Transcript Pediatric Epilepsy • Overview of seizures and epilepsy and medications

Pediatric Epilepsy
• Overview of seizures and epilepsy and
medications
• Management of specific issues
–
–
–
–
The first unprovoked seizure
The patient with known epilepsy
Febrile Seizures
Neonatal seizures
Does the patient have epilepsy?
Seizures vs. Epilepsy
• Epilepsy:
– Most recent ILAE definition: “a disorder of the brain
characterized by an enduring predispostion to generate epileptic
seizures and by the neurobiological cognitive psychological and
social consequences of this condition”
– occurrence of two or more unprovoked seizures
• Seizure:
– a transient occurrence of signs and symptoms due to
abnormal or excessive or synchronous neuronal activity
in the brain
Was it a seizure?
•
•
•
•
•
•
•
•
Syncope- vasovagal, cardiogenic
Sandifer syndrome
Breath holding spell
Migraine
Tics
Psychogenic
Sleep myoclonus
Paroxysmal dystonia
Classification of seizures
Generalized
Partial
• loss of consciousness
• whole brain at onset
• no loss of consciousness
• focal onset
Convulsive
Complex Partial
• tonic clonic
• tonic
• clonic
• change in level of consciousness
Nonconvulsive
•
•
•
•
absence
atypical absence
myoclonic
atonic
Simple Partial
• no change in consciousness
Partial Seizure evolving
to secondary
generalization
Epilepsy Syndromes
• Triad of seizure type or types, age and EEG
findings
• Different medications for different
syndromes!!
• Very different prognoses for different
syndromes
Epilepsy Syndromes
•
•
•
•
•
•
Benign Rolandic Epilepsy of Childhood
Absence Epilepsy
Juvenile Myoclonic Epilepsy
Benign Occipial Epilepsy
Lennox-Gastaut Syndrome
Infantile Spasms
Benign Rolandic Epilepsy of
Childhood
• Age: 5-16 years old
• Seizure type: nocturnal, partial (anarthria),
may generalize
• EEG: bilateral independent central
temporal spikes
• Prognosis: Excellent
• Meds: Tegretol, any medication for partial
seizures
Benign Rolandic Epilepsy
Absence epilepsy
• Age:
– Childhood absence epilepsy begins 5-10 years old
– Juvenile absence begins around puberty
• Seizure type: absence, may also have generalized
convulsions
• EEG: 3 HZ spike wave discharges
• Prognosis: excellent (particularly for childhood
onset)
• Medication:
– Ethosuccimide, valproic acid, lamotrigine
– Exacerbated by Tegretol
Absence epilepsy
Juvenile Myoclonic Epilepsy
• Age: begins 10-15 years old
• Seizure type: myoclonic jerks (usually in
morning), staring spells, convulsions
• EEG: 3-4 Hz generalized discharge with spike
and polyspike waves
• Prognosis: good (easily controlled usually,but
doesn’t usually grow out of it)
• Medications:
– Valproic acid, lamotrigine
– Exacerbated by tegretol and phenytoin
Juvenile Myoclonic Epilepsy
Lennox Gastaut Syndrome
• Age: 2-5 years
• Seizure types: generalized, atonic,
myoclonic, absence, partial
• EEG: “slow” spike and wave
• Prognosis: poor
• Medication: will usually need
polypharmacy; valproic acid, topamax,
lamotrigine
Anticonvulsants
First Generation Anticonvulsants
•
•
•
•
•
Phenobarbital
Phenytoin
Carbamazepine
Valproic acid
Ethosuximide
First Generation Anticonvulsants
• Phenobarbital
–
–
–
–
Broad spectrum, most seizure types
Excellent safety profile
Sedation, hyperactivity, decreased IQ
Used primarily for young infants
• Phenytoin
–
–
–
–
Partial, generalized seizures
Worsens absence and myoclonus
Gum hyperplasia, hirsutism, facial coarsening with long term use
