1. Epilepsy Morgan Feely Consultant Physician Target Meeting Tong, November 2006

2. Epilepsy  A person is said to have ‘epilepsy’ when they have exhibited a tendency to have recurring seizures  It is not a single disease  Manifest by underlying brain dysfunction from many known or unknown causes  Single seizures should not be diagnosed as epilepsy  A patient could be said to have ‘one of the epilepsies’ as there are a number of seizure types and causes.

3. Epidemiology  Bimodal incidence  440,000 active cases in UK  Typical practice: 15 patients per 2000

5. Age-specific incidence of treated epilepsy per 100,000 persons (Source: Wallace, Shorvon, Tallis: The Lancet, 1998 Dec 19–26;352 (9145):1952-3) Age Incidence/100,000

6. The epilepsies Generalised epilepsies (mostly idiopathic)  tonic-clonic (T-C)  and/or absences  and/or myoclonic seizures Location related epilepsies (mostly symptomatic)  partial seizures  partial +/- secondary (T-C) generalisation Over 200 epilepsy syndromes described - mostly of relevance to young people

7. Seizures across the ages

8. Making the diagnosis 1 History History and / or Eye witness or…

9. First tonic-clonic seizure in an adult Clinical scenario Clinical scenario  You are asked to see a patient who collapsed and appeared to have a ‘fit’ within the last few days and is now back to normal  What are the key issues?  Seizure versus (convulsive) syncope  Provocation (late nights and alcohol, drugs) ?  Is there any evidence of previous unrecognised seizures  What is the patient’s occupation / driving status?

10. Differences between seizures and syncope SeizuresSyncope  Any posture (e.g. in bed at night)  Blue lips during attack  Stiffness and tonic-clonic movements coincide with loss of consciousness and often last for several minutes  Patient is rigid as falls to ground  Urinary incontinence common  Disorientated or headache afterwards  Tongue biting and serious injuries are common  Seizures arising from secondary generalisation may be preceded by an aura or recognisable partial seizure  Occurs standing (or sitting if elderly)  Pale and clammy  Brief jerking movements may occur after loss of consciousness  Patient loses tone then falls to ground  Urinary incontinence can occur  Quick recovery  Tongue biting rarely; serious injuries occur in 5% of cases  Often preceded by feeling warm and light headed

11. Case 1 18 year old female law student attends your surgery after suffering a ‘blackout’ following breakfast. Her housemate had said to her she had a ‘grand mal convulsion’.  Seizure versus syncope  features to support syncope or convulsive syncope…WITNESS / TELEPHONE  Provocation  Studying for exams, started drinking at university, no illicit drugs  Is there any evidence of previous unrecognised seizures  Since the age of 16 occasionally ‘daydreams’, jerks in the morning, cup of tea  What is the patient’s occupation / driving status  Student, drives a car, NB. OCP

12. Diagnosis: JME

13. Case 2 42 year old businessman attends surgery following a generalised seizure. On record he has a heavy alcohol consumption (>50 units per week), but has recently cut down.  Seizure versus syncope  No clear witness account, any eye witnesses?  Provocation  Alcohol (ab)use and cut down  Is there any evidence of previous unrecognised seizures  ‘Has had a fit before’ after binge drinking  What is the patient’s occupation / driving status  Driver. DVLA issues. Provoked seizure?

15. Case 3 42 year old businessman attends surgery with his wife who is concerned he is behaving oddly at times, repeatedly saying things over and over. On record he has a heavy alcohol consumption (>50 units per week)  Seizure versus syncope  History from wife ‘Golf-traps! Golf-traps!’, detached : complex partial seizure(s)  Provocation  Alcohol use, but not in keeping with focal seizure  Is there any evidence of previous unrecognised seizures  No  What is the patient’s occupation / driving status  Driver. Urgent investigations

16. Diagnosis:Glioblastoma

17. Case 4 A 69 year old male attends with seven attacks of speech disturbance lasting 3 minutes over the last 4 months. He has been investigated previously for TIA / stroke.  Seizure versus syncope  No evidence of syncope. Recurrent stereotypical focal neurology. Clean stroke tests.  Provocation  No evidence. Not situational. Without warning.  Is there evidence of unrecognised seizures?  No  What is the patient’s occupation / driving status?  Driver. DVLA issues

19. Case 5 You are asked to see a 73 year old lady in her RH. She had a previous Left hemi-paresis. The staff think that she has ‘had another stroke.’  Seizure versus syncope?  Speak to RH witness. ‘Vacant’ at onset with ‘jerking movements’ of left upper limb.  Provocation  Recently started antidepressant for low mood, recent UTI and ‘antibiotics’  Is their evidence of unrecognised seizures?  RH staff say she occasionally ‘switches off’ and ‘stares into space’. Recurrent ‘strokes’  Occupation / driving status  Less relevant, ‘lifestyle issues’. Avoid unnecessary tests?

