Prediction of Postoperative Risk of Raised Intracranial Pressure After Spontaneous Skull Base Cerebrospinal Fluid Leak Repair

A relationship between idiopathic intracranial hypertension and spontaneous skull base cerebrospinal fluid (CSF) leaks has been proposed, by which CSF leak decreases intracranial pressure (ICP) and masks the symptoms and signs of elevated ICP. These patients are at risk of developing papilledema, symptoms of elevated ICP, or a recurrent CSF leak after CSF leak repair. The objective of this study was to assess whether radiographic signs of raised ICP on preoperative magnetic resonance or computed venography (MRI or CTV) are predictors of post- operative papilledema, recurrence of CSF leak, or need for CSF shunt surgery.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Prediction of Postoperative Risk of Raised Intracranial Pressure After Spontaneous Skull Base Cerebrospinal Fluid Leak Repair Bryce Buchowicz, MD, Benson S. Chen, MBChB, FRACP, Samuel Bidot, MD, Beau B. Bruce, MD, PHD, Nancy J. Newman, MD, Amit M. Saindane, MD, MBA, Joshua M. Levy, MD, MPH, Valérie Biousse, MD, for the CSF-Leak Study Group Background: A relationship between idiopathic intracranial hypertension and spontaneous skull base cerebrospinal fluid (CSF) leaks has been proposed, by which CSF leak decreases intracranial pressure (ICP) and masks the symptoms and signs of elevated ICP. These patients are at risk of developing papilledema, symptoms of elevated ICP, or a recurrent CSF leak after CSF leak repair. The objective of this study was to assess whether radiographic signs of raised ICP on preoperative magnetic resonance or computed venography (MRI or CTV) are predictors of postoperative papilledema, recurrence of CSF leak, or need for CSF shunt surgery. Methods: We performed a retrospective review of systematically collected demographics, fundus examination, and presurgical brain MRI and magnetic resonance venography/ computed tomography venography (MRV/CTV) in patients seen at 1 institution between 2013 and 2019 with spontaneous skull base CSF leak repair. Patients were divided into 2 groups depending on whether they developed papil- Departments of Ophthalmology (BB, BSC, BBB, NJN, VB); Pathology (SB); Epidemiology (BBB); Neurology (BBB, NJN, VB); Neurological Surgery (NJN); Radiology and Imaging Sciences (AMS); and Otolaryngology- Head and Neck Surgery (JML), Emory University School of Medicine, Atlanta, Georgia. Supported in part by NIH/NEI core grant P30-EY06360 (Department of Ophthalmology, Emory University School of Medicine). V. Biousse and N. J. Newman are consultants for GenSight Biologics. N. J. Newman is a consultant for Santhera Pharmaceuticals and Stealth BioTherapeutics. Presented in part as a poster at the North American NeuroOphthalmology Society annual meeting, March 10, 2020, Amelia Island, FL. B. S. Chen is the recipient of the VJ Chapman Research Fellowship awarded by the New Zealand Neurological Foundation. The remaining authors report no conflicts of interest. The members of CSF-Leak Study Group are listed in Acknowledgment section. Address correspondence to Valérie Biousse, MD, NeuroOphthalmology Unit, Emory Eye Center, The Emory Clinic, 1365-B Clifton Road NE, Atlanta, GA 30322; E-mail: [e-mail] e490 ledema, recurrent CSF leak, or required CSF shunting (Group 1) or not (Group 2). Results: Fifty-seven patients were included, among whom 19 were in Group 1. There was no difference in demographic characteristics or clinical features between patients in Group 1 and Group 2. Controlling for other imaging features, bilateral transverse venous sinus stenosis (TVSS) on preoperative imaging increased the odds of being in Group 1 by 4.2 times (95% confidence interval [CI], 1.04–21.2, P = 0.04), optic nerve tortuosity decreased the odds of being in Group 1 by 8.3 times (95% CI: 1.4–74.6, P = 0.02). Conclusion: Imaging of the intracranial venous system with MRV or CTV is warranted before repair of spontaneous CSF leak, as bilateral TVSS is an independent risk factor for postoperative papilledema, CSF leak recurrence, or need for a CSF shunting procedure. Journal of Neuro-Ophthalmology 2021;41:e490–e497 doi: 10.1097/WNO.0000000000001118 © 2020 by North American Neuro-Ophthalmology Society R ecent studies have emphasized that idiopathic intracranial hypertension (IIH) may be the main cause of spontaneous skull base cerebrospinal fluid (CSF) leak (1– 11). Patients with spontaneous CSF leak and those with IIH share similar demographics, including female gender and obesity, although CSF leak patients tend to be older at the time of diagnosis, probably