María Vázquez López

Objective: Inversion‐duplication syndrome of chromosome 15 (invdup15) is a chromosomal disorder characterized by an inverted duplication of 15q11.2‐q13.1. Epilepsy is highly prevalent (60%–80%), drug‐resistant, and may progress to developmental epileptic encephalopathies (DEEs) such as Lennox–Gastaut syndrome (LGS). Despite its impact, epilepsy and optimal treatments remain poorly described. Methods: A retrospective multicenter study across 37 Spanish hospitals analyzed 54 patients, divided into two genetic subgroups: invdup15q and intdup15q. Clinical and genetic data were reviewed, focusing on epilepsy onset, seizure types, syndrome progression, electroencephalographic (EEG) findings, and treatment response. Results: Epilepsy was present in 29 of 54 (54%) patients, with a mean age at onset of 7.4 years (range = 1 month–24 years, SD = 6.4). LGS (16/29, 55%) and focal epilepsy (15/29, 52%) were the most frequent epilepsy types, although infantile epileptic spasms predominated in younger patients (5/6, 83%). Late onset LGS (>8 years) occurred in 38%. Initial seizures were mostly focal motor (10/29, 34%) and generalized tonic–clonic seizures (8/29, 28%), later evolving to tonic, myoclonic, and atypical absence seizures. Twenty‐six of 29 (90%) reported drug‐resistant epilepsy. Epilepsy was more frequent (65% vs. 35%, p < .05) and had earlier onset (median = 5.7 vs. 12.3 years) in invdup15q than intdup15q. EEG demonstrated unusual activities including diffuse fast activity, along with repetitive trains of paroxysmal fast activity during sleep. The most effective antiseizure drugs were oxcarbazepine for focal (9/11, 81%) and for generalized (2/3, 67%) epilepsy and valproic acid (6/10, 60%) for generalized epilepsy, whereas vigabatrin, zonisamide, and brivaracetam showed limited efficacy. In LGS, oxcarbazepine (8/12, 66%), valproic acid (11/18, 61%), and cannabidiol (6/9, 66%) yielded the best responses. All patients had early developmental delay; autism spectrum disorder was diagnosed in 22 of 54 (41%) and behavioral disorders in 30 of 54 (56%). Significance: Epilepsy in invdup15 is highly drug‐resistant and exhibits features consistent with DEEs, particularly LGS. EEG findings may serve as disorder biomarkers. Oxcarbazepine and valproic acid were the treatments most often associated with seizure improvement in this sample.

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment for dystonia, yet clinical responses remain variable. Imaging-based identification of an optimal stimulation site or “sweet spot” may improve targeting and programming strategies.Objective: To identify the GPi sweet spot using clinically validated DBS software in a heterogeneous cohort of adults and children with dystonia and long-term follow-up.Methods: Thirty patients (60 electrodes) with generalized or cervical dystonia undergoing bilateral GPi DBS and ≥2.5 years of follow-up were included. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patient-specific volume of tissue activated (VTA) models were generated using Guide XT™ and aggregated into normative space via Brainlab Quentry®. VTA heat maps and centroid coordinates were analyzed at the group level.Results: Twenty-six patients (86.7%) were responders (≥30% improvement), including 15 optimal responders (≥65% improvement). VTA heat maps identified a consistent sweet spot in the posteroventral GPi and adjacent subpallidal white matter. Non-responders showed a dorsal displacement of stimulation despite comparable stimulated volumes. Minor spatial deviations (1–3 mm) were associated with poorer outcomes. In subgroup analyses, the sweet spot for cervical dystonia was located more medially than for generalized dystonia.Conclusions: A robust antidystonic sweet spot was identified in the posteroventral GPi and adjacent subpallidal white matter using clinically implemented DBS software. Small spatial deviations, particularly dorsal displacement, were associated with reduced efficacy. These findings may inform surgical targeting and programming strategies in GPi DBS for dystonia.

