Background: Hereditary sensory and autonomic neuropathy type 9 (HSAN9) is a rare genetic disorder caused by genetic alterations in the TECPR2 locus and is characterized by developmental and intellectual disability, respiratory dysfunction, gastroesophageal reflux disease (GERD), and sensory and autonomic dysfunction, which are shared among the HSAN family.
Methods: Whole-exome sequencing (WES) was performed on samples from both probands, and the relevant genetic variants were confirmed in their families using Sanger sequencing. Additionally, a comprehensive literature review was conducted on previously reported cases of HSAN9, and the clinical and genetic data were assessed to provide insight into the genetic and clinical characteristics of the disease.
Results: We identified two new cases of HSAN9 with a shared novel variant of TECPR2 (NM_014844.5), c.1568del: p.Ser523PhefsTer12, classified as pathogenic according to ACMG guidelines. The probands showed characteristics of GERD, respiratory dysfunction, gait abnormalities, and developmental and speech delay, and both cases were deceased as a result of severe respiratory infection. The results of the literature review included 34 cases from 9 studies, revealing a wide range of genetic and clinical characteristics.
Conclusions: Our study identified two new cases of HSAN9 with a novel variant in TECPR2, confirmed by WES. The clinical characteristics of the patients as well as the conduction of a comprehensive literature review are crucial in the early diagnosis and management of the disease and establishment of genotype-phenotype correlations.
{"title":"Novel TECPR2 variant in two cases of hereditary sensory and autonomic neuropathy type 9: insights from genetic characterization and comprehensive literature review.","authors":"Aysan Moeinafshar, Sahand Tehrani Fateh, Farzad Hashemi-Gorji, Parvaneh Karimzadeh, Elham Gholibeglou, Masoumeh Rostami, Hossein Sadeghi, Mohammad Miryounesi, Mohammad-Reza Ghasemi","doi":"10.1186/s12883-024-03963-y","DOIUrl":"https://doi.org/10.1186/s12883-024-03963-y","url":null,"abstract":"<p><strong>Background: </strong>Hereditary sensory and autonomic neuropathy type 9 (HSAN9) is a rare genetic disorder caused by genetic alterations in the TECPR2 locus and is characterized by developmental and intellectual disability, respiratory dysfunction, gastroesophageal reflux disease (GERD), and sensory and autonomic dysfunction, which are shared among the HSAN family.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed on samples from both probands, and the relevant genetic variants were confirmed in their families using Sanger sequencing. Additionally, a comprehensive literature review was conducted on previously reported cases of HSAN9, and the clinical and genetic data were assessed to provide insight into the genetic and clinical characteristics of the disease.</p><p><strong>Results: </strong>We identified two new cases of HSAN9 with a shared novel variant of TECPR2 (NM_014844.5), c.1568del: p.Ser523PhefsTer12, classified as pathogenic according to ACMG guidelines. The probands showed characteristics of GERD, respiratory dysfunction, gait abnormalities, and developmental and speech delay, and both cases were deceased as a result of severe respiratory infection. The results of the literature review included 34 cases from 9 studies, revealing a wide range of genetic and clinical characteristics.</p><p><strong>Conclusions: </strong>Our study identified two new cases of HSAN9 with a novel variant in TECPR2, confirmed by WES. The clinical characteristics of the patients as well as the conduction of a comprehensive literature review are crucial in the early diagnosis and management of the disease and establishment of genotype-phenotype correlations.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"455"},"PeriodicalIF":2.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680727","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 : 2024-11-19DOI: 10.1186/s12883-024-03956-x
Naghmeh Abbasi Kasbi, Fereshteh Ghadiri, Abdorreza Naser Moghadasi, Faezeh Khodaie, Kosar Kohandel, Nasim Rezaeimanesh, Maryam Karaminia, Mohammad Ali Sahraian
Background: Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. The first presentation's possible triggers are still controversial among scientists. The objective of this study is to investigate and compare the potential social, environmental, and physical factors that may have contributed to the onset of MS before and during the Coronavirus Disease 2019 (COVID-19) pandemic.
Methods: A questionnaire was designed in the MS research center of Sina Hospital and also distributed as an online Google Form on social media among Iranian MS patients. Demographic information, MS disease-related data, and possible patients reported MS triggers were recorded. They were containing stressful life events, COVID-19 and other infections, COVID-19 and other vaccines, pregnancy or labor, head trauma, surgery, and weight loss. Patients were divided into two groups regarding the time of MS diagnosis (before and during the COVID-19 pandemic).
Results: Of 920 participants, 670 (72.8%) were female, and the mean age ± SD was 35.63 ± 8.1. The majority of patients (69.2%) had non-progressive forms of MS, and only 7.6% needed assistance for ambulation. 69% of participants were diagnosed with MS before the onset of the COVID-19 pandemic. There was a statistically significant difference between the most common first MS symptom before and after the beginning of the pandemic (visual type (n: 317 (49.9%)) before and sensory type (n: 170 (59.6%)) after the COVID-19 pandemic). A stressful life event was the most common patient-reported trigger of MS first presentation in both groups. (56.1% before and 54% after the COVID-19 pandemic). Comparing two groups, economic problems (AOR: 1.81; 95% ACI: 1.23-2.65) and job losses (AOR: 2.89; 95% ACI: 1.37-6.08) were significantly more common triggers for the initial presentation of MS after the pandemic, while the stress of occupational or educational exams (AOR: 0.52; 95% ACI: 0.34-0.79) was more prevalent before the pandemic.
