some useful, general guidelines.
| Most Common | Common | Uncommon |
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Signs and symptoms of elevated intracranial pressure, such as headache, nausea, vomiting, and abducens paresis, should suggest the diagnosis of papilledema. However, caution should be applied in this regard, as patients may present with headache unrelated to their disc swelling. For instance, we have seen patients with migraine headaches and pseudopapilledema, and others with headache associated with optic neuritis.
Ophthalmoscopically, the disc swelling due to optic neuropathy and that due to papilledema may be similar ( Fig. 6.1 ). However, optic neuropathies such as optic neuritis or ischemic optic neuropathy typically lead to more severe visual loss, which is usually sudden in onset, unilateral, and associated with an afferent pupillary defect and impaired color vision. Papilledema, on the other hand, is more frequently bilateral and more commonly leads initially to visual deficits such as enlarged blind spots and peripheral field constriction, about which the patient may not be aware. The various optic neuropathies are discussed in more detail in Chapter 5 .
Pseudopapilledema
Pseudopapilledema (or pseudodisc edema) is the term used to describe optic nerve variants or abnormalities that mimic papilledema ophthalmoscopically, including congenital anomalies, tilting, hypoplasia, crowded hyperopic disc, optic disc hamartoma, myelinated nerve fibers, and optic nerve head drusen ( Figs. 6.2 and 6.3 ). Visual loss, which may occur in some cases, is long-standing, painless, and frequently unnoticed by the patient. The diagnosis may be aided by serial dilated fundus examinations and review of stereo disc photographs; pseudopapilledema will be stable over time, while untreated papilledema might change. Ophthalmoscopic hallmarks of pseudopapilledema include anomalous retinal vasculature (abnormal branching pattern, for instance), absence of a central cup, irregular disc margins, and vessels that pass over the disc normally without being obscured by the nerve fiber layer. They also tend to be less elevated without swelling of the nerve fiber layer, hemorrhages, or exudates, in contrast to discs with true disc edema.
The presence of spontaneous venous pulsations (SVPs) favors pseudopapilledema, although their absence does not always indicate true papilledema. SVPs are pulse-related dilations and contractions of large venous branches in or overlying the disc. They are best seen within the central cup of the disc and where the veins bend and are most evident in patients with deep and large cups. The presence of SVPs usually implies the intracranial pressure is less than 180 mm CSF H 2 O at the time of viewing ; however, this is not an absolute. Additionally, the absence of SVPs does not imply elevated intracranial pressure, because as much as 10% of the normal population may not have them in either eye.
In addition, discs with true papilledema will leak during fluorescein angiography, in contrast to those with pseudopapilledema, which tend to not leak or show only late staining. Discs with pseudopapilledema often have nerve fiber–related field defects, so visual field testing cannot be used to separate pseudopapilledema from true papilledema.
Optic Disc Drusen
Optic disc drusen (hyaline bodies) are calcium deposits within the nerve head. In general, they are not visible at birth or in infancy but become more noticeable by the end of the first decade of life. When on the surface of the disc, they appear as refractile, tapioca-like bodies that are easily identified ophthalmoscopically (see Fig. 6.3 ). If they are buried (between the surface and the lamina cribrosa), as they usually are in childhood, they may simply elevate the optic nerve head. Drusen are often associated with an anomalous retinal artery branching pattern which includes a spokelike appearance secondary to trifurcations of the first order vessels. The disc generally takes on a yellowish appearance.
On occasion suspected drusen can be more easily seen if the disc is retroilluminated by focusing a spot or beam of light from the direct ophthalmoscope or slit lamp on the nasal peripapillary retina. The disc is then observed in the darkened field next to the light. Drusen may give the disc a translucent appearance with the disc drusen highlighted.
Various types of hemorrhages can also be associated with disc drusen. The most typical is a peripapillary subretinal hemorrhage, which may ultimately cause peripapillary pigmentary disruption or hyperpigmentation. On occasion drusen-associated hemorrhages are related to a peripapillary subretinal neovascular membrane. In rare instances, papilledema may be superimposed upon underlying pseudopapilledema due to optic nerve head drusen.
Optic disc drusen are thought to consist of intracellular axonal debris, which accumulates throughout life because of a defect in axonal metabolism. A small scleral canal is thought to cause this defect, but this is uncertain. They are present in approximately 0.3–2.0% of the population and in about two-thirds of cases are bilateral. Some instances are familial, inherited presumably in an autosomal dominant fashion with incomplete penetrance. Rarely they are associated with angioid streaks and retinitis pigmentosa.
If optic disc drusen are suspected but cannot be definitively identified ophthalmoscopically, then adjunctive imaging may confirm their presence. They may autofluoresce when photographed through a fluorescein filter (without dye injection) ( Fig. 6.4A ), and fluorescein angiography may demonstrate nodular staining. Combined A- and B-scan ultrasonography is probably the best modality, because it may demonstrate disc elevation secondary to highly reflective material ( Fig. 6.4B ). Computed tomography (CT) with axial sections through the nerve–globe junction may also reveal calcifications secondary to drusen ( Fig. 6.4C ), but thick slices can miss smaller-sized drusen.
Spectral-domain (SD) optical coherence tomography (OCT) is an emerging diagnostic modality for detecting optic nerve head drusen, but whether it can readily distinguish papilledema from pseudopapilledema is uncertain unless optic nerve drusen ( Fig. 6.4D ) and an associated “boot sign” are seen. In addition, in optic disc edema there may be a thicker nerve fiber layer in all sections, but particularly nasally, than in pseudopapilledema due to optic disc drusen.
Other Causes
Other causes of disc swelling that should be contrasted from papilledema include (1) central retinal vein occlusion, which is characterized additionally by dilated, tortuous veins and intraretinal and peripheral retinal hemorrhages; (2) ocular hypotony; (3) intraocular inflammation (e.g., uveitis); (4) diabetic papillopathy; (5) optic perineuritis (idiopathic or due to syphilis, for instance); (6) intrinsic optic disc tumors, such as hemangiomas (in von Hippel–Lindau, for example), astrocytic hamartomas (in tuberous sclerosis), and optic disc gliomas; (7) Leber’s hereditary optic neuropathy; (8) optic nerve infiltration by neoplasms, antibodies in plasma cell dyscrasia, or sarcoidosis, for instance; (9) high altitudes; and (10) malignant hypertension—the associated disc swelling had been previously related to elevated cerebrospinal fluid (CSF) pressure; however, experimental and clinical observations have suggested that an ischemic optic neuropathy may also be responsible. Disc swelling due to malignant hypertension is frequently accompanied by cotton-wool spots in the retina, macular serous retinal detachment, and lipid star formation. Many of these entities are discussed in more detail in the chapters on retinal disorders and optic neuropathies ( Chapters 4 and 5 ).
Fundus Appearance of Papilledema
Mechanism
The force of elevated CSF is transmitted to tissue fluid between axons in the optic nerve head, leading to axoplasmic stasis in the prelaminar portion of the optic nerve ( Fig. 6.5 ). This causes axonal swelling which is observable ophthalmoscopically as a swollen optic disc. In one alternative hypothesis, papilledema may not be solely caused by raised intracranial pressure, but may result from compartmentalization of the subarachnoid space of the optic nerve.
