Antiepileptic drugs (AEDs) in pediatric epilepsy
1. Initial Evaluation and Classification:
- Accurate seizure classification is crucial (focal vs. generalized)
- Consider EEG findings
- Age of patient
- Comorbidities
- Access to medications and monitoring
2. First-line Monotherapy Selection:
For Focal Seizures:
- First choices: Oxcarbazepine, Levetiracetam, Carbamazepine
- Alternative: Lamotrigine
- Special considerations:
* Avoid carbamazepine in patients with cardiac conduction issues
* Levetiracetam preferred if liver dysfunction
* Oxcarbazepine may worsen hyponatremia
For Generalized Seizures:
- First choices: Valproate (not in females of childbearing potential), Levetiracetam
- Alternative: Lamotrigine
- Special considerations:
* Avoid valproate in liver disease
* Avoid valproate in mitochondrial disorders
* Consider lamotrigine in mood disorders
For Absence Seizures:
- First choices: Ethosuximide, Valproate
- Avoid: Carbamazepine, Oxcarbazepine, Phenytoin (may worsen absences)
3. When to Add Second Drug:
Consider add-on therapy when:
- Failed adequate trial of first drug at maximum tolerated dose
- Persistent seizures after 6-8 weeks of optimal dose
- Intolerable side effects preventing dose optimization
4. Choice of Second Drug:
For Focal Seizures:
- If on Levetiracetam → Add Oxcarbazepine/Lamotrigine
- If on Oxcarbazepine → Add Levetiracetam/Topiramate
- If on Carbamazepine → Add Levetiracetam/Lamotrigine
For Generalized Seizures:
- If on Valproate → Add Levetiracetam/Lamotrigine
- If on Levetiracetam → Add Valproate/Topiramate
- If on Lamotrigine → Add Levetiracetam/Valproate
5. Special Populations and Considerations:
Liver Disease:
- Prefer: Levetiracetam, Gabapentin, Pregabalin
- Avoid: Valproate, Carbamazepine
Kidney Disease:
- Dose adjustment needed for: Levetiracetam, Gabapentin, Pregabalin
- Prefer: Carbamazepine, Oxcarbazepine
Behavioral/Psychiatric Comorbidity:
- Prefer: Lamotrigine (mood stabilizing)
- Use caution with: Levetiracetam (may worsen behavior)
- Consider: Oxcarbazepine
6. When to Substitute Instead of Add:
Consider substitution when:
- Severe adverse effects to first drug
- Drug interactions making current therapy unsuitable
- Compliance issues due to dosing schedule
- Cost/availability issues
- Teratogenic concerns (e.g., switching from valproate in adolescent females)
7. Monitoring:
Before Starting:
- Baseline CBC, LFTs, electrolytes
- Consider EKG if starting carbamazepine
- Pregnancy test in adolescent females
During Treatment:
- Regular monitoring of drug levels
- CBC and LFTs as needed
- Monitor for specific drug-related adverse effects
- Growth monitoring
- Academic/behavioral monitoring
1. Initial Evaluation and Classification:
- Accurate seizure classification is crucial (focal vs. generalized)
- Consider EEG findings
- Age of patient
- Comorbidities
- Access to medications and monitoring
2. First-line Monotherapy Selection:
For Focal Seizures:
- First choices: Oxcarbazepine, Levetiracetam, Carbamazepine
- Alternative: Lamotrigine
- Special considerations:
* Avoid carbamazepine in patients with cardiac conduction issues
* Levetiracetam preferred if liver dysfunction
* Oxcarbazepine may worsen hyponatremia
For Generalized Seizures:
- First choices: Valproate (not in females of childbearing potential), Levetiracetam
- Alternative: Lamotrigine
- Special considerations:
* Avoid valproate in liver disease
* Avoid valproate in mitochondrial disorders
* Consider lamotrigine in mood disorders
For Absence Seizures:
- First choices: Ethosuximide, Valproate
- Avoid: Carbamazepine, Oxcarbazepine, Phenytoin (may worsen absences)
3. When to Add Second Drug:
