TOC  |  Neuro  | D-Dx    

Outlines in Clinical Medicine  on Physicians' Online 2001

A. Introduction

  1. Seizures are abnormal spontaneous discharges of brain neurons
  2. May affect part (focal) or all (general) of the brain
  3. Over 1.5 million patients with seizure disorder (epilepsy) in USA
    1. Overall incidence is ~70 per 100,000 per year
    2. Prevalence is ~9 per 1000 persons (0.9%)
    3. Highest incidences in age <10 and in age >60
    4. Overall, elderly persons have the highest incidence and prevalence of epilepsy
  4. Control of Epilepsy
    1. Medications control ~80% of these patients very well
    2. Thus, over 300,000 patients with intractable or poorly controlled seizures
    3. Refractory epilepsy often due to missed opportunities for good control
  5. Epilsepsy Foundation in USA 1-800-EFA-1000

B. Types of Seizures and Definitions

  1. Level of Consciousness
    1. Simple: no loss of consciousness
    2. Complex: impairment, alteration, or loss of consciousness
  2. Focus of Seizure activity
    1. Partial: begins at specific focus (may be idiopathic or structural or due to injury)
    2. Generalized: appear to begin diffusely in large part of the brain, loss of consciousness
  3. Tonic Clonic (grand mal)
    1. Entire body is involved
    2. Commonly these begin as focal seizure
  4. Absence Seizures (Petit mal)
    1. 1-2 minute staring episodes
    2. Infrequent patient with very short (1-10 second) "spells" who have absence seziures
  5. Complex Partial: lip smacking, fumbling, staring, guttural vocalization, confusion
  6. Myoclonic Seizures: associated with anoxia, ischemia, drug overdose, idiopathic
  7. Status Epilepticus: continuously repeating seizures [3]       
  8. Refractory Epilepsy: poor control with antiepileptic agents

C. International Classification of Epileptic Seziures (Summary)

  1. Partial Seizures
    1. Simple Partial Seizures (no impaired consciousness)
    2. Complex Partial Seziures (impaired consciousness)
    3. Partial Seizures evolving into secondary generalized seizures
  2. Generalized Seizures
    1. Absence Seizures
    2. Myoclonic Seizures
    3. Clonic Seizures
    4. Tonic Seizures
    5. Tonic-Clonic Seizures
    6. Atonic Seizures
  3. Unclassified Seizures

D. Causes of Seizures in Infants       

  1. Trauma
  2. Infection / Fever
  3. Tumor
  4. Degenerative
  5. Aminoaciduria
  6. Metabolic
    1. Hypoglycemia
    2. Hyponatremia
    3. Hypocalcemia
  7. Developmental
    1. Arteriovenous Malformation (AVM)
    2. Hyperactive focus - usually a scar
  8. Hereditary
  9. Idiopathic

E. Causes of Seizures in Children   

  1. Hemorrhage
  2. Toxins - drugs
  3. Renal Failure
  4. Cerebrovascular Abnormalities
  5. Metabolic
  6. Infection / Abscess
  7. Fever
  8. Idiopathic

