In the present study, it was found that IIH in Asians was characterized by lower BMIs, less pronounced female preponderance, and lower frequencies of papilledema and TVO when compared with Caucasian patients. A significant proportion of patients with a CSF pressure of 200–250 mm CSF had classical manifestations of IIH, and could meet commonly used diagnostic criteria for IIH. Although these patients had a less severe phenotype when compared with those in the > 250 mm CSF group, the risks of headache or visual field defect were similar. The findings bring up the issue whether a CSF pressure of > 250 mm CSF is the optimum cutoff for a diagnosis of IIH in Asian populations.

One of the most important strengths of the present study is the sample size. More than 100 patients were included, which constituted the largest cohort in Asian populations to date. A larger sample size could give more accurate estimates, and made comparisons between patients with CSF pressures > 250 and 200–250 mm CSF feasible. More importantly, data in Asian patients were under-presented in the literature, and there could be concerns whether the current diagnostic criteria and treatment guidelines could be suitable for IIH in Asians [6, 36]. Besides, ophthalmologic findings were re-evaluated in a standardized fashion, and interpretation of MRIs was carried out systemically based on the criteria proposed by Friedman et al. [18] and morphometric parameters reported in the literature [30,31,32,33]. In addition, all of the patients had been hospitalized, and secondary causes for IICP were excluded by meticulous diagnostic work-up.

According to the findings of the present study, obesity was less common in Asian IIH patients, and the female predominance was less significant when compared with Caucasian patients. The findings were consistent with the trend observed in prior small-scale studies from Korea (n = 14) [13], Taiwan (n = 12) [14], and China (n = 9) [37]. In those studies, the mean BMI ranged from 25.4 to 29.43 kg/m2, and the proportions of patients with obesity, i.e., BMI ≥ 30 kg/m2, were between 7.1% and 33.3%. In the present cohort, even in those with a CSF pressure of > 250 mm CSF, the mean BMI was 29.2 ± 6.2 kg/m2. Overall, 34.3% had a BMI of ≥ 30 kg/m2, and even when a threshold of ≥ 27.5 kg/m2 was used [11], only 45.1% were categorized as obese. In comparison, obesity was present in 75.6–85.0% in Caucasian cohorts, and the reported BMIs were between 35.0 and 39.9 kg/m2 [8, 29, 38, 39]. In the current study, men constituted 30.4%, which was close to those in other Asian series (35.7–41.7%) [13, 14]. In contrast, there has been a well-known female predominance in IIH, and in some of the largest IIH cohorts from Europe, the United States, Middle East, and North Africa, only 5.1–18.2% of the patients were men [2, 10, 40]. The demographic profile in Asian IIH patients could be different from those in other parts of the world, although further studies are needed to verify our findings.

It was found that ophthalmologic manifestations associated with IIH were less prominent in Asian IIH patients, and IIH without papilledema (IIHWOP) was not uncommon. In the literature, papilledema was seen in 93.1–95.8% in Caucasian and Middle East patients [4, 5, 41], and IIHWOP has been believed to be a relatively rare entity [41, 42]. However, papilledema was present in 62.6% in the current cohort, and it was 70.7% even among those with a CSF pressure of > 250 mm CSF. Also, TVO was less common in Asian patients (32.8% in those with a CSF pressure > 250 mm CSF) compared to their Caucasian counterparts (68.0–72%) [2, 16, 43]. Although the frequencies of papilledema and TVO were higher in some Asian studies [13, 14, 37], patients in those studies were recruited by ophthalmologists, and could have papilledema and other visual symptoms as the presenting symptoms which led to the diagnosis of IIH. As IIHWOP constituted nearly 40% of Asian IIH patients, the absence of papilledema could not be used as a reliable indicator to preclude the need for lumbar puncture when other clinical or radiological features suggestive of the diagnosis of IIH are present.

Patients in the > 250 mm CSF group had more MRI features typical of IIH, and there were trends toward higher frequencies of empty sella and flattening of the posterior aspect of the globe when compared with those in the 200–250 mm CSF group. In the current study, the proportions of patients with individual MRI signs were mostly within the ranges reported in the literature [20, 31, 33, 44], although distension of the perioptic subarachnoid space was more common (80.9%) than in other reports (51.0-69.8%) [20, 31]. The trend that MRI features were more commonly seen in patients with higher CSF pressures is in keeping with the report by Bono et al. [45]. However, the clinical relevance of these MRI features remains an issue of debate [46, 47], and needs to be further clarified.

