Idiopathic Intracranial Hypertension (IIH)

The Dandy criteria (described by Dandy in 1937 and later modified) were the original criteria used to diagnose IIH and are as follows[4] : 

• Symptoms and signs of increased ICP.
• No other localizing neurologic signs other than those related to increased ICP (eg, unilateral or bilateral sixth nerve paresis, papilledema, or papilledema-related visual loss).
• Cerebrospinal fluid (CSF) may show increased pressure, but there are no cytologic or chemical abnormalities.
• Neuroimaging reveals radiographic signs of increased ICP but no structural cause or hydrocephalus.
• No other causes of increased ICP are found through workup.

A subsequent article further refined the diagnostic criteria by adding the following two criteria[5] :

• The diagnostic lumbar puncture should be performed with the patient in the lateral decubitus position.
• MRI and MRV should be considered the ideal imaging studies to rule out intracranial venous sinus thrombosis. However, some patients cannot undergo MRI (eg, ferromagnetic foreign body, non-MRI compatible aneurysm clip or cardiac pacemaker), so CT scanning and CT venography (CTV) may be necessary as alternative neuroimaging studies.

The pathophysiology of IIH is unclear. An initial theory thought that cerebral edema played a role in the pathogenesis of elevated ICP in these patients, but later reports described the edema to represent fixation artifact (ie, from tissue preparation) rather than in vivo edema.[6]

Although the precise mechanism is not understood, IIH is likely due to a dysregulation of CSF dynamics involving a blend of hypersecretion of CSF at the choroidal plexus, reduced reabsorption at the arachnoid granulations and abnormal venous pressure gradients.[7]

In a series reported by Farb et al, 29 patients with IIH showed demonstrable narrowing of the transverse dural venous sinus on magnetic resonance (MR) venography, whereas none of the 59 control subjects had this finding. The authors suggested that the narrowing is a consequence of elevated ICP and that when the narrowing develops, it exacerbates the pressure elevation by increasing venous pressure in the superior sagittal sinus.ref11} Although not accepted as a method of primary surgical treatment for IIH, stenting of stenotic dural sinuses has been demonstrated to decrease ICP in patients with IIH.[8]  

Another pathway of CSF drainage that is under study, the glymphatics, may prove to have an important role in the pathophysiology of IIH. Several recent studies show that the CSF glymphatic function is congested in IIH, resulting in elevated intracranial pressure.[9, 10]

IIH commonly occurs in women who are overweight; however, the role obesity plays in this disorder is unclear. While it has been proposed that obesity increases intra-abdominal pressure and thereby raises cardiac filling pressures, this is likely not the sole underlying link between obesity and IIH. Some researchers are moving towards linking obesity, related neuroendocrine imbalances and IIH.[7, 11]  However, obesity appears to have no association with IIH in the pediatric population. An autoimmune component may play a role in pediatric IIH, given the high rate of atopy observed in this pediatric IIH patient cohort. [12]

Although a role for vitamin A in the pathogenesis of IIH was initially suspected, the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) demonstrated no difference in CSF vitamin A levels in patients with IIH versus obese controls over a 6 month period except in those treated with acetazolamide.[13]

Other medications that have been implicated for resulting in IIH include tetracycline, amiodarone, oral contraceptives such as levonorgestrel (Norplant), cyclosporine, cytarabine, growth hormone, isotretinoin, levothyroxine (children), lithium carbonate and acute change of steroid use. [14]

United States statistics

Studies of American-based populations have estimated that the incidence of IIH ranges from 0.9 to 1.0 per 100,000 in the general population, increasing to 3.5 per 100,000 in women and to 19 per 100,000 in women aged20 to 44 years who exceed ideal body weight by 20%.[7]  

International statistics

The incidence of IIH varies from country to country. Because of the disease’s relation to body habitus, its occurrence varies according to the incidence of obesity in the respective region. As an example, a far lower incidence has been noted in Asian countries (0.03/100,000), which is interpreted as the result of the markedly lower rate of obesity in these countries as compared to the United States.[7]

Age and race-related demographics

Although IIH may affect individuals of any age, most patients with this disease present in the third decade of life.

No evidence exists to suggest that IIH has a predilection for any particular racial or ethnic group.

IIH is not known to be associated with any specific mortality risk, but endovascular and surgical treatments (eg, venous sinus stenting or shunting) may cause morbidity and mortality. The increased mortality associated with morbid obesity has a selective expression in this group because of the strong predilection of the disease to affect obese females.

The morbidity of IIH mainly is related to the effects of papilledema on visual function. If left untreated, long-standing disc edema results in an irreversible optic neuropathy with accompanying constriction of the visual field and loss of color vision. In end-stage papilledema, central visual acuity also is involved. With timely and appropriate treatment of IIH, the visual prognosis can be encouraging.

