Pub Date : 2024-09-13DOI: 10.1186/s12883-024-03787-w
Renzhi Deng, Jianying Qin, Lei Wang, Haibin Li, Ning Wen, Ke Qin, Jianhui Dong, Jihua Wu, Dandan Zhu, Xuyong Sun
Glioma is the most common brain tumor. IDH mutations occur frequently in glioma, indicating a more favorable prognosis. We aimed to explore energy metabolism-related genes in glioma to promote the research and treatment. Datasets were obtained from TCGA and GEO databases. Candidate genes were screened by differential gene expression analysis, then functional enrichment analysis was conducted on the candidate genes. PPI was also carried out to help determine the target gene. GSEA and DO analysis were conducted in the different expression level groups of the target gene. Survival analysis and immune cell infiltrating analysis were performed as well. We screened 34 candidate genes and selected GLUD1 as the target gene. All candidate genes were significantly enriched in 10 KEGG pathways and 330 GO terms. GLUD1 expression was higher in IDH-mutant samples than IDH-wildtype samples, and higher in normal samples than tumor samples. Low GLUD1 expression was related to poor prognosis according to survival analysis. Most types of immune cells were negatively related to GLUD1 expression, but monocytes and activated mast cells exhibited significantly positive correlation with GLUD1 expression. GLUD1 expression was significantly related to 119 drugs and 6 immune checkpoint genes. GLUD1 was able to serve as an independent prognostic indicator of IDH-mutant glioma. In this study, we identified an energy metabolism-related gene GLUD1 potentially contributing to favorable clinical outcomes of IDH-mutant glioma. In glioma, GLUD1 related clinical outcomes and immune landscape were clearer, and more valuable information was provided for immunotherapy.
胶质瘤是最常见的脑肿瘤。IDH突变在胶质瘤中频繁出现，预示着胶质瘤的预后较好。我们旨在探索胶质瘤中的能量代谢相关基因，以促进研究和治疗。数据集来自 TCGA 和 GEO 数据库。通过差异基因表达分析筛选候选基因，然后对候选基因进行功能富集分析。还进行了 PPI 分析，以帮助确定靶基因。对目标基因的不同表达水平组进行了GSEA和DO分析。同时还进行了生存分析和免疫细胞浸润分析。我们筛选了 34 个候选基因，并选择 GLUD1 作为靶基因。所有候选基因都在 10 个 KEGG 通路和 330 个 GO 术语中明显富集。GLUD1在IDH突变样本中的表达高于IDH野生型样本，在正常样本中的表达高于肿瘤样本。根据生存分析，GLUD1的低表达与预后不良有关。大多数类型的免疫细胞与GLUD1表达呈负相关，但单核细胞和活化肥大细胞与GLUD1表达呈显著正相关。GLUD1的表达与119种药物和6个免疫检查点基因明显相关。GLUD1可作为IDH突变胶质瘤的独立预后指标。在这项研究中，我们发现了一个与能量代谢相关的基因GLUD1，它可能有助于IDH突变型胶质瘤的良好临床预后。在胶质瘤中，与GLUD1相关的临床预后和免疫格局更加清晰，为免疫疗法提供了更多有价值的信息。
{"title":"Energy metabolism-related GLUD1 contributes to favorable clinical outcomes of IDH-mutant glioma","authors":"Renzhi Deng, Jianying Qin, Lei Wang, Haibin Li, Ning Wen, Ke Qin, Jianhui Dong, Jihua Wu, Dandan Zhu, Xuyong Sun","doi":"10.1186/s12883-024-03787-w","DOIUrl":"https://doi.org/10.1186/s12883-024-03787-w","url":null,"abstract":"Glioma is the most common brain tumor. IDH mutations occur frequently in glioma, indicating a more favorable prognosis. We aimed to explore energy metabolism-related genes in glioma to promote the research and treatment. Datasets were obtained from TCGA and GEO databases. Candidate genes were screened by differential gene expression analysis, then functional enrichment analysis was conducted on the candidate genes. PPI was also carried out to help determine the target gene. GSEA and DO analysis were conducted in the different expression level groups of the target gene. Survival analysis and immune cell infiltrating analysis were performed as well. We screened 34 candidate genes and selected GLUD1 as the target gene. All candidate genes were significantly enriched in 10 KEGG pathways and 330 GO terms. GLUD1 expression was higher in IDH-mutant samples than IDH-wildtype samples, and higher in normal samples than tumor samples. Low GLUD1 expression was related to poor prognosis according to survival analysis. Most types of immune cells were negatively related to GLUD1 expression, but monocytes and activated mast cells exhibited significantly positive correlation with GLUD1 expression. GLUD1 expression was significantly related to 119 drugs and 6 immune checkpoint genes. GLUD1 was able to serve as an independent prognostic indicator of IDH-mutant glioma. In this study, we identified an energy metabolism-related gene GLUD1 potentially contributing to favorable clinical outcomes of IDH-mutant glioma. In glioma, GLUD1 related clinical outcomes and immune landscape were clearer, and more valuable information was provided for immunotherapy.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1186/s12883-024-03850-6
Sameen Haque, Karen Crawley, Deborah Schofield, Rupendra Shrestha, Carolyn M. Sue
