Pub Date : 2025-07-13eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001032
Siddarth Kannan, Kajal Patel, Daniela Di Basilio, Antonia Kirkby, Manoj Sivan, Anthony Jones, Rajiv Mohanraj, Abhijit Das
Background: Functional neurological disorder (FND) frequently co-exists with chronic pain (CP), notably nociceptive and nociplastic (primary) pain disorders. The considerable overlap implies shared underlying mechanisms because of their similar clinical and epidemiological profiles. Although standard neuroimaging and electrophysiological tests typically show normal results in both FND and primary pain disorders, recent advancements in neuroimaging techniques have begun identifying neural biomarkers common to both conditions, though these findings remain preliminary and require further exploration.
Method: We performed a detailed literature review of studies investigating neural activity in FND and chronic pain using electroencephalogram, magneto-encephalography, functional MRI, positron emission tomography and single photon emission computed tomography. Given the diverse nature of the reviewed studies, the synthesis is presented narratively.
Results: Despite methodological differences, convergent data suggest disrupted neural networks across both FND and CP. Common findings include (1) hyperactivation of sensorimotor networks, (2) altered activity within the default mode network-a critical region for self-referential thought-and (3) dysfunction in emotional processing regions, notably the anterior cingulate cortex and insula. Thalamocortical dysrhythmia was identified as a potential unifying concept, characterised by abnormal theta and beta oscillations that enhance pain perception in CP and trigger functional symptoms in FND. Both conditions also exhibit reduced alpha oscillations, likely amplifying sensory sensitivity and emotional responsiveness.
Conclusion: This review highlights shared neural abnormalities (Triple Network model) and introduces thalamocortical dysrhythmia as a novel explanatory framework linking FND and CP. Future research should target populations with coexisting disorders, potentially paving the way for innovative treatments, including hypnosis and neuromodulation/neurofeedback.
{"title":"Shared neural signatures in Functional Neurological Disorder and Chronic Pain: a multimodal narrative review.","authors":"Siddarth Kannan, Kajal Patel, Daniela Di Basilio, Antonia Kirkby, Manoj Sivan, Anthony Jones, Rajiv Mohanraj, Abhijit Das","doi":"10.1136/bmjno-2025-001032","DOIUrl":"10.1136/bmjno-2025-001032","url":null,"abstract":"<p><strong>Background: </strong>Functional neurological disorder (FND) frequently co-exists with chronic pain (CP), notably nociceptive and nociplastic (primary) pain disorders. The considerable overlap implies shared underlying mechanisms because of their similar clinical and epidemiological profiles. Although standard neuroimaging and electrophysiological tests typically show normal results in both FND and primary pain disorders, recent advancements in neuroimaging techniques have begun identifying neural biomarkers common to both conditions, though these findings remain preliminary and require further exploration.</p><p><strong>Method: </strong>We performed a detailed literature review of studies investigating neural activity in FND and chronic pain using electroencephalogram, magneto-encephalography, functional MRI, positron emission tomography and single photon emission computed tomography. Given the diverse nature of the reviewed studies, the synthesis is presented narratively.</p><p><strong>Results: </strong>Despite methodological differences, convergent data suggest disrupted neural networks across both FND and CP. Common findings include (1) hyperactivation of sensorimotor networks, (2) altered activity within the default mode network-a critical region for self-referential thought-and (3) dysfunction in emotional processing regions, notably the anterior cingulate cortex and insula. Thalamocortical dysrhythmia was identified as a potential unifying concept, characterised by abnormal theta and beta oscillations that enhance pain perception in CP and trigger functional symptoms in FND. Both conditions also exhibit reduced alpha oscillations, likely amplifying sensory sensitivity and emotional responsiveness.</p><p><strong>Conclusion: </strong>This review highlights shared neural abnormalities (Triple Network model) and introduces thalamocortical dysrhythmia as a novel explanatory framework linking FND and CP. Future research should target populations with coexisting disorders, potentially paving the way for innovative treatments, including hypnosis and neuromodulation/neurofeedback.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001032"},"PeriodicalIF":2.1,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-07eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001102
Benjamin Scrivener, Harry Jordan, Neil Anderson, Tony Zhang, P Alan Barber, Cathy Stinear
Background: Functional weakness is common, and the prognosis can be poor without treatment. Transcranial magnetic stimulation (TMS) and specialist physiotherapy have each been trialled separately as interventions for functional weakness. We tested a novel approach for treating functional weakness and gait disorder using TMS as a primer before specialist physiotherapy.
