Vitamin B12 deficiency in infancy can lead to global developmental delay or regression along with skin pigmentation, hair changes and tremors, commonly known as the infantile tremor syndrome (ITS). Although a treatable entity, the data on the long-term neuro-developmental outcomes of these infants is lacking. In this cross-sectional study, a follow-up cohort of 35 children (aged ≥2 years) with ITS, were assessed for neuro-developmental outcomes using Malin's adaptation of the Vineland Social Maturity Scale (VSMS). A total of 35 children (17 males) were enrolled. The mean age at the social quotient (SQ) assessment was 30 months (SD 7.4). The mean duration of follow-up was 16.3 months (SD 8.3). Only 9 cases (26 %) had an SQ in the average range (85–105), while 18 children (51 %) had a borderline disability (SQ, 70–84). Seven children had an SQ in the mild disability range (55–69), and one child had an SQ of <55. Despite rapid improvement in the immediate post-treatment phase, these infants have significant developmental delays in follow-up.
{"title":"Neuro-developmental outcomes in infants with vitamin B12-deficiency and neurologic features","authors":"Juhi Gupta , Pragati Jeenwal , Sayoni Roy Chawdhary , Richa Choudhary , Ankita Gupta , Gunjan Solanki , R.N. Sehra , Kusum Devpura","doi":"10.1016/j.ejpn.2025.10.003","DOIUrl":"10.1016/j.ejpn.2025.10.003","url":null,"abstract":"<div><div>Vitamin B12 deficiency in infancy can lead to global developmental delay or regression along with skin pigmentation, hair changes and tremors, commonly known as the infantile tremor syndrome (ITS). Although a treatable entity, the data on the long-term neuro-developmental outcomes of these infants is lacking. In this cross-sectional study, a follow-up cohort of 35 children (aged ≥2 years) with ITS, were assessed for neuro-developmental outcomes using Malin's adaptation of the Vineland Social Maturity Scale (VSMS). A total of 35 children (17 males) were enrolled. The mean age at the social quotient (SQ) assessment was 30 months (SD 7.4). The mean duration of follow-up was 16.3 months (SD 8.3). Only 9 cases (26 %) had an SQ in the average range (85–105), while 18 children (51 %) had a borderline disability (SQ, 70–84). Seven children had an SQ in the mild disability range (55–69), and one child had an SQ of <55. Despite rapid improvement in the immediate post-treatment phase, these infants have significant developmental delays in follow-up.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 107-113"},"PeriodicalIF":2.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 10.1016/j.ejpn.2025.10.002
Eva-Maria Wendel , John J. Chen , Annikki Bertolini , Astrid Blaschek , Fabienne Brilot , Russell C. Dale , Kumaran Deiva , Eoin P. Flanagan , Thomas Foiadelli , Laetitia Giorgi , Saif Huda , Michael Karenfort , Rachel Kneen , Vanessa Lee , Ming Lim , Sara Mariotto , Hadas Meirson , Maha Z. Mohammed , Margherita Nosadini , Sudarshini Ramanathan , Kevin Rostasy
Background
Data regarding treatment in pediatric relapsing MOGAD are limited.
Objective
To evaluate response of intravenous immunoglobulin (IVIG) compared to other therapies in relapsing pediatric MOGAD.
Methods
In this retrospective multicenter study, children with MOGAD were recruited from different medical centers. Inclusion criteria encompassed: age <18 years, MOGAD diagnosis, relapsing disease course, >6 months of maintenance treatment and >12 months follow-up.
Results
Seventy children with relapsing MOGAD were stratified into two groups. The first group received IVIG alone (n = 23), IVIG preceded by (n = 16) or in combination with other immunomodulating therapies (IMT) (n = 7). The second group received mycophenolate mofetil, azathioprine, rituximab, or other IMTs (n = 24). 13 % (6/46) of patients with IVIG relapsed in the first year, compared to 33 % (8/24) in the IMT group (relative risk 0.70, 95 % CI 0.53 to 0.99, p = 0.061). Annual relapse rate (ARR) was decreased under therapy compared to pre-treatment in both groups (IVIG: p < 0.001; other IMTs: p = 0.006). ARR was lower in the IVIG group (p = 0.040) in addition to a reduced risk of an early relapse compared to the other IMT group (hazard ratio 0.36, 95 % CI 0.15 to 0.87, p = 0.023).
Conclusion
Our study supports monthly IVIG as maintenance therapy in children after the second MOGAD episode.
