Fei Jiang, Haobing Cai, Hongliang Li, Weifan Yin, Song Ouyang, Jue Hu, Ewen Tu, Ke Fu, Junjie Yin, Zhen Zhao, Jieyu Yang, Qiuming Zeng, Huan Yang
Objective
This study aimed to investigate the clinical characteristics and predictors of relapse in double negative atypical inflammatory demyelinating disease (IDD) and to explore potential antigenic targets by tissue-based assays (TBA) using rat brain indirect immunofluorescence.
Methods
We compared the clinical, laboratory, and MRI data of double negative atypical IDD with other IDD patients. Serum samples were collected for TBA. The predictors of relapse were examined over a minimum of 24 months follow-up.
Results
In our cohort of 98 patients with double negative atypical IDD, there was no significant female predominance (58.2%, 57/98). The lesions primarily affected the spinal cord and brain stem, with fewer cases of involvement in the area postrema (5.1%, 5/98) and longitudinally extensive transverse myelitis (43.9%, 43/98). A total of 62.5% (50/80) patients tested positive for anti-astrocyte antibodies based on rat brain TBA. Over a median duration of 39.5 months, 80 patients completed the entire follow-up, and 47.5% (38/80) patients exhibited monophasic course. A total of 36% (18/50) patients positively for anti-astrocyte antibodies had a monophasic course, which is significantly lower than patients negatively for anti-astrocyte antibodies (66.7%, 20/30) (p = 0.008). The presence of anti-astrocyte antibodies (hazard ratio (HR), 2.243; 95% CI, 1.087–4.627; p = 0.029) and ≥4 cerebrum lesions at first attack (HR, 2.494; 95% CI, 1.224–5.078; p = 0.012) were risk factors for disease relapse, while maintenance immunotherapy during remission (HR, 0.361; 95% CI, 0.150–0.869; p = 0.023) was protective factor.
Interpretation
Double negative atypical IDD are unique demyelinating diseases with a high relapse rate. Maintenance immunotherapy is helpful to the prevention of relapse, particularly in patients with anti-astrocyte antibodies or ≥4 cerebrum lesions at first attack.
{"title":"Clinical characteristics of double negative atypical inflammatory demyelinating disease: A prospective study","authors":"Fei Jiang, Haobing Cai, Hongliang Li, Weifan Yin, Song Ouyang, Jue Hu, Ewen Tu, Ke Fu, Junjie Yin, Zhen Zhao, Jieyu Yang, Qiuming Zeng, Huan Yang","doi":"10.1002/acn3.52191","DOIUrl":"10.1002/acn3.52191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the clinical characteristics and predictors of relapse in double negative atypical inflammatory demyelinating disease (IDD) and to explore potential antigenic targets by tissue-based assays (TBA) using rat brain indirect immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared the clinical, laboratory, and MRI data of double negative atypical IDD with other IDD patients. Serum samples were collected for TBA. The predictors of relapse were examined over a minimum of 24 months follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our cohort of 98 patients with double negative atypical IDD, there was no significant female predominance (58.2%, 57/98). The lesions primarily affected the spinal cord and brain stem, with fewer cases of involvement in the area postrema (5.1%, 5/98) and longitudinally extensive transverse myelitis (43.9%, 43/98). A total of 62.5% (50/80) patients tested positive for anti-astrocyte antibodies based on rat brain TBA. Over a median duration of 39.5 months, 80 patients completed the entire follow-up, and 47.5% (38/80) patients exhibited monophasic course. A total of 36% (18/50) patients positively for anti-astrocyte antibodies had a monophasic course, which is significantly lower than patients negatively for anti-astrocyte antibodies (66.7%, 20/30) (<i>p</i> = 0.008). The presence of anti-astrocyte antibodies (hazard ratio (HR), 2.243; 95% CI, 1.087–4.627; <i>p</i> = 0.029) and ≥4 cerebrum lesions at first attack (HR, 2.494; 95% CI, 1.224–5.078; <i>p</i> = 0.012) were risk factors for disease relapse, while maintenance immunotherapy during remission (HR, 0.361; 95% CI, 0.150–0.869; <i>p</i> = 0.023) was protective factor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Double negative atypical IDD are unique demyelinating diseases with a high relapse rate. Maintenance immunotherapy is helpful to the prevention of relapse, particularly in patients with anti-astrocyte antibodies or ≥4 cerebrum lesions at first attack.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shruthi Mohan, Shannon McNulty, Courtney Thaxton, Marwa Elnagheeb, Emma Owens, May Flowers, Teagan Nunnery, Autumn Self, Brooke Palus, Svetlana Gorokhova, April Kennedy, Zhiyv Niu, Mridul Johari, Alassane Baneye Maiga, Kelly Macalalad, Amanda R. Clause, Jacques S. Beckmann, Lucas Bronicki, Sandra T. Cooper, Vijay S. Ganesh, Peter B. Kang, Akanchha Kesari, Monkol Lek, Jennifer Levy, Laura Rufibach, Marco Savarese, Melissa J. Spencer, Volker Straub, Giorgio Tasca, Conrad C. Weihl
Objective
Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.
