Idiopathic intracranial hypertension (pseudotumor cerebri)

Idiopathic intracranial hypertension (pseudotumor cerbri)

Definition

Idiopathic Intracranial Hypertension (IIH), also known as Pseudotumor Cerebri, is a condition of chronically elevated intracranial pressure (ICP) occurring without other intracranial conditions such ventricular enlargement or mass lesions. Patients with IIH manifest clinical signs and symptoms of elevated intracranial pressure (ICP) that significantly lessen their quality of life.

The incidence of IIH in the general US population is between 1 and 3/100,000. There is marked female predominance with over 90% of cases occurring in women and over 90% of women affected being obese. The mean age at diagnosis is 30 years. The number of cases reported are rising quickly and have tripled in the US from 1990 to 2006. Fortunately, because of the high disorders impact on the quality of life and its high economic cost (US $444 million annually), IIH is becoming an area of increased study.

SYMPTOMS OF IIH

Headaches are the most common symptom and have been reported in 99% of IIH patients presenting to neurologists. The headache is often diffuse and worse in the morning, a characteristic that can help differentiate IIH headache from Chiari I headache often varies during the day. However, IIH and Chiari headaches are both frequently aggravated with Valsalva maneuvers such as coughing, sneezing, straining, laughing, yelling, and singing.

Intracranial hypertension commonly affects the visual system. Blurred vision occurs in 88% of those affected. Known as transient visual obscurations, vision can briefly “grey out” for a few seconds to a minute or so, often during a change in position such as standing or bending or with Valsalva maneuvers. Fortunately, with greater recognition of IIH, deterioration of vision to blindness is now uncommon.

The effects of intracranial pressure on the extraocular nerves (the nerves controlling eye movements) can result in double vision. When the sixth cranial nerves are affected, there is double vision on lateral gaze (when looking to the right or left). Vertical double vision (when looking up or down) is less common. Persons with IIH often suffer from other neurological symptoms such as dizziness, nausea, vomiting, pulsatile tinnitus (a pulsatile ringing or sound in the ears), and difficulty with thinking, learning, and memory.

EXAMINATION AND DIAGNOSTIC EVALUATION

When IIH is suspected, it is important to calculate the patient’s body mass index (BMI). BMI is a ratio of one’s weight to their height, obesity being defined as a BMI of 30 kg/m2 or more.

Visual acuity and visual fields are assessed and both may be decreased. Extraocular movements are tested for signs of nerve weakness resulting in double vision. Findings may include weakness of the 6th nerve, and occasionally, of the 3rd or 4th nerves.

Among the most telling findings is swelling of the optic nerve at the back of the eye, the only part of the brain that can be seen on physical exam. Swelling of the optic nerve head, called papilledema, represents the swelling that is occurring in the brain. Papilledema causes the blind spot to enlarge and the visual fields to decrease. However, it is important to note that elevated intracranial pressure does not always result in papilledema. Some people with IIH will not papilledema until the pressure reaches a high level of 35 mmHg.

CT or MRI Scan of the Brain

An imaging study of the brain, a CT scan or preferably an MRI, is crucial to making the diagnosis of IIH. The MRI scans above show findings of severe IIH. The brain is tight and swollen, the cerebral ventricles, especially the frontal horns of the lateral ventricles, are tiny and markedly compressed, and the spinal fluid spaces around the brain are also compressed.

The multiple views available on a brain MRI may demonstrate a number of findings of IIH:

  • Small cerebral ventricles (though they can be normal in some cases)
  • Tight subarachnoid spaces
  • A small and crescent-shaped pituitary gland
  • A markedly compressed pituitary gland (a condition called partially empty sella)
  • The depth of the sella turcica (the bony cup that holds the pituitary) may be greater than normal
  • Flattening of the posterior globe of the eye
  • Protrusion of the optic nerve head
  • Distension of the optic nerve head
  • Vertical tortuosity of the optic nerve

Lumbar Puncture

The diagnosis of IIH is confirmed by measuring the intracranial pressure, usually assessed through a lumbar spinal tap. The opening pressure is measured while the patient is on their side with their legs relaxed. Many patients find transient improvement in their symptoms following the procedure. Although there is considerable variability and differing published values, the normal adult intracranial pressure is generally between 5-15 mm H2O. The opening pressure should be considered together with the patient’s clinical presentation.

CAUSES OF IIH

Several authors have listed the various toxicities, diseases, and conditions that can cause IIH. The combined list below serves as a guide for medical providers and patients in identifying possible causes of a patient’s IIH. It also includes a recently recognized cause, the Mirena IUD.