reflecting chronically raised intracranial pressure (ICP) leading to slowly progressive skull base erosion over years (8,12,13). One recent review (12) highlighted the difficulty of diagnosing IIH in CSF leak patients because the classic diagnostic criteria for IIH (14) are often absent. Few patients have papilledema or elevated CSF opening pressure, presumably because the active spontaneous CSF leak acts as a “CSF shunt,” thereby normalizing the ICP (10,12,15). It is well established that CSF leaks must be repaired to reduce the high risk of infectious complications (16–20). However, Buchowicz et al: J Neuro-Ophthalmol 2021; 41: e490-e497 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution patients with skull base spontaneous CSF leak and IIH are at risk of developing raised ICP postoperatively, potentially resulting in papilledema and consequent visual loss, recurrent CSF leak, and need for CSF shunting surgery (12,20– 23). Several studies have shown a higher primary repair success rate in spontaneous CSF rhinorrhea patients who received active ICP management with acetazolamide or permanent CSF shunting surgery compared with patients without any ICP management at the time of CSF leak repair (9,13,19,22–28), although this remains controversial (26). A few studies (9,21,22,24,25), suggested acetazolamide or CSF shunting surgery to treat raised ICP in the setting of CSF leak repair and showed that closure of the CSF leak site resulted in significant elevation of CSF pressure by about 10 cm of water a few hours later. It is unclear, however, whether these measures to prevent postoperative raised ICP should be systematically performed and which patients would benefit most from aggressive perioperative ICP management. The objective of our study was to assess whether radiographic signs of raised ICP are predictors of postoperative papilledema, recurrence of CSF leak, and/or need for CSF shunting surgery. METHODS potential precipitating factors for IIH such as history of obesity and weight gain. Demographic data, including age, sex, body mass index, and race were collected. We recorded patients’ clinical presentation, location of CSF leak, surgical procedures performed, and the use of acetazolamide perioperatively (Table 1). Imaging Protocol and Analysis MRI studies were obtained on either a 1.5-T or 3-T unit in the supine position using a standard head coil. The MRI protocol included sagittal T1-weighted, axial T2-weighted, and often postcontrast sagittal 3D T1-weighted images. Either contrast-enhanced MRV or 2D-time of flight MRV was selected for review. CTV was performed using a multidetector row CT after administration of intravenous iodinated contrast material with 0.625 mm slice thickness whenever MRI/MRV was not possible. One blinded neuroradiologist (A.M.S.) reviewed all imaging for radiographic signs of increased ICP according to previously described methods (Table 2) (29–32). Radiographic signs included empty sella (complete or partial), orbital signs of elevated ICP (flattening of the posterior portion of the ocular globe, vertical tortuosity of the optic nerve, and prominent perioptic CSF space), cephaloceles and enlarged Meckel’s cave, and bilateral transverse venous sinus stenosis (TVSS). Patients Statistical Analysis This retrospective study was approved by our institutional review board. Consecutive patients with skull base spontaneous CSF leak, defined as a leak of CSF fluid outside the dura not because of trauma or another identifiable cause and evaluated in our neuro-ophthalmology service between October 2013 and September 2019 were identified. We included adult patients who had been seen at our institution for CSF leak repair, underwent a neuro-ophthalmologic evaluation before and after surgical repair, and had a brain MRI and cerebral venous imaging (magnetic resonance venography or computed tomography venography [MRV or CTV]) performed preoperatively. Patients were excluded if they had secondary intracranial hypertension (from other causes than IIH, such as a mass or cerebral venous thrombosis), or if the quality of brain imaging did not allow for cerebral transverse venous sinus measurements. These patients were systematically evaluated as part of an interdisciplinary quality improvement project. Neuroophthalmologic assessment included examination of visual function, dilated fundus examination, and ophthalmic imaging. Optical coherence tomography (Cirrus HDOCT 4000 or Cirrus HD- OCT 5000; Zeiss, Oberkochen, Germany) of the peripapillary retinal nerve fiber layer was obtained in both eyes along with fundus photography to detect subtle