1. Neuromonitoring Techniques in the NeuroICU: Jed Hartings, PhD Department of Neurosurgery University of Cincinnati [email_address] 513-558-3567 ECoG

3. Spreading depression in human cortex Strong et al., Stroke 33:2738-43, 2002

4. Spreading depression in rabbit cortex

5. What are spreading depolarizations? ECoG DC potential Spreading depolarizations = class of pathologic waves characterized by near-complete sustained depolarization of neurons/astrocytes that propagate through gray matter at 1-5 mm/min Sustained depolarization

7. SD incidence in acute brain injury Traumatic brain injury: 50-60% Intracerebral hematomas: 50-60% Aneurysmal subarachnoid hemorrhage: 75% Malignant ischemic stroke: 100% > 200 neurosurgical patients monitored in 12 centres (Europe and USA)

9. Peri-lesion placement of electrode strip Pre-op Post-op

11. Recording requirements frequency (Hz) DC Shifts Depression (Traditional EEG Band) EEG Amplifier ECoG, 0.02 HPF attenuation 0 1

12. Recording equipment Conventional Clinical EEG System Low Frequency Limit: 0.1 Hz 1 st Generation Research System ADInstruments, Inc. • Amplifier, low freq limit: 0.02 Hz • A-to-D converter • Multi-modal data: ICP, ABP, Licox

13. Recording equipment

14. Analysis 2 3 4 5 a b c 6 d depression period propagation velocity = 10 mm/3 min = 3.3 mm/min

15. 1 sec

16. 5 min

17. Clinical relevance: SAH and stroke

19. SD and ICP Spreading Depolarizations Hartings et al., J Neurotrauma 26:1857-66, 2009 O’Phelan et al., Neurocrit Care 10:280-6, 2009

20. SD associated with hypotension, fever Hartings et al., J Neurotrauma 26:1857-66, 2009 280 SD in 17 of 32 (53%) patients

21. TBI case example rCBF (ml/100g/min) Brain temp ( ° C) depolarizations 0 2 4 6 8 Days post-TBI Licox P br O 2 > 20 mm Hg throughout ICP < 20 mm Hg throughout GCS: 7T  10T hypovolemic shock metabolic acidosis hyponatremia

22. tSAH is a risk factor for spreading depolarizations Fisher Scale Morris-Marshall Scale Depolarization Incidence (%) 4/17 13/26 8/10 4/16 5/12 16/25 p=0.01; χ 2 p=0.04; χ 2 No significant association with status of basal cisterns, midline shift, parenchymal lesions, subdural hemorrhage, or Rotterdam score.

23. SD and cerebral microdialysis Days post-trauma μ M SD (n=8) no SD (n=10) glutamate LPR

24. Seizures and spreading depolarizations Fabricius et al., Clin Neurophysiol 119:1973-1984, 2008

25. Seizures and spreading depolarizations 10 min 4 m V 1 sec 1000 μ V

26. ECoG-detected seizures are often focal 10 min 500 μ V

27. Sensitive seizure detection with ECoG

28. Depolarizations are independently associated with poor outcomes *p=0.26 ^p<0.001 Multivariate ordinal regression analysis † based on age, GCS motor score, pupils, hypoxia, hypotension, tSAH, Marshall CT category Estimated common odds ratio 95% confidence interval p-value Prognostic Score † 1.76 1.26 to 2.46 <0.001 Depolarization None 1.0 reference <0.001 CSD 1.56* 0.72 to 3.37 ISD 7.58^ 2.64 to 21.8

29. The Future? Smart catheter : CSF drainage Glucose Lactate Oxygen Temperature Pressure CBF ECoG

31. Acknowledgments COSBID-Europe Anthony Strong – London Martin Fabricius – Copenhagen Martin Lauritzen – Copenhagen Jens Dreier – Berlin Rudolf Graf – Cologne Johannes Woitzik – Berlin Oliver Sakowitz – Heidelberg COSBID-USA Ross Bullock - Miami David Okonkwo – Pittsburgh Bruce Mathern – Virginia Lori Shutter – Cincinnati Adam Wilson - Cincinnati COSBID