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Michelle Knight and Aideen Tarpey Epilepsy Specialist Nurses – Dorset Epilepsy Service • ‘Epilepsy’ is not a diagnosis per se but a symptom • Annual incidence of around 50 cases per 100,000 • Most common serious neurological condition • 40 types of seizures • Higher prevalence in young and elderly • Increased mortality & morbidity: – Standardised mortality ratio 2-4 times matched background: – Risk of death 23 times higher if uncontrolled seizures – Increased unemployment and dependency – Significant adverse side-effects associated with AEDs SEIZURE TYPES • Seizures previously classed as “Grand Mal” or “Petit Mal” • These terms were considered too general as over 40 types of seizures • Reclassified in 1981 by ILAE GENERALISED • • • • • Tonic – clonic Tonic Atonic Absence Myoclonic PARTIAL • Simple – Partial • Complex – Partial • Secondary Generalised Is treatment necessary? • • • • • • • Cumulative risk of single seizure 5% Risk of 2nd seizure 50-80% within 3 years 75% of these recur within 1 year Focal & tonic-clonic seizures more likely Syndromic diagnosis may provide more information After 2-5 years of seizure freedom: 60% seizure free (vs 80% of those still on AED) Available anticonvulsants • Acetazolamide (1952) • Phenobarbital (1912) • Benzodiazepines (1950’s) • Phenytoin (1952) • Carbamazepine (1964) • Piracetam (1967; myoclonus 1978) • Ethosuximide (1958) • Rufinamide (2008) • Felbamate (USA – 1980’s) • Stiripentol (2007) • Gabapentin (1990’s) • Tiagabine (1990’s) • Lacosamide (2008) • Topiramate (1990’s) • Lamotrigine (1990’s) • Valproate (late 1960’s) • Levetiracetam (2000) • Vigabatrin (1990’s) • Oxcarbazepine (1980’s; UK 2000) • Zonisamide (Japan 1970’s) Available AEDs 25 20 15 10 5 0 1900 1950 2000 Starting medication • Choice of AED depends on individual factors • Start low, go slow • If not tolerated or not effective substitute alternative • At least two trials of single agent at reasonable dose • Little additional benefit for more than 2 agents First Line Treatment • • • • • • • • Carbamazepine Lamotrigine Sodium Valproate Topirimate Oxcarbazepine Levetiracetam Ethosuximide Phenytoin Second line treatment • • • • • • • • Acetazolamide Clobazam Clonazepam Gabapentin Lacosamide Phenobarbitone Phenytoin Piracetam • • • • • • • • Zonisimide Pregabalin Vigabatrin Tiagabine Stiripentol Rufinamide Primidone Topirimate Levetiracetam (Keppra) • Monotherapy for partial onset seizures with or without • • • secondary generalisation in patients from 16 years of age Adjunctive therapy for partial onset seizures with or without secondary generalisation in adults and children from 4 years of age Adjuctive therapy for myoclonic seizures in adults and adolescents from 12 years of age with JME Adjunctive therapy for primary generalised tonic-clonic seizures in adults and adolescents from 12years of age with Idiopathic Generalised Epilepsy The future…… • Once daily preparation of Sodium Valproate Chrono (Episenta) already being widely used • Zebinix – Once daily, evolved from Carbamazepine (but without many of the side effects) adjunctive therapy • More drugs in development…… Response to medication • Remission on single drug 60-80% • Dose required often relatively modest • Failure on first drug due to: – Adverse reaction - 48% – Lack of efficacy - 21% • 92% who go into remission do so in 3yrs • Compliance with medication may be a significant issue • Interactions with other medications Rescue medication • Diazepam • Buccal midazolam (Epistatus) • Emergency care plan and training needed in administration, epilepsy awareness and first aid. Generic vs. branded • “changing the formulation or brand of AED is not recommended because different preparations may vary in bioavailability or have different pharmacokinetic profiles and, thus, increased potential for reduced effect or excessive side effects.” NICE Contraception • Enzyme inducing drugs (carbamazepine, • • • oxcarbazepine, phenobarbital, phenytoin, primidone, topirimate and lamotrigine) reduce the effectiveness of hormonal contraception Lamotrigine may make the COC less effective and the COC may reduce the amount of lamotrigine in the blood stream (HRT may also do the same) Contraception not affected by AED’s include Barrier methods, Depro-Provera, IUD’s and IUS (mirena coil) Morning after pill – if on enzyme inducing drug, need 3milligrams of levonorgestrel instead of 1.5 milligrams Pregnancy • Women of childbearing age with epilepsy should • • • • • take folic acid 5 milligrams a day. This should be continued throughout the pregnancy. (folic acid may interact with Phenytoin, phenobarbitone and primidone making them less effective) Sodium valproate – PCOS risk may increase if taken from an early age Pre-conceptual counselling – first three months of pregnancy, risk is greatest Sudden stopping of medication not advised Balance of risk of seizures / drug therapy MCM – damaged spine, heart problems, cleft palate, hernia. Minor malformations MCM’s • • • • • • • • • • • UK Epilepsy and Pregnancy register General population risk is 1-2 babies in 100 will have MCM Mothers who take AED’s, 4 in 100 will have MCM Higher risk if more than 1 AED Sodium Valproate is thought to carry highest risk (look at rationalising – Chrono) Fetal anti-convulsant syndrome Breast feeding Seizures during pregnancy Vitamin K 10-20mg during last month of pregnancy if on enzyme inducing drug Pethadine not recommended Management once baby is born Osteoporosis and AED’s • Using AED’s long term can be a risk factor for bone loss and fractures • In particular, carbamazepine, phenobarbital, phenytoin, primidone and sodium valproate • Assess each patient and if necessary, refer for bone density scan Thank you! Any Questions? Dorset Epilepsy Service – 01202 442231 / 01202 448486 [email protected]