Papilledema: Are We Any Nearer to a Consensus on Pathogenesis and Treatment?

Papilledema is a term generally reserved (at least in the English language use of the term) by neuro-ophthalmologists for optic disc edema due to increased intracranial pressure. The etiology for the intracranial hypertension may be known (e.g., brain tumor, meningitis, cerebral venous sinus thrombosis) or may be idiopathic (idiopathic intracranial hypertension [IIH]). IIH is a disorder that predominantly affects overweight women of childbearing age and these epidemiologic factors should offer clues to pathogenesis. The main morbidity of papilledema is visual loss and the major mechanism for permanent optic nerve damage is axoplasmic flow stasis and resultant intraneuronal ischemia. The current initial management of papilledema in IIH includes weight loss and medical therapy (e.g., acetazolamide or furosemide). Patients who fail, are intolerant to, or noncompliant with maximum tolerated medical therapy might require optic nerve sheath fenestration or cerebrospinal fluid diversion (i.e., shunting) procedures.     

Idiopathic intracranial hypertension (Pseudotumor cerebri)

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a disorder of elevated intracranial pressure of unknown cause. Patients present with daily headache, pulse-synchronous tinnitus, transient visual obscurations, papilledema with its associated visual loss, and diplopia from sixth nerve paresis. Many disease associations have been alleged, but few besides obesity, hypervitaminosis A and related compounds, steroid withdrawal, and female gender have been proven. Although absorption of cerebrospinal fluid (CSF) occurs through arachnoid granulations and extracranial lymphatics, outflow resistance is increased in IIH; therefore, intracranial pressure must increase for CSF to be absorbed. The mainstays of medical treatment are a reduced-sodium weight-reduction program and acetazolamide. If patients fail medical therapy, surgical procedures, most commonly optic nerve sheath fenestration and CSF shunting, are employed. The main morbidity of IIH is visual loss. This is present in most patients and can usually be reversed if recognized early in the course of the disease and treated. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a disorder of elevated intracranial pressure of unknown cause. Patients present with daily headache, pulse-synchronous tinnitus, transient visual obscurations, papilledema with its associated visual loss, and diplopia from sixth nerve paresis. Many disease associations have been alleged, but few besides obesity, hypervitaminosis A and related compounds, steroid withdrawal, and female gender have been proven. Although absorption of cerebrospinal fluid (CSF) occurs through arachnoid granulations and extracranial lymphatics, outflow resistance is increased in IIH; therefore, intracranial pressure must increase for CSF to be absorbed. The mainstays of medical treatment are a reduced-sodium weight-reduction program and acetazolamide. If patients fail medical therapy, surgical procedures, most commonly optic nerve sheath fenestration and CSF shunting, are employed. The main morbidity of IIH is visual loss. This is present in most patients and can usually be reversed if recognized early in the course of the disease and treated.     

Complete ophthalmoplegia: A rare presentation of idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) is a disorder defined by clinical criteria that include signs and symptoms isolated to those produced by increased intracranial pressure (ICP; e. g., headache, papilledema, and vision loss), elevated ICP with normal cerebrospinal fluid (CSF) composition, and no other cause of intracranial hypertension evident on neuroimaging or other evaluations. The most common signs in IIH are papilledema, visual field loss, and unilateral or bilateral sixth cranial nerve palsy. Here we report a case of IIH presenting as headache with vision loss, papilledema, complete ophthalmoplegia with proptosis in one eye, and sixth cranial nerve palsy in the other eye. Patient was managed with acetazolamide, topiramate, and diuretics. Symptoms remained static and she was planned for urgent CSF diversion procedure.     

