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Epilepsy and Seizures: Overview01:24

Epilepsy and Seizures: Overview

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Epilepsy is a chronic neurological disease marked by recurrent, unpredictable seizures. These seizures are caused by abnormal electrical discharges in the brain, leading to behavior, sensation, or consciousness alterations. They can also cause transient impairment of awareness, interfering with daily activities.
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Seizures: Classification01:13

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Epilepsy is primarily characterized by unpredictable seizures, either provoked by an identifiable factor, such as injury or illness, or unprovoked, occurring spontaneously without apparent cause.
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Antiepileptic Drugs: Potassium Channel Activators01:20

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Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
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Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein01:20

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Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
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Antiepileptic Drugs: Glutamate Antagonists01:14

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Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
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Electroconvulsive therapy (ECT), or shock therapy, remains a critical biomedical intervention for severe, treatment-resistant depression. While its origins can be traced back to Hippocrates' observations that malaria-induced convulsions alleviated mental illness, modern ECT has evolved significantly from its earlier, more primitive applications. First introduced in 1938 by Ugo Cerletti and his colleagues, ECT involves inducing controlled seizures using electrical currents. In its early...
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Ultra-refractory epilepsy: The newly described entity.

Jan Vinklárek1, Petra Búřilová2, Mojdeh Raouf Zadeh3

  • 1Brno Epilepsy Center, Member of European Reference Network (ERN)-EpiCARE, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Epilepsia Open
|December 9, 2025
PubMed
Summary

Ultra-refractory epilepsy (URE) is a severe condition where patients fail multiple treatments. New therapeutic strategies are urgently needed for this challenging epilepsy form.

Keywords:
antiseizure medicationdrug‐resistant epilepsyneurostimulationresective brain surgeryultra‐refractory epilepsy

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Area of Science:

  • Neurology
  • Epileptology

Background:

  • Drug-resistant epilepsy (DRE) affects ~30% of epilepsy patients.
  • Ultra-refractory epilepsy (URE) is a severe subtype characterized by failure of ≥6 treatment strategies.
  • URE presents a significant therapeutic challenge in specialized epilepsy centers.

Purpose of the Study:

  • To analyze the demographic and clinical data of URE patients.
  • To characterize the treatment landscape and outcomes in URE.

Main Methods:

  • Retrospective cohort study with prospective follow-up.
  • Analysis of adult URE patients managed at the Brno Epilepsy Center (2017-2023).
  • Data collection via medical records and structured telephone interviews.

Main Results:

  • 62 patients (6%) met URE criteria out of 1034 reviewed.
  • Median seizure onset at 9 years, median evaluation age 35 years.
  • High seizure burden (median 9 seizures/month), 42% with >20 seizures/month.
  • Structural etiology most common (47%); 92% received multimodal therapy (ASMs, surgery, neurostimulation).

Conclusions:

  • URE is an extreme therapeutic challenge with a high seizure burden.
  • Limited treatment response underscores the need for novel therapeutic strategies.
  • Further research into URE is critical due to the significant unmet medical need.