EpilepsyEpilepsy

Morgan FeelyMorgan Feely

Consultant Physician Consultant Physician Target MeetingTarget Meeting

Tong, November 2006Tong, November 2006

EpilepsyEpilepsy

A person is said to have ‘epilepsy’ when they have exhibited a A person is said to have ‘epilepsy’ when they have exhibited a tendency to have recurring seizurestendency to have recurring seizures

It is not a single diseaseIt is not a single disease

Manifest by underlying brain dysfunction from many known or Manifest by underlying brain dysfunction from many known or unknown causesunknown causes

Single seizures should not be diagnosed as epilepsySingle seizures should not be diagnosed as epilepsy

A patient could be said to have ‘one of the epilepsies’ as there A patient could be said to have ‘one of the epilepsies’ as there are a number of seizure types and causes.are a number of seizure types and causes.

EpidemiologyEpidemiology

Bimodal incidenceBimodal incidence

440,000 active cases in UK440,000 active cases in UK

Typical practice: 15 patients per 2000Typical practice: 15 patients per 2000

Age-specific prevalence of treated epilepsy per 1000 persons Source: Wallace, Shorvon, Tallis, Lancet

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

5.5

6

6.5

7

7.5

8

8.5

9

9.5

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

Prevalence/100

0

0

10

20

30

40

5060

70

80

90

100

110

120

130

140

150160

170

180

190

200

210

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-specific incidence of treated epilepsy per 100,000 personsAge-specific incidence of treated epilepsy per 100,000 persons(Source: Wallace, Shorvon, Tallis: The Lancet, 1998 Dec 19–26;352 (Source: Wallace, Shorvon, Tallis: The Lancet, 1998 Dec 19–26;352

(9145):1952-3)(9145):1952-3)

Age

Incid

en

ce/1

00

,00

0

The epilepsiesThe epilepsies

Generalised epilepsiesGeneralised epilepsies

(mostly idiopathic)(mostly idiopathic)

tonic-clonic (T-C)tonic-clonic (T-C) and/or absencesand/or absences and/or myoclonic and/or myoclonic

seizuresseizures

Location relatedLocation related

epilepsiesepilepsies

(mostly symptomatic)(mostly symptomatic)

partial seizurespartial seizures partial +/- secondary partial +/- secondary

(T-C) generalisation(T-C) generalisation

Over 200 epilepsy syndromes described - mostly of relevance to young people

Seizures across the agesSeizures across the ages

Teens/early 20’s Late 20’s – 50’s Late 50’s – 80+

JME Alcohol / drugs Cerebrovascular disease

Primary generalised (T-C)

Brain tumours

Dementias

SAH Brain tumours

Partial +/- secondary T-C

Head injury

Metabolic disorders eg low Na

Late presentation of earlier types

Continuation of childhood/earlier epilepsy

Making the diagnosis 1Making the diagnosis 1

History

History and / or

Eye witness or…

First tonic-clonic seizure in an adultFirst tonic-clonic seizure in an adult

Clinical scenarioClinical scenario

You are asked to see a patient who collapsed and You are asked to see a patient who collapsed and appeared to have a ‘fit’ within the last few days and is appeared to have a ‘fit’ within the last few days and is now back to normalnow back to normal

What are the key issues?What are the key issues? Seizure versus (convulsive) syncopeSeizure versus (convulsive) syncope Provocation (late nights and alcohol, drugs) ?Provocation (late nights and alcohol, drugs) ? Is there any evidence of previous unrecognised seizures Is there any evidence of previous unrecognised seizures What is the patient’s occupation / driving status?What is the patient’s occupation / driving status?

