Ana Flávia F. Ferreira, Marina Meira, Livia M. Lemuchi, Maria E. Bianchetti, Nicole M. Kamidai, Livia M. Kilinsky, Luiz R. G. Britto
The past few years have witnessed extensive research on the two most common neurodegenerative diseases, Alzheimer’s disease (AD), and Parkinson’s disease (PD). With an urgent need for new treatments, drug targets, and a better understanding of the pathophysiological mechanisms underlying these conditions, researchers have turned to animal models, especially rodents, to address these issues. However, the abundance of reported models poses a challenge when choosing the most suitable model for a specific study. In this critical review, we systematically scrutinized studies using rodent models of AD or PD over the past 5 years. A comprehensive literature search was conducted on PubMed, followed by the meticulous screening of the identified studies. Among the retrieved publications, 1,222 studies reported the use of rodent models of PD, with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, α-synuclein, and 6-hydroxydopamine emerging as the most frequently used models. Similarly, 2,961 studies reported the use of rodent models of AD, with APP/PS1, 5×FAD, APP-based models, and 3×Tg being the most prevalent. In this review, we summarize and highlight the main characteristics of these models. By providing a comprehensive overview of their features and applications, this review guides future studies in the AD and PD field, eventually aiding in the selection of the most appropriate animal model tailored to the specific research question under scrutiny.
在过去的几年里，人们对两种最常见的神经退行性疾病--阿尔茨海默病（AD）和帕金森病（PD）进行了广泛的研究。由于迫切需要新的治疗方法、药物靶点以及更好地了解这些疾病的病理生理机制，研究人员转而利用动物模型，尤其是啮齿类动物来解决这些问题。然而，大量报道的模型为特定研究选择最合适的模型带来了挑战。在这篇重要综述中，我们系统地审查了过去 5 年中使用啮齿动物模型进行的有关注意力缺失症或帕金森病的研究。我们在 PubMed 上进行了全面的文献检索，然后对确定的研究进行了细致的筛选。在检索到的文献中，有1,222项研究报告了使用啮齿动物模型治疗帕金森病的情况，其中1-甲基-4-苯基-1,2,3,6-四氢吡啶、α-突触核蛋白和6-羟基多巴胺是最常用的模型。同样，有2961项研究报告了啮齿动物AD模型的使用情况，其中APP/PS1、5×FAD、基于APP的模型和3×Tg最为普遍。在本综述中，我们总结并强调了这些模型的主要特点。通过对这些模型的特点和应用进行全面概述，本综述将为今后的 AD 和 PD 领域研究提供指导，最终帮助人们根据所研究的具体问题选择最合适的动物模型。
{"title":"Most utilized rodent models for Alzheimer’s and Parkinson’s disease: A critical review of the past 5 years","authors":"Ana Flávia F. Ferreira, Marina Meira, Livia M. Lemuchi, Maria E. Bianchetti, Nicole M. Kamidai, Livia M. Kilinsky, Luiz R. G. Britto","doi":"10.36922/an.2903","DOIUrl":"https://doi.org/10.36922/an.2903","url":null,"abstract":"The past few years have witnessed extensive research on the two most common neurodegenerative diseases, Alzheimer’s disease (AD), and Parkinson’s disease (PD). With an urgent need for new treatments, drug targets, and a better understanding of the pathophysiological mechanisms underlying these conditions, researchers have turned to animal models, especially rodents, to address these issues. However, the abundance of reported models poses a challenge when choosing the most suitable model for a specific study. In this critical review, we systematically scrutinized studies using rodent models of AD or PD over the past 5 years. A comprehensive literature search was conducted on PubMed, followed by the meticulous screening of the identified studies. Among the retrieved publications, 1,222 studies reported the use of rodent models of PD, with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, α-synuclein, and 6-hydroxydopamine emerging as the most frequently used models. Similarly, 2,961 studies reported the use of rodent models of AD, with APP/PS1, 5×FAD, APP-based models, and 3×Tg being the most prevalent. In this review, we summarize and highlight the main characteristics of these models. By providing a comprehensive overview of their features and applications, this review guides future studies in the AD and PD field, eventually aiding in the selection of the most appropriate animal model tailored to the specific research question under scrutiny.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141356076","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}
Liqun Zhang, Ying Chen, Jingxian Xu, Christopher P. Corpe, A. Shtaya, Philip Benjamin, Yun Xu
Stroke is the leading cause of disability and the second leading cause of death worldwide. Diabetes mellitus is a critical independent cardiovascular risk factor in patients, irrespective of age, smoking, and hypertension. Approximately one-third of first-time ischemic stroke patients have diabetes. Inflammation is among the most important pathological mechanisms in atheroma formation, the damage cascades of the acute phase, as well as during the subacute and chronic phases after stroke. Diabetes, as a common risk factor for stroke, is often present for a long time before a stroke occurs, causing low-grade inflammation, and disrupting the proper functioning of the neurovascular units. These proinflammatory processes and maladaptive immune mechanisms are further accelerated after cerebral ischemia and worsen the stroke outcome in diabetic patients. Clinical treatments for ischemic stroke are currently focused on restoring cerebral blood flow (reperfusion) in the acute phase, including thrombolysis and mechanical thrombectomy, which are not applicable to patients that fall outside of the treatment window and/or without large-vessel occlusion. There are few approved treatments targeting cellular injury caused by inflammation. There are even fewer data on effective treatment for diabetic stroke targeting inflammation. This paper presents the first part of a review focusing on the temporospatial aspects of inflammation in ischemic stroke pathophysiology in stroke patients with type 2 diabetes.
