Brain & Development最新文献

{"title":"A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies","authors":"Sareh Hosseinpour ,&nbsp;Ehsan Razmara ,&nbsp;Morteza Heidari ,&nbsp;Zahra Rezaei ,&nbsp;Mahmoud Reza Ashrafi ,&nbsp;Ali Zare Dehnavi ,&nbsp;Reyhaneh Kameli ,&nbsp;Ali Hosseini Bereshneh ,&nbsp;Hassan Vahidnezhad ,&nbsp;Reza Azizimalamiri ,&nbsp;Zahra Zamani ,&nbsp;Neda Pak ,&nbsp;Maryam Rasulinezhad ,&nbsp;Bahram Mohammadi ,&nbsp;Homa Ghabeli ,&nbsp;Mohammad Ghafouri ,&nbsp;Mahmoud Mohammadi ,&nbsp;Gholam Reza Zamani ,&nbsp;Reza Shervin Badv ,&nbsp;Sasan Saket ,&nbsp;Ali Reza Tavasoli","doi":"10.1016/j.braindev.2023.12.003","DOIUrl":"10.1016/j.braindev.2023.12.003","url":null,"abstract":"<div><h3>Objective</h3><p><span>Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial </span>respiratory chains<span>. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric<span> patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis<span> of leukodystrophies.</span></span></span></p></div><div><h3>Methods</h3><p>This study summarizes the clinical, imaging, and molecular data of these patients for five years.</p></div><div><h3>Results</h3><p><span>The three most common symptoms<span><span><span><span> were neurologic regression (58.5%), pyramidal signs (58.5%), and </span>extrapyramidal signs (43.9%). Because nuclear </span>DNA mutations<span> are responsible for a high percentage of pediatric MLs, whole exome sequencing<span> was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. </span></span></span>Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in </span></span><em>PDSS1, NDUFB9, FXBL4, SURF1</em>, and <em>NDUSF1</em><span> were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis.</span></p></div><div><h3>Conclusions</h3><p><span><span>The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and </span>periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of </span>corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823742","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}

{"title":"Risk factors for post-encephalopathic epilepsy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion","authors":"Makoto Nishioka ,&nbsp;Mitsuo Motobayashi ,&nbsp;Tetsuhiro Fukuyama ,&nbsp;Yuji Inaba","doi":"10.1016/j.braindev.2023.12.002","DOIUrl":"10.1016/j.braindev.2023.12.002","url":null,"abstract":"<div><h3>Background</h3><p><span>Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent </span>in patients<span> with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD.</span></p></div><div><h3>Methods</h3><p>We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 (“the PEE group”, n = 6; “the non-PEE group”, n = 14) according to inclusion criteria.</p></div><div><h3>Results</h3><p><span><span><span><span>The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1–32). The most common types of seizures were focal seizures, </span>epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had </span>intractable epilepsy. The median values of </span>alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (</span><em>p</em> &lt; 0.01).</p></div><div><h3>Conclusions</h3><p>This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818740","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}

{"title":"Risk factors for post-encephalopathic epilepsy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion.","authors":"Makoto Nishioka, Mitsuo Motobayashi, Tetsuhiro Fukuyama, Yuji Inaba","doi":"10.1016/j.braindev.2023.12.002","DOIUrl":"https://doi.org/10.1016/j.braindev.2023.12.002","url":null,"abstract":"<p><strong>Background: </strong>Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD.</p><p><strong>Methods: </strong>We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 (\"the PEE group\", n = 6; \"the non-PEE group\", n = 14) according to inclusion criteria.</p><p><strong>Results: </strong>The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1-32). The most common types of seizures were focal seizures, epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had intractable epilepsy. The median values of alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (p < 0.01).</p><p><strong>Conclusions: </strong>This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.</p>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813008","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}

{"title":"Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function","authors":"Yuki Ueda ,&nbsp;Kiyoshi Egawa ,&nbsp;Kentaro Kawamura ,&nbsp;Noriki Ochi ,&nbsp;Takeru Goto ,&nbsp;Shuhei Kimura ,&nbsp;Masashi Narugami ,&nbsp;Sachiko Nakakubo ,&nbsp;Midori Nakajima ,&nbsp;Atsushi Manabe ,&nbsp;Hideaki Shiraishi","doi":"10.1016/j.braindev.2023.12.001","DOIUrl":"10.1016/j.braindev.2023.12.001","url":null,"abstract":"<div><h3>Background</h3><p>Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established.</p></div><div><h3>Methods</h3><p>We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers’ evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes.</p></div><div><h3>Results</h3><p>All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration.</p></div><div><h3>Conclusions</h3><p>The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691521","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}

{"title":"Cover","authors":"","doi":"10.1016/S0387-7604(23)00190-0","DOIUrl":"10.1016/S0387-7604(23)00190-0","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0387760423001900/pdfft?md5=69040a81a224b8d36ca4ef331b9ff21c&pid=1-s2.0-S0387760423001900-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691905","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}

