Journal of Neuro-Ophthalmology, June 2004, Volume 24, Issue 2

Idiopathic Intracranial Hypertension

The syndrome of intracranial hypertension without structural brain or cerebrospinal fluid abnormalities and without identifiable cause, now most appropriately termed idiopathic intracranial hypertension, was described over a century ago. Although the pathogenesis of this condition remains unknown, diagnostic and therapeutic developments during the past two decades have substantially advanced patient management.

STATE OF THE ART Idiopathic Intracranial Hypertension Deborah I. Friedman, MD and Daniel M. Jacobson, MD Abstract: The syndrome of intracranial hypertension without structural brain or cerebrospinal fluid abnormali­ties and without identifiable cause, now most appropriately termed idiopathic intracranial hypertension, was described over a century ago. Although the pathogenesis of this con­dition remains unknown, diagnostic and therapeutic devel­opments during the past two decades have substantially ad­vanced patient management. ( JNeuro- Ophthalmol 2004; 24: 138- 145) DEFINITION The syndrome of increased intracranial pressure ( ICP) without ventriculomegaly or mass lesion, and with normal cerebrospinal fluid ( CSF) composition, was first de­scribed more than a century ago, yet we still know little about its pathogenesis ( 1). Often referred to as " pseudotu­mor cerebri" but more appropriately called " idiopathic in­tracranial hypertension" ( IIH), it is a surprisingly common disorder. In young overweight women, the annual inci­dence is as high as 20 per 100,000 persons ( 2). The definition of IIH has evolved with clinical expe­rience and advances in imaging technology. Currently, IIH can be diagnosed only if the following criteria are met ( Table 1): 1) symptoms and signs attributable to increased ICP or papilledema; 2) elevated ICP recorded during lum­bar puncture in the lateral decubitus position; 3) normal CSF composition; 4) no imaging evidence of ventriculo­megaly or a structural cause for increased ICP, such as a brain parenchymal, ventricular, meningeal, or venous sinus abnormality; and 5) no other cause of intracranial hyperten­sion identified, such as use of certain medications. The diagnosis and management of IIH remains based largely on anecdotal evidence. However, substantial devel­opments during the past two decades have provided clini­cians with more tools for excluding disorders that mimic IIH and for facilitating its diagnosis and management. Departments of Ophthalmology and Neurology, University of Rochester School of Medicine and Dentistry Rochester, New York ( DIF), and Departments of Neurology and Ophthalmology, Marshfield Clinic, Marshfield, Wisconsin ( DMJ). Address correspondence to Deborah I. Friedman, MD, 601 Elmwood Ave, Box 569, Rochester, NY 14642; E- mail: Deborah_ Friedman@ urmc. rochester. edu NOMENCLATURE The nomenclature for IIH remains controversial. " Benign intracranial hypertension" is no longer accepted, as significant visual morbidity may occur with this disorder ( 3). The term " pseudotumor cerebri," a historically popular and all- encompassing term, leaves the impression that IIH is not a real disease. IIH is currently the favored term for the primary ( idiopathic) disorder. For those patients with an identified cause of intracranial hypertension without struc­tural brain imaging or CSF constituent abnormalities, the appropriate diagnostic term would be " intracranial hyper­tension secondary to (...)." The typical patient with IIH is an obese woman of childbearing age ( 4). Atypical patients include men, slim women, prepubescent children, and pa­tients older than age 44 years. NATURAL HISTORY AND VISUAL PROGNOSIS There are few prospective data in the era of modern imaging ( computed tomography [ CT], magnetic resonance imaging [ MRI], and magnetic resonance venography [ MRV]) to document the natural history of the disorder. Clinical experience, however, suggests that it is common for patients to have a protracted course lasting months to years, during which they may be asymptomatic but have chronic papilledema, or have symptoms that require medi­cal agents to lower their ICP. This suggests that intracranial hypertension, symptomatic or not, persists in many patients with IIH. Indeed, one series found that 10 ( 83%) of 12 pa­tients in long- term follow- up who underwent repeated lum­bar punctures showed persistently elevated ICPs ranging from 220 to 550 mm H20 ( 5). Recurrent symptoms and papilledema have been reported in 8%> to 37%> of patients often years after the initial diagnosis ( 5,6). The principal morbidity of IIH is papilledema-associated visual loss. A prospective study of 50 patients with IIH found visual field defects at initial presentation in at least one eye in 96%> of patients assessed with the Gold-mann perimeter, and in 92% o of patients assessed with the Humphrey perimeter ( 4). After treatment, 60% o of patients improved, 30% o remained stable, and 10% worsened, as as­sessed with Goldmann perimetry ( 4). Assessed with the Humphrey perimeter, 50% o of patients improved, 28% o re­mained stable, and 22% o worsened ( 4). 