Methods
The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene–disease relationships (GDR) using the ClinGen gene–disease clinical validity framework to evaluate 31 genes implicated in LGMD.
Results
The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD.
Interpretation
The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.
{"title":"Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy","authors":"Shruthi Mohan, Shannon McNulty, Courtney Thaxton, Marwa Elnagheeb, Emma Owens, May Flowers, Teagan Nunnery, Autumn Self, Brooke Palus, Svetlana Gorokhova, April Kennedy, Zhiyv Niu, Mridul Johari, Alassane Baneye Maiga, Kelly Macalalad, Amanda R. Clause, Jacques S. Beckmann, Lucas Bronicki, Sandra T. Cooper, Vijay S. Ganesh, Peter B. Kang, Akanchha Kesari, Monkol Lek, Jennifer Levy, Laura Rufibach, Marco Savarese, Melissa J. Spencer, Volker Straub, Giorgio Tasca, Conrad C. Weihl","doi":"10.1002/acn3.52127","DOIUrl":"10.1002/acn3.52127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene–disease relationships (GDR) using the ClinGen gene–disease clinical validity framework to evaluate 31 genes implicated in LGMD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (<i>CAPN3</i>, <i>COL6A1</i>, <i>COL6A2</i>, and <i>COL6A3</i>) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, <i>POMGNT1</i> and <i>DAG1</i>, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farhan Khan, Narendra Kala, Kelvin Chang, Liqi Shu, Eric D. Goldstein, Radmehr Torabi, Krisztina Moldovan, Mahesh Jayaraman, Nahid Mohammadzadeh, Karen Furie, Shadi Yaghi
Objective
Carotid artery web is a possible cause of ischemic stroke, especially in young patients who lack conventional risk factors. The immediate and long-term outcomes are not well studied. We aimed to determine the association between an ipsilateral carotid web and in-hospital stroke recurrence.
Methods
We analyzed data from adult patients admitted with an acute anterior circulation large vessel occlusion at a Comprehensive Stroke Center between July 2015 and March 2023. The primary outcome was in-hospital stroke recurrence and secondary outcome was in-hospital recurrent LVO. Multivariable logistic regression was performed to examine the association between ipsilateral carotid web and recurrent ischemic stroke and recurrent LVO.
Results
Of the 1463 patients with anterior circulation large vessel occlusion, 27 (1.8%) had an ipsilateral carotid artery web. Patients with carotid web were younger (median age (IQR), 60 years (53–67 years) versus 74 years (62–84 years), P < 0.01) and less likely to be Caucasian (60% vs. 80%, p = 0.014). Of the 27 patients with carotid web, 18 (70%) had no identifiable competing stroke mechanism. When compared to patients without ipsilateral carotid web, those with an ipsilateral carotid web had a higher risk of recurrent ischemic stroke (adjusted RR: 4.38, 95% CI: 1.38–13.85) and recurrent ipsilateral large vessel occlusion (adjusted RR: 4.49, 95% CI: 1.41–14.21).
