EPILEPSY

Prof. Milda Endzinienė

Neurology Department
 EPILEPSY

chronic brain disorder of various etiologies

characterized by recurrent (two or more)
epileptic seizures, unprovoked by any
immediate identified cause
• An acute symptomatic seizure occurs only as a result of an external condition :
– Fever,
– Dysmetabolism (hypoglycaemia, uremia, hypocalcemia)),
– Intoxication,
– Encephalitis,
– Abrupt withdrawal of antiepileptic medications,
– Acute period of severe brain trauma,
– Intracranial haemorrhage.

• If these conditions are controlled or avoided, the patient will never suffer
another seizure.
• In epileptic patients, changes in the brain itself are the cause of the seizures.

• Unprovoked seizures:
• having no identifiable causual relationship to any external factor.
 Diagnosis of epilepsy
• At least two unprovoked seizures occurring greater than 24
hours apart
or
• One unprovoked seizure and an increased probability of
further seizures (similar to the general recurrence risk after two
unprovoked seizures, i.e., at least 60% )
or
• Diagnosis of a specific epilepsy syndrome

It means:
• Two unprovoked seizures, or
• One seizure with increased risk of recurrence
 Increased seizure recurrence risks

• Obvious epileptiform activity on EEG

• Structural brain damage:

– Clinically relevant findings on CT/MRI
– Obvious neurologic/cognitive dysfunction

• Family history of epilepsy

 Epilepsy is considered to be resolved

• for individuals who had an age-dependent epilepsy syndrome

but are now past the applicable age (e.g. Rolandic epilepsy)

or

• For those who have remained seizure-free for the last 10

years, with no seizure medicines for the last 5 years.
 An epileptic seizure

• An excessive or abnormal sudden high frequency

discharge of brain neurons.

• Difference form other cause of altered behaviour:

– start and stop suddenly, arising paroxysmally from the
patient`s ongoing physiological activity;

– seizures primarily involve neurones; changes in other

processes such as cerebral blood circulation are only
secondary.
 An epileptic seizure

The clinical manifestation consists of sudden and

transitory abnormal stereotyped phenomena which
may include:
– alterations of consciousness,
– motor,
– sensory,
– autonomic,
– psychic events,
perceived by the patient or an observer.
Bioelectric epileptic discharge during a partial seizure
 Etiology of epilepsy: structural/metabolic (2010)
„Symptomatic “ (International Classification of the Epilepsies and Epileptic Syndromes, 1989)

Structural brain damage

Exogenic
• Stroke
• Trauma
• Infection

Genetic mutations that are responsible for brain

damage, with epilepsy being just one of the symptoms:
• Tuberous sclerosis
• Brain malformations of genetic origin
• Down syndrome
• Mitochondrial and other neurometabolic disorders
 Etiology of epilepsy: genetic (2010)
“Idiopatic” (International Classification of the Epilepsies and Epileptic Syndromes, 1989)

• Epilepsy is the primary consequence of a gene defect (the

main symptom of the mutation is epilepsy);

• May be confirmed by molecular genetic investigations or

family history of epilepsy;

• The role of exogenic factors may be additional.

– Dravet syndrome - SCN1A

– Autosomal dominant nocturnal frontal lobe epilepsy -
CHRNA4, CHRNB2 ar CHRNA2 (nicotine acetilcholine receptors)
 Etiology of adult epilepsy

Idiopathic/cryptogenc
8%
Neuroinfections
15% Tumors
Trauma
Cerebrovascular
5%
Congenital

10%
60%
2%

Hauser 1995
Olafsson et al, 1996
Oun et al, 2003
Etiology of epilepsy
 Etiology of epilepsy by age
Chadwick et al, 1989
Congenital abnormalities
Tuberous sclerosis Cerebral tumours
Storage diseases

