24 Questions
What is the minimum age requirement for treatment with Epidiolex?
1 year
What percentage of patients with Tuberous Sclerosis Complex (TSC) develop autism or show signs of developmental delays?
25-50%
What is the approximate incidence of Tuberous Sclerosis Complex (TSC) in the general population?
1/6000
What is the primary endpoint of the CBD trials mentioned in the text?
% ↓ in focal seizures
What is the mechanism by which CBD and clobazam demonstrate potentiation of anticonvulsant effects?
Additive effect on positive allosteric modulation of GABAA receptors
What is the percentage of patients who achieved seizure-freedom with CBD treatment?
5%
What is the name of the drug-resistant epilepsy syndrome that is one of the indications for Epidiolex?
All of the above
What is the percentage decrease in focal seizures seen in the 50 mg/kg CBD group?
49%
What is the primary characteristic of a seizure?
A brief, temporary disturbance in the electrical activity of the brain
What is the minimum number of seizures required for a diagnosis of epilepsy?
2
What is the estimated prevalence of epilepsy worldwide?
1% of the world's population
What is the primary characteristic of Dravet syndrome?
Severe encephalopathy with a high seizure burden
At what age do seizures typically begin in Dravet syndrome?
In the 1st year of life
What is the distinguishing feature of Lennox-Gastaut syndrome?
Seizures develop from years 1-8
What is the estimated percentage of people with Lennox-Gastaut syndrome who develop from West syndrome?
30-40%
What is the term for a prolonged seizure that lasts for 5-10 minutes?
Status epilepticus
What is the typical age range for the development of Lennox-Gastaut Syndrome?
1-8 years
What type of seizures often precede the onset of Lennox-Gastaut Syndrome?
Infantile spasms
Which of the following antiseizure drugs acts by blocking ionotropic glutamate receptors?
Perampanel
What is the typical duration of seizures in Dravet Syndrome?
5-10 minutes
What is the common feature of developmental history in both Dravet Syndrome and Lennox-Gastaut Syndrome?
Delayed development before seizure onset
Which of the following antiseizure drugs acts by enhancing GABA-mediated inhibition?
Diazepam
What is the common feature of seizure types in both Dravet Syndrome and Lennox-Gastaut Syndrome?
Variable types of seizures
What is the common feature of encephalopathy severity in both Dravet Syndrome and Lennox-Gastaut Syndrome?
Severe encephalopathy
Study Notes
Epilepsy
- A disorder characterized by recurrent seizures (>2, >24 hours apart)
- Involves seizures due to enhanced electrical activity of neurons
- Usually diagnosed after a patient has 2 seizures
- Causes: genetics, brain injury, infection, or abnormalities in brain structure, immune function, or metabolism
- Often the cause is unknown (idiopathic epilepsy)
- 65 million people have epilepsy worldwide (about 1% of the world's population)
Seizure Types
- Seizures can occur due to:
- Enhanced electrical activity of neurons
- Abnormalities in brain structure, immune function, or metabolism
- Types of seizures:
- Febrile seizures
- Generalized tonic-clonic seizures
- Tonic seizures
- Atonic seizures
- Absence seizures
Epilepsy Syndromes
- Dravet Syndrome (DS):
- Severe encephalopathy with a high seizure burden
- Seizures often begin in the 1st year of life and may commence with febrile seizures
- Progresses to severe spontaneous generalized tonic-clonic seizures
- Status epilepticus possible
- Lennox-Gastaut Syndrome (LGS):
- Severe encephalopathy with a high seizure burden
- Seizures develop from years 1-8 (peak 3-5 years)
- Different types of seizures, including stiffening (tonic), drop (atonic), and generalized tonic-clonic seizures
- Status epilepticus possible
Antiepileptic Drugs
- Mechanism of action:
- Modulating voltage-gated ion channels
- Enhancing GABA-mediated inhibition
- Interacting with synaptic release machinery
- Blocking ionotropic glutamate receptors
- Combinations of mechanisms
- Examples of antiepileptic drugs:
- Phenytoin, carbamazepine, lamotrigine
- Benzodiazepines (e.g., diazepam)
- Tiagabine (inhibits GABA transporter 1)
- Levetiracetam (binds synaptic vesicle glycoprotein)
- Perampanel (AMPA)
CBD (Epidiolex)
- 98% CBD with no THC content
- Approved by FDA, EMA, and TGA
- Indicated to treat drug-resistant epilepsies:
- Dravet syndrome (DS)
- Lennox-Gastaut syndrome (LGS)
- Tuberous sclerosis complex (TSC)
- Age must be 1 year or older
- > 15,000 patients treated with Epidiolex
Tuberous Sclerosis Complex (TSC)
- Rare genetic disorder characterized by the growth of non-cancerous tumors or hamartomas in various organs
- Autosomal dominant genetic condition (often mutations in TSC1 or TSC2)
- Occurs in 1/6000 people
- Affects multiple organs, including the brain
- 25-50% develop autism or show signs of developmental delays
- > 90% of patients develop epilepsy, which may be intractable
CBD Trials
- DS trial and LGS trial 14w showed reduction in drop seizure frequency
- Primary endpoint (% ↓ in focal seizures): 49% ↓ in 50 mg/kg group, 48% ↓ in 25 mg/kg group, and 27% ↓ in placebo group
- Seizure-freedom was achieved in 5% of patients on CBD compared to 0% with placebo
- Side effects: diarrhea, somnolence, and elevated liver transaminase
Test your knowledge of epilepsy, including its definition, types of seizures and epilepsy syndromes, and the mechanism of action of antiepileptic drugs. Also, explore preclinical models of epilepsy and seizures.
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