Epilepsy (seizure disorder)

Epilepsy (Seizure Disorder)-QR

ACKNOWLEDGEMENTS:

Thanks to Dr. Mark Freedman, MSc, MD, FAAN, FRCPC, Professor of Medicine (Neurology), University of Ottawa, Director, Multiple Sclerosis Research Unit, The Ottawa Hospital-General Campus, Ottawa, ON Canada, and Suzette Mahabeer, RN, MScN, Nursing Faculty – McMaster University, Hamilton, ON Canada for their expertise with the initial review of this topic.

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.

Classification of Epileptic Seizures:

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

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.

Epidemiology

– Incidence

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

– Prevalence

  • Approximately 50 million affected worldwide
  • Approximately 5-10 persons per 1000
  • Approximately 0.6% of the Canadian population

– Gender: Male = Female

– Family history: Increases risk 3-fold

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 the 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 the spread of partial seizures within the brain.

3) Termination phase: Not fully understood but may involve the 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.

Clinical Manifestations:

Focal seizures:

Focal seizures with retained awareness:

  • 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 the 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

Focal seizures with a loss awareness:

Most common epileptic seizures in adults

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

Postictal phase, characterized by

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

Focal to bilateral tonic-clonic :

  • Focal onset (speech, motor, sensory) with evolution into generalized seizures
  • Todd’s paresis (described above)

Generalized seizures:

Absence seizures (formerly petit mal)-usually in childhood

  • Typical absence seizures
    • Abrupt onset and ending
    • Unresponsiveness/behavior arrest
    • Typically last <10 seconds
    • Eye rolling upwards/blinking
    • May be precipitated by hyperventilation
  • Atypical absence seizures
    • Gradual onset and ending
    • Slight movements of the lips
    • Often with tonic, atonic, myoclonic features
    • Not provoked by hyperventilation
    • Associated with Lennox-Gastaut syndrome
      A childhood epileptic encephalopathy, characterized by: Seizures, mental retardation and abnormal EEG with generalized slow spike-and-wave discharge
  • Absence with special features
    • Myoclonic absence:
    • Usually lasts 8 to 60 sec
    • Abrupt onset of staring and unresponsiveness
    • Accompanied by myoclonic jerks of the shoulders, arms, and legs with a concomitant tonic contraction
    • Rhythmic protrusion of the lips, twitching of the corners of the mouth, or jaw jerking
    • Not provoked by hyperventilation
    • Eyelid myoclonia: (also known as Jeavons Syndrome)
    • May or may not be associated brief loss of awareness
    • Often precipitated by eye closure
    • Eyelids jerking at frequencies at least 3 per second
    • Upward eye deviation
    • Patients are photosensitive

Tonic-clonic Seizures (formerly grand mal)

  • Loss of consciousness at onset
  • Usually, last >30 sec and <5 minutes
  • Eye deviation
  • Clenched teeth or jaw with cheek, lip or tongue biting
  • Frothy sputum
  • Labored breathing/cyanosis
  • Urinary/fecal incontinence
  • Tonic phase (generalized muscle contraction and rigidity)
  • Clonic phase (sustained contraction followed by rhythmic contractions of all 4 extremities)
  • Postictal phase (confusion, somnolence, fatigue, ± headache)
  • Todd’s paresis (as described above), suggests focal seizure onset with secondary generalization

Tonic seizures

  • Impaired consciousness
  • Sudden brief muscle stiffening
  • Jaw clenching
  • Brief periods of apnea (last usually <60 sec)

Clonic seizures

  • Impaired consciousness(may last up to 2 minutes)
  • Confusion
  • Rhythmical jerking muscle contractions that usually involve:
    • Arms/neck/face/upper body

Atonic seizures (also known as drop seizures)

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

Myoclonic seizures

  • Myoclonic:
  • Sudden, brief <100 ms and sometimes repetitive muscle contractions
  • Involuntary single or multiple contraction(s) of muscles(s) or muscle groups
  • Can result in a “drop attack”
  • Myoclonic atonic:
  • Generalized seizure type with a myoclonic jerk
  • Leading to an atonic drop
  • Myoclonic tonic:
  • Sudden, brief and sometimes repetitive muscle contractions
  • Followed by a tonic seizure

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

Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.

