Thinning of the Skull Base and Calvarial Thickness in Patients With Idiopathic Intracranial Hypertension

Background: Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure without secondary causes on neuroimaging. IIH typically occurs in young, obese female patients and, when severe, can cause permanent and irreversible vision loss. The association between skull base thinning in patients with intracranial hypertension and obesity has been previously reported; however, no study has reported these findings in IIH. The goal of our study is to determine whether IIH is independently associated with skull base and calvarial thinning. Methods: A retrospective, matched case-control study was performed. Each patient diagnosed with IIH (case) was matched with a patient diagnosed with headache (control) by age, gender, and race. Patients were included if they underwent computed tomographic imaging of the head, maxillofacial, or orbits within 3 months of their diagnosis. Exclusion criteria were history of skull base or frontal bone pathology because of surgery or skull trauma, central nervous system infections, or incomplete radiologic data. Patient demographics, medical history, clinical examination, and skull base, calvarial, and zygoma thickness were recorded. Skull base thickness was measured by the height of the auditory canal in the coronal plane. Calvarial thickness was measured just anterior to the foramen rotundum in the coronal plane. Extracranial zygoma thickness was measured and used as an internal imaging control because the zygoma is not subject to intracranial forces. Results: One hundred twenty-six patients were included in the study, 63 cases and 63 controls. Each group comprised 61 female patients (97%), 24 (38%) Caucasian, 23 (37%) black, 1 (2%) Asian, and 15 (24%) others. The average age was 31.5 ± 8.7 years. Patients with IIH were more likely to be obese (n = 60, 95%) compared with the control patients (n = 23, 37%, P < 0.001). All patients with IIH underwent lumbar puncture (LP) with an average opening pressure (OP) of 40.5 ± 15.6 cm H2O, whereas only 13 (20%) controls underwent an LP with a mean OP of 19.5 ± 8.5 cm H2O. There was no statistical difference in mean visual acuity between the IIH and control groups (logMar 0.22 [20/30] ± 0.45 vs logMar 0.09 [20/25] ± 0.30, P = 0.093, respectively). Compared with the controls, patients with IIH were more likely to have headache (97% vs 74%, P = 0.001), pulsatile tinnitus (48% vs 7%, P < 0.001), horizontal binocular diplopia (24% vs 4%, P = 0.006), confrontational visual field deficit (23% vs 2%, P = 0.003), and papilledema (74% vs 0%, P < 0.001). Patients with IIH had thinner skull base and calvarium width compared with the controls (mean skull base thickness 4.17 ± 0.94 mm vs 5.05 ± 1.12 mm, P < 0.001 and mean calvarial width 1.50 ± 0.50 mm vs 1.71 ± 0.61 mm, P = 0.024). Zygoma thickness was similar in both groups (mean zygoma thickness 1.18 ± 0.30 mm in the IIH group vs 1.26 ± 0.35 mm in the control group, P = 0.105). In a subgroup analysis controlling for obesity (body mass index >30 kg/m2), there was no statistically significant difference in skull base, calvarial, or zygoma thickness between obese and nonobese patients. Conclusions: Patients with IIH have thinner mean skull base and calvarial thickness compared with the controls. There was no difference in the mean extracranial zygoma thickness, which was the internal imaging control. Contrary to previous reports, we did not find an association between obesity and skull base or calvarial thinning. These findings suggest that IIH is associated with skull base and calvarial thinning.