Fospenytoin for status
• Carbamazepine
– Partial, generalized seizures
– Worsens absence and myoclonus
• Valproic acid
– Generalized (convulsive and nonconvulsive)
– Highest risk of hepatotoxicity
– Most teratogenic
• Ethosuximide
– Absence only
Phenobarbital
– Excellent for GTC, partial seizures
– Especially used in neonates
• Excellent safety profile
• Good absorption
• IV/IM/PO(liquid form)
– Long half life
• qD-bid dosing
– Side effects of sedation (acutely), hyperactivity and
decrease IQ (chronic use) limits its long term use
– Monitor drug level and LFTs
– Many drug interactions
• induces cyt p450
• OCPs, TCAs, VPA, tegretol, dilantin
– Usual dosing: 3-6mg/kg/d div qD-BID
Phenytoin (Dilantin)
• Useful for GTC and partial seizures
• Worsens absence and myoclonus
• Pharmacokinetics: Non linear pharamakonietics (small change
in dosage can lead to large change in level)
• Side effects: Short term: Ataxia, nystagmus vertigo, sedation,
dizziness. Long term: hirsutism, gum hyperplasia, facial
coarsening
• Idiosyncratic effects: Stevens-Johnson, bone marrow
depression, SLE, hepatitis
• Drug interaction: (induces cyt p450) erythro, dilantin, VPA,
INH, OCP, etc.
• Avg.Daily Maint: 4-7mg/kg/d div qD-BID
• Forms: tabs, chewable, sust release, susp., IV
• Therap. Lvl (mcg/ml):10-20
• Monitoring: follow drug level, CBC, LFTs
Carbamazepine (Tegretol)
•
•
•
•
•
•
•
•
•
•
Useful for GTC and partial seizures
Worsens absence and myoclonus
No IV form
Pharmacokinetics: Autoinduction of metabolism
Side effects:Ataxia,nystagmus,vertigo,dizziness,sedation, SIADH
Idiosyncratic effects:bone marrow depression,Stevens-Johnson,
hepatotoxicity
Drug interactions: (induces cyt p450) erythro, dilantin, VPA,
phenobarb, INH, OCPs, grapefruit juice
Avg.Daily Maint: 15-30mg/kg/d div. TID
Forms: tabs, chewable, liquid,Tegretol XR,Carbatrol
Monitoring: drug level,CBC, CMP, level
Valproic Acid
(Depakene/Depakote)
• Seizure Type:Absence, myoclonic, atonic, GTC
• Side effects: Thrombocytopenia, weight gain, tremor,
platelet dysfunction, sedation, polycystic kidneys, alopecia,
teratogenic
• Idiosyncratic effects:Hepatotoxicity, pancreatitis, aplastic
anemia, StevensJohnson
• Drug interactions:TCAs, lithium, OCPs, ASA, dilantin,
tegr, phenobarb
Avg.Daily Maint: 15-60 mg/kg/d div TID
• Forms: tabs, sprinkles, liquid, ER, IV
• Monitoring: CBC, LFTs, drug level
Ethosuximide
(Zarontin)
•
•
•
•
Seizure Type: Absence
Side effects: Nausea, GI distress, nightmares
Idiosyncratic effects: blood dyscrasias
Drug interact: (induce cyt p450) dilantin, tegr,
phenobarb, OCPs
• Avg.Daily Maint: 20-40mg/kg/d qD
• Forms: cap, liquid
• Monitoring:CBC, LFT, U/A, level
Limitation of First Generation
ACDS
•
•
•
•
•
Only work 70% of the time
Many drug interactions
Hepatic metabolism
Need monitoring with blood tests
Concerns over safety profile
The New Anticonvulsants
•
•
•
•
•
•
•
•
•
•
Felbamate (Felbatol)
Oxcarbazepine (Trileptal)
Gabepentin(Neurontin)
Levitaracetam(Keppra)
Lamotrigine(Lamictal)
Topiramate(Topamax)
Fosphenytoin
Zonisamide (Zonegran)
Tiagibine
Vigabatrim
The New Anticonvulsants
• Upside
–
–
–
–
–
Different mechanisms of action
Most BID or qD
Don’t need blood testing
Fewer side effects
Fewer drug interactions
• Downsides
– Long term side effects not known
– Lack of teratogenicity is not established
– Can’t monitor levels (and therefore can’t monitor
compliance)
– Expensive!