Interpretation
Carotid webs are an under recognized cause of acute large vessel occlusion and are associated with higher risk of early recurrence. Studies are needed to validate our findings and test early revascularization strategies in patients with symptomatic carotid artery webs.
{"title":"In-hospital recurrent stroke in ipsilateral carotid web patients undergoing thrombectomy","authors":"Farhan Khan, Narendra Kala, Kelvin Chang, Liqi Shu, Eric D. Goldstein, Radmehr Torabi, Krisztina Moldovan, Mahesh Jayaraman, Nahid Mohammadzadeh, Karen Furie, Shadi Yaghi","doi":"10.1002/acn3.52161","DOIUrl":"10.1002/acn3.52161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Carotid artery web is a possible cause of ischemic stroke, especially in young patients who lack conventional risk factors. The immediate and long-term outcomes are not well studied. We aimed to determine the association between an ipsilateral carotid web and in-hospital stroke recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from adult patients admitted with an acute anterior circulation large vessel occlusion at a Comprehensive Stroke Center between July 2015 and March 2023. The primary outcome was in-hospital stroke recurrence and secondary outcome was in-hospital recurrent LVO. Multivariable logistic regression was performed to examine the association between ipsilateral carotid web and recurrent ischemic stroke and recurrent LVO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 1463 patients with anterior circulation large vessel occlusion, 27 (1.8%) had an ipsilateral carotid artery web. Patients with carotid web were younger (median age (IQR), 60 years (53–67 years) versus 74 years (62–84 years), <i>P</i> < 0.01) and less likely to be Caucasian (60% vs. 80%, p = 0.014). Of the 27 patients with carotid web, 18 (70%) had no identifiable competing stroke mechanism. When compared to patients without ipsilateral carotid web, those with an ipsilateral carotid web had a higher risk of recurrent ischemic stroke (adjusted RR: 4.38, 95% CI: 1.38–13.85) and recurrent ipsilateral large vessel occlusion (adjusted RR: 4.49, 95% CI: 1.41–14.21).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Carotid webs are an under recognized cause of acute large vessel occlusion and are associated with higher risk of early recurrence. Studies are needed to validate our findings and test early revascularization strategies in patients with symptomatic carotid artery webs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Francesca Di Feo, Ali Oghabian, Ella Nippala, Mathias Gautel, Heinz Jungbluth, Francesca Forzano, Edoardo Malfatti, Claudia Castiglioni, Ilona Krey, David Gomez Andres, Angela F. Brady, Maria Iascone, Anna Cereda, Lidia Pezzani, Daniel Natera De Benito, Andres Nascimiento Osorio, Berta Estévez Arias, Sergei A. Kurbatov, Tania Attie-Bitach, Sheela Nampoothiri, Erin Ryan, Michelle Morrow, Svetlana Gorokhova, Brigitte Chabrol, Juha Sinisalo, Heli Tolppanen, Johanna Tolva, Francina Munell, Jessica Camacho Soriano, Maria Angeles Sanchez Duran, Mridul Johari, Homa Tajsharghi, Peter Hackman, Bjarne Udd, Marco Savarese
Objective
Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.
Methods
In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA-sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA-sequencing data was retrieved from ENCODE.
Results
We generated new RNA-seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case.
Interpretation
This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing.