Cascade testing can offer improved surveillance and timely introduction of clinical management for the at-risk biological relatives. Data on cascade testing and costs in mitochondrial diseases are lacking. To address this gap, we performed a cross-sectional retrospective study to provide a framework for cascade testing in mitochondrial diseases, to estimate the eligibility versus real-time uptake of cascade testing and to evaluate the cost of the genetic diagnosis of index cases and the cost of predictive cascade testing. Data was collected through retrospective chart review. The variant inheritance pattern guided the identification of eligible first-degree relatives: (i) Males with mitochondrial DNA (mtDNA) single nucleotide variants (SNVs) – siblings and mothers. (ii) Females with mtDNA SNVs – siblings, mothers and offspring. (iii) Autosomal Dominant (AD) nuclear DNA (nDNA) variants – siblings, offspring and both parents. (iv) Autosomal Recessive (AR) nDNA variants – siblings. We recruited 99 participants from the Adult Mitochondrial Disease Clinic in Sydney. The uptake of cascade testing was 55.2% in the mtDNA group, 55.8% in the AD nDNA group and 0% in AR nDNA group. Of the relatives in mtDNA group who underwent cascade testing, 65.4% were symptomatic, 20.5% were oligosymptomatic and 14.1% were asymptomatic. The mean cost of cascade testing for eligible first-degree relatives (mtDNA group: $694.7; AD nDNA group: $899.1) was lower than the corresponding index case (mtDNA group: $4578.4; AD nDNA group: $5715.1) (p < 0.001). The demand for cascade testing in mitochondrial diseases varies according to the genotype and inheritance pattern. The real-time uptake of cascade testing can be influenced by multiple factors. Early diagnosis of at-risk biological relatives of index cases through cascade testing, confirms the diagnosis in those who are symptomatic and facilitates implementation of surveillance strategies and clinical care at an early stage of the disease.
{"title":"Cascade testing in mitochondrial diseases: a cross-sectional retrospective study","authors":"Sameen Haque, Karen Crawley, Deborah Schofield, Rupendra Shrestha, Carolyn M. Sue","doi":"10.1186/s12883-024-03850-6","DOIUrl":"https://doi.org/10.1186/s12883-024-03850-6","url":null,"abstract":"Cascade testing can offer improved surveillance and timely introduction of clinical management for the at-risk biological relatives. Data on cascade testing and costs in mitochondrial diseases are lacking. To address this gap, we performed a cross-sectional retrospective study to provide a framework for cascade testing in mitochondrial diseases, to estimate the eligibility versus real-time uptake of cascade testing and to evaluate the cost of the genetic diagnosis of index cases and the cost of predictive cascade testing. Data was collected through retrospective chart review. The variant inheritance pattern guided the identification of eligible first-degree relatives: (i) Males with mitochondrial DNA (mtDNA) single nucleotide variants (SNVs) – siblings and mothers. (ii) Females with mtDNA SNVs – siblings, mothers and offspring. (iii) Autosomal Dominant (AD) nuclear DNA (nDNA) variants – siblings, offspring and both parents. (iv) Autosomal Recessive (AR) nDNA variants – siblings. We recruited 99 participants from the Adult Mitochondrial Disease Clinic in Sydney. The uptake of cascade testing was 55.2% in the mtDNA group, 55.8% in the AD nDNA group and 0% in AR nDNA group. Of the relatives in mtDNA group who underwent cascade testing, 65.4% were symptomatic, 20.5% were oligosymptomatic and 14.1% were asymptomatic. The mean cost of cascade testing for eligible first-degree relatives (mtDNA group: $694.7; AD nDNA group: $899.1) was lower than the corresponding index case (mtDNA group: $4578.4; AD nDNA group: $5715.1) (p < 0.001). The demand for cascade testing in mitochondrial diseases varies according to the genotype and inheritance pattern. The real-time uptake of cascade testing can be influenced by multiple factors. Early diagnosis of at-risk biological relatives of index cases through cascade testing, confirms the diagnosis in those who are symptomatic and facilitates implementation of surveillance strategies and clinical care at an early stage of the disease.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1186/s12883-024-03826-6
Lihong Jin, Weiqun Zhang, Fang Su, Youqi Ji, Yumei Ge
Nocardia is widely distributed in the natural environment and typically cause opportunistic infections. However, it is important to note that the pathogenicity of different Nocardia species may vary significantly. Here we reported the first case of brain abscess caused by Nocardia beijingensis (N. beijingensis) infection in China. A 70-year-old male immunocompetent individual came to our hospital for treatment due to headache. After examination, it was found that he had a brain abscess caused by N. beijingensis. By utilizing a combination of surgical intervention and antibiotic therapy, the patient ultimately achieved full recovery. In addition, we isolated this strain and displayed its ultrastructure through scanning electron microscopy. The phylogenetic tree was analyzed by 16 S rRNA sequence. A literature review of N. beijingensis infections in all immunocompetent and immunocompromised patients was presented. It highlighted that abscess formation appears to be a common manifestation of N. beijingensis infection, and N. beijingensis has become an emerging pathogen in immunocompetent individuals.
