Intracranial pressure following complete removal of a small demarcated brain tumor: a model for normal intracranial pressure in humans

Clinical article

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Object

Current published normal values for intracranial pressure (ICP) are extrapolated from lumbar CSF pressure measurements and ICP measurements in patients treated for CSF pressure disorders. There is an emerging agreement that true normal ICP values are needed for diagnostic and therapeutic purposes. This study documents normal ICP in humans.

Methods

In this study the authors included adult patients scheduled for complete removal of a solitary, clearly demarcated, small brain tumor. The mean age of these patients was 67 years old (range 58–85 years old). Exclusion criteria were intended to create a study population with as normal brains as possible. A new telemetric ICP monitoring device was implanted at the end of surgery and monitoring was conducted 2 and 4 weeks postoperatively.

Results

In the supine position, mean ICP was 0.5 ± 4.0 mm Hg at 4 weeks postoperatively. Postural change to the standing position resulted in a decrease in mean ICP to −3.7 ± 3.8 mm Hg. These results show ICP to be considerably lower than previously estimated.

Conclusions

This study provides a preliminary reference range for normal ICP in humans. It is the first study to show that ICP in the healthy human brain decreases to negative values when assuming the upright position. If these results are later confirmed in a larger series, they might provide reference values for diagnosis and treatment in patients with CSF-related disorders. New normal values also have implications for future shunt design and the ICP target range in hydrocephalus treatment.

Abbreviation used in this paper:ICP = intracranial pressure.

Object

Current published normal values for intracranial pressure (ICP) are extrapolated from lumbar CSF pressure measurements and ICP measurements in patients treated for CSF pressure disorders. There is an emerging agreement that true normal ICP values are needed for diagnostic and therapeutic purposes. This study documents normal ICP in humans.

Methods

In this study the authors included adult patients scheduled for complete removal of a solitary, clearly demarcated, small brain tumor. The mean age of these patients was 67 years old (range 58–85 years old). Exclusion criteria were intended to create a study population with as normal brains as possible. A new telemetric ICP monitoring device was implanted at the end of surgery and monitoring was conducted 2 and 4 weeks postoperatively.

Results

In the supine position, mean ICP was 0.5 ± 4.0 mm Hg at 4 weeks postoperatively. Postural change to the standing position resulted in a decrease in mean ICP to −3.7 ± 3.8 mm Hg. These results show ICP to be considerably lower than previously estimated.

Conclusions

This study provides a preliminary reference range for normal ICP in humans. It is the first study to show that ICP in the healthy human brain decreases to negative values when assuming the upright position. If these results are later confirmed in a larger series, they might provide reference values for diagnosis and treatment in patients with CSF-related disorders. New normal values also have implications for future shunt design and the ICP target range in hydrocephalus treatment.

The “golden age” of intracranial pressure (ICP) monitoring began in the 1950s with methods for continuous ICP measurement using intraventricular catheters, as reported by Guillaume and Janny8 and Lundberg.10 However, despite widespread use of ICP monitoring, normal ICP has never been thoroughly investigated, and current normal values are extrapolated from lumbar CSF pressure measurements and direct ICP measurements in patients with suspected CSF pressure disorders. Disagreement exists as to whether lumbar pressure measurements can adequately describe qualities of the “true” ICP,4,9 and certainly in the face of obstructive lesions, the two pressures will differ.

That more research is needed in this area becomes readily apparent when performing even a cursory review of diseases related to hydrodynamic variables. What is normal pressure hydrocephalus? Why do some patients with idiopathic intracranial hypertension and ICP within the accepted normal range exhibit clinical improvement upon shunt placement? Why do some patients with shunts show clinical signs of overdrainage upon reaching negative ICP values, while others are clinically unaffected? Similarly, we elect to operate on patients suspected of shunt failure based on an assumption of normal ICP values, and in a difficult case of hydrocephalus, we might place an adjustable valve and antisiphon devices to be able to “fine tune” the ICP to optimum values—but which values and why?

