stroke
Label
Epilepsy (Seizure Disorder)

DefinitionEtiologyEpidemiologyPathophysiologyClinical Presentation
WorkupGoalsMed ChoicesClinical TrialsPipeline AgentsResourcesRefs
Definition:

A chronic disorder characterized by recurrent (≥2) epileptic seizures, not due to any obvious underlying reversible trigger/stressor.

Epileptic Seizure: Paroxysmal event due to an abnormal, unregulated cerebral (neuronal) electrical discharge that transiently disrupts normal brain function.

  • Partial seizure: Affects only one part of the brain
  • Generalized seizure: Involves the whole brain
    • Primary generalized seizure: Generalized seizure at onset
    • Secondarily generalized seizure: Focal onset (partial seizure) progressing to generalized seizure activity (i.e. secondary generalization)

Classification of Epileptic Seizures:

There are more than 40 types of seizure; most are classified within 2 main categories.

1. Epilepsy Overview-Definition-1-Classification of Epileptic Seizures

EPILEPSY SYNDROMES

Epilepsy syndromes are disorders in which epilepsy is a main feature and have a relatively consistent seizure type, age of onset, etiology and prognosis.

 

Back to Top
Etiology:
Back to Top
Epidemiology:

- Incidence

  • ~0.3-0.5% in different populations worldwide
  • ~15,500 new cases per year in Canada
  • ~200,000 new cases of epilepsy are diagnosed in the US each year
  • ~45,000 new cases in children <15 years old
  • Incidence is growing most rapidly in the elderly

- Prevalence

  • ~5-10 persons per 1000
  • ~0.6% of the Canadian population

- Gender: Male = Female

- Family History: Increases risk 3-fold

 

Back to Top
Pathophysiology:

Seizure has three phases:

  • Initiation
  • Propagation
  • Termination

1) Initiation phase: Characterized by two simultaneous events:

  • High-frequency bursts of action potentials
  • Hypersynchronization of a neuronal population
  • Bursting activity is caused by:
    • Long-lasting depolarization of the neuronal membrane due to influx of extracellular calcium (Ca2+) and sodium (Na+)
  • This is followed by a hyperpolarizing after potential mediated by:
    • Gamma-aminobutyric acid (GABA) receptors
    • Potassium (K+) efflux
    • Chloride (Cl-) influx
  • Synchronized bursts from a sufficient number of neurons result in a spike discharge on EEG

2) Propagation phase: Characterized by spread of partial seizures within brain.

3) Termination phase: Not fully understood but may involve restoration of neuronal inhibitory processes and/or "neuronal exhaustion".

The mechanisms underlying absence seizures involve repetitive oscillations in a circuit between thalamic specific and reticular nuclei and the cerebral cortex. The abnormal neuronal firing in this circuit depends on calcium-T channels which are activated by GABA-mediated membrane hyperpolarization.

 

Back to Top
Clinical Presentation:

Partial seizures

Simple partial seizures (formerly known as focal seizures)

  • Patient is conscious
  • Contractions (tonic) or rhythmic jerking (clonic) movements
    • May involve 1 entire side of body OR
    • May be more localized (e.g., hands, feet, face)
  • Jacksonian march:
    • Sequential spread of seizure activity along a limb or hemibody
      (e.g., beginning in hand, progressing up arm, to face); can be motor or sensory
  • Todd's paresis:
    • Focal symptoms, usually weakness (but may include speech dysfunction etc.) for up to several hours post-ictally; reflects the function of the focus of origin of the seizure

Complex partial seizures (formerly psychomotor seizures)

Most common epileptic seizures in adults

  • Most commonly originate from temporolimbic structures
  • Typically last <3 minutes
  • Loss of contact with surroundings
  • Aura may occur (often very individualized) and may include:
    • Dizziness, nausea, "epigastric rising" sensation, deja-vu, olfactory hallucination
  • Dystonic posturing
  • Brief, bilateral complex movements
  • Automatisms (stereotyped, repetitive behaviors, purposeless speech and oral movements, lip smacking)

Postictal phase, characterized by

  • Somnolence/confusion
  • ± Headache for up to several hours
  • Amnesia for the event

Partial seizures with secondary generalization:

  • Focal onset (speech, motor, sensory) with evolution into generalized seizures

Generalized seizures

Absence seizures (formerly petit mal)-usually in childhood

  • Typical absence seizures
    • Abrupt onset and ending
    • Unresponsiveness/behavior arrest
    • Typically last <10 seconds
  • Atypical absence seizures
    • Gradual onset and ending
    • Slight movements of the lips
    • Often with tonic, atonic, myoclonic features

Tonic-clonic seizures (formerly grand mal)