Differences between seizures and syncopeDifferences between seizures and syncope

SeizuresSeizures SyncopeSyncope

Any posture (e.g. in bed at night)Any posture (e.g. in bed at night) Blue lips during attackBlue lips during attack Stiffness and tonic-clonic movements Stiffness and tonic-clonic movements coincide with loss of consciousness and coincide with loss of consciousness and often last for several minutesoften last for several minutes Patient is rigid as falls to groundPatient is rigid as falls to ground Urinary incontinence commonUrinary incontinence commonDisorientated or headache afterwardsDisorientated or headache afterwardsTongue biting and serious injuries are Tongue biting and serious injuries are commoncommonSeizures arising from secondary Seizures arising from secondary generalisation may be preceded by an generalisation may be preceded by an aura or recognisable partial seizureaura or recognisable partial seizure

Occurs standing (or sitting if elderly)Occurs standing (or sitting if elderly) Pale and clammyPale and clammy Brief jerking movements may occur Brief jerking movements may occur

after loss of consciousnessafter loss of consciousness

Patient loses tone then falls to groundPatient loses tone then falls to ground Urinary incontinence can occurUrinary incontinence can occur

Quick recoveryQuick recovery

Tongue biting rarely; serious injuries Tongue biting rarely; serious injuries occur in 5% of casesoccur in 5% of cases

Often preceded by feeling warm and Often preceded by feeling warm and light headedlight headed

Case 1Case 1

18 year old female law student attends your surgery after 18 year old female law student attends your surgery after

suffering a ‘blackout’ following breakfast. Her housemate suffering a ‘blackout’ following breakfast. Her housemate

had said to her she had a ‘grand mal convulsion’.had said to her she had a ‘grand mal convulsion’.

Seizure versus syncopeSeizure versus syncope features to support syncope or convulsive syncope…WITNESS / TELEPHONEfeatures to support syncope or convulsive syncope…WITNESS / TELEPHONE

ProvocationProvocation Studying for exams, started drinking at university, no illicit drugsStudying for exams, started drinking at university, no illicit drugs

Is there any evidence of previous unrecognised seizuresIs there any evidence of previous unrecognised seizures Since the age of 16 occasionally ‘daydreams’, jerks in the morning, cup of teaSince the age of 16 occasionally ‘daydreams’, jerks in the morning, cup of tea

What is the patient’s occupation / driving statusWhat is the patient’s occupation / driving status Student, drives a car, NB. OCPStudent, drives a car, NB. OCP

Diagnosis: JMEDiagnosis: JME

Case 2Case 2

42 year old businessman attends surgery following a 42 year old businessman attends surgery following a generalised seizure. On record he has a heavy alcohol generalised seizure. On record he has a heavy alcohol consumption (>50 units per week), but has recently cut consumption (>50 units per week), but has recently cut down. down.

Seizure versus syncopeSeizure versus syncope No clear witness account, any eye witnesses?No clear witness account, any eye witnesses?

ProvocationProvocation Alcohol (ab)use and cut downAlcohol (ab)use and cut down

Is there any evidence of previous unrecognised seizuresIs there any evidence of previous unrecognised seizures ‘‘Has had a fit before’ after binge drinkingHas had a fit before’ after binge drinking

What is the patient’s occupation / driving statusWhat is the patient’s occupation / driving status Driver. DVLA issues. Provoked seizure?Driver. DVLA issues. Provoked seizure?

Case 3Case 3

42 year old businessman attends surgery with his wife who 42 year old businessman attends surgery with his wife who is concerned he is behaving oddly at times, repeatedly is concerned he is behaving oddly at times, repeatedly saying things over and over. On record he has a heavy saying things over and over. On record he has a heavy alcohol consumption (>50 units per week) alcohol consumption (>50 units per week)

Seizure versus syncopeSeizure versus syncope History from wife ‘Golf-traps! Golf-traps!’ , detached : complex History from wife ‘Golf-traps! Golf-traps!’ , detached : complex partial seizurepartial seizure(s)(s)

ProvocationProvocation Alcohol use, but not in keeping with focal seizureAlcohol use, but not in keeping with focal seizure

Is there any evidence of previous unrecognised seizuresIs there any evidence of previous unrecognised seizures NoNo

What is the patient’s occupation / driving statusWhat is the patient’s occupation / driving status Driver. Urgent investigationsDriver. Urgent investigations

Diagnosis:Diagnosis:

GlioblastomaGlioblastoma

Case 4Case 4

A 69 year old male attends with seven attacks of speech A 69 year old male attends with seven attacks of speech

disturbance lasting 3 minutes over the last 4 months. He disturbance lasting 3 minutes over the last 4 months. He

has been investigated previously for TIA / stroke.has been investigated previously for TIA / stroke.

