Anne-Katrin Güttsches, Johannes Forsting, Moritz Kneifel, Robert Rehmann, Alice De Lorenzo, Elena Enax-Krumova, Martijn Froeling, Matthias Vorgerd, Lara Schlaffke
Background and purpose: Quantitative muscle magnetic resonance imaging (MRI) is a promising non-invasive method in the diagnostic workup as well as follow-up of neuromuscular disorders. The aim of this study was to correlate quantitative MRI (qMRI) parameters to histopathological changes in skeletal muscle tissue and thus to verify the data from our pilot study.
Methods: Twenty-six patients (eight females, 46.4 ± 15.1 years) were examined within 72 h before and within 24 h after a skeletal muscle biopsy using quantitative muscle MRI. Post-biopsy MRI was employed to pinpoint the exact localization of the biopsy. qMRI parameters including fat fraction, water T2 relaxation time and diffusion metrics including fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were extracted from the localization of the biopsy and correlated with histopathological findings. Additionally, three different segmentation masks were applied to the qMRI dataset, to evaluate whether the whole muscle represents the exact biopsy location.
Results: Fat fraction and water T2 relaxation time in qMRI correlated significantly with the fat fraction in the muscle biopsy and histopathological inflammatory markers. Fractional anisotropy correlated with the quantity of type 2 fibres, whilst mean diffusivity correlated with p62. No differences were found using different segmentation masks in qMRI.
Conclusions: In this follow-up study, the results from our previous study were verified regarding the correlation of qMRI parameters with histopathological features in muscle biopsies, indicating that qMRI serves as a suitable non-invasive method in the follow-up of patients with neuromuscular disorders. If post-biopsy MRI is not available, whole muscle volume can be used for histopathological correlations.
{"title":"Pre- and post-skeletal muscle biopsy quantitative magnetic resonance imaging reveals correlations with histopathological findings.","authors":"Anne-Katrin Güttsches, Johannes Forsting, Moritz Kneifel, Robert Rehmann, Alice De Lorenzo, Elena Enax-Krumova, Martijn Froeling, Matthias Vorgerd, Lara Schlaffke","doi":"10.1111/ene.16479","DOIUrl":"https://doi.org/10.1111/ene.16479","url":null,"abstract":"<p><strong>Background and purpose: </strong>Quantitative muscle magnetic resonance imaging (MRI) is a promising non-invasive method in the diagnostic workup as well as follow-up of neuromuscular disorders. The aim of this study was to correlate quantitative MRI (qMRI) parameters to histopathological changes in skeletal muscle tissue and thus to verify the data from our pilot study.</p><p><strong>Methods: </strong>Twenty-six patients (eight females, 46.4 ± 15.1 years) were examined within 72 h before and within 24 h after a skeletal muscle biopsy using quantitative muscle MRI. Post-biopsy MRI was employed to pinpoint the exact localization of the biopsy. qMRI parameters including fat fraction, water T2 relaxation time and diffusion metrics including fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were extracted from the localization of the biopsy and correlated with histopathological findings. Additionally, three different segmentation masks were applied to the qMRI dataset, to evaluate whether the whole muscle represents the exact biopsy location.</p><p><strong>Results: </strong>Fat fraction and water T2 relaxation time in qMRI correlated significantly with the fat fraction in the muscle biopsy and histopathological inflammatory markers. Fractional anisotropy correlated with the quantity of type 2 fibres, whilst mean diffusivity correlated with p62. No differences were found using different segmentation masks in qMRI.</p><p><strong>Conclusions: </strong>In this follow-up study, the results from our previous study were verified regarding the correlation of qMRI parameters with histopathological features in muscle biopsies, indicating that qMRI serves as a suitable non-invasive method in the follow-up of patients with neuromuscular disorders. If post-biopsy MRI is not available, whole muscle volume can be used for histopathological correlations.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luigi Francesco Iannone, Marina Romozzi, Antonio Russo, Gennaro Saporito, Federico De Santis, Raffaele Ornello, Grazia Sances, Gloria Vaghi, Cristina Tassorelli, Maria Albanese, Simona Guerzoni, Alfonsina Casalena, Catello Vollono, Paolo Calabresi, Maria Pia Prudenzano, Edoardo Mampreso, Giorgio Dalla Volta, Maria Rosaria Valente, Gianluca Avino, Alberto Chiarugi, Simona Sacco, Francesca Pistoia
Background and purpose: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases.
