The historic evolution of intracranial pressure and cerebrospinal fluid pulse pressure concepts: Two centuries of challenges
- Department of Neurology, University of São Paulo, São Paulo-SP, Brazil.
- Department of Neurology and Neurosurgery, University Center Atenas, Paracatu-MG, Brazil.
- Department of Neurosurgery, Santa Marcelina Hospital, São Paulo-SP, Brazil.
- Department of Phisycs, Braincare Technological Development and Innovation, São Carlos-SP, Brazil.
DOI:10.25259/SNI_53_2021Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Nicollas Nunes Rabelo1, Josué da Silva Brito2, Jassiara Soares da Silva2, Nicolli Bellotti de Souza2, Giselle Coelho3, Sérgio Brasil1, Gustavo Frigeri4. The historic evolution of intracranial pressure and cerebrospinal fluid pulse pressure concepts: Two centuries of challenges. 14-Jun-2021;12:274
How to cite this URL: Nicollas Nunes Rabelo1, Josué da Silva Brito2, Jassiara Soares da Silva2, Nicolli Bellotti de Souza2, Giselle Coelho3, Sérgio Brasil1, Gustavo Frigeri4. The historic evolution of intracranial pressure and cerebrospinal fluid pulse pressure concepts: Two centuries of challenges. 14-Jun-2021;12:274. Available from: https://surgicalneurologyint.com/surgicalint-articles/10893/
Background: There is a consensus on the importance of monitoring intracranial pressure (ICP) during neurosurgery, and this monitoring reduces mortality during procedures. Current knowledge of ICP and cerebrospinal fluid pulse pressure has been built thanks to more than two centuries of research on brain dynamics.
Methods: Articles and books were selected using the descriptors “ICP,” “cerebrospinal fluid pulse,” “monitoring,” “Monro-Kellie doctrine,” and “ICP waveform” in electronic databases PubMed, Lilacs, Science Direct, and EMBASE.
Results: Several anatomists and physiologists have helped clarify the patterns of intracranial volumes under normal and pathological conditions. Monro-Kellie doctrine was an important step in a story that is reconstructed in this article. Through documentary research, we report the contribution of important medical figures, such as Monro, Kellie, Abercrombie, Burrows, Cushing, Langfitt, Marmarou, and other physiologists and anatomists who left their marks on the history of Medicine.
Conclusion: Understanding intracranial dynamics is an unfinished historical construction. Current knowledge is the result of two centuries of research that began with the investigations of Alexander Monro secundus.
Keywords: Cerebrospinal fluid pulse pressure, History of medicine, Intracranial pressure
In neurosurgery, there is a consensus on the importance of monitoring intracranial pressure (ICP), which reduces mortality.[
For more than 200 years, anatomists and physiologists have investigated brain dynamics in an attempt to understand how intracranial volumes affect ICP and also the different behavior of the cerebrospinal fluid (CSF) pulse at different pressure stages.[
The present paper reports several findings that contributed to the current knowledge of intracranial dynamics and to the use of CSF pulse pressure (CSFPP) in the interpretation of intracranial dynamics.
The Monro-Kellie doctrine was built on different researchers [
Alexander Monro secundus (1733–1817) is responsible for the first great contribution for the doctrine. Monro was born in Edinburgh and obtained his medical degree at the University of Edinburgh, where his father, Alexander Monro primus, was a professor of Anatomy and Surgery. At the same university, he became an adjunct professor even before finishing the course, and, from 1758 on, a full professor in his father’s place.[
The physiologist and anatomist George Kellie (1770–1829), a former student of Monro secundus in the University of Edinburg, deepened investigations on brain circulation.[
Based on this study, he stated that the skull was a firm and inflexible structure in adults, capable of isolating its interior from external mechanical pressures, with the brain occupying almost its interior totality, whereas the integrity of this system was in strict relation with intracranial volume, that is, the addition of any kind of volume would lead to the reduction of another equivalent.[
John Abercrombie (1780–1844), a pathologist also graduated at the University of Edinburgh, an eminent surgeon and physician of the King of Scotland, was actually responsible for spreading the doctrine among the medical community. Although his first publication occurred in 1811 — prior to Kellie’s —, his most famous manuscript[
However, Monro, Kellie, and Abercrombie were unable to complete the theory due to limitations of knowledge on the anatomy and physiology of the nervous system in that time. They ignored the role and even the presence of the CSF in the regulation of ICP.