诺卡氏菌广泛分布于自然环境中，通常会引起机会性感染。然而，值得注意的是，不同种类的诺卡氏菌的致病性可能存在很大差异。在此，我们报告了中国首例由北京诺卡菌（N. beijingensis）感染引起的脑脓肿病例。一名 70 岁的男性免疫功能正常者因头痛来我院就诊。经检查发现，他患有由北京诺卡菌引起的脑脓肿。通过外科手术和抗生素综合治疗，患者最终完全康复。此外，我们还分离出了这一菌株，并通过扫描电子显微镜展示了其超微结构。通过 16 S rRNA 序列分析了该菌株的系统发生树。文献综述了所有免疫功能健全和免疫功能低下患者感染北京痢疾杆菌的情况。它强调了脓肿形成似乎是北京痢疾杆菌感染的常见表现，北京痢疾杆菌已成为免疫功能健全者的一种新病原体。
{"title":"Brain abscesses: the first report of disseminated Nocardia beijingensis infection in an immunocompetent individual in China","authors":"Lihong Jin, Weiqun Zhang, Fang Su, Youqi Ji, Yumei Ge","doi":"10.1186/s12883-024-03826-6","DOIUrl":"https://doi.org/10.1186/s12883-024-03826-6","url":null,"abstract":"Nocardia is widely distributed in the natural environment and typically cause opportunistic infections. However, it is important to note that the pathogenicity of different Nocardia species may vary significantly. Here we reported the first case of brain abscess caused by Nocardia beijingensis (N. beijingensis) infection in China. A 70-year-old male immunocompetent individual came to our hospital for treatment due to headache. After examination, it was found that he had a brain abscess caused by N. beijingensis. By utilizing a combination of surgical intervention and antibiotic therapy, the patient ultimately achieved full recovery. In addition, we isolated this strain and displayed its ultrastructure through scanning electron microscopy. The phylogenetic tree was analyzed by 16 S rRNA sequence. A literature review of N. beijingensis infections in all immunocompetent and immunocompromised patients was presented. It highlighted that abscess formation appears to be a common manifestation of N. beijingensis infection, and N. beijingensis has become an emerging pathogen in immunocompetent individuals.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Associations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH). The associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively. We have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode. One hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (β = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (β = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (β = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (β = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (β = 1.88, 95% CI: -0.10, 3.86; P = 0.0649). We observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c.
HbA1c 与缺血性和出血性中风的不良预后之间的关系已得到证实。目前还不清楚 HbA1c 是否与伴有或不伴有脑出血（ICH）的复杂慢性病患者（CCP）的日常生活能力（ADL）评分有关。我们分别评估了有 ICH 和无 ICH 的复杂慢性病患者 HbA1c 与 ADL（Barthel 评分）之间的关系。我们分析了之前一项队列研究的数据，该研究涉及 3594 名基线时无 ICH 病史的 CCP，对他们进行了为期 5 年的随访，以评估 ICH 的发病情况。在为期 5 年的随访期间，共有 3594 名患者中发现了 161 例 ICH 病例。我们的非线性分析表明，在 ICH 和非 ICH 患者中，HBA1c 与 Barthel 评分之间的关系呈正相关趋势。多变量线性回归分析表明，在所有研究人群中，经调整年龄和性别后，HbA1c 升高与 Barthel 评分升高呈正相关（β = 1.25，95% CI：0.92，1.59；P <0.0001）。在非重症肌无力患者中，HbA1c 的增加仍与 Barthel 评分的增加呈正相关（β = 1.24，95% CI：0.90，1.58；P <0.001）。然而，在对年龄和性别进行调整后，HbA1c 似乎与 ICH 患者的 Barthel 评分没有任何关系（β = 1.87，95% CI：-0.07，3.82；P = 0.0613）。通过额外的敏感性分析，我们观察到非 ICH 患者（β = 0.90，95% CI：0.56，1.24；P <0.001）仍然存在这种密切关系，但 ICH 患者（β = 1.88，95% CI：-0.10，3.86；P = 0.0649）则不存在这种密切关系。我们首次观察到，HbA1c 升高与无 ICH 的 CCPs ADL 改善有关，但与 ICH 患者无关。这一有趣的发现与 HbA1c 升高的传统不利影响相矛盾。
{"title":"The relationship between HbA1c and the activities of daily living in complex chronic patients with and without intracerebral hemorrhage","authors":"Ying Zheng, Chenju Zhan, Qixi Liu, Chengsheng Chen","doi":"10.1186/s12883-024-03764-3","DOIUrl":"https://doi.org/10.1186/s12883-024-03764-3","url":null,"abstract":"Associations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH). The associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively. We have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode. One hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (β = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (β = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (β = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (β = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (β = 1.88, 95% CI: -0.10, 3.86; P = 0.0649). We observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12883-024-03847-1