Time point t1 indicates when treatment should be initiated, and time point t2 indicates when long-term consequences may appear

Workup and Diagnosis

History:

  • Family history for epilepsy
  • Detailed developmental history (including events of pregnancy and childbirth) and delays
  • Preexisting medical history
  • Head trauma
  • History of medication (current as well as recently discontinued)
  • Recreational drug use
  • Allergies
  • Any precipitating event
  • Any prodromal/aura experience
  • If the event was witnessed take details
    • Incontinence
    • Tongue/lip biting
    • Eyes rolling
    • Behavior once the episode was over
  • Seizure history to include precipitating factors, preceding events and seizure description including onset, duration, frequency, postictal state

Physical Examination:

Individuals who have sustained a seizure require a detailed neurological examination. Patients with non-convulsive seizures may display subtle signs such as automatisms (stereotyped, repetitive behaviors, purposeless speech, oral movements, and lip-smacking), facial/extremity twitching, eye deviation, and impaired consciousness alternating with normal mental status.

Other signs (lasting for few hours rarely a day) include:

  • Amnesia
  • Transient paresis of extremities
  • Transient speech disturbance
  • Confusion
  • Obtundation

Laboratory Studies

  • CBC, Serum electrolytes / calcium/ magnesium, blood urea nitrogen, serum glucose
  • Urinalysis and drug screen (alcohol, cocaine, narcotics, barbiturates, marijuana)
  • Anti-epileptic drug (AED) levels: Assessment of adherence and toxicity
  • Electroencephalography (EEG)
    • A negative EEG does not exclude seizure disorder
    • Various epileptiform abnormalities can also be seen in patients who have not had seizures
    • Focal spiking or generalized spike-wave discharges/bursts, however, have a high correlation with epilepsy
  • Note: Various epileptiform abnormalities can also be seen in patients who have not had seizures. Focal spiking or generalized spike-wave discharges/bursts, however, have a high correlation with epilepsy.
  • Intensive EEG-Video Monitoring
    • Used for differentiating non-epileptic from epileptic spells
    • Can be done as an out-patient or in-patient
    • Used for pre-surgical workup in candidates for epilepsy surgery to identify a focus and the nature of seizures
  • Ambulatory EEG monitoring
    • May be useful for some patients who are having seizures or spells in particular settings or infrequently
  • Brain electrical mapping
    • Sometimes done to locate a focal area of brain aberrant activity that has already been suggested on a regular EEG but rarely adds useful information

Imaging Studies
CT / MRI of brain:

  • Brain imaging should be considered as part of the neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure
  • Magnetic Resonance Imaging (MRI) is the preferred neuroimaging method presenting with first afebrile seizure
  • Rule-out acute intracranial pathology, such as tumors, hemorrhage, abscess, major developmental disorders, etc. MRI superior in evaluation of the temporal lobes, and particularly helpful for diagnosing subtle cortical dysplasias, migrational abnormalities, mesial temporal sclerosis, small tumors or hamartomatous lesions, cavernous hemangiomas
RN/Medical Management:

General Nursing Management during and after seizure:

The nature of seizure indicates, further management of the disease, so it is important to assess and document events just prior to, during, and after the seizure, as follows:

  • The circumstances before the seizure (e.g. sleep deprivation, visual or auditory stimuli, etc.)
  • If the seizure was preceded by an aura (i.e. any sensory stimuli, nausea, headache, irritability, etc.)
  • If the seizure was witnessed, what was the first thing noticed, e.g. where did the movement or stiffness/rigidity begin (limb ? trunk ?), or what was the position of the head, or was there any head-turning or eye deviation
  • What type of movements seen, duration of the seizure (tonic/clonic movements, limb posturing, limb or body rigidity, lip or tongue biting, urinary incontinence, lip-smacking, chewing motion)
  • Was there a loss of awareness and/or loss of consciousness, and if so, for what duration
  • Was there a post-ictal phase; typically somnolence/drowsiness, confusion inability to speak or limb weakness
  • How long did each phase of the seizure last (aura, actual seizure, post-ictal state)

Seizure care is focused on preventing injury, complications (e.g. aspiration, physical and cerebral injury), and patient support (i.e. physically as well as emotionally).

Documentation of all the above along with measures used to prevent complications during and after the seizure is crucial.

A. Status Epilepticus

Treatment of status epilepticus should begin immediately since the efficacy of treatment decreases as the duration of seizure increases. During repeated seizures, the brain uses more energy that can be supplied. Neurons become exhausted and stop functioning which may result in permanent brain damage.

