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Show Clinical Research: Epidemiology Meets Neuro-Ophthalmology Section Editors: Heather E. Moss, MD, PhD Stacy L. Pineles, MD, MS Identifying Incidence of and Risk Factors for FluoroscopyGuided Lumbar Puncture and Subsequent Persistent LowPressure Syndrome in Patients With Idiopathic Intracranial Hypertension Patricia Lu, BS, Manu Goyal, MD, Julia B. Huecker, MS, Mae O. Gordon, PhD, Gregory P. Van Stavern, MD Background: To explore the incidence of and potential risk factors for developing persistent low-pressure syndrome after lumbar puncture (LP) in patients with idiopathic intracranial hypertension (IIH), as measured by use of blood patches. Methods: A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and LP, comparing them to patients with multiple sclerosis (MS) as controls who also received diagnostic LPs. Demographic, clinical, and radiological data were collected for each patient. The main outcome measure was the rate of post-LP blood patches in IIH patients compared with MS patients. Secondary outcome measures were the likelihood of undergoing an epidural blood patch related to age, body mass index, volume removed, opening pressure, the difference between opening and closing pressure, and the level of puncture within the IIH cohort. Results: One hundred four IIH patients and 149 MS patients were included in the study. Among IIH patients, 12/104 (11.5%) underwent an epidural blood patch after LP as compared to 8/149 (5.4%) of the MS control patients (P = 0.086). Within the IIH population, none of the clinical or LP parameters were significantly correlated with increased risk of needing a blood patch. Department of Ophthalmology and Visual Sciences (PL, JBH, MOG, GPVS), Washington University School of Medicine, St. Louis, Missouri; Mallinckrodt Institute of Radiology (MG), Washington University School of Medicine, St. Louis, Missouri; and Department of Neurology (MG, GPVS), Washington University School of Medicine, St. Louis, Missouri. Supported by DOVS Core Grant 5 P30 EY02687, Institute for Clinical and Translational Sciences grant RR023496, Biostat Core Grant U54 RR023496, an unrestricted grant from Research to Prevent Blindness, NIH Core Vision Grant P30 EY02687, and Dean's Fellowship (Washington University School of Medicine, Washington University in St. Louis, Missouri). The authors report no conflicts of interest. Address correspondence to Gregory P. Van Stavern, MD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8096, St. Louis, MO 63110-1010; E-mail: vanstaverng@vision.wustl.edu Lu et al: J Neuro-Ophthalmol 2019; 39: 161-164 Conclusions: The incidence of low-pressure syndrome, as measured by blood patches, is similar in IIH patients and MS controls. This suggests that having elevated intracranial pressure before an LP is not protective against developing postpuncture low-pressure syndrome, contrary to common assumptions. Journal of Neuro-Ophthalmology 2019;39:161-164 doi: 10.1097/WNO.0000000000000719 © 2018 by North American Neuro-Ophthalmology Society I diopathic intracranial hypertension (IIH) is a neurologic disorder characterized by elevated intracranial pressure (ICP) of an unknown cause. Patients most often present with headache but can also experience transient visual obscurations, pulsatile tinnitus, and papilledema leading to vision loss (1). IIH is relatively uncommon, with an annual incidence of 0.9/100,000 persons and 3.5/100,000 in women 15-44 years of age, but there is increased incidence in obese women (2). A diagnosis of IIH must meet the modified Dandy criteria (3), which includes no known cause of the elevated ICP. Clinically, ICP is determined by lumbar puncture (LP) and one common side effect of LP is low-pressure syndrome, a condition caused by persistent leak of cerebrospinal fluid (CSF) from the puncture site. This occurs in up to 30% of patients with normal ICP and is characterized by headache occurring within 7 days of LP, worsened when standing and improved when supine (4,5). This LP low-pressure syndrome is usually self-limited and can be managed with supportive treatment such as rehydration, analgesics, caffeine, and antiemetics, but refractory cases can be incapacitating and require an epidural blood patch (6). An epidural blood patch is a procedure in which autologous blood is injected into the lumbar epidural space, where it clots and seals the perforation from the 161 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Research: Epidemiology Meets Neuro-Ophthalmology LP, preventing further CSF loss (7). The incidence of persistent post-LP low-pressure syndrome in IIH patients is unknown but traditionally believed to be low, because of their baseline elevated ICP (8). The purpose of our study was to examine the incidence of and potential risk factors for developing persistent low-pressure syndrome in IIH patients, as measured by use