Conclusion: Patients believe that stressful life events are closely linked to triggering their first MS symptoms. Since the beginning of the COVID-19 pandemic, economic problems and job losses have increased; however, occupational or educational exams stress decreased. Caring for social stress by societies may affect MS development or delay MS onset.
{"title":"The impact of social and environmental factors on triggering multiple sclerosis onset, before and during the COVID-19 pandemic: a retrospective study from Iran.","authors":"Naghmeh Abbasi Kasbi, Fereshteh Ghadiri, Abdorreza Naser Moghadasi, Faezeh Khodaie, Kosar Kohandel, Nasim Rezaeimanesh, Maryam Karaminia, Mohammad Ali Sahraian","doi":"10.1186/s12883-024-03956-x","DOIUrl":"https://doi.org/10.1186/s12883-024-03956-x","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. The first presentation's possible triggers are still controversial among scientists. The objective of this study is to investigate and compare the potential social, environmental, and physical factors that may have contributed to the onset of MS before and during the Coronavirus Disease 2019 (COVID-19) pandemic.</p><p><strong>Methods: </strong>A questionnaire was designed in the MS research center of Sina Hospital and also distributed as an online Google Form on social media among Iranian MS patients. Demographic information, MS disease-related data, and possible patients reported MS triggers were recorded. They were containing stressful life events, COVID-19 and other infections, COVID-19 and other vaccines, pregnancy or labor, head trauma, surgery, and weight loss. Patients were divided into two groups regarding the time of MS diagnosis (before and during the COVID-19 pandemic).</p><p><strong>Results: </strong>Of 920 participants, 670 (72.8%) were female, and the mean age ± SD was 35.63 ± 8.1. The majority of patients (69.2%) had non-progressive forms of MS, and only 7.6% needed assistance for ambulation. 69% of participants were diagnosed with MS before the onset of the COVID-19 pandemic. There was a statistically significant difference between the most common first MS symptom before and after the beginning of the pandemic (visual type (n: 317 (49.9%)) before and sensory type (n: 170 (59.6%)) after the COVID-19 pandemic). A stressful life event was the most common patient-reported trigger of MS first presentation in both groups. (56.1% before and 54% after the COVID-19 pandemic). Comparing two groups, economic problems (AOR: 1.81; 95% ACI: 1.23-2.65) and job losses (AOR: 2.89; 95% ACI: 1.37-6.08) were significantly more common triggers for the initial presentation of MS after the pandemic, while the stress of occupational or educational exams (AOR: 0.52; 95% ACI: 0.34-0.79) was more prevalent before the pandemic.</p><p><strong>Conclusion: </strong>Patients believe that stressful life events are closely linked to triggering their first MS symptoms. Since the beginning of the COVID-19 pandemic, economic problems and job losses have increased; however, occupational or educational exams stress decreased. Caring for social stress by societies may affect MS development or delay MS onset.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"453"},"PeriodicalIF":2.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675191","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}
Background: We assessed the correlation between optic nerve sheath diameter (ONSD) values measured by bedside ultrasound and intracranial pressure (ICP) changes among patients under neurocritical care and evaluated the diagnostic performance of ONSD for increased ICP.
Methods: Sixty-seven neurologically critical patients who were hospitalised in the intensive care unit (ICU) of Jining No.1 People's Hospital between September 2023 and March 2024 and underwent lumbar puncture were included. The ONSD was measured and recorded using bedside ultrasound before the lumbar puncture. Patients were divided into normal and increased ICP groups on the basis of the initial lumbar puncture pressure on admission, and both groups were compared. Spearman's correlation analysis was used for evaluating the correlation between ONSD values and ICP. Receiver operating characteristic (ROC) curves were employed for evaluating the diagnostic performance of ONSD for increased ICP.
Result: At admission, the Glasgow Coma Scale scores of patients in the increased ICP group were significantly lower than those of patients in the normal ICP group (P < 0.05). The ONSD level of patients in the increased ICP group was significantly higher than that of patients in the normal ICP group (P < 0.05). Spearman's correlation analysis revealed that ONSD positively correlated with ICP among patients with severe neurological diseases (r = 0.777, P < 0.001). The area under the ROC curve when using ONSD for diagnosing lumbar puncture opening pressure ≥ 200 mmH2O was 0.896 (95% confidence interval, 0.817-0.974). When using ONSD ≥ 4.74 mm as the threshold for diagnosing lumbar puncture opening pressure ≥ 200 mmH2O, the sensitivity and specificity were 0.909 and 0.765, respectively.
Conclusion: In patients with critical neurological illness, ONSD measured using bedside ultrasound positively correlated with ICP. Increased ICP can be diagnosed for ONSD ≥ 4.74 mm. The ONSD value measured by bedside ultrasound can be used for evaluating ICP among patients with critical neurological illness.
