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Keywords:

  • intensive care;
  • intracranial pressure;
  • neuromonitoring;
  • optic nerve sheath;
  • ultrasound

Abstract.

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

Purpose:  To determine the distensibility and elastic characteristics of the optic nerve sheath for development of a basic understanding of ultrasound studies aimed to measure optic nerve sheath diameter (ONSD) for detection of acutely elevated intracranial pressure (ICP).

Methods:  Isolated human optic nerves preparations obtained from autopsies were submitted to predefined pressure alterations, and consecutive changes in ONSD were measured by B-scan ultrasound under defined conditions.

Results:  Following submission to pressure, the diameter of the nerve sheath increased up to 140% of its baseline value. The increase (mean 1.97 mm, SD 0.52 mm) corresponded to the magnitude of pressure steps measured in the perineural subarachnoidal space (SAS). Similarly, the ONSD declined in each of the preparations within a few minutes after the optic nerve was decompressed. However, it did not reach its baseline value again when pressure loads of 45–55 mmHg or more had been applied.

Conclusions:  The elasticity of the anterior sheath of the optic nerve is sufficient for the detection of pressure changes in the SAS especially for upward pressure steps. This is basically important for the application of clinical monitoring of the sheath diameter to facilitate the identification of patients with elevated ICP non-invasively (screening). However, further implementation of this procedure in neurointensive care and emergency medicine has to consider that the sheath diameter reversibility may be impaired after episodes of prolonged intracranial hypertension and a model for hysteresis is proposed.


Introduction

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

Intracranial pressure (ICP) is of significant importance for the prognosis and the adjustment of treatment to acute neurological conditions, e.g. brain trauma and stroke. Although not delivering accurate ICP data, the non-invasive measurement of the diameter of the optic nerve sheath is shown to be a promising method to estimate the ICP in children (Helmke & Hansen 1996a; Wiegand & Richards 2001) and adults (Geeraerts et al. 2001; Hayreh 1968). With increasing ICP, the local compartment of the cerebrospinal fluid (CSF) predominantly in the anterior part of the optic nerve (Hansen & Helmke 1996) is extended by hydrostatic transmittance of CSF pressure in the SAS. Elevated pressure results in an increase in the local optic nerve sheath diameter (ONSD), even before papilloedema appears (Hayreh 1968, 1984; Liu & Kahn 1993; Hansen & Helmke 1996).

In vivo, the optic nerve and its sheath can be imaged reliably by ultrasound techniques that correspond well with nuclear magnetic resonance imaging (Lagrèze et al. 2007). Normative data obtained by ultrasound have been established in children (Helmke & Hansen 1996a,b; Newman et al. 2002; Ballantyne et al. 1999, 2002) and adults (Hansen et al. 1994; Ballantyne et al. 2002) and allow the distinction between normal, borderline and clearly pathological findings. High interobserver reliability of the method was reported even under emergency conditions like hospital admission or intensive care units (Helmke & Hansen 1996b; Tsung et al. 2005; Tayal et al. 2007; Helmke et al. 2000; Geeraerts et al. 2001, 2008).

Sonographically based investigations showed increased ONSDs in patients with acute elevation of ICP by about 30–90% of the baseline values irrespective of the patient’s age (Helmke & Hansen 1996b; Newman et al. 2002; Hansen et al. 1994; Blaivas et al. 2003), age or body mass index (Bäuerle et al. 2011). However, several own observations of the ONSD time–course in intensive-care patients demonstrated a complex elastic behaviour of the ONS: Unlike rapid recompensation of the ICP, which resulted in rapid restitution of dilated optic nerve sheaths, long-term dysregulation of ICP leads to persisting dilatation of the CSF compartment surrounding the optic nerve. As any nonelastic behaviour would clearly limit the use of optic nerve ultrasound studies for the non-invasive estimation of ICP, we investigated this phenomenon in isolated human preparations under controlled pressure conditions.