背景：关于儿童复发性MOGAD治疗的数据有限。目的：评价静脉注射免疫球蛋白（IVIG）治疗小儿复发性MOGAD的疗效。方法：在这项回顾性多中心研究中，从不同的医疗中心招募了患有MOGAD的儿童。纳入标准包括：年龄6个月维持治疗和>12个月随访。结果：70例复发性MOGAD患儿分为两组。第一组仅接受IVIG治疗（n = 23）， IVIG治疗前（n = 16）或联合其他免疫调节疗法（IMT）治疗（n = 7）。第二组接受霉酚酸酯、硫唑嘌呤、利妥昔单抗或其他imt治疗（n = 24）。13%（6/46）的IVIG患者在第一年复发，而IMT组为33%(8/24)（相对危险度0.70,95% CI 0.53 ~ 0.99, p = 0.061）。与治疗前相比，治疗后两组的年复发率（ARR）均有所下降（IVIG: p）。结论：我们的研究支持每月IVIG作为儿童第二次MOGAD发作后的维持治疗。
{"title":"Treatment response in children with relapsing MOG-antibody associated disease","authors":"Eva-Maria Wendel , John J. Chen , Annikki Bertolini , Astrid Blaschek , Fabienne Brilot , Russell C. Dale , Kumaran Deiva , Eoin P. Flanagan , Thomas Foiadelli , Laetitia Giorgi , Saif Huda , Michael Karenfort , Rachel Kneen , Vanessa Lee , Ming Lim , Sara Mariotto , Hadas Meirson , Maha Z. Mohammed , Margherita Nosadini , Sudarshini Ramanathan , Kevin Rostasy","doi":"10.1016/j.ejpn.2025.10.002","DOIUrl":"10.1016/j.ejpn.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Data regarding treatment in pediatric relapsing MOGAD are limited.</div></div><div><h3>Objective</h3><div>To evaluate response of intravenous immunoglobulin (IVIG) compared to other therapies in relapsing pediatric MOGAD.</div></div><div><h3>Methods</h3><div>In this retrospective multicenter study, children with MOGAD were recruited from different medical centers. Inclusion criteria encompassed: age <18 years, MOGAD diagnosis, relapsing disease course, >6 months of maintenance treatment and >12 months follow-up.</div></div><div><h3>Results</h3><div>Seventy children with relapsing MOGAD were stratified into two groups. The first group received IVIG alone (n = 23), IVIG preceded by (n = 16) or in combination with other immunomodulating therapies (IMT) (n = 7). The second group received mycophenolate mofetil, azathioprine, rituximab, or other IMTs (n = 24). 13 % (6/46) of patients with IVIG relapsed in the first year, compared to 33 % (8/24) in the IMT group (relative risk 0.70, 95 % CI 0.53 to 0.99, p = 0.061). Annual relapse rate (ARR) was decreased under therapy compared to pre-treatment in both groups (IVIG: p < 0.001; other IMTs: p = 0.006). ARR was lower in the IVIG group (p = 0.040) in addition to a reduced risk of an early relapse compared to the other IMT group (hazard ratio 0.36, 95 % CI 0.15 to 0.87, p = 0.023).</div></div><div><h3>Conclusion</h3><div>Our study supports monthly IVIG as maintenance therapy in children after the second MOGAD episode.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 45-51"},"PeriodicalIF":2.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-03DOI: 10.1016/j.ejpn.2025.10.001
Jielu Ren , Yicheng Yu , Xinli Zou , Yijie Feng, Danhui Zhu, Yue Yan, Liya Jiang, Jianing Jin, Siyi Huang, Feng Gao, Shanshan Mao
Background
The search for convenient and effective biomarkers is a critical and pressing need for spinal muscular atrophy (SMA) in the era of disease-modifying treatment.
Methods
Data from 65 SMA children treated with nusinersen and followed up for 18 months were retrospectively collected. Motor function was assessed at baseline, 6, 10, 14 and 18 months using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), the Hammersmith Functional Motor Scale Expanded (HFMSE), and the Revised Upper Limb Module (RULM). Serum creatine kinase (CK) and creatinine (Crn) levels were measured, and the correlations were further analyzed.