Seizure versus syncopeSeizure versus syncope No evidence of syncope. Recurrent stereotypical focal neurology. Clean stroke tests.No evidence of syncope. Recurrent stereotypical focal neurology. Clean stroke tests.

ProvocationProvocation No evidence. Not situational. Without warning.No evidence. Not situational. Without warning.

Is there evidence of unrecognised seizures?Is there evidence of unrecognised seizures? NoNo

What is the patient’s occupation / driving status?What is the patient’s occupation / driving status? Driver. DVLA issuesDriver. DVLA issues

Case 5Case 5

You are asked to see a 73 year old lady in her RH. She had a 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 ‘hadprevious Left hemi-paresis. The staff think that she has ‘had

another stroke.’another stroke.’

Seizure versus syncope?Seizure versus syncope? Speak to RH witness. ‘Vacant’ at onset with ‘jerking movements’ of left upper limb. Speak to RH witness. ‘Vacant’ at onset with ‘jerking movements’ of left upper limb.

ProvocationProvocation Recently started antidepressant for low mood, recent UTI and ‘antibiotics’Recently started antidepressant for low mood, recent UTI and ‘antibiotics’

Is their evidence of unrecognised seizures?Is their evidence of unrecognised seizures? RH staff say she occasionally ‘switches off’ and ‘stares into space’. Recurrent ‘strokes’RH staff say she occasionally ‘switches off’ and ‘stares into space’. Recurrent ‘strokes’

Occupation / driving statusOccupation / driving status Less relevant, ‘lifestyle issues’. Avoid unnecessary tests?Less relevant, ‘lifestyle issues’. Avoid unnecessary tests?

Making the diagnosis 2Making the diagnosis 2

Making the diagnosis 3Making the diagnosis 3

ManagementManagement

ManagementManagement

AIMSAIMS

Prevention of seizuresPrevention of seizures

Minimal side effectsMinimal side effects

Optimise QOLOptimise QOL

PRINCIPALSPRINCIPALS

Appropriate drug for Appropriate drug for patient’s seizure(s)patient’s seizure(s)

Appropriate drug for Appropriate drug for individual patientindividual patient

Through trial and errorThrough trial and error

Starting AED treatment in newly diagnosed epilepsyStarting AED treatment in newly diagnosed epilepsy

1840 1860 1880 1900 1920 1940 1960 1980 2000

0

5

10

15

20

BromidePhenobarbital

Phenytoin

Primidone

Ethosuximide

Sodium valproate

BenzodiazepinesCarbamazepine

VigabatrinZonisamide

LamotrigineFelbamate

GabapentinTopiramate Fosphenytoin

Oxcarbazepine

Tiagabine

Levetiracetam

More

Year

AEDS

Antiepileptic drug developmentAntiepileptic drug development

Choice of drugChoice of drug

Seizure typeSeizure type

Women of childbearing ageWomen of childbearing age

PregnancyPregnancy

BreastfeedingBreastfeeding

ChildrenChildren

ElderlyElderly

Learning disabilityLearning disability

GENERALISED-ONSET SEIZURESGENERALISED-ONSET SEIZURES PARTIAL-ONSET SEIZURESPARTIAL-ONSET SEIZURESAbsence Absence myoclonic tonic / atonic primary T-C simple complex-partialmyoclonic tonic / atonic primary T-C simple complex-partial

secondary generalisationsecondary generalisation

EthosuxamideEthosuxamide CARBAMAZEPINECARBAMAZEPINEPhenytoinPhenytoinVigabatrinVigabatrinGabapentinGabapentinOxcarbazepineOxcarbazepine

VALPROATEVALPROATELAMOTRIGINELAMOTRIGINELevetiracetamLevetiracetamTopiramateTopiramatePhenobarbitalPhenobarbitalBenzodiazepinesBenzodiazepines

Treatment options by seizure type

Initial (first line) treatmentInitial (first line) treatment

Drugs for generalised seizuresDrugs for generalised seizures

Valproate (Epilim Chrono)Valproate (Epilim Chrono)

LamotrigineLamotrigine

[Topiramate][Topiramate]