Consider add-on therapy when:
- Failed adequate trial of first drug at maximum tolerated dose
- Persistent seizures after 6-8 weeks of optimal dose
- Intolerable side effects preventing dose optimization
4. Choice of Second Drug:
For Focal Seizures:
- If on Levetiracetam → Add Oxcarbazepine/Lamotrigine
- If on Oxcarbazepine → Add Levetiracetam/Topiramate
- If on Carbamazepine → Add Levetiracetam/Lamotrigine
For Generalized Seizures:
- If on Valproate → Add Levetiracetam/Lamotrigine
- If on Levetiracetam → Add Valproate/Topiramate
- If on Lamotrigine → Add Levetiracetam/Valproate
5. Special Populations and Considerations:
Liver Disease:
- Prefer: Levetiracetam, Gabapentin, Pregabalin
- Avoid: Valproate, Carbamazepine
Kidney Disease:
- Dose adjustment needed for: Levetiracetam, Gabapentin, Pregabalin
- Prefer: Carbamazepine, Oxcarbazepine
Behavioral/Psychiatric Comorbidity:
- Prefer: Lamotrigine (mood stabilizing)
- Use caution with: Levetiracetam (may worsen behavior)
- Consider: Oxcarbazepine
6. When to Substitute Instead of Add:
Consider substitution when:
- Severe adverse effects to first drug
- Drug interactions making current therapy unsuitable
- Compliance issues due to dosing schedule
- Cost/availability issues
- Teratogenic concerns (e.g., switching from valproate in adolescent females)
7. Monitoring:
Before Starting:
- Baseline CBC, LFTs, electrolytes
- Consider EKG if starting carbamazepine
- Pregnancy test in adolescent females
During Treatment:
- Regular monitoring of drug levels
- CBC and LFTs as needed
- Monitor for specific drug-related adverse effects
- Growth monitoring
- Academic/behavioral monitoring
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20 common pediatric epilepsy scenarios with treatment approaches.
1. Typical Absence Epilepsy (7-year-old)
- First: Ethosuximide
- Second add-on: Valproate
- Third add-on: Lamotrigine
- Replacement options: Levetiracetam if both fail
2. Juvenile Myoclonic Epilepsy (14-year-old male)
- First: Valproate
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Lamotrigine, Zonisamide
3. Juvenile Myoclonic Epilepsy (13-year-old female)
- First: Levetiracetam
- Second add-on: Lamotrigine or valproate
- Third add-on: Topiramate
- Replacement: Zonisamide
4. Benign Rolandic Epilepsy (8-year-old)
- First: Oxcarbazepine or valproate if there is paradoxical worsening
- Second add-on: Levetiracetam
- Third add-on: Carbamazepine
- Replacement: Gabapentin
5. West Syndrome (6-month-old)
- First: ACTH/Vigabatrin
- Second add-on: Topiramate
- Third add-on: Levetiracetam
- Replacement: Valproate, clobazam
6. Lennox-Gastaut Syndrome (5-year-old)
- First: Valproate
- Second add-on: Clobazam
- Third add-on: Rufinamide
- Replacement: Lamotrigine
7. Focal Epilepsy with Normal MRI (10-year-old)
- First: Oxcarbazepine
- Second add-on: Levetiracetam
- Third add-on: Lamotrigine
- Replacement: Carbamazepine
8. Focal Epilepsy with Cortical Dysplasia (4-year-old)
- First: Levetiracetam
- Second add-on: Oxcarbazepine
- Third add-on: Topiramate
- Replacement: Lacosamide
9. Dravet Syndrome (2-year-old)
- First: Valproate
- Second add-on: Clobazam
- Third add-on: Stiripentol
- Replacement: Topiramate, Fenfluramine
10. Childhood Absence Epilepsy with Myoclonic Components (8-year-old)
- First: Valproate
- Second add-on: Levetiracetam
- Third add-on: Lamotrigine
- Replacement: Topiramate
11. Post-traumatic Epilepsy (12-year-old)
- First: Levetiracetam
- Second add-on: Carbamazepine
- Third add-on: Lacosamide
- Replacement: Oxcarbazepine
12. Tuberous Sclerosis with Focal Seizures (3-year-old)
- First: Vigabatrin
