Naveen Kumar Paramasivan, Majed Masoud, Carley Karsten, Anza Zahid, Haidara Kherbek, Anastasia Zekeridou, Sri Raghav Sista, Surendra Dasari, Andrew M. Knight, Georgios Mangioris, John R. Mills, Andrew McKeon, Sean J. Pittock, Divyanshu Dubey
Objective
To describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti-Hu) autoimmunity.
Methods
A retrospective review of patients with ANNA1-IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP-Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.
Results
Of 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (p < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (p < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP-Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240–289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long-term outcomes.
Interpretation
Young adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long-term outcomes in ANNA1 autoimmunity.
{"title":"Phenotypic and oncological insights in ANNA1 autoimmunity: Age stratification and biomarker analysis","authors":"Naveen Kumar Paramasivan, Majed Masoud, Carley Karsten, Anza Zahid, Haidara Kherbek, Anastasia Zekeridou, Sri Raghav Sista, Surendra Dasari, Andrew M. Knight, Georgios Mangioris, John R. Mills, Andrew McKeon, Sean J. Pittock, Divyanshu Dubey","doi":"10.1002/acn3.52254","DOIUrl":"10.1002/acn3.52254","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti-Hu) autoimmunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review of patients with ANNA1-IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP-Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (<i>p</i> < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (<i>p</i> < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP-Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240–289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long-term outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Young adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long-term outcomes in ANNA1 autoimmunity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"280-290"},"PeriodicalIF":4.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabio Taddeini, Erica Ordali, Alessandra Govoni, Francesca Piattellini, Simone Valente, Luca Caremani, Alberto A Vergani, Ahmet Kaymak, Aldo Rustichini, Eleonora Russo, Chiara Rapallini, Silvia Ramat, Alberto Mazzoni
Impulsive-compulsive behaviors (ICB) are common non-motor symptoms of Parkinson's disease (PD) often associated with dopaminergic drugs (DD) therapy. We investigated the acute effects of DD on decision-making in PD patients with ICB (ICB+) and without it (ICB−), and in healthy controls (HC). Participants performed a risk-based decision-making task twice, with PD patients tested before (DD OFF) and after (DD ON) DD intake. In DD OFF, all groups developed a risk-averting strategy. In DD ON, ICB+ patients (but not ICB− nor HC) reverted to riskier choices. We conclude that DD has a specific strong acute effect on ICB+ patients' decision-making.
冲动-强迫行为（ICB）是帕金森病（PD）常见的非运动症状，通常与多巴胺能药物（DD）治疗有关。我们研究了多巴胺能药物对有 ICB（ICB+）和无 ICB（ICB-）帕金森病患者以及健康对照组（HC）决策的急性影响。参与者进行了两次基于风险的决策任务，其中帕金森病患者分别在接受 DD 治疗之前（DD OFF）和之后（DD ON）进行了测试。在 "DD OFF "状态下，所有组别都制定了风险规避策略。在 DD ON 时，ICB+ 患者（而不是 ICB- 或 HC）会重新做出更冒险的选择。我们的结论是，DD 对 ICB+ 患者的决策具有特定的强烈急性影响。
{"title":"Dopaminergic therapy disrupts decision-making in impulsive-compulsive Parkinsonian patients","authors":"Fabio Taddeini, Erica Ordali, Alessandra Govoni, Francesca Piattellini, Simone Valente, Luca Caremani, Alberto A Vergani, Ahmet Kaymak, Aldo Rustichini, Eleonora Russo, Chiara Rapallini, Silvia Ramat, Alberto Mazzoni","doi":"10.1002/acn3.52249","DOIUrl":"10.1002/acn3.52249","url":null,"abstract":"<p>Impulsive-compulsive behaviors (ICB) are common non-motor symptoms of Parkinson's disease (PD) often associated with dopaminergic drugs (DD) therapy. We investigated the acute effects of DD on decision-making in PD patients with ICB (ICB+) and without it (ICB−), and in healthy controls (HC). Participants performed a risk-based decision-making task twice, with PD patients tested before (DD OFF) and after (DD ON) DD intake. In DD OFF, all groups developed a risk-averting strategy. In DD ON, ICB+ patients (but not ICB− nor HC) reverted to riskier choices. We conclude that DD has a specific strong acute effect on ICB+ patients' decision-making.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"631-636"},"PeriodicalIF":4.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jack A. Reeves, Alexander Bartnik, Maryam Mohebbi, Murali Ramanathan, Niels Bergsland, Dejan Jakimovski, Gregory E. Wilding, Fahad Salman, Ferdinand Schweser, Bianca Weinstock-Guttman, David Hojnacki, Svetlana Eckert, Francesca Bagnato, Michael G. Dwyer, Robert Zivadinov
Objective
Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS-related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision-making and guiding development of novel disease-modifying treatments (DMTs).
