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Seizure Disorders

Epidemiology and Societal Costs. 6.5/1000 Prevalence; 2.5 million in the US147,000 Newly diagnosed pts./year28% of pts. with epilepsy visit ED annually82,000 Hospitalizations/year$3.6 Billion, annual cost. Status Epilepticus: Epidemiology. 50,000-150,000 Cases annually50 Cases/100,000 populationInfants and elderly are a greater risk20% of pts with epilepsy develop SE by age 5Etiology: 1/3 acute insult, 1/3 chronic,1/3 new onset.

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Seizure Disorders

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    1. Seizure Disorders Abraham Berger, MD, F.A.C.E.P. Department of Emergency Medicine Beth Israel Medical Center, N.Y.

    2. Epidemiology and Societal Costs 6.5/1000 Prevalence; 2.5 million in the US 147,000 Newly diagnosed pts./year 28% of pts. with epilepsy visit ED annually 82,000 Hospitalizations/year $3.6 Billion, annual cost

    3. Status Epilepticus: Epidemiology 50,000-150,000 Cases annually 50 Cases/100,000 population Infants and elderly are a greater risk 20% of pts with epilepsy develop SE by age 5 Etiology: 1/3 acute insult, 1/3 chronic,1/3 new onset

    4. Emergency Department Seizures Epidemiology of acute Seizures in 200 Pts. Krumholtz;Epilepsia;1989:30;175 Epilepsy Patients 46% New Onset 35% Febrile 15% Secondary Seizures 4%

    5. Seizure Outcomes Injury/Death 15% Head contusions/Lacerations (Common) Mortality 1.2% of all seizures 3% to 26% in Status Epilepticus 10X higher in adults (Vs..... Children) Highest with hypoxic or ischemic insult

    6. Status Epilepticus: Duration & Mortality Status Epilepticus > 60 Min: 10-fold greater 30-day mortality(32% Vs..... 2.7%) Worse outcome associated with: Longer duration SE SE refractory to first-line therapy

    7. Seizure Mechanisms Abnormal discharge by unstable neurons Propagation by recruitment of normal neurons Failure of normal inhibitory neurotransmitters GABA Enhancement of excitatory neurotransmitters glutamate, aspartate, acetylcholine Interference with normal metabolic processes Glucose, 02 metabolism Na+, Ca++, K+, Cl- ion shifts

    8. Acute Symptomatic Seizures Precipitating Causes Review of 696 Pts: Annegers. Epilepsia 1995;36:327

    9. Status Epilepticus: Etiology Lowenstien and Aldredge: Neurology 1993;43:483 Studied 154 Patients, found SE Non Compliance 25% ETOH 25% Other Etiologies divided equally: Tox,CNS ID/CA,Trauma,Stroke,Metabolic, Cardiac arrest,Refractory, Unknown

    10. New-Onset Seizures Recurrence Risks Tardy Am J Emerg Med 1995;13:1 51% recurrence risk after 1st unprovoked SZ 75% recurrence rate within 2 yrs of a 1st SZ 20% will seize again within 24H Predictors of recurrent risk SZ Etiology (Partial and remote > risk) EEG Findings SE does not increase recurrence risk in Idiopathic SZs

    11. Classification Mosewich Mayo Clin Proc 1996;71;405 Partial Simple Partial Complex Partial Generalized Primary Secondary Duration Self - limited Status Epilepticus

    12. SE: Definition Historical Definitions 2 seizures within 30 min w/o lucid interval 1 seizure greater than 30 min duration Recent definitions 2 seizures over ant interval w/o lucidity 1 seizure of greater than 10 min duration Treiman. Epilepsia 1993;34(Suppl 1)

    13. Refractory SE Lack of response to first line drugs Benzodiazepines Phenytoin Phenobarbital 2000-6000 cases yearly in USA 6%-9% of all SE cases Bleck. Neurology Chronicle 1992;2:1