Birth trauma Brain injuries

Intracranial haemorrhage

Intracranial infections

Drugs and alcohol

Febrile seizures

Genetic epilepsies
Hypoxia
Hypoglycaemia Cerebrovascular degenerations
Hypocalcaemia

0 1 5 10 20 60
Age (years)
Right focal cortical dysplasia:
partial epilepsy, cerebral palsy
 Band heterotopia (double cortex):
severe complex partial seizures, behavioural disorder
Hypothalamus hamarthoma:
resistant complex partial seizures,
mental retardation, diabetes incipidus
 Tuberous sclerosis:
subependymal and right hemisphere calcification (CT),
cortical tubers (MRI)
 Consequences of herpetic encephalitis:
epilepsy and mental disorder (I), epilepsy and spastic tetraparesis (II)

I II
Mesial temporal sclerosis
 Cerebral tumours

Oligodendroglioma

Dysembrioblastic neuroepitelial tumor (DNET)

 Epidemiology of epilepsy
Active epilepsy – seizures within the recent 5 years

• Incidence (new cases per year): Epilepsy often

– Adults 43 / 100 000 starts in childhood

– Children 82/100 000

• Prevalence: 4 – 6 / 1000

• Lifetime prevalence: 10/1000 (~1%)

• Lifetime prevalence of any epileptic seizure,

incl. acute symptomatic: 5%
 Concomitant disorders

• 40% just seizures, no concomitant abnormalities

• 60% have concomitant disorders:

- intellectual (~ 30% of children and ~ 23% of adults)

- motor (~ 20% of chldren and 14% of adults)
- depression (55% of PWE, 30% in healthy controls)
 Pathogenesis of epileptic seizures

Excitability Inhibition
Glutamate GABA
 Signalling in the brain

• Neurotransmitters
– GABA,
– glutamate, aspartate, glycin

• Specific ion channels

• Neuronal networks
Pathogenesis of epileptic seizures:
excitation
Pathogenesis of epileptic seizures:
inhibition
Pathogenesis of epileptic seizures:
action potential of neuronal membrane
 Pathogenesis of epileptic seizures
(by H. Bertram and F.E.Dreifuss

• Altered neurotransmitter balance

– Inceased glutamate (excitatory)
– Decreased GABA (inhibitory)
– Altered neuromodular activity

• Altered ionic homeostasis

– Potassium, calcium, chloride

• Rearranged neuronal circuits

– Loss of inhibitory synapses
– 'Overgrowth' of excitatory synapses
– Simplified circuits that improve neuronal synchronization
Epileptiform discharges on EEG
 Epileptogenesis: “kindling” phenomenon:

• Spreading like a flame

• When a stimulus in the brain is regularly repeated, it

becomes as strong as to manifest by a clinical seizure

• Each seizure is a consequence of a previous one and a

predisposition of the next one
 International organization scheme of
epileptic seizures (2010)

• Generalized:
– Tonic-clonic

– Absence

– Myoclonic

– Tonic

– Clonic

– Atonic
 International organization scheme of
epileptic seizures (2010): focal seizures

I. Without impairment of consciousness or awareness

(“simple partial,” 1981)

uncontrolable movements
sensations
emotions
autonomic phenomena

II. With impairment of consciousness or awareness (dyscognitive)

(“complex partial,” 1981)
III. Evolving to bilateral convulsive seizure
(“partial secondarily generalized” 1981)
Focal seizure
 Consciousness disturbed

• Inadequate reaction to external stimuli during the seizure,

• Inability to recall the events after the seizure is over.

