Post-anoxic status epilepticus and EEG patterns

Transcription

1 Post-anoxic status epilepticus and EEG patterns Nicolas Gaspard, MD, PhD Université Libre de Bruxelles Hôpital Erasme, Bruxelles, Belgique Yale University School of Medicine, New Haven, CT, USA

2 DISCLOSURES (NONE ARE RELEVANT TO THIS TALK SAVE ONE ) Research funding Fonds de la Recherche Scientifique (FNRS) Fonds Erasme pour la Recherche Médicale Daniel Raymond Wong Neurological Research Fund Consulting activities UCB SAGE Therapeutics I don t have all the answers! (no one does ) 2

3 PLAN Post-anoxic EEG patterns: Criteria (ACNS) for interpretation of EEG phenomena Prognostic significance Routine EEG or continuous EEG monitoring (CEEG)? Post-anoxic myoclonus: what s in a name? Post-anoxic seizures and status epilepticus: Criteria Prevalence and significance 3

4 DESCRIPTION AND INTERPRETATION OF EEG PATTERNS IN THE CRITICALLY ILL Synek, Clin Electroencephalogr and 1990 Brenner et al., J Clin Neurophysiol Young et al., Can J Neurol Sci The ACNS Terminology 2005 version Multiple rounds of IRA assessment, public review and revisions 2013 version 4

5 2013 ACNS TERMINOLOGY: FRAMEWORK Main term 1 Lateralized (L) Generalized (G) Bilateral independent (BI) Multifocal (Mf) Main term 2 Periodic discharges (PD) Rhythmic delta activity (RDA) Spike-and-wave (SW) Modifiers Sharpness Amplitude Frequency «+» (fast activity, spike, rhythmic delta) Etc. Background description Continuity Voltage Dominant frequency Variability Reactivity Symmetry Hirschet al., Journal Clin Neurophysiol care- eeg- monitoring- research- consortium- ccemrc/education

6 Disclaimer This does not imply that these patterns are not ictal, but simply that they may or may not be.

7 SUPPRESSION

8 SUPPRESSION-BURST

9 SUPPRESSION- GPDS

10 GSW

11 ACNS TERMINOLOGY: INTER-RATER AGREEMENT Terminology item Choices Agreement (%) Kappa (j), % (95% CI) Seizure Yes, no ( ) Main term 1 G, L, BI, M ( ) Main term 2 PD, RDA, SW ( ) Plus (+) modifier F, R, S, FR, FS, No ( ) Any + Yes, no ( ) +Fast activity (F) Yes, no, not applicable ( ) +Rhythmic activity (R) Yes, no, not applicable ( ) +Spike or sharply Yes, no, not applicable ( ) contoured (S) Sharpness Spiky, sharp, sharply contoured, blunt, not applicable ( ) Absolute amplitude Very low, low, medium, high ( ) Relative amplitude <2, >2, not applicable ( ) Frequency <1, 1 2, 2 3, 3 4, >4 Hz ( ) Phases 1, 2, 3, >3, not applicable ( ) Evolution Static, evolving, fluctuating ( ) Triphasic morphology Yes, no, not applicable ( ) Gaspard et al., Epilepsia 2014

12 ACNS TERMINOLOGY IN ANOXIC BRAIN INJURY: INTER- RATER AGREEMENT Percent agreement Kappa Strength of interrater agreement All 4 raters (%) Median 6 pairs (%) Median 6 pairs (range) Prespecified EEG patterns: Highly malignant EEG ( ) Substantial Malignant EEG ( ) Moderate Malignant periodic or rhythmic pattern ( ) Substantial Malignant background EEG ( ) Moderate Unreactive EEG ( ) Fair Benign EEG ( ) Moderate Background EEG: Continuity ( ) Substantial Voltage ( ) Substantial Predominant frequency ( ) Moderate Reactivity to sound ( ) Fair Reactivity to pain ( ) Slight Periodic or rhythmic patterns: Periodic or rhythmic discharges ( ) Moderate Prevalence ( ) Moderate Typical frequency ( ) Substantial Maximum frequency ( ) Substantial Sharpness (predominant phase) ( ) Substantial Absolute amplitude ( ) Moderate Stimulus induced pattern ( ) Slight Evolution ( ) Slight Plus Modifier present ( ) Slight Triphasic morphology ( ) Poor Westhall et al., ClinNeurophysiol 2015