    14. Cerebral Changes in SE CNS injury independent of systemic effects Neuronal injury due to repetitive firing and excessive metabolic needs CNS injury will occur even if systemic disturbances are treated (fever, HTN,motor activity) Early in SE, BP and CBF inc. Late in SE, BP and CBF dec. Aminoff. Am J Med 1980;69:657 Wijdcks. Mayo Clin Proc 1994;69:1044

    15. Systemic Changes in SE BP: early Inc followed by hypotension Fever: 50% have t > 100.5 F Lactic acidosis: 30% pH <7.00 Hypercarbia: 84% will have inc paco2 Leukocytosis w/o bands CSF pleocytosis: 2-18% have >5 PMNs Aminoff. Am J Med 1980;69:657 Wijdcks. Mayo Clin Proc 1994;69:1044

    16. Post Ictal Physical Findings Focal findings anisocoria plantar response hyperreflexia evidence of trauma (tongue lacerations) Altered Mental Status improvement should occur within 20-30 min

    17. Laboratory Testing Turnbull. Ann Emerg Med 1990;19:373 Metabolic tests 2.5% of Szs due to chemical derangement Drug levels Tox and ETOH levels (when indicated) Finger stick Pulse Oximetry HCG EKG

    18. Lumbar Puncture Indications Immunocomprimised Meningeal signs Persistent AMS Fever alone not an indication ACEP Ann Emerg Med 1993;22:987

    19. Neuroimaging-Emergent Rec. ACEP Guidelines; Ann Emerg Med 1996;27:114 Recent Trauma Cancer Anticoagulation AIDS New focal deficit Persistent AMS Fever Persistent Headache

    20. Neuroimaging-Options ACEP Guidelines; Ann Emerg Med 1996;27:114 Consider Imaging First time seizure patients Older than 40 Y Partial onset seizure Prior history of Sz New pattern or type prolonged postictal Worsening mental status

    21. CT Scan Abnormal CT; most likely Abnormal neuro exam post recovery Malignancy history Abnormal CT; less likely ETOH related Szs (w/o trauma) Initial CT should be non-contrast

    22. MRI Bronen. AJR 1992;159:1165 Intractable epilepsy 25% positive CT 50% positive MRI After a negative non-contrast CT in ED ? appropriate in ED due to off site location

    23. Emergent EEG Indications Prolonged (>30 min) AMS SE requiring Neuromuscular paralysis SE requiring Barbiturate coma or general anesthesia Privitera. Emerg Med Clin N Am;1994;12:1089

    24. Pharmacological RX Benzodiazepines Phenytoin Fosphenytoin Phenobarbital Propofol Valproic Acid Lidocaine

    25. Benzodiazepines GABA inhibition of repetitive firing 80% Control of SE in 47 studies Lorazepam Vs..... diazepam adult SE - comparable efficacy pediatric seizures Lorazepam may be more effective intubation more common with diazepam Chiulli. J Emerg Med 1991;9:13/Treiman. Neurology 1990;40(suppl2)32

    26. Phenytoin Stabilizes membrane Na+ channels Regulates Ca++ Effective in gen..... SZs and SE 18 mg/kg loading dose results in Rx levels up to 24h (10mcg/ml) Constant infusion preferred to slow IVP use

    27. Phenytoin Advantages Extensive experience Low risk of respiratory depression Little effect on consciousness Jordan. Neurosurg Clin n Am 1994;5:671 Limitations Toxic diluents (high pH) Cardiac and soft tissue complications Hypotension Rate/infusion related Cardiac monitoring Used as post-resuscitation drug in acute szs

    28. Phenytoin: PO 18 mg/kg oral load 65% achieve level of 10mcg/ml by 8 h Delay in achieving Rx level did not result inc. Sz recurrence within 8 h Osborn, H. Ann Emerg Med 1987;16:407

    29. Fosphenytoin H2O sol. pro drug Complete conversion in vivo to phenytoin Rx levels within 2.7 min (IV) Conversion comparable in all demographic groups and all disease states No toxic diluents pH 8.7 Less infusion site complications Available IM dose Dosing in “equivalents” 1gm FP=1gm Phenytoin Wilder Arch Neurol 1996;53:784