Results
Significant differences in CK and Crn levels were found among different types before treatment. Baseline CK levels in children with SMA type 3 were higher than those with types 1 and 2 (P = 0.008 and 0.042, respectively), while baseline Crn levels were higher in type 3 than in type 2 (P < 0.001). During the follow-up, baseline Crn levels in types 2 and 3 patients with clinically meaningful improvements in HFMSE scores were higher than those without such improvements (P = 0.013). Additionally, a correlation was observed between HFMSE scores and CK and Crn levels in types 2 and 3 patients (CK: P < 0.001, ρ = 0.473; Crn: P < 0.001, ρ = 0.642). RULM scores were correlated with Crn levels (P < 0.001, ρ = 0.642).
Conclusions
Serum CK and Crn levels appear to correlate with clinical severity in later-onset SMA. Moreover, baseline serum Crn may serve as a potential biomarker for predicting the degree of motor function improvement under nusinersen treatment in children with later-onset SMA.
{"title":"Value of creatine kinase and creatinine as biomarkers in nusinersen-treated children with spinal muscular atrophy","authors":"Jielu Ren , Yicheng Yu , Xinli Zou , Yijie Feng, Danhui Zhu, Yue Yan, Liya Jiang, Jianing Jin, Siyi Huang, Feng Gao, Shanshan Mao","doi":"10.1016/j.ejpn.2025.10.001","DOIUrl":"10.1016/j.ejpn.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div>The search for convenient and effective biomarkers is a critical and pressing need for spinal muscular atrophy (SMA) in the era of disease-modifying treatment.</div></div><div><h3>Methods</h3><div>Data from 65 SMA children treated with nusinersen and followed up for 18 months were retrospectively collected. Motor function was assessed at baseline, 6, 10, 14 and 18 months using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), the Hammersmith Functional Motor Scale Expanded (HFMSE), and the Revised Upper Limb Module (RULM). Serum creatine kinase (CK) and creatinine (Crn) levels were measured, and the correlations were further analyzed.</div></div><div><h3>Results</h3><div>Significant differences in CK and Crn levels were found among different types before treatment. Baseline CK levels in children with SMA type 3 were higher than those with types 1 and 2 (<em>P</em> = 0.008 and 0.042, respectively), while baseline Crn levels were higher in type 3 than in type 2 (<em>P</em> < 0.001). During the follow-up, baseline Crn levels in types 2 and 3 patients with clinically meaningful improvements in HFMSE scores were higher than those without such improvements (<em>P</em> = 0.013). Additionally, a correlation was observed between HFMSE scores and CK and Crn levels in types 2 and 3 patients (CK: <em>P</em> < 0.001, ρ = 0.473; Crn: <em>P</em> < 0.001, ρ = 0.642). RULM scores were correlated with Crn levels (<em>P</em> < 0.001, ρ = 0.642).</div></div><div><h3>Conclusions</h3><div>Serum CK and Crn levels appear to correlate with clinical severity in later-onset SMA. Moreover, baseline serum Crn may serve as a potential biomarker for predicting the degree of motor function improvement under nusinersen treatment in children with later-onset SMA.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 38-44"},"PeriodicalIF":2.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-02DOI: 10.1016/j.ejpn.2025.09.007
Suzanne Gough , Emma Cooke , Adrian Goldsworthy , Maria Carmen Miguel , James Birt , Oliver Baumann , Jasneek Chawla
Objective
This research sought to understand the experiences of healthcare providers working at the coalface of paediatric sleep medicine in a large tertiary children's hospital with a focus on the current service needs, challenges, and strategies.
Method
This qualitative study utilised semi-structured focus groups undertaken in an Australian tertiary paediatric sleep medicine department. There were 17 participants, encompassing paediatric sleep medicine specialists, clinical nurses, sleep scientists and administrative staff. Focus group interviews were transcribed verbatim, and member checked. Thematic analysis was undertaken.
Results
Three themes were identified: 1) Patient care optimisation, 2) Families' unrealistic expectations for their child's diagnostic testing and treatment adherence, 3) Families' difficult experiences with diagnostic and specific sleep therapies.
Conclusion
This study provides unique insights and perspectives of healthcare providers regarding the current challenges faced within the growing demand and complexity of patients accessing paediatric sleep medicine service. Despite clinicians optimising sleep medicine services, wait lists continue to grow, which in turn impact staff workload and patient care. Innovation in areas of sleep diagnostics, monitoring and therapy continue to be explored by tertiary services. Education and training for both primary healthcare providers and the public are still urgently required to optimise sleep and sleep disorders.
