A Multidisciplinary Treatment Approach for Idiopathic Intracranial Hypertension

Acknowledgments

We would like to thank Dr. Hitoshi Ganaha and Dr. Tabiko Ganaha for critically reviewing this manuscript.

Introduction

Idiopathic intracranial hypertension (IIH) is a complex disease whose incidence has been increasing since 1990. ^, It is highly correlated with an increase in obesity, and is associated with headaches, papilledema, and raised cerebral spinal fluid (CSF) pressure in the absence of an intracranial lesion, which can be complicated with permanent visual loss. The worldwide incidence of IIH is 12 to 20 per 100,000 per year in women who are obese and of childbearing age, and is 0.5 to 2 per 100,000 per year in the general population, ^, with the incidence lower in males, in pediatric populations, and familial cases. ^, ^, ^,

Pathophysiology

Currently, there is no general consensus on the underlying pathogenesis of IIH. However, several characteristic clinical findings offer valuable insights into the mechanism of disease progression. IIH is thought to occur via CSF hypersecretion, CSF outflow obstruction, and/or increased venous sinus pressure, but the cause is still largely unknown. Furthermore, IIH is divided into primary and secondary forms. The primary form generally develops in females with high body mass index, and/or with recent weight gain. Unlike the primary form, the secondary form is associated with an underlying etiology that contributes to the constellation of symptoms and signs of IIH (to be mentioned below). Secondary IIH is often associated with medications (e.g., retinoic acid, tetracycline), infections (e.g., meningitis), nutrition (e.g., iron deficiency), venous sinus thrombosis, and endocrine disorders (e.g., hypothyroidism).

Clinical Presentation

The general symptoms of IIH can be categorized into three groups: (1) symptoms of elevated intracranial pressure (ICP): headaches, diplopia due to cranial nerve VI involvement, pulsatile tinnitus, and radicular pain, usually in the arms. (2) Symptoms of papilledema, which can be associated with transient visual obscurations, and/or progressive or sudden vision loss. (3) arcuate retinal nerve fiber layer (RNFL)–related defects sparing visual acuity may also occur in the later stages. These symptoms may be accompanied by loss of peripheral vision or loss of color vision; the central vision may be blurred and distorted. Although rare, sudden visual loss may also occur; this may be as a result of intraocular hemorrhage secondary to peripapillary subretinal neovascularization due to chronic papilledema.

Ophthalmologic Manifestations

A thorough visual and funduscopic examination are important in patients presenting with new-onset headaches. However, it is necessary to keep in mind that there are many patients with IIH who have no symptoms of papilledema. Important ocular concerns associated with IIH are progressive visual field loss and optic nerve damage arising from chronic papilledema. Acute visual loss is uncommon; however, it may occur from conditions such as ischemic optic neuropathy, retinal vascular occlusion, subretinal hemorrhage from a choroidal neovascular membrane, exudates affecting the macula, or from papilledema alone as seen in malignant IIH. Symptoms can range from papilledema without apparent visual loss to rapid visual loss. Fulminant IIH is the primary concern for patients presenting with significant papilledema. Urgent surgical intervention is indicated in these cases; however, patients may still end up with poor visual outcomes.

A standard ophthalmic examination for IIH consists of tests for visual acuity, color vision, and examination of the pupils and optic discs. Visual field testing is a sensitive indicator of progressive vision loss ^, and remains the best overall indicator of visual status. Automated static perimetry is the gold standard due to its reproducibility and generation of statistical data ( Fig. 87.1A ).

FIGURE 87.1, Ophthalmologic testing for idiopathic intracranial hypertension. (A) Humphrey 24-2 perimetry documents enlargement around the blind spot, and beginning of inferior arcuate field defect in the left eye. (B) Optical coherence tomography documents elevation of both optic nerves above normal (green area) . (C) En face display of optic nerve documenting micron elevation by clock hours; only the 8:00 sector appears normal (green wedge) . (D) Ocular coherence tomography cross section through left optic nerve documents elevation of the nerve. (E) Disc edema of the left eye; note the obscuration of vessels coursing over the nerve border (yellow arrow) , and retinal folds (blue arrow) .

Photographic documentation of the optic nerve appearance is extremely helpful in following the course of the disease, as are serial visual fields. Ocular coherence tomography (OCT), which uses reflected infrared light to capture cross-sectional images in high resolution, may also be useful in following the course of IIH ( Fig. 87.1B –D).

Diagnosis

The diagnosis for IIH is based on clinical manifestations, which include neurological physical examination, ophthalmic and radiological evidence, and CSF findings from lumbar puncture (spinal tap). Recent advances in medical imaging have led to the establishment of the new diagnostic criteria for IIH. ^, A suspected diagnosis of IIH may be made in certain special instances when there are a series of suggestive symptoms. Even in the absence of papilledema, neurological deficits, or abnormal findings on MRV (magnetic resonance venogram) and CSF studies, a suspected diagnosis of IIH can be made with the presence of a sixth-nerve palsy with increased lumbar puncture (LP) opening pressure. However, the diagnosis of IIH without papilledema or sixth-nerve palsy is rare, and care should be taken when one makes such a diagnosis.

