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LITERATURE REVIEW

IDIOPATHIC INTRACRANIAL HYPERTENSION

Devin K. Binder, M.D.,Ph.D.Department of NeurologicalSurgery, University of California,San Francisco, San Francisco,California

Jonathan C. Horton, M.D.Department of Ophthalmology,University of California, SanFrancisco, San Francisco,California

Michael T. Lawton, M.D.Department of NeurologicalSurgery, University of California,San Francisco, San Francisco,California

Michael W. McDermott,M.D.Department of NeurologicalSurgery, University of California,San Francisco, San Francisco,California

Reprint requests:Michael W. McDermott, M.D.,Department of NeurologicalSurgery, University of California,San Francisco, 505 ParnassusAvenue, M-774, San Francisco, CA94143-0112.Email:[email protected]

Received, April 11, 2003.

Accepted, September 15, 2003.

OBJECTIVE: The history, diagnosis, and therapy of idiopathic intracranial hypertension(IIH) (pseudotumor cerebri) are reviewed. Theories of pathogenesis are considered, theclinical presentation is described, and potential diagnostic and therapeutic challengesare explored.METHODS: An extensive literature review of IIH and related conditions (secondarypseudotumor syndromes) was performed. The history of and rationale for the diagnosisand medical and surgical approaches to treatment are reviewed. Available outcomestudies are presented.RESULTS: Diagnosis of IIH requires that the modified Dandy criteria be satisfied.Multiple potential contributing causes of intracranial hypertension must be identifiedor excluded. The clinical presentation most often includes headaches and papill-edema, but many other findings have been described. The most important goal oftherapy is to prevent or arrest progressive visual loss. Medical therapies includealleviation of associated systemic diseases, discontinuation of contributing medica-tions, provision of carbonic anhydrase inhibitors, and weight loss. Surgical therapiesinclude lumboperitoneal shunting, ventriculoperitoneal shunting, and optic nervesheath fenestration. On the basis of the advantages and disadvantages of these treat-ment modalities, a suggested treatment paradigm is presented.CONCLUSION: Idiopathic intracranial hypertension is the term to be adopted insteadof pseudotumor cerebri. IIH remains an enigmatic diagnosis of exclusion. However,prompt diagnosis and thorough evaluation and treatment are crucial for preventingvisual loss and improving associated symptoms.

KEY WORDS: Headache, Idiopathic intracranial hypertension, Lumboperitoneal shunt, Optic nerve sheathfenestration, Papilledema, Venous sinus thrombosis, Ventriculoperitoneal shunt

Neurosurgery 54:538-552, 2004 DOI: 10.1227/01.NEU.0000109042.87246.3C www.neurosurgery-online.com

Idiopathic intracranial hypertension (IIH),or pseudotumor cerebri, was originally de-scribed as meningitis serosa by Quincke

(131) in 1893. He reported several cases ofincreased intracranial pressure (ICP) withouta brain tumor. Nonne (124) described the syn-drome more fully and coined the term pseudo-tumor cerebri in 1904. Other syndromes result-ing in increased ICP without a brain tumorhad a variety of names, including arachnoiditis(38), otitic hydrocephalus (178), toxic hydroceph-alus (110), and hypertensive meningeal hydrops(40). In 1937, Dandy (39) described 22 patientswith increased ICP without brain tumor. In1955, Foley (53) attempted to simplify the no-menclature by describing the various condi-tions as benign intracranial hypertension. How-ever, in view of the potential for devastatingloss of vision associated with papilledema,

Corbett and Thompson (34) removed the ad-jective “benign” and substituted “idiopathic.”Idiopathic intracranial hypertension denotes thecondition of increased ICP without an obviousunderlying brain pathological condition (andno evidence of venous thrombosis).

Dandy (39) originally described the pres-ence of symptoms of increased ICP, docu-mented cerebrospinal fluid (CSF) pressures of250 to 550 mm H2O with normal CSF findings,and excluded the possibility of brain tumorswith ventriculography. The modern modifiedDandy criteria are similar and include symp-toms of increased ICP, no or false localizingneurological signs (see below), normal brainimaging results, an awake and alert patient,ICP of more than 250 mm H2O, normal CSFfindings, and no identifiable cause of in-creased ICP (Table 1). As Digre and Corbett

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(44) emphasized, these modified Dandy criteria must be metfor a condition to be called IIH (167, 188, 189). Increased ICPattributable to other causes, such as choroid plexus papilloma,venous sinus thrombosis, or venous hypertension attributableto obstructive sleep apnea, do not meet the modified Dandycriteria and are better referred to as secondary pseudotumorsyndromes (see below).

EPIDEMIOLOGICAL CHARACTERISTICS

IIH occurs most commonly among women. The prevalenceis approximately 1 case/100,000 women but increases to 13cases/100,000 women of ages 20 to 44 years who are 10%above ideal body weight and 19 cases/100,000 women of ages20 to 44 years who are obese (�20% above ideal body weight)(47). Depending on the exact criteria used, large proportions ofpatients in virtually all series were obese (39, 44, 53, 82, 195).Most studies demonstrated an age of onset between 11 and 58years, with a mean of approximately 30 years (47, 133, 134,189).

Men are affected less frequently. The incidence is 0.3 cases/100,000 men but increases to 1.5 cases/100,000 obese men(�20% above ideal body weight). Female-to-male ratios areapproximately 4.3:1 to 8:1 (44).

IIH may also be observed in the pediatric population. ACanadian study of children demonstrated equal incidencesamong boys and girls, of approximately 1 case/100,000 indi-viduals (2). No racial predilection has been noted. Isolatedfamilial cases (54, 81, 142, 149, 158, 181) raise the possibility ofa genetic component in the disorder, but no linkage studieshave been performed to date.

PATHOGENESIS

Many theories have been advanced to explain the patho-genesis of IIH. According to the Monro-Kellie rule (115), any-

thing added to the blood, CSF, or brain volume or anythingimpeding CSF or venous egress would be expected to increaseICP. A first possibility is that the CSF volume could be in-creased because of excess CSF production. Quincke (132) sug-gested that hypersecretion of CSF accounted for the syndromebut, except for rare cases of choroid plexus papilloma (49), noclear evidence exists for elevated CSF production as an etio-logical factor in intracranial hypertension (46).