138 J Neuro- Ophthalmol, Vol. 24, No. 2, 2004 Idiopathic Intracranial Hypertension JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 TABLE 1. Clinical criteria for diagnosing idiopathic intracranial hypertension* Symptoms, if present, represent increased intracranial pressure or papilledema Signs represent increased intracranial pressure or papilledema Documented elevated intracranial pressure during lumbar puncture measured in the lateral decubitus position Normal cerebrospinal fluid composition No evidence of ventriculomegaly, mass, structural, or vascular lesion on magnetic resonance imaging or contrast- enhanced computed tomography for typical patients, and magnetic resonance imaging and magnetic resonance venography for all others No other cause ( including medication) of intracranial hypertension identified * Adapted from reference 7. DIAGNOSIS Imaging With advances in neuroimaging techniques and a growing understanding of the pathophysiology of IIH, the diagnostic criteria for this condition have recently been re­vised ( 7) ( Table 1). A noncontrast CT was previously con­sidered an adequate imaging study because it can exclude ventriculomegaly or a mass lesion. However, conditions that increase ICP without producing ventriculomegaly or mass lesions, such as gliomatosis cerebri, meningitis, and cerebral venous thrombosis, may mimic IIH yet not have associated CT abnormalities to provide a clue to the true underlying condition. Accordingly, this imaging technique may be suboptimal, particularly for atypical patients. Un­less there are external constraints ( weight limitations, avail­ability), MRI with MRV is currently the study of choice. Using a special technique, three- dimensional gadolinium-enhanced MRV appears to be more sensitive than conven­tional MRV for detecting areas of subtle cerebral venous stenosis ( 8). The clinical relevance of these changes is un­certain, and likely reflects a compensatory response to in­creased ICP. CSF Opening Pressure The medical literature contains various, and some­times conflicting, recommendations regarding the mini­mum CSF opening pressure required for diagnosing IIH. In general, however, a CSF pressure greater than 250 mm H20 is consistent with the diagnosis, less than 200 mm H20 is normal, and 201 to 249 mm H20 is nondiagnostic ( 9). Con­trary to popular belief, there is no evidence that body weight influences these cutoff values. The upper limit of normal CSF pressure in children is generally considered to be 180 to 200 mm H20; the effect of obesity in children has not been studied. Visual Fields Although visual acuity and color perception are gen­erally preserved in papilledema unless it enters a chronic and atrophic stage ( 10- 12), visual fields and contrast sen­sitivity may be abnormal earlier. Visual field testing is far more sensitive for detecting optic nerve damage producing visual loss, particularly in the early stages of the disorder. Quantitative perimetry with static or kinetic methods is the current standard for assessing visual fields in IIH. The sen­sitivity to the detection of visual field defects is similar us­ing either technique, assuming an experienced perimetrist performs the kinetic test ( 11,13). Newer perimetric techniques, such as frequency-doubling technology perimetry, short- wavelength auto­mated perimetry, tendency- oriented perimetry, and high-pass resolution ( ring) perimetry have been examined in pa­tients with glaucoma, but, with the exception of high- pass resolution perimetry ( 14), not well- studied in other optic neuropathies or in IIH. Motion perimetry, in which com­puter graphics generate small circular regions of coherent motion perception targets throughout the central visual field, identified the visual field defects in patients with IIH detected with conventional automated perimetry, as well as some defects that were not identified using automated pe­rimetry ( 15). These results, and those elicited with other newer perimetric techniques, must be confirmed and vali­dated before the newer tools replace the current visual field testing methods. Monitoring the Optic Nerve Head Whereas the results of visual field testing provide functional information concerning the degree of optic nerve damage, assessment of the degree of papilledema change over time often provides a useful structural measure of the clinical course and effect of treatment. In some patients, however, papilledema never resolves completely despite resolution of symptoms and stabilization of visual function. It is important to document the appearance of the optic disc with photographs, ideally at the first evaluation and when­ever there is a change. Confocal scanning tomography is a new tool that can quantify the degree of papilledema and measure changes over time ( 16). Tomographic parameters of the optic nerve head seem to correlate with visual field sensitivity loss ( 17). For routine patient care, however, confocal scanning to­mography is not a practical tool and may not provide more useful information than carefully performed and interpreted visual fields. Future studies are needed before deciding if this technique will find a place in routine patient management. 