{"title":"Inferring disease course from differential exon usage in the wide titinopathy spectrum","authors":"Maria Francesca Di Feo, Ali Oghabian, Ella Nippala, Mathias Gautel, Heinz Jungbluth, Francesca Forzano, Edoardo Malfatti, Claudia Castiglioni, Ilona Krey, David Gomez Andres, Angela F. Brady, Maria Iascone, Anna Cereda, Lidia Pezzani, Daniel Natera De Benito, Andres Nascimiento Osorio, Berta Estévez Arias, Sergei A. Kurbatov, Tania Attie-Bitach, Sheela Nampoothiri, Erin Ryan, Michelle Morrow, Svetlana Gorokhova, Brigitte Chabrol, Juha Sinisalo, Heli Tolppanen, Johanna Tolva, Francina Munell, Jessica Camacho Soriano, Maria Angeles Sanchez Duran, Mridul Johari, Homa Tajsharghi, Peter Hackman, Bjarne Udd, Marco Savarese","doi":"10.1002/acn3.52189","DOIUrl":"10.1002/acn3.52189","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA-sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA-sequencing data was retrieved from ENCODE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We generated new RNA-seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soo Jean Shin, Yoonhyuk Jang, Soo Hyun Ahn, Su Yee Mon, Ji Hye You, Hong Yul An, Choong Hyun Sun, Youngil Koh, Kon Chu, Sang Kun Lee, Soon-Tae Lee
Objective
Leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e.
Methods
Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status.
Results
A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP-associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, p = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes.
Interpretation
LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression.
{"title":"Clonal hematopoiesis in LGI1-antibody encephalitis","authors":"Soo Jean Shin, Yoonhyuk Jang, Soo Hyun Ahn, Su Yee Mon, Ji Hye You, Hong Yul An, Choong Hyun Sun, Youngil Koh, Kon Chu, Sang Kun Lee, Soon-Tae Lee","doi":"10.1002/acn3.52192","DOIUrl":"10.1002/acn3.52192","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP-associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, <i>p</i> = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Freya Schulte, Johannes T. Reiter, Tobias Bauer, Julia Taube, Felix Bitzer, Juri-Alexander Witt, Rory Piper, Anoja Thanabalasingam, Randi von Wrede, Attila Racz, Tobias Baumgartner, Valeri Borger, Louisa Specht-Riemenschneider, Hartmut Vatter, Elke Hattingen, Ralf Deichmann, Christoph Helmstaedter, Alexander Radbruch, Alon Friedman, Rainer Surges, Theodor Rüber
Objective
The piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood–brain barrier. We investigated blood–brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1-relaxometry.
Methods
Gadolinium-based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1-relaxometry. Postictal and interictal images were co-registered, and subtraction maps were created as biomarkers for peri-ictal (∆qT1interictal-postictal) and interictal (∆qT1noncontrast-interictal) blood–brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex.
Results
In temporal lobe epilepsy (n = 14), ∆qT1noncontrast-interictal was significantly higher in the piriform cortex than in the whole cortex (p = 0.02). In extratemporal lobe epilepsy (n = 23), ∆qT1noncontrast-interictal was higher in the hippocampus than in the whole cortex (p = 0.05). Across all individuals (n = 37), duration of epilepsy was correlated with ∆qT1noncontrast-interictal (ß = 0.001, p < 0.001) in all regions, while the association was strongest in the piriform cortex. Impaired verbal memory was associated with ∆qT1noncontrast-interictal only in the piriform cortex (p = 0.04). ∆qT1interictal-postictal did not show differences in any region.
Interpretation
Interictal blood–brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.