Early and Acute Papilledema
Early disc swelling associated with elevated intracranial pressure appears first superiorly and inferiorly, then nasally, and finally temporally ( Fig. 6.6 ). This pattern follows the relative thickness of the nerve fiber layer, in descending order, at different locations around the optic disc. Elevation of the nerve fiber layer obscures the underlying vessels and blurs the disc margins (see Fig. 6.6 ).
Usually, the development of papilledema requires at least 1–5 days of persistently elevated intracranial pressure. However, sudden rises in intracranial pressure, caused by an acute subarachnoid or intraparenchymal hemorrhage, for instance, occasionally may result in papilledema that develops rapidly within hours. Selhorst et al. witnessed the development of papilledema within 1 hour in a patient with acute aneurysmal rupture. Because axoplasmic stasis could not develop so quickly, they surmised that a sudden, severe rise in intracranial pressure could force axoplasm retrogradely from the intraorbital optic nerve into the optic nerve head.
The vascular changes associated with papilledema are secondary to the nerve fiber swelling. Compression of capillaries and venules on the disc cause venous stasis and dilation, formation of microaneurysms, and disc and peripapillary radial hemorrhages. The disc becomes hyperemic because of the capillary dilation. Cotton-wool spots represent ischemic areas within the nerve fiber layer (see Fig. 6.6 ). Compression of the central retinal vein can lead to retinal venous engorgement and tortuosity and disappearance of SVPs.
Grading systems for papilledema have been devised, but these are susceptible to interobserver disagreement. Therefore, more descriptive terminology is often used. The term mild papilledema refers to slight disc elevation with some or no peripapillary hemorrhages. High-grade or florid papilledema is characterized by severe disc elevation with cotton-wool spots, peripapillary hemorrhages, and venous engorgement (see Fig. 6.6 ). The degree of papilledema is usually symmetric in both eyes, but asymmetric and even unilateral papilledema may occur. A subarachnoidal meshwork within the optic canal can act as an incomplete barrier to transmission of CSF pressure between the intracranial vault and anterior optic nerve. Anatomic differences in this meshwork may account for asymmetric papilledema as well as interpersonal variation in disc swelling with the same CSF pressure. Alternatively, Lepore proposed that age-related changes in the lamina cribrosa due to increased collagen and decreased elasticity might protect the optic nerve head from elevated intracranial pressure. Atrophic portions of an optic nerve head cannot develop disc swelling, but intact portions can (see Foster Kennedy Syndrome ).
Chronic Papilledema
Box 6.1 compares the features of acute and chronic papilledema. The disc takes on a “champagne-cork” appearance ( Fig. 6.7 ) when papilledema has been present for weeks or months. Typically, peripapillary hemorrhages are conspicuously absent. White exudates, representing extruded axoplasm, commonly overlie the disc (pseudodrusen). Chronic papilledema may also be associated with venous collateral vessels ( Fig. 6.8 ) and peripapillary subretinal neovascularization. The collateral vessels form when decreased flow through the central retinal vein causes compensatory dilation of preexisting communications between retinal and ciliary venous circulations.
Common to Both Acute and Chronic Papilledema
Disc elevation
Venous distention and tortuosity
Obscuration of the normal disc margin and overlying retinal vessels
Absence of spontaneous venous pulsations
Characteristic Typical of Acute Papilledema
Disc hyperemia
Cotton-wool spots
Peripapillary hemorrhages
Characteristics Typical of Chronic Papilledema
“Champagne-cork” appearance
Overlying gliosis and extruded axoplasm (pseudodrusen)
Disc atrophy
Venous collateral vessels
Peripapillary subretinal neovascularization
Atrophic Papilledema
When swollen nerve fibers die, the disc atrophies and swelling becomes pale and less prominent (see Fig. 6.8 ). Arterial branches, especially peripapillary, become attenuated.
Treated Papilledema
If the elevated intracranial pressure is treated before atrophy of nerve fibers, papilledema usually resolves completely over the ensuing weeks or months ( Fig. 6.9 ). However, some patients, particularly those with permanent visual loss, are left with some degree of disc pallor and residual disc elevation because of gliosis (secondary disc pallor) ( Fig. 6.10 ).
Foster Kennedy Syndrome
Foster Kennedy described patients with ipsilateral disc pallor, secondary to optic nerve compression, and contralateral papilledema. Preexisting optic atrophy precludes the development of papilledema, because there are no fibers to swell. Classically, the culprit lesion in Foster Kennedy syndrome is a subfrontal mass, typically a meningioma, which compresses the ipsilateral optic nerve, causing disc atrophy. If the lesion is large enough to cause elevated intracranial pressure, papilledema results in the contralateral eye only, owing to the ipsilateral nerve atrophy ( Fig. 6.11 ). Bilateral optic nerve compression is another possible mechanism. Nontumor causes, resulting in pseudo–Foster Kennedy syndrome, are actually more common. One example is consecutive anterior ischemic optic neuropathy, characterized by new ischemic disc swelling in one eye accompanied by long-standing disc atrophy resulting from a previous ischemic event in the other eye (see Fig. 5.44 ). Unlike the true Foster Kennedy syndrome, the eye with the disc swelling will usually have impaired visual acuity.
Retinal Findings Associated With Papilledema
Secondary effects on the macula are common causes of acute reduction in visual acuity and metamorphopsia in papilledema ( Table 6.2 ). For instance, in severe disc swelling, fluid may extend to the macula by dissecting between the axons of the nerve fiber layer. Macular edema is difficult to see with a direct ophthalmoscope but is more readily visible using biomicroscopy and is best demonstrated with OCT (see later discussion). Retinal or choroidal folds, lipid (hard exudate) stars, hemorrhages, and pigment epithelial and photoreceptor disturbances in the macula may also be associated with papilledema ( Fig. 6.12 ). Indentation or flattening of the posterior globe by a rigid optic nerve sheath is one proposed mechanism for choroidal folds in papilledema. Shortening of the globe’s axial length or flattening of the posterior pole may also account for the association between intracranial hypertension, papilledema, folds, and acquired hyperopia. Choroidal folds actually occur in Bruch’s membrane.
| Common | Uncommon |
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Hemorrhages associated with papilledema are usually peripapillary and retinal (within the nerve fiber layer) but occasionally can be found more than one or two disc diameters away from the optic nerve head or in the subhyaloid and vitreous spaces. Rarely, hemorrhages are due to peripapillary subretinal neovascular membranes, seen best on fluorescein angiography. When these membranes extend toward the fovea, photocoagulation may be indicated. Venous stasis retinopathy and central or branch retinal artery occlusion, due to compression of vascular structures in the optic nerve, are rare but have been documented.
Once the papilledema improves with the appropriate treatment, hemorrhages, folds, macular edema, and lipid stars tend to resolve over weeks as well. One may see residual macular pigment epithelial disturbances if lipid, folds, or edema were present, or circumpapillary “high-water” marks delineating the prior extent of peripapillary retinal elevation caused by disc swelling (see Fig. 6.12 ); in contrast these retinal abnormalities may require months or years to resolve. Unfortunately, subretinal neovascular membranes and associated subretinal hemorrhages may cause irreversible visual loss.