13 ACNS TERMINOLOGY IN ANOXIC BRAIN INJURY: PROGNOSTIC VALUE Time After Resuscitation (hrs) Predicting Sensitivity (95% CI) Specificity (95% CI) Positive Predicting Value (95% CI) Negative Predictive Value (95% CI) Somatosensory evoked potential N20 absent <24 Poor outcome EEG continuous 12 Good outcome EEG isoelectric or 24 Poor low voltage outcome EEG isoelectric, 24 Poor low voltage, outcome or burst suppression CI, confidence interval; EEG, electroencephalogram. 24 (10 44) 100 (87 100) 100 (59 100) 55 (40 60) 43 (23 66) 100 (86 100) 100 (69 100) 67 (50 81) 40 (19 64) 100 (86 100) 100 (63 100) 68 (51 82) 95 (75 100) 96 (80 100) 96 (80 100) 95 (75 100) Some patients with SB <24h did well. Cloostermans et al., CCM 2012

14 ACNS TERMINOLOGY IN ANOXIC BRAIN INJURY: PROGNOSTIC VALUE % Patients B 100% 80% 60% 40% 20% 0% C 100% Poor Outcome Time from ROSC to EEG (h) Good Outcom e SB always associatedwithpoor outcome! % Poor Outcome 100% 80% 60% 40% 20% 0% ime from ROSC to EEG (h) n = % Patients 80% 60% 40% 20% 0% Time from ROSC to EEG (h) EEG at 24h Outcome Se Sp FPR Benign Good 72% (53-86%) Malignant Poor 84% (73-92%) 97% (87-99%) 100% (84-100%) 8% (1-27%) 0% (0-8%) Sivaraju et al., ICM 2015

15 ACNS TERMINOLOGY IN ANOXIC BRAIN INJURY: PROGNOSTIC VALUE Malignant patterns included non reactive continuous background. The only patients with a malignant EEG pattern at 24h who had a good outcome had this type of pattern. SB always associated with a poor outcome Lamartine Monteiro et al., Neurocritical Care 2016

16 ACNS TERMINOLOGY IN ANOXIC BRAIN INJURY: PROGNOSTIC VALUE Outcome Using Electroencephalogram Variable Time After Resuscitation (hr) Predicting Sensitivity (95% CI) Specificity (95% CI) Positive Predictive Value (95% CI) Negative Predictive Value (95% CI) Electroencephalogram diffuse slowed or normal 12 Good outcome 56 (41 70) 96 (86 100) 93 (78 99) 68 (55 78) Electroencephalogram isoelectric, low voltage, or burstsuppression with identical bursts 24 Poor outcome 48 (35 61) 100 (94 100) 100 (89 100) 66 (56 76) Tjepkema- Cloostermans et al., CCM 2015

17 SUPPRESSION-BURST WITH IDENTICAL BURSTS * * Hofmeijer et al., Clin Neurophysiol 2014

18 ACNS TERMINOLOGY IN ANOXIC BRAIN INJURY Voorspelde uitkomst Specificiteit (95% BI) Sensitiviteit (95% BI) PPV (95% BI) NPV (95% BI) Gunstig EEG patroon na 12 uur Goed 91%* (86-95) 55% (46-64) 84%* (75-91) 70% (63-76) Ongunstig EEG patroon na 24 uur Slecht 100% (98-100) 42% (36-49) 100% (96-100) 55% (49-61) Most patients who do poorly despite a favorable EEG pattern do so because of non- neurological complications! Hofmeijer et al., TNN 2016 based on data from Hofmeijer et al., Neurology 2015 and Sivaraju et al., ICM 2015

19 STANDARD EEG OR CONTINUOUS MONITORING? Standard EEG during hypothermia missed 1/21 patient with reactivity and 2/8 patients with epileptiform discharges. Median duration of CEEG was 26h (50% of comatose post- anoxic patients had <26h of CEEG) Unclear how many patients had seizures Timing from CA to EEG assessment is key Alvarez et al., Critical Care 2013

20 Disclaimer (reminder) This does not imply that these patterns are not ictal, but simply that they may or may not be. GPDs? GSW? Suppression-burst?

