Professor Ley Sander

Department of Clinical and Experimental Epilepsy

UCL Institute of Neurology
National Hospital for Neurology & Neurosurgery
Queen Square, London WC1N 3BG
The Medical and Surgical
Treatment of Epilepsy
The Treatment of Epilepsy

The incidence and prevalence

Aetiologies and risk factors

Aims of treatment

Clinical settings

Principles of treatment
Medical treatment
Surgical treatment

Guidelines

Conclusions
Incidence and Prevalence
Incidence of new cases of epilepsy:
50/100,000/year

Incidence of single seizures:
20 - 30/100,000/year

Prevalence of active epilepsy
5 - 10/1,000 (50% because on AEDs)
Severe epilepsy: 1 - 2/1,000

Cumulative Incidence (lifetime prevalence):
2 - 5%




Incidence and Prevalence in the UK

30 000 new cases a year

300 000 - 400 000 cases

72 000 - 80 000 cases of severe
epilepsy
Incidence and Prevalence in the UK

GP
1 - 2 new cases of epilepsy/year
10 - 12 cases of active epilepsy

Neurologist
150 cases of epilepsy/single seizures/year
1,200 cases of active epilepsy


Epilepsy: Aetiologies and Risk Factors
Risk factors varies with age and geographic location

Congenital, developmental and genetic conditions in childhood,
adolescence and young adults

Head trauma, infection and tumours at any age although
tumours more likely over age 40

Cerebrovascular disease common in elderly

Endemic infections are associated with epilepsy in certain areas
malaria, neurocysticercosis, paragonomiasis,
no adequate large scale study of attributable risk yet





Antiepileptic Treatment
AEDs are mainstay treatment

Non-pharmacological options feasible in only few
selected cases
Surgery
Curative
Palliative
Ketogenic diet (children)
Behaviour modification
Avoidance therapy in cases with clear precipitants



Aims of Antiepileptic Treatment
Complete seizure freedom
50% seizure reduction of little benefit

No adverse effects
long term treatment - long term effects ?
cognitive effects debilitating
teratogenicity

Non-obtrusive treatment
once or twice daily
No PK or PD interactions

Maintenance of a normal lifestyle

Reduction in morbidity and mortality
AED Treatment: Clinical Settings
Prophylactic Treatment

Newly Diagnosed Epilepsy
Single seizure
Recurrent seizures

Chronic Epilepsy

Prophylactic use of AEDs
Often advocated after
Head injury
Craniotomy

There are considerable compliance problems

There is no evidence of a protective effect of this
policy
No place for this!
Better wait for the event to happen

Is it Epilepsy ?
Newly diagnosed or suspected cases at Primary
Care level
> 50% not epilepsy
commonest differential diagnosis: syncope
Chronic cases
15 - 20% not epilepsy
mostly psychological in nature

Careful diagnostic assessment a must in all
cases


The Single Seizure
A controversial area!

Single unprovoked attack usually not treated: practice to defer
treatment until 2 or more seizures, although patients at high risk
may be treated after a first attack

Incidence of epilepsy much greater than of single seizures

Community-based studies show that overall risk of a second
seizure greater than previously accepted
selection bias
Patients
Seizure type
time to entry bias


The Single Seizure
AED treatment following a single seizure reduce risk
of recurrence in the short term although long term
prognosis not changed

This may eventually lead to changes in the way single
seizures are managed
treatment after first seizure
- for six months, for a year?
tailored treatment and not symptomatic

Meanwhile, involve patient and or guardians in the
decision
Recurrent Seizures
Treatment recommended after two or
more seizures

Exceptions:
- Long interval between seizures
- Clear identifiable precipitant factor
- Patient against treatment
- Unlikely compliance
Precipitating Factors
Fever
Drugs
Alcohol
Photo-Sensitivity
Sleep Deprivation
Reflex Mechanisms
Acute Metabolic Stress
Emotional Stress/Major Life Events

Starting an AED
Starting AED treatment is a major event and should
not be undertaken without careful evaluation of all
relevant factors

Therapy is a long term prospect

All implications must be fully explained to the
individual and or guardian

Paramount that the patient or guardians are kept
informed about the treatment process and the
rationale behind it

Starting Treatment
Treatment should always be started with a single
drug at a small dose

All common side-effects must be discussed
teratogenicity and contraception if applicable

Importance of compliance should be stressed

Careful titration is a must
- start low, go slow

Choice of AEDs treatment

Choice of AED influenced by:
Type of seizure and or epileptic syndrome
Individual circumstances of patient
Side effect profile of drug
Personal preferences

No clear cut evidence based medicine is available!

Clinical practice is based more on dogmatic teaching
than on scientific knowledge

Empirical rather than rational



Principles of AED treatment
Diagnosis clearly established

Appropriate first line drug for syndrome and patient

One drug at a time as a rule:
If first drug ineffective add another first line drug and then
withdraw first drug

Combination therapy only when single drug
ineffective
What Is Chronic Epilepsy ?

