Idiopathic Intracranial Hypertension

Elevated pressure of cerebrospinal fluid leads to RGC damage and degeneration

Idiopathic intracranial hypertension (IIH), also called pseudotumor cerebri, is a disorder of elevated intracranial pressure of unknown cause. It typically affects overweight women of childbearing age. The incidence of IIH is rising in parallel with the obesity epidemic. Most patients suffer from debilitating headaches. IIH also causes pressure on the optic nerve (papilledema), leading to ganglion cell death. Many patients experience visual loss which can be severe. Interventions to prevent loss of sight, all with unproven efficacy, include low-sodium and low-calorie diet, diuretics (acetazolamide), repeated spinal taps, optic nerve sheath fenestration surgery, and CSF shunting procedures.

The etiology of IIH has not been determined. Both the apparent sex-linked nature as well as the reported familial cases of IIH suggest that genetic factors may contribute to the development of the disease. In view of the strong association of IIH with energy storage metabolism and female sex, genomic variations of genes mediating these processes are most likely to affect an individual’s risk of developing IIH.

In collaboration with Dr. Michael Wall and the Neuro-Ophthalmology Research Disease Investigation Consortium (NORDIC) we are evaluating genes that may be involved in the development of IIH in a large cohort of patients and controls. In this case-control genetic association study we are determining the frequencies of intragenic single nucleotide polymorphism (SNP) alleles in both groups and are analyzing the data to identify both disease-causing mutations and IIH risk alleles.

In addition, we have identified mouse strains that develop elevated intracranial pressure when fed vitamin A, which occasionally leads to IIH in humans. We are planning on detecting which gene regulates this response to vitamin A in the mice. Variatios in the same, or related, genes may also play a role in human IIH.

We believe that the identification of genes associated with this disease will not only allow recognition of persons at risk for developing this condition, but may also teach us how IIH develops.

A brief overview of IIH can be found here