To determine the effect of long-term tobramycin (TOB) inhalation therapy on recurrent pneumonia among ventilator-dependent children with profound neurological disabilities.
Methods
TOB inhalation was performed in eight series of trials in seven ventilator-dependent children who had intratracheal Pseudomonas aeruginosa and suffered from recurrent pneumonia. Their age at the initiation of therapy was 68 ± 50 months (mean ± standard deviation), whereas the duration of treatment was 30 ± 22 months. The participants were followed after the termination of therapy for a period of 38 ± 32 months.
Results
The annual rate of pneumonia was 5.6 episodes per year (n = 8) preceding the initiation of inhalation, which decreased to 3.7 (n = 8), 1.6 (n = 5), and 0.67 (n = 3) in the periods of 0–12, 12–24, and 24–36 months after initiation, respectively. The rates were 1.0 (n = 6), 0.6 (n = 5), and 1.4 (n = 5) in the periods of 0–12, 12–24, and 24–36 months after the termination of therapy.
Interpretation
Extended TOB inhalation therapy was effective in decreasing the morbidity of pneumonia in ventilator-dependent children with severe motor and intellectual disabilities.
{"title":"Prevention of chronic pneumonia in children with severe motor and intellectual disabilities by long-term tobramycin inhalation: Its benefits and limitations","authors":"Yoshiaki Saito , Yuto Arai , Takanori Omae , Keisuke Watanabe , Yusuke Saiki , Toshiaki Tanaka , Chika Hosoda , Akiko Tamasaki-Kondo , Yoshihiro Maegaki , Kensaku Okada","doi":"10.1016/j.braindev.2024.104317","DOIUrl":"10.1016/j.braindev.2024.104317","url":null,"abstract":"<div><h3>Aim</h3><div>To determine the effect of long-term tobramycin (TOB) inhalation therapy on recurrent pneumonia among ventilator-dependent children with profound neurological disabilities.</div></div><div><h3>Methods</h3><div>TOB inhalation was performed in eight series of trials in seven ventilator-dependent children who had intratracheal <em>Pseudomonas aeruginosa</em> and suffered from recurrent pneumonia. Their age at the initiation of therapy was 68 ± 50 months (mean ± standard deviation), whereas the duration of treatment was 30 ± 22 months. The participants were followed after the termination of therapy for a period of 38 ± 32 months.</div></div><div><h3>Results</h3><div>The annual rate of pneumonia was 5.6 episodes per year (<em>n</em> = 8) preceding the initiation of inhalation, which decreased to 3.7 (n = 8), 1.6 (<em>n</em> = 5), and 0.67 (<em>n</em> = 3) in the periods of 0–12, 12–24, and 24–36 months after initiation, respectively. The rates were 1.0 (<em>n</em> = 6), 0.6 (n = 5), and 1.4 (n = 5) in the periods of 0–12, 12–24, and 24–36 months after the termination of therapy.</div></div><div><h3>Interpretation</h3><div>Extended TOB inhalation therapy was effective in decreasing the morbidity of pneumonia in ventilator-dependent children with severe motor and intellectual disabilities.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104317"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Safe pediatric magnetic resonance imaging (MRI) ideally relies on non-sedative techniques, as avoiding risky sedation is inherently safer. However, in practice, sedation often becomes unavoidable, particularly for younger children or those with anxiety, to ensure motion-free, high-quality imaging. This narrative review explores the current practices and proposes strategies to enhance safety in pediatric MRI examinations.
Methods
We identified and analyzed 247 studies addressing various aspects of pediatric MRI safety, including sedation protocols, patient monitoring, and team-based management approaches.
Results
Safe sedation requires careful drug selection tailored to individual needs, continuous monitoring, and robust emergency preparedness. While efforts are underway to minimize sedation, safer drug protocols and improved monitoring technologies remain essential. Assembling dedicated MRI teams trained in both technical and non-technical skills—such as situational awareness, communication, and teamwork—supports these strategies. Structured team briefings covering monitoring procedures, emergency scenarios, response protocols, and specific resuscitation roles are also critical. Developing a strong organizational culture that promotes patient safety and continuous learning from incident reports helps ensure ongoing improvements.
Conclusions
Achieving safe pediatric MRI examinations requires balancing the need for sedation with the goal of minimizing its use. Strengthening collaboration, refining sedation protocols, and implementing advanced safety monitoring systems are essential steps. Further advancements in imaging technologies are also necessary to reliably obtain high-quality scans without sedation, reducing risks and improving patient outcomes.