{"title":"Correlation between optic nerve sheath diameter measured by bedside ultrasound and intracranial pressure in neurologically ill patients in a Chinese population.","authors":"Xiuli Zhang, Dandan Ma, Wenqiang Li, Jinluan Ma, Kexia Bi, Yuling Qiao, Zhen Li","doi":"10.1186/s12883-024-03961-0","DOIUrl":"https://doi.org/10.1186/s12883-024-03961-0","url":null,"abstract":"<p><strong>Background: </strong>We assessed the correlation between optic nerve sheath diameter (ONSD) values measured by bedside ultrasound and intracranial pressure (ICP) changes among patients under neurocritical care and evaluated the diagnostic performance of ONSD for increased ICP.</p><p><strong>Methods: </strong>Sixty-seven neurologically critical patients who were hospitalised in the intensive care unit (ICU) of Jining No.1 People's Hospital between September 2023 and March 2024 and underwent lumbar puncture were included. The ONSD was measured and recorded using bedside ultrasound before the lumbar puncture. Patients were divided into normal and increased ICP groups on the basis of the initial lumbar puncture pressure on admission, and both groups were compared. Spearman's correlation analysis was used for evaluating the correlation between ONSD values and ICP. Receiver operating characteristic (ROC) curves were employed for evaluating the diagnostic performance of ONSD for increased ICP.</p><p><strong>Result: </strong>At admission, the Glasgow Coma Scale scores of patients in the increased ICP group were significantly lower than those of patients in the normal ICP group (P < 0.05). The ONSD level of patients in the increased ICP group was significantly higher than that of patients in the normal ICP group (P < 0.05). Spearman's correlation analysis revealed that ONSD positively correlated with ICP among patients with severe neurological diseases (r = 0.777, P < 0.001). The area under the ROC curve when using ONSD for diagnosing lumbar puncture opening pressure ≥ 200 mmH<sub>2</sub>O was 0.896 (95% confidence interval, 0.817-0.974). When using ONSD ≥ 4.74 mm as the threshold for diagnosing lumbar puncture opening pressure ≥ 200 mmH<sub>2</sub>O, the sensitivity and specificity were 0.909 and 0.765, respectively.</p><p><strong>Conclusion: </strong>In patients with critical neurological illness, ONSD measured using bedside ultrasound positively correlated with ICP. Increased ICP can be diagnosed for ONSD ≥ 4.74 mm. The ONSD value measured by bedside ultrasound can be used for evaluating ICP among patients with critical neurological illness.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"452"},"PeriodicalIF":2.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675188","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 : 2024-11-19DOI: 10.1186/s12883-024-03943-2
Amirreza Nasirzadeh, Mohammad Mohammadi, Melika Arab Bafrani, Aynaz Mohammadi, Hossein Bakhtiari-Dovvombaygi
Background: Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system, leading to a range of symptoms that impact physical, psychiatric, and cognitive functions. Cognitive dysfunction is prevalent among patients with MS (pwMS), affecting at least 65% of patients, and includes deficits in processing speed, attention, learning, memory, and executive function. Despite the significant impact on daily life, cognitive impairment in MS patients is often underrecognized in clinical settings.
Methods: This systematic review and meta-analysis aimed to evaluate cognitive function using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery among pwMS patients and healthy controls (HCs). A comprehensive search of the Web of Science, PubMed, Scopus, and Cochrane Library databases was conducted on January 2024 following the PRISMA guidelines. Eligible studies included peer-reviewed research assessing the validity of the MACFIMS in adult MS patients. Data extraction and quality assessment were performed using standardized tools, and statistical analyses were conducted using R4.2.3.
Results: Eight studies met the inclusion criteria, including a total of 1,481 pwMS and 1,072 HCs. The meta-analysis revealed significant cognitive deficits in pwMS patients compared to HCs across all the MACFIMS subtests, including language, spatial processing, new learning and memory, processing speed, and executive function. Processing speed and working memory were the most affected domains, with 36% of pwMS showing impairment on the Symbol Digit Modalities Test (SDMT). Subgroup analyses indicated that the Expanded Disability Status Scale (EDSS) score significantly influenced cognitive impairment, while disease duration had a limited impact.
Conclusions: The MACFIMS effectively discriminates between pwMS patients and HCs, demonstrating its validity as a comprehensive cognitive assessment tool for MS. Routine cognitive screening, particularly for processing speed and working memory, is crucial for early detection and intervention. Future research should focus on the sensitivity and specificity of the MACFIMS across diverse MS subtypes and cultural contexts to enhance its global applicability in clinical practice.
