The black box revelationWhat’s new in neuromonitoring?

Giuseppe Citerio

! Water and the brain

! Monitoring

! Conclusions

Capillary structure: central nervoussystem “BBB”

Adrogue HJ, Madias NE. Review article : HYPONATREMIA. N Engl J Med 2000 ; 342 : 1581-9.

Amiry-Moghaddam, M., & Ottersen, O. P. (2003). The molecular basis of water transport in the brain. Nature Reviews Neuroscience, 4(12), 991–1001. doi:10.1038/nrn1252

Distribution in brainof aquaporin-1(AQP1, blue)and AQP4(orange)

Architecture of theaquaporin-1

Amiry-Moghaddam, M., & Ottersen, O. P. (2003). The molecular basis of water transport in the brain. Nature Reviews Neuroscience, 4(12), 991–1001. doi:10.1038/nrn1252

Amiry-Moghaddam, M., Frydenlund, D. S., & Ottersen, O. P. (2004). Anchoringof aquaporin-4 in brain: molecular mechanisms and implications for thephysiology and pathophysiology of water transport. Neuroscience, 129(4),999–1010. doi:10.1016/j.neuroscience.2004.08.049

Postischemic edema (22 h following 90 min ofMCAO)

Amiry-Moghaddam, M., Frydenlund, D. S., & Ottersen, O. P. (2004). Anchoringof aquaporin-4 in brain: molecular mechanisms and implications for thephysiology and pathophysiology of water transport. Neuroscience, 129(4),999–1010. doi:10.1016/j.neuroscience.2004.08.049

Withaquaporins

NOaquaporins

VasogenicBE CytotoxicBE OsmoticBE

Development Increasedpermeabilityofcapillaryendothelialcells(BBBdisruption)

1.IncreasedcellmembraneNa/Kpermeability2.Na/K-ATPasefailure3.Uptakeofosmoticallyactivesolutes

Osmoticgradient(plasma➔tissue)

Permeability Increased Unchanged Unchanged

Edemafluid Richinprotein NoproteinsRichinelectrolytes

Richinelectrolytes(tissuehyper-osmolality)Lowinelectrolytes(serumhyposmolality)

Morphology NocellswellingIncreasedinterstitialspace

CellswellingDecreasedinterstitialspace

Cellswelling

Modified from Unterberg, A (2004). Edema andbrain trauma. NSC, 129(4), 1021–1029.

VasogenicBE CytotoxicBEOsmoticBE

Development Increasedpermeabilityofcapillaryendothelialcells(BBBdisruption)

1.IncreasedcellOsmoticgradientmembrane(plasma➔tissue)Na/Kpermeability2.Na/K-ATPasefailure3.Uptakeofosmoticallyactivesolutes

Permeability Increased UnchangedUnchanged

Edemafluid Richinprotein NoproteinsRichinelectrolytesRichinelectrolytes(tissuehyper-osmolality)

Lowinelectrolytes(serumhyposmolality)

Morphology NocellswellingIncreasedinterstitialspace

CellswellingCellswellingDecreasedinterstitialspace

Modified from Unterberg, A (2004). Edema andbrain trauma. NSC, 129(4), 1021–1029.

How to monitor it ?

The “net” effect: increase in volume

ICP

P

V

Langfitt TW et al, J Neurosurg,1964

Normal

Brain edema

CT scan is suggestive but can’t measure it

Invasive monitoring systems

Odds ratios and 95% confidence intervals [95% CI] of neurological outcomes at 1year, comparing intracranial pressure (ICP) patterns

Glasgow Outcome Score: GR, Good Recovery; MD, Moderate Disability; SD, SevereDisability; V, Vegetative; D, Death

Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review.Treggiari. Neurocrit Care (2007) 6:104–112

Odds ratios of neurological outcomes at 1 year,comparing intracranial pressure (ICP) patterns

Helbok, R., Ko, S. B., Schmidt, J. M., Kurtz, P., Fernandez, L., Choi, H. A., Connolly, E. S., et al. (2011). Global Cerebral Edema and Brain Metabolism After Subarachnoid Hemorrhage.Stroke. doi:10.1161/STROKEAHA.110.604488

patients with (■) and without (☐) globalcerebral edema (GCE)

Ultrasonography of optic nerve sheath diameter fordetection of raised intracranial pressure

Soldatos, T., Chatzimichail, K., Papathanasiou, M., & Gouliamos, A. (2009). Opticnerve sonography: a new window for the non-invasive evaluation of intracranialpressure in brain injury. Emergency Medicine Journal, 26(9), 630–634. doi:10.1136/emj.2008.058453

Geeraerts, T., Newcombe, V. F. J., Coles, J. P., Abate, M. G., Perkes, I. E., Hutchinson, P. J. A.,Outtrim, J. G., et al. (2008). Use of T2-weighted magnetic resonance imaging of the optic nervesheath to detect raised intracranial pressure. Critical care (London, England), 12(5), R114. doi:10.1186/cc7006

Dubourg J Ultrasonography of optic nerve sheath diameter for detectionof raised intracranial pressure: a systematic review and meta-analysis.Intensive Care Med. 2011;37(7):1059–1068.

