3. What are they?
• Medications
– Anti Epileptic Drugs (AEDs)
– IVIG
• Epilepsy Surgery
• Ketogenic Therapy
• VNS
4. Medications
• Making the choice as to what medication to
use for seizure treatment is a difficult
decision.
• Seizures are the result of abnormal electrical
activity. This is the results of an imbalance
between the excitation and inhibition.
• Anti-seizure medications impact the key
players to prevent seizure activity.
6. AEDs: Molecular and
Cellular Mechanisms
• Phenytoin (Dilantin, Phenytek),
carbamazepine (Tegretol, Carbatrol)
– Block voltage-dependent sodium
channels
American Epilepsy Society
2011
7. AEDs: Molecular and
Cellular Mechanisms
• barbiturates
– Prolong GABA-mediated
chloride channel openings
– Phenobarbital
• benzodiazepines
– Increase frequency of GABA-
mediated chloride channel
openings
– Clobazepam
– Clobazam (Onfi)
American Epilepsy Society
2011
8. AEDs: Molecular and
Cellular Mechanisms
• felbamate (Felbatol)
– Blocks voltage-dependent
sodium channels
– Modulates NMDA receptor and
GABA receptors
• gabapentin (Neurontin)
– Blocks calcium channels
– Suppressed presynaptic vesicle
release
American Epilepsy Society
2011
9. AEDs: Molecular and
Cellular Mechanisms
• lamotrigine (Lamictal, Lamictal
XR)
– Blocks voltage-dependent sodium
channels
American Epilepsy Society
2011
10. AEDs: Molecular and
Cellular Mechanisms
• Ethosuximide
(Zarontin)
– Blocks low threshold,
“transient” (T-type) calcium
channels in thalamic neurons
• Valproate,
Divalproex Sodium
– May enhance GABA
transmission in specific
circuits
– Blocks voltage-dependent
sodium channels
– Modulates T-type calcium
channels
American Epilepsy Society
2011
11. AEDs: Molecular and
Cellular Mechanisms
• Topiramate (Topamax)
– Blocks voltage-dependent Na+
channels
– Increases frequency at which
GABA opens Cl- channels
– Antagonizes glutamate action
• zonisamide (Zonegran)
– Blocks voltage-dependent sodium
channels and
T-type calcium channels
American Epilepsy Society
2011
12. AEDs: Molecular and
Cellular Mechanisms
• Levetiracetam (Keppra,
Keppra XR)
– Action is unknown, suspect it acts on
GABA
• Oxcarbazepine
(Trileptal, Oxtellar XR)
– Blocks voltage-dependent sodium
channels
– Exerts effect on K+ channels
American Epilepsy Society
2011
13. AEDs: Molecular and
Cellular Mechanisms
• Lacosamide (Vimpat)
–Enhances slow inactivation of voltage
gated sodium channels
American Epilepsy Society
2011
14. AEDs: Molecular and
Cellular Mechanisms
• rufinamide
– Unclear: Possibly
stabilization of the sodium
channel inactive state
• vigabatrin
– Irreversibly inhibits GABA-
transaminase
American Epilepsy Society
2011
15. • For Generalized seizures:
– Levetiracetam (Keppra)
– Lamotrigine
– Topiramate
– Zonegran
– Valproic Acid
– Ethosuximidate – specifically used for absence seizures
• For Partial seizures:
– Oxcarbazepine
16. IVIG Therapy
• Inflammation is known to cause several
neurological disorders.
• Recently, it is being acknowledged to have a
role in Epilepsy.
• IVIG – Intravenous immunoglobulin – contains
pooled, polyvalent, IgG antibodies that work to
suppress inflammation.
• It’s on the horizon as an effective treatment
for Epilepsy.
19. Ketogenic Therapy
• This is a rigid, mathematically calculated, doctor-
supervised diet. It can only be attempted under close
medical and dietary supervision.
