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Treatment of focal epilepsy ( short )
- 2. Approach to a child with Epilepsy 0 Is it an Epileptic seizure ? 0 Classify the Seizure : Epilepsy , Epilepsy Syndrome 0 Order the appropriate investigations 0 Treatment Modalities
- 3. Treatment of Seizures Goals: 0 Block repetitive neuronal firing. 0 Block synchronization of neuronal discharges. 0 Block propagation of seizure. Strategies 0 Modification of ion conductances. 0 Increase inhibitory (GABAergic) transmission. 0 Decrease excitatory (glutamatergic) activity.
- 4. Classification of Anticonvulsants Classical 0 Phenytoin 0 Phenobarbital 0 Primidone 0 Carbamazepine 0 Ethosuximide 0 Valproic Acid 0 Trimethadione Newer 0 Lamotrigine 0 Felbamate 0 Topiramate 0 Gabapentin 0 Tiagabine 0 Vigabatrin 0 Oxycarbazepine 0 Levetiracetam 0 Fosphenytoin 0 Others
- 5. Classification of Anti-Convulsants Action on Ion Channels Enhance GABA Transmission Inhibit EAA Transmission Na+: Phenytoin, Carbamazepine, Lamotrigine Topiramate Valproic acid Ca++: Ethosuximide Valproic acid Benzodiazepines (diazepam, clonazepam) Barbiturates (phenobarbital) Valproic acid Gabapentin Vigabatrin Topiramate Felbamate Felbamate Topiramate Na+: For general tonic-clonic and partial seizures Ca++: For Absence seizures Most effective in myoclonic but also in tonic-clonic and partial Clonazepam: for Absence
- 10. Choice of anti-convulsants 0 Seizure type 0 Epilepsy syndrome 0 Pharmacokinetic profile 0 Interactions/other medical conditions 0 Efficacy 0 Expected adverse effects 0 Cost 0 ALL FEMALES: Folate 1-4 mg/day supplementation
- 11. AEDs by Seizure type Partial Generalized Tonic-clonic PHT, CBZ, PB, GBP, TGB, LVT, OCBZ ACTH TPM? TGB? VGB? Tonic Myoclonic Atonic Infantile Spasms Absence ESX PHT, PB, VPA, LTG, TPM, (FBM), ZNS Simple Complex Secondary generalized
- 12. 1st Generation AEDs 0 Incomplete Efficacy 0 Unfavorable Kinetics (M-M, protein binding) 0 Narrow Therapeutic Range 0 Adverse CNS Effects 0 Adverse Non-CNS Effects 0 Drug-Interactions
- 13. Adverse Effects Hematologic damage 0 Marrow aplasia, agranulocytosis 0 Early symptoms: abnormal bleeding, acute onset of fever, symptoms of anemia 0 Felbamate : aplastic anemia approx. 1:5,000 treated patients 0 Patient education
- 14. Long term adverse effects 0 Endocrine/Metabolic Effects Osteomalacia, osteoporosis : Carbamazepine, Phenobarbital, Phenytoin, Oxcarbazepine, Valproate Folate (anemia, teratogenesis) : Phenobarbital, Phenytoin, Carbamazepine, Valproate Altered connective tissue metabolism or growth (facial coarsening, hirsutism, gingival hyperplasia or contractures) : Phenytoin, Phenobarbital 0 Neurologic Neuropathy ⦁ Cerebellar syndrome – phenytoin 0 Sexual Dysfunction - 30-60% Phenytoin Carbamazepine Phenobarbital Primidone
- 15. Focal Epilepsy 0 With secondary generalization 0 First-line drugs :carbamazepine and phenytoin (equally effective) 0 Valproate, phenobarbital, and primidone 0 Without generalization 0 Phenytoin and carbamazepine 0 Phenytoin and carbamazepine can be used together
- 16. Focal Epilepsy – Newer Drugs 0 Adjunctive (add-on) therapy - felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide 0 Lamotrigine, oxcarbazepine, felbamate - monotherapy where phenytoin and carbamazepine have failed. 0 Topiramate - refractory partial seizures.
- 17. Non - Conventional AED treatment 0Non-AED medical treatment Steroids (ACTH, prednisolone) IvIG Vitamins (B6, biotin, folinic acid) Melatonin 0Dietary manipulation Ketogenic diet Classical ketogenic diet MCT diet Atkins diet Oligoantigenic diet
- 18. Epilepsy Surgery Techniques 0 Lesional surgery 0 Specific surgical techniques (Eg. Sub-pial transection for Landau-Kleffner syndrome) 0 Palliative surgery
- 19. Indications for Surgery 0Medically intractable epilepsy (> 3 AEDs) 0Structural lesion 0Intolerable adverse effects of AEDs 0Psychosocial dysfunction 0Recurrent injury
- 20. Evaluation for Surgery 0MRI 0PET 0Ictal/interictal SPECT 0MR Spectroscopy
Editor's Notes
- Epilepsy in Children Idiopathic epilepsy more common Generalized more Epileptic syndromes more important Difficult to assess sensorium disturbances Auras often can’t be reported All Seizures can’t be accurately classified Data about new and old AEDs limited May have important effects on learning, memory and intelligence Seizures that may not require treatment Solitary Seizures with normal EEG/CT Febrile Seizures Metabolic Seizures Drug induced: Quinolines Benign Rolandic epilepsy Some reflex epilepsies Post traumatic impact seizures Seizures associated with syncope, pallid syncope or BHS
- Minimize side effects with the simplest drug regimen. MONOTHERAPY IS RECOMMENDED IN MOST CASES
- Phenytoin, Carbamazepine Block voltage-dependent sodium channels at high firing frequencies—use dependent Oxcarbazepine Blocks voltage-dependent sodium channels at high firing frequencies Also effects K+ channels Zonisamide Blocks voltage-dependent sodium channels and T-type calcium channels
- Benzodiazepines (diazapam, clonazapam) Increase frequency of GABA-mediated chloride channel openings Barbiturates (phenobarbital, primidone) Prolong GABA-mediated chloride channel openings Some blockade of voltage-dependent sodium channels Gabapentin May modulate amino acid transport into brain May interfere with GABA re-uptake Tiagabine Interferes with GABA re-uptake Vigabatrin elevates GABA levels by irreversibly inhibiting its main catabolic enzyme, GABA-transaminase
- Vast Clinical Experience Small window between efficacy & toxicity
- Laboratory monitoring probably not helpful in early detection
- 2. may be slightly more effective 3. (but both are enzyme inducers)
- Lesional Surgery (for example, tumour, amygdalo-hippocampectomy, temporal lobectomy, extra-temporal resections, anatomical hemispherectomy or functional hemispherotomy, removal of cortical seizure foci) Palliative surgery (for example, callosotomy or vagus nerve stimulator implantation)
- Structural lesions Vascular malformations Tumor Cortical Dysplasia Granulomatous Lesions
- MRI Hippocampal volumetrics > 0.5cc difference increases chances for seizure remission 1.5 mm coronal cuts with sequences sensitive to gray-white differentiation and to gliosis inversion recovery/high resonance for cortical dysplasia