A case of chronic hypertrophic cranial pachymeningitis causing cranial polyneuropathy and unilateral central retinal vein occlusion]

We presented a 70-year-old woman who developed unilateral visual loss due to central retinal vein occlusion caused by chronic hypertrophic cranial pachymeningitis. She had developed right blindness with optic atrophy due to chronic intracranial pachymeningitis one year before admission. In June 1999, she noticed visual loss of the left eye. On admission, neurological examination revealed left visual loss and sensory impairment in the first branch area of bilateral trigeminal nerves. Ophthalmological examination revealed central retinal vein occlusion of the left eye. Brain MRI showed dural thickening with gadolinium enhancement of the cavernous sinus near the left optic nerve and dilatation of the left supraorbital vein. There was no compression of the left optic nerve. We suggest that central retinal vein occlusion may be caused by compression of the supraorbital vein by dural thickening. This is the first case report of central retinal vein occlusion associated with chronic hypertrophic cranial pachymeningitis.     

Transient visual obscurations with elevated optic discs

The pathogenesis of the transient obscurations of vision that occur with papilledema is a subject of speculation and debate. We present four examples of transient obscurations of vision that were clinically indistinguishable from those of papilledema; they occurred in patients with elevated optic discs from causes not related to increased intracranial pressure. The underlying mechanism for visual obscurations in all of these patients appear to be transient ischemia of the optic nerve head consequent to increased tissue pressure. Axonal swelling, intraneural masses, and increased influx of interstitial fluid may all contribute to increases in tissue pressure in the optic nerve head. The consequent reduction in perfusion pressure renders the small, low-pressure vessels that supply the optic nerve head vulnerable to compromise. Brief fluctuations in intracranial or systemic blood pressure may then result in transient loss of function in the eyes. We postulate that such mechanisms may apply in all cases of optic disc elevation, including papilledema.     

Current concepts and strategies in the diagnosis and management of idiopathic intracranial hypertension in adults

Since obesity has become an epidemic in industrialized nations, idiopathic intracranial hypertension (IIH) is now a more common neuro-ophthalmic disorder that causes visual loss and headaches. This review highlights the new diagnostic criteria for IIH and the new insights into the pathophysiologic mechanisms of IIH. Key diagnostic and monitoring techniques for papilledema include not only neuroimaging and the measurement of cerebrospinal fluid (CSF) pressure, but also perimetry, optical coherence tomography, and ocular sonography. The main findings of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) support acetazolamide as the mainstay for medical therapy. CSF diversion procedures, endovascular venous sinus stenting, and optic nerve sheath fenestration are all surgical options when IIH is refractory to medical treatment or when it presents fulminantly. Future clinical trials comparing these procedures will help develop better paradigms in the surgical management of IIH.     

Optical coherence tomography for the diagnosis and monitoring of idiopathic intracranial hypertension

The objectives of the study were to investigate the value of optical coherence tomography in detecting papilledema in patients with idiopathic intracranial hypertension (IIH), a disease which is difficult to monitor and which can lead to permanent visual deficits; to analyze retinal changes over time. In this non-interventional case–control study, spectral-domain optical coherence tomography (SD-OCT) was used to analyze the retinal and optic nerve head (ONH) morphology of 21 patients with IIH and 27 age- and sex-matched healthy controls over time. We analyzed the ONH volume using a custom-made algorithm and employed semi-automated segmentation of macular volume scans to assess the macular retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer complex as well as the total macular volume. In IIH patients, the ONH volume was increased and correlated with cerebrospinal fluid (CSF) pressure. The ONH volume decreased after the initiation of treatment with acetazolamide. The macular RNFL volume decreased by 5% in 3.5 months, and a stepwise multivariate regression analysis identified CSF pressure as the main influence on macular RNFL volume at diagnosis. The only factor predicting macular RNFL volume loss over time was ONH volume. SD-OCT can non-invasively monitor changes in retinal and ONH morphology in patients with IIH. Increased ONH volume leads to retinal atrophy in the form of macular RNFL volume loss, presumably due to mechanic jamming of the optic nerve at the disc and subsequent axonal loss.     