    30. Phenobarbital Crosses BBB slowly Long 1/2 life (21-42 h) Enhances GABA inhibition Infuse @ 100 mg/min up to 10 mg/kg Monitor for: Resp. depression Hypotension 3rd line Rx for refractory gen.... conv. SE Stops SZ motor activity and suppresses EEG burst patterns Intubation, Vent support, HD and EEG monit. req.. Shaner. Neurology 1988;38:202 Jagoda. Ann Emerg Med 1993;22:1337

    31. Propofol Anesthetic agent; GABA Mechanism Provides burst suppression Loading dose: 2 mg/kg Requires cont.. infusion EEG monitoring required

    32. Lidocaine Membrane stabilization effect @ Na+ /K+ pump Reduces neuronal excitability Possible role in refractory SE 3rd line agent Load at 1.5 mg to 3 mg/kg Walker. Acad Emerg Med 1997;4:918

    33. Primary Causes of Drug Induced Seizures Antidepressants 28% Stimulants 28% Other 26% Antihistamines 8% INH 5% Theophylline 5% Olson. Am J Emerg Med 1993;11:565/ SF Poison Control Data

    34. Cocaine Consider multiple etiologies (inhale,body stuffing) Indirect CNS causes: Ischemia, hemorrhage, vasculitis DX work up low yield in pts with brief Sz who return to nl cns status RX: Benzo’s AVOID Beta-Blockers Holland. Ann Emerg Med 1992;21:772

    35. Isoniazid (INH) Inhibits pyridoxine kinase enzyme that forms pyridoxal phosphate cofactor in GABA formation Rx: pyridoxine 1 g for 1 g of INH unknown overdoses:5g IVP, repeat q 5hX6

    36. Theophylline Sz’s common in chronic ingestions Rx with benzo and barbiturates Phenytoin probably not effective Enhance elimination multiple doses of activated charcoal hemodialysis or hemoperfusion

    37. Cyclic Antidepressants Sz (40%) and coma (60%) common in TCA deaths Sz’s “more” likely when QRS > 100 msec Rx: Benzo’s consider pentobarbital or Propofol in ref. SE phenytoin,NaHCO3 Callahan. Ann Emerg Med 1985;14:1

    38. ETOH Withdrawal SZ’s 60% occur within 24 h of last drink Peak incidence by 12 h of last drink 60% recurrence 44% of Sz due to ETOH Prolonged post ictal state-gen.. good outcome Alderedge. Epilepsia 1993;34:1033

    39. Diagnosis & Treatment Baseline chemistries CT for head trauma, or focal findings IV D5NS, thiamine,K,Mg,Benzo. Avoid progression of disease to DT’s Alderedge. Epilepsia 1993;34:1033

    40. Pregnancy and Seizures Changes in SZ frequency and medication levels may occur SE rare; mortality inc with SE Fetal monitoring necessary Evaluate for eclampsia Jagoda. Ann Emerg Med 1991;20:80

    41. Magnesium Sulfate Prevention of Eclampsia Smooth muscle relaxant Superior to phenytoin for prophylaxis Lower risk of recurrence Vs..... diazepam and phenytoin Lucas. 1995;333:201

    42. SZ’s in the Elderly Increased risk for drug-drug and or drug-disease state interactions inc drug utilization inc freq.. Co-morbid dis. Non-convulsive SE may present as new onset AMS Greatest Sz frequency and incidence at ages <1&>60 Common Etiologies CVA 60% Tumors 10-15% Metabolic or drug/etoh toxicity 10% Kugler. Neurology 1996;46:(suppl.A)176

    43. Conclusion Sz’s and SE are medical emergencies Optimal outcome depends on early interventions appropriate drugs Dosing based on mg/kg requirements Aggressive Rx needed Develop plan (mgmt,met studies, imaging)

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