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Papilledema: The Vexing Issues

Trobe, Jonathan D MD

Section Editor(s): Hoyt, William F MD

Journal of Neuro-Ophthalmology: June 2011 - Volume 31 - Issue 2 - pp 175-186
doi: 10.1097/WNO.0b013e31821a8b0b
The Ninth Hoyt Lecture
Japanese Abstract

Papilledema has long been recognized as a valuable sign of increased intracranial pressure (ICP). But because papilledema is based on interruption of the energy-dependent process of axoplasmic flow, it appears late after a rise in ICP. Papilledema is usually present in chronically high ICP but sometimes asymmetrically in the 2 eyes and rarely in 1 eye only. Distinguishing it from other optic neuropathies that produce elevated optic discs is challenging, especially in the chronic phase, when visual function may be impaired. Papilledema is often an unrecognized cause of optic disc edema in inflammatory and compressive meningeal disorders that interfere with cerebrospinal fluid (CSF) passage through the arachnoid granulations. Its detection is particularly critical in patients with noncompliant ventricles or extraventricular blockage of cerebrospinal flow because imaging may fail to disclose conventional signs of high ICP. Therefore, patients with indwelling CSF shunts, tuberous sclerosis, chronic granulomatous meningitis, or meningiomatosis should be periodically examined for papilledema so that timely ICP-lowering measures can be instituted to preserve vision.

William Fletcher Hoyt, MD, received his medical education at the University of California, San Francisco (UCSF), followed by a year's study at the Wilmer Institute, Johns Hopkins University, under the mentorship of Frank B. Walsh, MD. Dr. Hoyt returned to UCSF in 1958 to found the neuro-ophthalmology service. During a 36-year academic career—all of it at UCSF—he authored 266 journal articles, co-authored (with Frank B. Walsh, MD) the third edition of Clinical Neuro- Ophthalmology, and trained 71 neuro-ophthalmology fellows. In 1983 he received the title of Honorary Doctor ofMedicine from the Karolinska Institute. Currently he serves as Professor Emeritus of Ophthalmology, Neurology, and Neurosurgery at UCSF. In recognition of his contributions, in 2001 the North American Neuro-Ophthalmology Society (NANOS), in conjunction with the American Academy of Ophthalmology, initiated the Hoyt Lecture to be delivered each year at the Annual Meeting William F. Hoyt, MD of the American Academy of Ophthalmology.

Departments of Ophthalmology and Visual Sciences and Neurology, University of Michigan Kellogg Eye Center, Ann Arbor, Michigan.

The author reports no conflicts of interest.

Address correspondence to Jonathan D. Trobe, MD, University of Michigan Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48109; E-mail:

William Fletcher Hoyt, MD, trained more than 70 fellows and coauthored the biblical textbook Clinical Neuro-Ophthalmology, bringing pathophysiologic rigor to a discipline that had been rich in anecdote but thin in science. His acolytes, many of whom became the leaders of the next generation of neuro-ophthalmologists, are still looking over their shoulders at the master. I am grateful for the invitation to deliver the ninth Hoyt Lecture in his honor and on a subject that greatly interested him.

Papilledema, or optic disc edema resulting from high intracranial pressure (ICP), has always intrigued physicians not merely because it may be the only accessible sign of high ICP but because it behaves differently from other forms of optic disc edema. Visual function in papilledema is relatively spared in the early stages. But if high ICP continues unabated, permanent visual impairment may occur. Who will suffer this consequence and why the optic nerves should be so selectively vulnerable to high ICP are puzzles that remain unsolved. Even the mechanism by which high ICP gives rise to papilledema is still a mystery.

I will review the development of ideas about the pathophysiology of papilledema and show how they apply to the vexing clinical issues.

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Before the 20th century, physicians labeled all forms of optic disc edema “optic neuritis.” But it was apparent that the optic disc edema associated with brain tumors lasted relatively long and produced relatively little visual impairment at outset as compared to other types of optic neuropathy. Yet if the brain tumors were unattended, disabling visual loss might occur much later, when the optic discs were flattening and turning pale. Accordingly, early in the 20th century, the term “papilledema” was adopted to distinguish this form of optic disc edema (1,2).

