Severe Epilepsy Syndromes in Childhood: A Comprehensive Review of Clinical Features, Etiologies, and Advancing Therapeutic Landscapes

Paediatric Epilepsy: Current Advances in Diagnosis and Management

Paediatric epilepsy is one of the most common chronic neurological disorders of childhood, characterised by recurrent unprovoked seizures resulting from abnormal neuronal activity. Accurate diagnosis is essential and is based on a detailed clinical history, seizure semiology, neurological examination, and electroencephalography (EEG), with neuroimaging such as magnetic resonance imaging (MRI) used to identify structural abnormalities. Classification according to seizure type and underlying aetiology genetic, structural, metabolic, immune, infectious, or unknown—guides appropriate management strategies. The primary goal of treatment is to achieve optimal seizure control while minimising adverse effects and supporting normal neurodevelopment. First-line management typically involves antiseizure medications (ASMs) selected according to seizure type, patient age, comorbidities, and potential drug interactions. Approximately two-thirds of affected children achieve seizure remission with pharmacological therapy. However, a significant proportion develop drug-resistant epilepsy (DRE), requiring alternative approaches such as ketogenic diet therapy, vagus nerve stimulation, or epilepsy surgery. Early identification of DRE is critical to reduce the risk of cognitive, behavioural, and psychosocial impairment. Comprehensive care extends beyond seizure management and includes addressing developmental, educational, and psychosocial needs. A multidisciplinary, family-centred approach involving neurologists, dietitians, psychologists, and educators is essential. Advances in genetic testing and precision medicine are improving diagnostic accuracy and enabling more personalised treatment strategies in (PE).

New and emerging pharmacotherapeutic options for the treatment of pediatric focal epilepsies.

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Paediatric posterior reversible encephalopathy syndrome: a review of aetiologies, clinical and radiological spectrum, pathophysiology, diagnostic criteria and management

Posterior reversible encephalopathy syndrome (PRES) is a rare clinico-radiological syndrome postulated to be due to disturbed cerebral autoregulation characterized by acute onset seizures, altered sensorium, headache, visual disturbances, and typical neuroimaging findings of vasogenic oedema in parietooccipital white matter. Although originally described in adults, PRES is increasingly recognized in children, particularly in association with renal disease, hypertension, autoimmune disorders, malignancy, chemotherapy, transplantation, infections, and immune-mediated conditions. Paediatric PRES differs from adult PRES in having a higher frequency of atypical imaging findings involving brainstem, spinal cord, basal ganglia; and broader etiological diversity. Advances in neuroimaging, molecular biology, and endothelial dysfunction research have improved understanding of disease mechanisms. However, diagnostic criteria remain largely clinico-radiological. This review summarizes current evidence regarding diagnosis, typical and atypical radiological findings, aetiologies, tertiary-care experiences, pathophysiological mechanisms, emerging genetic associations, and an algorithmic approach to management.

Pediatric occipital lobe epilepsy: A modern review of etiological classification, management, and outcomes.

Pediatric occipital lobe epilepsy (OLE) comprises syndromes with seizures originating from the posterior cerebral cortex. Previously "benign", recent International League Against Epilepsy (ILAE) updates reclassified these as self-limited or structural focal epilepsies, reflecting their complex causes and morbidity potential. The 2017 ILAE guidelines shifted from syndromic recognition to an etiology-driven approach. High-resolution magnetic resonance imaging is crucial to differentiate self-limited genetic syndromes from structural OLE (e.g., focal cortical dysplasia), as the latter often requires surgery. Self-limited epilepsy with autonomic seizures (formerly Panayiotopoulos syndrome) presents with prolonged nocturnal autonomic seizures. Childhood occipital visual epilepsy (previously Gastaut type) manifests as frequent, brief daytime visual hallucinations. Despite high seizure freedom rates with monotherapy, patients face neurocognitive challenges in visuospatial processing and academic performance. For drug-resistant structural cases, surgery offers high seizure freedom rates, though with risk of visual deficits. Accurate differentiation between idiopathic and structural OLE is essential for improving outcomes. The shift from "benign" to "self-limited" terminology emphasizes the need to monitor cognitive comorbidities and syndrome evolution. Early diagnosis is critical to avoid clinical mimics and enhance neurodevelopmental outcomes. This review examines the evolving landscape of pediatric OLE, highlighting the shift from syndromic to etiological classification and management strategies.

Epilepsy of infancy with migrating focal seizures: A scoping review of clinical features, diagnostic testing including genetics, long-term outcomes, mortality, and current and emerging therapeutic strategies.

BACKGROUND Epilepsy of infancy with migrating focal seizures (EIMFS) is among the most severe developmental and epileptic encephalopathies (DEEs), marked by intractable multifocal seizures migrating across both hemispheres, profound developmental arrest, and high early mortality. Advances in next-generation sequencing have revealed a heterogeneous genetic architecture dominated by KCNT1 gain-of-function variants across more than 30 implicated genes, creating opportunities for precision therapeutics. OBJECTIVE To systematically map published evidence on the clinical, electrophysiological, neuroimaging, genetic, and therapeutic landscape of EIMFS, and to delineate critical knowledge gaps and future research priorities. METHODS A scoping review was conducted following the Arksey and O'Malley framework, searching PubMed, Ovid MEDLINE, Embase, Cochrane Library/CENTRAL, and ClinicalTrials.gov. RESULTS Of 643 articles screened, 89 met inclusion criteria. Beyond confirmation of the canonical electroclinical phenotype, several gaps emerged: neonatal versus post-neonatal onset stratification by genetic etiology remains largely uncharacterized; genotype-specific EEG biomarkers are lacking except for a single small KCNT1 study; and the clinical significance of atypical EEG features-including burst suppression and hypsarrhythmia-is undefined. Neuroimaging literature documents progressive cerebral atrophy and myelination abnormalities without quantitative volumetry, diffusion tractography markers, or attribution to seizure burden, medication effects, or underlying etiology. Genetic diagnostic yield was 70-80%, with KCNT1 accounting for 30-50% of solved cases; however, genotype-outcome stratification is limited. Seizures were broadly refractory; potassium bromide, ketogenic diet, cannabidiol, and quinidine (in KCNT1-confirmed cases) showed partial efficacy. Emerging precision approaches include sodium channel blockers for SCN2A gain-of-function variants, novel small molecules, fluoxetine, antisense oligonucleotides, and divalent siRNA targeting KCNT1. Systemic-to-pulmonary collateral circulation causing severe cardiopulmonary complications was reported across multiple cases, yet no consensus screening protocol exists. CONCLUSIONS EIMFS remains one of the most refractory epilepsy syndromes of infancy. Precision genetic diagnosis is essential to guide targeted therapy. International collaborative registries, standardized outcome measures, genotype-stratified biomarker studies, and rapid point-of-care genomic testing are urgently needed to advance evidence-based care for this highly vulnerable population.