Papilledema

Jade S. Schiffman, MD · Rosa A. Tang. MD, MPH

Introduction

Papilledema is a condition that is usually reflected in both eyes as bilateral disc edema. It is secondary to raised intracranial pressure (ICP), and often denotes a serious process. The cause of raised ICP cannot be determined by looking into the eyes. Patients with papilledema require an urgent evaluation because elevated ICP may be caused by a process that, if not reversed, may lead to death or serious neurological sequelae. Papilledema may not be life-threatening, but it is vision-threatening. In this tutorial, an overview of papilledema and its causes is provided, as well as a brief review of the ways in which vision loss from papilledema may occur.

The causes of papilledema are divided into two groups:

1. Conditions with an abnormality of neuroimaging and/or cerebrospinal fluid (CSF) content, including mass lesions, meningitis, and hydrocephalus.

2. Conditions with normal neuroimaging and CSF content. Patients have raised ICP and papilledema, but no obvious cause. This condition is called pseudotumor cerebri syndrome because it may mimic a brain tumor with increased ICP. Secondary pseudotumor cerebri conditions are described below. Primary pseudotumor cerebri or idiopathic intracranial hypertension is a syndrome in which no obvious offending agent is found. The syndrome is seen mostly in young obese woman and children.

It is important to note that not all cases of disc swelling are due to raised ICP. There are 11 causes of optic disc edema (Slide 1). Discrimination among all of the causes of disc edema is related to careful history, detailed examination, and understanding of these entities.

Slide 1

Slide 2

This tutorial is confined to disc edema due to ICP, which is known as papilledema. Disc edema is usually associated with elevation of the optic nerve head, although not all cases of optic nerve elevation are secondary to swelling (Slide 2). Usually, elevated discs that are not swollen are referred to as pseudopapilledema. A common condition that may mimic papilledema is optic disc drusen (Slides 3 and 4). In this condition, the disc is elevated due to material deposited at the level of the lamina; however, the disc is not swollen. To diagnose papilledema, one must prove that the ICP is elevated. A papilledema may be suspected if a patient has bilateral optic disc swelling. Once the ICP is proven to be elevated, the term papilledema is appropriate.

Slide 3

Slide 4

Mechanisms of disc swelling depend on cause. In most cases of disc swelling, the mechanism of axoplasmic flow stasis that occurs in the region of the lamina cribrosa is the underlying cause (Slide 5).1 The mechanism of axoplasmic flow stasis in papilledema is discussed in the next section. In other cases of disc edema, the mechanism of axoplasmic flow stasis is related to the particular pathology. For example, in anterior ischemic optic neuropathy (ischemia of the anterior portion of the optic nerve) the mechanism of axoplasmic stasis is due to the ischemia. Axons abutting the lamina cribrosa cause swelling and impede the axoplasmic flow (Slide 6). In cases of papillitis or anterior optic neuritis, the inflammation abuts the lamina cribrosa, causing swelling, which also impedes axoplasmic flow (Slide 7). In cases of extreme elevation of intraocular pressure (IOP) or extreme depression of IOP (hypotony), the lamina cribrosa is the source of the axoplasmic flow barrier (Slide 8) due to its mechanical change. The lamina cribrosa bows backward in cases of extreme increased IOP and bows inward in cases of hypotony. There are other causes of disc edema that may not be wholly due to an axoplasmic transport problem . For example, in venous occlusions, the edema of the disc may be, in part, interstitial edema due to lack of venous return and transudation of fluid into the disc head (Slide 9). Additionally, uveitis may cause prostaglandin release that may lead to transudation of fluid into the disc head (Slide 9). Some congenital disorders also mimic disc edema (Slide 10).

Slide 5

Slide 6

Slide 7

Slide 8

Mechanisms of Disc Swelling

The following are mechanisms of disc swelling in papilledema:

• The increased ICP is transmitted to the subarachnoid space.
• The subarachnoid space encircles the optic nerve 360°.
• The subarachnoid space stops at the globe. Here, the subarachnoid space encircles the distal optic nerve and mechanical pressure from the fluid encircling the nerve is transmitted to the lamina cribrosa.
• The lamina cribrosa is the posterior sclera containing apertures through which approximately 1.2 million nerve fibers travel from the retina toward the optic chiasm. The mechanical pressure of the surrounding CSF under elevated pressure on the lamina cribrosa causes the axoplasmic flow in this region to be impeded (Slide 11).
• Radioactive tracer studies have determined that axoplasmic flow becomes stagnant at the region of the lamina cribrosa when there is raised ICP and papilledema.
• Axoplasmic flow stasis occurs first in the slow axoplasmic transport system.
• Axonal distention or "constipation" causes a secondary delay in fast axoplasmic transport system.
• Accumulation of both slow and fast components of axonal transport in the region of lamina cribrosa leads to distension of the 1.2 million axons, which results in an edematous optic
• The postlaminar optic nerve is usually normal.
• Vaginal subarachnoid spaces around the optic nerve are distended, which may be assessed with an orbital ultrasound and/or a magnetic resonance image (MRI).