Materials and Methods

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

Ten optic nerve preparations obtained from approved post-mortem examinations in patients between 18 and 80 years of age who died from other than neurological causes were used in this study. All patients involved had no known orbital or ophthalmologic disease. To exclude artefacts because of autolysis (Anders et al. 1979), the time between death and initiation of the experiments did not exceed 50 (18–49) hrs. The preparation involved four steps:

  • 1
     Insertion of two blunt injection cannulae into the SAS; fixation of the cannulae and sealing of the SAS preparation at its end with a fast hardening plastic material (‘Technovit 7143’; Heraeus Holding GmbH, D-63450 Hanau, Germany). To rule out leakage and to remove residual air from the SAS, contrast medium was injected by a cannula for verification using X-ray.
  • 2
     Thread fixation of the sclera on a plastic frame in two opposing positions (Fig. 1), followed by lowering into a water tank. Reproducible pressure conditions in all the preparations were generated by placing the sample 55 mm below the surface of the water. The first cannula was connected with a height-adjustable fluid reservoir of isotonic sodium chloride solution to apply controlled pressures of up to 65 mmHg. The pressure within the SAS was measured using a second cannula by means of a Statham element.
  • 3
     For measurements of the ONSD, a 10-MHz ultrasound probe (‘Philips-ATL HDI 5000’; Philips Electronics NA Corporation, New York, NY, USA) was installed above the tank (Fig. 1). Sheath distance was measured between cursor positions marked ‘x’ constantly located 3 mm off the lamina cribrosa along the axis of the optic nerve (Fig. 2).
  • 4
     Following the calibration of the Statham element, the pressure was increased instantaneously to seven different levels (5, 15, 25, 35, 45, 55 and 65 mmHg). Each of these upward pressure steps was followed by a sudden pressure decline to 0 mmHg (decompression phase). The experiment took place in the following order: 5 mmHg up, 5 mmHg down, 15 mmHg up, 15 mmHg down to 65 mmHg up and 65 mmHg down.
  • 5
     All ONSD measurements were performed exactly 200 seconds after initiation of the pressure step.
image

Figure 1.  The optic nerve is arrested with no tension 5.5 cm below the water surface (see horizontal line). Two cannulae are inserted into the SAS of the optic nerve with one of them connected with a pressure sensor (Statham element) and the other one with the height adjustable water tank. Before initiating the measurement, the ultrasound device in the tank is adjusted parallel to the longitudinal axis of the optic nerve and focussed to its anterior section.

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image

Figure 2.  Ultrasound series of the same optic nerve preparation with increasing pressure load. Top row: pressure 15 mmHg, optic nerve sheath diameter (ONSD) 5.5 mm. Middle row: pressure 45 mmHg, ONSD 6.4 mm, bottom row: pressure 55 mmHg, ONSD 7.0 mm. Note dilatation of the dural layer distance marked x.

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Statistical analysis

Data are presented as mean ± standard deviation (SD) unless otherwise stated. Statistical comparisons (Sigma-Stat 3.1; SPSS, Chicago, IL, USA) were performed using Pearson’s correlation coefficient.

All procedures used in this study were performed in accordance with our institutional guidelines and the Declaration of Helsinki. All experiments were performed in a blinded manner using two experimenters (HCH, KH).

Results

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

ONSD behaviour following stepwise pressure increase

Elevations of pressure in the SAS were invariably followed by an increase in the ONSD (Fig. 3A). The pressure-induced dilatation (difference of ONSD, or ΔONSD) ranged between 0.9 and 2.5 mm (mean: 1.97 mm, SD: 0.52). With baseline levels ranging between 3.8 and 5.1 mm (mean: 4.69 mm, SD: 0.40), the mean increment of the ONSD was 40.2%.

image

Figure 3.  (A) Optic nerve sheath response to pressure increase: optic nerve sheath diameter (ONSD) values (open circles) after pressure increase (‘+p’) in n = 10 preparations, depicted as mean and standard deviation. Experimentally applied increasing pressure levels (open bars) in the SAS result in ONSD elevations, even after exposure to pressures as low as 5 mmHg. Referring to baseline values (baseline, square), there is a continuous elevation of the ONSD with increasing pressure burden. Optic nerve sheath diameter has gained more than 2 mm at 65 mmHg. (B) Optic nerve sheath response to pressure decrease: After experimental pressure decreases (‘−p’) in the SAS, a residual dilatation of the ONSD (full circles) remains above the baseline value (ONSD baseline, square). The decompression after increasingly higher pressure levels (open bars), particularly when reaching 45 mmHg or more, leads to increasingly higher residual ONSD (here given as mean and standard deviation of n = 10 preparations). After decompression from SAS pressure 65 mmHg, a mean residual dilatation of 0.5 mm remains.

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Concerning the degree of dilatation (ΔONSD), no difference was found between high and low baseline diameters (ONSD at baseline < 4.6 mm: ΔONSD 1.84; ONSD at baseline > 4.6 mm; ΔONSD 1.95 mm).

