Pub Date : 2024-11-10DOI: 10.1016/j.jns.2024.123303
Sergey A. Kornilov , Nathan D. Price , Richard Gelinas , Juan Acosta , Mary E. Brunkow , Tiffany Gervasi-Follmar , Ryan C. Winger , Dmitri Aldershoff , Christopher Lausted , Pamela Troisch , Brett Smith , James R. Heath , Pavle Repovic , Stanley Cohan , Andrew T. Magis
The study examined changes in the plasma proteome, metabolome, and lipidome of N = 14 patients with relapsing-remitting multiple sclerosis (RRMS) initiating treatment with ocrelizumab, assayed at baseline, 6 months, and 12 months. Analyses of >4000 circulating biomarkers identified depletion of B-cell associated proteins as the early effect observed following ocrelizumab (OCR) initiation, accompanied by the reduction in plasma abundance of cytokines and cytotoxic proteins, markers of neuronaxonal damage, and biologically active lipids including ceramides and lysophospholipids, at 6 months. B-cell depletion was accompanied by decreases in B-cell receptor and cytokine signaling but a pronounced increase in circulating plasma B-cell activating factor (BAFF). This was followed by an upregulation of a number of signaling and metabolic pathways at 12 months. Patients with higher baseline brain MRI lesion load demonstrated both higher levels of cytotoxic and structural proteins in plasma at baseline and more pronounced biomarker change trajectories over time. Digital cytometry identified a putative increase in myeloid cells and a pro-inflammatory subset of T-cells. Therapeutic effects of ocrelizumab extend beyond CD20-mediated B-cell lysis and implicate metabolic reprogramming, juxtaposing the early normalization of immune activation, cytokine signaling and metabolite and lipid turnover in periphery with changes in the dynamics of immune cell activation or composition. We identify BAFF increase following CD20 depletion as a tentative compensatory mechanism that contributes to the reconstitution of targeted B-cells, necessitating further research.
该研究检测了N = 14名开始接受奥克立珠单抗治疗的复发性缓解型多发性硬化症（RRMS）患者在基线、6个月和12个月时血浆蛋白质组、代谢组和脂质组中的变化。对超过4000种循环生物标记物的分析表明，B细胞相关蛋白的耗竭是奥克立珠单抗（OCR）起效后观察到的早期效应，伴随而来的是细胞因子和细胞毒性蛋白、神经轴突损伤标记物以及生物活性脂质（包括神经酰胺和溶血磷脂）在6个月时血浆丰度的降低。伴随着 B 细胞耗竭的是 B 细胞受体和细胞因子信号的减少，但循环血浆中的 B 细胞活化因子（BAFF）却明显增加。随后在 12 个月时，一些信号传导和代谢通路出现上调。基线脑磁共振成像病变负荷较高的患者，其血浆中的细胞毒性蛋白和结构蛋白水平在基线时较高，随着时间的推移，生物标志物的变化轨迹也更为明显。数字细胞仪发现髓系细胞和T细胞促炎亚群可能有所增加。奥克立珠单抗的治疗效果超越了 CD20 介导的 B 细胞溶解，并牵涉到代谢重编程，将免疫激活、细胞因子信号传导以及外周代谢物和脂质周转的早期正常化与免疫细胞激活或组成的动态变化并列起来。我们发现，CD20耗竭后BAFF的增加是一种暂时性的补偿机制，有助于靶向B细胞的重建，这还需要进一步研究。
{"title":"Multi-Omic characterization of the effects of Ocrelizumab in patients with relapsing-remitting multiple sclerosis","authors":"Sergey A. Kornilov , Nathan D. Price , Richard Gelinas , Juan Acosta , Mary E. Brunkow , Tiffany Gervasi-Follmar , Ryan C. Winger , Dmitri Aldershoff , Christopher Lausted , Pamela Troisch , Brett Smith , James R. Heath , Pavle Repovic , Stanley Cohan , Andrew T. Magis","doi":"10.1016/j.jns.2024.123303","DOIUrl":"10.1016/j.jns.2024.123303","url":null,"abstract":"<div><div>The study examined changes in the plasma proteome, metabolome, and lipidome of <em>N</em> = 14 patients with relapsing-remitting multiple sclerosis (RRMS) initiating treatment with ocrelizumab, assayed at baseline, 6 months, and 12 months. Analyses of >4000 circulating biomarkers identified depletion of B-cell associated proteins as the early effect observed following ocrelizumab (OCR) initiation, accompanied by the reduction in plasma abundance of cytokines and cytotoxic proteins, markers of neuronaxonal damage, and biologically active lipids including ceramides and lysophospholipids, at 6 months. B-cell depletion was accompanied by decreases in B-cell receptor and cytokine signaling but a pronounced increase in circulating plasma B-cell activating factor (BAFF). This was followed by an upregulation of a number of signaling and metabolic pathways at 12 months. Patients with higher baseline brain MRI lesion load demonstrated both higher levels of cytotoxic and structural proteins in plasma at baseline and more pronounced biomarker change trajectories over time. Digital cytometry identified a putative increase in myeloid cells and a pro-inflammatory subset of T-cells. Therapeutic effects of ocrelizumab extend beyond CD20-mediated B-cell lysis and implicate metabolic reprogramming, juxtaposing the early normalization of immune activation, cytokine signaling and metabolite and lipid turnover in periphery with changes in the dynamics of immune cell activation or composition. We identify BAFF increase following CD20 depletion as a tentative compensatory mechanism that contributes to the reconstitution of targeted B-cells, necessitating further research.