Slide 9

Slide 10

Slide 11

Measurement of ICP

The following are parameters for measuring ICP:

• Intracranial hypertension is seen with ICP values of more than 200 mm of water when the lumbar puncture is performed with a patient of normal weight in the lateral recumbent position. In obese patients, the ICP may increase to 230 mm to 250 mm of water and still be considered normal.
• Normal CSF pressure varies between 100 mm and 200 mm of water in a nonobese patient.
• Diurnal fluctuations of ICP occur under normal conditions so that one determination of ICP may not be diagnostic with regard to the presence of high ICP.²
• ICP value can have wide variations in the same patient.
• ICP increases with Valsalva maneuvers such as straining, coughing, holding breath, and vomiting. It is not unusual for patients to have a spinal tap to increase their intra-abdominal pressure and, thus, elevate the ICP. Therefore, the elevated ICP may be falsely interpreted as being the ICP under normal conditions.
• With lumbar puncture, many complications exist including bleeding into the subarachnoid space (patients on coumadin or heparin should not have a spinal tap unless weaned from the medication if possible). Rarely, spinal meningitis may be induced. If the cause of intracranial hypertension is due to mass or asymmetric pressure elevations within the brain, a lumbar puncture may lead to herniation and respiratory arrest. Therefore, a spinal tap should only be performed on a patient who does not have a risk of herniation. However, herniation is seldom due to the performance of imaging preceding the lumbar puncture in most cases. The neurosurgery department should be consulted immediately when patients with intracranial mass lesions or asymmetric ICP (e.g., sagittal sinus thrombosis) require a spinal fluid analysis.

Clinical Signs for Diagnosis

Mechanical signs of papilledema include (Slide 12):

• Elevation of optic nerve hypoplasia (ONH). Each 1 mm of elevation represents 1 D, as seen with the direct ophthalmoscope.
• Blurring of the disc margins.
• Filling of the physiologic cup.
• Edema of the peripapillary nerve fiber layer (NFL) with lack of luster and a possible subtle grayish appearance. The normal NFL superficial linear light reflex is lost.
• Retinal striae may be horizontal, oblique, or circumferential. When the striae are circumferential around the disc, they are referred to as Paton lines (Slide 13).
• Chorioretinal folds, which are usually horizontal.

Slide 12

Slide 13

Vascular signs of papilledema include (Slide 14):

• Spontaneous venous pulsations. If these pulsations were known to be present and then disappear, this may be the first vascular sign of increased ICP. However, 20% to 25% of the normal population do not have observable spontaneous venous pulsations, or one eye may have it while the other eye does not.³
• The vessels on the disc margin, as well as on the disc surface, become faded as they are buried within the swollen nerve fibers.
• Venous engorgement and tortuous arterioles surrounding the disc.
• Hyperemic disc due to dilation of capillaries on the disc surface.
• Hemorrhages in the peripapillary region as well as on the disc head itself.
• Splinter NFL-related hemorrhages may be seen off disc. The number is believed to correlate with the speed of development of intracranial hypertension.²
• Peripapillary edema and cotton-wool patches.
• Hard exudates in a fan or star shape are more prominent nasally to the fovea. In advanced cases, hard exudates may appear in the superficial disc substance as pseudodrusen.
• Microaneurysms may form on the disc surface.
• The presence of retinal hemorrhages, venous engorgement, or exudates have no prognostic significance.
• Rarely, subhyaloid hemorrhages, vitreal hemorrhages, retinal periphery hemorrhages, and macular and peripapillary choroidal neovascular membranes may be seen (Slide 15).
• Optociliary shunt vessels may appear late in the course due to the obstruction of the retinal venous drainage. These have also disappeared when the disc edema resolves favorably (Slide 15 ).²

Slide 14

Slide 15

Development and Course

The development of papilledema is dependent on its cause. The most rapid appearance of papilledema is caused by entities that facilitate a rapid increase in the ICP, as seen with intracranial hemorrhage within 2 to 4 hours.² The more rapid the development of papilledema, the greater is the danger of sight loss from postpapilledema optic atrophy if the increased ICP does not abate. Papilledema can progress from Frisen scale stage 0 to fully developed papilledema in a few hours (Table 1). In a trauma, the onset of papilledema can be delayed, constituting a diagnostic challenge. Papilledema may persist or worsen for several days up to 2 weeks following relief of increased ICP. Vascular signs are first to improve following relief of increased ICP. Last to improve is the mechanical sign of peripapillary NFL edema.

