Idiopathic intracranial hypertension (IIH or pseudotumor cerebri) is a rare neurological disorder in which cerebrospinal fluid (CSF) pressure is elevated, leading to papilledema and visual disturbances. Patients present with a variety of symptoms, including transient visual obscurations (TVOs), blurred vision, tinnitus, diplopia, or headaches (^1–4). The etiology of IIH is unknown, and the diagnosis of IIH is determined by a set of criteria that has served as the standard for IIH diagnosis (modified Dandy criteria) (⁵). These criteria include 1) signs and symptoms of increased intracranial pressure, 2) normal neuroimaging, 3) absence of focal neurological signs aside from cranial nerve VI paresis, and 4) elevated CSF pressure with normal CSF composition.

IIH is of concern to ophthalmologists and neurologists, as untreated disease can lead to significant morbidity from visual loss, including visual field defects and visual acuity loss, which in some cases is severe and permanent (^6–9). Up to 25% of patients with IIH may be asymptomatic (¹⁰) that may delay diagnosis, leading to higher risk of permanent visual loss. Thus, it may be prudent to screen patients at the highest risk for IIH to prevent the development of this blinding disorder.

Screening of the general population is unlikely to be cost-effective, as IIH is rare in the general population, occurring with an annual incidence in the order of 1 to 2 per 100,000 (^11–14). While obesity has not been shown to be a cause of IIH, obesity is clearly associated with IIH (^3,15), and the incidence of IIH rises to 20 per 100,000 in obese females (^11,12). As the prevalence of obesity has increased in the United States, defining the association between obesity and IIH has become increasingly more urgent. Recent updates from the Centers for Disease Control and Prevention place the percentage of obese individuals in the United States more than 30% (¹⁶). The percentage of morbidly obese individuals (body mass index [BMI] >40 kg/m²) is estimated to be roughly 6% (¹⁶). Interestingly, the risk of IIH increases with increasing BMI (¹⁷), and morbidly obese patients with IIH may have even worse visual outcomes (¹⁸). Thus, morbidly obese individuals may be at particularly high risk for severe and permanent visual loss from IIH.

In this study, morbidly obese patients presenting for bariatric surgery evaluation at UC Davis were screened for the presence of undiagnosed or asymptomatic papilledema. The goal of our study was to determine if screening morbidly obese patients for IIH is a worthwhile endeavor and to gain insight into the association of IIH with obesity.

METHODS

The study design was approved by the University of California, Davis, Institutional Review Board. Patients between the age of 18 and 65 years who presented to the UC Davis Bariatric Surgery Program between February 2008 and January 2011 and met the National Institutes of Health requirements for bariatric surgery (¹⁹) were asked to participate in the study (Table 1). All patients presenting for evaluation were questioned about headaches and visual symptoms, but patients who consented to the study were asked to fill out a screening questionnaire (Table 2) and had nonmydriatic fundus photographs taken (Nidek nonmydriatic auto fundus camera, AFC 210 camera [Nidek Inc., Fremont, CA]). Patients were excluded if they had a preexisting diagnosis of IIH or if 1 or both of the fundus photographs were inadequate for interpretation. There were no monocular patients in this population.

Patients who had at least 1 optic disc suspicious for edema were referred for neuro-ophthalmic evaluation. One patient had suspicious symptoms based on screening questions but did not have fundus photographs taken due to unavailability of the camera. This patient was also referred for neuro-ophthalmic testing (Patient P1) (Table 6). This included visual fields with automated perimetry (automated visual fields, SITA-standard 24-2), optic nerve and macula optical coherence tomography (OCT; Stratus [Carl Zeiss Meditec, Inc., Dublin, CA]), and fundus photography. Optic nerve images were graded for papilledema according to the modified Frisén scale (^20,21). All of this information was used to diagnose optic disc edema by a single neuro-ophthalmologist (J.L.K.) and ophthalmology residents (C.M.K, D.G.C). Patients with confirmed disc edema underwent neuroimaging and were referred to neurology for evaluation and lumbar puncture. Final diagnosis and treatment of IIH was determined by the Neurology Department at UC Davis. The diagnosis of IIH did not preclude patients from undergoing bariatric surgery.

RESULTS

From February 2008 to January 2011, 1,148 patients presented for evaluation for bariatric surgery. Of the 1,148 patients, 647 met the initial inclusion criteria and consented to the study. Of the excluded patients, 7 reported having a previous diagnosis of IIH. Those patients who declined enrollment did so for various reasons, including history of migraine headache, photophobia, mobility limitations preventing appropriate positioning for the fundus photography, and time constraints. Patients with migraine headache generally declined participation due to fear that the flash of the camera would trigger a migraine and were not further evaluated.

Because fundus photographs were inadequate for evaluation in 41 patients, a total of 606 patients were included in the study. Seventy-seven percent of these patients were women, and the average age was 45.3 years. The average BMI was 47.5 kg/m², which is considered morbidly obese. Demographics of these patients are shown inTable 3.

Of the 606 patients, 17 were identified on initial screening (either with photographs or with screening questions) as suspicious for having IIH and 11 underwent neuro-ophthalmic evaluation (Table 4). The patients who were not evaluated either failed to return at least 3 phone calls or declined evaluation for other reasons. Patients who declined evaluation were educated on the risks of their decisions.