Transient bilateral oculomotor palsy in pseudotumor cerebri

Pseudotumor cerebri is a clinical condition marked by papilledema, normal cerebrospinal fluid composition, normal or small ventricles on radiography, and absence of an intracranial mass. In this condition, headache, tinnitus, dizziness, blurred vision, and diplopia are frequently observed. The cause is often unknown but can occur with certain drug ingestions or systemic inflammatory and metabolic diseases. The treatment is primarily focused on the correction of the underlying cause with measures to reduce the raised intracranial pressure. The most important complication is optic atrophy, which results in visual loss. The sixth cranial nerve is most commonly affected. The involvement of the third cranial nerve is distinctly unusual. The present report describes a unique case of bilateral oculomotor palsy with sparing of the papillary fibers. It resolved promptly on administration of acetazolamide.     

Blindness, ophthalmoplegia and extensive radiculopathy: an unusual clinical syndrome in intracranial sino-venous thrombosis

Isolated intracranial hypertension is a common manifestation of intracranial sino-venous thrombosis (ISVT). Markedly elevated intracranial tension presents with unusual features including cranial neuropathies and radiculopathy. We report two cases with ISVT, which presented with headache, papilledema, progressive visual loss, complete ophthalmoplegia and flaccid areflexic quadriparesis along with a normal sensorium. Magnetic resonance imaging (MRI) of the brain and cervical spinal cord showed no lesions that could account for the neurological deficits. Markedly elevated lumbar CSF pressure was noted in both cases. Nerve conduction study favored radiculopathy in one case and was normal in the other. Raised intracranial pressure was found to be the sole cause for the clinical manifestations. Visual impairment persisted in one patient despite lumbo-peritoneal shunting while the other died of septicemia. To our knowledge there are no previous reports of a syndrome comprising blindness, ophthalmoplegia and flaccid quadriplegia due to intracranial hypertension in ISVT.     

Spinal cord astrocytoma presenting as "idiopathic" intracranial hypertension

Increased intracranial pressure is rarely seen in association with spinal tumors. We describe a young, non-obese man who presented with increased intracranial pressure, papilledema and visual obscuration. Multiple cerebrospinal fluid (CSF) examinations with normal or minimally elevated CSF protein lead to the initial diagnosis of idiopathic intracranial hypertension. After a lumboperitoneal shunt placement a progressive thoracic myelopathy developed 7 months after onset of symptoms. The spinal MRI showed a low cervical-upper thoracic intramedullary tumor. Open biopsy confirmed a grade 3 fibrillary astrocytoma. The suspected mechanisms of spinal tumors causing increased intracranial pressure are reviewed as well as three other cases of spinal astrocytomas previously reported in the literature that presented with papilledema and increased intracranial pressure without hydrocephalus. This case illustrates that increased intracranial pressure may in exceptional cases of spinal tumors precede the more typical myelopathic presentation by months and mimic idiopathic intracranial hypertension.     

Visual dysfunction caused by gauze wrapping of an intracranial aneurysm.

A 43-year-old woman developed right frontal headache and decreased vision in her OD 14 months after treatment of an intracranial aneurysm by wrapping with cotton gauze. A junctional visual field defect was present, and an MRI revealed a contrast-enhancing mass involving the right optic nerve, lateral chiasm, optic tract, and cavernous sinus. Biopsy demonstrated a marked inflammatory reaction mixed with strands of birefringent cotton gauze. Despite treatment with high-dose corticosteroids, visual loss progressed to bilateral blindness. This is the 30th reported case of an intracranial inflammatory tumor developing from a gauze-wrapped aneurysm ("gauzoma" or "muslinoma") and the worst reported visual outcome. Most cases have occurred in women and involved the optic nerves or chiasm. Visual improvement has sometimes occurred after treatment with abscess drainage, debulking, and/or corticosteroids. A rare complication of aneurysm wrapping, gauzomas causing visual loss have been reported up to 54 months after surgery.     

Subretinal hemorrhage from a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension.