{"title":"Comparing cognitive impairment using MACFIMS in patients with multiple sclerosis and healthy controls: a systematic review and meta-analysis.","authors":"Amirreza Nasirzadeh, Mohammad Mohammadi, Melika Arab Bafrani, Aynaz Mohammadi, Hossein Bakhtiari-Dovvombaygi","doi":"10.1186/s12883-024-03943-2","DOIUrl":"https://doi.org/10.1186/s12883-024-03943-2","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system, leading to a range of symptoms that impact physical, psychiatric, and cognitive functions. Cognitive dysfunction is prevalent among patients with MS (pwMS), affecting at least 65% of patients, and includes deficits in processing speed, attention, learning, memory, and executive function. Despite the significant impact on daily life, cognitive impairment in MS patients is often underrecognized in clinical settings.</p><p><strong>Methods: </strong>This systematic review and meta-analysis aimed to evaluate cognitive function using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery among pwMS patients and healthy controls (HCs). A comprehensive search of the Web of Science, PubMed, Scopus, and Cochrane Library databases was conducted on January 2024 following the PRISMA guidelines. Eligible studies included peer-reviewed research assessing the validity of the MACFIMS in adult MS patients. Data extraction and quality assessment were performed using standardized tools, and statistical analyses were conducted using R4.2.3.</p><p><strong>Results: </strong>Eight studies met the inclusion criteria, including a total of 1,481 pwMS and 1,072 HCs. The meta-analysis revealed significant cognitive deficits in pwMS patients compared to HCs across all the MACFIMS subtests, including language, spatial processing, new learning and memory, processing speed, and executive function. Processing speed and working memory were the most affected domains, with 36% of pwMS showing impairment on the Symbol Digit Modalities Test (SDMT). Subgroup analyses indicated that the Expanded Disability Status Scale (EDSS) score significantly influenced cognitive impairment, while disease duration had a limited impact.</p><p><strong>Conclusions: </strong>The MACFIMS effectively discriminates between pwMS patients and HCs, demonstrating its validity as a comprehensive cognitive assessment tool for MS. Routine cognitive screening, particularly for processing speed and working memory, is crucial for early detection and intervention. Future research should focus on the sensitivity and specificity of the MACFIMS across diverse MS subtypes and cultural contexts to enhance its global applicability in clinical practice.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"454"},"PeriodicalIF":2.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675180","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 : 2024-11-18DOI: 10.1186/s12883-024-03955-y
Weichao Wang, Jie Zhang, Man Zhang, Chengyuan Zhang, Huanli Liu, Wanlin Li, Yimeng Fan
Background: The impact of diabetes on the risk of Alzheimer's disease remains uncertain. This study aimed to explore this issue from multiple perspectives by using the Mendelian randomization (MR) approach.
Methods: Instrumental variables for predicting six diabetic traits (including insulin and blood glucose), eight metabolic risk factors for diabetes (including total cholesterol and blood pressure), and seven diabetic genes were extracted from their summary data. These data were derived from multiple European cohorts and included 31,684 to 810,865 subjects respectively. The two-sample MR, multivariate MR, and summary-data-based Mendelian randomization (SMR) methods were employed to determine the associations of these traits or genes with the risk of Alzheimer's disease.
Results: The two-sample MR showed that elevated fasting insulin and total cholesterol levels were associated with an increased risk of dementia in Alzheimer's disease (P = 0.022, P = 0.041). Elevated systolic and diastolic blood pressure levels were associated with a decreased risk of dementia in Alzheimer's disease (P = 0.036, P = 0.025). The multivariate MR reported that adjusting for telomere length (a well-established biomarker of aging) did not change these findings (P < 0.05). Additionally, the two-sample MR showed that type 1 and type 2 diabetes did not affect the risk of Alzheimer's disease. The SMR also indicated that the diabetic genes did not affect the risk of this disease.
Conclusion: Multiple MR approaches concluded that fasting insulin, total cholesterol, and blood pressure, rather than diabetes, were potential metabolic variables that had an impact on the risk of Alzheimer's disease. However, aging might not be involved in these correlations.
{"title":"Impact of diabetes mellitus on the risk of Alzheimer's disease: a mendelian randomization study.","authors":"Weichao Wang, Jie Zhang, Man Zhang, Chengyuan Zhang, Huanli Liu, Wanlin Li, Yimeng Fan","doi":"10.1186/s12883-024-03955-y","DOIUrl":"10.1186/s12883-024-03955-y","url":null,"abstract":"<p><strong>Background: </strong>The impact of diabetes on the risk of Alzheimer's disease remains uncertain. This study aimed to explore this issue from multiple perspectives by using the Mendelian randomization (MR) approach.</p><p><strong>Methods: </strong>Instrumental variables for predicting six diabetic traits (including insulin and blood glucose), eight metabolic risk factors for diabetes (including total cholesterol and blood pressure), and seven diabetic genes were extracted from their summary data. These data were derived from multiple European cohorts and included 31,684 to 810,865 subjects respectively. The two-sample MR, multivariate MR, and summary-data-based Mendelian randomization (SMR) methods were employed to determine the associations of these traits or genes with the risk of Alzheimer's disease.</p><p><strong>Results: </strong>The two-sample MR showed that elevated fasting insulin and total cholesterol levels were associated with an increased risk of dementia in Alzheimer's disease (P = 0.022, P = 0.041). Elevated systolic and diastolic blood pressure levels were associated with a decreased risk of dementia in Alzheimer's disease (P = 0.036, P = 0.025). The multivariate MR reported that adjusting for telomere length (a well-established biomarker of aging) did not change these findings (P < 0.05). Additionally, the two-sample MR showed that type 1 and type 2 diabetes did not affect the risk of Alzheimer's disease. The SMR also indicated that the diabetic genes did not affect the risk of this disease.</p><p><strong>Conclusion: </strong>Multiple MR approaches concluded that fasting insulin, total cholesterol, and blood pressure, rather than diabetes, were potential metabolic variables that had an impact on the risk of Alzheimer's disease. However, aging might not be involved in these correlations.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"448"},"PeriodicalIF":2.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1186/s12883-024-03959-8
Sol A Cataldo, Andrea Micciulli, Laura Margulis, Melina Cibeyra, Sabrina Defeo, Silvina G Horovitz, Analía Martino, Raul Melano, Milagros Mena, Francisco Parisi, Diego Santoro, Florencia Sarmiento, Martin A Belzunce
Objective: Long COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina.