F. Causes of Seizures in Adults

  1. Idiopathic
  2. Post-Traumatic
  3. Cerebrovascular Disease
    1. Post- or peri-stroke      
    2. Recurrent chronic ischemia
    3. Seizures most common with large hemorrhagic areas of infarction
  4. Tumor - ~10% of new onset seizures      
  5. Recreational Drugs
    1. Alcohol - withdrawal seizures more common than during use    
    2. Cocaine      
    3. MDMA ("ecstasy")
  6. Eclampsia      
  7. Autoimmune Disease
    1. Vasculitis     
    2. Systemic Lupus      
  8. Medial Temporal Sclerosis
  9. Metabolic
    1. Hypoglycemia
    2. Hyponatremia
    3. Hypocalcemia
    4. Hypernatremia
    5. Reduced calcium and magnesium levels increased risk of seizures
    6. Uremia
    7. Cirrhosis / Liver Failure
  10. Infection
    1. Meningitis - usually bacterial     
    2. Encephalitis - usually viral      
    3. Brain Abscess
    4. Parasitic - malarium, hydatid, toxoplasma, leishmania, helminths, cysticercosis
  11. Medications
    1. Anti-psychotics - phenothiazines lower seizure threshhold more than butyrphenones
    2. Tricyclic antidepressants - particularly as overdose
    3. Lidocaine
    4. ß-Lactams - especially imipenam, high dose penicillin
    5. Meperidine (Demerol®) - metabolites are epileptogenic
    6. Theophylline
    7. Interferons - may increase risk of seizures, particularly in multiple sclerosis
    8. Tramadol (Ultram®) - only in overdoses >500mg
    9. Narcotic or benzodiazepine withdrawal
  12. Multiple Sclerosis - occasional seizures
  13. Organ Transplantation
  14. Postoperative - anesthesia related, underlying systemic disease, organ failure
  15. Seizures in Elderly
    1. Cerebrovascular Disease: Post-Stroke and Stroke Related, particularly with hemorrhage
    2. Post-carotid endarterectomy hyperperfusion syndrome (1% of endarterectomy)
    3. Intracranial tumors
    4. Degenerative Disorders - mainly Alzheimer Dementia and Amyloid Angiopathy
    5. Metabolic - mainly hyperglycemia related
  16. Hereditary - sickle cell disease, others
  17. Seizures are precipitated in many medical patients without clear seizure focus

G. Diagnosis

  1. History and observer histories
  2. Confirmation and classification by laboratory testing is important
  3. Ruling in or out differential diagnostic possibilities is required
  4. Electroencephalogram (EEG) within 24 hours of even if possible
  5. Sleep deprived EEG should follow if regular EEG is negative
  6. Neuroimaging with MRI aids diagnosis and should be done in all adult patients
  7. Epilepsy classification can be made in most first-seizure patients
  8. Refractory epilepsy may be suspected early as it is more common in patients with :
    1. More than 6 seizures before initial therapy (>40% were subsequently refractory)
    2. Poor response to first drug
    3. Only 13% of first drug failures were seizure free on second drug
  9. Confirmation of accurate diagnosis should be made in all patients considered "refractory"

H. Differential Diagnosis       

  1. Syncope, Presyncope       
  2. Transient ischemic attack       
  3. Transient global amnesia       
  4. Cardiac Arrhythmia       
  5. Migraine (atypical)      
  6. Vertigo
  7. Tremor      
  8. Breath-Holding / Functional
  9. Sleep Apnea
  10. Pseudoseizures (including malingering)

I. Therapy Overview

  1. Abbreviations
    1. cbz = carbamazepine
    2. clon = clonazepam, clonazepate
    3. esm = ethosuximide
    4. lam = lamotrigine
    5. pb = phenobarbital
    6. pht = phenytoin (Dilantin®)
    7. prim = primidone
    8. tiag = tiagibine
    9. vpa - valproic acid (Depakote®); val = valproate NA IV
    10. vig = vigabatrin
  2. Treating Symptomatic Partial Epilepsy
    1. Simple partial seizures: cbz = vpa > pht = vig
    2. Complex partial seizures: vpa > cbz > pht and/or gaba > vpa > pb = prim
    3. Evolution to Generalized (tonic-clonic) seizures: cbz > pht > pb > vpa
  3. Treating Idiopathic Generalized Epilepsy (mainly children)
    1. Absence seizures (onset in childhood): esm > vpa = lam
    2. Absence seizures (onset in adulthood): vpa > esm = lam
    3. Myoclonic seizures: vpa > clon = lam = prim
    4. Generalized tonic-clonic seizures: vpa > cbz > pht > prim = lam = pb
  4. Neonatal Seizures [28]
    1. Phenobarbital
    2. Phenytoin
    3. Single agents are effective in ~45% of cases of neonatal seizures
    4. Combination therapy should be considered
  5. Seizures in Elderly [29]      
    1. Thorough understanding of drug metabolism is required
    2. Lamotrigine is better tolerated than most of the older drugs
    3. Gabapentin is well tolerated as an adjunctive therapy
    4. Controlled release valproate is reasonably well tolerated
    5. Oxcarbamazepine is easier to use than carbamazepine and has less drug interactions
  6. Other Epilepsy Syndromes
    1. Juvenile Monoclonic Epilepsy: vpa > lam = clon = prim
    2. Infantile Spasms (West's Syndrome): corticotropin > clon = vpa
    3. Lennox-Gastaut Syndrome: vpa = lam > cbz
  7. Surgery for Seizures [11]
    1. Surgery may be helpful for temporal lobe seizures
    2. Anterior temporal lobectomy has been used in most cases
    3. Recent study shows that ~70% of patients are seizure free at 5 years [12]
  8. Vagus nerve stimulation - for some patients with refractory seizures
  9. Discontinuing Agents [30]
    1. >60% of persons who remain free of seizures can have medications discontinued
    2. Most physicians wait 2-5 years of seizure-free time before slow reductions in dose
    3. About 77% of those who respond to initial drug are seizure free on its discontinuation [8]
    4. Patients on single agents who are seizure free are most likely to discontinue therapy
  10. All of the studied agents cause birth defects with 1% Risk of spina bifida (see below)