J. Patrick Neary, Jyotpal Singh, Jane Alcorn, Robert B. Laprairie, Payam Dehghani, Cameron S. Mang, Bruce H. Bjornson, Thomas Hadjistavropoulos, Holly A. Bardutz, Lanishen Bhagaloo, Zachary Walsh, Michael Szafron, Kim D. Dorsch, Elizabeth S. Thompson
Cannabinoids such as cannabidiol (CBD) exhibit anti-inflammatory properties and have the potential to act as a therapeutic following mild traumatic brain injury. There is limited evidence available on the pharmacological, physiological and psychological effects of escalating CBD dosages in a healthy, male, university athlete population. Furthermore, no dosing regimen for CBD is available with implications of improving physiological function. This study will develop an optimal CBD dose based on the pharmacokinetic data in contact-sport athletes. The physiological and psychological data will be correlated to the pharmacokinetic data to understand the mechanism(s) associated with an escalating CBD dose. Forty participants will receive escalating doses of CBD ranging from 5 mg CBD/kg/day to 30 mg CBD/kg/day. The CBD dose is escalated every two weeks in increments of 5 mg CBD/kg/day. Participants will provide blood for pharmacological assessments at each of the 10 visits. Participants will complete a physiological assessment at each of the visits, including assessments of cerebral hemodynamics, blood pressure, electrocardiogram, seismocardiogram, transcranial magnetic stimulation, and salivary analysis for genomic sequencing. Finally, participants will complete a psychological assessment consisting of sleep, anxiety, and pain-related questionnaires. This study will develop of an optimal CBD dose based on pharmacological, physiological, and psychological properties for future use during contact sport seasons to understand if CBD can help to reduce the frequency of mild traumatic injuries and enhance recovery. Clinicaltrials.gov: NCT06204003.
{"title":"Pharmacological and physiological effects of cannabidiol: a dose escalation, placebo washout study protocol","authors":"J. Patrick Neary, Jyotpal Singh, Jane Alcorn, Robert B. Laprairie, Payam Dehghani, Cameron S. Mang, Bruce H. Bjornson, Thomas Hadjistavropoulos, Holly A. Bardutz, Lanishen Bhagaloo, Zachary Walsh, Michael Szafron, Kim D. Dorsch, Elizabeth S. Thompson","doi":"10.1186/s12883-024-03847-1","DOIUrl":"https://doi.org/10.1186/s12883-024-03847-1","url":null,"abstract":"Cannabinoids such as cannabidiol (CBD) exhibit anti-inflammatory properties and have the potential to act as a therapeutic following mild traumatic brain injury. There is limited evidence available on the pharmacological, physiological and psychological effects of escalating CBD dosages in a healthy, male, university athlete population. Furthermore, no dosing regimen for CBD is available with implications of improving physiological function. This study will develop an optimal CBD dose based on the pharmacokinetic data in contact-sport athletes. The physiological and psychological data will be correlated to the pharmacokinetic data to understand the mechanism(s) associated with an escalating CBD dose. Forty participants will receive escalating doses of CBD ranging from 5 mg CBD/kg/day to 30 mg CBD/kg/day. The CBD dose is escalated every two weeks in increments of 5 mg CBD/kg/day. Participants will provide blood for pharmacological assessments at each of the 10 visits. Participants will complete a physiological assessment at each of the visits, including assessments of cerebral hemodynamics, blood pressure, electrocardiogram, seismocardiogram, transcranial magnetic stimulation, and salivary analysis for genomic sequencing. Finally, participants will complete a psychological assessment consisting of sleep, anxiety, and pain-related questionnaires. This study will develop of an optimal CBD dose based on pharmacological, physiological, and psychological properties for future use during contact sport seasons to understand if CBD can help to reduce the frequency of mild traumatic injuries and enhance recovery. Clinicaltrials.gov: NCT06204003.\u0000","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12883-024-03845-3
Jungyon Yum, Sang-Won Lee, Yumie Rhee, Kyoung Heo
Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.
