Seizure

The mTOR pathway plays a critical role in neuronal development and migration. Several genes associated with this pathway, including genes from the GATOR1 complex (DEPDC5, NPRL2, and NPRL3), have been implicated in epilepsy. Pathogenic variations in DEPDC5 (DEP domain-containing protein 5) were linked to epilepsy in 2013 [1,2]; while NPRL2 (Nitrogen permease regulator 2-like protein) and NPRL3 (Nitrogen permease regulator 3-like protein) were associated in 2016 [3]. The GATOR1 pathogenic variations have been described in various types of focal epilepsies.

Epilepsy is a chronic neurological disorder affecting approximately 70 million people worldwide[1]. One-third of patients experiencing recurrent seizures despite appropriate pharmacological management[2,3]. Among these individuals with chronic refractory epilepsy, sudden unexpected death in epilepsy (SUDEP) remains the most prevalent cause of mortality, with an incidence rate of approximately three per thousand, accounting for 10-50% of all epilepsy-related deaths[4,5]. Generalized tonic-clonic seizures (GTCS) constitute one of the primary risk factors for SUDEP[6].

A 27-year-old woman had epilepsy since she was 21 years old, with seizures starting as an aura of “the surrounding sound become louder” with giddiness followed by blank stare and oral automatism with impaired awareness. She did not have febrile seizures, head trauma, central nervous system infection or perinatal insult. Her older brother (III-2) has adolescent-onset temporal lobe epilepsy (TLE) with auditory aura described as “surrounding environment become very noisy” and déjà vu, followed by right head and eye version ...

Voltage-gated potassium (Kv) channels control excitability and firing properties of neurons and muscle cells[1], and Kv channel dysfunction can result in pathophysiological states, including epilepsy and cardiac arrhythmia[2,3]. Kv channels are classified into 12 subfamilies (Kv1-12) encoded by a number of gene families, and each Kv channel gene encodes a specific α-subunit (see Gutman et al. (2005) for a comprehensive overview[4]). Ether-à-go-go (EAG) channels (Kv10, Kv11, and Kv12), which are encoded by the KCNH gene family[4,5], represent a structurally and ...

The SCN1A gene encodes the apha-1 subunit (NaV1.1) of the voltage-gated sodium channel, which is critical for the functioning of GABAergic interneurons, and dysfunction causes neuronal hyperexcitability. SCN1A is polymorphic, with over 1500 different variants identified. Most disease-causing variants are heterozygous loss-of-function (LOF) variants that arise de novo [1–3].

Drug-resistant epilepsy (DRE) is defined by the International League Against Epilepsy (ILAE) as the failure of two appropriately chosen and tolerated antiseizure medications (ASMs), either as monotherapy or in combination, to achieve sustained seizure freedom[1]. While focal epilepsies (FEs)—the most common epilepsy type in adults—have the highest rates of drug resistance[2], DRE also significantly affects patients with generalized epilepsies (GEs), combined generalized and focal epilepsies (CGFEs), and developmental and epileptic encephalopathies (DEEs)[3–5].

Drug-resistant epilepsy (DRE), which accounts for about 30% of children with epilepsy, is defined as the failure to obtain persistent seizure independence with two well-tolerated, carefully selected, and used antiepileptic medications [1,2] DRE poses a significant burden. Uncontrolled seizures may cause disruptions in daily activities, impairment in cognitive functions, and increased risk of injury. DRE has also been linked to an increased risk of developmental delays, cognitive disabilities, and psychosocial issues including anxiety and depression.

Epilepsy requires consistent management to improve patient outcomes, minimize its impact on the quality of life, and reduce seizure risk [1,2]. However, variability persists in clinical practices, despite advances in treatment. Consequently, standardization is essential to ensure equitable and high-quality care for all patients [3–5]. A considerable proportion of the global population faces extremely short consultation times. A systematic review reported that in 18 countries, patients had ≤5 min per consultation [6], resulting in poor quality of care [7].

Epilepsy ranks among the most prevalent chronic neurological disorders worldwide. According to epidemiological data from China, the overall prevalence of epilepsy ranges from 4‰ to 7‰, with active epilepsy specifically showing a prevalence of 4.6‰ and an annual incidence rate of approximately 30/100,000 [1]. The 2017 International League Against Epilepsy (ILAE) classification framework categorizes epileptic seizures into three main types: focal, generalized, and unknown [2]. Focal seizures represent the predominant form, and several studies have indicated that approximately 61% of ...

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