J. Specific Anti-Convulsant Agents

  1. Acute Therapy for Generalized Seizures       
    1. Dilantin 1gm load iv (hypotension common side effect)
    2. Phenobarbital 30-60mg iv repeated every 5-10 minutes
    3. Benzodiazapines: mainly for alcohol-related seizures (see below)
    4. Pentobarbital: status epilepticus; induce coma
  2. Benzodiazepines      
    1. Benzodiazepines bind to alpha subunit of GABA-R, augment endogenous GABA actions
    2. Especially useful for alcoholic and alcohol withdrawal seizures
    3. Diazapam (Valium®): grand mal (tonic-clonic), alcoholic related seizures; 5mg IV/IM
    4. Lorazepam (Ativan®): shorter t1/2 than diazapam; easier to use for alcohol withdrawal
    5. Lorazepam 2mg IV after acute alcohol related seizure reduces second seizures 90% [
    6. Diazepam (Valium®) more effective than lorazepam (Ativan®)
    7. Clonazepam (Klonopin®): myoclonic seizures, also useful for anxiety
    8. Midazolam: effective for halting seizures, may be given in buccal cavity as liquid
    9. Buccal (liquid) midazolam as effective as rectal diazapam in stopping seizures
  3. Phenytoin (pht; Dilantin®)
    1. Use: Partial Epilepsy, Generalized Tonic-Clonic seizures
    2. Side Effects: cognitive changes, gum hyperplasia, hirsutism, nystagmus, ataxia
    3. Hypotension often occurs with intravenous loading (usually 50mg per minute to 1gm)
    4. Overdose: ataxia, nystagmus (especially vertical), induction of seizures, lethargy
    5. Note that phenytoin overdose usually occurs when patients on drug are given iv loading
    6. Blood level monitoring required for optimal dosing
  4. Fosphenytoin (Cerebyx®)
    1. Metabolite of phenytoin which allows IV or IM loading
    2. Rapid IV loading is not associated with significant hypotension
    3. Blood level monitoring required for optimal dosing
  5. Carbamazapine (cbz; Tegretol®)
    1. Use: Complex-partial seizures, Generalized Seizures, Second Line Myoclonic Seizures
    2. Effects likely due to blockade of voltage-sensitive sodium channels
    3. Side Effects: drowsiness, diplopia, GI upset, low WBC (5-10%), rash, allergy
    4. Severe Side Effects: Agranulocytosis, platelet decrease, aplastic anemia (1/20,000)
    5. WBC and Platelets should be monitored each week initially, then each month
    6. Metabolized by CYP3A4 and can reduce effectiveness of oral contraceptives
    7. Drug Interactions: warfarin, estrogens, theophylline, alcohol, naproxen
    8. Blood level monitoring required for optimal dosing
  6. Oxcarbazepine (Trileptal®)
    1. Analog of carbamazepine, pro-drug requires liver metabolism
    2. FDA approved for oral use in partial seizures
    3. May be used as monotherapy or adjunctive therapy in adults; adjunctive in children
    4. Effects likely due to blockade of voltage-sensitive sodium channels
    5. Monotherapy as effective as carbamazepine, valproate, or phenytoin in adults
    6. Side effects include somnolence, dizziness, nausea, vomiting, rash; less than cbz
    7. Hematologic and hepatic toxicity has NOT been reported
    8. Cross-reactivity of oxcarbazepine in patients with hypersensitivity to cbz is 20-30%
    9. Can inhibit CYP 2C19, CYP3A4/5; not affected by CYP3A4 inhibitors
    10. Starting dose 300mg bid; increase to maximum 1200-2400mg po divided
    11. Can convert from cbz to 1.5 fold increased dose of oxcarbazepine immediately
  7. Valproic Acid / Valproate (vpa; Depokene®, Depokote®):
    1. Divalproex is now the preferred agent
    2. Use: All seizure types, especially generalized epilepsy