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123303"},"PeriodicalIF":3.6,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676128","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 : 2024-11-08DOI: 10.1016/j.jns.2024.123291
Dhamidhu Eratne , Matthew J.Y. Kang , Courtney Lewis , Christa Dang , Charles Malpas , Suyi Ooi , Amy Brodtmann , David Darby , Henrik Zetterberg , Kaj Blennow , Michael Berk , Olivia Dean , Chad Bousman , Naveen Thomas , Ian Everall , Chris Pantelis , Cassandra Wannan , Claudia Cicognola , Oskar Hansson , Shorena Janelidze , Dennis Velakoulis
Objective
Timely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP.
Methods
We investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD.
Results
Plasma GFAP levels were significantly (all p < 0.001) elevated in bvFTD (n = 22, mean (M) = 273 pg/mL) compared to BPAD (n = 121, M = 96 pg/mL), MDD (n = 42, M = 105 pg/mL), TRS (n = 82, M = 67.9 pg/mL), and HC (n = 120, M = 76.8 pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95 % confidence interval [0.76, 0.95]. The optimal cut-off of 105 pg/mL was associated with 73 % specificity and 86 % sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3 pg/mL cut-off, 88 % specificity, 86 % sensitivity, and was superior to GFAP (p = 0.02863) and combination of GFAP and NfL (p = 0.04726).
Conclusions
This study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD.
{"title":"Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders","authors":"Dhamidhu Eratne , Matthew J.Y. Kang , Courtney Lewis , Christa Dang , Charles Malpas , Suyi Ooi , Amy Brodtmann , David Darby , Henrik Zetterberg , Kaj Blennow , Michael Berk , Olivia Dean , Chad Bousman , Naveen Thomas , Ian Everall , Chris Pantelis , Cassandra Wannan , Claudia Cicognola , Oskar Hansson , Shorena Janelidze , Dennis Velakoulis","doi":"10.1016/j.jns.2024.123291","DOIUrl":"10.1016/j.jns.2024.123291","url":null,"abstract":"<div><h3>Objective</h3><div>Timely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP.</div></div><div><h3>Methods</h3><div>We investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD.</div></div><div><h3>Results</h3><div>Plasma GFAP levels were significantly (all <em>p</em> < 0.001) elevated in bvFTD (<em>n</em> = 22, mean (M) = 273 pg/mL) compared to BPAD (<em>n</em> = 121, M = 96 pg/mL), MDD (<em>n</em> = 42, M = 105 pg/mL), TRS (<em>n</em> = 82, M = 67.9 pg/mL), and HC (<em>n</em> = 120, M = 76.8 pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95 % confidence interval [0.76, 0.95]. The optimal cut-off of 105 pg/mL was associated with 73 % specificity and 86 % sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3 pg/mL cut-off, 88 % specificity, 86 % sensitivity, and was superior to GFAP (<em>p</em> = 0.02863) and combination of GFAP and NfL (<em>p</em> = 0.04726).</div></div><div><h3>Conclusions</h3><div>This study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123291"},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692406","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 : 2024-11-05DOI: 10.1016/j.jns.2024.123289
Guy Vishnevsky , Tali Fisher , Polina Specktor
Background and objectives
The clock drawing test (CDT) is a widely recognized neurocognitive test for executive and visuospatial functions. However, no normative data exist for Generation Z young adults (born on or after 1997). The widespread use of digital displays among this generation may impair performance on the analog CDT.
