Pediatric Seizures

Obtain the greatest possible seizure control with minimal side effects
Prevent the occurrence of emotional and behavioral aberrations

❖ Establish diagnosis and exclude remedial causes
❖ Select primary drug most appropriate for seizure type and your patient

❖ Choosing an antiepileptic drug
❖ Seizure type & severity
❖ Medication history
❖ Ageender
❖ Drug interactions
❖ Concurrent diseases

Desired serum concentration

Free

Compliant

❖Phenobarbital
❖Phenytoin (Dilantin®)
❖Ethosuximide (Zarontin®)
❖Diazepam (Valium®)
❖Carbamazepine (Tegretol®)
❖Valproic acid (Depakene®, Depakote®, Depacon®)

❖ Felbamate (Felbatol®)
❖ Gabapentin (Neurontin®)
❖ Lamotrigine (Lamictal®)
❖ Topiramate (Topamax®)
❖ Tiagabine (Gabitril®)
❖ Levetiracetam (Keppra®)
❖ Oxcarbazepine (Trileptal®)
❖ Zonisamide (Zonegran®)
❖ Vigabatrin (Sabril®)
❖ Rufinamide (Banzel®)
❖ Clobazam (Onfi®)

❖Comparison between first and second generation agents
❖ Efficacy
❖ Safety
❖ First generation agents associated with high incidence and intolerable neurotoxicity
❖ Second generation agents - fewer side effects
❖ Second generation agents have less drug interaction potential
❖ Second generation agents less likely to require therapeutic drug monitoring

❖ Initiate with monotherapy
❖ Recurrence of absence, myoclonic, and infantile spasms is certain $\rightarrow$ initiate anticonvulsant

❖ Single episode of afebrile tonic-clonic seizure with normal EEG $\rightarrow$ advised not to initiate anticonvulsant
❖ Have not shown to improve long-term prognosis
❖ > 2 afebrile seizures within 6-12 months $\rightarrow$ initiate anticonvulsant

❖ At the initiation of drug therapy
❖ During accelerated growth
❖ $\uparrow$ seizure or toxicity
❖ Other considerations

● Definition: an epileptic disorder of infancy and early childhood
● Incidence: 2 to 3 cases per 10,000 live births

● Risk factors:
● Genetic predisposition
● Brain injury

● Typical onset: 4-8 months old but can happen after infancy (epileptic spasms)

● Pathophysiology of infantile spasms unknown
● Abnormalities in the hypothalamic-pituitary-adrenal axis are likely involved

● West Triad:
○ Arrest of psychomotor development
○ Hypsarrhythmia
○ Spasms

● Infantile spasms involve a bilateral forward flexion of the arms and trunk

● Spasms typically occur in clusters of 2 to 100 within a minute

● Clusters generally occur upon waking up or before falling asleep

● Poor prognosis
● 50% of patients will experience seizures later in life
● 90% develop psychomotor retardation

EEG findings: hypsarrhythmia

First line for infantile spasms
MOA: Promotes the release of adrenal steroids, decreasing production of corticotropin-releasing hormone (CRH)

After 2 weeks of treatment, dosing is gradually tapered and discontinued over a 2-week period

AE: Increase in BP, risk of infection, fever, changes in mood/behavior, allergic reactions
Long term use: cardiac and cerebral hypertrophy
Effect on adrenal glands: decreased/increased cortisol

Place in Therapy:
•2nd-line for infantile spasms
Exception: patients with infantile spasms AND tuberous sclerosis complex (then used first line)

MOA: Irreversibly inhibits GABA transaminase (GABA-T), increasing GABA levels within the brain

AE: Skin rash, constipation, vomiting, diarrhea, drowsiness, irritability
BBW: Vision loss - REMS program
Administration: powder packets in 10 mL of water

The evidence is insufficient to recommend the use of prednisolone, dexamethasone, and methylprednisolone as being as effective as ACTH for short-term treatment of infantile spasms

❖ 5 minutes or more of
 Continuous clinical and/or electrographic seizure activity
OR
 Recurrent seizure activity without recovery (returning to baseline) between seizures
❖ Classifications
 Generalized convulsive SE (GCSE)
 Non-convulsive SE (NCSE)
 Refractory SE (RSE)