Methods
This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5- or 10-year follow-ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow-up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures.
Results
DMT use was associated with lower odds of new PRL appearance (for high-efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24-month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power.
Interpretation
Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.
目的：基线顺磁边缘病变（PRL）负荷可预测多发性硬化症患者（pwMS）的疾病进展。了解PRL与其他已知多发性硬化症相关因素的关系以及PRL在临床试验中的实际效用，对于为临床决策提供信息和指导新型疾病修饰治疗（DMT）的开发至关重要：本研究纳入了152名参加大型前瞻性纵向队列研究的帕金森病患者，他们在基线和5年或10年随访时接受了3T磁共振成像扫描和临床评估。在基线3T定量易感图上确定了PRL，并在随访时将其分为持续存在、消失或新出现。评估了PRL演变与临床、放射学、环境和遗传特征之间的关系，并以PRL出现或消失作为结果测量指标估算了临床试验样本量：使用DMT与较低的新PRL出现几率相关（高效DMT：几率比=0.088，p=0.024），但与消失无关。目前的吸烟状况与更多的基线 PRL 数量相关（B = 0.527 个额外的 PRL，p = 0.013）。对进展期多发性硬化症患者进行为期24个月的临床试验，如果DMT能使PRL边缘消失率增加一倍，则每组估计需要118名进展期多发性硬化症患者，统计功率为80%：早期多发性硬化症诊断和随后的DMT治疗可减少新的慢性活动性炎症。然而，PRL消失或新的PRL出现作为临床试验的结果测量指标，其实用性受到中等疗效药物所需的潜在大样本量的限制。
{"title":"Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis","authors":"Jack A. Reeves, Alexander Bartnik, Maryam Mohebbi, Murali Ramanathan, Niels Bergsland, Dejan Jakimovski, Gregory E. Wilding, Fahad Salman, Ferdinand Schweser, Bianca Weinstock-Guttman, David Hojnacki, Svetlana Eckert, Francesca Bagnato, Michael G. Dwyer, Robert Zivadinov","doi":"10.1002/acn3.52253","DOIUrl":"10.1002/acn3.52253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS-related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision-making and guiding development of novel disease-modifying treatments (DMTs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5- or 10-year follow-ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow-up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DMT use was associated with lower odds of new PRL appearance (for high-efficacy DMTs: odds ratio = 0.088, <i>p</i> = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (<i>B</i> = 0.527 additional PRLs, <i>p</i> = 0.013). A 24-month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"267-279"},"PeriodicalIF":4.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Micheline Lagacé, Saeed Montazeri, Daphne Kamino, Eva Mamak, Linh G. Ly, Cecil D. Hahn, Vann Chau, Sampsa Vanhatalo, Emily W. Y. Tam
Objective
Assess the capacity of brain state of the newborn (BSN) to predict neurodevelopment outcomes in neonatal encephalopathy.
Methods
Trends of BSN, a deep learning-based measure translating EEG background to a continuous trend, were studied from a three-channel montage long-term EEG monitoring from a prospective cohort of 92 infants with neonatal encephalopathy and neurodevelopmental outcomes assessed by Bayley Scales of Infant Development, 3rd edition (Bayley-III) at 18 months. Outcome prediction used categories “Severe impairment” (Bayley-III composite score ≤70 or death) or “Any impairment” (score ≤85 or death).
Results
“Severe impairment” was predicted best for motor outcomes (24 h area under the curve (AUC) = 0.97), followed by cognitive (36 h AUC = 0.90), overall (24 h AUC = 0.84), and language (24 h AUC = 0.82). “Any impairment” was best predicted for motor outcomes (12 h AUC = 0.95), followed by cognitive (24 h AUC = 0.85), overall (12 h AUC = 0.75), and language (12 and 24 h AUC = 0.68). Optimal BSN cutoffs for outcome predictions evolved with the postnatal age. Low BSN scores reached a 100% positive prediction of poor outcomes at 24 h of age.
