Pub Date : 2025-10-01DOI: 10.1016/j.braindev.2025.104462
Nihal Akçay
{"title":"Response to the letter to the editor “When details matter: Critical considerations in the study of meningitis”","authors":"Nihal Akçay","doi":"10.1016/j.braindev.2025.104462","DOIUrl":"10.1016/j.braindev.2025.104462","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104462"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246062","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}
Objective: This study examined whether encephalopathy vitamin therapy (EVT) with vitamins B1, B6, and carnitine, administered following febrile status epilepticus (FSE), could prevent acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), improve neurological outcomes, and reduce pediatric intensive care unit (PICU) length of stay.
Methods: We conducted a single-center retrospective cohort study comparing patients hospitalized with suspected post-FSE acute encephalopathy and treated with EVT (2016-2022) with a historical control group of patients who did not receive EVT (2009-2010). The primary endpoint was the incidence of AESD, and the secondary endpoints were a ≥2-point worsening in the Pediatric Cerebral Performance Category (PCPC) score at PICU discharge and a decrease in PICU length of stay.
Results: The AESD incidence did not differ significantly between 43 EVT cases and 14 controls (47 % vs. 57 %, p = 0.55), even with early EVT cases starting within 24 h of the inaugural seizure (43 % vs. 57 %, p = 0.53). EVT was associated with a lower rate of ≥2-point worsening in the PCPC score (23 % vs. 57 %, p = 0.025). Moreover, EVT was associated with significantly shorter PICU length of stay (median 7.0 vs. 13.5 days; p = 0.0012).
Conclusion: EVT may mitigate acute neurological deterioration and shorten PICU length of stay; however, it has limited preventive efficacy against AESD, especially in severe cases.
{"title":"Effect of vitamin administration on the prevention of acute encephalopathy with biphasic seizures and late reduced diffusion.","authors":"Tatsuya Takahashi, Yuichi Abe, Itaru Hayakawa, Saeko Irie, Nobuaki Tsuiki, Atsushi Nishioka, Hiroto Ida, Tsuyoshi Aihara, Kentaro Ide","doi":"10.1016/j.braindev.2025.104415","DOIUrl":"10.1016/j.braindev.2025.104415","url":null,"abstract":"<p><strong>Objective: </strong>This study examined whether encephalopathy vitamin therapy (EVT) with vitamins B1, B6, and carnitine, administered following febrile status epilepticus (FSE), could prevent acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), improve neurological outcomes, and reduce pediatric intensive care unit (PICU) length of stay.</p><p><strong>Methods: </strong>We conducted a single-center retrospective cohort study comparing patients hospitalized with suspected post-FSE acute encephalopathy and treated with EVT (2016-2022) with a historical control group of patients who did not receive EVT (2009-2010). The primary endpoint was the incidence of AESD, and the secondary endpoints were a ≥2-point worsening in the Pediatric Cerebral Performance Category (PCPC) score at PICU discharge and a decrease in PICU length of stay.</p><p><strong>Results: </strong>The AESD incidence did not differ significantly between 43 EVT cases and 14 controls (47 % vs. 57 %, p = 0.55), even with early EVT cases starting within 24 h of the inaugural seizure (43 % vs. 57 %, p = 0.53). EVT was associated with a lower rate of ≥2-point worsening in the PCPC score (23 % vs. 57 %, p = 0.025). Moreover, EVT was associated with significantly shorter PICU length of stay (median 7.0 vs. 13.5 days; p = 0.0012).</p><p><strong>Conclusion: </strong>EVT may mitigate acute neurological deterioration and shorten PICU length of stay; however, it has limited preventive efficacy against AESD, especially in severe cases.</p>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"104415"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818403","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}
Ventilated very-low-birth-weight infants (VLBWIs) frequently receive hydrocortisone (HDC). The HDC dose increases in more serious cases, but the association between the actual HDC dose and neurodevelopmental outcomes is unclear.
