Disease Course and Long-term Outcomes in Pregnant Women With Idiopathic Intracranial Hypertension: The IIH Prospective Maternal Health Study.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) most typically occurs in women of childbearing age with increased weight as a key risk factor for development or exacerbation of the disease. Pregnancy is common in this group of patients. The longer-term effect of pregnancy on IIH has not been established and was the aim of this study. METHODS: A prospective cohort study (IIH Life) recruited consecutive patients with IIH between 2012 and 2021 and evaluated outcomes including vision (logarithm of the minimum angle of resolution visual acuity, Humphrey visual field perimetric mean deviation, and optical coherence tomography [OCT] imaging) and headache. Four cohorts were evaluated: those with IIH diagnosed for the first time while pregnant, those with established IIH who became pregnant, those with a pregnancy prior to their diagnosis of IIH, and those with IIH who never became pregnant. RESULTS: Three hundred seventy-seven people with IIH agreed to participate in the IIH Life maternal health study. Mean follow-up was 17.5 months (SD 20.5). IIH diagnosed in pregnancy was rare. Patients diagnosed with IIH while pregnant had greater papilledema (mean OCT total retinal thickness +11.59 µm/mo [95% CI 1.25-21.93]), although they had comparable visual field and acuity measures compared with those with established IIH who became pregnant during their disease course (-1.2 µm/mo [95% CI -2.6 to 0.21]). In those with established IIH, pregnancy did not adversely affect visual or headache outcomes over time, and the trajectory was akin to those with IIH who never had a pregnancy. Headache outcomes showed variability reflecting the IIH cohort as a whole. DISCUSSION: A diagnosis of IIH while pregnant was rare but associated with more severe papilledema. Long-term visual outcomes in IIH were analogous irrespective of the timing of the pregnancy. These data are reassuring; however, close vigilance of IIH clinical features during pregnancy is recommended.

Weight Management Interventions for Adults With Idiopathic Intracranial Hypertension: A Systematic Review and Practice Recommendations.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this systematic review was to evaluate weight loss interventions in people with IIH to determine which intervention is superior in terms of weight loss, reduction in intracranial pressure (ICP), benefit to visual and headache outcomes, quality of life, and mental health. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42023339569). MEDLINE and CINAHL were searched for relevant literature published from inception until December 15, 2022. Screening and quality appraisal was conducted by 2 independent reviewers. Recommendations were graded using Scottish Intercollegiate Guidelines Network methodology. RESULTS: A total of 17 studies were included. Bariatric surgery resulted in 27.2-27.8 kg weight loss at 24 months (Level 1- to 1++). Lifestyle weight management interventions resulted in between 1.4 and 15.7 kg weight loss (Level 2+ to 1++). Bariatric surgery resulted in the greatest mean reduction in ICP (-11.9 cm H2O) at 24 months (Level 1++), followed by multicomponent lifestyle intervention + acetazolamide (-11.2 cm H2O) at 6 months (Level 1+) and then a very low-energy diet intervention (-8.0 cm H2O) at 3 months (Level 2++). The least ICP reduction was shown at 24 months after completing a 12-month multicomponent lifestyle intervention (-3.5 cm H2O) (Level 1++). Reduction in body weight was shown to be highly correlated with reduction in ICP (Level 2++ to 1++). DISCUSSION: Bariatric surgery should be considered for women with IIH and a body mass index (BMI) ≥35 kg/m2 since this had the most robust evidence for sustained weight management (grade A). A multicomponent lifestyle intervention (diet + physical activity + behavior) had the most robust evidence for modest weight loss with a BMI <35 kg/m2 (grade B). Longer-term outcomes for weight management interventions in people with IIH are required to determine whether there is a superior weight loss intervention for IIH.

Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study.

BACKGROUND AND OBJECTIVES: Physician prescribing habits for opiates and headache therapies have not been previously evaluated in a large, matched cohort study in idiopathic intracranial hypertension (IIH). Our objective was to evaluate opiate and headache medication prescribing habits in women with IIH compared to matched women with migraine and population controls. We also investigated the occurrence of new onset headache in IIH compared to population controls. METHODS: We performed a population-based matched, retrospective cohort study to explore headache outcomes. Cross-sectional analyses were used to describe medication prescribing patterns. We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from 1st January 1995 to 25th September 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls). RESULTS: 3411 women with IIH, 13,966 migraine controls and 33,495 population controls were included. The adjusted hazard ratio (aHR) for new onset headache in IIH compared to population controls was 3.09 (95%CI 2.78-3.43). In the first year after diagnosis, 58% of women with IIH were prescribed acetazolamide and 20% topiramate. 20% of women with IIH were prescribed opiates within the first year of their diagnosis, reducing to 17% after six years, compared to 8% and 11% among those with migraine, respectively. Twice as many women with IIH were prescribed opiates compared to migraine controls and three times as many women with IIH were prescribed opiates compared to population controls. Women with IIH were also prescribed more headache preventative medications compared to migraine controls. DISCUSSION: Women with IIH were more likely to be prescribed opiate and simple analgesics compared to both migraine and population controls. Women with IIH trialled more preventative medications over their disease course suggesting that headaches in IIH may be more refractory to treatment.

