Should Lumbar Puncture Be Required to Diagnose Every Patient With Idiopathic Intracranial Hypertension?

Abstract

Drs. A. G. Lee and G. P. Van Stavern Idiopathic intracranial hypertension (IIH) is a disorder uniquely within the purview of neuro-ophthalmologists. Although overall a rare condition, patients with IIH are commonly diagnosed and managed primarily by neuro-ophthalmologists. Although the criteria for IIH has changed over the years, a constant feature of the modified Dandy criteria for IIH has been the requirement for lumbar puncture (LP) to confirm the diagnosis and to exclude alternative etiologies. Given the advancements in neuroimaging technology and better understanding of the range of intracranial pressure (ICP), 2 experts debate whether LP is still necessary for the diagnosis of IIH. Should Lumbar Puncture Be Required to Diagnose Idiopathic Intracranial Hypertension in Every Patient—Yes!—H. E. Moss, MD, PhD High ICP causes IIH's major morbidities of vision loss and headache. Accordingly, ICP is the target of both medical and surgical therapies for IIH, and measurement of ICP is the cornerstone of diagnosis. Although what constitutes abnormally high ICP has evolved over the years, all past and current diagnostic criteria require LP for measurement of opening pressure (OP). Furthermore, LP enables cerebrospinal fluid (CSF) analysis to exclude secondary causes of high ICP. Some criteria allow for diagnosis of possible or probable IIH without LP, but none allow for definitive diagnosis of IIH without LP and CSF analysis. Thus, LP is necessary in every patient to diagnose definitive IIH by current guidelines. LP is an invasive procedure, one that is increasingly harder to arrange and not enjoyed by patients. Thus, it has been proposed that LP may not be necessary to diagnose IIH in every patient. As with any clinical decision risk, benefit analysis can be helpful (Table 1). By deferring LP, procedure complications and false results are avoided, which may increase both doctor and patient satisfaction. However, by deferring LP, the diagnosis is not confirmed and alternative diagnoses are not excluded. Specifically, measurement of OP, CSF analysis, and evaluating patient response to short-term ICP lowering are not accomplished. TABLE 1. - Risks and benefits of doing or not doing an LP in suspected cases of IIH Risks Benefits Perform LP Procedure complicationsFalse-positive/negative results Diagnostic confirmationShort-term treatment of ICP Defer LP Failure to diagnose normal ICP (necessitating evaluation for other causes of symptoms)Failure to diagnose secondary cause of high ICPInappropriate medical or surgical treatment because of incorrect diagnosis No procedure complicationsMoney savedResources saved There are some patients who have high pretest probability for IIH based on weight, papilledema, and neuroimaging findings suggestive of high ICP, and some diagnostic criteria allow for diagnosis of probable IIH on this basis. In these patients, it has been proposed that LP is unlikely to change management and that they can be treated presumptively. My debate opponent has compiled a series of 68 patients with mild papilledema from presumed IIH who, despite lack of LP, were managed without negative outcomes (1). Similarly, a multicenter study reports 156 patients with probable IIH in whom LP did not change management (2). However, both of these studies suffer from selection bias in that the subjects were all seen by expert neuro-ophthalmologists. Scaling their success to other practitioners less expert in optic nerve assessment is fraught with the risk of missed diagnoses and overdiagnosis. Even in expert hands, the pretest probability that a patient has IIH never reaches 100%. A risk of not doing LP in these patients is failure to diagnose and treat a condition other than IIH that is causing their symptoms and signs. For example, compression of the optic nerve in the posterior orbit or canal can cause bilateral optic nerve edema similar to papilledema but without high ICP. An LP with normal OP would lead to consideration of this and further anatomical evaluation of the posterior orbit. In addition, some secondary causes of high ICP require CSF analysis for diagnosis. Multiple studies in the literature illustrate the nonzero likelihood of conditions with substantial morbidity being overlooked in the setting of presumed IIH diagnosis. A single center study of 86 previously diagnosed cases of IIH included one with cerebral venous sinus thrombosis (3). In a multicenter study of 496 consecutive new neuro-ophthalmology referrals (102 referred for papilledema or abnormal optic disc appearance), one of these (0.2% of all patients and 1% of patients with papilledema) was a previously missed diagnosis of secondary elevated ICP (4). Another multicenter study of 206 patients referred to neuro-ophthalmology for the assessment of papilledema included 4 who were found to have non-IIH diagnoses requiring directed therapy including uveitis, meningitis, and leptomeningeal carcinomatosis (Helen Danesh-Meyer, MD, PhD, FRANZCO, personal written communication, May 2021). All these had positive neuroimaging findings suggesting high ICP and no neuroimaging findings suggesting a secondary cause. The previous paragraph discussed the problem of overdiagnosis of IIH leading to missed diagnosis of other conditions with high morbidity needing directed treatment. The corollary of this is overdiagnosis of IIH leading to unnecessary diagnostic testing and treatment. In the Fisayo study, 16 of 86 patients previously diagnosed with IIH had pseudopapilledema (3), which is a clinical diagnosis not necessitating