Idiopathic intracranial hypertension

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Overview
Idiopathic intracranial hypertension (IIH), sometimes called benign intracranial hypertension (BIH) or pseudotumor cerebri (PTC) is a neurological disorder that is characterized by increased intracranial pressure (ICP), in the absence of a tumor or other diseases affecting the brain or its lining. The main symptoms are headache and visual problems. Diagnosis requires brain scans and lumbar puncture. There are various medical and surgical treatments.

Terminology
The terms "benign" and "pseudotumor" derive from the fact that increased intracranial pressure was, especially in the era before computed tomography (CT), associated by brain tumors. Those patients in whom no tumour was found were therefore diagnosed with "pseudotumor cerebri" (a disease mimicking a brain tumor). The disease was renamed "benign intracranial hypertension" to distinguish it from intracranial hypertension due to malignancy (i.e. cancer); this was also felt to be misleading, and the name was therefore revised to "idiopathic (of no identifiable cause) intracranial hypertension".

Raised ICP due to another cause (e.g. meningitis, tumor) can be classified as "secondary intracranial hypertension". The term "intracranial hypertension" is sometimes used (see IHRF) as a blanket term to describe intracranial hypertension of all aetiologies.

Signs and symptoms
Characteristic features of IIH are headache (worse in the morning, associated with nausea) and vision problems, such as double vision, transient visual obscurations, loss of peripheral sight or blurring of vision. If untreated, complete loss of vision is possible. While IIH may develop in any age group and in both males and females, it is more likely in females of fertile age (15-45) who are overweight or obese. Certain medications (hormonal contraception, vitamin A, tetracycline antibiotics) may increase risk of IIH.

Physical findings in IIH are is characterized by papilledema, loss of visual acuity and visual fields, and absence of focal neurological findings (e.g. face, arm or leg weakness, sensory disturbance or coordination loss). Diplopia (double vision), if present, may be due to abducens nerve palsy (the sixth cranial nerve). Absence of papilledema, while making IIH less likely, is possible.

Diagnosis
The diagnosis may be suspected on the basis of the history and examination. To confirm the diagnosis, as well as excluding alternative causes (such as a brain tumor), several investigations are required; more investigations may be performed if the history is not typical or the patient is more likely to have an alternative problem (e.g. children, the elderly).

Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), rules out mass lesions. In IIH these scans may be normal, although small or slit-like ventricles and "empty sella sign" (flattening of the pituitary gland due to increased pressure) may be seen. Some propose MRI as preferred mode of imaging in atypical cases, and suggest performance of MR venography to exclude venous obstruction or cerebral venous sinus thrombosis.

Once a mass lesion has been ruled out, lumbar puncture is generally performed to measure the opening pressure, as well as to obtain cerebrospinal fluid to exclude alternative diagnoses such as low-grade viral meningitis. If the opening pressure is increased, CSF may be removed for relief (see below).

Criteria
The original criteria for IIH were described by the American neurosurgeon Walter E. Dandy in 1937. They were modified by Smith in 1985 to become the "modified Dandy criteria".

A 2002 review proposed a 6-point set of criteria that required no unexplained symptoms or signs, measurement of the CSF opening pressure in the lateral decubitus (i.e. lying on the side), exclusion of any other causes on specific forms of imaging.

Pathogenesis
At least two primary mechanisms for the development of increased CSF pressure in primary IIH have been postulated: increased production of CSF and reduced resorption. Increased production may be the result of vasogenic extracellular brain edema, while decreased rebsorption may be due to low conductance of CSF outflow at the arachnoid villi. Sørensen et al found evidence for increased water diffusion in the brain of IIH patients when compared to normal subjects. It was argued that this evidence indicates abnormal convective transependymal water flow leading to brain edema. However, this theory remains controversial, as a similar study conducted by Bastin et al that used significantly disparate MR imaging protocols was unable to reproduce these findings. Normal CSF flow involves production at the choroid plexuses and absorption at the cranial and spinal nerve root arachnoid villi and granulations. Impaired CSF absorption at the superior sagittal sinus or along the spinal nerve roots could therefore explain IIH and has been documented in 75-100% of IIH patients. Permeability along the blood-CSF barrier varies, producing an increasing oncotic pressure gradient between the CSF and venous system in a rostral to caudal progression. It is speculated that variations in this oncotic pressure contribute to or impede CSF absorption. The mechanism remains unclear however, since high CSF protein concentrations, as commonly found in Guillain-Barré syndrome or spinal tumors, can manifest as intracranial hypertension, whereas individuals with IIH frequently present with normal-to-low CSF protein findings.

Treatment
The primary goal in treatment of IIH is the prevention of visual loss and blindness. IIH is treated mainly through the attempted reduction of CSF pressure and, where applicable, weight loss. IIH may resolve after initial treatment, may go into remission and relapse at a later stage, or may continue chronically.

Lumbar puncture
CSF pressure may be temporarily decreased by repeated "therapeutic" (as opposed to diagnostic) lumbar punctures (to remove excessive cerebrospinal fluid). However, this is generally regarded as a "holding measure" until medical or surgical treatment has been instituted.

Medication
The best studied medical treatment is the carbonic anhydrase inhibitor acetazolamide, which reduces CSF production. Other drugs such as furosemide and various diuretics, topiramate and prednisone may be used in an attempt to reduce ICP.

Surgery
Surgical treatments include optic nerve sheath decompression and fenestration. In this procedure, a slit is made in the sheath of the optic nerve, which can alleviate swelling and slow or halt loss of vision. Optic nerve sheath fenestration is less effective in controlling the CSF pressure (and in controlling most symptoms, such as headache), but is more effective in protecting the optic nerve from the effects of pressure.

Shunting is a neurosurgical procedure to facilitate the drainage of excess CSF (thereby reducing ICP). A shunt is essentially a silicone tube inserted somewhere in the fluid spaces of the central nervous system, which then drains CSF to the circulatory system or one of the body cavities. There are various types and configurations of shunts; lumboperitoneal (LP) shunts drain from the lumbar spine to the peritoneal cavity, while ventriculoatrial (VA) shunts run from the cerebral ventricles to the heart. Although shunts can dysfunction due to occlusion, infection, malfunction, etc., they are very effective in normalizing CSF pressures. The absence of papilledema or longstanding symptoms make successful shunting less likely. Studies have shown that shunting procedures are becoming more common as the rate of severe obesity rises.

In cases of severe obesity, gastric bypass surgery has been shown to lead to a marked improvement in symptoms.

Epidemiology
The reported annual incidence of IIH is <20 per 100,000 persons.