Since IIH tends to be chronic, visual function (visual acuity, visual fields, optic nerve appearance) must be monitored for years after presentation. If necessary, medical treatment should be continued on a long-term basis.

Loss of visual function

The frequency and degree to which vision loss occurs in IIH is difficult to establish from the existing literature. Depending on the referral population and the rigor with which visual function is tested, the prognosis for vision loss in IIH has varied considerably in different series. Authors writing in the 1960s and 1970s indicated that fewer than 25% of these patients had functionally significant blindness; however, this figure has since been revised upward.

As outlined by Radhakrishnan et al in 1994, the reported incidence of vision impairment is much higher in series from referral centers (as many as 96% of cases with some degree of visual field loss) than in population-based series (eg, 22% in Iowa).[15, 16]  Two equally valid explanations for this discrepancy have been proposed:

• The referral centers perform more extensive vision testing, including Goldmann and computerized automated threshold perimetry; thus, they discover visual deficits that are not tested for in the community-based studies
• The worst cases are referred for tertiary care consultation; thus, the referral center series are biased toward more severe vision loss cases than the community-based studies are

In a major prospective study of visual function in IIH, Wall and George found that 96% of the 50 patients in a series had some degree of visual field loss on Goldmann-type perimetry, whereas 92% had abnormal findings on automated perimetry[17] ; 50% had abnormal contrast sensitivity, and 22% had abnormal Snellen visual acuity. During follow-up (2-39 months; average, 12.4 months), visual fields improved in 60% of patients and deteriorated in 10%.

The University of Iowa observed 20 patients with IIH for more than 10 years and found that whereas 11 of the 20 had followed a stable course without visual-field changes or papilledema, nine had experienced deterioration after initially following a stable course for a time.[18]  In 6 of the 9, the deterioration occurred late (28-135 months after initial presentation), and in 3 of the nine, recurrences after resolution of papilledema developed 12 to 78 months after the initial resolution of IIH.

In the IIHTT the 3 most important negative risk factors for poor prognosis related to progressive visual field loss were male gender, high-grade papilledema and decreased visual acuity at baseline.[19]

It is important to inform patients with IIH that weight control along with a low sodium diet are key long-term factors in the management of their disease. Asking patients about their weight loss at the beginning of each visit reinforces this concept. In addition, it is worthwhile to stress that the loss of as little as 6% of body weight may lead to the termination of this disorder and significantly diminishes the risk of its recurrence.[20]

In particular, it is essential to educate patients regarding the potential for disabling blindness. The importance of weight loss as the only effective means of reducing the papilledema, and with it the threat of progressive blindness, cannot be overemphasized.

Patients should be urged to enroll in an aggressive weight-loss program, ideally one using a multidisciplinary approach that includes diet and exercise along with psychological and lifestyle counseling. Even when such a program is followed, many patients cannot sustain significant weight reduction and may require drastic steps such as gastric stapling or resection. 

Although IIH may appear to be self-limiting, it is considered to be a chronic disorder; therefore, once the medications given to treat it are tapered off, patients should be instructed to return to an ophthalmologist if symptoms of increased ICP recur.

IIH predominantly affects overweight females of childbearing age. In the landmark study of this disorder, the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT), women accounted for 97% of case.[21]  These patients typically present with symptoms related to increased ICP and papilledema. These can include headache (84%), transient visual obscurations (68%), pulse synchronous tinnitus (52%), subjective decrease in vision (32%) and horizontal diplopia (18%).[1]  Other symptoms may include dizziness (51%), photophobia (48%), neck pain (42%) and radicular pain (19%).[22]  In order to ensure that the diagnosis is limited to IIH, a detailed medical and medication history should be taken focused on symptoms suggestive of obstructive sleep apnea,[23]  exogenous substances, and underlying systemic/neurological disorders.

Symptoms of elevated intracranial pressure

The presenting headaches typically are nonspecific and vary in type, location, and frequency. Pain generally is described as being diffuse, worse in the morning, and exacerbated by the Valsalva maneuver. In a large case series, men were less likely than women to report headache (79% vs 89%; P = 0.01).[24]

Trials that assessed headache-related disability found significant patient-reported quality-of-life implications in the physical, mental, and visual domains.[25, 26]

Patients who present with double vision most frequently complain of horizontal displacement of the images. While horizontal diplopia has been reported to occur in 18% of patients, curiously, only a minority are found to have a VI palsy.