{"title":"Inflammation in ischemic stroke patients with type 2 diabetes – Part II: Potential therapeutic targets","authors":"Liqun Zhang, Ying Chen, Jingxian Xu, Christopher P. Corpe, A. Shtaya, Philip Benjamin, Yun Xu","doi":"10.36922/an.1694","DOIUrl":"https://doi.org/10.36922/an.1694","url":null,"abstract":"Stroke is the leading cause of disability and the second leading cause of death worldwide. Diabetes mellitus is a critical independent cardiovascular risk factor in patients, irrespective of age, smoking, and hypertension. Approximately one-third of first-time ischemic stroke patients have diabetes. Inflammation is among the most important pathological mechanisms in atheroma formation, the damage cascades of the acute phase, as well as during the subacute and chronic phases after stroke. Diabetes, as a common risk factor for stroke, is often present for a long time before a stroke occurs, causing low-grade inflammation, and disrupting the proper functioning of the neurovascular units. These proinflammatory processes and maladaptive immune mechanisms are further accelerated after cerebral ischemia and worsen the stroke outcome in diabetic patients. Clinical treatments for ischemic stroke are currently focused on restoring cerebral blood flow (reperfusion) in the acute phase, including thrombolysis and mechanical thrombectomy, which are not applicable to patients that fall outside of the treatment window and/or without large-vessel occlusion. There are few approved treatments targeting cellular injury caused by inflammation. There are even fewer data on effective treatment for diabetic stroke targeting inflammation. This paper presents the first part of a review focusing on the temporospatial aspects of inflammation in ischemic stroke pathophysiology in stroke patients with type 2 diabetes.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"11 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141382569","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}
Kelsey L. Lewis, Menzi Sun, Barry Joyner, Barr Munkasy, Li Li
Peripheral neuropathy is characterized by decreased foot sole sensitivity and slowed nerve conduction velocity, leading to impaired postural control and functional gait performance. This study assessed the differential effects of reduced foot sole sensitivity and slowed nerve conduction velocity on postural control and functional gait. Thirty-five participants were evaluated for two main clinical symptoms: the H-index and foot sole sensitivity. Two times the square of the height (H) of the individual divided by the latency (T) between the onsets of the M- and H-waves of the H-reflex were used to calculate the H-index (2 × [H/T]2). Foot sole sensitivity was evaluated using a monofilament on five sites at the bottom of the foot. Participants were categorized into three symptomological groups: (i) less affected (LA), (ii) moderately affected (MA), and (iii) severely affected (SA), based on their H-index ranges of 78.0 – 109.4, 42.8 – 76.6, and 45.6 – 75.5 cm2/ms2, respectively, and foot sole sensitivity score ranges of 6 – 10, 6 – 10, and 0 – 5, respectively. Outcome variables included center of pressure (COP) standard deviation in the anteroposterior direction and COP average velocity (Vavg) during 30 s of eyes-open quiet standing, as well as 6-min walk distance (6MWD) and timed-up-and-go duration (TUG). Multivariate analysis revealed significant group differences (P < 0.05), with post hoc analysis showing significant differences between LA and SA in Vavg (F4,30 = 3.752; P = 0.014). Discriminant analysis revealed Vavg as the primary determinant, while 6MWD and TUG were secondary determinants of group separation. Notably, enhanced functional gait was associated solely with sensitive foot soles and heightened nerve conduction velocity within the LA group, not in the MA or SA groups. Disease severity mediated the specific effects on postural control and functional gait, underscoring the importance of tailoring rehabilitation protocols to address individual symptoms.