Methods: Single-pulse TMS, therapeutic education and limb pressure feedback were used as a primer for immediate specialist physiotherapy. TMS-primed physiotherapy was used for the first time in three consecutive patients with functional limb weakness and immobility.
Results: Two women and one man (aged 30-55 years) with severe functional limb weakness such that they were unable to stand or walk independently, with symptom duration between 3 weeks and 7 years, were studied. All three had a rapid return of voluntary limb movement and achieved unassisted walking within a few hours of a single TMS-primed physiotherapy session. Treatment was well-tolerated, and outcomes were sustained at follow-up.
Conclusions: These cases provide preliminary evidence supporting the efficacy of this approach, which may be further developed with future research. They also illustrate a practical approach for treating a clinically challenging population with severe functional weakness.
{"title":"Transcranial magnetic stimulation as a primer for rapid improvement in functional neurological disorder: a case series.","authors":"Benjamin Scrivener, Harry Jordan, Neil Anderson, Tony Zhang, P Alan Barber, Cathy Stinear","doi":"10.1136/bmjno-2025-001102","DOIUrl":"10.1136/bmjno-2025-001102","url":null,"abstract":"<p><strong>Background: </strong>Functional weakness is common, and the prognosis can be poor without treatment. Transcranial magnetic stimulation (TMS) and specialist physiotherapy have each been trialled separately as interventions for functional weakness. We tested a novel approach for treating functional weakness and gait disorder using TMS as a primer before specialist physiotherapy.</p><p><strong>Methods: </strong>Single-pulse TMS, therapeutic education and limb pressure feedback were used as a primer for immediate specialist physiotherapy. TMS-primed physiotherapy was used for the first time in three consecutive patients with functional limb weakness and immobility.</p><p><strong>Results: </strong>Two women and one man (aged 30-55 years) with severe functional limb weakness such that they were unable to stand or walk independently, with symptom duration between 3 weeks and 7 years, were studied. All three had a rapid return of voluntary limb movement and achieved unassisted walking within a few hours of a single TMS-primed physiotherapy session. Treatment was well-tolerated, and outcomes were sustained at follow-up.</p><p><strong>Conclusions: </strong>These cases provide preliminary evidence supporting the efficacy of this approach, which may be further developed with future research. They also illustrate a practical approach for treating a clinically challenging population with severe functional weakness.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001102"},"PeriodicalIF":2.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-03eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2024-000954
Sophie Schumann, Jens Jürgen Schwarze, Silvio Brandt, Korinna Jöhrens, Olaf Dirsch, Karim Ibrahim, Bernhard Rosengarten
Objective: Atrial fibrillation (AF) is an important risk factor for cerebral stroke. We studied whether anticoagulation affected histological age aspects of thrombi retrieved from patients with AF-related stroke.
Methods: In this monocentric study, AF patients according to criteria (Trial of Org 10 172 in Acute Stroke Treatment) with occlusion of the middle cerebral artery were prospectively and consecutively included. They were assigned to three groups: anticoagulation naïve, adequately anticoagulated, and with paused anticoagulation. In addition to patient characteristics and stroke workup, extracted thrombi were histologically classified into different age categories according to their cellular to fibrotic transition.
Results: A total of 244 patients were studied, from which 136 (58 females; 78±9 years) were drug naïve, 34 (15 females; 78±8 years) had paused anticoagulation, and 74 (29 females; 79±9 years) were adequately anticoagulated. Groups did not differ regarding stroke severity at admission (modified Rankin Score, mRS: median, IQR: 5 (1); 5 (0.75); 5 (1), respectively; National Institutes of Health Stroke Scale (NIHSS): median, IQR: 16 (8); 16 (8); 16 (7), respectively). Due to thrombectomy, median scores declined in all groups without differences between groups (mRS: 3.5 (4); 4 (4); 4 (4); NIHSS: 5 (16); 11 (31); 7 (18)). With a small but significant effect (p=0.043), thrombus age differed between the groups due to significantly younger thrombi in the paused medication group as compared with the adequately anticoagulated patients.
Conclusions: Thrombus age distribution seems not to be affected by anticoagulation. The younger thrombi in patients with paused anticoagulation possibly point to a rebound effect needing further investigations.
