Can Lumbar Puncture Be Safely Deferred in Patients With Mild Presumed Idiopathic Intracranial Hypertension?

Lumbar puncture (LP) is considered an essential component of the diagnosis of idiopathic intracranial hypertension (IIH) and ruling out IIH mimics, such as meningeal inflammation and neoplastic disease. Such mimics are unlikely in patients who are systemically well and fit the clinical demographic of IIH. It is important to take into account the risks of performing a LP as patients commonly experience mild adverse effects and infrequently more serious ones including psychological distress. LP can also be difficult to obtain in some health care settings, requiring inpatient admission. We examined the clinical course of a subset of presumed patients with IIH with mild vision loss and papilledema to determine whether LP can be safely deferred in this group.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Can Lumbar Puncture Be Safely Deferred in Patients With Mild Presumed Idiopathic Intracranial Hypertension? Amir R. Vosoughi, BSc, Edward A. Margolin, MD, Jonathan A. Micieli, MD, CM Background: Lumbar puncture (LP) is considered an essential component of the diagnosis of idiopathic intracranial hypertension (IIH) and ruling out IIH mimics, such as meningeal inflammation and neoplastic disease. Such mimics are unlikely in patients who are systemically well and fit the clinical demographic of IIH. It is important to take into account the risks of performing a LP as patients commonly experience mild adverse effects and infrequently more serious ones including psychological distress. LP can also be difficult to obtain in some health care settings, requiring inpatient admission. We examined the clinical course of a subset of presumed patients with IIH with mild vision loss and papilledema to determine whether LP can be safely deferred in this group. Methods: This was a retrospective study looking at the clinical characteristics, final visual outcome, and diagnosis of patients with presumed IIH and papilledema determined by clinical examination who did not undergo LP. The inclusion criteria included i) no symptoms suspicious for systemic infectious/neoplastic/inflammatory processes, ii) no secondary causes of raised intracranial pressure seen on magnetic resonance imaging/magnetic resonance venography, iii) optical coherence tomography (OCT)-RNFL thickness #300 mm, and iv) automated mean deviation (MD) # 25.00 dB v) at least one follow-up visit. Results: A total of 132 eyes of 68 patients (66 female and 2 male) were included in the study. The mean ± SD age was 31.4 ± 10.2 years, and body mass index was 35.1 ± 6.8 kg/m2. Systemic symptoms included headache (n = 47), pulsatile tinnitus (n = 28), transient visual obscurations (n = 10), and diplopia (n = 2). Presenting logarithm of the minimum angle of resolution visual acuity was 0.020 ± 0.090, automated MD was 22.23 ± 1.38 dB, and OCT RNFL thickness was 150.8 ± 48.4 mm. Patients were followed for a mean number of 63.3 ± 78.3 weeks. No addiRady Faculty of Health Sciences (ARV), Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Department of Ophthalmology and Vision Sciences (EAM, JAM), University of Toronto, Toronto, Canada; Division of Neurology (EAM, JAM), Department of Medicine, University of Toronto, Toronto, Canada; and Kensington Vision and Research Centre (JAM), Kensington Health, Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Jonathan A. Micieli, MD, CM, Kensington Vision and Research Centre, 501-340 College Street, Toronto, ON M5T3A9, Canada; E-mail: [e-mail] Vosoughi et al: J Neuro-Ophthalmol 2022; 42: 505-508 tional cause of intracranial hypertension was discovered, and all patients remained systemically well. Two patients were started on acetazolamide, and 31 patients lost at least some weight. There was a significant improvement in the automated MD (21.73 ± 1.74 dB; P , 0.001) and OCT RNFL thickness (128.1 ± 38.6 mm; P , 0.001) at final follow-up. Seventy-six eyes of 38 patients were considered to have resolved papilledema at the final follow-up. Conclusions: Some patients with presumed IIH may not be able to undergo LP because of patient factors such as refusal, failed attempts, or the environment in which neuroophthalmologists practice. This study suggests that it may be acceptable to defer LP for patients with suspected IIH who are under the care of a neuro-ophthalmologist with experience in diagnosing and managing IIH. These patients should be systemically well, in a typical demographic for IIH patients, have mild optic disc edema, and preserved visual function. Patients should be informed about the controversial nature of this decision. Journal of Neuro-Ophthalmology 2022;42:505–508 doi: 10.1097/WNO.0000000000001411 © 2021 by North American Neuro-Ophthalmology Society L umbar puncture (LP) is considered an essential component of diagnosis of patients with idiopathic intracranial hypertension (IIH) (1). Diagnostic criteria indicate that all patients investigated for IIH must receive a LP after the presence of normal imaging findings (2,3). LP is mainly performed to confirm an elevated opening pressure and rule out meningeal inflammation and, in rare circumstances, neoplastic disease. Both of these are extremely uncommon in patients who are systemically well and fit the clinical profile of IIH. Previous cases have described IIH mimickers where cerebrospinal fluid (CSF) analysis was helpful in