Fluorescein Angiography, Echography, Optical Coherence Tomography, and Other Optic Nerve Imaging Techniques in Papilledema
Several modalities aid in the diagnosis and sometimes the follow-up of papilledema.
Fluorescein angiography . Hayreh has detailed the typical fluorescein angiographic findings associated with papilledema. In the retinal arterial phase, fluorescence may be absent when disc swelling is severe enough to delay the prelaminar circulation. During the retinal arteriovenous phase, dilated capillaries, microaneurysms, and flame-shaped hemorrhages may be demonstrated on the surface of the disc and peripapillary retina. Fluorescein may leak from superficial dilated capillaries during the retinal venous phase. During the late phase, classically there is hyperfluorescence of the superficial and deep portions of the optic disc.
Ultrasound . Ultrasonography is used frequently in our practice to help distinguish papilledema from pseudopapilledema, particularly when optic disc drusen are suspected. In patients with papilledema, A-scan echography of the optic nerve can suggest increased subarachnoid fluid within the nerve sheath by demonstrating a reduction in nerve sheath diameter by 10% when the eye rotates laterally 30 degrees (“positive 30-degree test”). However, increased subarachnoid fluid is nonspecific and may be seen in optic neuritis, optic nerve trauma, and compressive optic neuropathy. Furthermore, caution in its interpretation must be applied, as echography is extremely operator–dependent, and false negatives and positives can occur.
Optic nerve and retinal imaging . OCT may demonstrate increased retinal nerve fiber layer (RNFL) thickness in papilledema. OCT RNFL thickness and total retinal thickness correlate with low grades of papilledema, but the RNFL thickness algorithms may fail with higher grades. Following papilledema with OCT may be problematic since a decrease in swelling could be consistent with either improvement or ganglion cell atrophy. RNFL thickness on OCT may but does not consistently correlate with mean deviation on computerized perimetry. Another option is to follow the ganglion cell layer plus inner plexiform layer (GCL-IPL) thickness in the macula, which can be reduced by retrograde and transsynaptic degeneration of damaged retinal ganglion cell axons at the optic nerve head. This measurement is less likely to be influenced by axoplasmic stasis at the optic disc and therefore may be a more reliable correlate of axonal damage in the optic nerve. Other retinal abnormalities which may be detected by OCT include photoreceptor damage, inner nuclear layer cysts, and subretinal fluid. Ultimately, it is best to correlate OCT parameters with perimetry and fundus appearance.
Laser scanning tomography also can quantify the degree of change in papilledema. Tomography measurements correlate with CSF opening pressures and visual field deficits.
Visual Deficits Associated With Papilledema and Their Mechanism
Visual loss due to papilledema is, for the most part, related to optic nerve head dysfunction. The field deficits are similar to those in other disorders which affect the anterior optic nerve, such as glaucoma, and they do not align along the vertical meridian, as in chiasmal or retrochiasmal lesions. It is less certain whether ischemia or axoplasmic stasis causes axonal dysfunction. Rapid improvement in vision following optic nerve sheath decompression suggests that axoplasmic stasis plays at least some part, but cases with frank optic nerve ischemia have been documented as well. Preexisting anemia or hypertension may be associated with more severe visual loss, perhaps by aggravating optic nerve head ischemia.
Blind spot enlargement is commonly associated with papilledema ( Fig. 6.13 ). The etiology is either mechanical displacement and folding of the peripapillary retina or a refractive scotoma caused by relative hyperopia due to peripapillary retinal elevation. Nasal defects (especially inferiorly ) are also common initially, in part because the temporal arcuate bundles are densest, and hence more susceptible to axoplasmic stasis and compression. Further involvement of nerve fibers leads to arcuate defects then field constriction (see Fig. 6.13 ). Once sufficient nerve fiber layer loss develops, central visual acuity loss results. Central visual defects and metamorphopsia in acute papilledema are uncommon, but when they occur with relatively normal color vision, they are almost always due to retinal processes affecting the macula (discussed previously).
Visual Field Testing
Computerized threshold static perimetry of the central 24 or 30 degrees of vision (Swedish Interactive Threshold Algorithm (SITA) standard program) is a reasonably reproducible test for patients with neuro-ophthalmic conditions, such as papilledema. Each field can be quantified using the average of all the threshold values (in decibels (dB)) for each measured area, allowing for objective, numerical comparison of serial fields. Kinetic Goldmann perimetry is more appropriate for patients with significant visual loss and those who are less cooperative, such as children. However, automated perimeters are more widely available, and because of the advantages outlined previously, most patients with papilledema should be tested, and, if necessary, followed with serial threshold field examinations. Finger confrontation methods and tangent screen examinations are too insensitive to detect subtle visual loss.
It is often difficult to correlate the severity of disc swelling with the amount of visual loss. As the papilledema becomes more chronic, nerve fibers atrophy, reducing the amount of disc swelling. Hence chronically atrophic swollen discs, likely associated with severe visual loss, tend not to be grossly elevated. However, in the acute setting it may be useful to generalize that mild disc elevation is usually associated with more minor field deficits than high-grade, florid papilledema. Furthermore, at presentation, a normally shaped and colored disc without swelling should be associated with a normal visual field.
Transient Visual Obscurations
Transient visual obscurations are unilateral or bilateral episodes of visual loss lasting for seconds. They can occur rarely or several times per day and are associated with changes in posture such as standing or bending over. Patients may describe a gray cloud or “puff of smoke”–like phenomenon that lasts for a few seconds. Likely they result from transient ischemia at the optic nerve head. Transient visual obscurations do not correlate with intracranial pressure, extent of visual loss, or severity of disc edema. They have also been reported in patients with other conditions causing optic nerve swelling or elevation.
Differential Diagnosis in Patients With Papilledema
Table 6.3 outlines causes of papilledema, categorized according to frequency. A history of seizures, unilateral motor or sensory findings on examination, reflex asymmetry, or extensor plantar reflexes suggests a mass or other focal lesion. A sudden onset of severe headache, altered mentation, and neurologic deficits would be consistent with an acute intracranial hemorrhage. In a young female who is overweight or has a history of recent weight gain and has papilledema and a normal neurologic examination, pseudotumor cerebri syndrome is a likely possibility. Limb weakness might suggest a spinal tumor or demyelinating polyneuropathy. Hypertension should be excluded. Special considerations in children are discussed later.
| Common | Uncommon |
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Evaluation of Patients With Papilledema
In patients with papilledema, we recommend urgent neurologic evaluation and neuroimaging (magnetic resonance imaging (MRI) or CT with contrast) to rule out an intracranial mass lesion, hemorrhage, hydrocephalus, or venous thrombosis ( Box 6.2 ). Magnetic resonance (MR) venography should be requested as well when a venous clot is suspected. MR angiography may be ordered if a dural arteriovenous malformation (AVM) is considered as a possible cause of elevated intracranial pressure. If neuroimaging is normal, a lumbar puncture (LP) is necessary to rule out meningitis and to document the CSF opening pressure. In patients with pseudotumor cerebri syndrome, the LP often alleviates the headache. The LP should be performed with the patient relaxed in a lateral decubitus position, with the head and spine at the same level and the neck and knees slightly flexed; however, one study in children found no clinically meaningful difference in pressure if legs were extended or flexed.