自身免疫性疾病患者可能会在很长一段时间内患上多种自身免疫性疾病，一名患者同时患有一种以上的自身免疫性疾病被定义为多自身免疫。多自身免疫可能是自身免疫性疾病具有相似免疫机制的临床证据。我们报告了一名 30 岁女性患者，她患有多种独特的自身免疫性疾病，主要影响中枢神经系统，甲状旁腺功能减退症、肾上腺皮质功能减退症、延髓受累、脑桥和颞叶受累，并伴有原发性斯约格伦综合征（pSS），这些疾病长期独立发生。患者曾有肌肉痉挛和一次癫痫发作的病史，并伴有呕吐和视力模糊。她被诊断为肾上腺皮质功能减退症和甲状旁腺功能减退症，基底节和小脑出现钙化。她在接受了四个月的皮质类固醇治疗后康复，并开始接受甲状旁腺功能减退症的治疗。八个月后，她出现呕吐、打嗝、眩晕和共济失调，延髓出现局灶性病变。经过两年的免疫抑制治疗后，她恢复了健康。肾上腺皮质功能减退症发病 58 个月后，她出现了复视、口干和眼干。核磁共振成像显示左侧脑桥和左侧颞叶有浸润性病变。根据抗舍格伦综合征相关抗原 A 抗体阳性和低非刺激性全唾液流量，她被诊断为 pSS。她接受了皮质类固醇治疗，并继续接受霉酚酸酯治疗，神经症状有所恢复。本病例强调了长期随访的必要性，以发现涉及各种器官的自身免疫性疾病过程。
{"title":"Hypophysitis and central nervous system involvement in association with Sjögren’s syndrome along with hypoparathyroidism: a case report","authors":"Jungyon Yum, Sang-Won Lee, Yumie Rhee, Kyoung Heo","doi":"10.1186/s12883-024-03845-3","DOIUrl":"https://doi.org/10.1186/s12883-024-03845-3","url":null,"abstract":"Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1186/s12883-024-03844-4
Cyrus A. Raji, Somayeh Meysami, Verna R. Porter, David A. Merrill, Mario F. Mendez
Brain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments. To investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD). We utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes across diagnostic groups. Discriminant analysis was done with leave-one-out cross validation on Neuroreader metrics to determine diagnostic delineation across groups. LOAD was the oldest compared to other groups (F = 27.5, p < .001). There were no statistically significant differences in sex (p = .58) with women comprising 54.7% of the entire cohort. EOAD and LOAD had the lowest Mini-Mental State Exam (MMSE) scores compared to TBI (p = .04 for EOAD and p = .01 for LOAD). LOAD had lowest hippocampal volumes (Left Hippocampus F = 13.1, Right Hippocampus F = 7.3, p < .001), low white matter volume in TBI (F = 5.9, p < .001), lower left parietal lobe volume in EOAD (F = 9.4, p < .001), and lower total gray matter volume in bvFTD (F = 32.8, p < .001) and caudate atrophy (F = 1737.5, p < .001). Areas under the curve ranged from 92.3 to 100%, sensitivity between 82.2 and 100%, specificity of 78.1-100%. TBI was the most accurately delineated diagnosis. Predictive features included caudate, frontal, parietal, temporal lobar and total white matter volumes. We identified the diagnostic utility of regional volumetric differences across multiple neurocognitive disorders. Brain MRI volumetry is widely available and can be applied in distinguishing these disorders.
{"title":"Diagnostic utility of brain MRI volumetry in comparing traumatic brain injury, Alzheimer disease and behavioral variant frontotemporal dementia","authors":"Cyrus A. Raji, Somayeh Meysami, Verna R. Porter, David A. Merrill, Mario F. Mendez","doi":"10.1186/s12883-024-03844-4","DOIUrl":"https://doi.org/10.1186/s12883-024-03844-4","url":null,"abstract":"Brain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments. To investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD). We utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes across diagnostic groups. Discriminant analysis was done with leave-one-out cross validation on Neuroreader metrics to determine diagnostic delineation across groups. LOAD was the oldest compared to other groups (F = 27.5, p < .001). There were no statistically significant differences in sex (p = .58) with women comprising 54.7% of the entire cohort. EOAD and LOAD had the lowest Mini-Mental State Exam (MMSE) scores compared to TBI (p = .04 for EOAD and p = .01 for LOAD). LOAD had lowest hippocampal volumes (Left Hippocampus F = 13.1, Right Hippocampus F = 7.3, p < .001), low white matter volume in TBI (F = 5.9, p < .001), lower left parietal lobe volume in EOAD (F = 9.4, p < .001), and lower total gray matter volume in bvFTD (F = 32.8, p < .001) and caudate atrophy (F = 1737.5, p < .001). Areas under the curve ranged from 92.3 to 100%, sensitivity between 82.2 and 100%, specificity of 78.1-100%. TBI was the most accurately delineated diagnosis. Predictive features included caudate, frontal, parietal, temporal lobar and total white matter volumes. We identified the diagnostic utility of regional volumetric differences across multiple neurocognitive disorders. Brain MRI volumetry is widely available and can be applied in distinguishing these disorders.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1186/s12883-024-03854-2
Enzo G. Plaitano, Rebecca A. Scharf, Pakinam E. Aboutaleb, Andrea L. Glennon, Emiliya Melkumova, Deborah M. Green-LaRoche
Amantadine hydrochloride has been increasingly prescribed as a neurostimulant for neurocritical care stroke patients to promote wakefulness during inpatient recovery. However, a lack of guidelines makes it difficult to decide who may benefit from this pharmacotherapy and when amantadine should be initiated during the hospital stay. This study aims to determine some factors that may be associated with favorable response to amantadine to inform future randomized controlled trials of amantadine in critical care or post-critical care stroke patients. Retrospective chart review for this study included neurocritical care and post-neurocritical care patients with acute ischemic or hemorrhagic stroke who were started on amantadine (N = 34) in the years 2016–2019. Patients were labeled as either responders or nonresponders of amantadine within 9 days of initiation using novel amantadine scoring criteria utilized and published in Neurocritical Care in the year 2021, which included spontaneous wakefulness and Glasgow Coma Scale (GCS). Amantadine response status and predictive variables were analyzed using nonparametric tests and adjusted multivariable regression models. There were large but nonsignificant variations in the median total milligrams of amantadine