Physicians of various specialties put forward their ideas about how high ICP caused papilledema (1,2). Among the imaginative but ultimately incorrect postulates were compression of the veins of the cavernous sinus, transudation of parenchymal brain edema or third ventricular cerebrospinal fluid (CSF) into the optic chiasm and thence into the optic nerves, leakage of vessels within the optic discs from vasomotor instability, and a toxic substance within the CSF.

In 1910 (3) and 1911 (4), Leslie Paton, an ophthalmologist, and Gordon Holmes, a neurologist, reported the results of the first definitive light microscopic study of papilledema. It came from 50 eyes and optic nerves of 39 patients who had died of brain tumors at the National Hospital for the Paralysed and Epileptic in London (now known as the National Hospital for Neurology and Neurosurgery, Queen Square).

In this landmark publication, the authors made 3 important observations: 1) the optic discs and the retrolaminar and distal retrobulbar nerves contained excessive edema, which they assumed was extra-axonal, 2) the prelaminar axons were “varicose” and “fragmented” where they were most deviated by the optic disc swelling, and 3) the central retinal vein was dilated in the retrolaminar and prelaminar optic nerve but flattened in the subarachnoid space around the optic nerve (Fig. 1). From these observations, they concluded that papilledema came from compression of the subarachnoid portion of the central retinal vein by high ICP. This mechanical process, they believed, led to dilation of the vein's optic disc segment. Leakage from this dilated vein and its feeding capillaries caused prelaminar optic disc swelling and bending of axons, which sometimes led to their fracture.

The Paton-Holmes venous compression doctrine held sway for most of the 20th century. However, critics asked why retinal edema, hemorrhages, and cotton wool spots—features associated with occlusion of the central retinal vein—were not usually evident with the papilledema. Moreover, optic disc edema is known to be an unimpressive finding even in severe central retinal vein occlusion (2).

In 1948 came the discovery that organelles normally flow back and forth between cell bodies and their synaptic terminals in an energy-dependent process called axoplasmic transport (5). In 1976 and 1977, a flurry of publications reported electron microscopic studies on the anatomy and physiology of optic nerve axons and axoplasmic transport in acute glaucoma, ocular hypotony, and increased ICP (6-9). In all 3 conditions, electron microscopy showed edema of the optic disc that was mostly intra-axonal. Studies of axoplasmic flow within the optic nerve, as measured by the progress of tritiated leucine injected into the vitreous cavity and incorporated into retinal ganglion cells, showed that axoplasm was arrested in the region of the lamina cribrosa (Fig. 2). Considering that these 3 conditions share a high pressure gradient across the lamina cribrosa—albeit in opposite directions in acute glaucoma and ocular hypotony/increased ICP—investigators reasoned that this abnormal pressure gradient caused or contributed to the axoplasmic pileup.

As an explanation for papilledema, the doctrine of venous hypertension gave way to the doctrine of axoplasmic stasis. But still unanswered was the question of how high ICP caused this axoplasmic stasis. Was it by direct compression of axons (mechanical theory) or by reduced perfusion of axons (ischemic theory) (1,2,10-13) (Fig. 3)?

Although the mechanical theory has generally been favored, there is compelling support for the ischemic theory. For example, experimental occlusion of the ciliary arteries leads to axoplasmic stasis and axonal swelling (14,15). Fluorescein angiography in patients with papilledema shows delayed filling of the optic disc and peripapillary choroidal vessels (11). Patients with arteriosclerosis seem to be especially prone to optic neuropathy in the setting of chronic idiopathic intracranial hypertension (IIH) (16).

There are some tantalizing similarities between the optic neuropathy of papilledema and the optic neuropathy of acute systemic hypotension. First, there is a shared proclivity to affect the inferior arcuate nerve fiber bundles and to spare the maculopapillar bundles. Second, just as papilledema may be the only important neurologic finding in chronic high ICP, so ischemic optic neuropathy may be the only important neurologic finding in acute systemic hypotension (17). These phenomena converge on the ciliary arterial circle, which might be the site of acute hypoperfusion in systemic hypotension and chronic hypoperfusion in sustained high ICP (Fig. 3).

