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Drug-resistant epilepsy

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The definition of epilepsy is two or more unprovoked seizures​. Epilepsy can be defined by two or more unprovoked seizures​. Abnormal neuronal firing leads to a clinical alteration of neurologic function, be it motor​, sensory​, autonomic​ or psychological​. Hallmarks of a seizure are neuronal hyperexcitability – reduced threshold for action potential at level of single neuron​, and neuronal hypersynchrony – neurons in a given area firing together​.

Epilepsy is one of the most prevalent neurological conditions, with no predilection for race or age. It is more common than Parkinson's disease, muscular dystrophy, cerebral palsy, and multiple sclerosis combined. Fifty million people worldwide have epilepsy with 2.4 million diagnosed with epilepsy each year​. In-high income countries, this equates to 30-50 new cases per 100 000 and it is up to two times higher in low- and middle-income countries​.

Of the 50 000 000 people with epilepsy​, 75% have inadequate treatment. This ​is based on poor knowledge and stigma​, poor prioritisation within the healthcare system​ and high costs​.

Less than 1% of patients are referred to a full epilepsy centre. Of those who are, the referral may be 20 years after seizure onset.​

Pharmacological treatment options​

Antiepileptic drug (AED) therapy, the mainstay of treatment for most patients, has four goals: ​

  • Eliminate seizures or reduce their frequency​
  • Evade the adverse effects associated with long-term treatment​
  • Aid patients in maintaining or restoring their usual psychosocial and vocational activities​
  • Aid patients in maintaining a normal lifestyle​.

AED therapy decisions should balance these factors to provide optimal seizure relief and QoL for patients.

Despite the development of new AEDs (of which there are now ​more than 24) many patients still suffer from continued seizures.

The failure of ​two appropriately chosen and tolerated AEDs ​(whether as monotherapies or in combination) ​to control seizures when used for an ​adequate period. After adequate trials of at least two AEDs, ​overall seizure freedom rates with subsequent treatment trials are dramatically decreased​. Adding drugs in drug-resistant epilepsy (DRE) may not reduce seizures.

Failure of previous AEDs diminishes seizure-free rates for future AEDs. Patients with DRE suffer the physical, psychological and societal consequences of intractable seizures with a heavy drug burden and an increased mortality.

Sudden unexpected death in epilepsy occurrence is unanticipated and highly traumatic to the families of patients. Sudden cardiac death (SCD) risk is high in epilepsy and sodium channel blocking AEDs contribute to SCD susceptibility​. Risk of accidental death is higher in patients with epilepsy. Status epilepticus is a direct cause of premature death​. Suicide is an external cause of elevated mortality in epilepsy​.

Unmet needs in DRE​

Tackling DRE is one of the most important challenges in epilepsy management​.

Patients may experience complete resistance to AED treatment or may be deemed only partially responsive if seizures are reduced in frequency and/or intensity but not eliminated​.

Conclusion

Early identification of patients with DRE allows effective treatment that may reduce mortality and the potential irreversible psycho-social consequences of continuing seizures​.

Treatment options are evolving rapidly.

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