{"title":"Effect of anticoagulation on the age distribution of thrombi in stroke patients with non-valvular atrial fibrillation.","authors":"Sophie Schumann, Jens Jürgen Schwarze, Silvio Brandt, Korinna Jöhrens, Olaf Dirsch, Karim Ibrahim, Bernhard Rosengarten","doi":"10.1136/bmjno-2024-000954","DOIUrl":"10.1136/bmjno-2024-000954","url":null,"abstract":"<p><strong>Objective: </strong>Atrial fibrillation (AF) is an important risk factor for cerebral stroke. We studied whether anticoagulation affected histological age aspects of thrombi retrieved from patients with AF-related stroke.</p><p><strong>Methods: </strong>In this monocentric study, AF patients according to criteria (Trial of Org 10 172 in Acute Stroke Treatment) with occlusion of the middle cerebral artery were prospectively and consecutively included. They were assigned to three groups: anticoagulation naïve, adequately anticoagulated, and with paused anticoagulation. In addition to patient characteristics and stroke workup, extracted thrombi were histologically classified into different age categories according to their cellular to fibrotic transition.</p><p><strong>Results: </strong>A total of 244 patients were studied, from which 136 (58 females; 78±9 years) were drug naïve, 34 (15 females; 78±8 years) had paused anticoagulation, and 74 (29 females; 79±9 years) were adequately anticoagulated. Groups did not differ regarding stroke severity at admission (modified Rankin Score, mRS: median, IQR: 5 (1); 5 (0.75); 5 (1), respectively; National Institutes of Health Stroke Scale (NIHSS): median, IQR: 16 (8); 16 (8); 16 (7), respectively). Due to thrombectomy, median scores declined in all groups without differences between groups (mRS: 3.5 (4); 4 (4); 4 (4); NIHSS: 5 (16); 11 (31); 7 (18)). With a small but significant effect (p=0.043), thrombus age differed between the groups due to significantly younger thrombi in the paused medication group as compared with the adequately anticoagulated patients.</p><p><strong>Conclusions: </strong>Thrombus age distribution seems not to be affected by anticoagulation. The younger thrombi in patients with paused anticoagulation possibly point to a rebound effect needing further investigations.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e000954"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-03eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001092
Lene von Kappelgaard, Elisabeth Framke, Ditte Vassard, Anja Pinborg, Juan Enrique Schwarze, Meritxell Sabidó, Melinda Magyari
Background: Evidence is scarce concerning the impact on postpartum relapse activity of disease-modifying therapy (DMT) use during pregnancy after assisted reproductive technology (ART) treatment. We investigated relapse activity before pregnancy, during pregnancy and 3 and 12 months postpartum overall and according to DMT exposure during pregnancy.
Methods: Women with relapsing-remitting multiple sclerosis (MS) from the Danish MS Registry who gave birth after ART from 1995 to 2018 were eligible for inclusion. Annualised relapse rate (ARR) before pregnancy, during pregnancy and postpartum was evaluated using a negative binomial regression model with relapse count as the dependent variable overall and according to DMT exposure during pregnancy. Logistic regression was used to identify predictors of being relapse-free 12 months postpartum.
Results: A total of 111 women, median age 32 years (IQR: 29-35), were included. Overall, ARR (95% CI) was 0.14 (0.08 to 0.24) before pregnancy, 0.13 (0.07 to 0.25) during pregnancy and 0.33 (0.17 to 0.61) 3 months postpartum; rate ratio difference between before pregnancy and postpartum was 2.42 (1.03 to 5.67), and between during pregnancy and postpartum was 2.46 (1.18 to 5.13). Age ≥35 years and no DMT exposure before pregnancy were predictors of being relapse-free 12 months postpartum.
Conclusions: Relapse activity was more than two times higher 3 months postpartum than before and during pregnancy. Stratified for DMT exposure during pregnancy, rate ratios were similar and did not reach statistical significance. Postpartum relapse activity more than doubled from both low ARR (unexposed to DMT during pregnancy) and higher ARR (exposed to DMT during pregnancy) pre-pregnancy.