The goal is to:

  • To stop the seizure as quickly as possible
  • Ensure adequate oxygen supply to the brain

Management of Status Epilepticus

Additional Nursing Management in Status Epilepticus:

  • Continue monitoring of respiratory and cardiac functions to avoid the risk of delayed respiratory depression
  • Suction equipment should always be ready, to remove pharyngeal secretions to avoid aspiration
  • Older patients and those on prolonged use of some AEDs may lead to osteoporosis, osteomalacia, and hyperparathyroidism (side effects of the therapy), and maybe prone to fractures, hence special care is required to protect them from injury, during and after the seizure
  • While steps should be taken to prevent patients from injury, nurses should also protect themselves from injury by the seizing patients (e.g. thrashing)

B. New-onset seizure episode (non-status epilepticus)

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 increased risk of recurrence 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 discuss treatment options and potential for medication-induced teratogenicity with their neurologist
  • Valproic acid is associated with the 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, AEDs levels may drop significantly and levels should be monitored closely
  • Following delivery AEDs 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 is acceptable

Medical Management:

  1. Eliminate underlying cause if possible (drugs, infection, metabolic derangements, etc.)
  2. 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 the 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
  3. 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
  4. Combination therapy should be considered:
    • After the failure of independent use of 2 first-line AEDs OR
    • The first well-tolerated drug substantially improves seizure control but fails to produce complete seizure control at a maximal dosage
  5. Seizure precautions:
  6. 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
  7. Primary and secondarily generalized seizures (drugs options):
    • Many AEDS can be effective in both primary and secondarily generalized seizures
    • Newer agents (partial and secondarily generalized seizures) such as levetiracetam, lamotrigine, and lacosamide may have better tolerability
  8. AED withdrawal:
  9. May be considered if:
    • Patient is seizure-free for at least 2 years
    • Normal neurological examination
    • Normal EEG and brain imaging
    • Drugs should withdraw slowly over a period of 1-3 months
  10. Neurosurgical treatment:
  11. May be considered in select cases if:
    • Epilepsy is refractory to AED management
    • Clearly defined epileptic focus in the non-eloquent brain
Medications:

Antiepileptic drugs considered in first-line treatment of epilepsy

  • Carbamazepine/Carbamazepine-CR
  • Oxcarbazepine
  • Lamotrigine
  • Levetiracetam
  • Phenytoin
  • Topiramate
  • Divalproex sodium or valproic 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; Maximum dose 1800 mg/day in most patients, can go higher up to 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; Maximum 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 enzyme inhibitor (cytochrome P450 3A4) 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; Maximum 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; Maximum 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 25 mg 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 >10 yrs 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; Maximum 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; Maximum 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:

  • Brivaracetam
  • Clobazam
  • Clonazepam
  • Eslicarbazepine
  • Felbamate
  • Gabapentin
  • Lacosamide
  • Perampanel
  • Primidone
  • Rufinamide
  • Tiagabine
  • Vigabatrin
  • Zonisamide

Potential Mechanism(s):

Brivaracetam:

  • Exact mechanism of action is unknown
  • Displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect

Clobazam/Clonazepam:

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

Eslicarbazepine:

  • Exact mechanism of action is unknown
  • It is thought to involve inhibition of voltage-gated sodium channels

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

Gabapentin:

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

Lacosamide:

  • Enhances slow inactivation of sodium channels

Perampanel:

  • Selective, non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons

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

Zonisamide:

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

Dose:

Brivaracetam:

  • Initial 50 mg PO/IV BID; Max. 100 mg PO/IV BID
  • Hepatic Impairment: Initial 25 mg PO/IV BID; Max. 75 mg PO/IV BID

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; Maximum 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 doses; may increase 0.5-1 mg every 3rd day until seizures are controlled; Max. 20 mg/daily in divided doses

Eslicarbazepine:

  • Initial 400 mg PO once daily; maintenance dose 800 mg once daily adjust after one or two weeks; max. 1200 mg once daily
  • Renal Impairment (CrCl <50 mL/min): Initial 200 mg PO once daily; maintenance dose 400 mg once daily adjust after two weeks; Max. 600 mg once daily

Felbamate:

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

Gabapentin:

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

Perampanel:

  • In the presence of enzyme-inducing AEDs: Initial 2 mg PO once daily; May be increased in 2 mg at weekly intervals as tolerated; Max. 12 mg PO once daily
  • In the absence of enzyme-inducing AEDs: Initial 2 mg PO once daily; May be increased in 2 mg at 2-week intervals as tolerated; Max. 12 mg PO once daily