Although most of what has been described about CSF and ICP is owed to Western researchers, the first reference to the CSF is found in an Egyptian manuscript dated from 1500 BC, which probably dates back to another document from 3000 to 2500 BC of uncertain authorship, perhaps from Imhotep.[
In the Western world, both Hippocrates (460–375 BC) and Galen (AD 130–200) recognized the presence of some liquid around the brain.[
The ancient anatomists either ignored the existence of any liquid filling the cerebral ventricles or admitted that it only existed after death, resulting from the condensation of vapor after death. This erroneous idea was conceived from autopsies in which incisions in the cervical region resulted in fluid drainage. As it was not found, its existence was denied.[
The absence of dissections during the Middle Age restricted anatomical studies as a whole, with no major advances in the field. CSF and brain structures were again investigated only during Renaissance, after reintroduction of dissections.[
During the Renaissance, different authors reinforced the existence of the CSF, such as Leonardo da Vinci (1452–1519), Andreas Vesalius (1514–1564), and Constantius Varolius (1543–1575), and started the basis for understanding the CSF circulation. Gerard Blasius (1627–1682), in 1666, named the arachnoid membrane and several authors expanded their knowledge about it well as subarachnoid space, such as Raymond Vieussens (1635–1715), Frederik Ruysch (1638–1731), and Antonio Pacchioni (1665–1726), who described the arachnoid granulations.[
The understanding of the liquid and its flow has advanced with the discovery of CSF in different spaces and with greater understanding on the anatomy of the nervous system. Domenico Cotugno (1736–1822), in 1764, described CSF around the spinal cord, in the ventricular spaces, below the spinal cord, and also in the labyrinth of fishes and turtles. Alexander Monro secundus described the intraventricular foramen and François Magendie (1783–1855) discovered the communication between the lateral ventricles and the third ventricle. It also led to the idea that the medulla and the brain were suspended in the liquid, along with the erroneous conclusion that it was produced by the pia mater. Hubert von Luschka consolidated the idea that the choroid plexus was in fact responsible for the production of CSF, defended by Willis.[
In 1842, Magendie’s publication defined CSF as a physiological fluid inside the skull. Despite creating the notion of a third volume, it did not lead immediately to the reformulation Monro-Kellie doctrine. Only in 1846, the English physician George Burrows clarified some mistakes made in the initial formulations.[
Many other researchers after Burrows helped clarify the missing points. Henry Duret (1849–1921) showed that increased pressure could cause blood vessel compression, reducing cerebral blood flow, and also demonstrated that CSF absorption, vertebral ligament extensibility and venous sinus collapse would alleviate the increase in pressure in the early stages of intracranial hypertension. Ernst von Bergmann (1836–1907) demonstrated CSF drainage into the elastic spinal canal as a mean of controlling this pressure. Theodor Kocher (1841–1917), in turn, established that in ICP first stage of the elevation there would be compensation through drainage of the CSF, compression of veins and capillaries and displacement of brain tissue through the foramen magnum, adding to Bergmann and Duret contributions.[
In the 20th century, it was Harvey Cushing (1869–1939), the father of modern neurosurgery, who demonstrated the clinical and physiological importance of the doctrine. Indeed, he consolidates Burrows’ discoveries regarding CSF importance in intracranial dynamics and the presence of three volumes that act compensating the depletion or insertion of volume inside the skull.[
Neurosurgeon Lewis H. Weed (1886–1952)[
Since Cushing, little progress in the theory was made. Therefore, the assumptions of constant intracranial volume and inelastic skull are accepted worldwide.[