    3. Side Effects: gastrointestinal upset, weight and apetite increase, fatigue, tremor, hair loss (5-10%; reversible)
    4. Severe: hepatotoxic reactions (usually on other drugs). Monitor liver function tests
    5. May also cause hyperandrogenism, polycystic ovaries, and oligomenorrhea [16]
    6. Also used for manic-depressive disorder, and for migraine prophylaxis
    7. Blood level monitoring required for optimal dosing
  8. Phenobarbital (pb) or Primidone (prim; Mysoline®)
    1. Second line therapy in adults with resistant seizures
    2. Side Effects: Sleepiness, depression, personality changes
    3. Encephalopathy and hyperammonemia can also occur in adults
    4. Barbiturates bind to ß-subunit of GABA-R to potentiate endogenous GABA actions [13]
    5. GABA stimulates chloride entry into neurons and is inhibitory
  9. Ethosuximide (esm; Zarontin®)
    1. Use: petit mal only (without other seizure types)
    2. Side Effects: blood dyscrasias, ataxia, dizziness, hepatitis (monitor CBC, liver function)
    3. Dose: 500mg po qd initially, increase by 250mg q4-7 days to maximum 1.5gm/d
    4. Increases valproate, phenobarbital, phenytoin levels
    5. Blood level monitoring required for optimal dosing
  10. Phenyl Dicarbamates [17]
    1. Meprobamate (Equanil®)
    2. Felbamate (Felbatol®): oral only; approved for partial seizures ± generalization
    3. Blocks sodium channels and some NMDA receptors, enhances g-aminobutyric acid (GABA)
    4. Felbamate has shown efficacy in highly refractory patients
    5. Less behavior and other side effects than earlier agents
    6. Side Effects: mild to moderate, HA, insomnia, fatigue, anorexia, nausea, and/or vomiting
    7. Serious side effects include aplastic anemia and drug-induced hepatitis
    8. Aplastic anemia risk with felbamate requires close monitoring
  11. Gabapentin (gaba; Neurontin®) [18,19]       
    1. Efficacy for partial and secondary generalized seizures, as add on agent
    2. Decrease incidence in secondary generalized seizures
    3. Inhibits sodium channels and affects amino acid transport in CNS
    4. Drug interactions: does not alter plasma concentrations of other agents
    5. Increasing use for chronic pain management with good initial effects
    6. Far safer than other agents; long term effects are generally insignificant
    7. Side Effects: mild in general; somnolence, dizziness, ataxia, fatigue, nystagmus, nausea
  12. Lamotrigine (lamo; Lamictal®) [18,20]       
    1. Approved in USA for use in partial seizures in adults
    2. Blocks voltage dependent sodium channels
    3. Metabolism by glucuronidation, does not induce P450 enzymes, few drug interactions
    4. Valproate inhitibs metabolism of lamo, and lamo decreases valproate levels
    5. Generally very well tolerated when added to other drugs or used alone
    6. Most patients begin at 50mg po qd x 2 weeks, increase slowly to 300-500mg/day
    7. Elderly may be started at 25mg po qd x 2 weeks, the bid, with slow increases [29]
    8. Effective and well tolerated in children with the Lennox-Gastaut Syndrome [21]
  13. Vigabatrin [6,22]
    1. Structural analog of GABA
    2. Enzyme-activated irreversible inhibitor of GABA transaminase
    3. Increases GABA levels in CNS
    4. Used in combination with other drugs reduces seizure frequency and severity
    5. Carbamazepine is superior to, but had more side effects than, vigabatrin [22]
    6. Minimal mental effects, mild increased depression, 30% decrease in phenytoin levels
    7. Weight gain ~10% and psychiatric symptoms do occur