A second possibility is an increase in cerebral blood volumeor brain water content. The original hypothesis proposed byDandy (39) was that the cerebral blood or CSF volume mightbe increased. Foley (53) proposed a similar hypothesis ofincreased cerebral blood flow underlying elevated ICP.Raichle et al. (136) demonstrated with positron emission to-mography that patients with IIH have little change in cerebralblood flow but exhibit markedly increased cerebral blood orwater volumes. Other investigators focused on increased brainwater content. Sahs and Joynt (147) provided histological ev-idence of edema in brain biopsy specimens obtained at thetime of subtemporal decompression for treatment of IIH, al-though this was challenged by later observations (190). Morerecent studies using magnetic resonance imaging (MRI)among patients with IIH demonstrated increased water ap-parent diffusion coefficients and increased white matter watersignals (60, 119, 168, 169). The authors suggested that thismight result from convective transependymal flow causinginterstitial brain edema and increased brain water content(168).

A third possibility is obstruction of CSF or venous outflowas the cause of intracranial hypertension in IIH (82, 143). Manystudies (5, 78, 84, 162) have suggested that the underlyingmechanism involves disturbed CSF absorption secondary toincreased sagittal sinus pressure (necessitating higher CSFpressure to drive bulk flow of CSF across the meninges). Arecent study using pressure measurements during intracranialvenography demonstrated elevated dural sinus pressuresamong patients with IIH (88). Although some of the patients inthat study exhibited dural sinus thrombosis, venous pressureswere elevated even among patients with no obvious evidenceof dural sinus obstruction. Those authors hypothesized thatthe final common pathway for increased ICP in IIH involveselevated venous pressure, leading to increased resistance toCSF absorption and subsequently increased ICP (88). Indeed,among nine patients with IIH who were subjected to directretrograde cerebral venography, Owler et al. (125) recentlyidentified a subset (five of nine patients) with venous sinusobstruction that was treatable with endoluminal stenting. Di-rect measurements of the CSF production rate, CSF outflowresistance, and CSF pressure-volume index (an index of intra-cranial elastance) (159, 166) at various stages of the illnesswould improve our understanding of the mechanisms under-lying IIH (51).

Because there is a female preponderance in IIH, endocrino-logical dysfunction has been hypothesized to contribute to thedisease. Many theories of how obesity might be related to IIHhave been proposed, including increased intra-abdominal

TABLE 1. Modified Dandy criteria for idiopathicintracranial hypertensiona

Symptoms of increased ICP (headaches, nausea, vomiting,transient visual obscurations, or papilledema)

No localizing findings in neurological examinations (except forfalse localizing signs such as abducens or facial palsies)

Awake and alert patient

Normal CT/MRI findings without evidence of dural sinusthrombosis

ICP of �250 mm H2O with normal cerebrospinal fluidcytological and chemical findings

No other cause of increased ICP found

a Adapted from Reference 44. ICP, intracranial pressure; CT, computedtomographic; MRI, magnetic resonance imaging.


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pressure leading to increased right heart filling pressure andsubsequently increased central venous pressure (174, 175).Interestingly, weight loss (94) and bariatric surgery (surgicaltreatment of obesity) (175, 176) have been demonstrated toreduce papilledema and lower CSF pressures. Furthermore,recent weight gain may be associated with relapses of IIH (62).Obesity-associated sleep apnea may also lead to increased ICP(13, 79, 111).

SECONDARY PSEUDOTUMOR SYNDROMES

Associations of various medications and medical conditionswith IIH have been suggested (Table 2). As described above,the association of any medication or condition with IIH is bestdescribed as a secondary pseudotumor syndrome or a second-ary cause of intracranial hypertension, with the term IIH beingreserved for the purely idiopathic condition. For such condi-tions, adequate proof of association requires that withdrawalof the medication or treatment of the underlying conditionimprove the CSF pressure. According to this criterion, manyassociations have not been well substantiated.

Association with Medications

Many case reports and case series describe associationsbetween certain medications and intracranial hypertension.Such medications include vitamin A (hypervitaminosis A)(117, 118) and the vitamin A derivatives isotretinoin (144, 170)and all-trans-retinoic acid (121, 185, 186), antibiotics(tetracycline/minocycline [25, 61], nalidixic acid [30], fluoro-quinolones [58, 199], and sulfa drugs [24]), hormonal medica-

tions (growth hormone [140], oral contraceptives [191], pro-gesterone [177], and danazol [68]), corticosteroid withdrawal(especially among children) (122), and lithium (100, 150). Themost convincing evidence involves tetracyclines and vitaminA and its derivatives. Many case reports have documentedpatients receiving vitamin A who developed increased ICPwith papilledema; the papilledema resolved after withdrawalof the vitamin A source. Symptoms usually develop withdoses of more than 50,000 international units among adultsand 20,000 international units among children (44). Similarly,many case reports have documented the association betweentetracycline and minocycline use and IIH, with resolutionwhen the medication was discontinued (10, 25, 56, 61, 96, 114,114a, 129).

Association with Systemic Diseases

Various systemic diseases have been associated with IIH,including systemic lupus erythematosus (22, 101, 127), under-lying malignancies (193), anemia (21), Addison’s disease (32),hyperthyroidism and hypothyroidism (18, 74, 135), and ure-mia (23, 66, 123). Of these, the association with uremia isprobably the strongest but is complicated by the fact thaturemia may lead to hypervitaminosis A (66) and uremia itselfcan lead to optic neuropathy without papilledema (148).

Association with Venous Obstruction

Dural venous sinus thrombosis has long been recognized asbeing associated with intracranial hypertension (37, 59). Foley(53) and others (64, 178) reported on cases of “otitic hydro-cephalus” caused by transverse sinus thrombosis secondary tootitis and mastoiditis. This led some early investigators toconsider dural sinus thrombosis as a cause of IIH (137). How-ever, on the basis of the modern modified Dandy criteria,dural sinus thrombosis is best considered a secondary pseudo-tumor syndrome. Dural sinus occlusion leads to increasedvenous pressure and higher CSF pressures, with clinical find-ings of papilledema and headaches (37). Therefore, a specificevaluation for venous disease with imaging studies (especiallymagnetic resonance venography), to exclude the possibility ofdural sinus thrombosis, may be advisable for atypical patients(e.g., nonobese patients) with suspected IIH, before the diag-nosis of IIH is established (98).