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Oxcarbazepine
13. GLUT-1 Deficiency Syndrome (2-year-old)
- First: Ketogenic Diet
- Second add-on: Levetiracetam
- Third add-on: Zonisamide
- Replacement: Topiramate
14. Juvenile Absence Epilepsy (12-year-old)
- First: Valproate
- Second add-on: Lamotrigine
- Third add-on: Levetiracetam
- Replacement: Topiramate
15. Focal Epilepsy with Language Dysfunction (6-year-old)
- First: Levetiracetam
- Second add-on: Lamotrigine
- Third add-on: Oxcarbazepine
- Replacement: Topiramate (avoid phenytoin/phenobarbital)
16. Myoclonic-Atonic Epilepsy (Doose Syndrome) (4-year-old)
- First: Valproate
- Second add-on: Lamotrigine
- Third add-on: Clobazam
- Replacement: Levetiracetam
17. Early Myoclonic Encephalopathy (2-month-old)
- First: Phenobarbital
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Valproate
18. KCNQ2 Encephalopathy (neonate)
- First: Carbamazepine/Oxcarbazepine
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Phenobarbital
19. Rasmussen Encephalitis (7-year-old)
- First: Levetiracetam
- Second add-on: Carbamazepine
- Third add-on: Clobazam
- Replacement: Consider immunotherapy/surgery
20. Focal Epilepsy with Autism (5-year-old)
- First: Levetiracetam (though may need to monitor behavior)
- Second add-on: Oxcarbazepine
- Third add-on: Lamotrigine
- Replacement: Valproate (if no behavioral worsening)
Key Considerations for All Cases:
- Monitor side effects closely
- Consider drug interactions
- Adjust based on comorbidities
- Consider ketogenic diet in refractory cases
- Evaluate for surgical candidacy in focal cases
- Regular EEG monitoring
- Growth monitoring
- Development/cognitive monitoring
- Quality of life assessment
1. Typical Absence Epilepsy (7-year-old)
- First: Ethosuximide
- Second add-on: Valproate
- Third add-on: Lamotrigine
- Replacement options: Levetiracetam if both fail
2. Juvenile Myoclonic Epilepsy (14-year-old male)
- First: Valproate
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Lamotrigine, Zonisamide
3. Juvenile Myoclonic Epilepsy (13-year-old female)
- First: Levetiracetam
- Second add-on: Lamotrigine or valproate
- Third add-on: Topiramate
- Replacement: Zonisamide
4. Benign Rolandic Epilepsy (8-year-old)
- First: Oxcarbazepine or valproate if there is paradoxical worsening
- Second add-on: Levetiracetam
- Third add-on: Carbamazepine
- Replacement: Gabapentin
5. West Syndrome (6-month-old)
- First: ACTH/Vigabatrin
- Second add-on: Topiramate
- Third add-on: Levetiracetam
- Replacement: Valproate, clobazam
6. Lennox-Gastaut Syndrome (5-year-old)
- First: Valproate
- Second add-on: Clobazam
- Third add-on: Rufinamide
- Replacement: Lamotrigine
7. Focal Epilepsy with Normal MRI (10-year-old)
- First: Oxcarbazepine
- Second add-on: Levetiracetam
- Third add-on: Lamotrigine
- Replacement: Carbamazepine
8. Focal Epilepsy with Cortical Dysplasia (4-year-old)
- First: Levetiracetam
- Second add-on: Oxcarbazepine
- Third add-on: Topiramate
- Replacement: Lacosamide
9. Dravet Syndrome (2-year-old)
- First: Valproate
- Second add-on: Clobazam
- Third add-on: Stiripentol
- Replacement: Topiramate, Fenfluramine
10. Childhood Absence Epilepsy with Myoclonic Components (8-year-old)
- First: Valproate
- Second add-on: Levetiracetam
- Third add-on: Lamotrigine
- Replacement: Topiramate
11. Post-traumatic Epilepsy (12-year-old)
- First: Levetiracetam
- Second add-on: Carbamazepine
- Third add-on: Lacosamide
- Replacement: Oxcarbazepine
12. Tuberous Sclerosis with Focal Seizures (3-year-old)
- First: Vigabatrin
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Oxcarbazepine
13. GLUT-1 Deficiency Syndrome (2-year-old)