{"title":"Optimising patient care, expectations and experiences: Healthcare providers’ experiences of delivering sleep medicine services within an Australian tertiary paediatric facility","authors":"Suzanne Gough , Emma Cooke , Adrian Goldsworthy , Maria Carmen Miguel , James Birt , Oliver Baumann , Jasneek Chawla","doi":"10.1016/j.ejpn.2025.09.007","DOIUrl":"10.1016/j.ejpn.2025.09.007","url":null,"abstract":"<div><h3>Objective</h3><div>This research sought to understand the experiences of healthcare providers working at the coalface of paediatric sleep medicine in a large tertiary children's hospital with a focus on the current service needs, challenges, and strategies.</div></div><div><h3>Method</h3><div>This qualitative study utilised semi-structured focus groups undertaken in an Australian tertiary paediatric sleep medicine department. There were 17 participants, encompassing paediatric sleep medicine specialists, clinical nurses, sleep scientists and administrative staff. Focus group interviews were transcribed verbatim, and member checked. Thematic analysis was undertaken.</div></div><div><h3>Results</h3><div>Three themes were identified: 1) Patient care optimisation, 2) Families' unrealistic expectations for their child's diagnostic testing and treatment adherence, 3) Families' difficult experiences with diagnostic and specific sleep therapies<strong>.</strong></div></div><div><h3>Conclusion</h3><div>This study provides unique insights and perspectives of healthcare providers regarding the current challenges faced within the growing demand and complexity of patients accessing paediatric sleep medicine service. Despite clinicians optimising sleep medicine services, wait lists continue to grow, which in turn impact staff workload and patient care. Innovation in areas of sleep diagnostics, monitoring and therapy continue to be explored by tertiary services. Education and training for both primary healthcare providers and the public are still urgently required to optimise sleep and sleep disorders.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 31-37"},"PeriodicalIF":2.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.ejpn.2025.09.005
Anne T. Berg , Mary Wojnaroski , Natasha N. Ludwig , Rebecca Hommer , Kelly Muzyczka , Sara Te , Gabrielle Conecker , JayEtta Hecker , Gerry Nesbitt , Jenny Downs
Objectives
This study assessed impacts of non-seizure outcomes and caregiver priorities for improvement in individuals with severe neurodevelopmental encephalopathy with or without epilepsy (SNDE ± E).
Methods
In an online survey of parents recruited from several patient advocacy groups, parents rated the impacts of 17 non-seizure outcome domains on their children and identified their top three priority domains for improvement. Bivariate and stratified analyses compared impacts and priorities by burden of severe functional impairments, age, and diagnoses.
Results
Of 267 participants, 149 (56 %) were female (median [interquartile range] age: 8.7y [4.2y – 14.7y) and 169 (63 %) had epilepsy diagnoses. Profound impairments were reported for mobility (N = 142, 53 %), communication (N = 208, 78 %), eating (N = 100, 37 %), and hand use (N = 93, 35 %). Expressive communication had overwhelming or significantly negative impacts in 217 (83 %) followed by receptive communication (N = 185, 70 %). Parents identified expressive communication as a top (N = 211, 79 %) priority for improvement. The impact and prioritization of expressive communication were independent of other functional impairments, age, and other diagnoses. For those with epilepsy, relative to non-seizure outcomes, seizures were rated as more important by 35 % and of similar or less importance by 65 %; this strongly depended on recency of the last seizure (p < 0.0001).
Conclusions
Improvement in expressive communication is a top priority in the SNDEs ± E and could be a valuable non-seizure outcome in future therapeutic trials for these rare diseases.
