Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension.

OBJECTIVE: Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure. METHODS: IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed. RESULTS: Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36). CONCLUSIONS: We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures. TRIAL REGISTRATION: This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486 .

European Headache Federation recommendations for neurologists managing giant cell arteritis.

BACKGROUND AND AIM: Giant cell arteritis (GCA) remains a medical emergency because of the risk of sudden irreversible sight loss and rarely stroke along with other complications. Because headache is one of the cardinal symptoms of cranial GCA, neurologists need to be up to date with the advances in investigation and management of this condition. The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based recommendations on GCA. METHODS: The working group identified relevant questions, performed systematic literature review and assessed the quality of available evidence, and wrote recommendations. Where there was not a high level of evidence, the multidisciplinary (neurology, ophthalmology and rheumatology) group recommended best practice based on their clinical experience. RESULTS: Across Europe, fast track pathways and the utility of advanced imaging techniques are helping to reduce diagnostic delay and uncertainty, with improved clinical outcomes for patients. GCA is treated with high dose glucocorticoids (GC) as a first line agent however long-term GC toxicity is one of the key concerns for clinicians and patients. The first phase 2 and phase 3 randomised controlled trials of Tocilizumab, an IL-6 receptor antagonist, have been published. It is now been approved as the first ever licensed drug to be used in GCA. CONCLUSION: The present article will outline recent advances made in the diagnosis and management of GCA.

A new era for giant cell arteritis.

The landscape of the investigation and management of giant cell arteritis (GCA) is advancing. In this review we will outline the recent advances by searching the current English literature for relevant articles using key words of giant cell arteritis, temporal arteritis, Horton's disease, investigation, and treatment. Delay in diagnosis, diagnostic uncertainty and glucocorticoid (GC) morbidity are among the highest concerns of clinicians and patients in this disease area. The positive news is that fast track pathways, imaging techniques and new therapies are emerging for routine management of GCA. Future directions for intervention in the treatment paradigm will be discussed.

Differing presenting features of idiopathic intracranial hypertension in the UK and US.

AIM: Demographic factors potentially influencing the presentation and severity of idiopathic intracranial hypertension (IIH) in the US vs. UK populations include obesity and ethnicity. We aimed to compare the presenting features of IIH between populations in the UK and US tertiary referral centres, to assess what population differences exist and whether these cause different presentations and impact on visual function. METHODS: Clinical data were collected on 243 consecutive UK IIH patients and 469 consecutive US IIH patients seen after 2012 in two tertiary centres. Visual function was defined as severe visual loss when Humphrey visual field mean deviation was <-15 dB, when Goldmann visual fields showed constriction or when visual acuity was <20/200. RESULTS: US patients were more commonly of self-reported black race (58.9% vs. 7.1%) than UK patients, but had a similar mean body mass index (38.3 ± 0.63kg/m2 UK vs. 37.7 ± 0.42kg/m2 US; p = 0.626). The UK cohort had lower presenting Frisén grade (median 1 vs. 2; p < 0.001) and severe visual loss less frequently (15.4% vs. 5%; p = 0.014), but there was no difference in mean cerebrospinal fluid-opening pressure (CSF-OP) (35.8 ± 0.88cmH2O UK vs. 36.3 ± 0.52cmH2O US; p = 0.582). African Americans had poorer visual outcomes compared with US whites (19.4% vs. 10% severe visual loss; p = 0.011). Visual function was weakly associated with CSF-OP (R2 = 0.059; p = 0.001), which was similar between UK and US patients. CONCLUSIONS: The UK and the US cohorts had a similar average presenting BMI. However, the worse presenting visual function in the US IIH cohort was partially attributable to differences in the black populations in the two countries.

The use of transdermal optical coherence tomography to image the superficial temporal arteries.

PurposeThe diagnosis of Giant Cell Arteritis (GCA) is an area of major challenge. This is the first reported use of the directed use of transdermal optical coherence tomography (OCT) to image the superficial temporal artery (STA).MethodsThis proof of concept study used a commercially available transdermal OCT instrument to identify and image the STA in eight patients (suspected GCA, confirmed GCA, and in healthy controls). Three cases are presented to demonstrate the preliminary imaging findings.ResultsIn all eight cases the STA was identified. Imaging findings from three cases are presented. A hyper-reflective signal was seen, which distinguishes the artery from vein. In two cases, a ratio of band thickness (BT) to arterial lumen diameter (ALD) could be calculated (BT : ALD ratio) where the whole circumference of the artery was imaged.DiscussionUsing dermal OCT to image the temporal arteries is a novel concept. With ongoing advances in resolution, penetration, and blood flow detection; this non-invasive technology warrants further investigation to determine its role in Giant Cell Arteritis.

Cranial ultrasound for the diagnosis of giant cell arteritis. A retrospective cohort study.

