Epilepszia.Antiepileptikumok.GYAKORLATI SZEMPONTOK

Dr. Szok DéliaSZTE ÁOK Neurológiai Klinika

Rezidens képzés2017. február 28.

Epilepszia

• Anyone can develop epilepsy, at any time of life.

• It happens in people of all ages, races and social classes.

• Epilepsy is most commonly diagnosed in children (idiopathic forms) and in people over 65 (symptomatic forms).

Epilepszia definíciója

Epilepsy is defined as a brain disorder

characterized by an enduring predisposition to generate epileptic seizures and

by the neurobiologic, cognitive, psychological, and social consequences of this condition.

Epilepszia // Rohamok

• Nota bene!

•SEIZURE ≠ EPILEPSY• but:

• EPILEPSY IS A SEIZURE DISORDER

Definition of epilepsy(ILAE: International League Against Epilepsy, 2014)

http://www.ilae.org/

Elektro-klinikai epilepszia szindrómákAge-dependent

Neonatal period

Infancy

Childhood

Adolescence – Adult Juvenile absence epilepsy, Juvenile myoclonic epilepsy, Progressive myoclonic epilepsy, etc.

Not age-dependent

Distinctive constellations •Mesial TLE with hippocampal sclerosis•Rasmussen syndrome•Gelastic seizures with hypothalamic hamartoma, etc.

Epilepsies with structural-metabolic causation •Malformations of cortical development(hemimegalencephaly, heterotopias,

focal cortical dysplasia, etc.)

•Neurocutaneous syndromes/Phacomatoses(sclerosis tuberosa, Sturge-Weber syndrome, etc.)

•Tumor / Infection / Trauma / Stroke•Perinatal cerebral insults

Epilepsies of unknown cause („cryptogenic”)

Others •Benign neonatal seizures•Febrile seizures

Berg AT et al Epilepsia 2010

‘Roham’ terminológia

• „Roham”:– Epilepsziás roham

– Migrénes fejfájás-roham

– Pánik-roham (attack)

– Szívroham (angina pectoris)

– Tranziens ischaemiás attack (TIA)

• Görcsroham/Konvulzív roham– eszméletvesztéssel/tudatzavarral vagy anélkül

• Eszméletvesztéssel járó „rosszullét”– görcs/konvulzió nem kötelező !

– pl. collapsus, syncope, stb.

‘Minek nevezellek?’

‘Típusos’ GM (GTKR)

1. Szimplex parciális roham2. Komplex parciális roham vagy egyéb fokális roham vagy

absence roham3. A generalizáció kezdeti szakasza

– „Négyes jel”: fej-verzió, törzs-elfordulás, vokalizáció

4. Pretónusos-tónusos szakasz– Irreguláris és aszimmetriás klónusok

5. Tónusos szakasz– A test összes izmának tartós kontrakciója

6. Remegéses szakasz7. Klónusos szakasz

– Szabályos, ritmusos klónusok (+ izomtónus-csökkenéssel)

Theodore et al. 1994

Az epilepszia kezelése: AED terápia

• Treatment of epilepsy = pharmaco-therapy

– with antiepileptic/anticonvulsive drugs (AEDs)

• Treatment-responders:

– up to 70% (7 in 10) people with epilepsy could have their seizures completely controlled with AEDs

– vica versa: pharmacoresistant epilepsies: about 30%

cca. 26 AEDs

AEDs – generic names

1. Acetazolamide2. Carbamazepine3. Clobazam4. Clonazepam5. Eslicarbazepine

acetate6. Ethosuximide7. Gabapentin8. Lacosamide9. Lamotrigine

10.Levetiracetam11.Nitrazepam12.Oxcarbazepine13.Perampanel14.Piracetam15.Phenobarbital16.Phenytoin17.Pregabalin18.Primidone19.Retigabine

20.Rufinamide21.Sodium

valproate22.Stiripentol23.Tiagabine24.Topiramate25.Vigabatrin26.Zonisamide

https://www.epilepsysociety.org.uk

Melyiket a sok közül?

• Roham-specifikus terápia

• Szindróma-specifikus terápia

• Terápiás guideline-ok

AEDs – seizure-typesAbsence seizures:

Acetazolamide | Clonazepam | Ethosuximide|Lamotrigine | Sodium valproate

Atonic seizures:Phenobarbital | Phenytoin | Primidone | Sodium valproate

Catamenial seizures (menstrual-related):Acetazolamide | Clobazam

Cluster seizures:Clobazam

Episodic disorders:Acetazolamide

Dravet syndrome (SMEI):Stiripentol

Focal (partial) seizures:Acetazolamide | Carbamazepine | Clobazam |Clonazepam | Eslicarbazepineacetate | Gabapentin| Lacosamide | Lamotrigine | Levetiracetam | Oxcarbazepine | Perampanel | Phenobarbital | Phenytoin | Pregabalin |Primidone | Retigabine | Sodiumvalproate | Tiagabine | Topiramate | Vigabatrin | Zonisamide

Focal (partial) seizures with secondarygeneralisation:Gabapentin | Lacosamide | Levetiracetam | Perampanel | Phenobarbital | Phenytoin | Pregabalin| Primidone | Retigabine | Sodiumvalproate | Tiagabine | Topiramate | Vigabatrin| Zonisamide

Focal (partial) seizures with secondary GTCS:Carbamazepine | Eslicarbazepineacetate | Lamotrigine | Oxcarbazepine

https://www.epilepsysociety.org.uk

AEDs – seizure-types

Infantile spasms (West syndrome):Nitrazepam | Sodiumvalproate | Vigabatrin

Juvenile Myoclonic Epilepsy (JME):Levetiracetam

Lennox-Gastaut syndrome :Lamotrigine | Rufinamide | Topiramate

Myoclonic seizures:Clonazepam | Ethosuximide | Phenobarbital | Phenytoin | Primidone | Piracetam | Sodium valproate

