Pub Date : 2024-07-30eCollection Date: 2024-01-01DOI: 10.2147/DNND.S471174
Yi Zhang, Kefan Bi, Linfu Zhou, Jie Wang, Lingtong Huang, Yan Sun, Guoping Peng, Wei Wu
Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagnosis. The advent of ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay and immunoprecipitation-mass spectrometry, has revolutionized the detection of AD plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement in detection technology facilitates the more accurate quantification of pathological brain proteins and AD-associated biomarkers in the bloodstream. This manuscript meticulously reviews the landscape of current research on immunological markers for AD, anchored in the National Institute on Aging-Alzheimer's Association AT(N) research framework. It highlights a selection of forefront ultra-sensitive detection technologies now integral to assessing AD blood immunological markers. Additionally, this review examines the crucial pre-analytical processing steps for AD blood samples that significantly impact research outcomes and addresses the practical challenges faced during clinical testing. These discussions are crucial for enhancing our comprehension and refining the diagnostic precision of AD using blood-based biomarkers. The review aims to shed light on potential avenues for innovation and improvement in the techniques employed for detecting and investigating AD, thereby contributing to the broader field of neurodegenerative disease research.
阿尔茨海默病是一种神经退行性疾病,会逐渐降低认知能力,因此已成为公共卫生领域的一个重要问题。阿兹海默症被认为是一种持续恶化且目前无法治愈的疾病,它凸显了早期诊断和干预以延缓智力功能衰退的必要性。尽管脑脊液和正电子发射断层扫描技术在诊断注意力缺失症方面的疗效已得到证实,但这些技术的高成本和侵入性限制了其更广泛的应用。因此,血液生物标志物(如淀粉样蛋白-β、磷酸化陶氏体、总陶氏体等)以其高灵敏度、微创性、可及性和成本效益等特点,成为诊断 AD 的一个有前途的途径。超灵敏检测方法的出现,包括单分子酶联免疫吸附测定法和免疫沉淀-质谱法,彻底改变了 AD 血浆生物标志物的检测方法,取代了以前的低灵敏度技术。检测技术的飞速发展有助于更准确地量化血液中的病理性脑蛋白和注意力缺失症相关生物标志物。本手稿以美国国家老龄化研究所-阿尔茨海默氏症协会AT(N)研究框架为基础,细致回顾了当前有关AD免疫标志物的研究概况。它重点介绍了目前评估阿兹海默症血液免疫标志物不可或缺的前沿超灵敏检测技术。此外,这篇综述还探讨了对研究成果有重大影响的 AD 血液样本分析前处理的关键步骤,并讨论了临床检测过程中面临的实际挑战。这些讨论对于提高我们的理解力和利用血液生物标记物完善对 AD 的诊断精度至关重要。本综述旨在阐明检测和研究 AD 所用技术的潜在创新和改进途径,从而为更广泛的神经退行性疾病研究领域做出贡献。
{"title":"Advances in Blood Biomarkers for Alzheimer's Disease: Ultra-Sensitive Detection Technologies and Impact on Clinical Diagnosis.","authors":"Yi Zhang, Kefan Bi, Linfu Zhou, Jie Wang, Lingtong Huang, Yan Sun, Guoping Peng, Wei Wu","doi":"10.2147/DNND.S471174","DOIUrl":"10.2147/DNND.S471174","url":null,"abstract":"<p><p>Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagnosis. The advent of ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay and immunoprecipitation-mass spectrometry, has revolutionized the detection of AD plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement in detection technology facilitates the more accurate quantification of pathological brain proteins and AD-associated biomarkers in the bloodstream. This manuscript meticulously reviews the landscape of current research on immunological markers for AD, anchored in the National Institute on Aging-Alzheimer's Association AT(N) research framework. It highlights a selection of forefront ultra-sensitive detection technologies now integral to assessing AD blood immunological markers. Additionally, this review examines the crucial pre-analytical processing steps for AD blood samples that significantly impact research outcomes and addresses the practical challenges faced during clinical testing. These discussions are crucial for enhancing our comprehension and refining the diagnostic precision of AD using blood-based biomarkers. The review aims to shed light on potential avenues for innovation and improvement in the techniques employed for detecting and investigating AD, thereby contributing to the broader field of neurodegenerative disease research.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India.
