Pediatric Seizures Flashcards
A seizure is:
a) Excessive asynchronous neuronal activity
b) Reduced asynchronous neuronal activity
c) Excessive synchronous neuronal activity
d) Reduced synchronous neuronal activity
c.
Adjusting antiseizure medications (ASMs) is:
a) Complex
b) A unique opportunity to flex pharmacist knowledge
c) Best left to neurologists
d) A & B
e) A & C
d
Status epilepticus is a _______ _________
medical emergency
What is status epilepticus? (2)
- 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 mins - Any seizure that does not stop within 5 minutes should be treated as impending SE
- Operationally seizures lasting >5 mins or repetitive seizures for > 5 min are treated as SE to prevent consequences and increase response to tx
Explain what t1 and t2 of seizure frequency means
t1 = When a seizure is likely to be prolonged leading to continuous seizure activity
t2 = When a seizure may cause long term consequences (including neuronal injury, neuronal death, alteration of neuronal networks and functional deficits)
What class of drugs and what dosing frequency is often given to pts for acute seizure treatment to reduce risk of progression to status epilepticus?
On demand BZDs to use prn at the onset of seizures to decrease risk of progression to SE
What are the treatment options for pediatrics (> 3 months) to treat acute seizure/reduce risk of progression to status epilepticus? (2)
- Midazolam intranasal 0.2 to 0.3 mg/kg/dose or buccal 0.2 to 0.5 mg/kg/dose (max 10mg)
- Injectable midazolam (5 mg/mL concentration preferred)
- Via nasal atomizer for nasal administration; split dose into each nostril - Not as common but lorazepam buccal 0.1mg/kg (max 4mg) could be used too.
What are the treatment options for infants (< 3 months) to treat acute seizure/reduce risk of progression to status epilepticus?
Rectal diazepam 0.5mg/kg/dose (max 20mg) - tend not to use because pretty traumatic for both the patient and the caregivers
Explain how to administer intranasal midazolam
- Nasal atomizer - creates fine mist as you push the solution through it. (That’s the cone looking thing).
- Key things are midazolam need syringes, mucosal atomizer needed to administer. Atomizer can be re-used. Tilt the pt’s head back. Go in, give a quick push and gently atomize it. Split the dose between both nostrils to maximize surface area for absorption.
The etiology of seizures is unknown, but what are some potential factors/causes? (6)
- Structural
- Genetic
- Infectious
- Metabolic
- Immune
- Unknown
Define a focal seizure
Starting/affecting one hemisphere of the brain
Define a generalized seizure
Starting/affecting both hemispheres at the same time
Define 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 the 2 main epilepsy syndromes we talked about?
- Lennox-Gastaut Syndrome (LGS)
- Dravet syndrome
What are the clinical features of LGS? (2)
- Tonic, atonic, myoclonic seizures
- Atypical absences
What are the clinical features of Dravet syndrome? (3)
- Prolonged, often febrile, clonic seizures.
- Repeated febrile and afebrile seizures.
- Myoclonus common
1st line for absence seizures is?
Ethosuximide
Ethosuximide for other seizure types?
No, only absence seizures. Do not use as monotherapy if mixed seizure types, even if one of these is absence seizures
What are the advantages of ethosuximide? (4)
- Lower rates of attention difficulties compared to VPA
- Works quickly
- Generally well-tolerated
- Few drug interactions
What is the disadvantage of ethosuximide? (1)
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? (3)
- CNS effects
- Drowsiness, dizziness, behavioural changes - GI effects
- Dose-related 🡪 Can divide dose to minimize - Rare: blood dyscrasias, skin rashes
What should be monitored when on ethosuximide? (2)
CBC and platelets (annually)
What is infantile epileptic spasms syndrome? (3)
- Epileptic spasms most often occur in “clusters” on awakening and involve tonic limb (+/- head) flexion or extension:
- Each spasm lasts less than 3 seconds
- Repeats every 5 to 10 seconds
- For a period of 5 to 15 mins - May have a distinctive, disordered EEG pattern called hypsarrhythmia
- May have psychomotor arrest
How should infantile epileptic spasms syndrome be treated?
Treat early and aggressively to prevent long-term sequelae (e.g., intellectual delays, refractory seizures)
Treatment options for infantile epileptic spasms syndrome include: (2)
- Hormonal therapy (oral prednisolone or IM/subcut ACTH)
- Vigabatrin
Other ASMs are ineffective
True or False? Vigabatrin acts on GABA receptors
False - structural analog of GABA, but does NOT act on GABA receptors
What is the MOA of vigabatrin?
