Treatment of Seizures and Postanoxic Status Epilepticus

Abstract

Seizures are a common occurrence following cardiac arrest and may occur both during targeted temperature management and after rewarming. Postanoxic seizures may be nonconvulsive and very difficult to diagnose without electroencephalography (EEG) or associated with prominent myoclonus. Importantly, to date no randomized controlled trials are available to guide the management of seizures in patients with cardiac arrest. Seizure prophylaxis is not recommended, and when seizures are diagnosed they are typically treated the same as seizures in other patients with acute brain injury. Electroencephalographic abnormalities that are highly epileptiform, but do not fulfill classic seizure criteria, also known as the ictal–interictal continuum, occur frequently and there is no consensus on how to treat these. Several EEG patterns have been associated with poor outcome in retrospective studies. Increasing evidence has emerged that patients may have a favorable outcome, even with status myoclonus and malignant EEG patterns, if aggressive management is pursued.

Keywords

myoclonus - electrographic status epilepticus - nonconvulsive seizures - generalized periodic epileptiform discharges - hypoxic–ischemic encephalopathy

• References

• 1 Venkatesan A, Frucht S. Movement disorders after resuscitation from cardiac arrest. Neurol Clin 2006; 24 (1) 123-132
• 2 Benbadis SR, Chen S, Melo M. What's shaking in the ICU? The differential diagnosis of seizures in the intensive care setting. Epilepsia 2010; 51 (11) 2338-2340
• 3 Hirsch LJ, LaRoche SM, Gaspard N , et al. American Clinical Neurophysiology Society's standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol 2013; 30 (1) 1-27
• 4 Gerard EE, Hirsch LJ. Generalized myoclonic status epilepticus. In: Panayiotopoulos CP, , ed. Atlas of Epilepsies. London: Springer London; 2010: 523-531
• 5 Hofmeijer J, van Putten MJAM. Ischemic cerebral damage: an appraisal of synaptic failure. Stroke 2012; 43 (2) 607-615
• 6 van Dijk JG, Thijs RD, van Zwet E , et al. The semiology of tilt-induced reflex syncope in relation to electroencephalographic changes. Brain 2014; 137 (Pt 2): 576-585
• 7 Brierley JB, Graham DI, Adams JH, Simpsom JA. Neocortical death after cardiac arrest. A clinical, neurophysiological, and neuropathological report of two cases. Lancet 1971; 2 (7724): 560-565
• 8 Cervós-Navarro J, Diemer NH. Selective vulnerability in brain hypoxia. Crit Rev Neurobiol 1991; 6 (3) 149-182
• 9 Björklund E, Lindberg E, Rundgren M, Cronberg T, Friberg H, Englund E. Ischaemic brain damage after cardiac arrest and induced hypothermia--a systematic description of selective eosinophilic neuronal death. A neuropathologic study of 23 patients. Resuscitation 2014; 85 (4) 527-532
• 10 Steriade M, Amzica F, Contreras D. Cortical and thalamic cellular correlates of electroencephalographic burst-suppression. Electroencephalogr Clin Neurophysiol 1994; 90 (1) 1-16
• 11 Amzica F. What does burst suppression really mean?. Epilepsy Behav 2015; 49: 234-237
• 12 Foreman B, Claassen J, Abou Khaled K , et al. Generalized periodic discharges in the critically ill: a case-control study of 200 patients. Neurology 2012; 79 (19) 1951-1960
• 13 Claassen J, Hirsch LJ, Frontera JA , et al. Prognostic significance of continuous EEG monitoring in patients with poor-grade subarachnoid hemorrhage. Neurocrit Care 2006; 4 (2) 103-112
• 14 Claassen J, Jetté N, Chum F , et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology 2007; 69 (13) 1356-1365
• 15 Yemisci M, Gurer G, Saygi S, Ciger A. Generalised periodic epileptiform discharges: clinical features, neuroradiological evaluation and prognosis in 37 adult patients. Seizure 2003; 12 (7) 465-472
• 16 van Putten MJAM, Hofmeijer J. Generalized periodic discharges: pathophysiology and clinical considerations. Epilepsy Behav 2015; 49: 228-233