• Who is a candidate?
– In general, individuals with uncontrolled seizures that have failed
at least two medications for seizure control can be considered
for this therapy.
– Research shows that it is more effective for certain seizures
types. These include infantile spasms, Doose Syndrome, Rett
Syndrome, and tuberous sclerosis complex.
20. Ketogenic Therapy
• The Basics:
– The ketogenic diet is a medical treatment for controlling seizures
by switching the body's primary energy source to fat-based
(ketones) verses sugar-based (glucose).
– We are not sure why this diet is successful.
– The diet can be adapted using table foods or given formula based.
– There are potential side effects associated with the diet, however,
all are treatable and reversible without having to stop the diet.
• They include, lack of weight gain, slightly decreased growth, somewhat high
cholesterol, constipation, kidney stones, and acidosis.
• There are a number of common misunderstandings about
this therapy.
• Additional Resources:
– On the Web - The Charlie Foundation -
www.charliefoundation.org
21. Vagus Nerve Stimulation
• The Basics
– The vagus nerve is one of the primary communication
pathways between the body and the brain.
– This is not drug therapy! VNS Therapy is delivered by a
surgically implanted generator and lead. It's best to think of
it as similar to a pacemaker.
• Side Effects:
– Cough*
– Hoarseness*
– Paraesthesia
– Shortness of Breath
– Vocal Cord Paralysis/weakness
– Infection
– Increased/Improved Mood
– Increased Alertness
– Improved Memory
23. During a Seizure
Caring for a child during a seizure is all about safety. The following is
needed of you:
•Keep calm.
•Time the seizure.
•Don't hold the child down or try to stop any movements.
•Clear the area of any hard or sharp objects and loosen ties or anything around the
neck that may make breathing difficult.
•Place something flat and soft under the head.
•Turn the child gently onto one side. This will help keep the airway clear.
•Do not try to force the mouth open with any hard objects or with fingers. A person
having a seizure CANNOT swallow their tongue. Efforts to hold the tongue down can
injure teeth or the jaw.
•Remain with child the entire time.
•The child may be disoriented and confused as they wake from the seizure, be
reassuring during this time.
•Assess for injury and respiratory status.
•If the child is sleepy following the seizure, allow them to rest.
•Nothing to eat or drink until able to swallow.
24. When to Call 911
• When seizures approach 5 minutes in duration or
per patient's seizure action plan (administering
rescue med for the first time).
• If the child has seizures back to back
• If it's the child's first seizure
• If injury is suspected
• If child is pregnant or diabetic
• If child does not return to baseline in an expected
amount of time post seizure activity
24
25. Potential Injuries from Seizures
• Immediate: lacerations, bruises, burns, head
trauma, fractures, and drowning/near
drowning.
• Delayed: fever, aspiration pneumonia,
subdural hematomas, and fractures.
25
26. Tips for Seizure Observation and
Documentation
• What happened before,
during, and after the
event
• Be detailed
• Include lots of
information from the
start to the end
26
27. Seizure Safety
• There are some restrictions that must be in place for a period of time
following a seizure in order to keep the child safe. These restrictions are
in place for 90 days, they include:
– No driving a motor vehicle or operating heavy machinery (this is mandated
by the State of Wisconsin Department of Transportation).
– No high climbing, this means nothing higher then 2 steps off the ground or
the child’s height.
– No swimming in lakes or rivers due to concerns with currents and the worry
that if a seizure occurred the child could be swept away or under.
– If swimming in a pool or soaking in a hot tub, must have an adult in the
water at all times within an arms reach.
– No tub baths. Children should only shower during this period.
• Any individual who is being treated for seizures should avoid sports
where a moment’s inattention could lead to injury these include such
activities as skydiving, bungee-jumping, scuba-diving, or motor racing.
• We strongly encourage Medical Alert use.