Seizure without impairment of consciousness or awareness
Focal versive seizure
Without impairment of consciousness or awareness:
with somatosensory signs
Special focal sensory seizure
(visual aura)
Special focal sensory seizure
(gustatory aura)
Autonomic focal seizure
Epileptic spread during focal seizure
Dyscognitive seizure with automatisms (pervasive)
Dyscognitive seizure with automatisms (de novo)
Focal frontal seizure with automatisms
Evolution of versive focal seizure to bilateral convulsions
Evolution of awareness and motor phenomena during
focal seizures
Bilateral convulsions (tonic-clonic)
Bilateral convulsions (tonic-clonic),
followed by postictal sleep
Absence seizure
Absence seizure
Myoclonia
Juvenile myoclonic epilepsy
Tonic anteropulsive seizure
Clonic convulsion
 Important signs for seizure evaluation:
• Level of consciousness during seizure
(preserved, impaired, absent)

• Focal features:
any functional assymetry during seizure or afterwards
speech disorders
aura
automatisms

• Seizure duration

• Evolution of signs during the seizure (onset-seizure-recovery)

Seizure description

Level of consciousness
Position of eyes and pupils

Face: convulsions, colour

Breathing

Position and movements of extremities

Urination
 Classification and organization of the epilepsies

Focal Generalized
CLINICAL

Genetic ETIOLOGICAL Structural

 Electroclinical epileptic syndrome

• An epileptic disorder characterized by a cluster of

signs and symptoms occuring together
– type of the seizure,
– etiology,
– anatomy,
– precipitating factors,
– age of onset,
– severity,
– chronicity,
– diurnal and circadian cycling,
– sometimes prognosis,
– EEG discharges (shape, spread, provocation, etc.)
 Investigations in epilepsy

• EEG (electroencephalography)
• Neuroimaging (CT, MRI, SPECT, PET, fMRI)
• Neuropsychology
• Haematology
• Blood biochemistry – hepatic functioning
medication plasma levels
 Electroencephalography
• Background (awake), including :
– hyperventilations,
– intermittent photic stimulation,
– Berger (eye opening-closure)

• Sleep EEG

• Video EEG monitoring:

– Simultaneously reicords of the seizure signs and EEG
– Allows better classification of seizure/syndrome
– Allows better diagnosis of psychogenic non-epileptic fits
– Presurgical work-up
 Seizure precipitators

• Fever (small children)

• Sleep deprivation
• Emotional stress
• Alcohol
• Hyperventilation
• Intermittent photic stimulation
 Management of epilepsy

• Long-term
(3 – 5 years after the last seizure, depending on the epileptic syndrome)

• According to seizure type and epileptic syndrome

• Sustained and regular
• Adequate doses of antiepileptic medications
• Doses may be regulated according to the positive or adverse effects
• Slow up- titration, slow down-titration (“Start low, go slow”)
• Abrupt treatment cessation may cause relapse or status epilepticus
 Antiepileptic drugs

Partial Both partial or Generalized

generalized

Carbamazepin Valproic acid Ethosuximid

Oxcarbazepin Lamotrigin
Gabapentin Topiramate
Tiagabin Levetiracetam
Pregabalin Clonazepam
Vigabatrin Nitrazepam
Phenytoin Diazepam
Zonisamid Clobazam
Retigabin Phenobarbital
Lacosamide
Perampanel
Sutiam
 Adverse effects of AEDs:

Dose-related

• dizziness
• somnolence
• diplopia
• ataxia
• headache
• blurred vision

• irritability
• insomnia
• hand tremor
 Adverse effects of AEDs:

Idiosynchratic

• skin rash
• leucopenia
• thrombocitopenia
• anemia
• hepatic disorder
 Adverse effects of AEDs:

Chronic intoxication
• Behavioural and sleep disorder (PB)

• Gum hyperplasia, coarse facial features, hirsutism, folate

deficiency (PHT)

• Weight gain, alopetia, ovarian dysfunction, teratogenicity (VPA)

• Wight loss, speech disorder, renal calculi (TPM, ZNS)

• Development of tolerance (benzodiazepines, PB)

 Prognosis of treated epilepsy

Remission Persisting

70 – 75% 20 – 25 (30) %

True resistance Pseudo-

resistance
10 - 15 %
~ 10 - 15%
Seizure first aid

• Loosen tight clothes

• Turn of one side (semi-prone)

