Pediatric Epilepsy Flashcards
What is status epilepticus?
Medical emergency
Any recurrent or continuous seizure activity lasting over 30 minutes in which the patient does not regain baseline mental status
When is a seizure treated for status epilepticus?
Any seizure that does not stop within 5 minutes should be treated as impending status epilepticus
What is given to patients to reduce risk of seizure progression to status epilepticus?
Midazolam intranasal or buccal
Injectable midazolam is given to kids via a nasal atomizer
Why is midazolam preferred over diazepam for treatment of impending status epilepticus?
Midazolam has a shorter onset and offset of action
Midazolam also offers a reasonable recovery from sedative effects
How to use a nasal atomizer properly?
Can be reused if cost is an issue for families
Give quick push on syringe plunger
What are epilepsy syndromes?
Refers to clusters of features that may occur together, including:
- Seizure type
- EEG findings
- Imaging findings
- Age-dependent features (ex. age at onset or remission)
- Specific comorbidities (ex. psychiatric illnesses)
- Triggers and sometimes prognosis
What are some examples of epilepsy syndromes?
Childhood absence epilepsy
Juvenile absence epilepsy
Lennox-Gastaut Syndrome
Dravet syndrome
What is the role of ethosuximide in treatment of seizures in children?
Narrow spectrum ASM
1st line for absence seizures (generally pediatric condition)
Not for any other seizure type (do not use as monotherapy if mixed seizure, even if absence seizures are a component)
What are the characteristics of absence seizures?
2-10 second episodes of blanking
If blanking lasts longer, then lower likelihood that the patient has absence seizures
What are some advantages of using ethosuximide in children for seizures?
- Lower rates of attention difficulties compared to valproate
- Works quickly
- Generally well-tolerated
- Few drug interactions
What are some disadvantages of using ethosuximide in children for seizures?
Narrow-spectrum of activity (only a good choice to use for uncomplicated absence seizures)
Does not confer protection for generalized tonic-clonic seizures
What are some adverse effects associated with ethosuximide?
CNS effects (drowsiness, dizziness, behavioural changes)
GI effects (dose related, can divide dose to minimize)
Rare (blood dyscrasias, skin rashes)
Monitoring (CBC & platelets)
What is infantile epileptic spasms syndrome?
Epileptic spasms most often occur in “clusters” on awakening and involve tonic limb (+/-) head flexion or extension
Each spasm lasts less than 3 seconds, repeasts every 5-10 seconds for a period of 5 to 15 minutes
What does the EEG for a patient with infatile epileptic spasms syndrome look like?
May have a distinctive, disordered EEG pattern called hypsarrhythmia
May have psychomotor arrest
What is the treatment strategy for infantile epileptic spasms syndrome?
Treat early and aggressively to prevent long-term sequelae (intellectual delays, refractory seizures)
Treatment options:
- Hormonal therapy (oral prednisolone)
- Vigabatrin
- other ASMs are ineffective
What is MOA of vigabatrin?
Structural analog of GABA, but does not act on GABA receptors
MOA: irreversible inhibition of GABA-transaminase leads to increased GABA in the CNS = increased neuroinhibition
How long should vigabatrin be trialed if no clinical response?
If no clinical response in 7-14 days, change therapy
In most cases, switch to steroid
What are some ADRs associated with vigabatrin?
- Visual abnormalities, including permanent vision loss (black box warnings)
- Vomiting and upper respiratory tract infections (more common in infants)
- Asymptomatic MRI changes (resolves on d/c)
What is Lennox-Gastaut Syndromes?
Developmental and epileptic encephalopathy with:
- Multiple drug-resistant seizure types (tonic, atonic, atypical absence, generalized tonic-clonic)
- Intellectual disability
The children with LGS may be medically complex with comorbid neurodevelopmental and behavioural disorders, sleep disorders, mobility requirements, feeding tubes
Review slide 21 for treatment of Lennox-Gastaut Syndrome
According to NICE 2022 guidelines:
VPA: 1st line
Lamotrigine: 2nd line (monotherapy or adjunct)
What is the official indication for rufinamide?
Only officially indicated for adjunct therapy in LGS for patients over four
What are some ADRs associated with rufinamide?
- Shortened QT interval (46-65%)
- Headaches, drowsiness, dizziness
What is Dravet Syndrome?
Drug-resistant developmental and epileptic encephalopathy
- Seizures of various types, often starting with early-onset febrile seizures in infancy
- Progressive cerebral and cerebellar atrophy
- Developmental delays and intellectual disability
What is the prognosis of Dravet Syndrome?
Poor prognosis:
- Average life expectancy is about 9 years
- Historically (93% of deaths occur by age 20, associated with SUDEP)
- Earlier diagnosis and newer treatments are leading to 80% survival beyond 20 years
Review slide 26 for a list of sodium channel blocking ASMs
How is Dravet Syndrome treated?
Fenfluramine
Although CI in children, valproate + levocarnitine can be used if valproate therapy is absolutely necessary
Stiripentol
What is the MOA of fenfluramine?
Not fully understood but may promote serotonin release, acts as a serotonin agonist, and inhibit serotonin transporters and reuptake
What is the clinical efficacy of efficacy of fenfluramine?
Efficacy has been shown to be maintained out to 3 years and decreases risk of SUDEP and all cause mortality in Dravet Syndrome
What are some concerns with using fenfluramine in children with Dravet Syndrome?
Pulmonary Arterial Hypertension and valvulopathy has not been described at anti-seizure doses
SIgnificant interaction with stiripentol (another drug used to treat Dravet Syndrome)
What is the official indication for stiripentol in children?
Combined treatment with clobazam+valproate for refractory generalized tonic-clonic seizures in patients with Dravet Syndrome
What are some ADRs associated with stiripentol?
Drowsiness (67%)
Agitation (27%)
Decreased appetite (45%)
Serious ADRs: Delirium, hallucinations
What is the role of cannabinoids in treatment of seizures in children?
Not first line for any seizure disorder
FDA approval for seizures in LGS or Dravet syndrome for patients over 2 years old
50% reduction in convulsive seizure frequency vs. placebo (patients may experience 50-100 seizures per day, so 50% reduction is especially significant)
What are some non-pharmacologcal therapy options for seizures in children?
Ketogenic diet
Surgery
Vagus Nerve Stimulation (VNS)
What does a ketogenic diet look like for seizure prevention?
High fat, low carb diet (ketogenic)
- Requires strict compliance (CHO count includes drug excipients)
- Poorly tolerated (esp. in children)
May reduce seizure frequency (can be tried as adjunct if patient has experienced treatment failure
What are some surgical options for reducing seizure frequency?
Not the first option considered
An option for some patients with refractory epilepsy (usually focal epilepsy)
Can either resect troublesome region or disconnect nerve fibers
Up to 70% of patients acheive seizure-freedom
What is the role of vagus nerve stimulation in reducing seizure frequency in children?
Implant an electrical pulse generator and attach electrodes to the vagus nerve
Pulse generator stimulates vagus nerve on a regularly scheduled basis (MOA unknown)
Option in refractory focal onset or generalized seizures
Can take up to 1 to 1.5 years to see full benefit (patients still remain on ASMs)
Review slides 37-42 for a pediatric epilepsy management case
When are anti-seizure medications stopped?
Children with epilepsy often go into remission
Evidence supports stopping therapy after at least 2 years of seizure freedom
Consider ASM ADRs vs. risk of seizures when deciding to stop
Review slide 44 for pediatric epilepsy pearls
