Idiopathic intracranial hypertension (idiopathic pseudotumor cerebri)

Clinical background

Key symptoms and signs

The signs and symptoms of increased intracranial pressure (ICP) are headache, subjective pulse-synchronous bruit, and papilledema ( Box 39.1 ). Papilledema can cause fleeting visual obscurations in one or both eyes. Occasional diplopia is attributed to presumed sixth-nerve compression. Visual field loss and decreased acuity are unusual early in the course of disease, but may become devastating over time.

Box 39.1

Key symptoms and signs of increased intracranial pressure in idiopathic pseudotumor cerebri

  • Increased intracranial pressure (over 250 mm H 2 O)

  • Headache

  • Papilledema

  • Pulsatile bruit (noise)

  • Transient visual obscurations

  • Obesity

  • Child-bearing age

  • Female

  • Diplopia (uncommon)

  • Visual field loss (uncommon)

Historical development

Helmholtz’s 1851 invention of the ophthalmoscope allowed visualization of the optic nerves, and of their dramatic engorgement with the swelling of papilledema that accompanied the increased ICP of brain tumors. The development of the first effective neurosurgical procedures by Harvey Cushing around 1910, which allowed life-saving treatment by urgent removal or decompression of such tumors, made recognition of papilledema and its connection to brain tumors critically important. It was an association, which when recognized and acted upon, might save a patient’s life. For that reason it became a high-priority sign in the routine medical examination, so that papilledema, or any optic disc edema, needed to be quickly categorized as “brain tumor” or “otherwise.” The “otherwise” became known as pseudotumor cerebri (PTC), a brain tumor-mimicking form of papilledema. The most common cause before 1950 was bacterial meningitis, a nonsurgical cause of increased ICP, as shown by the early work of Paton and Holmes. A frequent cause of meningitis, with an associated element of adjacent venous thrombosis, in that preantibiotic era, was mastoiditis. An infection of the mastoid air spaces in the petrous bone, it might start as a routine nasopharyngitis, extend to the eustachian tube and inner ear, then a petrous bone infection with mastoiditis. The sequential adjacent meningitis and lateral sinus thrombosis became recognized as “otitic hydrocephalus”.

All of this changed after World War II with the availability of penicillin. Bacterial meningitis and otitic hydrocephalus became unusual, but the appearance of a patient with papilledema still required a determination of brain tumor versus pseudotumor as the first diagnostic step. Despite the availability of cerebral angiography and ventriculography, many patients had exploratory craniotomies as the last step in ruling out a brain tumor and in establishing their diagnoses as pseudotumor. It was not until the evolution of neuroimaging to modern computed tomography and magnetic resonance techniques that this became unnecessary. Until then all increased ICP, meaning all papilledema, was regarded, and needed to be so regarded, as due to brain tumor.

Nomenclature for PTC syndromes is varied. “Benign intracranial hypertension” is flawed, in that the disorder is anything but benign. We prefer “idiopathic pseudotumor cerebri” or iPTC for cases where the etiology is unclear, although in deference to common use, we will use the term “idiopathic intracranial hypertension” (IIH) in this chapter. “Secondary PTC” is used when there is a detectable etiology, e.g., cerebral venous thrombosis or use of tetracycline, doxycycline, minocycline, or retinoids ( Box 39.2 ).

Box 39.2

Secondary causes of pseudotumor cerebri

  • Head trauma (including posttraumatic brain injury)

  • Underlying disease: liver or kidney failure

  • Sleep apnea

  • Venous thrombosis (cerebral blood clots)

  • Stroke (subarachnoid hemorrhage)

  • Cystinosis


  • Accutane (isotretinoin)

  • Tetracycline

  • Growth hormone

  • Corticosteroids

  • Tetracyclines

  • ATRA (acute promyelocytic leukemia)

  • Vitamin A (hypervitaminosis A; retinoids)

  • Amiodarone

  • Nitrofurantoin

  • Nalidixic acid

  • Sulfa antibacterials

  • Leuprorelin (luteinizing hormone-releasing hormone analog)

  • Lithium

  • Levonorgestrel (Norplant)

  • Steroid withdrawal

Underlying infectious diseases

  • Meningitis (bacterial or viral)

  • Lyme disease

  • Human immunodeficiency virus (HIV)

  • Poliomyelitis

  • Coxsackie B viral encephalitis

  • Guillain–Barré syndrome

  • Infectious mononucleosis

  • Syphilis

  • Malaria


IIH is a disease that most frequently affects obese women of child-bearing age. The incidence of IIH in the general population is 1 : 100 000; however, the incidence rises to 19.3 : 100 000 in women aged 20–44 who are at least 20% over ideal body weight. The incidence of IIH appears to be rising dramatically, and the Centers for Disease Control recently released statistics indicating that the rate of obesity in the USA has doubled in the past decade.


Rare, but verified, examples of a mother with known IIH, and her son with the same diagnosis, a father with a daughter, and dizygotic twin brothers, are consistent with a genetic link. Twins have been reported, both heterozygous and homozygous, e.g., homozygous twin sisters with similar onset of symptoms in both.

