KORB-Seizure - Hospitalist Presentation with Cases [31576].pptx

A review of seizure and status epilep3cus evalua3on and management through cases Pearce J. Korb MD I have no relevant financial disclosures. There is some discussion of off label use of certain medica8ons. These are all based on real and recent cases in the hospital. DISCLOSURES Learning Objec4ves Contents Iden4fy status epilep4cus and treat the ini4al stages of status epilep4cus. Appropriately recognize and diagnose a first-­‐4me seizure and discuss common differen4al diagnoses. Apply current guidelines to the diagnos4c workup of a first 4me seizure. Understand the difficult nature of diagnosing epilep4c versus non-­‐epilep4c seizures. Case #1 65 year-­‐old woman with history of stroke is admiLed to your medicine service. She has a GTC and recovers fully but an hour later has another. She is given 2 mg of lorazepam but is s4ll having tonic clonic movements. You arrive at bedside 5 minutes later. Case #1 Does she meet criteria for status epilep4cus and why or why not? a.  No, her seizure has lasted < 30 minutes b.  No, she fully recovered between the two seizures c.  Yes, this is definitely status epilep4cus d.  a. and b. Case #1 Case #1 Original defini4on GCSE > 30 minutes of recurrent epilep4c seizures without full recovery of consciousness before next seizure begins con4nuous clinical and/or electrical seizure ac4vity, whether or not consciousness is impaired Case #1 Revised working defini4on of GCSE (1999) 5 minutes of con4nuous seizures or 2 or more discrete seizures between which there is incomplete recovery of consciousness Case #1 You are concerned about status epilep4cus. She is s4ll having convulsions. What is the next best step? Case #1 Of the choices what is the next best step? a.  Load with an an4-­‐epilep4c drug b.  Give more lorazepam IV c.  EEG stat d.  Administer propofol or other anesthe4c e.  Intubate Case #1 Case #1-­‐ Treatment of GCSE Don’t forget the basics 0-­‐5m • 
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ABC! (oral airway, O2, IV, EKG) Hx & Physical Labs: AED levels, chemistries, CBC, LFTs, tox screen, ABG 2-­‐10m • 
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Begin NS IVF • 
100 mg B1, Amp D50 Case #1 You load her with 20 mg PE (phenytoin equivalents)/kg of IV fosphenytoin. Her seizure has not stopped by minute 10 (2 min aker start of infusion) and you call for possible rapid sequence intuba4on (RSI) for airway protec4on in case you need to use seda4on. The seizure stops as the infusion finishes. Case #1 Her daughter overhears you talking about intuba4on and possible ven4la4on. She is relieved the seizure is stopped but wants to know why we would go so far as to put her on the ven4lator? Case #1 -­‐ Complications Complica3ons of Generalized Convulsive Status Epilep3cus •  Rhabdomyolysis •  Hyperthermia •  Orthopaedic •  Aspira4on pneumonia •  Neuronal Injury •  Cerebral edema •  Cardiac/Resp. Arrest •  Hepa4c Failure •  Renal Failure •  Hypotension •  Death Case #1 -­‐ Mortality Mortality Status Epilep4cus Mortality from SE can range from 3% to as high as 53% (GCSE) Most dependent on underlying e4ology Poor predictors: Older age Status > 1 hour Underlying anoxia/hypoxic injury