received in the first 9 days (IQR = 700-1,450 mg, p = 0.727). GCS on the day before amantadine initiation was significantly higher for responders (median = 12, IQR = 9–14) than nonresponders (median = 9, IQR = 8–10, p = 0.009). Favorable responder status was significantly associated with initiation in the critical care unit versus the step-down unit or the general medical/surgical floor [��=1.02, 95% CI (0.10, 1.93), p = 0.031], but there was no significant associations with hospital day number started [��=-0.003, 95% CI (-0.02, 0.02), p = 0.772]. Future randomized controlled trials of amantadine in hospitalized stroke patients should possibly consider examining dose-dependent relationships to establish stroke-specific dosing guidelines, minimum GCS threshold for which amantadine is efficacious, and the impact of patients’ determined level of acuity on clinical outcomes instead of solely examining the impact of earlier amantadine initiation by hospital day number. Future research with larger sample sizes is needed to further examine these relationships and inform future clinical trials.
{"title":"Informing future randomized controlled trials of amantadine hydrochloride in neurocritical care and post-neurocritical care stroke patients through a retrospective study","authors":"Enzo G. Plaitano, Rebecca A. Scharf, Pakinam E. Aboutaleb, Andrea L. Glennon, Emiliya Melkumova, Deborah M. Green-LaRoche","doi":"10.1186/s12883-024-03854-2","DOIUrl":"https://doi.org/10.1186/s12883-024-03854-2","url":null,"abstract":"Amantadine hydrochloride has been increasingly prescribed as a neurostimulant for neurocritical care stroke patients to promote wakefulness during inpatient recovery. However, a lack of guidelines makes it difficult to decide who may benefit from this pharmacotherapy and when amantadine should be initiated during the hospital stay. This study aims to determine some factors that may be associated with favorable response to amantadine to inform future randomized controlled trials of amantadine in critical care or post-critical care stroke patients. Retrospective chart review for this study included neurocritical care and post-neurocritical care patients with acute ischemic or hemorrhagic stroke who were started on amantadine (N = 34) in the years 2016–2019. Patients were labeled as either responders or nonresponders of amantadine within 9 days of initiation using novel amantadine scoring criteria utilized and published in Neurocritical Care in the year 2021, which included spontaneous wakefulness and Glasgow Coma Scale (GCS). Amantadine response status and predictive variables were analyzed using nonparametric tests and adjusted multivariable regression models. There were large but nonsignificant variations in the median total milligrams of amantadine received in the first 9 days (IQR = 700-1,450 mg, p = 0.727). GCS on the day before amantadine initiation was significantly higher for responders (median = 12, IQR = 9–14) than nonresponders (median = 9, IQR = 8–10, p = 0.009). Favorable responder status was significantly associated with initiation in the critical care unit versus the step-down unit or the general medical/surgical floor [��=1.02, 95% CI (0.10, 1.93), p = 0.031], but there was no significant associations with hospital day number started [��=-0.003, 95% CI (-0.02, 0.02), p = 0.772]. Future randomized controlled trials of amantadine in hospitalized stroke patients should possibly consider examining dose-dependent relationships to establish stroke-specific dosing guidelines, minimum GCS threshold for which amantadine is efficacious, and the impact of patients’ determined level of acuity on clinical outcomes instead of solely examining the impact of earlier amantadine initiation by hospital day number. Future research with larger sample sizes is needed to further examine these relationships and inform future clinical trials.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurately predicting the walking independence of stroke patients is important. Our objective was to determine and compare the performance of logistic regression (LR) and three machine learning models (eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Random Forest (RF)) in predicting walking independence at discharge in stroke patients, as well as to explore the variables that predict prognosis. 778 (80% for the training set and 20% for the test set) stroke patients admitted to China Rehabilitation Research Center between February 2020 and January 2023 were retrospectively included. The training set was used for training models. The test set was used to validate and compare the performance of the four models in terms of area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. Among the three ML models, the AUC of the XGBoost model is significantly higher than that of the SVM and RF models (P < 0.001, P = 0.024, respectively). There was no significant difference in the AUCs between the XGBoost model and the LR model (0.891 vs. 0.880, P = 0.560). The XGBoost model demonstrated superior accuracy (87.82% vs. 86.54%), sensitivity (50.00% vs. 39.39%), PPV (73.68% vs. 73.33%), NPV (89.78% vs. 87.94%), and F1 score (59.57% vs. 51.16%), with only slightly lower specificity (96.09% vs. 96.88%). Together, the XGBoost model and the stepwise LR model identified age, FMA-LE at admission, FAC at admission, and lower limb spasticity as key factors influencing independent walking. Overall, the XGBoost model performed best in predicting independent walking after stroke. The XGBoost and LR models together confirm that age, admission FMA-LE, admission FAC, and lower extremity spasticity are the key factors influencing independent walking in stroke patients at hospital discharge. Not applicable.
