Pediatric Seizures Flashcards
True or false: status epilepticus is a medical emergency
true
What is status epilepticus?
any recurrent or continuous seizure activity lasting > 30 minutes in which the patient does not regain baseline mental status
-or a cluster of seizures that does not return to baseline for > 30 minutes
How should a seizure lasting greater than 5 minutes be treated?
any seizure that does not stop within 5 minutes should be treated as impending SE
-operationally seizures lasting > 5 minutes or repetitive seizures for > 5 mins are treated as SE to prevent consequences and increase response to tx
What are patients given to decrease risk of progression to SE?
patients are often given “on demand” benzodiazepines to use “prn” at the onset of seizures to decrease risk of progression to SE
Which benzodiazepine is often give to reduce risk of progression to SE?
midazolam intranasal or buccal
-injectable: via nasal atomizer for nasal administration
rectal diazepam an option for < 3 months
-not really used b/c its traumatic
What are epilepsy syndromes?
refers to clusters of features that may occur together, including seizure type, EEG findings, imaging findings, age-dependent features (e.g., age at onset or remission), specific comorbidities (e.g. psychiatric illness), triggers and sometimes prognosis
What are examples of epilepsy syndromes?
childhood absence epilepsy
juvenile absence epilepsy
juvenile myoclonic epilepsy
Lennox-Gastaut syndrome
Dravet syndrome
What is the spectrum of ethosuximide?
narrow-spectrum ASM
What is the role of ethosuximide?
1st line for absence seizures
-drug of choice
not for any other seizure type
-do not use as monotherapy if mixed seizure types, even if one of these is absence seizures
What are the advantages of ethosuximide?
lower rates of attention difficulties compared to VPA
works quickly
generally well-tolerated
few drug interactions
What are the disadvantages of ethosuximide?
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 the adverse effects of ethosuximide?
CNS effects
-drowsiness, dizziness, behavioral changes
GI effects
-dose related –> can divide dose to minimize
rare: blood dyscrasias, skin rashes
What are some monitoring parameters for ethosuximide?
CBC & platelets (annually)
What is infantile epileptic spasms syndrome?
epileptic spasms most often occur in “clusters” on awakening and involve tonic limb (+/- head) flexion or extension
-each spasms lasts less than 3 seconds
-repeat every 5-10 seconds
-for a period of 5-15 minutes
What is distinctive about the EEG of a patient with infantile epileptic spasms syndrome?
hypsarrhythmia
How aggressively should infantile epileptic spasms syndrome be treated?
treat early and aggressively to prevent long-term sequelae (e.g. intellectual delays, refractory seizures)
What are the treatment options for infantile epileptic spasms syndrome?
hormonal therapy (oral prednisolone or IM/SC ACTH)
vigabatrin
other ASMs are ineffective
What is the MOA of vigabatrin?
irreversible inhibition of GABA-transaminase leads to increased GABA in the CNS = increased neuro-inhibition
-structural analog of GABA, but does NOT act on GABA receptors
True or false: vigabatrin is titrated slowly
false
titrated q2-3 days
When should we switch off vigabatrin?
no clinical response in 7-14 days, change therapy
What are the CYP interactions of vigabatrin?
no CYP effects
-insignificant metabolism; mainly excreted unchanged in the urine –> renally adjust
What are the adverse effects of vigabatrin?
visual abnormalities
-including permanent vision loss
-ophtho follow-up
vomiting and upper resp tract infections
-more common in infants than adults
asymptomatic MRI changes
-resolves on d/c (may resolve with continued use)
What is Lennox-Gastaut syndrome?
developmental and epileptic encephalopathy with:
1. multiple drug-resistant seizure types. including but not limited to:
-tonic
-atonic (“drop attacks”)
-atypical absence
-generalized tonic-clonic
2. typical EEG pattern
-generalized slow spike-and-wave
-generalized paroxysmal fast activity
3. intellectual disability
children may be medically complex with comorbid neurodevelopmental and behavioral disorders, sleep disorders, mobility requirements, feeding tubes
What is 1st line for Lennox-Gastaut syndrome?