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Thinning of the Skull Base and Calvarial Thickness in Patients With Idiopathic Intracranial Hypertension Matthew Barke, BS, Hannah Muniz Castro, MD, Ore-ofe O. Adesina, MD, Alice Z. Chuang, PhD, Thai Do, MD, Rajan P. Patel, MD, Karina Richani, MD, Background: Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure without secondary causes on neuroimaging. IIH typically occurs in young, obese female patients and, when severe, can cause permanent and irreversible vision loss. The association between skull base thinning in patients with intracranial hypertension and obesity has been previously reported; however, no study has reported these findings in IIH. The goal of our study is to determine whether IIH is independently associated with skull base and calvarial thinning. Methods: A retrospective, matched case–control study was performed. Each patient diagnosed with IIH (case) was matched with a patient diagnosed with headache (control) by age, gender, and race. Patients were included if they underwent computed tomographic imaging of the head, maxillofacial, or orbits within 3 months of their diagnosis. Exclusion criteria were history of skull base or frontal bone pathology because of surgery or skull trauma, central nervous system infections, or incomplete radiologic data. Patient demographics, medical history, clinical examination, and skull base, calvarial, and zygoma thickness were recorded. Skull base thickness was measured by the height of the auditory canal in the coronal plane. Calvarial thickness was measured just anterior to the foramen rotundum in the coronal plane. Extracranial zygoma thickness was meaRuiz Department of Ophthalmology and Visual Science (MB, HMC, O-oOA, AZC, KR), McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth); Robert Cizik Eye Clinic (HMC, O-oOA, KR); Department of Neurology at the University of Texas Health Science Center at Houston (UTHealth) (O-oOA), Houston, Texas; Department of Opthhalmology (TD), Kresge Eye Institute, Detroit, Michigan; and Department of Diagnostic and Interventional Imaging at the University of Texas Health Science Center at Houston (UTHealth) (RPP), Houston, Texas. Supported by National Eye Institute Vision Core Grant P30EY028102 and Research to Prevent Blindness. Presented at the American Society of Ophthalmic Plastic and Reconstructive Surgery Fall Virtual Meeting, November 20–22, 2020. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Karina Richani, MD, Robert Cizik Eye Clinic, 6400 Fannin Street, Suite 1800, Houston, TX 77030; E-mail: [e-mail] 192 sured and used as an internal imaging control because the zygoma is not subject to intracranial forces. Results: One hundred twenty-six patients were included in the study, 63 cases and 63 controls. Each group comprised 61 female patients (97%), 24 (38%) Caucasian, 23 (37%) black, 1 (2%) Asian, and 15 (24%) others. The average age was 31.5 ± 8.7 years. Patients with IIH were more likely to be obese (n = 60, 95%) compared with the control patients (n = 23, 37%, P , 0.001). All patients with IIH underwent lumbar puncture (LP) with an average opening pressure (OP) of 40.5 ± 15.6 cm H2O, whereas only 13 (20%) controls underwent an LP with a mean OP of 19.5 ± 8.5 cm H2O. There was no statistical difference in mean visual acuity between the IIH and control groups (logMar 0.22 [20/30] ± 0.45 vs logMar 0.09 [20/25] ± 0.30, P = 0.093, respectively). Compared with the controls, patients with IIH were more likely to have headache (97% vs 74%, P = 0.001), pulsatile tinnitus (48% vs 7%, P , 0.001), horizontal binocular diplopia (24% vs 4%, P = 0.006), confrontational visual field deficit (23% vs 2%, P = 0.003), and papilledema (74% vs 0%, P , 0.001). Patients with IIH had thinner skull base and calvarium width compared with the controls (mean skull base thickness 4.17 ± 0.94 mm vs 5.05 ± 1.12 mm, P , 0.001 and mean calvarial width 1.50 ± 0.50 mm vs 1.71 ± 0.61 mm, P = 0.024). Zygoma thickness was similar in both groups (mean zygoma thickness 1.18 ± 0.30 mm in the IIH group vs 1.26 ± 0.35 mm in the control group, P = 0.105). In a subgroup analysis controlling for obesity (body mass index .30 kg/m2), there was no statistically significant difference in skull base, calvarial, or zygoma thickness between obese and nonobese patients. Conclusions: Patients with IIH have thinner mean skull base and calvarial thickness compared with the controls. There was no difference in the mean extracranial zygoma thickness, which was the internal imaging control. Contrary to previous reports, we did not find an association between obesity and skull base or calvarial thinning. These findings suggest that IIH is