Journal of Neuro-Ophthalmology, September 2014, Volume 34, Issue 3

Cerebrospinal Fluid Pressure in Adults

Lumbar puncture (LP) is a widely-used investigative procedure. It allows relatively non-invasive measurement of intracranial pressure (ICP) which may have a significant impact on diagnosis and/or patient management. Over the years there has been considerable discussion about various aspects of the procedure, including what constitutes a normal opening pressure, what factors might influence this, and how LP is best performed. A review of the literature was carried out by searching PubMed and Medline, scanning relevant medical journals for recent publications, and carrying out secondary referencing and contacting other clinicians, where appropriate. The normal range of ICP measured by LP in adults in a typical clinical setting should now be regarded as 6 to 25 cmH2O (95% confidence intervals), with a population mean of about 18 cmH2O. There is, however, considerable variability: some normal individuals have pressures of 30 cmH2O (or, occasionally, even higher) meaning that pressure measurements must be interpreted in the clinical context. This article aims to provide the practicing neuro-ophthalmologist with up-to-date information about the ways in which various factors can influence pressure measurements obtained at LP.

Cerebrospinal Fluid Pressure in Adults Sarah C. M. Lee, MBBS, BSc, Christian J. Lueck, PhD, FRACP, FRCP Background: Lumbar puncture (LP) is a widely-used inves-tigative procedure. It allows relatively non-invasive measure-ment of intracranial pressure (ICP) which may have a significant impact on diagnosis and/or patient manage-ment. Over the years there has been considerable discus-sion about various aspects of the procedure, including what constitutes a normal opening pressure, what factors might influence this, and how LP is best performed. Evidence Acquisition: A review of the literature was carried out by searching PubMed and Medline, scanning relevant medical journals for recent publications, and carrying out secondary referencing and contacting other clinicians, where appropriate. Results: The normal range of ICP measured by LP in adults in a typical clinical setting should now be regarded as 6 to 25 cmH2O (95% confidence intervals), with a population mean of about 18 cmH2O. There is, however, considerable variability: some normal individuals have pressures of 30 cmH2O (or, occasionally, even higher) meaning that pressure meas-urements must be interpreted in the clinical context. Conclusions: This article aims to provide the practicing neuro-ophthalmologist with up-to-date information about the ways in which various factors can influence pressure measurements obtained at LP. Journal of Neuro-Ophthalmology 2014;34:278-283 doi: 10.1097/WNO.0000000000000155 © 2014 by North American Neuro-Ophthalmology Society Lumbar puncture (LP) is a widely used procedure in the diagnosis of infectious, inflammatory, and neoplastic conditions. It also plays a crucial role in the diagnosis and management of conditions involving elevated intracranial pressure (ICP), most notably idiopathic intracranial hyper-tension (IIH) (1). The procedure was first described over 100 years ago (2), and millions of patients around the world have subsequently been subjected to it. Somewhat surpris-ingly, there are still areas of uncertainty and confusion, most notably what constitutes the normal range of cerebrospinal fluid opening pressure (CSF-OP), and what factors (e.g., the patient's weight or position during the procedure) might influence this. A century of investigation has shown that normal ICP is influenced by a number of factors, both internal (e.g., arterial pressure, respiration, temperature, pCO2, and sleep) and external (e.g., gravity and position). A detailed review of these factors is beyond the scope of this article and the interested reader is referred elsewhere (3,4). This article will review recent findings related to the normal range of CSF-OP as measured clinically at LP, and then look at the technique of LP itself, specifically addressing factors such as patient positioning and choice of needle size. CEREBROSPINAL FLUID OPENING PRESSURE: WHAT IS NORMAL? LP was introduced into clinical practice toward the end of the nineteenth century by clinicians including Quincke, Wynter and Queckenstedt (2). During the early twentieth century, many studies looked at CSF-OP (5-8), and the reference ranges derived from these studies are still cited in the latest editions of many major textbooks defining the upper limit of the normal range of CSF-OP as 15 cmH2O (9), 18 cmH2O (10), or 20 cmH2O (4,11-13). Clinical experience suggests that these upper limits are too low (14), and, indeed, studies as early as 1974 found that