Methods
Young Generation Z adults with at least 12 years of education, who were evaluated at the Israel Defense Forces (IDF) outpatient neurology clinic between 2021 and 2022, completed a CDT using the Manos-Wu method and drew a digital clock. Patients with possible cognitive impairment were excluded.
Results
Three hundred Generation Z patients were recruited, with a mean age of 19.7 ± 1.2 years. 171 (57.0 %) were female. Mean CDT score was 8.1 ± 2.5 out of 10 (Manos & Wu). A lower CDT score was associated with younger age (p = 0.031). No association was found with chief complaint, presence of ADHD diagnosis, gender, or postsecondary education. Digital clock drawing (4/4 digits) was successful in 100 % of patients.
Discussion
Generation Z adults demonstrate lower CDT scores than previously reported for older generations. The CDT may require revision to maintain its specificity for this population. Developing an alternative, digital-based tool for cognitive screening in young generations could be advisable.
{"title":"The clock drawing test (CDT) in the digital era: Underperformance of Generation Z adults","authors":"Guy Vishnevsky , Tali Fisher , Polina Specktor","doi":"10.1016/j.jns.2024.123289","DOIUrl":"10.1016/j.jns.2024.123289","url":null,"abstract":"<div><h3>Background and objectives</h3><div>The clock drawing test (CDT) is a widely recognized neurocognitive test for executive and visuospatial functions. However, no normative data exist for Generation Z young adults (born on or after 1997). The widespread use of digital displays among this generation may impair performance on the analog CDT.</div></div><div><h3>Methods</h3><div>Young Generation Z adults with at least 12 years of education, who were evaluated at the Israel Defense Forces (IDF) outpatient neurology clinic between 2021 and 2022, completed a CDT using the Manos-Wu method and drew a digital clock. Patients with possible cognitive impairment were excluded.</div></div><div><h3>Results</h3><div>Three hundred Generation Z patients were recruited, with a mean age of 19.7 ± 1.2 years. 171 (57.0 %) were female. Mean CDT score was 8.1 ± 2.5 out of 10 (Manos & Wu). A lower CDT score was associated with younger age (<em>p</em> = 0.031). No association was found with chief complaint, presence of ADHD diagnosis, gender, or postsecondary education. Digital clock drawing (4/4 digits) was successful in 100 % of patients.</div></div><div><h3>Discussion</h3><div>Generation Z adults demonstrate lower CDT scores than previously reported for older generations. The CDT may require revision to maintain its specificity for this population. Developing an alternative, digital-based tool for cognitive screening in young generations could be advisable.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123289"},"PeriodicalIF":3.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622986","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 : 2024-11-04DOI: 10.1016/j.jns.2024.123288
Alessandra Morano , Emanuele Cerulli Irelli , Francesco Fortunato , Sara Casciato , Chiara Panzini , Chiara Milano , Salvatore Versace , Biagio Orlando , Raffaele Iorio , Emanuele Tinelli , Gabriele Ruffolo , Chiara Pizzanelli , Alberto Vogrig , Pierpaolo Quarato , Anna Teresa Giallonardo , Giancarlo Di Gennaro , Antonio Gambardella , Carlo Di Bonaventura
Objective
Diagnosing autoimmune limbic encephalitis (ALE) in adults with new-onset seizures can be challenging, especially when seizures represent the predominant manifestation and MRI findings are not straightforward. By comparison with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), this study aimed to identify ictal electro-clinical features that might help clinicians recognize ALE-related seizures.
Methods
This retrospective, multi-centre study analysed the ictal semiology and EEG correlate of 116 video-EEG-captured seizures in 40 ALE patients and 45 ones recorded in 21 MTLE-HS subjects. The proportion of patients presenting each clinical feature on at least one occasion was compared between the study groups. Latent class analysis (LCA) was also performed.
