Pub Date : 2024-03-12DOI: 10.1016/j.braindev.2024.03.001
Tatsuo Mori , Mutsuki Nakano , Takahiro Tayama , Aya Goji , Yoshihiro Toda , Shinichi Kameyama , Takeshi Mizuguchi , Maki Urushihara , Naomichi Matsumoto
Background
Heterozygous L1CAM variants cause L1 syndrome with hydrocephalus and aplasia/hypoplasia of the corpus callosum. L1 syndrome usually has an X-linked recessive inheritance pattern; however, we report a rare case occurring in a female child.
Case presentation
The patient’s family history was unremarkable. Fetal ultrasonography revealed enlarged bilateral ventricles of the brain and hypoplasia of the corpus callosum. The patient was born at 38 weeks and 4 days of gestation. Brain MRI performed on the 8th day of life revealed enlargement of the brain ventricles, marked in the lateral and third ventricles with irregular margins, and hypoplasia of the corpus callosum. Exome sequencing at the age of 2 years and 3 months revealed a de novo heterozygous L1CAM variant (NM_000425.5: c.2934_2935delp. (His978Glnfs * 25). X-chromosome inactivation using the human androgen receptor assay revealed that the pattern of X-chromosome inactivation in the patients was highly skewed (96.6 %). The patient is now 4 years and 11 months old and has a mild developmental delay (developmental quotient, 56) without significant progression of hydrocephalus.
Conclusion
In this case, we hypothesized that the dominant expression of the variant allele arising from skewed X inactivation likely caused L1 syndrome. Symptomatic female carriers may challenge the current policies of prenatal and preimplantation diagnoses.
背景：杂合子 L1CAM 变异可导致 L1 综合征，并伴有脑积水和胼胝体发育不全/发育不良。L1 综合征通常为 X 连锁隐性遗传，但我们报告了一例发生在一名女性儿童身上的罕见病例：病例介绍：患者的家族史并无异常。胎儿超声波检查显示双侧脑室增大，胼胝体发育不良。患者在妊娠38周零4天时出生。出生后第 8 天进行的脑磁共振成像显示脑室增大，侧脑室和第三脑室明显增大，边缘不规则，胼胝体发育不良。2 岁零 3 个月时进行的外显子组测序发现了一个新发的 L1CAM 杂合子变异体（NM_000425.5: c.2934_2935delp.(His978Glnfs * 25）。使用人类雄激素受体检测法进行的 X 染色体失活检测显示，患者的 X 染色体失活模式高度偏斜（96.6%）。患者现年 4 岁 11 个月，有轻度发育迟缓（发育商为 56），脑积水无明显进展：在这个病例中，我们推测由偏斜 X 失活引起的变异等位基因的显性表达很可能导致 L1 综合征。有症状的女性携带者可能会对现行的产前和植入前诊断政策提出挑战。
{"title":"A female case of L1 syndrome that may have developed due to skewed X inactivation","authors":"Tatsuo Mori , Mutsuki Nakano , Takahiro Tayama , Aya Goji , Yoshihiro Toda , Shinichi Kameyama , Takeshi Mizuguchi , Maki Urushihara , Naomichi Matsumoto","doi":"10.1016/j.braindev.2024.03.001","DOIUrl":"10.1016/j.braindev.2024.03.001","url":null,"abstract":"<div><h3>Background</h3><p>Heterozygous <em>L1CAM</em> variants cause L1 syndrome with hydrocephalus and aplasia/hypoplasia of the corpus callosum. L1 syndrome usually has an X-linked recessive inheritance pattern; however, we report a rare case occurring in a female child.</p></div><div><h3>Case presentation</h3><p>The patient’s family history was unremarkable. Fetal ultrasonography revealed enlarged bilateral ventricles of the brain and hypoplasia of the corpus callosum. The patient was born at 38 weeks and 4 days of gestation. Brain MRI performed on the 8th day of life revealed enlargement of the brain ventricles, marked in the lateral and third ventricles with irregular margins, and hypoplasia of the corpus callosum. Exome sequencing at the age of 2 years and 3 months revealed a de novo heterozygous <em>L1CAM</em> variant (NM_000425.5: c.2934_2935delp. (His978Glnfs * 25). X-chromosome inactivation using the human androgen receptor assay revealed that the pattern of X-chromosome inactivation in the patients was highly skewed (96.6 %). The patient is now 4 years and 11 months old and has a mild developmental delay (developmental quotient, 56) without significant progression of hydrocephalus.</p></div><div><h3>Conclusion</h3><p>In this case, we hypothesized that the dominant expression of the variant allele arising from skewed X inactivation likely caused L1 syndrome. Symptomatic female carriers may challenge the current policies of prenatal and preimplantation diagnoses.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121454","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}
Niemann–Pick type C (NPC) is a rare lysosomal storage disease characterized by hepatosplenomegaly and progressive neurological deterioration due to abnormal intracellular cholesterol transport. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPBCD) is an effective treatment for NPC; however, few reports have shown its long-term efficacy and safety. To demonstrate long-term efficacy and safety of intrathecal HPBCD (IT-HPBCD) treatment for NPC, we herein reports five patients with NPC treated using IT-HPBCD for 4–11 years.