    8. Dose 500-3000mg po bid
  14. Topiramate (Topamax®) [18,23]       
    1. Blocks sodium channels, attenuates kainite responses, enhances GABA effects
    2. Approved for use as adjunctive therapy in adults with partial seizures
    3. Side effects include mental slowing, fatigue, somnolence; generally well tolerated
    4. Renal stones occurred in 1.5% of patients taking this agent
    5. Like nearly all other anti-seizure agents, showed teratogenic effects in animals
    6. May increase serum phenytoin levels up to 25%; other agents decrease topiramate levels
    7. Dose is 200-400mg po qd as adjunctive therapy
  15. Tiagabine (Gabitril®)
    1. Low concentrations of brain GABA have been associated with poor seizure control
    2. This agent inhibits neuronal and glial uptake of GABA
    3. Approved in USA as add-on therapy in refractory partial seizures in adults
    4. Starting dose is 4mg/day, increased weekly to 4-8mg/day
    5. Dose is 32-56mg / day, taken with food (maximum dose ~60mg/d)
    6. Main side effects are dizziness, headache, somnolence
    7. Pht, cbz and pb increase metabolism and decrease half-life of tiagabine
  16. Levetiracetam (Keppra®) [10]
    1. FDA approved for adjunctive therapy for partial seizures in adults
    2. Unclear mechanism of action
    3. Effective in refractory partial seizures (50% seizure reduction in ~35% of patients)
    4. Side effects: somnolence, asthenia, psychiatric symptoms
    5. Cognitive symptoms (difficulty in speech, concentration) have not been reported
    6. No significant drug interactions, and does not require dose titration
    7. Dose is 500mg po bid, up to a total dose of 1500mg po bid
    8. Reduce dose in renal insufficiency and in elderly (250mg tablets available)
  17. Zonisamide (Zonegran®) [32]
    1. FDA approved for adjunctive therapy for partial seizures in adults
    2. Blocks sodium and calcium channels; blocks carbonic anhydrase weakly
    3. Dose 100mg qd initially, up to 600mg (increase q2 weeks) given as once or twice
    4. Dizziness, ataxia, somnolence reported
    5. Nephrolithiasis reported in 4%, likely due to carbonic anhydrase inhibition
  18. Clobazam [18]
    1. Benzodiazepine with reduced cognative effects, used in refractory seizures
    2. Not yet available in USA
  19. Experimental Agents
    1. Losigamone
    2. Remacemide
    3. Calcium Blockers: flunarizine, cinnarizine
  20. Considerations in choice of agent
    1. Use of single agent recommended whenever possible (~65% of patients)
    2. Above section (F) outlines preferred agents in most patient settings (not in elderly)
    3. Surgical evaluation may be considered if drug combinations fail
    4. Special attention to drug interactions in elderly patients [6]
    5. Newer agents (gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin and zonisamide) showed no detectable differences in efficacy in partial epilepsy [25]
  21. Choice of Agent in Elderly [6]
    1. Oxcarbazepine should be substituted for carbamazepine whenever possible
    2. Gabapentin, vigabatrin and lamotrigine are reasonable add-on choices
    3. These three agents may be used first line in partial or secondarily generilized epilepsy
    4. Gabapentin is probably best tolerated of all, and may be first line choice in elderly
    5. Pheobarbital, primidone, and clobazam are best avoided
  22. Combination Therapy (Refractory) [30]
    1. Valproate and lamogrigine
    2. Valproate and carbamazepine
    3. Carbamazepine and vigabatrin
    4. Lamogrigine and topiramate


