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Richard E. Frye, M.D., Ph.D. Assistant Professor of Pediatrics and Neurology

Subclinical epileptiform discharges in atypical cognitive development, and a Review of Antiepileptic Drugs. Richard E. Frye, M.D., Ph.D. Assistant Professor of Pediatrics and Neurology University of Texas Health Science Center. Subject Population. 22 children

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Richard E. Frye, M.D., Ph.D. Assistant Professor of Pediatrics and Neurology

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  1. Subclinical epileptiform discharges in atypical cognitive development, and a Review of Antiepileptic Drugs. Richard E. Frye, M.D., Ph.D. Assistant Professor of Pediatrics and Neurology University of Texas Health Science Center

  2. Subject Population 22 children 1 - Atypical cognitive development 2 - Subclinical epileptiform discharges on EEG 3 - Two or more EEG Studies. Age: Average: 5 years 11 months Range: 1 year 11 months to 11 years 1 month MRI: 26% Abnormal 80% Left Hippocampus Abnormalities 20% Cortical Dysplasias

  3. Presenting Symptoms. FEW WITH REGRESSION OR FLUCTUATIONS

  4. Specific Developmental Cognitive Profile

  5. Location of Epileptiform Discharges IS NOT Consistent Probably Not Specific to Disorder

  6. Magnetoencephalography (MEG) “Recording neuromagnetic signals is like listening for the footsteps of an ant in the middle of a rock concert” Dewar filled with helium Magnetically-shielded room VectorView system Neuromag

  7. Does Discharge Lateralization on MEG? Only Consistent across two MEGs in 66% Lateralization of MEG match EEG in 40% Lateralization of MEG Spikes May Match Cognitive Symptoms but Sample Size Small

  8. AED treatment Improves Symptoms

  9. Could this be due to Chance or Placebo Effect? 50% of patients were followed for several months to years before starting AED treatment

  10. Does Discontinuing Medication Result in Regression ? AEDs were withdrawn in three patients. This resulted in regression. Reinstitution of AED Improved Cognitive Function

  11. Children with subclinical discharges and developmental delays • Represent a specific phenotype? Yes • Language, Learning or Memory Difficulties • Regression not typical • Current of History of Speech of Language Disorder • ADHD and mild symptoms of PDD common • 2) Do Specific EEG findings that correlate with symptoms? No • Appears to be a True Encephalopathy • Sharp waves on EEG without specific • or consistent lateralization or localization • 3) Is this syndrome treatable? Yes • Good Response to AEDs

  12. Mechanism of Action for Antiepileptic Drugs

  13. Antiepileptic Drugs • Classical • Phenytoin • Phenobarbital • Primidone • Carbamazepine • Ethosuximide • Valproic Acid • Trimethadione • Newer • Lamotrigine • Felbamate • Topiramate • Gabapentin • Tiagabine • Vigabatrin • Oxycarbazepine • Levetiracetam

  14. Phenytoin • Slow, incomplete and variable absorption. • Extensive binding to plasma protein. • Complicated Kinetic • Can be Difficult to Manage in Children • Toxicity / Side Effects • Dose related vestibular/cerebellar effects • Behavioral changes • Gingival Hyperplasia • GI Disturbances • Sexual-Endocrine Effects: • Osteomalacia, Hirsutism, Hyperglycemia

  15. Valproic Acid • Effective for a wide spectrum of seizure types. • Effective for subclinical discharges and LKS • Effective for behavior & psychiatric disorders • Requires Monitoring Blood Tests • Liver, Pancreas and Blood Counts Toxicity / Side Effects Fulminate hepatic failure. Most common in children < 2 yo. Cotreat w/ L-Carnitine to Protect the Liver Pancreatitis Anemia, Thrombocytopenia

  16. Ethosuximide • Effective for Absence seizures • Long Half-life Toxicity / Side Effects Gastric distress—pain, nausea, vomiting. Weight Loss Behavior Changes Changes in Blood Counts.

  17. Oxcarbazepine (Trileptal) • Good for Partial (Focal) seizures • Unlike Carbamazapine it has linear kinetic • Effective for behavior & psychiatric disorders Toxicity / Side Effects • Usually Mild Side Effects • Behavioral and Cognitive Problems • CAN MAKE SOME SEIZURES WORSE • Hyponatremia

  18. Lamotrigine • Effective against generalized seizures • Wide Spectrum of Effectiveness. • Effective for behavior & psychiatric disorders • Possibly Cognitively Enhancing in bipolar disorder • NEED TO INCREASE SLOWLY Toxicity / Side Effects • Side Effects Mild • Potentially life-threatening Rash (Stevens-Johnson Reaction) in 1-2% of pediatric patients. This depends on the initial rate of increase in the dose. SO GO SLOW

  19. Levetiracetam (Keppra) • Reportedly very effective on multiple seizure types but too soon to know specifics effectiveness • Minimal Drug Interactions • IV and Liquid Formulation • Extended Release Formulation Toxicity / Side Effects • Side Effects Mild • Behavioral Side Effects Potentially Severe in a small number of patients. May respond to B6

  20. Topiramate (Topomax) • Effective for a Wide Range of Seizure Types • Effective in Neonatal Seizures. • Effective for behavior & psychiatric disorders • Very Effective for Migraine Headaches Toxicity / Side Effects • Psychomotor slowing and concentration prob • Speech Difficulties • Metabolic Acidosis • Weight Loss, Appetite Suppression • Glaucoma, Oligohidrosis, Nephrolithiasis

  21. Subclinical epileptiform discharges in atypical cognitive development, and a Review of Antiepileptic Drugs. Questions ?

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