Cases and results
Patients’ ages at the onset ranged from 1.5 to 20 years. Notably, all patients showed rapid disease progression despite treatment with miglustat before IT-HPBCD treatment. Similarly, some patients showed transient improvement; however, all patients’ conditions stabilized after long-term IT-HPBCD therapy. Mild-to-moderate hearing loss was observed in three patients. Furthermore, long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, patients still experience some disease progression.
Conclusions
Long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, the treatment outcome is dependent on the neurological status at the time of diagnosis, and disease progression is not completely inhibited. Awareness of the disease and newborn screening is needed for earlier disease detection. In addition, further optimization of the treatment protocol and additional treatments are needed to improve patient outcomes.
{"title":"Long-term efficacy of intrathecal cyclodextrin in patients with Niemann-Pick disease type C","authors":"Muneaki Matsuo , Takafumi Sakakibara , Yoshio Sakiyama , Tetsumin So , Motomichi Kosuga , Toshihiko Kakiuchi , Fumio Ichinose , Takuji Nakamura , Yoichi Ishitsuka , Tetsumi Irie","doi":"10.1016/j.braindev.2024.03.002","DOIUrl":"10.1016/j.braindev.2024.03.002","url":null,"abstract":"<div><h3>Background and objectives</h3><p>Niemann–Pick type C (NPC) is a rare lysosomal storage disease characterized by hepatosplenomegaly and progressive neurological deterioration due to abnormal intracellular cholesterol transport. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPBCD) is an effective treatment for NPC; however, few reports have shown its long-term efficacy and safety. To demonstrate long-term efficacy and safety of intrathecal HPBCD (IT-HPBCD) treatment for NPC, we herein reports five patients with NPC treated using IT-HPBCD for 4–11 years.</p></div><div><h3>Cases and results</h3><p>Patients’ ages at the onset ranged from 1.5 to 20 years. Notably, all patients showed rapid disease progression despite treatment with miglustat before IT-HPBCD treatment. Similarly, some patients showed transient improvement; however, all patients’ conditions stabilized after long-term IT-HPBCD therapy. Mild-to-moderate hearing loss was observed in three patients. Furthermore, long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, patients still experience some disease progression.</p></div><div><h3>Conclusions</h3><p>Long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, the treatment outcome is dependent on the neurological status at the time of diagnosis, and disease progression is not completely inhibited. Awareness of the disease and newborn screening is needed for earlier disease detection. In addition, further optimization of the treatment protocol and additional treatments are needed to improve patient outcomes.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S038776042400041X/pdfft?md5=8e5bad62db3da27a2ad5f8a9e372a2f5&pid=1-s2.0-S038776042400041X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051146","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 : 2024-02-22DOI: 10.1016/j.braindev.2024.02.001
Sthephanie Yannin Hernández-de la Cruz , Thania Ordaz-Robles (Methodology, Data curation, Validation, Writing – review & editing) , Marco Antonio Villaldama-Soriano , Cristian Emmanuel Luna-Guzmán , Tomas Almeida-Becerril , Judith Villa-Morales , Alan Cárdenas-Conejo , Eugenia Dolores Ruíz-Cruz , Jorge Maldonado-Hernandez , Mariela Bernabe-Garcia , Lourdes Barbosa-Cortés , Maricela Rodríguez-Cruz
Background
In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown.