Results
Ictal features were overall more numerous in ALE than in MTLE-HS (33 vs 22), and LCA confirmed the intrinsic variability of ALE-related seizures. Hyperventilation served as a trigger only in ALE (4/40). Awareness impairment (p = 0.032), limb dystonic posturing (p = 0.009) and manual automatisms (p < 0.001) were significantly less common in ALE cases. Conversely, piloerection was observed only in ALE subjects, although it did not reach statistical significance (p = 0.289), as was the case for déjà-vu (p = 0.084), and sensory symptoms (p = 0.079). Regarding EEG, the type of ictal pattern differed significantly (p = 0.007).
Significance
This study shows that, despite the wide overlap with MTLE-HS, some ictal electro-clinical features could help clinicians suspect the autoimmune origin of adult-onset seizures. Moreover, autoimmune limbic seizures apparently shared similarities with ‘temporal plus’ epilepsy, which could partly account for the poor surgical outcomes and provide an interesting conceptual framework for future research.
{"title":"Distinguishing seizures in autoimmune limbic encephalitis from mesial temporal lobe epilepsy with hippocampal sclerosis: Clues of a temporal plus network","authors":"Alessandra Morano , Emanuele Cerulli Irelli , Francesco Fortunato , Sara Casciato , Chiara Panzini , Chiara Milano , Salvatore Versace , Biagio Orlando , Raffaele Iorio , Emanuele Tinelli , Gabriele Ruffolo , Chiara Pizzanelli , Alberto Vogrig , Pierpaolo Quarato , Anna Teresa Giallonardo , Giancarlo Di Gennaro , Antonio Gambardella , Carlo Di Bonaventura","doi":"10.1016/j.jns.2024.123288","DOIUrl":"10.1016/j.jns.2024.123288","url":null,"abstract":"<div><h3>Objective</h3><div>Diagnosing autoimmune limbic encephalitis (ALE) in adults with new-onset seizures can be challenging, especially when seizures represent the predominant manifestation and MRI findings are not straightforward. By comparison with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), this study aimed to identify ictal electro-clinical features that might help clinicians recognize ALE-related seizures.</div></div><div><h3>Methods</h3><div>This retrospective, multi-centre study analysed the ictal semiology and EEG correlate of 116 video-EEG-captured seizures in 40 ALE patients and 45 ones recorded in 21 MTLE-HS subjects. The proportion of patients presenting each clinical feature on at least one occasion was compared between the study groups. Latent class analysis (LCA) was also performed.</div></div><div><h3>Results</h3><div>Ictal features were overall more numerous in ALE than in MTLE-HS (33 vs 22), and LCA confirmed the intrinsic variability of ALE-related seizures. Hyperventilation served as a trigger only in ALE (4/40). Awareness impairment (<em>p</em> = 0.032), limb dystonic posturing (<em>p</em> = 0.009) and manual automatisms (<em>p</em> < 0.001) were significantly less common in ALE cases. Conversely, piloerection was observed only in ALE subjects, although it did not reach statistical significance (<em>p</em> = 0.289), as was the case for déjà-vu (<em>p</em> = 0.084), and sensory symptoms (<em>p</em> = 0.079). Regarding EEG, the type of ictal pattern differed significantly (<em>p</em> = 0.007).</div></div><div><h3>Significance</h3><div>This study shows that, despite the wide overlap with MTLE-HS, some ictal electro-clinical features could help clinicians suspect the autoimmune origin of adult-onset seizures. Moreover, autoimmune limbic seizures apparently shared similarities with ‘temporal plus’ epilepsy, which could partly account for the poor surgical outcomes and provide an interesting conceptual framework for future research.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123288"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639207","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 : 2024-11-04DOI: 10.1016/j.jns.2024.123286
Gadi Maayan Eshed , Tal Levinson , Yair Mina , Adi Ashkenazi , Michal Dekel , Ronit Cohen-Poradosu , Yifat Alcalay , Ora Halutz , Orna Aizenstein , Yael Paran , Avi Gadoth
Purpose
To compare functional outcomes and help differentiate between important causative agents of acute infectious encephalitis in adults, focusing on West Nile virus encephalitis (WNVE).
Methods
The electronic database of Tel Aviv Medical Center was screened for patients admitted during 2010–2020 with acute encephalitis. Additionally, patient laboratory results during the same period were screened for CSF samples positive for common pathogens causing encephalitis. The main patient groups were compared in terms of clinical characteristics and functional outcomes.