{"title":"Impact of non-seizure outcomes and caregiver priorities for young people with severe neurodevelopmental encephalopathy with or without epilepsy: A community survey","authors":"Anne T. Berg , Mary Wojnaroski , Natasha N. Ludwig , Rebecca Hommer , Kelly Muzyczka , Sara Te , Gabrielle Conecker , JayEtta Hecker , Gerry Nesbitt , Jenny Downs","doi":"10.1016/j.ejpn.2025.09.005","DOIUrl":"10.1016/j.ejpn.2025.09.005","url":null,"abstract":"<div><h3>Objectives</h3><div>This study assessed impacts of non-seizure outcomes and caregiver priorities for improvement in individuals with severe neurodevelopmental encephalopathy with or without epilepsy (SNDE <sup>± E</sup>).</div></div><div><h3>Methods</h3><div>In an online survey of parents recruited from several patient advocacy groups, parents rated the impacts of 17 non-seizure outcome domains on their children and identified their top three priority domains for improvement. Bivariate and stratified analyses compared impacts and priorities by burden of severe functional impairments, age, and diagnoses.</div></div><div><h3>Results</h3><div>Of 267 participants, 149 (56 %) were female (median [interquartile range] age: 8.7y [4.2y – 14.7y) and 169 (63 %) had epilepsy diagnoses. Profound impairments were reported for mobility (N = 142, 53 %), communication (N = 208, 78 %), eating (N = 100, 37 %), and hand use (N = 93, 35 %). Expressive communication had overwhelming or significantly negative impacts in 217 (83 %) followed by receptive communication (N = 185, 70 %). Parents identified expressive communication as a top (N = 211, 79 %) priority for improvement. The impact and prioritization of expressive communication were independent of other functional impairments, age, and other diagnoses. For those with epilepsy, relative to non-seizure outcomes, seizures were rated as more important by 35 % and of similar or less importance by 65 %; this strongly depended on recency of the last seizure (p < 0.0001).</div></div><div><h3>Conclusions</h3><div>Improvement in expressive communication is a top priority in the SNDEs <sup>± E</sup> and could be a valuable non-seizure outcome in future therapeutic trials for these rare diseases.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 52-59"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-29DOI: 10.1016/j.ejpn.2025.09.004
Maria Nedelcu , Dana Craiu , Elena Neagu , Carmen Magdalena Burloiu , Catrinel Mihaela Iliescu , Magdalena Budisteanu , Ioana Minciu , Diana Gabriela Barca , Carmen Sandu , Oana Tarta-Arsene , Cristina Pomeran , Cristina Motoescu , Alice Dica , Cristina Anghelescu , Dana Surlica , Daniela Iancu , Niculina Butoianu
Duchenne muscular dystrophy (DMD) is a rare fatal genetic disorder with a tight correlation between the genotype and the phenotype of the patients. However, the relationship between genotype and phenotype is yet incompletely understood, with some cases manifesting a different phenotype than predicted from their genotype. Since the genetic diagnosis is often targeted to specific gene sections, and the genotype-phenotype correlations guide early treatment decisions, accumulating clinical and epidemiological data for these rare disorders is required to refine local management strategies. This article describes the genotype and phenotype landscape of 239 patients treated in the Pediatric Neurology Clinic of the Clinic Psychiatry Hospital ”Prof. Dr. Alexandru Obregia” in Bucharest, using randomly collected data from a ten-year interval (2012–2022). It revealed a significant improvement in the quality of care, highlighted by a notable reduction in the average age at diagnosis in recent years, although considerable variability remains across counties. The study identified three mutations that were not previously described in the Edystrophin or TREAT-NMD DMD Global Database. The accuracy of the Reading-Frame rule was 88.4 % for deletions. For exceptions from the rule, the involvement of different isoforms, binding domains, structural domains, and the disturbance of the three-dimensional structure of the rod domain were not reliable indicators of the phenotype. 12.9 % of all patients had nonsense mutations with a DMD phenotype that could benefit from Ataluren treatment within the National Treatment Program, and 15 % were eligible for exon-skipping therapies, with exon 51 having the broadest applicability (7.1 %).
{"title":"Duchenne and Becker Muscular Dystrophies in Romania: a 10-year Retrospective Study","authors":"Maria Nedelcu , Dana Craiu , Elena Neagu , Carmen Magdalena Burloiu , Catrinel Mihaela Iliescu , Magdalena Budisteanu , Ioana Minciu , Diana Gabriela Barca , Carmen Sandu , Oana Tarta-Arsene , Cristina Pomeran , Cristina Motoescu , Alice Dica , Cristina Anghelescu , Dana Surlica , Daniela Iancu , Niculina Butoianu","doi":"10.1016/j.ejpn.2025.09.004","DOIUrl":"10.1016/j.ejpn.2025.09.004","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a rare fatal genetic disorder with a tight correlation between the genotype and the phenotype of the patients. However, the relationship between genotype and phenotype is yet incompletely understood, with some cases manifesting a different phenotype than predicted from their genotype. Since the genetic diagnosis is often targeted to specific gene sections, and the genotype-phenotype correlations guide early treatment decisions, accumulating