Interpretation
BSN is an excellent predictor of adverse neurodevelopmental outcomes in survivors of neonatal encephalopathy after therapeutic hypothermia, even at 24 h of life. The trend provides a fully automated, objective, quantified, and reliable interpretation of EEG background. The high temporal resolution supports continuous bedside brain assessment and early prognostication during the initial dynamic recovery phase.
{"title":"Automated assessment of EEG background for neurodevelopmental prediction in neonatal encephalopathy","authors":"Micheline Lagacé, Saeed Montazeri, Daphne Kamino, Eva Mamak, Linh G. Ly, Cecil D. Hahn, Vann Chau, Sampsa Vanhatalo, Emily W. Y. Tam","doi":"10.1002/acn3.52233","DOIUrl":"10.1002/acn3.52233","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Assess the capacity of brain state of the newborn (BSN) to predict neurodevelopment outcomes in neonatal encephalopathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Trends of BSN, a deep learning-based measure translating EEG background to a continuous trend, were studied from a three-channel montage long-term EEG monitoring from a prospective cohort of 92 infants with neonatal encephalopathy and neurodevelopmental outcomes assessed by Bayley Scales of Infant Development, 3rd edition (Bayley-III) at 18 months. Outcome prediction used categories “Severe impairment” (Bayley-III composite score ≤70 or death) or “Any impairment” (score ≤85 or death).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>“Severe impairment” was predicted best for motor outcomes (24 h area under the curve (AUC) = 0.97), followed by cognitive (36 h AUC = 0.90), overall (24 h AUC = 0.84), and language (24 h AUC = 0.82). “Any impairment” was best predicted for motor outcomes (12 h AUC = 0.95), followed by cognitive (24 h AUC = 0.85), overall (12 h AUC = 0.75), and language (12 and 24 h AUC = 0.68). Optimal BSN cutoffs for outcome predictions evolved with the postnatal age. Low BSN scores reached a 100% positive prediction of poor outcomes at 24 h of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>BSN is an excellent predictor of adverse neurodevelopmental outcomes in survivors of neonatal encephalopathy after therapeutic hypothermia, even at 24 h of life. The trend provides a fully automated, objective, quantified, and reliable interpretation of EEG background. The high temporal resolution supports continuous bedside brain assessment and early prognostication during the initial dynamic recovery phase.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 12","pages":"3267-3279"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qihan Zhang, Qing Wang, Feiyang Jin, Dan Huang, Xunming Ji, Yuan Wang
Objective
Brief exposure to intermittent hypoxia has been shown to potentially induce protective effects in the body. Animal studies suggest that intermittent hypoxia could increase cerebral blood flow and confer resistance to subsequent hypoxic–ischemic injury, yet clinical investigations are limited. This study aimed to evaluate the impact of a moderate short-term intermittent hypoxia protocol on cerebral blood flow and cognitive performance.
Methods
Subjects who met the inclusion criteria were recruited to this study and randomized into the intermittent hypoxia group or the control group, which receives intermittent hypoxia training and sham-intermittent hypoxia training, respectively. Cerebral hemodynamics, cognitive performance, cerebral perfusion pressure, and oxygen saturation were assessed before and after the intervention.
Results
A total of 100 healthy participants were included in this study. Compared to the control group, the intermittent hypoxia group exhibited higher peak systolic blood flow velocity (108.64 ± 22.53 vs. 100.21 ± 19.06, p = 0.049) and cerebrovascular conduction index (0.74 ± 0.17 vs. 0.66 ± 0.21, p = 0.027), and lower cerebrovascular resistance index (1.41 ± 0.29 vs. 1.54 ± 0.36, p = 0.044) following intermittent hypoxia training. Additionally, within-group comparisons revealed that intermittent hypoxia training led to increased cerebral blood flow velocity, elevated cerebrovascular conductance index, and decreased cerebrovascular resistance index (p < 0.05). Other indicators including cognitive function, cerebral perfusion pressure, and oxygen saturation did not exhibit significant differences between groups.
Interpretation
These findings revealed that intermittent hypoxia may represent a safe and effective strategy for improving cerebral blood flow.