Results
One hundred and five infectious encephalitis patients were identified. WNVE patients (n = 31) and VZV encephalitis (VZVE) patients (n = 31) were older than HSV1 encephalitis (HSV1E) patients (n = 15) (median ages 73, 76, 51, respectively). WNVE patients had a more prominent inflammatory profile. CSF characteristics significantly differed between groups, with an extreme mononuclear white blood cell predominance in VZVE patients (median 98%).
Functional outcomes at discharge were significantly worse in WNVE patients (median modified Rankin Scale score 4 at hospital discharge, 2.5 at last follow-up) when compared with HSV1E patients (2.5, 1, respectively) and VZVE patients (1.5, 1, respectively).
Conclusion
In odds with previous reports, WNVE and VZVE in this study were far more prevalent than HSV1E. Differences in clinical characteristics could prove clinically useful early in encephalitis, including an association of WNVE with a relatively prominent inflammatory profile (somewhat resembling a bacterial infection) and an extreme mononuclear white blood cell predominance in VZVE. The detrimental outcome of WNVE emphasizes the need to advance research on WNV infection.
{"title":"West Nile virus encephalitis: Clinical characteristics and a comparison to other infectious encephalitides","authors":"Gadi Maayan Eshed , Tal Levinson , Yair Mina , Adi Ashkenazi , Michal Dekel , Ronit Cohen-Poradosu , Yifat Alcalay , Ora Halutz , Orna Aizenstein , Yael Paran , Avi Gadoth","doi":"10.1016/j.jns.2024.123286","DOIUrl":"10.1016/j.jns.2024.123286","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare functional outcomes and help differentiate between important causative agents of acute infectious encephalitis in adults, focusing on West Nile virus encephalitis (WNVE).</div></div><div><h3>Methods</h3><div>The electronic database of Tel Aviv Medical Center was screened for patients admitted during 2010–2020 with acute encephalitis. Additionally, patient laboratory results during the same period were screened for CSF samples positive for common pathogens causing encephalitis. The main patient groups were compared in terms of clinical characteristics and functional outcomes.</div></div><div><h3>Results</h3><div>One hundred and five infectious encephalitis patients were identified. WNVE patients (<em>n</em> = 31) and VZV encephalitis (VZVE) patients (n = 31) were older than HSV1 encephalitis (HSV1E) patients (<em>n</em> = 15) (median ages 73, 76, 51, respectively). WNVE patients had a more prominent inflammatory profile. CSF characteristics significantly differed between groups, with an extreme mononuclear white blood cell predominance in VZVE patients (median 98%).</div><div>Functional outcomes at discharge were significantly worse in WNVE patients (median modified Rankin Scale score 4 at hospital discharge, 2.5 at last follow-up) when compared with HSV1E patients (2.5, 1, respectively) and VZVE patients (1.5, 1, respectively).</div></div><div><h3>Conclusion</h3><div>In odds with previous reports, WNVE and VZVE in this study were far more prevalent than HSV1E. Differences in clinical characteristics could prove clinically useful early in encephalitis, including an association of WNVE with a relatively prominent inflammatory profile (somewhat resembling a bacterial infection) and an extreme mononuclear white blood cell predominance in VZVE. The detrimental outcome of WNVE emphasizes the need to advance research on WNV infection.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123286"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648437","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 : 2024-11-02DOI: 10.1016/j.jns.2024.123290
Erik P. Pioro , Benjamin Rix Brooks , Ying Liu , Jeffrey Zhang , Stephen Apple
Introduction
Subjects with amyotrophic lateral sclerosis (ALS) treated with Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA], hereafter “MTPA IV edaravone”) in Study MCI186‐19 had a significantly slower physical functional decline vs placebo-treated subjects as measured by the revised ALS Functional Rating Scale (ALSFRS-R) and analyzed by the linear mixed model for repeated measures (MMRM). This Study 19 post hoc analysis of MTPA IV edaravone-treated and placebo-treated subjects evaluated linear and nonlinear latent class mixed models defining trajectories based on identifying the model with the lowest Bayesian information criterion. The best model differentiated 4 nonlinear trajectories in ALS subjects. ALSFRS-R total score in MTPA IV edaravone-treated and placebo-treated subjects was evaluated for these 4 nonlinear latent class trajectory groups.
Methods
Disease trajectories of MCI186‐19 MTPA IV edaravone-treated or placebo-treated ALS subjects who completed the double-blind period were investigated using latent class analysis (LCA) statistical models to identify potential unique nonlinear ALSFRS-R disease trajectories.