Methods: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded.
Results: Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%).
Conclusions: In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.
{"title":"Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.","authors":"Luigi Francesco Iannone, Marina Romozzi, Antonio Russo, Gennaro Saporito, Federico De Santis, Raffaele Ornello, Grazia Sances, Gloria Vaghi, Cristina Tassorelli, Maria Albanese, Simona Guerzoni, Alfonsina Casalena, Catello Vollono, Paolo Calabresi, Maria Pia Prudenzano, Edoardo Mampreso, Giorgio Dalla Volta, Maria Rosaria Valente, Gianluca Avino, Alberto Chiarugi, Simona Sacco, Francesca Pistoia","doi":"10.1111/ene.16450","DOIUrl":"https://doi.org/10.1111/ene.16450","url":null,"abstract":"<p><strong>Background and purpose: </strong>Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases.</p><p><strong>Methods: </strong>Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded.</p><p><strong>Results: </strong>Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%).</p><p><strong>Conclusions: </strong>In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Young Ju Kim,Jihwan Yun,Sang Won Seo,Jun Pyo Kim,Hyemin Jang,Hee Jin Kim,Duk L Na,Sookyoung Woo,Min Young Chun,
BACKGROUND AND PURPOSEAmyloid β (Aβ), a major biomarker of Alzheimer's disease, leads to tau accumulation, neurodegeneration and cognitive decline. Modelling the trajectory of Aβ accumulation in cognitively unimpaired (CU) individuals is crucial, as treatments targeting Aβ are anticipated. The evolution of Aβ levels was investigated to determine whether it could lead to classification into different groups by studying longitudinal Aβ changes in older CU individuals, and differences between the groups were compared.METHODSA total of 297 CU participants were included from the Alzheimer's Disease Neuroimaging Initiative database, and these participants underwent apolipoprotein E (APOE) genotyping, neuropsychological testing, brain magnetic resonance imaging, and an average of 3.03 follow-up 18F-florbetapir positron emission tomography scans. Distinct Aβ trajectory patterns were classified using latent class growth analysis, and longitudinal cognitive performances across these patterns were assessed with a linear mixed effects model.RESULTSThe optimal model consisted of three classes, with a high entropy value of 0.947. The classes were designated as follows: class 1, non-accumulation group (n = 197); class 2, late accumulation group (n = 70); and class 3, early accumulation group (n = 30). The late accumulation and early accumulation groups had more APOE ε4 carriers than the non-accumulation group. The longitudinal analysis of cognitive performance revealed that the early accumulation group showed the steepest decline (modified Preclinical Alzheimer's Cognitive Composite with digit symbol substitution [mPACCdigit], p < 0.001; modified Preclinical Alzheimer's Cognitive Composite with trails B [mPACCtrailsB], p < 0.001) and the late accumulation group showed a steeper decline (mPACCdigit, p = 0.014; mPACCtrailsB, p = 0.007) compared to the non-accumulation group.CONCLUSIONSOur study showed the heterogeneity of Aβ accumulation trajectories in CU older individuals. The prognoses for cognitive decline differ according to the Aβ trajectory patterns.