A new approach

Goldstein, B., Tasker, R. C., & Wakeland, W. (2012). From Lundberg to SIM-ICP: Computational Physiology and Modeling Intracranial Pressure.Science translational medicine, 4(129), 129fs6. doi:10.1126/scitranslmed.3003925

Kashif, F. M., Verghese, G. C., Novak, V., Czosnyka, M., & Heldt, T. (2012). Model-based noninvasive estimation of intracranial pressure from cerebral bloodflow velocity and arterial pressure. Science translational medicine, 4(129), 129ra44. doi:10.1126/scitranslmed.3003249

Kashif, F. M., Verghese, G. C., Novak, V., Czosnyka, M., & Heldt, T. (2012). Model-based noninvasive estimation of intracranial pressure from cerebral bloodflow velocity and arterial pressure. Science translational medicine, 4(129), 129ra44. doi:10.1126/scitranslmed.3003249

(A) ICP and nICP on 2665 nonoverlappingwindows from 45 patient records.

(B) ICP and nICP on 1673 nonoverlappingwindows from 30 records with bilateralCBFV recordings,

(C) ICP and nICP averaged across allwindows in each of 45 patient records.

Intracranial pressure

When water content increases, volume increases.

Therefore, ICP could rise.

Invasive ICP monitoring

✓ Sensitivity: HIGH

✓ Not specific !!

Brain tissue oxygenation

PbrO2and edema

Moppett, I. K., & Hardman, J. G. (2007). Modeling the causes of variation in brain tissue oxygenation.Anesthesia & Analgesia, 105(4), 1104–12– table of contents. doi:10.1213/01.ane.0000281934.99076.89

Leach RM and Treacher DF BMJ 1998; 317:1370-73

Helbok, R., Ko, S. B., Schmidt, J. M., Kurtz, P., Fernandez, L., Choi, H. A., Connolly, E. S., et al. (2011). Global Cerebral Edema andBrain Metabolism After Subarachnoid Hemorrhage. Stroke. doi:10.1161/STROKEAHA.110.604488

patients with (■) and without (☐) globalcerebral edema (GCE

Fletcher, J. J., Bergman, K., Blostein, P. A., & Kramer, A. H. (2010). Fluid balance, complications, and brain tissue oxygen tensionmonitoring following severe traumatic brain injury. Neurocritical Care, 13(1), 47–56. doi:10.1007/s12028-010-9345-2

PbrO2

When water content increases, diffusivity of O2 is decreased.

Therefore, PbrO2could decrease.

PbrO2

! Sensitivity: MEDIUM

! Not specific !!

Microdyalisis

Helbok, R., Ko, S. B., Schmidt, J. M., Kurtz, P., Fernandez, L., Choi, H. A., Connolly, E. S., et al. (2011). Global Cerebral Edema andBrain Metabolism After Subarachnoid Hemorrhage. Stroke. doi:10.1161/STROKEAHA.110.604488

patients with (■) and without (☐) globalcerebral edema (GCE

Microdyalisis

When water content increases, ischemia could develop.

Therefore, L/Pcould increase.

L/P

! Sensitivity: MEDIUM

! Not specific !!

How to increase specificity?

Lescot, T., Bonnet, M.-P., Zouaoui, A., Muller, J.-C., Fetita, C., Coriat, P., & Puybasset, L. (2005). A quantitative computed tomography assessment of brain weight,volume, and specific gravity in severe head trauma. Intensive Care Medicine, 31(8), 1042–1050. doi:10.1007/s00134-005-2709-y

H2O

Apparent diffusion coefficient - ADC

Vasogenic Cytotoxic

Axial diffusivity

Axial diffusivity

Active thermistor

Thermal Diffusion Flowmetry

Passive Thermistor

Tem

pera

ture

Mea

sure

men

t dia

met

er =

8m

m

conduction = ThermalConductivity [K-value] in braintissue•  Extraction of convection= heat transfer within the field•  Calculation of perfusion= amount of power to maintaintemperature increment of 2-3°C above baseline

Activethermistor

Passivethermistor

8mm

Thermal Diffusion Flowmetry1mm

•  Determination of tissue

Ko, S.-B., Alex Choi, H., Parikh, G., Michael Schmidt, J., Lee, K., Badjatia, N., Claassen, J., et al. (2012). Real time estimation of brainwater content in comatose patients. Annals of Neurology, n/a–n/a. doi:10.1002/ana.23619

Ko, S.-B., Alex Choi, H., Parikh, G., Michael Schmidt, J., Lee, K., Badjatia, N., Claassen, J., et al. (2012). Real time estimation of brainwater content in comatose patients. Annals of Neurology, n/a–n/a. doi:10.1002/ana.23619

Ko, S.-B., Alex Choi, H., Parikh, G., Michael Schmidt, J., Lee, K., Badjatia, N., Claassen, J., et al. (2012). Real time estimation of brainwater content in comatose patients. Annals of Neurology, n/a–n/a. doi:10.1002/ana.23619

! Water in the brain is tightly controlled.

! Brain edema is associated with HICP and worse outcome

! Increase in water content could be evaluated (even if NOTSPECIFIC) with:! ICP! PbrO2

! Microdyalisis

! Imaging could help in defining brain edema

! Water content in the brain could be monitored with ThermalDiffusion Flowmetry

Thank you for the attention