Table 1. The Frisen scale for grading papilledema⁴

Stage 0. Blurring of superior and inferior poles of disc.
Stage 1. Obscuration of nasal borders of disc, graying opacity of radial NFL, concentric folds.
Stage 2. Obscuration of all borders and nasal elevation.
Stage 3. Moderate obscuration and elevation of all borders and some vessels, leaving the disc with an early peripapillary halo.
Stage 5. Dome-shaped protrusion (champagne cork appearance) of the disc with smoothly demarcated peripapillary halo and total obliteration of disc vessels as well as the cup. There may also be marked hyperemia, vessel tortuosity, hemorrhages, hard exudates, and cotton wool spots (Slide 16).

Slide 16

Papilledema in some patients may persist for months and, rarely, years if the ICP remains elevated without change in the swelling or visual field. In other patients, papilledema may progress to postpapilledema optic atrophy. The rate of development of postpapilledema optic atrophy depends on the cause of the ICP elevation and may be seen as early as 5 to 6 weeks following its onset in cases of rapid development of papilledema (e.g., sagittal sinus thrombosis) and in cases where the pressure is not significantly lowered. In such cases, bilateral blindness may result. Postpapilledema may progress into optic atrophy with pallor, disc flattening, gliosis, sheathing, and narrowing of retinal vessels if intervention does not occur. Pallor represents axonal loss and is seen with loss of vision or visual field. High water marks in the peripapillary region may be clues to the presence of previous disc edema. (Slide 17).

Slide 17

Postpapilledema optic atrophy may leave a patient with various visual scenarios dependent on the persistence of raised ICP, other risk factors, and predisposition of the affected nerve. The visual scenarios range from minor ventricular fibrillation cuts such as nasal step and arcuate scotomas to severe peripheral constriction mimicking end-stage glaucoma where a patient may be legally blind despite good central vision. Once central vision is affected, the vision may be totally lost (Slide 18). Narrowing of arterioles with or without sheathing is the most ominous sign regarding threat of permanent loss of vision. Another ominous sign is loss of peripapillary NFL.² Most cases of papilledemas are bilateral and asymmetric (see below). In up to 2% of patients with raised intracranial hypertension, strictly unilateral papilledema may be seen.² Rarely, superimposed anterior ischemic optic neuropathy (AION) may occur suddenly with severe visual loss. Postdecompression optic neuropathy involves patients who may become blind soon after they are treated for the cause of the increased ICP.⁵ The most important test to determine if and how fast a particular patient is developing postpapilledema optic atrophy is quantitative visual field testing.

Slide 18

The most important medical decision for the clinician following diagnosis of a patient with papilledema from any cause is to determine how often visual fields should be followed and when intervention should occur, medically and/or surgically. This requires that the clinician know how to interpret ventricular fibrillation artifacts, unmask any superimposed functional overlay, and correlate visual field changes and visual acuity changes with pupillary responses. If a patient does not have papilledema, there may still be a mass lesion causing increased ICP. Not infrequently, slow growing intracranial lesions with significant mass effect do not cause clinically visible papilledema. In fact, a series of cases describing clinical findings in adults and children with brain tumors showed papilledema present in only 28 % of adults with brain tumors,⁶ whereas 65% of children with brain tumors were found to have papilledema.⁷

Asymmetric or Unilateral Papilledema

Asymmetric papilledema may have some localizing value in cases of intracranial abscesses (Slide 19). A more swollen disc is usually ipsilateral to the lesion.² Most unilateral cases have asymmetric papilledema, although true unilateral disc swelling has been reported in patients with pseudotumor cerebri (Slide 20). Unilateral disc swelling may also occur in cases of contralateral optic atrophy (Foster-Kennedy syndrome). Anomalous discs do not swell with increased ICP (Slide 21). Unilateral papilledema may be seen if the non-swollen nerve has nonpatent perioptic meningeal spaces. Patients with segmental atrophy of the optic nerve may only have swelling in the portion of the discs that are not atrophied. For example, patients with lesions anterior to the lateral geniculate body who also have increased ICP may have a band atrophy configuration, and swelling may occur in the area of remaining fibers.⁸

Slide 19

Slide 20

Slide 21

Clinical Diagnosis

Diagnosing papilledema may be challenging and clinically difficult if using only direct ophthalmoscopy. Diagnosis may require the use of a slit lamp stereoscopic viewing technique using special lenses such as noncontact lenses (e.g., Rhuby, 78 D, 90 D, and superfield) or contact lenses for better visualization. In other cases, stereo photographic analysis and red free photos may be most helpful, particularly in early subtle cases, which allow documentation of changes over time. Orbital ultrasonography is helpful in distinguishing true disc edema from pseudo-disc edema due to optic disc drusen. Additionally, an experienced ultrasonographer may determine if there is subarachnoid fluid around the optic nerve by the 30° test⁹ (Slide 22).