{"title":"Difference in trajectories according to early amyloid accumulation in cognitively unimpaired elderly.","authors":"Young Ju Kim,Jihwan Yun,Sang Won Seo,Jun Pyo Kim,Hyemin Jang,Hee Jin Kim,Duk L Na,Sookyoung Woo,Min Young Chun,","doi":"10.1111/ene.16482","DOIUrl":"https://doi.org/10.1111/ene.16482","url":null,"abstract":"BACKGROUND AND PURPOSEAmyloid β (Aβ), a major biomarker of Alzheimer's disease, leads to tau accumulation, neurodegeneration and cognitive decline. Modelling the trajectory of Aβ accumulation in cognitively unimpaired (CU) individuals is crucial, as treatments targeting Aβ are anticipated. The evolution of Aβ levels was investigated to determine whether it could lead to classification into different groups by studying longitudinal Aβ changes in older CU individuals, and differences between the groups were compared.METHODSA total of 297 CU participants were included from the Alzheimer's Disease Neuroimaging Initiative database, and these participants underwent apolipoprotein E (APOE) genotyping, neuropsychological testing, brain magnetic resonance imaging, and an average of 3.03 follow-up 18F-florbetapir positron emission tomography scans. Distinct Aβ trajectory patterns were classified using latent class growth analysis, and longitudinal cognitive performances across these patterns were assessed with a linear mixed effects model.RESULTSThe optimal model consisted of three classes, with a high entropy value of 0.947. The classes were designated as follows: class 1, non-accumulation group (n = 197); class 2, late accumulation group (n = 70); and class 3, early accumulation group (n = 30). The late accumulation and early accumulation groups had more APOE ε4 carriers than the non-accumulation group. The longitudinal analysis of cognitive performance revealed that the early accumulation group showed the steepest decline (modified Preclinical Alzheimer's Cognitive Composite with digit symbol substitution [mPACCdigit], p < 0.001; modified Preclinical Alzheimer's Cognitive Composite with trails B [mPACCtrailsB], p < 0.001) and the late accumulation group showed a steeper decline (mPACCdigit, p = 0.014; mPACCtrailsB, p = 0.007) compared to the non-accumulation group.CONCLUSIONSOur study showed the heterogeneity of Aβ accumulation trajectories in CU older individuals. The prognoses for cognitive decline differ according to the Aβ trajectory patterns.","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renato De Donato, Natale Vincenzo Maiorana, Maurizio Vergari, Angelica De Sandi, Anisa Naci, Giada Aglieco, Tommaso Albizzati, Matteo Guidetti, Rosanna Ferrara, Tommaso Bocci, Sergio Barbieri, Roberta Ferrucci, Alberto Priori
Background and purposeBoxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub‐concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data.MethodsTwenty‐one boxers were selected (mean ± SD, age 28.38 ± 5.5 years; weight 67.55 ± 8.90 kg; years of activity 6.76 ± 5.45; education 14.19 ± 3.08 years) and divided into ‘beginner’ and ‘advanced’ groups. The Montreal Cognitive Assessment and the Frontal Assessment Battery were administered; EEG data were collected in both eyes‐open (EO) and eyes‐closed (EC) conditions during resting states. Analyses of EEG data included normalized power spectral density (nPSD), power law exponent (PLE), detrended fluctuation analysis and multiscale entropy. Statistical analyses were used to compare the groups.ResultsSignificant differences in nPSD and PLE were observed between the beginner and advanced boxers, with advanced boxers showing decreased mean nPSD and PLE (nPSD 4–7 Hz, p = 0.013; 8–13 Hz, p = 0.003; PLE frontal lobe F3 EC, p = 0.010). Multiscale entropy analysis indicated increased entropy at lower frequencies and decreased entropy at higher frequencies in advanced boxers (F3 EC, p = 0.024; occipital lobe O1 EO, p = 0.029; occipital lobe O2 EO, p = 0.036). These changes are similar to those seen in Alzheimer's disease.ConclusionNonlinear analysis of EEG data shows potential as a neurophysiological biomarker for detecting the asymptomatic phase of chronic traumatic encephalopathy in boxers. This methodology could help monitor athletes' health and reduce the risk of future neurological injuries in sports.
