A. LeBron Paige, M.D. Director, Epilepsy Program UT Erlanger Neurology

Transcription

1 A. LeBron Paige, M.D. Director, Epilepsy Program UT Erlanger Neurology Acute NeuroCare Symposium & Expo 10/20/2017

2 Conflict of Interest Statement Conflict of Interest Declaration: I am a paid consultant for pharmaceuticals manufacturer Eisai, Inc.

3 Definitions A Seizure (Sz) is a sudden and progressive sequence of rhythmic and excessively synchronized high amplitude electrical discharge within the brain that over a period of seconds escapes normal inhibitory mechanisms. A Seizure is not everything else! Seizure symptoms may be positive or negative, impacting motor, sensory, psychic, or autonomic function. 1 Begley CE, et al. Epilepsia. 2000;41: Kandel ER, et al. Principles of Neural Science. 4th ed. 1991:

4 Seizures vs Epilepsy Epilepsy, also called a seizure disorder, is a neurological condition in which recurrent unprovoked seizures occur EPILEPSY: Chronic, recurrent ( 2) seizures that are not otherwise provoked by acute injury or health emergency Epilepsy is a neurological disorder, while seizures are a symptom of that disorder (e.g., Parkinson s = tremor) The management of Epilepsy in the acute care setting IS the management of seizures + the underlying cause.

5 Seizure Classification - Origin

6 Seizure Classification - Spread 2 nd GTC SP CP

7 Generalized Onset Seizure EKG

8 Localization of Partial Seizure Based on EEG

9 Localization of Partial Seizures Based on Semiology Frontal Motor, bizarre, often brief and nocturnal Temporal Fear, LOC, Amnesia, Automatisms Parietal Somatosensory, dizziness Occipital Visual, often propagate with false localization

10 Seizures in Acute/Critical Care DEFINITION: Status epilepticus is when a seizure lasts longer than 5 minutes or when seizures occur close together and the person does not fully recover between seizures Any type of discrete seizure may develop into SE Simple partial, complex partial, generalized, myoclonic, absence, etc. Non-Convulsive Status Epilepticus (NCSE) - SE with clinical manifestations that lack shaking, and are limited to a change from baseline in behavior and/or mental processes, but are associated with a seizure pattern on EEG. SE that is not immediately brought under control may evolve into Refractory Status Epilepticus (RSE), which if not braught under control may evolve into super-refractory SE (SRSE).

11 Seizures in Acute/Critical Care Shorvon S1, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol Brain Oct;134(Pt 10):

12 5 THINGS: 1. The Incidence of Seizures in the Acute/Critical Care Setting is Significant 2. Seizure Morbidity & Mortality in the Acute/Critical Care Setting is Significant 3. The Negative Impact of Delayed Seizure Diagnosis & Treatment is Significant 4. Continuous Video-EEG is Essential to Optimum Critical Care Seizure Diagnosis & Treatment 5. Early & aggressive use of Benzodiazepines remain the mainstay of seizure treatment in Acute Care.

13 1.) The Incidence of Seizures in the Acute / Critical Care Setting In a now classic study, Jordan (1995) recorded Continuous EEG (ceeg) studies in 124 sequential patients admitted to a neuroscience ICU, with admission diagnoses of stroke, intracerebral hemorrhage, seizures, metabolic coma, brain tumors, and brain trauma. Overall, seizures occurred in 35% of patients during their ICU course, with > 75% suffering nonconvulsive seizures or non-convulsive status epilepticus (NCSE). Jordan KG. Neurophysiologic monitoring in the neuroscience intensive care unit. Neurol Clin 1995; 13:

14 1.) The Incidence of Seizures in the Acute / Critical Care Setting PRIMARY DIAGNOSIS ADULT Sz PEDI Sz Convulsive Status Epilepticus 48% 36% - 37% Aneurysmal Subarachnoid Hem (SAH) 10% - 19% UNKNOWN Intra-parenchymal Hemorrhage (IPH) 16% - 23% 11% - 100% Traumatic Brain Injury (TBI, Mod-Sev) 18% - 23% 11% - 70% CNS Infection 10% - 33% 16% - 100% Recent neurosurgical Procedure 23% 71% Brain Tumors 23% - 37% 19% - 66% Acute Ischemic Stroke 6% - 27% 20% - 71% Hypoxic-ischemic Injury (Cardiac) 10% - 59% 16% - 79% Sepsis with Encephalopathy 32% 58% Epilepsy related 33% - 39% 11% - 71% Herman, S.T., et. al., Consensus Statement on Continuous EEG in Critically Ill Adults and Children, Part I: Indications, Journal of Clinical Neurophysiology Volume 32, Number 2, April 2015

15 2.) Seizure Morbidity & Mortality in Acute/Critical Care is Significant Discrete Seizures (Szs) In 201 medical ICU patients, recurrent seizures on ceeg were associated with death or poor outcome in 89% (vs 39% in those without Szs). Seizures in this study remained associated with worse outcome even when controlled for age, examination, and organ dysfunction 1 Status Epilepticus (SE) DEFINITION: Status epilepticus is when a seizure lasts longer than 5 minutes or when seizures occur close together and the person does not fully recover between seizures 1 Oddo M, Carrera E, Claassen J, et al. Continuous electroencephalography in the medical intensive care unit. Crit Care Med 2009;37(6):

16 2.) Seizure Morbidity & Mortality in Acute/Critical Care is Significant Status Epilepticus (SE) Etiology Proportion of cases of SE Associated Acute Mortality in SE AED Reduction / Withdrawal 10-20% 0-10% Cerebrovascular Disease 10-40% 20-60% Metabolic Disorders 5-15% 10-40% Acute CNS Infections 1-12% 0-33% Anoxia-Hypoxia 5-12% 60-80% Alcohol 5-15% 0-10% Head Trauma 0-10% 0-25% Brain Tumors 0-10% 0-20% Cryptogenic / Idiopathic 5-15% 5-20% Neligan A, Shorvon SD. Frequency and prognosis of convulsive status epilepticus of different causes: a systematic review. Arch Neurol 2010; 67: Meta-analysis of 529 studies

17 2.) Seizure Morbidity & Mortality in Acute/Critical Care is Significant DEFINITION: Refractory status epilepticus (RSE) is SE that continues despite treatment with BZD + one Anticonvulsant (AED). RSE occurs in approximately 30% of patients with SE, typically associated with acute, severe, and potentially fatal underlying cause: encephalitis, massive stroke, rapidly progressive primary brain tumors. RSE is associated with estimated short-term fatality rates of between 16% and 39%, increased hospital length of stay, and functional disability Mortality after RSE is about THREE times higher than for SE. Novy J, Logroscino G, Rossetti AO. Refractory status epilepticus: a prospective observational study. Epilepsia 2010; 51: Holtkamp M, Othman J, Buchheim K, Meierkord H. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry 2005; 76: Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ, Fitzsimmons B-F Arch Neurol 2002; 59:

18 3.) The Negative Impact of Delayed Seizures Diagnosis is Significant The impact of delay in SE treating is very difficult to study because it is confounded by the various etiologies of the status epilepticus. The overall duration of status Epilepticus (SE) has been correlated with mortality. 1 Studies stratifying SE duration show a mortality of: 2.7% mortality at less than 30 min 19% mortality at <60 min 32% mortality at >60 min Logarithmically increasing (from 32%) up to 6 hours thereafter (>60 min). Up to 33% of convulsive seizure patients continue to have nonconvulsive electrographic seizure activity even after convulsive activity stops. In a study of adults with status epilepticus, response to the initial treatment occurred in 80% of patients when treatment began within 30 minutes, but in only 40% when treatment began 2 hours after the onset of SE 2 1 Towne AR, Pellock JM, Ko D, et al. Determinants of mortality in status epilepticus. Epilepsia 1994; 35(1): Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital. Neurology 1993;43:483

19 3.) The Negative Impact of Delayed Seizures Diagnosis is Significant At Baseline After 10 Seizures INHIBITORY GABA A Receptors EXCITATORY Glutamate (NMDA) Receptors James WY Chen, MD, Prof Claude G Wasterlain, Status epilepticus: pathophysiology and management in adults MD, The Lancet Neurology, Volume 5, Issue 3, Pages (March 2006)