Etiologies •  Adults •  Divided into acute and chronic •  Acute causes are –  More common and –  associated with worse morbidity and mortality Case #1 Take – home points: • The working defini4on of status epilep4cus is > 5 minutes (not 30) • Associated with a high mortality that worsens the longer the status/seizure lasts • Early treatment is essen4al and some of the steps can occur concurrently Case #2 A 42 year-­‐old woman with a history of grand mal seizures now well controlled is admiLed for kidney stones. She has a typical grand mal seizure (1-­‐2 min) but is taking a while to wake up per her husband (3-­‐4 hours ago). Case #2 On exam she is obtunded and not aler4ng with noxious s4muli. She has noisy breathing but is protec4ng her airway. Case #2 Of the choices what is the next best step? a.  Load with an an4-­‐epilep4c drug b.  Give lorazepam (2mg) IV c.  EEG stat d.  Administer propofol or other anesthe4c e.  Intubate Case #2 Case #2 Non-­‐convulsive status epilep4cus Convulsive vs. Non-­‐convulsive Status Epilep4cus Generalized Convulsive Status (GCSE) Non-­‐
convulsive (NCSE) Focal or Par4al Generalized Subtle Generalized Status Absence Status Simple Par4al Status (SPS) Epilepsy Par4alis Con4nua (EPC) Complex Par4al Status Non-­‐Convulsive Status Epilepticus (NCSE) -­‐ Subtypes Generalized Complex Par3al •  No overt motor manifesta4ons •  Impaired consciousness/coma •  Impaired consciousness •  May have motor manifesta4ons -­‐ automa4sms, focal clonic ac4vity, dystonic posturing •  Impaired consciousness, staring •  A.K.A -­‐ spike-­‐wave stupor Absence Simple Par3al Status •  No impairment of consciousness •  A.k.a /Epilepsy par4alis con4nua (EPC) •  Oken focal motor manifesta4ons, jerking of limb etc. Mortality of NCS/NCSE Case #2 Take – home points: • Non-­‐convulsive status epilep4cus can be harmful (although not as much as GCSE) • EEG necessary for diagnosis • Needs to be treated with an4-­‐epilep4c medica4ons Case #3 You are caring for a pa4ent with newly discovered lung cancer with metasta4c disease to the brain. She is having a new onset GTC. You have already given 6 mg of lorazepam (3 x 2mg every 2 min); loaded with fosphenytoin (20 mg PE/
kg) and she is s4ll seizing aker 10 min. Case #3 Of the choices what is the next best step? (This one is not always clear) a.  Reload with fosphenytoin b.  Load with an alterna4ve AED (valproate) c.  Give addi4onal lorazepam (2 mg) d.  Call anesthesia to prepare for intuba4on Case #3-­‐ Treatment of GCSE Don’t forget the basics 0-­‐5m • 
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ABC! (oral airway, O2, IV, EKG) Hx & Physical Labs: AED levels, chemistries, CBC, LFTs, tox screen, ABG 2-­‐10m • 
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Begin NS IVF • 
100 mg B1, Amp D50 Treatment Protocol for Refractory Status Epilepticus >30m Induce an anesthe4c coma with EEG in ICU: Midazolam 0.2 mg/kg slow IV bolus; Propofol 3-­‐5 mg/kg IV bolus; Pentobarbital 5-­‐15 mg/kg IV bolus; maintenance of 0.1-­‐2 mg/kg/hr maintenance 1-­‐15mg/kg/hr maintenance of 1-­‐10 mg/kg/hr
OR Phenobarbital load 20 mg/kg Valproate IV load 30-­‐40 mg/kg 50-­‐100 mg/min 3-­‐5 mg/kg/min Treatment of Refractory SE
Claassen J, Epilepsia 2002;43:145-153.