{"title":"‘Knock down the brain’: a nonlinear analysis of electroencephalography to study the effects of sub‐concussion in boxers","authors":"Renato De Donato, Natale Vincenzo Maiorana, Maurizio Vergari, Angelica De Sandi, Anisa Naci, Giada Aglieco, Tommaso Albizzati, Matteo Guidetti, Rosanna Ferrara, Tommaso Bocci, Sergio Barbieri, Roberta Ferrucci, Alberto Priori","doi":"10.1111/ene.16411","DOIUrl":"https://doi.org/10.1111/ene.16411","url":null,"abstract":"Background and purposeBoxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub‐concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data.MethodsTwenty‐one boxers were selected (mean ± SD, age 28.38 ± 5.5 years; weight 67.55 ± 8.90 kg; years of activity 6.76 ± 5.45; education 14.19 ± 3.08 years) and divided into ‘beginner’ and ‘advanced’ groups. The Montreal Cognitive Assessment and the Frontal Assessment Battery were administered; EEG data were collected in both eyes‐open (EO) and eyes‐closed (EC) conditions during resting states. Analyses of EEG data included normalized power spectral density (nPSD), power law exponent (PLE), detrended fluctuation analysis and multiscale entropy. Statistical analyses were used to compare the groups.ResultsSignificant differences in nPSD and PLE were observed between the beginner and advanced boxers, with advanced boxers showing decreased mean nPSD and PLE (nPSD 4–7 Hz, <jats:italic>p</jats:italic> = 0.013; 8–13 Hz, <jats:italic>p</jats:italic> = 0.003; PLE frontal lobe F3 EC, <jats:italic>p</jats:italic> = 0.010). Multiscale entropy analysis indicated increased entropy at lower frequencies and decreased entropy at higher frequencies in advanced boxers (F3 EC, <jats:italic>p</jats:italic> = 0.024; occipital lobe O1 EO, <jats:italic>p</jats:italic> = 0.029; occipital lobe O2 EO, <jats:italic>p</jats:italic> = 0.036). These changes are similar to those seen in Alzheimer's disease.ConclusionNonlinear analysis of EEG data shows potential as a neurophysiological biomarker for detecting the asymptomatic phase of chronic traumatic encephalopathy in boxers. This methodology could help monitor athletes' health and reduce the risk of future neurological injuries in sports.","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saim Mahmood Khan, Jawairya Muhammad Hussain, Areeb Bin Khalid, Ramsha Sultan
{"title":"Improved comprehension of influenza‐related headaches: Perspectives and suggestions for incidence and prevalence of headache in influenza","authors":"Saim Mahmood Khan, Jawairya Muhammad Hussain, Areeb Bin Khalid, Ramsha Sultan","doi":"10.1111/ene.16477","DOIUrl":"https://doi.org/10.1111/ene.16477","url":null,"abstract":"","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M.‐L. Sumelahti, A. Verkko, V. Kytö, J. O. T. Sipilä
Background and purposeMultiple sclerosis (MS) is associated with excess mortality. The use of disease‐modifying treatments (DMTs) has recently been associated with survival benefits.MethodsA regional MS database was linked with national registries. People with MS (pwMS) diagnosed in 1971–2010 were included and followed up until the end of the year 2019. Five matched controls were acquired for every person with MS. DMTs included in the analyses were interferon and glatiramer acetate.ResultsMedian follow‐up time of the 1795 pwMS was 20.0 years (range 0.1–48.7 years). Survival did not differ between decades of diagnosis (p = 0.20). Amongst pwMS, male sex (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI] 1.41–2.06), higher age at diagnosis (aHR 1.83; 95% CI 1.65–2.03 per 10‐year increment) and primary progressive disease course (aHR 1.29; 95% CI 1.04–1.60) were independently associated with poorer survival. DMT use was associated with better survival (p < 0.0001) and better survival during follow‐up (aHR 0.56; 95% CI 0.38–0.81). Compared to matched controls, median life expectancy was 8–9 years shorter in pwMS with survival diverging from controls during the first decade after diagnosis, more clearly in men than women.ConclusionDespite DMT use being associated with better survival, relative life expectancy of pwMS did not change over five decades in Western Finland. Male sex was an independent risk factor for death amongst pwMS, but excess mortality was higher in women. More work and methods are needed to improve survival in pwMS.