Tonic seizures:Phenobarbital | Phenytoin | Primidone | Sodium valproate

Tonic-clonic seizures:Acetazolamide | Carbamazepine | Clobazam | Clonazepam | Eslicarbazepineacetate | Lamotrigine | Phenobarbital | Phenytoin | Primidone | Sodium valproate | Topiramate

West Syndrome with TuberousSclerosis:Vigabatrin

https://www.epilepsysociety.org.uk

The epilepsies: the diagnosis and management of the epilepsies in adults and children

in primary and secondary care

NICE clinical guideline 137, NICE, 2012.Clinical guideline [CG137]

Published date: January 2012 Last updated: February 2016

Treatment of focal seizures

• First line treatment: – carbamazepine, lamotrigine

• Alternative first line treatment: – levetiracetam, oxcarbazepine, sodium valproate

• Cautions: be aware of potential effect of sodium alproatve in pregnancy !!

• Adjunctive treatment (if first line treatment is not effective or not tolerated): – carbamazepine, clobazam, gabapentin, lamotrigine,

levetiracetam, oxcarbazepine, sodium valproate, topiramate• Cautions: be aware of potential effect of sodium valproate in pregnancy !!

• Action if adjunctive treatment is not effective or tolerated: – consider referral to tertiary epilepsy services/ epilepsy surgery centres

https://www.nice.org.uk

Valproát és reproduktív korú nőkValproát teratogén potenciálja

European Medicines Agency (EMA)

The statement of EMA:

VALPROATE “should not be used• in female children,• in female adolescents, • in women of childbearing potential and• in pregnant womenunless alternative treatments are ineffective or

not tolerated.”

http://www.ema.europa.euTomson et al. Epilepsia 2015

Sodium valproate / Valproic acid / Divalproex sodium

• Convulex® 150 / 300 / 500 mg lágy caps.– valproinsav

• Convulex Retard® 300 / 500 mg filmtbl.• Convulex® 50 mg/ml szirup (gyermekeknek)

• Convulex® iv. (100 mg/ml) oldatos injekció

• Depakine Chrono® 300 / 500 mg filmtbl.– 87 mg valproinsavat (megfelel 100,2 mg nátrium-valproátnak) és

199,8 mg nátrium-valproátot tartalmaz 300 mg-os Chronofilmtablettánként

• Depakine® 50 mg/ml szirup• Depakine® iv. (100 mg/ml) oldatos injekció

• (Orfiril retard® filmtbl.)https://www.pharmindex-online.hu

AEDs – teratogenic potentials/risks

Gooneratne and Wimalaratna Postgrad Med J 2016

AEDs: enziminduktorok // nem enziminduktorok

Gooneratne and Wimalaratna Postgrad Med J 2016

AEDs --- CYP450 rendszer

Reddy DS Expert Rev Clin Pharmacol 2010

bidirectional

Treatment of generalised tonic-clonicseizures (GTCS)

• First-line treatment: – sodium valproate, lamotrigine (if sodium valproate is not

suitable)• Cautions: be aware of potential effect of sodium valproate in pregnancy !!

If the person has myoclonic seizures or may have juvenile myoclonic epilepsy (JME)lamotrigine may worsen myoclonic seizures !!

• Alternative first-line treatment:– carbamazepine, oxcarbazepine

• Cautions: be aware that these drugs may worsen myoclonic or absence seizures !!• Adjunctive treatment (if first line treatment is not effective or not tolerated):

– clobazam, lamotrigine, levetiracetam, sodium valproate, topiramate

• Cautions: be aware of potential effect of sodium valproate in pregnancy !!If the person also has absences or myoclonic seizures, or may have juvenilemyoclonic epilepsy (JME) do NOT offer:– carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine, vigabatrin

https://www.nice.org.uk

Treatment of absence seizures

• ethosuximide or sodium valproate as first-line treatment

– if there is a high risk of GTC seizures, offer sodium valproate first, unless it is unsuitable

– Be aware of the teratogenic and developmental risks of sodium valproate !!!

• lamotrigine

– if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated

https://www.nice.org.uk

Treatment of myoclonic seizures

• Offer sodium valproate as first-line treatment to children, young people and adults with newly diagnosed myoclonic seizures, unless it is unsuitable. – Be aware of the teratogenic and developmental risks

of sodium valproate!

• Consider levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. – Be aware that topiramate has a less favourable side-effect

profile than levetiracetam and sodium valproate.

https://www.nice.org.uk

Treatment of tonic or atonic seizures

• Offer sodium valproate as first-line treatment to children, young people and adults with tonic or atonic seizures.

– Be aware of the teratogenic and developmental risks of sodium valproate!

https://www.nice.org.uk

First-line treatments

SEIZURE-TYPES AEDs

FOCAL seizures CBZ/OXC, LTG, LEV, VPA

GENERALIZED seizures:

GTCSs CBZ/OXC, LTG, VPA

Absence seizures ETS, LTG, VPA

Myoclonic seizures LEV, TOP, VPA

Tonic / Atonic seizures VPA

https://www.nice.org.uk

A lényeg…• Az epilepsziás rohamtünetek = sokfélék!

– bizarr tünet ≠ pszichogén• csakis: video-EEG !!

• (hetero)Anamnézis = MINDEN !!!– információ !!!

• Az epilepszia biztos diagnózisa– Differenciál diagnózis !!!

• a kezelt epilepsziák 30-40%-a NEM epilepszia !!

• után: jön a gyógyszeres terápia !!– az ajánlott napi dózisban ! www.pharmindex-online.hu

KÖSZÖNÖM A FIGYELMET!