{"title":"Disease-modifying therapy during pregnancy and postpartum relapse activity in women with multiple sclerosis undergoing assisted reproductive technology treatment: a nationwide cohort study.","authors":"Lene von Kappelgaard, Elisabeth Framke, Ditte Vassard, Anja Pinborg, Juan Enrique Schwarze, Meritxell Sabidó, Melinda Magyari","doi":"10.1136/bmjno-2025-001092","DOIUrl":"10.1136/bmjno-2025-001092","url":null,"abstract":"<p><strong>Background: </strong>Evidence is scarce concerning the impact on postpartum relapse activity of disease-modifying therapy (DMT) use during pregnancy after assisted reproductive technology (ART) treatment. We investigated relapse activity before pregnancy, during pregnancy and 3 and 12 months postpartum overall and according to DMT exposure during pregnancy.</p><p><strong>Methods: </strong>Women with relapsing-remitting multiple sclerosis (MS) from the Danish MS Registry who gave birth after ART from 1995 to 2018 were eligible for inclusion. Annualised relapse rate (ARR) before pregnancy, during pregnancy and postpartum was evaluated using a negative binomial regression model with relapse count as the dependent variable overall and according to DMT exposure during pregnancy. Logistic regression was used to identify predictors of being relapse-free 12 months postpartum.</p><p><strong>Results: </strong>A total of 111 women, median age 32 years (IQR: 29-35), were included. Overall, ARR (95% CI) was 0.14 (0.08 to 0.24) before pregnancy, 0.13 (0.07 to 0.25) during pregnancy and 0.33 (0.17 to 0.61) 3 months postpartum; rate ratio difference between before pregnancy and postpartum was 2.42 (1.03 to 5.67), and between during pregnancy and postpartum was 2.46 (1.18 to 5.13). Age ≥35 years and no DMT exposure before pregnancy were predictors of being relapse-free 12 months postpartum.</p><p><strong>Conclusions: </strong>Relapse activity was more than two times higher 3 months postpartum than before and during pregnancy. Stratified for DMT exposure during pregnancy, rate ratios were similar and did not reach statistical significance. Postpartum relapse activity more than doubled from both low ARR (unexposed to DMT during pregnancy) and higher ARR (exposed to DMT during pregnancy) pre-pregnancy.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001092"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-26eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001107
Alessandro Padovani, Irene Mattioli, Tiziana Comunale, Nicola Zoppi, Cinzia Zatti, Enis Guso, Marcello Catania, Andrea Morotti, Chiara Agosti, Stefano Gipponi, Lynne Turner-Stokes, Andrea Pilotto
Abstract:
Background: Given the increasing diversity among neurological patients, standardised protocols are essential for evaluating the severity and complexity of the variety of conditions. The aim of the present work was to standardise the assessment of the severity and complexity of neurological impairment in an acute setting by using a modified version of the Neurological Impairment Scale (mNIS).
Methods: Consecutively hospitalised neurological inpatients underwent a multidimensional standardised assessment of multimorbidity, frailty, functional dependency and neurological impairment using mNIS and other validated scales. Inter-rater reliability of the mNIS total and subscores was evaluated. Construct validity was assessed separately in patients with cerebrovascular disease, performing correlations between corresponding subscores of mNIS, original NIS and National Institutes of Health Stroke Scale. mNIS Complexity Index (mNIS-CI) for neurological severity was used to classify patients into subtle, mild, moderate and severe impairment.
Results: 1081 neurological patients admitted to a neurological ward from the emergency setting were enrolled. The inter-rater reliability was remarkable for mNIS total and subscores (intraclass correlation coefficient 0.90, 95% CI 0.82 to 0.95). The mNIS showed strong construct validity for total and subscores compared with other clinical scales (r 0.47-0.97, p<0.001) and 52.7% of patients scored at least one in one of the four newly listed items. The stratification of patients according to mNIS-CI exhibited high construct validity, distinguishing the extent of impairment and involved domains.
Conclusions: The mNIS is valuable for measuring neurological severity and complexity in acute inpatients and holds significant potential for application in different settings.