clinical and epidemiological data for these rare disorders is required to refine local management strategies. This article describes the genotype and phenotype landscape of 239 patients treated in the Pediatric Neurology Clinic of the Clinic Psychiatry Hospital ”Prof. Dr. Alexandru Obregia” in Bucharest, using randomly collected data from a ten-year interval (2012–2022). It revealed a significant improvement in the quality of care, highlighted by a notable reduction in the average age at diagnosis in recent years, although considerable variability remains across counties. The study identified three mutations that were not previously described in the Edystrophin or TREAT-NMD DMD Global Database. The accuracy of the Reading-Frame rule was 88.4 % for deletions. For exceptions from the rule, the involvement of different isoforms, binding domains, structural domains, and the disturbance of the three-dimensional structure of the rod domain were not reliable indicators of the phenotype. 12.9 % of all patients had nonsense mutations with a DMD phenotype that could benefit from Ataluren treatment within the National Treatment Program, and 15 % were eligible for exon-skipping therapies, with exon 51 having the broadest applicability (7.1 %).</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 23-30"},"PeriodicalIF":2.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-25DOI: 10.1016/j.ejpn.2025.09.002
Guido Goj , Jelte Helfferich , Ines El Naggar , Ulrike Noßwitz , Eva Bültmann , Deiva Kumaran , Jena Chung , Ariane Biebl , Leon Steigleder , Dorothea Holzwarth , Eva-Maria Wendel , Andrea Bevot , Hannes Andreas Nobel , Jan G. Hengstler , Robert Cleaveland , Andreas Panzer , K. Rostasy
Background
Acute flaccid myelitis (AFM) is characterized by acute onset of flaccid limb weakness, MRI abnormalities in the spinal cord grey matter and CSF pleocytosis often associated with enterovirus infections. MOG-associated diseases (MOGAD) can manifest with similar neuroradilogical features.
Objective
To analyze MRI findings in patients with AFM at baseline and follow-up in comparison to other forms of childhood transverse myelitis such as MOGAD.
Patients and methods
Children from 11 European centers who fulfilled the clinical criteria of AFM were included. Brain and spinal MRI was performed at various stages of the disease course. MRI scans were evaluated using a previously established scoring table and compared with MRI scans of a recently published cohort of children with different forms of transverse myelitis including MOGAD.
Results
We included 15 patients (8 females, 7 males, age range: 9 months-9,11 years). In 10/15 patients enterovirus was detected in respiratory/rectal specimens. At first presentation 13/15 patients presented with a longitudinal extensive transverse myelitis like involvement. Cervical grey matter was involved in almost all children. Axial involvement either manifested as grey matter alone or a mixture of white matter and grey matter hyperintensity in T2. Nerve root enhancement was found in 2/15 and leptomeningeal enhancement in 1/15 patients. 5/15 children had brainstem lesions. Follow-up MRI revealed residual T2 hyperintensities in 7/11 patients. Compared to patients with MOGAD AFM patients showed equally good resolution of MRI lesions overtime.
Conclusion
Longitudinal spinal cord lesions mainly affecting the grey matter are characteristic of AFM whereas supratentorial lesions are less common. There is no significant difference between AFM and MOGAD concerning the resolution of lesions overtime.
{"title":"Evolution of neuroimaging features in children with acute flaccid myelitis compared to other forms of childhood myelitis","authors":"Guido Goj , Jelte Helfferich , Ines El Naggar , Ulrike Noßwitz , Eva Bültmann , Deiva Kumaran , Jena Chung , Ariane Biebl , Leon Steigleder , Dorothea Holzwarth , Eva-Maria Wendel , Andrea Bevot , Hannes Andreas Nobel , Jan G. Hengstler , Robert Cleaveland , Andreas Panzer , K. Rostasy","doi":"10.1016/j.ejpn.2025.09.002","DOIUrl":"10.1016/j.ejpn.2025.09.002","url":null,"abstract":"<div><h3>Background</h3><div>Acute flaccid myelitis (AFM) is characterized by acute onset of flaccid limb weakness, MRI abnormalities in the spinal cord grey matter and CSF pleocytosis often associated with enterovirus infections. <em>MOG-associated diseases (MOGAD) can manifest with similar neuroradilogical features</em>.</div></div><div><h3>Objective</h3><div>To analyze MRI findings in patients with AFM at baseline and follow-up <em>in comparison to other forms of childhood transverse myelitis such as MOGAD.</em></div></div><div><h3>Patients and methods</h3><div>Children from 11 European centers who fulfilled the clinical criteria of AFM were included. Brain and spinal MRI was performed at various stages of the disease course. MRI scans were evaluated using a previously established scoring table and <em>compared with MRI scans of a recently published cohort of children with different forms of transverse myelitis including MOGAD</em>.</div></div><div><h3>Results</h3><div>We included 15 patients (8 females, 7 males, age range: 9 months-9,11 years). In 10/15 patients enterovirus was detected in respiratory/rectal specimens. At first presentation 13/15 patients presented with a longitudinal extensive transverse myelitis like involvement. Cervical grey matter was involved in almost all children. Axial involvement either manifested as grey matter alone or a mixture of white matter and grey matter hyperintensity in T2. Nerve root enhancement was found in 2/15 and leptomeningeal enhancement in 1/15 patients. 