Febrile and Absence Seizures

The risk of children having a recurrent simple seizure who is under 1

50% probability for recurrent seizures

Which medication would you recommended for a simple febrile seizure

Acetaminophen or Ibuprofen

Which two drugs can be used in outpatient and inpatient settings but is usually reserved for patients without IV access

Buccal Midazolam, Intranasal Midazolam

What are anticonvulsants that can worsen an absence seizure?

Carbamazepine Oxcarbazepine Tiagabine Vigabatrin

What are the risk factors for future epilepsy?

Complex febrile seizures Family history of epilepsy Neurodevelopmental Impairment

IS ABSENCE SEIZURE MORE COMMON in males or females

Females

Etiology of Absence Seizures

Genetic •Lower seizure threshold •Alterations in ion channels, particularly T-type Ca current channels •Risk Factors-Hyperventilation •Prognosis •80% of children respond to medication •Remission is variable •Generalized tonic-clonic seizures may develop •Normal cognitive development •Educational and behavioral problems stem from unrecognized seizures

Which drug is first choice for hospitalized patients for complex or status febrile seizure ?

Lorazepam IV

What are anticonvulsants that are not effective in absence seizure?

Phenobarbital Phenytoin Gabapentin

Rectal Diazepam

Terminates ~ 80% to 90% of complex/status febrile seizures in < 10 minutes Indications: •High risk of complex/status febrile seizures •Prolonged or repetitive complex febrile seizures •Geographical residence is far away from a hospital setting • •Drug of choice in outpatient setting •Available as gel formulation •Instruct caregiver not to administer unless seizure lasts > 5 minutes

Risk Factors for Recurrent Febrile Seizures

Vaccinations do not increase the risk of febrile seizure •Family history of febrile seizure •Age of onset < 18 months •Viral infections •Herpesvirus-6 •Otitis •Influenza •Day care attendance •Low grade of fever associated with seizure •Shorter duration of fever before seizure (< 1 hour)

Simple Febrile Seizure

a single, brief, generalized seizure

The risk of children having a recurrent seizure older than 1

•30% probability for recurrent seizures

Status Febrile Seuizures

•A febrile convulsion lasting > 30 minutes •Rare •Occurrence in normal healthy child does not increase risk for subsequent febrile or afebrile seizures •Neurologically impaired children are at risk for subsequent febrile or afebrile seizures

Seizure

•A sudden electrical discharge in the brain that causes alterations in behavior, sensation, or consciousness •Transient disturbance of electrical activity

Typical Absence Seizure

•Abrupt and brief impairment of consciousness •Brief vacant staring spells •Duration < 30 seconds •May be accompanied by blinking or fluttering eyelids, lip smacking, or limb jerking •No post-ictal phase; children typically "snap out of it" and resume activities they were doing prior to the seizure •No recollection of the episodes

Treatment of Febrile Seizures

•Antipyretics •Acetaminophen 10 - 15 mg/kg PO q 4 - 6 hours PRN fever •Ibuprofen 10 mg/kg PO q 6 hours PRN fever •Anticonvulsants:Simple febrile seizure: anticonvulsant therapy is not recommended •Complex or status febrile seizure: •Benzodiazepines may be used as abortive therapy •Rectal Diazepam •Buccal Midazolam •Intranasal Midazolam •IV Lorazepam/Diazepam

Febrile Seizures: Prevention

•Antipyretics and anticonvulsants have been used to prevent recurrence of febrile seizures •Antipyretics have been shown to NOT be effective in the prevention of febrile seizures •Valproic acid and phenobarbital have been shown to prevent recurrence of febrile seizure •High risk of serious adverse reactions •Low risk of complications associated with febrile seizures • •Preventative anticonvulsant therapy is NOT recommended

Seizures in childhood

•Approximately 150,000 children in the United States are seen annually for a first unprovoked seizure. • •Most common risk factors: first-degree relatives, age •Common causes: •Infection (e.g., meningitis, encephalitis) •Intraventricular hemorrhage •Hypoxic-ischemic encephalopathy •Metabolic (e.g., hypoglycemia) •Inborn errors of metabolism (e.g., pyridoxine deficiency) •Maternal drug dependency (e.g., alcohol, cocaine)

Complex or status febrile seizure treamtment

•Benzodiazepines may be used as abortive therapy •Rectal Diazepam •Buccal Midazolam •Intranasal Midazolam •IV Lorazepam/Diazepam

Epilepsy

•Characterized by recurrent seizures •At least 2 seizures that occur without acute provoking factors