Other Potential Options Medica3on (IV) Efficacy Advantages Valproate No serious side Status resolved in effects 60-­‐79% Disadvantages Doses References Hepatotoxicity, 25 mg/kg Pancrea44s, à 100 Thrombo-­‐cytopenia, mg/hr Encephalopathy Olsen et al 2007; Misra et al, 2006 Ramael et al, 2006 Leve4racetam No interac4ons; few side effects; non-­‐hepa4c metabolism No FDA label for status; case studies 1500 – 2500 mg load Lacosamide No interac4ons; few side effects; non-­‐hepa4c metabolism No FDA label for status; case studies LiLle experience 100-­‐200 mg load over 30 min Even more options for super refractory status No controlled clinical trials, small pa4ent series only Shorvon, S. and M. Ferlisi (2012). Topiramate Ketamine Inhaled anesthe4cs Hypothermia Magnesium IV Steroids ACTH IVIG & Plasma exchange TMS, VNS, DBS, ECT Neurosurgery Review Status Epilep4cus: • A medical emergency! • Prolonged electrical seizure ac4vity causes neuronal damage and memory deficits à harm • EEG monitoring essen4al for subclinical seizures/ status epilep4cus • Longer the dura4on à worse outcomes • A predetermined Rx protocol is most effec4ve Case #4 A 55 year-­‐old man is admiLed to the hospital for a new onset spell that is described by EMS as a convulsion or “seizure”. He has fully recovered when you are admitng him. Case #4 You are considering star4ng him on an an4-­‐
epilep4c. What do you need to know or what is important for that decision? (Free response) Case #4 Terminology/deKinitions Seizure(s) • Abnormal electrical activity in the brain • Different symptoms or expression • Example includes a “grand-­‐mal” seizures Epilepsy • Simply 2 or more unprovoked seizures • Or a tendency towards having seizures • Many different types Provoked seizures Provoked – seizure triggered by an brain injury or insult that would have reasonably resulted in a seizure in any person AND if removed or avoided would likely lead to cessation of seizures. Alcohol Traumatic brain injury Hypoglycemia Febrile seizures Differential Diagnosis Seizure •  Epilepsy if 2 or more unprovoked Syncope •  Multiple causes Migraine •  Classic migraine with aura, complicated migraine Stroke/ TIA •  Todd’s paralysis looks like stroke/TIA Non-­‐epileptic spells (psychogenic) •  Can appear identical to epileptic seizures Seizure recurrence 21% reoccurrence 2 years (Hauser ’82) 39% reoccurrence 5 years (Cleveland ’81) 71% reoccurrence 5 years (Elewes ’85) Take home: Approximately 50% of those with new onset seizures will suffer reoccurrence Differential Diagnosis Pro-­‐
Onset drome LOC Durati
on Injury Convul
sions Offset Other Seizure Auras diverse Sudden Common Minutes Yes, head injury, tongue biting Common Post-­‐ictal confusions; min-­‐hrs Pallor, ictal scream Syncope Light-­‐
headed Sudden Common Seconds Yes, can occur with falls Rare* Rapid recovery Cyanosis Migraine Auras diverse Gradual No Hours No No Gradual offset Complex – focal neuro, headache Stuttering Sudden Uncommon Variable Gradual offset Can mimic Todd’s Variable Sudden Decreased responsive-­‐
ness Variable: min-­‐hrs Variable DifKicult to distinguish Stroke/ TIA Non-­‐
epileptic Yes, can Seizures can occur with occur falls Yes, less common than epilepsy Common Diagnostic algorithm First Encounter History (ED, PCP) Exam Referral Tests Cardiologic Holter monitor Echocardiogram Tilt table test Neurologic MRI brain EEG Long-­‐term EEG & video monitoring Epilepsy Drugs Old and New “Old” • 
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“Newer” Phenobarbital Phenytoin Ethosuxamide Benzodiazpines Carbamazepine Valproate • 
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Gabapentin Lamotrigine Levetiracetam Oxcarbamazepine Pregabalin Topiramate Zonisamide Felbamate Tiagabine “Newest” • 
