2. ‘Sacred illness’
• ‘Sacred illness’: 600 BC
• Hippocrates 400 BC: It is thus with regard to the disease called
sacred: it appears to me to be in no way more divine nor more
sacred than other diseases [...].
The brain is the cause of this affliction [...].
Alexander the Great Julius Caesar Napoleon F. Dostoyevsky
3. Epileptic seizure
Abnormal synchronous
discharge of the cortex
leading to transient
dysfunction of the brain
A seizure can be evoked
by any pathology
affecting the brain,
transient or permanent
Epileptic seizure =
symptom
4. Acute symptomatic seizure versus
epilepsy disease
Acute symptomatic seizure: symptom of a
transient pathological state of the brain
Withdrawal of alcohol, drugs
Hypoglycemia
Fever etc.
Epilepsy disease: lasting epileptic dysfunction
of the brain → spontaneous seizures
5. Types of seizures
Generalised seizures
Tonic - clonic
Tonic
Clonic
Atonic
Absence
Myoclonus
Focal (partial)
seizures
Simplex partial
Complex partial
Partial onset with
secondary
generalisation
Seizures of undetermined type
6. Generalised tonic-clonic seizure
(grand mal)
The most common seizure
Acute symptomatic seizures are
generalised tonic-clonic seizures
Course:
Cry, loss of consciousness, fall
Tonic phase- generalised muscle
contraction, apnoea
Clonic phase- rhythmic
contraction of muscles, tongue
bite, foaming, enuresis
Terminal sleep and gradual
regaining of consciousness
(transient confusion)
7. Absence
Cognitive dysfunction with a
sudden onset and end,
lasting 5-10 seconds
Stare, expressionless face;
arrest of ongoing activity;
generally no motor
phenomena
EEG: generalised 3 Hz spike
and wave activity
Occurs in genetic (idiopathic)
epilepsies, mostly in children
8. Myoclonic seizure
Sudden, quick, arrhythmic
muscle contraction, twitch
of a limb; no loss of
consciousness
EEG: generalised
polyspike and wave activity
Occurs in genetic (idiopathic)
epilepsies
Not only an epileptic
phenomenon- it can be the
sign of diffuse
encephalopathies
9. Simplex partial seizures
No loss of consciousness
Symptoms depend on area
of brain involved:
Motor
Sensory
Autonomic
Psychosensory
It can be the introductory
phase of a complex partial
or generalised tonic-clonic
seizure (‘aura’)
10. Complex partial seizures
Origin is most often in the temporal
lobe
A common seizure type in
adulthood
Can be introduced by a simplex
partial psychosensory seizure:
olfactory hallucination
déjà vu, jamais vu
feeling of alienation
Loss of consciousness: stare,
‘going blank’
Automatisms:
oral automatisms
fiddling with the hands
12. Genetics
Risk of a non-provoked
seizure in offsprings of a
parent with epilepsy: 6%
Idiopathic generalised
epilepsies: 9-12%
Over 140 single gene
diseases are accompanied by
epilepsy
Inborn metabolic, storage
diseases
Mitochondrial diseases
Neurocutaneous diseases
Chromosomal diseases
Tuberous sclerosis
13. Benign centrotemporal epilepsy
Age of onset: 3-15 years
Seizure types: facial, oro-bucco-
pharyngeal motor and sensory
simplex partial seizures; speech
arrest
Nocturnal seizures
Mild disease, therapy not always
needed
No neurological or mental
alterations
EEG: centrotemporal spike
waves
Spontaneous remission by
puberty
14. Childhood absence epilepsy
Age of onset: 3-10 years
Seizure types: absence; often in clusters; hyperventillation and
fotostimulation are provoking
No neurological or mental alterations
EEG: generalised 3 Hz spike and wave activity
Good response to treatment
Spontaneous remission by puberty
15. Juvenile myoclonic epilepsy
Most common form of idiopathic
generalised epilepsy
Family history positive in 40%
Age of onset: 15-18 years
Seizure types:
myoclonic
generalised tonic-clonic
absence
EEG: generalised 3-4 Hz spike
and wave, polyspike and wave,
hyperventillation and
fotostimulation are provoking
Good response to treatment, but
needs life-long treatment
16. Common causes of symptomatic
epilepsies
Head injury
Tumors
Infarcts, hemorrhages
Blood vessel malformations
Infections
Cortical dysgenesis
Cause of newly diagnosed
epilepsies is unknown in 60-
65% (cryptogenic).