周围神经病变的特点是足底敏感性降低和神经传导速度减慢，从而导致姿势控制和功能性步态表现受损。本研究评估了足底敏感性降低和神经传导速度减慢对姿势控制和功能性步态的不同影响。35 名参与者接受了两项主要临床症状的评估：H 指数和足底敏感度。用个人身高（H）的平方除以 H 反射的 M 波和 H 波之间的潜伏期（T）的二倍来计算 H 指数（2 × [H/T]2）。脚底敏感度是用单丝在脚底的五个部位进行评估的。根据参与者的 H 指数范围（分别为 78.0 - 109.4、42.8 - 76.6 和 45.6 - 75.5 cm2/ms2）和足底敏感度评分范围（分别为 6 - 10、6 - 10 和 0 - 5），将他们分为三个症状组：(i) 轻度受影响 (LA)、(ii) 中度受影响 (MA) 和 (iii) 重度受影响 (SA)。结果变量包括睁眼安静站立 30 秒期间前后方向的压力中心 (COP) 标准偏差和 COP 平均速度 (Vavg)，以及 6 分钟步行距离 (6MWD) 和定时起立行走时间 (TUG)。多变量分析显示组间存在显著差异（P < 0.05），事后分析显示 LA 和 SA 在 Vavg 方面存在显著差异（F4,30 = 3.752; P = 0.014）。判别分析显示，Vavg 是决定分组的主要因素，而 6MWD 和 TUG 则是决定分组的次要因素。值得注意的是，在 LA 组中，功能步态的增强仅与敏感的足底和神经传导速度的提高有关，而在 MA 或 SA 组中则无关。疾病的严重程度对姿势控制和功能性步态的具体影响起着中介作用，这强调了针对个体症状定制康复方案的重要性。
{"title":"Impact of foot sole insensitivity and reduced nerve conduction velocity on postural control and functional gait","authors":"Kelsey L. Lewis, Menzi Sun, Barry Joyner, Barr Munkasy, Li Li","doi":"10.36922/an.2900","DOIUrl":"https://doi.org/10.36922/an.2900","url":null,"abstract":"Peripheral neuropathy is characterized by decreased foot sole sensitivity and slowed nerve conduction velocity, leading to impaired postural control and functional gait performance. This study assessed the differential effects of reduced foot sole sensitivity and slowed nerve conduction velocity on postural control and functional gait. Thirty-five participants were evaluated for two main clinical symptoms: the H-index and foot sole sensitivity. Two times the square of the height (H) of the individual divided by the latency (T) between the onsets of the M- and H-waves of the H-reflex were used to calculate the H-index (2 × [H/T]2). Foot sole sensitivity was evaluated using a monofilament on five sites at the bottom of the foot. Participants were categorized into three symptomological groups: (i) less affected (LA), (ii) moderately affected (MA), and (iii) severely affected (SA), based on their H-index ranges of 78.0 – 109.4, 42.8 – 76.6, and 45.6 – 75.5 cm2/ms2, respectively, and foot sole sensitivity score ranges of 6 – 10, 6 – 10, and 0 – 5, respectively. Outcome variables included center of pressure (COP) standard deviation in the anteroposterior direction and COP average velocity (Vavg) during 30 s of eyes-open quiet standing, as well as 6-min walk distance (6MWD) and timed-up-and-go duration (TUG). Multivariate analysis revealed significant group differences (P < 0.05), with post hoc analysis showing significant differences between LA and SA in Vavg (F4,30 = 3.752; P = 0.014). Discriminant analysis revealed Vavg as the primary determinant, while 6MWD and TUG were secondary determinants of group separation. Notably, enhanced functional gait was associated solely with sensitive foot soles and heightened nerve conduction velocity within the LA group, not in the MA or SA groups. Disease severity mediated the specific effects on postural control and functional gait, underscoring the importance of tailoring rehabilitation protocols to address individual symptoms.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"31 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141385103","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}
Liqun Zhang, Ying Chen, Jingxian Xu, Christopher P. Corpe, A. Shtaya, Philip Benjamin, Yun Xu
Stroke is the leading cause of disability and the second leading cause of death worldwide. Diabetes mellitus is a critical independent cardiovascular risk factor in patients, irrespective of age, smoking, and hypertension. Approximately one-third of first-time ischemic stroke patients have diabetes. Inflammation is among the most important pathological mechanisms in atheroma formation, the damage cascades of the acute phase, as well as during the subacute and chronic phases after stroke. Diabetes, as a common risk factor for stroke, is often present for a long time before a stroke occurs, causing low-grade inflammation, and disrupting the proper functioning of the neurovascular units. These proinflammatory processes and maladaptive immune mechanisms are further accelerated after cerebral ischemia and worsen the stroke outcome in diabetic patients. Clinical treatments for ischemic stroke are currently focused on restoring cerebral blood flow (reperfusion) in the acute phase, including thrombolysis and mechanical thrombectomy, which are not applicable to patients that fall outside of the treatment window and/or without large-vessel occlusion. There are few approved treatments targeting cellular injury caused by inflammation. There are even fewer data on effective treatment for diabetic stroke targeting inflammation. This paper presents the first part of a review focusing on the temporospatial aspects of inflammation in ischemic stroke pathophysiology in stroke patients with type 2 diabetes.
