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An introduction to idiopathic intracranial hypertension
Patients rarely present to their eye doctor expecting to be referred to the nearest emergency room. However, eye care providers are confronted with various neuro-ophthalmic emergencies that warrant an immediate, same-day referral to the emergency room for prompt evaluation. These patients may have a life-threatening underlying condition and time is of the essence.
One of the more common neuro-ophthalmic emergencies that can present is papilledema (bilateral swollen optic nerves). This presentation is one of the main reasons eye care practitioners will refer younger patients to the emergency room: in order to rule out the presence of an intracranial mass lesion.
Papilledema can be caused by many different conditions, one of which is idiopathic intracranial hypertension (IIH). This disease process has also been previously referred to as pseudotumor cerebri. A diagnosis of IIH is a diagnosis of exclusion, and cannot be definitively made without same-day neuroimaging and lumbar puncture.
In this article, we’ll discuss the pathophysiology of IIH, clinical manifestations, and various approaches to management and treatment for patients.
Epidemiology and pathophysiology
The first documented case of IIH occurred in the late 1800s. Today, the incidence in the US general population is approximately one per 100,000. This number is significantly higher among obese women of childbearing age (~20 per 100,000) and is directly correlated with body mass index.
Up to 96% of patients with IIH will experience some changes to their vision. This primarily occurs by increased intracranial pressure (ICP) significantly compromising axoplasmic flow along the visual axis, leading to variable changes in vision. Since the optic nerve is surrounded by the meninges and cerebrospinal fluid (CSF), it is directly affected by elevated ICP. In IIH, the relationship between intraocular pressure and retrolaminar pressure is altered. The combination of axoplasmic flow stasis, intraneuronal ischemia, and increased mechanical pressure on the optic nerve can result in irreversible vision loss for the patient if left untreated.
Approximately 600mL of CSF is produced on a daily basis, gradually decreasing with age. This may partly explain why IIH primarily occurs in younger demographics.
It is thought that excessive secretion of CSF by the choroid plexus or abnormal CSF reabsorption through the subarachnoid space leads to elevated ICP and IIH. While the literature is sparse with definitive evidence on excessive CSF production in IIH, increased resistance to CSF reabsorption has been established in cases of IIH.
Pro-thrombotic disorders (e.g., polycythemia), as well as endocrinological disorders like obesity and polycystic ovarian syndrome (PCOS), are thought to increase resistance to CSF reabsorption thus also contributing to IIH.
Aldosterone is a mineralocorticoid involved with CSF production. Hyperaldosteronism has been linked with PCOS and obesity, and may partly explain the correlation with IIH among these patient demographics. It is also thought that elevated intra-abdominal pressure in obesity can lead to increased ICP via the venous vessels in the spine. This, however, does not entirely explain the marked female predominance in IIH.
Other medications can also cause IIH as an unwanted side effect. Exogenous substances linked with IIH include lithium, hormones, vitamin A derivatives (e.g., isoretinoids), tetracycline antibiotics (e.g., minocycline, doxycycline), and intake/withdrawal of corticosteroids. Accutane is a common vitamin A derivative used to treat severe acne and can be a common culprit for IIH. If possible, any potential medications that contribute to IIH should be discontinued upon diagnosis. This may require co-management with the patient’s primary care physician.
Estrogen has also been linked with a prothrombotic state and has been shown to increase retinoic acid synthesis, both of which can alter CSF outflow. This may partly explain the preponderance for IIH in young females, as well as the role of hormonal contraceptives in IIH pathogenesis. Oral/implantable contraceptives and intrauterine devices have also been linked with IIH and must be addressed accordingly.
Diagnosing idiopathic intracranial hypertension
Patients presenting with IIH will likely have severe, new-onset headaches as their primary new symptom. In fact, up to 90% of patients have been shown to report new onset daily severe headaches as their primary symptom. Transient visual obscurations (TVO), blurred vision, nausea, and even vomiting are also symptoms likely to accompany the patient’s initial presentation. Binocular diplopia can also occur from a non-localizing unilateral/bilateral sixth nerve palsy.
