Idiopathic intracranial hypertension (IIH), previously known as pseudotumor cerebri and benign intracranial hypertension, is a condition characterized by increased intracranial pressure (pressure around the brain) without a detectable cause. The main symptoms are headache, vision problems, ringing in the ears, and shoulder pain. Complications may include vision loss.
This condition is idiopathic, meaning there is no known cause. Risk factors include being overweight or a recent increase in weight. Tetracycline may also trigger the condition. The diagnosis is based on symptoms and a high opening pressure found during a lumbar puncture with no specific cause found on a brain scan.
Treatment includes a healthy diet, salt restriction, and exercise. The medication acetazolamide may also be used along with the above measures. A small percentage of people may require surgery to relieve the pressure.
About 2 per 100,000 people are newly affected per year. The condition most commonly affects women aged 20–50. Women are affected about 20 times more often than men. The condition was first described in 1897.
Signs and symptoms The most common symptom of IIH is severe headache, which occurs in almost all (92–94%) cases. It is characteristically worse in the morning, generalized in character and throbbing in nature. It may be associated with nausea and vomiting. The headache can be made worse by any activity that further increases the intracranial pressure, such as coughing and sneezing. The pain may also be experienced in the neck and shoulders. Many have pulsatile tinnitus, a whooshing sensation in one or both ears (64–87%); this sound is synchronous with the pulse. Various other symptoms, such as numbness of the extremities, generalized weakness, pain and/or numbness in one or both sides of the face, loss of smell, and loss of coordination, are reported more rarely; none are specific for IIH. In children, numerous nonspecific signs and symptoms may be present.
The increased pressure leads to compression and traction of the cranial nerves, a group of nerves that arise from the brain stem and supply the face and neck. Most commonly, the abducens nerve (sixth nerve) is involved. This nerve supplies the muscle that pulls the eye outward. Those with sixth nerve palsy therefore experience horizontal double vision which is worse when looking towards the affected side. More rarely, the oculomotor nerve and trochlear nerve (third and fourth nerve palsy, respectively) are affected; both play a role in eye movements. The facial nerve (seventh cranial nerve) is affected occasionally – the result is total or partial weakness of the muscles of facial expression on one or both sides of the face.
The increased pressure leads to papilledema, which is swelling of the optic disc, the spot where the optic nerve enters the eyeball. This occurs in practically all cases of IIH, but not everyone experiences symptoms from this. Those who do experience symptoms typically report "transient visual obscurations", episodes of difficulty seeing that occur in both eyes but not necessarily at the same time. Long-term untreated papilledema leads to visual loss, initially in the periphery but progressively towards the center of vision.
Physical examination of the nervous system is typically normal apart from the presence of papilledema, which is seen on examination of the eye with a small device called an ophthalmoscope or in more detail with a fundus camera. If there are cranial nerve abnormalities, these may be noticed on eye examination in the form of a squint (third, fourth, or sixth nerve palsy) or as facial nerve palsy. If the papilledema has been longstanding, visual fields may be constricted and visual acuity may be decreased. Visual field testing by automated (Humphrey) perimetry is recommended as other methods of testing may be less accurate. Longstanding papilledema leads to optic atrophy, in which the disc looks pale and visual loss tends to be advanced.
Causes "Idiopathic" means of unknown cause. Therefore, IIH can only be diagnosed if there is no alternative explanation for the symptoms. Intracranial pressure may be increased due to medications such as high-dose vitamin A derivatives (e.g., isotretinoin for acne), long-term tetracycline antibiotics (for a variety of skin conditions). Hormonal contraceptives, particularly the oral contraceptive pill (OCP), are not associated with IIH. A systematic review published in 2020 suggests the use of the term "drug-induced intracranial hypertension (DIIH)" after having applied a 'strict drug-causality algorithm' in determining IIH cases likely caused by the drugs they evaluated.
There are numerous other diseases, mostly rare conditions, that may lead to intracranial hypertension. If there is an underlying cause, the condition is termed "secondary intracranial hypertension". Common causes of secondary intracranial hypertension include obstructive sleep apnea (a sleep-related breathing disorder), systemic lupus erythematosus (SLE), chronic kidney disease, and Behçet's disease.
On July 1, 2022, the FDA issued an update that gonadotropin-releasing hormone agonists, drugs that are approved for treating precocious puberty, may be a risk factor for developing pseudotumor cerebri.
Mechanism The cause of IIH is not known. The Monro–Kellie rule states that the intracranial pressure is determined by the amount of brain tissue, cerebrospinal fluid (CSF) and blood inside the bony cranial vault. Three theories therefore exist as to why the pressure might be raised in IIH: an excess of CSF production, increased volume of blood or brain tissue, or obstruction of the veins that drain blood from the brain.
The first theory, that of increased production of cerebrospinal fluid, was proposed in early descriptions of the disease. However, there is no experimental data that supports a role for this process in IIH.