associated with skull base and calvarial thinning. Journal of Neuro-Ophthalmology 2022;42:192–198 doi: 10.1097/WNO.0000000000001504 © 2022 by North American Neuro-Ophthalmology Society I diopathic intracranial hypertension (IIH) is a syndrome of elevated intracranial pressure (ICP) with associated Barke et al: J Neuro-Ophthalmol 2022; 42: 192-198 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution symptoms and signs, normal cerebrospinal fluid (CSF) composition, and without secondary causes of elevated ICP on neuroimaging (1). It commonly affects women of childbearing age, with an annual incidence of approximately 12–20 per 100,000 compared with 1–2 per 100,000 in the general population (2). Known risk factors are female gender, obesity or weight gain, endocrine disorders, and hypervitaminosis A (3). The predilection toward young and working-age populations results in a significant economic impact, with annual direct costs estimated to exceed $444 million in the United States (4). Symptoms and signs of intracranial hypertension include headaches, pulsatile tinnitus, disc edema, and abducens nerve palsy. Alterations in visual function because of optic nerve involvement manifest as transient visual obscurations, blurry vision, or visual field defects (5–7). Left untreated, permanent vision loss has been observed in up to 10% of patients (7). Neuroimaging is key for diagnosis and demonstrates normal brain parenchyma without hydrocephalus, masses, structural lesions, or abnormal meningeal enhancement on MRI (1,5). Neuroimaging signs of elevated ICP can include empty sella, posterior globe flattening, distension of the perioptic subarachnoid space with or without a tortuous optic nerve, and transverse venous sinus stenosis (1,5). Diagnosis of IIH is based on a constellation of the above clinical and radiological findings and a lumbar puncture (LP) with an opening pressure (OP) $25 cm H2O in adults with normal CSF composition. If papilledema or abducens nerve palsy is not observed, the diagnosis can only be suggested (1,5). Skull base abnormalities are sometimes seen in patients with elevated ICP and have been associated with CSF leaks (8,9), and although CSF leaks are frequently secondary to trauma or iatrogenic injury, nontraumatic and spontaneous cases have been associated with IIH (8,10). Furthermore, patients with spontaneous CSF leaks are likely to be female, obese, middle-aged, and have obstructive sleep apnea (OSA), with thinning of their entire calvarium (10–18). Given the predilection of IIH and spontaneous CSF leaks toward a similar population, an underlying association is of high interest. Previous studies have linked thinning of the skull base and calvarium in patients with spontaneous CSF leaks (14,19,20). It is unknown whether inherently thin skull bases are more prone to develop elevated ICP and spontaneous CSF leak or whether chronically elevated ICP leads to thinning of the skull base and resulting CSF leak. Although the association between skull base thinning in patients with intracranial hypertension has recently been reported (17), no study has reported findings in patients with IIH. The goal of our study is to determine whether IIH is independently associated with skull base and calvarial thinning and to identify risk factors that affect the skull base and calvarial thickness. Barke et al: J Neuro-Ophthalmol 2022; 42: 192-198 METHODS This study was approved by the institutional review board at the University of Texas Health Science Center at Houston (protocol HSC-MS-19-0741). Patients were selected from charts from the Robert Cizik Eye Clinic and Memorial Hermann Hospital Texas Medical Center between January 1, 2011, and July 31, 2019. Subjects were divided into 2 groups: IIH and controls. Inclusion criteria for patients with IIH (case) were $18 years old, diagnosis of IIH based on the modified Dandy criteria (see Supplemental Digital Content, Appendix 1, http://links.lww.com/WNO/A556), LP with OP, and highresolution computed tomographic (CT) imaging of the head, including maxillofacial area, orbit, and paranasal sinus within 3 months from LP. Inclusion criteria for control patients were $18 years