papilledema. At their preoperative evaluation, patients were asked whether they had any symptoms or signs that would suggest a previous history of IIH and Patients were divided into 2 groups based on their status after CSF leak repair: patients in Group 1 had postoperative papilledema, postoperative recurrence of CSF leak, and/or needed a CSF shunting procedure. Patients in Group 2 did not have any postoperative papilledema, postoperative CSF leak, or need for CSF shunt (Fig. 1). Statistical analysis was performed with R: a language and environment for statistical computing (R Foundation for Statistical Computing, http://www.R-project.org). Medians and interquartile ranges were used to report continuous variables. Continuous variables were compared using the Wilcoxon rank-sum test. The Fisher exact test was used to compare the distribution of categorical variables. Ninety-five percent confidence intervals (95% CI) were obtained by normal approximation to the binomial. Logistic regression was used to control for possible confounding by the other variables. Because of the small number of subjects, Firth’s bias corrected logistic regression was used to assess the risk of qualifying for Group 1 based on radiological features. These tests were 2-tailed, and significance was set at 5%. Buchowicz et al: J Neuro-Ophthalmol 2021; 41: e490-e497 RESULTS Seventy patients with spontaneous skull base CSF leak who had undergone preoperative imaging and had a neuroophthalmologic evaluation were identified, and 57 were e491 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Demographic and clinical features of spontaneous skull base cerebrospinal fluid leak patients Demographics Group 1 (n = 19) Group 2 (n = 38) Age, years Gender, women Race: Black White Others Body mass index, kg/m2 Presenting symptoms: Rhinorrhea Otorrhea Origin of leak: Ethmoid bone Sphenoid bone Frontal sinus Temporal bone Pre-existing known IIH Treatment: Acetazolamide CSF Shunt 46 [39.5–57] 19 (95%) 51 [46–69.25] 36 (95%) 16 (84%) 3 (16%) 0 (0%) 35.6 [31.1–45.6] 19 (50%) 15 (40%) 4 (10%) 35.6 [29.1–39.6] 0.29 16 (84%) 4 (21%) 24 (63%) 16 (42%) 0.13 0.15 7 6 2 5 4 (37%) (32%) (11%) (26%) (21%) 11 (29%) 9 (24%) 1 (3%) 17 (45%) 2 (5%) 0.56 0.54 0.26 0.25 0.09 13 (72%) 8 (62%) 25 (63%) 0 (0%) 0.29 P 0.24 1.00 0.07 All values displayed as n (%) or median [interquartile range, IQR]. CSF, cerebrospinal fluid; IIH, idiopathic intracranial hypertension. Four patients from Group 1 underwent a CSF shunting procedure (ventriculoperitoneal shunt [VPS]) at the time of CSF leak repair, and their outcome was analyzed separately from the remaining 15 patients (Fig. 2). Two of these 4 patients had a previous diagnosis of IIH, one of whom had a previous nonfunctioning lumboperitoneal shunt with secondary optic atrophy. The third patient presented with papilledema and subsequently developed a brain abscess complicating the CSF leak. CSF opening pressure of this patient was 22 cm of water preoperatively (while actively leaking). This patient was treated with acetazolamide before CSF leak repair and shunting procedure. The fourth patient who had a VPS at the time of CSF leak repair presented simultaneously with papilledema and a CSF leak and had included (Figs. 1 and 2). Patients were seen in neuroophthalmology follow-up 2–4 weeks after surgery, and then every 2–3 months for a mean duration of 27.6 ± 64 weeks (1.6–330 weeks); they all received standard postoperative follow-up with otolaryngology or neurosurgery. Group 1 included 19 patients, and Group 2 included 38 patients. There was no significant demographic difference between the 2 groups, although 84% of patients in Group 1 were of black race compared with 50% in Group 2 (Table 1). The median age of onset of CSF leak symptoms was similar in both groups. Rhinorrhea was the most common presentation of CSF leak in both groups. The number of patients treated with acetazolamide and dosage (500–1500 mg daily) was similar in each group. TABLE 2. Summary of MRI and MRV/CTV findings of raised intracranial pressure MRI/MRV/CTV Characteristics Partial/empty sella Optic nerve head protrusion Scleral flattening Perioptic cerebrospinal fluid Optic nerve tortuosity Enlarged Meckel’s cave Cephaloceles Multiple osseous defects Bilateral transverse venous sinus stenosis Group 1 (n = 19) 17 1 10 10 7 14 16 17 15 (89%) (5%) (53%) (53%) (37%) (74%) (84%) (89%) (79%) Group 2 (n = 38) 32 3 12 11 18 23 32 30 20 (84%) (5%) (21%) (19%) (32%) (40%) (56%) (53%) (35%) P 0.71 1.00 0.15 0.09 0.57 0.39 1.00 0.47 0.08 All values displayed as n (%). CTV, computed tomography venogram; MRV, magnetic