Patients can present with seemingly normal central visual acuity, but report changes in their peripheral vision or alterations in how they perceive moving objects. Enlarged blindspots on formal visual field testing are classic with papilledema (and IIH). After prolonged periods of elevated ICP and swollen optic nerves, nerve fiber layer defects (eg. arcuate patterns) can also occur. The papillomacular bundle, thus central acuity, appears to be spared until later in the disease process. Up to 24% of patients with IIH have been shown to develop severe visual impairment or blindness. More recent studies suggest this number is slightly lower at ~10%.
The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) also found that almost 70% of IIH patients experienced transient visual obscurations. This is due to the compromise in afferent function. Over half of these patients also experienced pulsatile tinnitus.
It is important for eye care practitioners to AVOID immediately jumping to IIH as a diagnosis when patients present with bilateral swollen optic nerves. Elevated ICP can occur through any number of mechanisms, which must all be ruled out prior to concluding with IIH as a diagnosis. It is important to remember that IIH is a diagnosis of exclusion.
The clinical manifestation of papilledema appears as bilateral swollen/blurred disc margins likely with peripapillary hemorrhaging. Due to nerve fiber swelling, peripapillary retinal vessels tend to be obscured. Enlarged blindspots on visual field testing are also present and correlate with enlarged optic nerves. Visual acuity and pupillary testing tend to remain normal but can be affected in severe cases. The absence of spontaneous venous pulsation (SVP) is also important to identify in IIH (and may be better assessed with an ophthalmoscope). Patients may present with binocular horizontal diplopia due to CN6’s high vulnerability with elevated ICP.
It is also important to be aware of physiologic variations of normal to the optic nerve that could present as “pseudopapilledema.” These can include myopic/tilted discs as well as optic nerve drusen. These patients, however, will likely be asymptomatic for any of the aforementioned symptoms of IIH.
Other causes of papilledema can include intracranial mass lesions (e.g., brain tumor, hemorrhage, arteriovenous malformation), hydrocephalus, meningitis, and cerebral edema (e.g., recent trauma, toxicity). The literature varies widely on what percentage of patients with brain tumors will present with papilledema, ranging from 30% to 80%.
It is also important to check blood pressure on all papilledema patients in order to rule out malignant hypertension.
Figure 1: Initial presentation of IIH in 19 y/o Female with history of obesity and implantable contraceptive use (Nexplanon). IIH may initially be more difficult to discern in patients with lighter fundi. Optic nerve hypoplasia shown in left eye.
Figure 2: Swollen optic nerves in papilledema can also be appreciated on optical coherence tomography.
The modified Dandy criteria are used to make a formal diagnosis of IIH
- Symptoms and signs of increased ICP (e.g., headaches, papilledema)
- Unremarkable neuroimaging—no structural cause (e.g., brain tumor), no hydrocephalus
- MRI or contrast-enhanced CT scan
- Documented high opening pressure on lumbar puncture (LP)
- Normal CSF chemistry
- Absence of localizing neurologic signs (CN6 palsy is an exception)
- No other causes of increased ICP noted throughout workup
Patients with IIH will almost always present with papilledema; however, IIH without papilledema has been reported. Papilledema is typically bilateral and symmetric; however, in about 10% of cases can be asymmetric or unilateral.
TIP! It is important to AVOID immediately jumping to IIH as a diagnosis when a patient presents with papilledema. Elevated ICP can occur through any number of mechanisms, which must all be ruled out prior to concluding with IIH as a diagnosis. It is important to remember that IIH is a diagnosis of exclusion.
It is important to have the contact information to the nearest emergency department(s) at your disposal in order to facilitate a prompt referral for these patients. When referring papilledema patients for workup, it is important to call ahead (while the patient is still in your office) and let the emergency department know the situation and that you’ll be sending a patient over for prompt neuroimaging followed by lumbar puncture.
Only after confirmation of unremarkable MRI (preferably with and without contrast) of the brain and normal CSF composition with elevated opening pressure can a diagnosis of IIH be made. Some EDs may opt for a contrast-enhanced CT scan in lieu of MRI. Patients with confirmed IIH will have elevated opening pressures on LP, typically in excess of 25cm/250mm of water. In some cases, patients with IIH may have CSF pressures less than 25cm. A lumbar puncture opening pressure less than or equal to 20cm is considered normal in adults.
TIP! It is important that neuroimaging is always performed prior to lumbar puncture in a papilledema workup. This is done to rule out the presence of an intracranial mass/tumor, which has the potential to herniate during lumbar puncture.