  • Loss of consciousness at onset
  • Usually last >30 sec and <5 minutes
  • Eye deviation (vertical or horizontal)
  • Clenched teeth or jaw with cheek, lip or tongue biting
  • Labored breathing/frothy sputum
  • Urinary/fecal incontinence
  • Todd's paresis-focal symptoms, usually weakness (but may include speech dysfunction) for up to several hours post ictus

Atonic seizures (also known as drop seizures)

  • usually last <15 seconds
  • Impaired consciousness
  • Sudden, brief loss of muscle tone
  • Falls, sometimes with injury

Myoclonic seizures

  • Sudden, brief and sometimes repetitive muscle contractions
  • Head nodding
  • Abrupt arm movements
  • Shoulder may shrug
  • Foot may kick
  • Sudden falls
  • Consciousness is usually not impaired

Status Epilepticus: (SE)

Neurological emergency

  • Seizures may be generalized convulsive (tonic-clonic or myoclonic seizures), non-convulsive (absence) or partial (focal)
  • Generalized tonic-clonic status: Presents as either
    • Continuous generalized seizures lasting >10 minutes
    • Patients do not fully regain consciousness between ≥2 generalized tonic-clonic seizures

 

Back to Top
Investigation and Workup:

Seizures history:

A detailed history of the event, preferably with an eye witness account, would greatly assist the diagnosis of seizures, and should include:

  • How the event started (triggers, fall, etc.)
  • Duration of the event
  • Description of the seizure itself
  • Whether patient was aware or not
  • What happened after seizure (post ictal phase)

Assessment of past history should include:

  • History of prior seizures, including febrile seizures as well as unexplained nocturnal events
  • History of previous unexplained syncopal episodes
  • Family history of seizures
  • History of developmental delay
  • History of head trauma, stroke, intracranial infections-includes tumors or brain lesions
  • Medication adherence for those already on anticonvulsants
  • Assessment of prescribed medication including interactions which can reduced efficacy of AEDs
  • Excess or chronic use of alcohol and/or recreational/illicit drugs
  • Triggering or threshold-lowering factors including sleep deprevation, infections and emotional upset, stress, flashing lights, hyperventilation (particularly in absence or partial seizures), alcohol

Physical examination:

  • Complete neurological examination is conducted on presentation
  • Consider the evidence of any systemic disorder
  • Examine any injury sustained during the event

Laboratory studies

Check for serum glucose, electrolytes, including Ca, Mg, and PO4 to assess for:

  • Hypo/hyperglycemia
  • Hypo/hypernatremia
  • Hypomagnesemia
  • Hypocalcemia
  • Hypophosphatemia

Complete blood count (CBC):

  • Rule out infection (elevated WBC)
  • Rule out thrombocytopenia
  • Rule out leucopenia (or other blood dyscrasias)
  • LFTs

Toxicology screens:

  • Include alcohol, cocaine, narcotics, barbiturates, marijuana

Antiepileptic drug (AED) levels:

  • Assessment of adherence and toxicity-includes side effects of AEDs already tried - especially idiosyncratic reactions (CBC, LFTs, etc.) as well as rash, weight loss or gain, etc.
  • Review of AEDs already tried and there effectiveness or lack thereof
  • Review special populations needs (women with epilepsy, elderly, children etc.)
  • Review any drug interactions or possibility of drug interactions

Electroencephalography (EEG):

  • Focal spikes or generalized spike and wave discharges/bursts suggestive of epilepsy
  • A negative EEG does not exclude seizure disorder

Imaging studies

  • CT scan of brain
  • MRI of brain: Preferred on CT if assessing for structural lesions

 

Back to Top
Treatment Goals:
  • Once a physician has decided that antiepileptic drugs (AEDs) are indicated for seizure prophylaxis, emphasize the importance of reduce/manage risk factors that can precipitate seizures
  • To decrease the frequency and severity of seizures (goal would be zero, if possible), by advocating strict treatment compliance
  • To encourage compliance with written and verbal instructions on treatment regimens, along with periodic laboratory assessments of blood concentrations of antiepileptic drugs (AEDs)
  • Prevent or minimize adverse effects of (AEDs)
  • Provide education, support, and counseling to patients and their families
  • Optimize quality of life by advising patient to contact different social organizations/support groups that might assist with for employment, transportation alternatives (in case of loss of license) psychosocial interaction to help patients to function within the society

Other potential goals could include:

  • Encouraging adherence to treatment guidelines with regards to titration schedules of antiepileptic agents
  • Help identify and avoid precipitant for seizures
  • To chart seizure frequency to guide treatment changes
  • To optimize compliance by offering strategies for medication adherence, alternatives for expensive regimens, etc.
  • To decrease potential drug interactions - or to monitor drug interactions and adjust as needed