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; Maximum dose 2 gm/day

Rufinamide:

  • In adults and children ≥30 kg: 200 mg PO BID may be increased every two weeks intervals by 5 mg/kg/day as tolerated

Tiagabine:

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

Vigabatrin:

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

Zonisamide:

  • Start 100 mg/day; may increase dose by 100 mg/day after at least every 2 weeks; Maximum 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 the 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 maximum 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; Maximum 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; Maximum 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 the 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 effects are promoting 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
Diagnosis and Goals:

Diagnosis:

  • The risk for injury related to seizure activity and subsequent impaired physical mobility secondary to post-ictal weakness or paralysis
  • Fear of having a seizure, self-concept disturbances related to the diagnosis of epilepsy
  • Ineffective individual coping related to a perceived loss of control, denial of diagnosis or misconceptions regarding disease
  • Deficient knowledge about epilepsy and its control
  • Ineffective airway clearance related to tracheobronchial obstruction
  • Ineffective breathing pattern related to neuromuscular impairment secondary to the prolonged tonic phase of seizure or during the post-ictal period

Potential Complication:

  • Inadequate brain (cerebral) perfusion may ensue during status epilepticus
  • Toxicity of medications

Goals:

  • Prevention of injuries, and control seizure quickly
  • Achieving satisfactory psychological adjustment with the disease
  • To provide in-depth knowledge about the disease and its complications
Nursing Intervention:

A nurse caring for an epileptic/seizure patient should focus on:

  • Observation
  • Treatment
  • Education
  • Psychosocial intervention

If a seizure occurs, careful observation and recording of details of the event will assist with the diagnosis of the type of seizure and subsequent treatment plan

Assessment of the post-ictal phase should include a detailed description of the level of consciousness, vital signs, memory loss, muscle soreness, speech disorders (aphasia, dysarthria), weakness or paralysis, sleep period, and the duration of each sign or symptom.

Maintaining Cerebral Tissue Perfusion (during status epilepticus)

  • Secure airway and maintain BP until after a seizure subsides
  • Administer O2 inhalation if the colour change is observed during an episode
  • Turn the patient on the side to avoid aspiration
  • During a seizure, the patient should be protected from injury
  • Maintain an IV line, for blood sampling (glucose, BUN, electrolytes) and drug administration as prescribed
  • Monitor the patient continuously
  • Check for respiratory depression and BP changes
  • Monitor serum levels for a therapeutic range of antiepileptic drugs
  • Monitor patient for toxic adverse effects of medications
  • Monitor platelet and liver functions for toxicity due to medications

General care and injury prevention:

  • Pad side rails and removes clutter
  • Place the bed in a low position to avoid injury from falls
  • Consider placing the patient on the floor
  • Do not restrain or put anything in the patient’s mouth during a seizure
  • Place the patient on the side during a seizure to prevent aspiration
  • Cradle or cushion the patient’s head during a seizure
  • Stay with the patient during a seizure and in the immediate postictal phase when patients are often confused, particularly if patient ambulatory

Reducing fear of seizures:

  • Patients may become fearful of the unexpected nature of seizures. This may be alleviated by encouraging adherence to prescribed medication
  • Patients cooperation is essential for seizure control
  • Periodic monitoring is necessary for adequate treatment
  • Patient should know that medication should be taken continuously without having a fear of dependence
  • Identify the factors that may precipitate the seizures(e.g. fever, stress, sleep deprivation, alcohol consumption and the onset of menstruation in females, etc.) to control the seizures
  • The nurse should assess the patient’s level of understanding and provide information about how and why the event occurs (upon identifying precipitating factors)

Improving coping mechanisms:

  • For social, psychological and behavioral problems consult social worker for community resources
  • Vocational rehabilitation, counselors, and support groups can provide different coping solutions like unemployment, etc.
  • Teach stress reduction techniques that will fit into patient’s lifestyle
  • Initiate appropriate consultation for management of behaviors related to personality disorders, brain damage secondary to chronic epilepsy
  • Answer questions related to the use of computerized video EEG monitoring and surgery for epilepsy management

Maintaining a patent airway

  • It is crucial to maintain a patent airway during the seizure, this includes: supporting and protecting the head; turning the patient on the side; loosening constricting clothing, or easing the person to floor if sitting in a chair. After the seizure, the patient may require suctioning and oxygen administration

Providing patient and family education:

  • Educate the patient and family to modify the attitude towards the disorder
  • Depression, hostility, anxiety, and secrecy are all to be overcome by the patient through encouragement
  • Patient should be advised to carry a medical identification card
  • Provide in-depth knowledge of medication and care during the seizure to the patient and family
  • Patient on medications should be aware of the need for therapeutic monitoring depending on the agents used. The patient should be cautioned not to adjust the medication amount or schedule without professional guidance as this can increase the frequency of seizures and may lead to status epilepticus
  • Complete pharmacological profile should be provided to the patient and every health care personnel to avoid any drug interactions-the patient should be encouraged to report any medication side effects and to keep regular appointments with the health care provider
  • Patient should recognize the condition or state which may lead to seizures

Promoting home and community-based care:

  • Advise patient for thorough oral hygiene to prevent or control gingival hyperplasia that may be a side effect of some medications
  • Be aware of general seizure precautions:
    • Counsel patients with uncontrolled seizures about not driving or operating dangerous equipment
    • No unsupervised swimming or use of bathtubs
    • Suggests the use of showers instead of bathtubs
    • Avoid climbing into high places
    • Avoid standing on alone on balconies of high rise buildings
    • Avoid prolonged standing on staircases
  • Be familiar with state/provincial regulations for driving and working
  • Assess home environment for safety hazards
    • Crowded furniture arrangement
    • Sharp edges on tables, glass
    • Suggests soft flooring and furniture
    • Advise for padded surfaces where indicated
  • Support patient in a discussion about seizures with the employer, school, and so forth

Expected outcomes:

  • During the seizure, no injury is sustained by the patient
  • Recognize the importance of compliance and hazards of stopping the treatment
  • Patient and family can adopt correct care during the seizure
  • Shows decrease in fear related to seizures and is able to cope appropriately with the disease
  • Recognize and is able to avoid factors leading to seizure, and adopts a healthy lifestyle
  • Determine the side effects of the medication and knows how to monitor them
  • Do not exhibit any of the potential complications
Nursing Alerts:
  • Non-adherence to medication regimen as well as the toxicity of antiepileptic medications can increase seizure frequency. The main goal of antiepileptic drug therapy is to attain optimal seizure control with a minimum of toxic side effects
  • Obtain drug levels before implementing medication changes even if the patient may appear to be on a low dose, as drug interaction, as well as variation in metabolism, may lead wide elevated drug levels and toxicity even at low doses

References

Core Resources:

  • Bautista RED. Understanding the self-management skills of persons with epilepsy. Epilepsy Behav. 2017;69:7-11. doi:10.1016/j.yebeh.2016.11.022
  • 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
  • Dirksen, S., Lewis, S., & Collier, I., Heitkemper, M., O’Brien, P., & Bucher, L. (2010). Medical-Surgical Nursing in Canada: Assessment and management of clinical problems (2nd ed.). Toronto: Mosby Elsevier.
  • 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
  • Hill CE, Thomas B, Sansalone K, et al. Improved availability and quality of care with epilepsy nurse practitioners. Neurol Clin Pract. 2017;7(2):109-117. doi:10.1212/CPJ.0000000000000337
  • 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
  • Louis ED, Mayer SA, Rowland LP (2016) Merritt’s Neurology (13th ed.) Philadelphia: Wolter Kluwer
  • McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
  • Miller WR, Bakas T, Weaver MT, Buelow JM, Sabau D. The life changes in epilepsy scale: development and establishment of content and face validity. Clin Nurse Spec. 2015;29(2):95-99. doi:10.1097/NUR.0000000000000109
  • 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: Lippincott 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
  • Buelow J, Miller W, Fishman J. Development of an Epilepsy Nursing Communication Tool: Improving the Quality of Interactions Between Nurses and Patients With Seizures. J Neurosci Nurs. 2018;50(2):74-80. doi:10.1097/JNN.0000000000000353
  • 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
  • Higgins A, Downes C, Varley J, Doherty CP, Begley C, Elliott N. Supporting and empowering people with epilepsy: Contribution of the Epilepsy Specialist Nurses (SENsE study). Seizure. 2019;71:42-49. doi:10.1016/j.seizure.2019.06.008
  • 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
  • Smith G, Wagner JL, Edwards JC. Epilepsy update, part 2: nursing care and evidence-based treatment. Am J Nurs. 2015;115(6):34-46. doi:10.1097/01.NAJ.0000466314.46508.00
  • 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