Certain systemic conditions and medications may be asso-ciated with IIH via a hypercoagulable state leading to duralsinus thrombosis. These conditions include malignancies(193), systemic lupus erythematosus (22, 101, 127), protein Cand S deficiencies (128), antithrombin III deficiency, Factor VLeiden mutations (104, 194), anticardiolipin antibodies (97,116), oral contraceptive use (191), and pregnancy (19). Stan-dard treatment of dural sinus thrombosis involves heparin orwarfarin anticoagulation therapy or direct endovascularthrombolytic therapy (11).

Other venous abnormalities that can elevate intracranialvenous pressures, including dural arteriovenous fistulae (29)and carotid-cavernous fistulae (67), have been associated with

TABLE 2. Clinical associations with idiopathicintracranial hypertension

Ref. no.

Female sex 47

Obesity and weight gain 39, 44, 53, 62, 82, 195

Sleep apnea 13, 79, 111

Hypothyroidism 18, 74, 135

Addison’s disease 32

Uremia 23, 66, 123

Systemic lupus erythematosus 22, 101, 127

MedicationsVitamin A and derivatives 117, 118, 121, 144, 170,

185, 186Antibiotics (especiallyminocycline and tetracycline)

25, 61

Hormonal medications 68, 140, 177, 191Corticosteroid withdrawal 122Lithium 100, 150

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IIH. Iatrogenic disruption of venous drainage, for example,after acoustic neuroma resection (184), radical neck dissection(91, 95, 106), or catheter-induced subclavian vein thrombosis(9, 95), has also been associated with elevated intracranialvenous and CSF pressures. Venous sinus compression bytumors (e.g., meningiomas) has also been reported (107).

CLINICAL PRESENTATION

Symptoms

Headache is the most common symptom and is observedfor nearly all patients (Table 3). IIH headaches are typicallygeneralized, episodic, throbbing, and worse in the morning (1,187). They are often aggravated by Valsalva maneuvers(straining or coughing) and may be associated with retro-orbital pain (187). Neck, shoulder, and arm pain is ofteninvolved (62). The neck pain may be associated with electricshock-like sensations similar to Lhermitte’s sign (31). In addi-tion, transient visual symptoms (obscurations, blurring, andscotomata) and diplopia are frequently noted (62, 82, 146, 195).Pulsatile tinnitus is common (87% in one study [164]) and maybe the initial complaint (8, 62, 163–165). The cause of tinnitusis thought to be turbulence resulting from higher-to-lowervenous pressures around the jugular bulb, which can be aus-cultated in some patients (8, 112, 164). Other symptoms caninclude numbness, incoordination, decreased sense of smell,weakness, and dizziness (Table 3).

Signs

After recording of a complete history, specifically focusingon possible disease associations (as described above), the eval-uation of a patient with potential IIH should continue withcomplete neurological and ophthalmological examinations.Papilledema, as a criterion for the condition, is observed forvirtually all patients with IIH and is the most important sign(see below). However, there have been numerous case reportsof patients with IIH for whom papilledema was not observed,and the absence of papilledema is thus not an exclusionarycriterion (92, 102, 105, 108, 192, 198). Abducens palsy, a falselocalizing sign thought to be attributable to traction of the VIthcranial nerve resulting from intracranial hypertension, is ob-served in approximately 20% of cases (82, 146, 195). Facialpalsy may also be observed (20, 28, 153). An afferent papillarydefect may signal asymmetric optic neuropathy.

Ophthalmoscopic Findings

With the development of computed tomography and MRI,clinicians rely more heavily on imaging to support the clinicallocalization of disease. In cases of suspected IIH, however, anophthalmoscopic examination is critical. Papilledema is usu-ally the only objective finding in physical examinations forpatients with IIH. The ophthalmoscopic appearance of IIH ismost often characterized by bilateral optic nerve head swelling(Fig. 1). However, this can be quite subtle, and cases of IIHwithout papilledema have been reported (92, 102, 105, 108,192, 198). Papilledema may be asymmetric or unilateral (99,

TABLE 3. Symptoms of idiopathic intracranial hypertension

Symptom Approximate incidence (%) Ref. no.

Papilledema Virtually all cases Case reports without: 92, 102, 105, 108, 192, 198

Headaches 92–94 62, 187

Transient visual obscurations 30–68 1, 62, 82, 195

Pulsatile tinnitus Case reports, 64–87 in two small series 8, 62, 120, 146, 163, 164

Neck, shoulder, and/or arm pain 44–48 31, 62, 188, 189

Diplopia 20–38 1, 62, 82, 195

Numbness 24 62

Abducens palsy 20 82, 146, 195

Incoordination 14 62

Decreased smell 12 62

Weakness 10 62

Dizziness 9 86

Facial palsy Case reports 20, 28, 153



160, 180). The degree of optic nerve head swelling is poorlycorrelated with ICP.

Optic Disc Edema versus Papilledema

It is important to distinguish the terms optic disc edema andpapilledema. Optic disc edema is a general term used to de-scribe any swelling of the optic disc. Its causes include in-creased ICP, structural diseases, vascular/circulatory dis-eases, hematological conditions, tumors, collagen vascularand inflammatory diseases, infections, demyelinating dis-eases, and metabolic and toxic conditions (Table 4). Papill-edema refers only to optic disc edema caused by increasedICP.

Most cases of optic disc swelling are caused by optic neu-ritis, anterior ischemic optic neuropathy (AION), or papill-edema. Optic neuritis and AION are usually unilateral,whereas papilledema is bilateral. Papilledema is often asym-metric, however, and optic neuritis and AION can occur bi-laterally, creating the potential for diagnostic confusion.