5/15 children had brainstem lesions. Follow-up MRI revealed residual T2 hyperintensities in 7/11 patients. Compared to patients with MOGAD AFM patients showed equally good resolution of MRI lesions overtime.</div></div><div><h3>Conclusion</h3><div>Longitudinal spinal cord lesions mainly affecting the grey matter are characteristic of AFM whereas supratentorial lesions are less common. There is no significant difference between AFM and MOGAD concerning the resolution of lesions overtime.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 18-22"},"PeriodicalIF":2.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.ejpn.2025.09.003
Sophie M. Coffeng , Harm J. van der Horn , Manon L. Out , Zwany Metting , Roos M.D. van der Jagt , Joukje van der Naalt
Introduction
Information on health-related quality of life (HRQoL) after traumatic brain injury (TBI) for paediatric patients is scarce. Therefore, the aim of this study was to determine HRQoL and its risk factors in children several years after TBI.
Methodology
Data were obtained from a prospectively follow-up cohort study of paediatric TBI patients (aged 0–18 years) admitted to the emergency department of the UMCG between 2008 and 2016. Long-term HRQoL was measured by the PedsQL 4.0 questionnaire. Patient and trauma characteristics were collected from digital patient files and posttraumatic complaints were evaluated by a health questionnaire.
Results
416 children completed the PedsQL and the health questionnaire (17 % minor TBI, 65 % mild TBI, 8 % moderate TBI, and 10 % severe TBI). 52 % Of the children experienced long-term concentration problems, 52 % headache problems and 39 % memory problems. Memory problems were more present in the moderate-severe TBI group (p < 0.01). The mean total PedsQL score for the total group of children was good: 84.8 ± 13.3 (SD) with a comparable score for parent-proxies (84.5 ± 14.0). Lower HRQoL was associated with lower GCS score at the ED (B 0.31 (95% CI 0.02 to 0.59)), posttraumatic memory problems (B −6.97 (95% CI -9.66 to −4.28)), concentration problems (B −6.76 (95% CI -9.36 to −4.15) and headache (B −4.06 (95% CI -6.33 to −1.78)).
Conclusions
Most paediatric TBI patients score their HRQoL as good several years after injury despite posttraumatic cognitive complaints and headache experienced by half of the patients. These complaints and lower GCS score have a negative influence on HRQoL.
{"title":"Determinants of long-term health-related quality of life in paediatric traumatic brain injury","authors":"Sophie M. Coffeng , Harm J. van der Horn , Manon L. Out , Zwany Metting , Roos M.D. van der Jagt , Joukje van der Naalt","doi":"10.1016/j.ejpn.2025.09.003","DOIUrl":"10.1016/j.ejpn.2025.09.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Information on health-related quality of life (HRQoL) after traumatic brain injury (TBI) for paediatric patients is scarce. Therefore, the aim of this study was to determine HRQoL and its risk factors in children several years after TBI.</div></div><div><h3>Methodology</h3><div>Data were obtained from a prospectively follow-up cohort study of paediatric TBI patients (aged 0–18 years) admitted to the emergency department of the UMCG between 2008 and 2016. Long-term HRQoL was measured by the PedsQL 4.0 questionnaire. Patient and trauma characteristics were collected from digital patient files and posttraumatic complaints were evaluated by a health questionnaire.</div></div><div><h3>Results</h3><div>416 children completed the PedsQL and the health questionnaire (17 % minor TBI, 65 % mild TBI, 8 % moderate TBI, and 10 % severe TBI). 52 % Of the children experienced long-term concentration problems, 52 % headache problems and 39 % memory problems. Memory problems were more present in the moderate-severe TBI group (p < 0.01). The mean total PedsQL score for the total group of children was good: 84.8 ± 13.3 (SD) with a comparable score for parent-proxies (84.5 ± 14.0). Lower HRQoL was associated with lower GCS score at the ED (B 0.31 (95% CI 0.02 to 0.59)), posttraumatic memory problems (B −6.97 (95% CI -9.66 to −4.28)), concentration problems (B −6.76 (95% CI -9.36 to −4.15) and headache (B −4.06 (95% CI -6.33 to −1.78)).</div></div><div><h3>Conclusions</h3><div>Most paediatric TBI patients score their HRQoL as good several years after injury despite posttraumatic cognitive complaints and headache experienced by half of the patients. These complaints and lower GCS score have a negative influence on HRQoL.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 11-17"},"PeriodicalIF":2.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-07DOI: 10.1016/j.ejpn.2025.09.001
Lynn B. Orriëns , Karen van Hulst , Joyce M. Geelen , Frank J.A. van den Hoogen , Anne T.M. Dittrich , Michèl A.A.P. Willemsen , Corrie E. Erasmus
Introduction
Anticholinergic medication is an important treatment option for paediatric drooling. We explored the practical application of glycopyrronium, an anticholinergic medicine registered for the paediatric population, focusing on treatment patterns, effectiveness and impact, adverse drug reactions (ADRs), and caregiver satisfaction.