Case presentation: We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD.
Conclusion: ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.
{"title":"Childhood Cerebral Adrenoleukodystrophy: Case Report and Literature Review Advocating for Newborn Screening.","authors":"Hamrish Kumar Rajakumar, Varsha Coimbatore Sathyabal, Revathi Nachiappan, Sivakumar Krishnaswamy Vijayaramanujam","doi":"10.2147/DNND.S442985","DOIUrl":"10.2147/DNND.S442985","url":null,"abstract":"<p><strong>Background: </strong>X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India.</p><p><strong>Case presentation: </strong>We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD.</p><p><strong>Conclusion: </strong>ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,以认知能力下降、记忆力减退和日常功能受损为特征。虽然目前还无法治愈阿尔茨海默病,但人们已经探索出了多种药物治疗目标和管理策略。此外,传统药用植物在治疗注意力缺失症方面的潜在作用也受到了关注。AD 的药物治疗靶点包括淀粉样蛋白-β(Aβ)聚集、tau 蛋白过度磷酸化、神经炎症、氧化应激和胆碱能功能障碍。银杏叶、蛇床子、姜黄和人参等传统药用植物已证明能够通过其生物活性化合物调节这些靶点。例如,银杏叶含有黄酮类和萜类化合物,可通过减少 Aβ 沉积和增强脑血流量来发挥神经保护作用。蛇床子是蛇床子碱 A 的天然来源,具有乙酰胆碱酯酶抑制特性,从而改善胆碱能功能。莪术富含姜黄素,具有抗炎和抗氧化作用,可减轻神经炎症和氧化应激。人参的人参皂苷具有神经保护和抗淀粉样蛋白生成的作用。研究传统药用植物作为治疗注意力缺失症的补充方法具有多种优势,包括较低的不良反应风险和潜在的多靶点相互作用。此外,这些植物的文化知识和利用方式也为新疗法的开发提供了丰富的信息来源。然而,要阐明这些天然疗法的确切作用机制、实现制剂标准化以及评估其安全性和有效性,还需要进一步的研究。将以传统药用植物为基础的疗法与现代药物疗法相结合,可能是更全面、更有效地治疗注意力缺失症的关键。本综述旨在探讨 AD 的药物治疗靶点,并评估传统药用植物在治疗 AD 方面的潜力。
{"title":"Review of Pharmacotherapeutic Targets in Alzheimer's Disease and Its Management Using Traditional Medicinal Plants.","authors":"Prabhash Nath Tripathi, Ankit Lodhi, Sachchida Nand Rai, Nilay Kumar Nandi, Shweta Dumoga, Pooja Yadav, Amit Kumar Tiwari, Santosh Kumar Singh, Abdel-Nasser A El-Shorbagi, Sachin Chaudhary","doi":"10.2147/DNND.S452009","DOIUrl":"10.2147/DNND.S452009","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as <i>Ginkgo biloba, Huperzia serrata, Curcuma longa</i> (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. <i>Ginkgo biloba</i>, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. <i>Huperzia serrata</i>, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. <i>Curcuma longa</i>, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11114142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer’s Disease Risk in Older Men with Prostate Cancer","authors":"Manisha Singh, Vinayak Agarwal, Pranav Pancham, Divya Jindal, S. Agarwal, Sachchida Rai, Santosh Singh, Vivek Gupta","doi":"10.2147/dnnd.s445130","DOIUrl":"https://doi.org/10.2147/dnnd.s445130","url":null,"abstract":"","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer’s disease (AD) based on the expression of miRNAs in AD patients. Methods We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. Results 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1–67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. Conclusion The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways.