Imaging Findings

Computed tomographic scans demonstrate that, for the vastmajority of patients with IIH, ventricular size is either normalor small (138). Patients with IIH have traditionally beenthought to have slit ventricles, but a review of computedtomographic findings for 35 patients with IIH demonstratedslit-like ventricles for only 11%; enlarged optic nerve sheaths(47%) and empty sella syndrome (46%) were more common(197). A quantitative analysis of ventricular volume by Jacob-son et al. (77) noted no difference between patients with IIHand age-matched control subjects.

The MRI findings in IIH are generally reported as unre-markable, but in fact abnormalities are usually present. Theabnormalities include a partially empty sella, flattening of theposterior sclera, dilation and tortuosity of the optic nervesheath, and sometimes gadolinium enhancement of the optic

disc (Fig. 2) (14, 57). However, the findings are often too subtleand nonspecific to allow the diagnosis of increased ICP on thebasis of MRI scans alone. Ophthalmoscopic examinationsmust be performed to identify patients with increased ICP. Acommon error in the treatment of patients with headaches andnormal MRI results is making the diagnosis of migraine with-out an adequate ophthalmoscopic examination.

Lumbar Puncture Findings

If the findings on standard MRI scans do not provide com-pelling evidence of ICP elevation, then a lumbar puncture,with direct measurement of the lumbar subarachnoid pres-sure, should be performed in cases of suspected papilledema(Fig. 3). A pressure of greater than 250 mm H2O (measuredwith the patient relaxed, in the lateral decubitus position) isone of the modified Dandy criteria mentioned above. How-ever, it is important to recognize that 42% of asymptomaticobese female patients have opening pressures of greater than250 mm H2O (69). Conversely, a pressure of less than 250 mmH2O is consistent with papilledema in some cases. ICP mon-itoring with intraparenchymal pressure monitors may occa-sionally be necessary if diagnostic doubt persists.

CLINICAL COURSE

The most significant sequela of IIH is blindness or perma-nent visual impairment caused by prolonged papilledema,with secondary optic atrophy. Because visual loss is usuallyinsidious, patients may be nonchalant regarding vision testingand follow-up monitoring until irreversible damage to theoptic nerve occurs. The best corrected Snellen visual acuityshould be recorded at each office visit. However, becausepapilledema affects peripheral vision first, central acuity canbe the last to be affected among patients with papilledema. Asin glaucoma, the optic disc can sustain substantial and irre-versible damage before central visual acuity fails.

Testing of the visual fields with finger confrontation isnotoriously insensitive. Wall and George (189) observedSnellen acuity loss in 22% of patients among a cohort of 50patients with IIH. Only 32% of patients demonstrated abnor-mal visual fields with confrontation testing, but 92% of pa-tients demonstrated abnormal visual fields with quantitativetesting methods. This discrepancy emphasizes that confronta-tion visual field testing is inadequate for detection of visualfield loss among patients with IIH.

Therefore, all patients with a suspected diagnosis of IIHshould undergo regular testing of the visual fields with quan-titative perimetry. The tangent screen and Goldmann perim-eter tests have poor reproducibility and are barely adequatefor this purpose. The best method is automated perimetry(Humphrey perimetry), because it allows more accurate mea-surement of retinal thresholds throughout the visual field. Inaddition to visual acuity and visual field testing, it is helpful toobtain stereophotographs of the optic discs, to document theirappearance over time. These assessments (automated perim-

FIGURE 1. Fundus appearance for a woman with IIH, showing severepapilledema in the right eye (A) and moderate papilledema in the left eye(B). In the right eye (A), there are lines (arrow) of exudate radiating outfrom the fovea, forming a macular star. The white clumps on the swollenoptic disc represent infarctions of the nerve fiber layer, known as cottonwool spots. Numerous areas of splinter hemorrhage are present in bothretinae.

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TABLE 4. Causes of optic disc edemaa

General causes ofoptic disc edema

Specific causes

Increased ICP Brain tumorsIdiopathic intracranial hypertensionDural sinus obstruction/thrombosisCarotid-cavernous fistulaeAVMs (dural or parenchymal)

Structural Optic disc drüsenGlial remnants

Vascular/circulatory

HypertensionNonarteritic AIONArteritic AION (temporal arteritis)Congestive heart failureCOPD/emphysemaCongenital heart diseasePickwickian syndrome/obstructive sleepapneaHypoxiaOcular ischemiaCentral retinal vein occlusionPapillophlebitisRadical neck dissection

Hematological AnemiaAcute hemorrhage/acute hypotensionPolycythemia veraIdiopathic thrombocytopenic purpuraHyperviscosity syndromeWaldenström’s macroglobulinemia

Tumors MeningiomasGliomasHemangiomasHemangiopericytomasMetastasesOrbital tumorsSpinal tumors, especially paragangliomas

Infiltrative tumors Lymphomas/leukemiaMultiple myelomaPolyneuropathy, organomegaly,endocrinopathy, monoclonalgammopathy, skin changesHistiocytosis syndromesMeningeal carcinomatosisParaneoplastic syndromes

Disc tumors HemangiomasHamartomasGliomasHemangioblastomasAstrocytomas

Collagen vasculardisease

Systemic lupus erythematosusPolyarteritis nodosa

TABLE 4. Continued

General causes ofoptic disc edema

Specific causes

Lupus anticoagulant syndromesWegener’s granulomatosis

Inflammatory Uveitis (HLA-B27, Behcet’s syndrome, orVogt-Koyanagi-Harada syndrome)Ocular hypotonyOrbital pseudotumor/myositisSarcoidosisPachymeningitisGranulomatous meningitisInflammatory bowel disease

Infectious TuberculosisHansen’s disease (leprosy)SyphilisHIVViral and postviral (polio, CMV,coxsackievirus, HSV, EBV, rubella)Orbital cellulitisBacterial meningitisFungal/parasitic diseases (Aspergillus,Candida, Cryptococcus, Mucor,Coccidioides, Histoplasma, Toxoplasma)Cat scratch disease (Bartonella)SinusitisMucoceleNeuroretinitisBig blind spot syndrome/MEWDSWhipple’s disease (Tropheryma whippelii)LeptospirosisBrucellosisLyme disease (Borrelia burgdorferi)

Demyelinating Optic neuritis (associated with multiplesclerosis)Schilder’s disease

Hereditary Leber’s optic neuropathyMucopolysaccharidoses

Metabolic/endocrine

Diabetic papillopathy, diabetic ketoacidosisEclampsiaHypoparathyroidismThyrotoxicosisGraves’ orbitopathy (compressive)UremiaPuberty/menarche

Toxic Hypervitaminosis A, ethambutol, methanol,ethylene glycol, lithium, tetracycline,radiotherapy

a ICP, intracranial pressure; AVM, arteriovenous malformation; HIV, hu-man immunodeficiency virus; CMV, cytomegalovirus; HSV, herpes sim-plex virus; EBV, Epstein-Barr virus; COPD, chronic obstructive pulmonarydisease; AION, anterior ischemic optic neuropathy; MEWDS, multipleevanescent white dot syndrome.



etry and optic disc photographs) usually require collaborationwith an ophthalmologist.