{"title":"Inflammation in ischemic stroke patients with type 2 diabetes – Part I: Atherosclerosis formation, acute ischemia, post-stroke infection, and long-term sequelae","authors":"Liqun Zhang, Ying Chen, Jingxian Xu, Christopher P. Corpe, A. Shtaya, Philip Benjamin, Yun Xu","doi":"10.36922/an.1683","DOIUrl":"https://doi.org/10.36922/an.1683","url":null,"abstract":"Stroke is the leading cause of disability and the second leading cause of death worldwide. Diabetes mellitus is a critical independent cardiovascular risk factor in patients, irrespective of age, smoking, and hypertension. Approximately one-third of first-time ischemic stroke patients have diabetes. Inflammation is among the most important pathological mechanisms in atheroma formation, the damage cascades of the acute phase, as well as during the subacute and chronic phases after stroke. Diabetes, as a common risk factor for stroke, is often present for a long time before a stroke occurs, causing low-grade inflammation, and disrupting the proper functioning of the neurovascular units. These proinflammatory processes and maladaptive immune mechanisms are further accelerated after cerebral ischemia and worsen the stroke outcome in diabetic patients. Clinical treatments for ischemic stroke are currently focused on restoring cerebral blood flow (reperfusion) in the acute phase, including thrombolysis and mechanical thrombectomy, which are not applicable to patients that fall outside of the treatment window and/or without large-vessel occlusion. There are few approved treatments targeting cellular injury caused by inflammation. There are even fewer data on effective treatment for diabetic stroke targeting inflammation. This paper presents the first part of a review focusing on the temporospatial aspects of inflammation in ischemic stroke pathophysiology in stroke patients with type 2 diabetes.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266750","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}
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, followed by the Middle East respiratory syndrome coronavirus (MERS-CoV) that causes fatal illness in 2012, has made coronaviruses a public health concern. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection does not only affect the respiratory system but has also been observed to elicit neurological manifestations, with anosmia and ageusia being the most common, followed by headache, seizures, neuropathies, and encephalopathy. In addition to SARS-CoV and MERS-CoV which have been proven to be neuroinvasive, SARS-CoV-2 has been found to worsen preexisting long-term neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, apart from triggering the acute neurological symptoms. The association between COVID-19 and relatively rare neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease has yet to be corroborated due to limited significant data. Studies have shown that COVID-19 does not seem to exacerbate these disorders, and the severity of COVID-19-related disease and fatalities is not significantly higher in the affected patients than in the general population. However, increased complications have been reported among the patients in advanced stages of these diseases. Hence, it is imperative to conduct long-term, comprehensive investigations on the effects of SARS-CoV-2 on neurodegenerative disorders, with the ultimate aim of developing appropriate interventions. Studies involving larger cohorts of people of varying ages, disease duration, and ethnicity are urgently warranted.
{"title":"Linkage between SARS-CoV-2 infection and neurodegenerative disorders: Review and current update","authors":"Amaan Javed, Anika Batra, Mehak Singh, Parnica Sarkar","doi":"10.36922/an.2200","DOIUrl":"https://doi.org/10.36922/an.2200","url":null,"abstract":"The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, followed by the Middle East respiratory syndrome coronavirus (MERS-CoV) that causes fatal illness in 2012, has made coronaviruses a public health concern. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection does not only affect the respiratory system but has also been observed to elicit neurological manifestations, with anosmia and ageusia being the most common, followed by headache, seizures, neuropathies, and encephalopathy. In addition to SARS-CoV and MERS-CoV which have been proven to be neuroinvasive, SARS-CoV-2 has been found to worsen preexisting long-term neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, apart from triggering the acute neurological symptoms. The association between COVID-19 and relatively rare neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease has yet to be corroborated due to limited significant data. Studies have shown that COVID-19 does not seem to exacerbate these disorders, and the severity of COVID-19-related disease and fatalities is not significantly higher in the affected patients than in the general population. However, increased complications have been reported among the patients in advanced stages of these diseases. Hence, it is imperative to conduct long-term, comprehensive investigations on the effects of SARS-CoV-2 on neurodegenerative disorders, with the ultimate aim of developing appropriate interventions. Studies involving larger cohorts of people of varying ages, disease duration, and ethnicity are urgently warranted.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"17 S1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140244496","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}
Dementia with Lewy bodies (DLBs) is the second most common cause of neurodegenerative dementia in the United States, after Alzheimer’s disease, and is often misdiagnosed. A history of substance use disorder (SUD) complicates the diagnosis process, and side effects of substance misuse can mirror or mask signs of degenerative dementia. The fluctuating cognition and mobility which would normally point toward DLB are erroneously seen as signs of SUD or polypharmacy. However, a history of SUD should not preclude the diagnosis of DLB or other forms of proteinopathy, as substance misuse can contribute to the development of neurodegenerative dementias. Both alcohol and benzodiazepines have a sedative effect as ligands to gamma-aminobutyric acid (GABA) receptors. Long-term use, misuse, and withdrawals can upset the delicate GABAergic/glutamatergic balance, resulting in adverse neuroimmune and neuroinflammatory responses which contribute to the pathologies seen in degenerative dementias, such as DLB. In this paper, we review the challenges, including limitations of standardized instruments for dementia and the harms of delayed diagnosis, in DLB diagnosis, in combination with our experiences drawn from studying a polypharmacy-practicing 68-year-old man with a 40-year history of benzodiazepine and alcohol use. Understanding the underlying mechanisms of SUD serves to destigmatize the condition to expedite treatment and further our knowledge of the relationship between neuroinflammation and dementia.