目的 探讨血清外泌体 miRNA 的诊断价值,并根据 AD 患者体内 miRNA 的表达预测其靶基因在阿尔茨海默病(AD)中的作用。方法 我们通过高通量二代测序和实时定量 PCR 测定外泌体 miRNA 的相对浓度。结果 收集了 71 例 AD 患者和 71 例 ND 受试者。研究表明,与健康受试者相比,hsa-miR-125b-1-3p、hsa-miR-193a-5p、hsa-miR-378a-3p、hsa-miR-378i和hsa-miR-451a在AD患者的血清外泌体中有不同程度的表达。根据 ROC 分析,hsa-miR-125b-1-3p 在 AD 组与健康组相比的 AUC 为 0.765,灵敏度和特异性分别为 82.1%-67.7% 。对其靶基因的富集分析表明,这些基因与神经活性配体-受体相互作用、PI3K-Akt 信号通路、Hippo 信号通路和神经系统相关通路有关。而且,hsa-miR-451a的AUC为0.728,其区分AD组与健康组的敏感性和特异性分别为67.9%和72.6%。对其靶基因的富集分析表明,它与细胞因子-细胞因子受体相互作用和 PI3K-Akt 信号通路有关。结论 AD 患者血清外泌体 microRNA 的失调可能有助于 AD 的诊断。miRNAs的靶基因可能通过不同途径参与AD的发生和发展。
{"title":"Serum Exosomal miRNA-125b and miRNA-451a are Potential Diagnostic Biomarker for Alzheimer’s Diseases","authors":"Xian Duan, Qing Zheng, Lihui Liang, Lin Zhou","doi":"10.2147/DNND.S444567","DOIUrl":"https://doi.org/10.2147/DNND.S444567","url":null,"abstract":"Aim To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer’s disease (AD) based on the expression of miRNAs in AD patients. Methods We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. Results 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1–67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. Conclusion The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways.","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140775692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01eCollection Date: 2024-01-01DOI: 10.2147/DNND.S451611
Jinrong Yang, Liping Pan, Yaping Liu, Yanrong Wang
Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.
{"title":"Transient Neonatal Myasthenia Gravis Born to a Mother with Asymptomatic MG: A Case Report.","authors":"Jinrong Yang, Liping Pan, Yaping Liu, Yanrong Wang","doi":"10.2147/DNND.S451611","DOIUrl":"10.2147/DNND.S451611","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-31eCollection Date: 2023-01-01DOI: 10.2147/DNND.S388579
Paul J Kueck, Jill K Morris, John A Stanford
Obesity is increasing in prevalence across all age groups. Long-term obesity can lead to the development of metabolic and cardiovascular diseases through its effects on adipose, skeletal muscle, and liver tissue. Pathological mechanisms associated with obesity include immune response and inflammation as well as oxidative stress and consequent endothelial and mitochondrial dysfunction. Recent evidence links obesity to diminished brain health and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD are associated with insulin resistance, an underlying syndrome of obesity. Despite these links, causative mechanism(s) resulting in neurodegenerative disease remain unclear. This review discusses relationships between obesity, AD, and PD, including clinical and preclinical findings. The review then briefly explores nonpharmacological directions for intervention.
{"title":"Current Perspectives: Obesity and Neurodegeneration - Links and Risks.","authors":"Paul J Kueck, Jill K Morris, John A Stanford","doi":"10.2147/DNND.S388579","DOIUrl":"10.2147/DNND.S388579","url":null,"abstract":"<p><p>Obesity is increasing in prevalence across all age groups. Long-term obesity can lead to the development of metabolic and cardiovascular diseases through its effects on adipose, skeletal muscle, and liver tissue. Pathological mechanisms associated with obesity include immune response and inflammation as well as oxidative stress and consequent endothelial and mitochondrial dysfunction. Recent evidence links obesity to diminished brain health and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD are associated with insulin resistance, an underlying syndrome of obesity. Despite these links, causative mechanism(s) resulting in neurodegenerative disease remain unclear. This review discusses relationships between obesity, AD, and PD, including clinical and preclinical findings. The review then briefly explores nonpharmacological directions for intervention.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: A risk prediction model to predict the risk of stroke has been developed for hypertensive patients. However, the discriminating power is poor, and the predictors are not easily accessible in low-income countries. Therefore, developing a validated risk prediction model to estimate the risk of stroke could help physicians to choose optimal treatment and precisely estimate the risk of stroke.