Pulsatile tinnitus or pulse synchronous tinnitus is a common symptom. Due to its unusual nature it must be elicited by direct questioning as patients may not readily admit to its occurrence. It can be heard in 1 or both ears, as a pulsing synchronous rhythm that may be exacerbated by the supine or bending position. Its underlying pathophysiology has not been definitively determined.

Symptoms of papilledema

Transient visual obscurations occur in 68% of patients. The disturbance can last up to 30 seconds and is described as a dimming or "graying out" of vision in 1 or both eyes. These obscurations may be predominantly or uniformly orthostatic (ie, developing with standing up or bending over) and can be precipitated by bright light or eye movement. Visual obscurations are not predictive of visual loss or correlated with degree of elevated ICP.

Progressive loss of peripheral vision in 1 or both of the eyes may be noted. Typically, the vision field loss begins insidiously in the nasal inferior quadrant and can progress to overall constriction with subsequent involvement of the central visual field.

Blurring and distortion (ie, metamorphopsia) of central vision is caused by macular wrinkling and subretinal fluid extension from the swollen optic disc.

Sudden visual loss can occur due to a retinal vascular occlusive event, ischemic optic neuropathy or an intraocular hemorrhage secondary to peripapillary subretinal neovascularization related to chronic papilledema.

Vision

Upon presentation, visual acuity is usually normal in all but the most fulminant cases. Patients who present with poor visual acuity are to be assessed and treated on an emergent basis.

Color vision

Color vision is not usually affected in early to moderate cases of IIH.

Ocular motility examination

Occasionally, limited abduction of 1 or both eyes results from increased ICP. This false-localizing CN VI palsy typically resolves with the lowering of the ICP. 

Fundus examination

The most significant physical finding in patients with IIH is bilateral disc edema due to increased ICP.

Papilledema varies from patient to patient and is indistinguishable from optic nerve swelling caused by intracranial space-occupying lesions. In more pronounced cases of disc swelling, macular involvement with subsequent edema and diminished central vision may be present. High-grade and atrophic papilledema and subretinal hemorrhage are poor visual prognostic signs. In some cases, the disc swelling is asymmetric; in the IIHTT, 7% of papilledema cases were asymmetric.[27] In rare instances, the appearance of the optic nerve is relatively normal. Risk of permanent visual loss is higher with more severe papilledema.[28]

Peripapillary flame hemorrhages, venous engorgement, and hard exudates are features consistent with acute papilledema. Telangiectatic vessels on the disc surface, optociliary shunt veins (which exit the disc at its margin), and optic disc pallor are associated with chronic papilledema. The severity of papilledema can be assessed using the Frisen grade. The grading scale is 0 to 5, with 0 being no papilledema and 5 being severe edema with obscured vessels on the surface of the optic nerve head. Unfortunately, in day to day clinical use, the Frisen grading of papilledema is not practical as it is subject to inter and intra observer variability.

Left optic disc with moderate chronic papilledema in a patient with idiopathic intracranial hypertension (pseudotumor cerebri). Paton lines (arc-shaped retinal wrinkles concentric with the disc margin) are seen along the temporal side of the optic nerve head.

Right optic disc with postpapilledema optic atrophy in a patient with idiopathic intracranial hypertension (pseudotumor cerebri). Diffuse pallor of disc and absence of small arterial vessels on surface are noted, with very little disc elevation. The disc margin at the upper and lower poles and the nasal border is obscured by some residual edema in the nerve fiber layer and secondary gliosis that persists despite the resolution of acute edema.

Visual fields

Static perimetry is the foundation of determining the impact of IIH on the visual function of IIH patients. Goldmann-type kinetic perimetry and computerized static perimetry are both options for testing the visual field. However, while Goldmann-type kinetic perimetry provides reliable information concerning the most peripheral parts of the visual field, the testing is highly operator-dependent and the use of this device has become practically obsolete. Although static perimetry usually does not test beyond 30° of eccentricity, it is less operator-dependent and far more readily available in the modern clinical setting. Despite the presence of reliability indices that the static perimetry software provides, performance failures were quite commonly noted in the IIHTT.[29]  It is important to have serial visual fields in close succession to avoid overcalling treatment failures when in fact the visual field defects may be due to so called "performance failures".

In the IIHTT, there was an overall depression of the visual field with progressive loss linked to increased eccentricity.[30]  Untreated or inadequately treated papilledema will eventually lead to clinically significant visual loss. Although almost all patients present with enlarged blind spots during their initial perimetry, uncontrolled papilledema results in progressive peripheral visual field constriction or nerve fiber bundle defects.

Typically, the first sign of incipient papilledema related optic neuropathy is constriction of the inferior nasal quadrant of the visual field with a border reflecting the nasal horizontal midline (nasal step). This starts in the most peripheral points in the visual field (ie, 50° from fixation) and progresses inward.

