Jun 2026· Iranian journal of child neurology· Vol 20, pp. 87 - 93· 0 citations· 17 references
Medicine
TL;DR
A boy with normal early development who developed progressive aphasia and non-motor seizures around age three is described, with electroencephalographic findings consistent with spike-wave activation during slow sleep, while neuroimaging and metabolic evaluations were normal.
Abstract
Landau-Kleffner syndrome and related epilepsy-aphasia spectrum disorders are characterized by childhood-onset language regression, sleep-activated epileptiform activity, and frequently refractory seizures. This case report describe a boy with normal early development who developed progressive aphasia and non-motor seizures around age three, with electroencephalographic findings consistent with spike-wave activation during slow sleep, while neuroimaging and metabolic evaluations were normal. Standard antiseizure medications and repeated immunotherapy provided no sustained benefit. Genetic testing at age 12 identified a pathogenic heterozygous GRIN2A gain-of-function missense variant (p.T531M), guiding initiation of targeted therapy with memantine, and an NMDA receptor antagonist. Following memantine treatment, the patient showed marked improvement in speech and social interaction together with reduced sleep-related epileptiform discharges, although some deficits persisted. This case underscores the value of early genetic evaluation in refractory epilepsy-aphasia syndromes and supports the potential role of precision NMDA-modulating therapy in GRIN2A-associated epileptic encephalopathy.
Lennox–Gastaut Syndrome (LGS) is a severe childhood-onset epileptic encephalopathy characterised by multiple daily seizures of varying semiology, intellectual disability, and a characteristic electroencephalographic pattern. Neuropsychiatric comorbidities - including attention-deficit/hyperactivity disorder (ADHD), autistic spectrum manifestations, and learning difficulties - are well documented in this population. Management is challenging owing to poor seizure response to conventional antiepileptic medications and the complexity introduced by co-occurring psychiatric disorders.
We report the case of a patient with LGS severely resistant to antiepileptic therapy and complicated by worsening ADHD symptoms. Following years of trialling multiple antiseizure medications with limited benefit, memantine was initiated alongside other medications and was associated with meaningful improvement in seizure frequency, cognition, and behavioural manifestations. ADHD medications were subsequently reintroduced, were well tolerated, and further improved the patient’s attention and behaviour.
This case highlights a novel application of memantine - an agent most commonly used in the management of Alzheimer’s disease - and suggests its potential utility as adjunctive therapy for improving both seizure control and neuropsychiatric symptoms in patients with LGS. Further research is warranted to evaluate this therapeutic approach systematically.
Akuti Khanna, Özge Özkan, Aditi Pajiyar et al.· Journal of Global Health Neu...· 0 citations
Abstract Introduction Rasmussen’s encephalitis (RE) is a rare immune-mediated neurological disorder characterized by refractory focal epilepsy, progressive neurological deficits, and unilateral cerebral atrophy. Although typically a pediatric disease, adult-onset cases account for fewer than 10% of reported diagnoses and remain poorly characterized. Early recognition and prompt immunotherapy are critical to limit irreversible neurological damage. Case Presentation We report the case of a 46-year-old woman with adult-onset RE presenting with focal non-motor seizures and progressive cognitive impairment. Neuroimaging demonstrated progressive left hemispheric atrophy with hippocampal and mammillary involvement, while continuous electroencephalographic monitoring revealed persistent left frontotemporal epileptogenic activity. Cerebrospinal fluid analysis showed intrathecal antibody synthesis. Immunotherapy with oral tacrolimus was initiated, resulting in stabilization of cognitive decline and reduction of seizure frequency from approximately 30–40 to 15–20 episodes per day. Due to persistent seizures and intolerance to multiple antiseizure medications (ASMs), a classical ketogenic diet was introduced as adjunctive therapy, leading to an additional reduction in seizure frequency of approximately 50% 6 months after initiation, and subjective stabilization of cognitive symptoms despite minimal change in screening scores. Seizure control and clinical state have remained stable up to current follow-up, almost 5 years after combined treatment initiation. Conclusion This case highlights the potential therapeutic benefit of combining immunomodulatory therapy with ketogenic dietary intervention in adult-onset RE. Beyond its established role in refractory epilepsy, ketogenic therapy may exert anti-inflammatory and neurometabolic effects through modulation of microglial activation, cytokine signaling, and cellular metabolism pathways implicated in RE pathogenesis. The combination of tacrolimus and a ketogenic diet was associated with substantial seizure reduction and stabilization of cognitive impairment in this patient with adult-onset RE. These findings suggest that ketogenic dietary therapy may represent a promising adjunctive therapeutic strategy alongside immunomodulatory treatment in this rare and challenging condition. Further studies are needed to clarify its role in disease progression and seizure control.