A 42-year-old man with idiopathic intracranial hypertension and chronic papilledema had severe visual loss in his left eye caused by subretinal bleeding from a peripapillary choroidal neovascular membrane (CNVM). After optic nerve sheath fenestration in his left eye, the papilledema improved, allowing improved visualization of the CNVM. Visual function did not improve after the surgery. CNVM can complicate chronic papilledema and account for sudden worsening of vision. The appropriate management of this type of CNVM is unresolved.     

Sudden monocular visual loss in pseudotumor cerebri.

We describe a patient with papilledema due to benign intracranial hypertension who had sudden, painless monocular visual loss. Fear of further visual deterioration prompted vigorous therapeutic efforts to reduce intracranial pressure. Subsequent neuro-ophthalmologic evaluation disclosed that the visual loss was due to a subretinal neovascular membrane. Vision continued to improve after medical therapy was discontinued, and was accompanied by complete resolution of papilledema and headache. In any patient with minimal papilledema, sudden visual deterioration should initiate a search for other causes rather than zealous therapeutic efforts to reduce intracranial pressure.     

Mucocele of the sphenoid sinus: A rare cause of reversible 3rd nerve palsy

Ophthalmoplegia due to 3^rd nerve palsy is a common occurrence, and is usually a sign of diabetes mellitus or a serious intracranial disease. We report a rare case of pupil sparing 3^rd nerve palsy caused by mucocele of the sphenoid sinus. The patient regained 3^rd nerve functions after successful decompression of the mucocele. Early and correct diagnosis of this relatively benign condition is important to prevent permanent neurological deficits, including visual loss by optic nerve atrophy. Etiology, clinical manifestations and treatment of the sphenoid mucoceles is discussed and available literature is reviewed.     

A Large Ruptured Anterior Communicating Artery Aneurysm Presenting with Bitemporal Hemianopsia

Anterior communicating artery (ACoA) aneurysms sometimes present with visual symptoms when they rupture or directly compress the optic nerve. Giant or large ACoA aneurysms producing bitemporal hemianopsia are extremely rare. Here we present an unusual case of bitemporal hemianopsia caused by a large intracranial aneurysm of the ACoA. A 41-year-old woman was admitted to our neurosurgical department with a sudden-onset bursting headache and visual impairment. On admission, her vision was decreased to finger counting at 30 cm in the left eye and 50 cm in the right eye, and a severe bitemporal hemianopsia was demonstrated on visual field testing. A brain computed tomography scan revealed a subarachnoid hemorrhage at the basal cistern, and conventional cerebral catheter angiography of the left internal carotid artery demonstrated an 18×8 mm dumbbell-shaped aneurysm at the ACoA. Microscopic aneurysmal clipping was performed. An ACoA aneurysm can produce visual field defects by compressing the optic chiasm or nerves. We emphasize that it is important to diagnose an aneurysm through cerebrovascular study to prevent confusing it with pituitary apoplexy.     

Optic neuropathies for the neurologist

Before embarking on expensive ancillary testing, it is crucial for the neurologist to distinguish visual loss due to optic nerve dysfunction from other causes of visual loss. This can usually be accomplished based on specific features of the history and bedside examination. Once it has been established that a patient has some form of optic neuropathy, several clinical features are helpful in determining the etiology. The most important of these is the time course. Other factors include presence or absence of pain, pattern of visual loss (particularly visual field defects), and funduscopic appearance. In most cases, by using this information it is possible to differentiate among the common forms of optic neuropathy: papilledema, ischemic optic neuropathy, optic neuritis, compressive lesions, toxic/nutritional deficiencies, and hereditary forms. This article also reviews recent information concerning the evaluation and treatment of optic neuritis, how to recognize conditions that mimic optic neuritis (e.g., neuroretinitis, papillophlebitis), distinguishing arteritic from non-arteritic AION, and new developments in the genetics of Leber's Hereditary Optic Neuropathy. There is also a discussion of various forms of toxic/nutritional visual loss including Cuban Epidemic Optic Neuropathy and visual loss due to commonly prescribed medications.     