between 16% and 25% of normal subjects had CSF-OPs higher than these values (15,16). Four recent studies have looked carefully at CSF-OP (Table 1). The first was a prospective study of 242 adults undergoing LP for routine investigation of non-pressure-related neurological conditions. The authors found a median CSF-OP of 17 cmH2O with an upper 95% confidence interval (CI) of 25 cmH2O (14). A similar prospective study of 348 adult patients found a median CSF-OP of 19 cmH2O with an upper quartile of 23 cmH2O (17). A study of 197 children (aged 1-18 years) found very similar results with a median Department of Neurology (SCML, CJL), The Canberra Hospital, Canberra, Australia; Department of Neuroscience (SCML), Box Hill Hospital, Box Hill, Australia; and Australian National University Medical School (CJL), Canberra, Australia. The authors report no conflicts of interest. Address correspondence to Christian J. Lueck, PhD, FRACP, FRCP, Department of Neurology, The Canberra Hospital, PO Box 11, Woden, ACT 2606, Australia; E-mail: [e-mail] 278 Lee and Lueck: J Neuro-Ophthalmol 2014; 34: 278-283 State-of-the-Art Review Section Editors: Valérie Biousse, MD Steven Galetta, MD Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. CSF-OP of 19 cmH2O and an upper 95% CI of 28 cmH2O (18). A much larger retrospective chart review of 12,118 adults found a slightly lower median pressure of 15.6 cmH2O (19), but this result was probably artifi-cially low because the authors excluded any subject with a CSF-OP of .25 cmH2O, stating that this value repre-sented the upper limit of normal. In fact, 25 cmH2O refers to the upper 95% CI, not the absolute upper limit of the normal range so their study would have excluded 3%-5% of normal subjects with pressures higher than this (14,18). Taken together, these 4 studies suggest that the values quoted in many textbooks are incorrect, and that the upper limit of CSF-OP in normal adults should now be regarded as 25 cmH2O. Indeed, some otherwise normal individuals can have pressures above this value, occasion-ally above 30 cmH2O (14,17). The upper limit of 25 cmH2O has been incorporated into the most recent defi-nition of IIH (1), whereas a lower limit of normal of 6 cmH2O has been incorporated into the most recent defi-nition of headache induced by reduced ICP (20). BODY MASS INDEX IIH has a clear association with obesity (21,22). It has been suggested that obesity is associated with increased CSF-OP in otherwise normal people (23), but this is the subject of some controversy. Smaller studies of over 50 subjects have often failed to show a clear correlation between body mass index (BMI) and CSF-OP (24,25). Slightly, larger studies have shown a nonsignificant increase in mean CSF-OP in obese subjects (16), but not if patients with abnormal mag-netic resonance venograms were excluded (26). Even larger studies of over 200 subjects have demonstrated a significant correlation between BMI and CSF-OP: these studies sug-gested that mean CSF-OP rises by about 0.3 cmH2O for every unit increase in BMI (14,18,27). However, the cor-relation coefficients are low in these studies, meaning that the association is not clinically useful because of interindi-vidual variability. One factor which, in theory, might influence CSF-OP in "normal" individuals is as-yet undiagnosed obstructive sleep apnea (OSA). In one study, 6 patients with known OSA demonstrated significant elevations in ICP during pro-longed periods of apnea while asleep (28). The authors reported ICP was also elevated while awake in these pa-tients, but only 3 of their 6 patients had awake pressures of .25 cmH2O. Another study of 4 patients with OSA found normal awake CSF-OP in all 4, despite the fact that they all had papilledema (29). Recent studies have suggested that there is no increase in the frequency of papilledema in patients with OSA (30,31) nor, there is a clear increase in the incidence of OSA in patients with IIH (32). These results suggest that a single measurement of CSF-OP while the patient is awake might not be adequate, and the rela-tivity of OSA and ICP requires further study. AGE AND OTHER FACTORS CSF-OP in children is addressed in an accompanying article, which suggests that normal children may have a CSF-OP as high as 28 cmH2O (33). A recent study of 40 healthy older subjects aged between 60 and 82 years found a median CSF-OP of 15.8 cmH2O (95% CI, 10.6-19.4 cmH2O) (34), and the authors concluded that these results were similar to those found in young and middle-aged patients. However, their numbers were small. According to a very large retrospective chart review of over 12,000 patients, mean CSF-OP declines steadily after the age of 50 years. This study found the mean CSF-OP in patients aged 90-95 years to be only 11.4 ± 3.2 cmH2O, about 