28. Home “Rescue” Medications
• We typically prescribe a specific medication to be used when a
child has a prolonged seizure or a cluster of seizure activity (a
series of seizures in a short amount of time) that can be used at
home. This medication is a rescue medication.
• These medications can be administered in a variety of ways.
We typically used two routes, buccal or rectal.
• The medication that is prescribed depends on the type of
seizure a child has and the age of the child.
We prescribed either rectal Diastat or buccal Midazolam.
29. Diastat
• Diastat is a rectal form of diazepam that is used to stop
a seizure.
• It is effective, well tolerated, and side effects such as
changes in breathing are not common.
• Dosing of this medication is dependent on a child’s age
and weight.
• The biggest advantage of giving a medication rectally
during a seizure is that it can be given and absorbed
quickly.
• Education on Diastat administration should be
preformed while inpatient. The drug company provides
a DVD as well as teaching sheets.
30. Midazolam
• Midazolam is a short acting benzodiazepine.
• It can be administered in two ways for rescue with a
single prolonged seizure or cluster, buccal or intranasal.
• The most common side effects are drowsiness,
tiredness, weakness, and nausea. There is a chance
that a child may experience breathing problems
following this medication. We advise families that the
first time they use this, they call 911 to ensure it is well
tolerated.
• To administer buccally, simply divide the prescribed
dose in half, giving on each side between the cheek and
gum.
31. Communication and Collaboration with Healthcare Providers
• Medication Administration Forms
• Any concerns about medication compliance or
safety risks.
• Any letters for special privileges (water bottles,
activity restrictions, etc.)
• Any general questions about medications
• Any general questions about plan of care
• We encourage you to fax us updates or
concerns. This is recommended as we know we
will likely recieve this correspondence.
Editor's Notes
Meghan starts here…
As we know, Epilepsy is the tendency to have recurrent unprovoked seizures. Antiepileptic drugs also termed AED's are those which decrease the frequency and/or severity of seizures in people with epilepsy. The older term, anticonvulsant drug, is still sometimes used as a synonym for AED, but is less accurate because many seizures do not involve convulsive movements. There is no convincing evidence that any AED “cures” or alters the natural history of epilepsy. However, many patients whose seizures have been completely controlled for two or more years can be successfully withdrawn from AEDs. The therapeutic goal is maximizing seizure control while minimizing adverse drug effects, thus improving the patient’s quality of life.
Making the choice as to what medication to use for seizure treatment is a difficult decision. We need to consider:
Seizure Type
Coexisting conditions and the current medications being used
The long term tolerability and safety risk
As we discussed briefly earlier, seizure occur as a result of abnormal electrical activity. It is the clinical manifestation of a hyper-excitable neuronal network, in which the electrical balance underlying normal neuronal activity is pathologically altered—excitation predominates over inhibition. Effective seizure treatments generally augment inhibitory processes or oppose excitatory processes. The key players involved are:
From the Excitation standpoint:
Inward movement of positively charged sodium and calcium
Neurotransmitter – glutamate
From the Inhibition standpoint:
Inward movement of negatively changed chloride and outward movement of positively charged potassium
Neurotransmitter – GABA
And we are working with pediatrics. Drug metabolism and disposition in children can differ significantly from that in adults. Beyond the neonatal period, when protein binding and drug metabolic rates are low, children usually have faster drug elimination rates and reduced serum half-lives relative to adults. Some children require almost twice the adult mg/kg dosage. Furthermore, because of shorter pediatric half-lives, many AEDs require at least 3 times daily administration in children 1-10 years of age.
Despite frequent drug administration, large swings in peak-to-peak concentrations are possible, especially in young children, because of their fast elimination rates. Solid oral dosage forms overcome this problem by providing a longer absorption phase that reduces peak and increases trough concentrations. Crushed tablets are preferable to liquids in younger children for similar reasons. Rapid gastrointestinal transit times in children may, however, impede absorption.