Why might the ciliary arterial circle be so vulnerable to low blood pressure and high ICP? Because it competes with the choroidal circulation, which draws off a voluminous flow to furnish oxygen to the highly metabolic visual transduction process and to dissipate the heat that transduction generates. Under normal circumstances, there is enough arterial blood flow to go around. But if systemic blood pressure falls or subarachnoid pressure rises, the optic nerve might suffer from “choroidal steal.” Notably, one postulate as to how optic nerve sheath fenestration protects the optic nerve in papilledema is that it forms a scar around the nerve that isolates the ciliary arterial circle from transmission of high subarachnoid pressure (12).

The issue about whether axons lose function from compression or ischemia also applies to primary open-angle glaucoma (POAG), where it remains unresolved. Papilledema and POAG share a pressure gradient across the lamina cribrosa and visual field loss that affects principally the arcuate bundles in the nasal field with sparing of visual acuity. But there is a profound difference between papilledema and POAG: the optic neuropathy of chronic papilledema does not include excavation of the neuroretinal rim tissue. Thus, there must be something else besides chronic ischemia to the pathogenetic mechanism for POAG (18).

The relationship between axoplasmic stasis and optic nerve dysfunction is uncertain. The optic nerve is evidently able to conduct visual signals adequately as long as the stasis is not severe, given that visual function is relatively preserved in papilledema in the early stages—even when there is considerable optic disc elevation.

Axoplasmic stasis is not unique to papilledema, having been found or surmised in many other optic neuropathies (19). But in papilledema, the axoplasm presumably accumulates more slowly as optic nerve dysfunction usually takes a longer time to develop.

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Is papilledema a reliable clinical indicator of a recent rise in intracranial pressure?

No—at least not in humans. In one monkey experiment, ICP elevation induced by subarachnoid balloon inflation led to the development of papilledema in 30% within 24 hours and in 90% within 120 hours. The faster the balloon was inflated and the higher the ICP, the greater the likelihood and degree of papilledema (20). But in humans, papilledema lags. Among 37 patients who had documented high ICP from acute intracranial hemorrhage in trauma or ruptured aneurysm and who were examined for several days in an intensive care unit, only 1 patient had papilledema. Five patients had peripapillary hemorrhages, a phenomenon known as Terson syndrome (21). Other studies have affirmed that fewer than 20% of patients examined within a few days of sustaining head trauma (22) or ruptured aneurysm (23) have papilledema. The shortcoming in the evidence about the prevalence of papilledema in acutely high ICP is that authors do not consistently report how long they continued performing ophthalmoscopy in these patients.

The delay in the appearance of papilledema in acutely elevated ICP is consistent with the idea that papilledema is not based on dilated veins, as is the case in Terson syndrome, but rather on interruption of the metabolic process that mediates axoplasmic flow. Based on examination of patients in a neurointensive care unit for several decades, I believe that Terson syndrome is more common than papilledema within the first few days of a sudden rise in ICP. I have also found papilledema to be generally absent in hydrocephalic children who sustain acute shunt failure, a topic that requires further study.

Is papilledema a reliable indicator of chronically high ICP?

Yes, but there are no published studies that correlate papilledema with ICP. Older studies found that papilledema occurred in 50%-80% of brain tumors (1). That range is now probably an overestimate as modern brain imaging detects tumors before ICP has risen enough to cause papilledema.

In a study of 252 brain tumors, Paton (1) found that papilledema appears more rapidly in cerebellar tumors than cerebral tumors. That observation fits with my experience, namely that a very large amount of supratentorial mass effect is necessary to cause papilledema, whereas a relatively inconspicuous tumor may cause elevated ICP and papilledema if it blocks convexity arachnoid granulations (24), ventricular CSF egress (25,26), or dural venous sinuses (27).

The papilledema of chronically high ICP may be of different severity in the 2 eyes. It may be entirely absent from 1 eye, but rarely from both eyes! The frequency of strictly unilateral papilledema has never been adequately documented, but in my experience, it occurs in fewer than 5% of cases. This phenomenon is attributed to anatomic variations that impede transmission of ICP through the optic canal to the distal optic nerve.