准确预测中风患者的行走独立性非常重要。我们的目的是确定并比较逻辑回归（LR）和三种机器学习模型（极梯度提升（XGBoost）、支持向量机（SVM）和随机森林（RF））在预测脑卒中患者出院时步行独立性方面的性能，并探索预测预后的变量。回顾性纳入了中国康复研究中心在 2020 年 2 月至 2023 年 1 月期间收治的 778 例脑卒中患者（80% 用于训练集，20% 用于测试集）。训练集用于训练模型。测试集用于验证和比较四个模型在曲线下面积（AUC）、准确率、灵敏度、特异性、阳性预测值（PPV）、阴性预测值（NPV）和 F1 分数方面的性能。在三种 ML 模型中，XGBoost 模型的 AUC 明显高于 SVM 和 RF 模型（分别为 P < 0.001 和 P = 0.024）。XGBoost 模型和 LR 模型的 AUC 没有明显差异（0.891 vs. 0.880，P = 0.560）。XGBoost 模型的准确性（87.82% 对 86.54%）、灵敏度（50.00% 对 39.39%）、PPV（73.68% 对 73.33%）、NPV（89.78% 对 87.94%）和 F1 分数（59.57% 对 51.16%）均优于 LR 模型，只是特异性（96.09% 对 96.88%）略低。XGBoost 模型和逐步 LR 模型共同确定了年龄、入院时的 FMA-LE、入院时的 FAC 和下肢痉挛是影响独立行走的关键因素。总体而言，XGBoost 模型在预测卒中后独立行走方面表现最佳。XGBoost 模型和 LR 模型共同证实，年龄、入院时的 FMA-LE、入院时的 FAC 和下肢痉挛是影响卒中患者出院时独立行走的关键因素。不适用。
{"title":"Prediction of poststroke independent walking using machine learning: a retrospective study","authors":"Zhiqing Tang, Wenlong Su, Tianhao Liu, Haitao Lu, Ying Liu, Hui Li, Kaiyue Han, Md. Moneruzzaman, Junzi Long, Xingxing Liao, Xiaonian Zhang, Lei Shan, Hao Zhang","doi":"10.1186/s12883-024-03849-z","DOIUrl":"https://doi.org/10.1186/s12883-024-03849-z","url":null,"abstract":"Accurately predicting the walking independence of stroke patients is important. Our objective was to determine and compare the performance of logistic regression (LR) and three machine learning models (eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Random Forest (RF)) in predicting walking independence at discharge in stroke patients, as well as to explore the variables that predict prognosis. 778 (80% for the training set and 20% for the test set) stroke patients admitted to China Rehabilitation Research Center between February 2020 and January 2023 were retrospectively included. The training set was used for training models. The test set was used to validate and compare the performance of the four models in terms of area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. Among the three ML models, the AUC of the XGBoost model is significantly higher than that of the SVM and RF models (P < 0.001, P = 0.024, respectively). There was no significant difference in the AUCs between the XGBoost model and the LR model (0.891 vs. 0.880, P = 0.560). The XGBoost model demonstrated superior accuracy (87.82% vs. 86.54%), sensitivity (50.00% vs. 39.39%), PPV (73.68% vs. 73.33%), NPV (89.78% vs. 87.94%), and F1 score (59.57% vs. 51.16%), with only slightly lower specificity (96.09% vs. 96.88%). Together, the XGBoost model and the stepwise LR model identified age, FMA-LE at admission, FAC at admission, and lower limb spasticity as key factors influencing independent walking. Overall, the XGBoost model performed best in predicting independent walking after stroke. The XGBoost and LR models together confirm that age, admission FMA-LE, admission FAC, and lower extremity spasticity are the key factors influencing independent walking in stroke patients at hospital discharge. Not applicable.","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1186/s12883-024-03837-3
Simone Pierro, Federico Verde, Alessio Maranzano, Anna De Gobbi, Eleonora Colombo, Alberto Doretti, Stefano Messina, Luca Maderna, Antonia Ratti, Floriano Girotti, Francesca Andreetta, Vincenzo Silani, Claudia Morelli, Nicola Ticozzi