摘要:背景:鉴于神经系统患者的多样性日益增加,标准化的方案对于评估各种疾病的严重性和复杂性至关重要。本研究的目的是通过使用改良版的神经损伤量表(mNIS)对急性环境中神经损伤的严重程度和复杂性进行标准化评估。方法:对连续住院的神经系统住院患者采用mNIS及其他经验证的量表对其多病、虚弱、功能依赖和神经功能损害进行多维标准化评估。评估了mNIS总分和分值的评分间信度。在脑血管疾病患者中单独评估结构效度,将mNIS、原始NIS和美国国立卫生研究院卒中量表的相应亚分进行相关性分析。神经系统严重程度的mNIS复杂性指数(mNIS- ci)将患者分为轻度、轻度、中度和重度。结果:1081名急诊科神经病房的患者入组。mNIS总分和分值的组间信度显著(组内相关系数0.90,95% CI 0.82 ~ 0.95)。与其他临床量表相比,mNIS在总分和亚分上显示出较强的结构效度(r = 0.47-0.97)。结论:mNIS在衡量急性住院患者神经系统严重程度和复杂性方面具有重要价值,在不同的环境中具有显著的应用潜力。
{"title":"Measuring neurological severity and complexity in acute setting: the modified Neurological Impairment Scale.","authors":"Alessandro Padovani, Irene Mattioli, Tiziana Comunale, Nicola Zoppi, Cinzia Zatti, Enis Guso, Marcello Catania, Andrea Morotti, Chiara Agosti, Stefano Gipponi, Lynne Turner-Stokes, Andrea Pilotto","doi":"10.1136/bmjno-2025-001107","DOIUrl":"10.1136/bmjno-2025-001107","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Background: </strong>Given the increasing diversity among neurological patients, standardised protocols are essential for evaluating the severity and complexity of the variety of conditions. The aim of the present work was to standardise the assessment of the severity and complexity of neurological impairment in an acute setting by using a modified version of the Neurological Impairment Scale (mNIS).</p><p><strong>Methods: </strong>Consecutively hospitalised neurological inpatients underwent a multidimensional standardised assessment of multimorbidity, frailty, functional dependency and neurological impairment using mNIS and other validated scales. Inter-rater reliability of the mNIS total and subscores was evaluated. Construct validity was assessed separately in patients with cerebrovascular disease, performing correlations between corresponding subscores of mNIS, original NIS and National Institutes of Health Stroke Scale. mNIS Complexity Index (mNIS-CI) for neurological severity was used to classify patients into subtle, mild, moderate and severe impairment.</p><p><strong>Results: </strong>1081 neurological patients admitted to a neurological ward from the emergency setting were enrolled. The inter-rater reliability was remarkable for mNIS total and subscores (intraclass correlation coefficient 0.90, 95% CI 0.82 to 0.95). The mNIS showed strong construct validity for total and subscores compared with other clinical scales (r 0.47-0.97, p<0.001) and 52.7% of patients scored at least one in one of the four newly listed items. The stratification of patients according to mNIS-CI exhibited high construct validity, distinguishing the extent of impairment and involved domains.</p><p><strong>Conclusions: </strong>The mNIS is valuable for measuring neurological severity and complexity in acute inpatients and holds significant potential for application in different settings.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 1","pages":"e001107"},"PeriodicalIF":2.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND. This study confirmed positive signs of functional limb weakness (hereafter positive signs) in patients with long COVID.
Methods: This was an observational, retrospective, single-centre study at an outpatient clinic conducted from 1 June 2021 to 31 May 2024. We collected patients' clinical data, including positive signs. The primary outcome was the prevalence of positive signs. Patients with positive signs were followed up over 2 months, and subjective patient perceptions of symptomatic improvements and changes in positive signs were analysed.
Results: Overall, 502 were diagnosed with long COVID, and 100 assessed patients had positive signs. Female sex, time of infection after 2022, comorbidity of psychiatric diseases, fatigue, headache and muscle weakness were statistically significant in patients with positive signs compared with those in patients without positive signs. 89 patients (41 with positive signs and 48 without positive signs) were followed up, and 28 (68.3%) with positive signs and 33 (68.8%) without positive signs reported improvements. Positive signs disappeared in patients with symptomatic improvements but not in patients without symptomatic improvements (p=0.0001).
Conclusions: Positive signs were found in over one-third of patients (33.9%) who were investigated in this study. Some positive signs disappeared concurrently with their symptomatic improvement.