{"title":"Improving pediatric magnetic resonance imaging safety by enhanced non-technical skills and team collaboration","authors":"Masashi Uramatsu , Hidekuni Takahashi , Paul Barach , Yoshikazu Fujisawa , Megumi Takahashi , Shiro Mishima , Gaku Yamanaka","doi":"10.1016/j.braindev.2024.104311","DOIUrl":"10.1016/j.braindev.2024.104311","url":null,"abstract":"<div><h3>Background</h3><div>Safe pediatric magnetic resonance imaging (MRI) ideally relies on non-sedative techniques, as avoiding risky sedation is inherently safer. However, in practice, sedation often becomes unavoidable, particularly for younger children or those with anxiety, to ensure motion-free, high-quality imaging. This narrative review explores the current practices and proposes strategies to enhance safety in pediatric MRI examinations.</div></div><div><h3>Methods</h3><div>We identified and analyzed 247 studies addressing various aspects of pediatric MRI safety, including sedation protocols, patient monitoring, and team-based management approaches.</div></div><div><h3>Results</h3><div>Safe sedation requires careful drug selection tailored to individual needs, continuous monitoring, and robust emergency preparedness. While efforts are underway to minimize sedation, safer drug protocols and improved monitoring technologies remain essential. Assembling dedicated MRI teams trained in both technical and non-technical skills—such as situational awareness, communication, and teamwork—supports these strategies. Structured team briefings covering monitoring procedures, emergency scenarios, response protocols, and specific resuscitation roles are also critical. Developing a strong organizational culture that promotes patient safety and continuous learning from incident reports helps ensure ongoing improvements.</div></div><div><h3>Conclusions</h3><div>Achieving safe pediatric MRI examinations requires balancing the need for sedation with the goal of minimizing its use. Strengthening collaboration, refining sedation protocols, and implementing advanced safety monitoring systems are essential steps. Further advancements in imaging technologies are also necessary to reliably obtain high-quality scans without sedation, reducing risks and improving patient outcomes.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104311"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.braindev.2024.104309
Basma AlFaris , Fahad B. AlBader , Rawan AlSheikh , Fahad A. Bashiri , Muddathir H. Hamad , Amal Kentab , Malak Alghamdi
Background
Carbonic anhydrase type II deficiency (CAII-D) syndrome is a rare autosomal recessive genetic disorder characterized by osteopetrosis, renal tubular acidosis, and brain calcifications. Understanding the clinical and radiological features of CAII-D is key to effective management.
Aim
This study aimed to comprehensively analyze and measure intracranial parenchymal calcium score in pediatric CAII-D in relation to the severity of neurological clinical presentation.
Methods
A retrospective chart review at King Saud University Medical City included pediatric CAII-D patients diagnosed between June 2015 and December 2022. Study variables included age, gender, genetic results, developmental status, developmental quotient (DQ), CT findings, optic canal diameter, intracranial calcium score, and neuropsychiatric symptoms.
Results
Ten CAII-D patients, median age 10.5 years, were included. Most patients displayed homozygous pathogenic CA2 gene variants. For neurodevelopmental symptoms, 60.0 % of patients presented with global developmental delay, 20.0 % had intellectual disability, and the remaining 20.0 % had normal development. The median DQ score was 63.50, with 80.0 % categorized as delayed. Neuropsychiatric disorders were present in 20.0 %. Optic nerve atrophy was observed in 22.2 %, while brain calcifications were present in 70.0 % of cases. Correlation analysis revealed no significant associations between intracranial parenchymal calcium score and age, DQ score, or optic canal diameter. Neurodevelopmental symptoms, neuropsychiatric symptoms, and DQ were not associated with intracranial parenchymal calcium score.
Conclusion
Intraparenchymal calcifications in CAII-D are common but unrelated to developmental delay and neuropsychiatric symptoms, suggesting complex pathophysiology. Follow-up brain imaging may not aid in prognosis or severity assessment, highlighting the need for further research.