背景和目的多发性硬化症(MS)与高死亡率有关。方法将一个地区多发性硬化症数据库与国家登记处连接起来。方法将一个地区多发性硬化症数据库与国家登记处连接起来,纳入 1971-2010 年确诊的多发性硬化症患者(pwMS),并随访至 2019 年底。每名多发性硬化症患者可获得五个匹配的对照组。结果1795名多发性硬化症患者的平均随访时间为20.0年(范围为0.1-48.7年)。不同诊断年代的存活率没有差异(P = 0.20)。在 PwMS 中,男性(调整后危险比 [aHR] 1.70;95% 置信区间 [CI]1.41-2.06)、较高的诊断年龄(aHR 1.83;95% CI 1.65-2.03,每 10 年递增)和原发性进展病程(aHR 1.29;95% CI 1.04-1.60)与较差的生存率独立相关。使用 DMT 与较高的生存率(p < 0.0001)和随访期间较高的生存率(aHR 0.56; 95% CI 0.38-0.81)相关。与匹配的对照组相比,重症肌无力患者的中位预期寿命短8-9年,在确诊后的头十年中,他们的存活率与对照组存在差异,男性的差异比女性更为明显。男性是导致重症肌无力患者死亡的一个独立风险因素,但女性的死亡率更高。需要开展更多的工作和采用更多的方法来提高重症肌无力患者的存活率。
{"title":"Stable excess mortality in a multiple sclerosis cohort diagnosed 1970–2010","authors":"M.‐L. Sumelahti, A. Verkko, V. Kytö, J. O. T. Sipilä","doi":"10.1111/ene.16480","DOIUrl":"https://doi.org/10.1111/ene.16480","url":null,"abstract":"Background and purposeMultiple sclerosis (MS) is associated with excess mortality. The use of disease‐modifying treatments (DMTs) has recently been associated with survival benefits.MethodsA regional MS database was linked with national registries. People with MS (pwMS) diagnosed in 1971–2010 were included and followed up until the end of the year 2019. Five matched controls were acquired for every person with MS. DMTs included in the analyses were interferon and glatiramer acetate.ResultsMedian follow‐up time of the 1795 pwMS was 20.0 years (range 0.1–48.7 years). Survival did not differ between decades of diagnosis (<jats:italic>p</jats:italic> = 0.20). Amongst pwMS, male sex (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI] 1.41–2.06), higher age at diagnosis (aHR 1.83; 95% CI 1.65–2.03 per 10‐year increment) and primary progressive disease course (aHR 1.29; 95% CI 1.04–1.60) were independently associated with poorer survival. DMT use was associated with better survival (<jats:italic>p</jats:italic> < 0.0001) and better survival during follow‐up (aHR 0.56; 95% CI 0.38–0.81). Compared to matched controls, median life expectancy was 8–9 years shorter in pwMS with survival diverging from controls during the first decade after diagnosis, more clearly in men than women.ConclusionDespite DMT use being associated with better survival, relative life expectancy of pwMS did not change over five decades in Western Finland. Male sex was an independent risk factor for death amongst pwMS, but excess mortality was higher in women. More work and methods are needed to improve survival in pwMS.","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clément Tarrano, Giuseppe Zito, Cécile Galléa, Cécile Delorme, Eavan M. McGovern, Cyril Atkinson‐Clement, Vanessa Brochard, Stéphane Thobois, Christine Tranchant, David Grabli, Bertrand Degos, Jean Christophe Corvol, Jean‐Michel Pedespan, Pierre Krystkowiak, Jean‐Luc Houeto, Adrian Degardin, Luc Defebvre, Mélanie Didier, Romain Valabrègue, Emmanuelle Apartis, Marie Vidailhet, Emmanuel Roze, Yulia Worbe
Background and PurposeMyoclonus dystonia due to a pathogenic variant in SGCE (MYC/DYT‐SGCE) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT‐SGCE.MethodsWe used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT‐SGCE patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis.ResultsEighteen MYC/DYT‐SGCE patients and 24 HVs were analyzed. MYC/DYT‐SGCE patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters.ConclusionsIn MYC/DYT‐SGCE, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia.
