Cerebrospinal fluid dynamics

Cerebrospinal fluid (CSF) dynamics is disturbed in patients with hydrocephalus and idiopathic intracranial hypertension (IIH). Diagnostics include (but are not limited to) infusion tests and overnight monitoring of ICP. During an infusion test, the model of CSF dynamics is identified using computer monitoring. As the results, a set of parameters like resistance to CSF outflow, elasticity, compensatory reserve is estimated. These variables are helpful in making a clinical decision about shunt implantation. Special studies are aimed at assessment of CSF dynamics jointly with cerebral blood flow (1).

In hydrocephalic patients with a shunt implanted, shunt failure may lead to recurrence of adverse clinical symptoms of hydrocephalus. The methodology invented in our laboratory permits objective shunt testing in-vivo. This avoids unnecessary shunt revision – a yearly saving in our hospital amounts to £1,000,000. 

IIH leads to an abnormal increase in ICP causing headaches, vision impairment and even ischaemic brain damage in sub-optimally managed cases. Overnight ICP monitoring facilitates diagnosis both in adults and in paediatric cases. The model of interaction between high ICP and venous outflow (3) is investigated in selected cases.

References

• Momjian S, Owler BK, Czosnyka Z, Czosnyka M, Pena A, Pickard JD. Pattern of white matter regional cerebral blood flow and autoregulation in normal pressure hydrocephalus. Brain. 2004 May;127(Pt 5):965-72. doi: 10.1093/brain/awh131. Epub 2004 Mar 19. PMID: 15033897.
• Lalou AD, Czosnyka M, Garnett MR, Nabbanja E, Petrella G, Hutchinson PJ, Pickard JD, Czosnyka Z. Shunt infusion studies: impact on patient outcome, including health economics. Acta Neurochir (Wien). 2020 May;162(5):1019-1031. doi: 10.1007/s00701-020-04212-0. Epub 2020 Feb 20. PMID: 32078047; PMCID: PMC7156359.
• Lalou AD, Czosnyka M, Czosnyka ZH, Krishnakumar D, Pickard JD, Higgins NJ. Coupling of CSF and sagittal sinus pressure in adult patients with pseudotumour cerebri. Acta Neurochir (Wien). 2020 May;162(5):1001-1009. doi: 10.1007/s00701-019-04095-w. Epub 2019 Dec 12. PMID: 31832847; PMCID: PMC7156361.

Reversible Dementia Project (REVERT)

REVERT is cross-border research project to improve care and quality of life for patients with normal pressure hydrocephalus. It involves a partnership of hospitals, universities and a medical software company in the UK and France.

Learn more about the REVERT project, which is co-financed by the European Regional Development Fund via the France (Channel) England Programme.

Non-invasive intracranial pressure monitoring

Accurate measurement and monitoring of intracranial pressure (ICP), the pressure within the craniospinal compartment, is a central pillar of neurocritical care, and has been used in the management of traumatic brain injury (TBI) patients since the 1960s. Following a TBI, dramatic changes in this metric are common and often harmful. Intracranial hypertension (IH), or abnormally high ICP, poses the threat of displacing brain tissue and leading to brain herniation, which can be fatal. It is therefore critical to continuously monitor ICP to detect any sudden changes or long-term trends in order to ensure that it does not rise above a critical value. Common methods of ICP monitoring include the placement of an intraventricular drain (IVD) in connection with an external pressure transducer, as well as the use of an intraparenchymal microsensor. While these give accurate ICP recording within 2 mmHg of error, they are invasive procedures that can introduce infection.

There are numerous research studies exploring the non-invasive monitoring of ICP. Examples of such techniques include correlating parameters such as pulsatility index and optic nerve sheath diameter with ICP. More recently, there have been endeavours to use machine learning for non-invasive monitoring of ICP, the majority of which use classification models to detect IH in the present or near future, using input data such as ICP, arterial blood pressure (ABP), and demographic information. We have been investigating the use of the cerebral blood flow velocity waveform (CBFV), collected using transcranial doppler ultrasonography (TCD), in conjunction with the ABP and ICP signals to assess novel machine learning models’ usefulness in estimating current ICP and predicting future ICP.