Oxcarbazepine(Trileptal)
• Similar profile to carbamazepine, but with fewer side effects, bid
dosing, no blood monitoring needed
• Converts to 10-hydroxy-carbazepine
• Side Effects: hyponatremia, headache, somnolence, dizziness
• Drug interactions: OCPs, pheytoin, lamotrigine, VPA
• Avg.Daily Maint: 20-40 mg/kg/d div BID (can switch over from
tegretol by increasing dose by 1.5x overnight)
• Forms: tabs, liquid
• Monitoring: not routinely needed; consider monitor sodium
Lamotrigine(Lamictal)
• Broad spectrum- useful for convulsive and
nonconvulsive seizures
• Side effects: dizzy, somnolence, tremor, weight gain
• Idiosyncratic effects: rash, Stevens-Johnson
• Drug interactions: VPA, dilantin, tegretol
• Avg.Daily Maint: 5-15 mg/kg/d div BID (1-5 mg/k/d if
on VPA)
• Forms: tabs, chewable dispersible
Levitaracetam(Keppra)
• Broad spectrum. Approved for JME, GTC
• Indic: adjunctive for GTC> 6yo, myoclonic seizures >12
yo with juvenile myoclonic epilepsy, partial onset >4 yo.
• Side effects: somnolence, agitation, behavior
change
• Drug interactions: none
• Avg.Daily Maint: 20-40mg/kg/d div BID
• Form: tabs (can be chewed), liquid, parenteral
Topiramate(Topamax)
• Indic: adjunct. for partial,GTC>2,Lennox-Gastaut >2;
monotherapy >10 partial, GTC
• Mech. Of Action: potentiate GABA effect; carbonic anhydrase
inhibitor
• Side effects/Idiosync. Effects: word finding difficulty,
psychmotor slowing, weight loss, kidney stones, myopia,
glaucoma, oligohydrosis
• Drug interactions: (induce cyt p450) dilantin, tegret, VPA,
acetazolamide
• Avg.Daily Maint: 5-9 mg/kg/d div BID
• Form: tabs, sprinkle caps
• Therap. Lvl (mcg/ml): not routinely sent
• Monitoring: no routine blood testing
Initiating Drug Treatment of
Epilepsy
• In general, long term anticonvulsants rarely started after a
first seizure
• Obtain baseline bloods (depending on which ACD used)
• Start low and build up to low end of maintenance over two
to four weeks (increase weekly)
• When at steady dose for approximately one week, check
trough level and blood parameters (depends on ACD)
• Continue to (slowly) push ACD until either seizure free or
drug toxicity
• For “first line” medications, I monitor CBC, CMP and
drug level every 3 months in first year and every 6 months
after that
First Unprovoked Seizure in
Childhood
1. Was it a seizure?
2. Look for etiology of seizure (acute
symptomatic seizures)
3. Treat any underlying causes of seizure
Was it a seizure?
•
•
•
•
•
•
•
•
Syncope- vasovagal, cardiogenic
Sandifer syndrome
Breath holding spell
Migraine
Tics
Psychogenic
Sleep myoclonus
Paroxysmal dystonia
Acute Symptomatic Seizures
• Fever
• Infectious
– Meningitis
– Abscess
– Encephalitis
• Neurovascular
– Ischemic stroke
– Hemorrhagic stroke (AVM, aneurysm, etc)
• Trauma
• Tumor
• Metabolic
– Hypoglycemia
– Hypocalcemia
– Hyponatremia
Managing a First Unprovoked Seizure in Childhood
History
•
•
Describe seizure very carefully
– Length of seizure- do not take parents estimate of time lapsed at face value!