Objective
We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers.
Methods
This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation.
Results
Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω −3 LCPUFAs group than placebo at month six of supplementation.
Conclusion
FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.
{"title":"The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy","authors":"Sthephanie Yannin Hernández-de la Cruz , Thania Ordaz-Robles (Methodology, Data curation, Validation, Writing – review & editing) , Marco Antonio Villaldama-Soriano , Cristian Emmanuel Luna-Guzmán , Tomas Almeida-Becerril , Judith Villa-Morales , Alan Cárdenas-Conejo , Eugenia Dolores Ruíz-Cruz , Jorge Maldonado-Hernandez , Mariela Bernabe-Garcia , Lourdes Barbosa-Cortés , Maricela Rodríguez-Cruz","doi":"10.1016/j.braindev.2024.02.001","DOIUrl":"10.1016/j.braindev.2024.02.001","url":null,"abstract":"<div><h3>Background</h3><p>In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown.</p></div><div><h3>Objective</h3><p>We analyzed the expression of the muscle regeneration markers (<em>FOXP3</em> and <em>AREG</em>) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers.</p></div><div><h3>Methods</h3><p>This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (<em>n</em> = 18) or placebo (sunflower oil, <em>n</em> = 13) for six months. <em>FOXP3</em> and <em>AREG</em> mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation.</p></div><div><h3>Results</h3><p>Patients with assisted ambulation expressed higher (<em>P =</em> 0.015) <em>FOXP3</em> mRNA levels than ambulatory patients. The <em>FOXP3</em> mRNA expression correlated (<em>Rho</em> = -0.526, <em>P</em> = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (<em>P =</em> 0.037) in the ω −3 LCPUFAs group than placebo at month six of supplementation.</p></div><div><h3>Conclusion</h3><p><em>FOXP3</em> is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on <em>FOXP3</em> needs more research.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934470","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 : 2024-02-17DOI: 10.1016/S0387-7604(24)00011-1
{"title":"Acknowledgments to Anonymous Reviewers in 2023","authors":"","doi":"10.1016/S0387-7604(24)00011-1","DOIUrl":"https://doi.org/10.1016/S0387-7604(24)00011-1","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0387760424000111/pdfft?md5=a425de4811acebb131f238882528c89a&pid=1-s2.0-S0387760424000111-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749721","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 : 2024-02-07DOI: 10.1016/j.braindev.2024.01.001
Constanze Weber , Anne Müller , Maren Freigang , Maja von der Hagen , René Günther
Background
Innovative RNA modifying and gene replacement therapies are currently revolutionizing the therapeutic landscape in 5q-associated spinal muscular atrophy (SMA). In order to provide individual recommendations for choice of treatment and therapy (dis-) continuation, objective outcome measures are needed. The purpose of this study was to determine whether maximum isometric voluntary grip and finger flexion strength is a useful sensitive outcome measure in children and adult patients with SMA.
Methods
In this non-interventional, longitudinal pilot study, we assessed grip and finger flexion strength on 39 patients with SMA II and III (n = 16 children, mean age = 10.0; n = 23 adults, mean age = 38.4) using the Weber hand and finger dynamometer HFD 200. Grip and finger flexion strength, clinical examinations and motor function scores (Revised Upper Limb Module, Hammersmith Functional Motor Scale Expanded) were assessed over a 12-month treatment period concurrent with the nusinersen treatment.
Results
Grip and finger flexion strength was highly associated with motor function and disease severity, SMA type and SMN2 copy number. During nusinersen treatment, grip and finger flexion strength significantly increased in children and adults with SMA.
Conclusion
Grip and finger flexion strength measured with the HFD 200 is a promising sensitive outcome measure for SMA.