Methods: We conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons.
Results: Long COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02).
Conclusions: This study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.
{"title":"Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina.","authors":"Sol A Cataldo, Andrea Micciulli, Laura Margulis, Melina Cibeyra, Sabrina Defeo, Silvina G Horovitz, Analía Martino, Raul Melano, Milagros Mena, Francisco Parisi, Diego Santoro, Florencia Sarmiento, Martin A Belzunce","doi":"10.1186/s12883-024-03959-8","DOIUrl":"10.1186/s12883-024-03959-8","url":null,"abstract":"<p><strong>Objective: </strong>Long COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina.</p><p><strong>Methods: </strong>We conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons.</p><p><strong>Results: </strong>Long COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02).</p><p><strong>Conclusions: </strong>This study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"450"},"PeriodicalIF":2.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Infectious brain abscesses and granulomas, characterized by localized collections of pus or inflammatory tissue within the brain parenchyma, pose significant clinical challenges due to their potentially life-threatening nature and complex management requirements.
Methods: This cross-sectional study investigated patients diagnosed with infectious brain abscesses and granulomas from March 1, 2012, to October 22, 2021, in Mashhad, Iran. Data were collected from adult patients admitted to the two primary referral centers for community-acquired neuroinfections and neuroinflammations. Demographic information, clinical features, laboratory and neuroimaging characteristics, and clinical outcomes were analyzed.
Results: A total of 110 episodes were identified in 106 patients, with a median age of 45 years (IQR 30-56.3) and 62.7% male. Predisposing conditions included immunocompromised states (27.5%), preceding otitis/mastoiditis (16.2%), sinusitis (13.3%), and pulmonary infections (17.2%). The most common clinical manifestations were headache (57.3%), fever (49.1%), altered consciousness (44.4%), and seizures (31.8%). Neuroimaging revealed that brain lesions were solitary in 51% and multiple in 48% of episodes. Surgical intervention was performed in 46.4% of cases. The in-hospital mortality rate was 24.5%, with significant associations found between mortality and factors such as age, altered consciousness, multiple brain lesions, and cerebellum and brainstem involvement. The median length of hospital stay was 28 days (IQR 16-46.5).
Conclusion: Our study underscores challenges in diagnosing and treating brain abscesses and granulomas, with high mortality rates (24.5%) despite advanced techniques. Age, altered consciousness, and lesion characteristics predict death. Addressing changing microbial patterns and improving diagnostics are vital for better outcomes, especially in low- and middle-income countries.
{"title":"Infectious brain abscesses and granulomas: analysis of 110 episodes in adults.","authors":"Zahra Hesari, Mahboubeh Haddad, Fereshte Sheybani, Farzaneh Khoroushi, Ehsan Keykhosravi, Negar Morovatdar","doi":"10.1186/s12883-024-03953-0","DOIUrl":"10.1186/s12883-024-03953-0","url":null,"abstract":"<p><strong>Background: </strong>Infectious brain abscesses and granulomas, characterized by localized collections of pus or inflammatory tissue within the brain parenchyma, pose significant clinical challenges due to their potentially life-threatening nature and complex management requirements.</p><p><strong>Methods: </strong>This cross-sectional study investigated patients diagnosed with infectious brain abscesses and granulomas from March 1, 2012, to October 22, 2021, in Mashhad, Iran. Data were collected from adult patients admitted to the two primary referral centers for community-acquired neuroinfections and neuroinflammations. Demographic information, clinical features, laboratory and neuroimaging characteristics, and clinical outcomes were analyzed.</p><p><strong>Results: </strong>A total of 110 episodes were identified in 106 patients, with a median age of 45 years (IQR 30-56.3) and 62.7% male. Predisposing conditions included immunocompromised states (27.5%), preceding otitis/mastoiditis (16.2%), sinusitis (13.3%), and pulmonary infections (17.2%). The most common clinical manifestations were headache (57.3%), fever (49.1%), altered consciousness (44.4%), and seizures (31.8%). Neuroimaging revealed that brain lesions were solitary in 51% and multiple in 48% of episodes. Surgical intervention was performed in 46.4% of cases. The in-hospital mortality rate was 24.5%, with significant associations found between mortality and factors such as age, altered consciousness, multiple brain lesions, and cerebellum and brainstem involvement. The median length of hospital stay was 28 days (IQR 16-46.5).</p><p><strong>Conclusion: </strong>Our study underscores challenges in diagnosing and treating brain abscesses and granulomas, with high mortality rates (24.5%) despite advanced techniques. Age, altered consciousness, and lesion characteristics predict death. Addressing changing microbial patterns and improving diagnostics are vital for better outcomes, especially in low- and middle-income countries.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"449"},"PeriodicalIF":2.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1186/s12883-024-03932-5
Kotaro Tsutsumi, Matthew Nguyen, Victoria Nguyen, Zhu Zhu, Mohammad Shafie, Jay Shah, Masaki Nagamine, Dana Stradling, Diana Dench, Wengui Yu
Background: End stage renal disease (ESRD) requiring hemodialysis (HD) increases mortality among patients with intracerebral hemorrhage (ICH). The aim of this study is to investigate the clinical characteristics and outcome of ICH patients with ESRD on HD versus propensity-score matched controls.