How often is papilledema completely absent in chronically high ICP? Studies of IIH indicate that about 6% of such patients lack papilledema (IIH without papilledema or IIHWOP) (28). The weakness of this evidence is that without papilledema as an anchor, the diagnosis of IIH depends on the accuracy of the lumbar puncture opening pressure measurement, which is egregiously error-ridden (29). Are these patients suffering from chronic migraine or tension headache and generating falsely high opening pressures because of poorly performed lumbar punctures? Reversal of headache with ICP-lowering treatment in IIHWOP, often used as support for the diagnosis, is not convincing.

Can patients develop optic neuropathy from chronically high ICP if they do not have papilledema?

No. In a series of 20 patients with IIHWOP (28), many had constricted visual fields, but all were judged to be “nonphysiologic,” that is, faked. Apparently, optic neuropathy will not occur unless the optic disc swells to the point of being visible on ophthalmoscopy. Thus, IIHWOP remains an issue of headache, not vision loss.

Can a sudden rise in ICP cause vision loss from optic neuropathy without first causing papilledema?

Such a phenomenon has never been properly documented, but there are hints that it may rarely occur. In a study of the long-term visual outcome in 30 patients with Terson syndrome (30), 2 patients developed optic disc pallor and markedly impaired vision. In those patients, papilledema was not described but may have been hidden behind peripapillary retinal hemorrhages. Although persistent visual loss in Terson syndrome in that series was attributed mostly to epiretinal membrane, cystic maculopathy, or macular hole, a contribution from optic neuropathy may have been overlooked.

I have encountered a patient who developed severe vision loss and optic disc pallor after postpartum dural sinus thrombosis. A retinal specialist had examined the patient several times during the first 14 days after the thrombosis and found no papilledema! I urge my colleagues to look out for this phenomenon and to report it if they come upon it.

Can papilledema linger after ICP has normalized?

Yes. Because papilledema is based on axoplasmic stasis, which is a failure of an energy-dependent metabolic process, it lags not only on the way up but also on the way down. The attendant visual deficit may linger as well. As a consequence, errors in patient management may occur, and I have made them.

For example, a young man developed transient obscurations of vision in the left eye and had asymmetric optic disc elevation and nerve fiber bundle visual field loss worse in the symptomatic eye. MRI showed triventriculomegaly from aqueductal stenosis owing to a presumed low-grade tectal astrocytoma. The patient underwent third ventriculostomy. Three weeks after the procedure, the visual obscurations had ceased, but the papilledema was unchanged and the visual fields had only slightly improved. I suggested that the ventriculostomy had failed and recommended ICP monitoring. It was normal. Eight weeks later, the papilledema and visual fields had finally recovered. The correct diagnosis, which had eluded me, was prompt resolution of high ICP and delayed resolution of papilledema.

In many cases, papilledema never goes away—even months after ICP has normalized. A 40-year-old woman shunted for hydrocephalus in infancy had undergone several shunt revisions for recurrent headache. She came under my care for a new headache with features similar to those that had triggered previous shunt revisions. Visual acuity was normal, visual fields were unreliable, and optic discs showed mild elevation. A thorough evaluation showed no new ventricular enlargement, a functioning shunt reservoir, and a normal opening pressure and normal CSF formula on lumbar puncture. Six weeks later, the optic discs were unchanged and visual function remained normal. The diagnosis was residual optic disc elevation, perhaps related to surface gliosis but not to high ICP. She was treated symptomatically for headache and improved.

Can vision loss from optic neuropathy develop after ICP has normalized in patients who previously had papilledema?

Yes. Vision loss from optic neuropathy can develop immediately after ICP has been normalized or months to years later, long after papilledema has disappeared.

The immediate type of visual loss has been amply documented in patients who undergo surgery for brain tumor or CSF diversion for high ICP. Such patients have always had a mixture of optic disc elevation and pallor, together with optic nerve dysfunction, before the decompressive procedure occurred (31). I encountered this sad phenomenon in a 10-year-old boy with hydrocephalus from a suprasellar ganglioglioma who presented with slowly progressive binocular visual loss and best-corrected visual acuities of 20/400 in the right eye and finger counting in the left eye. Visual fields were severely compromised, and optic discs displayed a mixture of elevation and pallor. One day after ventriculoperitoneal shunting and partial tumor removal, visual acuities fell to finger counting in the right eye and no light perception in the left eye. Months later, visual acuity was unchanged and optic discs had flattened and become profoundly pale (Fig. 4).