resonance venogram. e492 Buchowicz et al: J Neuro-Ophthalmol 2021; 41: e490-e497 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Summary of patients included in our study. CSF, cerebrospinal fluid. CSF opening pressure of 32 cm of water preoperatively. None of these patients who had a VPS placed at the time of CSF leak repair developed postoperative papilledema or recurrence of CSF leak. Those with preoperative papilledema improved after the CSF shunt and the CSF leak repair. Of the 19 patients in Group 1, 4 patients had a preexisting diagnosis of IIH (Fig. 2). At their preoperative evaluation, 1 of these 4 patients had bilateral peripapillary changes suggestive of previous papilledema, and another patient had bilateral secondary optic atrophy. Two of these patients underwent a VPS at the time of CSF leak repair (these 2 patients are included in the CSF repair patient mentioned above). The 2 IIH patients who did not receive a CSF shunt at the time of leak repair had postoperative complications, including 1 with recurrent papilledema and CSF leak and 1 with recurrent CSF leak without papillede- ma. Three additional patients in Group 1 were found to have papilledema at the time of CSF leak diagnosis but did not have a known history of IIH. Two of these 3 patients with papilledema underwent a VPS at the time of CSF leak repair (included in the 4 patients mentioned above), and the third patient received acetazolamide before and after CSF leak repair. After the CSF leak repair, 5 patients in Group 1 developed papilledema alone, 7 patients had CSF leak recurrence alone, and 3 patients developed both papilledema and CSF leak recurrence postoperatively (Fig. 2). Of the 5 patients in Group 1 who had postoperative recurrence of papilledema alone, all were treated with acetazolamide (500 mg–1000 mg daily) and weight loss, and none required a subsequent CSF shunting procedure. All 10 patients with CSF leak recurrence but 1 had a repeat CSF leak repair in addition to treatments of raised ICP. Two of the 7 patients FIG. 2. Characteristics and outcomes of patients in Group 1. [*] indicates a patient with a pre-existing diagnosis of IIH. Two of these patients underwent a CSF shunting procedure at the time of CSF leak repair, 1 developed recurrence of papilledema and CSF leak after CSF leak repair, and 1 developed CSF leak recurrence alone. [¶] indicates a patient found to have papilledema preoperatively but was not known to have IIH. Two of these patients underwent a CSF shunting procedure at the time of CSF leak repair, and 1 was treated with perioperative acetazolamide alone. CSF, cerebrospinal fluid. Buchowicz et al: J Neuro-Ophthalmol 2021; 41: e490-e497 e493 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution with only postoperative recurrence of CSF leak and no papilledema required a VPS (1 with elevated CSF opening pressure on lumbar puncture of 33 cm of water). Five of these CSF leak recurrence patients were treated with acetazolamide therapy and weight loss. Of the 3 patients who had both CSF leak recurrence and papilledema, 2 ultimately had a VPS (1 of these did not need a repeat CSF leak repair because the leak resolved after the VPS), and the third patient was successfully treated with acetazolamide therapy and weight loss alone. There were no significant differences in the radiologic findings between the 2 groups on univariate analysis. However, patients in Group 1 tended to have a higher proportion of scleral flattening (53% vs 21%, P = 0.15), enlarged perioptic CSF space (53% vs 19%, P = 0.09), multiple osseous defects (89% vs 53%, P = 0.47), and bilateral TVSS (79% vs 35%, P = 0.08) compared with those in Group 2. After controlling for empty sella, optic nerve head protrusion, scleral flattening, enlarged perioptic CSF space, enlarged Meckel’s cave, cephaloceles, and osseous defects using multivariable Firth logistic regression, bilateral TVSS was found to increase the odds of the patient having postoperative papilledema, recurrent CSF leak, or requiring a CSF shunting procedure by 4.2 times (95% CI, 1.04–21.2, P = 0.04). Optic nerve tortuosity decreased the odds by 8.3 times (95% CI, 1.4–74.6, P = 0.02) (Table 3). DISCUSSION Our study found that the presence of bilateral TVSS on preoperative brain imaging increased the odds of a patient having post-CSF leak repair papilledema, CSF leak recurrence, or need for a CSF shunting procedure by 4.2 times. This finding may help predict which spontaneous skull base CSF leak patients are more likely to have a poor outcome once their CSF leak is repaired, and thus facilitate the most appropriate perioperative