Selected key publications

[1] F. Guiza, B. Depreitere, I. Piper, G. Van Den Berghe, and G. Meyfroidt, “Novel methods to predict increased intracranial pressure during intensive care and longterm neurologic outcome after traumatic brain injury: Development and validation in a multicenter dataset,” Critical Care Medicine, vol. 41, no. 2, pp. 554–564, 2013.

[2] H.-J. Lee, H. Kim, Y.-T. Kim, K. Won, M. Czosnyka, and D.-J. Kim, “Prediction of Life-Threatening Intracranial Hypertension During the Acute Phase of Traumatic Brain Injury Using Machine Learning,” IEEE Journal of Biomedical and Health Informatics, vol. PP, pp. 1–1, 2021.

[3] F. Wadehn, D. Walser, M. Bohdanowicz, M. Czosnyka, and T. Heldt, “Non-invasive detection of intracranial hypertension using random forests,” Computing in Cardiology, vol. 44, pp. 1–4, 2017.

Cerebral autoregulation

Cerebral autoregulation is a protective physiological mechanism that maintains an adequate cerebral blood flow despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation is associated with poor outcome after acute brain injury. We can assess cerebral autoregulation continuously thanks to different methods, which include both time and frequency domain techniques, that allow to derive indices of the autoregulatory mechanism. Patient populations include traumatic brain injury, subarachnoid haemorrhage, neonatal hypoxic brain injury, and many others. Our indices have also been explored and validated in experimental studies.

Our research focuses on:

• Development of methods for monitoring cerebral autoregulation
• Understanding the pathophysiology that drives impairment of the mechanism
• Understanding the dynamics of the mechanism
• Exploring the relationship with clinical variables

Key references

• Czosnyka M, Smielewski P, Kirkpatrick P, Laing RJ, Menon D, Pickard JD (1997) Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 41(1):11-7
• Budohoski K, Czosnyka M, Smielewski P, et al. Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke 2012;43(12): 3230-7
• Liu X, Donnelly J, Czosnyka M, et al. Cerebrovascular pressure reactivity monitoring using wavelet analysis in traumatic brain injury patients: A retrospective study. PLoS Med. 2017;14(7). doi:10.1371/journal.pmed.1002348

Individualising Cerebral Perfusion Pressure Management

Continuous monitoring of cerebral autoregulation allows to identify values of cerebral perfusion pressure at which autoregulation is best preserved (CPPopt). We have implemented advanced signal processing techniques and developed methods for monitoring CPPopt in real time. CPPopt dynamic time trend can be displayed at the bedside, offering the opportunity for clinicians to target cerebral perfusion pression at CPPopt for each patient. The COGiTATE trial showed that this approach is feasible and safe in traumatic brain injury patients. When cerebral perfusion pressure cannot be assessed, arterial blood pressure can be optimized in order to maintain the brain within the autoregulatory range (ABPopt). The assessment of the lower limit of autoregulation and the upper limit of autoregulation offer further means for individualising cerebral perfusion pressure management.

Our research focuses on:

• Development of methods for assessment of individualised cerebral perfusion pressure targets
• Development of methods for visualisation of the targets at the bedside
• Implementation of autoregulation-based cerebral perfusion pressure management in clinical protocols

Key references

• Steiner LA, Czosnyka M, Piechnik SK, et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med 2002;30(4):733-8
• Tas J, Beqiri E, van K RC, et al. Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial. J Neurotrauma. Published online August 16, 2021
• da Costa CS, Czosnyka M, Smielewski P, Mitra S, Stevenson GN, Austin T. Monitoring of Cerebrovascular Reactivity for Determination of Optimal Blood Pressure in Preterm Infants. J Pediatr. 2015;167(1):86-91