{"title":"Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia","authors":"Clément Tarrano, Giuseppe Zito, Cécile Galléa, Cécile Delorme, Eavan M. McGovern, Cyril Atkinson‐Clement, Vanessa Brochard, Stéphane Thobois, Christine Tranchant, David Grabli, Bertrand Degos, Jean Christophe Corvol, Jean‐Michel Pedespan, Pierre Krystkowiak, Jean‐Luc Houeto, Adrian Degardin, Luc Defebvre, Mélanie Didier, Romain Valabrègue, Emmanuelle Apartis, Marie Vidailhet, Emmanuel Roze, Yulia Worbe","doi":"10.1111/ene.16460","DOIUrl":"https://doi.org/10.1111/ene.16460","url":null,"abstract":"Background and PurposeMyoclonus dystonia due to a pathogenic variant in <jats:italic>SGCE</jats:italic> (MYC/DYT‐<jats:italic>SGCE</jats:italic>) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT‐<jats:italic>SGCE</jats:italic>.MethodsWe used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT‐<jats:italic>SGCE</jats:italic> patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis.ResultsEighteen MYC/DYT‐<jats:italic>SGCE</jats:italic> patients and 24 HVs were analyzed. MYC/DYT‐<jats:italic>SGCE</jats:italic> patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters.ConclusionsIn MYC/DYT‐<jats:italic>SGCE</jats:italic>, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia.","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin‐Yu Shen, Ying‐Jie Dai, Thanh N. Nguyen, Hui‐Sheng Chen
Background and PurposeThe benefit of remote ischaemic conditioning (RIC) in acute moderate ischaemic stroke has been demonstrated by the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) study. This prespecified exploratory analysis aimed to determine whether there was a difference of RIC efficacy in anterior versus posterior circulation stroke based on RICAMIS data.MethodsIn this analysis, eligible patients presenting within 48 h of stroke onset were divided into two groups: anterior circulation stroke (ACS) and posterior circulation stroke (PCS) groups. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) score 0–1 at 90 days.ResultsIn all, 1013 patients were included in the final analysis, including 642 with ACS and 371 with PCS. Compared with the control group, RIC was significantly associated with an increased proportion of mRS scores 0–1 within 90 days in the PCS group (unadjusted odds ratio 1.6, 95% confidence interval 1.0–2.4, p = 0.04; adjusted odds ratio 2.0, 95% confidence interval 1.2–3.3, p = 0.005), but not in the ACS group (p = 0.29). Similar results were found regarding secondary outcomes including mRS score 0–2 at 90 days, mRS distribution at 90 days and change in National Institutes of Health Stroke Scale score at day 12 from baseline. However, there was no significant interaction effect between stroke location and intervention on the primary outcome (pinteraction = 0.21).ConclusionAmongst patients with acute PCS who are not candidates for reperfusion treatment, RIC may be associated with a higher probability of improved functional outcomes. These findings need to be validated in prospective trials.
{"title":"Differential efficacy of remote ischaemic conditioning in anterior versus posterior circulation stroke: A prespecified secondary analysis of the RICAMIS trial","authors":"Xin‐Yu Shen, Ying‐Jie Dai, Thanh N. Nguyen, Hui‐Sheng Chen","doi":"10.1111/ene.16458","DOIUrl":"https://doi.org/10.1111/ene.16458","url":null,"abstract":"Background and PurposeThe benefit of remote ischaemic conditioning (RIC) in acute moderate ischaemic stroke has been demonstrated by the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) study. This prespecified exploratory analysis aimed to determine whether there was a difference of RIC efficacy in anterior versus posterior circulation stroke based on RICAMIS data.MethodsIn this analysis, eligible patients presenting within 48 h of stroke onset were divided into two groups: anterior circulation stroke (ACS) and posterior circulation stroke (PCS) groups. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) score 0–1 at 90 days.ResultsIn all, 1013 patients were included in the final analysis, including 642 with ACS and 371 with PCS. Compared with the control group, RIC was significantly associated with an increased proportion of mRS scores 0–1 within 90 days in the PCS group (unadjusted odds ratio 1.6, 95% confidence interval 1.0–2.4, <jats:italic>p</jats:italic> = 0.04; adjusted odds ratio 2.0, 95% confidence interval 1.2–3.3, <jats:italic>p</jats:italic> = 0.005), but not in the ACS group (<jats:italic>p</jats:italic> = 0.29). Similar results were found regarding secondary outcomes including mRS score 0–2 at 90 days, mRS distribution at 90 days and change in National Institutes of Health Stroke Scale score at day 12 from baseline. However, there was no significant interaction effect between stroke location and intervention on the primary outcome (<jats:italic>p</jats:italic><jats:sub>interaction</jats:sub> = 0.21).ConclusionAmongst patients with acute PCS who are not candidates for reperfusion treatment, RIC may be associated with a higher probability of improved functional outcomes. These findings need to be validated in prospective trials.","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgia Stimpson, Deborah Ridout, Anna Sarkozy, Adnan Manzur, Francesco Muntoni, Giovanni Baranello
Background and purpose: Treatment with glucocorticoids (GCs) is part of the standard of care in Duchenne muscular dystrophy, but excess weight gain and height stunting are common side-effects. It is still unclear how these growth-related side-effects affect motor function.
Methods: This retrospective cohort study utilized 2228 observations from 648 participants in the UK NorthStar database who had growth and ambulation data recorded between 2006 and 2020. Joint modelling was used to analyse the effect of longitudinal growth centiles on loss of ambulation with respect to GC type and regimen.