21. Making the diagnosis 2

22. Making the diagnosis 3

23. Management

24. Management

25. AIMS  Prevention of seizures  Minimal side effects  Optimise QOL PRINCIPALS  Appropriate drug for patient’s seizure(s)  Appropriate drug for individual patient  Through trial and error Starting AED treatment in newly diagnosed epilepsy

26. 184018601880190019201940196019802000 0 5 10 15 20 Bromide Phenobarbital Phenytoin Primidone Ethosuximide Sodium valproate Benzodiazepines Carbamazepine Vigabatrin Zonisamide Lamotrigine Felbamate Gabapentin Topiramate Fosphenytoin Oxcarbazepine Tiagabine Levetiracetam More Year AEDS Antiepileptic drug development

27. Choice of drug  Seizure type  Women of childbearing age  Pregnancy  Breastfeeding  Children  Elderly  Learning disability

28. GENERALISED-ONSET SEIZURES PARTIAL-ONSET SEIZURES Absence myoclonic tonic / atonic primary T-C simple complex-partial secondary generalisation EthosuxamideCARBAMAZEPINE PhenytoinVigabatrinGabapentinOxcarbazepineVALPROATELAMOTRIGINELevetiracetamTopiramatePhenobarbitalBenzodiazepines Treatment options by seizure type

29. Initial (first line) treatment Drugs for generalised seizures  Valproate (Epilim Chrono)  Lamotrigine  [Topiramate] Drugs for partial seizures (+/- secondary generalisation)  Carbemazepine (Tegretol Retard)  Lamotrigine  Valproate (Epilim Chrono)  Levetiracetam  [Topiramate ]

30. Sodium valproate (Epilim Chrono)  Useful for location related and generalised epilepsy  Can be brought up to therapeutic dose quickly  Low(er) doses tolerated and possibly drug of choice for elderly patients  Can cause tiredness, tremor, weight gain, alopecia  Teratogenic (spina bifida)

31. Carbamazepine (Tegratol)  Good drug for partial seizures in young(er) adults  Needs gradual build up to a therapeutic dose  Enzyme-inducer, therefore interactions/oestoporisis  Most specialists use MR (Tegretol Retard)

32. Lamotrigine (Lamictal)  Broad spectrum  Good tolerability as monotherapy  Well tolerated by the elderly  Synergistic effect with sodium valproate  Least teratogenic  Needs to build up slowly (months) to reduce AEs  Rash common, sometimes severe and associated with Steven- Johnson’s syndrome  Blood dyscrasias

33. Newer second line agents - Levetiracetam (Keppra)  Relatively new but appears well tolerated and efficacious  Monotherapy licence  Licensed for partial seizures +/- secondary generalisation (may be effective in other seizure types)  Can be started at close to therapeutic range  Sedation common, though tends to resolve  Long-term experience still lacking

34. Newer second line agents - Topiramate  Potent anticonvulsant activity  Useful for most forms of epilepsy  Often not tolerated due to side effects: confusion, word-finding difficulties, weight loss  Needs slow induction

35. When to start treatment  What is the cause?  What is the risk of recurrence?  First Vs second seizure?  What does the patient / carer think?

36. Poor control Concurrent pro-convulsant drugsAlcohol prescription LifestyleSleep Stress Concordance / complianceWhy? ADR other drugs Social aspects

37. Treatment errors Incorrect / incomplete detection of seizure(s) resulting in inappropriate drug choice. Appropriate drug for the seizure(s), but not the patient. Wrong dose (high or low) Seizures are controlled, but intolerance / SE are a problem. The occurrence of a progressive neurological condition

38. Prognosis 70 – 80% prolonged remission Poor controlStructural lesion EEG abnormality Associated neuropsychiatric disorder More than one drug ? SUDEP

39. AED withdrawal Seizure free (remission) > 3 (2?) years Overall risk of recurrence is 40% Most relapses occur within the first year off treatment Factors increasing relapse; syndrome, structural abnormality, severe epilepsy before remission, age. Discussion risk versus continued therapy DVLA – 6 month suspension Leisure pursuits Contraception / pregnancy etc

40. Service Level Primary Care GMS Referral First seizure Poor control Special cases AED withdrawal Follow-up if stable Re-refer Secondary care Establish diagnosis initiate treatment Follow up Difficult control Tertiary referral Neuro-oncologyObstetricsElderly Epilepsy Nurse specialists