NICE 2022: valproate
Ontario 2020: rufinamide, valproate
What is the approved indication for rufinamide?
adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients > 4 yrs old
What are the drug interactions for rufinamide?
weak CYP 3A4 inhibitor
valproate may increase rufinamide levels
What is the MOA of rufinamide?
exact MOA unknown
-prolongs the inactive state of Na+ channels, limiting the repetitive firing of Na+ dependent action potentials
What are the adverse effects of rufinamide?
shortened QT interval (dose related)
tremor
headache
drowsiness
dizziness, fatigue
ataxia, diplopia
multiorgan hypersensitivity
vomiting, nausea
leukopenia
What is Dravet syndrome?
drug-resistant developmental and epileptic encephalopathy with:
-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 ~ 9 years
-historically: ~ 93% of deaths occur by age 20 years
-earlier diagnosis and newer treatments are leading to 80% survival beyond 20 yrs
What is a major contributor to the development of Dravet syndrome?
80% due to loss of function in SCN1A (Na+ channel gene)
What is the role of Na+ blocking ASMs in Dravet syndrome?
Na+ blocking ASM not effective, may worsen seizures
Is valproic acid used to treat Dravet syndrome in children?
CI in children less than 2 years old due to fatal hepatotoxicity
-if absolutely necessary, can use levocarnitine to mitigate risk
What is the MOA of fenfluramine?
not fully understood but may promote 5HT serotonin release, act as a 5HT agonist, and inhibit 5HT transporters and reuptake
What is the efficacy of fenfluramine for Dravet syndrome?
efficacy has been shown to be maintained out to 3 years and decrease risk of SUDEP and all cause mortality in Dravet syndrome
Why was fenfluramine withdrawn from the market?
deaths for pulmonary HTN and valvulopathy when used in combo with phentermine for weight loss
-PAH and valvulopathy has not been described at anti-seizure doses
What is a significant drug interaction for fenfluramine?
stiripentol
What is the approved indication for stiripentol?
combined treatment with clobazam + valproate for refractory GTC seizures in patients with Dravet syndrome not controlled with valproate and clobazam alone
What is the MOA of stiripentol?
precise MOA unknown
-may increase GABAergic inhibitory neurotransmission
What are drug interactions of stiripentol?
moderately inhibits CYP 1A2, 2C19
major substrate for CYP 1A2, 2C19, 3A4
What are the adverse effects of stiripentol?
serious: delirium, hallucinations
decreased appetite
weight loss
vomiting
drowsiness, agitation
ataxia
aggressive behavior
tremor
thrombocytopenia
What is the FDA approved cannabis product for seizures associated with Lennox-Gastaut or Dravet?
Epidiolex (cannabidiol)
What are the adverse effects of Epidiolex?
diarrhea, vomiting
fatigue
pyrexia
somnolence
LFT abnormalities
Which epilepsy syndromes have most data for cannabis?
Dravet and Lennox-Gastaut
-but has been used in many epilepsies as a 3rd or 4th line agent
True or false: cannabis is 1st line for certain seizure disorders
false
not 1st line for any seizure disorder
What are the drug interactions of cannabis?
2C19 inhibition decreases metabolism of clobazam and its active metabolite norclobazam
additive risks of hepatotoxicity with VPA
What are some non-pharm therapies for pediatric seizures?
ketogenic diet
surgery
vagus nerve stimulation
Describe the ketogenic diet.
high fat, low CHO, adequate protein diet mimics state of starvation
-CHO count includes medication excipients
-requires strict compliance
-poorly tolerated
-may require nutritional supplements to minimize ADRs
may reduce seizure frequency
-antiseizure MOA not fully established
When is the ketogenic diet considered?
have not responded to appropriate ASM therapy
treatment of choice in GLUT1DS
When is surgery an option for epilepsy?
some pts with refractory epilepsy (usually focal epilepsy)
-resections
-disconnective
What is the efficacy of surgery for epilepsy?
up to ~70% achieve seizure-freedom
-~10% will continue to have frequent seizures
What is vagus nerve stimulation?
surgical procedure to implant an electrical pulse generator in the chest and attach electrodes to the vagus nerve in the neck
-pulse generator stimulates the vagus nerve on a regularly scheduled basis
-may reduce seizure frequency
-option in refractory focal onset or generalized seizures
When might antiseizure medications be stopped?
evidence supports stopping therapy after at least 2 years of seizure freedom
-children with epilepsy often go into remission
-the approach taken considers adverse effects with chronic tx and risk of szs when deciding to stop or continue