Methods
A longitudinal, observational study was performed, including 22 children (3–18 years) newly treated with glycopyrronium for anterior and/or posterior drooling in our tertiary children's hospital between November 2020 and February 2024. We assessed a verbal numerical rating scale for drooling severity, Drooling Severity and Frequency Scale (DSFS), Measure of Performance and Satisfaction for Saliva Control (MPS), prevalence of ADRs, and dosage adjustments.
Results
At baseline, drooling was typically profuse and occurred frequently to constantly. The majority of children (86 %) took glycopyrronium thrice daily, with dose titration tailored to each child and medication primarily administered with food (56 %). A clinically important reduction in DSFS was observed in 53 % at the first follow-up appointment. Correspondingly, median MPS scores increased from 0.0 at baseline to 5.6 at follow-up (p < .001) (0 = not dry; 10 = perfectly dry), indicating improved saliva control in situations impacted by drooling. ADRs were reported in 73 %, leading to treatment cessation in 36 %, primarily due to gastrointestinal issues and behavioural changes.
Conclusions
Our findings confirm the applicability of glycopyrronium under real-world conditions, complementing results from studies with more rigid designs. Insights into inter-individual differences in dose titration, timing of medication administration, and changes in effect or ADRs over time highlight the relevance of a tailored treatment approach.
{"title":"The ins and outs of glycopyrronium treatment for paediatric drooling: exploring the treatment journey using real-world data","authors":"Lynn B. Orriëns , Karen van Hulst , Joyce M. Geelen , Frank J.A. van den Hoogen , Anne T.M. Dittrich , Michèl A.A.P. Willemsen , Corrie E. Erasmus","doi":"10.1016/j.ejpn.2025.09.001","DOIUrl":"10.1016/j.ejpn.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Anticholinergic medication is an important treatment option for paediatric drooling. We explored the practical application of glycopyrronium, an anticholinergic medicine registered for the paediatric population, focusing on treatment patterns, effectiveness and impact, adverse drug reactions (ADRs), and caregiver satisfaction.</div></div><div><h3>Methods</h3><div>A longitudinal, observational study was performed, including 22 children (3–18 years) newly treated with glycopyrronium for anterior and/or posterior drooling in our tertiary children's hospital between November 2020 and February 2024. We assessed a verbal numerical rating scale for drooling severity, Drooling Severity and Frequency Scale (DSFS), Measure of Performance and Satisfaction for Saliva Control (MPS), prevalence of ADRs, and dosage adjustments.</div></div><div><h3>Results</h3><div>At baseline, drooling was typically profuse and occurred frequently to constantly. The majority of children (86 %) took glycopyrronium thrice daily, with dose titration tailored to each child and medication primarily administered with food (56 %). A clinically important reduction in DSFS was observed in 53 % at the first follow-up appointment. Correspondingly, median MPS scores increased from 0.0 at baseline to 5.6 at follow-up (p < .001) (0 = not dry; 10 = perfectly dry), indicating improved saliva control in situations impacted by drooling. ADRs were reported in 73 %, leading to treatment cessation in 36 %, primarily due to gastrointestinal issues and behavioural changes.</div></div><div><h3>Conclusions</h3><div>Our findings confirm the applicability of glycopyrronium under real-world conditions, complementing results from studies with more rigid designs. Insights into inter-individual differences in dose titration, timing of medication administration, and changes in effect or ADRs over time highlight the relevance of a tailored treatment approach.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"59 ","pages":"Pages 1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145098681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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