• 17 Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med 2011; 17 (4) 439-447
• 18 Knight WA, Hart KW, Adeoye OM , et al. The incidence of seizures in patients undergoing therapeutic hypothermia after resuscitation from cardiac arrest. Epilepsy Res 2013; 106 (3) 396-402
• 19 Sadaka F, Doerr D, Hindia J, Lee KP, Logan W. Continuous electroencephalogram in comatose postcardiac arrest syndrome patients treated with therapeutic hypothermia: outcome prediction study. J Intensive Care Med 2015; 30 (5) 292-296
• 20 Bouwes A, van Poppelen D, Koelman JHTM , et al. Acute posthypoxic myoclonus after cardiopulmonary resuscitation. BMC Neurol 2012; 12: 63
• 21 Seder DB, Sunde K, Rubertsson S , et al; International Cardiac Arrest Registry. Neurologic outcomes and postresuscitation care of patients with myoclonus following cardiac arrest. Crit Care Med 2015; 43 (5) 965-972
• 22 Cloostermans MC, van Meulen FB, Eertman CJ, Hom HW, van Putten MJAM. Continuous electroencephalography monitoring for early prediction of neurological outcome in postanoxic patients after cardiac arrest: a prospective cohort study. Crit Care Med 2012; 40 (10) 2867-2875
• 23 Amorim E, Rittenberger JC, Baldwin ME, Callaway CW, Popescu A. Post Cardiac Arrest Service. Malignant EEG patterns in cardiac arrest patients treated with targeted temperature management who survive to hospital discharge. Resuscitation 2015; 90: 127-132
• 24 Sandroni C, Nolan JP. Neurologically favorable outcome is still possible despite myoclonus in comatose survivors of cardiac arrest. Crit Care Med 2015; 43 (9) e396-e397
• 25 van Zijl JC, Beudel M, vd Hoeven HJ, Lange F, Tijssen MAJ, Elting JWJ. Electroencephalographic findings in posthypoxic myoclonus. J Intensive Care Med 2016; 31 (4) 270-275
• 26 Legriel S, Bruneel F, Sediri H , et al. Early EEG monitoring for detecting postanoxic status epilepticus during therapeutic hypothermia: a pilot study. Neurocrit Care 2009; 11 (3) 338-344
• 27 Rundgren M, Westhall E, Cronberg T, Rosén I, Friberg H. Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients. Crit Care Med 2010; 38 (9) 1838-1844
• 28 Cronberg T, Rundgren M, Westhall E , et al. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology 2011; 77 (7) 623-630
• 29 Rittenberger JC, Popescu A, Brenner RP, Guyette FX, Callaway CW. Frequency and timing of nonconvulsive status epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit Care 2012; 16 (1) 114-122
• 30 Legriel S, Hilly-Ginoux J, Resche-Rigon M , et al. Prognostic value of electrographic postanoxic status epilepticus in comatose cardiac-arrest survivors in the therapeutic hypothermia era. Resuscitation 2013; 84 (3) 343-350
• 31 Mani R, Schmitt SE, Mazer M, Putt ME, Gaieski DF. The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia. Resuscitation 2012; 83 (7) 840-847
• 32 Schmitt FC, Buchheim K, Meierkord H, Holtkamp M. Anticonvulsant properties of hypothermia in experimental status epilepticus. Neurobiol Dis 2006; 23 (3) 689-696
• 33 Kowski AB, Kanaan H, Schmitt FC, Holtkamp M. Deep hypothermia terminates status epilepticus—an experimental study. Brain Res 2012; 1446: 119-126
• 34 Niquet J, Gezalian M, Baldwin R, Wasterlain CG. Neuroprotective effects of deep hypothermia in refractory status epilepticus. Ann Clin Transl Neurol 2015; 2 (12) 1105-1115
• 35 Ommaya AK, Baldwin M. Extravascular local cooling of the brain in man. J Neurosurg 1963; 20 (1) 8-20
• 36 Vastola EF, Homan R, Rosen A. Inhibition of focal seizures by moderate hypothermia. A clinical and experimental study. Arch Neurol 1969; 20 (4) 430-439
• 37 Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for refractory status epilepticus. Neurocrit Care 2008; 9 (2) 189-197
• 38 Guilliams K, Rosen M, Buttram S , et al. Hypothermia for pediatric refractory status epilepticus. Epilepsia 2013; 54 (9) 1586-1594
