Mapping of the brain in unconscious patients Quantitative EEG
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1 Mapping of the brain in unconscious patients Quantitative EEG Jan Claassen, MD, PhD Division of Critical Care Neurology Columbia University College of Physicians & Surgeons New York, NY Disclosures: Columbia University Clinical Translational Science Award (CTSA), Irving Institute for Clinical and Translational Research
2 EEG vs outcome: many are associated with prognosis Seizures Status epilepticus Generalized or lateralized periodic epileptiform discharges Nonreactivity Absent sleep architecture Bricolo EGCN 1978; Jaitly JClinNeurophys 1997; DeLorenzo Epil 1998; Lawn ClinNeurophys 2000; Vespa Neurol 2003; Claassen NCC 2006 and Neurol 2007; Young NCC 2005, Wijdicks Neurol 2006, Rosetti Ann Neurol 2010 Can EEG be used to quantify and study recovery of consciousness after acute brain injury?
3 Quantitative EEG tools Spectrograms: power Connectivity measures: coherence, phase lag Others: BIS, microstates Confounders Seizures and other ictal patterns Ischemia Medications Structural brain injury Skull defects Artifacts
4 Spectrograms Raw EEG Claassen et al, Ann Neurol 2013 Fast Fourrier Transform Goldfine et al Clin Neurophys 2011
5 Spectral analysis: anesthesia Frontal alpha (% relative to baseline) Group-level spatial distribution of power Hz Alpha Gamma Frontal power group level over time (Fz) Supp et al, Curr Biol 2011 Purdon et al, PNAS 2013
6 Task based Spectral analysis: chronic DOC Motor imagery in chronic DOC after TBI Cleaning data, Laplacian montage, multitaper FFT Calculate power spectral density (4 to 24 Hz) Control TBI: LIS TBI: MCS Goldfine et al Clin Neurophys 2011
7 Acute brain injury: Visual scoring vs spectral analysis Brain tumours, vascularlesions or head injuries (N=34) Compared: EEG indicators and clinical scores based on the Reaction Level Scale 85 Visual scoring QEEG technique FFT, 5s epochs Spectrograms: square root of power Results Visual EEG indicators: R and 0.57 (P<O.Ol). qeeg spectral values R (P<O.Ol) Matousek et al Acta Neurol Scand 1996
8 Acute brain injury ROC Pilot study: 4/2013 to 6/10/13 Cardiac arrest (N=15) Age 66+/-12 years, 80% male In-hospital arrest 53%, ROSC mean 14.3+/-11 min Rhythm: PEA 60%, VFIB 27%, Asyst 13% Impaired consciousness that recovered in 60% (9/15) CPS : 47% dead, 13% 3-4, 20% 1-2, 20% still in hospital
9 84 yo W, VFIB, 25 min ROSC, GCS 3, no TH, NSE 23.6, CPC 3 discharge and 1 month R-CRS total Dexmedetomidine
10 84 yo W, VFIB, 25 min ROSC, GCS 3, no TH, NSE 23.6, CPC 3 discharge and 1 month Alpha power Delta power Dexmedetomidine R-CRS total
11 84 yo W, VFIB, 25 min ROSC, GCS 3, no TH, NSE 23.6, CPC 3 discharge and 1 month Dexmedetomidine R-CRS total
12 Coherence Evaluates the stability of the phase shift between homologous electrodes Raw EEG John et al, Consc and Cogn 2001 Global coherence computed at each frequency: ratio of the largest eigenvalue to the sum of eigenvalues of the cross-spectral matrix at a given frequency and time Cimenser A et al. PNAS 2011
13 Anesthesia model Coherence Chronic DOC Severe neurologic deficit vs MCS task-free resting state EEG Coherence analysis Granger causality Supp et al, Curr Biol 2011 Induction: ant alpha coherence Emergence: loss of ant and emergence of post alpha Leon-Carrion et al Brain Res 2012 Purdon et al. PNAS 2013 Connectivity measures: coherence, imaginary part of coherency, phase lag index VS (N=10) lower connectivity than MCS (N=21) Power spectra using multitaper: Lower for VS in alpha and theta band, correlated with CRS-R Lehembre et al Funct Neurol 2012
14 Acute DOC: EEG entropy TBI (N=29) acute and chronic: Time-frequency balanced spectral entropy with sliding window EEG entropy calculations: over range Hz (response entropy from Hz) Arbitrary value for each frequency range: 0 (suppression of EEG) to 91 (alertness), whereas response entropy ranges from 0 to 100 Correlated with CRS-R (R=0.49) Higher in MCS than coma Gossieres Funct Neurol 2011