Anti-IgLON5 disease is an autoimmune encephalitis overlapping with neurodegenerative disorders due to pathological accumulation of hyperphosphorylated tau. It is characterized by several clinical manifestations determined by involvement of different brain areas, and mild response to first-line immunotherapies. We report a case of anti-IgLON5 disease with a multifaceted semiology and an unusually good response to glucocorticoid monotherapy. A 68-year-old man with type 2 diabetes was evaluated for an 8-month history of progressive gait disorder causing frequent falls. He also suffered from obstructive sleep apneas and complained of dysphonia, dysarthria, occasional dysphagia, urinary incontinence, and upper limb action tremor. Neurological examination demonstrated bilateral eyelid ptosis, limitation of ocular horizontal smooth pursuit movements, slow horizontal saccades, and lack of inhibition of the vestibulo-ocular reflex during rapid horizontal head torsions. The patient also displayed involuntary, slow, rhythmic movements of the left periorbital and perioral muscles, spreading to the ipsilateral hemipalate and hemitongue, along with bilateral negative upper limb myoclonus. There were proximal muscle wasting in the upper limbs, proximal weakness of the four limbs, and diffuse fasciculations. Ataxia of stance and gait and of the four limbs was noted. MRI of the brain and spine was unremarkable; nerve conduction studies revealed a chronic, predominantly demyelinating, sensory-motor polyneuropathy, probably due to diabetes. Routine CSF examination was unrevealing and serum GFAP level was 89.6 pg/mL; however, the autoimmunity tests revealed a high-titer positivity for anti-IgLON5 autoantibodies in both CSF and serum, leading to the diagnosis of anti-IgLON5 disease. Symptoms improved significantly after intravenous methylprednisolone. Hemifacial and hemiorolingual myorhythmia along with peculiar oculomotor abnormalities characterizes the multifaceted clinical picture of our case. The complex semiology of our patient may reflect multifocal targeting of the autoimmune process or sequential spreading of tau inclusions in different brain areas. Our patient’s optimal response to glucocorticoid monotherapy could be underpinned by a slightly different phenotype in which autoimmunity plays a greater pathogenic role than tauopathy, with a lower burden of tau deposition. In such patients, neurodegeneration and tau accumulation could be merely secondary to immune-mediated neuronal dysfunction, supporting the existence of a group of glucocorticoid-responsive patients.
抗 IgLON5 病是一种自身免疫性脑炎，由于高磷酸化 tau 的病理堆积而与神经退行性疾病重叠。它有多种临床表现，由不同脑区受累决定，对一线免疫疗法反应轻微。我们报告了一例抗 IgLON5 病，该病具有多方面的半身像，对糖皮质激素单药治疗的反应异常良好。一名 68 岁的 2 型糖尿病患者因 8 个月的进行性步态障碍导致频繁跌倒而接受评估。他还患有阻塞性睡眠呼吸暂停，主诉发音障碍、构音障碍、偶尔吞咽困难、尿失禁和上肢震颤。神经系统检查显示，患者双侧眼睑下垂，眼球水平平滑追逐运动受限，水平眼球移动缓慢，头部快速水平扭转时缺乏前庭眼反射抑制。患者还表现出左侧眶周肌和口周肌肉不自主的、缓慢的、有节律的运动，并扩散到同侧半腭和半舌，同时伴有双侧上肢负性肌阵挛。上肢近端肌肉萎缩，四肢近端无力，弥漫性筋束。站立、步态和四肢共济失调。脑部和脊柱的核磁共振检查没有发现异常；神经传导检查显示，患者患有慢性、以脱髓鞘为主的感觉运动性多发性神经病，可能是糖尿病引起的。常规脑脊液检查未发现异常，血清GFAP水平为89.6 pg/mL；但自身免疫检查显示，脑脊液和血清中抗IgLON5自身抗体均呈高滴度阳性，因此诊断为抗IgLON5疾病。静脉注射甲基强的松龙后，症状明显改善。半面肌和半口肌节律失常以及特殊的眼球运动异常是本病例多方面临床表现的特征。我们患者的复杂症状可能反映了自身免疫过程的多灶靶向性或 tau 包涵体在不同脑区的相继扩散。我们的患者对糖皮质激素单药治疗的最佳反应可能是由于表型略有不同，在这种表型中，自身免疫的致病作用大于tau病，而tau沉积物的负担较轻。在这类患者中，神经退行性变和tau堆积可能只是继发于免疫介导的神经元功能障碍，从而支持糖皮质激素反应性患者群体的存在。
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