27% lower than the normal range quoted above (19) (as discussed previously, however, all patients with CSF-OP above 25 cmH2O were excluded from this study, so the absolute value of CSF-OP may have been somewhat underestimated; this would be unlikely to influence the finding of an age-related effect of lowering ICP). On average, men may have a slightly higher mean CSF-OP than women by about 1-2 cmH2O (17,19), but this is not clinically significant. Pain from headache may have a similar, small effect on CSF-OP (17). To the best of our knowledge, there are no studies showing a significant effect of race, mean arterial pressure, or diabetes mellitus on CSF-OP. POSITIONING: WHAT MATTERS? Lateral Decubitus, Sitting, or Prone? LP has traditionally been performed in the left lateral decubitus (recumbent) position (35-37). CSF-OP being determined manometrically against a zero at the level of the needle in the spinal canal. It is technically easier to perform an LP with the patient sitting up and leaning for-ward because this increases the distance between lumbar spinous processes (38,39). However, a manometrically derived pressure in the sitting position is misleading, mean values being elevated by approximately 25 cmH2O (5). Accordingly, CSF-OP should never be measured with the patient in the seated position; the patient must be horizon-tal so that the head (strictly speaking, the right atrium), and LP needle are level with each other. Because LPs can be technically difficult, particularly in overweight individuals, there is an increasing tendency to ask radiologists to perform them under image guidance. In this situation, the LP needle is generally inserted with the patient in the prone position. Only a minority of radiologists rotate patients from prone to left lateral decubitus position before measuring CSF-OP (40). There are 2 issues which need consideration when measuring CSF-OP in the prone posi-tion. First, the reading from the manometer must be Lee and Lueck: J Neuro-Ophthalmol 2014; 34: 278-283 279 State-of-the-Art Review Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. TABLE 1. Details of 4 recent studies evaluating CSF-OP at LP in normal individuals Study Number; Gender Ratio Age, yr BMI; Median (range), kg/m2 CSF-OP; Median, cmH2O Range of CSF-OP, cmH2O Comments Whiteley et al (14) 242; 45% M:55% F 45 (18-88), median (range) 26.0 (13.0-52.0) 17.0 9-28 (range); 10-25 (95% CI) Prospective study Bø et al (17) 348; 43% M:57% F 46.7 ± 16.6 (mean ± SD) - 19.0 15-23 (interquartile range) Prospective study BMI information not available Avery et al (18) 197; 47% M:53% F 1-18 (range) 18.5 (12.9-49.1) 19.0 6-47 (range); 10-32 (95% CI) Prospective study Fleischman et al (19) 12,118; 49% M:51% F 55 (20-95), median (range) 26.1 (10.1-49.1)* 15.6† 6.0-25.0 (range)† Retrospective chart review Results quoted from 20 to 49 year age range and converted from mm Hg to cmH2O for comparison †All pressures above 25 cmH2O were excluded *BMI recorded in only 35.5% of subjects. BMI, body mass index; CI, confidence interval; CSF-OP, cerebrospinal fluid opening pressure; LP, lumbar puncture. 280 Lee and Lueck: J Neuro-Ophthalmol 2014; 34: 278-283 State-of-the-Art Review Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. corrected to a zero at the level of the spinal canal, either by adding the length of the spinal needle to the measurement from the manometer or by inserting a flexible rubber tube so that the position of the manometer can be adjusted (Fig. 1). Second, particularly in obese patients, abdominal compres-sion in the prone position may elevate CSF-OP. Studies differ regarding how much this matters. In one study, CSF-OP measured in prone was elevated by about 3 cmH2O (24) compared with the left lateral decubitus position. Another study found the difference was only 1.2 cmH2O and, therefore, clinically insignificant (25). Interestingly, the patients in the latter study were, on average, slightly more overweight than in the former (mean BMI, 35 vs 31 kg/m2). Leg Extension and Valsalva Maneuver It is widely recommended that patients be asked to extend their legs and neck before measuring CSF-OP because that hip flexion may increase CSF-OP by increasing intra-abdominal pressure (16,41). Two earlier studies found that a tightly flexed position elevates CSF-OP by, on aver-age, 6-8 cmH2O (42,43), whereas more recent studies have found differences of only 1-2 cmH2O (44,45). Occasional subjects paradoxically demonstrate increased CSF-OP with leg extension (42,44,46), so the practice of extending legs may not be that important. This is particularly relevant to performing LPs in children when it can be difficult to get the patient into an extended position (45,47). However, the practice of extending legs does reduce the chance