The relation of step magnitude and corresponding ONSD changes was nearly linear within a wide range. The initial pressure increase from 0 mmHg (baseline) to 5 mmHg resulted in a rather large increase in diameter (ΔONSD mean 0.7 mm). Later, this ΔONSD became somewhat smaller (diameters of 5.46, 5.76, 5.85, 6.09, 6.30, 6.45 and 6.66 mm after exposure to 5, 15, 25, 35, 45, 55 and 65 mmHg, respectively). The mean slope of the diameter–pressure plot was calculated as 0.025 mm per mmHg (r = 0.94, p < 0.01, two-tailed Pearson correlation). Thus on average, an additional ONS dilatation of 0.25 mmHg resulted from every 10-mmHg pressure increment.

ONSD behaviour following stepwise pressure decrease

All reductions of pressure in the SAS likewise resulted invariably in a decrease in the dilated ONSD. However, the diameter reduction was mostly incomplete as it did not reach baseline again. The mean relative decreases of the ONSD ranged around 81.4% (90.9–74.6 %). The residual deviation from baseline ranged between 0.1 and 1.1 mm (mean: 0.50 mm, SD: 0.52).

This remaining ΔONSD was related to the pressure level previously applied (Fig. 3B). Therefore, no linear correlation was present between pressure drops and ONSD decline.

Comparing lower to higher levels of previously applied pressure, the ONSD level recovered only to baseline coming from SAS pressure lower than 35 mmHg. In contrary, following decompression from higher pressure levels (45 mmHg and above), a clear residual dilatation remained (above 0.34 mm, see Table 1).

Table 1.   Averaged ONSD data from 10 preparations measured before and after negative pressure steps. Baseline pressure level is equivalent to pressure 0 mmHg at the beginning of the experiment. Decompression from higher levels leads to increasing residual dilatations. The resulting ONSD difference to baseline (ΔONSD) increases above 0.24 mm once pressure steps exceed 35 mmHg. The decrement was calculated as ONSD ratio before and after decompression, and it gradually decreases because of a decline in elasticity.
Negative pressure step [mmHg]05152535455565
  1. ONSD, optic nerve sheath diameter.

Residual mean ONSD [mm]4.694.764.864.894.935.035.125.19
ΔONSD to baseline [mm]00.070.170.200.240.340.430.50
Decrement (%) 90.984.182.882.978.975.674.6

Comparison among the 10 preparations revealed some variation of their threshold values for this irreversible dilatation. The loss of complete diameter recovery always occurred after previous exposure to a pressure level of 55 mmHg or more. In three preparations, this phenomenon was already present after exposure to lower levels of pressure in the SAS (45 mmHg, n = 2 and 35 mmHg, n = 1).

Discussion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

In this paper, we describe for the first time the pressure-dependent behaviour of the ONSD in vitro after controlled application of incremental pressure steps in the SAS surrounding the human optic nerve. To create nearly physiological conditions, we kept the pressure outside the optic nerve sheath at about 2–3 mmHg equivalent to the physiological orbital tissue pressure (Møller 1955) simply by using a constant depth within the experimental tank. Its temperature was also kept constant at 37°C. Interferences resulting from autolysis were ruled out by controlling of the preparation time after autopsy (Anders et al. 1979). Under these conditions, our ONSD baseline data correspond nicely to anatomical measurements reported from the anterior portion of the optic nerve and its sheath (Lang & Reiter 1985).

Dilatation of the optic nerve sheath was confirmed in all 10 preparations. This dilatation response depends exclusively on the SAS pressure step and not on the baseline ONSD. Already, the initial experimental pressure change of 5 mmHg in the SAS invariably induced some opening of the sheath. Therefore, in the lower range of CSF pressure, ONSD measurements should nicely allow detection of small pressure changes by an initial dilatation. Most clinical studies reported this dilation response, however with varying ONSD threshold values for the detection of elevated ICP (Hansen et al. 1994; Blaivas et al. 2003; Kimberley et al. 2008; Moretti & Pizzi 2009; Bäuerle et al. 2011; Major et al. 2011).

However, when the pressure rises to higher values (50 mmHg and above), the ONSD increased up to 140% of the baseline (i.e. mean change of about 2.0 mm). Therefore, our experiments support the proposed use of ONSD examination in emergency and intensive care settings (Girisgin et al. 2007; Major et al. 2011). As shown earlier (Helmke & Hansen 1996a,b and Helmke et al. 2000) that ONSD changes of this magnitude can easily be identified using a 10-MHz B-scan ultrasound in the clinical field.