15 84 yo W, VFIB, 25 min ROSC, GCS 3, no TH, NSE 23.6, CPC 3 discharge and 1 month Coherence total Coherence alpha Dexmedetomidine R-CRS total
16 Acute brain injury: Bispectral index - BIS 25 unconscious brain injured pts (TBI, SAH, AIS) in whom sedation was withdrawn Bispectral Index (BIS) is a weighted sum of EEG subparameters containing time domain, frequency domain, and higher-order spectral information 40 and 60 ensures adequate hypnotic effect during general anesthesia Major concerns: BIS trained on intraoperative dataset Consciousness based on 6 mo GOS 1-3 vs 4-5 but this is a functional scale Fabergas et al Anesthesiol 2004
17 CONFOUNDERS That may affect the EEG Some may also be underlying causes for impaired consciousness
18 Structural injury Chronic impaired consciousness after TBI with unilateral subcortical damage Power spectrum: modest change Coherence: marked reduction ipsilateral Davey et al, Clin Neurophys 2000
19 Ictal activity and suppression burst after acute brain injury DIAGNOSIS PEDs (N=1071) NCS (N=570) NCSE (N=570) Combined (N=1071) CNS infection 23% 9% 17% 49% Toxic-metabolic encephalopathy 26% 13% 8% 47% Epilepsy-related seizures 11% 11% 20% 42% Brain tumor 17% 11% 12% 40% Post neurosurgery 13% 15% 8% 36% SAH 16% 5% 13% 34% TBI 13% 10% 8% 31% ICH 17% 4% 9% 30% Unexplained decrease in LOC 10% 10% 5% 25% AIS 16% 2% 7% 24% Claassen et al Neurol 04/07, NCC 2006, and unpublished 17% - 24% NCSz after TBI Vespa et al Neurol 2010 and CCM 2007, Szaflarski et al NCC 2010
20 Confounders: seizures 39 yo W, 20 wks pregnant, Hx epil, p/w RSE A B C D
21 Impact of seizures on qeeg
22 QEEG: Cyclic PLEDs Kurtz CurrOpCCM 2009
23 CSA: compressed spectral array NCSZ NCSZ MDZ NCSE CO2 retention & acidosis intubation Courtesy of LJ Hirsch
24 Cerebral blood flow and EEG Foreman and Claassen Crit Care 2012
25 Ischemia from vasospasm after SAH EEG changes may precede clinical detection Labar EEGClinNeurophys 1991 Relative alpha variability may detect angiographic spasm 2 d prior to TCD/angio Vespa EEGClinNeurophys 1997 Post-stim ADR may reliably detect DCI in poor grades patients Claassen ClinNeurophys L ant R ant 0.5 Day 4 Day 6 Day 7 Day 8 Claassen ClinNphys 2004
26 Secondary complication detected on ICE: Ischemic stroke in setting of vasospasm Bilat ACA and left MCA infarction Waziri AnnNeurol 2009
27 55 yo man with IVH who developed refractory hypotension AIE R SB R and L AIE L CSA R CSA L 50 ICP CPP MAP HR :00 01:15 01:30 01:45 9/30/ Kurtz CurrOpCCM
28 Medications 25 yo M with TBI with refractory ICP crises, CSA with pentobarbital bolus 100 mg and the initiation of hypothermia.
29 Muscle artifact
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32 Chest percussion artifact
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34 Chewing artifact
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36 Ventilator artifact
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38 Virtual patient
39 Challenges for tracking Consciousness in acute setting Technical as outlined Dynamic effects of evolving underlying disease process (primary and sec brain injury) Toxic metabolic effects of medical complications Brain circuit specific/non-specific effects of meds Therapeutic interventions: surgeries, Risks of stopping sedation may outweigh the benefits (ICP crises, hypertension, recurrence of seizures, resp complications) Helbok et al, JNNP 2012
40 Acknowledgements Depart. of Biomedical Informatics Adler Perotte, MD Samantha Kleinberg, PhD David Albers, PhD George Hripcsak, MD, MS Division Critical Care Neurology J Michael Schmidt, PhD Stephan A. Mayer, MD Deborah Pugin Brandon Foreman NICU Fellows NICU nurses Neurology residents Department of Neurosurgery E Sander Connolly, MD Neurosurgery residents Comprehensive Epilepsy Center Bin Tu, MD EEG Technicians Epilepsy attendings Epilepsy fellows
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