In cases of marked increases in ICP, there is no doubt that an intervention is required, but in the face of the above questions and scenarios, our decisions regarding treatment are based on considerably more uncertain estimates of what is normal and what is not. However, our challenges in obtaining “true” normal values for clinical use are 2-fold: 1) the invasive nature of ICP measurement poses ethical challenges in obtaining values from normal healthy persons; and 2) in attempting to evaluate ICP, we are forced to perform an invasive procedure, which might in fact change the parameter we are trying to evaluate.

The noninvasive estimations of ICP are not yet at a stage where they can replace conventional methods of ICP measurement, and in our attempts to estimate normal ICP, we are then left with different trade-offs that seek to minimize these problems. In this paper, we report the results of long-term telemetric ICP monitoring in 4 adults, following curative surgical removal of solitary, clearly demarcated brain tumors. At the time of ICP measurement, the patients were thus without any mass lesion or structural abnormalities causing elevations of physiological ICP or CSF dynamics. We show the ICP to be lower than previously estimated, with marked posture-related variations. These results have a direct and immediate impact on clinical practice.

Methods

The study was approved by the regional ethics committee, and the study was performed according to the standards set by the Helsinki declaration. All patients gave written informed consent.

Study Population

Because completely normal and healthy persons cannot ethically be recruited for studies of invasive ICP measurements, we opted to construct a patient population that was as normal as possible in regard to their CSF dynamics. Inclusion and exclusion criteria of the study are highlighted in Table 1. In this study we included adult patients scheduled for complete removal of a solitary, clearly demarcated, small brain tumor. Patients were included from July 2011 to August 2013. Patient acceptance of inclusion proved extremely difficult, and we therefore chose to publish the results in a small group, because thus far it is the only existing report on normal ICP values.

TABLE 1:

Inclusion and exclusion criteria for the study population

Inclusion CriteriaExclusion Criteria*
age >18 yrsfocal or global edema w/ mass effect
clearly demarcated solitary intracranial tumorCSF leakage
maximum tumor diameter 4 cmcurrent or previous treatment for hydrocephalus or idiopathic intracranial hypertension
postop CT- or MRI-confirmed radical tumor removalprevious insertion of a CSF shunt
patients w/ increased surgical or anesthesiological risk of morbidity
patients w/ increased risk of infection
patients w/ coagulopathies
surgical complications or difficulties in relation to the primary surgical procedure
acute surgical intervention required
gliomas or other infiltrating tumors
pregnancy

Exclusion criteria were purposefully set to be very strict, leaving us with a study population that—following the operations—could be described as “disease free” in the brain.

Surgery and the Telemetric Device

At the end of the patient's scheduled surgery, a commercially available telemetric ICP probe (Neurovent-Ptel, Raumedic GmBH), was inserted 2 cm into the brain parenchyma. Calibration is not necessary before insertion. Before insertion we ensured the 0-point accuracy by measuring ICP in a cup of isotonic saline in the OR.

All probes were placed supratentorially through a bur hole related to the primary surgical access to the tumor. The telemetric connector was placed outside the cranium with full skin cover. This form of implantation allows long-term and repeated monitoring of ICP with no risk of infection beyond the immediate postoperative period. Published initial clinical experiences with the device, as well as results on zero drift, have been favorable.13 In that study, 4 probes explanted after 14, 15, 16, and 28 days all showed a zero drift of 0 mm Hg. Measurements were obtained for as long as 180 days after implantation, without incident. Thus, the probe can be left in situ, and measurements performed as a scheduled follow-up. We have previously shown home monitoring with a conventional ICP probe to be safe in both the adult and pediatric population,2 and similarly, there should be no reservations about using the telemetric probe in the home setting.