Monro-Kellie’s theory was a starting point for understanding pathological phenomena and possible variations on ICP. One of the elements investigated, even during the consolidation of the theory, was the intracranial pulse. Furthermore, Burrows,[
Angelo Mosso (1846–1910), an Italian physiologist born in Chieri, Piemonte, was a prominent researcher on brain activity, having laid the foundation for the current understanding of functional neuroimaging.[
In 1955, Edgar Bering Jr. (1917–1994)[
Furthermore, obstinately studying cerebral blood flow, Thomas Langfitt (1927–2005) and collaborators carried out different investigations in monkeys during the 1960s, in which they gradually increased intracranial volume by means of an extradural supratentorial balloon. The authors found that the pressure did not increase linearly. At first, the CSF was drained, preventing significant pressure variation, however, after overcoming the compensation mechanisms, the increase would occur exponentially. Therefore, even small volume variations would produce a large increase in volume. In the experiments, 1 mL, at the end of the curve, was able to raise the ICP by 70 mmHg, although at the beginning of the curve there was almost no pressure change.[
For some years, the pressure x volume curve and the understanding of the intracranial pulse seemed disconnected. Marmarou’s investigations contributed to a better understanding of the relationship between these two phenomena. In his study on intracranial compliance, he demonstrated changes in the amplitude of this pulse at different points on the volume and pressure curve.[
Portnoy and Chopp,[
Gega et al.[
In 2016, Nucci et al.[
Understanding intracranial dynamics is an unfinished historical construction. Current knowledge is the result of two centuries of research that began with the investigations of Alexander Monro secundus. From the Monro-Kellie doctrine, it was possible to understand the behavior of intracranial volumes and to investigate new pressure parameters such as CSFPP.
Patient’s consent not required as patients identity is not disclosed or compromised.
Publication of this article was made possible by the James I. and Carolyn R. Ausman Educational Foundation.
There are no conflicts of interest.
1. Abercrombie J.editors. Pathological and Practical Researches on Disease of the Brain and Spinal Cord. Edinburgh: Waugh and Innes; 1828. p.
2. Arribas MA. The history of cerebrospinal fluid: From classical antiquity to the late modern period. Neurosci Hist. 2017. 5: 105-13
3. Bering EA. Choroid plexus and arterial pulsation of cerebrospinal fluid; demonstration of the choroid plexuses as a cerebrospinal fluid pump. AMA Arch Neurol Psychiatry. 1955. 73: 165-72
4. Blomstedt P. Imhotep and the discovery of cerebrospinal fluid. Anat Res Int. 2014. 2014: 256105
5. Breasted JH. The Edwin Smith Surgical Papyrus: Published in Facsimile and Hieroglyphic Transliteration with Translation and Commentary in Two Volumes. Chicago: University of Chicago; 1930. 3:
6. Burrows G.editors. On Disorders of the Cerebral Circulation and on the Connection between Affections of the Brain and Diseases of the Heart. Philadelphia, PA: Lea and Blanchard; 1848. p.
7. Cardoso ER, Rowan JO, Galbraith S. Analysis of cerebrospinal fluid pulse wave in intracranial pressure. J Neurosurg. 1983. 59: 817-21
8. Cushing H.editors. The Third Circulation in Studies in Intracranial Physiology and Surgery. London: Oxford University Press; 1926. p. 1-51
9. Deisenhammer F, Deisenhammer F, Sellebjerg F, Teunissen C, Tumani H.editors. The history of cerebrospinal fluid. Cerebrospinal Fluid in Clinical Neurology. Cham: Springer; 2015. p.
10. di Ieva A, Yaşargil MG. Liquor cotunnii: The history of cerebrospinal fluid in Domenico Cotugno’s work. Neurosurgery. 2008. 63: 352-8
11. Galen , CG Kühn.editors. Opera Omnia. Lipsiae: C. Cnoblock; 1821-1833. p.
12. Gega A, Utsumi S, Iida Y, Tsuncda S, Shulman K, Marmarou A, Miller JD, Becker DP, Hochwald GM, Brock M.editors. Analysis of the wave pattern of CSF pulse wave. Intracranial Pressure IV. Berlin, Heidelberg, New York: Springer-Verlag; 1980. p. 188-90