IV lorazepam/IV Diazepam

•Drug of choice in hospitalized patients •Lorazepam preferred •Management of prolonged febrile seizure is the same as treatment of status epilepticus •Benzodiazepine (lorazepam preferred) •Phenytoin/Fosphenytoin •Valproic acid •Levetiracetam •Phenobarbital

Valproic acid(Depakene®, depakote®) in absence seizure

•FDA approved for absence seizures •Broad spectrum AED •Available in multiple formulations •Tablets, extended release tablets, liquid, sprinkles •Multiple drug interactions •ADRs: •Common: nausea, vomiting, weight gain, alopecia, sedation, emotional lability •Warnings: pancreatitis, hyperammonemia, blood disorders, congenital malformations, hepatic impairment* •Therapeutic drug level: 50-100mcg/ml

Ethosuximide (Zarontin®)

•FDA approved in children > 3 years old •Only indicated for absence seizures •Available in liquid formulation •Multiple drug interactions ADRs: •Common: nausea, vomiting, drowsiness, sleep disturbances, hyperactivity •Warnings: abnormal renal/hepatic function, SLE, Stevens-Johnson syndrome, aplastic anemia •Therapeutic drug level: 40-100mcg/ml FIRST DRUG OF CHOICE

Types Seizures in childhood

•Febrile seizures •Absence seizures •Benign neonatal seizures •Non-epileptic spasms •Juvenile myoclonic epilepsy •Lennox-Gastaut syndrome •West syndrome •Dravet's syndrome

Clinical Presentation of Febrile Seizure

•Fever •Possible loss of consciousness •Body jerking •Eye rolling •Post-ictal phase •Confusion, agitation, drowsiness •Brief •Children typically return to normal baseline quickly after a simple febrile seizure

Absence Seizures

•Incidence: 1.9-8 cases per 100,000 US population •Females > males •Onset: 4-8 years of age, peak incidence 6-7 years •Females > males

Lamotrigine(Lamictal®) absence seizure

•Less efficacy for absence seizures •Available in multiple formulations •Tablets, extended release tablets, ODT, chewable tablet •Multiple drug interactions •ADRs: •Common: sedation, nausea, rash •Warnings: serious rash, risk increases with rapid dose escalation •No therapeutic drug levels •It is added on to other therapy because it is less effective

Pathophysiology

•Mechanisms that promote seizure activity •Alteration in ion channel function •Increased excitatory neurotransmission •Decreased inhibitory neurotransmission •Alteration of intra- or extra-cellular ion concentrations • •Key differences in children (all seizure types) Excitatory receptors >> inhibitory receptors

Complex Febrile Seizures

•Much less common, but more serious •: a focal seizure, a prolonged seizure that lasts > 10-15 minutes or seizures that occur more than once during a febrile illness •Risk of future epilepsy 5-50%, with more risk factors equating to higher risk •Risk factors for future epilepsy •Complex febrile seizure •Family history of epilepsy •Neurodevelopmental impairment •There is no evidence that preventing febrile seizures prevents the development of epilepsy

Status Epilepticus

•Recurrent seizures without a period of consciousness between seizures • •Any seizure > 30 minutes • •Considered a "neurological emergency" • •Can occur in people with seizures and epilepsy •

Pathophysiology of Febrile Seizure

•Seizure is provoked by an increase in temperature which changes a variety of cellular processes in the body •Strongly age-specific •Strong genetic component; several genes have been implicated •Higher fevers are associated with increased risk of seizure •"rate of rise" is higher risk factor than degree of fever

Buccal Midazolam/Intranasal midazolam

•Terminates complex/status seizures within 10 min •Outpatient and inpatient use •Usually reserved for patients without IV access Buccal-Administer between lower jaw and cheek Intranasal-Divide dose and deliver half in each nare •Maximum 1 ml per nare

Anticonvulsants

•Treatment •Ethosuximide •Valproic acid •Lamotrigine Anticonvulsants that are NOT effective •Phenobarbital •Phenytoin •Gabapentin Anticonvulsants that may WORSEN absence seizures •Carbamazepine •Oxcarbazepine •Tiagabine •Vigabatrin

Which drugs can be used to prevent reccurence of febrile seizure

•Valproic acid and phenobarbital have been shown to prevent recurrence of febrile seizure •High risk of serious adverse reactions •Low risk of complications associated with febrile seizures

What is the rate of rise?

•higher risk factor than degree of fever-- the faster the fever rises the higher the chance of a seizure

Which class of drugs are not recommended in Febrile Seizure

Anticonvulsants