Follow-Up Measurements

Following surgery, ICP monitoring sessions were performed after 2 and 4 weeks. We chose these intervals to ascertain the stability of ICP across the measurement period. At the time of our study, the telemetric device was certified for valid measurements for as long as 4 weeks. The manufacturer-guaranteed period of valid measurements has since been extended to 3 months.

At each monitoring session, a standardized exercise program was performed by the patient to ensure baseline measurements for a number of activities. Each body posture was maintained for 10 minutes. Upon switching to a new body posture, we waited for ICP to stabilize before commencing the next 10-minute monitoring session.

Statistical Analysis

The statistical software package R was used for descriptive statistics as well as for visual analysis of the obtained ICP curves.

Results

We present the results of 4 patients (1 man, 3 women), with a mean age of 67 years old (range 58–85 years old). Three had meningiomas, and 1 had an adenocarcinoma metastasis from a primary lung cancer.

Pre- and postoperative images are shown in Fig. 1. We excluded 3 patients. One patient experienced postoperative breakthrough bleeding to the lateral ventricles (not related to the telemetric probe). We excluded this patient because bleeding into the ventricular system was likely to affect ICP. Another patient had significant postoperative edema with persistent clinical neurological symptoms, mass effect, and headaches. The third excluded patient was diagnosed with sleep apnea. Thus, all 3 patients had or developed pathologies that are known to alter ICP, and subsequently could not be included in a patient population aimed at providing normal reference values.

Fig. 1.
Fig. 1.

Axial preoperative T1-weighted contrast-enhanced MR images (left) and postoperative images (right) for all 4 cases. The postoperative scans were performed for clinical follow-up evaluation to demonstrate radical tumor removal, and were thus not performed in direct connection to the ICP monitoring sessions. Minor postoperative changes have been considered acceptable for inclusion into the study. A: Case 1. The postoperative T1-weighted MR image at 3 months shows only minimal changes. B: Case 2. The postoperative T1-weighted MR image at 3 months demonstrates demarcated reactive changes and hemosiderin deposits in a small area. C: Case 3. The postoperative CT scan at 4 weeks shows a small area with encephalomalacia just laterally to the posterior ventricular horn. D: Case 4. The postoperative CT scan obtained at 1 week shows only minimal postoperative changes. If the minor postoperative reactive changes noted in Cases 2 and 3 have an effect on ICP, these effects are minimal, and if there are any changes, they would increase rather than decrease ICP.

Standardized measurements after 2 and 4 weeks in the group of included patients (Table 2) showed small variations in both positive and negative directions but, in general, minimal change from the first to the second monitoring session. Accompanying results for the group of excluded patients are shown in Table 3.

TABLE 2:

Intracranial pressure values at 2 and 4 weeks postoperatively for the study patients*

Postop PeriodBody Posture
HorizontalSittingStandingWalking
2 wks
 Case 1−0.8 (−2.4 to 1.6)−6.3 (−8.7 to −3.2)−9.1 (−11.6 to −6.3)−8.4 (−11.0 to −5.0)
 Case 21.8 (0.3 to 2.9)−4.8 (−6.1 to −3.1)−1.1 (−3.8 to 1.8)−4.2 (−5.9 to −2.2)
 Case 34.0 (3.2 to 4.6)−0.2 (−1.6 to 1.3)−0.5 (−1.9 to 0.9)−1.2 (−3.0 to 0.3)
 Case 4−2.8 (−3.8 to −1.6)−8.7 (−10.3 to −3.7)−9.3 (−10.6 to −7.7)−7.8 (−9.5 to −5.4)
 mean ± SD0.6 ± 3.0−5.0 ± 3.6−5.0 ± 4.9−5.4 ± 3.4
4 wks
 Case 1−3.0 (−4.5 to −1.2)−8.1 (−10.3 to −5.6)−9.0 (−11.7 to −6.2)−10.3 (−12.4 to −7.5)
 Case 2−1.0 (−1.8 to 0.0)−5.9 (−7.1 to −4.3)−3.4 (−5.1 to −1.5)−5.0 (−6.6 to −3.3)
 Case 36.2 (5.1 to 7.2)−0.1 (−2.2 to 2.1)−0.1 (−2.2 to 2.8)−2.0 (−3.6 to 0.0)
 Case 4−0.1 (−1.2 to 1.2)−4.2 (−6.1 to −1.8)−2.3 (−4.2 to −0.5)−5.0 (−6.9 to −2.8)
 mean ± SD0.5 ± 4.0−4.5 ± 3.4−3.7 ± 3.8−5.6 ± 3.5