139 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Friedman and Jacobson Visual Acuity Loss of visual acuity generally does not occur in acute papilledema unless there is macular edema. As untreated papilledema becomes more chronic, however, progressive impairment of visual acuity can be expected from a variety of causes ( Table 2). Contrast Sensitivity Loss of contrast sensitivity is frequently identified in patients with IIH, regardless of the technique used ( 10- 12). For that reason, some investigators recommend contrast sensitivity testing as an adjunctive measure to assess optic nerve function. Whereas this tool may detect a global ab­normality of optic nerve function when other standard mea­sures are normal ( 11), its specificity for optic nerve dys­function is low. Visual Evoked Potentials Assessment of visual evoked potentials ( VEP) is of­ten performed to screen for injury to the optic nerve. How­ever, this technique probes only the central 10 degrees of visual field, a region that is insensitive to visual loss in pap­illedema ( 11). Thus, there is no role for VEP in evaluating patients with IIH. The future role of multifocal VEP, which is capable of assessing nonfoveal neurotransmission, re­mains to be determined. RISK FACTORS FOR VISUAL LOSS Several clinical series have identified factors that may influence visual outcome in patients with IIH ( Table 3) ( 2,18- 22). The reliability of these variables in clinical prac­tice may be limited on an individual case basis because they were determined from retrospective studies. Some reports provide conflicting results. MIMICKERS OF IIH As long as the diagnostic guidelines outlined in Table 1 are followed, there is little chance of failing to diagnose an ominous mimicker of IIH. Still, some cases of cerebral ve­nous sinus thrombosis, gliomatosis cerebri, and leptomen-ingeal infiltration by a chronic neoplastic or infectious pro­cess may escape detection with brain imaging and CSF TABLE 2. Causes of loss of visual acuity in idiopathic intracranial hypertension Chronic ( atrophic) papilledema Chorioretinal folds Macular edema or exudates Infarction of the optic disc Subretinal peripapillary hemorrhage extending through the fovea Subretinal peripapillary neovascular membrane TABLE 3. Predictors and nonpredictors of visual loss in patients with idiopathic intracranial hypertension* Factors predictive of visual loss Recent weight gain High- grade papilledema Atrophic papilledema Subretinal hemorrhage Significant visual field loss at presentation Hypertension Factors not predictive of visual loss Duration of symptoms Transient visual obscurations Double vision Pulsatile intracranial noises Degree of headache Opening pressure during lumbar puncture Pregnancy * Adapted from references 2, 17- 21. analysis until late in their course. Red flags that should sig­nal the possible presence of a mimicker are outlined in Table 4 ( 23- 26). One should be particularly cautious about falsely di­agnosing IIH in patients with abnormal visual fields that are psychogenic in nature, in those with anomalous optic discs, and when the opening pressure during lumbar puncture was improperly measured. Because concentric visual field con­striction is a finding common to both psychogenic visual loss and IIH, misinterpretation of this visual field defect is a particularly frequent problem ( 5). TREATMENT Indications for Treatment Not all patients with IIH require treatment. After es­tablishing the diagnosis, asymptomatic individuals with TABLE 4. " Red flags" that suggest the presence of a mimicker of idiopathic intracranial hypertension Atypical demographic profile Cranial nerve palsies other than sixth nerve palsy Alteration in level of consciousness Focal neurologic signs apart from sixth nerve palsy Abnormal CSF profile ( low glucose or high protein concentrations) Explosive onset of symptoms Rapid development of visual loss and progression of symptoms Global ophthalmoparesis Internuclear ophthalmoplegia Vertical gaze disorder 140 © 2004 Lippincott Williams & Wilkins Idiopathic Intracranial Hypertension JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 normal vision and minimal papilledema can be monitored frequently for the development of symptoms or visual de­cline. A small percentage of patients improve after their di­agnostic lumbar puncture ( LP). The reason for the apparent cure is uncertain and may relate to re- establishing normal CSF homeostasis or cerebral venous pressure when normal CSF pressure is temporarily restored ( 27). Patients experi­encing transient visual obscurations with normal visual function may be observed unless they have moderately se­vere papilledema. Some patients with headaches and mini­mal visual signs ( visual field loss limited to a slightly en­larged blind spot) may also be managed conservatively. Therapy is initiated in the presence of visual acuity or visual field loss ( apart from mild enlargement of the blind spot), moderate to severe ( Frisen grade 3- 5) papilledema or persistent headaches ( 28). Visual signs and symptoms often co- exist with headache, but the two manifestations are ap­proached independently. Treatment is always indicated when patients are aware of their visual deficit. Dietary Management Dietary management and weight loss are time-honored treatments, supported by several observational studies ( 29- 36). The earliest report described rapid resolu­tion of papilledema in nine obese patients treated with a very low- calorie ( 400- 1,000 calories daily) rice diet ( 29). One