Results
ALSFRS-R trajectories revealed 4 unique nonlinear trajectory latent classes per treatment group in MTPA IV edaravone-treated and placebo-treated ALS subjects completing the MCI186‐19 double-blind period. Latent classes 2‐4 had statistically significant slowing of ALSFRS-R total score decline in the predicted nonlinear trajectories of MTPA IV edaravone-treated vs placebo-treated ALS subjects.
Conclusions
This post hoc analysis suggests MTPA IV edaravone treatment results in slower ALSFRS-R decline vs placebo in most predicted nonlinear trajectories. LCA is a novel approach that may benefit future trial analyses.
导言：在 MCI186-19 研究中，接受 Radicava® （依达拉奉）静脉注射（静脉注射；三菱田边制药美国公司 [MTPA]，以下简称 "MTPA IV 依达拉奉"）治疗的肌萎缩性脊髓侧索硬化症（ALS）受试者与接受安慰剂治疗的受试者相比，其身体功能衰退速度明显较慢，这是由修订后的 ALS 功能评定量表（ALSFRS-R）衡量的，并通过重复测量线性混合模型（MMRM）进行了分析。这项研究 19 对 MTPA IV 依达拉奉治疗和安慰剂治疗受试者进行了事后分析，评估了线性和非线性潜类混合模型，并根据贝叶斯信息标准确定了具有最低贝叶斯信息标准的模型。最佳模型区分了 ALS 受试者的 4 种非线性轨迹。针对这4个非线性潜类轨迹组，评估了MTPA IV依达拉奉治疗和安慰剂治疗受试者的ALSFRS-R总分：使用潜类分析（LCA）统计模型研究了完成双盲期的MCI186-19 MTPA IV依达拉奉治疗或安慰剂治疗的ALS受试者的疾病轨迹，以识别潜在的独特非线性ALSFRS-R疾病轨迹：在完成 MCI186-19 双盲期的 MTPA IV 依达拉奉治疗和安慰剂治疗 ALS 受试者中，每个治疗组的 ALSFRS-R 轨迹显示出 4 个独特的非线性轨迹潜类。在 MTPA IV 依达拉奉治疗与安慰剂治疗 ALS 受试者的预测非线性轨迹中，潜伏类别 2-4 在统计学上显著减缓了 ALSFRS-R 总分的下降：结论：这项事后分析表明，在大多数预测的非线性轨迹中，MTPA IV 依达拉奉治疗与安慰剂相比会导致 ALSFRS-R 下降更慢。LCA是一种新颖的方法，可能对未来的试验分析有所裨益。
{"title":"Efficacy of Radicava® IV (intravenous edaravone) in subjects with differing trajectories of disease progression in amyotrophic lateral sclerosis: Use of a novel statistical approach for post hoc analysis of a pivotal phase 3 clinical trial","authors":"Erik P. Pioro , Benjamin Rix Brooks , Ying Liu , Jeffrey Zhang , Stephen Apple","doi":"10.1016/j.jns.2024.123290","DOIUrl":"10.1016/j.jns.2024.123290","url":null,"abstract":"<div><h3>Introduction</h3><div>Subjects with amyotrophic lateral sclerosis (ALS) treated with Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA], hereafter “MTPA IV edaravone”) in Study MCI186‐19 had a significantly slower physical functional decline vs placebo-treated subjects as measured by the revised ALS Functional Rating Scale (ALSFRS-R) and analyzed by the linear mixed model for repeated measures (MMRM). This Study 19 post hoc analysis of MTPA IV edaravone-treated and placebo-treated subjects evaluated linear and nonlinear latent class mixed models defining trajectories based on identifying the model with the lowest Bayesian information criterion. The best model differentiated 4 nonlinear trajectories in ALS subjects. ALSFRS-R total score in MTPA IV edaravone-treated and placebo-treated subjects was evaluated for these 4 nonlinear latent class trajectory groups.</div></div><div><h3>Methods</h3><div>Disease trajectories of MCI186‐19 MTPA IV edaravone-treated or placebo-treated ALS subjects who completed the double-blind period were investigated using latent class analysis (LCA) statistical models to identify potential unique nonlinear ALSFRS-R disease trajectories.</div></div><div><h3>Results</h3><div>ALSFRS-R trajectories revealed 4 unique nonlinear trajectory latent classes per treatment group in MTPA IV edaravone-treated and placebo-treated ALS subjects completing the MCI186‐19 double-blind period. Latent classes 2‐4 had statistically significant slowing of ALSFRS-R total score decline in the predicted nonlinear trajectories of MTPA IV edaravone-treated vs placebo-treated ALS subjects.</div></div><div><h3>Conclusions</h3><div>This post hoc analysis suggests MTPA IV edaravone treatment results in slower ALSFRS-R decline vs placebo in most predicted nonlinear trajectories. LCA is a novel approach that may benefit future trial analyses.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123290"},"PeriodicalIF":3.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622980","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 : 2024-10-28DOI: 10.1016/j.jns.2024.123287
Meiko Maeda , Takuya Kawahara , Akatsuki Kubota , Jun Shimizu , Tatsushi Toda
Background
Anti-mitochondrial antibody (AMA)-positive myositis is a chronic disease characterized by skeletal muscle atrophy and is associated with cardiac complications and restrictive ventilatory impairment. This study aimed to determine the prevalence, rate of organ complications, and prognostic risk factors of AMA-positive myositis.