 

Back to Top
Therapeutic Choices:

1. Non-pharmacological Intervention:

  • In known epileptics avoid known triggers/stressors
  • Avoid sleep deprivation
  • In cases where seizures are preceded by an aura, patients should use this warning to take necessary precautions to prevent injury
  • Advise to eliminate or keep alcohol intake to a minimum
  • Avoid illicit drug use e.g. cocaine and amphetamines

2. Pharmacological Intervention:

i) Choice of an AEDs depends on:

  • Type of seizure, potential drug interaction, side effects, affordability and adherence to the treatment

ii) Basic treatment principles:

  • Treatment usually begins with monotherapy
  • Initiate fraction of target dose and titrate up as tolerated and for efficacy
  • A lower starting dose may also help to minimize the dose dependant adverse effects
  • Be aware of potential risk factors (e.g. sleep deprivation, stress, etc.), and avoid them
  • Evaluate clinical efficacy and steady state serum levels (where appropriate) after target dose achieved or when patient is seizure free
  • Consider dose increase (as tolerated) for seizure recurrence
  • When the maximum tolerated dose of the initial AED fails to achieve seizure control, patient may be switched to another agent (as monotherapy) or a second AED, can be added
  • The first AED should be withdrawn gradually to prevent withdrawal seizures, once the maintenance dose of the second AED is established

iii) Medical Management:

a) Status Epilepticus (SE)

  • Any seizure type can potentially evolve into SE
  • Psychogenic nonepileptic seizures, can be confused with SE
  • SE are associated with high mortality and requires aggressive treatment

Management of Status Epilepticus

b) New-onset seizure episode (non-status epilepticus):

  • Eliminate underlying cause if possible (drugs, infection, metabolic derangements etc.)
  • If decision made to treat with anticonvulsants then:
    • Obtain baseline blood work: CBC, LFTs, electrolytes, glucose, creatinine, albumin
    • Initiate monotherapy and titrate to average dose as tolerated or titrate to minimally therapeutic dose
    • Obtain blood work for drug levels at steady state and when seizure free and repeat as required
    • Switch to alternative monotherapy or add additional agents as required; titrate as tolerated; be aware of potential drug-drug interactions and decreased efficacy; monitor drug levels and blood work as required
  • Patients with resistance to monotherapy-consider:
    • Diagnostic possibilities other than epilepsy (e.g. pseudoseizures, presyncope/syncope)
    • Life-style issues aggravating seizures (e.g. poor sleep, drugs, alcohol)
    • Assess medication adherence
    • Reduced AED efficacy due to drug-drug interaction
    • Progressive neurological condition/lesion
  • Combination therapy should be considered:
    • After failure of independent use of 2 first-line AEDs tried at maximally effective doses for a reasonable length of time or failure to control symptoms is related to drug intolerance (with or without failure to achieve therapeutic doses) rather than non-effectiveness of the agent
    • The first well-tolerated drug substantially improves seizure control but fails to produce complete seizure control at maximal dosage
  • Seizure precautions:
  • Until condition controlled, patients should be advised to discontinue, restrict or avoid:
    • Operating heavy machinery/driving
    • Solo use of bathtubs/hot-tubs or swimming alone
    • Heights (e.g. ladders; balconies in high rise buildings)
    • Potentially dangerous sports such as scuba diving, rock climbing, sky-diving, horseback riding
    • Avoid cooking or operating stove/oven alone
  • Primary and secondarily generalized seizures (drugs options):
    • Many AEDs can be effective in both primary and secondarily generalized seizures
    • Newer agents like levetiracetam, lamotrigine and lacosamide may have better tolerability

iv) Neurosurgical Treatment:

Considered if:

  • Epilepsy is refractory to AED management
  • Clearly defined epileptic focus in non-eloquent brain

 

v) General consideration according to the type of presentation:

The first seizure:

  • A single unprovoked seizure is usually not treated unless there is an underlying cerebral lesion or EEG abnormalities such as generalized spike-wave bursts associated with a high likelihood of recurrence-in which case the patient may be treated
  • An increase risk is suggested by the presence of:
    • Established remote cause (e.g. head trauma, stroke etc.)
    • Focally originating seizures
    • Abnormal neurological examination
    • Abnormal EEG

Women with epilepsy:

  • Enzyme inducing AEDs may increase the risk of oral contraceptive failure
  • Women who wish to conceive should be discuss treatment options and potential for medication induced teratogenicity with their neurologist
  • Valproic acid is associated with highest risk of congenital malformation
  • Women of childbearing age who are using AEDs should receive folic acid supplements
  • For patients who are on polytherapy, the least helpful AEDs might be withdrawn
  • During pregnancy AED levels may drop significantly and levels should be monitored closely
  • Following delivery AED levels they may rise sharply, and should be monitored closely
  • Close obstetric follow-up, counseling and ultrasonography is advised for detection of fetal malformation (if any)
  • Advise Vitamin-K in last 4 weeks of pregnancy
  • Breastfeeding with some AEDs acceptable-monitor for CNS side effects in babies

 

MEDICATIONS:

Antiepileptic drugs considered in first line treatment of epilepsy

  • Carbamazepine/Carbamazepine-CR
  • Oxcarbazepine
  • Lamotrigine
  • Levetiracetam
  • Phenytoin
  • Topiramate
  • Divalproex sodium or valporic acid
  • Ethosuximide (used in absence seizure)

Mechanism

Carbamazepine, Oxcarbazepine, Phenytoin, Lamotrigine

  • Blocks sodium channels

Topiramate

  • Blocks sodium channels
  • Enhances GABA activity
  • Decreases glutamate activity by blocking AMPA receptors
  • Inhibits carbonic anhydrase

Valproate

  • Blocks sodium channels
  • Blocks calcium channels
  • Enhances GABA activity

Levetiracetam

  • Possibly acts by binding to synaptic vesicular protein

Ethosuximide

  • The exact mechanism is unknown but suggested to involve reduction of the current in neuronal T-type calcium channels

Dose:

Carbamazepine

  • Tablet: 100 mg PO BID for 3-7 days then increase to 200 mg PO BID or TID as tolerated; Max dose 1800 mg/day in most patients, can go higher upto 2400 mg/day in patients with inducers
  • Suspension: Start with1 teaspoonful (100 mg/5 ml) PO once daily up to usual of 400 mg/day in 3-4 divided doses; increasing by 200 mg/ week in divided doses; Max dose 1200 mg/day

Caution: Monitor CBC, LFTs, carbamazepine levels within first 1-2 months of initiation to assess for blood dyscrasias. Neutropenia is often dose related, and seldom requires discontinuation. However, if lower doses used to avoid neutropenia, efficacy may also be compromised

Note: Drug levels may fall after approximately 3 weeks due to autoinduction of metabolism, therefore steady state levels are only achieved about 3-4 weeks after a steady dose has been established

Lamotrigine: Depends on whether lamotrigine is being used as a monotherapy, or combined with an (cytochome P450 3A4) enzyme inhibitor such as valproate or an enzyme inducer agent such as carbamazepine, or both.

Dose initiation and maintenance:

  • Monotherapy or concomitant use of both enzyme inducer (e.g. carbamazepine) and enzyme inhibitor (e.g. valproate):
    • 25 mg PO once daily for 1-2 week; then 25 mg PO BID for 1-2 weeks, then increase every 1-2 weeks by 25-50 mg until at 50-100 mg BID as maintenance
  • If used with concomitant CYP450 enzyme inducer alone (e.g. carbamazepine):
    • 50 mg PO once daily for 1-2 week; then 50 mg PO BID for 1-2 weeks, then increase every 1-2 weeks by 100 mg until at 150-300 mg BID as maintenance
  • If used with concomitant enzyme inhibitor alone (e.g. valproate):
    • 25 mg PO every other day for 1-2 week; then 25 mg PO once-a-day for 1-2 weeks, then increase every 1-2 weeks by 25-50 mg until at 50-100 mg BID as maintenance

Levetiracetam

  • 250-500mg PO BID; then increase by 250-500 mg every 1-2 weeks; Max. 4000 mg/day

Oxcarbazepine:

  • 300 mg PO BID; usual dose of 1200 mg/day in 2 divided doses. Can be increased by 600 mg/day at weekly intervals; Max. 2400 mg/day

Phenytoin:

  • 300 mg/day PO, (single or divided dose); effective total serum level are 40-80 umol/L (10-20 µg/mL)
  • Note:
    • Assess for steady state serum levels after 7days and adjust weekly by adjusting daily dose by 50-100 mg increments/decrements
    • Serum albumin (normal 35-50 g/L) affects total phenytoin levels and should be assessed at the same time
    • Low doses may be required in hypoalbuminemic states
  • Corrected phenytoin equation:

1-Epilepsy Overview-Treatment-Meds-Corrected Phenytoin equation

Phenytoin loading dose:

  • Intravenous: 20 mg/kg (15 mg/kg in the elderly) IV adult single dose or in 2-3 divided doses every 2-4 hrs. Cardiac monitoring usually required if single dose of 1 g is being administered
  • Infusion rates: In adults 25-50 mg/min, diluted in 1 liter 0.9% NaCl
  • Oral load (not for status epilepticus): 300-400 mg PO BID for 2 days
  • Maintenance dose: 200 to 300 mg PO or IV once-a-day, may be used initially and adjust in 50-100 mg/day increments every 2-7 days, depending on clinical response and serum levels