- I.
Distinguish from other causes of disc swelling (see Table 6.1 ), based upon clinical, fundus, and adjunctive laboratory features.
- II.
Clinical history
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Rapidity of onset of headache and/or visual symptoms which might suggest a hemorrhage, venous thrombosis, or quickly expanding mass lesion
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Other neurologic symptoms such as hemiparesis, sensory loss, or ataxia that suggest a mass lesion
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Body habitus (overweight female suggests idiopathic intracranial hypertension)
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- III.
Neuro-ophthalmic examination
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Including careful visual field testing looking for field defects associated with papilledema
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- IV.
Neurologic examination
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Evidence of mental status abnormalities, focal neurologic abnormalities, or long tract signs suggest a mass lesion.
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Fever and stiff neck suggest meningitis.
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- V.
Neuroimaging
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Magnetic resonance imaging or computed tomography with contrast to exclude a mass lesion or hydrocephalus
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Magnetic resonance venography, if venous sinus thrombosis suspected
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- VI.
Lumbar puncture
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Measurement of opening pressure when neuroimaging is unrevealing or if a venous sinus thrombosis is detected
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Cerebrospinal fluid tests to exclude meningitis, for example: protein, glucose, cell count with differential, Gram stain, culture, cryptococcal antigen, and India ink.
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When the clinical scenario requires the consideration of other entities: syphilis serologies, acid-fast staining, cytology for malignant cells, angiotensin-converting enzyme, Lyme titers
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Normal CSF opening pressure in an adult is less than 250 mm CSF. In children, normal CSF opening pressure is less than 280 mm CSF; however, if the child is not sedated and not obese, the pressure should be less than 250 mm CSF.
CSF measurements should also include at least those for protein, glucose, cell count and differential, Gram stain, culture, and cytology. In an immunocompromised patient, CSF testing for opportunistic infections could include cryptococcal antigen and India ink. Presence of papilledema, normal neuroimaging, and elevated CSF opening pressure but normal CSF constituents strongly suggests pseudotumor cerebri syndrome. CSF pleocytosis with or without elevated protein suggests meningitis. Bloody CSF or xanthochromia implies an intracranial hemorrhage, even if the neuroimaging is normal.
In the emergency setting, the presence of papilledema may alter management in patients with fever, stiff neck, and decreased mentation suggestive of bacterial meningitis. Papilledema, indicative of elevated intracranial pressure, may reflect an abscess or hydrocephalus in these patients and a tendency to herniate. In one approach, emergent empiric intravenous (IV) antibiotics can be given, then neuroimaging performed before a lumbar puncture. However, the absence of papilledema should not be used to rule out elevated intracranial pressure.
Papilledema in Children
Much of the differential diagnosis of papilledema in children overlaps that of adults, but there are some special considerations in younger age groups. Of the patients seen by the neuro-ophthalmology service at the Children’s Hospital of Philadelphia, the two most common causes of papilledema are a brain neoplasm or pseudotumor cerebri syndrome. Other commonly seen etiologies are meningitis (particularly Lyme), hydrocephalus, venous thrombosis, and craniosynostoses—a craniofacial condition characterized by premature closure of the cranial sutures. If brain growth exceeds that of the skull, elevated intracranial pressure and papilledema may result.
Papilledema is rare in infants because the cranial sutures have not closed, allowing the cranial vault to expand in response to elevated intracranial pressure. However, if the pressure is exceedingly high or elevates rapidly, papilledema is still possible. A bulging anterior fontanelle, enlarging head size, and irritability are better indications of elevated intracranial pressure in this age group.
The most common ocular finding in nonaccidental injury (shaken-baby syndrome, nonaccidental trauma, abusive head trauma, etc. ) is retinal hemorrhages in any layer of the retina. While papilledema is seen in only 5% of such cases, it usually indicates an accompanying subdural hematoma. In these unfortunate instances, other evidence of nonaccidental trauma, such as ecchymoses, fractures, or burns, should be sought. Generally, only a small proportion of children with nontraumatic elevated intracranial pressure have retinal hemorrhages, and they are associated with intraretinal hemorrhages located adjacent to a swollen optic disc. The peripapillary pattern is distinct from the multilayered, widespread pattern of retinal hemorrhages in abusive head trauma.
Intracranial Neoplasms
Although papilledema is an excellent sign of elevated intracranial pressure, the absence of disc swelling does not necessarily rule out an intracranial mass lesion such as a neoplasm or abscess. In a series of patients (age range 0–90 years) with brain tumors presenting to an emergency department, only 28% had papilledema. Van Crevel studied the relationship between papilledema and brain tumors and suggested that disc swelling is less likely if (1) the patients were older, because age-related cerebral atrophy may allow for greater tumor expansion without causing elevated intracranial pressure, or (2) the tumor were located in the parietal lobe. In his study, tumor size correlated poorly with the presence of papilledema. In contrast, childhood brain tumors, which are more commonly located in the posterior fossa and frequently cause fourth ventricular compression and noncommunicating hydrocephalus, may be more likely to present with papilledema (34% from one large pediatric metaanalysis ).
Two types of cerebral neoplasms, gliomatosis cerebri and leptomeningeal primitive neuroectodermal tumors, may mimic pseudotumor cerebri syndrome (see later discussion). Affected patients may present initially with papilledema, elevated CSF opening pressure with normal constituents, and relatively normal neuroimaging. However, subsequent mental status changes and neurologic deterioration are inevitable with these tumors, and MRI at this point will likely demonstrate the characteristic infiltrative lesions of the cerebral hemispheres, brainstem, or leptomeninges.
Cerebral Hemorrhage
The types of intracranial hemorrhages associated with papilledema include aneurysmal or AVM-related subarachnoid hemorrhage, acute subdural hematoma, and intraparenchymal hemorrhage. CT scanning is better than MRI at identifying the presence and location of acute blood. Hemorrhagic or xanthochromic CSF can confirm a subarachnoid hemorrhage, and formal cerebral angiography should be performed when an aneurysm or AVM is suspected. CT or MR angiography can be used as a screening tool, but they do not have the sensitivity of conventional angiography in excluding aneurysms. Elevated intracranial pressure results from mass effect produced by a hematoma or obstructive hydrocephalus from subarachnoid blood. As discussed previously, acute rises in intracranial pressure associated with intracranial hemorrhages may result in the development of papilledema within hours. However, for unclear reasons, papilledema due to subarachnoid or intraparenchymal hemorrhage occurs in only a minority of patients, despite the presence of elevated intracranial pressure. Therefore, normal optic nerve appearance should not be the sole criterion to exclude the presence of elevated intracranial pressure.