All data given as ICP medians (interquartile range) in mm Hg unless otherwise indicated.

TABLE 3:

ICP values at 2 and 4 weeks postoperatively for the excluded patients*

Postop PeriodBody Posture
HorizontalSittingStandingWalking
2 wks
 Patient X12.2 (1.4–3.0)−9.8 (−10.5 to −9.0)−4.0 (−5.7 to −2.2)−9.3 (−12.3 to −6.6)
 Patient X310.8 (9.3–12.5)−2.1 (−3.6 to −0.4)−2.2 (−3.9 to −0.3)−2.7 (−5.6 to 0.8)
4 wks
 Patient X111.8 (10.8–13.0)−3.3 (−4.7 to −1.8)−2.1 (−3.8 to −0.3)−3.7 (−5.7 to −1.8)
 Patient X38.1 (6.1–10.4)−2.7 (−3.9 to −0.9)0.3 (−2.0 to 4.2)1.8 (−1.3 to 6.6)

All data given as ICP medians (interquartile range) in mm Hg. Patient X2 had postoperative breakthrough bleeding to the lateral ventricles and was unable to participate in monitoring sessions. X = excluded.

Discussion

In this group of 4 patients without CSF dynamic disturbances who underwent uncomplicated complete tumor removal, we measured a lower ICP compared with previously published normal values, which are currently estimated at 7–15 mm Hg in the horizontal position. Our results are the first based on actual long-term ICP measurements in patients not investigated for, or suspected of, CSF dynamic disturbances, or ICP estimations based on recumbent lumbar CSF pressure measurements in healthy volunteers.9

Using ventricular ICP measurements, Lundberg10 estimated a normal supine ICP between 0 and 11 mm Hg based on a single case, which he noted “… can, however, be regarded as probably representative of a normal [ventricular fluid pressure].” This person was a 45-year-old woman with bilateral papilledema of unknown origin, and had complaints of headache and symptoms of “mental insufficiency” for a period of 2 years after acute meningoencephalitis. Most subsequent authors1,5–7,12 have performed estimations of the ICP based on pressure measurements obtained by lumbar puncture. Some investigations were performed on healthy volunteers, while others included patients suspected of CSF dynamic disturbances, and subsequently were classified as “probably” normal. These reports typically estimate an ICP ranging from 7 to 15 mm Hg.

In later years, more attempts have been made to measure ICP using telemetric sensors, with a single study3 investigating 5 patients who had developed obstructive hydrocephalus due to brain tumors or ventricular cysts. Upon removal of these lesions, the patients were defined as normal, and ICP measurement was obtained in the immediate postoperative setting, with values in the horizontal position ranging from 4 to 14 mm Hg. While this report is one of the only estimations of normal ICP using intracranial measurements instead of lumbar estimations, it appears questionable to assume a normal ICP in patients specifically treated for conditions with abnormal CSF dynamics, or with ventricular dilation due to obstructions.

Of note, the only previous results of intraparenchymal pressure monitoring in a confirmed somatically healthy person11 produced negative ICP values similar to our group of patients. The case report concerned a 19-year-old male with episodes of “hysterical stupor” and showed an ICP of −10 to +10 by direct intraparenchymal measurement. The patient had “an apparently normal brain” on direct visual inspection. Thus, despite claims that lumbar pressure monitoring provides comparable ICP values to true intracranial monitoring, this is probably only true in very select circumstances.

