Metabolic Concepts in Idiopathic Intracranial Hypertension and Their Potential for Therapeutic Intervention

Abstract

Background: Traditional risk factors associated with idiopathic intracranial hypertension (IIH) include obesity, weight gain, and female sex. The incidence of IIH is increasing and yet the underlying trigger and the fueling pathological mechanisms are still poorly understood.

Evidence acquisition: Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, and neurosurgery literature was made.

Results: The facts that implicate sex and obesity in IIH and headache are examined. The role of fat distribution in IIH is questioned, and the concept of adipose tissue functioning as an endocrine organ driving IIH is discussed. The impact of androgen metabolism in IIH is reviewed as is the emerging role of glucagon-like-peptide-1 analogues in modulating intracranial pressure. This introduces the concept of developing targeted disease-modifying therapeutic strategies for IIH.

Conclusions: This review will discuss the possible role of the adipose/gut/brain metabolism axis in IIH and speculate how this may impact the pathogenesis of IIH and therapeutic opportunities.

FIG. 1.

Glucagon-like peptide 1 (GLP-1) mechanism of action in IIH. Normally GLP-1 (purple circles) is produced by L-cells in the small intestine in response to food. GLP-1 mimetics are used to treat diabetes and obesity and are administered by subcutaneous injection. GLP-1 mimetics could be beneficial for patients with IIH as they act on the hypothalamus to reduce food intake and on adipose tissue to increase lipolysis resulting in weight loss. In addition, GLP-1 mimetics bind to GLP-1 receptors (GLP-1R) on the choroid plexus, leading to a reduction in CSF secretion and ICP. CSF, cerebrospinal fluid; ICP, intracranial pressure; IIH, idiopathic intracranial hypertension.

FIG. 2.

Metabolic pathogenesis and treatment in IIH. IIH is most prevalent in obese women of childbearing age, similar to migraine and polycystic ovary syndrome. A combination of dysregulated adipose tissue and hormones may be involved in IIH pathogenesis. Weight loss through bariatric surgery and diet has been shown to improve IIH symptoms. GLP-1R agonists may have additional benefits for patients with IIH by directly affecting ICP and causing weight loss. GLP-1R, glucagon-like-peptide-1 receptor; ICP, intracranial pressure; IIH, idiopathic intracranial hypertension.