exenatide and Pseudotumor-Cerebri

Idiopathic intracranial hypertension (IIH) affects predominantly overweight women of childbearing age, causing chronically-disabling headaches and visual loss. Weight loss remains the most effective management strategy, but innovative treatments and randomized control trials (RCTs) remain few. This paper will review recent IIH research.. Pregnancy-related complications, but not losses, are increased in IIH, while symptom severity is not affected. Weight loss of 24% results in normalization of intracranial pressure (ICP) and improvement in papilledema. Prolonged periods of papilledema result in delayed thinning of the ganglion cell layer. Less-invasive telemetry has improved understanding of the positional effects on ICP with rises seen in the supine and lateral positions. Exenatide, a GLP-1 agonist, may reduce ICP and improve symptoms. Venous sinus stenting is increasingly popular but its benefits over CSF diversion remain unclear.. Early involvement of obstetric care is recommended with pregnancy in IIH. Early intervention is required to avoid chronic papilledema that confers worse visual outcomes. Positional changes may affect ICP readings. The use of novel ICP telemetric devices has significant potential in future disease monitoring. The dual benefits of weight loss and ICP reduction with exenatide have significant potential in IIH management. Surgical RCTs are still required.

Topics: Exenatide; Female; Humans; Intracranial Pressure; Papilledema; Pregnancy; Pseudotumor Cerebri; Weight Loss

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h 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, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -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. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.

Topics: Adult; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Peptides; Pseudotumor Cerebri; Venoms; Young Adult