Idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a syndrome with signs and symptoms of increased intracranial pressure but where a causative mass or hydrocephalus is not identified.

Terminology

The older term benign intracranial hypertension is generally frowned upon due to the fact that some patients with idiopathic intracranial hypertension have a fairly aggressive clinical picture with rapid visual loss. 

Interestingly, as it has become evident that at least some patients present with IIH due to identifiable venous stenosis, some authors now advocate reverting to the older term pseudotumor cerebri as in these patients the condition is not idiopathic ¹⁵. An alternative approach is to move these patients into a group termed secondary intracranial hypertension ¹⁵. 

Epidemiology

By far the most commonly affected demographic is middle-aged obese females, although the etiological link between being female, overweight and developing idiopathic intracranial hypertension remains to be elucidated.

As the prevalence of obesity is increasing, so too is the incidence of this diagnosis ³¹.

Less commonly IIH can also be encountered in males, usually older and less likely to be obese ¹⁵. It is rare in the pediatric population, being more common in the 12-17 year age group than in the 2-12 year age group ^15,29.

Associations

A variety of conditions are known to be associated with idiopathic intracranial hypertension including:

• endocrine

  • adrenal insufficiency

  • Cushing disease

  • hypoparathyroidism

  • hypothyroidism

  • excessive thyroxine replacement in children

• drugs

  • tetracyclines, such as doxycycline ²

  • growth hormone

  • hypervitaminosis A from dietary intake or other retinoids, such as all-trans retinoic acid, isotretinoin, or retinol

• chronic renal failure

• systemic lupus erythematosus (SLE)

Diagnosis

The diagnosis is commonly based on the modified Dandy criteria, which has been updated for the Idiopathic Intracranial Hypertension Treatment Trial as follows ²⁴:

1. presence of signs and symptoms of increased intracranial pressure

2. absence of localizing findings on neurologic exam except those known to occur from increased intracranial pressure

3. absence of deformity, displacement, or obstruction of the ventricular system and otherwise normal neurodiagnostic studies, except for evidence of increased CSF pressure (>20.0 cm H₂O)*; abnormal neuroimaging except for empty sella turcica, optic nerve sheath with filled out CSF spaces, and smooth-walled non-flow-related venous sinus stenosis or collapse should lead to another diagnosis

4. awake and alert patient

5. no other cause of increased intracranial pressure present

*The opening CSF pressure should be either >25.0 cm H₂O or 20.0-25.0 cm H₂O with at least one of the following additional findings: 

• pulse-synchronous tinnitus

• abducens nerve palsy

• Frisen grade II papilledema

• echography negative for drusen or other disc anomalies mimicking disc edema (pseudopapilledema)

• lateral sinus stenosis or collapse

• partially empty sella and optic nerve sheaths with filled out CSF spaces

Clinical presentation

Patients usually present with headaches, visual problems (transient or gradual visual loss), pulse-synchronous tinnitus, photopsia, and/or eye pain ^15,31. 

Papilledema is the hallmark finding on fundoscopic examination, which is typically bilateral but uncommonly may be unilateral or even absent, making the clinical diagnosis difficult ⁶. Neurological examination is usually normal, except visual field deficit or sixth cranial nerve palsy are sometimes encountered.

Lumbar puncture is central to diagnosis. The CSF composition is normal but the opening pressure is elevated (with 20-25 cm H₂O considered equivocal and >25 cm H₂O considered definitely abnormal). It is controversial whether positioning during lumbar puncture is clinically important, with some insisting that lateral decubitus is the most accurate but others believing the default position for fluoroscopy-guided lumbar puncture, prone, is close enough ²⁵. It should also be noted that opening pressure can vary during the day. One study continuously measuring CSF pressures demonstrated many patients had intermittent pressure waves with amplitudes of 50–80 mmHg (68–109 cm H₂O) that lasted 5 to 20 minutes ²⁶.

Aberrant arachnoid granulations, also referred to as meningoceles, can result in secondary CSF leaks that can present as rhinorrhea, otorrhea, intracranial hypotension, and recurrent bacterial meningitis ^7,9. In such patients it is often only after dural repair that intracranial hypertension becomes evident; presumably, the CSF leak from the meningocele normalized pressure ⁹.

Pathology

The pathogenesis is poorly understood. Various mechanisms have been proposed, including decreased CSF absorption, increased CSF production, increased intravascular volume, increased intracranial venous pressure, and hormonal changes ^1,15. 