retrospective study correlated weight loss to papillede­ma in 15 women with IIH who were treated with acetazol-amide at the time of diagnosis ( 30). Within the 24- week study period, 11 patients had improvement or resolution of papilledema. The six patients who had complete resolution of marked papilledema underwent a mean weight loss of 6.2% total body weight. Patients who were unable to achieve the same degree of weight loss had lesser degrees of improvement in their papilledema grade. The four patients with unchanged optic disc swelling had no weight loss dur­ing the study period. Another retrospective series evaluated the effect of weight loss on visual function and papilledema grade in 58 patients ( 31). There was more rapid improvement in papil­ledema and visual fields in overweight women with IIH who lost weight ( mean weight loss 13.3 ± SD 9.9 lb) than in those who did not lose weight ( mean weight loss 0.2 ± SD 0.6 lb). Surgically induced weight loss ( mean loss 57 ± 5 kg) was associated with decreased CSF pressure and reso­lution of papilledema in eight patients examined 34 ± 8 months postoperatively ( 32). Various procedures used over the 11- year study period included horizontal gastroplasty, vertical banded gastroplasty, proximal Roux- en- Y gastric bypass, and distal gastric bypass. There is little scientifically robust information re­garding specific dietary measures for IIH. Limiting vitamin A consumption and a low tyramine diet may be beneficial ( 33- 36). Dietary sources rich in vitamin A include fish, eggs, carrots, sweet potatoes, leafy greens, broccoli, red bell peppers, tomatoes, apricots, and cantaloupe. Supplemental vitamin A preparations are available over- the- counter. Ty­ramine naturally accumulates in food during the aging pro­cess. Foods and beverage that have high tyramine content include aged cheese and meat, pickled foods, overripe or dried fruit, beer, and wine. As many of the high- tyramine foods are also migraine triggers, patients may be instructed to use resources that are available to migraineurs regard­ing diet. Repeated Lumbar Punctures Repeated LPs are sometimes used in patients with oc­casional symptom relapses, in pregnant women, or in the setting of rapidly declining vision to temporarily lower the CSF pressure while planning a more aggressive treatment. However, the procedure may be painful, technically diffi­cult to perform, and cause a low- pressure headache ( 37). Other complications of LP, such as infection, tonsillar her­niation, radiculopathy, and arachnoiditis, are rare. Consid­ering that 50 mL of CSF are produced in a day in humans at a rate of approximately 0.35 mL/ min, 20 mL of CSF re­moved by LP is replenished in one hour, provided there is no persistent CSF loss through the dural puncture site or alteration in CSF production caused by the LP ( 38). Carbonic Anhydrase Inhibitors Acetazolamide is generally accepted as a first- line medication for lowering the intracranial hypertension in pa­tients with IIH. Its carbonic anhydrase inhibition decreases the secretion of CSF by the choroid plexus. Doses of 1 to 2 g are generally used and some advocate increasing to the maximum tolerated dose if necessary. Side effects are com­mon but are better accepted when patients are aware of their potential occurrence and medication doses are built up gradually. Alternatively, methazolamide may be used but it has no particular therapeutic advantage over acetazolamide. Topiramate, an anti- epileptic medication with carbonic an­hydrase inhibitory properties, may prove to be useful for IIH, particularly because it is also useful for headache pro­phylaxis and often produces weight loss ( 39). Currently, treatment of IIH with topiramate has not been studied and is considered off- label usage. Other Diuretics Furosemide also has beneficial effects on CSF secre­tion and may be used ( 39). Other diuretics are used but no consistent therapeutic trend has been reported. Most diuret­ics contain a sulfa moiety that may be problematic in pa­tients who are allergic to sulfa. Triamterene and spironolac­tone are useful in this circumstance, although they have no proven effect on CSF production. 141 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Friedman and Jacobson Corticosteroids Corticosteroids are not advocated for routine or long-term management of IIH. They are useful as an adjunctive treatment in patients with rapid deterioration while arrang­ing a surgical procedure ( see " malignant" IIH) ( 40). With­drawal of corticosteroids may lead to a rebound increase in ICP ( 41,42). Moreover, their side effects ( weight gain, fluid retention, hyperglycemia) are problematic in IIH patients. Management of Headaches The chronic headaches of IIH are best treated with conventional headache prophylaxis, although in some cases lowering the ICP with medical methods is effective ( 37). Because of the potential dangers, we do not advocate CSF shunting procedures for headache alone. At the same time, many of the agents used for headache prophylaxis in IIH ( tricyclic antidepressants, selective serotonin reuptake in­hibitors, sodium valproate, calcium channel blockers) may produce weight gain or edema that is undesirable in this population. Many patients with IIH also have migraine, ten­sion- type