In the case of our patient, it appears that she developed IIH due to the abrupt cessation of the GLP-1 receptor agonist prescribed to her with resultant rapid weight gain, with her BMI increasing from 29 to 34 in a little over a month. She did not previously have any features of IIH, and she had brain imaging without stigmata of IIH. Additionally, it is interesting that she did not present with IIH previously when at a BMI of 34 but only developed the condition when the weight was regained over a short period of time instead of the gradual build up over the years that led to her initially developing obesity.

As mentioned before, the precise pathophysiology of IIH has yet to be elucidated. Various theories postulate that IIH is either a problem of CSF overproduction or a result of difficulty with CSF drainage or absorption, but no unifying theory exists to fully explain the exact mechanism by which a patient develops IIH or the causation underlying the issues with CSF dynamics [9]. There is similarly limited information on why only certain individuals with obesity develop IIH [9]. A study using dual-energy X-ray absorptiometry (DEXA) scanning to determine if there was a difference in adipose distribution among patients with IIH and obesity and those without IIH and obesity showed a correlation between increased truncal adiposity and increased CSF pressure [3•]. The exact mechanism of this increase in CSF pressure is unknown, but it is postulated that increased truncal adiposity ultimately increases central venous pressure, though this mechanism still does not completely explain this phenomenon [10]. Weight loss with resultant loss of truncal adiposity correlated with decreased CSF pressure [3•]. Women with IIH also have twice the risk of cardiovascular disease than those of similar weight without IIH, but again, the pathophysiology underlying this is still not known [5].

The rapid rate of weight gain has also been implicated in the development of IIH. A study by Ko et al. showed that individuals who have recurrent IIH after weight loss and resolution gained back approximately 6% of their body weight and had an average rate of BMI gain of 1.3 kg/m(2)/year [11]. There is also thought to be a correlation with the rate of weight gain and IIH, with a case series showing women who rapidly gained weight within several months of receiving an implantable contraceptive developed IIH [10]. The women recovered with medication and weight loss while still having the implantable contraceptive device in place, suggesting that the etiology of the IIH was the rapidity of the weight gain, to which the implantable contraceptive device may have contributed [10].

Additionally, adipose tissue functions as an endocrine organ; proteins and hormones secreted by adipose tissue may also play a role in the development of IIH [9]. Leptin is a hormone which helps to regulate satiety in the hypothalamus; leptin receptors are located in the choroid plexus, where CSF is also produced [9]. Patients with IIH have increased leptin levels in the CSF, whereas other patients with obesity (but without IIH) have decreased leptin levels in the CSF [9]. The significance of this finding remains unclear, but it does remind us that adipose tissue secretes proteins and hormones which may be involved in the pathogenesis of IIH.

GLP-1 is a peptide hormone, an incretin, which is typically secreted by the distal small intestine after ingesting food [7••]. GLP-1 is involved in multiple processes, including the secretion of insulin, delaying gastric emptying, lipolysis of adipose tissue, increasing satiety through interactions with the hypothalamus, and decreasing CSF production in the choroid plexus [7••]. Capitalizing off of GLP-1’s appetite suppressing and metabolic effects, multiple GLP-1 receptor agonists are currently available for the treatment of obesity, as well as Type II diabetes mellitus. As GLP-1 receptor agonists decrease weight and promote lipolysis of adipose tissues, these medications could help treat IIH through weight loss and reduction in hormone-secreting adipose tissue. Recent studies in rat models have shown that GLP-1 receptor agonists decreased the CSF production and the intracranial pressure in rats [12••]. While further study is needed in humans, this could be another possible mechanism for GLP-1 receptor agonists to treat IIH. The risk of using GLP-1 receptor agonists to treat IIH seems to lie primarily in the potential for individuals to rapidly regain the lost weight after cessation of treatment, as seen in the above case. As this class of medication can be very expensive, loss of insurance coverage can lead to an abrupt cessation of medication. After stopping treatment, patients still need careful and continued treatment and monitoring to ensure that they do not rapidly regain the lost weight [13].