In Terson syndrome, acute subarachnoid bleeding (more typically) or an acute subdural hematoma causes intraocular hemorrhage in the vitreous, preretinal (subhyaloid), intraretinal, or subretinal spaces ( Fig. 6.14 ). In a prospective series, intraocular hemorrhages occurred in 18% of adults with subarachnoid hemorrhages, and the presence of Terson syndrome was related to the severity of the subarachnoid hemorrhage. Terson syndrome is uncommon (8%) in children with intracranial hemorrhages not related to abusive head trauma.
Preretinal hemorrhages in Terson syndrome usually occur between the temporal vascular arcades and can characteristically layer out. When present, vitreous hemorrhages can prevent adequate visualization of retinal hemorrhages. Severe, sudden rises in intracranial pressure can be transmitted to the optic nerve, and subsequent compression of both the central retinal vein and retinochoroidal anastomoses could result in an acute decrease in venous drainage from the retina and cause stasis and intraocular hemorrhage. Tracking of blood within the optic nerve sheath subarachnoid space and into the vitreous has been proposed, but similar ocular hemorrhages may be seen in patients with sudden elevations in intracranial pressure without subarachnoid hemorrhage (see Fig. 6.14 ).
In a study by Schultz et al., affected eyes in Terson syndrome had visual acuities ranging from 20/20 to light perception, and the natural history was for spontaneous resorption of the blood and moderate to good spontaneous recovery in vision within 9 months. Epiretinal membranes developed commonly, but their etiology was unclear. Vitrectomy allowed faster recovery, but the visual prognosis was no different. Thus, vitreous surgery might be reserved for young children with immature visual systems at risk for amblyopia and adults with bilateral involvement or hemorrhage that does not clear after 3 months.
Trauma
In one study, papilledema was identified in only 3.5% of patients with acute head injury. Its presence had little correlation with the degree of elevated intracranial pressure, and its absence did not rule out increased intracranial pressure. On the other hand, papilledema is much more common (approximately 50%) in chronic subdural hematomas. There are numerous reports of trauma-related papilledema in the setting of depressed skull fractures overlying a venous sinus leading to venous outflow obstruction. Once imaging studies (CT or MR venography) exclude the presence of a venous sinus thrombosis, surgical elevation of the depressed skull fracture overlying the sinus is one treatment approach.
Meningitis
Patients with infectious meningitis can develop papilledema and sixth nerve palsies associated with elevated intracranial pressure. Infectious etiologies include bacteria (e.g., pneumococcus), Lyme borreliosis, tuberculosis, and cryptococcus, for instance. When basilar meningitis causes obstructive hydrocephalus, shunting is usually required.
Of the patients with Lyme meningitis, papilledema and sixth nerve palsies seem more common in children affected with the disorder. In fact, in our experience the most common mimicker of pseudotumor cerebri syndrome (see later discussion) in children with normal imaging is Lyme meningitis. Almost all patients do extremely well with resolution of symptoms within weeks after treatment with IV antibiotics such as ceftriaxone, and some evidence suggests oral doxycycline may be effective in Lyme meningitis as well. We have added acetazolamide in affected patients until disc swelling resolves, but there is no evidence that this is necessary. Several authors have used the term “pseudotumor cerebri due to Lyme disease” in these cases; however, that is a misnomer, because these patients have abnormal CSF contents.
Cryptococcal meningitis is notorious for causing catastrophic visual loss associated with disc swelling. The mechanism is due either to the effects of high intracranial pressure or to direct optic nerve invasion by the cryptococci. In addition to antifungal agents, acetazolamide can be used in cases with mild visual loss secondary to disc swelling. However, optic nerve sheath decompression has become the treatment of choice for severe visual loss in this infection, particularly when there is elevated intracranial pressure.
Papilledema due to viral or other causes of aseptic meningitis, such as chemical or drug-induced, is much less common. Papilledema may occur in patients with elevated intracranial pressure due to carcinomatous or sarcoid meningitis, and hydrocephalus is the usual cause in these instances.
Papilledema in association with elevated intracranial pressure and idiopathic CSF lymphocytic pleocytosis is well recognized but is a diagnosis of exclusion. In most cases the condition is self-limited, but we have treated such patients with acetazolamide.
Hydrocephalus
Obstructive (noncommunicating) hydrocephalus results from compression of the ventricular system or its associated foramina (e.g., Monro, Sylvian aqueduct) ( Fig. 6.15 ). As outlined previously, common causes included neoplasms, intraventricular or subarachnoid blood, and meningitis. Other etiologies which should be considered include congenital aqueductal stenosis, myelomeningocele, and, in endemic areas, cysticercosis.
In addition to treatment of the primary problem, many patients with obstructive hydrocephalus will require a CSF diversion procedure. Papilledema, if present preoperatively, usually resolves following successful CSF shunting or endoscopic third ventriculostomy. However, some require periodic ophthalmic or neuro-ophthalmic examinations, because ocular signs may signify shunt failure even in the absence of headache, nausea, vomiting, or ventriculomegaly.
A postdecompression optic neuropathy has been described in which patients with papilledema develop acute visual loss following rapid decreases in CSF pressure due to shunting or decompressive craniotomy. The postulated mechanism is hypoperfusion to the prelaminar portion of the optic nerve, and the visual prognosis is poor. Fortunately, we have found this complication to be an uncommon one.
In addition, children who are shunted for hydrocephalus early in life may later develop slit-ventricle syndrome, an uncommon condition characterized by headaches and subnormal ventricular sizes. Affected patients may develop elevated intracranial pressure and papilledema, in part due to skull noncompliance, despite normal shunt function. Treatment in these cases consists of either acetazolamide or neurosurgical cranial vault expansion. In some reports, lumboperitoneal and cisterna magna-ventricular shunting were used. In another subset of patients, the ventricles are normal or subnormal in size during asymptomatic periods, but when symptomatic with headaches, mild ventriculomegaly is evident. Intermittent proximal shunt malfunction is the cause in these cases, and these individuals respond to proximal shunt revision.
Pseudotumor Cerebri Syndrome (PTCS), Including Idiopathic Intracranial Hypertension (IIH)
Features characteristic of patients with PTCS are elevated intracranial pressure measured during a lumbar puncture, normal spinal fluid constituents, and neuroimaging that excludes a mass lesion or hydrocephalus and demonstrates normal brain parenchyma. Primary pseudotumor cerebri syndrome includes IIH, while secondary pseudotumor cerebri syndrome includes etiologies such as medications, medical conditions, and cerebral venous abnormalities ( Box 6.3 ). The diagnosis is formally established when the revised PTCS diagnostic criteria are satisfied ( Table 6.4 ). The greatest morbidity from this disorder is visual loss related to optic disc swelling.
