ランドウ・クレフナー症候群

OBJECTIVE: Epilepsy-aphasia spectrum (EAS) represents the most common group of childhood epilepsy syndromes, however, the precise source localization of epileptiform discharges remains undetermined. This study aimed to localize and compare the sources of epileptiform discharges across different EAS subtypes using magnetoencephalography (MEG). METHODS: In this prospective MEG-based study, we recruited 70 patients with EAS, including 52 with self-limited epilepsy with centrotemporal spikes (SeLECTS), 12 with atypical benign partial epilepsy (ABPE), 3 with Landau-Kleffner syndrome (LKS), and 3 with Epileptic Encephalopathy with continuous Spike-and-Waves during sleep (EE-SWAS). Ten independent epileptiform discharges per patient were analyzed using distributed source modeling with standardized low-resolution electromagnetic brain tomography (sLORETA). The spike source density was quantified as current amplitude, and source locations were mapped according to the Desikan-Killiany atlas. RESULTS: The source locations of epileptiform discharges differed significantly across EAS subtypes. EE-SWAS exhibited the highest overall current source density, followed by ABPE, whereas SeLECTS and LKS showed the lowest values. Lobar analysis revealed frontal-predominant discharges in EE-SWAS and ABPE, contrasting with temporal-predominant discharges in SeLECTS and LKS. Moreover, patients with secondary generalized tonic‑clonic seizures exhibited higher current source densities than those with only focal seizures, consistent with broader EEG discharge spread. CONCLUSIONS: This first systematic MEG source analysis across the full EAS reveals a hierarchical gradient from temporo-centric to fronto-centric distribution, paralleling the clinical severity gradient. Our findings highlight the potential of MEG source imaging for phenotyping and pathophysiological stratification in EAS.

Developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS), previously described as continuous spike-wave during slow-wave sleep (CSWS) or electrical status epilepticus in sleep (ESES), is a childhood-onset disorder characterized by cognitive, language, behavioral, and/or motor regression or stagnation associated with marked activation of epileptiform discharges during non-rapid eye movement sleep. Three themes are central to the evolving understanding of D/EE-SWAS. First, it is a network disorder in which thalamocortical dysfunction, impaired sleep-dependent synaptic homeostasis, and potentially neuroinflammatory mechanisms contribute to neurodevelopmental deterioration. Second, increasing recognition of its genetic and structural heterogeneity is reshaping diagnostic evaluation. Monogenic etiologies are identified in up to one-third of cases, with a higher yield in the developmental and epileptic encephalopathy subtype, supporting early genomic testing alongside prolonged sleep EEG, MRI, and serial neuropsychological assessment. Third, treatment remains empiric and constrained by limited comparative evidence. Corticosteroids retain the strongest evidence base for cognitive improvement, although the overall certainty of this evidence remains low to moderate. Benzodiazepines are commonly used alternatives, and epilepsy surgery can provide substantial benefit in appropriately selected patients with focal structural abnormalities. Emerging etiology-directed therapies, including L-serine for selected GRIN loss-of-function variants and primidone for TRPM3-related disease, illustrate a broader transition from syndrome-based to precision management. However, no pharmacological therapy is specifically approved for D/EE-SWAS, long-term neurodevelopmental morbidity remains common, and adequately powered trials using standardized EEG and neurocognitive outcomes are urgently needed.

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.

AIM: To reach an agreed approach to define developmental regression, to improve understanding of aetiology, prevalence, and timing of investigations, and provide standardized and consistent care. METHOD: Developmental regression is a symptom of several developmental, epileptic, genetic, and metabolic conditions (e.g. autism, Rett syndrome, childhood dementias, and Landau-Kleffner syndrome). An expert interdisciplinary clinician panel reviewed the literature for existing definitions and formulated a survey using the Delphi method. Health care clinician perspectives on key elements required for a definition were sought. The survey was completed over two rounds and consensus was defined as a minimum of 70% agreement. RESULTS: Of the 76 clinicians who completed the first-round survey, 41 completed the second round (54%). Consensus was reached on the following definition. Developmental regression refers to: (1) skill(s) loss experienced during childhood lasting a minimum of 4 weeks, and (2) occurring in at least 1 of 6 developmental domains (verbal communication, nonverbal communication, functional motor skills, cognition, social skills, and self-help skills). INTERPRETATION: A working definition of developmental regression is proposed. The intention is that this definition will undergo improvements through use and evaluation to increase its utility and uptake in clinical care and research.

INTRODUCTION: Symptomatic hyperprolactinemia is rarely seen in children, particularly among those with complex neurodevelopmental disorders. While risperidone is known to raise prolactin levels, cases with clear clinical symptoms are uncommon. This report describes an unusual presentation of hyperprolactinemia in a 12-year-old girl with Landau-Kleffner syndrome, autism spectrum disorder, and intellectual disability, whose symptoms closely resembled pituitary pathology. CASE PRESENTATION: The 12-year-old Hispanic Peruvian female was under long-term behavioral control therapy of risperidone. With time, she got galactorrhea, visual impairments, and falls. Laboratory revealed high serum prolactin (40.2 ng/mL) and normal thyroid and negative beta-hCG level. No pituitary lesion was seen on neuroimaging. Behavioral symptoms increased following the discontinuation of risperidone, after which the substitution of the latter with olanzapine led to complete restoration. Three months later galactorrhea disappeared, vision improved, and prolactin level was restored (2.2 ng/mL). The mother of the patient was relieved to find out that it was a medication-related issue, but not a tumor and indicated a significant enhancement in the overall behavior and quality of life of her child. CONCLUSIONS: The case shows the significance of following prolactin levels in children who are on risperidone therapy particularly those who are non-verbal or those who cannot communicate any discomfort. Clinicians are to remember that risperidone leads to hyperprolactinemia which can simulate pituitary malfunctions. Early identification, educating caregivers, and substitution of prolactin-stimulating drugs with prolactin-sparing ones like olanzapine will allow avoiding unnecessary investigations and enhancing the clinical and family outcomes.