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 onsetCarbamazepineValproate, lamotrigine, oxcarbazepine, ?

topiramate (less efficacy, more tolerability?)

Generalised seizuresValproateLamotrigine, 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 retard2/3 efficacy of “regular” CBZ dose for doseDrug levels may be of no value

Epilim chronoDose for dose equivalenceOnce daily dosing

New drugs… old

LamotrigineNa channels like CBZ & PHTOther mysterious mechanisms

Slow build up to avoid rash (up to 10%)Halve dose of LTG if adding VPAUse starter packs for adding into othersNTD 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 possibleMaintenance 1.5X CBZ600-2400mg/day usual

High dose pill needed

New drug

LevetiracetamUnique mysterious mode of actionBroad 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 lesionClinical seizure type and EEG consistent with

the lesionNot an “important” bit of brainCareful 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