Venous sinus stenosis is increasingly recognized as an important factor although whether it is the primary inciting abnormality or a potentiating factor remains to be fully established. The increasingly established clinical efficacy of venous stenting suggests that it is, however, not merely a biomarker ³¹. It has also been shown that the pressure within the torcula or the dural venous sinues and the opening pressure measured at lumbar puncture are very closely correlated ³¹.

Radiographic features

CT/MRI

Imaging of the brain with CT and MRI is essential in patients with suspected idiopathic intracranial hypertension, to exclude elevated CSF pressure due to other causes such as brain tumor, dural sinus thrombosis, hydrocephalus, etc. 

In the absence of a cause for intracranial hypertension, imaging features that support the diagnosis of idiopathic intracranial hypertension include ^3,6-9,15,23:

• optic nerves

  • prominent subarachnoid space around the optic nerves (~45%)

  • vertical tortuosity of the optic nerves (~40%)

  • papilledema

    • flattening of the posterior sclera (~80%)

    • intraocular protrusion of the optic nerve head

  • enhancement of the prelaminar (intraocular) optic nerves (~50%)

• enlarged arachnoid outpouchings

  • partially empty sella turcica (~70%) *

  • enlarged Meckel cave ^9,18

  • prominent arachnoid pits/aberrant arachnoid granulations/small meningoceles typically within the temporal bone and sphenoid wing ⁹

  • enlarged CSF space around the oculomotor nerve in the lateral wall of the cavernous sinus ¹⁸

  • prominent perivascular spaces ³⁰

• slit-like ventricles (relatively uncommon compared to other findings) ¹⁵

• acquired tonsillar ectopia (mimicking Chiari I malformation) ¹⁶

• increased subcutaneous fat thickness in the scalp and neck (a slim patient is unlikely to develop idiopathic intracranial hypertension) ¹⁷

• venous outflow obstruction

  • bilateral venous sinus stenosis: most sensitive/specific finding ²³

    • identified in 30%–90% of cases ³¹

    • lateral segments of the transverse sinuses (most important finding)

    • no evidence of current or remote thrombosis ⁸

  • styloidogenic jugular venous compression syndrome (compression of the internal jugular vein by the styloid process)

Although bony changes are permanent, the rest are dynamic and may be reversible with treatment ³.

* It is important to take into account the age and gender of a specific patient in assessing the significance of this finding, as in older patients, especially in males, a partially empty non-enlarged sella is not only common but normal. 

Catheter angiography and venography

In addition to enabling venous stenting, catheter venography allows for venous manometry to be performed ³¹.

Serial measurements of pressure from the superior sagittal sinus down to the internal jugular vein and right atrium allows for the detection of a focal pressure differential across of stenosis (so-called trans-stenosis gradient) ³¹.

Treatment and prognosis

First-line treatment options include ^13,31:

• weight loss in patients with a BMI >30 kg/m²

  • weight loss of ~15% is possibly curative

• carbonic anhydrase inhibitors

  • acetazolamide

  • topiramate

Invasive treatment options, usually reserved for refractory cases, include ¹³:

• venous sinus stenting

  • typically reserved for severe cases with a trans-stenotic gradient of >8 mmHg ³¹

  • increasingly show to be effective ^4,10,14,31

    • 80% improved headache, 90% improved tinnitus, 94% improved papilledema; treatment failure 12% ¹⁴

• internal jugular venous decompression

  • less well established

  • relies on either stenting or removal of compressing structure (e.g. styloidectomy, mastoid process, muscles, masses, etc.) ³¹

• bariatric surgery as a surgical weight loss strategy

• optic nerve sheath fenestration

• serial CSF letting

• shunting (e.g. ventriculoperitoneal shunt, lumboperitoneal shunt)

History and etymology

Idiopathic intracranial hypertension was first reported in 1893 by Heinrich Quincke, and termed "meningitis serosa". The term "pseudotumor cerebri" was later introduced in 1904, and later still "benign intracranial hypertension" in 1955 (not to be confused with benign intracranial hypotension) ¹⁵.

Differential diagnosis

Other causes of intracranial hypertension and papilledema should be sought. Causes of venous obstruction (e.g. venous sinus thrombosis and venous outflow obstruction in the neck) can very closely mimic the intracranial findings. 

Additionally, in patients with prominent cerebellar tonsillar ectopia, the possibility that all findings are in fact due to a Chiari I malformation should be considered, particularly as there is substantial overlap in the demographics and clinical presentation of the two patient groups ^16,19. It has even been suggested that some cases of symptomatic intracranial hypertension are secondary to a Chiari I malformation ²⁰. Importantly, however, every attempt should be made to distinguish between the two entities as treatment is different and symptom relief for patients with idiopathic intracranial hypertension with posterior fossa decompression is insignificant ²¹.