17. Temporal lobe epilepsy
Most common epilepsy in adulthood;
can be heralded by a few seizures in
childhood, but typical age of onset is
20-22 years
Seizure types:
olfactory hallucination (simplex
partial)
psychosensory seizures (simplex
partial)
complex partial
generalised tonic-clonic
Febrile convulsions in childhood
Hippocampal sclerosis
Often refractory to therapy
Characteropathy, memory
dysfunction
18. West syndrome
Age of onset: 3-5 months
Seizure types: infantile spasms
Causes: inborn metabolic, storage diseases, perinatal
hipoxic brain damage
Cryptogenic in 40-50%
Neurological symptoms, mental retardation; bad
prognosis; can transform into Lennox-Gastaut
syndrome
EEG: hypsarrhythmia
19. Lennox-Gastaut syndrome
Age of onset: 1-8 years
Seizure types: atonic, axial
tonic, myoclonic, atypical
absence, tonic-clonic
Injuries are common
Causes: same as in West
syndrome; can develop from
West syndrome
Neurological symptoms,
mental retardation
Unfavourable prognosis,
refractory to treatment
20. Diagnosis / differential diagnosis
Is it an epileptic
seizure? ?
Yes No
1. Seizure type?
2. Acute symptomatic
seizure or epilepsy?
Epilepsy
Idiopathic or
symptomatic?
Acute symptomatic seizure
Cause?
Symptomatic epilepsy
Cause?
Syncope?
TIA?
Psychogenic?
21. Epileptic seizure versus syncope
Syncope Tonic-clonic seizure
Position Upright Any
Facial colour Paleness Cyanosis
Onset Gradual; introduced by
dizziness, blurring of vision
Sudden; can start by ‘aura’
(simplex partial seizure)
Twitchings Rarely (‘convulsive syncope’) Always
Enuresis Rarely Often
Tongue bite No Often
Duration 10-20 seconds Few minutes
Postictal confusion No Yes
Perspiration Pronounced Not typical
22. Diagnostic steps
History
EEG
Negative EEG does not
exclude epilepsy
Pozitive EEG without clinical
signs does not prove
epilepsy
EEG after sleep withdrawal or
during sleep
Long-term EEG / video
monitoring
CT, MRI
Epilepsy is a clinical diagnosis.
23. Medical treatment of epilepsy
When do we start antiepileptic medication
(AED)?
Which AED to choose?
When and how do we switch AEDs?
When is polytherapy needed?
When can AEDs be discontinued?
Pregnancy
Driver’s licence
24. When do we start treatment?
More than one non-provoked, well-documented
seizure
AEDs are usually not started after the first seizure
(needs individual assessment)
Preventive treatment is not justified
29. Pharmacology of AEDs II.
Phenytoin 7-20 days
Phenobarbital 10-30
Primidon 2-5
Valproate 2-5
Carbamazepine 3-5
Ethosuximid 7-12
Clobazam 4-5
Lamotrigine 3-10
Topiramate 3-6
Gabapentin 2-5
Vigabatrin 2-5
Steady state Binding to plasma proteins
Pronounced
(>90%) binding
phenytoin
valproate
Moderate (30-80%)
binding
carbamazepine
clobazam
lamotrigine
No or minimal
(<20%) binding
gabapentin
vigabatrin
topiramate
ethosuximid
30. Side effects of AEDs
Allergy
Central nervous system side
effects (dose dependent)
drowsiness, headache
dizziness, dysequilibrium
cognitive dysfunction (memory)
Idiosynchratic reactions / chronic
side effects
bone marrow suppression
hepatic failure
rash
weight gain, weight loss
tremor
polycystic ovary syndrome
visual field defect
31. Selection of AEDs
Selection of AED is based on:
Seizure type / epilepsy syndrome
Other: side effects, pharmacology, drug interactions,
comorbidities
As there are no major differences among first-line AEDs, safety
and tolerability must be of paramount consideration in choosing
AED.