Topiramate:

  • Initial dose 25mg PO BID for the first week; increase by 25mg PO BID every week to 50 mg BID. May continue to increase further by 25-50 mg weekly until at 200-400 mg PO daily
  • Monotherapy is 200-400 mg PO daily given BID in children >10yrs and adults in partial seizures

Valproic acid/Divalproex sodium:

  • Initial 10-15 mg/kg/day, increase by 5-10 mg/kg/week; Adults dosing 250 mg BID for 3 days, then increase to TID for 3 days.
    May further titrate to 500 mg BID or TID if needed; Max dose: 60 mg/kg/day
  • Note: Monitor plasma trough levels to determine therapeutic levels (50-150 mg/ml or 350-700 μmol/L)

Ethosuximide:

  • Initial 500 mg/day PO in single or divided dose; Slowly increase dose by 250 mg/day after every 4-7 days until seizures are controlled; Max. dose 1.5 g/day, if it exceeds 1.5 mg/day clinician should monitor very closely

Agents that are more often used in combination therapy are:

  • Clobazam
  • Clonazepam
  • Felbamate (not available in Canada)
  • Gabapentin
  • Primidone
  • Tiagabine (not available in Canada)
  • Vigabatrin
  • Zonisamide (not available in Canada)
  • Lacosamide

Potential Mechanism(s):

Gabapentin:

  • Binds to voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit located presynaptically and may modulate release of excitatory neurotransmitters

Felbamate:

  • Mechanism of action is unknown but has properties in common with other marketed anticonvulsants; has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex

Zonisamide:

  • May stabilize neuronal membranes and suppress neuronal hypersynchronization through action at sodium and calcium channels. Does not affect GABA activity

Lacosamide:

  • Enhances slow inactivation of sodium channels

Clobazam/Clonazepam:

  • Benzodiazepines binding to GABA receptor, increases permeability to chloride ions-results in membrane stabilization

Primidone/Tiagabine:

  • Enhances GABA activity. Phenobarbital and primidone (metabolized partially to Phenobarbital) also block sodium channels

Vigabatrin:

  • Irreversibly inhibits GABA-T, increasing GABA levels within the brain

Dose:

Clobazam:

  • Initial starting dose 5-10 mg PO at bedtime; maintenance from 10-80 mg/day PO at bedtime; usual dose 10-20 mg/day PO at bedtime; Max. 80 mg/day in 2 divided doses (1/3 a.m. and 2/3 at bedtime)

Clonazepam:

  • Initial starting 1.5 mg/daily PO in 3 divided dose; may increased 0.5-1 mg every 3rd day until seizures are controlled; Max. 20 mg/daily in divided doses

Felbamate:

  • 1,200 mg/d in 3-4 divided doses; Max. 3,600 mg/d

Gabapentin:

  • Initial 100-300 mg PO TID; Usual dose is 900-1800 mg/day in 3 divided doses; Max.2400 mg/day are well tolerated
  • Note: Doses are to be adjusted according to the ClCr

Primidone:

  • Start 100-125 mg PO at bedtime for 3 days; continue with the same dose by increases frequency from Day 4-6 BID and Day 7-9 TID; Maintaining 250 mg/dose BID or TID, from Day 10 onwards; Max dose 2 gm/day

Tiagabine:

  • 4 mg PO daily; adjust weekly to max. 56 mg PO in 2-4 divided doses

Vigabatrin:

  • Initial 500 mg PO BID; may be increased in 500 mg at weekly intervals; Max. 1.5gm PO BID

Zonisamide:

  • Start 100 mg/day; may increase dose by 100 mg/day after at least every 2 weeks; Max. 400 mg/day

Lacosamide:

  • 50 mg BID; may be increased at weekly intervals by 100 mg/day; usual 200-400 mg/day

Agents that are commonly used in status epilepticus:

  • Benzodiazepines
  • Hydantoin
  • Barbiturates
  • General anesthetic
  • Electrolyte supplement included in anticonvulsant category

Benzodiazepines

  • Diazepam
  • Lorazepam
  • Midazolam

Mechanism:

  • Benzodiazepines bind to the gamma sub-unit of the GABA receptor and enhance the inhibitory effect of GABA
  • Increase the frequency of channel opening events, leads to increase in chloride ion conductance and inhibition of the action potential
  • All benzodiazepines exert five major effects: (i) Anxiolytic (ii) Hypnotic (iii) Muscle relaxant (iv) Anticonvulsant (v) Amnesic (impairment of memory)