any additional workup. In the Stunkel study, 15 of 89 patients with suspected papilledema due to IIH were rediagnosed to have pseudopapilledema (4). Although I do not advocate for LP to be performed for workup of pseudopapilledema, in cases where there is diagnostic uncertainty due to nonexpert or equivocal optic nerve examination, LP would prevent a false diagnosis of IIH and reduce harm due to unnecessary medical or even surgical treatment, which was proposed for 4 of 34 patients found to be misdiagnosed with IIH in the Fisayo study (3). In conclusion, LP is an important component of IIH diagnostic criteria because it confirms high ICP and excludes secondary causes of high ICP. Presumptive diagnosis of IIH on the basis of high body mass index (BMI), headache, bilateral optic disc abnormalities, and/or neuroimaging findings of high ICP leads to overdiagnosis of IIH due to failure to confirm the diagnosis and exclude other diagnoses. The consequences are inadequate treatment for a missed diagnosis or inappropriate testing and/or treatment for IIH. It is therefore important to follow the accepted diagnostic criteria including LP for diagnosing this condition. Is Lumbar Puncture Necessary for the Diagnosis of Idiopathic Intracranial Hypertension? Not Always—E. Margolin, MD LP is part of the modified Dandy criteria for establishing the diagnosis of IIH and is considered by many to be the cornerstone for making the diagnosis. The purpose of LP is 2-fold: To confirm increased OP of CSF during the procedure, which is an indirect indication of ICP, and to check its composition to rule out other more ominous causes of increased ICP, either an infection or, very rarely, a neoplasm. The main disadvantage of obtaining an LP is of course the pain and discomfort to the patient during the procedure as well as intraprocedural and postprocedural side effects of which the most common is severe headache due to persistent CSF leak from the site of dural puncture (5). LP can also be difficult to arrange for practitioners who are nonneurologists, and the technical difficulties in performing an LP are often exacerbated by the fact that most patients with IIH have increased BMI. As more and more LPs are performed through fluoroscopic guidance, radiation exposure from fluoroscopy is also not trivial. As most neuro-ophthalmologists are aware though, the LP in a patient who is in a typical demographic group for IIH (women of childbearing age with increased BMI) will demonstrate expected results: elevated OP and normal CSF composition. We know that OP during LP does not correlate with the severity of the disease nor with visual prognosis (6,7). Neuroimaging, which would have been performed before an LP, should demonstrate indirect neuroimaging signs in nearly all patients suspected of having IIH. As experienced neuro-ophthalmologists are also aware, the composition of CSF in patients who are in a typical demographic group for IIH, have typical symptoms, and are systemically well is nearly always normal. Thus, the question of this point counter-point article: “Does one really need to obtain an LP for patients who are in a typical demographic group for IIH, have typical symptoms, and are otherwise systemically well?” The incidence of side effects of LP is not trivial. Post-LP headache occurs in up to 25% of patients (5) and requires placement of a blood patch in a significant minority of patients. Rarer side effects include meningitis, nerve root pain, infection at the skin site, and very rarely an epidural abscess (8). One should also be aware that the OP number obtained during LP is not always an “absolute truth” and is prone to error. Multiple factors can influence OP on LP including positioning of the patient, inadvertent Valsalva maneuver during the procedure, needle positioning, and characteristics of the needle being some of the confounders (9,10). Thus, if the OP is under 25 cm of water in a patient who is in a typical demographic group for IIH and has bilateral optic nerve head edema with indirect neuroimaging signs of ICP, one would have to assume that either the OP is erroneous or that the normal value is not the same for all individuals and proceed with treating the patient for IIH. There are definitely many situations when obtaining OP and CSF analysis is very useful: It should be performed in all patients who are not in a typical demographic group for IIH, in those who have symptoms not typical for IIH, and where pseudopapilledema is difficult to rule out and the clinician is suspecting increased ICP as an additional cause for optic nerve head edema. LP is also needed for those patients who have a severe disease that is typically defined by abnormal visual function [decreased central acuity and/or decreased mean deviation (MD) on automated perimetry, previously defined as MD worse than −7.0 dB] and for those patients in whom surgical treatments are planned (11). Although there are only a few studies (1,2) evaluating the management of patients with IIH without an LP, several IIH cohorts reported on the findings of the LP. One study evaluating 53 patients with IIH in Kuwait reported normal CSF composition in all (12). In the IIH Treatment Trial, although the explicit data regarding the number of patients who were found to have abnormal CSF composition at the study entry were not provided, Dr. Michael Wall, one of the study's founders, kindly provided the spreadsheet with the details of each excluded patient for the purposes of this article. Abnormal CSF composition is not listed for any of them (13). My colleagues at the University of Toronto and myself followed a cohort of 68 patients with mild