目的：研究表明，短暂暴露于间歇性缺氧环境可能会对人体产生保护作用。动物研究表明，间歇性缺氧可增加脑血流量，并对随后的缺氧缺血性损伤产生抵抗力，但临床研究还很有限。本研究旨在评估中度短期间歇性缺氧方案对脑血流量和认知能力的影响：方法：本研究招募了符合纳入标准的受试者，并将其随机分为间歇性缺氧组和对照组，对照组分别接受间歇性缺氧训练和假间歇性缺氧训练。干预前后对脑血流动力学、认知能力、脑灌注压和血氧饱和度进行评估：结果：本研究共纳入了 100 名健康参与者。与对照组相比，间歇性缺氧组在间歇性缺氧训练后表现出更高的收缩期峰值血流速度（108.64 ± 22.53 vs. 100.21 ± 19.06，p = 0.049）和脑血管传导指数（0.74 ± 0.17 vs. 0.66 ± 0.21，p = 0.027），以及更低的脑血管阻力指数（1.41 ± 0.29 vs. 1.54 ± 0.36，p = 0.044）。此外，组内比较显示，间歇性缺氧训练导致脑血流速度增加、脑血管传导指数升高和脑血管阻力指数降低（p 解释：间歇性缺氧训练导致脑血流速度增加、脑血管传导指数升高和脑血管阻力指数降低（p = 0.044）：这些研究结果表明，间歇性缺氧可能是一种安全有效的改善脑血流的策略。
{"title":"Intermittent hypoxia training improves cerebral blood flow without cognitive impairment","authors":"Qihan Zhang, Qing Wang, Feiyang Jin, Dan Huang, Xunming Ji, Yuan Wang","doi":"10.1002/acn3.52248","DOIUrl":"10.1002/acn3.52248","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Brief exposure to intermittent hypoxia has been shown to potentially induce protective effects in the body. Animal studies suggest that intermittent hypoxia could increase cerebral blood flow and confer resistance to subsequent hypoxic–ischemic injury, yet clinical investigations are limited. This study aimed to evaluate the impact of a moderate short-term intermittent hypoxia protocol on cerebral blood flow and cognitive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Subjects who met the inclusion criteria were recruited to this study and randomized into the intermittent hypoxia group or the control group, which receives intermittent hypoxia training and sham-intermittent hypoxia training, respectively. Cerebral hemodynamics, cognitive performance, cerebral perfusion pressure, and oxygen saturation were assessed before and after the intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 100 healthy participants were included in this study. Compared to the control group, the intermittent hypoxia group exhibited higher peak systolic blood flow velocity (108.64 ± 22.53 vs. 100.21 ± 19.06, <i>p</i> = 0.049) and cerebrovascular conduction index (0.74 ± 0.17 vs. 0.66 ± 0.21, <i>p</i> = 0.027), and lower cerebrovascular resistance index (1.41 ± 0.29 vs. 1.54 ± 0.36, <i>p</i> = 0.044) following intermittent hypoxia training. Additionally, within-group comparisons revealed that intermittent hypoxia training led to increased cerebral blood flow velocity, elevated cerebrovascular conductance index, and decreased cerebrovascular resistance index (<i>p</i> < 0.05). Other indicators including cognitive function, cerebral perfusion pressure, and oxygen saturation did not exhibit significant differences between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings revealed that intermittent hypoxia may represent a safe and effective strategy for improving cerebral blood flow.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"86-96"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter N. Hadar, Pranav Nanda, Katherine G. Walsh, John McLaren, Alexandra Geffrey, Mirela Simon, Kristopher Kahle, R. Mark Richardson, Catherine J. Chu
Focal status epilepticus, particularly the motor variant of epilepsia partialis continua (EPC), is a rare condition characterized by near-continuous, chronic focal motor seizures, and associated with poor outcomes. Medications, including anesthetics, are often unsuccessful. Surgical resection can result in motor deficits. We report a medically complex pediatric case of super-refractory EPC that was successfully managed with combined focal resection and responsive neuromodulation. This case introduces neuromodulation as a treatment modality for this challenging condition.
