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refractory epilepsy dr ali Allahabi-3.pptx
- 1. Refractory Epilepsy: Challenges andManagement Presented by: Ali Mohammed Hizam Allahabi Pediatric Arabic &yemen board residents 02/01/2025
- 2. Objectives - Define refractoryepilepsy. - Understand its epidemiology and causes. -pathophysiology. - Discuss the diagnostic criteria and challenges. -Management - Review current treatment options. -conclusion.
- 3. Introduction Synonyms -Drug-resistant -Treatment-resistant -Intractable -Difficult-to-control, etc • Refractoryepilepsy, also known as drug-resistant epilepsy, refers to seizures that persist despite treatment with two or more appropriately chosen and tolerated antiepileptic drugs (AEDs). - It significantly affects quality of life, cognitive function, and increases morbidity and mortality.
- 5. Epidemiology - Epilepsy affectsapproximately 50 million people worldwide. - Around 30% of patients with epilepsy are drug- resistant. - Higher prevalence in individuals with structural or genetic predispositions.
- 6. Causes and RiskFactors - Causes: • Structural abnormalities (e.g., cortical dysplasia, old stroke,tumors). • Genetic factors (e.g., Dravet syndrome , other see table 1). • Metabolic and immune-related causes(see table 2). • Infectious causes : (e.g. meningaitis , neurocysticercosis). - Risk Factors: • Early onset of seizures.. • High seizure frequency before treatment. • Inappropriate initial therapy.
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- 9. Altered Excitatory-Inhibitory Balance NetworkReorganization - Epileptogenesis: Formation of hyperexcitable networks. - Synaptic plasticity changes enhance seizure propagation. Pathophysiology - Overactivation of excitatory glutamate receptors (NMDA, AMPA). - Impaired GABAergic inhibition due to receptor dysfunction or interneuron loss.
- 10. physiopathology Cellular and MolecularFactors Neuronal Damage - Recurrent seizures lead to neuronal injury, perpetuating a cycle of resistance. - Inflammatory mediators (e.g., cytokines) contribute to hyperexcitabili - Ion channel mutations (e.g., Na+, K+, Ca2+ channels). - Increased expression of drug-efflux transporters (e.g., P-glycoprotein).
- 12. 3. Associated Comorbidities -Motor dysfunction (e.g., spasticity, ataxia). - Sleep disturbances. 4. Impact on Quality of Life - Impaired daily functioning. - Psychosocial challenges (e.g., anxiety, depression). Clinical Feature 1. Seizure Characteristics: - Frequent, prolonged seizures resistant to standard AEDs - Clusters of seizures or status epilepticus. 2. Neurological Symptoms - Cognitive decline or developmental regression. - Behavioral changes (e.g., irritability, hyperactivity).
- 13. Diagnostic Criteria - ILAEDefinition: Failure of adequate trials of two tolerated and appropriately chosen AED regimens. - Diagnostic tools: • intial invstgation (CBC- electrolytes - RBS- csf analysis, urine tests,LFT, KFT) • EEG and advanced imaging techniques (e.g., MRI). • Genetic and metabolic testing.
- 14. Challenges in Management -Poor seizure control and its implications. - Associated cognitive and behavioral comorbidities - Significant impact on daily life and mental health.