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Lacosamide Vigabatrin Clobazam Ezogabine Factors in Choosing an AED EfKicacy Other medical issues •  Epilepsy type matters •  Otherwise nearly equivalent Safety •  Psychiatric disease •  Headache •  Pain •  Obesity •  Elderly •  Pregnancy •  Children •  Titration rate •  Compliance Dosing schedule Side effect proKile Cost •  Expected side effects •  Severity •  Newer medications •  Newer formulations Factors in Choosing an AED Elderly •  reduced doses •  Avoid certain medication Pregnancy •  close monitoring •  dosing changes •  concern about birth defects Children •  liquid formulations •  reduced doses •  certain medications approved Case #5 A 30 year-­‐old man is admiLed to your service for having mul4ple “seizure” events over a day. His mother shows you a video of the a typical event. Case #5 Case #5 You get a con4nuous EEG on him and he has a typical event and you diagnose him with non-­‐epilep4c spells. Non-­‐epileptic spells •  Several names: –  Psychogenic seizures, pseudoseizures, stress induced seizures •  Form of conversion disorder •  One-­‐third have identiKiable risk factor: –  Psychiatric disorder: depression, anxiety, PTSD –  Psychological trauma (PTSD): abuse history, combat •  Caution!!! often coexists with epilepsy = mixed disorder •  Treatment – cognitive-­‐behavioral therapy (CBT) •  Prognosis – variable (1/3 immediate resolution; 1/3 resolution within 1 year of therapy; 1/3 refractory) Case #5 Counseling Patients •  Safety –  Driving, Bathing, Machinery, Heights •  Compliance –  Pill boxes, dosing schedule •  Cost of Medica4ons –  Generic vs. Brand name •  Psychosocial Impact –  Ask about depression, anxiety •  Women –  Birth control, child bearing plan, folic acid •  Bones –  Calcium and Vitamin D supplements, bone density scans Driving and Epilepsy •  Law varies by state •  Colorado – No specific seizure freedom 4me but falls to na4onal prac4ce standard: –  No driving un4l seizure free for 3 months (involving altera4on of consciousness) •  Repor4ng vs. Non-­‐repor4ng Seizure First Aid • 
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Keep Calm! Don’t hold person down Time the seizure Clear the area, loosen 4es, shirt Turn on side Do NOT put anything in the mouth When to Call 911 • 
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Seizures longer than 5 minutes Turning blue, choking A second seizure immediately aker Does not wake up aker the seizure Pregnant, diabe4c, injured Seizures in the water First seizure ever, no prior history of epilepsy Other resources Epilepsy Foundation www.epilepsyfoundation.org Epilepsy Foundation of Georgia www.epilepsyga.org @epilepsyfdn Epilepsy.com @epilepsyga Seizure Tracker www.seizuretracker.com Websites C.U.R.E. www.cureepilepsy.org Tuberous Sclerosis Alliance www.tsalliance.org Twitter feeds www.epilepsy.com @cureepilepsy @amepilespysoc @epilepsycongres @drpearcekorb CDC – Epilepsy www.cdc.gov/epilepsy/ References 1. 
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Claassen, J., et al. (2002). "Treatment of refractory status epilep4cus with pentobarbital, propofol, or midazolam: a systema4c review." Epilepsia 43(2): 146-­‐153. DeLorenzo, R. J., et al. (1998). "Persistent nonconvulsive status epilep4cus aker the control of convulsive status epilep4cus." Epilepsia 39(8): 833-­‐840. Jaitly, R., et al. (1997). "Prognos4c value of EEG monitoring aker status epilep4cus: a prospec4ve adult study." J Clin Neurophysiol 14(4): 326-­‐334. Misra, U. K., et al. (2006). "Sodium valproate vs phenytoin in status epilep4cus: a pilot study." Neurology 67(2): 340-­‐342. Olsen, K. B., et al. (2007). "Valproate is an effec4ve, well-­‐tolerated drug for treatment of status epilep4cus/serial aLacks in adults." Acta Neurol Scand Suppl 187: 51-­‐54. Ramael, S., et al. (2006). "Leve4racetam intravenous infusion: a randomized, placebo-­‐controlled safety and pharmacokine4c study." Epilepsia 47(7): 1128-­‐1135. Rosset, A. (2010). "Treatment Op4ons in the Management of Status Epilep4cus." Current Treatment Op4ons in Neurology 12(2): 100-­‐112. Schmidt, D. and S. C. Schachter (2014). "Drug treatment of epilepsy in adults." Bmj 348: g254. Shorvon, S. M. H. E. M. (2008). The drug treatment of status epilep4cus in Europe: Consensus document from a workshop at the first London Colloquium on Status Epilep4cus, Wiley-­‐Blackwell. 49: 1277-­‐1285. Shorvon, S. and M. Ferlisi (2012). "The outcome of therapies in refractory and super-­‐refractory convulsive status epilep4cus and recommenda4ons for therapy." Brain 135(8): 2314-­‐2328. Walker, M. (2005). "Status epilep4cus: an evidence based guide." Bmj 331(7518): 673-­‐677. Young, G. B., et al. (1996). "An assessment of nonconvulsive seizures in the intensive care unit using con4nuous EEG monitoring: an inves4ga4on of variables associated with mortality." Neurology 47(1): 83-­‐89. Questions Picture from my trip to Mongolia Questions