{"title":"Emergent responsive neurostimulation in pediatric super-refractory epilepsia partialis continua","authors":"Peter N. Hadar, Pranav Nanda, Katherine G. Walsh, John McLaren, Alexandra Geffrey, Mirela Simon, Kristopher Kahle, R. Mark Richardson, Catherine J. Chu","doi":"10.1002/acn3.52199","DOIUrl":"10.1002/acn3.52199","url":null,"abstract":"<p>Focal status epilepticus, particularly the motor variant of epilepsia partialis continua (EPC), is a rare condition characterized by near-continuous, chronic focal motor seizures, and associated with poor outcomes. Medications, including anesthetics, are often unsuccessful. Surgical resection can result in motor deficits. We report a medically complex pediatric case of super-refractory EPC that was successfully managed with combined focal resection and responsive neuromodulation. This case introduces neuromodulation as a treatment modality for this challenging condition.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 12","pages":"3320-3327"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingwei Song, Xiaoxia Zhou, Chunyu Wang, Heng Wu, Xinxiang Yan, Jifeng Guo, Beisha Tang, Lifang Lei, Qian Xu, Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC)
Objective
We established a prospective cohort study to investigate the differences in motor and non-motor symptoms between idiopathic Parkinson's disease (IPD) and Parkinson's disease in carriers of leucine-rich repeat kinase 2 (LRRK2) gene risk variants (LRRK2-PD).
Methods
The study included 1407 individuals with IPD and 649 individuals with LRRK2-PD (comprising 304 with LRRK2-G2385R, 220 with LRRK2-R1628P, and 105 with LRRK2-A419V). Differences in symptoms between LRRK2-PD and IPD were analyzed using LCMM modeling and Cox regression analysis.
Results
The LRRK2-G2385R variant showed slower progression in tremor symptoms and excessive daytime sleepiness compared with IPD. In contrast, symptoms associated with LRRK2-R1628P and LRRK2-A419V were more similar to those of IPD. Survival analysis revealed that LRRK2-PD does not affect life expectancy compared with IPD.
Interpretation
Our extended longitudinal follow-up of LRRK2-PD in the Chinese population provided valuable insights, further confirming the clinical characteristics of the three LRRK2 variants.
{"title":"Clinical features and progression of Parkinson's disease with LRRK2 variants: A prospective study","authors":"Tingwei Song, Xiaoxia Zhou, Chunyu Wang, Heng Wu, Xinxiang Yan, Jifeng Guo, Beisha Tang, Lifang Lei, Qian Xu, Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC)","doi":"10.1002/acn3.52244","DOIUrl":"10.1002/acn3.52244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We established a prospective cohort study to investigate the differences in motor and non-motor symptoms between idiopathic Parkinson's disease (IPD) and Parkinson's disease in carriers of leucine-rich repeat kinase 2 (LRRK2) gene risk variants (LRRK2-PD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 1407 individuals with IPD and 649 individuals with LRRK2-PD (comprising 304 with LRRK2-G2385R, 220 with LRRK2-R1628P, and 105 with LRRK2-A419V). Differences in symptoms between LRRK2-PD and IPD were analyzed using LCMM modeling and Cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The LRRK2-G2385R variant showed slower progression in tremor symptoms and excessive daytime sleepiness compared with IPD. In contrast, symptoms associated with LRRK2-R1628P and LRRK2-A419V were more similar to those of IPD. Survival analysis revealed that LRRK2-PD does not affect life expectancy compared with IPD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our extended longitudinal follow-up of LRRK2-PD in the Chinese population provided valuable insights, further confirming the clinical characteristics of the three LRRK2 variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"34-42"},"PeriodicalIF":4.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janet Mei, Hamza Adel Salim, Dhairya A. Lakhani, Licia Luna, Aneri Balar, Mona Shahriari, Nathan Z. Hyson, Francis Deng, Adam A. Dmytriw, Adrien Guenego, Vaibhav Vagal, Victor C. Urrutia, Elisabeth B. Marsh, Hanzhang Lu, Risheng Xu, Rich Leigh, Dylan Wolman, Gaurang Shah, Benjamin Pulli, Kambiz Nael, Gregory W. Albers, Max Wintermark, Jeremy J. Heit, Tobias D. Faizy, Argye E. Hillis, Raf Llinas, Vivek Yedavalli
Objective
Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90-day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS-LVO patients who have undergone successful reperfusion.
Methods
We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change.
Results
In 119 patients of median (IQR) age 71 (63–81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT− patients (17 [14–23.5] vs. 13 [9.5–19], p = 0.011, and 7.5 [4–12] vs. 3 [1–7], p < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (B = −0.163, 95%CI −0.326 to −0.001, p = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127–0.863, p = 0.024).
Interpretation
PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS-LVO patients, highlighting the critical role of VO impairment in short-term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO.