management of ICP. The literature on spontaneous skull base CSF leaks over the past several years supports the concept that most spontaneous CSF leak patients have IIH (1–13,15– 28,32,33). One of the proposed mechanisms for spontaneous skull base CSF leak is indeed that chronically elevated ICP, most commonly from IIH, causes progressive insidious remodeling of the skull base bones, leading to a skull base defect that opens the dura and results in a CSF leak into the ear or nasal cavities (6,8–12,16,19,22,33). The fact that spontaneous CSF leak patients have similar demographics but are on average 10 years older than most IIH patients supports this hypothesis (1–5,7,10,11,16,17,22,27,28,33). Repairing the CSF leak, will logically result in increased ICP, with concerns that patients with active IIH may develop rebound raised ICP with subsequent papilledema or recurrent CSF leak (12,13,17–28). Recent studies have emphasized that findings of radiologic signs of intracranial hypertension on brain imaging should prompt further evaluation for possible IIH (6,8,11–13,33). However, many of the radiologic signs are nonspecific, and their presence does not necessarily implies that ICP is elevated at the time of imaging. TVSS is highly prevalent in IIH patients, with studies reporting TVSS in up to 90%–100% of IIH patients (29,31,34). Bilateral TVSS likely contributes to intracranial hypertension by venous hypertension when the stenosis is severe enough to compromise cerebral venous outflow (31,35). Not only do findings of bilateral TVSS support a diagnosis of active or previous IIH as the main cause of a spontaneous skull base leak but it potentially may open the door to treatment of the venous hypertension, when present. Indeed, endovascular venous sinus stenting has been proposed in patients with medically refractive IIH or in those unable to tolerate medical therapy and lose weight (36,37). A few reports (20,38,39) showed endovascular venous sinus stenting to be effective in treating a patient with likely IIH and recurrent spontaneous CSF leak, bilateral TVSS, and other signs of raised ICP on brain MRI. Our finding that bilateral TABLE 3. Preoperative imaging characteristics as predictors of poor postsurgical outcome using a multivariable Firth logistic regression model MRI/MRV/CTV Characteristics Odds Ratio (95% CI, P) Partial/empty sella Optic nerve head protrusion Scleral flattening Perioptic cerebrospinal fluid Optic nerve tortuosity Enlarged Meckel’s cave Cephaloceles Multiple osseous defects Bilateral transverse venous sinus stenosis 0.98 0.48 3.32 3.00 0.12 2.35 0.14 1.61 4.23 (0.13–7.64, (0.04–4.44, (0.67–22.7, (0.64–16.5, (0.01–0.71, (0.64–10.8, (0.07–4.05, (0.26–12.4, (1.04–21.2, 1.0) 0.5) 0.1) 0.2) 0.02)* 0.2) 0.6) 0.6) 0.04)* *Significant result. CI, confidence interval; CTV, computed tomography venogram; MRV, magnetic resonance venogram. e494 Buchowicz et al: J Neuro-Ophthalmol 2021; 41: e490-e497 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TVSS is a risk factor for poor outcome in patients undergoing a spontaneous CSF leak repair is therefore not surprising, supporting the need to systematically look for signs of raised ICP and TVSS on MRIs preoperatively in addition to other signs of raised ICP. Such patients may require more aggressive management of perioperative ICP and close postoperative follow-up for signs of raised ICP to prevent further complications, including papilledema, headaches, and recurrent CSF leak (12,17–25). Interestingly, there were slightly more patients of black race in the group with complications, which may reflect the previously described worse outcome in IIH patients of black race (40). Although most of our patients were treated postoperatively with acetazolamide, the number of patients treated, and the dosages prescribed (500–1500 mg daily), were similar within each group. Acetazolamide use did not seem to influence which patients developed papilledema or CSF leak recurrence postoperatively. Concern for postoperative intracranial hypertension prompted a CSF shunting procedure at the time of CSF leak repair in 4 patients who had a very good outcome. An additional 4 patients with recurrent CSF leak (2 of whom also had developed papilledema) subsequently underwent a VPS. An unexpected finding of this study was that the presence of optic nerve tortuosity on MRI decreased the odds of a poor outcome by 8.3 times. Tortuosity of the optic nerve has been described in the setting of raised ICP and is included as a supportive neuroimaging criterion in the diagnosis of IIH (14,29). There is no study evaluating optic nerve