The first effective AED was potassium bromide, discovered in the mid-nineteenth century. Phenobarbital came into use in the early twentieth century, followed by phenytoin in the 1930s. Many of the early AEDs were modifications of these compounds.
The next slides review medications used for seizures. As we review this information, we will also discuss the common side effects of each agent. I have included, just for fun, the chemical make-up but as this isn’t a chemistry lecture, we won’t focus on this. I also included some pictures of the tablets but remember that things may look different out in practice depending on the manufacturing and Brand vs. Generic. It is important that whatever form is being used is consistent. I teach all of my families to questions the pharmacist if there medication ever looks different.
Phenytoin (Dilantin, Phenytek)
- Most Common Side Effects: agranulocytosis, pancytopenia, nausea, vomiting, ataxia, dizziness, headache, gingival hyperplasia
- Black Box Warnings: Cardiovascular risks but this is only seen with IV Infusion
Carbamazepine (Tegretol, Carbatrol)
- Most Common Side Effects: agranulocytosis, thrombocytopenia, pancytopenia, water intoxication, dizziness, drowsiness, unsteadiness, nausea, fatigue, photo sensitivity
Barbituate: Phenobarbital
- Side Effects: drowsiness, lethargy, hyperactivity, nausea, physical dependence
- Available as a liquid or tablet which is round and white.
- Used with infants
Benzodiazepines:
Clonazepam:
- Side Effects: drowsiness, dizziness, amnesia, irritability, hypotension
- Available as a tablet, is round and is available in a number of different colors based on the manufacturer
Clobazam (Onfi):
- Side Effects: sedation, lethargy, aggression, ataxia, vomiting
- Available as a tablet and suspension
Felbamate (Felbatol)
- Side Effects: headache, nausea, dizziness, ataxia, pancytopenia
- Black Box Warning: Aplastic Anemia
Gabapentin (Neurotin)
- Side Effects: dizziness, fatigue, nausea, emotional liability, headache, weight gain
Lamotrigine (Lamictal, Lamictal XR)
- Side Effects: headache, dizziness, nausea, ataxia, photo sensitivity
- Black Box Warning: Stevens-Johnson Syndrome and because of this it’s important that dosing instructions be followed during titration and tapering. There should also be no missed doses.
- The color of the XR tablets determine the dose size
Ethosuximide (Zarontin)
- Side Effects: nausea, abdominal pain, drowsiness,
Valproate (Depakote, Depakene, divalproex)
- Side Effects: aplastic anemia, PCOS, nausea, dizziness, tremor, increased appetite, weight gain, photosensitivity
- Black Box Warning: Hepatotoxicity
Topiramate (Topamax)
- Side Effects: metabolic acidosis, fatigue, weight loss, taste change, cognitive slowing
- Black Box Warning: Acute Glaucoma
Zonisamide (Zonegran) Considered the newer form of Topamax, has similar side effects but less severe.
- Side Effects: dizziness, anorexia, fatigue, mental slowing, weight loss, reduced ability to sweat so we need to watch for over-heating
- Comes as a capsule
Levetriacetam (Keppra, Keppra XR)
- Side Effects: fatigue, behavior changes specifically increased irritability, suicidality, aggressive behavior, and depression
Advantage of Keppra is no labs are needed for monitoring
Oxcarbazepine (Trileptal, Oxtellar XR)
- Side Effects: hyponatremia, thrombocytopenia, pancytopenia, agranulocytosis, dizziness, headache, nausea/vomiting, fatigue, photosensativity
- Also available as a liquid
Rufinamide (Banzel)
- Side Effects: suicidality, QT Shortening, fatigue, headache, dizziness, nausea, tremor, decreased appetite, attention disturbance, vertigo
Vigabatrin (Sabril) - used only with Infantile Spasms
- Side Effects: headache, dizziness, fatigue, irritability, weight gain, nausea, constipation,
- Black Box Warning: Vision loss
For Generalized seizures:
Levetiracetam (Keppra) – used most frequently because it does not require monitoring of levels or routine lab work to evaluate liver and kidney function, there are very few drug interactions; has a wide range of dosing; most common side effect is behavior change, kids can become more irritable so we give vitamin B6 to off-set this.