Neuroimaging

IIH diagnosis is a disease diagnosed by the process of elimination. Neuroimaging allows exclusion of other pathologies, and magnetic resonance imaging (MRI) is the modality of choice. Chronic IIH can manifest with findings such as the flattening of the posterior globes, protrusion of the head of the optic nerves, distention of the optic nerve sheath, transverse venous stenosis, and an empty sella, among others ( Fig. 87.2 ). MRI and MRV are helpful to screen for hydrocephalus, intracerebral masses, meningeal infiltrative or inflammatory disease, dural venous sinus stenosis (VSS), and obstruction such as thrombosis.

FIGURE 87.2, Radiographic findings of idiopathic intracranial hypertension. (A) Flattening of the posterior sclera, (B) intraocular protrusion of the optic nerve head, (C) tortuous optic nerve and optic disk elevation, (D) prominent subarachnoid space around the optic nerves, (E) bilateral transverse venous sinus stenosis, and (F) partial empty sella turcica.

Medical and Pharmacological Management

The primary goal of IIH treatment is to preserve vision, and the secondary goal is to relieve the patient’s symptoms. The initial management of IIH is directed toward confirming the diagnosis and identifying secondary causes. Conservative management with weight loss and pharmacotherapy are initiated. Corticosteroids or surgical interventions are used to treat rapidly declining vision symptoms.

Acetazolamide

The carbonic anhydrase inhibitor acetazolamide is commonly used in IIH treatment. Acetazolamide reduces the production of CSF by inhibiting carbonic anhydrase, an enzyme involved in ion transport in the choroid plexus. The inhibition of carbonic anhydrase has been shown to decrease CSF production by up to 50%. In addition, ICP is reduced further through a secondary mechanism of the sulfonamide-derivative which acts as a mild diuretic. Higher doses (1000 to 2000 mg/day) are initially administrated to achieve the desired reduction of ICP. Common side effects of acetazolamide include malaise, perioral and finger paresthesia, increased incidence of renal stones, and altered taste sensation.

Given that IIH typically occurs in women of childbearing age, pregnancy warrants special concerns for treatment. One study of over 100 patients has shown no convincing evidence for adverse effects for acetazolamide during pregnancy, even when prescribed before the 13th week of gestation. Although the use of acetazolamide should be avoided as much as possible during pregnancy, the medication may be considered as a treatment option in pregnant women if necessary. Lee and colleagues found no adverse effects in twelve pregnant patients using acetazolamide ; however, an incidental case of sacrococcygeal teratoma has been reported in a neonate whose mother used acetazolamide. Metabolic acidosis with hypocalcemia and hypomagnesemia has also been reported in a preterm infant whose mother was treated with the drug. Pregnant patients are managed similarly to other female patients with IIH; however, caloric restriction and the use of diuretics are done with caution in pregnant patients. Furthermore, LP shunts are well tolerated with a small maternal-fetal risk, and visual outcomes of IIH have been reported to be similar between pregnant and non-pregnant patients. ^,

Randomized controlled trials have shown the effectiveness of acetazolamide in treating visual acuity and managing headache severity. The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) randomized controlled trial by the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC) showed that acetazolamide was effective for visual loss, weight loss, CSF opening pressure, and papilledema; however, its effectiveness was unclear on headaches. ^, A randomized controlled trial by Ball and colleagues showed that acetazolamide was effective in managing headaches, transient visual obscuration, visual loss, and binocular contrast sensitivity. Nonetheless, no clear improvements in papilledema and visual fields were noted. There were insufficient data to declare the universal efficacy of acetazolamide on visual acuity, management of headache severity, and papilledema in these studies.

Topiramate

Topiramate has been shown to be effective in decreasing ICP. This drug used to treat migraine has also been shown to have an effect on weight loss. In a small study, topiramate was found to be effective for IIH; in this study, weight loss was more common in patients treated with topiramate compared to acetazolamide. It is important to note that the use of topiramate concomitantly with acetazolamide can lead to metabolic acidosis, and that topiramate is contraindicated in pregnancy.

Other Diuretics

Furosemide and chlorthalidone are occasionally utilized to treat IIH; however, their effects are inferior compared to acetazolamide or topiramate. The combined use of diuretics and carbonic anhydrase inhibitors must be monitored carefully due to potential induction of hypokalemia.

Surgical Management

Management of IIH is performed surgically when conservative and medical management have been exhausted, and if the patient has no contraindications to surgery. Indications for surgery include progressive visual loss and the inability to tolerate medication.

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