Seizures and Epilepsy Dr. Khalid El-Salem American Board of Neurology American Board of Clinical Neurophysiology Assistant Prof of Neurology JUST
Concepts Seizure: sudden temporary change in brain function caused by an abnormal rhythmic excessive electrical discharge Epilepsy: a state of recurrent seizures
Epidemiology of Epilepsy Lifetime risk of developing epilepsy is 3.2% 10% of population experience at least one seizure before the age of 80 years Higher prevalence at the extremes of age
Seizure Type Versus Epileptic Syndrome A seizure type is determined by the patient’s behavior and EEG pattern during the ictal event An epileptic syndrome is defined by - Seizure type(s) - Natural history - EEG (ictal and interictal) - Response to AEDs - Etiology
Classification of Seizures Partial seizures - Simple partial seizures - Complex partial seizures Impaired consciousness at outset Simple partial evolving to lost consciousness - Partial seizures evolving to general tonic-clonic seizures (GTCS)
Absence Seizure Simple: abrupt onset and cessation of motionless stare, with unresponsiveness and no post ictal state ( few-30 sec) Complex: typical+clonic/myoclonic activity or automatism Activated by hyperventilation
Complex Partial Seizures Prodrome: Lethargy Aura: common Oral or motor automatism, alteration of consciousness, head and eye deviation, contralateral twitching or clonic movements, posturing Rt temporal often hypermobile Lt temporal often behaviour arrest
Frontal lobe seizures are partial seizures that can be easily confused with psychiatric disease
Acquired Epilepsy Trauma Infection Vascular disease Metabolic changes Tumor Age effects on brain
Applications of New AEDs in EpilepsyMedication Application in Epilepsy Felbamate Some efficacy in all seizure types Gabapentin Partial and sec generalized tonic clonic seizures only Lamotrigine Some efficacy in all seizure typesLevetiracetam Partial and sec generalized tonic clonic seizuresOxcarbazepine Partial and sec generalized tonic clonic seizures Tiagabine Partial and sec generalized tonic clonic seizures only Topiramate Some efficacy in all seizure types Vigabatrin Infantile spasms, Partial seizures Zonisamide Some efficacy in all seizure types
Cognetive Effects of AEDs Minimal- some Significant None Gabapentin Phenytoin Phenobarbital Tiagabine Carbamazepine Primidone Lamotrigine Valproate TopiramateOxcarbazepine ZonisamideLevitiracetam
Therapeutic Drug Monitoring for Newer AEDs• Not widely practiced• No generally accepted target ranges• A wide range is associated with clinical efficacy.• Considerable overlap in drug concentrations related to toxicity and non response.
Tentative Target Concentration Ranges Medication Range Felbamate 40-100 mic g/ml Gabapentin >2 mic g/ml Lamotrigine 1-4 mic g/ml Levetiracetam 35-120 mic m/L Oxcarbazepine 4-12 mic g/ ml Tiagabine 50-250 nmol/L Topiramate 2-4 mic g/ml Vigabatrin 6-278 mic m/L Zonisamide 10-30 mic g/ml
AAN Evidence Based Guidelines Level A or B Recommendations Newly Diagnosed Epilepsy Medication Monotherapy for newly Newly diagnosed absence diagnosed partial/mixedFelbamateGabapentin Yes NoLamotrigine Yes YesLevetiracetam No NoOxcarbazepine Yes NoTiagabine No NoTopiramate Yes NoVigabatrinZonisamide No No
AAN Evidence Based Guidelines Level A or B Recommendations Refractory EpilepsyMedication Partial Partial Primary Symptomatic Peds Add on/adult Monotherapy Generalized Generalized PartialFelbamateGabapentin Yes No No No YesLamotrigine Yes Yes No Yes YesLevetiracetam Yes No No No NoOxcarbazepine Yes Yes No No YesTiagabine Yes No No No NoTopiramate Yes Yes Yes Yes YesVigabatrinZonisamide Yes No No No No
Conclusions New AED’s are not more effective than classical ones Classical AEDs remain first line of treatment Pharmacokinetics and dynamics are more determinent than efficacy.