Fluorescein angiography may also be helpful in early cases when there is subtle partial disc blurring. Findings in the early frames include disc capillary dilation, dye leakage, and microaneurysm formation. Findings in late frames include dye leakage beyond disc margins and late disc fluorescence. However, a normal fluorescein angiogram test does not preclude the diagnosis of papilledema^10,11 (Slide 23).

Slide 22

Slide 23

Clinical Manifestations

Ocular Manifestations
Ocular manifestations of papilledema associated with all forms of increased ICP include the following:

Early papilledema typically does not affect central acuity, color vision, or pupillary function.
• Patients may be totally asymptomatic and have papilledema on fundoscopy (Slide 24).
• Contrast sensitivity is normal initially and may be a good early indicator of optic nerve dysfunction.
• Transient visual obscurations are described by patients as brief episodes of monocular or binocular blurring that last a few seconds and may be positional. These obscurations are believed to be related to local transient disc ischemia, rather than being cortical in nature. They may be described as blackouts or grayouts of vision.²
• Visual field defects are common. Early disc edema causes enlargement of the blind spot in more than 90% of patients. As papilledema progresses, there is usually inferior nasal loss (mimicking the nasal step of glaucoma). Generalized concentric field constriction (Slide 25), arcuate defects, paracentral defects, and tunnel vision with preserved temporal islands (similar to glaucoma) progressing to complete blindness may be seen with severe optic nerve dysfunction due to chronic disc edema leading to postpapilledema optic atrophy. These findings tend to correlate with the degree of NFL loss.¹²
• Nerve fiber layer changes are present in 60% to 70% of chronic cases. These changes usually correlate with the severity of the optic nerve dysfunction and precede the visual field loss.
• Diplopia due to sixth cranial nerve paresis is a nonlocalizing sign of papilledema and may be seen in up to 30% of cases. Diplopia may be unilateral or bilateral. Other cranial nerve paresis or motility disorders are uncommon in papilledema unless due to specific etiologies (e.g., Parinaud syndrome in hydrocephalus and, rarely, forth nerve palsy in hydrocephalus).
• Uveitis may be the only clue for the cause of the increased ICP as might occur in the uveal-meningeal syndromes (e.g., sarcoid, syphilis).

Slide 24

Slide 25

Nonfocal Manifestations
Nonfocal manifestations of papilledema associated with all forms of increased ICP include the following:

• Most patients with papilledema experience headaches that occur daily, are moderate in intensity, worsen with eye movement, and on occasion are described as retro-ocular. Headaches may be severe upon waking and improve toward the latter part of the day.
• Occasionally, patients experience nausea and vomiting. These cases may mimic common migraines if nausea and vomiting are seen with throbbing headaches.
• Neck pain and back pain may also be present with neck stiffness in some cases, especially if there is concomitant meningeal irritation or impending herniation.
• Pulsatile tinnitus described as a heart beat or whooshing sound in one or both ears is seen in 60% of patients and may be due to a local process in the labyrinth or remote in the venous sinuses.²

Focal manifestations of papilledema are associated with all forms of increased ICP in the pneumonic MOVIES (see below) include the following:

• Focal neurological signs may include weakness and paresthesias in cases of intracranial mass lesions (e.g., tumors, abscesses, blood clots).
• Cognitive changes may occur that are localized (e.g., aphasia) or nonlocalized (e.g., global change in higher cortical functions) in cases in which there is hydrocephalus, a mass lesion, or meningitis.
• Changes in level of consciousness, irritability (more common in children), dizziness, unsteady gait, and seizures may also be seen.
• Motor rigidity is an ominous sign in most cases signaling tentorial herniation.

Understanding CSF Dynamics

The maintenance of a normal ICP level is multifactorial and depends on CSF production, contents of the brain, CSF drainage, and resorption through the arachnoid granulations. After CSF formation by the choroid plexus within the ventricular system, the CSF exits from the lateral ventricles through the foramen of Monro into the third ventricle. CSF then flows caudally through the cerebral aqueduct of Sylvius in the midbrain into the fourth ventricle. It leaves the ventricular system through the foramina of Magendie and Luschka to enter the subarachnoid space. These foramina are not considered to be within the ventricular system, but rather in the CSF outflow system from the fourth ventricles to around the subarachnoid space. Here, the majority of the CSF is absorbed over the convexities, mostly by the arachnoid villi within the arachnoid granulations. The remainder of the CSF flows rostrally from the posterior fossa through the ventral basal cisterns, the tentorial notch to the chiasmatic cisterns, and to the cisterns of Sylvian fissure. Dorsally, the CSF flows to dorsal cisterns.

