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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
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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
Age-specific incidence of treated epilepsy per 100,000 persons(Source: Wallace, Shorvon, Tallis: The Lancet, 1998 Dec 19–26;352 (9145):1952-3) Incidence/100,000 Age
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 The epilepsies Over 200 epilepsy syndromes described - mostly of relevance to young people
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?
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
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?
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
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?
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
Antiepileptic drug development More AEDS 20 Levetiracetam Oxcarbazepine Tiagabine Fosphenytoin 15 Topiramate Gabapentin Felbamate Lamotrigine Zonisamide 10 Vigabatrin Sodium valproate Carbamazepine Benzodiazepines Ethosuximide 5 Primidone Phenobarbital Bromide Phenytoin 0 1840 1860 1880 1900 1920 1940 1960 1980 2000 Year
Choice of drug • Seizure type • Women of childbearing age • Pregnancy • Breastfeeding • Children • Elderly • Learning disability
Treatment options by seizure type GENERALISED-ONSET SEIZURESPARTIAL-ONSET SEIZURES Absence myoclonic tonic / atonic primary T-C simple complex-partial secondary generalisation EthosuxamideCARBAMAZEPINE Phenytoin Vigabatrin Gabapentin Oxcarbazepine VALPROATE LAMOTRIGINE Levetiracetam Topiramate Phenobarbital Benzodiazepines
Drugs for generalised seizures Valproate (Epilim Chrono) Lamotrigine [Topiramate] Drugs for partial seizures (+/- secondary generalisation) Carbemazepine (Tegretol Retard) Lamotrigine Valproate (Epilim Chrono) Levetiracetam [Topiramate ] Initial (first line) treatment
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) Sodium valproate (Epilim Chrono)
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)
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 Lamotrigine (Lamictal)
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 - Levetiracetam (Keppra)
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 Newer second line agents - Topiramate
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 • Concordance / compliance Why? • ADR • other drugs • Social aspects
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
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 Service Level Epilepsy Nurse specialists