Treatment of visual loss in pseudotumor cerebri associated with uremia

Ten patients with pseudotumor cerebri associated with renal insufficiency had papilledema and elevated intracranial pressure, but neurologic examinations and CT were normal. The 40% frequency of severe visual loss, 20/100 or worse, was higher than expected for pseudotumor cerebri. While furosemide was effective in 3 patients with renal transplants, administration of corticosteroids to 2 other patients did not halt progressive loss of vision. The visual function of 2 patients deteriorated even after lumboperitoneal shunting. Five patients underwent fenestration of the optic nerve sheath. This procedure improved the visual acuity of 3 patients and stabilized vision in the others. While the pathogenesis of pseudotumor cerebri in renal insufficiency is unknown, optic nerve sheath fenestration is the surgical treatment of choice for visual loss unresponsive to medical therapy.     

Long-term evolution of papilledema in idiopathic intracranial hypertension: observations concerning two cases

Chronic headaches, associated with papilledema and pulsatile tinnitus without any neuroradiologic, cytobiochemical or cerebrospinal fluid abnormalities are suggestive of idiopathic intracranial hypertension (IIH). However the absence of the papilledema does not rule out this diagnosis. The reason why some patients do not develop papilledema in IIH is ignored, however there are some hypotheses concerning the structure of the optical nerve. In this study we described two female patients that presented diagnosis of IIH with papilledema, with subsequent resolution of papilledema without the due resolution of intracranial hypertension. The long-term behavior of the optic nerve (ON) facing an increased intracranial pressure was evaluated through repeated measurements of the intracranial pressure. We concluded that the ON submitted to high intracranial pressure for a certain length of time can adapt itself with subsequent disappearance of the papilledema. The presence or not of papilledema in IIH can be related to the period in which the diagnosis is accomplished.     

The rational management of idiopathic intracranial hypertension

Idiopathic intracranial hypertension is a diagnosis most frequently made in young, overweight women. The chief hazard to the patient is permanent visual loss due to chronic papilledema. After the diagnosis has been clearly established using lumbar puncture and imaging techniques, the neurologist is involved in helping to lower the intracranial pressure, control the headaches, and encourage weight loss. Careful vision monitoring is essential and should be done in collaboration with an ophthalmologist. Visual fields, fundus photographs, intraocular pressure measurement, and visual acuity should be performed at each follow-up visit. The use of visual evoked response and repeated measurement of intracranial pressure by lumbar puncture do not provide data that help to guide therapeutic decisions. Indications for surgery are loss of visual field or decline in visual acuity in the fact of medical therapy, persistent headache, or the inability to perform visual-function studies. Optic nerve sheath fenestration and lumbar peritoneal shunt both appear to be effective surgical means to reduce the pressure on the optic disc. A neurologist and an ophthalmologist working together provide the evidence on which to base rational decisions in the care of the patient with idiopathic intracranial hypertension.     

Visual evoked potentials in pseudotumor cerebri

Pattern reversal visual evoked potentials in 13 patients with pseudotumor cerebri were significantly delayed (99 +/- 7.3 ms [mean +/- SD]) compared with the findings in 20 normal subjects (94 +/- 2.7 ms), although only four patients had latencies outside the normal range. There was, however, a significant correlation between the intracranial pressure and the latency of visual evoked potentials. After medical treatment of the intracranial hypertension, visual evoked potential latencies decreased in patients who recovered and in whom the papilledema disappeared. In one patient with progressive visual failure, the visual evoked potentials were abnormal before disturbances of visual fields and visual acuity were evident. Repeated examinations of visual evoked potentials might be of value in patients with pseudotumor cerebri to ensure neurosurgical intervention in due time to prevent visual loss in patients with impending optic nerve atrophy.