IFAD 2012

1. The black box revelation
What’s new in neuromonitoring?
Giuseppe Citerio

2. Water and the brain
Monitoring
Conclusions
No conflict of interest for this presentation

3. Capillary structure: central nervous
system “BBB”

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

5. 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 brain
of aquaporin-1
(AQP1, blue)
and AQP4
(orange)

6. Architecture of the
aquaporin-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

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

8. Postischemic edema
(22 h following 90 min of MCAO)
Amiry-Moghaddam, M., Frydenlund, D. S., & Ottersen, O. P. (2004).
Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for
the physiology and pathophysiology of water transport. Neuroscience, 129(4),
999–1010. doi:10.1016/j.neuroscience.2004.08.049
With
aquaporins
NO
aquaporins

9. Vasogenic BE Cytotoxic BE Osmotic BE
Development Increased permeability
of capillary endothelial
cells (BBB disruption)
1. Increased cell
membrane
Na/Kpermeability
2. Na/K-ATPase failure
3. Uptake of
osmotically
active solutes
Osmotic gradient
(plasma  tissue)
Permeability Increased Unchanged Unchanged
Edema fluid Rich in protein No proteins
Rich in electrolytes
Rich in electrolytes
(tissue
hyper-osmolality)
Low in electrolytes
(serum
hyposmolality)
Morphology No cell swelling
Increased interstitial
space
Cell swelling
Decreased interstitial
space
Cell swelling
Modified from Unterberg, A (2004). Edema and
brain trauma. NSC, 129(4), 1021–1029.

10. Vasogenic BE Cytotoxic BE Osmotic BE
Development Increased permeability
of capillary endothelial
cells (BBB disruption)
1. Increased cell
membrane
Na/Kpermeability
2. Na/K-ATPase failure
3. Uptake of
osmotically
active solutes
Osmotic gradient
(plasma  tissue)
Permeability Increased Unchanged Unchanged
Edema fluid Rich in protein No proteins
Rich in electrolytes
Rich in electrolytes
(tissue
hyper-osmolality)
Low in electrolytes
(serum
hyposmolality)
Morphology No cell swelling
Increased interstitial
space
Cell swelling
Decreased interstitial
space
Cell swelling
Modified from Unterberg, A (2004). Edema and
brain trauma. NSC, 129(4), 1021–1029.

11. How to monitor it ?

12. The “net” effect: increase in volume
ICP
V
P
Langfitt TW et al, J Neurosurg,1964

13. Normal
Brain edema
CT scan is suggestive but can’t measure it

14. Invasive monitoring systems

15. 1 4 6.9
1 2.8
100
1 2.2
88
0
10
20
30
40
50
60
70
80
90
100
Normal ICP Raised but reducible
ICP
Refractory ICP
SD/V versus GR/MD
D versus GR/MD
D versus all other outcomes
Odds ratios and 95% confidence intervals [95% CI] of neurological outcomes at 1
year, comparing intracranial pressure (ICP) patterns
Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review.
Treggiari. Neurocrit Care (2007) 6:104–112
Glasgow Outcome Score: GR, Good Recovery; MD, Moderate Disability; SD, Severe
Disability; V, Vegetative; D, Death
Odds ratios of neurological outcomes at 1 year,
comparing intracranial pressure (ICP) patterns

16. 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 (☐) global
cerebral edema (GCE)

17. Ultrasonography of optic nerve sheath diameter for
detection of raised intracranial pressure
Soldatos, T., Chatzimichail, K., Papathanasiou, M., & Gouliamos, A. (2009). Optic
nerve sonography: a new window for the non-invasive evaluation of intracranial
pressure 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 nerve
sheath to detect raised intracranial pressure. Critical care (London, England), 12(5), R114.
doi:10.1186/cc7006

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

19. 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

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

21. Kashif, F. M., Verghese, G. C., Novak, V., Czosnyka, M., & Heldt, T. (2012). Model-based noninvasive estimation of intracranial pressure from cerebral blood
flow velocity and arterial pressure. Science translational medicine, 4(129), 129ra44. doi:10.1126/scitranslmed.3003249
(A) ICP and nICP on 2665 nonoverlapping
windows from 45 patient records.
(B) ICP and nICP on 1673 nonoverlapping
windows from 30 records with bilateral
CBFV recordings,
(A) ICP and nICP averaged across all
windows in each of 45 patient records.

22. Intracranial pressure
When water content increases, volume increases.
Therefore, ICP could rise.
Invasive ICP monitoring
 Sensitivity: HIGH
 Not specific !!

23. Brain tissue oxygenation

24. PbrO2 and 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

25. 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

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

27. PbrO2
When water content increases, diffusivity of O2 is decreased.
Therefore, PbrO2 could decrease.
PbrO2
Sensitivity: MEDIUM
Not specific !!

28. Microdyalisis

29. 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

30. Microdyalisis
When water content increases, ischemia could develop.
Therefore, L/P could increase.
L/P
Sensitivity: MEDIUM
Not specific !!

31. How to increase specificity?

32. 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

33. H2O
Apparent diffusion coefficient - ADC
Vasogenic Cytotoxic

35. Axial diffusivity

36. Axial diffusivity

37. Passive Thermistor
Active thermistor
Thermal Diffusion Flowmetry

38. • Determination of tissue
conduction
= Thermal Conductivity [K-
value] in brain tissue
• Extraction of convection
= heat transfer within the
field
• Calculation of perfusion
= amount of power to
maintain temperature
increment of 2-3 °C above
baseline
Thermal Diffusion Flowmetry
Measurementdiameter=8mm
Temperature
Passive
thermistor
Active
thermistor 8mm
1mm

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

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

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

43.  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 NOT
SPECIFIC) with:
 ICP
 PbrO2
 Microdyalisis
 Imaging could help in defining brain edema
 Water content in the brain could be monitored with Thermal
Diffusion Flowmetry

44. Thank you for the attention