The appearance of papilledema can be deceptive. The swell-ing may decrease among patients with papilledema due toprogressive optic atrophy. Therefore, it is difficult to interpretthe appearance of the optic disc in cases of chronic papill-edema; optic nerve function is most important.

For some patients, IIH is a self-limiting condition that spon-taneously remits before significant damage to the optic nerve

occurs (52). However, Corbett et al. (36) emphasized thatsevere visual loss is not infrequent. In a follow-up study of 57patients, 5 to 41 years after the initial diagnosis, blinding orsevere visual impairment was noted for one or both eyes of 14patients (24.6%). That finding is similar to a 17.6% occurrenceof optic atrophy and permanent loss of visual acuity noted inan earlier study (139). Of the 12 patients (of 14 patients) whoconsented to repeat lumbar punctures, 10 exhibited persistentpressure elevation (220–550 mm H2O). That finding empha-sizes the need for aggressive management of visual loss re-sulting from papilledema. Visual loss is usually gradual, butpatients with severe papilledema can rapidly become blind.For patients with papilledema, decreased visual acuity, andfrequent transient obscurations, vision should be monitoredextremely closely and surgical intervention should be per-formed before it is too late. Visual function can decline rapidlyin a matter of hours, creating the potential for a neurologicalemergency.

TREATMENT

Medical Treatment

Carbonic anhydrase inhibitors (e.g., acetazolamide) are theonly effective medications for treatment of papilledema. Ac-etazolamide was originally demonstrated by Rubin et al. (145)to variably decrease CSF production by 6 to 57% amonghuman subjects. A standard dosage is a 500-mg time-releasecapsule twice daily. Acetazolamide has teratogenic effects inanimals (Pregnancy Category C), including limb malforma-tions and cortical dysgenesis (6, 151, 161). Although adequatecontrolled trials have not been performed, case reports havedocumented neonatal metabolic acidosis and electrolyte ab-normalities (113, 126). Therefore, acetazolamide should beavoided, if possible, among pregnant women. Furosemide isalso a diuretic but has little effect on CSF production; it may beused for patients who cannot tolerate acetazolamide. The roleof corticosteroids in the treatment of papilledema is contro-versial. A short course of high-dose corticosteroid therapymay be helpful for patients with acute visual loss resultingfrom fulminant papilledema (103). However, corticosteroidsshould not be used chronically for treatment of papilledema.

Weight loss can be beneficial for patients with papilledemaresulting from IIH. Professional dietary counseling andweight loss programs may be recommended. It is difficult toprove that weight loss improves papilledema in IIH because 1)acetazolamide administration is often initiated concurrently(80), 2) few patients lose enough weight to test the theory, and3) the disease can remit spontaneously. However, a history ofrecent weight gain often accompanies the initial presentationof IIH. Interestingly, Sugerman et al. (175) demonstrated dra-matic decreases in CSF pressure and symptoms among obesepatients treated with gastric stapling.

Because certain medications, such as vitamin A, vitamin Aderivatives, and tetracycline, have been associated with intra-cranial hypertension (see above), these medications should be

FIGURE 2. A, sagittal, T1-weighted, MRI scan, showing a partiallyempty sella (arrow). This finding is common among patients with IIH. B,axial, T1-weighted, orbital, MRI scan with fat saturation and gadoliniumenhancement, showing dilation of the optic nerve sheath (between pairsof arrows) and flattening of the posterior globe (between two singlearrows) resulting from increased ICP.

FIGURE 3. Diagnosis and treatment algorithms for IIH (also see Tables1–4). HA, headache; MRV, magnetic resonance venography.

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discontinued if possible to assess the clinical response. Forpediatric patients receiving all-trans-retinoic acid as chemo-therapy for leukemia (121, 185, 186), it may be preferable totreat the secondary pseudotumor syndrome, rather than dis-continuing the medication. It is not necessary to discontinueoral contraceptives in women with IIH.

Some neurologists advocate serial lumbar punctures (e.g.,twice weekly) as an alternative to surgery for patients withpapilledema that cannot be controlled medically. However,serial lumbar punctures are a poor approach because 1) mostobese patients with chronic papilledema are difficult to treatwith lumbar punctures and 2) patients generally dislike seriallumbar punctures. At best, lumbar puncture and drainage of alarge volume of CSF are useful emergency measures for pa-tients with severe papilledema and sudden extinction of vi-sion. In some cases, it is necessary to hospitalize patients withlumbar subarachnoid drains until surgery can be scheduled.This is a good strategy if lumboperitoneal (LP) shunting isplanned, although it may increase the risk of infection. Opticnerve sheath fenestration is easier to perform when the sheathis turgid; therefore, the drain should be removed or clampedbefore surgery.

Surgical Treatment

Surgical intervention is required as soon as medical treat-ment fails. A common management error is to delay too longbefore recommending surgery. Corbett (33) emphasized that“there is no ‘acceptable’ level of visual field or acuity losswhich one should wait for—visual loss which continues de-spite optimum medical therapy is sufficient reason to turn todecompression” (33, p 228). Surgery should also be consideredfor patients who are unlikely to return for follow-up visits orwho are unable to cooperate with medical therapy. Surgeryshould be considered not only for treatment of visual loss butalso for treatment of intractable headaches.

