CHAIR SUMMIT 7TH ANNUAL #CHAIR2014. Master Class for Neuroscience Professional Development. September 11 13, Westin Tampa Harbour Island

Transcription

1 #CHAIR2014 7TH ANNUAL CHAIR SUMMIT Master Class for Neuroscience Professional Development September 11 13, 2014 Westin Tampa Harbour Island Sponsored by

2 #CHAIR2014 Clinical Case Challenge: Seizure Emergency Joseph I. Sirven, MD Mayo Clinic College of Medicine Phoenix, AZ

3 Joseph I. Sirven, MD Disclosures Research/Grants: NeuroPace, Inc.; MAP Consultant: Upsher-Smith Laboratories, Inc.; Acorda Therapeutics

4 #CHAIR2014 Learning Objective 1 Accurately identify and document the seizure type or syndrome and seizure frequency from the patient s history to develop a treatment strategy.

5 Case: Outside Clinical History 21 year old, right-handed female Depression treated with escitalopram and clonazepam 3 months later diagnosed with migraine and started on ondansetron, frovatriptan, hydroxyzine One week later, crying, language difficulties, confusion, agitation, auditory hallucinations, and first generalized, tonic-clonic seizure lasting seconds Two days later-multiple clinical seizures without intervening recovery

6 Diagnostic Tests in All SE Patients All Patients Fingerstick glucose Monitor vital signs. Head computed tomography (CT) scan (appropriate for most cases) Order laboratory test: blood glucose, complete blood count, basic metabolic panel, calcium (total and ionized), magnesium, antiepileptic drug (AED) levels. Continuous electroencephalograph (EEG) monitoring Consider Based on Clinical Presentation Brain magnetic resonance imaging (MRI) Lumbar puncture (LP) Comprehensive toxicology panel including toxins that frequently cause seizures (i.e. isoniazid, tricyclic antidepressants, theophylline, cocaine, sympathomimetics, alcohol, organophosphates, and cyclosporine) Other laboratory tests: liver function tests, serial troponins, type and hold, coagulation studies, arterial blood gas, AED levels, toxicology screen (urine and blood), and inborn errors Brophy GM, et al. Neurocrit Care. 2012;17(1):3-23. PMID:

7 Definition of Status Epilepticus (SE) Status Epilepticus is defined as 5 minutes or more of:! Continuous clinical and/or electro-graphic seizure activity or! Recurrent seizure activity without recovery (returning to baseline) between seizures This definition was adopted for the following reason:! Most clinical and electrographic seizures last less than 5 min and seizures that last longer often do not stop spontaneously Brophy GM, et al. Neurocrit Care. 2012;17(1):3-23. PMID:

8 Case: Investigations MRI and CT brain/spinal cord and lumbar puncture: normal Pelvic MRI! No teratoma! New moderate amount of pelvic ascites Immunoglobulin G index: elevated! Synthesis rate: 10 bands Anti-N-methyl D-aspartate (NMDA) encephalitis! Receptor: absent! CSF: positive! Serum: negative

9 Treatment Recommendations Emergent Initial Therapy Strong Recommendations High or Moderate Quality Evidence High or Moderate Quality Evidence Benzodiazepines should be given as emergent initial therapy Lorazepam is the drug of choice for IV administration Midazolam* is the drug of choice for IM administration Rectal diazepam can be given when there is no IV access and IM administration of midazolam is contraindicated Urgent Control Therapy Strong Recommendations Urgent control AED therapy recommendations include use of IV fosphenytoin/phenytoin, valproate sodium*, or levetiracetam* *Not an FDA approved agent for status epilepticus Brophy GM, et al. Neurocrit Care. 2012;17(1):3-23. PMID:

10 New Delivery Systems IM midazolam* vs. IV lorazepam dosing study! N = 448! IM 10 mg midazolam* vs. IV 4 mg lorazepam! Seizures were absent without rescue therapy in 73.4% (IM midazolam*) vs. 63.4% (IV lorazepam)! Time to active treatment 1.2 minutes (IM midazolam*) vs. 4.8 minutes (IV lorazepam)! Time from treatment to cessation of convulsions 3.3 minutes (IM midazolam*) vs. 1.6 minutes (IV lorazepam) Inhalation/nasal benzodiazepines! 3 products under investigation with midazolam* *Not an FDA approved agent for status epilepticus Silbergleit R, et al. N Engl J Med. 2012;366(7): PMID:

11 Discussion Question What would you do next?

12 Try the Following: Propofol* 3-5 mg/kg load then 1-15 mg/kg/hour Add midazolam* 0.2 mg/kg load then mg/kg/hour Then add levetiracetam* 20 mg/kg given IV over 15 minutes Fosphenytoin given, but discontinued Valproic acid* 20 mg/kg IV (at 3-6 mg/kg/min Solumedrol* 1 gram daily * Not an FDA approved agent for status epilepticus.

13 Discussion Question What would you do next?

14 Therapy Options Continue propofol* Pursue intravenous immunoglobulin* (IVIG) Try urgent vagus nerve stimulation (VNS) Try magnesium Go back to the basics (fosphenytoin etc.) * Not an FDA approved agent for status epilepticus.

15 Therapy Options Discontinue coma-inducing meds Stop EEG Emergency callosotomy A trial of immunosuppressants*! Solumedrol* 1000 mg IV x 8 days! Plasma exchange* (PLEX) x 4 days:! IVIG* 25 g x 5 days * Not an FDA approved agent for status epilepticus.

16 Systemic Issues Arise Pneumonia! Infectious diseases consult! Pseudomonas, Enterobacter cloacae! Ciprofloxacin, gentamycin prescribed Urinary tract infection Laparoscopic bilateral salpingooopherectomy performed by gynecological surgery Initial pathology: Positive for teratoma

17 Current Condition Maintained on levetiracetam*, lacosamide*, fosphenytoin, midazolam* drip, phenobarbital EEG shows prolonged periods of monomorphic rhythmic delta frequency activity alternating with periods of suppression! Largely unchanged since before surgery * Not an FDA approved agent for status epilepticus.

18 Discussion Questions What would you do next?

19 Therapy Options EEG monitoring at bedside Switch to pentobarbital? Discontinue care Stop coma-inducing agents Ketogenic diet

20 Definition: Refractory SE Patients who continue to experience either clinical or electrographic seizures after receiving adequate doses of an initial benzodiazepine followed by a second acceptable antiepileptic drug are considered refractory. Brophy GM, et al. Neurocrit Care. 2012;17(1):3-23. PMID:

21 Refractory SE: Which Agent? Pentobarbital vs propofol* vs. midazolam*! No difference in mortality! Pentobarbital has a lower frequency of acute treatment failure! Hypotension more frequent with pentobarbital * Not an FDA approved agent for status epilepticus. Claassen J, et al. Epilepsia. 2002;43(2): PMID:

22 Status Epilepticus: Management Overview Dx Status Epilepticus Pre-Hospital Treatment Emergent Initial Therapy Urgent Control Therapy: if convulsions continue Urgent Control Therapy: if convulsions stopped Initial Rx of RSE Advanced Rx of RSE Brophy GM, et al. Neurocrit Care. 2012;17(1):3-23. PMID:

23 Clinical Connections Benzodiazepine trial; administer anti-epileptic drugs per guidelines Continuous EEG Monitoring MRI with Diffuse Weighted Imaging and spectroscopy Consider immune-based pathology! Malignant drug-resistant status epilepticus with non-lesional MRI! Paraneoplastic screening! Manage with immunomodulators

24 Questions & Answers #CHAIR2014