{"title":"Unraveling the challenges of diagnosing dementia with Lewy bodies in a patient with alcohol and benzodiazepine misuse: A case study-based review","authors":"Kelly Tuchman, Fraser C. Henderson Sr","doi":"10.36922/an.2232","DOIUrl":"https://doi.org/10.36922/an.2232","url":null,"abstract":"Dementia with Lewy bodies (DLBs) is the second most common cause of neurodegenerative dementia in the United States, after Alzheimer’s disease, and is often misdiagnosed. A history of substance use disorder (SUD) complicates the diagnosis process, and side effects of substance misuse can mirror or mask signs of degenerative dementia. The fluctuating cognition and mobility which would normally point toward DLB are erroneously seen as signs of SUD or polypharmacy. However, a history of SUD should not preclude the diagnosis of DLB or other forms of proteinopathy, as substance misuse can contribute to the development of neurodegenerative dementias. Both alcohol and benzodiazepines have a sedative effect as ligands to gamma-aminobutyric acid (GABA) receptors. Long-term use, misuse, and withdrawals can upset the delicate GABAergic/glutamatergic balance, resulting in adverse neuroimmune and neuroinflammatory responses which contribute to the pathologies seen in degenerative dementias, such as DLB. In this paper, we review the challenges, including limitations of standardized instruments for dementia and the harms of delayed diagnosis, in DLB diagnosis, in combination with our experiences drawn from studying a polypharmacy-practicing 68-year-old man with a 40-year history of benzodiazepine and alcohol use. Understanding the underlying mechanisms of SUD serves to destigmatize the condition to expedite treatment and further our knowledge of the relationship between neuroinflammation and dementia.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"29 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140247662","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}
June Egiguren-Ortiz, Celtia Domínguez-Fernández, Jone Razquin, Laura De las Heras-García, E. Astigarraga, Cristina Miguelez, G. Barreda-Gómez
The aging of the population, attributed to increased life expectancy, coincides with a rise in the prevalence of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. The symptoms of these disorders, such as motor disturbances and cognitive impairment, occur only after significant neurological damage, greatly diminishing the effectiveness of treatments. Consequently, achieving early diagnosis of neurodegenerative diseases stands as a paramount global health challenge. These conditions are characterized by the progressive loss of specific neuronal groups in the nervous system, resulting in dysfunction and eventual cell death in the brain. Although the exact cause of neuronal degeneration remains largely unknown, recent studies have revealed the significant involvement of the immune system in the pathogenesis of these diseases. Notably, the identification of reactive antibodies targeting specific antigens has highlighted a close association between immune mechanisms and the neurodegenerative process. Thus, the aim of this review is to explore the mechanisms of the adaptive immune system and their impact on the pathogenesis of neurodegenerative diseases, with a particular focus on reactive antibodies and their potential as diagnostic biomarkers.