Dilation of the optic nerve sheath, which is derived from dural tissue (Lang & Reiter 1985), can be explained in several ways. First, the elements of the sheath ONS may be initially unfolded and collapsed, so any increase in pressure will open a preformed reserve space. Second, the ONS may possess exceptional elasticity properties that allow rapid and considerable distension different from the typical dura mater. Interestingly, experiments using bovine optic nerve sheath showed a specific arrangement of connective tissue fibres (Raspanti et al. 1992) which allows augmented distensibility. It remains to be shown whether a corresponding ultrastructure in human material explains the elasticity we observed. Of course, this high elasticity would meet the biological requirements for the high mobility of this segment of the optic nerve during ocular movements.

Furthermore, our experimental results demonstrate a more or less limited capability for retraction of the optic nerve sheath because there often was not a complete diameter restoration after pressure normalization, similar to a behaviour known as hysteresis. Thus, restoring forces, which have been undetected until now, must operate within the structures of the dilated optic nerve sheath. This may be a further characteristic of special elastic properties of the complex tissue composite consisting of the optic nerve and the surrounding perineural structures. One way to explain hysteresis is that restoration is also mediated by trabecular fibres which connect the sheath with the pia mater of the nerve itself. The hypothesized concomitant distension of both trabecles and dura because of increased pressure is depicted schematically in Fig. 4.

image

Figure 4.  Schematic drawing of the optic nerve before and after pressure change in the sub-arachnoidal space (SAS). The left figure shows the condition at low pressures relaxed small optic nerve sheath diameter (ONSD) with presumably folded trabecles. The right figure describes the situation with increased pressure and dilated sheath, corresponding to elevated ONSD and tensed trabecles. Restoring forces, explained by properties of dura mater and trabecles alone, are effective only within an elastic working range. Above this range of operation, plastical deformation occurs.

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Within the range of reversible dilation, the ONSD structure does not undergo plastical deformation or trabecular damage-like overdistension. This range with complete reversibility was reported earlier using ultrasound monitoring of the optic nerve during spinal infusion tests (Hansen & Helmke 1997). The mean ΔONSD of 1.97 mm found in preparations corresponds nicely to the pressure-induced ONSD changes we reported in that study (mean 1.80 mm, range 0.7–3.1 mm). Notably, longer exposures to higher pressure above 40 mmHg were avoided in these tests. i.e. a reduced capability for retraction, was To explain the irreversibility of dilation, we hypothesize that a pressure-dependent structural remodelling in the trabecular tissue and/or the dural elements takes place (plastical deformation) whenever higher pressures act in the SAS. We found that the ONSD did not return completely to its baseline value after exposure to SAS pressures of 55 mmHg (even in some preparations at levels of 35 mmHg).

Clinically, this finding is important for correct interpretation of the ONSD time–course in patients having been exposed to massively elevated ICP. Once the ICP has exceeded a certain limit, restoration of the ONSD can be delayed and incomplete despite effective therapy. Under these conditions, the ONSD must be interpreted with caution in relation to the course of pressure.

However, keeping these principles of dilatation and retraction responses of the ONSD in mind, serial ONSD measurements can offer an estimate of the course of ICP. Most reliable results can be expected in the time interval of ascending pressure as opposed to pressure descent.

Conclusion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

By showing that (i) stable diameters of the optic nerve sheath are achieved within a few minutes after subarachnoidal pressure changes and (ii) a direct correlation between distension and pressure exists for pressure values between 5 and 45 mmHg, we demonstrated the physiological basis for non-invasive monitoring of the ICP by ultrasound ONSD measurement. Apart from minor limitations under special conditions (local optic nerve disorder, free CSF circulation, etc.), one has to bear in mind that false-positive ONSD findings may occur following antecedent massive ICP increases (45 mmHg or higher), most likely because of structural changes within the ONS.

Our study could not clarify whether a long-term recovery or restitution of the ONSD is possible or whether some permanent surplus expansion remains. Further investigations are required to monitor the course of the ONSD increase or decrease with time (especially regarding faster responses below 4 min and changes occurring later) and to become familiar with modifications of the ONSD behaviour following exposure to increased pressure.

Ethical standard

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

References

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Ethical standard
  9. References
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