The central visual field is affected only in end-stage chronic papilledema. 

Although routine blood tests are not essential, it is advised that patients with IIH should have a baseline complete blood count, electrolytes, bicarbonate, and coagulation profile (PT,PTT). These baseline tests may elucidate abnormalities that prompt consideration of alternative differential diagnoses.

The role of anemia in patients with IIH was recently investigated in a matched case-control retrospective study, which found that there was no significant association between IIH and anemia when comparing standardized CBC values. [32]

As mentioned above, patients with bilateral disc swelling should undergo urgent neuroimaging studies to rule out an intracranial mass or a dural sinus thrombosis. This applies to all patients as even "typical" IIH patients may harbor intracranial pathology.

Brain MRI with gadolinium enhancement and Magnetic resonance venography (MRV) is the study of choice in patients with IIH, in that it provides sensitive screening for hydrocephalus, intracerebral masses, meningeal infiltrative or inflammatory disease, and dural venous sinus thrombosis. Flattening of the globes, an empty sella, distended optic nerve sheaths and slit like ventricles are common neuroradiology findings in IIH.[33]

In addition to a brain MRI, MRV is now becoming the standard of practice in IIH to rule out a dural venous sinus thrombosis. Sagittal T1-weighted images provide excellent views of the superior sagittal sinus, and these should be included in routine brain MRI's. Extraluminal narrowing of the transverse sinuses is a common neuroradiologic finding in IIH.[33]

Brain CT scanning is less expensive and faster than MRI and is usually adequate to rule out an intracranial lesion. However, MRI and MRV are more effective in ruling out a mass lesion and a dural sinus thrombosis, respectively. CT scanning with contrast enhancement may be necessary in patients with contraindications to MRI (ie, pacemakers, metallic clips/foreign bodies).

Once an intracranial mass lesion is ruled out, a lumbar puncture is indicated. The opening pressure should be measured with the patient relaxed in the decubitus position to prevent a falsely elevated pressure reading. If any specific difficulty is encountered that may have caused such a false elevation, the clinician performing the procedure must communicate this to the ophthalmologist. Unfortunately, some patients demonstrate a transiently normal pressure despite harboring IIH. An opening pressure of greater than 25 cm H2O is considered high, however patients with typical presenting symptoms of IIH and normal opening pressures may be considered to have "probable" IIH.[34]  However, the range of normal cerebrospinal fluid (CSF) pressure in children (10th to 90th percentil) at the time of lumbar puncture is 12 to 28 cm H2O, which is slightly higher than that in adults. [35, 36, 37]

Besides the value of the opening pressure, the clarity and color of the CSF should be noted. In addition, the CSF should be forwarded for cell count, cytology, culture, and measurement of glucose, protein, and electrolyte concentrations. All of these findings are normal in patients with IIH.

In obese patients, finding landmarks may be difficult; consequently, the tap is often performed with the patient seated. The normal CSF pressure at the foramen magnum in the seated position is nearly 50cm H2O from the lumbar entry point in persons of average height. Therefore, the position of the patient during lumbar puncture should be considered when interpreting the CSF pressure. If possible, the patient should be moved to the lateral decubitus position before the pressure is measured.

Another approach to lumbar puncture in obese patients involves fluoroscopic guidance in the radiology department. Prone positioning on the x-ray table and increased abdominal pressure in this position may falsely elevate the CSF pressure. If the pressure is normal with the patient in the prone position, then the measurement is probably accurate. However, if it is high, the patient must be rolled into the lateral decubitus position and allowed to relax before a reliable pressure reading can be completed.

Obviously, such maneuvers carry a risk of displacing the needle from the thecal space. However, no alternative method exists for obtaining an accurate pressure reading.

The treatment goal in patients with idiopathic intracranial hypertension (IIH) is to preserve optic nerve function while managing increased ICP. Weight control and a low sodium diet are strongly and repeatedly recommended for obese patients. Exogenous agents potentially related to increased ICP should be discontinued.

First-line treatment is the administration of acetazolamide in a dose related to the symptoms, tolerance and visual function of the patient

When progressive visual field loss is documented despite maximal medical treatment, urgent surgical intervention should be considered.

One of the standard teachings regarding this condition has been that pregnancy exacerbates or triggers the onset of symptomatic IIH. At present, however, there is little statistical evidence of a causal association between pregnancy and IIH, beyond the fact that pregnancy is common in the age group and gender that is predominantly affected by IIH.