Sergio Andrés Salgado Rueda, Nicolás Moreno Guerra, Jorge Luis Vargas Rojas· Case Reports in Neurology· 0 citations
Mutations in the GRIN gene family, which encode subunits of the NMDA (N-methyl-D-aspartate) receptor, have been increasingly associated with a spectrum of neurodevelopmental disorders. Among them, GRIN2A mutations play a crucial regulatory role in the receptor's function, affecting synaptic transmission and brain plasticity.
This case study presents the clinical and genetic profile of a pediatric patient with a pathogenic GRIN2A mutation, highlighting the associated neurological phenotype, diagnostic process, and treatment approach.
Clinical data were collected through neurological assessments, EEG, MRI, and comprehensive genetic testing, including next-generation sequencing (NGS), with confirmation by Sanger sequencing. The patient's symptoms, including developmental delay, epileptic episodes, and behavioral abnormalities, were analyzed in the context of current literature on GRIN-related disorders
The identified pathogenic GRIN2A mutation correlated with a neurodevelopmental phenotype characterized by early-onset epilepsy, hypotonia, and intellectual disability.
The above case highlights the importance of early genetic testing in children with neurodevelopmental disorders and aphasia, as well as co-occurring epilepsy. Understanding the functional impact of specific GRIN2A mutations can guide personalized treatment strategies and contribute to a better characterization of the GRINopathy spectrum.
A. Bryzik, Dawid Larysz, Patrycja Larysz et al.· Polish Annals of Medicine· 0 citations
Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is a rare neurodegenerative disorder caused by pathogenic variants in NAXE gene. Movement disorders are among the clinical features of PEBEL1; however, no case presenting with paroxysmal exercise-induced dyskinesia (PED) has been reported. We reported the case of a 14-year-old girl who presented with PED episodes. Six months after the onset of episodes, she developed encephalopathy and focal status epilepticus. Exome sequencing analysis identified a homozygous pathogenic variant in NAXE gene, and she was diagnosed with PEBEL1. She was started on mitochondrial cocktail and multiple antiseizure medications; however, no response was observed. With the ketogenic diet (KD), seizure control was achieved and improvement in cognitive functions was observed. PED is a clinical feature not previously reported in PEBEL1 cases, and our case expands the phenotypic spectrum of this disorder. Additionally, our case highlights that KD may be a treatment option in PEBEL1.
Mert Altıntaş, M. Yıldırım, Ömer Bektaş et al.· Journal of Child Neurology· 0 citations
It is proposed that FFA's effectiveness stems from its ability to address two core pathologies of SV2A deficiency: correction of the excitatory/inhibitory imbalance by restoring inhibitory tone through its serotonergic mechanism, and mitigation of neuroinflammation, thereby stabilizing the neuronal network.
Ettiologic heterogeneity and phenotype overlapping between PDE and PRE, atypical presentations, and good initial response to pyridoxine regardless of genetic and neuroimaging findings suggest the introduction of pyridoxine in all infants when two ASMs have failed.
Ružica Kravljanac, Biljana Vucetic Tadic, Vladimir Oparnica· Frontiers in Neurology· 0 citations