- 15. Management initial : 1- ABCD 2-.Confirm Seizures Perform EEG to ensure events are epileptic and not mimics like jitteriness or autonomic disturbances. 3. Identify and Treat Underlying Causes Hypoglycemia: Correct with IV glucose. Hypocalcemia: Treat with calcium gluconate. Infections: Start antibiotics/antivirals for suspected meningitis or TORCH infections. 4. First-line Antiepileptic Drugs (AEDs):BDZ as blouse dose Phenobarbital: The first-line AED, given as a loading dose (20 mg/kg) IV, followed by maintenance dosing
- 17. TREATMENT OPTIONS 1-PHARMACOLOGICAL • firstline & second line SEIZUR DURATION INTERVANTION SPECIFIC INTERVENTION 0 TO 5MIN A B C BZD 5 TO 20MIN ABCD • IV BZD • PHENOBARBTON / VALBORAT • PHENYTOIN / LEVETIRACETAM
- 18. -THIRD LINE THERAPY SEIZUR DURATION INTERVANTION 40-60MINABCDE INFUSION: • midazolam: 0.2mg/kg/dos bolus followed by M.D of 2-20mcg/kg/min • thiopental: 3-5mg/kg iv bolus followed by 0.5 -5mg /kg/hour • Propofol: 1 -2 mg /kg/dose iv bolus followed by 1-5mg/kg/ hour. • intubation • ECG monitoring, inotropic as needed • continues EEG monitoring • Control for BP • metabolic , autoimmune epilepsy workup • consider co-enzyme cocktail therapy • thiamin: 100mg TDS • biotin :10mg BD • carnitine: 50mg/kg/dose BD (MAX 1000mg) • riboflavin: 20mg TDS
- 19. • Polytherapy Seizure TypeFirst Drug Second Drug Third Drug Focal (Partial) Epilepsy Lamotrigine Levetiracetam Topiramate Generalized Tonic- Clonic Seizures Valproic Acid Clobazam Lamotrigine Absence Seizures Ethosuximide Lamotrigine Valproic Acid Myoclonic Seizures Valproic Acid Levetiracetam Topiramate
- 20. Anti-Epileptic Drugs (AEDs) Content:AEDs aimto control seizures by modifying the excitability of neurons in the brain. Description: Common medications include valproate, levetiracetam, carbamazepine, and lamotrigine. Indication: First-line treatment for most types of epilepsy. Considerations: Requires dose adjustments and careful monitoring of side effects.
- 21. • No pharmacological AdvancedTherapies for Refractory Seizures - Dietary therapies (e.g., ketogenic diet). - Neurostimulation (e.g., vagus nerve stimulation). - Surgical Options: Resective surgery and palliative surgeries (e.g., corpus callosotomy) -Immunomodulatory Therapy. -Corticosteroids. - Plasma Exchange.
- 22. Advanced Therapies forRefractory Seizures 1-Ketogenic Diet Ketogenic Diet Content: 1. Fats: 70-80% of total daily calories 2. Proteins: 10-20% of total daily calories 3. Carbohydrates: 5-10% of total daily calories Description: High-fat, low-carbohydrate diet to reduce seizure frequency. Indication: Particularly useful in pediatric refractory epilepsy. Considerations: Requires careful monitoring by healthcare providers
- 23. 2-Vagus Nerve Stimulation(VNS) Content: VNS is a medical treatment that involves delivering electrical impulses to the vagus nerve. Description: Implantable device that sends electrical impulses to the vagus nerve. Indication: For drug-resistant epilepsy. Considerations: Surgery required; side effects include hoarseness.
- 24. 3-Responsive Neurostimulation (RNS) ResponsiveNeurostimulation (RNS) Description: Device that monitors and responds to brain activity in real-time. Indication: Intractable focal epilepsy. Considerations: Involves surgery; results may vary.
- 25. 4-Surgical Resection Surgical Resection Description:Removal of the brain area responsible for seizures. Indication: Refractory focal epilepsy. Considerations: Pre-surgical evaluations and potential cognitive risks.
- 26. 5-Laser Ablation Laser Ablation Description:Minimally invasive laser technique to remove seizure foci. Indication: Focal epilepsy. Considerations: MRI-guided; risks include tissue injury.
- 27. 6-Deep Brain Stimulation(DBS) Description: Electrodes implanted in the brain to modulate abnormal electrical activity. Indication: Refractory epilepsy. Considerations: Requires surgery; may not work for all patients.
- 28. 7-Corticosteroids Corticosteroids: Description: Used inautoimmune or inflammatory epilepsy. Indication: Autoimmune-related epilepsy. Considerations: Long-term use can cause significant side effects.
- 29. 8-Plasma Exchange (PLEX) PlasmaExchange (PLEX): Description: Removes harmful antibodies or substances from the blood. Indication: Autoimmune epilepsy. Considerations: Invasive procedure with potential complications.
- 30. 9-Immunomodulatory Therapy Immunomodulatory Therapy Description:Uses drugs like rituximab or IVIG to modulate the immune response. Indication: Autoimmune epilepsy. Considerations: Requires close monitoring due to immune suppression.
- 31. Conclusion • - Multidisciplinaryapproach is essential for management. • - Need for patient-specific treatment plans. • - Emphasis on ongoing research and patient support systems.
- 32. References • - FisherRS, et al. Definition of drug-resistant epilepsy: ILAE consensus. • - Latest research articles on refractory epilepsy. • - Relevant clinical guidelines and textbooks. • Uptodate • Medical website • CHILD NEUROLOGY AND BEYOND2023 )India academy of pediatric)
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