Antikonvulsiva, die bei fokalen Krampfanfällen eingesetzt werden

Focal seizures (now referred to as focal rather than partial) originate in a focal region of the cortex and can be subdivided into those that do not impair consciousness (simple focal) and those that do (focal dyscognitive seizures). Both types of focal seizure can spread rapidly to other cortical areas, resulting in secondary generalised tonic-clonic (GTC) seizures.

Relevant separate articles include Epilepsy in Children and Young People, Epilepsy in Adults and Epilepsy in Elderly People.

Pregnancy¹

Simple focal seizures

• Presentation depends on the site of origin of the discharge - eg, those arising from the motor cortex cause rhythmic movements of the contralateral face, arm or leg (Jacksonian seizures).

• Seizures arising from sensory regions or areas responsible for emotions and memory may produce olfactory, visual or auditory hallucinations, feelings of déjà vu or jamais vu, fear, panic or euphoria.

Focal dyscognitive seizures

• An epileptic seizure that is limited to one cerebral hemisphere and causes impairment of awareness or responsiveness.

• Temporal lobe epilepsy may be simple focal seizures without loss of awareness (with or without aura) or focal dyscognitive seizures (with loss of awareness).

Antiepileptic drugs used for focal seizures^{3 4 5}

Not all epilepsy is lifelong and it is defined as having resolved when people have remained seizure-free for more than ten years, with no drug treatment for at least five years. Approximately 70% of all adults and children with epilepsy will go into remission. The chances of remission vary with the type of epilepsy, the response to antiepileptic drugs (AEDs) and the frequency of seizures. Withdrawal of medication, if wanted, should be done slowly, with the acknowledgement that it always carries a risk of further seizures.⁶

The National Institute for Health and Care Excellence (NICE) advice on treatment of focal seizures is as follows. Unsuccessful treatment is defined as treatment which either does not reduce or stop seizures, or has intolerable side-effects.

• First-line treatment: offer lamotrigine or levetiracetam, moving to the other of these two drugs if the first one tried is unsuccessful.

• If both of these first-line monotherapies are unsuccessful, consider a second-line monotherapy option, choosing between carbamazepine, oxcarbazepine or zonisamide. Try all of these three in turn if the first one is unsuccessful.

• Consider lacosamide as third-line monotherapy if all the second-line drugs are unsuccessful.

• If monotherapy is unsuccessful, consider any of the drugs listed above, or topiramate, as first-line add-on options, considering other drugs from this list if the first one tried is unsuccessful.

• Wenn eine Monotherapie nicht erfolgreich ist, sollte eine ergänzende Behandlung in Betracht gezogen werden:
  

  • First-line options for adjunctive treatment include carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate, or zonisamide.

  • Second-line options include brivaracetam, cenobamate⁷ , eslicarbazepine acetate, perampanel, pregabalin, or sodium valproate (in males, and females unable to have children).

  • Third-line add-on treatments include phenobarbital, phenytoin, tiagabine and vigabatrin.

Some drugs used in clinical practice can exacerbate seizures in those with absence or myoclonic seizures, including juvenile myoclonic epilepsy.

Interactions⁵

• Interactions between AEDs are complex and may enhance toxicity without a corresponding increase in antiepileptic effect.

• These interactions are very variable and unpredictable.

• Changes in medication should therefore always be done by a neurologist.

Initiation of drug treatment^{3 4}

• Eine AED-Therapie sollte nur dann begonnen werden, wenn die Diagnose Epilepsie bestätigt ist, es sei denn, es liegen außergewöhnliche Umstände vor. Die AED-Therapie sollte von einem Facharzt eingeleitet werden.

• Eine AED-Therapie wird in der Regel nach einem zweiten epileptischen Anfall empfohlen. Eine AED-Therapie sollte nach einem ersten unprovozierten Anfall erwogen und diskutiert werden, wenn:
  

  • Es besteht ein neurologisches Defizit.

  • The electroencephalograph (EEG) shows unequivocal epileptic activity (however a normal EEG should not be used to exclude the diagnosis of epilepsy, and should prompt consideration of a sleep-deprived EEG).

  • The patient or their family or carers consider the risk of having a further seizure unacceptable.

  • Die Bildgebung des Gehirns zeigt eine strukturelle Abnormität.

• Die Dosis jedes Medikaments sollte langsam bis zur maximal verträglichen Dosis oder der in der British National Formulary empfohlenen Höchstmenge titriert werden. Die Wirkung kann anhand der vom Patienten aufgezeichneten Anfallshäufigkeit überwacht werden.