Dose:

Diazepam:

  • IV: May be used for seizure status; 5-10 mg IV push (every 5-10 min) prn seizure to max of 30-40 mg
    • Note: Monitor for respiratory depression at higher doses. May require intubation
  • Rectal gel: Initial dose 0.2 mg/kg

Lorazepam:

  • May be used for seizure status: 1-2 mg IV push every 5-10 min prn; Max of 6-8 mg
    • Note: Monitor for respiratory depression at higher doses. May require intubation

Midazolam:

  • 2.5 mg IV over 2 minutes. May be used for seizure status
    • Note: Monitor for respiratory depression at higher doses. May require intubation

Hydantoin

  • Phenytoin
  • Fosphenytoin

Mechanism:

After administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin as the active moiety.

  • Inhibits calcium flux across neuronal membranes
  • Blocks sodium channels

Dose:

Phenytoin: Status epilepticus

  • Adults: 15-20 mg/kg IV administered at a rate of 25-50 mg/minute. If seizures are not controlled, additional doses of 5-10 mg/kg IV (maximum 30 mg/kg) may be given

Fosphenytoin:

  • Status epilepticus: Loading dose 15-20 mg PE/kg IV administered at 100-150 mg PE/minute
  • Nonemergent loading and maintenance dosing (IV or IM): Loading dose 10-20 mg PE/kg (IV rate: Infuse over 30 minutes; maximum rate: 150 mg PE/minute). Initial daily maintenance dose: 4-6 mg PE/kg/day

Note: Infusion rates for fosphenytoin are expressed as phenytoin sodium equivalent (PE).

Barbiturates

  • Phenobarbital
  • Thiopental
  • Pentobarbital

Mechanism:

  • Acts on GABA-A receptors, enhances the synaptic action of gamma-aminobutyric acid (GABA)
  • Also inhibit sodium and calcium channels

Dose:

Phenobarbital (status epilepticus):

  • Loading dose: 10-20 mg/kg IV (maximum rate ≤60 mg/minute in patients ≥60 kg); may repeat dose in 20-minute intervals; Max dose: 30 mg/kg
  • Maintenance: 1-3 mg/kg/day IV in divided doses; 50-100 mg PO 2-3 times/day
    • Note: Monitor for respiratory depression at higher doses. May requires intubation

Thiopental:

  • Seizures: 75-250 mg/dose IV; repeat as needed, administer slowly over 20-30mins

Pentobarbital:

Refractory Status Epilepticus (IV):

  • Loading dose: 5-15 mg/kg IV administered slowly over 1 hour. Begin in lower dose range in hypotensive patients. Maintenance infusion 0.5-1 mg/kg/hr titrated up to 10 mg/kg/hour as required to maintain burst suppression on EEG
    • Note:Adjust dose based on hemodynamics, seizure activity, and EEG

General Anesthetic

  • Propofol

Mechanism:

  • Short acting intravenous general anesthetic, with several mechanisms
  • It causes CNS depression through GABAA receptors by its agonist action
  • It also decreases glutamatergic activity

Dose:

Propofol (increasingly used in status epilepticus not responding to initial therapy in ED)

  • 2-10 mg/kg/hr IV titrate to desired effect
  • More than 5 mg/kg/hour IV or if used >48 hrs, increases the risk of hypotension, consider alternative treatment to avoid risk associated with long term infusion

Electrolyte Supplement

  • Magnesium sulfate (MgSO4)
  • Used mainly in seizures due to severe hypomagnesemia or eclampsia

Mechanism:

  • Essential for the activity of many enzymatic reactions and plays an important role in neurotransmission and muscular excitability
  • Prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse
  • Other effect are promote bowel evacuation, slowing heart rate/conduction, smooth muscle relaxation, vasodilation

Dose:

Hypomagnesemia:

  • Magnesium sulfate 2 g IV over 10 minutes; calcium administration may also be appropriate as many patients are also hypocalcemic

Eclampsia:

  • Maximal rate of infusion 2 g/hour IV to avoid hypotension; doses of 4 g/hour have been employed in emergencies; optimally, should add magnesium to IV fluids, but bolus doses are also effective

 

Back to Top
Clinical Trials:
Back to Top
Pipeline Agents:
Back to Top
Pharmacist Resources:

Core Resources:

  • Brust JCM (2007) Current Diagnosis and Treatment (Neurology) (2nd ed.) New York: McGraw Hill
  • Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
  • Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth's Textbook of Canadian Medical-Surgical Nursing. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
  • Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
  • Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6th ed. Toronto: Webcom Inc. 2011
  • Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 1th ed. New York: McGraw-Hill; 2009
  • Longo D, Fauci A, Kasper D, et al (eds). Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2011
  • McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
  • Pagana KD, Pagana TJ eds. Mosby's Diagnostic and Laboratory Test Reference. 9th ed. St. Louis: Elsevier-Mosby; 2009
  • Rowland LP et al. (2010) Merritt's Neurology (9th ed.) Philadelphia: Lippincoot Williams and Wilkins
  • Skidmore-Roth L. ed. Mosby's drug guide for nurses. 9th ed. St. Louis: Elsevier-Mosby; 2011
  • Skidmore-Roth L, ed. Mosby's nursing drug reference. 24th ed. St. Louis: Elsevier-Mosby; 2011

 

Online Pharmacological Resources:

  • e-therapeutics
  • Lexicomp
  • RxList
  • Epocrates Online

 

Journals/Clinical Trials:

  • Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia, 2007;48:1308-17
  • Brodie M.J., Perucca E., Rylin P. et al, for the Levetiracetam Monotherapy Study Group. Comparison of Levetiracetam and controlled-release Carbamazepine in newly diagnosed epilepsy. Neurology, 2007;68:402-408
  • Brodie M.J., Overstall P.W., Giorgi L. and The UK Lamotrigine Elderly Study Group. Comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res., 1999 ;37:81-7
  • Cunnington MC, Weil JG, Messenheimer JA et al. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology, 2011;76:1817-23
  • Chung S, Ben-Menachem E, Sperling MR et al. Examining the Clinical Utility of Lacosamide: Pooled analyses of three Phase II/III clinical trials. CNS Drugs, 2010;24:1041-1054
  • Elger C, Halász P, Maia J, et al; BIA-2093-301 Investigators Study Group. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Epilepsia, 2009;50:454-63
  • French JA, Costantini C, Brodsky A, von Rosenstiel P; N01193 Study Group. Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial. Neurology, 2010;75:519-25
  • Glauser T.A., Cnaan A., Shinnar S. et al, for the Childhood Absence Epilepsy Study Group. Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy. N Engl J Med, 2010; 362:790-799
  • Glauser T, Kluger G, Sachdeo R et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology, 2008;70:1950-8
  • Holmes LB, M.D., Harvey EA, Coull BA et al. The Teratogenicity of Anticonvulsant Drugs. N Engl J Med, 2001;344:1132-8
  • Kwan P, Brodie MJ, et al. Effectiveness of first antiepileptic drug. Epilepsia, 2001;42:1255-60
  • Marson AG, Al-Kharusi AM, Alwaidh M et al. on behalf of the SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy. The Lancet, 2007;369:1000-1015
  • Marson AG, Al-Kharusi AM, Alwaidh M et al. on behalf of the SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalized and unclassifiable epilepsy. The Lancet, 2007;369:1016-1026
  • M.J. Brodie, MD, H. Lerche, MD, A. Gil-Nagel, MD, and On behalf of the RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology, 2010;75:1817-1824
  • Rowan A.J., Ramsay T.E., Collins J.F. et al and the VA Cooperative Study 428 Group. A randomized study of gabapentin, lamotrigine, and carbamazepine. N Engl J Med, 2010;362:790-799
  • Wiebe S, Blume W, Girvin JP, et al, for the Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy drug. N Engl J Med, 2001;345:311-318

 

Back to Top
References:

Core Resources:

  • Brust JCM (2007) Current Diagnosis and Treatment (Neurology) (2nd ed.) New York: McGraw Hill
  • Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
  • Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth's Textbook of Canadian Medical-Surgical Nursing. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
  • Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
  • Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6th ed. Toronto: Webcom Inc. 2011
  • Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009
  • Longo D, Fauci A, Kasper D, et al (eds). Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2011
  • McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
  • Pagana KD, Pagana TJ eds. Mosby's Diagnostic and Laboratory Test Reference. 9th ed. St. Louis: Elsevier-Mosby; 2009
  • Rowland LP et al. (2010) Merritt's Neurology (9th ed.) Philadelphia: Lippincoot Williams and Wilkins
  • Skidmore-Roth L. ed. Mosby's drug guide for nurses. 9th ed. St. Louis: Elsevier-Mosby; 2011
  • Skidmore-Roth L, ed. Mosby's nursing drug reference. 24th ed. St. Louis: Elsevier-Mosby; 2011

 

Online Pharmacological Resources:

  • e-therapeutics
  • Lexicomp
  • RxList
  • Epocrates Online

 

Journals/Clinical Trials:

  • Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia, 2007;48:1308-17
  • Brodie M.J., Perucca E., Rylin P. et al, for the Levetiracetam Monotherapy Study Group. Comparison of Levetiracetam and controlled-release Carbamazepine in newly diagnosed epilepsy. Neurology, 2007;68:402-408
  • Brodie M.J., Overstall P.W., Giorgi L. and The UK Lamotrigine Elderly Study Group. Comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res., 1999 ;37:81-7
  • Cunnington MC, Weil JG, Messenheimer JA et al. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology, 2011;76:1817-23
  • Chung S, Ben-Menachem E, Sperling MR et al. Examining the Clinical Utility of Lacosamide: Pooled analyses of three Phase II/III clinical trials. CNS Drugs, 2010;24:1041-1054
  • Elger C, Halász P, Maia J, et al; BIA-2093-301 Investigators Study Group. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Epilepsia, 2009;50:454-63
  • French JA, Costantini C, Brodsky A, von Rosenstiel P; N01193 Study Group. Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial. Neurology, 2010;75:519-25
  • Glauser T.A., Cnaan A., Shinnar S. et al, for the Childhood Absence Epilepsy Study Group. Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy. N Engl J Med, 2010; 362:790-799
  • Glauser T, Kluger G, Sachdeo R et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology, 2008;70:1950-8
  • Holmes LB, M.D., Harvey EA, Coull BA et al. The Teratogenicity of Anticonvulsant Drugs. N Engl J Med, 2001;344:1132-8
  • Kwan P, Brodie MJ, et al. Effectiveness of first antiepileptic drug. Epilepsia, 2001;42:1255-60
  • Marson AG, Al-Kharusi AM, Alwaidh M et al. on behalf of the SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy. The Lancet, 2007;369:1000-1015
  • Marson AG, Al-Kharusi AM, Alwaidh M et al. on behalf of the SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalized and unclassifiable epilepsy. The Lancet, 2007;369:1016-1026
  • M.J. Brodie, MD, H. Lerche, MD, A. Gil-Nagel, MD, and On behalf of the RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology, 2010;75:1817-1824
  • Rowan A.J., Ramsay T.E., Collins J.F. et al and the VA Cooperative Study 428 Group. A randomized study of gabapentin, lamotrigine, and carbamazepine. N Engl J Med, 2010;362:790-799
  • Wiebe S, Blume W, Girvin JP, et al, for the Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy drug. N Engl J Med, 2001;345:311-318

 

Back to Top
explore
Reviewers

EXPERT REVIEWER:
Alan Guberman, MD, FRCPC, Professor of Medicine (Neurology)University of Ottawa, The Ottawa Hospital-Civic Campus, Ottawa, ON Canada
.......................................... PHARMACY REVIEWER:
Tejal Patel, B.Sc.(Pharm), Pharm.D., Clinical Assistant Professor, School of Pharmacy, University of Waterloo, ON Canada

Upcoming eDucate Webinar Series
 
Copyright © 2011-2017 Innovate R&D
stroke

educate Are you a Healthcare professional or patient?

Healthcare Professionals would include: Physicians (MD,OD), Physician assistants, Nurses, Pharmacists,Allied Health Workers (PT, OT, SLP, etc), Chiropractors, Paramedics, Optometrists, Dentists, Podiatrists etc, and students within these disciplines.

educate ** You are required to register **

eDucate is committed to optimizing the delivery of health information across the Healthcare continuum. To this end eDucate uses a wide array of learning tools, including Webinars, Quick Review Charts, Graphs, Brochures, Videos and Slide Presentations.

Register and join over 65,000 individuals have leveraged the eDucate portal for their medical information needs during the past 2 years.

Professional Membership Benefits include free access to all archived and upcoming Webinars:

educate DISCLAIMER: This website is owned and operated by The Innovate Research and Development LP (Innovate R&D). All references herein to Innovate R&D shall be deemed to include any subsidiary, affiliate, associate or successor corporation of Innovate R&D. By entering and using this site, you agree to the "Terms of Use"for this website. If you do not agree to these terms and conditions then exit from this site immediately. Although Innovate R&D updates this website regularly with material believed to be accurate at the time of posting, Innovate R&D does not guarantee the accuracy, completeness, timeliness or currency of the material and consequently Innovate R&D expressly disclaims any liability for errors or omissions in the material contained in the website. The Innovate R&D website and all contents are provided as-is, and all representations and warranties, express or implied, relating to the website or the content are disclaimed, including any implied warranty of merchantability, fitness for a particular purpose or non-infringement, as well as any warranty of quality, functionality, accuracy, currency, completeness, reliability, operability, use performance or absence of viruses. In no way or event will Innovate R&D or any party that has been involved in the creation, production, promotion and marketing be liable to you or any other party for perceived direct or indirect damages. You assume all responsibility and risk of loss resulting from the use of our website.