Rating papilloedema: an evaluation of the Frisén classification in idiopathic intracranial hypertension.

The appearance of the optic disc is a key measure of disease status in idiopathic intracranial hypertension (IIH). The Frisén classification describes stages of optic disc swelling (grades 0-5). It is the only classification of papilloedema, and is used internationally in clinical and research practice. Despite this, there has been very limited evaluation of the scale. We assessed the inter-rater reproducibility and ability to discriminate optic disc changes over time using the Frisén classification compared with a system of ranking papilloedema severity in patients with IIH. Paired disc photographs (before and after treatment) were obtained from 47 patients with IIH (25 acute and 22 chronic). Six neuro-ophthalmologists blinded to patient identity, clinical information and chronology of the photographs reviewed the discs and allocated a Frisén grade and ranked the paired discs in order of papilloedema severity (disc ranking). A total of 188 optic disc photographs were reviewed. All six reviewers agreed in only three comparisons (1.6%) when using the Frisén classification, compared with 42 comparisons (45.2%) when using disc ranking. The probability of agreement between any two reviewers was 36.1% for Frisén grade and 70.0% for disc ranking. Disc ranking had significantly greater sensitivity for finding differences in degree of disc oedema, identifying a difference in 75.3% of paired photographs compared to 53.2% detected using the Frisén classification (p < 0.001). This study demonstrated the limited reproducibility and discriminative ability of the Frisén classification in identifying changes in serial optic disc photographs in IIH. Simple optic disc ranking appears to be a more sensitive and reliable tool to monitor changes in optic disc appearance. The use of disc ranking in clinical practice and research studies is recommended to monitor alterations in optic disc appearance until alternative schemes, specific to IIH, have been developed.

A randomised controlled trial of treatment for idiopathic intracranial hypertension.

The cause of idiopathic intracranial hypertension (IIH) remains unknown, and no consensus exists on how patients should be monitored and treated. Acetazolamide is a common treatment but has never been examined in a randomised controlled trial. The objectives of this pilot trial are to prospectively evaluate the use of acetazolamide, to explore various outcome measures and to inform the design of a definitive trial in IIH. Fifty patients were recruited from six centres over 23 months and randomised to receive acetazolamide (n = 25) or no acetazolamide (n = 25). Symptoms, body weight, visual function and health-related quality-of-life measures were recorded over a 12-month period. Recruited patients had typical features of mild IIH and most showed improvement, with 44% judged to have IIH in remission at the end of the trial. Difficulties with recruitment were highlighted as well as poor compliance with acetazolamide therapy (12 patients). A composite measure of IIH status was tested, and the strongest concordance with final disease status was seen with perimetry (Somers' D = 0.66) and optic disc appearance (D = 0.59). Based on the study data, a sample size of 320 would be required to demonstrate a 20% treatment effect in a substantive trial. Clinical trials in IIH require pragmatic design to involve sufficiently large numbers of patients. Future studies should incorporate weighted composite scores to reflect the relative importance of common outcome measures in IIH.

Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study.

OBJECTIVE: To observe intracranial pressure in women with idiopathic intracranial hypertension who follow a low energy diet. DESIGN: Prospective cohort study. SETTING: Outpatient department and the clinical research facility based at two separate hospitals within the United Kingdom. PARTICIPANTS: 25 women with body mass index (BMI) >25, with active (papilloedema and intracranial pressure >25 cm H(2)O), chronic (over three months) idiopathic intracranial hypertension. Women who had undergone surgery to treat idiopathic intracranial hypertension were excluded. INTERVENTION: Stage 1: no new intervention; stage 2: nutritionally complete low energy (calorie) diet (1777 kJ/day (425 kcal/day)); stage 3: follow-up period after the diet. Each stage lasted three months. MAIN OUTCOME MEASURE: The primary outcome was reduction in intracranial pressure after the diet. Secondary measures included score on headache impact test-6, papilloedema (as measured by ultrasonography of the elevation of the optic disc and diameter of the nerve sheath, together with thickness of the peripapillary retina measured by optical coherence tomography), mean deviation of Humphrey visual field, LogMAR visual acuity, and symptoms. Outcome measures were assessed at baseline and three, six, and nine months. Lumbar puncture, to quantify intracranial pressure, was measured at baseline and three and six months. RESULTS: All variables remained stable over stage 1. During stage 2, there were significant reductions in weight (mean 15.7 (SD 8.0) kg, P<0.001), intracranial pressure (mean 8.0 (SD 4.2) cm H(2)O, P<0.001), score on headache impact test (7.6 (SD 10.1), P=0.004), and papilloedema (optic disc elevation (mean 0.15 (SD 0.23) mm, P=0.002), diameter of the nerve sheath (mean 0.7 (SD 0.8) mm, P=0.004), and thickness of the peripapillary retina (mean 25.7 (SD 36.1) micro, P=0.001)). Mean deviation of the Humphrey visual field remained stable, and in only five patients, the LogMAR visual acuity improved by one line. Fewer women reported symptoms including tinnitus, diplopia, and obscurations (10 v 4, P=0.004; 7 v 0, P=0.008; and 4 v 0, P=0.025, respectively). Re-evaluation at three months after the diet showed no significant change in weight (0.21 (SD 6.8) kg), and all outcome measures were maintained. CONCLUSION: Women with idiopathic intracranial hypertension who followed a low energy diet for three months had significantly reduced intracranial pressure compared with pressure measured in the three months before the diet, as well as improved symptoms and reduced papilloedema. These reductions persisted for three months after they stopped the diet.

NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases--a diagnostic tool?

We sought to evaluate the diagnostic accuracy of metabolomic biomarker profiles in neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) compared to controls with either no neurological disease or mixed neurological diseases). Spectra of CSF (n = 87) and serum (n = 72) were acquired using (1)H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease-specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a second cohort of patients (n = 25). CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity:specificity of 63:75% and 67:75%, respectively). These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease-unique metabolites may also impart information on disease pathology.

Exploring the pathogenesis of IIH: an inflammatory perspective.

Idiopathic intracranial hypertension (IIH) is a common blinding condition amongst the young obese female population (20 per 100,000) characterised by elevated intracranial pressure (ICP). The aetiology of IIH is not known. In this review we explore the literature investigating the pathogenesis of IIH and suggest additional hypotheses. Chronic inflammation is emerging as an aetiological factor in the pathogenesis of obesity and we propose that this may be a feature of IIH. Obesity is also related to dysregulation of cortisol production by the pre-receptor enzyme, 11beta-hydroxysteroid dehydrogenase, and we speculate that this may have a role in the pathogenesis of obesity and raised ICP seen in IIH.