• Die Formulierungen von AEDs sind nicht austauschbar, und eine generische Substitution sollte nicht routinemäßig vorgenommen werden. Ein routinemäßiger Wechsel zwischen verschiedenen Herstellern von AEDs sollte vermieden werden.

Continuation of drug treatment^{3 4}

• Halten Sie ein hohes Maß an Wachsamkeit für unerwünschte Wirkungen der Behandlung aufrecht.

• Continuing AED therapy should be planned by a specialist as part of an agreed treatment plan and the needs of the child, young person or adult and their family and/or carers should be taken into account.

• If management is straightforward, continuing AED therapy can be prescribed in primary care if local pathways and/or licensing allow.

• Die Therapietreue kann durch folgende Maßnahmen optimiert werden:
  

  • Aufklärung von Kindern, Jugendlichen und Erwachsenen sowie ihrer Familien und/oder Betreuer über ihre Erkrankung und die Gründe für die Behandlung.

  • Verringerung der mit der Krankheit verbundenen Stigmatisierung.

  • Verwendung einfacher Medikamentenschemata.

  • Positive Beziehungen zwischen Fachkräften des Gesundheitswesens, dem Kind, dem Jugendlichen oder dem Erwachsenen mit Epilepsie und seiner Familie und/oder seinen Betreuern.

• Regular blood test monitoring is not recommended as routine and should be done only if clinically indicated. The pharmacokinetics of some AEDs are non-linear, so specialist knowledge is needed to interpret drug levels. Indications for monitoring of AED blood levels include:

  • Detection or suspicion of non-adherence to the prescribed medication.

  • Unkontrollierte Krampfanfälle.

  • Nebenwirkungen.

  • A specific clinical condition needing closer supervision (eg, pregnancy or renal failure).

  • Anpassung der Phenytoin-Dosis.

  • Assessment of toxicity.

  • Otherwise unexplained loss of seizure control.

Treatment of drug-resistant epilepsy⁴

• Drug-resistant epilepsy has been defined as failure to achieve sustained seizure freedom after trials of two tolerated and appropriate AED schedules (as monotherapy or in combination). The majority of patients with newly diagnosed epilepsy respond well to AEDs. Failure to do so may be due to:

  • Eine falsche Diagnose der Epilepsie.

  • Eine ungeeignete Wahl von AED für das Epilepsiesyndrom.

  • Unterlassung der Einnahme des verordneten AED.

  • An underlying cerebral neoplasm, metabolic condition, or immune process.

  • Gleichzeitiger Drogen- oder Alkoholmissbrauch.

• Given a correct diagnosis of epilepsy, failure to control seizures completely with the first well-tolerated AED is a predictor of drug-resistant epilepsy. Once two AEDs have failed as monotherapy the chance of seizure freedom with further monotherapy is low. Improvement in seizure control may be obtained by combining AEDs.

• A range of different AEDs appropriate to the epilepsy syndrome should be added as necessary in sequence, increasing the dose of each slowly to obtain the best response. It may be worthwhile trying the addition of a small dose of a third AED but it may be necessary to accept the persistence of some seizures.

• Failure to respond to appropriate AEDs should prompt a review of the diagnosis of epilepsy and adherence to medication.

• The guidance gives specific regimes for various epilepsy syndromes which are too numerous to list here.

Withdrawal of drug treatment^{3 4}

• The decision to continue or withdraw medication should be taken after a full discussion of the risks and benefits of continuing or withdrawing AED therapy. Withdrawal of AEDs must be managed by, or be under the guidance of, the specialist, after an individualised assessment which considers the risk of seizure recurrence and sudden unexplained death in epilepsy (SUDEP).

• Die Risiken und der Nutzen einer Fortsetzung oder eines Absetzens der AED-Therapie sollten besprochen werden, wenn die Person mit Epilepsie seit mindestens zwei Jahren anfallsfrei ist.

• Das Absetzen der AED-Behandlung sollte langsam erfolgen (mindestens 2-3 Monate), und es sollte jeweils ein Medikament abgesetzt werden.

• Besondere Vorsicht ist geboten, wenn Benzodiazepine und Barbiturate abgesetzt werden (dies kann bis zu sechs Monate oder länger dauern), da die Möglichkeit besteht, dass drogenbedingte Entzugssymptome und/oder erneute Krampfanfälle auftreten.

• Es sollte ein Plan vereinbart werden, der vorsieht, dass bei einem erneuten Auftreten von Anfällen die letzte Dosisreduzierung rückgängig gemacht und ärztlicher Rat eingeholt wird.

• Discontinuation of medications after epilepsy surgery should be done under guidance from the epilepsy surgery centre.