Irreversible inhibition of GABA-transaminase leads to ↑ [GABA] in the CNS = ↑ neuro-inhibition
Vigabatrin metabolized how?
Insignificantly - mainy excreted unchanged in the urine –> renally adjust
What are the ADRs of vigabatrin? (3)
- Visual abnormalities, including permanent vision loss
- Vomiting and upper resp tract infections
- Asymptomatic MRI changes
Lennox-Gastaut Syndrome (LGS) is developmental and epileptic encephalopathy with: (3)
- Multiple drug-resistant seizure types, including but not limited to:
- Tonic
- Atonic (“drop attacks”)
- Atypical absence
- Generalized tonic-clonic - Typical EEG pattern
- Generalized slow spike-and-wave
- Generalized paroxysmal fast activity - Intellectual disability
What is first-line treatment for LGS?
Valproate
(Maybe rufinamide if in Ontario)
What is 2nd-line treatment for LGS?
Lamotrigine (monotherapy or adjunct)
What is 3rd-line adjunctive treatment for LGS (NICE guidelines)? (4)
- Topiramate
- Rufinamide
- Cannabidiol
- Clobazam
What is 4th-line adjunctive treatment for LGS (NICE guidelines)? (2)
- Ketogenic diet
- Felbamate
What is the approved indication for rufinamide?
Adjunctive treatment of seizures associated with LGS in patients 4+
What is the MOA of rufinamide?
- Exact MOA unknown.
- Prolongs the inactive state of Na+ channels, limiting repetitive firing of Na+ dependent action potentials.
What drug interactions to be aware of with rufinamide? (2)
- Weak CYP3A4 inhibitor
- Valproate may ↑ rufinamide levels
What are the ADEs of rufinamide? (5)
- Headache
- Shortened QT interval
- Tremor
- Vomiting, nausea
- Leukopenia
What is Dravet Syndrome? (3)
Drug-resistant developmental and epileptic encephalopathy [DEE] with:
- Seizures of various types, often starting with early-onset febrile seizures in infancy
- Progressive cerebral and cerebellar atrophy
- Developmental delays and intellectual disability
Dravet syndrome is 80% due to what?
Due to loss of function mutation in SCN1A (a Na+ channel gene)
What are the sodium channel blocking ASMs? (9)
- Carbamazepine
- Oxcarbazepine
- Eslicarbazepine
- Lacosamide
- Lamotrigine
- Rufinamide
- Phenytoin
- Topiramate
- VPA
How is Dravet Syndrome treated?
Valproic acid (VPA) in children?
- Contraindicated in children less than 2 years old due to fatal hepatotoxicity
- If absolutely necessary, can use levocarnitine to mitigate risk (usually at 50 mg/kg/day)
What is the MOA of fenfluramine?
Not fully understood but may promote serotonin release, act as a serotonin agonist, and inhibit serotonin transporters and reuptake
How efficacious is fenfluramine?
Efficacy has been shown to be maintained out to 3 years and decreases risk of SUDEP and all cause mortality in Dravet Syndrome
Fenfluramine has a significant interaction with ___________
stiripentol
Fenfluramine is only available through…?
the Health Canada Special Access Program
What are the approved indications for stiripentol?
Combined treatment with clobazam + valproate for refractory GTC seizures in patients with Dravet Syndrome not controlled with clobazam and valproate alone
True or False? Stiripentol capsules and powder is interchangeable
True - BUT not totally bioequivalent, so slight differences in efficacy
What is the MOA of stiripentol?
- Precise MOA unknown.
- May ↑ GABAergic inhibitory neurotransmission
What are the DIs of stiripentol? (2)
- Moderately inhibits CYP1A2, CYP2C19
- Major substrate for CYP1A2, CYP2C19, CYP3A4
What are the ADEs of stiripentol? (5)
Serious:
1. Delirium
2. Hallucinations
Other:
3. Drowsiness
4. Decreased appetite
5. Thrombocytopenia
What is the cannabidiol that is FDA approved for LGS or Dravet syndrome?
Epidiolex (2+ years old)
What are the 3 big non-pharm treatments for pediatric seizures?
- Keto diet - consider if have not responded to appropriate ASM therapy (treatment of choice in GLUT1DS)
- Surgery
- Vagus Nerve Stimulation (VNS)
What to know/consider about stopping ASM treatment in peds? (3)
- Children with epilepsy often go into remission (become “seizure free”)
- Although risk of relapse still depends on many factors - Evidence supports stopping therapy after at least 2 years of seizure freedom
- The approach taken considers adverse effects with chronic treatment and risk of seizures when deciding to stop or continue
