A recent Cochrane review on interventions for the treatment of IIH found insufficient information to create an evidence-based strategy for the condition. However, there are several widely accepted treatments for IIH available, with varying degrees of supportive evidence and with variable success in the management of IIH-related headache.
Acetazolamide. Acetazolamide is a carbonic anhydrase inhibitor, which decreases CSF production and thereby decreases ICP and presumably the associated headache. Although the mainstay of treatment for IIH for both headache and vision loss, there has never been a randomized controlled trial to show its effectiveness over placebo. A recent randomized study of acetazolamide versus placebo attempted to do so, but was unfortunately not adequately powered to show a treatment effect. Currently the Idiopathic Intracranial Hypertension Treatment Trial is evaluating the efficacy of acetazolamide plus weight loss versus weight loss alone in mild to moderate IIH. The recommended dose of acetazolamide is between 1 and 4 g, titrated to improvement in symptoms and intolerance of side effects, including tingling of the hands and feet, alteration in taste (especially with carbonated beverages), and anorexia. Lower doses may help headache symptoms but probably do not affect ICP. Rare complications can include aplastic anemia and kidney stones. The extended release form of the medication is generally better tolerated. Acetazolamide is contraindicated in patients with liver failure or a significant history of kidney stones. Acetazolamide is listed as a category C medicine in pregnancy; however, Lee et al have suggested the drug is safe in the second and third trimesters, and a recent retrospective review of patients taking acetazolamide in even the first trimester showed no increase in birth defects or other complications.
Topiramate. Topiramate was initially marketed as an antiepileptic medication but is also FDA approved for the treatment of primary headache disorders such as migraine. Topiramate is a weak carbonic anhydrase inhibitor and therefore can be used to help reduce ICP. In addition, topiramate suppresses appetite, which can facilitate weight loss. Topiramate is thought to be most efficacious in the treatment of IIH with a prominent headache component. In a small open-label study comparing the relative efficacy of acetazolamide and topiramate in the treatment of IIH, topiramate was as effective as acetazolamide in relieving headache (mean time to resolution, 3.75 vs. 3.3 mo). In addition, patients taking topiramate lost statistically significantly more weight than patients taking acetazolamide, with a mean of 9.76 kg over 12 months. The topiramate dose ranged between 100 and 150 mg per day, whereas acetazolamide doses were between 1000 and 1500 mg daily—a notably lower dose than many treatment regimens.
Topiramate is typically started at 25 mg daily and can be titrated up to 100 mg twice daily. It is frequently given in addition to acetazolamide in the treatment of headaches not controlled with acetazolamide monotherapy. However, patients should be counseled on the increased risk of kidney stones with dual therapy. The main side effects of topiramate include paresthesias, difficulties with concentration, drowsiness, and decreased appetite. Patients should be made aware of the increased risk of acute angle closure glaucoma secondary to topiramate therapy.
Topiramate is contraindicated in patients with liver failure and has a relative contraindication in patients with a history of kidney stones. It is a category D medication in pregnancy, and female patients should be counseled that the medication may reduce the effectiveness of estrogen-containing oral contraceptives.
Weight Loss. IIH is a disease most commonly seen in obese individuals and weight loss is regarded as an important element of any treatment regimen. Newborg first reported on a series of 9 patients with IIH treated with a low-calorie, low sodium diet, leading to weight loss and resolution of papilledema. Johnson et al showed that approximately 6% weight loss is associated with resolution of papilledema. This was independent of treatment with acetazolamide. Kupersmith et al reported significant improvement in papilledema and visual field defects in patients with modest weight loss of <10 kg. However, change in headache severity was not a measured endpoint in any of the aforementioned studies. More recently, Sinclair et al followed up women with IIH given a low-calorie diet. Patients placed on a 425 kcal/d liquid diet for 3 months lost an average of 15.7 kg and were shown to have lowered ICP and reduced papilledema. In addition, subjects reported improved headache severity, frequency, and reduced need for analgesics. Moderate weight loss has therefore been shown to be effective in the treatment of IIH, including symptomatic relief from headache, and thus should be a key component of every treatment plan, potentially reducing the need for both medical and surgical intervention.
When diet and exercise alone are not successful in achieving weight loss, bariatric surgery can be considered, particularly in the morbidly obese with other complications of obesity. Case reports and small cases series have demonstrated efficacy both for weight loss and headache relief.[19,20] A recent meta-analysis included 62 patients initially presented in 11 publications who underwent bariatric procedures for weight loss in the setting of IIH. Although headache improvement was not a specific endpoint, 74% reported headache as a presenting symptom, and 92% of patients had resolution of their presenting symptoms after bariatric surgery.
Surgical management for IIH is typically reserved for those patients who fail medical management either due to progressive symptoms or intolerance to medical treatment. The surgical options include optic nerve sheath fenestration (ONSF) and CSF diversion procedures.
ONSF. ONSF is often the surgical treatment of choice in patients with vision loss and uncontrolled IIH. The retrobulbar optic nerve is identified through an orbital approach and the nerve sheath is fenestrated by several slits or a window defect, thereby rapidly reducing pressure locally on the optic nerve head. Complications can include diplopia, a tonic pupil, and rarely vision loss secondary to trauma to the optic nerve or central retinal artery.
ONSF does not have a significant effect on ICP or outflow resistance.[23,24] Despite the local effect of ONSF, patients can have improvement in headache after the procedure. Corbett and Thompson reported approximately two thirds of patients with headache experience relief after ONSF. In a series of 17 patients with IIH and severe vision loss who underwent ONSF, 9 of 10 patients with preoperative headache symptoms had persistent relief after surgery. However, in a separate series of 86 patients who underwent ONSF for IIH, only 8/61 (13%) of patients with headache as a presenting symptom expressed subjective improvement during follow-up. In conclusion, some patients may have an improvement in their headache after ONSF; however, the likelihood of persistent improvement is somewhat variable, perhaps due to differing surgical techniques.
CSF Diversion Surgery. Shunting procedures divert CSF to another part of the body, thereby reducing ICP. The 2 most commonly performed procedures are lumboperitoneal and ventriculoperitoneal shunts; both are discussed in detail elsewhere in this issue. McGirt et al reviewed patients over 30 years who underwent shunt placement for intractable headache due to IIH. Of note, 42 patients required 115 shunt placement procedures, an average of 2.74 surgeries per patient, with 12% of patients requiring >=6 procedures. Ninety-five percent of patients experienced significant improvement in headache symptoms at 1 month after shunt placement. Severe headaches recurred in 19% of patients at 12 months and 48% at 36 months, despite a properly functioning shunt. Patients with symptoms >2 years before shunt placement had a 2.5-fold risk of experiencing recurrent headache.
There is significant risk of complication related to the placement of shunts for IIH, including shunt failure, and intracranial hypotension and infection, requiring revision, explantation, and potentially multiple procedures. Rosenberg et al reviewed the efficacy of shunts for the treatment of IIH in 37 patients who underwent 82 shunt placement surgeries, including 73 lumboperitoneal and 9 ventriculoperitoneal shunts. Fewer than half of patients had only a single procedure, with 9 months as the average time before shunt replacement and 64% lasting <6 months.
Although shunts can be effective for immediate improvement of headache related to IIH, there is significant risk of recurrence and need for repeated revisions in long-term follow-up.
Int Ophthalmol Clin. 2014;54(1):103-114. © 2014 Lippincott Williams & Wilkins