Comparison of the Range of Lumbar Cerebrospinal Fluid Pressure in Adults With Normal Cerebrospinal Fluid Pressure and in Idiopathic Intracranial Hypertension

Lumbar puncture CSF pressure measurements in a large group of adults (116) having lumbar puncture (LP) for diagnostic reasons with no clinical indication of raised intracranial pressure were used to establish the normal range of CSF pressure. The cerebrospinal fluid (CSF) pressure was also measured in a smaller unselected series of patients (35) with the syndrome of idiopathic intracranial hypertension (IIH). All the lumbar punctures were performed by the same highly skilled operator, a consultant nurse, to ensure accuracy of measurement.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Comparison of the Range of Lumbar Cerebrospinal Fluid Pressure in Adults With Normal Cerebrospinal Fluid Pressure and in Idiopathic Intracranial Hypertension David E. Bateman, MD, FRCP, Barbara Wingrove, MS Background/Methods: Lumbar puncture CSF pressure measurements in a large group of adults (116) having lumbar puncture (LP) for diagnostic reasons with no clinical indication of raised intracranial pressure were used to establish the normal range of CSF pressure. The cerebrospinal fluid (CSF) pressure was also measured in a smaller unselected series of patients (35) with the syndrome of idiopathic intracranial hypertension (IIH). All the lumbar punctures were performed by the same highly skilled operator, a consultant nurse, to ensure accuracy of measurement. Results: The results showed that the mean CSF pressure was 18.7 cm H2O with a range of 1–29 cm H2O in the group with normal CSF pressure. Ninty-five percentage of values was below 29 cm H2O in the group with normal CSF pressure. In the series with IIH, the mean and range were 37.7 cm H2O and 29.5–66 cm H2O, respectively. The lowest recorded pressure in the IIH group was 29.5 cm H2O with 95% of values above 31. Conclusions: This is the first time that the normal range of CSF pressure and that found in a group of patients with IIH has been reported after LP performed by the same operator to ensure inaccuracy of measurement has not biased the results. It suggests that the current upper limit of normal adopted by the revised diagnostic criteria for IIH (25 cm H2O) may be too low. The range of normal CSF pressure and that found in patients with IIH in our study suggests that consideration should be given to revising the upper limit of normal CSF pressure to around 30 cm H2O. Journal of Neuro-Ophthalmology 2022;42:502–504 doi: 10.1097/WNO.0000000000001578 © 2022 by North American Neuro-Ophthalmology Society T he diagnosis of IIH (idiopathic intracranial hypertension) requires the finding of a raised CSF opening City Hospitals Sunderland (DEB), United Kingdom; and RN City Hospitals (BW), Sunderland, United Kingdom. The authors report no conflicts of interest. Address correspondence to David E. Bateman, Department Neurology, South Tyneside and Sunderland NHS Foundation Trust, Kayll Road, Sunderland SR4 7LQ, United Kingdom; E-mail: david. [e-mail] 502 pressure (OP). Many neurology textbooks previously defined the upper limit of normal CSF OP as low as 20 cm H2O (1,2), but an influential study of adults with neurology conditions that do not affect the CSF pressure suggested that the 97.5th centile upper limit is 25, some 25% higher (3). This was then adopted as the upper limit of normal for the revised diagnostic criteria for pseudotumor cerebri syndrome in adults and children (4). Values above 25 cm H2O are now regarded as above the upper limit of normal sufficient to diagnose IIH. Subsequent authors (5,6) have examined the range of normal CSF pressure, further looking at how factors such as BMI and sex might affect it. Bo et al (4) showed that women on average have a slightly lower pressure (by a mean of 1.7) than men (18.5 cm H2O) but women with an increased body mass index (BMI) over 30 a higher mean of 22. Bo et al (4) suggested that the upper limit of normal CSF pressure should be 30. Wang et al (5) in a series of older patients found a mean of 15.5 with some elevation to 18 in the obese patients, but 95% of pressures were less than 26. A recent systematic review (7) of studies of 27 published series of normal lumbar CSF pressure measurements found that the mean was 16.1 cm H2O with a range of 9.8 cm H2O to 22.8 cm H2O. Few of these studies (5) had more than 100 participants. Because the study of Bo (4) with 339 participants was included, this influenced the mean of the results of the systematic review which were therefore very similar. The upper limit of the reference interval