Continuous monitoring of the Monro-Kellie doctrine: is it possible?

Abstract

The Monro-Kellie doctrine describes the principle of homeostatic intracerebral volume regulation, which stipulates that the total volume of the parenchyma, cerebrospinal fluid, and blood remains constant. Hypothetically, a slow shift (e.g., brain edema development) in the irregular vasomotion-driven exchanges of these compartmental volumes may lead to increased intracranial hypertension. To evaluate this paradigm in a clinical setting and measure the processes involved in the regulation of systemic intracranial volume, we quantified cerebral blood flow velocity (CBFv) in the middle cerebral artery, arterial blood pressure (ABP), and intracranial pressure (ICP), in 238 brain-injured subjects. Relative changes in compartmental compliances C(a) (arterial) and C(i) (combined venous and CSF compartments) were mathematically estimated using these raw signals through time series analysis; C(a) and C(i) were used to compute an index of cerebral compliance (ICC) as a moving correlation coefficient between C(a) and C(i). Conceptually, a negative ICC would represent a functional Monro-Kellie doctrine by illustrating volumetric compensations between C(a) and C(i). Clinical observations show that Lundberg A-waves and arterial hypertension were associated with negative ICC, whereas in refractory intracranial hypertension, a positive ICC was observed. In subjects who died, ICC was significantly greater than in survivors (0.46 ± 0.027 versus 0.22 ± 0.017; p<0.01) over the first 5 days of intensive care. The mortality rate is 5% when ICC is less than 0, and 43% when above 0.7. ICC above 0.7 was associated with terminally elevated ICP (chi-square p=0.026). We propose that the Monro-Kellie doctrine can be monitored in real time to illustrate the state of intracranial volume regulation.

FIG. 1.

Changes of ICC, C_a%, and C_i% during strong, hemodynamically-relevant stimulation: (a) Arterial hypertension due to transient change in arterial blood pressure (ABP). Changes in C_a and C_i have clearly inverse direction, index of cerebral compliance (ICC) is negative, and therefore the Monro-Kellie doctrine works. (b) Plateau wave of ICP index ICC becomes negative. This is caused by increasing C_a (vasodilation), and a further decrease in C_i (rise in intracranial pressure [ICP]; CBFVa, cerebral blood flow velocity in basal arteries).

FIG. 2.

Example of rising intracranial pressure (ICP) in a subject who died of intracranial hypertension. The index of cerebral compliance (ICC) is continuously positive during uniformly rising ICP. Both C_a and C_i decrease (ABP, arterial blood pressure; CBFVa, cerebral blood flow velocity in basal arteries; C_a% and C_i%, compliances per unit of cross-sectional area of insonated vessel).

FIG. 3.

Distribution of index of cerebral compliance (ICC) among four different Glasgow Outcome Scale (GOS) groups (G, good outcome; M, moderate disability; S.D., severe disability; D, died). Vertical bars indicate 95% confidence intervals for means.

FIG. 4.

(a) Distribution of intracranial pressure (ICP), and (b) mortality rate over the range of observed values of index of cerebral compliance (ICC). For negative ICC, the mortality rate is 0 and mean ICP is lower than 20 mm Hg. The mortality rate increases when ICC is greater than 0.7.