Keira Markey

Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions

Idiopathic intracranial hypertension is a disorder characterised by raised intracranial pressure that predominantly affects young, obese women. Pathogenesis has not been fully elucidated, but several causal factors have been proposed. Symptoms can include headaches, visual loss, pulsatile tinnitus, and back and neck pain, but the clinical presentation is highly variable. Although few studies have been done to support evidence-based management, several recent advances have the potential to enhance understanding of the causes of the disease and to guide treatment decisions. Investigators of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) reported beneficial effects of acetazolamide in patients with mild visual loss. Studies have also established weight loss as an effective disease-modifying treatment, and further clinical trials to investigate new treatments are underway. The incidence of idiopathic intracranial hypertension is expected to increase as rates of obesity increase; efforts to reduce diagnostic delays and identify new, effective approaches to treatment will be key to meeting the needs of a growing number of patients.

A practical approach to, diagnosis, assessment and management of idiopathic intracranial hypertension

Adult patients who present with papilloedema and symptoms of raised intracranial pressure need urgent multidisciplinary assessment including neuroimaging, to exclude life-threatening causes. Where there is no apparent underlying cause for the raised intracranial pressure, patients are considered to have idiopathic intracranial hypertension (IIH). The incidence of IIH is increasing in line with the global epidemic of obesity. There are controversial issues in its diagnosis and management. This paper gives a practical approach to assessing patients with papilloedema, its investigation and the subsequent management of patients with IIH.

Headache determines quality of life in idiopathic intracranial hypertension.

BackgroundThe effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) is poorly understood. Our objectives were to compare QOL in IIH to the normal UK population; to investigate QOL changes with treatment of IIH, using a weight loss intervention, and to determine which clinical factors influence QOL.MethodsThis was a prospective cohort evaluation of QOL, using the 36-Item Short Form (SF-36) Health Survey questionnaire, before and after a therapeutic dietary intervention which resulted in significant reduction in body mass index (BMI), intracranial pressure (ICP), papilloedema, visual acuity, perimetric mean deviation (Humphrey 24–2) and headache (six-item headache impact test (HIT-6) and headache diary). Baseline QOL was compared to an age and gender matched population. The relationship between each clinical outcome and change in QOL was evaluated.ResultsAt baseline, QOL was significantly lower in IIH compared to an age and gender matched population in most domains, p < 0.001. Therapeutic weight loss led to a significant improvement in 10 out of 11 QOL domains in conjunction with the previously published data demonstrating significant improvement in papilloedema, visual acuity, perimetry and headache (p < 0.001) and large effect size. Despite significant improvement in clinical measures only headache correlated significantly (p < 0.001) with improving QOL domains.ConclusionsQOL in IIH patients is significantly reduced. It improved with weight loss alongside significant improvement in clinical measures and headache. However, headache was the only clinical outcome that correlated with enhanced QOL. Effective headache management is required to improve QOL in IIH.

Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases.

Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11β-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH.

Therapeutic lumbar puncture for headache in idiopathic intracranial hypertension: Minimal gain, is it worth the pain?:

Background Headache is disabling and prevalent in idiopathic intracranial hypertension. Therapeutic lumbar punctures may be considered to manage headache. This study evaluated the acute effect of lumbar punctures on headache severity. Additionally, the effect of lumbar puncture pressure on post-lumbar puncture headache was evaluated. Methods Active idiopathic intracranial hypertension patients were prospectively recruited to a cohort study, lumbar puncture pressure and papilloedema grade were noted. Headache severity was recorded using a numeric rating scale (NRS) 0–10, pre-lumbar puncture and following lumbar puncture at 1, 4 and 6 hours and daily for 7 days. Results Fifty two patients were recruited (mean lumbar puncture opening pressure 32 (28–37 cmCSF). At any point in the week post-lumbar puncture, headache severity improved in 71% (but a small reduction of −1.1 ± 2.6 numeric rating scale) and exacerbated in 64%, with 30% experiencing a severe exacerbation ≥ 4 numeric rating scale. Therapeutic lumbar punctures are typically considered in idiopathic intracranial hypertension patients with severe headaches (numeric rating scale ≥ 7). In this cohort, the likelihood of improvement was 92% (a modest reduction of headache pain by −3.0 ± 2.8 numeric rating scale, p = 0.012, day 7), while 33% deteriorated. Idiopathic intracranial hypertension patients with mild (numeric rating scale 1–3) or no headache (on the day of lumbar puncture, prior to lumbar puncture) had a high risk of post- lumbar puncture headache exacerbation (81% and 67% respectively). Importantly, there was no relationship between lumbar puncture opening pressure and headache response after lumbar puncture. Conclusion Following lumbar puncture, the majority of idiopathic intracranial hypertension patients experience some improvement, but the benefit is small and post-lumbar puncture headache exacerbation is common, and in some prolonged and severe. Lumbar puncture pressure does not influence the post-lumbar puncture headache.

