Idiopathic Intracranial Hypertension (IIH) Treatment & Management

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.