{"title":"Contemporary positive signs of functional limb weakness in post-acute sequelae of SARS-CoV-2: an exploratory analysis of their utility in diagnosis and follow-up.","authors":"Masayuki Ohira, Takashi Osada, Hiroaki Kimura, Terunori Sano, Masaki Takao","doi":"10.1136/bmjno-2024-000995","DOIUrl":"10.1136/bmjno-2024-000995","url":null,"abstract":"<p><strong>Background: </strong>Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND. This study confirmed positive signs of functional limb weakness (hereafter positive signs) in patients with long COVID.</p><p><strong>Methods: </strong>This was an observational, retrospective, single-centre study at an outpatient clinic conducted from 1 June 2021 to 31 May 2024. We collected patients' clinical data, including positive signs. The primary outcome was the prevalence of positive signs. Patients with positive signs were followed up over 2 months, and subjective patient perceptions of symptomatic improvements and changes in positive signs were analysed.</p><p><strong>Results: </strong>Overall, 502 were diagnosed with long COVID, and 100 assessed patients had positive signs. Female sex, time of infection after 2022, comorbidity of psychiatric diseases, fatigue, headache and muscle weakness were statistically significant in patients with positive signs compared with those in patients without positive signs. 89 patients (41 with positive signs and 48 without positive signs) were followed up, and 28 (68.3%) with positive signs and 33 (68.8%) without positive signs reported improvements. Positive signs disappeared in patients with symptomatic improvements but not in patients without symptomatic improvements (p=0.0001).</p><p><strong>Conclusions: </strong>Positive signs were found in over one-third of patients (33.9%) who were investigated in this study. Some positive signs disappeared concurrently with their symptomatic improvement.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 1","pages":"e000995"},"PeriodicalIF":2.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-23eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001076
Lesley-Ann Miller-Wilson, Joel Arackal, Yuriy Edwards, Jennifer Schwinn, Kristen Elizabeth Rockstein, Brett Venker, Richard J Nowak
Background: The epidemiology of myasthenia gravis (MG), a rare autoimmune disease, is not completely understood. This retrospective claims analysis assessed the epidemiologic rates of MG in the USA and the characteristics of the incident and prevalent MG populations.
Methods: Patients with MG were identified using Inovalon closed claims data; those with ≥2 International Classification of Diseases, 10th Revision (ICD-10) codes for MG from 2016 to 2019, separated by ≥30 days, were eligible. Patients in the prevalent cohort had continuous insurance coverage from January to December 2019. Patients in the incident cohort had continuous insurance coverage from January 2018 to December 2019 and no MG claims before 2019. Incidence and prevalence rates were adjusted using US census data. Treatment utilisation was assessed in both cohorts and grouped by provider type. Exacerbations were identified using ICD-10 code G70.01; codes occurring ≤30 days following a previous exacerbation code were considered as part of a single event.
Results: The incident cohort included 1442 patients (adjusted incidence: 4.3 per 100000); the prevalent cohort included 14 373 patients (adjusted prevalence: 35.7 per 100 000). In 2019, approximately two-thirds of patients in both cohorts (incident, 67.7%; prevalent, 61.6%) received MG treatments, most commonly acetylcholinesterase inhibitors, followed by oral steroids. Among incident patients with ≥1 year of continuous follow-up (n=1204), 32.1% (n=387) experienced ≥1 exacerbation, with 50% (n=194) having ≥2 exacerbations and 41% (n=159) having an exacerbation as the index MG event.
Conclusions: Estimates of MG incidence and prevalence were comparable to findings from two recent US studies. Acetylcholinesterase inhibitors and corticosteroids remain widely used. Exacerbations occurred in >30% of incident patients with ≥1 year of continuous follow-up, including 13% who had a relapse as their index event. These results highlight the need for earlier detection and use of more effective therapies in the treatment paradigm to achieve sustained disease control.
{"title":"Epidemiology and patient characteristics of the US myasthenia gravis population: real-world evidence from a large insurance claims database.","authors":"Lesley-Ann Miller-Wilson, Joel Arackal, Yuriy Edwards, Jennifer Schwinn, Kristen Elizabeth Rockstein, Brett Venker, Richard J Nowak","doi":"10.1136/bmjno-2025-001076","DOIUrl":"10.1136/bmjno-2025-001076","url":null,"abstract":"<p><strong>Background: </strong>The epidemiology of myasthenia gravis (MG), a rare autoimmune disease, is not completely understood. This retrospective claims analysis assessed the epidemiologic rates of MG in the USA and the characteristics of the incident and prevalent MG populations.</p><p><strong>Methods: </strong>Patients with MG were identified using Inovalon closed claims data; those with ≥2 <i>International Classification of Diseases, 10th Revision</i> (ICD-10) codes for MG from 2016 to 2019, separated by ≥30 days, were eligible. Patients in the prevalent cohort had continuous insurance coverage from January to December 2019. Patients in the incident cohort had continuous insurance coverage from January 2018 to December 2019 and no MG claims before 2019. Incidence and prevalence rates were adjusted using US census data. Treatment utilisation was assessed in both cohorts and grouped by provider type. Exacerbations were identified using ICD-10 code G70.01; codes occurring ≤30 days following a previous exacerbation code were considered as part of a single event.</p><p><strong>Results: </strong>The incident cohort included 1442 patients (adjusted incidence: 4.3 per 100000); the prevalent cohort included 14 373 patients (adjusted prevalence: 35.7 per 100 000). In 2019, approximately two-thirds of patients in both cohorts (incident, 67.7%; prevalent, 61.6%) received MG treatments, most commonly acetylcholinesterase inhibitors, followed by oral steroids. Among incident patients with ≥1 year of continuous follow-up (n=1204), 32.1% (n=387) experienced ≥1 exacerbation, with 50% (n=194) having ≥2 exacerbations and 41% (n=159) having an exacerbation as the index MG event.</p><p><strong>Conclusions: </strong>Estimates of MG incidence and prevalence were comparable to findings from two recent US studies. Acetylcholinesterase inhibitors and corticosteroids remain widely used. Exacerbations occurred in >30% of incident patients with ≥1 year of continuous follow-up, including 13% who had a relapse as their index event. These results highlight the need for earlier detection and use of more effective therapies in the treatment paradigm to achieve sustained disease control.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 1","pages":"e001076"},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2023-000459ret
[This retracts the article DOI: 10.1136/bmjno-2023-000459.].