• 39 Pásztor E, Tomka I. Changes of electrocorticographic activity in response to direct brain surface cooling in epileptic patients. Acta Physiol Acad Sci Hung 1969; 36 (3) 277-292
• 40 Karkar KM, Garcia PA, Bateman LM, Smyth MD, Barbaro NM, Berger M. Focal cooling suppresses spontaneous epileptiform activity without changing the cortical motor threshold. Epilepsia 2002; 43 (8) 932-935
• 41 Claassen J, Vespa P. Participants in the International Multi-disciplinary Consensus Conference on Multimodality Monitoring. Electrophysiologic monitoring in acute brain injury. Neurocrit Care 2014; 21 (Suppl. 02) S129-S147
• 42 Callaway CW, Donnino MW, Fink EL , et al. Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015; 132 (18) (Suppl. 02) S465-S482
• 43 International Liason Committee on Resuscitation (ILCOR). Part I: Executive Summary: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2015; 132 (16) (Suppl. 01) S1
• 44 Crepeau AZ, Fugate JE, Mandrekar J , et al. Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest. Resuscitation 2014; 85 (6) 785-789
• 45 Caviness JN, Brown P. Myoclonus: current concepts and recent advances. Lancet Neurol 2004; 3 (10) 598-607
• 46 Cassim F, Houdayer E. Neurophysiology of myoclonus. Neurophysiol Clin 2006; 36 (05/06) 281-291
• 47 Brophy GM, Bell R, Claassen J , et al; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17 (1) 3-23
• 48 Hofmeijer J, Tjepkema-Cloostermans MC, Blans MJ, Beishuizen A, van Putten MJAM. Unstandardized treatment of electroencephalographic status epilepticus does not improve outcome of comatose patients after cardiac arrest. Front Neurol 2014; 5: 39
• 49 Cronberg T. Should postanoxic status epilepticus be treated agressively? Yes!. J Clin Neurophysiol 2015; 32 (6) 449-451
• 50 Ko S-B, Ortega-Gutierrez S, Choi HA , et al. Status epilepticus-induced hyperemia and brain tissue hypoxia after cardiac arrest. Arch Neurol 2011; 68 (10) 1323-1326
• 51 Rossetti AO. Should postanoxic status epilepticus be treated aggressively?-No!. J Clin Neurophysiol 2015; 32 (6) 447-448
• 52 Ruijter BJ, van Putten MJAM, Horn J , et al; TELSTAR study group. Treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation (TELSTAR): study protocol for a randomized controlled trial. Trials 2014; 15: 433
• 53 Levy A, Chen R. Myoclonus: pathophysiology and treatment options. Curr Treat Options Neurol 2016; 18 (5) 21
• 54 Galldiks N, Timmermann L, Fink GR, Burghaus L. Posthypoxic myoclonus (Lance-Adams syndrome) treated with lacosamide. Clin Neuropharmacol 2010; 33 (4) 216-217
• 55 Frucht S, Fahn S. The clinical spectrum of posthypoxic myoclonus. Mov Disord 2000; 15 (Suppl. 01) 2-7
• 56 San-Juan OD, Chiappa KH, Costello DJ, Cole AJ. Periodic epileptiform discharges in hypoxic encephalopathy: BiPLEDs and GPEDs as a poor prognosis for survival. Seizure 2009; 18 (5) 365-368
• 57 Chong DJ, Hirsch LJ. Which EEG patterns warrant treatment in the critically ill? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns. J Clin Neurophysiol 2005; 22 (2) 79-91
• 58 Jirsch J, Hirsch LJ. Nonconvulsive seizures: developing a rational approach to the diagnosis and management in the critically ill population. Clin Neurophysiol 2007; 118 (8) 1660-1670
• 59 Claassen J, Perotte A, Albers D , et al. Nonconvulsive seizures after subarachnoid hemorrhage: multimodal detection and outcomes. Ann Neurol 2013; 74 (1) 53-64
• 60 Koutroumanidis M, Sakellariou D, Tsirka V. “Paradoxical” EEG response to propofol may differentiate post-cardiac arrest non-convulsive status epilepticus from diffuse irreversible cerebral anoxia. Epileptic Disord 2014; 16 (4) 510-517
• 61 Koutroumanidis M, Sakellariou D. Low frequency nonevolving generalized periodic epileptiform discharges and the borderland of hypoxic nonconvulsive status epilepticus in comatose patients after cardiac arrest. Epilepsy Behav 2015; 49: 255-262