The explanation for this “postdecompression optic neuropathy” is uncertain. Perhaps tumor decompression and restoration of normal ICP disturb compensatory blood flow to the optic nerve. To prevent this phenomenon, preoperative administration of ICP-lowering medication has been advocated, but its efficacy is unproven (31).

Optic nerve dysfunction can also occur progressively or develop suddenly months to years after decompression, even when ICP is normal (32). For example, an 18-year-old girl with chronic optic disc edema and severely compromised visual fields from IIH underwent ventriculoperitoneal shunting under my care. Visual function improved after the shunt and remained stable until 18 months later, when she suddenly lost all vision in 1 eye. Both optic discs were profoundly pale. ICP monitoring was normal, as performed with an intraparenchymal Codman ICP Monitoring System (33). In this delayed form of postdecompression optic neuropathy, I presume that damaged axons are prone to die, much as muscles are in the postpolio syndrome. I know of no effective way to guard against this tragic phenomenon, but I recommend measures to avoid systemic hypotension.

Can we reliably predict who is at risk for irreversible optic neuropathy from papilledema?

No. In one IIH study, the amount of papilledema appeared to be an independent risk factor, as judged by the fact that the eye with the greater amount of papilledema had the worse visual field. But there was poor correlation between the amount of papilledema and the visual field loss (34). Other putative risk factors in IIH, not necessarily independent of each other, are the amount of preexisting optic nerve dysfunction (35), superimposed optic disc atrophic features (35), narrowed retinal arterioles (35), sustained systemic hypertension (16), weight gain, anemia (36), and African American race (37). Transient obscurations of vision and the height of the lumbar puncture opening pressure, which are intuitive risk factor candidates, have not been adequately dispelled as contributory (38).

We lack reliable data on the prevalence of clinically meaningful visual loss in papilledema. Data on this point come entirely from the studies of IIH in referral centers. Reviews of these data affirm that on automated static perimetry, nearly all patients with IIH have visual field defects initially affecting the inferior nasal visual field (39,40). But how often is the visual loss disabling? One study of 57 IIH patients at a Philadelphia eye hospital reported that 25% had severe visual loss, but that figure is likely inflated by accrual of sicker patients (16). A long-term study of IIH in England found poor long-term vision from optic neuropathy in 17% of patients, but at least half of them had poor visual function at outset (41). A study of 54 IIH patients at 4 Israeli medical centers followed for 2-28 years (average, 6.2 years) (42) and a study of 68 patients in 2 London hospitals followed for an average of 4 years (38) reported that 6% had severe visual field loss on final examinations (42).

In common with other studies, I have found that most patients with severe visual loss from papilledema already have advanced visual loss when the papilledema is first detected. Shunts or optic nerve sheath decompressions performed on my patients have nearly always occurred within hours to days of the first clinical encounter!

Among my patients, I have found that severe visual loss from papilledema occurs in 3 groups: 1) Group 1: young women with IIH who have florid and/or atrophic papilledema and severe optic neuropathy at diagnosis, 2) Group 2: children with long-standing obstructive hydrocephalus from aqueductal stenosis or brain tumors who have atrophic papilledema and severe optic neuropathy at diagnosis, and 3) Group 3: children or adults shunted for hydrocephalus in infancy who have not been regularly monitored by ophthalmologists and who eventually appear for consultation when vision fails from chronically high ICP owing to shunt malfunction. Ophthalmoscopy typically discloses atrophic papilledema. In this third group, brain imaging usually does not show ventriculomegaly because shunted hydrocephalus is associated with stiff ventricular walls (43).

Patients in all 3 groups present late because the visual loss of chronic papilledema proceeds silently and because chronic high ICP often causes no headache. Symptoms are ignored by children, dismissed by their parents, or attributed to other causes by their physicians. I recommend intensified instruction in ophthalmoscopy to pediatricians and internists and periodic ophthalmologic examination of patients at high risk for papilledema, such as those with indwelling shunts, tuberous sclerosis (proclivity for obstructing giant cell astrocytomas), and neurofibromatosis (proclivity for meningiomatosis).