❖ Most common
 Prolonged febrile seizures
❖ Frequent
 CNS infections, especially bacterial meningitis
 Inborn errors of metabolism
 Rare genetic disorders affecting energy production
 Ex: galactosemia, phenylketouria
 Ingestion

❖ Timeline: 0-5 minutes
❖ Interventions
1. Stabilize patient
2. Time seizure from its onset, monitor vital signs
3. Assess and address oxygenation
4. Initiation EEG monitoring
5. Collect finger stick blood glucose and address as needed
6. Attempt IV access and collect applicable labs

❖ Timeline: 5-20 minutes
❖ Benzodiazepines are the initial therapy of choice
 Choose one of the following 3 equivalent first line options with dosing and frequency:
 IM midazolam (Level A)
 IV lorazepam (Level A)
 IV diazepam (Level A)
❖ If none of the three options above are available, choose one of the following:
 IV phenobarbital (Level A)
 Rectal diazepam (Level B)
 Intranasal or buccal midazolam (Level B)

❖ Timeline: 20-40 minutes
❖ No evidence based preferred second therapy of choice:
 Choose one of the following second line options and give as a single dose
 IV fosphenytoin (Level U)
 IV valproic acid (Level B)
 IV levetiracetam (Level U)
 If none of the options above are available, IV phenobarbital is an alternative (Level B)

❖ Timeline: 40-60 minutes
❖ No clear evidence to guide therapy in this phase (Level U)

❖ Choices include:
 Repeat second line therapy OR
 Anesthetic doses of either midazolam, pentobarbital, or propofol

Absorbed by the rectum’s blood vessels through the
gastrointestinal tract to the circulatory system

Rapidly absorbed to CNS due to richly vascular tissue of rectum

Some AEDs cannot be absorbed rectally due to poor
absorption/solubility (e.g. lorazepam)

Preferred agent: Diazepam (Diastat ®)
Onset: 2-10 minutes, Tmax: 5-20 minutes
Bioavailability: highly variable (50-100%)
Rectal instillation

Delivers AED directly to the blood and cerebrospinal fluid via the nasal mucosa
 Attributed to vascular tissue of nares
 Rapid onset of action

Under ideal conditions, most medication absorbed and reaches cerebral cortex within 2-5 minutes

Indication: > 6 years of age; Acute treatment of intermittent, stereotypic episodes offrequent seizure activity that are different from patient’s usual seizure pattern in patients with epilepsy

Contraindications
Hypersensitivity to diazepam
Acute narrow angle glaucoma

Indication: > 12 years of age; acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are different from patient’s usual seizure pattern in patients with epilepsy

Contraindications
Hypersensitivity to midazolam
Acute narrow angle glaucoma

❖ Febrile seizures are the most common neurologic disorder of children
 Age-dependent phenomenon
 Common between 14–18 months of age
 May appear within 6 months and 5 years of age
 Affects ≈ 2 - 4 percent of children < 5 years of age
❖ Up to 5% of children will have a febrile seizure in their life
 1 of 3 children with a febrile seizures will have at least one more during childhood

Appears on 1st day of illness; initial sign of illness w/ increased temperature.

Sudden tightening and contracting of muscles on both sides of the body: rhythmic jerking of body

Loss of control of bodily fluids
Vomiting
Bite their tongue
Cyanosis

High fever, viral infection, and a family history of febrile seizures

❖ Age at onset < 18 months
❖ History of febrile seizure in 1st degree relative
❖ Relatively low grade fevers associated with seizure
▪ <102.2 °F or 39°C
❖ Shorter duration of fever before seizure
▪ <1 hour
❖ Multiple seizures during the same febrile illness
❖ Day nursery attendance

Recurrent brief febrile seizures do not warrant treatment: increased risk factors $\rightarrow$ increased recurrence
No $\uparrow$ risk of brain injury
No benefit in preventing febrile seizures with intermittent medications

Prolonged or repetitive seizures despite BZDs: may be treated with additional AEDs; status epilepticus treatment