presumed IIH without an LP for at least 63 weeks, with no alternate diagnosis made in any of the patients and all the patients remaining well (this manuscript is currently under consideration), again providing data about the reasonableness of following patients with mild presumed IIH without an LP. Modern neuroimaging has allowed us to be able to presume a diagnosis of IIH with a high degree of certainty as most patients will demonstrate several indirect neuroimaging features associated with increased ICP with transverse sinus stenosis been reported to be present in nearly all patients with IIH (14). Adequate neuroimaging (MRI with venography and contrast administration) can also effectively rule out many alternate diagnoses. Thus, if LP is not performed, a high-quality MR scan of the brain with venography sequences and contrast administration is paramount. When searching previous reported cases of misdiagnosis of IIH when LP was not performed, no definitive reports were found where the patient was in a typical demographic category for IIH who did not have “red-flag” symptoms at presentation. One study retrospectively reviewed all patients who were diagnosed with aseptic meningitis and who also had increased OP on LP (15). Seven patients met both criteria and had an increased number of white blood cells in CSF with lymphocytic predominance. However, all patients were younger than 19 years, 6 were male, and papilledema was documented in 3 patients only, 2 of whom had neck stiffness with only 1 patient without other constitutional symptoms at presentation, who was 10-year-old. This study highlights the rarity of aseptic meningitis presenting with isolated papilledema and no other red flags on history or examination. Another study reported 3 patients with cryptococcal meningitis all of whom had papilledema; however, 2 were immunocompromised and the third patient had neuroretinitis-like picture at presentation (16). One report highlighted a 21-year-old male patient who presented with papilledema that was eventually linked to aseptic meningitis because of acute HIV infection; the patient had decreased central visual acuity at presentation and a low-grade fever (17). Another report described a 9-year-old boy who presented with symptoms of increased ICP and papilledema and was eventually diagnosed with neuroborreliosis (18). Another article described a 32-year-old woman who had papilledema and increased OP on LP and was found to have human herpesvirus-6 in the CSF. She had a BMI of 48 kg/m2; however, she had a new onset of thunderclap headaches associated with photophobia, nausea, and vomiting, which were not responsive to oral analgesics and sumatriptans (19). Several reports described spinal cord tumors misdiagnosed as IIH: In one, the patient was a 41-year-old woman, who was not obese (exact BMI was not reported), had bilaterally decreased vision and a “left nasal hemianopia” with mildly dilated ventricles on MRI; in the second report, the patient was a 48-year-old man with normal neuroimaging whose BMI was not reported; in the third report, a 41-year-old man complained of distortion of peripheral vision and was found to have papilledema, and his OP on LP was normal, but because of the increased protein in CSF, he was eventually diagnosed with spinal cord plasmacytoma; in the fourth report, a morbidly obese 41-year-old woman experienced progressive visual loss, headaches, nausea, and vomiting and was found to have papilledema and and was eventually diagnosed with as a elevated CSF protein Another report highlighted a man who presented with papilledema and was eventually diagnosed with meningitis due to of the the patient was a very man cases of spinal leptomeningeal were reported that IIH: A woman, whose BMI was not reported had symptoms of headaches and for a was found to have papilledema and elevated CSF protein and eventually abnormal spinal to the the second was that of a whose BMI was also not reported and who also had symptoms of increased ICP, was found to have papilledema of the brain was normal, and LP was performed increased and of the to the diagnosis reports that although very rarely patients with central infection or can present with isolated symptoms of increased IIH and normal brain they never all the criteria that up the characteristics of a patient with presumed IIH where LP can be an important for the that LP is not necessary for the diagnosis of IIH in patients who are in a typical demographic category is that the of an experienced is who can features of the disease at presentation or during In conclusion, the purpose of performing LP before diagnosing a patient with IIH is 2-fold: To confirm elevated OP and to rule out of IIH by establishing its normal composition. In a cohort of patients with typical IIH reported in this of where LP was performed at it did not change the management in any patient and an alternate diagnosis was not in any patient (2). Several cohorts of patients with typical IIH reported in the literature this of reports misdiagnosis of IIH in the of LP did not any results where the patient was both in the typical demographic group for IIH and did not have any red flags on their presentation. Thus, one can that in a patient with presumed papilledema who is in a typical demographic group for IIH (women with increased has no symptoms at presentation and is systemically had neuroimaging that confirmed expected indirect neuroimaging findings of increased ICP and no other and has mild to IIH where surgical treatment is not LP may not be for the diagnosis if the by an experienced is E. Dr. and I about many on the current diagnostic criteria for IIH require LP, LP