History of Surgical Treatment of Papilledema

Optic nerve sheath fenestration, which was introduced byde Wecker (43), was the first treatment devised for the surgicalrelief of papilledema. The operation involved insertion of aguarded neurotome into the orbit to slit the optic nerve sheathvia a conjunctival incision. However, subtemporal decompres-sion, which was introduced by Dandy (39) in 1937, became theoperation of choice for papilledema. Dandy performed a rightsubtemporal craniectomy for decompression and reported ex-cellent initial results in alleviating headaches and preventingvisual loss. However, the longer-term efficacy was uncertainand morbidity and complications were significant, includingseizures, infections, focal brain damage, cosmetic disfigure-ment, intracranial hematomas, and further visual deteriora-tion (65).

LP Shunting

Subtemporal decompression rapidly became obsolete afterthe introduction of intracranial shunting procedures by Ingra-

ham et al. (75) and Matson (109). However, the ventriculoperi-toneal (VP) shunts devised by those pioneers were difficult toinsert among patients with IIH, because the ventricles wereoften small. The development of LP shunting circumventedthis problem. Vander Ark et al. (183) published the first de-scription of LP shunting for patients with IIH. Soon thereafter,Spetzler et al. (171) developed a method for percutaneousinsertion of the shunt into the lumbar sac, greatly facilitatingplacement of LP shunts.

After the introduction of LP shunting, few studies docu-menting its efficacy for the treatment of papilledema werepublished. Anecdotal reports of success suggested that it wasa curative procedure, as long as the shunt functioned prop-erly. In 1981, Johnston et al. (85) published a major review of134 cases of IIH treated between 1942 and 1979, with a meanfollow-up period of 11.6 years. Fourteen patients receivedshunts (six VP shunts and eight LP shunts). Of the six patientswho received VP shunts, four demonstrated resolution of allsymptoms within 6 months. One patient developed a shuntobstruction that necessitated revision, and another patientexperienced a shunt infection that necessitated removal. Ofthe eight patients who received LP shunts, all demonstratedimprovement within 1 month. One patient experienced ashunt infection, and one patient exhibited severe low-pressuresymptoms as a result of overshunting. In a follow-up study,Johnston et al. (83) reported on 36 patients who receivedshunts for treatment of IIH. The patients required a total of 86shunting procedures, with a complication rate of 52% and afailure rate of 48%; the lowest revision and complication rateswere associated with LP shunts.

A multicenter review of the outcomes of shunting for 37patients was performed in the late 1980s (141). In that study,37 patients received a total of 73 LP shunts and 9 VP shunts,and only 14 patients remained “cured” after a single surgicalprocedure. Sixty-four percent of shunts lasted less than 6months, with shunt failure (55%) and low-pressure headaches(21%) being the most common reasons for reoperation. Thevision of most patients either improved (13 patients) or stabi-lized (13 patients) postoperatively. That report initially led toa resurgence of interest in optic nerve sheath fenestrationamong ophthalmologists. However, the finding that manyoptic nerve sheath fenestrations fail within 1 year, as well asmounting evidence of serious complications (see below), hasrestored LP shunting as the favored surgical treatment option.Two major studies recently demonstrated the efficacy of LPshunting for treatment of IIH. Eggenberger et al. (48) con-ducted a retrospective study of 27 patients with IIH, who weremonitored for a median of 47 months after shunting. Visualloss was the main reason for surgery for 14 patients; head-aches were the reason for the remaining 13 patients. Visionimproved or remained the same for all 14 patients, and head-aches improved for all patients. There were no serious com-plications, except for shunt failure. Fifteen patients (56%) re-quired shunt revision, sometimes more than once (range, 1–13revisions). The average number of revisions per patient was2.4, with one revision being performed every 2.6 years. The



authors concluded that LP shunting was a satisfactory treat-ment for the majority of patients.

Burgett et al. (17) reported data for 30 patients who under-went LP shunting for treatment of IIH. The mean follow-upperiod was 35 months. Of 14 eyes with impaired acuity, 10eyes (71%) improved by at least two chart lines; only 1 eyeexperienced a decline in vision. Goldmann perimetry docu-mented improvement for 64% of eyes with abnormal fields,and no eyes exhibited any worsening. Again, the only com-plication was frequent shunt obstruction. Twelve patients re-quired no shunt revision. The remainder underwent a mean of2.5 revisions/patient (excluding four patients who underwentexceptionally high numbers of revisions, i.e., 38, 29, 10, and10).

Those two studies provided encouraging data regarding theefficacy of LP shunting; the operation seems effective, as longas the shunt remains patent. As in most large reviews (27, 83,141), obstruction was the most common complication of LPshunts (accounting for 65% of revisions in the study byEggenberger et al. [48]). In all patients with suspected shuntobstruction, lumbar subarachnoid pressure should be mea-sured. Neuroimaging findings may not be revealing, becausethe ventricles are not enlarged in IIH (89). Technetium-99shunt function studies can provide valuable data by demon-strating tracer flow into the abdomen and providing a half-time for radionuclide clearance (4, 73).

Other complications associated with LP shunting in thosestudies were less common (Table 5). Secondary intracranialhypotension caused by CSF overdrainage accounted for 15%of revisions in the study by Eggenberger et al. (48), and lumbarradiculopathy accounted for 4.5% of all revisions. Shunt infec-

tions occur in only approximately 1% of cases of LP shunting(154). Tonsillar herniation (acquired Chiari malformation) (26,196) and syringomyelia (50) are other recognized complica-tions of LP shunting, but they only rarely necessitate revision(70). Tonsillar herniation may create a “new” headache syn-drome. A problem common to all obese patients is technicaldifficulty with excessive subcutaneous abdominal fat, whichnecessitates large incisions. In this respect, the use of laparo-scopic techniques for insertion of the peritoneal catheter ispotentially advantageous.

LP shunt valve pressure mechanisms with external pressurecontrol are now being developed. We currently prefer LPshunting with an inline horizontal-vertical valve, rather thanstereotactic VP shunting. One commercially available systemdescribes two pressure ranges, depending on ventricular sizeand/or body habitus. For each patient group, there is a fixedhorizontal pressure setting (50–80 mm H2O or 85–125 mmH2O) and three different vertical pressure settings. For pa-tients with IIH (small ventricles, large body habitus, and sus-pected intracranial hypertension), the senior author prefers tobegin with the higher horizontal pressure setting (85–125 mmH2O) and the midrange vertical pressure setting (265–365 mmH2O).