Methods: This is a single center retrospective study. Consecutive ICH admissions at the University of California, Irvine Medical Center from January 1, 2018 to July 31, 2022 were analyzed.
Results: Among 347 ICH admissions that met inclusion criteria, 24 patients (6.92%) had ESRD on HD. Compared to patients without ESRD, patients with ESRD on HD had significantly higher rate of diabetes mellitus (79.2% vs. 36.8%, p < 0.01) and in-hospital mortality (25% vs. 7.43%, p < 0.01). There were no significant differences in demographics, other comorbidities, clinical characteristics, good (mRS score 0-3) or poor (mRS score 4-5) functional outcomes, rate of comfort care and the time to comfort care decision between the 2 groups. After propensity score matching, the ESRD group had a significantly higher in-hospital mortality rate (27.3% vs. 8%, p = 0.012) and a lower rate of obesity (9.1% vs. 34.1%, p = 0.02). Among patients who died during admission, ESRD on HD status did not inadvertently influence end-of-life care decisions. Univariate logistic regression and area under curve analysis showed that ICH score ≥ 3 was a predictor of increased mortality in both ESRD and non-ESRD groups.
Conclusions: ICH patients with ESRD on HD had significantly higher in-hospital mortality and lower rate of obesity than propensity score matched controls, suggesting a survival benefit from obesity. ICH score ≥ 3 is an independent predictor for poor outcomes in both ESRD and non-ESRD groups.
背景：需要进行血液透析（HD）的终末期肾病（ESRD）会增加脑内出血（ICH）患者的死亡率。本研究旨在调查接受血液透析的 ESRD ICH 患者与倾向分数匹配对照组的临床特征和预后：这是一项单中心回顾性研究。分析了 2018 年 1 月 1 日至 2022 年 7 月 31 日期间加州大学尔湾分校医疗中心连续收治的 ICH 患者：在符合纳入标准的 347 例 ICH 入院患者中，有 24 例患者（6.92%）在接受 HD 治疗时患有 ESRD。与没有 ESRD 的患者相比，接受 HD 治疗的 ESRD 患者的糖尿病患病率明显更高（79.2% vs. 36.8%，P 结论：ESRD 患者的糖尿病患病率明显高于非 ESRD 患者：与倾向评分匹配的对照组相比，接受血液透析治疗的有 ESRD 的 ICH 患者的院内死亡率明显更高，而肥胖率却更低，这表明肥胖对患者的生存有利。在 ESRD 组和非 ESRD 组中，ICH 评分≥ 3 是不良预后的独立预测因子。
{"title":"Comparison of functional outcome after intracerebral hemorrhage in patients with or without end stage renal disease on hemodialysis: a propensity-score matched study.","authors":"Kotaro Tsutsumi, Matthew Nguyen, Victoria Nguyen, Zhu Zhu, Mohammad Shafie, Jay Shah, Masaki Nagamine, Dana Stradling, Diana Dench, Wengui Yu","doi":"10.1186/s12883-024-03932-5","DOIUrl":"10.1186/s12883-024-03932-5","url":null,"abstract":"<p><strong>Background: </strong>End stage renal disease (ESRD) requiring hemodialysis (HD) increases mortality among patients with intracerebral hemorrhage (ICH). The aim of this study is to investigate the clinical characteristics and outcome of ICH patients with ESRD on HD versus propensity-score matched controls.</p><p><strong>Methods: </strong>This is a single center retrospective study. Consecutive ICH admissions at the University of California, Irvine Medical Center from January 1, 2018 to July 31, 2022 were analyzed.</p><p><strong>Results: </strong>Among 347 ICH admissions that met inclusion criteria, 24 patients (6.92%) had ESRD on HD. Compared to patients without ESRD, patients with ESRD on HD had significantly higher rate of diabetes mellitus (79.2% vs. 36.8%, p < 0.01) and in-hospital mortality (25% vs. 7.43%, p < 0.01). There were no significant differences in demographics, other comorbidities, clinical characteristics, good (mRS score 0-3) or poor (mRS score 4-5) functional outcomes, rate of comfort care and the time to comfort care decision between the 2 groups. After propensity score matching, the ESRD group had a significantly higher in-hospital mortality rate (27.3% vs. 8%, p = 0.012) and a lower rate of obesity (9.1% vs. 34.1%, p = 0.02). Among patients who died during admission, ESRD on HD status did not inadvertently influence end-of-life care decisions. Univariate logistic regression and area under curve analysis showed that ICH score ≥ 3 was a predictor of increased mortality in both ESRD and non-ESRD groups.</p><p><strong>Conclusions: </strong>ICH patients with ESRD on HD had significantly higher in-hospital mortality and lower rate of obesity than propensity score matched controls, suggesting a survival benefit from obesity. ICH score ≥ 3 is an independent predictor for poor outcomes in both ESRD and non-ESRD groups.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"451"},"PeriodicalIF":2.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1186/s12883-024-03952-1
Dan Cai, Liqiang Kuang, Fan Hu, Yaoyao Shen
Background: 1,2-dichloroethane (DCE) induced toxic encephalopathy, a rare toxic disease of the central nervous system, is mainly reported in developing countries. Although clinicians have got some understanding about the clinical and neuroimaging features of 1,2-DCE-induced toxic encephalopathy, abnormality along the cortico-medullary junction on diffusion-weighted image (DWI) mimicking neuronal intranuclear inclusion disease (NIID) has not yet been described in this entity.