Rate of CSF Production and Volume
Normally, the rates of CSF production average 0.55 mL/min to 1 mL/min. The rate of production normally equals the rate of absorption. The total CSF volume averages 100 mL to 150 mL in adults and 60 mL to 140 mL in children. Rapid increases in CSF volume, adding an average of 70 mL to 100 mL to the normal value, raise the ICP to levels that are lethal. The CSF replenishes itself approximately three times daily.²

Mechanisms of Increased ICP
Any decrease in the CSF resorption mechanism, increase in the resistance to the CSF flow, or blockage along the CSF flow pathway may increase the CSF volume and raise the ICP. Increased protein content of the CSF as seen in certain tumors may also cause increased ICP (Guillain-Barre, ependymomas, and spinal tumors) by raising the CSF osmotic pressure and blocking the absorptive pathways. Increases in volume due to cerebral edema and increases in intracranial total mass volume due to space occupying lesions may also cause increased ICP.

Increased production of CSF as seen with choroidal plexus papilloma may also cause intracranial hypertension. Poor uptake of CSF at the level of the arachnoid granulations is postulated to occur in cases of pseudotumor cerebri (IIH) and uremic syndromes.

In addition, the ICP is also dependent on the venous pressure so any increase in this pressure, as seen with extracranial disease (superior vena cava obstruction, congestive heart failure) and intracranial disease (cerebral venous sinus thrombosis), may cause intracranial hypertension.

Diagnostic Workup

A basic diagnostic workup includes the following:

• Taking a history is the most important step.
• Imaging. Computed tomography (CT) scan of the brain with and without contrast and MRI of the brain with and without contrast.
• MRI changes in papilledema. flattening of posterior sclera (Slide 26), widening of perioptic space (Slide 27), more obvious laminar portion, vertical tortuosity (Slide 28), and empty sella (Slide 29).¹³
• If there is no mass or hydrocephalus, a lumbar puncture should be performed: opening pressure, protein and glucose, cultures and cytology.
• The possibility of malignant hypertension is always present. The blood pressure must be checked.
• Other testing (labs, electroencephalography, angiography, etc) will depend on the findings of the initial studies.

Slide 26

Slide 27

Slide 28

Slide 29

Causes of Papilledema

Papilledema may be due to any cause of increased ICP. A patient who has presumed papilledema should be considered a medical emergency because some causes of papilledema may indicate serious disease that may lead to herniation and death. Two pneumonics - MOVIES and U DEVILS - have been created to quickly determine the differential diagnosis of raised ICP.

MOVIES refers to the conditions that must immediately be excluded or included on an emergent basis.

MOVIES (Slide 30):

Slide 30

Once the above criteria have been excluded with a blood pressure test, neurological evaluation, MRI with and without contrast, and spinal fluid analysis, and assuming all of the above are normal except for raised ICP, the next step is to determine if the patient has a condition raising ICP that is unassociated with a mass lesion or any of the conditions mentioned above.

Secondary pseudotumor cerebri syndromes is the term for raised ICP due to an underlying cause once MOVIES are excluded. The pneumonic U DEVILS defines these syndromes.

U DEVILS:

U	Uremia
D	Drugs (tetracycline, lithium, acutane, nalidixic acid, retinoids, cyclosporin, kepone, amiodarone, growth hormone, norplant, sulfa, vitamin A and supplements, e.g., retinoids )
E	Endocrine (hypoparathyroidism, Addison disease)
V	Vitamin A overuse
I	Iron deficiency anemia
L	Last menstrual period (pregnancy, birth control such as Norplant, menstrual irregularities)
S	Sleep apnea14 Steroid withdrawal

If MOVIES and UDEVILS are excluded and the patient is a young obese female who recently gained weight, the likely diagnosis is primary pseudotumor cerebri syndrome or idiopathic intracranial hypertension.

Syndromes of Increased ICP

Of all of the entities that cause raised ICP (e.g. MOVIES and U DEVILS), only three are discussed in this tutorial:

• Obstructive hydrocephalus (O in MOVIES)
• Venous cerebral thrombosis (V in MOVIES)
• Primary pseudotumor cerebri

Hydrocephalus

Increased ICP may be caused by obstructive hydrocephalus, which is defined as enlargement of the intracranial ventricles due to some obstruction within the ventricular system or to the blockage of CSF absorption. Additionally, hydrocephalus with increased ICP is rarely due to overproduction of CSF. Hydrocephalus may also result from a compensatory mechanism in cases where there has been loss of cerebral tissue. This type of compensatory hydrocephalus is due to loss of brain substance referred to as atrophy and is usually without increased CSF pressure.