{"title":"The correlation of intracranial parenchymal calcium score and the severity of neurological clinical presentation in carbonic anhydrase deficiency type 2","authors":"Basma AlFaris , Fahad B. AlBader , Rawan AlSheikh , Fahad A. Bashiri , Muddathir H. Hamad , Amal Kentab , Malak Alghamdi","doi":"10.1016/j.braindev.2024.104309","DOIUrl":"10.1016/j.braindev.2024.104309","url":null,"abstract":"<div><h3>Background</h3><div>Carbonic anhydrase type II deficiency (CAII-D) syndrome is a rare autosomal recessive genetic disorder characterized by osteopetrosis, renal tubular acidosis, and brain calcifications. Understanding the clinical and radiological features of CAII-D is key to effective management.</div></div><div><h3>Aim</h3><div>This study aimed to comprehensively analyze and measure intracranial parenchymal calcium score in pediatric CAII-D in relation to the severity of neurological clinical presentation.</div></div><div><h3>Methods</h3><div>A retrospective chart review at King Saud University Medical City included pediatric CAII-D patients diagnosed between June 2015 and December 2022. Study variables included age, gender, genetic results, developmental status, developmental quotient (DQ), CT findings, optic canal diameter, intracranial calcium score, and neuropsychiatric symptoms.</div></div><div><h3>Results</h3><div>Ten CAII-D patients, median age 10.5 years, were included. Most patients displayed homozygous pathogenic <em>CA2</em> gene variants. For neurodevelopmental symptoms, 60.0 % of patients presented with global developmental delay, 20.0 % had intellectual disability, and the remaining 20.0 % had normal development. The median DQ score was 63.50, with 80.0 % categorized as delayed. Neuropsychiatric disorders were present in 20.0 %. Optic nerve atrophy was observed in 22.2 %, while brain calcifications were present in 70.0 % of cases. Correlation analysis revealed no significant associations between intracranial parenchymal calcium score and age, DQ score, or optic canal diameter. Neurodevelopmental symptoms, neuropsychiatric symptoms, and DQ were not associated with intracranial parenchymal calcium score.</div></div><div><h3>Conclusion</h3><div>Intraparenchymal calcifications in CAII-D are common but unrelated to developmental delay and neuropsychiatric symptoms, suggesting complex pathophysiology. Follow-up brain imaging may not aid in prognosis or severity assessment, highlighting the need for further research.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104309"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to elucidate the distribution of intracranial gamma-aminobutyric acid (GABA) receptors in patients with infantile epileptic spasms syndrome (IESS) of normal brain MRI findings using 123I-iomazenil single-photon emission computed tomography (IMZ-SPECT).
Methods
This retrospective study compared IMZ-SPECT images from 20 patients with IESS of unknown etiology with normal brain MRI (unknown IESS group) and 23 patients with developmentally normal epilepsy of the same age (developmentally normal group). A three-dimensional stereotactic region of interest (ROI) template was used to divide the brain into 24 segments (left and right callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum), and the mean accumulation of 123I-iomazenil in each ROI was calculated. The IMZ ratio for each ROI was calculated by dividing the ROI count by the mean cerebellar count of the left and right sides for the same patient. IMZ ratios for 22 ROIs, excluding the cerebellum, between the unknown IESS group and the developmentally normal group were compared.
Results
No significant differences were observed between the background characteristics of the unknown and developmentally normal groups. Hypsarrhythmia were observed in 16 patients in the IESS group. The IMZ ratio showed no significant differences between the two groups across all 22 ROIs.
Conclusion
The IMZ ratio of the unknown IESS group was not significantly different from that of the developmentally normal group across the 22 ROIs, suggesting that GABA receptor distribution has little effect on epileptic spasms and hypsarrhythmia, and vice versa.