Drugs for partial seizures (+/-Drugs for partial seizures (+/-

secondary generalisation)secondary generalisation)

Carbemazepine (Carbemazepine (Tegretol Tegretol RetardRetard))

LamotrigineLamotrigine

Valproate (Valproate (Epilim ChronoEpilim Chrono))

LevetiracetamLevetiracetam

[Topiramate ][Topiramate ]

Sodium valproate Sodium valproate (Epilim Chrono)(Epilim Chrono)

Useful for location related Useful for location related and generalised epilepsyand generalised epilepsy

Can be brought up to Can be brought up to therapeutic dose quicklytherapeutic dose quickly

Low(er) doses tolerated Low(er) doses tolerated and possibly drug of and possibly drug of choice for elderly patientschoice for elderly patients

Can cause tiredness, Can cause tiredness, tremor, weight gain, tremor, weight gain, alopeciaalopecia

Teratogenic (spina bifida)Teratogenic (spina bifida)

Carbamazepine Carbamazepine (Tegratol)(Tegratol)

Good drug for partial seizures in young(er) adultsGood drug for partial seizures in young(er) adults

Needs gradual build up to a therapeutic doseNeeds gradual build up to a therapeutic dose

Enzyme-inducer, therefore interactions/oestoporisisEnzyme-inducer, therefore interactions/oestoporisis

Most specialists use MR (Tegretol Retard)Most specialists use MR (Tegretol Retard)

Lamotrigine Lamotrigine (Lamictal)(Lamictal)

Broad spectrum Broad spectrum

Good tolerability as Good tolerability as monotherapymonotherapy

Well tolerated by the Well tolerated by the elderlyelderly

Synergistic effect with Synergistic effect with sodium valproatesodium valproate

Least teratogenicLeast teratogenic

Needs to build up slowly Needs to build up slowly (months) to reduce AEs(months) to reduce AEs

Rash common, Rash common, sometimes severe and sometimes severe and associated with Steven-associated with Steven-Johnson’s syndromeJohnson’s syndrome

Blood dyscrasiasBlood dyscrasias

Newer second line agents - Levetiracetam Newer second line agents - Levetiracetam (Keppra)(Keppra)

Relatively new but appears Relatively new but appears well tolerated and well tolerated and efficaciousefficacious

Monotherapy licenceMonotherapy licence

Licensed for partial seizures Licensed for partial seizures +/- secondary generalisation +/- secondary generalisation (may be effective in other (may be effective in other seizure types)seizure types)

Can be started at close to Can be started at close to therapeutic rangetherapeutic range

Sedation common, Sedation common, though tends to resolvethough tends to resolve

Long-term experience Long-term experience still lackingstill lacking

Newer second line agents - TopiramateNewer second line agents - Topiramate

Potent anticonvulsant Potent anticonvulsant activityactivity

Useful for most forms of Useful for most forms of epilepsyepilepsy

Often not tolerated due to Often not tolerated due to side effects: confusion, side effects: confusion, word-finding difficulties, word-finding difficulties, weight lossweight loss

Needs slow inductionNeeds slow induction

When to start treatmentWhen to start treatment

What is the cause?What is the cause?

What is the risk of recurrence?What is the risk of recurrence?

First Vs second seizure?First Vs second seizure?

What does the patient / carer think?What does the patient / carer think?

Poor control

• Concurrent pro-convulsant drugs Alcoholprescription

• Lifestyle SleepStress

• Concordance / compliance Why?ADRother drugsSocial

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 therapyDVLA – 6 month suspensionLeisure pursuitsContraception / pregnancy etc

Service LevelService Level

Primary CarePrimary Care

GMSGMS

Referral Referral First seizureFirst seizure

Poor controlPoor control

Special Special casescases

AED AED withdrawalwithdrawal

Follow-up if stableFollow-up if stable

Re-referRe-refer

Secondary careSecondary care

Establish diagnosisEstablish diagnosis

initiate treatmentinitiate treatment

Follow upFollow up

Difficult controlDifficult control

Tertiary Tertiary referralreferral

Neuro-oncologyNeuro-oncology

ObstetricsObstetrics

ElderlyElderly

Epilepsy Nurse specialistsEpilepsy Nurse specialists