of blood patches. METHODS Study Population A retrospective chart review was conducted of patients seen in our neuro-ophthalmology and neuroradiology clinics from March 1999 through June 2016. Inclusion criteria were definite diagnosis of IIH using established diagnostic criteria (9), at least one fluoroscopy-guided LP, and patient age of 18 years or older. Inclusion criteria for controls included possible or established diagnosis of multiple sclerosis (MS), at least one fluoroscopy-guided LP, and patient age of 18 years or older. The patients with MS were used as controls because they also received diagnostic LPs but would not be expected to have papilledema or elevated ICP. Data Collection Approval for this study was obtained from the Washington University Human Research Protection Office before data accumulation, and all HIPAA regulations regarding the use of personal health information were strictly followed. As this was a retrospective study, requirement for informed consent was waived. The following demographic, clinical, and radiological data were collected for all patients: age, sex, race, body mass index (BMI), opening and closing pressure on LP, volume of CSF removed, needle size and type used, and spinal level of LP. Finally, we recorded whether patients received an epidural blood patch within 30 days of their diagnostic LP based on electronic chart review and review of a database kept by neuroradiology. Main Outcome Measures The primary outcome analysis compared the rate of postLP blood patches in IIH patients with MS patients, with blood patch frequency used as a surrogate for significant and persistent low-pressure syndrome. All patients included in the study were evaluated by the same neuro-ophthalmologist who used consistent clinical thresholds to make the determination that the post-LP headache was positional in nature and a separate entity from their baseline IIH headache. Both populations received their LPs from the same radiology practice and were given the same routine post-LP recommendations of rest, fluids and caffeine. The decision to proceed to blood patch also was made by the same neuro-ophthalmologist whose criteria consisted of a refractory positional headache that did not improve with 3-5 days of conventional treatment. The timing of the blood patch was determined by the severity and disability caused by the headache. Within IIH patients, we also evaluated whether the likelihood of undergoing an epidural blood patch was related to age, BMI, needle gauge, volume removed, opening pressure, the difference between opening and closing pressure, and level of puncture. Needle type and size were evaluated. However, because of the overwhelming use of the Quincke needle with a wide range of needle lengths, there was insufficient data for comparative analysis. Statistical Analysis Chi-square tests and t tests were used to compare the IIH patients with the MS patients, and a univariate logistic regression model was used to identify potential predictors of blood patch use within the IIH cohort using SAS V9.4 (Cary, NC) software. RESULTS One hundred four IIH patients (102 women, 2 men) with a mean age of 30.5 ± 9.0 years and 149 MS patients (112 women, 37 men) with a mean age of 40.5 ± 9.7 years were included in the study. Of the IIH patients, 79 (76%) were white and 25 (24%) were African American. Of the patients with MS, 118 (79%) were white, 27 (18%) were African American, and 4 (3%) were other. Demographic and selected clinical parameters of the 2 populations are found in Table 1. Among IIH patients, 12/104 (11.5%) underwent an epidural blood patch after LP as compared to 8/149 (5.4%) of the MS control patients (P = 0.086, odds ratio TABLE 1. Demographic information of patients with IIH and MS Patient Demographics Age (yr) BMI (kg/m2) Sex (% female) Volume removed (mL) Opening pressure (cm of H2O) IIH (n = 104) 30.5 ± 37.0 ± 98 15.2 ± 28.5 ± 9.0 9.8 9.7 7.8 MS (n = 149) 40.5 ± 29.5 ± 75 13.5 ± 14.5 ± 9.7 8.0 5.0 5.3 P value ,0.001 ,0.001 ,0.001 0.058 ,0.001 BMI, body mass index; IIH, idiopathic intracranial hypertension; MS, multiple sclerosis. 162 Lu et al: J Neuro-Ophthalmol 2019; 39: 161-164 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Research: Epidemiology Meets Neuro-Ophthalmology TABLE 2. Odds ratios of needing a blood patch given the clinical parameters of patients with IIH Age (yr) BMI (kg/m2) Needle gauge Volume removed (mL) Opening pressure (cm of H2O) Opening-closing pressure (cm of H2O) Odds Ratio 95% Confidence Interval P value 0.99 0.94 1.16 0.98 0.94 0.94 0.93-1.07 0.87-1.01 0.50-2.69 0.92-1.06 0.85-1.04 0.88-1.01 0.95 0.08 0.12 0.65 0.20 0.08 BMI, body mass index; IIH, idiopathic intracranial hypertension. 