{"title":"Quantitative analysis of 123I-iomazenil single-photon emission computed tomography findings from patients with infantile epileptic spasm syndrome","authors":"Hirokazu Takeuchi , Kenjiro Kikuchi , Rikako Takeda , Yuko Hirata , Ryuki Matsuura , Reiko Koichihara , Shin-ichiro Hamano","doi":"10.1016/j.braindev.2024.104314","DOIUrl":"10.1016/j.braindev.2024.104314","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to elucidate the distribution of intracranial gamma-aminobutyric acid (GABA) receptors in patients with infantile epileptic spasms syndrome (IESS) of normal brain MRI findings using <sup>123</sup>I-iomazenil single-photon emission computed tomography (IMZ-SPECT).</div></div><div><h3>Methods</h3><div>This retrospective study compared IMZ-SPECT images from 20 patients with IESS of unknown etiology with normal brain MRI (unknown IESS group) and 23 patients with developmentally normal epilepsy of the same age (developmentally normal group). A three-dimensional stereotactic region of interest (ROI) template was used to divide the brain into 24 segments (left and right callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum), and the mean accumulation of <sup>123</sup>I-iomazenil in each ROI was calculated. The IMZ ratio for each ROI was calculated by dividing the ROI count by the mean cerebellar count of the left and right sides for the same patient. IMZ ratios for 22 ROIs, excluding the cerebellum, between the unknown IESS group and the developmentally normal group were compared.</div></div><div><h3>Results</h3><div>No significant differences were observed between the background characteristics of the unknown and developmentally normal groups. Hypsarrhythmia were observed in 16 patients in the IESS group. The IMZ ratio showed no significant differences between the two groups across all 22 ROIs.</div></div><div><h3>Conclusion</h3><div>The IMZ ratio of the unknown IESS group was not significantly different from that of the developmentally normal group across the 22 ROIs, suggesting that GABA receptor distribution has little effect on epileptic spasms and hypsarrhythmia, and vice versa.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104314"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.braindev.2024.104308
Kher Hui Ng , Choong Yi Fong , Mohd Fazrul Shafiq Kamarudzaman , Wei Hong Lo , Farah Khalid , Lee Ai Chong
Objectives
Children with cerebral palsy (CP) can experience a substantial amount of pain. Effective pain management hinges on precise and prompt assessment. We designed a mobile-based application NeuroPAIN app to monitor pain among children with CP. NeuroPAIN app allowed parents to record pain symptoms, pain duration, and rate the perceived pain their child was facing. We evaluated the usefulness of NeuroPAIN app in pain recognition and monitoring among Malaysian parents of children with bilateral CP.
Method
Prospective cohort study of all parents of children with bilateral non-ambulant CP who owned Android devices. NeuroPAIN app was installed in all participants. At 3-month follow-up, data of the NeuroPAIN app was analyzed and participants were given a feedback questionnaire to complete.
Results
Total of 60 parents participated in the study (child's median age 7 years, interquartile range 4–8.75 years). The vast majority (95 %) of parents reported pain in their children. Children with assisted tube feeding was associated with reported increased pain frequency. Majority (77 %) felt it was easy to navigate the NeuroPAIN app. Two-thirds regularly tracked their child's pain using the app over a 2-month period. Parents of children with prolonged periods of pain ≥25 s were associated with reduced app usage.
Conclusion
Majority of Malaysian children with bilateral CP often experience pain particularly among those with assisted tube feeding highlighting the importance for clinicians to be vigilant in monitoring pain among these children. Prolonged pain periods among children with CP may lead to parental fatigue in monitoring pain through the NeuoPAIN app.
{"title":"NeuroPAIN app: Usefulness of a mobile pain application evaluation system for children with cerebral palsy","authors":"Kher Hui Ng , Choong Yi Fong , Mohd Fazrul Shafiq Kamarudzaman , Wei Hong Lo , Farah Khalid , Lee Ai Chong","doi":"10.1016/j.braindev.2024.104308","DOIUrl":"10.1016/j.braindev.2024.104308","url":null,"abstract":"<div><h3>Objectives</h3><div>Children with cerebral palsy (CP) can experience a substantial amount of pain. Effective pain management hinges on precise and prompt assessment. We designed a mobile-based application NeuroPAIN app to monitor pain among children with CP. NeuroPAIN app allowed parents to record pain symptoms, pain duration, and rate the perceived pain their child was facing. We evaluated the usefulness of NeuroPAIN app in pain recognition and monitoring among Malaysian parents of children with bilateral CP.</div></div><div><h3>Method</h3><div>Prospective cohort study of all parents of children with bilateral non-ambulant CP who owned Android devices. NeuroPAIN app was installed in all participants. At 3-month follow-up, data of the NeuroPAIN app was analyzed and participants were given a feedback questionnaire to complete.</div></div><div><h3>Results</h3><div>Total of 60 parents participated in the study (child's median age 7 years, interquartile range 4–8.75 years). The vast majority (95 %) of parents reported pain in their children. Children with assisted tube feeding was associated with reported increased pain frequency. Majority (77 %) felt it was easy to navigate the NeuroPAIN app. Two-thirds regularly tracked their child's pain using the app over a 2-month period. Parents of children with prolonged periods of pain ≥25 s were associated with reduced app usage.</div></div><div><h3>Conclusion</h3><div>Majority of Malaysian children with bilateral CP often experience pain particularly among those with assisted tube feeding highlighting the importance for clinicians to be vigilant in monitoring pain among these children. Prolonged pain periods among children with CP may lead to parental fatigue in monitoring pain through the NeuoPAIN app.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104308"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.braindev.2025.104322
Sergiusz Jóźwiak , Paolo Curatolo , Katarzyna Kotulska
Tuberous sclerosis complex (TSC) is classified among developmental epileptic encephalopathies, where epilepsy is often associated with comorbidities such as intellectual disability and autistic behavior. The recently introduced term TAND (TSC-associated neuropsychiatric disorders) encompasses the wide range of cognitive, behavioral, psychiatric, and psychosocial manifestations seen in TSC. The severity of these comorbidities is influenced by several factors, including the TSC1/TSC2 genotype, the age of epilepsy onset, the number, volume and type of cortical tubers, the interval between epilepsy onset and treatment initiation, and the presence of infantile spasms, hypsarrhythmia, or drug-resistant epilepsy. Clinical, genetic, EEG, and neuroimaging biomarkers enable the early identification of infants at high risk of developing intellectual disability or autism spectrum disorder. Early preventive intervention targeting seizures and tailored strategies during a sensitive developmental window may modify these contributing factors, leading to improved neurodevelopmental outcomes in infants with TSC.