Diagnostic workup

IIH is diagnosed when the following are all true:

  • 1.

    Symptoms and signs all attributable to increased ICP or papilledema

  • 2.

    No medications known to elevate ICP (see Box 39.2 )

  • 3.

    Normal neurological examination except for papilledema and possibly evidence of sixth-nerve dysfunction

  • 4.

    Normal magnetic resonance imaging and magnetic resonance venography

  • 5.

    Elevated ICP recorded during lumbar puncture in the standard lateral decubitus position (cerebrospinal fluid (CSF) opening pressure greater than 250 mm H 2 O; pressures of 200–250 mm H 2 O should remain suspect)

  • 6.

    Normal CSF composition.


Normalizing and maintaining the CSF pressure can be challenging. Fluid removal is often temporary, and shunting to another location is invasive and often impermanent. Medical treatment can decrease fluid formation, but does so incompletely and with side-effects that can be unpleasant and sometimes dangerous.

Most patients are managed with medical treatment to lower the CSF pressure. The typical treatment progression for IIH is shown in Box 39.3 . Carbonic anhydrase inhibitors (CAIs), usually acetazolamide, are used to impair CSF formation and can improve symptoms of headache and visual obscurations in most patients. Despite unpleasant sensory disturbances (tingling fingers and toes, and taste distortions), malaise, diuresis, and even the risks of abreaction (sulfa allergies and aplastic anemia), the CAIs are the most common form of medical treatment. The effect of CAIs on CSF outflow is unknown; however, receptors for CAIs have been identified in the arachnoid membrane, suggesting a role in modulating CSF outflow.

Box 39.3

Typical treatment progression for idiopathic pseudotumor cerebri

  • 1.

    Carbonic anhydrase inhibitors (CAIs)

  • 2.

    Other pharmaceuticals

    • a.

      Lasix (furosemide)

    • b.

      Beta-blockers (propranolol)

    • c.

      Octreotide (somatostatin)

  • 3.


    • a.

      Optic nerve sheath fenestration

    • b.

      Neurosurgical shunts

      • i.

        Lumboperitoneal (LP) shunt

      • ii.

        Ventriculoperitoneal (VP) shunt

      • iii.

        Cisterna magnum shunt

    • c.

      Cortical venous stents

More effective agents than CAIs are not known. Furosemide has been tried and adds little beyond the risk of potassium imbalance. Somatostatin analogs may be encouraging, demonstrated by our clinical experience with octreotide (not published), but remain at the research level.

Shunting procedures include lumbar peritoneal shunts, ventriculoperiotoneal shunts, and optic nerve sheath fenestration. These procedures have significant limitations. They each need a patent opening to allow persistent drainage of CSF from the subarachnoid or intraventricular space into the peritoneal cavity or orbit. A critical limitation in both is failure to work consistently and predictably over the years.

A controversial alternative to surgery of the intracranial or orbital subarachnoid space for lowering ICP is cortical venous sinus stenting.

Prognosis and complications

Patients with IIH are carefully followed with perimetry and fundoscopy in order to detect visual field deterioration (which may be asymptomatic until late) and worsening papilledema. Retinal nerve fiber layer analysis by optical coherence tomography is a promising complement to the clinical examination.


Normal CSF homeostasis relies on a careful balance between CSF production and absorption. Alterations in the rate of CSF formation, absorption, or outflow resistance can lead to a buildup of ICP, causing multiple neurological deficits.

While the mechanisms explaining secondary PTCs remain obscure, their clarification is a worthwhile objective. Neurophysiologists and neuroscience-oriented physicians are quick to presume that such agents somehow impair CSF outflow by damage to outflow channels. Likely that is true, but except for seeing red blood cells in the subarachnoid space and in the arachnoid villi after intracranial hemorrhage, we don’t know what happens, or how it happens, at the molecular level of the CSF outflow pathways.

Isolating the “distilled” group of patients labeled as IIH now permits us to focus on their common findings and characterize them in a way that should help our clinical perspective, while recognizing that later information will regroup them more accurately. The following factors should be considered in any discussion of pathogenesis:

  • 1.


  • 2.


  • 3.


  • 4.


  • 5.


A simplified model circuit shows the movement of CSF in Figure 39.1 . Basic fluid mechanics shows that the driving force for fluid movement is a pressure difference. This implies that a pressure gradient must occur prior to any movement of CSF. Any of the fluid reservoirs shown in Figure 39.1 may be affected by changes in pressure gradients and the resultant fluid redistribution. The subarachnoid space (SAS) acts like a variable fluid capacitor, taking up excess CSF when needed or giving it up if necessary. The ability of the SAS to do so is affected by age and other factors that stiffen the arachnoid trabeculae. The vasculature responds to changes by dilation or constriction (autoregulation), with a redistribution of fluid, and a rebalance of pressure gradients, which leads us to mechanistic theories.

Aug 26, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Idiopathic intracranial hypertension (idiopathic pseudotumor cerebri)

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