Causes of Pseudotumor Cerebri

Metabolic and Endocrinopathic

  • Addison’s disease
  • Anabolic corticosteroids
  • Chronic kidney failure
  • Cushing’s disease
  • Galactosemia
  • Hypophosphatasia
  • Norplant levonorgestrel implant system
  • Oral contraceptives
  • Pregnancy
  • Prolonged corticosteroid therapy or too rapid corticosteroid withdrawal
  • Pseudohypoparathyroidism

Drug Toxicity

  • Clomiphene
  • Cyclosporin
  • Doxycycline
  • Hypervitaminosis A
  • Isotretinoin
  • Lithium
  • Minocycline
  • Mirena IUD (levonorgestrel-releasing intrauterine system)
  • Nalidixic acid
  • Nitrofurantoin
  • Phenytoin
  • Clomiphene
  • Sulfa drugs
  • Tamoxifen
  • Tetracycline

Venous sinus thrombosis and elevated central venous pressure

  • Guillian-Barre’ syndrome
  • Chronic otitis media and mastoiditis
  • Sinusitis
  • Jugular venous thrombosis
  • Venous sinus stenosis
  • Thrombophilic states (including hematologic disorders and hyper-estrogenic states)
  • Systemic lupus erythematosus
  • Chronic obstructive pulmonary disease

Anemia

  • Acquired aplastic anemia
  • Iron deficiency anemia
  • Megaloblastic anemia
  • Paroxysmal nocturnal hemoglobinuria
  • Sickle cell disease
  • Wiskott-Aldrich syndrome

Other Causes

  • Head injury
  • Menarche onset
  • Sleep apnea

TREATMENT OF IIH

The first step in treatment of IIH is determining its possible from the many listed above. When a toxic agent is suspected, it should be discontinued. Any suspected disease or disorder should be treated as best as possible. For many patients, however, the etiology of IIH is obesity. The mechanism by which obesity results in IIH is debated. A leading suspect is an abnormality in CSF regulation, possibly due to over-secretion or reduced absorption of spinal fluid. Other possible causes include increased intracranial venous pressure or cerebral inflammation.

When the patient is obese and no other cause of IIH has been found, weight loss is the most effective long-term treatment. Since weight loss is difficult, a nutritionist guided or structured weight loss program is the best option. A number of medical, interventional, and surgical options are available to control elevated intracranial pressure while weight is being reduced. These are treatment options also available to those of normal weight or during the management of identified IIH toxicities, diseases, and conditions.

Medications

The most commonly used medication for the initial treatment of IIH is acetazolamide. This powerful carbonic anhydrase inhibitor works by reducing secretion of spinal fluid by the choroid plexus within each brain ventricle. Acetazolamide was found to be effective in reducing symptoms in a randomized study of 165 patients with IIH.

The anticonvulsant topiramate is as effective as acetazolamide in improving visual field loss. (Pollan) It also can reduce migraine headaches that may coexist with IIH. However, some patients on topiramate have cognitive side effects. Furthermore, topiramate is not recommended in patients with severe depression. If acetazolamide and topiramate are not tolerated, furosemide or octreotide are considered.

Serial Lumbar Punctures

Repeated lumbar punctures with drainage of up to 30 to 40 cc of spinal fluid can improve IIH symptoms temporarily, sometimes for a month or more. Occasionally, the condition has been brought under remission following one lumbar puncture (Pollan). Serial lumbar punctures are a useful approach in pregnancy by reducing symptoms without the need for additional medications or other more invasive treatments.

Overall, while useful, serial lumbar punctures are not ideal for long term management and can result in intracranial hypotension. Low spinal pressure can result in herniation of the cerebellar tonsils, essentially creating a “secondary” Chiari I malformation. In addition, repeated lumbar punctures should not be performed in patients with the Chiari/pseudotumor syndrome (discussed below).

CSF Shunting

As noted above, normal intracranial pressure is 5-15 mm H2O. When associated with symptoms, mild elevations of pressure can be treated with medications and weight loss. If the pressure is 25 mmH2O or greater, and a Chiari I malformation is not present, a spinal fluid shunt can be considered. These shunts drain spinal fluid into the abdominal cavity and reduce intracranial and spinal pressure.

While some neurosurgeons insert the shunt in one of the lateral ventricles of the brain, in many patients, the ventricles are too small and the shunt is likely to obstruct. The most common procedure is a lumbar-peritoneal (LP) shunt. A shunt catheter is inserted into the lumbar spinal canal and the other end is run under the skin tissue to the abdominal cavity. Unfortunately, shunt complications are common and include shunt obstruction, malfunction, dislodgement, infection, and abdominal pain. Shunt over-drainage can cause intracranial hypotension resulting in intracranial subdural hygromas or hematomas. Intracranial hypotension can also result in tonsillar herniation and syringomyelia. Finally, while CSF shunts lower the intracranial pressure, they do not cure IIH.