– What was child doing when the seizure occurred?
– What did seizure look like at its onset? During the seizure?
– What happened after the seizure?
– What does the child remember?
Possible precipitants of seizure
– Head trauma? Possible ingestion? New medication or supplement?Fever?
Dehydration? Rash? Change in mental status? Recent travel?
•
Ask about other seizure types!
•
– Absence: does your child ever stop an stare and not respond
– Myoclonus
Review of systems
– Headaches, double vision, weakness, numbness, vomiting, etc
– General ROS
• PMH
• Developmental History
Managing a First Unprovoked Seizure in Childhood
Physical
• General exam
– Including: vital signs, signs of head trauma, signs of meningitis and sepsis,
rash, etc
• Directed general exam
–
–
–
–
–
Head circumference
Dysmorphic features
Neurocutaneous stigmata
Extremity abnormality
Organomegaly
• Neurologic Exam
–
–
–
–
–
–
–
Mental status, including assessment of developmental level
Cranial Nerves
M otor
Reflexes
Tone
Gait
Cerebellar
Managing a First Unprovoked Seizure in Childhood
Laboratory Evaluation
• “The decision to perform other studies, including LP,
laboratory tests, and neuroimaging, for the purpose of
determining the cause of the seizure and detecting
potentially treatable abnormalities, will depend on the age
of the patient and the specific clinical circumstances.
Children of different ages may require different
management strategies” Hertz D et al: Practice Parameter:
Evaluating a first nonfebrile seizure in children. Neurology
2000; 55:616.
Managing a First Unprovoked Seizure in Childhood
Laboratory Evaluation
• Blood: CBC, CMP
• Urine: Utox; urinalysis
• Neuroimaging
– CT
• If focal onset seizure, Todd’s paralysis, focal exam, possibility of
trauma
• If onset of seizure not witnessed
• If follow up not assured
– MRI
• May be done as outpatient if felt to be warranted
• EEG: outpatient
Recurrence Risk for Unprovoked Seizure
• Children with a first unprovoked seizure have a one-third
rate of recurrence
• Children with a second unprovoked seizure have a 75%
rate of recurrence; children with a third unprovoked
seizure have a 90% rate of recurrence
• Most recurrences occur within the first year; 90% occur
within 2 years.
• Risk factors for recurrence:
–
–
–
–
–
–
–
Family history of epilepsy
Abnormal EEG
Abnormal neuroimaging
First seizure in sleep
Todds paralysis
Remote symptomatic seizures
Developmental delay ornneurologic abnormality
General consensus is not to treat
patients after a first unprovoked
seizure.
•do not forget to find out whether or not this is
indeed the first seizure!!!
•Ask about prior seizures, history of staring
spells, history of myoclonic jerks
First unprovoked seizure
Discharge planning
• General consensus is not to treat patients with
anticonvulsants after a first unprovoked seizure (do not
forget to find out whether or not this is indeed the first
seizure!!!)
• Counseling
– Seizure precautions: anything in which loss of consiouness can be
extremely dangerous (eg., water, bicycling in street)
– Basic first aid: Don’t place anything in mouth, turn head to side if
vomiting, tilt chin up if trouble breathing
– Consider Diastat prescription (for the patient who presented with status
epilepticus or cluster of seizures)
• Follow up
– Schedule outpatient EEG
– Pediatric neurology follow up
Diastat
• Dosage: 0.5 mg/kg, round up
• DIASTAT AcuDial
– 10mg delivery system with a 4.4 cm tip
(delivers doses of 5, 7.5 and 10 mg)
– 20 mg delivery system with a 6.0 cm tip
(delivers doses of 10, 12.5 and 20 mg)
– Twin Pack of 2 pre-filled configurations (pharmacist
locks in proper dosage)
Management of the known epilepsy
patient with a breakthrough seizure
• Take the time to get accurate history
– Medication
• Dosage in mg/kg/d.