headaches, or analgesic overuse headaches ( 43). Headache prevention is recommended in IIH as long as the patient is monitored for medication- induced weight gain ( 43). Medical treatment of IIH is seldom life- long. When the patient's visual status and optic nerve appearance have stabilized, or when the disease has been in remission for at least six months, ICP- lowering agents may be tapered and discontinued. Patients should still be periodically moni­tored at this point because recurrences are not rare. Weight gain is associated with recurrence in some patients ( 44). Recurrence of symptoms may warrant reinstitution of medications but headaches are typically managed without diuretics or carbonic anhydrase inhibitors unless there is evidence of elevated ICP. SURGICAL TREATMENT Surgery is considered under the following circum­stances: 1) progressive loss of vision despite maximal medical therapy; 2) severe or rapid visual loss at onset ( see " malignant IIH"), including the development of an afferent pupillary defect or signs of advancing optic nerve dysfunc­tion; and 3) severe papilledema causing macular edema or exudates ( 37,45). Surgical procedures used for the treatment of visual loss include optic nerve sheath decompression ( ONSD) and CSF diversion procedures. Whether one procedure is supe­rior to the other is controversial and the decision often de­pends on available resources and expertise. The success rate is comparable between ONSD and lumboperitoneal shunt ( 46). Advantages of ONSD are shorter anesthesia and hos­pitalization times. ONSD avoids the complications of 142 shunting ( Table 6). Approximately 50% of patients experi­ence improvement in the nonoperated eye after a single ONSD ( 47). Optic Nerve Sheath Decompression The mechanism by which ONSD benefits IIH is un­certain. One possibility is a filtering effect with local CSF pressure reduction improving the peripapillary circulation ( 47). A second possibility is a generalized decrease in ICP, which has been demonstrated after ONSD ( 48,49). A third possibility is that scarring of the arachnoid after the proce­dure may protect the nerve head from the elevated CSF pressure. ONSD in monkeys produces connective tissue proliferation and obliteration of the subarachnoid space near the area of operation ( 50); similar changes were found in one human postmortem study ( 51). The complication rate of ONSD ranges broadly from 4.8% to 45%, with a mean of 12.9% ( 52- 62). Meta- analysis is difficult because there are so many variables, including the surgical approach ( medial versus lateral), surgical ex­perience, duration of follow- up, criteria for an event to be considered a complication, and primary procedure versus reoperation. Complications of ONSD are listed in Table 5. In a review of 317 published cases by Anthony Arnold, MD ( presented at the International Neuro- Ophthalmology Soci­ety Meeting, 2002), failure ( progressive visual loss postop­eratively or need for reoperation) occurred in 42 cases ( 13%). The most commonly reported complications are ex­traocular motility dysfunction ( often transient) and pupil­lary abnormalities. Extraocular movement dysfunction, usually caused by lateral rectus palsy, generally resolves. Visually threatening complications are rare. Transient and protracted postoperative blindness have been reported ( 59,60) and are attributed to ischemic injury to the optic nerve. The complication risks after reoperation are approxi­mately the same as those for the first procedure ( 61,62). TABLE 5. Complications of optic nerve sheath decompression Extraocular movement dysfunction Pupillary dysfunction Vascular occlusion Central retinal artery occlusion Branch retinal artery occlusion Choroidal ischemia/ infarction New visual field defect Orbital hemorrhage Transient or protracted blindness Globe perforation © 2004 Lippincott Williams & Wilkins Idiopathic Intracranial Hypertension JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 TABLE 6. Complications of lumboperitoneal shunting Shunt valve or tubing obstruction Over- shunting ( low pressure headache) Catheter migration/ abdominal pain Lumbar radiculopathy Infection CSF leak Cerebellar tonsillar herniation ( acquired Chiari malformation) Shunt dependency CSF Diversion Procedures A CSF diversion procedure treats IIH by lowering ICP but requires insertion of a foreign body. Lumboperito­neal shunting is more commonly performed than ventricu-loperitoneal ( VP) shunting because insertion and mainte­nance of patency may be more difficult in the latter procedure. However, VP and cisterna magna shunting may be successfully used ( 63,64,67). Complications of shunts are summarized in Table 6. The revision rate for lumboperi­toneal shunts ranges from 38% to 64%, with an overall re­vision rate of 52% ( 78 of 150 cases) ( 46,61- 66). The num­ber of revisions per patient is 2.3% to 6.6% ( mean 3.9%), but this value may be skewed because of the small number of reported patients. The reported interval between shunt placement to first revision is 9 to 27 months ( 46,66,67). Ma­jor causes of shunt failure include catheter obstruction, low ICP, catheter migration, and lumbar radiculopathy ( 66,68). A programmable shunt valve usually prevents low- pressure headaches, obviating the need for reoperation; this