K. Summary Of Uses Of Anti-Convulsive Agents [30]
Drug                  Generalized      Absence     Myoclonic     Partial
Carbamazapine (Tegretol®) ++ - - +
Clonazepate - + ++ +
Clonazapam (Klonopin®) + + + +
Diazapam (Valium®) + - + +
Ethosuximide - ++ - -
Felbamate (Felbatol®) + ++ - +
Gabapentin (Neurontin®) + - - +
Lamotrigine (Lamictal®) ++ + + +
Oxcarbazepine (Trileptal®) ++ - - +
Phenobarbital ++ - + +
Phenytoin (Dilantin®) ++ - - -
Primidone + - ? +
Topiramate (Topamax®) + ? + +
Tiagabine (Gabitril®) + ? ? +
Valproate (Depokote®) +++ ++ ++ +
Zonisamide + ? + +

L. Drug Treatment During Pregnancy

  1. Seizures are generally well controlled during pregnancy
  2. Phenytoin levels may fall during pregnancy
  3. Small increase in serious fetal malformations (~3% vs. 2% for average pregnancy)
  4. Women on valproate or carbamazepine should take folic acid 5mg po qd during pregnancy
  5. Slight increase in risk of Vitamin K depletion on cbz, pht, pb, and prim
  6. Recommend 20mg vitamin K during last few weeks of pregnancy if on these medications

M. Temporal Lobe Epilepsy

  1. Arise in:
    1. Medial temporal lobe
    2. Amygdaloid Nucleus
    3. Hippocampus
  2. Propagation to amygdala
  3. Symptoms
    1. Feelings of depersonalization
    2. Emotionality
    3. Automatic Behavior
    4. Loss of memory during bizarre behavior
    5. Hypersexuality
  4. Cannot distinguish from partial complex seizures arising from frontal lobes without EEG
  5. Treatment
    1. Carbamazapine
    2. Dilantin
    3. Valproate
    4. Phenobarbital

N. Prognosis

  1. Over 60% of patients whose seizures begin in childhood are seizure-free as adults
  2. For those that become seizure-free, there was no difference in socioeconomic status compared with matched controls
  3. There is an increased risk of death in patients whose seizures continue into adulthood
  4. Likewise, a reduction in socioeconomic status is found when seizures continue as adults
  5. Children with febrile seizures have no long term consequences compared with children who do not have febrile seizures