This paper presents preliminary results with the aim of providing a reference range for normal ICP. We show that ICP decreases significantly in all 4 patients with change of posture from supine to upright, highlighting the adaptive capabilities of the ventricular and spinal fluid system. If these results are later confirmed in a larger series, they may provide reference values for diagnosis and treatment for patients with CSF-related disorders. The reference ranges would provide the greatest benefit in situations in which the difference from “normal” is most in question, such as normal pressure hydrocephalus and overdrainage situations.

Conclusions

The purpose of the study was to provide reference values for ICP in humans. Ethical limitations prevent true ICP monitoring in truly normal patients. Based on these limitations we propose a model that includes patients who require surgery but are without any disturbances of ICP or CSF dynamics. Our results suggest that ICP is lower than previously estimated and that negative ICP could be considered normal. Additionally, our results highlight the continuing lack of understanding of even basic physiological parameters of the brain in daily neurological and neurosurgical clinical practice; mechanisms that we take for granted have actually not been investigated thoroughly.

Disclosure

Drs. Andresen and Juhler received research grants from The Hetland Olsen Fund, The Aase og Ejnar Danielsen Fund, The Augustinus Fund, and Dagmar Marshall's Fund.

Author contributions to the study and manuscript preparation include the following. Conception and design: both authors. Acquisition of data: both authors. Analysis and interpretation of data: both authors. Drafting the article: Andresen. Critically revising the article: both authors. Reviewed submitted version of manuscript: both authors. Approved the final version of the manuscript on behalf of both authors: Andresen. Statistical analysis: Andresen. Administrative/technical/material support: Juhler. Study supervision: Juhler.

Preliminary results were presented in abstract form at the conference of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, in Kyoto, Japan, October 2012.

References

  • 1

    Albeck MJBørgesen SEGjerris FSchmidt JFSørensen PS: Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects. J Neurosurg 74:5976001991

  • 2

    Andresen MJuhler MMunch TN: Quality and safety of home ICP monitoring compared with in-hospital monitoring. Acta Neurochir Suppl 113:1871912012

  • 3

    Chapman PHCosman ERArnold MA: The relationship between ventricular fluid pressure and body position in normal subjects and subjects with shunts: a telemetric study. Neurosurgery 26:1811891990

  • 4

    Eide PKDue-Tønnessen BJHelseth ELundar T: Assessment of intracranial pressure volume relationships in childhood: the lumbar infusion test versus intracranial pressure monitoring. Childs Nerv Syst 17:3823902001

  • 5

    Ekstedt J: CSF hydrodynamic studies in man. 2. Normal hydrodynamic variables related to CSF pressure and flow. J Neurol Neurosurg Psychiatry 41:3453531978

  • 6

    Gilland O: Normal cerebrospinal-fluid pressure. N Engl J Med 280:9049051969

  • 7

    Gilland OTourtellotte WWO'Tauma LHenderson WG: Normal cerebrospinal fluid pressure. J Neurosurg 40:5875931974

  • 8

    Guillaume JJanny P: [Continuous intracranial manometry; importance of the method and first results.]. Rev Neurol (Paris) 84:1311421951. (Fr)

  • 9

    Lenfeldt NKoskinen LODBergenheim ATMalm JEklund A: CSF pressure assessed by lumbar puncture agrees with intracranial pressure. Neurology 68:1551582007

  • 10

    Lundberg N: Continuous recording and control of ventricular fluid pressure in neurosurgical practice. Acta Psychiatr Scand Suppl 36:11931960

  • 11

    Martin G: Lundberg's B waves as a feature of normal intracranial pressure. Surg Neurol 9:3473481978

  • 12

    Tourtellotte WWA selected review of reactions of the cerebrospinal fluid to disease. Fields WS: Neurological Diagnostic Techniques Springfield, ILCharles C Thomas1966. 2550

  • 13

    Welschehold SSchmalhausen EDodier PVulcu SOertel JWagner W: First clinical results with a new telemetric intracranial pressure-monitoring system. Neurosurgery 70:1 Suppl Operative44492012

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Article Information

Address correspondence to: Morten Andresen, M.D., Clinic of Neurosurgery, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen Ø DK-2100, Denmark. email: andresen@gmail.com.

