Evolution of the Monro-Kellie Doctrine from Static Intracranial Pressure to Dynamic Intracranial Physiology: A Critical Review of the Monro-Kellie 1.0 Through 4.0 Framework and Its Implications for Contemporary Neurocritical Care

The Monro-Kellie doctrine, first articulated in 1783, established that intracranial volume remains constant within the rigid cranium. However, this static three-compartment model has proven inadequate to explain the full complexity of intracranial pathophysiology. Sequential paradigm shifts—designated Monro-Kellie (MK) 1.0 through 4.0—have progressively transformed this foundational framework. MK 2.0 (Wilson, 2016) demonstrated that cerebral venous outflow dynamics, rather than static volume compensation, are the dominant determinant of acute intracranial pressure (ICP) fluctuations, with arterial inflow of approximately 700 mL/min dwarfing CSF production of 0.35 mL/min. MK 3.0 (Mangalore et al., 2019; Benson et al., 2022) revealed that brain tissue viscoelastic remodeling and calvarial structural adaptation constitute previously unrecognized compensatory mechanisms in chronic pressure dysregulation. MK 4.0 (Brasil et al., 2025) integrates cerebrovascular autoregulation assessment, glymphatic system physiology, and the novel concept of Intracranial Compartment Syndrome into a multimodal dynamic framework that challenges threshold-based ICP management. The Brussels International Consensus (B-ICONIC, 2025) has provided 34 evidence-based recommendations for noninvasive ICP monitoring implementation. This evolution necessitates a transition from threshold-driven management to individualized, physiology-guided neurocritical care incorporating continuous assessment of intracranial compliance, cerebrovascular reactivity, and glymphatic function.