SEIZURE DISORDERS llkkjjjj epilepsy

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					 Seizure Disorders


Abraham Berger, MD, F.A.C.E.P.
Department of Emergency Medicine
Beth Israel Medical Center, N.Y.
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
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
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%
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
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
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
 Acute Symptomatic Seizures
Precipitating Causes
Review of 696 Pts: Annegers. Epilepsia 1995;36:327




18%
16%
14%
12%
10%
 8%
 6%
 4%
 2%
 0%




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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
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
Classification
Mosewich Mayo Clin Proc 1996;71;405




   Partial
        • Simple Partial
        • Complex Partial
   Generalized
        • Primary
        • Secondary
   Duration
        • Self - limited
        • Status Epilepticus
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)
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
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
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
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
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
Lumbar Puncture

   Indications
    • Immunocomprimised
    • Meningeal signs
    • Persistent AMS
       • Fever alone not an indication

       ACEP Ann Emerg Med 1993;22:987
Neuroimaging-Emergent Rec.
ACEP Guidelines; Ann Emerg Med 1996;27:114




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




Consider Imaging             Prior history of Sz
 First time seizure          New pattern or type
  patients                    prolonged postictal
 Older than 40 Y             Worsening mental
 Partial onset seizure        status
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
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
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
Pharmacological RX

   Benzodiazepines
   Phenytoin
   Fosphenytoin
   Phenobarbital
   Propofol
   Valproic Acid
   Lidocaine
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
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
Phenytoin

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

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

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

   Anesthetic agent; GABA Mechanism
   Provides burst suppression
   Loading dose: 2 mg/kg
   Requires cont.. infusion
   EEG monitoring required
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
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
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
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
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
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
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
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
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
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
SZ’s in the Elderly

   Increased risk for drug-      Common Etiologies
    drug and or drug-               •   CVA      60%
    disease state
    interactions
                                    •   Tumors 10-15%

     • inc drug utilization         •   Metabolic or drug/etoh
                                        toxicity 10%
     • inc freq.. Co-morbid
        dis.
   Non-convulsive SE may         Kugler. Neurology
    present as new onset           1996;46:(suppl.A)176
    AMS
   Greatest Sz frequency
    and incidence at ages
    <1&>60
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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