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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 prevalence of treated epilepsy per 1000 persons
Source: Wallace, Shorvon, Tallis, Lancet
9.5
9
8.5
8
7.5
7
Prevalence/100 0
6.5
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
Age
85+
Incidence/100,000
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
Age
55-59
60-64
65-69
70-74
75-79
80-84
85+
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
Late 20’s – 50’s
Late 50’s – 80+
JME
Alcohol / drugs
Primary
generalised (T-C)
Brain tumours
Cerebrovascular
disease
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 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
Syncope
 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
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?
 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?
Making the diagnosis 2
Making the diagnosis 3
Management
Management
Starting AED treatment in newly diagnosed epilepsy
AIMS
PRINCIPALS
 Prevention of seizures
 Appropriate drug for
patient’s seizure(s)
 Minimal side effects
 Optimise QOL
 Appropriate drug for
individual patient
 Through trial and error
Antiepileptic drug development
More
AEDS
20
Levetiracetam
Tiagabine
15
Topiramate
Felbamate
Zonisamide
10
Ethosuximide
Gabapentin
Lamotrigine
Carbamazepine
Benzodiazepines
Primidone
Phenobarbital
Bromide
Fosphenytoin
Vigabatrin
Sodium valproate
5
Oxcarbazepine
Phenytoin
0
1840
1860
1880
1900
1920
Year
1940
1960
1980
2000
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)
 Carbemazepine (Tegretol
Retard)
 Lamotrigine
 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
 Sedation common,
though tends to resolve
 Monotherapy licence
 Long-term experience
still lacking
 Licensed for partial
seizures +/- secondary
generalisation (may be
effective in other seizure
types)
 Can be started at close to
therapeutic range
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
• 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
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