Results: Loss of ambulation was observed in 113 patients. National estimates of loss of ambulation age were updated by GC group and showed no significant association between loss of ambulation risk and absolute growth centile. However, yearly drift in weight and/or height centile had an associated risk effect on loss of ambulation. Over a 2-year period, a yearly drift in weight from the 50th to the 75th, 75th to the 90th and 90th to the 95th centile was associated with 138%, 118% and 64% increased risk of loss of ambulation, respectively. Conversely, a 2-year drift in height from the 50th to the 25th, 25th to the 10th and 10th to the 5th centile was associated with 53%, 49% and 35% decreased risk of loss of ambulation, respectively.
Conclusions: Our results suggest a complex relationship between growth and loss of ambulation in Duchenne muscular dystrophy boys on chronic GCs, the first step in understanding the effects of drugs which also affect growth patterns.
{"title":"Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids.","authors":"Georgia Stimpson, Deborah Ridout, Anna Sarkozy, Adnan Manzur, Francesco Muntoni, Giovanni Baranello","doi":"10.1111/ene.16415","DOIUrl":"https://doi.org/10.1111/ene.16415","url":null,"abstract":"<p><strong>Background and purpose: </strong>Treatment with glucocorticoids (GCs) is part of the standard of care in Duchenne muscular dystrophy, but excess weight gain and height stunting are common side-effects. It is still unclear how these growth-related side-effects affect motor function.</p><p><strong>Methods: </strong>This retrospective cohort study utilized 2228 observations from 648 participants in the UK NorthStar database who had growth and ambulation data recorded between 2006 and 2020. Joint modelling was used to analyse the effect of longitudinal growth centiles on loss of ambulation with respect to GC type and regimen.</p><p><strong>Results: </strong>Loss of ambulation was observed in 113 patients. National estimates of loss of ambulation age were updated by GC group and showed no significant association between loss of ambulation risk and absolute growth centile. However, yearly drift in weight and/or height centile had an associated risk effect on loss of ambulation. Over a 2-year period, a yearly drift in weight from the 50th to the 75th, 75th to the 90th and 90th to the 95th centile was associated with 138%, 118% and 64% increased risk of loss of ambulation, respectively. Conversely, a 2-year drift in height from the 50th to the 25th, 25th to the 10th and 10th to the 5th centile was associated with 53%, 49% and 35% decreased risk of loss of ambulation, respectively.</p><p><strong>Conclusions: </strong>Our results suggest a complex relationship between growth and loss of ambulation in Duchenne muscular dystrophy boys on chronic GCs, the first step in understanding the effects of drugs which also affect growth patterns.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Serine Ferhat, Guillaume Bellanger, Malgorzata Milnerowicz, Maeva Kyheng, Julien Labreuche, Igor Sibon, Mehdi Khobzi, Joe-Marie Abousleiman, Dan-Adrian Popica, Solene Moulin, Cyril Dargazanli, Arturo Consoli, Omer Eker, Louis Veunac, Kevin Premat, Benjamin Gory, Jean-Christophe Gentric, Ricardo Moreno, Wagih Ben Hassen, Maxime Gauberti, Raoul Pop, Aymeric Rouchaud, Romain Bourcier, Bertrand Lapergue, Gaultier Marnat
Background and purpose: Vasospasm is a common iatrogenic event during mechanical thrombectomy (MT). In such circumstances, intra-arterial nimodipine administration is occasionally considered. However, its use in the treatment of iatrogenic vasospasm during MT has been poorly studied. We investigated the impact of iatrogenic vasospasm treated with intra-arterial nimodipine on outcomes after MT for large vessel occlusion stroke.
Methods: We conducted a retrospective analysis of the multicenter observational registry Endovascular Treatment in Ischemic Stroke (ETIS). Consecutive patients treated with MT between January 2015 and December 2022 were included. Patients treated with medical treatment alone, without MT, were excluded. We also excluded patients who received another in situ vasodilator molecule during the procedure. Outcomes were compared according to the occurrence of cervical and/or intracranial arterial vasospasm requiring intraoperative use of in situ nimodipine based on operator's decision, using a propensity score approach. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 90 days. Secondary outcomes included excellent outcome (mRS score 0-1), final recanalization, mortality, intracranial hemorrhage and procedural complications. Secondary analyses were performed according to the vasospasm location (intracranial or cervical).