Method
A total of 274 VLBWIs were divided into four groups according to the total HDC dose: zero (0 mg/kg), low (1–25 mg/kg), moderate (25–75 mg/kg), high (>75 mg/kg). The developmental quotient (DQ) in each group were compared. Using simple and multiple linear regression analyses, we evaluated the presence of a significant relationship between total DQ and total HDC dose in 274 and 153 VLBWIs receiving HDC therapy. In addition, the association between HDC therapy and the total DQ was investigated in 274 VLBWIs.
Results
The total DQ in the zero group was significantly higher than that in the moderate and high groups but equivalent to that in the low group. Despite a significant association between total DQ and total HDC dose in the single linear regression analysis, no significant association was found between total DQ and total HDC dose in 274 VLBWIs (p = 0.07) and 153 VLBWIs receiving HDC (p = 0.18) using a multiple linear regression analysis, after adjusting for the days of artificial ventilation, gestational age, and the onset of late-stage circulatory collapse. No significant association was observed between total DQ and HDC therapy (p = 0.58).
Conclusion
HDC therapy during NICU admission may not have a significant effect on total DQ at three years old in VLBWIs.
{"title":"Association between total hydrocortisone dose and neurodevelopmental outcome at 3 years old in newborns under 28 weeks of gestation","authors":"Toshimitsu Takayanagi, Mizuko Hashimoto , Tada-Aki Shiraishi , Hiroyuki Tomino, Shun Ogiwara, Akinori Shichijo, Masakazu Egashira, Tomoko Mizukami, Tomoko Egashira","doi":"10.1016/j.braindev.2025.104452","DOIUrl":"10.1016/j.braindev.2025.104452","url":null,"abstract":"<div><h3>Background</h3><div>Ventilated very-low-birth-weight infants (VLBWIs) frequently receive hydrocortisone (HDC). The HDC dose increases in more serious cases, but the association between the actual HDC dose and neurodevelopmental outcomes is unclear.</div></div><div><h3>Method</h3><div>A total of 274 VLBWIs were divided into four groups according to the total HDC dose: zero (0 mg/kg), low (1–25 mg/kg), moderate (25–75 mg/kg), high (>75 mg/kg). The developmental quotient (DQ) in each group were compared. Using simple and multiple linear regression analyses, we evaluated the presence of a significant relationship between total DQ and total HDC dose in 274 and 153 VLBWIs receiving HDC therapy. In addition, the association between HDC therapy and the total DQ was investigated in 274 VLBWIs.</div></div><div><h3>Results</h3><div>The total DQ in the zero group was significantly higher than that in the moderate and high groups but equivalent to that in the low group. Despite a significant association between total DQ and total HDC dose in the single linear regression analysis, no significant association was found between total DQ and total HDC dose in 274 VLBWIs (<em>p</em> = 0.07) and 153 VLBWIs receiving HDC (<em>p</em> = 0.18) using a multiple linear regression analysis, after adjusting for the days of artificial ventilation, gestational age, and the onset of late-stage circulatory collapse. No significant association was observed between total DQ and HDC therapy (<em>p</em> = 0.58).</div></div><div><h3>Conclusion</h3><div>HDC therapy during NICU admission may not have a significant effect on total DQ at three years old in VLBWIs.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104452"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202227","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 : 2025-10-01DOI: 10.1016/j.braindev.2025.104457
Yasuhiro Takeshima, Tomoko Lee, Hideki Shimomura
Duchenne muscular dystrophy (DMD) is an inherited progressive muscle disease that is caused by variants in the DMD gene. The development of therapies for DMD that promote dystrophin protein production or ameliorate dystrophin deficiency-induced pathology is currently underway. Therapies that promote dystrophin production are known as disease-modifying therapies, and include exon-skipping therapy using antisense oligonucleotides (AS-oligo). This therapy suppresses the function of a splicing enhancer sequence within an exon using AS-oligo and removes the exon from the mRNA, thereby converting an out-of-frame deletion (as occurs in DMD) to an in-frame deletion and inducing the expression of functional dystrophin protein. In 2016, eteplirsen, which induces exon 51 skipping, received accelerated approval in the United States. AS-oligo that induce the skipping of exons 45 and 53 are also currently being applied in clinical practice. AS-oligo that induce skipping of other exons are expected to be developed in the future, as well as modified nucleic acids that act more potently. Notably, however, the evaluation of the efficacy of these therapies in clinical practice after accelerated approval remains insufficient. In addition, many issues, such as the effectiveness of early treatment and the combination of these therapies with other novel therapeutic agents, need to be considered. It is therefore important to establish a system to follow-up the long-term efficacy and safety of treatment in the future. The establishment of an early diagnostic system may also need to be considered. The present review outlines the development and future challenges of exon-skipping therapy for DMD and the expansion of splice-switching therapy (a therapy that uses AS-oligo to control splicing), including exon-skipping therapy, to other diseases.