arriving at a correct diagnosis such as primary leptomeningeal lymphoma (4), viral meningitis (5), and other inflammatory or infectious conditions (6–8). However, in all of these cases, either neuroimaging was misinterpreted or not typical for IIH (with optic nerve or chiasmal enhancement) (4,8), patients had associated neurological and/or systemic symptoms or were not in the typical IIH 505 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution demographic (5–7), or CSF abnormalities did not change the RESULTS treatment course (5). It is important to consider whether LP can be safely deferred in selected patients who are at low risk of visual loss from IIH as evident by clinical symptoms and severity of papilledema. LPs can be a technically challenging procedure in obese patients and difficult to obtain in certain geographic areas and may require inpatient hospital admission and interventional radiology resources. Moreover, it may induce significant patient anxiety (9) and can result in complications including headache from intracranial hypotension and infrequent complications such as infection, nerve injury, cerebral herniation, and epidermoid tumors. The opening pressure obtained through LP can also be variable, influenced by natural variations in CSF and variations imposed by patient positioning and technical issues (10,11). Furthermore, a low opening pressure may not change the diagnosis in a patient with typical symptoms of IIH and papilledema (3). The goal of this study was to determine whether LP can be safely deferred in a group of presumed IIH patients with preserved visual function and nonsevere optic disc edema (ODE) who are followed regularly by neuro-ophthalmologists experienced in managing and treating IIH. A total of 132 eyes of 68 patients (66 female and 2 male) met the inclusion criteria for the study. An additional 166 patients were referred for possible papilledema/IIH without previous workup and were excluded because of the presence of optic disc drusen (n = 66) and pseudopapilledema from various other causes such as myopic tilted discs (n = 89) or were found to have normal optic nerves (n = 11). The mean age ± SD was 31.4 ± 10.5 years and body mass index (BMI) was 35.1 ± 6.8 kg/m2. Forty-one patients (60.3%) were referred because of an incidental finding of ODE, whereas 27 patients (39.7%) sought medical attention because of symptoms of intracranial hypertension. Systemic symptoms of headache (n = 47), pulsatile tinnitus (n = 28), transient visual obscurations (n = 10), and diplopia (n = 2) were reported at presentation. The diplopia was considered unrelated to raised intracranial pressure in the 2 patients (decompensated pre-existing strabismus). LP was deferred because of patient refusal (n = 12), failed attempts (n = 2), or clinical judgment by neuro-ophthalmologists (n = 54) who practice in a clinical setting where interventional radiology does not accept regular outpatient referrals. The presenting logarithm of the minimum angle of resolution visual acuity was 0.020 ± 0.090, automated MD was 22.23 ± 1.38 dB, and OCT RNFL thickness was 150.8 ± 48.4 mm. No secondary cause for intracranial hypertension was found on neuroimaging. An empty or partially empty sella was present in 91% of patients, and average sella grade was 3.20 ± 1.15. Patients were followed for a mean number of 63.3 ± 78.3 weeks. All patients remained systemically well, and no additional cause of intracranial hypertension was discovered. All patients were counseled on weight loss, 31 patients lost at least some weight, and 2 patients were started on acetazolamide. There was a significant improvement in the automated MD (21.73 ± 1.74 dB; P , 0.001) and OCT RNFL thickness (128.1 ± 38.6 mm; P , 0.001) at the final follow-up. No patient lost significant vision or required surgical intervention. 76 eyes of 38 patients were considered to have resolved papilledema at the final followup. METHODS This was a retrospective review of consecutive patients with presumed IIH presenting to tertiary neuro-ophthalmology clinics at the University of Toronto between June 2012 and April 2020 who did not have a LP. Research ethics approval was obtained from the University of Toronto Research Ethics Board. The inclusion criteria included i) true ODE determined clinically by neuro-ophthalmologists experienced in treating patients with IIH with other causes of pseudopapilledema reasonably ruled out with ancillary testing such as enhanced depth imaging (EDI)-optical coherence tomography (OCT), fundus autofluorescence, and B-scan ultrasound; ii) nonsevere ODE characterized by OCT retinal nerve fiber layer thickness of 300 mm or less; iii) preserved visual function with automated 24-2 SITAFast mean deviation (MD) of 25.00 dB or less; iv) magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) with contrast without signs of a secondary cause of raised intracranial pressure (ICP); and v) absence of systemic or clinical signs suggestive of a neoplastic or infectious process. The presence of an empty or partially empty sella was determined by review of the MRI images. An empty or partially empty sella was defined as complete or partial CSF filling of the sella turcica associated with the lack of visible pituitary gland on midsagittal T1 MRI and graded as per previous studies (12). 