There are three mechanisms for the appearance of intracranial hypertension from hydrocephalus:

1. Obstruction/blockage of CSF ventricular flow, which is seen with aqueductal stenosis or obstruction of the fourth ventricle from a cerebellar tumor.
2. Decreased absorption of CSF as might occur both during the acute and the residual effect of meningitis and subarachnoid bleeding.
3. CSF overproduction, as seen with choroidal plexus papilloma.

The obstructive mechanism is divided into noncommunicating and communicating. During noncommunicating obstruction, flow obstruction occurs inside the ventricular system, including the fourth ventricle, and is due to tumors, aqueductal stenosis and, more commonly, arachnoidal cysts. Communicating obstructions means that flow obstruction occurs within arachnoid granulations in the sub-arachnoid space or cisterns distal to the ventricular system, which causes a slower rate of ventricular dilation. This may occur due to dural sinus thrombosis, post-meningitis, post-subarachnoid hemorrhage, and in choroid plexus papilloma (high protein obstructs the outflow). Normal pressure hydrocephalus is a form of communicating hydrocephalus and is characterized by the presence of dementia, gait ataxia, and urinary incontinence that occurs in elderly individuals. The pressure is low, yet there may be a response to lowering the CSF pressure further with a shunt.

Signs and Symptoms¹⁵
Nonocular symptoms include headaches, dementia, leg weakness and spasticity, gait disturbances, and incontinence. Ocular symptoms include all of the symptoms and signs due to increased ICP previously mentioned. The "setting sun" sign is seen in small children. There may also be two false localizing signs in addition to a sixth nerve palsy:

1. 1. Inferior bitemporal hemianopia due to posterior chiasmal compression by a dilated third ventricular supra-chiasmatic recess.
2. 2. Dorsal midbrain syndrome due to a dilated supra-pineal recess of the third ventricle as well as in aqueductal stenosis. There may be proximal bulging of the aqueduct that also adds to the pretectal compression.

Treatment Treatment should first be aimed at the underlying cause. CSF shunting procedures are often required in addition to treating the underlying disease or as the primary treatment. These shunts, however, have a high rate of failure in the first year (up to 70%).

Obstruction of cerebral venous outflow

Raised ICP may result from obstruction of the cerebral dural venous sinuses, which drain blood from the brain. Any flow impairment in the sinuses will likely lead to venous hypertension and secondary decreased CSF absorption.

Three categories have been described¹⁶:

1. If contiguous neoplasia compress the venous sinuses, clot formation may occur. This has been described with medulloblastoma, sarcomas, melanomas, parasagittal meningiomas affecting the superior sagittal sinus, glomus jugulare, and base of skull tumors affecting the jugular veins.
2. Due to contiguous infection. Although a mastoiditis is rare, septic thrombosis can occur due to thrombophlebitis.
3. 3. Associated to hypercoagulable states. Obstruction of the dural venous sinuses can also result from coagulopathies associated with pregnancy, oral contraceptive use, polycythemia, thrombocytosis, thrombocytopenia, paroxysmal nocturnal hemoglobinuria, leukemia and other forms of cancer, systemic lupus, and the antiphospholipid antibody syndrome.

An increase in the risk for thrombosis has been described in patients with antithrombin deficiency and protein C and S deficiency. Factor V Leiden deficiency has also been implicated, although there is no current evidenced-based data to support its role in isolation.¹⁷ Vasculitis associated with Behcet disease, Wegener granulomatosis, and sarcoidosis has also been implicated. In 25% of patients, the underlying cause is not identified.

Clinical Profiles
There are three distinct clinical profiles for the condition of thrombosis of the dural venous sinuses described by Purvin and colleagues as follows¹⁸:

Profile I. Intrinsic sagittal or lateral venous sinus thrombosis. Acute/dramatic onset of symptoms with:

1. Sudden and severe headache
2. Diplopia with esodeviation due to sixth cranial nerve paresis
3. Marked papilledema
4. Rapid severe visual field loss due to sudden and substantial increased ICP

Profile II. Tumor or thrombus compression of intracranial or cervical venous channels. Subacute onset of symptoms with:

1. Moderate headaches
2. Moderate papilledema
3. Not diagnosed if imaging fails to include the neck
4. Better visual prognosis
5. This may happen after radical neck dissection or venous catheterization (jugular or subclavian)

Patients with isolated intracranial hypertension as the only sign of cerebral venous thrombosis have been described and, hence, may be confused with the more benign entity of primary pseudotumor cerebri¹⁹:

Thrombosis of the transverse and sigmoid sinuses. Patients may present with seventh and/or eighth cranial nerve dysfunction.

Syndrome of deep venous drainage obstruction (internal cerebral veins, vein of Galen). Patients present more acutely with altered consciousness and long tract signs and less prominent signs and symptoms of increased ICP.