2.23, 95% CI 0.88-5.65). The average time between LP and blood patch was similar for the 2 groups, 4.3 days for the IIH cohort and 4.1 days for the patients with MS. Within the IIH population, none of the clinical or LP parameters were significantly correlated with increased risk of needing a blood patch. Level of LP was assessed but given that 92% of the blood patches occurred after LPs performed at either L2-L3 or L3-L4, no statistical comparisons were made with the other regions. Table 2 shows the odds ratios of undergoing a blood patch given various clinical parameters of the IIH cohort. DISCUSSION We sought to determine whether the frequency of persistent post-LP low-pressure syndrome was comparable in IIH patients and controls, as well as what factors might increase risk in the IIH cohort. This arose out of concern of traditional thinking that elevated ICP is protective from developing low-pressure syndrome. This is especially important given that every diagnosis of IIH involves performing an LP. Thus, despite their baseline elevated level of ICP, they are an at-risk population. Our results indicate that the persistent low-pressure syndrome, as measured by rate of blood patches, is similar in IIH patients and controls. This suggests that having elevated ICP before an LP is not protective against developing persistent postpuncture lowpressure syndrome, contrary to common assumptions (8). With a blood patch rate of 11.5% in IIH patients, the prevalence of persistent low-pressure syndrome in IIH is higher than previously believed. We also acknowledge that we may have underestimated the occurrence of persistent low-pressure syndrome because only patients with more severe headaches that did not resolve on their own proceeded to blood patches. Both groups of patients received LPs in the same practice with consistent clinical thresholds for progression to blood patch, making physician-related factors less likely as an explanation for our findings. All patients also were given the same post-LP recommendations of rest, fluids, and caffeine. However, the use of blood patches as a surrogate marker is still an important caveat. We Lu et al: J Neuro-Ophthalmol 2019; 39: 161-164 acknowledged that there may be other factors that we failed to recognize leading to persistent low-pressure syndrome and blood patches. Our secondary analysis centered on factors that may increase the risk of persistent low-pressure syndrome in the IIH cohort, but our data were not sufficient to identify any predictors. A larger number of patients and controls would have been beneficial because we may have been able to detect significant differences and would have had more power for analysis. In addition, a larger study would have allowed us to test the efficacy of preventative measures such as noncutting needles, which have been shown to reduce the risk of post-LP low-pressure syndrome (10,11). The main limitations of our study include small sample size; patient data were not completely consistent because it was obtained retrospectively and the use of blood patch as a surrogate for persistent low-pressure syndrome. There were also significant demographic differences between the 2 groups of patients studied; however, this was expected given the at-risk population for IIH. Although this may be a confounding factor, given that most IIH patients were reproductive-age women with a higher BMI and opening pressure, the ramifications of this research are still clinically applicable. An important caveat is that these data were collected from a single center with most clinical decisions made by a single physician, providing consistency but potentially lacking generalizability. Future research on this topic would benefit from a larger, prospective multicenter study with more rigorous criteria for low-pressure syndrome with analysis of clinical parameters including as needle type (cutting vs noncutting). Another variable worth exploring is the number of attempts of LP required to obtain CSF, as obesity is a risk factor for technically difficult LPs that may predispose patients to multiple dural punctures and subsequent low-pressure syndrome. Nevertheless, our results show that persistent lowpressure syndrome requiring blood patches is as frequent in IIH patients as those with normal ICP, and increased ICP does not protect against the potential need for a blood patch. 163 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Research: Epidemiology Meets Neuro-Ophthalmology STATEMENT OF AUTHORSHIP Category 1: a. conception and design: G. P. Van Stavern, M. Goyal, and P. Lu; b. acquisition of data: G. P. Van Stavern, M. Goyal, and P. Lu; c. analysis and interpretation of data: J. B. Huecker and M. O. Gordon. Category 2: a. drafting the manuscript: P. Lu; b. revising it for intellectual content: G. P. Van Stavern, M. Goyal, J. B. Huecker, and M. Gordon. Category 3: a. final approval of the completed manuscript: G. P. Van Stavern, M. Goyal, J. B. Huecker, and M. Gordon. REFERENCES 1. Wall M. Idiopathic intracranial hypertension. 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