Seizure Disorders

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

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Emergency Department Seizures

• Epidemiology of acute Seizures in 200 Pts.
• KrumholtzEpilepsia198930175
• 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 gt 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

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Acute Symptomatic SeizuresPrecipitating Causes
Review of 696 Pts Annegers. Epilepsia
199536327
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Status Epilepticus Etiology

• Lowenstien and Aldredge
• Neurology 199343483
• 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

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New-Onset SeizuresRecurrence RisksTardy Am J
Emerg Med 1995131

• 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 gt risk)
• EEG Findings
• SE does not increase recurrence risk in
  Idiopathic SZs

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ClassificationMosewich Mayo Clin Proc 199671405

• Partial
• Simple Partial
• Complex Partial
• Generalized
• Primary
• Secondary
• Duration
• Self - limited
• Status Epilepticus

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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 199334(Suppl 1)

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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 199221

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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 198069657
• Wijdcks. Mayo Clin Proc 1994691044

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Systemic Changes in SE

• BP early Inc followed by hypotension
• Fever 50 have t gt 100.5 F
• Lactic acidosis 30 pH lt7.00
• Hypercarbia 84 will have inc paco2
• Leukocytosis w/o bands
• CSF pleocytosis 2-18 have gt5 PMNs
• Aminoff. Am J Med 198069657
• Wijdcks. Mayo Clin Proc 1994691044

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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

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Laboratory TestingTurnbull. Ann Emerg Med
199019373

• Metabolic tests
• 2.5 of Szs due to chemical derangement
• Drug levels
• Tox and ETOH levels (when indicated)
• Finger stick
• Pulse Oximetry
• HCG
• EKG

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Lumbar Puncture

• Indications
• Immunocomprimised
• Meningeal signs
• Persistent AMS
• Fever alone not an indication
• ACEP Ann Emerg Med 199322987

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Neuroimaging-Emergent Rec.ACEP Guidelines Ann
Emerg Med 199627114

• Recent Trauma
• Cancer
• Anticoagulation
• AIDS

• New focal deficit
• Persistent AMS
• Fever
• Persistent Headache

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Neuroimaging-Options ACEP Guidelines Ann Emerg
Med 199627114

• 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

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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
MRIBronen. AJR 19921591165

• Intractable epilepsy
• 25 positive CT
• 50 positive MRI
• After a negative non-contrast CT in ED
• ? appropriate in ED due to off site location

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Emergent EEG

• Indications
• Prolonged (gt30 min) AMS
• SE requiring Neuromuscular paralysis
• SE requiring Barbiturate coma or general
  anesthesia
• Privitera. Emerg Med Clin N Am1994121089

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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 1991913/Treiman. Neurology
  199040(suppl2)32

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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

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Phenytoin

• Advantages
• Extensive experience
• Low risk of respiratory depression
• Little effect on consciousness
• Jordan. Neurosurg Clin n Am 19945671

• Limitations
• Toxic diluents (high pH)
• Cardiac and soft tissue complications
• Hypotension
• Rate/infusion related
• Cardiac monitoring
• Used as post-resuscitation drug in acute szs

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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 198716407

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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 FP1gm Phenytoin
• Wilder Arch Neurol 199653784

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Phenobarbital

• Crosses BBB slowly
• Long 1/2 life (21-42 h)
• Enhances GABA inhibition
• Infuse _at_ 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 198838202
• Jagoda. Ann Emerg Med 1993221337

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Propofol

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

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Lidocaine

• Membrane stabilization effect _at_ 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 19974918

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Primary Causes of Drug Induced Seizures

• Antidepressants 28
• Stimulants 28
• Other 26
• Antihistamines 8
• INH 5
• Theophylline 5
• Olson. Am J Emerg Med 199311565/ SF Poison
  Control Data

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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 Benzos
• AVOID Beta-Blockers
• Holland. Ann Emerg Med 199221772

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Isoniazid (INH)

• Inhibits pyridoxine kinase
• enzyme that forms pyridoxal phosphate
• cofactor in GABA formation
• Rx pyridoxine 1 g for 1 g of INH
• unknown overdoses5g IVP, repeat q 5hX6

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Theophylline

• Szs common in chronic ingestions
• Rx with benzo and barbiturates
• Phenytoin probably not effective
• Enhance elimination
• multiple doses of activated charcoal
• hemodialysis or hemoperfusion

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Cyclic Antidepressants

• Sz (40) and coma (60) common in TCA deaths
• Szs more likely when QRS gt 100 msec
• Rx Benzos
• consider pentobarbital or Propofol in ref. SE
• phenytoin,NaHCO3
• Callahan. Ann Emerg Med 1985141

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ETOH Withdrawal SZs

• 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 1993341033

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Diagnosis Treatment

• Baseline chemistries
• CT for head trauma, or focal findings
• IV D5NS, thiamine,K,Mg,Benzo.
• Avoid progression of disease to DTs
• Alderedge. Epilepsia 1993341033

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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 19912080

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Magnesium Sulfate

• Prevention of Eclampsia
• Smooth muscle relaxant
• Superior to phenytoin for prophylaxis
• Lower risk of recurrence Vs..... diazepam and
  phenytoin
• Lucas. 1995333201

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SZs 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 lt1gt60

• Common Etiologies
• CVA 60
• Tumors 10-15
• Metabolic or drug/etoh toxicity 10
• Kugler. Neurology 199646(suppl.A)176

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Conclusion

• Szs 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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