Aug 2026· Journal of Neuroscience Research· Vol 104· 0 citations· 272 references
Medicine
TL;DR
The existing literature on astrocyte dysfunction in genetic epilepsy syndromes and neurodevelopmental disorders with seizures is reviewed and several key studies that highlight alterations in crucial astrocyte functions including calcium signaling and ion homeostasis are identified.
Abstract
ABSTRACT Epilepsy is one of the most common neurological disorders worldwide, affecting around 1% of the population. The epilepsies represent a diverse group of conditions, ranging from acquired forms resulting from neurological insults to common multifactorial epilepsies and rare, often monogenic epilepsies caused by highly penetrant genetic variants. The genetic epilepsies demonstrate frequent comorbidity with a range of neurodevelopmental and psychiatric disorders, and epileptic seizures are also a common feature of neurodevelopmental disorders such as Fragile X syndrome and Rett syndrome. Astrocytes, the most numerous glial cells in the central nervous system, have emerged as crucial players in the pathophysiology of acquired epilepsies. Whilst the contribution of astrocytes to acquired epilepsy has been widely reviewed, astrocyte dysfunction in rare genetic epilepsies or neurodevelopmental disorders has been neglected, despite the fact that the genes implicated are expressed in astrocytes, albeit to a lesser extent than in neurons. Additionally, affected individuals with rare genetic epilepsies are more likely to exhibit drug‐resistant seizures, highlighting the need to identify novel therapeutic targets. In this paper, we review the existing literature on astrocyte dysfunction in genetic epilepsy syndromes and neurodevelopmental disorders with seizures. We have identified several key studies that highlight alterations in crucial astrocyte functions including calcium signaling and ion homeostasis. Our review highlights the need for further research to establish the contribution of astrocyte dysfunction to neuronal health and seizure activity in rare genetic epilepsies.
This review synthesizes contemporary insights into the genetic and molecular pathophysiology of seizures and epilepsy, with emphasis on mechanisms that destabilize excitation–inhibition balance, promote epileptogenesis, and drive pharmacoresistance and supports more refined approaches to epilepsy classification and future precision medicine strategies.
Mohammad Reza Seyedtaghia, Jina Babanzadeh, Marcello Scala et al.· Epilepsia Open· 0 citations
Abstract Autoimmune epilepsy, once regarded as a rare and poorly understood subset of seizure disorders, has now emerged as a clinically significant and potentially reversible cause of epilepsy. Advances in neuroimmunology have substantially broadened the spectrum of neural autoantibodies implicated in epileptogenesis—particularly those directed against neuronal cell surface and synaptic proteins, such as the N-methyl-D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65). Distinct autoantibody profiles are now recognized to correlate with characteristic clinical syndromes, facilitating earlier and more targeted diagnosis. For instance, faciobrachial dystonic seizures are highly suggestive of LGI1 antibody-mediated encephalitis, while neuropsychiatric manifestations and movement disorders are typical of NMDAR antibody encephalitis, and chronic temporal lobe epilepsy frequently accompanies GAD65 autoimmunity. Early identification of these immune-mediated forms is critical, as antibody-mediated epilepsies involving cell surface antigens often respond favorably to immunotherapy, leading to substantial recovery. In contrast, epilepsies associated with intracellular antigen targets or cytotoxic T-cell–driven mechanisms, such as Rasmussen encephalitis, typically show poor therapeutic response due to irreversible neuronal injury. Some autoimmune encephalitides also occur as paraneoplastic syndromes, underscoring the importance of comprehensive oncological evaluation in affected patients. Moreover, immune dysregulation has been implicated in catastrophic epileptic conditions such as new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome, further broadening the clinical spectrum of autoimmune-mediated seizures. Although seizures may arise from diverse etiologies, immune mechanisms have gained increasing recognition as an important and potentially modifiable contributor to epileptogenesis. This recognition has been formally endorsed by the International League Against Epilepsy, which classifies autoimmune epilepsy as a distinct diagnostic entity. Nevertheless, true autoimmune epilepsy, in which seizure susceptibility persists after resolution of encephalitic activity, remains relatively uncommon. In most cases, seizures associated with autoimmune encephalitis are acute and reversible with timely immunotherapy. Thus, precise terminology—differentiating acute symptomatic seizures from chronic autoimmune-associated epilepsy—is essential for appropriate management, prognostication, and research standardization.
Monika Singla, Abhishek Dixit, M. Mehndiratta· International Journal of Epi...· 0 citations
This review synthesizes advances in neuroimmunology, clinical phenotyping, diagnostics, immunomodulatory and antiseizure therapies, neuromodulation, and patient and family centered outcomes, and outlines future directions focused on biomarker-driven precision medicine, disease-modifying strategies, and interdisciplinary care models.
Alica M. Goldman, Nora Wong, A. Vezzani et al.· Epilepsy Currents· 0 citations
This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.