Can papilledema be reliably distinguished ophthalmoscopically from congenitally elevated optic discs?

No. Although there are reasonable ophthalmoscopic clues to congenitally anomalous optic disc elevation (drusen, dome-shaped elevation, anomalous surface vessels, and clear peripapillary nerve fiber layer), there are many cases in which one simply cannot tell if the optic disc elevation is congenital or acquired. Such diagnostic difficulty should not be surprising, given that anomalous optic discs contain axons that are crowded into small scleral canals (44). Although congenitally elevated optic discs associated with buried drusen can be readily identified by ultrasound or CT, the confusing cases I encounter have minimal optic disc elevation without drusen. Fluorescein angiography and optical coherence tomography probably cannot reliably distinguish minimal papilledema from a congenitally anomalous elevated optic disc (45). If I find no visual field loss or manifestations of a neurologic illness, I perform fundus photography, defer brain imaging, and re-examine for optic disc changes after several months. With this approach, I do not believe that I have overlooked high ICP.

Can papilledema be distinguished from other acquired optic neuropathies?

Not always. Yes, there are some ophthalmoscopic signs that allow a presumptive diagnosis of other types of optic neuropathy, such as segmental and pallid edema in ischemic optic neuropathy, peripapillary telangiectasia in Leber hereditary optic neuropathy, and optociliary shunt vessels in juxta-ocular optic nerve sheath meningioma. But unless these signs are present, an ophthalmoscopic diagnosis of papilledema is difficult. After all, the optic disc edema of all acquired optic neuropathies arises from axoplasmic stasis (19).

Therefore, distinguishing papilledema from other optic neuropathies with optic disc edema is typically based on 2 nonophthalmoscopic criteria: 1) binocular involvement and 2) relatively preserved visual function for the amount of nonatrophic optic disc edema. But these criteria will often fail to make a clear distinction. Papilledema can be monocular. Binocular optic disc edema can occur in inflammatory, ischemic, diabetic, neoplastic, and hypertensive optic neuropathies. Relative preservation of visual function may occur in those conditions. As papilledema becomes chronic, visual dysfunction develops. These facts create clinical errors as follows.

A 30-year-old mildly overweight woman developed blurred vision in both eyes. Both optic discs were mildly swollen, and visual fields showed mild inferior nasal nerve fiber bundle defects. Brain MRI was interpreted as normal. Lumbar puncture showed an opening pressure of 35 cm H2O and a normal cerebrospinal formula. A diagnosis of IIH was made elsewhere, and the patient was treated with acetazolamide. When vision continued to worsen, I examined her and made the same observations, but an orbit-centered MRI showed enhancement of both optic nerves, and a chest CT showed hilar adenopathy. Bronchoscopic biopsy disclosed granulomas. The diagnosis was changed to sarcoidosis, the patient was treated with corticosteroid, and vision gradually recovered. The mistake was interpreting bilateral chronic optic disc elevation as papilledema when it was likely due to inflammation.

The opposite scenario can also occur.

A 20-year-old man with acquired immunodeficiency syndrome developed cryptococcal meningitis, but no opening pressure had been performed on lumbar puncture. He complained of diminished vision in both eyes. Brain imaging showed enhancement of the optic nerves and meninges; there was no ventriculomegaly. On ophthalmoscopy, the optic discs were elevated. The explanation for the visual loss was cryptococcal infiltration of the optic nerves. When vision declined precipitously, he underwent another lumbar puncture that showed a markedly elevated opening pressure. Ventriculoperitoneal shunting improved headache and vision, but as papilledema turned into optic disc pallor, he was left with considerable optic nerve dysfunction. The error was in attributing vision loss entirely to optic nerve infiltration and in not recognizing papilledema as an important contributor.

This last case exemplifies a common situation, namely that optic disc edema may be the result of a mixed mechanism—inflammation of the optic nerve and increased ICP. Such a mixed mechanism often occurs in meningitis, where the optic nerves may be directly attacked and the arachnoid granulations blocked to cause high ICP. In viral meningitis, the high ICP is usually well tolerated, but in bacterial, fungal, protozoal, or neoplastic meningitis, it may be vision threatening. CSF diversion is critical.