{"title":"Prolonged venous transit is associated with worse neurological recovery in successfully reperfused large vessel strokes","authors":"Janet Mei, Hamza Adel Salim, Dhairya A. Lakhani, Licia Luna, Aneri Balar, Mona Shahriari, Nathan Z. Hyson, Francis Deng, Adam A. Dmytriw, Adrien Guenego, Vaibhav Vagal, Victor C. Urrutia, Elisabeth B. Marsh, Hanzhang Lu, Risheng Xu, Rich Leigh, Dylan Wolman, Gaurang Shah, Benjamin Pulli, Kambiz Nael, Gregory W. Albers, Max Wintermark, Jeremy J. Heit, Tobias D. Faizy, Argye E. Hillis, Raf Llinas, Vivek Yedavalli","doi":"10.1002/acn3.52243","DOIUrl":"10.1002/acn3.52243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90-day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS-LVO patients who have undergone successful reperfusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 119 patients of median (IQR) age 71 (63–81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT− patients (17 [14–23.5] vs. 13 [9.5–19], <i>p</i> = 0.011, and 7.5 [4–12] vs. 3 [1–7], <i>p</i> < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (<i>B</i> = −0.163, 95%CI −0.326 to −0.001, <i>p</i> = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127–0.863, <i>p</i> = 0.024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS-LVO patients, highlighting the critical role of VO impairment in short-term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"26-33"},"PeriodicalIF":4.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omri Zveik, Tal Friedman-Korn, Ariel Rechtman, Tal Ganz, Garrick Hoichman, Lyne Shweiki, Dana Ekstein, Adi Vaknin-Dembinsky
Objectives
Psychological stress has been suggested as a contributory factor in the onset and progression of multiple sclerosis (MS). The 7 October 2023 terrorist attacks in Israel caused significant psychological stress, providing a unique context to study its impact on MS activity. This study aims to assess the impact of war-related psychological stress on MS activity using magnetic resonance imaging (MRI) scans and clinical follow-up.
Methods
This observational retrospective case–control study includes 93 patients with MS (pwMS) who had routine annual MRI scans from three periods (7 October 2021 to 7 January 2022; 7 October 2022 to 7 January 2023; and 7 October 2023 to 7 January 2024). Data were collected from medical records and MRI scans at Hadassah Medical Center. MRI scans were classified as active if new or enlarging T2 lesions and/or enhancing T1 lesions were present.
Results
MRI activity significantly increased among pwMS during the first 3 months of the war compared to the corresponding period in the preceding year (11/93 vs. 23/93, P = 0.0139), with an OR of 4.0 (95% confidence interval: 1.29–16.442). pwMS with an EDSS score ≥4 showed a significant increase in MRI activity (P = 0.045), whereas no significant increase was observed in patients with an EDSS score ≤3.5 (P = 0.23). Additionally, MRI activity increased later during the war compared to the previous year (P < 0.0001).
Interpretation
This study provides evidence of increased MRI-detected disease activity in pwMS during periods of war-related psychological stress. Our findings highlight the importance of considering psychological stress in MS management. Healthcare providers should be aware of the potential for increased disease activity in pwMS during extreme stress and may consider more frequent monitoring, including MRI scans, or treatment adjustments during such periods.
{"title":"Subclinical imaging activity in multiple sclerosis patients during war-related psychological stress","authors":"Omri Zveik, Tal Friedman-Korn, Ariel Rechtman, Tal Ganz, Garrick Hoichman, Lyne Shweiki, Dana Ekstein, Adi Vaknin-Dembinsky","doi":"10.1002/acn3.52241","DOIUrl":"10.1002/acn3.52241","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Psychological stress has been suggested as a contributory factor in the onset and progression of multiple sclerosis (MS). The 7 October 2023 terrorist attacks in Israel caused significant psychological stress, providing a unique context to study its impact on MS activity. This study aims to assess the impact of war-related psychological stress on MS activity using magnetic resonance imaging (MRI) scans and clinical follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational retrospective case–control study includes 93 patients with MS (pwMS) who had routine annual MRI scans from three periods (7 October 2021 to 7 January 2022; 7 October 2022 to 7 January 2023; and 7 October 2023 to 7 January 2024). Data were collected from medical records and MRI scans at Hadassah Medical Center. MRI scans were classified as active if new or enlarging T2 lesions and/or enhancing T1 lesions were present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MRI activity significantly increased among pwMS during the first 3 months of the war compared to the corresponding period in the preceding year (11/93 vs. 23/93, <i>P</i> = 0.0139), with an OR of 4.0 (95% confidence interval: 1.29–16.442). pwMS with an EDSS score ≥4 showed a significant increase in MRI activity (<i>P</i> = 0.045), whereas no significant increase was observed in patients with an EDSS score ≤3.5 (<i>P</i> = 0.23). Additionally, MRI activity increased later during the war compared to the previous year (<i>P</i> < 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study provides evidence of increased MRI-detected disease activity in pwMS during periods of war-related psychological stress. Our findings highlight the importance of considering psychological stress in MS management. Healthcare providers should be aware of the potential for increased disease activity in pwMS during extreme stress and may consider more frequent monitoring, including MRI scans, or treatment adjustments during such periods.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"17-25"},"PeriodicalIF":4.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa R. Greco, Mabel A. Lopez, Maria L. Beltran-Quintero, Ecenur Tuc Bengur, Michele D. Poe, Maria L. Escolar
Objective
Krabbe disease is due to deficiency of galactocerebrosidase, resulting in progressive neurodegeneration due to demyelination. The purpose of this study is to document disease progression in the newly classified infantile-onset (0–12 months). We evaluated the outcomes of hematopoietic stem cell transplantation (HSCT) and described meaningful clinical endpoints.