{"title":"Interictal blood–brain barrier dysfunction in piriform cortex of people with epilepsy","authors":"Freya Schulte, Johannes T. Reiter, Tobias Bauer, Julia Taube, Felix Bitzer, Juri-Alexander Witt, Rory Piper, Anoja Thanabalasingam, Randi von Wrede, Attila Racz, Tobias Baumgartner, Valeri Borger, Louisa Specht-Riemenschneider, Hartmut Vatter, Elke Hattingen, Ralf Deichmann, Christoph Helmstaedter, Alexander Radbruch, Alon Friedman, Rainer Surges, Theodor Rüber","doi":"10.1002/acn3.52176","DOIUrl":"10.1002/acn3.52176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood–brain barrier. We investigated blood–brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1-relaxometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gadolinium-based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1-relaxometry. Postictal and interictal images were co-registered, and subtraction maps were created as biomarkers for peri-ictal (∆qT1<sub>interictal-postictal</sub>) and interictal (∆qT1<sub>noncontrast-interictal</sub>) blood–brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In temporal lobe epilepsy (<i>n</i> = 14), ∆qT1<sub>noncontrast-interictal</sub> was significantly higher in the piriform cortex than in the whole cortex (<i>p</i> = 0.02). In extratemporal lobe epilepsy (<i>n</i> = 23), ∆qT1<sub>noncontrast-interictal</sub> was higher in the hippocampus than in the whole cortex (<i>p</i> = 0.05). Across all individuals (<i>n</i> = 37), duration of epilepsy was correlated with ∆qT1<sub>noncontrast-interictal</sub> (<i>ß</i> = 0.001, <i>p</i> < 0.001) in all regions, while the association was strongest in the piriform cortex. Impaired verbal memory was associated with ∆qT1<sub>noncontrast-interictal</sub> only in the piriform cortex (<i>p</i> = 0.04). ∆qT1<sub>interictal-postictal</sub> did not show differences in any region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Interictal blood–brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Franziska Pellegrini, Nicoló G. Pozzi, Chiara Palmisano, Giorgio Marotta, Andreas Buck, Stefan Haufe, Ioannis U. Isaias
Objective
Locomotion is an automated voluntary movement sustained by coordinated neural synchronization across a distributed brain network. The cerebral cortex is central for adapting the locomotion pattern to the environment and alterations of cortical network dynamics can lead to gait impairments. Gait problems are a common symptom with a still unclear pathophysiology and represent an unmet therapeutical need in Parkinson's disease. Little is known about the cortical network dynamics of locomotor control in these patients.
Methods
We studied the cortical basis of parkinsonian gait by combining metabolic brain imaging with high-density EEG recordings and kinematic measurements performed at rest and during unperturbed overground walking.
Results
We found significant changes in functional connectivity between frontal, sensorimotor, and visuomotor cortical areas during walking as compared to resting. Specifically, hypokinetic gait was associated with poor information flow from the supplementary motor area (SMA) to precuneus and from calcarine to lingual gyrus, as well as high information flow from calcarine to cuneus.
Interpretation
Our findings support a role for visuomotor integration processes in PD-related hypokinetic gait and suggest that reinforcing visual information may act as a compensatory strategy to allow SMA-mediated feedforward locomotor control in PD.
{"title":"Cortical networks of parkinsonian gait: a metabolic and functional connectivity study","authors":"Franziska Pellegrini, Nicoló G. Pozzi, Chiara Palmisano, Giorgio Marotta, Andreas Buck, Stefan Haufe, Ioannis U. Isaias","doi":"10.1002/acn3.52173","DOIUrl":"10.1002/acn3.52173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Locomotion is an automated voluntary movement sustained by coordinated neural synchronization across a distributed brain network. The cerebral cortex is central for adapting the locomotion pattern to the environment and alterations of cortical network dynamics can lead to gait impairments. Gait problems are a common symptom with a still unclear pathophysiology and represent an unmet therapeutical need in Parkinson's disease. Little is known about the cortical network dynamics of locomotor control in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied the cortical basis of parkinsonian gait by combining metabolic brain imaging with high-density EEG recordings and kinematic measurements performed at rest and during unperturbed overground walking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found significant changes in functional connectivity between frontal, sensorimotor, and visuomotor cortical areas during walking as compared to resting. Specifically, hypokinetic gait was associated with poor information flow from the supplementary motor area (SMA) to precuneus and from calcarine to lingual gyrus, as well as high information flow from calcarine to cuneus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our findings support a role for visuomotor integration processes in PD-related hypokinetic gait and suggest that reinforcing visual information may act as a compensatory strategy to allow SMA-mediated feedforward locomotor control in PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear.
Objective
Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing–remitting MS (RRMS).
Methods
Thirty-one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality-of-life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed-effects models.