Arteriovenous malformations of the dural sinuses. Arteriovenous fistulas may cause intracranial hypertension with papilledema and no ventriculomegaly by increasing blood flow within the sinuses or by causing clot formation. If a dural arteriovenous malformation (AVM) drains into the transverse sinus the patient will complain of pulsatile tinnitus. In this group of patients, formal conventional angiography is required to delineate the anatomy, as treatment is surgical excision or embolization of the AVM when possible.

When the cerebral venous obstruction is accompanied by cortical venous thrombosis the patient may present with an acute severe encephalopathy and altered mentation, hemispheric deficits, seizures, and even herniation leading to death.¹⁸

Diagnosis is made by the clinical presentation, history of associated disorder, and proper use of imaging techniques such as contrast brain MRI and magnetic resonance venography (Slides 31 through 33). Axial computerized tomography (CT) scan of the brain with contrast may show the "empty delta sign." An underlying cause should be sought and treated considering that in one of four patients no underlying cause is found.

Slide 31

Slide 32

Slide 33

Treatment is directed toward finding the underlying cause and keeping patients with normal volemia because dehydration and hypotension may increase thrombosis and overhydration may worsen the already raised ICP. Anticoagulation with intravenous heparin for 5 to 7 days followed by oral warfarin for an average of 3 months is instituted unless there is evidence of hemorrhage. Interventional radiology with catheterization and urokinase infusion is controversial, as may be the use of diuretics that may worsen the thrombosis in some cases. Optic nerve sheath fenestration and/or shunting procedures are used in patients refractory to medical treatment who have progressive visual field loss.

Primary Pseudotumor Cerebri

Primary pseudotumor cerebri, also known as idiopathic intracranial hypertension syndrome (IIHS), is always a diagnosis of exclusion. This entity is seen commonly in young obese females who usually have had a recent weight gain. This diagnosis is made after MOVIES and U DEVILS are excluded.

Dandy's diagnostic criteria:

• Signs and symptoms of increased ICP such as papilledema (Slide 34)
• No focal neurological signs except for a sixth cranial nerve paresis, which is nonlocalizing
• Normal radiological studies (small ventricles)
• Normal cerebrospinal fluid except for elevated CSF pressure

Slide 34

IIHS should be considered as the "brain glaucoma" problem. Initial loss of vision is peripheral. Central visual acuity, color vision, and pupils are normal until after optic atrophy develops. First, treat medically (lower ICP) and later surgically if vision is threatened (e.g., drainage by optic nerve sheath fenestration or shunt). Patients with IIHS who also have ocular hypertension, glaucoma, or arterial hypertension, or are pregnant may develop severe visual field loss much faster.

The incidence of pseudotumor cerebri in prepuberty has no sex predilection and is not related to obesity. These patients may or may not have papilledema. Predominantly, there is irritability, somnolence, strabismus, and good response to treatment

Treatment of IIHS
Weight reduction and diuretics (Diamox [acetazolamide]) is the most common medical management of IIHS. In cases of visual field loss or in noncompliant patients, surgical intervention with optic nerve sheath fenestration and/or lumbo-peritoneal shunting procedures may be necessary.

Patient Follow-up
Visual fields with quantitative perimetry at regular intervals are the main modality of follow-up. Changes in central acuity and color vision are late findings. Contrast sensitivity changes are an early indication of optic nerve dysfunction. Stereo disc photographs are best to monitor disc changes over time, paying special attention to changes in the retinal arteriole caliber (Slide 35).

Slide 35

Treatment of Increased ICP

• Treatment of increased ICP is generally etiology driven (Slide 36).
• A mass such as hemorrhage, abscess, or tumor when present must be treated medically and/or surgically (e.g., surgical excision, antibiotics).
• A hydrocephalus must be shunted.
• Concomitant cerebral edema must be treated with steroids, diuretics, osmotic agents, or hyperventilation.
• For thrombosis, anticoagulation therapy is required.
• For sleep apnea, assisted ventilation (C-PAP) is recommended.
• Stop offending agent or reverse withdrawal (see D and S in the DEVILS pneumonic).

Slide 36

Papilledema: Long-term monitoring

If a patient has a reversible cause of increased ICP and the cause can be treated as stated above, the papilledema will also resolve. Some of these conditions can also be pharmacologically treated. For example, a brain tumor with surrounding cerebral edema may be managed with steroids. Especially dangerous are conditions that are associated with rapid development of raised ICP with intracranial bleeding (2 to 4 hours).²⁰ Additionally, cases of raised ICP without obvious edema may be treated with Diamox. Surgical modalities may be considered when a patient is on appropriate medications and does not have a reversible cause of increased ICP or a patient already has visual field loss (Slide 37). A local surgical procedure is called optic nerve sheath fenestration. The optic nerve sheath/perioptic space posterior to the globe is approached surgically via a medial conjunctival incision or a temporal orbitotomy approach to create a filter and allow CSF to drain.