• 62 Ribeiro A, Singh R, Brunnhuber F. Clinical outcome of generalized periodic epileptiform discharges on first EEG in patients with hypoxic encephalopathy postcardiac arrest. Epilepsy Behav 2015; 49: 268-272
• 63 Feng G, Jiang G, Li Z, Wang X. Prognostic value of electroencephalography (EEG) for brain injury after cardiopulmonary resuscitation. Neurol Sci 2016; 37 (6) 843-849
• 64 Claassen J. How I treat patients with EEG patterns on the ictal-interictal continuum in the neuro ICU. Neurocrit Care 2009; 11 (3) 437-444
• 65 Sivaraju A, Gilmore EJ. Understanding and managing the ictal-interictal continuum in neurocritical care. Curr Treat Options Neurol 2016; 18 (2) 8
• 66 Rodríguez V, Rodden MF, LaRoche SM. Ictal-interictal continuum: A proposed treatment algorithm. Clin Neurophysiol 2016; 127 (4) 2056-2064
• 67 Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, Wiebe S. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 67 (2) 203-210
• 68 Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 1994; 35 (2) 239-243
• 69 Thömke F, Marx JJ, Sauer O , et al. Observations on comatose survivors of cardiopulmonary resuscitation with generalized myoclonus. BMC Neurol 2005; 5: 14
• 70 Rossetti AO, Oddo M, Liaudet L, Kaplan PW. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology 2009; 72 (8) 744-749
• 71 Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol 2010; 67 (3) 301-307
• 72 Lucas JM, Cocchi MN, Salciccioli J , et al. Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclonus. Resuscitation 2012; 83 (2) 265-269
• 73 Accardo J, De Lisi D, Lazzerini P, Primavera A. Good functional outcome after prolonged postanoxic comatose myoclonic status epilepticus in a patient who had undergone bone marrow transplantation. Case Rep Neurol Med 2013; 2013: 872127
• 74 Westhall E, Rundgren M, Lilja G, Friberg H, Cronberg T. Postanoxic status epilepticus can be identified and treatment guided successfully by continuous electroencephalography. Ther Hypothermia Temp Manag 2013; 3 (2) 84-87
• 75 Rossetti AO, Logroscino G, Liaudet L , et al. Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology 2007; 69 (3) 255-260
• 76 Sandroni C, Cariou A, Cavallaro F , et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Resuscitation 2014; 85 (12) 1779-1789
• 77 Hovland A, Nielsen EW, Klüver J, Salvesen R. EEG should be performed during induced hypothermia. Resuscitation 2006; 68 (1) 143-146
• 78 Sunde K, Dunlop O, Rostrup M, Sandberg M, Sjøholm H, Jacobsen D. Determination of prognosis after cardiac arrest may be more difficult after introduction of therapeutic hypothermia. Resuscitation 2006; 69 (1) 29-32
• 79 Kaplan PW, Morales Y. Re: Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology 2008; 70 (15) 1295, author reply 1295-1296
• 80 Ruijter BJ, van Putten MJAM, Hofmeijer J. Generalized epileptiform discharges in postanoxic encephalopathy: Quantitative characterization in relation to outcome. Epilepsia 2015; 56 (11) 1845-1854
• 81 Friberg H, Westhall E, Rosén I, Rundgren M, Nielsen N, Cronberg T. Clinical review: continuous and simplified electroencephalography to monitor brain recovery after cardiac arrest. Crit Care 2013; 17 (4) 233
• 82 Dragancea I, Backman S, Westhall E, Rundgren M, Friberg H, Cronberg T. Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest. Epilepsy Behav 2015; 49: 173-177
• 83 Fugate JE, Wijdicks EFM, Mandrekar J , et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol 2010; 68 (6) 907-914
• 84 Milani P, Malissin I, Tran-Dinh YR , et al. Prognostic EEG patterns in patients resuscitated from cardiac arrest with particular focus on generalized periodic epileptiform discharges (GPEDs). Neurophysiol Clin 2014; 44 (2) 153-164
• 85 Youn CS, Callaway CW, Rittenberger JC. Post Cardiac Arrest Service. Combination of initial neurologic examination and continuous EEG to predict survival after cardiac arrest. Resuscitation 2015; 94: 73-79