Association of Amount of Weight Lost After Bariatric Surgery With Intracranial Pressure in Women With Idiopathic Intracranial Hypertension.

BACKGROUND AND OBJECTIVES: The idiopathic intracranial hypertension randomized controlled weight trial (IIH:WT) established that weight loss through bariatric surgery significantly reduced intracranial pressure when compared with a community weight management intervention. This substudy aimed to evaluate the amount of weight loss required to reduce intracranial pressure and to explore the effect of different bariatric surgical approaches. METHODS: IIH:WT was a multicenter randomized controlled trial. Adult women with active idiopathic intracranial hypertension and a body mass index ≥35 kg/m2 were randomized to bariatric surgery or a community weight management intervention (1:1). This per-protocol analysis evaluated the relationship between intracranial pressure, weight loss, and the weight loss methods. A linear hierarchical regression model was used to fit the trial outcomes, adjusted for time, treatment arm, and weight. RESULTS: Sixty-six women were included, of whom 23 had received bariatric surgery by 12 months; the mean age was 31 (SD 8.7) years in the bariatric surgery group and 33.2 (SD 7.4) years in the dietary group. Baseline weight and intracranial pressure were similar in both groups with a mean weight of 119.5 (SD 24.1) and 117.9 (SD 19.5) kg and mean lumbar puncture opening pressure of 34.4 (SD 6.3) and 34.9 (SD 5.3) cmCSF in the bariatric surgery and dietary groups, respectively. Weight loss was significantly associated with reduction in intracranial pressure (R2 = 0.4734, p ≤ 0.0001). Twenty-four percentage of weight loss (weight loss of 13.3 kg [SD 1.76]) was associated with disease remission (intracranial pressure [ICP] ≤ 25 cmCSF). Roux-en-Y gastric bypass achieved greater, more rapid, and sustained ICP reduction compared with other methods. DISCUSSION: The greater the weight loss, the greater the reduction in ICP was documented. Twenty four percentage of weight loss was associated with disease remission. Such magnitude of weight loss was unlikely to be achieved without bariatric surgery, and hence, consideration of referral to a bariatric surgery program early for those with active idiopathic intracranial hypertension may be appropriate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02124486; ISRCTN registry number ISRCTN40152829; doi.org/10.1186/ISRCTN40152829. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that weight loss after bariatric surgery results in reduction in intracranial pressure in adult women with idiopathic intracranial hypertension. This study is Class II because of the use of a per-protocol analysis.

Nuclear Magnetic Resonance Spectroscopy Metabolomics in Idiopathic Intracranial Hypertension to Identify Markers of Disease and Headache.

BACKGROUND AND OBJECTIVE: We evaluated the metabolomic profile in CSF, serum and urine of participants with idiopathic intracranial hypertension (IIH) compared to controls and measured changes in metabolism associated with clinical markers of disease activity and treatment. METHODS: A case-control study compared women aged 18-55 years with active IIH (Friedman diagnostic criteria), to a sex, age and body mass index matched control group. IIH participants were identified from neurology and ophthalmology clinics from National Health Service hospitals and underwent a prospective intervention to induce disease remission through weight loss with re-evaluation at 12 months. Clinical assessments included lumbar puncture, headache, papilledema and visual measurements. Spectra of CSF, serum and urine metabolites were acquired utilizing proton nuclear magnetic resonance spectroscopy. RESULTS: Urea was lower in IIH (CSF; controls median ±IQR 0.196 ±0.008, IIH 0.058 ±0.059, p<0.001, urine; controls 5971.370 ±3021.831, IIH 4691.363 ±1955.774, p=0.009), correlated with ICP (urine p=0.019) and headache severity (CSF p=0.031) and increased by 12 months (CSF 12 months; 0.175 ±0.043, p=0.004, urine; 5210.874 ±1825.302, p=0.043). The lactate:pyruvate ratio was increased compared to controls (CSF; controls 49.739 ±19.523, IIH 113.114 ±117.298, p=0.023, serum; controls 38.187 ±13.392, IIH 54.547 ±18.471, p=0.004) and decreased at 12 months (CSF; 113.114 ±117.298, p<0.001). Baseline acetate was higher in IIH (CSF; controls 0.128 ±0.041, IIH 0.192 ±0.151, p=0.008), correlated with headache severity (p = 0.030) and headache disability (p = 0.003) and was reduced at 12 months (0.160 ±0.060, p = 0.007). Ketones 3-hydroxybutyrate and acetoacetate were altered in CSF at baseline in IIH (3-hydroxybutyrate; controls 0.074 ±0.063, IIH 0.049 ±0.055, p = 0.019, acetoacetate; controls 0.013 ±0.007, IIH 0.017 ±0.010, p = 0.013) and normalized at 12 months (0.112 ±0.114, p = 0.019, 0.029 ±0.017, p = 0.015 respectively). DISCUSSION: We observed metabolic disturbances that are evident in CSF, serum and urine of IIH participants, suggesting global metabolic dysregulation. Altered ketone body metabolites normalized following therapeutic weight loss. CSF:serum urea ratio was altered which may influence ICP dynamics and headache. Elevated CSF acetate, known to stimulate trigeminal sensitization, was associated with headache morbidity. These alterations of metabolic pathways specific to IIH provide biological insight and warrants mechanistic evaluation.