Abstract Objectives Intracranial pressure (ICP) has been thought to vary diurnally. This study evaluates diurnal ICP measurements and quantifies changes in ICP occurring with changes in body posture in active idiopathic intracranial hypertension (IIH). Methods This prospective observational study utilized telemetric ICP monitoring in people with active IIH. Participants had the Raumedic p-Tel ICP intraparenchymal device (Raumedic, Hembrechts, Germany) surgically inserted. Changes in ICP in the supine position were evaluated. Then, the ICP was measured in the standing, sitting, supine, left lateral decubitus positions and with coughing and bending. Ultimately, changes in ICP over the course of 24 h were recorded. ISRCTN registration number 12678718. Results 15 women were included, mean (standard deviation) age 29.5 (9.5) years, body mass index 38.1 (6.2) kg/m2, and baseline mean ICP of 21.2 (4.8) mmHg (equivalent to 28.8 (6.5) cmCSF). Mean ICP rose with the duration in the supine position 1.2 (3.3) mmHg over 5-minutes (p = 0.175), 3.5 (2.8) mmHg over 30-minutes (p = 0.0002) and by a further 2.1 (2.2) mmHg over 3 h (p = 0.042). Mean ICP decreased by 51% when moving from the supine position to standing (21.2 (4.8) mmHg to 10.3 (3.7) mmHg respectively, p = 0.0001). Mean ICP increased by 13% moving from supine to the left lateral decubitus position (21.2 (4.8) mmHg to 24.0 (3.8) mmHg, p = 0.028). There was no significant difference in ICP measurements at any point during the daytime, or between 5-minute standing or supine recordings and prolonged ambulatory daytime and end of night supine recordings respectively. ICP, following an initial drop, increased progressively in conjunction with lying supine position from 23:00 h to 07:00 h by 34% (5.2 (1.9) mmHg, p = 0.026). Conclusion This analysis demonstrated that ICP does not appear to have a diurnal variation in IIH, but varies by position and duration in the supine position. ICP rose at night whilst the patient was continuously supine. Furthermore, brief standing and supine ICP measures in the day predicted daytime prolonged ambulatory measures and end of night peak ICP respectively. This knowledge gives reassurance that ICP can be accurately measured and compared at any time of day in an ambulant IIH patient. These are useful findings to inform clinical measurements and in the interpretation of ICP analyses in IIH. Trial registration ISTCRN (12678718).

Therapeutics to reduce intracranial pressure (ICP) are an unmet need. Pre-clinical data has demonstrated a novel strategy to lower ICP using glucagon-like peptide-1 receptor (GLP-1R) signaling. Here, we translate these findings into patients by conducting a randomized, placebo controlled, double-blind trial to assess the effect of exenatide, a GLP-1R agonist, on ICP in idiopathic intracranial hypertension (IIH). Telemetric ICP catheters enabled long-term ICP monitoring. The trial enrolled adult women with active IIH (ICP >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The primary outcome was ICP at 2.5 hours, 24 hours and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 9, body mass index 38.1 6.2 kg/m2, ICP 30.6 5.1 cmCSF). Exenatide significantly and meaningfully lowered ICP at 2.5 hours -5.7 2.9 cmCSF (p=0.048); 24 hours of -6.4 2.9 cmCSF (p=0.030); and 12 weeks -5.6 3.0 cmCSF (p=0.058). No serious safety signals were noted. This data provides confidence to proceed to a phase 3 trial in IIH and highlights the potential to utilise GLP-1R agonist in other conditions characterised by raised ICP.