Acetazolamide

In the 2014 NIH-funded study of 165 patients with IIH and mild vision loss (the Idiopathic Intracranial Hypertension Treatment Trial), researchers found that acetazolamide treatment for 6 months in conjunction with a low-sodium weight-reduction diet modestly improved vision, reduced ICP, improved quality of life, and reduced papilledema. Average improvement in perimetric mean deviation (PMD) was 1.43 dB with acetazolamide and 0.71 dB with placebo. Data showed that the drug’s effect was independent of weight loss.[38] Compared with the placebo group, patients on acetazolamide treatment had statistically significant improvement of retinal nerve fiber layer thickness, total retinal thickness, and optic nerve volume based on OCT measurements.[39]

Acetazolamide appears to be the most effective agent for lowering ICP. The majority of patients experience adequate relief of increased ICP symptoms (typically, headache) with this first-line agent.

Using the Headache Impact Test-6 (HIT-6) questionnaire, the IIHTT demonstrated a comparable improvement in the level of headache in the acetazolamide versus placebo group at 6 months. The lack of correlation between headache disability and CSF pressure at baseline implies that the headache in IIH may be related to factors other than intracranial hypertension and that specific headache treatment may be required in addition to therapies directed at lowering CSF pressure.[26]

In a long-term follow up study of 54 patients, recurrent episodes of IIH occurred in 38% of cases over a mean period of 6.2 years; no reoccurrences occurred in patients receiving ongoing acetazolamide treatment.[40]

The initial acetazolamide dosage should be 0.5-1 g/day. Although many physicians start patients on 250 mg twice daily, others consider this dosage too low. A 500-mg oral dose of acetazolamide twice daily is often preferred; however, some insurers cover only an oral dose of 250 mg 4 times per day. Most patients respond to a dosage of 1-2 g/day. This can be increased to 3-4 g/day, but many patients cannot tolerate the adverse side effects (eg, extremity paresthesias, fatigue, metallic taste from carbonated beverages, and decreased libido) that occur at this high dosage. In the Idiopathic Intracranial Hypertension Treatment Trial, of the 86 patients in the acetazolamide treatment group, 38 patients (44.1%) tolerated the maximum dose of 4 g/day.[41] Seventy-seven (89.5%) of the 86 patients taking acetazolamide tolerated dosages of 1 g/day or more. Compared with the 79 patients from the placebo group, the 86 patients taking acetazolamide were more likely to experience paresthesias, dysgeusia (foul or metallic taste), vomiting and diarrhea, nausea, and fatigue.[41]

In the event of intolerance to acetazolamide, furosemide may be used as a replacement diuretic in this group. Unfortunately, it does not appear to be as effective as acetazolamide.

Headache prophylaxis

In patients with stable visual function but inadequate headache relief with first-line pressure-lowering drugs, primary headache prophylaxis should be considered. Patients with IIH may experience headaches that have many of the features of migraine. These headaches can often be controlled with amitriptyline, propranolol, or other commonly prescribed migraine prophylaxis agents. Topiramate is also an excellent choice, in that one of its side effects is weight loss which can help put the disease in remission. One open-label study suggested that topiramate appears to have similar efficacy to acetazolamide in terms of visual field improvement and symptom relief.[42]

Corticosteroids

Corticosteroids may rarely be used as a supplement to acetazolamide to hasten recovery in patients who present with severe papilledema. Because of their significant adverse effects, corticosteroids should not be considered as a long-term solution. In addition, a rebound in the ICP may occur during the tapering of the corticosteroid dosage.

Serial lumbar puncture

Serial lumbar puncture has fallen out of favor as CSF reforms within 6 hours.

Mannitol

Preliminary data suggest that intravenous bolus of mannitol in patients with severe and rapidly progressively IIH may reduce CSF pressure, but further investigation is required to evaluate the efficacy of mannitol in the acute treatment of IIH. 

Patients with IIH should be closely monitored while on medical treatment. The frequency of visits is determined by the initial state of the patient’s visual function and the response to medical treatment. Despite close follow-up care and maximum medical treatment, some patients experience deterioration of visual function. Others fail to respond, are noncompliant, are intolerant to medication, have intractable headaches or progressive visual loss. In these situations, surgical intervention should be considered. Such intervention most often takes one of the following two general approaches:

• Optic nerve sheath fenestration
• Cerebrospinal fluid diversion (ie, via a lumboperitoneal or ventriculoperitoneal shunt)

Intracranial venous sinus stenting may also be considered in patients wtih significant transverse sinus stenosis.