Methods
Patients with infantile Krabbe disease were prospectively evaluated between 2000 and 2022. All patients underwent comprehensive and standardized protocols. Descriptive statistics and Kaplan–Meier survival curves were used for analysis.
Results
One hundred and thirty-seven children with infantile Krabbe disease were included (68 males and 69 females). Of the 137, 96 were not treated and 41 underwent hematopoietic stem cell transplantation. Twenty-three were asymptomatic and 18 symptomatic. Initial symptoms included irritability, developmental delay or loss of milestones, feeding difficulties, spasticity, and reflux with an average survival of 2.2. Abnormalities in nerve conduction studies, auditory brainstem responses, and brain MRIs were evident in both groups of patients. Age at transplantation and signs and symptoms determined functional outcomes. Symptomatic and asymptomatic transplanted patients showed an increase in galactocerebrosidase and a decrease in psychosine, but did not reach the normal range. The median survival for transplanted symptomatic patients was 5 years while asymptomatic was extended to 15.5 years.
Interpretation
Infantile Krabbe disease with onset before 12 months is rapidly progressive. Irreversible brain damage occurs unless timely HSCT is performed. HSCT does not prevent the progression of peripheral nerve disease. This study can be used to monitor patients and evaluate the effects of future therapies.
{"title":"Infantile Krabbe disease (0–12 months), progression, and recommended endpoints for clinical trials","authors":"Melissa R. Greco, Mabel A. Lopez, Maria L. Beltran-Quintero, Ecenur Tuc Bengur, Michele D. Poe, Maria L. Escolar","doi":"10.1002/acn3.52114","DOIUrl":"10.1002/acn3.52114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Krabbe disease is due to deficiency of galactocerebrosidase, resulting in progressive neurodegeneration due to demyelination. The purpose of this study is to document disease progression in the newly classified infantile-onset (0–12 months). We evaluated the outcomes of hematopoietic stem cell transplantation (HSCT) and described meaningful clinical endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with infantile Krabbe disease were prospectively evaluated between 2000 and 2022. All patients underwent comprehensive and standardized protocols. Descriptive statistics and Kaplan–Meier survival curves were used for analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred and thirty-seven children with infantile Krabbe disease were included (68 males and 69 females). Of the 137, 96 were not treated and 41 underwent hematopoietic stem cell transplantation. Twenty-three were asymptomatic and 18 symptomatic. Initial symptoms included irritability, developmental delay or loss of milestones, feeding difficulties, spasticity, and reflux with an average survival of 2.2. Abnormalities in nerve conduction studies, auditory brainstem responses, and brain MRIs were evident in both groups of patients. Age at transplantation and signs and symptoms determined functional outcomes. Symptomatic and asymptomatic transplanted patients showed an increase in galactocerebrosidase and a decrease in psychosine, but did not reach the normal range. The median survival for transplanted symptomatic patients was 5 years while asymptomatic was extended to 15.5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Infantile Krabbe disease with onset before 12 months is rapidly progressive. Irreversible brain damage occurs unless timely HSCT is performed. HSCT does not prevent the progression of peripheral nerve disease. This study can be used to monitor patients and evaluate the effects of future therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 12","pages":"3064-3080"},"PeriodicalIF":4.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号