Syed Ahmer Raza¹, Haseeb Noor Akhtar²

¹Moorfields Eye Hospital

²University College London

Introduction

Idiopathic Intracranial Hypertension is a neurological disorder caused by raised cerebrospinal fluid (CSF) pressure without any known intracranial abnormalities or secondary causes of intracranial hypertension. In this review, we consider the pathophysiology/aetiology, risk factors, how it presents and the general management of the condition.

Epidemiology and Pathophysiology

The condition is strongly associated with obese females of a reproductive age. The worldwide incidence is 12-20 per 100,000 people per year in this group, with the incidence dropping to 0.5-2 per 100,000 people per year in the general population (1).

The pathological mechanisms of how idiopathic intracranial hypertension develops is unclear, but to summarise, these three mechanisms are purported to be involved:

1. Increased venous sinus pressure: This usually results from venous sinus stenosis. Studies have shown that venous sinus stenosis is relieved following CSF removal or diversion, which suggests it is more of a consequence rather than a causation factor of IIH (1)
2. CSF hypersecretion: Most CSF is secreted by the choroid plexus – initial studies showed a possible involvement of increased CSF production in IIH, but subsequent trials have not supported this theory. In choroid plexus papilloma, a condition known to cause CSF hypersecretion, subsequent hydrocephalus and ventricular enlargement occurs, which has not been shown in IIH studies (1)
3. CSF outflow obstruction: The arachnoid granulations are thought to be primarily responsible for CSF clearance. The predominant theory is that resistance to absorption is possibly caused by increased venous pressure from venous outflow obstruction. Isotope infusion studies have demonstrated a delay in CSF clearance in IIH patients (1)

It has been difficult to pinpoint the course of progression of the condition, but what is likely is that altered CSF dynamics is the main contributing factor to the disorder.

Aetiology and Risk Factors

Obesity

Obesity is seen in most cases of IIH, showing a strong association with the condition. One theory is that the higher abdominal mass increases the intrathoracic pressure leading to increased venous pressure. Obesity has also recently been recognised as a chronic inflammatory state. Weight loss has been shown in trials to improve the symptoms and signs of the condition (1).

Hormones

Most patients are women of childbearing age, and thus it has been hypothesised that hormonal factors may play a role. Case reports have shown a link between IIH and polycystic ovarian syndrome but studies have remained unconvincing in determining whether this link is significant (2).

Other associated conditions with IIH include anaemia, respiratory conditions such as OSA, autoimmune disorders (such as SLE and Sjogren’s), renal failure. Iatrogenic causes include excess vitamin A, retinoids, tetracycline antibiotics and steroids (1).

Presentation

The presentation of IIH is highly variable, hence challenging to diagnose. The prevalent symptom is headache which accounts for 75-95% of the patient cohort. These headaches tend to be described as pressure-like frontal/retro-orbital headaches which are worse on waking up and on Valsalva manoeuvres (2). The condition mimics migrainous features, such as nausea, photophobia, phonophobia.

Transient visual obscurations have been described in approximately 68-72% of patients, brief episodes of loss of vision which often occur with postural change. Pulsatile tinnitus, generally bilaterally is seen in two-thirds of patients and is commonly described as a ‘whooshing sound’. Other common symptoms include neck pain, back pain, dizziness and horizontal diplopia (2).

The cardinal sign of IIH is papilloedema, which is seen in almost all patients. Visual function tests are a necessity in assessment of IIH, and any abnormality requires urgent consideration. IIH is known to cause both loss of visual field and, in later progression of disease, visual acuity. Most common visual field defects include enlarged blind spot, loss of nasal visual field and visual field constriction (2). Sixth nerve palsies have also been seen in IIH patients (4).

Diagnosis and Investigations

IIH is considered a diagnosis of exclusion, and so importantly, other causes need to be ruled out from the differential, such as venous sinus thrombosis, hydrocephalus, space-occupying lesions, hypertensive encephalopathy and optic disc abnormalities. IIH requires 3 factors for diagnosis: 1) Normal neuroimaging 2) raised CSF pressure 3) no other cause identified for raised CSF pressure.

These have been compiled in the ‘Modified Dandy Criteria’ for diagnosing IIH, which include the 3 previous points plus symptoms and signs of generalised intracranial hypertension or papilloedema. Therefore, a lumbar puncture is required to diagnose IIH. The opening pressure should be greater than 25cm³H20 and the patient ideally in a lateral decubitus position (2). An MRI is seen as gold standard for diagnosing IIH. MRI can show narrowing of the venous transverse sinus (3). OCT imaging can be used to show retinal nerve fibre layer thickness, which can play a role in assessing progression and aiding management of the condition (4).

Management

There is no consensus on the therapeutic interventions for this condition. Weight loss is known to be key – multiple studies have shown even weight loss of 6-10% has resulted in marked improvement or resolution of papilloedema and reduced ICP (2). Referral to a dietician can be considered. A low sodium diet has also been recommended and to only drink water when thirsty to prevent excessive water intake as it may contribute to increased intracranial pressure, and can be beneficial to patients with orthostatic oedema (4).

Medical management includes drugs to reduce CSF production. Acetazolamide is a carbonic anhydrase inhibitor which reduces production of CSF. Usually started at low dose to ensure tolerance and subsequently titrated upwards to a maintenance dose of 1000mg-2000mg per day. The IHTT trial showed beneficial effect of acetazolamide on vision and had the greatest effect on visual field function and those patients with optic nerve swelling (5). Additionally, acetazolamide and diet together have been proven to considerably improve CSF pressure, quality-of-life indicators, and papilloedema grade after six months (4). Other drugs such as furosemide and topiramate can be used, with topiramate yielding similar results to acetazolamide in regards to visual improvement (2).

Other possible interventions include serial lumbar punctures to relieve increasing ICP. Surgical interventions can be used when medical management is ineffective or severe optic neuropathy is present – procedures such as optic nerve sheath fenestration (ONSF) have shown improvement in papilloedema in patients, but complication risk is high. Shunts such as Lumboperitoneal shunts have proven to be effective in drastic resolution of symptoms to facilitate drainage of excess CSF (2).

Frequent surveillance from a neuro-ophthalmologist is optimal to assess response to treatment (if any), and comprehensive visual assessment including acuity and quantitative visual fields is paramount to detect any impending visual loss (3).

References

(1) Markey KA, Mollan SP, Jensen RH, Sinclair AJ. Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. The Lancet Neurology. 2016 Jan 1;15(1):78-91.  

(2) Dhungana S, Sharrack B, Woodroofe N. Idiopathic intracranial hypertension. Acta Neurologica Scandinavica. 2010 Feb;121(2):71-82.  

(3) Silberstein, S., 2021. Idiopathic Intracranial Hypertension – Neurologic Disorders – MSD Manual Professional Edition. [online] MSD Manual Professional Edition. Available at: <https://www.msdmanuals.com/en-gb/professional/neurologic-disorders/headache/idiopathic- intracranial-hypertension> [Accessed 29 September 2022].  

(4) Wall, M. and Mughal, M., 2022. Idiopathic Intracranial Hypertension. [online] BMJ Best Practice. Available at: <https://bestpractice.bmj.com/topics/en-gb/1070> [Accessed 29 September 2022].   (5)   Wall, M., 2015. Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). What have we learnt? [online] Webeye.ophth.uiowa.edu. Available at: <https://webeye.ophth.uiowa.edu/eyeforum/article/IIHTT/index.htm> [Accessed 29 September 2022].