Optic nerve sheath fenestration

This ophthalmic surgical approach to managing progressive vision loss and papilledema involves cutting slits or rectangular patches in the dura surrounding the optic nerve immediately behind the globe. This allows direct egress of CSF into the orbital fat, where it is absorbed into the venous circulation. There are various options for the anatomic approach to the optic nerve, with the medial transconjunctival approach being most common.[43] A recent retrospective chart review also reports the superomedial eyelid crease approach to be safe and effective. [44]

Optic nerve sheath fenestration (ONSF) has been demonstrated to reverse optic nerve edema and to bring about some recovery of optic nerve function. In addition, it may decrease headache in many patients. The approach to the optic nerve may be from either the medial or the lateral aspect of the orbit; each approach has its benefits and drawbacks.[45]  ONSF has also been shown to be safe and effective in children.[46, 47]

Although ICP typically remains elevated in these patients postoperatively, the local filtering effect of the fenestration acts as a safety valve and keeps the pressure from being transmitted to the optic nerve. Despite the general lack of an ICP-lowering effect, unilateral surgery occasionally has a bilateral curative effect on the papilledema. However, if this is not the case, the opposite nerve must undergo the same procedure.

Complications related to optic nerve sheath fenestration include diplopia, tonic pupil, and corneal dellen.[48]  Fortunately these typically are transient and visual loss due to optic nerve or vascular compromise is rare.

Unfortunately, ONSF may not have lasting benefits. In most cases, visual function stabilizes or improves postoperatively. In at least one third of cases, secondary visual decline may occur within 3 to 5 years and may necessitate repeat surgery or an alternative treatment; Spoor and McHenry found the long-term success rate of this operation to be only 16%.[49]

CSF diversion procedures

CSF diversion procedures are highly effective in lowering ICP. In most facilities they are the procedures of choice for treating patients with IIH who do not respond to maximum medical treatment. Shunts are also indicated in patients with intractable headaches, patients in regions where there is no access to a surgeon comfortable with optic nerve sheath fenestration, and patients in whom optic nerve sheath fenestration has failed.

Lumboperitoneal shunting is the traditional method for providing prompt reduction of ICP in patients with IIH. However, this procedure has a high one-year failure rate. Some neurosurgeons prefer ventriculoperitoneal or ventriculoatrial shunting over lumboperitoneal shunting. 

Uncontrolled studies report shunting results in the alleviation of headache, diplopia, papilledema, and visual loss. Stabilization and remission of visual remission was reported in up to 95%-100% in some studies, while one study showed worsening of visual function in 32% of patients.[50, 51, 52, 53, 54, 55] One case series reported that headache relief was not sustained, with nearly 50% of patients experiencing recurring severe headaches despite a working shunt.[56]

The surgical arm of the IHTT (SIGHT) will help elucidate the impact of CSF diversion procedures on patients with medically unresponsive IIH.

Intracranial venous sinus stenting

Venous stenting is a relatively new intervention and remains somewhat controversial. Patient selection is the key factor in the success of this procedure in that transverse sinus stenosis and a trans stenotic gradient must be demonstrated in order to recommend this procedure.[8]

A literature review of 143 patients treated with venous stenting showed that 88% of patients experienced improved headache and 87% reported improved visual symptoms. Follow-up was limited, effects on vision were not consistent, and complications were reported in 6% of cases.[57]

Comparison of visual outcomes

In a meta-analysis of the literature comparing visual outcomes after optic nerve sheath decompression, ventriculoperitoneal and lumboperitoneal shunting, and intracranial venous sinus stenting, Feldon reported the following findings[58] :

• Optic nerve sheath decompression: Visual defects were improved or resolved in 80% of 252 cases.
• Ventriculoperitoneal (VP) shunt placement: Visual defects were improved or resolved in 38.7% of 31 cases.
• Lumboperitoneal (LP) shunt placements: Visual defects were improved or resolved in 44.6% of 44 cases.
• Intracranial venous sinus stent placement: Visual defects were improved or resolved in 47% of 17 cases.

Visual worsening was rare for all procedures. The author concluded that visual outcome was best documented for optic nerve sheath fenestration, which appeared to be the best surgical procedure for vision loss in IIH. While optic nerve sheath decompression may improves visual defects, many patients continue to have significant headaches that require CSF shunt placement.[47]

Reduction of body weight by 5%-10% was found to be effective with resulting improvement of papilledema and visual fields.[59]

In a literature review of bariatric surgery in 62 obese patients with IIH, Fridley et al found that 52 (92%) experienced resolution of the presenting symptoms.[60] Of 35 patients who underwent postoperative funduscopy, 34 had resolution of papilledema. Of 12 patients who underwent preoperative and postoperative visual field examinations, 11 showed resolution of visual field defects.

Among 13 patients in whom CSF pressures were measured preoperatively and postoperatively, there was an average postoperative decrease of 254 mm water.[60] The authors called for prospective controlled studies to confirm the effectiveness of this surgical approach for patients with IIH in long-term follow-up.