{"title":"Intellectual disability and autistic behavior and their modifying factors in children with tuberous sclerosis complex","authors":"Sergiusz Jóźwiak , Paolo Curatolo , Katarzyna Kotulska","doi":"10.1016/j.braindev.2025.104322","DOIUrl":"10.1016/j.braindev.2025.104322","url":null,"abstract":"<div><div>Tuberous sclerosis complex (TSC) is classified among developmental epileptic encephalopathies, where epilepsy is often associated with comorbidities such as intellectual disability and autistic behavior. The recently introduced term TAND (TSC-associated neuropsychiatric disorders) encompasses the wide range of cognitive, behavioral, psychiatric, and psychosocial manifestations seen in TSC. The severity of these comorbidities is influenced by several factors, including the TSC1/TSC2 genotype, the age of epilepsy onset, the number, volume and type of cortical tubers, the interval between epilepsy onset and treatment initiation, and the presence of infantile spasms, hypsarrhythmia, or drug-resistant epilepsy. Clinical, genetic, EEG, and neuroimaging biomarkers enable the early identification of infants at high risk of developing intellectual disability or autism spectrum disorder. Early preventive intervention targeting seizures and tailored strategies during a sensitive developmental window may modify these contributing factors, leading to improved neurodevelopmental outcomes in infants with TSC.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 2","pages":"Article 104322"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Most cases of spinal muscular atrophy (SMA) can be diagnosed by copy number analysis of survival motor neuron (SMN) 1. However, a small number of cases of SMA can only be diagnosed by sequencing analysis. We present a case of SMA diagnosed 7 years after the onset of symptoms.
Case report
She was a 12-year-old girl of Sri Lankan origin. At age 5, she began to fall easily. She had normal intellectual development, and electromyography suggested a neurogenic disorder. Copy number analysis of SMN1 exons 7 and 8 via polymerase chain reaction revealed at least one copy of SMN1. Exome sequence analysis for neuromuscular disorders panel could not detect the pathogenic mutation. She moved to Japan at the age of 12 years. Sequencing analysis later identified a novel mutation in SMN1 at the same locus as previously reported (c.284G>A: p.Gly95Glu). Multiple ligation-dependent probe amplification indicated she had two copies of SMN2. She was diagnosed with SMA type 3b and treated with nusinersen.
Discussion
In patients with SMA, 2–5 % have a point mutation or a small insertion/deletion in SMN1. Since copy number analysis cannot detect such mutations, sequencing analysis is required. Two copies of SMN2 often result in SMA type 1 or 2, but her mild symptoms of SMA type 3b may be due to a combination of a point mutation and a deletion in SMN1.
Conclusion
Even if genetic testing has been performed at previous institutions, sequencing analysis should be considered if the patient's symptoms are consistent with SMA.