Of the 11 patients who were evaluated, 7 were deemed not to have true optic disc edema (Table 5). The results of these 7 patients were as follows. Two patients had mildly blurred disc margins on the screening photographs but were not evaluated clinically until 2 and 6 months following bariatric surgery. In both the cases, optic disc appearance was unchanged compared to the screening photographs, and the nerves were deemed to be a congenitally full and a variant of normal. One patient had prior photographs from 2005 that were identical to those taken in 2009. One patient was diagnosed with a hyaloid remnant and 1 with nonarteritic anterior ischemic optic neuropathy. The remaining 2 patients were deemed to have normal optic discs on clinical examination.

Four of the 11 patients had optic disc edema (Table 5). None of these patients had ever been diagnosed with IIH nor were they familiar with the disease. Two of these patients (P2 and P3) had no symptoms of IIH (Table 6). One patient (P3) reported frequent severe headache associated with nausea but no visual symptoms. One patient (P1) reported previous episodes of diplopia, TVOs, and frequent severe headache. All 4 patients were women, and all had mild (Frisén stage 1) optic disc edema. All had fundus photographs and corresponding OCT images (Fig. 1). All 4 patients had visual acuity of 20/20 bilaterally without detectible visual field changes. One of these patients (P1) was evaluated on a day where the nonmydriatic screening camera was unavailable, but the bariatric surgeons were suspicious of IIH, given the patient's severe headache symptoms. Patient P4 declined lumbar puncture. The other 3 patients had opening pressures of 24, 25, and 32 cm H₂O, respectively (Table 6). Due to the body habitus, each of these patients had lumbar punctures performed by interventional radiology in the prone position rather than in the lateral decubitus position. Neuroimaging of these 4 patients did not identify an underlying cause for optic nerve edema and was consistent with a diagnosis of IIH. However, only 2 patients (Cases 1 and 2) had a magnetic resonance venography.

DISCUSSION

The diagnosis of IIH is traditionally made if the clinical findings meet the modified Dandy criteria (⁵). Of the 606 patients, 3 (0.50%) (Patient P1, P2 and P3) met these criteria for IIH. This number does not include Patient P4 who declined lumbar puncture. All cases identified in the current study had very mild papilledema, which was not visually significant at the time of diagnosis. Whether these patients would have progressed to more severe papilledema is unknown.

While obesity is clearly associated with IIH (^2,15), the relationship between obesity and IIH remains complex and is not fully understood. One study even suggested that IIH may have a role in causing obesity (²²). Several reports support the notion that recent weight gain contributes to the development of IIH (^17,23). Daniels et al (¹⁷) found that weight gain in previously nonobese patients was as much of a risk factor for development of IIH as obesity itself. The fact that weight loss (²), including due to bariatric surgery (^24,25), improves or resolves signs and symptoms of IIH supports the strong association of obesity and IIH. Yet, it is difficult to be certain of a direct causal link between changes in weight and IIH or possibly the relationship is due to the myriad of metabolic and inflammatory changes that occur with obesity, weight gain, and weight loss (³).

Our study examined a large population of morbidly obese patients and found that none had papilledema with significant visual loss. Whether the 6 patients with suspicious optic nerves who were not evaluated in clinic could have undiagnosed IIH is unknown. However, all 6 of these patients had mild optic disc edema (stage 1) on screening photographs (Fig. 2); therefore, it seems unlikely that any cases of papilledema with significant visual loss were excluded. One interpretation of these data is that obesity alone is not a direct causal factor in the development of IIH. Because our study population comprised chronically obese patients, we are unable to assess if recent weight gain is a major risk factor for developing IIH. Previous studies suggest that if this is the case, then treatment with aggressive weight loss, including bariatric surgery, may be beneficial (^2,25).

This study has several limitations. First, the large body habitus of our patients precluded in-office lumbar punctures in the lateral decubitus position. Normative data for opening pressures are known for the lateral decubitus position, but similar normative data do not exist for lumbar punctures performed in the prone position (²⁶). Therefore, it is unclear how to interpret these opening pressure values. We did not analyze the comorbidities of our patients. Obesity is associated with numerous chronic medical conditions that may affect the development of IIH, including obstructive sleep apnea, hypertension, diabetes mellitus, and hypercoagulability. Further research into this area is ongoing. Finally, only 2 of the 4 patients with mild optic disc edema had magnetic resonance venograms. The magnetic resonance venogram for patient P1 was inconclusive. The other 2 patients had MRI only. It is possible that these imaging studies could have missed cerebral venous thromboses causing papilledema.

To our knowledge, this is the first prospective study evaluating the prevalence of previously undiagnosed IIH in morbidly obese patients. We found that, in this patient population, asymptomatic or previously undiagnosed papilledema with significant visual loss is extremely low. Based on our results, routine screening for papilledema with nonmydriatic fundus photographs for asymptomatic obese patients is likely not warranted. However, bariatric surgeons should be vigilant in screening for any symptoms consistent with IIH and refer these patients promptly for neuro-ophthalmic evaluation.

ACKNOWLEDGMENT

The authors thank Raymond Kong for his assistance with creating the figures.

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