An additional study that investigated the long-term outcomes of bariatric surgery in IIH patients looked at 30 patients who underwent bariatric surgery at least 4 years prior and found that attaining and maintaining a BMI of 30 or below was associated with long-term improvement of signs and symptoms of IIH.[61]

Admission for pain management

Even for initial diagnosis, most patients do not require inpatient care, since lumbar puncture is usually performed in the ambulatory care setting. An occasional patient may develop an intractable low-tension headache after lumbar puncture and may require a short hospital stay for intravenous (IV) hydration and analgesic management. A "blood patch" is sometimes indicated if the post–lumbar puncture headache does not subside spontaneously within a few days.

Admission for surgical management of increased intracranial pressure

Patients who report rapidly progressive visual loss (typically, constriction of peripheral vision or dimming of vision in one or both eyes) particularly those who present with decreased visual acuity, and new visual field loss, may respond to high-dose corticosteroid therapy. They should be considered for hospital admission and should undergo daily monitoring of visual function. A low threshold for surgical intervention should be considered in these fulminant IIH patients.

If the visual field worsens or does not recover promptly (ie, within 24-48 hours) with corticosteroid therapy, emergency CSF shunting (lumboperitoneal, ventriculoperitoneal, or ventriculoatrial) or optic nerve sheath fenestration should be performed.

If any delay in implementing surgical decompression of the failing optic nerve is anticipated, the patient should be moved to the ICU or a stepdown unit for lumbar CSF drainage until the definitive procedure can be performed.

A very small number of patients with normal visual fields may require surgical relief of CSF pressure because of intractable headache. Optic nerve sheath fenestration does not provide reliable/adequate CSF pressure normalization or headache relief; thus, these patients require a shunting procedure. Because patients with IIH frequently have other types of headaches, the decision to choose ventriculoperitoneal shunting over optic nerve sheath fenestration should not be made based on the presence of headache alone.

Most patients with IIH are females who are overweight. Weight loss is a cornerstone in the long-term management of these patients. On initial diagnosis, a weight-reduction and low sodium diet should be strongly recommended to all patients. As little as a 5%-10% weight loss has been demonstrated to yield a reduction in ICP with accompanying resolution of papilledema. Unfortunately, weight reduction generally proves to be a difficult task for these patients.[62] To formalize the process of weight reduction, referral to a dietitian or a formal weight loss program is appropriate.

No activity restriction is required in managing IIH. In fact, exercise programs are strongly recommended in conjunction with a weight-reduction diet.

The frequency of the follow-up visits is determined by a number of factors, to include the following:

• Initial visual function of the patient
• Underlying disease causing increased ICP
• Perceived compliance of the patient with medical therapy

Once the initial diagnosis has been established, investigations have been performed, and therapy has been initiated, the patient can be observed every 3 to 4 weeks.

If, however, the patient presents with a significant visual function deficit or marked papilledema, frequent monitoring for 1 to 2 weeks is appropriate until some improvement and subsequent stability in visual function can be demonstrated. The clinician should be prepared to titrate the patient’s treatment to the status of visual function and should not hesitate to refer the patient for surgical treatment (optic nerve sheath fenestration or CSF diversion) if visual function does not stabilize.

During follow-up visits, the best-corrected visual acuity, color vision (with pseudoisochromatic plates), static perimetry, and optic nerve appearance (including the status of spontaneous venous pulsations) should be recorded. Patients who do not perform well on static perimetry testing may be better monitored with kinetic perimetry testing.

Spontaneous pulsation of large retinal veins generally indicates a normal ICP. If the patient continues to remark on the persistence of a significant headache despite the presence of spontaneous venous pulsations, a source other than IIH for the headache should be considered.

The Idiopathic Intracranial Hypertension Treatment Trial identified that the risk factors for treatment failure included male sex, high-grade papilledema, low baseline visual acuity, and increased number of transient visual obscuration episodes per month. Among patients with these risk factors, the IIHTT recommends closer monitoring while considering more aggressive treatment options.[63]

When a patient appears to have stabilized with respect to visual function and treatment, the frequency of follow-up visits can be extended to once every 2 to 4 months.

IIH has no known cause and no known methods of prevention. Among patients who have been diagnosed with IIH, the goal is to prevent further visual loss and comorbid symptoms, including headache. Progression of IIH is prevented through medical and surgical treatment, as well as diet and lifestyle modifications to reduce body weight. 

