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Updated: Jul 25, 2025

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The HCN1 p.Ser399Pro variant causes epileptic encephalopathy with super-refractory status epilepticus

Yu Kobayashi1, Jun Tohyama2, Noriyuki Akasaka3

  • 1Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital, Niigata, Japan.

Human Genome Variation
|June 23, 2023
PubMed

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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.
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
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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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Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types:
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γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
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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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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 are specialized medications that prevent seizures in individuals diagnosed with epilepsy. These drugs primarily function by blocking the movement of sodium ions through channels in the neuronal membrane, inhibiting the repetitive firing of action potentials often associated with seizures.
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