compli­cation is less frequent in VP than in lumboperitoneal shunt­ing. Visual loss may herald shunt malfunction, but may also occur with a functioning shunt ( 66- 75). Uncommonly, pa­tients may become " shunt dependent" after being in remis­sion for years, with worsening of signs and symptoms when the shunt is obstructed or removed. Severe, acute ICP el­evation upon insertion or removal of a shunt has been re­ported ( 70). Over- shunting may lead to an acquired Chiari malfor­mation or chronic intracranial hypotension. The symptoms and signs of low ICP are often similar to those of elevated ICP. Most patients will experience a postural headache that worsens with sitting or standing. Neck pain, vomiting, pho­tosensitivity, blurred vision, transient visual obscurations, peripheral visual field loss, and sixth nerve paresis may oc­cur ( 71). MRI changes of intracranial hypotension include leptomeningeal enhancement, tonsillar herniation, and sub­dural effusions ( 72,73). Bariatric Surgery Bariatric surgery may be considered in morbidly obese patients in whom medical and surgical treatments are ineffective ( 31). Although the procedure has risk, it offers the additional health benefits of reduced cardiovascular risk, type II diabetes, and lumbar disc degeneration that oc­cur with significant weight loss. Bariatric surgery may be considered for long- term management but is not an appro­priate treatment of patients with actively worsening vision. SPECIAL CONSIDERATIONS " Malignant" IIH Aggressive treatment is required for patients in whom rapid visual decline (" malignant" IIH) develops. Signifi­cant visual field loss and marked papilledema are evident at presentation, often with decreased visual acuity. Visual loss may occur rapidly over days to weeks. Temporizing man­agement includes serial lumbar punctures or insertion of a lumbar drain, and the administration of intravenous acet-azolamide and corticosteroids ( 76). Prompt surgical treat­ment is indicated with ONSD, shunting, or both procedures. Cerebral venous sinus thrombosis is an important diagnos­tic exclusion as it is managed with heparinization and, in some cases, thrombolytic treatment. Occasionally, the thrombosis may not be apparent on the initial MRI study, and re- imaging or catheter angiography may be fruitful. IIH in Pregnancy Although pregnancy is not considered an indepen­dent risk factor for IIH, the disease may start or worsen dur­ing pregnancy ( 21,77). IIH during pregnancy is managed in cooperation with the obstetrician. Often the condition is successfully controlled with headache management and se­rial LPs. Patients are advised to avoid excessive weight gain with guidance from their obstetrician. Low- calorie diets and weight reduction are not recommended. Acetazolamide is a category C medication in pregnancy ( risk cannot be ruled out because data are lacking). However, large clinical experience among neuro- ophthalmologists indicates over­all safety without known teratogenic effects on the fetus, especially if the medication is used after the first trimester. Another option is chlorthalidone, a diuretic with a category B rating ( no evidence of risk in humans). Corticosteroids may be administered without undue risk if needed for visual loss. Surgery is rarely required. If it is, ONSD is preferred over shunting because of potential shunt obstruction by the enlarging uterus ( 77). No special measures are required for delivery, and vaginal delivery is not contraindicated. IIH in Children Treatment of children with IIH is similar to that of adults, with the caveat that a secondary cause is often found in children ( 78- 81). IIH in children may follow a febrile 143 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Friedman and Jacobson illness, and common secondary causes are tetracycline ( in­cluding minocycline), hypervitaminosis A ( including reti­noid use), and cerebral venous sinus thrombosis ( 81). REFERENCES 1. Bandyopadhyay S. Pseudotumor cerebri. Arch Neurol 2001; 58: 1699- 701. 2. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cere­bri. Population studies in Iowa and Louisiana. Arch Neurol 1988; 45: 757- 7. 3. Corbett JJ, Savino PJ, Thompson HS, et al. Visual loss in pseudo­tumor cerebri. Follow up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neu-rol 1982; 39: 461- 74. 4. Wall M, George D. Idiopathic intracranial hypertension. A prospec­tive study of 50 patients. Brain 1991; 114: 155- 80. 5. Corbett JJ, Savino PJ, Thompson HS, et al. Visual loss in pseudo­tumor cerebri. Follow- up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neu-rol 1982; 39: 461- 74. 6. Rush JA. Pseudotumor cerebri. Clinical profile and visual outcome in 63 patients. Mayo Clin Proc 1980; 55: 541- 6. 7. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic in­tracranial hypertension. Neurology 2002; 59: 1492- 5. 8. Farb RI, Vanek I, Scott JN, et al. Idiopathic intracranial hyperten­sion. The prevalence and morphology of sinovenous stenosis. Neu­rology 2003; 60: 1418- 24. 9. Corbett JJ, Mehta MP. Cerebrospinal fluid pressure in normal obese subjects and patients with pseudotumor cerebri. Neurology 1983: 33: 1386- 8. 10. Wall M. Sensory visual testing in idiopathic intracranial hyperten­sion: measures sensitive to change. Neurology 1990; 40: 1859- 64. 