{"title":"Neuropsychiatric manifestations associated with Juvenile Systemic Lupus Erythematosus: An overview focusing on early diagnosis","authors":"Anna Nikolaidou ,&nbsp;Ioannis Beis ,&nbsp;Pinelopi Dragoumi ,&nbsp;Dimitrios Zafeiriou","doi":"10.1016/j.braindev.2023.11.008","DOIUrl":"10.1016/j.braindev.2023.11.008","url":null,"abstract":"<div><p>Juvenile systemic lupus erythematosus (jSLE) is a chronic multisystem inflammatory disease that manifests before the age of 16 years, following a remitting - relapsing course. The clinical presentation in children is multifaceted, most commonly including constitutional, hematological, cutaneous, renal, and neuropsychiatric symptoms. Neuropsychiatric manifestations range widely, affecting approximately 14–95 % of jSLE patients. They are associated with high morbidity and mortality, particularly at a younger age. Headaches, seizures, cognitive dysfunction, and mood disorders are the most frequent neuropsychiatric manifestations. The pathophysiological mechanism is quite complex and has not yet been fully investigated, with autoantibodies being the focus of research. The diagnosis of neuropsychiatric jSLE remains challenging and exclusionary. In this article we review the clinical neuropsychiatric manifestations associated with jSLE with the aim that early diagnosis and prompt treatment is achieved in children and adolescents with the disease.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566864","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}

{"title":"In patients with neurological complications, SARS-CoV-2 infection must be confirmed by PCR","authors":"Josef Finsterer","doi":"10.1016/j.braindev.2023.11.005","DOIUrl":"10.1016/j.braindev.2023.11.005","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500355","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}

{"title":"New Year’s greetings","authors":"Masafumi Morimoto (Editor-in-Chief)","doi":"10.1016/j.braindev.2023.11.010","DOIUrl":"10.1016/j.braindev.2023.11.010","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0387760423001808/pdfft?md5=5407c35808ad2464a70cffd9e30852c3&pid=1-s2.0-S0387760423001808-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500356","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}

{"title":"Splicing variant of WDR37 in a case of Neurooculocardiogenitourinary syndrome","authors":"Mai Samejima ,&nbsp;Mitsuko Nakashima ,&nbsp;Jun Shibasaki ,&nbsp;Hirotomo Saitsu ,&nbsp;Mitsuhiro Kato","doi":"10.1016/j.braindev.2023.11.007","DOIUrl":"10.1016/j.braindev.2023.11.007","url":null,"abstract":"<div><h3>Background</h3><p>Neurooculocardiogenitourinary syndrome (NOCGUS), a multisystemic syndrome characterized by motor disorder, intellectual disability, seizures, abnormal brain structure, ocular diseases, and cardiac diseases, has been reported with missense variant of WD repeat-containing protein 37 (WDR37) in humans. This report aimed to identify the cause of NOCGUS in an affected patient.</p></div><div><h3>Case presentation</h3><p>We identified a <em>de novo</em> intronic 4-bp deletion of <em>WDR37</em>, c.727-27_727-24del, which were predicted to cause abnormal splicing by SpliceAI, in the patient with NOCGUS. Reverse transcription polymerase chain reaction (RT-PCR) revealed intron retention of 63 base pairs before exon 10 in messenger RNA, which was predicted to insert 21 additional aberrant amino acids (p.S242_I243insLCQKKLKISRKCLFWPSLWQQ). The patient had novel phenotypes, anal atresia, and polycystic kidney, in addition to intellectual disability, seizures, cerebellar vermian anomaly, and coloboma, which are typical in NOCGUS. We did not observe motor impairments or cardiovascular anomalies.</p></div><div><h3>Conclusion</h3><p>This is the first reported case of NOCGUS with the splicing variant of <em>WDR37</em>, which manifests with distinctive but variable features. Our findings may expand a possible phenotypic expression of NOCGUS.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479438","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}

{"title":"Current state of hemispherectomy and callosotomy for pediatric refractory epilepsy in Denmark","authors":"Victoria Elizabeth De Knegt ,&nbsp;Malene Landbo Børresen ,&nbsp;Marianne Knudsen ,&nbsp;Katrine Moe Thomsen ,&nbsp;Peter Vilhelm Uldall ,&nbsp;Anne Vagner Jakobsen ,&nbsp;Christina Engel Hoei-Hansen","doi":"10.1016/j.braindev.2023.11.009","DOIUrl":"10.1016/j.braindev.2023.11.009","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate outcomes from hemispherectomy and callosotomy related to the need for anti-seizure medication (ASM), seizure frequency, and cognition.</p></div><div><h3>Methods</h3><p>A review of the medical charts of all Danish pediatric patients who underwent hemispherectomy or callosotomy from January 1996 to December 2019 for preoperative and postoperative ASM use, seizure frequency, and cognitive data.</p></div><div><h3>Results</h3><p>The median age of epilepsy onset was two years (interquartile range (IQR): 0.0–5.3) for the hemispherectomy patients (n = 16) and one year (IQR: 0.6–1.7) for callosotomy patients (n = 5). Median time from onset to final surgery was 3.4 years for hemispherectomy and 10.2 years for callosotomy, while the median follow-up time was 6.9 years and 9.0 years, respectively. Preoperatively, all patients had daily seizures and were treated with ≥ 2 ASM. Hemispherectomy resulted in a reduction in seizure frequency in 87.5 % of patients, with 78.6 % achieving seizure freedom. Furthermore, 81.3 % experienced a reduction in ASM use and 56.3 % stopped all ASM. Median IQ/developmental quotient (IQ/DQ) was low preoperatively (44.0 [IQR: 40.0–55.0]) and remained unchanged postoperatively (IQ change: 0.0 [IQR: −10.0–+4.0]). Callosotomy resulted in a seizure reduction of 86–99 % in four patients, and ASM could be reduced in three patients. Median IQ/DQ was 20.0 preoperatively (IQR: 20.0–30.0) and remained unchanged postoperatively (IQ change: 0.0 [IQR: 0.0]).</p></div><div><h3>Conclusion</h3><p>Hemispherectomy and callosotomy result in a substantial reduction in seizure frequency and ASM use without deterioration of IQ. Extensive epilepsy surgery should be considered early in children with drug-resistant epilepsy.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479437","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}