The second theory posits that either increased blood flow to the brain or increase in the brain tissue itself may result in the raised pressure. Little evidence has accumulated to support the suggestion that increased blood flow plays a role, but recently Bateman et al. in phase contrast MRA studies have quantified cerebral blood flow (CBF) in vivo and suggests that CBF is abnormally elevated in many people with IIH. Both biopsy samples and various types of brain scans have shown an increased water content of the brain tissue. It remains unclear why this might be the case.
The third theory suggests that restricted venous drainage from the brain may be impaired resulting in congestion. Many people with IIH have narrowing of the transverse sinuses. It is not clear whether this narrowing is the pathogenesis of the disease or a secondary phenomenon. It has been proposed that a positive biofeedback loop may exist, where raised ICP (intracranial pressure) causes venous narrowing in the transverse sinuses, resulting in venous hypertension (raised venous pressure), decreased CSF resorption via arachnoid granulation and further rise in ICP.
Diagnosis
The diagnosis may be suspected on the basis of the history and examination. To confirm the diagnosis, as well as excluding alternative causes, several investigations are required; more investigations may be performed if the history is not typical or the person is more likely to have an alternative problem: children, men, the elderly, or women who are not overweight.
Investigations Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), is used to exclude any mass lesions. In IIH these scans typically appear to be normal, although small or slit-like ventricles, dilatation and buckling of the optic nerve sheaths and "empty sella sign" (flattening of the pituitary gland due to increased pressure) and enlargement of Meckel's caves may be seen.
An MR venogram is also performed in most cases to exclude the possibility of venous sinus stenosis/obstruction or cerebral venous sinus thrombosis. A contrast-enhanced MRV (ATECO) scan has a high detection rate for abnormal transverse sinus stenoses. These stenoses can be more adequately identified and assessed with catheter cerebral venography and manometry. Buckling of the bilateral optic nerves with increased perineural fluid is also often noted on MRI imaging.
Lumbar puncture is performed to measure the opening pressure, as well as to obtain cerebrospinal fluid (CSF) to exclude alternative diagnoses. If the opening pressure is increased, CSF may be removed for transient relief (see below). The CSF is examined for abnormal cells, infections, antibody levels, the glucose level, and protein levels. By definition, all of these are within their normal limits in IIH. Occasionally, the CSF pressure measurement may be normal despite very suggestive symptoms. This may be attributable to the fact that CSF pressure may fluctuate over the course of the normal day. If the suspicion of problems remains high, it may be necessary to perform more long-term monitoring of the ICP by a pressure catheter.
Classification The original criteria for IIH were described by Dandy in 1937.
+ Dandy criteria 1 Signs & symptoms of increased ICP – CSF pressure >25 cmH2O 2 No localizing signs with the exception of abducens nerve palsy 3 Normal CSF composition 4 Normal to small (slit) ventricles on imaging with no intracranial mass
They were modified by Smith in 1985 to become the "modified Dandy criteria". Smith included the use of more advanced imaging: Dandy had required ventriculography, but Smith replaced this with computed tomography. In a 2001 paper, Digre and Corbett amended Dandy's criteria further. They added the requirement that the person is awake and alert, as coma precludes adequate neurological assessment, and require exclusion of venous sinus thrombosis as an underlying cause. Furthermore, they added the requirement that no other cause for the raised ICP is found.
+ Modified Dandy criteria 1 Symptoms of raised intracranial pressure (headache, nausea, vomiting, transient visual obscurations, or papilledema) 2 No localizing signs with the exception of abducens (sixth) nerve palsy 3 The patient is awake and alert 4 Normal CT/MRI findings without evidence of thrombosis 5 LP opening pressure of >25 cmH2O and normal biochemical and cytological composition of CSF 6 No other explanation for the raised intracranial pressure
In a 2002 review, Friedman and Jacobson propose an alternative set of criteria, derived from Smith's. These require the absence of symptoms that could not be explained by a diagnosis of IIH, but do not require the actual presence of any symptoms (such as headache) attributable to IIH. These criteria also require that the lumbar puncture is performed with the person lying sideways, as a lumbar puncture performed in the upright sitting position can lead to artificially high pressure measurements. Friedman and Jacobson also do not insist on MR venography for every person; rather, this is only required in atypical cases (see "diagnosis" above).
Treatment The primary goal in treatment of IIH is the prevention of visual loss and blindness, as well as symptom control. IIH is treated mainly through the reduction of CSF pressure and IIH may resolve after initial treatment, may go into spontaneous remission (although it can still relapse at a later stage), or may continue chronically. There are three main treatment approaches: weight loss, different medications and surgical interventions. Remission is seen for most patients that achieve a weight loss of around 6–10%. Bariatric surgery can be an option for those patients that don't achieve weight loss with lifestyle changes and diet.
Lumbar puncture