– That means I need a weight!
– Do not get dosage from the bottle; ask mother what she is giving
– Has the patient missed pills or started any new medication?,been sick,
hurt self, etc
– When was the dosage last changed?
– Epilepsy History:
• What epilepsy syndrome, if known?
• What is the baseline seizure frequency?
• What medications has the patient been on previously?
– Acute History
• Any fever, trauma, rash, possibility of ingestion
• Any new mediations, supplements
Management of the known epilepsy
patient with a breakthrough seizure
• Blood tests
– Check level if patient is on VPA, phenytoin, carbamazepine,
phenobarbital or ethosuximide
– Check cbc, cmp if patient on above medications
• Do not jump to CT scan!!
– Get CT scan if patient is not waking up to baseline (can give 4-6
hours for this)
– Consider CT there hs been a clear change in seizure type or
frequency
Adjust medications as neccessary
– What is the dosage; what is the dosage in mg/kg/d.
• That means I need a weight!
• Do not get dosage from the bottle; ask mother what she is
giving
• What is preparation?
– Can’t adjust medications unless know what they are taking
– Has the patient missed pills, started a new
medication,been sick, hurt self, etc
– What is the baseline seizure frequency?
– When was the dosage last changed?
– What medications has the patient been on previously?
Adjust medications as neccessary
• If level low
– Missed doses- give extra dose and leave maintenance
the same
– If no missed doses and daily dosage is within the
typical range for maintenance, then give bolus (usually
in the range of one extra dose) and raise daily dosage
by 10%
• If level high
– Is this peak or trough level?
– Is high level of ACD potentially a cause of seizure
– Eg, tegretol
11 year old boy with epilepsy who came in with two
GTCs, each 30 seconds long and spaced by 15
minutes. The patient is on carbamazepine and the
level is 4 (range 8-12)
•
•
•
•
•
•
Dosage: 200mg PO BID; 12 mg /k/d
Tegretol XR 200mg tabs
Dosage last increased 1 month ago
Has seizures around once a month
No missed doses
Has follow up appointment in 2 months
11 yo boy with epilepsy with
breakthrough seizure
• Plan
– Since had two seizures, observe for several
hours in the ED
– Increase carbamazepine
• Continue Tegretol XR : 200mg tab in AM and
300mg tab in PM (can only do 2 different tabs if
family has means to understand this)
– Mom needs to make follow up appointment
sooner
Examples of Histories Gone Bad
• 5 yo girl with epilpesy Dilantin, came in following a
seizure; level sent and given 5/kg dilantin in the meantime
. Level comes back 25.
– Dosage was 10/k/d- double what should be given. Had not been calculated
prior to dosing
• 6 month girl on phenobarbital comes in with seizure.
Bottle gives a dosage that is 5/k/d.
– I had written new prescription with higher dose 5 days previously which
mom filled However, she did not actually increase the dose.
• 7 yo girl on Tegretol arrives in status. Level was 14.
– Dosage was 30/k/d (high end of range). Dose had been increased (doubled
by outside MD) 2 weeks prior.
• I’m told the 3 year old girl is on 500mg lamictal 1 tab
twice a day.
– Ooops, patient is dead. And can’t get that size pill anyway.
Examples of Histories Gone Bad
• 8 yr old , first seizure 1 year ago, 6 mo ago had second
seizure and had medication adjusted. Now on
oxcarbazepine 2 tab in am and 3 tab in pm. Mom thinks
pills are 200mg
– Does this history make sense? Were meds really started after the
first seizure??
– Oxcarbazepine does not come in 200mg tabs.
• Patient comes in with third seizure, followed at
Montefiore. On Depakote and Keppra.
– Does this history make sense?