11. Rowe FJ, Sarkies NJ. Assessment of visual function in idiopathic intracranial hypertension: aprospective study. i?>> e 1988; 12: 111- 8. 12. VerplanckM, Kaufman DI, Parsons T, et al. Electrophysiology ver­sus psychophysics in the detection of visual loss in pseudotumor cerebri. Neurology 1988; 38: 1789- 92. 13. Wall M, George D. Visual loss in pseudotumor cerebri: incidence and defects related to visual field strategy. Arch Neurol 1987; 44: 170- 5 14. Frisen L. High- pass resolution perimetry. A clinical review. Doc Ophthalmol 1993; 83: 1- 25. 15. Wall M, Montgomery EB. Using motion perimetry to detect visual field defects in patients with idiopathic intracranial hypertension: a comparison with conventional automated perimetry. Neurology 1995; 45: 1169- 75. 16. Trick GL, Vesti E, Tawansy K, et al. Quantitative evaluation of papilledema in pseudotumor cerebri. Invest Ophthalmol Vis Sci 1998; 39: 1964- 71. 17. Salgarello T, Falsini B, Tedesco S, et al. Correlation of optic nerve head tomography with visual field sensitivity in papilledema. Invest Ophthalmol Vis Sci 2001; 42: 1487- 94. 18. Orcutt JC, Page NG, Sanders MD. Factors affecting visual loss in benign intracranial hypertension. Ophthalmology 1984; 91: 1303- 12. 19. Tolander LM, Corbett JJ, Cremer S. Pseudotumor cerebri: first pre­dictors of visual loss. Ann Neurol 1988; 24: 169- 70 ( Abstract). 20. Arseni C, Simoca I, Jipescu I, et al. Pseudotumor cerebri: risk fac­tors, clinical course, prognostic criteria. Rom J Neurol Psychiat 1992; 30: 115- 32. 21. Wall M, White WN. Asymmetric papilledema in idiopathic intra­cranial hypertension: prospective interocular comparison of sen­sory visual function. Invest Ophthalmol Vis Sci 1998; 39: 134^ 12. 22. Digre KB, Varner MW, Corbett JJ. Pseudotumor cerebri and preg­nancy. Neurology 1984; 34: 721- 9. 23. Corbett JJ. Problems in the diagnosis and treatment of pseudotumor cerebri. Can J Neurol Sci 1983; 10: 221- 9. 24. Friedman DI, Forman S, Levi L, et al. Unusual ocular motility dis­turbances with increased intracranial pressure. Neurology 1998; 50: 1893- 6. 25. Purvin VA, Trobe JD, Kosmorsky G. Neuro- ophthalmic features of cerebral venous obstruction. Arch Neurol 1995; 52: 880- 5. 26. Biousse V, Ameri A, Bousser MG. Isolated intracranial hyperten­sion as the only sign of cerebral venous thrombosis. Neurology 1999; 53: 1537^ 12. 27. King JO, Mitchell PJ, Thomson KR, et al. Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neu­rology 2002: 58: 26- 30. 28. Frisen L. Swelling of the optic nerve head: a staging scheme. JNeu­rol Neurosurg Psychiatr 1982; 45: 13- 8. 29. Newborg B. Pseudotumor cerebri treated by rice/ reduction diet. Arch Intern Med 1974; 133: 802- 7 30. Johnson LN, Krohel GB, Madsen RW, et al. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hyper­tension ( pseudotumor cerebri). Ophthalmology 1998: 105: 2313- 7. 31. Kupersmith MJ, Gamell L, Turbin R, et al. Effects of weight loss on the course of idiopathic intracranial hypertension in women. Neu­rology 1998; 50: 1094- 8. 32. Sugarman HJ, Felton WL III, Salvant JB, Jr, et al. Effects of surgi­cally induced weight loss in idiopathic intracranial hypertension in morbid obesity. Neurology 1995; 45: 1655- 9 33. Jacobson DM, Berg R, Wall M, et al. Serum vitamin A concentra­tion is elevated in idiopathic intracranial hypertension. Neurology 1999; 53: 1114- 8. 34. Selhorst JB, Kulkantrakorn K, Corbett JJ, et al. Retinol- binding pro­tein in idiopathic intracranial hypertension ( IIH). J Neuro-ophthalmol 2000; 20( 4): 250- 2. 35. Sirdofsky M, Kattah J, Macedo P. Intracranial hypertension in a dieting patient. JNeuro- ophthalmol 1994; 14: 9- 11. 36. Friedman DI, Ingram P, Rogers MAM. Low tyramine diet in the treatment of idiopathic intracranial hypertension: a pilot study. Neu­rology 1998; 50: A5. 37. Corbett JJ, Thompson HS. The rational management of idiopathic intracranial hypertension. Arch Neurol 1989; 46: 1049- 51. 38. Fishman RA. Cerebrospinal fluid in Diseases of the Nervous Sys­tem, 2nd edition. Philadelphia: W. B. Saunders; 1992: 25- 30. 39. Physicians' Desk Reference, 56th edition. Montvale, NJ: Medical Economics Company, Inc; 2002: 2590- 2595. 40. Liu GT, Glaser JS, Schatz NJ. High- dose mefhylprednisolone and acetazolamide for visual loss in pseudotumor cerebri. Am J Oph-thalmol 1994; 118: 88- 96. 41. Liu GT, Kay MD, Bienfang DC, et al. Pseudotumor cerebri associ­ated with corticosteroids withdrawal in inflammatory bowel dis­ease. Am J Ophthalmol 1994; 117: 352- 7. 42. Neville BG, Wilson J. Benign intracranial hypertension following corticosteroids withdrawal in childhood. Br Med J 1970; 3: 554- 6. 43. Friedman DI, Rausch EA. Headache diagnoses in patients with treated idiopathic intracranial hypertension. Neurology 2002; 58: 1551- 3. 44. Giuseffi V, Wall M, Siegel PZ, et al. Symptoms and disease asso­ciations in idiopathic intracranial hypertension ( pseudotumor cere­bri): A case- control study. Neurology 1991; 41: 239- 44. 45. Carter S, Seiff SR. Macular changes in pseudotumor cerebri before and after optic nerve sheath fenestration. Ophthalmology 1995; 102: 937^ 11. 46. Rosenberg ML, Corbett JJ, Smith C, et al. Cerebrospinal fluid di­version procedures in pseudotumor cerebri. Neurology 1993; 43: 1071- 2. 