old, high-resolution CT imaging of the head, including maxillofacial area, orbit, and paranasal sinus within 3 months from LP, and do not meet criteria for IIH diagnosis. We excluded patients with a history of skull base or frontal bone pathology because of surgery or trauma, central nervous system infections, lowresolution or poor-quality CT scan, or incomplete medical record or radiologic data. Each control was selected to match each case by gender and race (black/Caucasian/ Asian/other). If more than 1 control met the matching criteria, the most similar in age was selected. To identify charts for cases, charts were searched with the following diagnosis codes (ICD-10/ICD-9): a) papilledema from elevated ICP (H47.11/377.02), b) unspecified papilledema (H47.10/377.0), and c) benign intracranial hypertension (G93.2/348.2). Also used were the current procedural terminology (CPT) code for LP (62270) and CPT code for high-resolution CT imaging of a) head with contrast (70450), without contrast (70460), or with/ without contrast (70470) or b) orbit without contrast (70480) or with contrast (70481). When identifying charts for controls, charts with the following ICD-10/ICD-9 codes: headache (R51/784) and CPT code for LP (62270), CPT code for high-resolution CT imaging of a) head with contrast (70450), without contrast (70460), and with/ without contrast (70470) or b) orbit without contrast (70480) and with contrast (70481) were used. CT scans were deidentified and evaluated. If more than 1 CT scan met case or control criteria, the CT scan closest to the time of LP was used. Measurements were performed by a masked reader to cases and controls using Centricity Picture Archiving Communication System (GE Healthcare, Chicago, IL). Coronal and axial imaging was used to measure the thickness of the skull base (height of the internal auditory canal in the coronal plane) (Fig. 1) and the calvarium (measurement just anterior to foramen rotundum in the coronal plane) (Fig. 2). In addition, zygoma thickness was measured and used as an internal imaging control because it is not subject to intracranial forces (Fig. 3). 193 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Illustration of skull base thickness measurement. Measurements were bilateral, yielding 2 measurements for each patient. The descriptive MRI characteristics of intracranial hypertension were documented according to the radiology report. Best-corrected visual acuity was evaluated using logMAR, 2log10(VA). Data were summarized by mean, SD, minimum, and maximums for continuous variables and frequency (%) for categorical variables. The 2-sample t test was used in comparing continuous variables between FIG. 3. Illustration of skull base thickness measurement. the IIH and control groups, and the Fisher exact test was used in comparing categorical variables. A mixed-effect model was used to compare skull base, calvarial, and zygoma thickness between the groups using data from both eyes. A mixed-effect model with backward selection identified risk factors affecting the thickness measurements and estimated their effects. The potential risk factors are the demographics and clinical features that have a P value ,0.15 from the univariate analyses. All statistics were performed using SAS 9.4 for Windows (Cary, NC). P values ,0.05 are considered statistically significant. RESULTS FIG. 2. Illustration of skull base thickness measurement. 194 A total of 126 eligible patients (63 patients with IIH and 63 controls) were included. Table 1 reports demographics, medical history, and clinical examination of all patients. Each group consisted of 61 female patients (97%) and 24 (38%) Caucasian, 23 (37%) black, 1 (2%) Asian, and 15 (24%) others. The average age was 31.5 (±8.7) years. There were more obese patients in the IIH group (n = 60, 95%) compared with the control group (n = 23, 37%, P , 0.001). There was no difference (P . 