Please include this information when citing this paper: published online April 4, 2014; DOI: 10.3171/2014.2.JNS132209.

© AANS, except where prohibited by US copyright law.

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Figures

  • View in gallery

    Axial preoperative T1-weighted contrast-enhanced MR images (left) and postoperative images (right) for all 4 cases. The postoperative scans were performed for clinical follow-up evaluation to demonstrate radical tumor removal, and were thus not performed in direct connection to the ICP monitoring sessions. Minor postoperative changes have been considered acceptable for inclusion into the study. A: Case 1. The postoperative T1-weighted MR image at 3 months shows only minimal changes. B: Case 2. The postoperative T1-weighted MR image at 3 months demonstrates demarcated reactive changes and hemosiderin deposits in a small area. C: Case 3. The postoperative CT scan at 4 weeks shows a small area with encephalomalacia just laterally to the posterior ventricular horn. D: Case 4. The postoperative CT scan obtained at 1 week shows only minimal postoperative changes. If the minor postoperative reactive changes noted in Cases 2 and 3 have an effect on ICP, these effects are minimal, and if there are any changes, they would increase rather than decrease ICP.

References

  • 1

    Albeck MJBørgesen SEGjerris FSchmidt JFSørensen PS: Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects. J Neurosurg 74:5976001991

  • 2

    Andresen MJuhler MMunch TN: Quality and safety of home ICP monitoring compared with in-hospital monitoring. Acta Neurochir Suppl 113:1871912012

  • 3

    Chapman PHCosman ERArnold MA: The relationship between ventricular fluid pressure and body position in normal subjects and subjects with shunts: a telemetric study. Neurosurgery 26:1811891990

  • 4

    Eide PKDue-Tønnessen BJHelseth ELundar T: Assessment of intracranial pressure volume relationships in childhood: the lumbar infusion test versus intracranial pressure monitoring. Childs Nerv Syst 17:3823902001

  • 5

    Ekstedt J: CSF hydrodynamic studies in man. 2. Normal hydrodynamic variables related to CSF pressure and flow. J Neurol Neurosurg Psychiatry 41:3453531978

  • 6

    Gilland O: Normal cerebrospinal-fluid pressure. N Engl J Med 280:9049051969

  • 7

    Gilland OTourtellotte WWO'Tauma LHenderson WG: Normal cerebrospinal fluid pressure. J Neurosurg 40:5875931974

  • 8

    Guillaume JJanny P: [Continuous intracranial manometry; importance of the method and first results.]. Rev Neurol (Paris) 84:1311421951. (Fr)

  • 9

    Lenfeldt NKoskinen LODBergenheim ATMalm JEklund A: CSF pressure assessed by lumbar puncture agrees with intracranial pressure. Neurology 68:1551582007

  • 10

    Lundberg N: Continuous recording and control of ventricular fluid pressure in neurosurgical practice. Acta Psychiatr Scand Suppl 36:11931960

  • 11

    Martin G: Lundberg's B waves as a feature of normal intracranial pressure. Surg Neurol 9:3473481978

  • 12

    Tourtellotte WWA selected review of reactions of the cerebrospinal fluid to disease. Fields WS: Neurological Diagnostic Techniques Springfield, ILCharles C Thomas1966. 2550

  • 13

    Welschehold SSchmalhausen EDodier PVulcu SOertel JWagner W: First clinical results with a new telemetric intracranial pressure-monitoring system. Neurosurgery 70:1 Suppl Operative44492012

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