{"title":"Development and future prospects of exon-skipping therapy for Duchenne muscular dystrophy","authors":"Yasuhiro Takeshima, Tomoko Lee, Hideki Shimomura","doi":"10.1016/j.braindev.2025.104457","DOIUrl":"10.1016/j.braindev.2025.104457","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is an inherited progressive muscle disease that is caused by variants in the <em>DMD</em> gene. The development of therapies for DMD that promote dystrophin protein production or ameliorate dystrophin deficiency-induced pathology is currently underway. Therapies that promote dystrophin production are known as disease-modifying therapies, and include exon-skipping therapy using antisense oligonucleotides (AS-oligo). This therapy suppresses the function of a splicing enhancer sequence within an exon using AS-oligo and removes the exon from the mRNA, thereby converting an out-of-frame deletion (as occurs in DMD) to an in-frame deletion and inducing the expression of functional dystrophin protein. In 2016, eteplirsen, which induces exon 51 skipping, received accelerated approval in the United States. AS-oligo that induce the skipping of exons 45 and 53 are also currently being applied in clinical practice. AS-oligo that induce skipping of other exons are expected to be developed in the future, as well as modified nucleic acids that act more potently. Notably, however, the evaluation of the efficacy of these therapies in clinical practice after accelerated approval remains insufficient. In addition, many issues, such as the effectiveness of early treatment and the combination of these therapies with other novel therapeutic agents, need to be considered. It is therefore important to establish a system to follow-up the long-term efficacy and safety of treatment in the future. The establishment of an early diagnostic system may also need to be considered. The present review outlines the development and future challenges of exon-skipping therapy for DMD and the expansion of splice-switching therapy (a therapy that uses AS-oligo to control splicing), including exon-skipping therapy, to other diseases.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104457"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208585","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 : 2025-10-01Epub Date: 2025-08-09DOI: 10.1016/j.braindev.2025.104399
Hiroshi Kobayashi
Lysosomal storage diseases (LSDs) are metabolic disorders caused by the dysfunction of enzymes and other substances localized in lysosomes, known as intracellular organelles. There are many types of LSDs, with a wide range of clinical manifestations. LSDs are highly amenable to gene therapy due to various reasons, including the fact that they are essentially monogenic diseases and existence of cross-correction mechanisms. The only gene therapy product currently approved for lysosomal diseases is one for metachromatic leukodystrophy, but several have progressed to phase III clinical trials such as the products for Mucopolysaccharidosis or Fabry disease. However, serious adverse events have been reported even with gene therapy methods that have been considered safe. Therefore, research on the safety of gene therapy is becoming increasingly important.