Matching drugs to patients (holistic approach):
Side effects
Work
Sleep
Mood
Well being
33. Therapeutic principles
Aim: maximal seizure control, minimal side
effects
Monotherapy
Usually gradual introduction of AED
Assessment of AED effect (seizure frequency)
After AED has reached steady state
Depends on the average time interval of seizures
before treatment
34. Possible causes of AED inefficacy
Inadequate dose → dose escalation
Lack of compliance → measure blood AED levels
False diagnosis: the patient doesn’t have epilepsy
‘Pseudoseizures’ → precise description of seizure, EEG
/ video monitoring
Inadequate selection of AED
True inefficacy of AED → AED switch
Other AED on monotherapy
AED combination
35. AED combinations
Rules of AED combination:
Establish optimal dose of baseline AED
Avoid combining similar modes of action
Add drug with multiple mechanisms
Titrate new drug slowly
Be prepared to reduce dose of original drug
Replace either drug if response is poor
Some effective combinations:
valproate-lamotrigine
valproate-carbamazepine/oxcarbazepine
valproate-topiramate
etc.
36. Drug interactions
Enzyme inductors
carbamazepine, phenytoin
phenobarbital, primidon
Increase of metabolism / decrease
of efficacy
valproate, lamotrigine, topiramate,
carbamazepine
oral contraception
oral anticoagulation
Enzyme inhibitors
valproate
Decrease of metabolism /
increase in efficacy - toxicity
lamotrigine, carbamazepine,
phenytoin
Does not cause interaction
lamotrigine, gabapentin, topiramate,
vigabatrin, tiagabin
37. Therapeutic success- remission rates
Partial epilepsies
First AED in monotherapy: 43%
Second AED in monotherapy: 7%
Other monotherapies: 2%
AED combination: 5%
Total in remission: 57%
Juvenile myoclonic
epilepsy
First AED (valproate) in
monotherapy: 85%
Altogether 65-70% of patients with epilepsy
respond well to AED treatment.
38. Discontinuation of AED
After 3-5 seizure free years
A decision of both the doctor and patient
AED should be very slowly tapered, lasting weeks-
months.
Discontinuation of AED is not recommended:
Earlier unsuccessful AED withdrawal
Earlier refractoriness to treatment
Known brain lesion
Juvenile myoclonic epilepsy
39. Epilepsy and pregnancy
Teratogenic risk
In normal population: 2-3%
In women on AEDs: 4-9%
Teratogenic risk is increased
High AED dose
Fluctuating plasma levels
Polytherapy
Occurrence of spina bifida in the family
Folic acid deficiency
40. Epilepsy and pregnancy: what to do?
Before conception:
Attain the best possible seizure control with the lowest possible
AED dose, preferably in monotherapy
Folic acid profilaction 4 mg/day
During pregnancy:
During first trimester supplement folic acid 4 mg/nap
Change medication only if seizure control worsens
Screening of fetal malformations (ultrasound on week 16 and
20, AFP)
In case of enzyme inductor AEDs, give vitamin K in the third
trimester
41. Epilepsy and breast feeding
Breast feeding is not contraindicated with
women on AEDs.
Sleep deprivation can provoke seizures.
42. Epilepsy and driving
Driving is prohibited for one year after a seizure
with loss of consciousness
Driving is permitted:
2-3 years of seizure free interval with patients on
AEDs
2-3 years of seizure free interval after withdrawal of
AEDs