Epilepszia. Antiepileptikumok. GYAKORLATI SZEMPONTOK Dr. Szok Délia SZTE ÁOK Neurológiai Klinika Rezidens képzés 2017. február 28.
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.
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
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