Active 2 years after onset

Failed 2 first line AEDs

Great number of seizure in early history

Chronic Epilepsy 1
Review history of epilepsy
- Obtain and review old notes if possible
- Interview patient and witness
- Classify seizures

Review diagnosis
- Non-epileptic events
- Identifiable aetiology
- High resolution MRI scanning

Question Compliance
- Check serum AED levels

Review past and present AED treatment for efficacy
and side-effects


Chronic Epilepsy 2
Select the AED that is most likely to be efficacious
and with the least side-effects

Adjust the dose of the selected drug to the optimum

Attempt to reduce and taper other AEDs

If seizures continue despite a maximally tolerated
dose of a first-line drug:
- Check compliance
- tablet count, serum levels, counselling

Commence another first-line AED if there is one that
has not been used to its optimum


Chronic Epilepsy 3
If seizures continue try a combination of two AEDs

If combination unhelpful, AED which appears most
effective and with fewer side-effects should be
continued and the other AED replaced

If this drug is effective, withdrawal of the initial agent
should be considered; if not, it should be replaced by
another AED

Consider the possibility of surgical treatment

Consider using an experimental AED



Inappropriate use of AEDs
Inappropriate treatment of people who do not have
epilepsy

Inappropriate drug treatment of patients who do have
epilepsy
JME easily treated with some AEDs but poorly controlled with others
Partial epilepsies often misdiagnosed as generalised epilepsy

Incorrect dosages or inappropriate use of polytherapy
Overzealous adherance to therapeutic AED drug levels



AED drug levels monitoring

Measurement of AED levels:
drug toxicity occurs and needs to be documented
suspected non-compliance
suspected drug interactions
during pregnancy (free levels)
during systemic illness
phenytoin therapy

Not a guide to dosing!


Partial seizures: simple, complex, sec gen.
Stereotyped onset
No non-epileptic attacks
No contraindication for Neurosurgery
Active epilepsy for >2-3 yr, despite 3 + AEDs
Inadequate seizure control: > 1-2 c p s /month
Acceptance of best risk / benefit ratio


Who Should be Evaluated for Surgery
Best risk vs benefit ratio of
temporal lobe epilepsy surgery
Medical Surgical

Chance of seizure control
10% 70%

Risk
Morbidity from seizures 1/100 long-lasting impairment
Psychosocial handicap hemiparesis, aphasia
1/100 Annual mortality 1/20 quandrantanopia prevents
driving
70% Anterior temporal lobe resection

20% Extra-temporal cortical resection
Lesionectomy

10% Palliative Procedures
Hemispherectomy
Corpus callosotomy
Subpial transection
Vagal Nerve Stimulation
Range of Epilepsy Surgery
Convergence of data
One epileptogenic & dysfunctional area
Rest of brain normal
Clinical
Neuro-Imaging
EEG
Neuropsychology
Neuropsychiatry
Psychosocial
Components of Presurgical Evaluation
Realistic expectations?
Improvement in life from seizure control?
Intelligence, memory will not improve
Not more attractive, employable
Need to continue AEDs after

Social support
Family, friends, community, finances


Psychosocial

Fundamental
MRI predicts nature and extent of pathology
Unusual to resect area with normal imaging
Poor results if imaging normal
Neuro-imaging
TLE: Anterior Temporal Lobe resection
Focal pathology: 70% seizure free, 25% >90% reduced
DNT, cavernoma>HS>AVM>trauma>MCD
20% seizure free if no focal pathology

Extra Temporal Lobe
Focal pathology: 60% seizure free, 20% >90% reduced
DNT, cavernoma, glioma>AVM>trauma
MCD 20-30% seizure free, if focal

<20% seizure free if no focal pathology

Pathology and Outcome
Treatment Guidelines for Epilepsy
NICE = www.nice.org.uk National Institute
for Clinical Excellence (England and Wales)

SIGN = www.sign.ac.uk Scottish
Intercollegiate Guidelines Network (Scotland)

AAN = www.aan.com American Academy
of Neurology (USA)
Primary Care Guidelines for Epilepsy
Referral of ALL who experience a suspected seizure
Seen within 14 days by specialist
Risk and safety precautions documented
Care Plan in place
At least a yearly review
Early re-referral if
Treatment failure
Seizures not controlled
Diagnostic uncertainty
Considering pregnancy
Considering drug withdrawal

Managing People With Epilepsy
Holistic issues:
- Interest and continuity of care
- Clear plan
- Information provision
- SUDEP
- Easy access

- Practical Issues:
Cooking, Bathing, Driving, Contraception, Conception

- Reasonable Expectations:
Prognosis, Independent Living, Employment


AED Treatment: Conclusions
Correct diagnosis and classification paramount to
treatment

AEDs are mainstay treatment

Treatment empirical rather than rational!

> 70% of patients become seizure free

Potential complications: toxicity

Low threshold for s/effects





AED Treatment: Conclusions
Potential for misuse of AEDs not to be dismissed

New AEDs may be better tolerated, but more effective?

Chronic side effect profile of new AEDs not fully known

Surgical treatment very successful but only possible in a
few selected cases

Consider stopping AED if seizure free for years

New treatment still needed!