[本文撤回文章DOI: 10.1136/bmjno-2023-000459.]。
{"title":"Retraction: Novel IRF2BPL gene mutation manifesting as a broad spectrum of neurological disorders: a case report.","authors":"","doi":"10.1136/bmjno-2023-000459ret","DOIUrl":"10.1136/bmjno-2023-000459ret","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1136/bmjno-2023-000459.].</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 1","pages":"e000459ret"},"PeriodicalIF":2.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001160
Mohammed Almubayyidh, David A Jenkins, Edoardo Gaude, Adrian R Parry-Jones
Abstract:
Introduction: Accurate and timely differentiation of intracerebral haemorrhage (ICH) from other suspected stroke cases is crucial in prehospital settings, where early blood pressure reduction in the ambulance can improve outcomes. This study aims to assess whether combining clinical predictors and glial fibrillary acidic protein (GFAP) in prediction models can effectively distinguish ICH from other suspected stroke cases.
Methods: Data were derived from the Testing for Identification Markers of Stroke trial, a prospective diagnostic accuracy study. Suspected stroke patients within 6 hours of symptom onset were included. Clinical predictors were selected based on known associations with ICH, and a predefined GFAP cut-off of 290 pg/mL was applied. Logistic regression was used to assess the performance of clinical predictors and GFAP, individually and in combination. Internal validation and optimism correction were performed via bootstrapping, and comparisons of the area under the curve (AUC) were conducted using DeLong's test.
Results: We included 209 suspected stroke cases, of which 5% were finally diagnosed with ICH. Clinical predictors alone achieved an optimism-corrected AUC of 0.74 (95% CI 0.60 to 0.88), while GFAP alone resulted in an optimism-corrected AUC of 0.83 (95% CI 0.69 to 0.99). Combining clinical predictors with GFAP significantly enhanced the AUC, yielding an optimism-corrected value of 0.90 (95% CI 0.79 to 0.98). This combined model also demonstrated high predictive accuracy, with an optimism-corrected sensitivity of 60% (95% CI 29.0% to 90.0%) and a specificity of 98% (95% CI 96.1% to 100.0%).
Conclusions: Combining clinical predictors with GFAP shows promise for the prehospital identification of ICH to support transport decision-making and potentially initiate treatment while en route for these patients. Prospective validation using portable point-of-care devices is required to confirm the utility of this approach in the prehospital setting.