47. Keltner JL. Optic nerve sheath decompression. How does it work? Has its time come? Arch Ophthalmol 1988; 106: 1365- 9. 48. Ngyun R, Carta A, Geleris A, et al. Long- term effect of optic nerve sheath decompression on intracranial pressure in pseudotumor cere­bri. Invest Ophth Vis Sci 1997: 38: S388. 49. Mittra RA, Sergott RC, Flaharty PM, et al. Optic nerve decompres­sion improves hemodynamic parameters in papilledema. Ophthal­mology 1993; 100: 987- 97. 144 © 2004 Lippincott Williams & Wilkins Idiopathic Intracranial Hypertension JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 50. Hayreh SS. Pathogenesis of oedema of the optic disc. Doc Ophthal-mol 1968; 24: 289- 411. 51. Tsai JC, Petrovich MS, Sadun AA. Histopathological and ultra-structural examination of optic nerve sheath decompression. Br J Ophthalmol 1995; 79: 1825. 52. Brourman ND, Spoor TC, Ramocki JM. Optic nerve sheath decom­pression for pseudotumor cerebri. Arch Ophthalmol 1988; 106: 1378- 83. 53. Corbett JJ, Nerad JA, Tse DA, et al. Results of optic nerve sheath fenestration for pseudotumor cerebri: the lateral orbitotomy ap­proach. Arch Ophthalmol 1988; 106: 1391- 7. 54. Sergott RC, Savino PJ, Bosley TM. Modified optic nerve sheath decompression provides long- term visual improvement for pseudo­tumor cerebri. Arch Ophthalmol 1988; 106: 1384- 9. 55. Kelman SE, Heaps R, Wolf A, et al. Optic nerve decompression surgery improves visual function in patients with pseudotumor cerebri. Neurosurgery 1992; 30: 391- 5. 56. Spoor TC, McHenry JG. Long- term effectiveness of optic nerve sheath decompression for pseudotumor cerebri. Arch Ophthalmol 1993; 111: 632- 5. 57. Plotnik JL, Kosmorsky GS. Operative complications of optic nerve sheath decompression. Ophthalmology 1993; 100: 683- 90. 58. Sergott RC, Savino PJ, Bosley TM. Optic nerve sheath decompres­sion: A clinical review and proposed pathophysiologic mechanism. Aust N Z J Ophthalmol 1990; 18: 365- 73. 59. Flynn WJ, Westfall CT, Weisman JS. Transient blindness after op­tic nerve sheath fenestration. Am J Ophthalmol 1994; 117: 678- 9. 60. Brodsky MC, Rettele GA. Protracted postsurgical blindness with visual recovery following optic nerve sheath fenestration. Arch Ophthalmol 1998; 116: 107- 9. 61. Spoor TC, Ramocki JM, Madion MP, et al. Treatment of pseudotu­mor cerebri by primary and secondary optic nerve sheath decom­pression. Am J Ophthalmol 1991; 112: 177- 85. 62. Mauriello JA, Jr, Shaderowfsky BA, Gizzi M, et al. Management of visual loss after optic sheath decompression in patients with pseu­dotumor cerebri. Ophthalmology 1995; 102: 441- 5. 63. Howard J, Appen RE. Ventriculoperitoneal shunting for pseudotu-morcerebri. Presented at the Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL, 2002. 64. Johnston I, Besser M, Morgan M. Cerebrospinal fluid diversion in the treatment of benign intracranial hypertension. J Neurosurg 1988; 69: 195- 202. 65. Burgett RA, Purvin VA, Kawasaki A. Lumboperitoneal shunting for pseudotumor cerebri. Neurology 1997; 49: 734- 9. 66. Eggenberger ER, Miller NR, Vitale S. Lumboperitoneal shunt for the treatment of pseudotumor cerebri. Neurology 1996; 46: 1524- 30. 67. Johnston IH, Sheridan MM. CSF shunting from the cisterna magna: a report of 16 cases. Br J Neurosurgery 1993; 7: 39^ 13. 68. Alleyne CH Jr, Shutter LA, Colohan AR. Cranial migration of a lumboperitoneal shunt catheter. So Med J 1996; 89: 634- 6. 69. Lee AG. Visual loss as the manifesting symptom of ventriculoperi­toneal shunt malfunction. Am J Ophthalmol 1996; 122: 127- 9. 70. Liu GT, Volpe NJ, Schatz NJ, et al. Severe sudden visual loss caused by pseudotumor cerebri and lumboperitoneal shunt failure. Am J Ophthalmol 1996; 122: 129- 31. 71. Horton JC, Fishman RA. Neuro visual findings in the syndrome of spontaneous intracranial hypotension from dural cerebrospinal fluid leak. Ophthalmology 1994; 101: 244- 51. 72. Pannullo SC, Reich JB, Krol G, et al. MRI changes in intracranial hypotension. Neurology 1993; 43: 919- 26. 73. Mokri B. Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid hypovolemia - evolution of a concept. Mayo ClinProc 1999; 74: 1113- 23. 74. Kelman SE, Sergott RC, Cioffi GA, et al. Modified optic nerve de­compression in patients with functioning lumboperitoneal shunts and progressive visual loss. Ophthalmology 1991; 98: 1449- 53. 75. Wall M. Nerve sheath decompression in patients with functioning shunts. Ophthalmology 1992; 99: 480. 76. Liu GT, Glaser JS, Schatz NJ. High- dose mefhylprednisolone and acetazolamide for visual loss in pseudotumor cerebri. Am J Oph­thalmol 1994; 118: 88- 96 77. Shapiro S, Yee R, Brown H. Surgical management of pseudotumor in pregnancy: case report. Neurosurgery 1995; 37: 829- 31. 78. Lee AG, Patrinely JR, Edmond JC. Optic nerve sheath decompres­sion in pediatric pseudotumor cerebri. Ophthalmic Surgery & La­sers 1998; 29: 514- 7. 79. Cinciripini GS, Donahue S, Borchert MS. Idiopathic intracranial hypertension in prepubertal pediatric patients: characteristics, treat­ment and outcome. Am J Ophthalmol 1999; 127: 178- 82. 80. Schoeman JF. Childhood pseudotumor cerebri: clinical and intra­cranial pressure response to acetazolamide and fUrosemide treat­ment in a case series. J Child Neurol 1994; 9: 130- 4. 81. Lessell S. Pediatric pseudotumor cerebri ( idiopathic intracranial hy­pertension). Surv Ophthalmol 1992; 37: 155- 66. 145