Primary Pseudotumor Cerebri
Idiopathic intracranial hypertension
Secondary Pseudotumor Cerebri
Cerebral Venous Abnormalities
Arteriovenous fistulas
Bilateral jugular vein thrombosis or surgical ligation
Cerebral venous sinus thrombosis
Decreased cerebrospinal fluid absorption from previous intracranial infection or subarachnoid hemorrhage
Hypercoagulable state
Increase right heart pressure
Middle ear or mastoid infection
Superior vena cava syndrome
Medications
Antibiotics (tetracycline, minocycline, doxycycline)
Vitamin A and retinoids (hypervitaminosis A, all-trans retinoic acid, excessive liver ingestion)
Growth hormone
Withdrawal from chronic corticosteroids
Lithium
Medical Conditions
Endocrine disorders
Addison’s disease
Hypoparathyroidism
Hypercapnia
Sleep apnea
Pickwickian syndrome
Anemia
Renal failure
Down syndrome
Turner syndrome
| Comment | |||
|---|---|---|---|
| Diagnosis of pseudotumor cerebri syndrome (PTCS) | A | Papilledema | |
| B | Normal neurologic examination | May have cranial nerve abnormalities | |
| C | Normal cerebrospinal fluid (CSF) composition | ||
| D | Normal neuroimaging without signs of hydrocephalus, mass or structural defect, and without meningeal enhancement on magnetic resonance imaging (MRI) | MRI ± contrast in obese females MRI ± contrast with magnetic resonance venography in all others May use contrast computed tomography if MRI is unavailable | |
| E | Elevated lumbar puncture opening pressure | ≥250 mm H 2 O in adults ≥280 mm H 2 O in sedated, obese children ≥250 mm H 2 O in not sedated or obese children | |
| Diagnosis of PTCS without papilledema | 1 | B–E from above are satisfied | |
| 2 | Unilateral or bilateral abducens nerve palsy | ||
| Probable PTCS | 1 | A–D from above are satisfied | |
| 2 | Normal lumbar puncture opening pressure | ||
| Suggested PTCS | 1 | B–E from above are satisfied | |
| 2 | Neuroimaging shows at least 3 of: | Empty sella Flattening of posterior globe Distension of perioptic subarachnoid space ± tortuous optic nerve Transverse venous sinus stenosis |
Several terms have been used for this condition. “Benign intracranial hypertension” should be eschewed, because the condition may be associated with severe debilitating visual loss in as many as 25% of patients, and therefore it is not always “benign.” Some experts today advocate the use of the term “idiopathic intracranial hypertension.” However, we have found “pseudotumor cerebri syndrome” a more descriptive umbrella term, as it includes both idiopathic and secondary causes. It is also easier for patients and providers to remember and use due to familiarity.
Idiopathic Intracranial Hypertension (Primary Pseudotumor Cerebri Syndrome)
In cases that are idiopathic, the patients are almost uniformly females in early adulthood and are overweight or have a history of recent weight gain. In four large series, approximately 90% of the patients were women and the mean age was 27.8–34 years. The approximate annual incidence of IIH was 0.9–1.7/100 000 in the general population. However, among females 15–44 years of age the incidence is 3.3–12.0/100 000, and among obese females in this age group the incidence climbs to 7.9–21.4/100 000. Case-control studies confirm that obesity and recent weight gain of as little as 5% are more common among patients with IIH than among controls.
When men develop IIH, they tend to be either in a similar age distribution to affected women, or slightly older, and they are also usually obese. However, when pseudotumor cerebri syndrome in a man is suspected, other responsible etiologies (see later discussion) should be excluded. Sleep apnea may be more prevalent in men with IIH.
Patients with a normal body mass index and age older than 50 years can occasionally develop IIH. IIH in children is discussed in more detail at the end of this section.
Secondary Pseudotumor Cerebri Syndrome Associated With Medical Conditions and Medications
Box 6.3 lists the most notable medical conditions and medications that are associated with secondary pseudotumor cerebri syndrome, and affected patients satisfy the revised diagnostic criteria for PTCS. More comprehensive lists have been published elsewhere.
Anemia. Pseudotumor cerebri syndrome has been associated with several forms of acquired anemia, including iron deficiency, aplastic anemia, hemolytic anemia, and sickle cell disease. The mechanism by which anemia causes PTCS is unclear, but it has been theorized to result from tissue hypoxia leading to increased capillary permeability or abnormalities in hemodynamics leading to increased cerebral blood flow (high-flow state).
Steroid withdrawal and corticodeficient states. Steroid withdrawal (not steroid use) is a well-recognized, but not well-documented, risk factor, most commonly occurring in children receiving chronic corticosteroid therapy for respiratory, renal, or dermatologic disorders. Discontinuation of a short course of steroids taken for a few days or weeks is not a risk factor. Reports of PTCS occurring in corticosteroid-deficient states such as Addison’s disease, adrenocorticotropic hormone (ACTH) deficiency, primary and secondary hyperaldosteronism, and following removal of an ACTH-secreting pituitary adenoma have also been reported.
A possible association between papilledema and Addison’s disease (adrenal insufficiency despite elevated ACTH levels) has been suggested when glucocorticoid and mineralocorticoid replacement resulted in resolution of symptoms in two reports, with one patient requiring additional treatment with acetazolamide. Conversely, we have seen a patient who developed PTCS following removal of a long-standing ACTH-secreting pituitary tumor (Cushing disease; see Chapter 7 ).
Synthetic growth hormone . First reported in 1993, there have been multiple cases of secondary pseudotumor cerebri syndrome in children treated with recombinant (biosynthetic) human growth hormone (GH). In a large database analysis, the prevalence of PTCS in the GH-treated population was approximately 100 times greater than in the normal population. It appears that risk factors such as obesity, Turner syndrome, chronic renal failure, Prader–Willi syndrome, and delayed puberty can increase the risk of developing PTCS in this setting.
It has been proposed that GH passes the blood–brain barrier and acts locally to increase levels of insulin-like growth factor 1 (IGF-1), which in turn increases CSF production from the choroid plexus. Furthermore, it seems as though aggressive GH dosing places a child at a higher risk of developing PTCS; thus starting hormone therapy at the lowest recommended dose, with prudent gradual titration to higher doses if needed, has been advised.
Tetracycline derivatives . The evidence regarding the role of tetracycline and its synthetic relative, minocycline, in PTCS is convincing. They are commonly prescribed drugs, especially for acne. A true association was suggested in many affected patients who improved following removal of the drug and recurrence in some who then restarted the medication. A combination of other factors, including genetic susceptibility, female gender, and obesity, may predispose some individuals to developing PTCS when these medications are used.
Vitamin A, all-trans retinoic acid, and related compounds . Vitamin A intoxication may produce signs and symptoms consistent with PTCS. In a prospective study on adults, hypervitaminosis, either secondary to increased levels, altered metabolism, or hypersensitivity to vitamin A, was shown to be associated with PTCS. Infants given vitamin A supplementation were more likely to develop bulging fontanelles than those who did not receive supplementation. There have been several reports of cases of PTCS after acne treatment with isotretinoin (13-cis retinoic acid), a vitamin A derivative, with or without tetracyclines (discussed previously). Combination therapy seems to increase the risk.
In addition, there have also been several reports on the development of PTCS in patients with acute promyelocytic leukemia (APML) treated with all-trans retinoic acid (ATRA), a vitamin A derivative. Several studies have shown that children, especially those younger than 8 years, are more sensitive to the effects of ATRA on the central nervous system than are adults. Therefore, it has been suggested that lower-dose regimens of ATRA should be considered in children to avoid potential side effects such as the development of PTCS.