Results
Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (p-value <0.001, coefficient: −0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (p-value = 0.016, coefficient: −0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e-01, 95% CI: 6.83e-02, 9.09e-01, p-value = 3.15E-02).
Interpretation
In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement.
{"title":"Ocrelizumab alters the circulating metabolome in people with relapsing–remitting multiple sclerosis","authors":"Fatemeh Siavoshi, Dimitrios C. Ladakis, Ashley Muller, Bardia Nourbakhsh, Pavan Bhargava","doi":"10.1002/acn3.52167","DOIUrl":"10.1002/acn3.52167","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing–remitting MS (RRMS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality-of-life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (<i>p</i>-value <0.001, coefficient: −0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (<i>p</i>-value = 0.016, coefficient: −0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e-01, 95% CI: 6.83e-02, 9.09e-01, <i>p</i>-value = 3.15E-02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To evaluate the efficacy of rituximab (RTX) in stabilizing disability progression in secondary progressive multiple sclerosis (SPMS).
Methods
A systematic review was conducted, encompassing studies from inception to April 2023, utilizing the MEDLINE and EMBASE databases. Inclusion criteria comprised studies with a minimum of 3 SPMS patients receiving intravenous RTX in at least one infusion, with a follow-up duration of at least 6 months. Primary outcome measures included changes in Expanded Disability Status Scale (EDSS) scores. Mean differences in pre- and post-RTX EDSS scores were analyzed using a random-effects model. Meta-regression examined age at RTX initiation, pre-RTX EDSS scores, disease duration, and outcome reported time as variables. Secondary outcomes assessed changes in the annualized relapse rate (ARR).
Results
Thirteen studies, involving 604 SPMS patients, met the inclusion criteria. Following a mean follow-up of 2 years, the mean difference in EDSS scores (ΔEDSS = EDSSpre-RTX − EDSSpost-RTX) was −0.21 (95% CI −0.51 to 0.08, p = 0.16), indicating no significant variation. Multivariable meta-regression identified significant associations between EDSS score mean difference and pre-RTX EDSS scores, disease duration at RTX initiation, and outcome reported time. However, age at RTX initiation showed no significant association. Pre- and post-RTX ARR data were available for 245 out of 604 SPMS patients across seven studies, revealing a mean difference in ARR (ΔARR = ARRpre-RTX − ARRpost-RTX) of 0.74 (95% CI 0.19–1.29, p = 0.008).
Interpretation
RTX demonstrates efficacy in reducing relapse frequency and exhibits potential in stabilizing disability progression over a 2-year follow-up, particularly among individuals with shorter disease duration.
{"title":"Rituximab in secondary progressive multiple sclerosis: a meta-analysis","authors":"Pasin Intarakhao, Taksaporn Laipasu, Jiraporn Jitprapaikulsan, Natnasak Apiraksattayakul, Punchika Kosiyakul, Sasitorn Siritho, Naraporn Prayoonwiwat, Tatchaporn Ongphichetmetha","doi":"10.1002/acn3.52186","DOIUrl":"10.1002/acn3.52186","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the efficacy of rituximab (RTX) in stabilizing disability progression in secondary progressive multiple sclerosis (SPMS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was conducted, encompassing studies from inception to April 2023, utilizing the MEDLINE and EMBASE databases. Inclusion criteria comprised studies with a minimum of 3 SPMS patients receiving intravenous RTX in at least one infusion, with a follow-up duration of at least 6 months. Primary outcome measures included changes in Expanded Disability Status Scale (EDSS) scores. Mean differences in pre- and post-RTX EDSS scores were analyzed using a random-effects model. Meta-regression examined age at RTX initiation, pre-RTX EDSS scores, disease duration, and outcome reported time as variables. Secondary outcomes assessed changes in the annualized relapse rate (ARR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirteen studies, involving 604 SPMS patients, met the inclusion criteria. Following a mean follow-up of 2 years, the mean difference in EDSS scores (ΔEDSS = EDSS<sub>pre-RTX</sub> − EDSS<sub>post-RTX</sub>) was −0.21 (95% CI −0.51 to 0.08, <i>p</i> = 0.16), indicating no significant variation. Multivariable meta-regression identified significant associations between EDSS score mean difference and pre-RTX EDSS scores, disease duration at RTX initiation, and outcome reported time. However, age at RTX initiation showed no significant association. Pre- and post-RTX ARR data were available for 245 out of 604 SPMS patients across seven studies, revealing a mean difference in ARR (ΔARR = ARR<sub>pre-RTX</sub> − ARR<sub>post-RTX</sub>) of 0.74 (95% CI 0.19–1.29, <i>p</i> = 0.008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>RTX demonstrates efficacy in reducing relapse frequency and exhibits potential in stabilizing disability progression over a 2-year follow-up, particularly among individuals with shorter disease duration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Line B. Ulvin, Kristian B. Nilsen, Erik Taubøll, Lars Etholm, Kjell Heuser
Objective
The Salzburg EEG criteria for nonconvulsive status epilepticus (NCSE) have been proposed as consensus criteria for NCSE. We aimed to perform an independent study of their diagnostic accuracy.