{"title":"Reactive antibodies against brain antigens as serological biomarkers of neurodegenerative diseases","authors":"June Egiguren-Ortiz, Celtia Domínguez-Fernández, Jone Razquin, Laura De las Heras-García, E. Astigarraga, Cristina Miguelez, G. Barreda-Gómez","doi":"10.36922/an.2058","DOIUrl":"https://doi.org/10.36922/an.2058","url":null,"abstract":"The aging of the population, attributed to increased life expectancy, coincides with a rise in the prevalence of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. The symptoms of these disorders, such as motor disturbances and cognitive impairment, occur only after significant neurological damage, greatly diminishing the effectiveness of treatments. Consequently, achieving early diagnosis of neurodegenerative diseases stands as a paramount global health challenge. These conditions are characterized by the progressive loss of specific neuronal groups in the nervous system, resulting in dysfunction and eventual cell death in the brain. Although the exact cause of neuronal degeneration remains largely unknown, recent studies have revealed the significant involvement of the immune system in the pathogenesis of these diseases. Notably, the identification of reactive antibodies targeting specific antigens has highlighted a close association between immune mechanisms and the neurodegenerative process. Thus, the aim of this review is to explore the mechanisms of the adaptive immune system and their impact on the pathogenesis of neurodegenerative diseases, with a particular focus on reactive antibodies and their potential as diagnostic biomarkers.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"9 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140247434","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 : 2024-01-01Epub Date: 2024-06-14DOI: 10.36922/an.3122
Carmel Armon, Lisa A Cannon-Albright, Kristina Allen-Brady, Sharon Wolfson
Alzheimer's disease (AD) is a major cause of dementia. While maternal inheritance has been recognized for late-onset AD (LOAD), risk factors have not been identified consistently on the X chromosome. We recently developed a new method to identify an apparent risk of 70% mediated by the X chromosome in newly-presenting cognitive disorders clinic patients with amnestic mild cognitive impairment (aMCI) or early LOAD with unilateral parental lineage for AD or dementia. We sought to confirm our preliminary findings in the Utah Population Database (UPDB). We obtained previously published aggregate data on the risk of AD in the UPDB based on family history, stratified the data by the sex of the proband, and analyzed them using the new method. The X chromosome-attributable relative risk was estimated by calculating the following: Odds ratio (OR) = (women with paternal lineage: Women with maternal lineage)/(men with paternal lineage: Men with maternal lineage). The proportion of genetic risk attributable to the X chromosome is equal to (OR-1)/OR. The analysis did not reveal any risk mediated by the X chromosome, and the null result could be attributed to methodological limitations. Factors that impact the initial or early presentation (incidence) of LOAD, which are appropriate for consideration as risk factors, may not be detectable in a (prevalent) population of deceased individuals. Thus, epidemiological evidence for the contribution of the X chromosome to the development of LOAD will need to be sought prospectively in incident patient populations with newly diagnosed, biologically-confirmed aMCI or LOAD.
{"title":"Chasing shadows: Investigating X chromosome mediation in late-onset Alzheimer's disease.","authors":"Carmel Armon, Lisa A Cannon-Albright, Kristina Allen-Brady, Sharon Wolfson","doi":"10.36922/an.3122","DOIUrl":"10.36922/an.3122","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a major cause of dementia. While maternal inheritance has been recognized for late-onset AD (LOAD), risk factors have not been identified consistently on the X chromosome. We recently developed a new method to identify an apparent risk of 70% mediated by the X chromosome in newly-presenting cognitive disorders clinic patients with amnestic mild cognitive impairment (aMCI) or early LOAD with unilateral parental lineage for AD or dementia. We sought to confirm our preliminary findings in the Utah Population Database (UPDB). We obtained previously published aggregate data on the risk of AD in the UPDB based on family history, stratified the data by the sex of the proband, and analyzed them using the new method. The X chromosome-attributable relative risk was estimated by calculating the following: Odds ratio (OR) = (women with paternal lineage: Women with maternal lineage)/(men with paternal lineage: Men with maternal lineage). The proportion of genetic risk attributable to the X chromosome is equal to (OR-1)/OR. The analysis did not reveal any risk mediated by the X chromosome, and the null result could be attributed to methodological limitations. Factors that impact the initial or early presentation (incidence) of LOAD, which are appropriate for consideration as risk factors, may not be detectable in a (prevalent) population of deceased individuals. Thus, epidemiological evidence for the contribution of the X chromosome to the development of LOAD will need to be sought prospectively in incident patient populations with newly diagnosed, biologically-confirmed aMCI or LOAD.</p>","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781894","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}
Yannan Yu, Yu-yuan Xu, Xue Man, Ming-Li Li, Bo Hou, Shan Gao, Feng Feng, D. Liebeskind, Wei-Hai Xu
The Fried-Breadstick sign is characterized as a continuous signal loss at the center of the intracranial internal carotid artery (ICA) on time-of-flight magnetic resonance angiography (TOF-MRA). In this study, we present a novel imaging marker on TOF-MRA and investigate its potential association with ICA-middle cerebral artery (ICA-MCA) atherosclerosis and ischemic stroke. Vessel wall magnetic resonance imaging data were obtained from patients with recent clinical stroke or asymptomatic patients with suspected middle cerebral artery (MCA) atherosclerosis, covering the period from January 2007 to August 2015. We conducted a comparative analysis of ICA stenosis, MCA atherosclerosis and stenosis degree, and the terminal ICA bifurcation angle between ICA-MCAs with and without the Fried-Breadstick sign, involving a total of 1,005 ICA-MCAs from 553 patients. The Fried-Breadstick sign exhibited a higher prevalence in non-to-mild stenotic ICAs (57.5% vs. 9.8% in severely stenotic ICA, P < 0.001) and plaque-free MCAs (53.2% vs. 26.6% in MCAs with plaque, P < 0.001). Factors independently associated with the presence of the Fried-Breadstick sign included MCA stenosis degree (odds ratio [OR]: 0.85/10% increase, 95% confidence interval [CI]: 0.80 – 0.90), ICA stenosis (compared to non-to-mild stenosis, moderate stenosis: OR: 0.39, 95% CI: 0.28 – 0.54, severe stenosis: OR: 0.10, 95% CI: 0.06 – 0.17), and terminal ICA bifurcation angle (OR: 0.86/10° increase, 95% CI: 0.79 – 0.93). In atherosclerotic MCAs without luminal narrowing, the Fried-Breadstick sign was also less frequently observed than in plaque-free MCAs (34.6% vs. 53.2%, P = 0.012). In conclusion, the presence of the Fried-Breadstick sign is associated with healthier ICA-MCAs devoid of stenosis or plaque. The Fried-Breadstick sign may signify healthy ICA-MCA hemodynamics, serving as a potential screening tool for intracranial atherosclerosis without incurring additional cost or risk.