Methods
We conducted a cross-sectional study using a nationwide questionnaire from 2011 to 2021, enrolling participants from neurology departments at 811 facilities certified by the Japanese Society of Neurology.
Results
A total of 380 patients were identified, with a prevalence rate of 0.3 per 100,000 persons. The frequencies of cardiac complications and restrictive ventilatory impairment were 53 and 33 %, respectively; whereas, those of cardiac device and respirator introduction were 32 and 22 %, respectively. The frequencies of recurrence, subacute exacerbation, no muscle strength improvement, cardiac device introduction, respirator introduction, and death were 29, 25, 54, 32, 22, and 12 %, respectively. According to univariate analysis, abnormal echocardiograms (odds ratio [OR], 5.43), restrictive ventilatory impairment (OR, 3.70), and inflammatory changes revealed by muscle biopsy (OR, 0.34) were associated with subacute exacerbations, whereas abnormal echocardiograms (OR, 8.00) and durations from onset to admission and diagnosis (OR, 2.99) were associated with cardiac device introduction. Multivariable analysis showed that restrictive ventilatory impairment was associated with recurrence (adjusted OR, 3.01), adjusted for the duration from onset to admission and diagnosis, and with subacute exacerbations (adjusted OR, 3.86), adjusted for abnormal echocardiograms and inflammatory changes.
Conclusions
AMA-positive myositis is characterized by severe and urgent organ complications, and anticipatory management is critical for management of this disease.
{"title":"Prevalence and risk surveillance of anti-mitochondrial antibody-positive myositis: Outcomes of a nationwide survey","authors":"Meiko Maeda , Takuya Kawahara , Akatsuki Kubota , Jun Shimizu , Tatsushi Toda","doi":"10.1016/j.jns.2024.123287","DOIUrl":"10.1016/j.jns.2024.123287","url":null,"abstract":"<div><h3>Background</h3><div>Anti-mitochondrial antibody (AMA)-positive myositis is a chronic disease characterized by skeletal muscle atrophy and is associated with cardiac complications and restrictive ventilatory impairment. This study aimed to determine the prevalence, rate of organ complications, and prognostic risk factors of AMA-positive myositis.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study using a nationwide questionnaire from 2011 to 2021, enrolling participants from neurology departments at 811 facilities certified by the Japanese Society of Neurology.</div></div><div><h3>Results</h3><div>A total of 380 patients were identified, with a prevalence rate of 0.3 per 100,000 persons. The frequencies of cardiac complications and restrictive ventilatory impairment were 53 and 33 %, respectively; whereas, those of cardiac device and respirator introduction were 32 and 22 %, respectively. The frequencies of recurrence, subacute exacerbation, no muscle strength improvement, cardiac device introduction, respirator introduction, and death were 29, 25, 54, 32, 22, and 12 %, respectively. According to univariate analysis, abnormal echocardiograms (odds ratio [OR], 5.43), restrictive ventilatory impairment (OR, 3.70), and inflammatory changes revealed by muscle biopsy (OR, 0.34) were associated with subacute exacerbations, whereas abnormal echocardiograms (OR, 8.00) and durations from onset to admission and diagnosis (OR, 2.99) were associated with cardiac device introduction. Multivariable analysis showed that restrictive ventilatory impairment was associated with recurrence (adjusted OR, 3.01), adjusted for the duration from onset to admission and diagnosis, and with subacute exacerbations (adjusted OR, 3.86), adjusted for abnormal echocardiograms and inflammatory changes.</div></div><div><h3>Conclusions</h3><div>AMA-positive myositis is characterized by severe and urgent organ complications, and anticipatory management is critical for management of this disease.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123287"},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569038","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 : 2024-10-23DOI: 10.1016/j.jns.2024.123277
Brin E. Freund , Mariam Tsikvadze , Anteneh M. Feyissa , William D. Freeman , William O. Tatum IV
Objective
Rapid EEG devices (REDs) have demonstrated substantial benefit regarding reduced time to performance of study and diagnosis in cases where urgent EEG is needed to evaluate patients for potentially revealing nonconvulsive status epilepticus and seizures. However, urgent EEG is also important in identifying cases regarding the need for initiation of antiseizure medication as well as triaging the use of continuous EEG monitoring. Some forms of REDs have a reduced montage (RRME) with electrode derivations that are one-half of standard recordings. This could impact spatial resolution and therefore potentially limit recovery of epileptiform abnormalities.