is helpful to ICP and for secondary causes of high ICP, patients do not there is a risk of and and results can the that there are situations in which LP for workup of suspected IIH is include situations in which the pretest probability for a disease other than IIH is as for patients with or with “red-flag” also include situations in which the risk of incorrect IIH diagnosis and incorrect management is as for patients with severe vision loss or in whom a surgical is on the of an experienced being in the of patients with suspected IIH that features suggesting the diagnosis is not IIH can be and management Dr. the point that there are many patients for whom the is not by a lack of LP. Although I do not LP in I have managed of patients with IIH without LP because of their to the or more by not the or even I do not any outcomes as a However, I do not should as to LP, even for The pretest probability may but never reaches 100%. A risk of a severe disease consideration and with the patient. My other is that it is not to have a in every of suspected IIH because are in will be and it is on us to on diagnosis and that LP is is at risk of and us it and follow the diagnostic which require LP. a patient to the can still about what is and the diagnostic uncertainty that that E. I Dr. for an about LP is important as a part of diagnostic in patients with IIH. main is that an LP of diagnosis by OP of CSF and out of alternate diagnosis by evaluating CSF Dr. that both in this of suffer from selection bias because evaluation and management of patients was performed by expert neuro-ophthalmologists I with and the for the LP in a group of patients of expert and of optic nerve compression in the posterior orbit or optic canal has been provided as one where optic nerve head may be elevated but CSF OP will be normal an alternate diagnosis will be considered based on the LP. I would that in this one would central visual acuity to be In addition, optic nerve compression its should also be on of the brain and orbit with contrast a study that should be performed in all patients with suspected IIH where LP is not a study where there was one of dural venous sinus thrombosis in a cohort of 86 patients with IIH (3), I would again that if the study would have been performed, this misdiagnosis would have been Furthermore, LP in the of dural sinus thrombosis is not helpful in making the diagnosis because it would have increased OP with normal one making the erroneous diagnosis of IIH if neuroimaging has not been It is difficult to on a article by Stunkel where 1 of patients referred for papilledema or abnormal optic disc had a previously missed diagnosis of secondary elevated ICP because no details of this were provided in the study, and do not know whether LP was in making or the diagnosis. It is also difficult to on the study where 4 of 206 patients who were referred for papilledema were found to have a non-IIH diagnosis personal communication, Diagnostic of neuroimaging in suspected intracranial meningitis, and leptomeningeal because this study has not been however, would have been on examination, and a patient with meningitis is unlikely to have been systemically One patient with leptomeningeal carcinomatosis had normal do not know whether the was performed with contrast and whether there were other to an alternate diagnosis. It is also whether this patient had a history of and whether all these non-IIH patients a typical demographic group for IIH. I will the that not performing LP can lead to overdiagnosis of IIH in patients who have In all cases of pseudopapilledema, an expert and diagnostic testing as and would be to a on of it is unlikely that these patients would demonstrate indirect neuroimaging signs of increased of transverse sinus stenosis is in patients with IIH, and by only of patients in one study evaluating of signs of increased ICP and no papilledema on clinical had of transverse sinus stenosis Thus, the of transverse sinus stenosis is a very indirect the of increased ICP and can as a for OP on LP in these patients with pseudopapilledema most of the have normal or visual function and should not be treated even if suspected of having IIH. they a typical demographic group for IIH, have normal visual and are a for loss, this would not have any In if the of LP is to the group of patients LP can be without the risk of an alternate diagnosis that would a in the treatment. This group of patients should be of age with increased have no symptoms and be systemically have normal or visual function central acuity and mean deviation less than on automated visual have and of the brain and with contrast that is other than the of indirect signs of increased ICP, be under the of a experienced in diagnosing and treating patients with IIH. G. P. Van Stavern and A. G. Lee The diagnostic criteria of IIH have been modified several in the in response to in technology and understanding of the disease MR However, LP has been considered in each of the modified Dandy criteria for IIH. It is that in very patients, with clinical and neuroimaging LP be the clinical course from what is expected for IIH. The is the risk of and patients without IIH and and diagnosis of patients with more studies would better In and as described by I have patients who did not the modified Dandy criteria for IIH. Some patients not have or other or severe other patients not or would not have an LP. patients I have documented as having in contrast to other patients who I can as having by modified Dandy Dr. and I that the current of literature is to a definitive to this and it is to than to a on the

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