BACKGROUND: Establishing a diagnosis of giant cell arteritis, or indeed ruling it out, may be difficult. We describe an evaluation of temporal artery colour duplex ultrasound as first line investigation in patients with suspected giant cell arteritis. METHODS: A retrospective cohort study of all patients undergoing colour duplex ultrasound for suspected giant cell arteritis between January 2005 and January 2014 was undertaken at a teaching hospital. A minimum clinical follow-up of three months was required. Patients were classified on the basis of ultrasound reports, using described features such as a halo sign or arterial wall thickening and clinical diagnosis of giant cell arteritis after at least 3 months follow-up, determined by the treating physician. The relationship of colour duplex ultrasound to a final clinical diagnosis of giant cell arteritis was analysed. RESULTS: A total of 87 patients underwent colour duplex ultrasound: 36 (41%) had clinically confirmed giant cell arteritis at 3-month follow-up. The positive predictive value of colour duplex ultrasound for a clinical diagnosis at 3 months was 97% (95% confidence interval (CI) 93 to 99%) and negative predictive value 88% (95% CI 76 to 95%). Sensitivity was 81% (95% CI 64 to 92%) and specificity 98% (95% CI 90 to 100%). CONCLUSIONS: A high positive and negative predictive value of arteritis on colour duplex ultrasound indicates that temporal artery biopsy may be unnecessary in suspected giant cell arteritis, particularly where clinical suspicion of giant cell arteritis is high or low.

Idiopathic intracranial hypertension associated with iron deficiency anaemia: a lesson for management.

AIM: To document the causal association of iron deficiency anaemia (IDA) and intracranial hypertension (IH). METHODS: A consecutive case note review of patients with a clinical diagnosis of idiopathic intracranial hypertension (IIH) and anaemia presenting to a tertiary referral unit over a 2.5-year period. Demographics, aetiology and clinical details were recorded and analysed. RESULTS: Eight cases were identified from 77 new cases presenting with IIH. All 8 had documented microcytic anaemia with clinical evidence of raised intracranial pressure. There was no evidence of venous sinus thrombosis on MRI and MR venography in 7 subjects and on repeated CT venography in 1. On correction of anaemia alone, 7 cases resolved. One patient with severe progressive visual loss underwent ventriculoperitoneal shunt in addition to treatment of anaemia, with good outcome. The incidence of this association is 10.3%. CONCLUSION: These cases present an association between IDA and IH, in the absence of cerebral sinus thrombosis. As a clinically significant proportion of cases presenting with signs of IIH have IDA, we recommend all patients presenting with IIH have full blood counts and if they are found to be anaemic, they should be treated appropriately.

Occupational eye injuries: a continuing problem.

BACKGROUND: Ocular trauma is a worldwide cause of visual morbidity, a significant proportion of which occurs in the workplace. This is largely preventable with the use of protective eyewear and strict compliance. AIM: To analyse the type of occupational eye injuries that occur and to document the use of eye protection in patients presenting to a UK district general hospital. METHODS: A pilot retrospective case note analysis of all ocular injuries seen in one calendar month was performed. A prospective survey of consecutive occupational ocular injuries presenting to this district general accident and emergency (A&E) department over a 2-month period was then carried out. Demographics, aetiology, eye protection usage and clinical details were recorded and analysed. RESULTS: Of all eye patients attending this A&E, 31% (87/283) were due to occupational eye injuries. Of 55 prospectively reviewed patients with occupational eye injuries, the majority had minor injuries. Of the cases where eye protection was recorded, 56% (18/32) were not wearing any protection and 44% (14/32) wore eye protection at the time of injury. CONCLUSIONS: Occupational eye injuries are a commonly seen ocular complaint in the A&E department. Provision of appropriate eyewear protection and worker education is required to minimize the incidence of ocular injury in the workplace.

Aetiology and outcomes of adult superior oblique palsies: a modern series.

PURPOSE: To establish the contemporary aetiology of adult superior oblique palsy (SOP). MATERIALS AND METHODS: A retrospective consecutive case series of 150 persons diagnosed with SOP between 1 January 1999 and 31 May 2005 at a neuro-ophthalmology centre in the West Midlands, the United Kingdom. Interrogating two different hospital databases identified all cases. A case note review was performed on all participants to determine demographics and aetiology based on diagnostic criteria, neuroimaging used, and outcome. RESULTS: We identified 133 unilateral isolated, 7 unilateral associated with other cranial nerve involvement, and 10 bilateral cases of SOP. Eighty-six were acquired, 51 congenital, and 13 undetermined. Of the unilateral isolated cases, 38.3% were considered to be congenital, 29.3% followed trauma, 23.3% were presumed to be vasculopathic in origin, and no cause could be established in 7.5%. All presumed microvascular-associated palsies resolved within 6 months of presentation. Unilateral SOPs associated with other cranial nerve palsies were commonly caused by trauma (71.4%), followed by tumour and undetermined causes (both 14.3%). Trauma was the most frequent cause of bilateral SOP (50%), followed by tumours and undetermined causes (both 20%), with congenital causes being uncommon (10%). CONCLUSION: We present a contemporary aetiological spectrum for adult SOP, with the lowest incidence of undetermined cases published in the medical literature. Neuroimaging did not change the management for the vast majority of cases and should be prompted by atypical presentations.