506 DISCUSSION In our cohort of presumed patients with IIH, LP was deferred without systemic or visual complications with a mean follow-up of over 1 year. These data suggest that the circumstances in which LP may be deferred are i) systemically well patients, ii) typical IIH demographic (young women with increased BMI), iii) mild ODE (as guided by OCT RNFL average thickness ,300 mm), iv) preserved visual function with MD on automated VF better than 25.00 dB, v) no sign of secondary cause of raised intracranial pressure on MRI/MRV, and vi) regular follow-up by a neuro-ophthalmologist with experience in Vosoughi et al: J Neuro-Ophthalmol 2022; 42: 505-508 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution diagnosing and managing IIH. This can overcome the significant psychological burden regarding LP that exists for many patients with IIH and potential adverse effects from the procedure (9). It also has the potential to save health care resources and time, which can be significant and include hospital admission, interventional radiologists, and prolonged stays for post-LP headache or other adverse effects. Most of our patients did not require medical treatment, and none of our patients required surgical treatment, emphasizing the mild clinical course of the patients in our cohort. Differentiating papilledema from pseudopapilledema can be made with a high degree of certainty on clinical grounds by experienced neuro-ophthalmologists. The advent of newer technologies including EDI-OCT and FAF allow us to exclude causes of pseudopapilledema such as optic disc drusen and may provide confirmatory signs of papilledema including the shape of the Bruch-RPE complex (13). Following the patient, over time for variation in the appearance of optic nerves has also been found to be an important way to differentiate papilledema from pseudopapilledema when there is diagnostic uncertainty (14). Relying on opening pressure to differentiate pseudopapilledema from true papilledema can lead to diagnostic errors and overdiagnosis of IIH (15), and it is not advisable to perform LP in patients with chronic migraine in the absence of papilledema to assess for IIH (16). The opening pressure reading may not be reliable and depends on the experience of the operator and technical issues, which can be significant in obese patients (17). Unreliable opening pressures may lead to diagnostic confusion and additional unnecessary testing. Previous studies have found no correlation between LP opening pressure, OCT parameters, and headache severity (18,19), further calling to question its value in presumed IIH cases. It should be emphasized that LP does play an important role in many papilledema cases and not only helps with diagnosis but can be an important temporizing measure to protect the optic nerves. Red flags that should prompt an LP in patients with ODE consistent with papilledema include i) demographic factors (men, nonobese women, and older or younger age), ii) clinical factors (e.g., presence of focal neurological symptoms, seizures, and severe symptoms), iii) examination findings (e.g., severe papilledema and severe vision loss), and iv) neuroimaging findings (e.g., dural enhancement). The strength of this study is the large sample size of patients with IIH followed without LP with full neuro-ophthalmic examinations. All patients were seen in follow-up at least once. It is possible that some patients may not have had true ODE, but we argue this is unlikely as there was significant improvement in the OCT RNFL thickness at the final follow-up, which does not occur in pseudopapilledema. Over 90% of patients had a partially empty sella, consistent with raised ICP as the cause of the ODE. Furthermore, the absence of systemic or visual complications over the follow-up period is consistent with mild IIH as the likely underlying etiology of intracranial hypertension. Future prospective studies can aim to better define the patient population Vosoughi et al: J Neuro-Ophthalmol 2022; 42: 505-508 based on visual function and anatomic parameters that can be confidently followed without LP. In conclusion, some patients with presumed IIH may not be able to undergo LP because of patient factors such as refusal, technical difficulties while attempting the LP, or inability to find a provider who can perform it. This study suggests that LP may be deferred in systemically well patients in the typical IIH demographic who are under the care of neuro-ophthalmologists with experience in diagnosing and managing IIH. These patients should be in a typical demographic group for IIH, be systemically well, have preserved visual function, have mild ODE, have no concerning findings on MRI/MRV, and have a regular follow-up with an experienced neuro-ophthalmologist. Patients should be informed about the risks, benefits, and controversial nature of deferring LP in IIH diagnosis. Our cohort of presumed patients with IIH without systemic symptoms concerning for neoplastic or infectious causes, nonsevere ODE and preserved visual function showed significant improvement in the degree of ODE with only lifestyle modifications. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: J. A. Micieli; b. Acquisition of data: A. R. Vosoughi, E. A. Margolin, and J. A. Micieli; c. Analysis and interpretation of data: A. R. Vosoughi, E. A. Margolin, and J. A. Micieli. Category 2: a. Drafting the manuscript: A. R. Vosoughi, E. A. Margolin, and J. A. Micieli; b. Revising it for intellectual content: A. R. Vosoughi, E. 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