Benign febrile seizure
• Definition
–
–
–
–
–
–
6 months to 6 years
Fever
Neurologically normal before and after seizure
Generalized seizure
Lasts less than fifteen minutes
No other obvious cause of seizure
• AAP recommendations
– The evaluation should be directed towards the diagnosis of the cause of
the fever.
– Lumbar Puncture
• Over 18 months: not necessary as long as there is no clinical suspicion of
meningitis.
• 12 months and 18 months of age : consider
• Under 12 months of age: strongly consider, as signs of meningitis can be
subtle in this age group.
– EEG, blood studies and neuroimaging are generally not required.
• Long term anticonvulsants generally not used
• Diastat for home use indicated if there is a history of prolonged febrile
seizure or cluster of seizures (ie, not benign febrile seizures)
Home treatments
• Diastat
– Dosage: 0.5 mg/kg, round up
– DIASTAT AcuDial
• 10mg delivery system with a 4.4 cm tip
(delivers doses of 5, 7.5 and 10 mg)
• 20 mg delivery system with a 6.0 cm tip
(delivers doses of 10, 12.5 and 20 mg)
• Twin Pack of 2 pre-filled configurations (pharmacist locks in
proper dosage)
• Intranasal midazolam
Neonatal Seizures
Neonatal Seizures
Etiology
• Hypoxic ischemic encephalopathy
• CNS infection
• Metabolic Distubances
–
–
–
–
•
•
•
•
•
•
Hypoglycemia
Hypocalcemia
Hypomagnesemia
Pyridoxine dependency
Intracranial Hemorrhage
Cerebral Infarction
Chromosomal abnormalities
Congenital Brain abnormalities
Drug withdrawal or intoxication
Inborn errors of metabolism
Neonatal Seizures
Etiology
Time of Onset
Hypoxic ischemic encephalopathy
12-24 hour
Drug withdrawal
24-72 hour
Hypocalcemia (nutritional)
3-7 days
Aminoaciduria/organic aciduria
3-7 days
Diagnostic Assessment of Neonatal Seizures
•
Metabolic testing (screening)
–
–
–
–
–
–
•
LP
–
–
–
–
–
–
•
Blood glucose
Calcium
Ammonia
Lactate
pH
electrolytes
Cells
Protein/glucose
Cultures
Herpes PCR
Lactate/pyruvate
Aminoacids
Neuroimaging
– Head ultrasound
– Head CT
– Brain MRI
• EEG
Neonatal Status Epilepticus
Treatment
• Etiology specific treatment if possible
– Hypoglycemia
• Correct with 10% glucose solution IV 2cc/kg
• Maintenance glucose infusion to max of 8 mg/kg/min
– Hypocalcemia
• Treat with 10% calcium gluconate (100 mg/kg or 1ml/kg IV
over 5-10 minutes while monitoring heart rate and infusion
site; or calcium chloride (20mg/kg or 0.2 ml/kg)
– Hypomagnesemia
• Often associated with hypocalcemia
• Treat with 50% solution of magnesium sulfate IM, 0.25 ml/kg
– Pyridoxine dependency
• Used empirically in infants with refractory seizures
• While EEG monitoring, give 100 mg/kg IV
Neonatal Status Epilepticus
Treatment
• Phenobarbital
– Usually used first
– Prolonged half life—100 hours after day 5-7; therefore watch for toxicity
– 20 mg/kg IV (up to 40 mg); repeat 10/kg every 15-30 minutes times two
• Phenytoin/Fosphenytoin
– 20 mg/kg (over 30-45 minutes)
– Half-life 100 hours
– Nonlinear kinetics; redistribution, variable rate hepatic metabolism require
individualization of maintenance dosing
• Benzodiazepine
– Diazepam
• 0.25mg/kg IV bolus or 0.5 mg/kg PR
– Lorazepam
• 0.05 mg/kg IV over2-5 minutes
• Midazolam infusion