- First: Ketogenic Diet
- Second add-on: Levetiracetam
- Third add-on: Zonisamide
- Replacement: Topiramate
14. Juvenile Absence Epilepsy (12-year-old)
- First: Valproate
- Second add-on: Lamotrigine
- Third add-on: Levetiracetam
- Replacement: Topiramate
15. Focal Epilepsy with Language Dysfunction (6-year-old)
- First: Levetiracetam
- Second add-on: Lamotrigine
- Third add-on: Oxcarbazepine
- Replacement: Topiramate (avoid phenytoin/phenobarbital)
16. Myoclonic-Atonic Epilepsy (Doose Syndrome) (4-year-old)
- First: Valproate
- Second add-on: Lamotrigine
- Third add-on: Clobazam
- Replacement: Levetiracetam
17. Early Myoclonic Encephalopathy (2-month-old)
- First: Phenobarbital
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Valproate
18. KCNQ2 Encephalopathy (neonate)
- First: Carbamazepine/Oxcarbazepine
- Second add-on: Levetiracetam
- Third add-on: Topiramate
- Replacement: Phenobarbital
19. Rasmussen Encephalitis (7-year-old)
- First: Levetiracetam
- Second add-on: Carbamazepine
- Third add-on: Clobazam
- Replacement: Consider immunotherapy/surgery
20. Focal Epilepsy with Autism (5-year-old)
- First: Levetiracetam (though may need to monitor behavior)
- Second add-on: Oxcarbazepine
- Third add-on: Lamotrigine
- Replacement: Valproate (if no behavioral worsening)
Key Considerations for All Cases:
- Monitor side effects closely
- Consider drug interactions
- Adjust based on comorbidities
- Consider ketogenic diet in refractory cases
- Evaluate for surgical candidacy in focal cases
- Regular EEG monitoring
- Growth monitoring
- Development/cognitive monitoring
- Quality of life assessment
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ITP approach.
Petechiae are pinpoint hemorrhages <2 mm in size, purpura are 2 mm to 1 cm, and ecchymoses are >1 cm.
patient has all three. These lesions are the result of extravasation of blood from the vasculature into skin/mucosa and do not blanch.
platelet disorder could explain these symptoms and physical findings.
But is the platelet issue qualitative (platelets are normal in number but abnormal in function) or quantitative (platelets are normal in function, but abnormal in number)?.
There's a test for that.
Immature platelets = newly released platelets.
The immature platelet fraction If low/normal, there is decreased platelet production; if elevated, there is increased platelet destruction.
The elevated immature platelet fraction tells us we are dealing with a process causing platelet destruction.
The degree of thrombocytopenia narrows our differential to TMA and ITP. The absence of concomitant hemolytic anemia points us to the right diagnosis:
Petechiae are pinpoint hemorrhages <2 mm in size, purpura are 2 mm to 1 cm, and ecchymoses are >1 cm.
patient has all three. These lesions are the result of extravasation of blood from the vasculature into skin/mucosa and do not blanch.
platelet disorder could explain these symptoms and physical findings.
But is the platelet issue qualitative (platelets are normal in number but abnormal in function) or quantitative (platelets are normal in function, but abnormal in number)?.
There's a test for that.
Immature platelets = newly released platelets.
The immature platelet fraction If low/normal, there is decreased platelet production; if elevated, there is increased platelet destruction.
The elevated immature platelet fraction tells us we are dealing with a process causing platelet destruction.
The degree of thrombocytopenia narrows our differential to TMA and ITP. The absence of concomitant hemolytic anemia points us to the right diagnosis:
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