Treatment and management of idiopathic intracranial hypertension
Patients with IIH are initially followed closely to monitor for stability vs. progression. This can initially be on a weekly basis and then extended to monthly as signs/symptoms begin to improve for the patient.
IIH is typically treated conservatively with oral carbonic anhydrase inhibitors (e.g., acetazolamide/Diamox) in addition to discontinuing any high-risk medications/oral contraceptives while also encouraging weight loss. The diuretic effect of acetazolamide is effective at reducing ICP and has been shown in some cases to reduce CSF production by almost 50%.
According to the IIHTT, weight loss combined with Diamox is a safe and effective treatment strategy for patients with IIH. The typical starting dose for Diamox is 500mg twice daily. Starting at lower doses and working up to one gram daily can help patients get accustomed to any side effects (e.g., 250mg QID).
Contraindications to Diamox include liver/kidney disease, electrolyte imbalances, adrenal gland insufficiency, and a preexisting allergy to sulfa-based medications. Always remember to inquire about any allergies to medications.
Furosemide and topiramate have also been used as treatment alternatives for patients who may not tolerate the side effects of Diamox. These commonly include tingling in the hands/feet and a metallic taste. Depression, diarrhea, metabolic acidosis, thrombocytopenia, aplastic anemia, and transient myopic shifts can also occur. Patients on long-term treatment with Diamox may need periodic complete blood counts to monitor for changes to platelets, and white/red blood cell counts.
Unfortunately, some IIH patients may need oral CAI treatment for several years and are best co-managed with primary care and neurology. Coordination with the patient’s PCP is also important in cases where high-risk medications may need to be modified or discontinued.
Counseling patients on weight loss and nutrition is also an important component of IIH management. Patients may benefit from referrals to social workers and/or dieticians in addressing these areas. In many cases, weight loss and BMI optimization are the most effective long term strategies for avoiding IIH recurrence. Recurrence rates between eight and 38 percent have been shown in IIH but may be different based on each patient’s risk factors.
Only a modest amount of weight loss is required to improve IIH signs and symptoms. As little as ~6% reduction in total body weight has been shown to provide significant improvements for patients. For patients who are morbidly obese, referral and consultation for bariatric surgery may also be a viable treatment option.
There is also a link between sleep apnea and IIH, which may warrant a referral for a sleep study as part of a comprehensive treatment plan. Improving sleep quality can also help patients optimize insulin sensitivity and further promote weight loss.
Surgical intervention for IIH is less common and is generally reserved for patients who are intolerant, or fail to comply with maximum medical therapy. Surgical intervention is also a viable option in cases of progressive/severe vision loss. Surgical treatments include optic nerve sheath fenestration (ONSF), neurosurgical CSF shunting (e.g., lumboperitoneal shunt) and/or venous sinus stenting. These are chosen on a case-by-case basis and largely depend on local surgical expertise and institutional resources.
Figure 3: Idiopathic intracranial hypertension, initial clinical presentation in 36 y/o Female with history of obesity, hypertension, and oral contraceptive use (Estarylla).
Figure 4: Same patient as above, after six months of treatment with Diamox 250mg PO QID, weight loss, and discontinuation of oral contraceptive.
In conclusion, eye care providers must take a comprehensive approach to patients presenting with papilledema. Taking a thorough case history, clinical exam and obtaining appropriate neuroimaging and lumbar puncture are paramount in the care for these patients. IIH is a diagnosis of exclusion. Only after unremarkable neuroimaging in the presence of high opening pressure on LP can papilledema then be considered IIH as a definitive diagnosis. These patients are at a high risk for vision loss, primarily through axoplasmic stasis, and compression of axons and capillaries. This ultimately leads to hypoxic damage to the optic nerve.
Remember to be cautious in diagnosing IIH in patients who do not fit the typical profile, including kids, non-obese patients, elderly patients, and men, as well as those without the classic IIH symptoms (e.g., headache, TVO, pulsatile tinnitus). While the clinical presentation may be a bit unnerving, remember to take a deep breath before proceeding. The patient is less likely to feel anxious about their prognosis if their eye doctor also appears calm and composed. Know that you have the clinical skill set to diagnose, manage and treat this condition when it presents.
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