Characterising the patient experience of diagnostic lumbar puncture in idiopathic intracranial hypertension: a cross-sectional online survey

Objectives Patients with idiopathic intracranial hypertension (IIH) usually require multiple lumbar punctures (LPs) during the course of their disease, and often report significant morbidity associated with the procedure. The aim of this study was to assess the patient’s experience of diagnostic LP in IIH. Design, methods and participants A cross-sectional study of patients with IIH was conducted using an anonymous online survey, with the questions designed in collaboration with IIH UK (the UK IIH charity). Responses were collated over a 2-month period from April to May 2015. Patients were asked to quantify responses using a Verbal Rating Score (VRS) 0–10 with 0 being the minimum and 10 the maximum score. Results 502 patients responded to the survey, of which 463 were analysed for this study. 40% of patients described severe pain during the LP (VRS ≥8), and the median pain score during the LP was 7 (VRS, IQR 5–7). The majority of patients felt they received insufficient pain relief (85%). Levels of anxiety about future LPs were high (median VRS 7, IQR 4–10), with 47% being extremely anxious (VRS ≥8). LPs performed as an emergency were associated with significantly greater pain scores compared with elective procedures (median 7, IQR 5–7 vs 6, IQR 4–8, p=0.012). 10.7% went on to have an X-ray-guided procedure due to failure of the initial LP, and the body mass index was significantly higher in this group (mean kg/m240.3 vs 35.5, p=0.001). Higher LP pain scores (VRS) were significantly associated with poorly informed patients (Spearman’s correlation, r=−0.32, p<0.001). Patients felt more informed when the LP was performed by a specialist registrar compared with a junior doctor (median 7 vs 5, p=0.001) or a consultant compared with a junior doctor (median 8 vs 5, p<0.001). Conclusions This study was commissioned by the IIH patient group and is the first to document the patient experience of diagnostic LPs in IIH. It shows that the majority of these patients are experiencing significant morbidity from pain and anxiety. Patient experience of LP may be improved through changing clinical practice to include universal detailed preprocedural information, and where possible, avoiding emergency LPs in favour of LPs booked on an elective day-case unit.

THE ANDRO-METABOLIC SIGNATURE OF IIH COMPARED WITH PCOS AND SIMPLE OBESITY

Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP) of unknown cause. This condition is primarily seen in obese females of childbearing age, a phenotype similar to that in polycystic ovary syndrome (PCOS). We aimed to characterise the androgen metabolic signature in IIH compared to PCOS and simple obese controls. Age, gender and BMI matched groups of IIH (n=25), PCOS (n=31) and obese controls (n=15) were studied. The IIH group also underwent a weight loss intervention. Serum androgens were measured by liquid chromatography/tandem mass spectrometry (LCMS) and urinary steroids using gas chromatography/mass spectrometry (GCMS). Serum testosterone was significantly higher in IIH and PCOS than in controls (p=0.01). Serum androstenedione was significantly increased in PCOS compared to IIH and controls (p=0.008). Systemic 5a-reductase activity was significantly higher in IIH compared to controls (p=0.04). Following weight loss there were significant reductions in testosterone, 5a-reductase activity and disease activity (intracranial pressure and papilloedema). These results demonstrate a unique androgen metabolic signature in IIH (distinct from PCOS and simple obesity), characterised by increased testosterone but normal androstenedione, potentially driven by increased AKR1C3 activity (which converts androstenedione to its active metabolite testosterone). Further evaluation of AKR1C3 in IIH would be of interest.

CHARACTERISING FAT DISTRIBUTION AND RESPONSE TO WEIGHT LOSS IN IIH

Idiopathic intracranial hypertension (IIH) is a condition characterised by raised intracranial pressure of unknown pathogenesis. Over 94% of sufferers are young, obese women, but little is known about their metabolic phenotype. Previous studies measuring waist-hip ratios in IIH have suggested predominant lower body adiposity. We aimed to characterise the pattern of fat distribution using dual energy X-ray absorptiometry (DEXA) and metabolic phenotype (fasting lipids, glucose and insulin) and evaluate changes following weight loss. At baseline, IIH (n=29) had a similar centripetal fat distribution and lipid profile to BMI and gender matched obese controls (n=47). The glucose:insulin ratio (G:I) and HOMA-IR were elevated at baseline indicating insulin resistance in IIH, although akin to what was seen in simple obesity (G:I 0.4±0.2 vs 0.8±0.9 and HOMA-IR 2.1±2.1 vs 1.6±1.1). Weight loss resulted in a significant reduction in disease activity (ICP and papilloedema) alongside a significant reduction in fat mass (−4.1±2.7%, p<0.001), predominantly from the truncal region (−4.7±3.7%) compared to the limbs (1.1±2.1%, p<0.001). These results indicate that fat distribution in IIH is centripetal, similar to simple obesity. Clinical resolution of IIH is associated with preferential loss of truncal fat. The role of truncal adiposity in the pathogenesis of IIH warrants further investigation.

HEADACHE DETERMINES QUALITY OF LIFE IN IIH

Background There have been no previous studies assessing quality of life (QOL) in idiopathic intracranial hypertension (IIH). Our previously published prospective cohort study confirmed that weight loss, significantly reduced intracranial pressure (ICP) and treated chronic active IIH. Method We assessed QOL using the short form 36 questionnaires (SF-36) before and after a period of weight loss induced through a low calorie diet and compared to changes in clinical outcomes. Baseline QOL was compared to obese, age matched control data. Results At baseline, SF-36 scores were worse in the IIH group compared to an age-matched population. Weight loss and reduction of ICP lead to a significant reduction in 8 out of 11 domains of the SF-36. The improvement in SF-36 correlated significantly with headache recovery (severity and disability measured using the headache impact test-6), p<0.0001, but not reduction in ICP, papilloedema (measured by optical coherence tomography), perimetry (Humphrey visual field 24–2), LogMar visual acuity or body mass index. Conclusion We demonstrate a significant improvement in QOL in IIH following therapeutic weight loss and reduction in ICP. Improvement in headache was associated with enhanced QOL. We suggest that effective headache treatment will improve QOL in patients with IIH.