In the present study, although patients with higher pressures had more severe manifestations, the differences were not huge. In fact, when the criterion on CSF pressure was neglected, a significant proportion of patients in the 200–250 mm CSF group could meet other commonly used diagnostic criteria for IIH, such as the ICHD-3 [19] and Friedman criteria [18]. In other words, they could have clinical presentations indistinguishable from those in classical cases with a CSF pressure of > 250 mm CSF. More importantly, the proportions of patients with headache or visual field defect, and the average perimetric MDs in such patients were not only similar to those with CSF pressures > 250 mm CSF included in the present study, but also within the ranges reported in the literature [2, 48, 49]. Therefore, for Asian patients with a CSF pressure of 200–250 mm CSF and typical clinical features of IIH, it is not without doubt whether the diagnosis should be excluded based on the ICHD-3 [19] or the Friedman criteria [18] since such patients are still at substantial risks of developing headache and visual complications. Race or ethnicity should be taken into consideration in the evaluation of IIH patients, as clinical decisions based on traditional wisdom might not always be the best strategy. In particular, patients with lower CSF pressures were less likely to receive interventions in the current study. Whether such patients could benefit from a more aggressive approach in the diagnosis and management deserves further study.

There are some limitations. First, there could be concerns about generalizability, since patients in the present study were recruited from two tertiary medical centers, and only patients who were hospitalized were included in the analysis. However, IIH is a disorder that could lead to significant neurologic or ophthalmologic consequences, and most of the patients would be referred to medical centers for further evaluation and management. On the other hand, it is the common practice in Taiwan that lumbar punctures be done in an inpatient setting, and hospitalization does not necessarily correspond to greater disease severity. Besides, our National Health Insurance system has a ~ 99% coverage of the citizens in Taiwan, and copayment is generally limited [50]. Therefore, whether patients could be hospitalized was not related to their socioeconomic status. Second, the study participants are mostly ethnic Chinese, whether the findings could be applied to other Asian populations needs to be further confirmed. However, the findings were consistent with those in some small-scale Asian studies [13, 14, 37]. Third, the study involved patients admitted to neurology service, and it is possible that the patient characteristics could be different from those recruited by ophthalmologists. In fact, 89.2% of the current cohort were initially recruited for neurological presentations. Nevertheless, most of our patients were also evaluated by ophthalmologists, and all of the patients fulfilled the modified Dandy’s criteria, which are widely used in clinical practice and studies, including the IIHTT [16]. Fourth, data reliability could be another source of bias due to technical or methodological concerns. Because of the retrospective nature of the study, it could not be ascertained whether the CSF pressures were measured in a consistent manner or whether the results could have been influenced by treatment. Besides, there were no predefined protocols or platforms for perimetry and MRI, and the inter-rater reliability of ophthalmologic and radiologic signs has not been formally evaluated. However, 61.8% of the patients were treatment-naïve, the results of fundus photographs and MRIs were interpreted by an experienced neuro-ophthalmologist (H.C.C.) and a senior neuroradiologist (J.F.L.), respectively. Finally, as a retrospective study, some of the data variables were not available in a variable proportion of patients. For instance, digital photographs of optic discs were available in 61 patients only, whether the findings on funduscopy could be consistent in the entire study population is uncertain. Besides, MRV was available for review in 66 patients. Since only patients with TSS on MRV were rated as having that sign, under-diagnosis could be a concern for those in whom MRV was not available. However, the rates of papilledema between the medical record and data from re-evaluation by a neuro-ophthalmologist were generally consistent (agreement rate = 82.0%), which indicates the medical records were reliable to a certain extent. Besides, the rate of papilledema in these patients was close to the estimate of the entire study population.

In conclusion, in this relatively large cohort, it was found that obesity, papilledema, and TVO were less common in Asian IIH patients when compared with Caucasians. Besides, a significant proportion of patients with a CSF pressure of 200–250 mm CSF had clinical and radiologic features typical of IIH, and the risks of having headache or visual field defect were similar to those in the > 250 mm CSF group. A threshold of > 250 mm CSF could be more specific for the diagnosis, but is at the cost of missing a significant proportion of patients at risk of developing complications. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asian patients, although further studies are still needed to verify our findings.