0.05) in smoking status, diabetes, hypertension, OSA, or oral or intravenous steroid use between the groups. No patient in either group had a history of osteopenia, osteoporosis, or CSF leak. All patients with IIH underwent LP with an average OP of 40.5 (±15.6) cm H2O, whereas 13 (20%) controls underwent LP with an average OP of 19.5 (±8.5) cm H2O (P ,0.001). Barke et al: J Neuro-Ophthalmol 2022; 42: 192-198 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Table 1. Demographics, medical history, and clinical examination Demographics Age (years, mean [SD]) (range) Gender (female patients, %) Race (%) Caucasian Black Asian Others Medical history Obese (n, %) Current smokers (n, %) Osteopenia or osteoporosis (n, %) Diabetes (n, %) Hypertension Obstructive sleep apnea (n, %) History of CSF leak (n, %) History of oral or intravenous steroid within 1 yr of encounter (n, %) Clinical examination Underwent lumbar puncture (n, %) Opening pressure (cm H2O, mean [SD]) (range) Headache (n, %)† Underwent ophthalmology consultation (n, %) Visual acuity (logMAR obtained from both eyes, mean [SD]) (range)‡ Pulsatile tinnitus (n, %)‡ Transient visual obscurations (n, %)‡ Horizontal binocular diplopia (n, %)‡ Papilledema (n, %)§ Confrontation visual field deficit (n, %)║ Cranial nerve VI palsy (n, %)║ Other cranial nerve palsy (n, %)║ MRI Underwent MRI examination (n, %) Empty sella (n, %) Posterior globe flattening Bilateral tortuosity of the optic nerves (n, %) Transverse sinus stenosis (n, %) Enhancement of the optic nerve head (n, %) Skull base thickness (from both eyes) Skull base (mm, mean [SD]) (range) Calvarium width (mm, mean [SD]) (range) Zygoma width (mm, mean [SD]) (range) IIH (N = 63) Control (N = 63) P value 30.7 (7.8) (19–53) 61 (97%) 32.3 (9.6) (17–58) 61 (97%) 0.32 1.0 (38%) (37%) (2%) (24%) 24 23 1 15 60 10 0 2 17 2 0 3 (95%) (16%) (0%) (3%) (27%) (3%) (0%) (5%) 23 (37%) 6 (10%) 0 (0%) 3 (5%) 10 (16%) 1 (2%) 0 (0%) 1 (2%) ,0.001 0.42 — 1.0 0.19 1.0 — 0.62 13 (20%) 19.5 (8.5) [6–39] 37 (74%) 47 (75%) 0.09 (0.30) [0–1.9] ,0.001 ,0.001 0.001 0.015 0.093* 63 (100%) 40.5 (15.6) [5–95] 56 (97%) 58 (92%) 0.22 (0.45) [0–2.3] (38%) (37%) (2%) (24%) 1.0 24 23 1 15 28 20 14 43 13 5 1 (48%) (34%) (24%) (74%) (23%) (9%) (2%) 3 3 2 0 1 1 1 (7%) (7%) (4%) (0%) (2%) (2%) (2%) ,0.001 0.001 0.006 ,0.001 0.003 0.22 1.0 56 25 20 4 25 3 (89%) (45%) (36%) (7%) (45%) (5%) 34 1 1 0 2 0 (54%) (3%) (3%) (0%) (6%) (0%) ,0.001 ,0.001 ,0.001 0.29 ,0.001 0.29 4.17 (0.94) (2.49–7.21) 1.50 (0.50) (0.70–3.39) 1.18 (0.30) (0.71–1.91) 5.05 (1.12) (2.30–7.88) 1.71 (0.61) (0.82–4.28) 1.26 (0.35) (0.59–2.13) ,0.001* 0.024* 0.105* *P value obtained from a mixed-effect model. † Missing 5 data points in the IIH group and 13 data points in the control group. ‡ Of the eyes underwent ophthalmology consultation, 2 data points were missing in the control group. § Of the eyes underwent ophthalmology consultation, 1 data point was missing in the control group. k Of the eyes underwent ophthalmology consultation, 2 data points in the IIH group and 1 data point in the control group were missing. CSF, cerebrospinal fluid. The majority of patients (58 [92%] patients with IIH and 47 [75%] controls) had an inpatient ophthalmology evaluation (P = 0.015). There was no statistical difference in mean VA between IIH and control groups (logMar 0.22 [20/30] (±0.45) vs logMar 0.09 [20/25] (±0.30), respectively, P =0.093). Compared with controls, patients with IIH were more likely to have headache (56 [97%] vs 47 Barke et al: J Neuro-Ophthalmol 2022; 42: 192-198 [74%], P = 0.001), pulsatile tinnitus (28 [48%] vs 3 [7%], P , 0.001), horizontal binocular diplopia (14 [24%] vs 2 [4%], P = 0.006), confrontational visual field deficit (13 [23%] vs 1 [2%], P = 0.003), and disc edema (43 [74%] vs 0 [0%], P , 0.001) (Table 1). There were 56 (89%) patients with IIH and 34 (54%) controls with MRI examination (P = 0.015). Of those, 195 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 4. Comparison of mean skull base thickness (A), mean calvarial thickness (B), and mean zygoma thickness (C) in patients with IIH and controls. IIH, idiopathic intracranial hypertension. patients with IIH were more likely to have an empty sella (25 [45%] vs 1 [3%], P , 0.001), posterior globe flattening (20 [36%] vs 1 [3%], P , 0.001), and transverse sinus stenosis (25 [45%] vs 2 [6%], P , 0.001). There was no statistical difference in the incidence of bilateral