Objective: This study aims to develop and validate a risk prediction model to estimate the risk of stroke among hypertensive patients at the University of Gondar Comprehensive Specialized Hospital.
Methods: A retrospective follow-up study was conducted among 743 hypertensive patients between September 01/2012 and January 31/2022. The participants were selected using a simple random sampling technique. Model performance was evaluated using discrimination, calibration, and Brier scores. Internal validity and clinical utility were evaluated using bootstrapping and a decision curve analysis.
Results: Incidence of stroke was 31.4 per 1000 person-years (95% CI: 26.0, 37.7). Combinations of six predictors were selected for model development (sex, residence, baseline diastolic blood pressure, comorbidity, diabetes, and uncontrolled hypertension). In multivariable logistic regression, the discriminatory power of the model was 0.973 (95% CI: 0.959, 0.987). Calibration plot illustrated an overlap between the probabilities of the predicted and actual observed risks after 10,000 times bootstrap re-sampling, with a sensitivity of 92.79%, specificity 93.51%, and accuracy of 93.41%. The decision curve analysis demonstrated that the net benefit of the model was better than other intervention strategies, starting from the initial point.
Conclusion: An internally validated, accurate prediction model was developed and visualized in a nomogram. The model is then changed to an offline mobile web-based application to facilitate clinical applicability. The authors recommend that other researchers eternally validate the model.
{"title":"Development and Validation of a Risk Prediction Model to Estimate the Risk of Stroke Among Hypertensive Patients in University of Gondar Comprehensive Specialized Hospital, Gondar, 2012 to 2022.","authors":"Yazachew Moges Chekol, Mehari Woldemariam Merid, Getayeneh Antehunegn Tesema, Tigabu Kidie Tesfie, Tsion Mulat Tebeje, Negalegn Byadgie Gelaw, Nebiyu Bekele Gebi, Wullo Sisay Seretew","doi":"10.2147/DNND.S435806","DOIUrl":"10.2147/DNND.S435806","url":null,"abstract":"<p><strong>Background: </strong>A risk prediction model to predict the risk of stroke has been developed for hypertensive patients. However, the discriminating power is poor, and the predictors are not easily accessible in low-income countries. Therefore, developing a validated risk prediction model to estimate the risk of stroke could help physicians to choose optimal treatment and precisely estimate the risk of stroke.</p><p><strong>Objective: </strong>This study aims to develop and validate a risk prediction model to estimate the risk of stroke among hypertensive patients at the University of Gondar Comprehensive Specialized Hospital.</p><p><strong>Methods: </strong>A retrospective follow-up study was conducted among 743 hypertensive patients between September 01/2012 and January 31/2022. The participants were selected using a simple random sampling technique. Model performance was evaluated using discrimination, calibration, and Brier scores. Internal validity and clinical utility were evaluated using bootstrapping and a decision curve analysis.</p><p><strong>Results: </strong>Incidence of stroke was 31.4 per 1000 person-years (95% CI: 26.0, 37.7). Combinations of six predictors were selected for model development (sex, residence, baseline diastolic blood pressure, comorbidity, diabetes, and uncontrolled hypertension). In multivariable logistic regression, the discriminatory power of the model was 0.973 (95% CI: 0.959, 0.987). Calibration plot illustrated an overlap between the probabilities of the predicted and actual observed risks after 10,000 times bootstrap re-sampling, with a sensitivity of 92.79%, specificity 93.51%, and accuracy of 93.41%. The decision curve analysis demonstrated that the net benefit of the model was better than other intervention strategies, starting from the initial point.</p><p><strong>Conclusion: </strong>An internally validated, accurate prediction model was developed and visualized in a nomogram. The model is then changed to an offline mobile web-based application to facilitate clinical applicability. The authors recommend that other researchers eternally validate the model.