of Valsalva-induced increase in CSF-OP. In one study, performing a Valsalva maneuver transiently elevated CSF-OP by a mean of 17.7 cmH2O (the maximum increase being from 16 to 47 cmH2O in 1 subject) (48). In another study, there was a mean elevation of 14.3 ± 3.7 cmH2O (49). Accordingly, it is appropriate to continue to ask patients to extend their legs (and relax) when possible. Needle Size The choice of needle is important. There is considerable discussion in the literature regarding the use of atraumatic needles and/or smaller needles to minimize the risk of post- LP headache (50). The issue of needle type is beyond the scope of this article, but size matters when measuring pres-sure. One study found that CSF-OP measured through a larger, 22-gauge, needle was slightly lower (by about 1.2 cmH2O) than that measured through a smaller, 26- gauge, needle (15). Although this difference is probably FIG. 1. Diagram to demonstrate "zeroing" of the manometer reading when a LP is performed in the prone position. A. LP performed in the left lateral decubitus position. The needle is in the spinal canal (sc), and the fluid in the manometer rises so that the meniscus is at a level m. The cerebrospinal fluid opening pressure (CSF-OP) is the height of the column of CSF, h, that is, the difference between sc and m. B. When an LP is performed in the prone position, the hub of the needle is above the level of the spinal canal. The meniscus in the manometer will therefore give a lower reading, h9. To obtain the true CSF-OP, the length of the needle, N must be added to h9. C. Alternatively, the manometer tube can be separated from the needle by a flexible tube and repositioned so that the base of the manometer is at the level of the spinal canal. In this case, the height of the meniscus (h) will represent the true CSF-OP. LP indicates lumbar puncture; CSF-OP, cerebrospinal fluid opening pressure. Lee and Lueck: J Neuro-Ophthalmol 2014; 34: 278-283 281 State-of-the-Art Review Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. not clinically important (24,25), the time taken to reach equilibrium is significantly affected by needle size and this does matter: it takes 1-2 minutes for 90% of the total cerebrospinal fluid (CSF) height to be reached through most 22G needles. Equilibration time through larger (20G) nee-dles is only 30-60 seconds (51). Smaller needles (24G or 25G) require several minutes for equilibration and are best avoided if measurement of CSF-OP is important (51). Other Factors Choice of intervertebral space seems to have no significant effect on CSF-OP (24,25), but pain and anxiety increase it (17). Sedation or anesthesia may increase CSF-OP (25,45), and an effect as large as 8 cmH2O has been reported (52). This issue is particularly relevant to children and is dis-cussed further in an accompanying article (33). OTHER WAYS OF MEASURING CEREBROSPINAL FLUID PRESSURE A single measurement of ICP may not, by itself, confirm or refute a diagnosis. All measurements need to be interpreted in clinical context, and it may be necessary to undertake repeated measurements to clarify the diagnosis. On occasion, it may be necessary to consider more invasive techniques of measuring CSF pressures. The most accurate way of measuring ICP is a ventricular catheter connected to an external strain gauge (53,54). Although routinely used in neurosurgical intensive care units, partic-ularly in patients with head trauma, such devices are inap-propriate for most neuro-ophthalmic purposes. However, invasive monitoring of ICP is sometimes performed, partic-ularly if the diagnosis is unclear, either through direct intra-cranial monitoring (55) or through lumbar catheter (56,57). There are various different sites at which a pressure monitor can be located, and many different monitors are available, each with its own advantages and disadvantages (53,54). ICP measured at LP seems to correlate very well with intraventricular pressure (58). CONCLUSIONS LP is still the most practical and appropriate way to measure CSF-OP in neuro-ophthalmological practice. It should ideally be performed with the patient in the left lateral decubitus position and, though this is probably not crucial, patients should be asked to straighten their legs before making a measurement. Performing the LP in a prone position for the purposes of image guidance is acceptable provided the manometer reading is appropri-ately zeroed. For the purposes of measuring pressure, LP should be performed through a larger needle, preferably at least 20-gauge. Sedation or anesthesia is better avoided if possible. 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Lee and Lueck: J Neuro-Ophthalmol 2014; 34: 278-283 283 State-of-the-Art Review Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.