Systemic lupus erythematosus . Lupus has been described as causing PTCS. The mechanism is unclear, but patients may be predisposed because of renal insufficiency or a hypercoagulable state.
Renal failure and transplantation . Purportedly, children with impaired renal function may be at higher risk of developing PTCS. It has also been suggested that those who undergo renal transplantation may also be at greater risk posttransplantation. In one retrospective analysis of children undergoing renal transplant in the United Kingdom over an 11-year period, it was claimed that 4.4% developed PTCS posttransplantation. However, it must be noted that almost all of the reported patients were treated with chronic immunosuppressive medication, including corticosteroids, and many had other risk factors, including obesity and treatment with GH, that could have also increased their risk of developing PTCS.
Pulmonary disease . Elevated intracranial pressure and papilledema may develop in the setting of respiratory insufficiency as a result of hypercapnia-induced cerebral vasodilation. These patients can be distinguished by their lethargy, peripheral retinal hemorrhages (due to the venous hypertension), arterial blood gas results, and high serum bicarbonate.
Obese patients with Pickwickian syndrome (sleep apnea and obesity hypoventilation syndrome) may develop papilledema, and it is easy to mistakenly diagnose them with IIH. Excess fat in the hypopharynx leads to obstructive sleep apnea, chronic hypoxemia and hypercapnia, pulmonary hypertension, right-sided heart failure, and venous hypertension. The papilledema tends to respond to treatment of the lung abnormalities, including oxygenation, positive airway pressure, and weight reduction, under the direction of a pulmonologist. If there is mild visual field loss associated with the disc swelling, acetazolamide can be added.
Questionable and mistaken associations . The literature is replete with purported disease and drug associations, but many published cases must be reviewed skeptically because they fail to satisfy the revised diagnostic criteria. In some patients the neurologic examinations aside from cranial neuropathies were abnormal, and in others the CSF profile was abnormal due to pleocytosis.
Mechanism of Idiopathic Intracranial Hypertension
The cause of IIH is unclear, but any explanation must account for elevated intracranial pressure with normal neuroimaging (without hydrocephalus), CSF constituents, and neurologic examinations. Decreased CSF absorption by the arachnoid villi has been cited as the most likely explanation suggested by radioisotope cisternography and other observations. It is possible that decreased CSF absorption is a secondary phenomenon, resulting from compression of the arachnoid villi by elevated intracranial pressure from any cause. Recently, more attention is being directed beyond just the role of the arachnoid villi in CSF absorption to that of the extracranial lymphatics, which can amount to 50% of this process.
Abnormal CSF pressure gradients caused by increased intracranial venous pressure may also account for decreased absorption. Elevated intraabdominal pressure secondary to obesity may increase pleural pressure and cardiac filling pressure, thereby leading to increased intracranial venous pressure, and elevated intracranial pressure has been a postulated mechanism. However, the validity of this mechanism has been questioned.
King et al. performed cerebral venography and manometry in patients with IIH, and they found consistently elevated venous pressures. In addition, narrowing of the transverse (lateral) sinuses has been demonstrated in many patients with IIH ( Fig. 6.16 ), suggesting possible abnormalities in venous blood flow. It is unclear whether these pressure and anatomic abnormalities are the cause or the consequences of IIH, but the latter is more likely. Previously, it was thought that unrecognized thrombi may be the cause of tapered stenoses and filling defects in transverse sinuses in patients with pseudotumor. However, the elevated venous pressures and sinus narrowing often, but not always, resolve with lowering of CSF pressure. This implies that increased intracranial pressure caused the elevated venous pressures and collapse of the walls of the transverse sinuses.
Elevated brain volume secondary to cerebral edema or increased cerebral blood volume has also been proposed, but the pathologic evidence is unconvincing. An increased rate of CSF formation is also unlikely, as choroid plexus papillomas tend to cause hydrocephalus.
Recent studies have shown that both serum retinol binding protein (RBP) and levels of retinol and vitamin A in the CSF are elevated in those with IIH compared with normal controls. It has been proposed that excess retinol and RBP in the serum are transported to the CSF, where retinol is toxic to arachnoid granulations, thereby disrupting CSF absorption. Alternatively RBP could alter aquaporin expression or act as a signaling molecule, in either case leading to abnormal CSF secretion by the choroid plexus or CSF absorption by the arachnoid villi. However, the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) did not find any evidence of vitamin A toxicity in the blood or sera of patients with IIH.
The association between IIH and female gender and obesity suggests an endocrine basis for the disorder. Recent theories have unified various neuroendocrine effects on the mineralocorticoid receptor (MR) as a possible mechanism for the increased CSF production and intracranial pressure in secondary PTCS. The mineralocorticoid receptor is abundant in the choroid plexus epithelial cells, which regulate CSF production. When mineralocorticoid receptor or its downstream pathways are activated, this can create an osmotic gradient to drive CSF production and pressure. Furthermore, corticosteroids in many instances effectively treat pseudotumor cerebri, and corticosteroid withdrawal is associated with pseudotumor cerebri, suggesting that corticosteroids have an effect on CSF dynamics. A pathway governing CSF production or absorption at the level of the choroid plexus may be a key mechanism for secondary PTCS in patients with hyperaldosteronism, obesity, hypercortisolism, hypervitaminosis A, and recombinant GH.
In summary, the mechanism is likely to be decreased CSF absorption due either to dysfunction at the level of the arachnoid villi or lymphatics or to elevated intracranial venous pressures. The association of elevated intracranial pressure and many other medical conditions and medications suggests that these purported mechanisms may be the final common pathway, but the inciting factors may be multiple.
Presenting Signs and Symptoms of Idiopathic Intracranial Hypertension
The IIHTT provides the best data regarding frequency of presenting symptoms. Headache was the most common complaint, occurring in more than 80% of patients in the study. Many had related neck stiffness or retrobulbar pain, the latter sometimes exacerbated by eye movements. However, the headache features in IIH are nonspecific, as symptoms such as nausea, vomiting, and photophobia in IIH are also shared with migraine and tension headache.
Seventy percent of patients in the IIHTT reported transient visual obscurations. Diplopia (20%) and visual loss (30%) were less common ophthalmic complaints. Fifty percent of patients complained of a pulsatile intracranial noise, characterized either by tinnitus or a “whooshing.” The bruit sounds are usually subjective (internal), but occasionally they can be auscultated or externally audible. The cause of the noise is likely transmission of systolic pulsations of high-pressure CSF against the exposed walls of the dural venous sinuses, leading to turbulent blood flow through the venous sinuses. Mentation and level of alertness is normal in all patients. Gaze-evoked amaurosis (see Chapter 10 ) can also occur.
Eye movement abnormalities other than abducens palsies are unusual, but third and fourth nerve dysfunction, internuclear ophthalmoplegia, bilateral ophthalmoplegia, skew deviation, and nystagmus have been reported. Seventh nerve dysfunction is also commonly recognized and may result from brainstem shifts from elevated intracranial pressure leading to stretching and compression of the extraaxial facial nerve in the bony facial canal. Hemifacial spasm has also been reported. In addition, trigeminal and acoustic neuropathies have been observed.
