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GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18 years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12 months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3 months and 1 day before starting treatment and 1, 3, 6 and 12 months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8 years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Ceano-Vivas, García, Velázquez, Martín del Valle, Menasalvas, Cilla, Epalza, Romero, Cabrerizo and Calvo.)

Aim: Human parechoviruses (HPeV) are responsible for fever without a source (FWS), sepsis-like illness and encephalitis in neonates and children under 3 months of age. Short-term outcome is generally good, but there is great concern about medium and long- term outcome of infants after HPeV infection. The aim of this study is to assess the medium-term outcome in infants following HPeV infection without encephalitis., Methods: Patients who suffered HPeV infection involving cerebrospinal fluid were evaluated twice using Ages and Stages Questionnaire-3 (ASQ-3). The first evaluation was conducted at least one year after the infection and the second one year later., Results: Sixteen patients were evaluated in the first assessment, and three of them presented mild alterations in motor function domains. Moreover, hypotonia was observed in the neurologic exam in one case, and hemiparesis in another case. In the second assessment fifteen patients were included, and only the patient with hemiparesis continued presenting gross motor disfunction, with complete recovery of the remaining patients., Interpretation: We have observed a good medium-term prognosis in infants after HPeV infections, with improvement of mild motor alterations after at-home intervention. Infants who suffer HPeV infection without encephalitis seem to have a better prognosis than those with encephalitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever of unknown origin (FUO), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses., Patients and Methods: A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae., Results: Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae CONCLUSIONS: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FUO and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood, characterized by electro-clinical triad of generalized spike-wave activity, slow (POL) in the electroencephalogram (EEG), multiple types of seizures and development delay. This paper intends to describe the syndrome in a patient with a history of hypoxic-ischaemic encephalopathy and Lennox-Gastaut syndrome, and a good response to treatment with levetiracetam (LEV)., Method: Descriptive study on the development of a 3 year old child with intrauterine asphyxia, multiorgan failure, metabolic acidosis, hypovolemic shock, and seizures with cerebral oedema, who developed a West syndrome, resistant to drug treatment. The semiology of seizures progressively changed to generalized episodes of hypertonia and myoclonus, with slow spike-wave electroencephalographic activity., Results: With the diagnosis of Lennox-Gastaut syndrome the patient was treated with levetiracetam, showing a substantial improvement in the cognitive sphere, in the control of seizures, and electroencephalographic findings., Conclusions: Lennox-Gastaut syndrome is one of the most severe epileptic syndromes in paediatric patients. Levetiracetam can help cognitive improvement, and contribute to seizure control in these patients., (Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Aim: To report one patient with slowly progressive encephalopathy, ataxia, central hypomyelination, hypodontia and hypogonadotropic hypogonadism, the 4H syndrome. This clinical picture has been described recently and there are only four patients reported previously., Case Report: A girl with a previously normal early psychomotor development, presented a slowly progressive deterioration since 15 months of age. Now, she is 14 years old, and has a severe cerebellar ataxia, with tremor and dysmetria. She can't neither walk nor remain standing alone. She has lost the sphincter control and has an immature expressive language. She has no puberal development and definitive hypodontia of upper central incisors. The brain magnetic resonance imaging shows a diffuse hypomyelination, that is confirmed with diffusion and spectroscopy studies., Conclusion: The hypomyelinating leukoencephalopathies are disorders with abnormally low amount of myelin. The diagnosis is difficult in most of the patients. The hypomyelinating leukoencephalopathies include classic disorders and new leukoencephalopathies, described in the past few years.

Background: The routine use of chest radiograph in infants with bronchiolitis increases health costs and can often unnecessarily expose the patient to radiation., Objectives: To evaluate the prevalence of infiltrate/atelectasis in infants younger than 2 years who presented to the emergency department with bronchiolitis, to assess whether patient management is changed after viewing the chest radiograph and to determine which clinical variables can accurately identify children with normal radiographs, with a view to reducing unnecessary radiological investigations., Patients and Methods: From October 2003 to December 2004, infants aged < 24 months evaluated in the emergency department of the Severo Ochoa Hospital (Madrid) with a diagnosis of bronchiolitis were included in this study. The variables registered were age, sex, time since onset, respiratory rate, temperature, asymmetry on auscultation, oxygen saturation and the virus identified. A chest radiograph was obtained and the need for admission was evaluated before and after obtaining the results., Results: Two hundred fifty-two infants were included, of which 50 % were aged less than 5 months. Infiltrate/atelectasis was identified in 14.3 % (95 % CI: 10.1-18.5; kappa coefficient: 0.64). Patients with infiltrate/atelectasis were 2.5 times more likely to have a temperature of > or = 38 degrees C (p: 0.004), O2 saturation of < 94 % (p: 0,006) and to be admitted before the results of chest radiograph were known. No differences were found between children with and without infiltrate in age at presentation, sex, disease duration, respiratory rate or identified virus. Patient management was modified in 30 % of patients with infiltrate/ atelectasis. Patients with a temperature of < 38 degrees and O2 saturation of > 94 % had a 92 % probability of normal chest radiograph., Conclusions: Most infants presenting with bronchiolitis had a normal chest radiograph. Temperature >or = 38 degrees and O2 saturation < 94 % were significantly associated with infiltrate/atelectasis. In most infants with bronchiolitis, the absence of fever and hypoxia are good predictors of normal chest radiographs.

Background: Human metapneumovirus (hPMV) is a recently identified virus that is recognized as a cause of respiratory tract illness in the pediatric population., Objectives: To determine the incidence of respiratory tract infections caused by hPMV in hospitalized infants and to describe the clinical characteristics and possible presence of coinfection with other viral agents., Patients and Methods: We performed a prospective study from September to June 2003 in all children aged less than 24 months who were admitted to the Severo Ochoa Hospital (Leganés, Madrid) with a respiratory tract infection. Virological diagnosis was made with a direct immunofluorescent assay and/or reverse transcriptase-polymerase chain reaction on specimens obtained from nasopharyngeal washing. Demographic and clinical data from patients with an hPMV respiratory tract infection were analyzed., Results: During the study period, 200 infants were admitted with a respiratory tract infection, of which 18 (9 %) had an hPMV infection. HPMV was the viral agent isolated in 13.8 % of positive nasopharyngeal washings. All patients were admitted between March and April. The mean age was 6.7 +/- 6.1 months. The most common diagnoses were recurrent wheezing (55.5 %) and bronchiolitis (38.8 %). Oxygen therapy was required by 55.5 % of infants during hospitalization. Coinfection with other respiratory viruses was confirmed in 33.3 % of the patients., Conclusions: Human metapneumovirus is a major cause of respiratory tract illness in hospitalized infants. This virus causes mainly bronchiolitis and recurrent wheezing and is more frequent in spring. Coinfection with other respiratory viruses is frequent.