tortuosity as a protective factor in patients with IIH, but it is possible that increased optic nerve tortuosity may be a marker of intracranial compliance or the ability to autoregulate at a higher ICP after leak repair. Our study has several limitations. Although it was retrospective in nature, all included patients were evaluated systematically with a pre-established protocol as part of a collaborative quality improvement project, including otolaryngology, neurosurgery, and neuro-ophthalmology physicians at a single institution. All patients received the same neuro-ophthalmologic evaluation, and our strict inclusion criteria resulted in a relatively homogeneous group of consecutive patients. Our sample size was small and likely underpowered, and we had a large number of predictors in our model, but we used Firth logistic regression to reduce the bias in the OR estimates. All patients had at least one neuro-ophthalmology examination after CSF leak repair; however, the duration of follow-up varied and the mean neuro-ophthalmology follow-up was 27 weeks. It is possible that some patients may have developed papilledema from raised ICP at a later stage, resulting in underestimation of the rate of after CSF leak repair papilledema in our series. The most important limitation is the lack of standardization of treatment with acetazolamide. There is no clear scientific evidence to support the use of acetazolamide in the Buchowicz et al: J Neuro-Ophthalmol 2021; 41: e490-e497 perioperative setting of CSF leak repair. Hence, the decision to use acetazolamide was made by individual neurosurgery and otolaryngology clinicians based on their clinical suspicion of increased ICP. Similarly, there were no predefined criteria for which patients should undergo a CSF shunting procedure at the time of CSF leak repair. Systematic measurement of the CSF opening pressure at the time of CSF leak repair (usually by lumbar drain) and after surgery (usually by lumbar puncture) may be useful but was not deemed standard of clinical care unless a patient had definite symptoms or signs of raised ICP. Given the highly variable results of CSF pressure measurements with a single lumbar puncture (41), interpretation of the results would likely be very difficult, especially in patients with active CSF leak. CONCLUSIONS Spontaneous CSF leak patients who develop papilledema or a recurrent CSF leak postoperatively, or who are determined to require a CSF shunting procedure, have a higher prevalence of bilateral TVSS. Cerebral venous imaging with MRV or CTV is warranted preoperatively for decisionmaking because some findings of raised ICP could alter perioperative management of ICP. Further prospective studies are needed to determine the best strategies to control rebound elevation of ICP after surgical repair of spontaneous skull base CSF leaks in at risk patients. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: B. S. Chen, S. Bidot, N. J. Newman, V. Biousse, A. M. Saindane, and J. M. Levy; b. Acquisition of data: B. Buchowicz, B. S. Chen, S. Bidot, A. M. Saindane, and J. M. Levy; c. Analysis and interpretation of data: B. Buchowicz, B. S. Chen, B. B. Bruce, S. Bidot, and A. M. Saindane. Category 2: a. Drafting the manuscript: B. Buchowicz, B. S. Chen, B. B. Bruce, N. J. Newman, V. Biousse, and A. M. Saindane; b. Revising it for intellectual content: B. Buchowicz, B. S. Chen, B. B. Bruce, N. J. Newman, V. Biousse, A. M. Saindane, and J. M. Levy. Category 3: a. Final approval of the completed manuscript: B. Buchowicz, B. S. Chen, B. B. Bruce, N. J. Newman, V. Biousse, A. M. Saindane, and J. M. Levy. ACKNOWLEDGMENTS CSF leak study group: John M. DelGaudio, MD (7), Joshua M. Levy, MD MPH (7), Douglas E. Mattox, MD (7), Nelson M. Oyesiku, MD PhD (5), Arturo Solares, MD (7), Esther X. Vivas, MD (7), Sarah K. Wise, MD, MSCR (7), Valérie Biousse, MD (1,4), Samuel Bidot, MD (2), Michael Dattilo, MD, PhD (1), Nancy J. Newman, MD (1,4,5), and Jason Peragallo, MD (1). e495 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution REFERENCES 1. Clark D, Bullock P, Hui T, Firth J. Benign intracranial hypertension: a cause of CSF rhinorrhoea. J Neurol Neurosurg Psychiatry. 1994;57:847–849. 2. Yang Z, Wang B, Wang C, Liu P. Primary spontaneous cerebrospinal fluid rhinorrhea: a symptom of idiopathic intracranial hypertension? J Neurosurg. 2011;115:165–170. 3. Schlosser RJ, Woodworth BA, Wilensky EM, Grady MS, Bolger WE. Spontaneous cerebrospinal fluid leaks: a variant of benign intracranial hypertension. Ann Otol Rhinol Laryngol. 2006;115:495–500. 4. 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