Idiopathic intracranial hypertension
J.Sales-Llopis
Neurosurgery Department, University General Hospital of Alicante, Spain
Idiopathic intracranial hypertension, also known as pseudotumor cerebri, is a syndrome characterized by raised intracranial pressure of unknown cause. These patients present normal neuroimaging and cerebrospinal fluid analysis while increased intracranial pressure and associated symptoms and signs. Delay of treatment can cause severe visual impairment 1).
The definition of Idiopathic intracranial hypertension (IIH) has been reviewed over time and many hypotheses have been expressed as the cause of the disease.
It is characterized by increased cerebrospinal fluid pressure and normal or slit ventricles.
Heinrich Quincke in 1897 reported the first cases of IIH shortly after he introduced the lumbar puncture into medicine. It was named pseudotumor cerebri in 1904 but was not well delineated clinically until the 1940's when cerebral angiography was added to pneumoencephalography to identify cases of cerebral mass lesions. Foley coined the term benign intracranial hypertension in 1955 but reports from the 1980's demonstrated a high incidence of visual loss 2) 3) and the term “benign” is no longer appropriate.
The syndrome of increased intracranial pressure without hydrocephalus or mass lesion and with normal CSF composition, is a diagnosis of exclusion now termed idiopathic intracranial hypertension (IIH). Diagnostic criteria of this disorder have not been updated since the Modified Dandy Criteria were articulated in 1985. Since then, new developments, including advances in neuroimaging technology and recognition of additional secondary causes of intracranial hypertension, have further enhanced the ability to diagnose conditions that may mimic IIH. These factors are not addressed in the Modified Dandy Criteria 4).
Epidemiology
There is limited literature on the epidemiology of idiopathic intracranial hypertension (IIH).
It has an overall incidence of 1.6/100,000 per annum 5), although it has significantly higher incidence in obese females aged 20–44 at 19/100,000 6).
The prevalence of IIH in the USA is about 1 per 100,000, and it mainly affects adult women in their 20s and 30s 7) 8).
IIH usually occurs in obese women in the childbearing years.
The incidence of IIH in several Middle East countries has been estimated at 2.02-2.2/100,000 in the general population, which is higher than the Western rate. Obesity is a major risk factor globally and it is associated with an increased risk of severe vision loss due to IIH. There has been an increase in obesity prevalence in the Middle East countries mainly affecting the Gulf Council Countries (GCC), which parallels increased industrial development. This rise may be contributing to the increasing incidence of IIH in these countries. Other risk factors may also be contributing to IIH in Middle East countries and the differences and similarities to Western IIH merit further study 9).
Medical records of patients diagnosed with IIH between 2007 and 2014 in a general hospital in Northern Ireland were reviewed.
There were 45 patients with IIH, 44 women: 1 man. The mean age at presentation was 29.4 (SD 9.8) years and mean body mass index (BMI) 39.8 (SD 9.5) kg/ m2. All patients had neuroimaging, 44 (98%) had CT/MR venography and 41 (91%) had visual perimetry. The crude incidence of IIH was 2.36 per 100,000 (95% CI 1.65-3.37). For women, the incidence was 4.65 per 100,000/year (95% CI 3.25-6.66). The prevalence was 14.3 per 100,000 overall (95% CI 9.72-20.9) but 28.1 per 100,000 in women (95% CI 19.2-41.2). Visual field defects were identified in 25 of 41 (61%); 4 patients (9%) required shunting procedures. At follow-up, the mean BMI decreased by 1.6 kg/m2 (p = 0.024).
The incidence of IIH in the northwest of Northern Ireland is among the highest ever reported and probably reflects the known increase in obesity 10).
The chairpersons of all neurology and ophthalmology departments in Israel were asked to complete questionnaires regarding patients diagnosed with PTC/IIH from 1998 through 1999. Each questionnaire contained details regarding patient's age, sex, country of birth, age at diagnosis, weight, height, presence of obesity, and the results of lumbar puncture, brain computed tomography, magnetic resonance imaging, and/or magnetic resonance venography.
Ninety-one patients with PTC/IIH were diagnosed during the years 1998 to 1999. Eighty-five (93.4%) patients were females and six (6.6%) patients were males. The calculated incidence of PTC/IIH in the Israeli general population was 0.57 to 0.94 per 100,000 persons, with incidences of 1.82 per 100,000 for women and 0.034 per 100,000 for men. The incidence for women during the childbirth years was 4.02 per 100,000. The female to male ratio was higher than previously reported for Western countries.