Weight Loss Surgery

If the body mass index is very high (BMI of 35kg/m2 or more) spinal fluid shunts fail so often that they are not advised. The current recommendation when the BMI is 35kg/m2 or greater is to consider bariatric surgery.

Optic Nerve Sheath Fenestration

In those patients with deteriorating vision facing the risk of blindness, fenestration of the optic nerve sheath can be considered. The procedure is performed through a brain operation or through an endoscope placed in the nose – a procedure called an endonasal endoscopic optic nerve fenestration (ONSF). Small slits are performed in the optic nerve sheath to reduce the pressure on the nerve. ONSF has been found to improve vision in 59% and headache in 44%. (Mollan)

Intracranial Venous Sinus Stenting

IIH patients found to have stenosis (narrowing) of one of the venous sinuses in the brain are considered for dilation or stenting of the narrowed segment. Through a catheter placed in the large vein next to the groin, a catheter is navigated to the site of the venous sinus stenosis and the narrowing is dilated or stented as indicated. While the initial results are good, the long-term outcome is unknown and no randomized studies have yet been performed on this procedure.

CHIARI PSEUDOTUMOR CEREBRI SYNDROME (CHIARI IIH SYNDROME)

In the Chiari Pseudotumor Syndrome, both a Chiari I malformation and IIH are present in the same patient. This complex combination of conditions puts those affected at increased risk. While not well studied, it is thought that some patients with normally positioned cerebellar tonsils develop tonsillar herniation consistent with CM-I as the brain swells from IIH.

The brain MRI seen above is that of a patient who did not improve following a Chiari decompression. (Fortunately, she did not develop intraoperative or postoperative complications.) While the scan shows an adequate Chiari decompression, the very tight brain with compressed CSF spaces strongly suggest her tonsillar herniation was due to IIH and not from a congenital Chiari malformation.

A second possible presentation may occur in patients with a congenital Chiari I malformation who develop intracranial hypertension and increased tonsillar herniation, most often due to increasing body mass. Since patients with Chiari I generally do not undergo lumbar puncture due to the risk of worsening their tonsillar herniation, their IIH may not be identified pre-operatively.

A third presentation is the development of IIH sometime following a successful Chiari decompression. In a case of this author, a young woman had undergone a Chiari decompression that successfully controlled her symptoms. Three years later she called and to say “my Chiari is back!” Follow-up brain MRI showed a wide decompression without recurrence of her Chiari malformation. Since surgery, her weight had increased by 30 lbs. A lumbar puncture revealed an elevated intracranial pressure of 31 mmH20, confirming IIH. Since she found weight loss to be difficult, her symptoms where brought under control with bariatric surgery.

Risks in the Chiari Pseudotumor Cerebri Syndrome (CPCS)

A review by Fagan et al. of 192 patients having undergone posterior fossa decompression for CM-I revealed 36 had failed to improve. Of those, 15 were subsequently found to have elevated intracranial pressure consistent with IIH. Thus, in 4 out of 10 patients, Chiari surgery failed because of the co-existence of IIH.

Patients with CPCS are at risk for serious and life-threatening neurological complications when undergoing a Chiari decompression. In 2009, Furtado et al. described 2 cases of early deterioration following Chiari I decompression. The first was that of a 12 y/o girl who developed gait unsteadiness, headache, and vomiting 6 days following Chiari surgery. On evaluation, she was drowsy and had bilateral papilledema. A CT scan of the brain showed cerebral edema (brain swelling). Her intracranial pressure was elevated to 24 cm H2O. Fortunately, she recovered with treatment that included intravenous steroids and intravenous mannitol.

The second patient was not so fortunate. A 24-year-old woman presented to the emergency department 7 days following Chiari I decompression. She was comatose, bradycardic and had a dilated non-reactive left pupil and “florid papilledema.” She was intubated and placed on a ventilator. A CT of the brain showed diffuse cerebral edema and a stroke in the left occipital lobe. She was eventually weaned off ventilator but was left with double vision, left facial nerve weakness, and right visual loss.

CONCLUSION

Recognition of IIH, an increasingly frequent condition, deserves increased attention at all levels of patient care. The preponderant occurrence in obese women of child bearing age should alert us to having a heightened suspicion in these patients. However, cases also occur in children, nonobese women, and men. Sometimes the cause is a disease, disorder, or medication. An example is case of a thin teenage woman with severe congenital Chiari I and IIH with severe papilledema. The IIH and papilledema resolved following discontinuation of her acne medication. She subsequently was able to safely proceed with a Chiari decompression.

Increased awareness must also be coupled with prevention. The CDC reports that 75% percent of US healthcare expenditures are on “largely preventable” chronic diseases. Obesity is one of the most common of these chronic disorders. It is clear. Wellness must have a greater presence in the future of medicine.

REFERENCES

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Revised: 04/2018