This systematic review aimed to establish reference intervals for normal ICP and LCSFop. Through an extensive literature search, 44 studies examining either ICP or LCSFop in pseudo-normal or normal participants were identified, and of these, 36 provided sufficient pressure values and statistical data to calculate reference intervals. Nine studies reported ICP values, while 27 reported LCSFop values. The overall study quality was moderate. For ICP, the study material were scarce, and the reference intervals were based on a small sample size. Data on LCSFop were, in comparison, comprehensive in both lateral recumbent position and supine position. Finally, the reference intervals for both ICP and LCSFop were found to differ significantly between body positions, demonstrating the need for position-dependent reference intervals.
The literature further indicates that age, weight, neck position, zeropoint for measurement-site, and monitoring equipment is of great importance in measurement of ICP and LCSFop [10, 24, 37–42]. Especially zeropoint is of uttermost importance when measuring ICP in upright position. In supine and lateral recumbent position, zeropoint matters to the extend that it has to be in the midline of the patient which is a clinical standard in most neurological and neurosurgical departments. However, only nine of the included studies described the zeropoint of measurements. In terms of the studies reporting on measurement in upright position two out of six studies reported on zeropoint. Thus, for the purpose in this systematic review, data in the included studies were too scarcely reported for meaningful analysis, and thus the reference values were not corrected for the above mentioned factors.
The measured intracranial pressure is clearly dependent on the zero point of the measurements. In supine and lateral recumbent position, it is less imporant as long as it is in the midline of the patient. However, in Nine of the study reported on zero point,
Reference intervals for ICP
Due to the still invasive nature of obtaining ICP, it is ethically unacceptable to examine ICP in healthy normal individuals. Several non-invasive ICP measuring methods have been developed, and though they can be useful to estimate interpatient ICP differences, e.g., during follow-up, none are currently accurate enough to measure ICP values[43, 44].
The studies in this review included pseudo-normal patients[21, 45–47], and we identified no published studies of ICP on completely healthy participants. In the last decade, a new telemetric monitoring technique has become available, allowing for ICP measurements for several months after implantation[48–50]. This has resulted in ICP measurements in groups outside of the traditional patient-categories with suspected ICP disorders. Andresen et al. implanted a telemetric ICP monitor in patients who had a small demarcated intracranial tumor surgically removed, thus establishing a pseudo-normal cohort. Though this cohort is not completely healthy, long-term measurements via the telemetric ICP monitor provide ICP values at a time when intracranial conditions, including ICP, can be considered normal. This is an improvement to previous research, which have been mainly based on patients undergoing diagnostic evaluation for a suspected ICP disorder[21, 39, 51, 52]. Future research to establish normal ICP, until quantitative non-invasive technology is developed, could benefit from this telemetric monitoring technique and, hopefully, expand the material on ICP values obtained in pseudo-normal humans.
In this review, we found a reference interval for ICP in the supine position from 0.9 to 16.3 mmHg, based on six studies with a total of 62 participants[21, 45, 51, 53–55]. The reference intervals are based on a small sample size and differ substantially in their findings of normal ICP, and do, therefore, not represent a clinically applicable reference interval.
Since most humans, and in terms of patients specifically idiopathic intracranial hypertension and normal pressure hydrocephalus patients, spend the majority of their lives in the upright (vertical) position, a reference interval for this specific position is needed for interpretting diagnostic long-term ICP monitoring. Based on six studies with a total of 62 participants[21, 39, 45, 53–55], this review found a reference intervals for ICP in the upright position from − 6.2 to 8.0 mmHg. Though too wide to serve as a clinically applicable reference interval, the data show that negative ICP values can be normal in an upright position[45, 56].
For daytime ICP, the established reference intervals were likewise based on a limited number of studies (n = 2) and study participants (n = 45)[42, 57]. Furthermore, there are large interpersonal differences in the amount of time spend in an upright position during the day. These factors proberly result in the wide reference interval from − 12.0 to 12.2 mmHg. As with the reference interval for ICP in the upright position, this does not serve as a practical tool in clinical decision making.
For nighttime, we were able to establish a reference interval from − 15.8 to 28.2 mmHg. Besides a limited number of studies (n = 3) and participants (n = 57) addressing the matter[42, 57, 58], body position during sleep may vary considerably among patients. Furthermore, the degree of sleep apnoe has also been found to highly impact ICP. Combined, this could potentially cause significant variations in measured ICP and, result in the very wide and clinical unuseful reference interval. Unfortunately, the included studies did not provide information on body position nor sleep apnoe coherent to ICP values.
Reference intervals for LCSF op
The majority of included studies on LCSFop (81%) performed pressure measurement in a lateral recumbent position[6, 7, 34–36, 41, 59–64, 8, 65–70, 10, 23, 29–33], thus establishing a reference interval in this position from 7.2 to 16.8 mmHg. There were no significant difference between the reference intervals in healthy indidviduals versus pseudo-healthy individuals. The establish reference interval is similar to the reference of 7 to 15 mmHg routinely used in clinical practice[5, 18, 23, 24, 45].
Seven studies obtained LCSFop values in supine position[5, 8, 24, 28, 59, 71, 72], resulting in a reference interval from 5.7 to 15.5 mmHg. Participants in three out of the seven studies were completely healthy[5, 24, 28]. There was no significant difference between reference intervals in healthy indidviduals versus pseudo-healthy individuals.
When comparing supine LCSFop to supine ICP, we found a difference between the means corresponding to 2.1 mmHg (P = 0.03). These results suggest that supine LCSFop is not optimal as a surrogate marker of supine ICP. To our knowledge, there are no studies that comparing simultaneously measured supine ICP with supine LCSFop.
Posture-dependent pressure differences
Postural-dependent pressure changes have mainly been evaluated in studies investigating ICP[19, 54]. Andresen et al. compared lumbar recumbent position to supine position in 31 patients with intracranial ICP monitoring and found that ICP increased approximately 5 mmHg in the lateral recumbent position, thus a significantly higher difference than found between LCSFop in recumbent position versus supine position in this review. This postural-related difference in ICP may be caused by spine flexion and, in particular, flexion of the neck during lateral recumbent position in the study by Andresen et al. A flexed neck could theoretically compress the jugular veins, thus hindering the venous return to the heart from the head, thereby increasing ICP[40, 73–75]. Many studies have emphasized the importance of a neutral neck during the measurement of LCSFop[23, 24, 40, 73].
Though statistically significant, the mean LCSFop difference of 1.2 mmHg between the lateral recumbent position and supine position hardly has any clinical implications (Fig. 2). This relatively small difference might be explained by LCSFop in the lateral recumbent position having been measured with the neck in a neutral position. Unfortunately, the significant change in LCSFop caused by neck position alone has not previously been subject to much debate. Thus, only six of the included studies examining LCSFop documented that LCSFop was obtained simultaneously with a neutral neck position[6, 24, 29, 32, 35, 68]. To establish an accurate reference interval of LCSFop, the neck should be held in a neutral position during all LCSFop measurements.