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10728309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The increasing availability of high-efficacy disease-modifying therapies (DMT) for the management of relapsing multiple sclerosis (RMS) has increased the potential for individualised patient management but has added complexity to the design of treatment regimens. The long-term application of immune reconstitution therapy (IRT) is supported by an increasing database of real world studies that have added important information on the long-term safety and efficacy of this approach. Cladribine tablets (CladT) is an IRT given as two annual short courses of treatment, following which a majority of patients then demonstrate no significant MS disease activity over a period of years. Whether, and how, to treat patients beyond the first two years of treatment remains a matter for debate, as clinical evidence accumulates. We, a group of neurologists who manage people with RMS in Qatar, provide our expert consensus recommendations on the application and long-term management of CladT therapy based on our experience with treatment in the last 5 years. These include pragmatic recommendations for people with MS disease activity in years 3 and 4 (ie up to four years following first dose of CladT), and for people with or without MS disease activity in subsequent years. We believe our recommendations will help to ensure the optimal application of CladT-based IRT, with the potential benefit for the patient of achieving prolonged periods free of both MS disease symptoms and the burden of regular applications of immunosuppressive DMT.
{"title":"Practical Guidance on the Use of Cladribine Tablets in the Management or Relapsing Multiple Sclerosis: Expert Opinion from Qatar.","authors":"Dirk Deleu, Beatriz Garcia Canibano, Osama Elalamy, Mohamed Sayed Abdelmoneim, Amir Boshra","doi":"10.2147/DNND.S433459","DOIUrl":"https://doi.org/10.2147/DNND.S433459","url":null,"abstract":"<p><p>The increasing availability of high-efficacy disease-modifying therapies (DMT) for the management of relapsing multiple sclerosis (RMS) has increased the potential for individualised patient management but has added complexity to the design of treatment regimens. The long-term application of immune reconstitution therapy (IRT) is supported by an increasing database of real world studies that have added important information on the long-term safety and efficacy of this approach. Cladribine tablets (CladT) is an IRT given as two annual short courses of treatment, following which a majority of patients then demonstrate no significant MS disease activity over a period of years. Whether, and how, to treat patients beyond the first two years of treatment remains a matter for debate, as clinical evidence accumulates. We, a group of neurologists who manage people with RMS in Qatar, provide our expert consensus recommendations on the application and long-term management of CladT therapy based on our experience with treatment in the last 5 years. These include pragmatic recommendations for people with MS disease activity in years 3 and 4 (ie up to four years following first dose of CladT), and for people with or without MS disease activity in subsequent years. We believe our recommendations will help to ensure the optimal application of CladT-based IRT, with the potential benefit for the patient of achieving prolonged periods free of both MS disease symptoms and the burden of regular applications of immunosuppressive DMT.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice.
Objective: In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia.
Methods: We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice.
Results: In all leptin treatment group, the brain Aβ levels were decrease. We found increased levels of IL-1β, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1β/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference.
Conclusion: Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.
{"title":"Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.","authors":"Jing Ma, Yi-Hui Hou, Zhe-Yan Liao, Zheng Ma, Xiao-Xuan Zhang, Jian-Li Wang, Yun-Bo Zhu, Hai-Lei Shan, Ping-Yue Wang, Cheng-Bo Li, Ying-Lei Lv, Yi-Lan Wei, Jie-Zhi Dou","doi":"10.2147/DNND.S427781","DOIUrl":"10.2147/DNND.S427781","url":null,"abstract":"<p><strong>Background: </strong>Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice.</p><p><strong>Objective: </strong>In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia.</p><p><strong>Methods: </strong>We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice.</p><p><strong>Results: </strong>In all leptin treatment group, the brain Aβ levels were decrease. We found increased levels of IL-1β, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1β/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference.</p><p><strong>Conclusion: </strong>Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}