20 3.) The Negative Impact of Delayed Seizures Diagnosis is Significant Non-Convulsive Status Epilepticus (NCSE) A study in adults (Young, 1996) showed that duration and time to detection predicted the outcomes in patients with NCSE. NCSE Dx < 30 minutes -> 35% mortality NCSE Dx 24 hours resulted in 75% mortality NCSE lasting < 10 hours, 60% of patients returned home. NCSE lasting > 20 hours, none returned home, 85% Died. Young GB, Jordan KG, Doig DS. An assessment of non-convulsive seizures in the intensive care unit using continuous EEG monitoring: An investigation of variables associated with mortality. Neurology 1996;47:83-9.

21 4.) Continuous VEEG is Essential to Optimum Seizure Diagnosis & Treatment Kilbride et. al., reviewed 300 consecutive ceeg studies AEDs had been initiated in 199 patients prior to ceeg initiation Epileptiform abnormalities (without seizure activity) were seen in 22.3% of studies Electrographic seizures were detected in 28.0% of all 300 studies. RESULTS: 52% of cases ceeg led to an AED change 33% of studies led to a modification of ongoing AEDs 14% led to the initiation of AED 5% led to the discontinuation of AEDs Kilbride, DR, et al., How Seizure Detection by Continuous Electroencephalographic Monitoring Affects the Prescribing of Antiepileptic Medications Arch Neurol. 2009;66(6):

22 4.) Continuous VEEG is Essential to Optimum Seizure Diagnosis & Treatment Khawaja et. al. (UAB), studies ceeg clinical impact by compared 234 critical care patients with & 234 matched critical care patients without ceeg monitoring. Patients were matched by Admission Diagnosis & sex 72.6% of ceeg patients vs 24.2% of controls had 1 AED change Kilbride, DR, et al., How Seizure Detection by Continuous Electroencephalographic Monitoring Affects the Prescribing of Antiepileptic Medications Arch Neurol. 2009;66(6):

23 4.) Continuous VEEG is Essential to Optimum Seizure Diagnosis & Treatment In non-comatose patients, 24 hours of ceeg will identify up to 95% of patients with intermittent NCSzs. In comatose patients, only 80% will be diagnosed by 24 hours. Therefore, a full 48 hours of ceeg should be used in comatose patients to increase the sensitivity of NCSz detection to almost 90%. 1 Claassen J,Mayer SA,Kowalski RG,et al. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004;62(10):

24 5.) Early & aggressive use of BZD remain the mainstay of Acute Care seizure treatment The most useful data concerning drug therapy for the termination of SE are found in the United States Veteran s Affairs cooperative trial, a double-blind randomized study of four treatment regimens ( first-line drugs ). These regimes included lorazepam (0.1 mg/kg), phenobarbital (15 mg/kg), diazepam (0.15 mg/kg) followed by phenytoin (15 mg/kg), and phenytoin alone (15 mg/kg). The aggregate response rate in overt SE to the first treatment was 56%, 7% to the second treatment, 7%, and 2.3% to the third treatment, 2.3%. These data suggest that the duration of SE prior to treatment is probably a more important determinant of treatment success than the drug chosen. Thomas P. Bleck, Refractory status epilepticus, Curr Opin Crit Care 11:

25 5.) Early & aggressive use of BZD remain the mainstay of Acute Care seizure treatment Foreman, B., Hirsch, L., Epilepsy Emergencies: Diagnosis and Management, Neurologic Clinics, 2012

26 5.) Early & aggressive use of BZD remain the mainstay of Acute Care seizure treatment Pharmacotherapy in SE First-Line ATIVAN VALIUM VERSED Second-Line DILANTIN DEPAKOTE PHENOBARB TOPAMAX KEPPRA Third-Line VERSED PENTOBARB PROPOFOL

27 5. Early & aggressive use of BZD remain the mainstay of Acute Care seizure treatment Andrea O Rossetti, Daniel H Lowenstein, Management of refractory status epilepticus in adults: still more questions than answers, Lancet Neurol 2011; 10:

28 THANK YOU!