Accuracy of Goldmann, ocular response analyser, Pascal and TonoPen XL tonometry in keratoconic and normal eyes.

AIM: The aim of this study was to evaluate the practicality and accuracy of tonometers used in routine clinical practice for established keratoconus (KC). METHODS: This was a prospective study of 118 normal and 76 keratoconic eyes where intraocular pressure (IOP) was measured in random order using the Goldman applanation tonometer (GAT), Pascal dynamic contour tonometer (DCT), Reichert ocular response analyser (ORA) and TonoPen XL tonometer. Corneal hysteresis (CH) and corneal resistance factor (CRF), as calculated by the ORA, were recorded. Central corneal thickness (CCT) was measured using an ultrasound pachymeter. RESULTS: The difference in IOP values between instruments was highly significant in both study groups (p<0.001). All other IOP measures were significantly higher than those for GAT, except for the Goldmann-correlated IOP (average of the two applanation pressure points) (IOPg) as measured by ORA in the control group and the CH-corrected IOP (corneal-compensated IOP value) (IOPcc) measures in the KC group. CCT, CH and CRF were significantly less in the KC group (p<0.001). Apart from the DCT, all techniques tended to measure IOP higher in eyes with thicker corneas. CONCLUSION: The DCT and the ORA are currently the most appropriate tonometers to use in KC for the measurement of IOPcc. Corneal factors such as CH and CRT may be of more importance than CCT in causing inaccuracies in applanation tonometry techniques.

Efficacy of antiglaucoma fixed combination therapy versus unfixed components in reducing intraocular pressure: a systematic review.

AIM: To evaluate the efficacy of the fixed combination ocular hypotensive therapies compared with their non-fixed components used concomitantly for lowering intraocular pressure (IOP) in glaucoma and ocular hypertension. METHODS: A systematic review of the literature, up to May 2007, without limits on year or language of publication was performed. Seven randomised controlled trials (n = 2,083 eyes) were identified. Assessment of methodological quality was made using standardised criteria. Results were pooled quantitatively using meta-analysis methods, and statistical analysis was performed using STATA software. The difference in mean intraocular pressure (mm Hg) from baseline between the fixed combination and non-fixed component therapies was compared. Non-inferiority in terms of efficacy was set at an upper confidence limit of < or =1.5 mm Hg for all time points (hour (Hr)0, Hr2 and Hr8) and evaluated at 12 weeks. Safety was evaluated from data on adverse events as reported in the included studies. RESULTS: Of the 679 abstracts identified, seven randomised controlled trials met the selection criteria. The quality scores of included studies were high (mean of 29.4, maximum score 30). The mean differences (95% CI) and p values at 12 weeks were as follows: 0.200 mm Hg, (CI -0.106 to 0.507), p = 0.20 for Hr0, 0.393 mm Hg (CI 0.038 to 0.747), p = 0.03 for Hr2 and 0.501 mm Hg (CI 0.156 to 0.846), p = 0.004 for Hr8. Although both Hr2 and Hr8 showed statistical significance favouring the non-fixed combinations, the non-inferiority measure < or =1.5 mm Hg upper confidence limit was not exceeded. CONCLUSIONS: Fixed combination therapies are equally safe and effective at lowering IOP as their non-fixed components administered concomitantly.

Does use of isotretinoin rule out a career in flying?

AIM: To evaluate whether previous isotretinoin use induces permanent, measurable, and clinically significant abnormalities in night vision such that flying is precluded, and whether potential military and civilian commercial aviators should be screened routinely. METHODS: A retrospective, non-interventional, consecutive case series of 47 individuals with a confirmed history of oral isotretinoin use were compared to 20 age and sex matched controls. RESULTS: 47 individuals (44 males and three females), age range 17-33, underwent Goldmann-Weekers dark adaptation (DA) and standard electroretinogram (ERG) according to ISCEV protocols. 34 patients showed no abnormality in any parameters. Two patients had abnormal DA and ERGs. The mean scotopic ERG b wave amplitude of the isotretinoin group was 496.5 microV (SD 51.3 microV) compared with 501.7 microV (62.3.1 microV) among the controls. The group mean a:b ratio was 0.55 (0.04) compared to 0.69 (0.08) in the controls. CONCLUSION: Previous use of isotretinoin may have caused retinal toxicity in two subjects and laboratory evidence of night blindness in 11 further subjects. One subject had subclinical changes remaining in the ERG 96 months after cessation of isotretinoin. This may justify the directed use of electrophysiological screening in professions that are night vision critical.