Although the population of Israel is a mixture of people originating from Eastern and Western countries, the incidence of PTC/IIH was found to be similar to that of Western countries. This finding is an additional support to the notion that PTC/IIH is more common in obese populations 11).
Etiology
Clinical Features
Diagnosis
Differential diagnosis
Treatment
Outcome
Idiopathic intracranial hypertension (IIH) or pseudotumor cerebri is a potentially blinding disease.
Few studies have directly compared headache and visual outcomes across treatment modalities.
A systematic analysis of case series was conducted to compare therapeutic efficacies among currently available interventions. The electronic databases from EMBASE (1980-17 September 2013), Medline (1980-17 September 2013), Cochrane databases, and references of review articles was searched. All publications reporting headache and visual outcomes following intervention for IIH were included. A total of 457 manuscripts were selected and full text analysis produced 30 studies with extractable data. All studies constituted Class III evidence. Overall, 332 patients treated by optic nerve sheath fenestration (ONSF), 287 by lumboperitoneal shunt (LPS), 61 by ventriculoperitoneal shunt (VPS), and 88 by dural venous sinus stenting, were identified.
Visual acuity improved in 49.3%, 56.6%, 67.2% and 84.6% of patients following VPS, LPS, ONSF, and stent placements, respectively. Resolution of papilledema was noted in 59.9% to 97.1%. Postoperative headache improved in 36.5%, 62.5%, 75.2%, and 82.9% of patients treated with ONSF, VPS, LPS, and stenting, respectively. Shunt revision was more frequent for LPS compared to VPS (46% versus 36%; p<0.2). Among the LPS revisions, 87.5% occurred within the first 12months following initial surgery. A pooled analysis indicated an overall similar improvement in visual outcomes across treatment modalities, and a modest improvement in headache following cerebrospinal fluid shunting and endovascular stent placement. Based on currently available literature, there is insufficient evidence to recommend or reject any treatments modalities for IIH 12).
Quality of Life
IIH affects QOL at time of diagnosis even in patients with mild visual impairment. Vision-specific QOL in patients with newly diagnosed IIH may be as decreased as that for patients with other neuro-ophthalmic disorders. IIH treatment should target visual loss and other symptoms of increased intracranial pressure associated with reduced QOL. Reduced QOL does not simply reflect obesity, an underlying IIH risk factor 13).
Headache was the only clinical outcome that correlated with enhanced QOL. Effective headache management is required to improve QOL in IIH 14).
Patients with elevated CRP and patients with thrombophilia had an unfavorable visual outcome. Increased cortisol levels and abnormal calcium correlated with a higher rate of recurrence. The visual outcome of patients with elevated LDH was better than those with normal LDH. It seems that certain metabolic, inflammatory and coagulation abnormalities may influence the course of IIH. If confirmed in further studies, these findings could contribute to elucidation of the etiology and prognosis of IIH. 15).
Systematic reviews
A systematic review of the surgical treatment of IIH was carried out. Cochrane Library, MEDLINE and EMBASE databases were systematically searched from 1985 to 2014 to identify all relevant manuscripts written in English. Additional studies were identified by searching the references of retrieved papers and relative narrative reviews.
Forty-one (41) studies were included (36 case series and 5 case reports), totalling 728 patients. Three hundred forty-one patients were treated with optic nerve sheath fenestration (ONSF), 128 patients with lumboperitoneal shunting (LPS), 72 patients with ventriculoperitoneal shunting (VPS), 155 patients with venous sinus stenting and 32 patients with bariatric surgery. ONSF showed considerable efficacy in vision improvement, while CSF shunting had a superior headache response. Venous sinus stenting demonstrated satisfactory results in both vision and headache improvement along with the best complication profile and low relapse rate, but longer follow-up periods are needed. The complication rate of bariatric surgery was high when compared to other interventions and visual outcomes have not been reported adequately. ONSF had the lowest cost.
No surgical modality proved to be clearly superior to any other in IIH management. However, in certain contexts, a given approach appears more justified. Therefore, a treatment algorithm has been formulated, based on the extracted evidence of this review. The traditional treatment paradigm may need to be re-examined with sinus stenting as a first-line treatment modality 16).
Trial
The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. The data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection 17).