Methods
In this study we evaluated the use of the Ceribell® rapid response EEG system and compared it to conventional video EEG (CvEEG). After applying inclusion and exclusion criteria, a total of 20 subjects were included in our analysis.
Results
RRME was highly sensitive in detecting abundant and periodic discharges (p = 0.013) as well as discharges with a broad spatial distribution on CvEEG (p = 0.039). Sensitivity for detecting less prevalent discharges or those with more restricted spatial distribution was lower.
Significance
Given the possibility of less frequent and more restricted epileptiform discharges eluding detection on RRME, we propose a protocol for the approach of using RRME and when to consider CvEEG when RRME is negative for epileptiform activity and highlight that urgent CvEEG may still be warranted following RRME.
{"title":"Sensitivity of detecting interictal epileptiform activity using rapid reduced montage EEG","authors":"Brin E. Freund , Mariam Tsikvadze , Anteneh M. Feyissa , William D. Freeman , William O. Tatum IV","doi":"10.1016/j.jns.2024.123277","DOIUrl":"10.1016/j.jns.2024.123277","url":null,"abstract":"<div><h3>Objective</h3><div>Rapid EEG devices (REDs) have demonstrated substantial benefit regarding reduced time to performance of study and diagnosis in cases where urgent EEG is needed to evaluate patients for potentially revealing nonconvulsive status epilepticus and seizures. However, urgent EEG is also important in identifying cases regarding the need for initiation of antiseizure medication as well as triaging the use of continuous EEG monitoring. Some forms of REDs have a reduced montage (RRME) with electrode derivations that are one-half of standard recordings. This could impact spatial resolution and therefore potentially limit recovery of epileptiform abnormalities.</div></div><div><h3>Methods</h3><div>In this study we evaluated the use of the Ceribell® rapid response EEG system and compared it to conventional video EEG (CvEEG). After applying inclusion and exclusion criteria, a total of 20 subjects were included in our analysis.</div></div><div><h3>Results</h3><div>RRME was highly sensitive in detecting abundant and periodic discharges (<em>p</em> = 0.013) as well as discharges with a broad spatial distribution on CvEEG (<em>p</em> = 0.039). Sensitivity for detecting less prevalent discharges or those with more restricted spatial distribution was lower.</div></div><div><h3>Significance</h3><div>Given the possibility of less frequent and more restricted epileptiform discharges eluding detection on RRME, we propose a protocol for the approach of using RRME and when to consider CvEEG when RRME is negative for epileptiform activity and highlight that urgent CvEEG may still be warranted following RRME.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"467 ","pages":"Article 123277"},"PeriodicalIF":3.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676130","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 : 2024-10-23DOI: 10.1016/j.jns.2024.123279
Gabriel E. Vázquez-Vélez , Wei Zhao , Kelly Schaschl , Daniel G. Di Luca
{"title":"The Gunslinger's sign in a patient with Dementia with Lewy Bodies","authors":"Gabriel E. Vázquez-Vélez , Wei Zhao , Kelly Schaschl , Daniel G. Di Luca","doi":"10.1016/j.jns.2024.123279","DOIUrl":"10.1016/j.jns.2024.123279","url":null,"abstract":"","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"466 ","pages":"Article 123279"},"PeriodicalIF":3.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522239","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}
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