For patients with repeated LP shunt obstructions, the optionof VP shunting should be considered. First, although the tech-nique is more invasive, the long-term outcomes may be better(87). Second, technical innovations in stereotactic surgery en-able accurate targeting of the lateral ventricle. A recent studyof seven patients treated with stereotactic VP shunts (using aCosman-Roberts-Wells frame) for IIH demonstrated success-ful uncomplicated shunt placement in all cases (182). Five of

TABLE 5. Complications of surgical procedures for treatment of papilledema

Optic nerve sheath fenestration Lumboperitoneal shunt

Central retinal artery occlusion Obstruction

Branch retinal artery occlusion Infection

Central retinal vein occlusion Low-pressure headaches

Choroidal infarction Radiculopathy

Traumatic optic neuropathy Tonsillar herniation (acquired Chiari I malformation)

Hemorrhage (intrasheath or intraorbital) Syringomyelia

Diplopia Subdural hematoma

Pupil dilation resulting from sphincter denervation Shunt migration

Anterior segment ischemia

Compressive optic neuropathy resulting from orbital cyst

Corneal delle formation

Infection

BINDER ET AL.


the seven patients experienced resolution of papilledema andsix of the seven experienced resolution of headaches postop-eratively. Another study demonstrated the application of fra-meless stereotaxy and intraoperative fiberoptic endoscopy forprecise ventricular catheter insertion (179). Those studies sup-port the idea of routine stereotactic VP shunting in IIH, witheither frame-based or frameless stereotaxy. Third, VP shunt-ing may facilitate noninvasive assessment of shunt function,because it provides a reservoir for isotope shunt functiontesting; noninvasive analysis of LP shunt function has beenlimited to radiological findings (93).

Optic Nerve Sheath Fenestration

The failure rate associated with LP shunting renewed en-thusiasm for optic nerve sheath fenestration among ophthal-mologists in the 1980s. The procedure had continued to beperformed by a few surgeons (7, 41, 42, 55, 90) but onlysporadically. In 1988, three major reports appeared in theophthalmological literature, describing the outcomes of opticnerve sheath fenestration for treatment of IIH in large series ofpatients (15, 35, 157). The results were surprisingly good; theoperation seemed to provide effective treatment of papill-edema and maintained or improved visual acuity for 85 to100% of patients. However, the follow-up periods were shortin those studies.

In a study of 53 patients (101 eyes), Spoor et al. (173)reported that optic nerve sheath fenestration improved visualfunction for 69 eyes with acute papilledema and 10 eyes withchronic papilledema. In a later report with longer follow-upperiods, Spoor and McHenry (172) described the outcomes ofoptic nerve sheath fenestration for 75 eyes of 54 patients withIIH. After initial improvement in visual function, 24 eyes(32%) required repeat optic nerve sheath fenestration becauseof deteriorating visual function. Deteriorating vision was de-tected a mean of only 10.4 months after surgery, and 25% ofeyes continued to lose vision even after repeat surgery.

In 1989, Sergott et al. (156) reported improved visual func-tion for 12 of 14 patients with progressive nonarteritic AIONwho were treated with optic nerve sheath fenestration. In1995, the National Eye Institute-sponsored Ischemic OpticNeuropathy Decompression Trial Research Group reportedthe results of a multicenter study of optic nerve sheath fenes-tration for treatment of AION (76). The study found no benefitof optic nerve sheath fenestration for treatment of AION,contradicting the study by Sergott et al. (156), and docu-mented significant complications of the procedure, includingoptic nerve injury during surgery (Table 5). The incidence ofcatastrophic visual complications was 3 cases/115 patients, or2.6%. Another study reported postoperative blindness for 3 of200 patients (1.5%) (155). A 2% risk of outright blindness hasdiscouraged patients and ophthalmologists. Plotnik andKosmorsky (130) emphasized that the complication rate maybe as high as 40%, including vascular compromise (11%, cen-tral retinal artery occlusion, branch retinal artery occlusion, orouter retinal ischemia), transient ocular motility disturbances

(29%), and papillary dysfunction (11%). Although enthusiasmfor optic nerve sheath fenestration has moderated, the proce-dure remains a viable option for the prevention of visual lossresulting from papilledema (3, 12, 63, 71).

SUMMARY AND RECOMMENDATIONS

We recommend LP shunting over optic nerve sheath fenes-tration as the initial surgical treatment for IIH for the follow-ing reasons. 1) LP shunting involves no direct risk to the eye.The 2% risk of devastating optic nerve or retinal vascularinjury with optic nerve sheath fenestration is discouraging. 2)For most patients, surgical treatment of the optic nerve sheathof one eye improves papilledema in both eyes, but the benefitin the contralateral eye is usually less pronounced. For pa-tients with severe papilledema, optic nerve sheath fenestrationmay be required for both eyes (two operations, with twice therisk of complications). Successful LP shunting needs to beperformed only once. 3) Although shunt obstruction is a seri-ous problem (almost 50% in the first 2 yr after shunt place-ment), the data reported by Spoor and McHenry (172) suggestthat a similar number of optic nerve sheath fenestrations be-come closed by scarring over a similar period. 4) Many pa-tients with visual loss resulting from papilledema also expe-rience headaches attributable to increased ICP. After opticnerve sheath fenestration, ICP usually remains elevated (7, 16,35, 72, 90), suggesting that optic nerve sheath fenestrationworks without producing major decreases in CSF pressure (asmeasured with lumbar punctures). The operation probablyworks by filtering small quantities of CSF into the orbit, whichmay produce a local pressure reduction within the subarach-noid space immediately behind the optic nerve head (152). It istrue that optic nerve sheath fenestration can provide relief ofheadaches for some patients with papilledema (15, 35, 41, 55,157). However, LP shunting is more effective for treatingheadaches and thus has the advantage of improving bothpapilledema and headaches. For many patients, headachesrepresent the main reason to operate. 5) Some patients withIIH exhibit diplopia resulting from abducens palsy. This usu-ally resolves after LP shunting. In contrast, optic nerve sheathfenestration does not improve diplopia and can result in newdiplopia as a postoperative complication. 6) LP shunting usu-ally results in complete resolution of papilledema, as long asthe shunt is functioning properly. After optic nerve sheathfenestration, some residual papilledema often persists. 7)Some patients cannot cooperate with vision testing. For thosepatients, it is difficult to monitor visual function after surgicaltreatment of papilledema. In such cases, objective proof ofnormal ICP in lumbar punctures is desirable. This option isnot useful after optic nerve sheath fenestration, because pres-sure usually remains high.