Management guidelines are based on symptoms and extent of visual impairment at presentation. If there is no immediate threat to vision, medical therapy is recommended. In the event of an immediate threat to visual function, a temporary CSF draining procedure (ie, placement of a lumbar drain) is immediately performed, and a definitive surgical plan is made; either a ventriculoperitoneal shunt or optic nerve sheath fenestration.[64]

Specific therapy for idiopathic intracranial hypertension (IIH) is aimed at lowering ICP pharmacologically. Carbonic anhydrase inhibitors (eg, acetazolamide) and loop diuretics (eg, furosemide) are thought to exert their effect on ICP by reducing cerebrospinal fluid (CSF) production at the choroid plexus. Cardiac glycosides have a similar effect.

Corticosteroids are indicated on a short-term basis in patients who present with severe papilledema and compromised visual function. They are effective in reducing ICP, but the mechanism of action is unknown. Corticosteroids are often used as maximum medical management when rapid lowering of ICP is required.

Patients with IIH may experience headaches that have many of the features of migraine. These headaches can often be controlled with amitriptyline, propranolol, or other commonly prescribed migraine prophylaxis agents. Topiramate also is an excellent choice, in that one of its side effects is weight loss (a common association in IIH), which can help put the disease in remission.

Class Summary

Carbonic anhydrase (CA) is an enzyme found in many tissues. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid becomes dehydrated. These changes may result in a decrease in CSF production by the choroid plexus.

Acetazolamide (Diamox Sequels)

Acetazolamide is a nonbacteriostatic sulfonamide and a potent CA inhibitor that is effective in diminishing fluid secretion. It lowers ICP by decreasing production of CSF. Inhibition of CA results in a drop in sodium ion transport across the choroidal epithelium. Reduction of CSF production occurs within hours.

Acetazolamide commonly achieves long-lasting control of transient visual obscurations, headache, and diplopia, all of which are manifestations of intracranial hypertension, even though papilledema does not resolve completely. The effect on ICP is not sustained, and many patients develop adverse effects severe enough to hinder compliance.

Few patients tolerate dosages higher than 2 g/day, but 4 g/day may be required to produce a measurable pressure-lowering effect. Treatment is usually initiated at 1 g/day and increased to 2 g/day if symptoms are not controlled and adverse effects are not severe. Treatment with acetazolamide alone is not appropriate for patients who are experiencing progressive visual field loss.

Class Summary

Loop diuretics inhibit reabsorption of sodium in the ascending limb of the loop of Henle and have a weak inhibitory action on CA.

Furosemide (Lasix)

Furosemide inhibits CSF production, but the precise mechanism by which it does so is unclear. A combination of CA inhibition and an effect on sodium absorption across the choroid plexus may result in the decreased CSF production.

Class Summary

Cardiac glycosides reduce CSF production at choroid plexus and reduce ICP.

Class Summary

Glucocorticoids reduce ICP through an unknown mechanism.

Prednisone

The mechanism of action by which corticosteroids lower CSF pressure has not been established. Some believe that they may facilitate outflow at arachnoid granulations.

Prednisolone (Pediapred, Millipred, Orapred)

The mechanism of action by which corticosteroids lower CSF pressure has not been established. Some believe that they may facilitate outflow at arachnoid granulations.

Class Summary

Beta-blockers may prevent migraines by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues. Significant to their activity as migraine prophylactic agents is the lack of partial agonistic activity. Latency from initial treatment to therapeutic results may be as long as 2 months.

Propranolol (Inderal LA)

Propranolol is FDA approved for migraine prophylaxis.

Class Summary

Amitriptyline, nortriptyline, doxepin, and protriptyline have been used for migraine prophylaxis, but only amitriptyline has proven efficacy and appears to exert its antimigraine effect independent of its effect on depression.

Amitriptyline

Amitriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Class Summary

These drugs are effective in prophylaxis of migraine headache.

Topiramate (Topamax)

Topiramate is indicated for migraine headache prophylaxis. Its precise mechanism of action is unknown, but the following properties may contribute to its efficacy: (1) blockage of voltage-dependent sodium channels, (2) augmentation of activity of the neurotransmitter GABA at some GABA-A receptor subtypes, (3) antagonization of the AMPA/kainate subtype of the glutamate receptor, and (4) inhibition of the carbonic anhydrase enzyme, particularly isozymes II and IV. Topiramate is also an excellent choice, in that one of its side effects is weight loss (a common association in IIH), which can help put the disease in remission.

Divalproex sodium/valproate (Depakote, Stavzor, Depacon, Depakene)

Divalproex is now considered first-line preventive medication for migraine. This agent is believed to enhance GABA neurotransmission, which may suppress events related to migraine that occur in cortex, perivascular sympathetics, or trigeminal nucleus caudalis. Divalproex has been shown to reduce migraine frequency by 50%.

Gabapentin (Neurontin)

Gabapentin is used for migraine headache prophylaxis. It has shown efficacy in migraine and transformed migraine.