{"title":"Gene therapy for lysosomal storage diseases.","authors":"Hiroshi Kobayashi","doi":"10.1016/j.braindev.2025.104399","DOIUrl":"10.1016/j.braindev.2025.104399","url":null,"abstract":"<p><p>Lysosomal storage diseases (LSDs) are metabolic disorders caused by the dysfunction of enzymes and other substances localized in lysosomes, known as intracellular organelles. There are many types of LSDs, with a wide range of clinical manifestations. LSDs are highly amenable to gene therapy due to various reasons, including the fact that they are essentially monogenic diseases and existence of cross-correction mechanisms. The only gene therapy product currently approved for lysosomal diseases is one for metachromatic leukodystrophy, but several have progressed to phase III clinical trials such as the products for Mucopolysaccharidosis or Fabry disease. However, serious adverse events have been reported even with gene therapy methods that have been considered safe. Therefore, research on the safety of gene therapy is becoming increasingly important.</p>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"104399"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812740","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 : 2025-10-01DOI: 10.1016/j.braindev.2025.104458
Keiko Ishigaki , Mariko Taniguchi-Ikeda
{"title":"Response to the letter to the editor “Decoding the pathophysiological role of Fukutin in Fukuyama congenital muscular dystrophy”","authors":"Keiko Ishigaki , Mariko Taniguchi-Ikeda","doi":"10.1016/j.braindev.2025.104458","DOIUrl":"10.1016/j.braindev.2025.104458","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104458"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219616","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}
Visual search is a crucial behavior that supports learning, work, and other daily activities. However, the specific characteristics of visual search and the associated brain activity in Japanese elementary school children have not been thoroughly investigated. This study aimed to elucidate these characteristics by examining visual search behavior and prefrontal cortex (PFC) activity in this population.
Methods
Seventy-one schoolchildren were divided into three age groups (7–8 years, 9–10 years, and 11–12 years). Their PFC activity was measured using functional near-infrared spectroscopy (fNIRS) while they performed a cancellation task under two conditions: a structured array and a random array. Visual search behavior was evaluated using multiple indices, including the number of correct responses and the ratio of intersections, analyzed from multiple perspectives.
Results
The number of correct responses reflecting visual search processing ability, was significantly higher in the older age group. The ratio of intersections, an index of the systematicity of visual search, was significantly lower in the structured array condition compared to the random array condition, but only in the 11–12-year-old group. Additionally, this group showed significantly greater PFC activation during the structured array condition than during the random array, whereas the younger groups exhibited the opposite pattern.
Conclusion
These findings suggest a developmental relationship between the systematicity of visual search and changes in PFC activity. A multifaceted approach combining physiological and behavioral measures may offer deeper insights into the characteristics of visual search in elementary school children.
{"title":"Characteristics of visual search and brain activity in Japanese elementary schoolchildren: A cross-sectional study using functional near-infrared spectroscopy","authors":"Koji Yano , Akiko Suzuki , Yachun Qian , Akiko Megumi , Jungpil Shin , Makoto Wada , Akira Yasumura","doi":"10.1016/j.braindev.2025.104401","DOIUrl":"10.1016/j.braindev.2025.104401","url":null,"abstract":"<div><h3>Introduction</h3><div>Visual search is a crucial behavior that supports learning, work, and other daily activities. However, the specific characteristics of visual search and the associated brain activity in Japanese elementary school children have not been thoroughly investigated. This study aimed to elucidate these characteristics by examining visual search behavior and prefrontal cortex (PFC) activity in this population.</div></div><div><h3>Methods</h3><div>Seventy-one schoolchildren were divided into three age groups (7–8 years, 9–10 years, and 11–12 years). Their PFC activity was measured using functional near-infrared spectroscopy (fNIRS) while they performed a cancellation task under two conditions: a structured array and a random array. Visual search behavior was evaluated using multiple indices, including the number of correct responses and the ratio of intersections, analyzed from multiple perspectives.</div></div><div><h3>Results</h3><div>The number of correct responses reflecting visual search processing ability, was significantly higher in the older age group. The ratio of intersections, an index of the systematicity of visual search, was significantly lower in the structured array condition compared to the random array condition, but only in the 11–12-year-old group. Additionally, this group showed significantly greater PFC activation during the structured array condition than during the random array, whereas the younger groups exhibited the opposite pattern.</div></div><div><h3>Conclusion</h3><div>These findings suggest a developmental relationship between the systematicity of visual search and changes in PFC activity. A multifaceted approach combining physiological and behavioral measures may offer deeper insights into the characteristics of visual search in elementary school children.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104401"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849705","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}
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