{"title":"Fried-Breadstick sign: A novel marker for healthy vasculature in magnetic resonance angiography","authors":"Yannan Yu, Yu-yuan Xu, Xue Man, Ming-Li Li, Bo Hou, Shan Gao, Feng Feng, D. Liebeskind, Wei-Hai Xu","doi":"10.36922/an.1238","DOIUrl":"https://doi.org/10.36922/an.1238","url":null,"abstract":"The Fried-Breadstick sign is characterized as a continuous signal loss at the center of the intracranial internal carotid artery (ICA) on time-of-flight magnetic resonance angiography (TOF-MRA). In this study, we present a novel imaging marker on TOF-MRA and investigate its potential association with ICA-middle cerebral artery (ICA-MCA) atherosclerosis and ischemic stroke. Vessel wall magnetic resonance imaging data were obtained from patients with recent clinical stroke or asymptomatic patients with suspected middle cerebral artery (MCA) atherosclerosis, covering the period from January 2007 to August 2015. We conducted a comparative analysis of ICA stenosis, MCA atherosclerosis and stenosis degree, and the terminal ICA bifurcation angle between ICA-MCAs with and without the Fried-Breadstick sign, involving a total of 1,005 ICA-MCAs from 553 patients. The Fried-Breadstick sign exhibited a higher prevalence in non-to-mild stenotic ICAs (57.5% vs. 9.8% in severely stenotic ICA, P < 0.001) and plaque-free MCAs (53.2% vs. 26.6% in MCAs with plaque, P < 0.001). Factors independently associated with the presence of the Fried-Breadstick sign included MCA stenosis degree (odds ratio [OR]: 0.85/10% increase, 95% confidence interval [CI]: 0.80 – 0.90), ICA stenosis (compared to non-to-mild stenosis, moderate stenosis: OR: 0.39, 95% CI: 0.28 – 0.54, severe stenosis: OR: 0.10, 95% CI: 0.06 – 0.17), and terminal ICA bifurcation angle (OR: 0.86/10° increase, 95% CI: 0.79 – 0.93). In atherosclerotic MCAs without luminal narrowing, the Fried-Breadstick sign was also less frequently observed than in plaque-free MCAs (34.6% vs. 53.2%, P = 0.012). In conclusion, the presence of the Fried-Breadstick sign is associated with healthier ICA-MCAs devoid of stenosis or plaque. The Fried-Breadstick sign may signify healthy ICA-MCA hemodynamics, serving as a potential screening tool for intracranial atherosclerosis without incurring additional cost or risk.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"30 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948822","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}
Meng Yang, Sarah Eide, Emily W. Y. Tam, V. Chau, S.R. Wayne Chen, S. Miller, Hong-Shuo Sun, Zhong-ping Feng
Cerebral palsy (CP), the most common motor disorder in early childhood, arises from neonatal brain injury. The potential role of neonatal encephalopathy (NE) as a risk factor for cerebral palsy has been postulated, yet a systematic examination of its clinical impact on cerebral palsy patients remains absent. This meta-analysis aims to delineate the incidence of commonly reported complications associated with cerebral palsy following NE compared to those without a history of NE. A systematic search of PubMed and Google Scholar yielded 424 studies, with 7 meeting the inclusion criteria. These studies reported at least one comparison of cerebral palsy symptoms between patients with or without NE and provided the corresponding case numbers for each group. Utilizing RevMan 5.4, we analyzed the data and assessed potential publication bias. Among the 7 studies included, we compared the characteristics of 117 patients with cerebral palsy with preceding NE to 287 without such antecedents. Significantly, the incidence of the spastic quadriplegic subtype of cerebral palsy was higher in patients with NE (odds ratio [OR]: 4.34, 95% confidence interval [CI]: 2.69 – 7.00, P < 0.00001). CP patients following NE exhibited a significantly increased incidence of severe communication difficulties (OR: 2.33, 95% CI: 1.32 – 4.10, P = 0.003), difficulty swallowing (OR: 2.50, 95% CI: 1.31 – 4.77, P = 0.005), and cognitive impairment (OR: 2.73, 95% CI: 1.45 – 5.13, P = 0.002). Children with cerebral palsy born following NE were more predisposed to the most severe spastic quadriplegic subtype and encountered significant comorbidities. It is essential to acknowledge the limitations of this study, primarily the small number of studies that separately reported cerebral palsy cases with or without NE. Nevertheless, these findings contribute valuable insights for a more accurate clinical prognosis and the prospective development of targeted treatments for specific complications associated with cerebral palsy in patients with NE.