Case presentation: We reported a patient with 1,2-DCE-induced toxic encephalopathy who was admitted to our department due to a 7-day history of nausea, vomiting, and cognitive decline. Brain magnetic resonance imaging (MRI) showed symmetrical hyperintensities in bilateral subcortical white matte on T2-weghted and Fluid-attenuated inversion recovery (FLAIR) images. In addition, abnormal signal intensity could also be found in the cortico-medullary junction on DWI, mimicking NIID. After treated with glucocorticoid, dehydrating agents, neuroprotective agents, and hyperbaric oxygen, our patient received a partial recovery.
Conclusion: Our case highlights a special MRI finding-abnormalities along the cortico-medullary junction-that can be seen in 1,2-DCE-induced toxic encephalopathy. When confronted with patients with lesion located in the cortico-medullary junction and neuropsychiatric symptoms, our clinicians should not neglect the detailed inquiry of history of toxic exposure.
{"title":"Abnormalities along the cortico-medullary junction on brain MRI caused by 1,2-dichloroethane-induced toxic encephalopathy.","authors":"Dan Cai, Liqiang Kuang, Fan Hu, Yaoyao Shen","doi":"10.1186/s12883-024-03952-1","DOIUrl":"10.1186/s12883-024-03952-1","url":null,"abstract":"<p><strong>Background: </strong>1,2-dichloroethane (DCE) induced toxic encephalopathy, a rare toxic disease of the central nervous system, is mainly reported in developing countries. Although clinicians have got some understanding about the clinical and neuroimaging features of 1,2-DCE-induced toxic encephalopathy, abnormality along the cortico-medullary junction on diffusion-weighted image (DWI) mimicking neuronal intranuclear inclusion disease (NIID) has not yet been described in this entity.</p><p><strong>Case presentation: </strong>We reported a patient with 1,2-DCE-induced toxic encephalopathy who was admitted to our department due to a 7-day history of nausea, vomiting, and cognitive decline. Brain magnetic resonance imaging (MRI) showed symmetrical hyperintensities in bilateral subcortical white matte on T2-weghted and Fluid-attenuated inversion recovery (FLAIR) images. In addition, abnormal signal intensity could also be found in the cortico-medullary junction on DWI, mimicking NIID. After treated with glucocorticoid, dehydrating agents, neuroprotective agents, and hyperbaric oxygen, our patient received a partial recovery.</p><p><strong>Conclusion: </strong>Our case highlights a special MRI finding-abnormalities along the cortico-medullary junction-that can be seen in 1,2-DCE-induced toxic encephalopathy. When confronted with patients with lesion located in the cortico-medullary junction and neuropsychiatric symptoms, our clinicians should not neglect the detailed inquiry of history of toxic exposure.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"447"},"PeriodicalIF":2.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1186/s12883-024-03930-7
Zakia Zaman, Radia Islam, Bhavya Koganti, Vaibhavkumar Falki, Tammy Osentoski, Stewart Graham, Md Golam Sharoar
<p><strong>Background: </strong>The unprecedented increase in the older population and ever-increasing incidence of dementia are leading to a "silver tsunami" in upcoming decades. To combat multimorbidity and maintain daily activities, elderly people face a high prevalence of polypharmacy. However, how these medications affect dementia-related pathology, such as Alzheimer's β-amyloid (Aβ) fibrils formation, remains unknown. In the present study, we aimed to analyze the medication profiles of Alzheimer's disease (AD; n = 124), mild cognitive impairment (MCI; n = 114), and non-demented (ND; n = 228) patients to identify highly prevalent drugs and to determine the effects of those drugs on Aβ fibrils formation.</p><p><strong>Methods: </strong>Study subjects (≥ 65 years) were recruited from an academic geriatric practice that heavily focuses on memory disorders. The disease state was defined based on the score of multiple cognitive assessments. Individual medications for each subject were listed and categorized into 10 major drug classes. Statistical analysis was performed to determine the frequency of individual and collective drug classes, which are expressed as percentages of the respective cohorts. 10 µM monomeric β-amyloid (Aβ) 42 and fibrillar Aβ (fAβ) were incubated for 6-48 h in the presence of 25 µM drugs. fAβ was prepared with a 1:10 ratio of Aβ42 to Aβ40. The amount of Aβ fibrils was monitored using a thioflavin T (Th-T) assay. Neuronal cells (N2A and SHSY-5Y) were treated with 25 µM drugs, and cell death was measured using a lactose dehydrogenase (LDH) assay.