• Protect from trauma:

sharp objects, falls
protect the head
Seizure first aid

• Observe events and time

• Stay calm
 Seizure first aid:
“do not”

• Do not push anything into one’s

mouth to press the tongue

• Do not give water or medication

orally – it is dangerous and will
not help
 Seizure first aid:
“do not”

• Do not take any forceful

measures, do not provoke
patient’s resistance

• Do not perform artificial

ventilation nor external
heat massage
 Complications of epilepsy

• Status epilepticus

• Injuries

• Sudden unexpected death (SUDEP)

• Regression of mental and behavioural functions

Status epilepticus
 Status epilepticus

A single epileptic seizure or a cluster of seizures without

regaining of consciousness lasts >5 min.

Seizures are so frequent that each attack begins before the postictal
period of the preceding one ends

T1 – start of the actions to stop the seizure (5 min.)

T2 – the timing of the serious complications to begin (30-60 min.)

Life-threatening condition!
 Status epilepticus epidemiology (i)

Incidence:

• Overall population 18 - 24 (41)/ 100 000

• Children < 1 year 156 / 100 000

• Elderly (>60 years) 100 / 100 000

 Status epilepticus epidemiology (ii)

Mortality - 22%
(hypoxia, tumours, metabolic derangements)

Mortality depends on:

 underlying disorder

 secondary brain damage during status epilepticus

(systemic and metabolic)
 duration of status epilepticus
 patient’s age
(minimal in young age, maximal in elderly)
Pathogenesis of

status epilepticus
 Status epilepticus: pathophysiology
Phase I – compensatory Duration: up to 30-60 min.
Intensive metabolism in the brain and muscles

Increased brain blood flow

Increased O2 consumption
Increased glucose consumption
Increase of blood A ir NA
Increased ABP Anaerobic glycolysis Lactatacidosis
Increased HR
Hyperthermia
Hyperglycaemia
Mydriasis

Increased bronchial and saliva secretion Insufficiency of breathing

Insufficient thoracic movements Respiratory acidosis
 Status epilepticus: pathophysiology
Phase II-III – decompensation
(established SE: 30-90 min., refractory SE: >90 min.)

Seizures persist Growth of neuronal hypersynchronisation

Neuronal death

Dysfunction of internal organs

Brain metabolism detiorates
Failure of cerebral autoregulation
Hypoxia increases due to: high O2 utilisation
effects of AEDs
Falling glucose and energy state
Severe acidosis, electrolyte disbalance

Decreases cerebral blood flow Systemic hypotension, intracranial hypertension

Brain edema
 Management of status epilepticus:
early stage (5-30 min.)
(pre-hospital or hospital)

• Diazepam 10-20 mg (i/v bolus, not> 5 mg/min., or rectal);

– Repeat allowed 10 min. later- beware breathing failure!

• Midazolam: 5-10 mg adults 0.15-0.3 mg/kg children

• Lorazepam (i/v bolus);

– 4 mg adults and 0.1 mg/kg children
 Management of status epilepticus;
hospital

• Maintain adequate airway and blood flow

• Provide O2
• Blood draw (haematology, biochemistry, AED plasma level, toxicology)
• Glucose i/v (25-50 g) by direct push
• Thiamine 100 mg (if malnutrition or alcoholism)
• Determination of SE etiology

• Intavenuous AEDs – hospital with intubation possibility only!

• Monitoring of cardiovascular and breathing functions
 Management of status epilepticus:
established SE (30-60/90 min.)

• Fenobarbital (PB) 10 mg/kg Ventilation!

or
• Phenytoin (PHT) 15 (+5) mg
or
• Fosphenytoin 20 mg/kg
or
• Valproate (VPA) i/v 15-40 mg/kg

• Alternatives: BZD infusion

 Management of status epilepticus:
refractory SE (>90 min.)

• Thiopentone

• Midazolam

• Propofol

“Time is brain”
Thank you!