Does papilledema occur in malignant hypertension or in hypertensive encephalopathy?

No. This is a common misconception. Optic disc edema certainly occurs in malignant hypertension, but it represents leakage of serum from incompetent optic disc arterioles owing to protective vasoconstriction followed by autoregulatory breakthrough vasodilation (46) (Fig. 5). Vascular leakage from excessive autoregulation underlies hypertensive retinopathy (cotton wool spots, surface hemorrhages, and hard exudates), which is always present if the optic disc is swollen in malignant hypertension (46). The vasogenic edema of malignant hypertension is not enough to cause very high ICP, which occurs only when the brain becomes massively infarcted, a rare phenomenon now that there is earlier intervention with powerful blood pressure-lowering regimens (48,49). But the vasogenic edema may be enough to cause a mild elevation of the opening pressure. Unless the vasogenic edema of malignant hypertension turns into infarction in the optic disc, visual function will be relatively preserved, a feature that will tempt a mistaken impression of papilledema, particularly if the opening pressure is elevated (48).

I have encountered patients who have undergone lumbar puncture prompted by the finding of bilateral optic disc edema in the setting of malignant hypertension. The lumbar puncture has shown an elevated opening pressure and led to ill-advised placement of a ventriculoperitoneal shunt. I suggest that the optic disc edema of malignant hypertension be interpreted as a manifestation of high blood pressure rather than of high ICP. The appropriate intervention is gradual lowering of blood pressure, not CSF diversion or optic nerve sheath fenestration.

Can papilledema be present even if brain imaging shows no clear signs of high ICP?

Yes. The signs that radiologists look for in diagnosing high ICP—enlarged or enlarging ventricles, periependymal signal alteration, sulcal or cisternal obliteration—are not very sensitive to high ICP. First, patients with shunted hydrocephalus typically have stiff ventricular walls that do not expand with pressure (43). Second, patients whose obstruction to CSF outflow is in the arachnoid granulations or dural venous sinuses usually do not develop ventriculomegaly because there is no pressure gradient between the intraventricular and extraventricular spaces (27). Third, patients with parenchymal edema from head trauma or encephalitis or tight skulls from syndromic craniosynostosis may lack obvious radiologic signs of high ICP. Here is an example of how this issue plays out in clinical practice.

A 39-year-old man who had undergone ventriculoperitoneal shunting at age 12 for hydrocephalus developed new headache and vision loss 27 years later. Although papilledema was noted, shunt malfunction was initially dismissed as a diagnosis because MRI did not show definite signs of high ICP. The shunt was eventually revised, at which time ventricular pressure was very high. Following the revision, papilledema resolved to pallor but the patient had lost a substantial amount of vision (43) (Fig. 6).

Brain ventricles may be dilated yet the ICP is normal, a condition called “compensated hydrocephalus.” If there are no other compelling imaging signs of high ICP, radiologists typically look for an enlargement of ventricular size over time before suspecting high ICP. Here is an example of how imaging can be misleading, and the finding of papilledema can be critical.

A 54-year-old woman developed a confusional state, but her symptoms were disregarded because she carried an earlier diagnosis of bipolar disorder (50). She had undergone brain imaging a year earlier in follow-up of a known diagnosis of Osler-Weber-Rendu disease producing multiple brain cavernomas. Brain MRI showed ventriculomegaly but no change in the ventricular size as compared to an MRI performed a year earlier. The ventriculomegaly was considered compensated. But months later, she became incoherent, complained of blurred vision, and was found to have papilledema. ICP monitoring showed very high ICP. Ventriculoperitoneal shunting restored baseline mental status and normal vision and eliminated papilledema (Fig. 7).

The search for papilledema is especially important in patients who are prone to high ICP because they have an indwelling CSF shunt, a subependymal giant cell astrocytoma in tuberous sclerosis (Fig. 8), chronic granulomatous meningitis, or meningiomatosis. Such patients may be unaware of progressive visual loss from high ICP. Their imaging may be insensitive to high ICP, and their tests of shunt function may be unreliable. Finding papilledema may be vision saving and excluding it may spare them ICP monitoring or needless shunt revision (24-26,43).

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