What Is Intracranial Hypertension (Pseudotumor Cerebri)?

Thousands of women have filed lawsuits against Bayer HealthCare, claiming the company’s Mirena intrauterine device (IUD) causes severe side effects. While most of these legal claims revolve around perforation incidents and ectopic pregnancies, more than 100 product liability lawsuits say the IUD can also result in idiopathic intracranial hypertension, a rare brain disorder.

Idiopathic Intracranial Hypertension Infographic
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What Is Idiopathic Intracranial Hypertension?

The human brain, along with the spinal cord, is constantly bathed in cerebrospinal fluid, a clear cushioning fluid produced by four interconnected cavities deep inside the white matter. The brain produces cerebrospinal fluid continually, around 500 mL every day, but the fluid is also being reabsorbed by the organ at a constant rate. Thus, only around 100 to 160 mL of cerebrospinal fluid is actively protecting the brain at any one time.

For some reason, this continual give-and-take, the cycle of production and reabsorption, doesn’t work properly in people with idiopathic intracranial hypertension. Instead of being absorbed by the brain, cerebrospinal fluid builds up, increasing pressure within the skull and, in most cases, leading to unpleasant symptoms.

Is IIH A Brain Tumor?

No, but the condition’s symptoms closely mimic those caused by larger brain tumors, which is why intracranial hypertension is sometimes referred to as pseudotumor cerebri, Latin for “false brain tumor.”

  • Headaches, which usually vary in severity and location
  • Blurry or double vision
  • Pulsatile tinnitus – a rhythmic buzz or thump in the ears, often in time with the heartbeat
  • Dizziness
  • Nausea and vomiting
  • Radicular pain – a pain that radiates down a nerve of the spine into the arms, although this symptom is rare
  • Progressive vision loss, usually a narrowing of the visual field

While all of these effects are certainly distressing, and many are immediately painful, IIH rarely damages the brain itself. Rather, the crucial consequence of IIH is actually damage to nerves in the eye.

Young Womans Eyes

Increased cranial pressure places significant strain on the optic nerve. More specifically, the outer covering of the optic nerve is directly continuous with the subarachnoid space, a thin cavity filled with cerebrospinal fluid that surrounds the brain. Increases in fluid pressure are thus transmitted directly to the optic nerve, which becomes pinched and begins to protrude, in a disorder known as papilledema. In most cases, patients will experience headaches and various visual disturbances, including blurred vision, an enlarged blind spot or transient vision loss. If left untreated, the condition can result in permanent vision loss.

How Common Is IIH?

Idiopathic intracranial hypertension is exceedingly rare, although some studies have suggested that the condition’s prevalence is growing. Early estimates placed the disorder’s incidence at around 1 to 2 people per 100,000. A more recent analysis, published by the Archives of Neurology, found that between 1976 and 1990 around 3.3 out of every 100,000 women between the ages of 15 and 44 years old developed idiopathic intracranial hypertension.

What Causes Idiopathic Intracranial Hypertension?

In most individual cases, researchers aren’t sure what causes idiopathic intracranial hypertension (IIH). That’s why the condition is defined in part by its unknown, or “idiopathic,” origin.

Doctors have, however, suggested a wide variety of potential causes, along with risk factors that appear to increase the likelihood of developing IIH. The disorder occurs primarily in women, especially young women between the ages of 20 and 50 who would be classified as “obese.” It’s likely that many of these patients have conditions like Addison’s disease, Cushing disease or hypoparathyroidism, all of which have been associated with an increased risk of intracranial hypertension, according to the National Library of Medicine.

Pregnancy and menstruation have also been linked to IIH, as have a wide range of medications:

  • Birth control pills
  • Cyclosporine
  • Isotretinoin
  • Minocycline
  • Nalidixic acid
  • Nitrofurantoin
  • Phenytoin
  • Steroids
  • Sulfa drugs
  • Tamoxifen
  • Tetracycline
  • Vitamin A

If you’ve noticed a theme developing, you’re not imagining things. Idiopathic intracranial hypertension seems intimately tied to pregnancy in some way. The condition is most common in women of childbearing age and many birth control pills appear to increase the risk. More accurately, researchers believe that hormones, and alterations in a patient’s hormone levels, may contribute to IIH. This could explain the disease’s association with obesity, since fatty tissues actually secrete a variety of hormones, including steroid hormones.

Where Does Mirena Fit In?

Mirena is a hormonal intrauterine device. The small T-shaped implant continually releases a chemical called levonorgestrel, which is a laboratory-manufactured version of progesterone, a naturally-occurring steroid hormone.

Hormone’s Complex Link To Pseudotumor Cerebri

While levonorgestrel can effectively prevent pregnancy in many women, researchers have long suspected that hormones like it can increase the risk for idiopathic intracranial hypertension. In fact, physicians in Baltimore were already pondering a possible association in 1965, according to Eldar Rosenfeld, an ophthalmologist in Israel.

Despite such early warning signs, which surfaced in relation to women taking oral contraceptives, few authorities focused their research on the topic until more recently, with the 1991 approval of a levonorgestrel implant called Norplant.

Between 1995 and 1998, two reports were published suggesting a link between the use of Norplant and IIH hospitalizations, although both stopped short of ascribing a causal relationship. Further, neither paper attempted to evaluate the prevalence of obesity, a well-known risk factor for pseudotumor cerebri. These limited results were far from conclusive evidence, although doctors advised increased caution.

In 2000, British researchers went so far as to suggest that intracranial hypertension “should be regarded as a condition in which the potential risks of using progestogen-only methods [of contraception] generally outweigh the benefits.” Mirena gained approval for sale in the US market the same year. Case reports of patients, both obese and not, who developed idiopathic intracranial hypertension soon followed.

“Risk Must Be Clearly Conveyed To Young Women”

By 2012, over 1 million American women had received the IUD. But until 2015, no researchers had undertaken a rigorous epidemiological study to investigate the device’s link to IIH. In that year, a group of Canadian pharmaceutical researchers completed a large analysis of FDA data, finding that women with Mirena were 78% more likely to report intracranial hypertension and 50% more likely to report papilledema. The study concluded that “the risk of [intracranial hypertension] with Mirena must be clearly conveyed to young women who are planning to use [the IUD].”

The study was published in June of 2015 by Therapeutic Advances in Drug Safety.