13. Hajdu SI. A note from history: Discovery of the cerebrospinal fluid. Ann Clin Lab Sci. 2003. 33: 334-6
14. Herbowski L. The maze of the cerebrospinal fluid discovery. Anat Res Int. 2013. 2013: 596027
15. Jones WH.editors. Collected Works. London: W. Heinemann; 1923. p.
16. Kellie G. An account of the appearances observed in the dissection of two of three individuals presumed to have perished in the storm of the 3D, and whose bodies were discovered in the vicinity of Leith on the morning of the 4th November 1821 with some reflections on the pathology of the brain. Trans Med Chir Soc Edinb. 1824. 1: 84-169
17. Langfitt TW, Kassell NF, Weinstein JD. Cerebral blood flow with intracranial hypertension. Neurology. 1965. 15: 761-73
18. Langfitt TW. Increased intracranial pressure. Neurosurgery. 1969. 16: 436-71
19. Longatti P. Domenico Felice Cotugno and the rationale of his discovery of CSF. Childs Nerv Syst. 2008. 24: 161-2
20. Lundberg N, Ishii S, Nagai H, Brock M.editors. The saga of the Monro-Kellie doctrine in intracranial pressure V. Proceedings of the Fifth International Symposium on Intracranial Pressure, Tokyo, Japan, May 30-June 3, 1982. Berlin: Springer-Verlag; 1983. p. 68-76
21. Macintyre I. A hotbed of medical innovation: George Kellie (1770-1829), his colleagues at Leith and the Monro-Kellie doctrine. J Med Biogr. 2014. 22: 93-100
22. Marmarou A, Shulman K, LaMorgese J. Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system. J Nenrosurg. 1975. 43: 523-34
23. Marmarou A.editors. A Theoretical and Experimental Evaluation of the Cerebrospinal Fluid System, PhD Thesis. Pennsylvania: Drexel University; 1973. p.
24. Mascarenhas S, Vilela GH, Carlotti C, Damiano LE, Seluque W, Colli B. The new ICP minimally invasive method shows that the Monro-Kellie doctrine is not valid. Acta Neurochir Suppl. 2012. 114: 117-20
25. Mokri B. The Monro-Kellie hypothesis: Applications in CSF volume depletion. Neurology. 2001. 56: 1746-8
26. Monro A.editors. Observations on the Structure and Function of the Nervous System. Ediburgh: Creech and Johnson; 1783. p.
27. Mosso A.editors. Sulla Circolazione del Sangue nel Cervello Deel’Uomo: Ricerche Sfigmografiche. Roma: Coi Tipi del Salviucci; 1880. p.
28. Nag DS, Sahu S, Swain A, Kant S. Intracranial pressure monitoring: Gold standard and recent innovations. World J Clin Cases. 2019. 7: 1535-53
29. Nucci CG, de Bonis P, Mangiola A, Santini P, Sciandrone M, Risi A. Intracranial pressure wave morphological classification: Automated analysis and clinical validation. Acta Neurochir (Wien). 2016. 158: 581-8
30. Portnoy HD, Chopp M, Shulman K, Marmarou A, Miller JD, Becker DP, Hochwald GM, Kasner M.editors. Spectral analysis of intracranial pressure. Intracranial Pressure IV. New York: Springer-Verlag; 1980. p. 167-72
31. Shen L, Wang Z, Su Z, Qiu S, Xu J, Zhou Y. Effects of intracranial pressure monitoring on mortality in patients with severe traumatic brain injury: A meta-analysis. PLoS One. 2016. 11: e0168901
32. Sonig A, Jumah F, Raju B, Patel NV, Gupta G, Nanda A. The historical evolution of intracranial pressure monitoring. World Neurosurg. 2020. 138: 491-7
33. Swedenborg E.editors. The Brain, Considered Anatomically, Physiologically and Philosophically. London: Andesite Press; 1887. p.
34. Weed LH. Some limitations of the Monro-Kellie hypothesis. Arch Surg. 1929. 18: 1049-68
35. Wilson MH. Monro-Kellie 2-0 The dynamic vascular and venous pathophysiological components of intracranial pressure. J Cereb Blood Flow Metab. 2016. 36: 1338-50
36. Wu OC, Manjila S, Malakooti N, Cohen AR. The remarkable medical lineage of the Monro family: Contributions of Alexander primus, secundus, and tertius. J Neurosurg. 2012. 116: 1337-46
37. Zago S, Ferrucci R, Marceglia S, Priori A. The Mosso method for recording brain pulsation: The forerunner of functional neuroimaging. Neuroimage. 2009. 48: 652-6