Graziana Ceraolo, Giulia Spoto, M. Trivisano et al.· International Journal of Mol...· 0 citations
0.5–1% of children worldwide suffer from epilepsy, a widespread neurological condition that affects people of all genders and demographics. It is a collection of disorders rather than a single illness that is typified by frequent, erratic seizures brought on by aberrant brain activity. These seizures can take many different forms, such as convulsions, sensory or behavioral abnormalities, or loss of consciousness. Recurrent unprovoked seizures, a high likelihood of recurrence, or an epileptic syndrome are the criteria used by the International League Against epileptic (ILAE) to describe epilepsy. Patients' neurological, emotional, and social well-being are greatly impacted by epilepsy, which is caused by neuronal hyperexcitability. Seizure type, EEG results, and related neurological characteristics determine classification. All things considered, epilepsy is a complicated condition with a wide range of causes and symptoms. In children, epilepsy and Attention Deficincy Hyperactivity Disorder (ADHD) often co-occur; approximately 30–40% of children with epilepsy also have ADHD. There are two types of epileptic seizures: focal and generalized. Automatisms, atonic or tonic episodes, clonic jerks, spasms, hyperkinetic movements, or myoclonus are examples of motor symptoms that can accompany focal seizures. Non-motor symptoms include autonomic changes, behavior arrest, cognitive disturbances, emotional changes, or sensory abnormalities. Absence seizures, myoclonic seizures, atonic seizures, tonic seizures, and tonic-clonic seizures are examples of generalized seizures that affect both hemispheres of the brain. This categorization aids in the diagnosis, management, and comprehension of epileptic seizure patterns. A common neurological condition in children, epilepsy is most common in the first year of life and is more common in low- and middle-income nations, where the majority of cases go untreated. The six main categories of its causes are structural, genetic, infectious, metabolic, immunological, and unknown. An imbalance between neuronal excitation and inhibition causes aberrant electrical activity during seizures, which can extend to different parts of the brain. Ion channel malfunction, neurotransmitter imbalance, and altered neuronal circuitry are some of the factors that lead to epileptogenesis and can have long-term repercussions on cognition, particularly following protracted or frequent seizures. When assessing epilepsy, a physical examination is crucial. This includes measuring blood pressure, looking for signs of neurocutaneous syndromes on the skin, and looking for anomalies in the skull that can point to underlying neurological conditions. Electroencephalography (EEG), neuroimaging, and genetic testing are used to diagnose epilepsy in children. Sleep EEG is crucial for focal epilepsies and epileptic encephalopathies. EEG is an easy-to-use method for identifying aberrant cortical excitability. While genetic testing, including next-generation sequencing, has identified over 265 genes associated with epilepsy, increasing the identification of genetic epilepsies, neuroimaging detects structural abnormalities in the brain. Antiepileptic medications including carbamazepine, ethosuximide, and levetiracetam are used in treatment; each is customized for a particular type of seizure and age group while taking side effects and effectiveness into account. An alternate strategy is offered by dietary therapy, especially the ketogenic diet, which lowers seizure frequency by altering neurotransmitter activity and brain metabolism. Together, these therapeutic and diagnostic approaches allow children with epilepsy to be Effecetiveiy managed.
N. P. Patil, Divakar. R. Patil, Akash S. Jain et al.· Research Journal of Pharmaco...· 0 citations
Epilepsy is among the most prevalent chronic neurological disorders, affecting more than 50 million people worldwide and contributing substantially to the global burden of neurological disease. Beyond the seizures themselves, recurrent epileptic activity is increasingly recognized as a driver of progressive cognitive decline; however, cognitive comorbidity remains under-addressed in routine clinical management. This literature review synthesizes current evidence on the mechanisms, clinical manifestations, and assessment of cognitive impairment associated with recurrent seizures. Recurrent seizures arise from an imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission, producing neuronal hyperexcitability and hypersynchronization. During and after seizure episodes, cyclooxygenase-2–dependent cerebral vasoconstriction induces localized hypoperfusion and hypoxia; when repeated, these events accumulate, causing structural and functional brain injury. The hippocampus, essential for memory, is particularly vulnerable to hypoxic-ischemic damage, whereas temporal- and frontal-lobe involvement disrupts memory, language, attention, and executive function. Approximately 60–70% of patients with chronic epilepsy experience cognitive impairment, the severity of which is modulated by age at onset, seizure frequency, duration, and antiepileptic drug use. Practical screening tools such as the Montreal Cognitive Assessment (MoCA), including its validated Indonesian version (MoCA-Ina), demonstrate higher sensitivity than the Mini-Mental State Examination for detecting mild impairment, while brain-derived neurotrophic factor represents a promising biomolecular marker of cognitive dysfunction. Collectively, the evidence indicates that epilepsy management should extend beyond seizure control to incorporate routine cognitive surveillance. Early detection through sensitive screening instruments enables comprehensive, individualized treatment planning and may ultimately improve the long-term quality of life for people living with epilepsy.
Y. Imran, Ainaya Az Zahra· Journal of Society Medicine· 0 citations