1. 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

2. Does the patient have epilepsy? Seizures vs. 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

3. Was it a seizure? Syncope- vasovagal, cardiogenic Sandifer syndrome
Breath holding spell
Migraine
Tics
Psychogenic
Sleep myoclonus
Paroxysmal dystonia

4. Classification of seizures
Generalized
loss of consciousness
whole brain at onset
Partial
no loss of consciousness
focal onset
Convulsive
tonic clonic
tonic
clonic
Nonconvulsive
absence
atypical absence
myoclonic
atonic
Complex Partial
change in level of consciousness
Simple Partial
no change in consciousness
Partial Seizure evolving to secondary generalization

5. Epilepsy Syndromes
Triad of seizure type or types, age and EEG findings
Different medications for different syndromes!!
Very different prognoses for different syndromes
An epileptic syndrome is characterized by a constellation of specific signs, symptoms, seizure types, prognoses, and EEG findings. Determination of the epileptic syndrome provides information on prognosis and informs management decisions.

6. Epilepsy Syndromes Benign Rolandic Epilepsy of Childhood
Absence Epilepsy
Juvenile Myoclonic Epilepsy
Benign Occipial Epilepsy
Lennox-Gastaut Syndrome
Infantile Spasms

7. 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

8. Benign Rolandic Epilepsy

9. 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

10. Absence epilepsy

11. Juvenile Myoclonic Epilepsy
Age: begins 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

12. Juvenile Myoclonic Epilepsy

13. 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

14. Anticonvulsants

15. First Generation Anticonvulsants
Phenobarbital
Phenytoin
Carbamazepine
Valproic acid
Ethosuximide

16. 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
Valproic acid
Generalized (convulsive and nonconvulsive)
Highest risk of hepatotoxicity
Most teratogenic
Ethosuximide
Absence only

17. 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

18. 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

19. 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

20. 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: mg/kg/d div TID
Forms: tabs, sprinkles, liquid, ER, IV
Monitoring: CBC, LFTs, drug level

21. 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

22. 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

23. The New Anticonvulsants
Felbamate (Felbatol)
Oxcarbazepine (Trileptal)
Gabepentin(Neurontin)
Levitaracetam(Keppra)
Lamotrigine(Lamictal)
Topiramate(Topamax)
Fosphenytoin
Zonisamide (Zonegran)
Tiagibine
Vigabatrim
These drugs are being used increasingly in the pediatric population both as second line add on therapy and, increasingly, first line. Vigabatrin is used widely in Europe, but it is not currently approved for use in the United States. Lamotrigine has a similar anticonvulsant spectrum as valproic acid and is being used increasingly as first line therapy

24. 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!

25. 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: 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

26. 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

27. 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

28. 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
adjunctive therapy for adults and pediatric patients ages 2-16 years with partial onset seizures or primary generalized tonic-clonic seizures and in patients 2 years of age and older with seizures associated with Lennox-Gastaut Syndrome.

29. 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

30. First Unprovoked Seizure in Childhood
Was it a seizure?
Look for etiology of seizure (acute symptomatic seizures)
Treat any underlying causes of seizure

31. Was it a seizure? Syncope- vasovagal, cardiogenic Sandifer syndrome
Breath holding spell
Migraine
Tics
Psychogenic
Sleep myoclonus
Paroxysmal dystonia

32. Acute Symptomatic Seizures
Fever
Infectious
Meningitis
Abscess
Encephalitis
Neurovascular
Ischemic stroke
Hemorrhagic stroke (AVM, aneurysm, etc)
Trauma
Tumor
Metabolic
Hypoglycemia
Hypocalcemia
Hyponatremia

33. 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

34. 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

35. 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.

36. 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

37. 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
; 75% of these will have a third seizure and 75% of these will have a fourth.[1
The major risk are todds, abn eeg, abn neuroimaging,fam hx of epile, first sz in sleep.[2] These risk factors can guide the decision as to whether to place a child on long-term anticonvulsants. Overall, the

38. 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

39. 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

40. 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)

41. 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

42. 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

43. 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?

44. 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

45. Dosage: 200mg PO BID; 12 mg /k/d Tegretol XR 200mg tabs
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

46. 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

47. 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.

48. 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?

49. 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)

50. Home treatments Diastat Intranasal midazolam
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

51. Neonatal Seizures

52. 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

53. 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

54. Diagnostic Assessment of Neonatal Seizures
Metabolic testing (screening)
Blood glucose
Calcium
Ammonia
Lactate pH
electrolytes LP
Cells
Protein/glucose
Cultures
Herpes PCR
Lactate/pyruvate
Aminoacids
Neuroimaging
Head ultrasound
Head CT
Brain MRI
EEG

55. 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

56. 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 minutes times two
Phenytoin/Fosphenytoin
20 mg/kg (over 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