{"title":"A 7-year delayed diagnosis in a case of spinal muscular atrophy","authors":"Hideyuki Iwayama , Tatsuya Fukasawa , Yoshiteru Azuma , Hirokazu Kurahashi , Yoshinori Ito , Akihisa Okumura","doi":"10.1016/j.braindev.2025.104320","DOIUrl":"10.1016/j.braindev.2025.104320","url":null,"abstract":"<div><h3>Background</h3><div>Most cases of spinal muscular atrophy (SMA) can be diagnosed by copy number analysis of survival motor neuron (<em>SMN</em>) 1. However, a small number of cases of SMA can only be diagnosed by sequencing analysis. We present a case of SMA diagnosed 7 years after the onset of symptoms.</div></div><div><h3>Case report</h3><div>She was a 12-year-old girl of Sri Lankan origin. At age 5, she began to fall easily. She had normal intellectual development, and electromyography suggested a neurogenic disorder. Copy number analysis of <em>SMN1</em> exons 7 and 8 via polymerase chain reaction revealed at least one copy of <em>SMN1</em>. Exome sequence analysis for neuromuscular disorders panel could not detect the pathogenic mutation. She moved to Japan at the age of 12 years. Sequencing analysis later identified a novel mutation in <em>SMN1</em> at the same locus as previously reported (c.284G>A: p.Gly95Glu). Multiple ligation-dependent probe amplification indicated she had two copies of <em>SMN2</em>. She was diagnosed with SMA type 3b and treated with nusinersen.</div></div><div><h3>Discussion</h3><div>In patients with SMA, 2–5 % have a point mutation or a small insertion/deletion in <em>SMN1</em>. Since copy number analysis cannot detect such mutations, sequencing analysis is required. Two copies of <em>SMN2</em> often result in SMA type 1 or 2, but her mild symptoms of SMA type 3b may be due to a combination of a point mutation and a deletion in <em>SMN1</em>.</div></div><div><h3>Conclusion</h3><div>Even if genetic testing has been performed at previous institutions, sequencing analysis should be considered if the patient's symptoms are consistent with SMA.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 2","pages":"Article 104320"},"PeriodicalIF":1.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.braindev.2025.104323
Y.-H. Chien , W.-L. Hwu
In recent years, the number of diseases included in newborn screening (NBS) tests has increased rapidly, led by the development of both technology and treatments. Many neurometabolic diseases can now be screened, but direct involvement of the brain, especially in the severe forms of these diseases, causes challenges in NBS. For example, differentiating between neuropathic and nonneuropathic types of disease is difficult but critical because the treatments used can differ. For many diseases with neurological manifestations, the long-term outcomes of new treatments and the influence of NBS are both unclear. In this review, we introduce the “new” NBS test using data from the Screening Center at National Taiwan University as an example. Subsequently, we explore the current challenges in NBS for several neurometabolic diseases.
{"title":"Newborn screening of neurometabolic diseases for early treatment","authors":"Y.-H. Chien , W.-L. Hwu","doi":"10.1016/j.braindev.2025.104323","DOIUrl":"10.1016/j.braindev.2025.104323","url":null,"abstract":"<div><div>In recent years, the number of diseases included in newborn screening (NBS) tests has increased rapidly, led by the development of both technology and treatments. Many neurometabolic diseases can now be screened, but direct involvement of the brain, especially in the severe forms of these diseases, causes challenges in NBS. For example, differentiating between neuropathic and nonneuropathic types of disease is difficult but critical because the treatments used can differ. For many diseases with neurological manifestations, the long-term outcomes of new treatments and the influence of NBS are both unclear. In this review, we introduce the “new” NBS test using data from the Screening Center at National Taiwan University as an example. Subsequently, we explore the current challenges in NBS for several neurometabolic diseases.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 2","pages":"Article 104323"},"PeriodicalIF":1.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t1: at which the seizure should be regarded as an “abnormally prolonged seizure”; and t2: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the “Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023” (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.
{"title":"Japanese guidelines for treatment of pediatric status epilepticus – 2023","authors":"Kenjiro Kikuchi , Ichiro Kuki , Masahiro Nishiyama , Yuki Ueda , Ryuki Matsuura , Tadashi Shiohama , Hiroaki Nagase , Tomoyuki Akiyama , Kenji Sugai , Kitami Hayashi , Kiyotaka Murakami , Hitoshi Yamamoto , Tokiko Fukuda , Mitsuru Kashiwagi , Yoshihiro Maegaki","doi":"10.1016/j.braindev.2024.104306","DOIUrl":"10.1016/j.braindev.2024.104306","url":null,"abstract":"<div><div>The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t<sub>1</sub>: at which the seizure should be regarded as an “abnormally prolonged seizure”; and t<sub>2</sub>: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the “Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023” (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104306"},"PeriodicalIF":1.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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