After a surge in popularity between 1987 and 1993, outcomereports suggested that optic nerve sheath fenestration may beless effective than LP shunting for treatment of papilledemaand may be more prone to complications. LP shunting is thebetter option but is limited by shunt obstruction. Stereotactic



VP shunts may offer reduced rates of shunt obstruction. Allpatients with IIH require close postoperative follow-up be-cause there is a threat to vision even after surgery. A multi-center prospective trial comparing the efficacy of LP shuntingversus optic nerve fenestration or LP shunting versus VPshunting would be useful for determination of the optimalroles for these surgical treatment modalities.

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COMMENTS

The authors make a case for lumboperitoneal shunt as a treat-ment potentially superior to optic nerve sheath fenestration

as initial treatment for idiopathic intracranial hypertension.There is rationale for this, such as treating the intracranial pres-sure rather than only the visual symptoms of papilledema andvision loss. This does not explain the reports of improvement ofmultiple cranial symptoms after optic nerve sheath fenestration.In addition, the rather frightening incidence of shunt obstructionafter lumboperitoneal shunt and the possibility of other compli-cating deteriorations such as intracranial hypotension or brain-stem traction are not well quantified. Indeed, both treatments arevery poor at establishing a long-term treatment. It is safe to saythat no treatment has been universally effective and that thesearch for further treatments, both medical and surgical, shouldcontinue. A much stronger case could be made than the authorsdo for stereotactic ventriculoperitoneal shunt placement becauseof the improved ability to regulate intracranial pressure and thedecreased risk of foramen magnum compaction. The authors’decision to recommend lumboperitoneal shunt is not supportedby positive evidence in this article.

The discussion of idiopathic intracranial hypertension is interest-ing. The relationship of the syndrome to vitamin A is compellingand calls for further investigation as to pathogenesis. The authors domake an important point that patients with headaches and normalmagnetic resonance imaging scans are commonly misdiagnosed ashaving a migraine variant. Further investigation, especially formalophthalmological examination, should always be included in the



evaluation of such patients. This is especially important because thenormal range of intracranial pressure may vary widely in obesepatients. Although the article covers the pitfalls of the treatmentoptions discussed, I would recommend a more careful review ofother treatment options, including weight loss, venous studies, andstereotactic ventricular shunting.

Robert J. DempseyMadison, Wisconsin

The authors have provided a thorough and practical review ofidiopathic intracranial hypertension. The pathophysiology of

idiopathic intracranial hypertension/pseudotumor cerebri ismost likely related to cerebral venous hypertension. So-calledsecondary pseudotumor cerebri patients with dural sinus throm-boses represent only the extreme of a spectrum. I think that moreeffort should be placed on addressing the primary problem,venous hypertension, both diagnostically and therapeutically.From a diagnostic viewpoint, magnetic resonance venographylacks sufficient sensitivity to detect hemodynamically significantdural sinus obstructions. As the availability and use of percuta-neous retrograde venous sinus dynometry increases, an increas-ing number of “idiopathic” cases will instead be found to besecondary to sinus strictures (despite “normal” magnetic reso-nance venographic studies). The placement of dural sinus stentsis still relatively new, and long-term follow-up will be requiredbefore we can determine their efficacy and safety. Bariatric sur-gery, which lowers the cardiac right atrial pressure and second-arily the dural sinus pressure, may be indicated in obese patientsin whom a dural sinus pressure gradient (stricture) was notfound by dynometry. It is hoped that cerebrospinal fluid diver-sion procedures, which can be quite problematic in these pa-tients, will diminish in importance and frequency.

Marvin BergsneiderDaniel F. KellyLos Angeles, California

The authors have provided an excellent review of a verycontroversial topic. They have adopted the term idiopathic

intracranial hypertension in place of pseudotumor cerebri, and Iwould certainly support that change. I would disagree withtheir use of the term secondary pseudotumor syndrome to includethe known causes of intracranial hypertension. Certainly, if apatient has elevated intracranial pressure from an obstructedvenous sinus or from hypervitaminosis A, they have simply“intracranial hypertension” and no longer “idiopathic intra-cranial hypertension.” The term pseudotumor should beabandoned.

William F. ChandlerAnn Arbor, Michigan

The authors have reviewed the history, diagnosis, and ther-apy of intracranial hypertension. I agree with the authors’

statement that the term idiopathic intracranial hypertensionshould be adopted in place of pseudotumor cerebri. This is a nicereview, and the authors have put into perspective some his-torical and contemporary concepts regarding the pathophys-iology of and treatment options for this disorder.

Warren R. SelmanCleveland, Ohio

This article comes from the neurosurgery and ophthalmol-ogy departments at the University of California, San Fran-

cisco. The authors present a workman-like review of intracra-nial hypertension. For neurosurgeons, the greatest value of thearticle may be the extensive list of medications and medicalconditions that have been reported to be associated with id-iopathic intracranial hypertension and the compilation of theresults of optic nerve sheath decompression.

Robert G. GrossmanHouston, Texas

Spirit rover robot-generated image of the Martian landscape. An image taken on January 27, 2004, from Spirit’s PanCam looking west depicts thenearby hills named after the astronauts of the Apollo 1. The crew of Apollo 1 perished in a flash fire during a launch pad test of their Apollo spacecraft atKennedy Space Center, FL, on January 27, 1967. Miniaturization and increased sophistication in robotic technology make possible the exploration of Mars;such miniaturization and sophistication fuel technology transfer from aerospace engineering to medical, and especially neurosurgical, robotics. (Courtesy,NASA/JPL/Cornell.)

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