Ethosuximidate – specifically used for absence seizures
Lamotrigine (Lamictal) - concern is Steven Johnson’s Syndrome and need to titrate and taper slowly, missed doses is also a huge concern. I advise my families to contact the clinic if they miss more then 3 doses.
Topiramate (Topamax)
Zonisamide (Zonegran) – considered the new form of Topamax as it acts in a similar way but carries less risk of side effect
Valproic Acid (Depakote)
For partial seizures:
Oxcarbazepine (Trileptal)
Inflammation is known to cause several neurological disorders such as Parkinson’s disease, meningitis, and encephalitis. Inflammation associated with epilepsy has only recently been acknowledge and is the subject of discussion, abstracts and publications at professional epilepsy meetings worldwide.
IVIG - Intravenous immunoglobulin (IVIG) is a blood product administered intravenously. It contains the pooled, polyvalent, IgG antibodies extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months. It is used with acute infection as well as autoimmune processes to suppress harmful inflammation.
IVIg has demonstrated itself to be a promising treatment option.
Evaluation for epilepsy surgery is appropriate for anyone with seizures that are focal in origin, are continuing to occur despite treatment with AEDs, and cause a significant impairment in quality of life. Although the exact number of medication trials must be individualized, initial consideration is reasonable after two monotherapy trials with first line AEDs, and possibly one trial with dual therapy (combination of two AEDs). Many studies have shown the benefits of epilepsy surgery for seizure control, psychiatric symptoms, and overall quality of life. There is even evidence that successful epilepsy surgery may increase life expectancy.
Focality implies... an EEG that shows seizures originating from a specific area of the brain and an MRI that has a correlating abnormality.
The Basics:
The ketogenic diet is a medical treatment for controlling seizures by switching the body's primary energy source to fat-based (ketones) verses sugar-based (glucose).
We are not sure why this diet is successful in seizure management, but it has been shown to reduce seizures significantly. Studies have shown that about one-third of patients have a 90% improvement, few are 100% seizure-free.
The diet can be adapted using table foods or given formula based.
There are potential side effects associated with the diet, however, all are treatable and reversible without having to stop the diet. They include, lack of weight gain, slightly decreased growth, somewhat high cholesterol, constipation, kidney stones, and acidosis.
The diet is a significant commitment and requires the corporation of all caregivers.
Common misunderstandings about the diet:
"The diet will completely control the seizures." Some individuals do become seizure-free but more often we see a reduction in the number, duration, and severity of seizures.
"I will be able to stop all my medications." Likely, there will be a reduction in the number of needed medications or the dosing of the medication.
"If it doesn't work right away, we can just go back to medication." It may take as much as 3 months to fine-tune the diet, which is the initial commitment we ask.
Additional Resources:
On the Web - The Charlie Foundation - www.charliefoundation.org
The Basics
The vagus nerve is one of the primary communication pathways between the body and the brain.
This is not drug therapy! VNS Therapy is delivered by a surgically implanted generator and lead. It's best to think of it as similar to a pacemaker.
Stimulations are delivered at regular intervals all day, everyday to help prevent electrical irregularities that cause seizures.
Studies have shown added benefit over time, meaning that seizure control continues to improve months and years down the line.
Side Effects: (In general, side effects can be managed with program adjustments.)
Cough *
Hoarseness *
Paraesthesia
Shortness of Breath
Vocal Cord Paralysis/weakness
Infection
Increased/Improved Mood
Increased Alertness
Improved Memory
*Most common side effects and often used as a marker of therapy tolerability. These tend to be more severe initially and improve over time.