Methods
A prospective study was carried out at Oslo University Hospital, including all consecutive patients ≥15 years old who were referred for an EEG with an explicit or implicit question of NCSE from February 2020 to February 2022. Two independent EEG readers scored the included EEGs according to the Salzburg criteria and blinded to the clinical data. The reference standard was defined as the clinical diagnosis the patient received based on all available clinical and paraclinical data. Diagnostic accuracy in identifying “certain/possible NCSE” was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals.
Results
In total, 469 patients/EEGs were included in the study. The prevalence of NCSE according to the reference standard was 11% (n = 53). The criteria showed a sensitivity of 94% (95% CI: 92–96%), a specificity of 77% (95% CI: 73–81%), a positive predictive value of 34% (95% CI: 30–39%), and a negative predictive value of 99% (95% CI: 98–100%). False positives for “certain NCSE” (n = 16) included many serial seizures and stimulus-induced rhythmic and periodic discharges (SIRPIDs), as well as a focal cortical dysplasia. False positives for “possible NCSE” (n = 79) were mainly represented by different encephalopathies and postictality.
Interpretation
The low specificity of the Salzburg criteria calls for refinement before implementation into daily clinical practice.
{"title":"Sensitivity and specificity of the Salzburg EEG criteria for nonconvulsive status epilepticus","authors":"Line B. Ulvin, Kristian B. Nilsen, Erik Taubøll, Lars Etholm, Kjell Heuser","doi":"10.1002/acn3.52184","DOIUrl":"10.1002/acn3.52184","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The Salzburg EEG criteria for nonconvulsive status epilepticus (NCSE) have been proposed as consensus criteria for NCSE. We aimed to perform an independent study of their diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective study was carried out at Oslo University Hospital, including all consecutive patients ≥15 years old who were referred for an EEG with an explicit or implicit question of NCSE from February 2020 to February 2022. Two independent EEG readers scored the included EEGs according to the Salzburg criteria and blinded to the clinical data. The reference standard was defined as the clinical diagnosis the patient received based on all available clinical and paraclinical data. Diagnostic accuracy in identifying “certain/possible NCSE” was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 469 patients/EEGs were included in the study. The prevalence of NCSE according to the reference standard was 11% (<i>n</i> = 53). The criteria showed a sensitivity of 94% (95% CI: 92–96%), a specificity of 77% (95% CI: 73–81%), a positive predictive value of 34% (95% CI: 30–39%), and a negative predictive value of 99% (95% CI: 98–100%). False positives for “certain NCSE” (<i>n</i> = 16) included many serial seizures and stimulus-induced rhythmic and periodic discharges (SIRPIDs), as well as a focal cortical dysplasia. False positives for “possible NCSE” (<i>n</i> = 79) were mainly represented by different encephalopathies and postictality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The low specificity of the Salzburg criteria calls for refinement before implementation into daily clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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