背景：目前，创新的 RNA 修饰和基因替代疗法正在彻底改变 5q 相关性脊髓性肌萎缩症（SMA）的治疗格局。为了提供有关治疗选择和治疗（中断）持续性的个人建议，需要客观的结果测量。本研究的目的是确定最大等距自主握力和手指屈曲力是否是衡量儿童和成年 SMA 患者疗效的有用敏感指标：在这项非干预性纵向试验研究中，我们使用韦伯手部和手指测力计 HFD 200 评估了 39 名 II 期和 III 期 SMA 患者（n = 16 名儿童，平均年龄 = 10.0 岁；n = 23 名成人，平均年龄 = 38.4 岁）的握力和手指屈曲力。在12个月的治疗期内，在使用奴西那森治疗的同时，还对握力和手指屈伸力、临床检查和运动功能评分（修订的上肢模块、哈默史密斯功能性运动量表扩展版）进行了评估：结果：握力和手指屈曲力与运动功能、疾病严重程度、SMA类型和SMN2拷贝数高度相关。在努西能森治疗期间，SMA 儿童和成人的握力和手指屈曲力显著增加：结论：使用 HFD 200 测量握力和手指屈曲力是一种很有前景的 SMA 敏感结果测量方法。
{"title":"‘Reading the palm’ – A pilot study of grip and finger flexion strength as an outcome measure in 5q spinal muscular atrophy","authors":"Constanze Weber , Anne Müller , Maren Freigang , Maja von der Hagen , René Günther","doi":"10.1016/j.braindev.2024.01.001","DOIUrl":"10.1016/j.braindev.2024.01.001","url":null,"abstract":"<div><h3>Background</h3><p><span>Innovative RNA modifying and gene replacement therapies are currently revolutionizing the therapeutic landscape in 5q-associated </span>spinal muscular atrophy<span> (SMA). In order to provide individual recommendations for choice of treatment and therapy (dis-) continuation, objective outcome measures are needed. The purpose of this study was to determine whether maximum isometric voluntary grip and finger flexion strength is a useful sensitive outcome measure in children and adult patients with SMA.</span></p></div><div><h3>Methods</h3><p>In this non-interventional, longitudinal pilot study, we assessed grip and finger flexion strength on 39 patients with SMA II and III (n = 16 children, mean age = 10.0; n = 23 adults, mean age = 38.4) using the Weber hand and finger dynamometer HFD 200. Grip and finger flexion strength, clinical examinations and motor function scores (Revised Upper Limb Module, Hammersmith Functional Motor Scale Expanded) were assessed over a 12-month treatment period concurrent with the nusinersen treatment.</p></div><div><h3>Results</h3><p>Grip and finger flexion strength was highly associated with motor function and disease severity, SMA type and <em>SMN2</em><span> copy number. During nusinersen treatment, grip and finger flexion strength significantly increased in children and adults with SMA.</span></p></div><div><h3>Conclusion</h3><p>Grip and finger flexion strength measured with the HFD 200 is a promising sensitive outcome measure for SMA.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708674","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 : 2024-02-01DOI: 10.1016/j.braindev.2024.01.002
Tejas C. Sekhar
{"title":"Key considerations for the diagnosis of Guillain-Barré syndrome in pediatric populations","authors":"Tejas C. Sekhar","doi":"10.1016/j.braindev.2024.01.002","DOIUrl":"10.1016/j.braindev.2024.01.002","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662326","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}
The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics.
Methods
This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS).
Results
We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups.
Conclusions
Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.
{"title":"Exploration of urine metabolic biomarkers for new-onset, untreated pediatric epilepsy: A gas and liquid chromatography mass spectrometry-based metabolomics study","authors":"Tomoyuki Akiyama , Daisuke Saigusa , Takushi Inoue , Chiho Tokorodani , Mari Akiyama , Rie Michiue , Atsushi Mori , Eiji Hishinuma , Naomi Matsukawa , Takashi Shibata , Hiroki Tsuchiya , Katsuhiro Kobayashi","doi":"10.1016/j.braindev.2023.12.004","DOIUrl":"10.1016/j.braindev.2023.12.004","url":null,"abstract":"<div><h3>Objective</h3><p><span>The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under </span>treatment<span><span> and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine </span>metabolomics.</span></p></div><div><h3>Methods</h3><p>This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome<span> analysis of spot urine samples was conducted using gas chromatography<span> (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS).</span></span></p></div><div><h3>Results</h3><p>We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups.</p></div><div><h3>Conclusions</h3><p>Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089530","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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