Kami starts from here…
Caring for a child during a seizure is meant to keep them safe. Remember, most seizures stop on their own within 3-5 minutes. The most important thing you can do is to remain calm during this situation and stay with the child. The following is needed:
Keep calm.
Time the seizure.
Don't hold the child down or try to stop any movements.
Clear the area of any hard or sharp objects and loosen ties or anything around the neck that may make breathing difficult.
Place something flat and soft under the head.
Turn the child gently onto one side. This will help keep the airway clear.
Do not try to force the mouth open with any hard objects or with fingers. A person having a seizure CANNOT swallow their tongue. Efforts to hold the tongue down can injure teeth or the jaw.
The child may be disoriented and confused as they wake from the seizure, be reassuring during this time.
If the child is sleepy following the seizure, allow them to rest.
**Before the seizure documentation includes: what person was doing prior to seizure, change in mood or behavior, any triggers or auras, time of day, and length (including post ictal phase)
**During the seizure documentation includes: change in LOC, can they talk or understand you, change in sensory input (all 5 senses-see, hear, taste, sounds, tactile feeling), facial expression, change in pupil sizes, eye blinking, eye position, drooling, changes in muscle tone, movements-jerking, shaking, no movement, or falling, what part of body involved, were they wandering around (confused?), changes in color of skin-flushed, sweating, red, pale, or breathing issues.
**After the seizure documentation: response to voice/touch, LOC-name, time, place, memory, weakness/numbness, fatigue very common (post ictal phase)
**Document how long the whole episode lasted including the post ictal phase. When do they return to baseline?
Diastat is a rectal form of diazepam that is used to stop a seizure. It comes in a pre-filled syringe that delivers a specific dose. This medication is approved by the FDA for administration by family members and non-medical caregivers which allows its use out in the community.
It is effective, well tolerated, and side effects such as changes in breathing are not common.
Dosing of this medication is dependent on a child’s age and weight. It is important that this prescription be updated on a regular basis as a child grows. Families should be encouraged to contact our office if they have dosing concerns. In general, dosing is checked at routine follow-up appointments and families are instructed to call if there has been a 5 lb weight change.
The biggest advantage of giving a medication rectally during a seizure is that it can be given and absorbed quickly, often faster then an oral medication with no risk of aspiration.
Education on Diastat administration should be preformed while inpatient. The drug company provides a DVD as well as teaching sheets.
Midazolam is a short acting benzodiazepine. It is a sedative or hypnotic drug mainly used for medical and surgical procedures.
It can be administered in two ways for rescue with a single prolonged seizure or cluster, buccal or intranasal. Intranasal midazolam involves the IV form of the medication, an atomizer device, and a syringe. Our office does not currently prescribe the intranasal form because the atomizer needed for administration is not covered by insurance. The most common side effects are drowsiness, tiredness, weakness, and nausea. There is a chance that a child may experience breathing problems following this medication. We advise families that the first time they use this, they call 911 to ensure it is well tolerated.
Midazolam is preferred in our older children for use at home and school or for children who are aware during their seizures.
Midazolam does not require refrigeration and has a relatively long shelf life.
To administer, simply divide the prescribed dose in half, giving on each side between the cheek and gum. It absorbs through the mucous membranes which eliminates any swallowing.
**First and foremost, we have to have an authorization to speak with you on file that has been signed by the parent allowing us to speak with you about their child.
**We encourage all RN's to try and address things directly with parents who know their children the best (who can then contact us).
**Form used to give schools the authority to administer medications: either scheduled or rescue medications. These include date, administration route, dose, how often to dose, and who to call if given.
**Concern for a child's safety as in non-med compliance or safety issues (seizure precautions not followed at home).
**Letters of permission or restriction in regards to gym activities, diet needs-water bottles for h/a patients, computer usage, etc
**Med info and plans of care in general
** Feel free to fax any correspondence you think is appropriate. It can be updates, concerns, etc regarding patients.