of the systematic review however was found to be 22 cm H2O considerably less than the figure of 30 cm H2O suggested by Bo et al (4). Published data do not therefore show consistent agreement of the normal range of CSF pressure, particularly the upper limit. Accurate determination of the upper limit of the normal range clearly requires a large number of participants in this study. The other major difficulty in establishing the normal range with all these previous studies Bateman and Wingrove: J Neuro-Ophthalmol 2022; 42: 502-504 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution is the potential variability in measurement of CSF pressure because of different operators. The LPs in all the previous studies were performed by a number of different clinicians. Measurement of lumbar CSF pressure is not easy, particularly if the LP is performed by inexperienced clinicians and the patient is obese, which is often the case in patients suspected of IIH. The patient needs to be relaxed in the recumbent lateral position to obtain a reliable pressure measurement. LP is often performed in the sitting position because of ease which then requires repositioning of the patient in a relaxed lateral recumbent position to measure the pressure. For these reasons, measurement of CSF pressure is no longer routine in many departments which makes it more difficult to measure accurately when a reliable reading is required. The use of different operators in previous studies and in routine clinical practice is understandable, but nevertheless, measurement of the CSF pressure reliably and accurately is critical in some instances for correct diagnosis and treatment. Failure to ensure this is surely unacceptable particularly for the diagnosis of IIH because it is one of the main crucial defining features of the syndrome. It is also necessary in establishing the normal range of CSF pressure. To avoid this in our department, all LPs were performed by a single nurse consultant very experienced in the technique of LP. This therefore made it possible to obtain a series of pressure measurements for patients having an LP for a variety of neurology conditions with normal CSF pressure and also suspected cases of IIH, all performed by the same operator, thus avoiding the bias that might occur due to inaccuracy caused by different operators. We could therefore get a more accurate definition of the normal range of CSF opening pressure (OP) and the range of pressures in a group of patients with IIH. This would provide more reliable guidance for the correct criterion of CSF pressure required for a diagnosis of IIH. It would also help clarify whether there is a continuum or no overlap in the range of CSF pressure between normal and IIH. METHODS One hundred sixteen adult patients with neurology conditions with normal CSF pressure, such as peripheral neuropathy and suspected MS, had lumbar CSF pressure performed as part of their investigation (Group A), and 35 patients suspected of IIH (Group B). These were defined by the syndrome of symptoms of IIH (headache, pulsatile tinnitus, and visual obscurations) with swollen disks on routine fundoscopy (Frisen Grade 1 or above), a negative CT or MRI scan of the head, and acellular CSF on analysis (Table 1). The lumbar punctures were all performed by the same nurse consultant. LPs were performed as follows: Patients were positioned in the left lateral position, but if the BMI was significantly raised, the sitting position was used with repositioning to the left lateral position when the Bateman and Wingrove: J Neuro-Ophthalmol 2022; 42: 502-504 TABLE 1. Group A (normal) and Group B (IIH) CSF pressures cm water CSF pressures (cm H2O) Mean Median Max Min Range Standard deviation Variance N Group A Group B 18.7 18.30 30.5 1.0 29.5 5.2 26.7 116 37.7 35.0 66.0 29.5 36.5 8.2 66.5 35 needle was inserted successfully into the space. The pressure was allowed to settle, and a reading was taken when the fluid ceased to rise or fall but was pulsing gently because of respiration. Patients were then requested to give a gentle cough to ensure the fluid level was not prompted to rise further. A 90-mm needle was used unless the elevated BMI required a longer needle. Manometer extensions were also used if the pressure exceeded 40 to ensure accuracy of measurement. A 22-gauge needle was used exclusively. RESULTS There were 116 adult patients in Group A (normal) and 35 in Group B (IIH). The mean pressure for Group A was 18.7 cm H2O with a range of 1–30.5 (29.5) cm H2O. Ninty-five percentage of normal values was below 29 cm H2O. The mean and range for Group B were 37.7 cm H2O and 29.5–66 (36.5) cm H2O, respectively, with 95% values above 31. There was a highly significant difference between the 2 groups (P , 0.0005 Student 2-tailed t test). Figure 1 is a bar chart showing the 2 CSF pressure distributions, normal and raised in IIH, to demonstrate the range and overlap derived from a pivot table in Excel. DISCUSSION This is the first time that a series of 2 groups of patients with normal CSF pressure and IIH, respectively, has been reported with all the CSF pressure measurements performed by the same highly skilled operator. This is very important because it is imperative to avoid inaccuracies and bias in the measurements contributing to the results in defining the normal range of lumbar CSF pressure. Analysis of the CSF pressure measurements in this series of 116 adult neurology patients having LP for routine investigation with normal CSF pressure showed a range of pressures up to 30.5 cm H2O with only a single patient above 29 cm H2O (95% of values below 29). This is higher than in some of the previous series (3) where the 97.5% confidence limit was 25, which led to this value being used for the definition of CSF pressure to diagnose IIH. These LPs were likely however to have been 503 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Bar chart showing the range of CSF pressures in the 2 groups normal (A) and IIH (B) demonstrating the overlap in the 2 distributions derived from a pivot table in Excel. performed by a variety of different operators. The authors (3) comment that they did not control for the “neurologist’s proficiency at lumbar puncture” which may account for the difference. Loss of CSF can easily occur when attaching the manometer and performing the rest of the procedure. Both of these difficulties will result in lower pressures. More familiarity with the procedure is likely to make it easier to avoid this and also leaks while taking the measurement. The results of a recent systematic review (7) of studies of normal CSF pressures suggested a lower upper limit of normal (22 cm H2O). However, our results and those of Bo et al are probably more reliable, given the larger numbers of participants in both our studies (116 and 339) and the use of a single highly experienced reliable operator performing the LPs in our series. The mean number of participants in the series used for the systematic review was 49. Our findings are very close to those of Bo et al (4) who suggested an upper limit of 30 cm H2O for normal CSF pressure in men and 27.5 cm H2O for women with a BMI greater than 31 which is most commonly the case in patients with IIH. Their results and the confirmation by our large series performed by a single operator to minimize inaccuracy raise doubts that the upper limit of normal CSF pressure is 25 cm H2O or lower. Swollen disks are part of the definition of the core syndrome of IIH. They are an undoubted clinical manifestation of raised intracranial pressure. Our results show that the lowest recorded pressure with swollen disks was 29.5. Swollen disks appear unlikely therefore to develop with CSF pressures much below 30, further evidence that this is a reasonable upper limit of normal CSF pressure with values above this abnormal. Generally, however, our study shows that patients with IIH have substantially higher pressures with a mean of 37.7 cm H2O. Our results therefore suggest caution diagnosing IIH with CSF pressures below 30. They suggest that consider504 ation should be given to raising the CSF pressure required for the diagnosis of IIH. Values between 25 and 30 cm H2O should be regarded as equivocal requiring further monitoring before treatment. Given the discrepancies in the currently available data, further large series of the range of normal CSF pressure would be helpful in resolving definitively the normal range of CSF LP pressure. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: D. E. Bateman and B. Wingrove; b: Acquisition of data: D. E. Bateman and B. Wingrove; c. Analysis and interpretation of data: D. E. Bateman and B. Wingrove. Category 2: a. Drafting the manuscript: D. E. Bateman and B. Wingrove; b. Revising it for intellectual content: D. E. Bateman and B. Wingrove. Category 3: a. Final approval of the completed manuscript: D. E. Bateman and B. Wingrove. REFERENCES 1. Daroff RG, Bradley WG, Marsden C. Neurology in Clinical Practice. Boston, MA: Butterwoth Heinemann (Elsevier), 2004. 2. Warrell DA, Cox TM, Cox JD, Benz EJ, eds. Oxford Textbook of Medicine. 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Bateman and Wingrove: J Neuro-Ophthalmol 2022; 42: 502-504 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.