tortuosity of the optic nerve (4 [7%] vs 0 [0%], P = 0.29) nor enhancement of the optic nerve head (3 [5%] vs 0 [0%], P = 0.29). Patients with IIH demonstrated thinner skull base and calvarium compared with controls (mean skull base thickness 4.17 [±0.94] mm vs 5.05 [±1.12] mm, P , 0.001) and mean calvarial thickness (1.50 [±0.50] mm vs 1.71 [±0.61], P = 0.024). Zygoma thickness was similar in both groups (1.18 [±0.30] mm vs 1.26 [±0.35] mm, P = 0.105) (Fig. 4). In subgroup analysis controlling for obesity (body mass index [BMI] .30 kg/m2 or specified in chart), there was no significant difference between obese vs nonobese in skull base thickness (4.55 [±1.09] mm vs 4.73 [±1.19] mm, P = 0.37), calvarial thickness (1.59 [±0.57] mm vs 1.65 [±0.56] mm, P = 0.51), or zygoma thickness (1.22 [±0.33] mm vs 1.22 [±0.32] mm, P = 0.96). Results are shown in Table 2. CONCLUSIONS The association between intracranial hypertension and skull base thinning was first reported by Rabbani et al (17). That retrospective cohort study evaluated calvarial, zygoma, and skull base thickness in 58 middle-aged Caucasian patients with intracranial hypertension (.25 cm H2O) compared with patients with low ICP (,15 cm H2O). It remains unclear from their study whether the association remains true in patients with IIH. Our study is the first to report the association between IIH and skull base and calvarial thinning. Similar to the study by Rabbani et al (17), our study revealed that patients with IIH demonstrate skull base and calvarial thinning compared with age- and gender-matched controls. Interestingly, the measurements of our IIH population were thinner compared with the intracranial hypertension group in Rabbani et al’s study (17) (mean skull base thickness 4.17 [±0.94] mm vs 5.17 [±1.22] mm and mean calvarial thickness 1.50 [±0.50] mm vs 3.01 [±0.81] mm). These differences may be attributed to our different study populations. In this study, the majority were young (average age 30.7 years), female, and from diverse racial backgrounds. TABLE 2. Skull base and calvarium thickness in obese vs nonobese Variable Skull base (mm, mean [SD]) Calvarium width (mm, mean [SD]) Zygoma width (mm, mean [SD]) Nonobese N = 86 Eyes Obese N = 166 Eyes P value 4.73 (1.19) (2.30–7.88) 1.65 (0.56) (0.83–3.65) 1.22 (0.32) [0.65–2.00] 4.55 (1.09) (2.49–7.76) 1.59 (0.57) (0.70–4.28) 1.22 (0.33) (0.59–2.13) 0.37* 0.51* 0.96 *P value obtained from a mixed-effect model. 196 Barke et al: J Neuro-Ophthalmol 2022; 42: 192-198 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Rabbani et al (17) evaluated middle-aged (average age 53.1 years), Caucasian patients. Further study is needed because it remains unclear how age, gender, and race contribute to these anatomical changes. A growing body of evidence has supported the association between OSA with skull base and calvarial thinning (13,14,16,19,20). OSA is characterized by repeated and spontaneous apneic episodes during sleep because of an obstructive airway and is more commonly diagnosed in men (21). The correlation between OSA and obesity, as well as OSA and IIH, has been well studied (22–27). In a study of 53 patients with IIH, 37 patients reported a history of sleep disturbances, 6 with OSA and 7 with upper airway obstruction (26). In another study of 18 male patients with IIH, 6 (33%) were found to have OSA (27). Our study found no significant differences in the diagnosis of OSA between the IIH group (n = 3) and the control group (n = 1, P = 0.62). Because of the low prevalence of OSA in our study, we failed to show a statistically significant association between OSA and skull base or calvarial thinning. This may be explained by the large proportion of women and the retrospective design of our study. A prospective survey study would be valuable in determining whether our patients acquire the diagnosis of OSA based on polysomnography. Further studies validating these associations may prompt an evaluation for OSA in patients with IIH. Spontaneous CSF leaks are rare but have been reported in association with skull base and calvarial thinning (14,18,19,28). The annual incidence is 5 per 100,000, affecting more women and the