The aim of this study was to report the clinical features, disease-modifying treatment (DMT) response, and outcomes of children with MOG-IgG who fulfill the 2017 McDonald criteria for multiple sclerosis (MS). This prospective observational study included children (<18 years) with a suspected acquired demyelinating syndrome (ADS) whose serum or CSF was positive for MOG-IgG, who met the indicated MS criteria, and who had ≥1 year of clinical follow-up. MOG-IgG was tested using live cell-based assays. Of 554 children with confirmed ADS (196 with MOG-IgG), 8 (median age 11 years, interquartile range 9–14) harbored MOG-IgG and fulfilled MS criteria: 2 had typical MS and 6 had overlapping MOGAD-MS features at onset, but 5 of the latter group developed an MS-like course during follow-up. Five of 7 patients with assessable samples were Epstein-Barr virus seropositive at disease onset, and all 8 had persistent silent radiologic activity with lesional location and morphology suggestive of MS, leading to initiation of DMT. All initial treatments were well tolerated, but eventually, 7 of 8 children (88%) required high-efficacy DMT. In this pediatric cohort, 4% of patients with MOG-IgG met criteria for MS. The clinical-radiologic spectrum ranged from typical MS to overlapping MOGAD-MS, and patients usually required high-efficacy DMT.

Introducción: Se presenta el caso de un paciente de 14 años, diagnosticado de Síndrome de Kleine-Levin (SKL), que fue atendido por el Equipo de Psiquiatría de Interconsulta y Enlace Infanto-Juvenil presentó dos episodios de hipersomnia y alterciones conductuales. Dada la gravedad y la recurrencia de los episodios, se implementó un enfoque multidisciplinar para discutir el diagnóstico diferencial y el manejo terapéutico. Descripción del caso clínico: Ante la falta de respuesta a los tratamientos convencionales, se inició tratamiento con carbonato de litio, logrando una rápida remisión de los síntomas y la prevención de nuevos episodios a lo largo de 12 meses. Posteriormente, presentó una breve recaída, de menor intensidad y duración, estabilizada tras ajustar la dosis de litio. Discusión y Conclusiones: Este caso destaca la importancia del abordaje multidisciplinar en el manejo del SKL, así como del potencial terapéutico del litio como una opción en pacientes con SKL grave y refractario.

In the Indian subcontinent, traumatic brain injury stands as the leading cause of pediatric stroke, whereas in Europe, it is considered a rare or potentially underdiagnosed factor. The etiology of post-traumatic stroke is unknown, although it has been associated with the presence of calcification in the lenticulostriate arteries, a condition known as “mineralizing angiopathy.” The theory suggests that calcified lenticulostriate vessels in a brain with inadequate myelination could have an increased vulnerability to mechanical injuries, which may result in their obstruction. This ischemic stroke associated with mineralizing angiopathy usually occurs after mild traumatic brain injury, with an asymptomatic interval following the trauma. The typical age of presentation is between 6 and 24 months. Children with mineralizing lenticulostriate vasculopathy generally experience a favorable outcome after stroke, with the majority achieving complete or nearly complete recovery of their motor functions. Despite aspirin treatment, a small proportion of children may still face stroke recurrence following repeat head trauma. We present the cases of two male patients with clinical features compatible with childhood stroke after a mild traumatic brain injury.

TRAF7 syndrome, a multisystemic neurodevelopmental disorder caused by germline missense variants in the TRAF7 gene, exhibits heterogeneous clinical presentations. We present a detailed description of eleven new TRAF7 syndrome cases, featuring eight distinct variants, including a novel one. Phenotypic analysis and a comprehensive review of the 58 previously reported cases outline consistent clinical presentations, emphasizing dysmorphic features, developmental delay, endocrine manifestations, and cardiac defects. In this enlarged collection, novelties include a wider range of cognitive dysfunction, with some individuals exhibiting normal development despite early psychomotor delay. Communication challenges, particularly in expressive language, are prevalent, necessitating alternative communication methods. Autistic traits, notably rigidity, are observed in the cohort. Also, worth highlighting are hearing loss, sleep disturbances, and endocrine anomalies, including growth deficiency. Cardiac defects, frequently severe, pose early-life complications. Facial features, including arched eyebrows, contribute to the distinct gestalt. A novel missense variant, p.(Arg653Leu), further underscores the complex relationship between germline TRAF7 variants and somatic changes linked to meningiomas. Our comprehensive analysis expands the phenotypic spectrum, emphasizing the need for oncological evaluations and proposing an evidence-based schedule for clinical management. This study contributes to a better understanding of TRAF7 syndrome, offering insights for improved diagnosis, intervention, and patient care. Key Message: TRAF7 syndrome, a complex neurodevelopmental disorder, exhibits variable cognitive outcomes, complex behavioral presentation and clinical complications emphasizing the need for tailored interventions and follow-up.

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.