Other surgical modalities include CSF drainage via the use of shunts, such as a ventricular peritoneal shunt or lumbo-peritoneal shunt. Each of these techniques drains the CSF, leading to a reduction of the pressure to a normal level. Unfortunately, both types of shunts can malfunction, requiring revisions. Additionally, there are complications of infection or overdrainage. A serious, though rare, complication is the sudden decrease of the ICP in an patient with severe papilledema, which may cause acute blindness due to anterior optic nerve ischemia.⁵

Slide 37

Management of Papilledema

Suggested Algorithm
Because the finding of papilledema constitutes a neuro-ophthalmological emergency, caution should be taken in diagnosis. Diagnosing IIHS in svelte women and children and in any man should be done with caution. Children with increased ICP may present with irritability and may be misdiagnosed. Taking blood pressure will exclude the condition of malignant hypertension. It is important to obtain a contrast CT or MRI brain scan and in many cases a magnetic resonance venogram. Noncontrast imaging may be misleading. If contrast imaging is negative, it is necessary to obtain a lumbar puncture.

If the CSF is normal except for high pressure, the causes of secondary pseudotumor cerebri, including systemic associations, collagen vascular disease, and the use of systemic medications may be excluded. The most important role of an eyecare provider is to maintain vision with the most appropriate treatment modality in those cases of chronic papilledema with associated field loss.²¹

References

1. Wirtschafter JD, Rizzo FJ, Smiley BC. Optic nerve axoplasm and papilledema. Surv Ophthalmol. 1975;20:157-189.

2. Miller N, Newman N, ed. The Essentials: Walsh & Hoyt's. Clinical Neuro-Ophthalmology, 5th ed. Baltimore, Md: Williams & Wilkins; 1999:172-195.

3. Levin BE. The clinical significance of spontaneous pulsations of the retinal vein in the retina. Arch Neurol. 1978;35:37-40.

4. Frisen L. Swelling of the optic nerve head: A staging scheme. J Neurol Neurosurg Psychiatr. 1982;45:13-18.

5. Beck RW, Greenberg HS. Post-decompression optic neuropathy. J Neurosurg. 1985;63:196-199.

6. Van Crevel H. Papilloedema, CSF pressure, and CSF flow in cerebral tumours. J Neurol Neurosurg Psychiatr. 1979;42:493-500.

7. Allen ED, Byrd SE, Darling CF, et al. The clinical and radiological evaluation of primary brain tumors in children. Part I: Clinical Evaluation. J Natl Med Assoc. 1993;85:445-451.

8. Ing EB, Leavitt JA, Young BR. Papilledema following bowtie optic atrophy. Arch Ophthalmol. 1996;114:357.

9. Galetta SL, Byrne ST, Smith JL. Echographic correlation of optic nerve sheath size and cerebro-spinal fluid pressure. J Clin Neuro-Ophthalmol.1989;9:79-82.

10. Hayreh SS, Hayreh MS. Optic disc edema in increased ICP: II. Early detection with fluorescein fundus angiography and stereoscopic fundus photography. Arch Ophthalmol. 1977;95:1245-1254.

11. Cartlidge NEF, Ng RCY, Rilley PJB. Dilemma of the swollen optic disc: A fluorescein retinal angiography study. Br J Ophthalmol. 1977;61:385-389.

12. Hedges TR III, Legge RH, Peil E, et al. Retinal nerve fiber layer changes and visual field loss in idiopathic intracranial hypertension. Ophthalmology. 1995;102:1242-1247.

13. Brodsky MC, Vaphiades M. Magnetic resonance imaging in pseudotumor cerebri. Ophthalmology. 1998;105:1686-1693.

14. Purvin V, Kawaski A, Yee R. Papilledema in obstructive sleep apnea syndrome. Arch Ophthalmol. 2000;118:1626-1630.

15. Corbett JJ. Neuro-ophthalmic complications of hydrocephalus and shunting procedures. Semin Neurol. 1986;6:111-123.

16. Liu G, Volpe N, Galetta S. Neuro-Ophthalmology: Diagnosis and Management. Philadelphia, PA: WB Saunders; 2001:214-218.

17. Kearon C, Crowfher M, Hirsh J. Management of patients with hereditary hypercoagulable disorders. Ann Rev Med. 2000;51:169-185.

18. Purvin V, Trobe J, Kosmorsky G. Neuro-ophthalmic features of cerebral venous obstruction. Arch Neurol. 1995;52:880-885.

19. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999;53:1537-1542.

20. Pagani LF. The rapid appearance of papilledema. J Neurosurg. 1969;30:242-249.

21. Corbett J. Editorial: "Pseudotumor cerebri" by any other name. Arch Ophthalmol. 2000;118:1685.