Results: Among 13,678 patients in the registry during the study period, 434 received intra-arterial nimodipine for the treatment of MT-related vasospasm. In the main analysis, comparable odds of favorable outcome were observed, whereas excellent outcome was significantly less frequent in the group with vasospasm requiring nimodipine (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.63-0.97). Perfect recanalization, defined as a final modified Thrombolysis In Cerebral Infarction score of 3 (aOR 0.63, 95% CI 0.42-0.93), was also rarer in the vasospasm group. Intracranial vasospasm treated with nimodipine was significantly associated with worse clinical outcome (aOR 0.64, 95% CI 0.45-0.92), in contrast to the cervical location (aOR 1.37, 95% CI 0.54-3.08).
Conclusion: Arterial vasospasm occurring during the MT procedure and requiring intra-arterial nimodipine administration was associated with worse outcomes, especially in case of intracranial vasospasm. Although this study cannot formally differentiate whether the negative consequences were due to the vasospasm itself, or nimodipine administration or both, there might be an important signal toward a substantial clinical impact of iatrogenic vasospasm during MT.
{"title":"Iatrogenic arterial vasospasm during mechanical thrombectomy requiring treatment with intra-arterial nimodipine might be associated with worse outcomes.","authors":"Serine Ferhat, Guillaume Bellanger, Malgorzata Milnerowicz, Maeva Kyheng, Julien Labreuche, Igor Sibon, Mehdi Khobzi, Joe-Marie Abousleiman, Dan-Adrian Popica, Solene Moulin, Cyril Dargazanli, Arturo Consoli, Omer Eker, Louis Veunac, Kevin Premat, Benjamin Gory, Jean-Christophe Gentric, Ricardo Moreno, Wagih Ben Hassen, Maxime Gauberti, Raoul Pop, Aymeric Rouchaud, Romain Bourcier, Bertrand Lapergue, Gaultier Marnat","doi":"10.1111/ene.16467","DOIUrl":"https://doi.org/10.1111/ene.16467","url":null,"abstract":"<p><strong>Background and purpose: </strong>Vasospasm is a common iatrogenic event during mechanical thrombectomy (MT). In such circumstances, intra-arterial nimodipine administration is occasionally considered. However, its use in the treatment of iatrogenic vasospasm during MT has been poorly studied. We investigated the impact of iatrogenic vasospasm treated with intra-arterial nimodipine on outcomes after MT for large vessel occlusion stroke.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of the multicenter observational registry Endovascular Treatment in Ischemic Stroke (ETIS). Consecutive patients treated with MT between January 2015 and December 2022 were included. Patients treated with medical treatment alone, without MT, were excluded. We also excluded patients who received another in situ vasodilator molecule during the procedure. Outcomes were compared according to the occurrence of cervical and/or intracranial arterial vasospasm requiring intraoperative use of in situ nimodipine based on operator's decision, using a propensity score approach. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 90 days. Secondary outcomes included excellent outcome (mRS score 0-1), final recanalization, mortality, intracranial hemorrhage and procedural complications. Secondary analyses were performed according to the vasospasm location (intracranial or cervical).</p><p><strong>Results: </strong>Among 13,678 patients in the registry during the study period, 434 received intra-arterial nimodipine for the treatment of MT-related vasospasm. In the main analysis, comparable odds of favorable outcome were observed, whereas excellent outcome was significantly less frequent in the group with vasospasm requiring nimodipine (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.63-0.97). Perfect recanalization, defined as a final modified Thrombolysis In Cerebral Infarction score of 3 (aOR 0.63, 95% CI 0.42-0.93), was also rarer in the vasospasm group. Intracranial vasospasm treated with nimodipine was significantly associated with worse clinical outcome (aOR 0.64, 95% CI 0.45-0.92), in contrast to the cervical location (aOR 1.37, 95% CI 0.54-3.08).</p><p><strong>Conclusion: </strong>Arterial vasospasm occurring during the MT procedure and requiring intra-arterial nimodipine administration was associated with worse outcomes, especially in case of intracranial vasospasm. Although this study cannot formally differentiate whether the negative consequences were due to the vasospasm itself, or nimodipine administration or both, there might be an important signal toward a substantial clinical impact of iatrogenic vasospasm during MT.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}