ランドウ・クレフナー症候群

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.

Autism regression, defined by the loss of previously acquired social, communicative, and language skills, affects approximately 25%-30% of children on the autism spectrum, most commonly emerging between 12 months and 30 months of age. Once debated as a potential artifact of parental recall or observation bias, contemporary evidence-including home-video analyses and prospective sibling studies-establishes regression as a biologically grounded neurodevelopmental deviation rather than a psychogenic phenomenon. This review presents an integrated model of regression, conceptualizing it as a "neurobiological crisis" in which the convergence of physiological stressors unmasks latent genetic vulnerabilities during a critical period of brain reorganization. Central mechanistic pathways include excessive synaptic pruning, excitatory-inhibitory imbalance, neuroinflammation, mitochondrial dysfunction, and dysbiosis of the gut-brain axis. From a clinical perspective, the period immediately following skill loss represents a window of heightened neuroplasticity. Pediatricians are urged to move beyond a "wait-and-see" approach, adopting a dual-track strategy that combines rapid medical and genetic evaluation to exclude pathological mimics (e.g., Landau-Kleffner syndrome, metabolic disorders) and to initiate immediate intensive behavioral and developmental interventions. Leveraging naturalistic developmental and behavioral interventions, as well as and parent-mediated strategies, many children achieve a meaningful functional reacquisition of lost skills. Ultimately, this review advocates empowered realism, framing regression as a dynamic, modifiable process in which early identification, precision-guided assessment, and evidence-based intervention can optimize long-term developmental and adaptive outcomes.

INTRODUCTION: Previous research suggests that amantadine could be effective as an antiepileptic drug. We evaluate the use of the drug in children with refractory generalised epilepsy. METHOD: Retrospective study of children with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) or generalised epilepsy with refractory absence seizures treated with amantadine at a paediatric hospital in Madrid, Spain, over a 3-year period. RESULTS: We studied 12 children treated with amantadine for refractory epilepsy at a median age of 9.5 years (range, 3-11) and a median disease duration of 5 years (range, 1-8). Before initiation of amantadine, the patients had received 9.4 antiepileptic drugs on average (range, 6-14), and 9 had been placed on a ketogenic diet. Brain MRI displayed no structural lesion in any patient, except for one with a thalamic lesion. All patients had idiopathic epilepsy, and MRI results were normal. Five were diagnosed with D/EE-SWAS, and 7 had generalised epilepsy with refractory absence seizures (5 with refractory absence epilepsy, one with eyelid myoclonia with absence seizures, and one with Lennox-Gastaut syndrome). Amantadine was added to other antiepileptic drugs (mean number of drugs administered, 2.7) at a mean dose of 5.6mg/kg/day, with a maximum dose of 300mg/day. In the group with D/EE-SWAS, amantadine therapy achieved EEG activity normalisation and seizure control (myoclonic and absence seizures) in 80% (4/5). Among the patients with refractory epilepsy, only one (14.2%) achieved seizure control (75-99% response). One patient (10%) developed adverse effects (irritability and insomnia), leading to withdrawal of amantadine. CONCLUSION: Amantadine is an effective and safe treatment for drug-resistant generalised epilepsy, especially in patients with D/EE-SWAS.

This case report describes Landau-Kleffner syndrome (LKS) with adult-onset epilepsy in a 33-year-old man with preexisting developmental delay. We outline the clinical presentation, including language regression and seizures, and address the diagnostic challenges. The case highlights the importance of considering LKS in case of adult-onset epilepsy and underscores the critical role of electroencephalography, particularly the presence of continuous spike-wave activity during sleep. We also review the treatment options of LKS with adult-onset epilepsy, with the focus on the effectiveness of levetiracetam. An atypical finding of right hippocampal sclerosis on brain magnetic resonance imaging is also noted. This case contributes to the limited literature on LKS with adult-onset epilepsy and emphasizes the need for further research.