Less-specific symptoms of elevated intracranial pressure such as distal extremity paresthesias, joint pain, and low back pain are not uncommon in patients with IIH. These symptoms may be related to nerve root irritation or spinal root pouch enlargement. CSF rhinorrhea or otorrhea are also possible but unusual presentations.
The IIHTT also showed that quality of life for these patients is reduced, likely due to vision loss and headache more than obesity.
Neuro-Ophthalmic Findings in Idiopathic Intracranial Hypertension
Visual loss . When it occurs, visual loss is typically insidious, and most patients are unaware of minor deficits because central vision is usually spared. Severe loss of visual acuity in pseudotumor cerebri is uncommon except when the papilledema is severe or when there is retinal involvement, such as a neurosensory retinal detachment, macular lipid exudate, or hemorrhage. Most likely, the extent of visual loss does not correlate with the frequency of transient visual obscurations, but opinions are conflicting. Sudden visual loss can occur, although often it seems to be the result of sudden awareness, or rarely from acute optic nerve ischemia or retinal artery occlusion. An uncommon but well-recognized fulminant presentation can occur, in which patients develop acute and severe visual loss over days.
Visual field testing is the most sensitive method for detecting visual loss in these patients, and the most common abnormalities are blind spot enlargement and localized nerve fiber bundle defects such as a nasal step, pericentral, partial arcuate, or arcuate field loss (see Fig. 6.13 ). Because of reasons outlined previously, we prefer to test and follow patients with computerized threshold visual fields, which tend to be more objective and reproducible. In a prospective study by Wall and George, 96% of patients had some abnormality detected on Goldmann perimetry, while 92% had deficits on computerized testing. As a cautionary note, we have encountered many patients with IIH with advanced vision loss who have had a component of functional visual loss. Often in these individuals there are confounding psychiatric, medical, and psychosocial issues. Tangent screen visual field examination may be necessary to document nonphysiologic field constriction.
Visual acuity, color vision, and pupillary reactivity are typically normal in patients with IIH. Sixth nerve palsies occur also in just a minority (approximately one-fifth). Therefore, these parameters are felt to be insensitive measures of alteration in visual function compared with visual field testing. Most experienced clinicians do not use contrast sensitivity or visual-evoked potentials in the evaluation or follow-up of patients with IIH.
Risk factors for more severe visual loss at presentation include male gender, black race, morbid obesity, anemia, obstructive sleep apnea, and acute onset.
Papilledema . Papilledema, which is required for a definite diagnosis of IIH, is uniformly present, can be asymmetric, and in uncommon instances is unilateral. In asymmetric cases, the vision loss is usually worse in the eye with the more severe swelling. Pseudopapilledema mistaken for papilledema is a common reason for a misdiagnosis of IIH. There are patients in whom intracranial pressure is elevated but papilledema does not develop (see later discussion).
Neuroimaging . MRI of the brain with gadolinium is preferred over CT with contrast to exclude hydrocephalus or any cause of elevated intracranial pressure such as a mass lesion or dural AVM. Common radiographic findings in IIH include an empty sella, dilation and tortuosity of the optic nerve sheaths, and elevation of the optic disc (see Fig. 6.16 ). Occasionally on MRI the swollen optic disc will enhance. The empty sella is thought to result from chronically elevated intracranial pressure associated with a congenitally incompetent diaphragma sella. Many patients will have “slitlike” ventricles, but in at least two studies, age-matched controls had similar ventricular sizes.
Some studies have suggested sulci effacement on CT is a helpful radiologic sign, but we have found this to be an inconsistent feature. Less common radiographic abnormalities include low-lying cerebellar tonsils, widened foramen ovale, widening of the optic canal, and narrowing of Meckel’s cave.
Others have used formal venography in the workup of their patients with IIH. Because of the risks of the procedure, we have not done so. We prefer to use less-invasive, albeit less-sensitive, MR venograms in addition to regular MR sequences as a better screen for patients suspected of having a venous sinus thrombosis (see later discussion). The common narrowing of the transverse sinuses demonstrated on MR venography was discussed previously.
Cerebrospinal fluid . After normal neuroimaging, a lumbar puncture is necessary to rule out meningitis (for example) and to document the CSF opening pressure. When bedside LPs are difficult to obtain due to patient obesity, fluoroscopically guided LPs may be necessary. Of note, nearly 75% of neuroradiologists measure the opening pressure of fluoroscopic-guided LPs with the patient in the prone position, which then requires adding the needle length to the manometer when obtaining the opening pressure. There is no clinically significant difference between prone- and lateral decubitus–measured opening pressures. LPs should be performed judiciously in patients with low-lying cerebellar tonsils because of the risk of fatal herniation.
To establish a definite diagnosis of PTCS, the CSF opening pressure should exceed 250 mm CSF, the upper limit of normal for most obese and nonobese adults. Approximately 20–30 cc of CSF can be removed, although the optimal amount has not been studied. It is not necessary to measure the closing pressure. In suspected cases with a normal CSF opening pressure and no papilledema (see later discussion), for instance, invasive CSF monitoring may be considered to establish whether headache correlates with peaks in CSF pressure. The cell count and glucose should be normal and the protein normal or low. One study found an inverse relationship between CSF opening pressure and CSF protein, while another refuted this and documented a CSF protein level <20 mg/dl in only 26% of patients. Many patients experience relief of their headache after the first LP. Serial LPs, either to withdraw more fluid or follow the CSF pressures, have a limited role in the management of this disorder (see the next section).
Other imaging modalities . The use of SD-OCT to assess and follow papilledema is discussed in the previous section.
Management of Idiopathic Intracranial Hypertension and Secondary Causes of Pseudotumor Cerebri Syndrome
While the diagnosis requires a neurologist, the management of patients with IIH and secondary causes of PTCS also requires the skills of an ophthalmologist or neuro-ophthalmologist to assess the vision and fundi. The initial evaluation of a patient with suspected pseudotumor cerebri should include complete ophthalmic and neurologic examinations and computerized visual field testing. The MRI and LP, in that order, should then be performed. Follow-up examinations should include assessment of visual fields, visual acuity, color vision, pupillary reactivity, ocular motility and alignment, and fundus appearance. Patients should be followed either weekly or biweekly initially, then, if vision stabilizes or improves, the intervals between examinations can be lengthened. To monitor disc swelling, fundus photographs can be taken at presentation, then again once the papilledema resolves. The latter serves as a reference should the patient’s symptoms recur. Potentially inciting risk factors, such as systemic lupus erythematosus or Addison’s disease, should be treated, and offending medications such as tetracycline or vitamin A should be discontinued.
Corbett and Thompson have emphasized that treatment decisions should not rest on the frequency of transient visual obscurations, presence of diplopia, severity of the papilledema, or CSF opening or closing pressure. Instead, the modern management of PTCS is based largely upon the level of visual loss, as additional therapeutic strategies should be guided by visual fields and visual acuity ( Table 6.5 ). For the most part, patients with IIH are treated medically and strongly encouraged to lose weight.
