Epilepsy update Martin Sadler

Issues Who to treat and when to start? Who needs investigations? What to start with? Treatment aims New drugs What to do when it all goes pear shaped? Epilepsy surgery and gadgets When to stop?

Who to treat One seizure or two? (24-64% 2 year risk of recurrence) Benefits of treatment vs natural history (two year risk halved from 40 to 20%, but no effect on longer term remission rate) Overall prognosis (70% 5 year remission, 80% no seizures at 10 years, at 15 years 50% not on treatment) What to tell those who do not want treatment Mind over matter

Who to investigate Any epilepsy commencing after 25 years of age… imaging Epilepsy under 25 years which cannot be classified as partial or generalised… EEG and imaging Below 25, EEG and image if not IGE

What to start with Most adult seizures are focal onset  Carbamazepine  Valproate, lamotrigine, oxcarbazepine, ?topiramate (less efficacy, more tolerability?) Generalised seizures  Valproate  Lamotrigine, topiramate (?better tolerated, less ADR)

Women 40% of patients are women of childbearing age Women with epilepsy account for 0.5% of all pregnancies 2% women with epilepsy have fits during labour Uncontrolled epilepsy is a greater risk than drug therapy to mother and baby

Teratogenicity risk Monotherapy 4-6% Dual therapy 7-8% Polytherapy 15-20% NTD CBZ 0.5-1% VPA 2%+ (? At above 1g/day) Foetal anticonvulsant syndrome with orofacial clefts, distal digital anomalies and learning disability +/- cardiac defects attributed to several AEDs.

What to do Secure diagnosis Lowest effective doses Few drugs Add folate 5mg/d (NB distal neuropore closed 27d, palate fused 47d)

New drugs… retreads Tegretol retard  2/3 efficacy of “regular” CBZ dose for dose  Drug levels may be of no value Epilim chrono  Dose for dose equivalence  Once daily dosing

New drugs… old Lamotrigine  Na channels like CBZ & PHT  Other mysterious mechanisms  Slow build up to avoid rash (up to 10%)  Halve dose of LTG if adding VPA  Use starter packs for adding into others  NTD rate = CBZ

Further old new drugs Topiramate  5 mechanisms of action  Long half life, can be used once daily  Efficacious  Recent monotherapy licence  Begin v low (15mg sprinkle) and build slowly  Wt loss 10-20% patients (? Add to VPA). Renal stones  Teratogenic? Animal studies: distal limb abnormalities  Increases oestrogen metabolism

New drugs in UK Oxcarbazepine  “tegretol lite”  No self induced metabolism so rapid introduction possible  Maintenance 1.5X CBZ  mg/day usual  High dose pill needed

New drug Levetiracetam  Unique mysterious mode of action  Broad spectrum including in myoclonia, absence and photosensitivity  Effective dose 1-3g/day  ? Wt loss  ?teratogenicity

Others Tiagibine  Marred by vigabatrin worries  Raises GABA at GABAergic synapses  Add in for focal onset seizures (50% seizure reduction in 40% patients in studies)  30mg day divided doses usually  No important interactions but half life shortened by CBZ and PHT so tds needed (use 20mg tds)

Defunct drugs Vigabatrin  Suicidal inhibitor of GABA transaminase thus raising GABA  Effective AED  Concentric field reduction in 40-60%  If continued monitor fields every 6 months  No interactions  No teratogenicity so far  5% depression (esp if rapid changes)

Surgery Effective if:  Discrete lesion  Clinical seizure type and EEG consistent with the lesion  Not an “important” bit of brain  Careful selection needed  80% seizure freedom

Vagal nerve stimulator Left vagal nerve wrapped by stimulator electrode May be good for drop attacks May reduce seizures in otherwise intractable patients (similar to adding new AED) Expensive

Buccal midazolam As effective as rectal diazepam Easier to administer Off licence at present Epilepsy specialist nurse sends out information on use