  1. Devinsky O. 1999. NEJM. 340(20):1565
  2. Brodie MJ and Dichter MA. 1996. NEJM. 334(3):168
  3. Lowenstein DH and Alldredge BK. 1998. NEJM. 338(14):970
  4. Wallace SJ. 1997. Lancet. 349:1009
  5. Delanty N, Vaughan CJ, Freench JA. 1998. Lancet. 352(9125):383
  6. Thomas RJ. 1997. Arch Intern Med. 157(6):605
  7. King MA, Newton MR, Jackson GD, et al. 1998. Lancet. 352(9133):1007
  8. Kwan P and Brodie MJ. 2000. NEJM. 342(5):314
  9. Drugs for Epilepsy. 1995. Med Let. 37(947):37
  10. Oxcarbazepine and Levetiractetam. 2000. Med Let. 42(1076):33
  11. Engel J Jr. 1996. NEJM. 334(10):647
  12. Sperling MR, O'Connor JM, Saykin AJ, Plummer C. 1996. JAMA. 276(6):470
  13. Leach JP and Brodie MJ. 1998. Lancet. 351(9097):203
  14. D'Onofrio G, Rathlev NK, Ulrich AS, et al. 1999. NEJM. 340(12):915
  15. Scott RC, Besag FMC, Neville BGR. 1999. Lancet. 353(9153):623
  16. Isojarvi JIT, Laatikainen TJ, Pakarinen AJ, et al. 1993. NEJM. 329(19):1383
  17. Felbamate. 1993. Med Let. 35(910):107
  18. Dichter MA and Brodie MJ. 1996. NEJM. 334(23):1583
  19. Gabapentin. 1994. Med Let. 36(921):39
  20. Lamotrigine. 1995. Med Let. 1995.37(944):21
  21. Motte J, Trevathan E, Arvidsson JFV, et al. 1997. NEJM. 337(25):1807
  22. Chadwick D, et al. 1999. Lancet. 354(9172):13
  23. Topiramate. 1997. Med Let. 39(1001):51
  24. Tiagabine. 1998. Med Let. 40(1024):45
  25. Marson Ag, Kadir ZA, Chadwick DW. 1997. Brit Med J. 313:1169
  26. Sillanpaa M, Jalava M, Kaleva O, Shinnar S. 1998. NEJM. 338(24):1715
  27. Verity CM, Greenwood R, Golding J. 1998. NEJM. 338(24):1723
  28. Painter NJ, Scher MS, Stein AD, et al. 1999. NEJM. 341(7):485
  29. Stephen LJ and Brodie MJ. 2000. Lancet. 355(9213):1441
  30. Brodie MJ and French JA. 2000. Lancet. 356(9226):323
  31. Bromfield EB and Vonsattel JP. 2000. NEJM. 343(6):420 (Case Record)
  32. Zonisamide. 2000. Med Let. 42(1089):94

A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus
B. K. Alldredge and Others    NEJM August 30, 2001: Volume 345:631-637
Benzodiazepines IV diazepam/Valium (5 mg), lorazepam/Ativan (2 mg) are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Ativan/Lorazepam 2mg IV is likely to be a better therapy than diazepam.

Out-of-Hospital Treatment and Response
Status epilepticus was terminated by the time of arrival at the emergency department in 59.1 percent of patients given lorazepam, 42.6 percent of patients given diazepam, and 21.1 percent of patients given placebo
[*On the basis of these results, and given the preference for lorazepam as in-hospital therapy,2 we recommend lorazepam as out-of-hospital therapy for adults in status epilepticus. One practical concern is that refrigerated storage is recommended for lorazepam but not for diazepam. In a previous study, we found that lorazepam retained 90 percent of its original concentration for five months while stored in ambulances without refrigeration. However, lorazepam was less stable at 37°C and during the warmer months in San Francisco.6 We recommend that ambulances carrying lorazepam be restocked every 60 days when ambient temperatures are 30°C or more. In warmer climates, less frequent restocking or refrigerated storage is necessary.]


Antiepileptic Drug Therapy for Adults: When to Initiate and How to Choose  - Mayo Clinic Proceedings December 2002 Volume 77 Number 12 
Joseph I. Sirven

Antiepileptic Drug Withdrawal: Literature Review  
Jeffrey W. Britton - Mayo Clinic Proceedings December 2002 Volume 77 Number 12 

An Overview of Surgery for Chronic Seizures
Richard S. Zimmerman and Joseph I. Sirven - Mayo Clinic Proceedings January 2003 Volume 78 Number 1 

Demystifying Seizures and Epilepsy: Introduction to the Symposium on Seizures
Joseph I. Sirven - Mayo Clinic Proceedings September 2002 Volume 77 Number 9

Characteristics of the Epilepsies
David R. Chabolla - Mayo Clinic Proceedings September 2002 Volume 77 Number 9

Role and Limitations of Routine and Ambulatory Scalp Electroencephalography in Diagnosing and Managing Seizures
Gregory A. Worrell, Terrence D. Lagerlund, and Jeffrey R. Buchhalter - Mayo Clinic Proceedings September 2002 Volume 77 Number 9