脑瘫（CP）是儿童早期最常见的运动障碍，源于新生儿脑损伤。新生儿脑病（NE）作为脑瘫风险因素的潜在作用已被推测出来，但目前仍未对其对脑瘫患者的临床影响进行系统研究。本荟萃分析旨在明确与无 NE 病史的患者相比，NE 引起的脑瘫相关并发症的发生率。通过对 PubMed 和 Google Scholar 进行系统检索，共获得 424 项研究，其中 7 项符合纳入标准。这些研究至少对有无 NE 患者的脑瘫症状进行了一次比较，并提供了每组患者的相应病例数。我们利用 RevMan 5.4 对数据进行了分析，并评估了潜在的发表偏倚。在纳入的 7 项研究中，我们比较了 117 例有 NE 前兆的脑瘫患者和 287 例无 NE 前兆的脑瘫患者的特征。值得注意的是，患有 NE 的患者出现痉挛性四肢瘫亚型脑瘫的几率更高（几率比 [OR]：4.34，95% 置信区间[CI]：2.69 - 7.00，P < 0.00001）。NE 后的 CP 患者出现严重交流障碍（OR：2.33，95% CI：1.32 - 4.10，P = 0.003）、吞咽困难（OR：2.50，95% CI：1.31 - 4.77，P = 0.005）和认知障碍（OR：2.73，95% CI：1.45 - 5.13，P = 0.002）的几率明显增加。NE 后出生的脑瘫患儿更倾向于最严重的痉挛性四肢瘫亚型，且合并症显著。有必要承认本研究的局限性，主要是单独报告患有或未患有NE的脑瘫病例的研究数量较少。然而，这些研究结果为更准确地预测临床预后以及针对 NE 患者脑瘫相关并发症开发有针对性的治疗方法提供了宝贵的启示。
{"title":"Worsening of cerebral palsy following neonatal encephalopathy: A meta-analysis","authors":"Meng Yang, Sarah Eide, Emily W. Y. Tam, V. Chau, S.R. Wayne Chen, S. Miller, Hong-Shuo Sun, Zhong-ping Feng","doi":"10.36922/an.1719","DOIUrl":"https://doi.org/10.36922/an.1719","url":null,"abstract":"Cerebral palsy (CP), the most common motor disorder in early childhood, arises from neonatal brain injury. The potential role of neonatal encephalopathy (NE) as a risk factor for cerebral palsy has been postulated, yet a systematic examination of its clinical impact on cerebral palsy patients remains absent. This meta-analysis aims to delineate the incidence of commonly reported complications associated with cerebral palsy following NE compared to those without a history of NE. A systematic search of PubMed and Google Scholar yielded 424 studies, with 7 meeting the inclusion criteria. These studies reported at least one comparison of cerebral palsy symptoms between patients with or without NE and provided the corresponding case numbers for each group. Utilizing RevMan 5.4, we analyzed the data and assessed potential publication bias. Among the 7 studies included, we compared the characteristics of 117 patients with cerebral palsy with preceding NE to 287 without such antecedents. Significantly, the incidence of the spastic quadriplegic subtype of cerebral palsy was higher in patients with NE (odds ratio [OR]: 4.34, 95% confidence interval [CI]: 2.69 – 7.00, P < 0.00001). CP patients following NE exhibited a significantly increased incidence of severe communication difficulties (OR: 2.33, 95% CI: 1.32 – 4.10, P = 0.003), difficulty swallowing (OR: 2.50, 95% CI: 1.31 – 4.77, P = 0.005), and cognitive impairment (OR: 2.73, 95% CI: 1.45 – 5.13, P = 0.002). Children with cerebral palsy born following NE were more predisposed to the most severe spastic quadriplegic subtype and encountered significant comorbidities. It is essential to acknowledge the limitations of this study, primarily the small number of studies that separately reported cerebral palsy cases with or without NE. Nevertheless, these findings contribute valuable insights for a more accurate clinical prognosis and the prospective development of targeted treatments for specific complications associated with cerebral palsy in patients with NE.","PeriodicalId":72072,"journal":{"name":"Advanced neurology","volume":"7 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138970711","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}
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