epilepsy

Epilepsy Morgan Feely Consultant Physician Target Meeting Tong, November 2006 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. Epidemiology  Bimodal incidence  440,000 active cases in UK  Typical practice: 15 patients per 2000 9.5 9 8.5 8 7.5 7 6.5 Age-specific prevalence of treated epilepsy per 1000 persons Source: Wallace, Shorvon, Tallis, Lancet Prevalence/100 0 6 5.5 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Age Age-specific incidence of treated epilepsy per 100,000 persons (Source: Wallace, Shorvon, Tallis: The Lancet, 1998 Dec 19–26;352 (9145):1952-3) 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Incidence/100,000 Age 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 Seizures across the ages Teens/early 20’s JME Primary generalised (T-C) Partial +/secondary T-C Late 20’s – 50’s Alcohol / drugs Brain tumours SAH Head injury Late 50’s – 80+ Cerebrovascular disease Dementias Brain tumours Metabolic disorders eg low Na Late presentation of earlier types Continuation of childhood/earlier epilepsy Making the diagnosis 1 History History and / or Eye witness or… First tonic-clonic seizure in an adult 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? Differences between seizures and syncope Seizures  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 Syncope  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 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 Diagnosis: JME 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? Alcohol (ab)use and cut down  Provocation  Is there any evidence of previous unrecognised seizures   ‘Has had a fit before’ after binge drinking Driver. DVLA issues. Provoked seizure?  What is the patient’s occupation / driving status 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) Alcohol use, but not in keeping with focal seizure  Provocation  Is there any evidence of previous unrecognised seizures   No Driver. Urgent investigations  What is the patient’s occupation / driving status Diagnosis: Glioblastoma 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 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? Making the diagnosis 2 Making the diagnosis 3 Management Management Starting AED treatment in newly diagnosed epilepsy AIMS  Prevention of seizures  Minimal side effects  Optimise QOL  Appropriate drug for individual patient  Through trial and error PRINCIPALS  Appropriate drug for patient’s seizure(s) Antiepileptic drug development AEDS 20 More Levetiracetam Tiagabine Oxcarbazepine Fosphenytoin Gabapentin 15 Topiramate Felbamate 10 Zonisamide Sodium valproate Ethosuximide Lamotrigine Vigabatrin Carbamazepine Benzodiazepines 5 Bromide Phenobarbital Primidone Phenytoin 1880 1900 1920 1940 1960 1980 2000 0 1840 1860 Year Choice of drug  Seizure type  Women of childbearing age  Pregnancy  Breastfeeding  Children  Elderly  Learning disability Treatment options by seizure type GENERALISED-ONSET SEIZURES PARTIAL-ONSET SEIZURES Absence myoclonic tonic / atonic primary T-C simple complex-partial secondary generalisation Ethosuxamide CARBAMAZEPINE Phenytoin Vigabatrin Gabapentin Oxcarbazepine VALPROATE LAMOTRIGINE Levetiracetam Topiramate Phenobarbital Benzodiazepines Initial (first line) treatment Drugs for generalised seizures Drugs for partial seizures (+/secondary generalisation)  Valproate (Epilim Chrono)  Lamotrigine  Carbemazepine (Tegretol Retard)  Lamotrigine  [Topiramate]  Valproate (Epilim Chrono)  Levetiracetam  [Topiramate ] 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) 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) 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 StevenJohnson’s syndrome  Blood dyscrasias 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 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 When to start treatment  What is the cause?  What is the risk of recurrence?  First Vs second seizure?  What does the patient / carer think? Poor control • Concurrent pro-convulsant drugs Alcohol prescription • Lifestyle Sleep Stress Why? ADR other drugs Social aspects • Concordance / compliance 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 Prognosis • 70 – 80% prolonged remission • Poor control Structural lesion EEG abnormality Associated neuropsychiatric disorder More than one drug ? • SUDEP 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 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-oncology Obstetrics Elderly Epilepsy Nurse specialists