</p><p><strong>Results: </strong>We noticed a high prevalence (82-90%) of polypharmacy and diverse medication profiles including anti-inflammatory (65-77%), vitamin and mineral (64-72%), anti-cholesterol (33-41%), anti-hypersensitive (35-39%), proton pump inhibitor (23-34%), anti-thyroid (9-21%), anti-diabetic (5-13%), anti-constipation (9-11%), anti-coagulant (10-13%), and anti-insomnia (9-20%) drugs in the three cohorts. Our LDH assay with 18 highly prevalent drug components showed toxic effects of Norvasc, Tylenol, Colace, and Plavix on N2A cells, and of vitamin D and Novasc on SH-SY5Y cells. All these drugs except Colace significantly reduced the amount of Aβ fibril when incubated with Aβ42 for a short period (6 h). However, Lipitor, vitamin D, Levothyroxine, Prilosec, Flomax, and Norvasc prominently reduce the amount of fibrils when incubated with monomeric Aβ42 for a longer period (48 h). Furthermore, our disaggregation study with fAβ showed consistent results for cholecalciferol (vitamin D), omeprazole (Prilosec), clopidogrel hydrogensulfate (Flomax), levothyroxine, and amlodipine (Norvasc). The chemical structures of these four efficient molecules contain polyphenol components, a characteristic feature of the structures of polyphenolic inhibitors of Aβ fibrillation.</p><p><strong>Conclusion: </strong>A higher polypharmacy incidence was observed in an elderly population of 228
{"title":"Highly prevalent geriatric medications and their effect on β-amyloid fibril formation.","authors":"Zakia Zaman, Radia Islam, Bhavya Koganti, Vaibhavkumar Falki, Tammy Osentoski, Stewart Graham, Md Golam Sharoar","doi":"10.1186/s12883-024-03930-7","DOIUrl":"10.1186/s12883-024-03930-7","url":null,"abstract":"<p><strong>Background: </strong>The unprecedented increase in the older population and ever-increasing incidence of dementia are leading to a \"silver tsunami\" in upcoming decades. To combat multimorbidity and maintain daily activities, elderly people face a high prevalence of polypharmacy. However, how these medications affect dementia-related pathology, such as Alzheimer's β-amyloid (Aβ) fibrils formation, remains unknown. In the present study, we aimed to analyze the medication profiles of Alzheimer's disease (AD; n = 124), mild cognitive impairment (MCI; n = 114), and non-demented (ND; n = 228) patients to identify highly prevalent drugs and to determine the effects of those drugs on Aβ fibrils formation.</p><p><strong>Methods: </strong>Study subjects (≥ 65 years) were recruited from an academic geriatric practice that heavily focuses on memory disorders. The disease state was defined based on the score of multiple cognitive assessments. Individual medications for each subject were listed and categorized into 10 major drug classes. Statistical analysis was performed to determine the frequency of individual and collective drug classes, which are expressed as percentages of the respective cohorts. 10 µM monomeric β-amyloid (Aβ) 42 and fibrillar Aβ (fAβ) were incubated for 6-48 h in the presence of 25 µM drugs. fAβ was prepared with a 1:10 ratio of Aβ42 to Aβ40. The amount of Aβ fibrils was monitored using a thioflavin T (Th-T) assay. Neuronal cells (N2A and SHSY-5Y) were treated with 25 µM drugs, and cell death was measured using a lactose dehydrogenase (LDH) assay.</p><p><strong>Results: </strong>We noticed a high prevalence (82-90%) of polypharmacy and diverse medication profiles including anti-inflammatory (65-77%), vitamin and mineral (64-72%), anti-cholesterol (33-41%), anti-hypersensitive (35-39%), proton pump inhibitor (23-34%), anti-thyroid (9-21%), anti-diabetic (5-13%), anti-constipation (9-11%), anti-coagulant (10-13%), and anti-insomnia (9-20%) drugs in the three cohorts. Our LDH assay with 18 highly prevalent drug components showed toxic effects of Norvasc, Tylenol, Colace, and Plavix on N2A cells, and of vitamin D and Novasc on SH-SY5Y cells. All these drugs except Colace significantly reduced the amount of Aβ fibril when incubated with Aβ42 for a short period (6 h). However, Lipitor, vitamin D, Levothyroxine, Prilosec, Flomax, and Norvasc prominently reduce the amount of fibrils when incubated with monomeric Aβ42 for a longer period (48 h). Furthermore, our disaggregation study with fAβ showed consistent results for cholecalciferol (vitamin D), omeprazole (Prilosec), clopidogrel hydrogensulfate (Flomax), levothyroxine, and amlodipine (Norvasc). The chemical structures of these four efficient molecules contain polyphenol components, a characteristic feature of the structures of polyphenolic inhibitors of Aβ fibrillation.</p><p><strong>Conclusion: </strong>A higher polypharmacy incidence was observed in an elderly population of 228 ","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"24 1","pages":"445"},"PeriodicalIF":2.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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