21 STANDARDIZED (ARBITRARY ) CRITERIA FOR NCSE Beniczky et al., Epilepsia2013 modifiedfromkaplan, Epilpsia2007 andyoung et al., Neurology 1996

22 POST-ANOXIC MYOCLONUS: WHAT S IN A NAME? Early myoclonus Can be transient and not always associated with poor outcome Syncopal myoclonus Post-anoxic action myoclonus (a.k.a. Lance-Adams syndrome) Late (>1 week after arrest ) phenomenon in survivors Status myoclonus or Myoclonic status epilepticus?

23 STATUS MYOCLONUS VS. MYOCLONIC STATUS EPILEPTICUS Distinction advocated by Gastaut in the 60 s for PME Myoclonus can be pervasive (hence status) Myoclonus often of sub-cortical origin (hence NOT epilepticus) Myoclonus in post-anoxic status myoclonus can be of subcortical origin EEG correlate of post-anoxic status myoclonus often nonepileptiform Suppression-bursts (84%) or suppression-gpds (10%) Suppression (2%) Alpha coma (4%) Pathological correlate of status myoclonus is widespread cortical necrosis. Clinical outcome of status myoclonus is (almost) invariably poor. Young et al., Neurology 1990; Wijdicks et al., Ann Neurol 1994; Thöme et al., BMC Neurol 2005; Bouwes et al., BMC Neurol 2012;

24 POST-ANOXIC STATUS EPILEPTICUS Mani et al., Resuscitation 2012 Crepeau et al., Neurology 2013 Rossetti et al., Ann Neurol 2010 Rossetti et al., Critical Care 2010 Rittenberger et al., Neurocrital Care 2012 Ruijter et al., Epilepsia 2015 Tjepkema- Cloostermans et al., CCM 2015 Sivaraju et al., ICM 2015 N MSE NCSE (criteria) Outcome 38 3 (myoclonus +SE on EEG) (incl. 4 with both MSE and NCSE) (clinical assessment only) 34 8 (myoclonus + SB or S- GPDs) (myoclonus + SB or S- GPDs >30min) (myoclonus+se on EEG) 4 (consensus) All did poorly 1 (unclear) All did poorly Not studied Not studied 12 (consensus + 2,5Hz GPDs) 14 (consensus + GPDs >0,5Hz) 2 did well 1 did well (Post- rewarming MSE) All did poorly 10 did well (!), including 1 with rewarming MSE 142 Not studied 4 (unclear) All did poorly (Early NCSE) 100 Not studied 3 (consensus) All did poorly

25 GOOD OUTCOME IN A SUBGROUP OF PATIENTS WITH POST-ANOXIC MYOCLONIC STATUS EPILEPTICUS Rossetti et al., Neurology patients with post-anoxic MSE (GPDs + myoclonus) who regained consciousness Started >2 days after CA All 3 had present brainstem reflexes, present N20 and a reactive EEG All 3 required > 3 AEDs 2 developed Lance-Adams syndrome Sivaraju et al., ICM /4 patients with myoclonus who regained consciousness had post-anoxic MSE (GPDs + myoclonus) Started after rewarming Both had present brainstem reflexes and a reactive and continuous EEG None developed Lance-Adams syndrome Ruijter et al., Epilepsia /47 patients with post-anoxic SE had a good outcome;; one had MSE Started later (45 vs. 29h;; and always >39h post-ca) and always from a continuous background All had present brainstem reflexes, and present N20

26 PUTTING IT ALL TOGETHER Hyper acute phase CA CPR and admission Acute phase 12h Hypothermia Acute phase 24h Hypothermia Subacute phase 24h- 72h Rewarming Assessment 72h Syncopal myoclonus Early status myoclonus/myoclonic status epilepticus Early NCSE Suppression Suppression- burst (incl. w/ identical bursts) Suppression- GPDs Suppression- seizure Late SM/MSE Late NCSE GPDs GSW GRDA+S Suppression Motor response 1-2 Absent brainstem r. Absent N20 Suppression Attenuation Continuous background Motor response 3+ Continuous background Continuous background Latemyoclonic status epilepticus Late NCSE Present brainstem r. Present N20 GPDs on a continuous background Multifocal epileptiform discharges

27 Dank u wel! Questions and slides requests: nicolas.gaspard@erasme.ulb.ac.be 27