obese at a mean age of 40 years (11,29,30). IIH is recognized as a cause of spontaneous CSF leaks (8,9,12). In a study by Schlosser and Bolger (31), 100% of patients with multiple spontaneous CSF leaks had empty sella syndrome compared with 11% of patients with nonspontaneous CSF leaks. Spontaneous CSF leaks may result in intracranial hypotension, which manifests as daily persistent orthostatic headaches and diffuse meningeal enhancement on brain MRI (29). Nelson et al (14) examined CT scans of patients with confirmed spontaneous CSF leaks and found that patients with CSF leaks are more likely to be obese, diagnosed with OSA, and show thinning of their entire calvarium. In our study, no patient had a history of spontaneous CSF leak, which may be attributed to its overall low incidence. Obesity in the United States has risen since the 1960s, and its association with OSA, CSF leaks, and IIH has been well studied (3,13,14,23,32). In a previous study, obesity displayed an inverse correlation with skull base thinning (28). In addition, obese patients with spontaneous CSF leaks had greater thinning of their skull base than matched obese controls, suggesting obesity may be an independent risk factor of skull base thinning. In a subgroup analysis controlling for obesity, our study did not find an association between obesity and skull base or calvarial thinning. This might suggest there are unknown confounder(s) contributing to skull base and calvarial thinning that we have yet to Barke et al: J Neuro-Ophthalmol 2022; 42: 192-198 uncover. Results correlating BMI and skull base and calvarial thinning would be noteworthy; however, exact BMI values were unavailable because of our study’s retrospective nature. Future studies are needed to identify obesity-related factors with the potential to cause thinning of the skull base and calvarium. This study is limited by its retrospective nature; therefore, we cannot prove a cause–effect relationship between IIH and skull base and calvarial thinning. The retrospective nature also creates a source of potential selection bias. Furthermore, there is an innate source of error from obtaining measurements with radiographic calipers that compromises precision. Measuring zygoma thickness allows for internal control that mitigates this. Further studies with several masked readers obtaining measurements may confirm our findings. Finally, as we were restricted to data that already exist, we could not identify other potential factors contributing to skull base and calvarial thinning. Our study found that IIH was independently associated with skull base and calvarial thinning after controlling for known factors such as age, race, gender, OSA, and history of spontaneous CSF leaks. The development of skull base thinning is likely a multifactorial process in which IIH plays an important role. By analyzing CT scans, we found that patients with IIH had a thinner mean skull base and calvarial thickness compared with controls, although there was no difference in the mean extracranial zygoma thickness. This suggests that IIH is independently associated with skull base and calvarial thinning. Future studies are needed to assess the sequential nature and exact pathogenesis of the association between IIH and thinning of the skull base and calvarium. Furthermore, contrary to previous research, our study did not find obesity to be associated with skull base or calvarial thinning. Further studies are needed to evaluate additional processes that result in skull base and calvarial thinning. Overall, this study adds to the discussion of skull base thinning and its complex associations with obesity, OSA, spontaneous CSF leaks, and now IIH. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. Barke, H. M. Castro, O.-o. O. Adesina, T. Do, R. P. Patel, and K. Richani; b. Acquisition of data: M. Barke, H. M. Castro, T. Do, R. P. Patel, and A. Z. Change; c. Analysis and interpretation of data: A. Z. Chuang. Category 2: a. Drafting the manuscript: M. Barke and H. M. Castro; b. Revising it for intellectual content: M. Barke, H. M. Castro, O.-o. O. Adesina, A. Z. Chuang, T. 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