摘要:引言:准确和及时地区分脑出血(ICH)与其他疑似中风病例在院前环境中至关重要,在救护车中早期降低血压可以改善预后。本研究旨在评估在预测模型中结合临床预测因子和胶质纤维酸性蛋白(GFAP)是否能有效区分脑出血与其他疑似脑卒中病例。方法:数据来源于卒中识别标记物测试试验,这是一项前瞻性诊断准确性研究。纳入症状出现6小时内的疑似脑卒中患者。根据已知的与脑出血的关联选择临床预测因子,并采用预定义的GFAP临界值290 pg/mL。采用Logistic回归单独或联合评估临床预测指标和GFAP的表现。采用bootstrapping进行内部验证和乐观校正,采用DeLong’s test比较曲线下面积(AUC)。结果:我们纳入了209例疑似脑卒中病例,其中5%最终诊断为脑出血。单独的临床预测获得了0.74的乐观校正AUC (95% CI 0.60 - 0.88),而单独的GFAP导致了0.83的乐观校正AUC (95% CI 0.69 - 0.99)。结合临床预测因子和GFAP显著提高了AUC,得到了0.90的乐观校正值(95% CI 0.79 - 0.98)。该联合模型也显示出较高的预测准确性,乐观校正后的灵敏度为60% (95% CI 29.0%至90.0%),特异性为98% (95% CI 96.1%至100.0%)。结论:将临床预测指标与GFAP相结合,有望在院前识别脑出血,以支持转运决策,并可能在途中为这些患者启动治疗。需要使用便携式护理点设备进行前瞻性验证,以确认该方法在院前环境中的实用性。
{"title":"Integrating clinical predictors and glial fibrillary acidic protein in prediction models for the prehospital identification of intracerebral haemorrhage in suspected stroke.","authors":"Mohammed Almubayyidh, David A Jenkins, Edoardo Gaude, Adrian R Parry-Jones","doi":"10.1136/bmjno-2025-001160","DOIUrl":"10.1136/bmjno-2025-001160","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Introduction: </strong>Accurate and timely differentiation of intracerebral haemorrhage (ICH) from other suspected stroke cases is crucial in prehospital settings, where early blood pressure reduction in the ambulance can improve outcomes. This study aims to assess whether combining clinical predictors and glial fibrillary acidic protein (GFAP) in prediction models can effectively distinguish ICH from other suspected stroke cases.</p><p><strong>Methods: </strong>Data were derived from the Testing for Identification Markers of Stroke trial, a prospective diagnostic accuracy study. Suspected stroke patients within 6 hours of symptom onset were included. Clinical predictors were selected based on known associations with ICH, and a predefined GFAP cut-off of 290 pg/mL was applied. Logistic regression was used to assess the performance of clinical predictors and GFAP, individually and in combination. Internal validation and optimism correction were performed via bootstrapping, and comparisons of the area under the curve (AUC) were conducted using DeLong's test.</p><p><strong>Results: </strong>We included 209 suspected stroke cases, of which 5% were finally diagnosed with ICH. Clinical predictors alone achieved an optimism-corrected AUC of 0.74 (95% CI 0.60 to 0.88), while GFAP alone resulted in an optimism-corrected AUC of 0.83 (95% CI 0.69 to 0.99). Combining clinical predictors with GFAP significantly enhanced the AUC, yielding an optimism-corrected value of 0.90 (95% CI 0.79 to 0.98). This combined model also demonstrated high predictive accuracy, with an optimism-corrected sensitivity of 60% (95% CI 29.0% to 90.0%) and a specificity of 98% (95% CI 96.1% to 100.0%).</p><p><strong>Conclusions: </strong>Combining clinical predictors with GFAP shows promise for the prehospital identification of ICH to support transport decision-making and potentially initiate treatment while en route for these patients. Prospective validation using portable point-of-care devices is required to confirm the utility of this approach in the prehospital setting.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 1","pages":"e001160"},"PeriodicalIF":2.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19eCollection Date: 2025-01-01DOI: 10.1136/bmjno-2025-001114
Vivek Pidugun, Daniel Wardman, Peter Thomas, Helen Badge, Jing Ji, Chushuang Chen, Timmy Pham, Andrew K Cheung, Nathan Manning, Christopher Blair, Cecilia Cappelen-Smith, Longting Lin, Suzanne J Hodgkinson, Alan McDougall, Mark Parsons, Dennis Cordato
Background: Access to endovascular thrombectomy (EVT) for acute ischaemic stroke (AIS) and the outcome disparities in culturally and linguistically diverse (CALD) populations are understudied. South-Western Sydney (SWS), characterised by high prevalence of CALD populations, provides an ideal setting to explore these disparities. This study aimed to assess whether being born in a country where English is not the primary language ('language other than English'; LOTE) affects access to EVT and outcomes for acute ischaemic stroke while also identifying demographic risk factors influencing stroke severity and outcomes.
Methods: A retrospective cohort study was conducted on consecutive patients with AIS who underwent EVT at Liverpool Hospital, Sydney, from 2018 to 2023. Participants were categorised based on country-of-origin Australia/New Zealand/United Kingdom or LOTE. Primary outcomes included time metrics-onset-to-arrival (OTA) and arrival-to-puncture (ATP)-and 3-month modified Rankin Score (mRS). Statistical analyses included multivariate logistic regression to evaluate predictors of functional outcomes.
Results: Of 911 EVT referrals, 721 patients were included. LOTE patients (50.3%) were more likely to have diabetes mellitus (30% vs 16%; p<0.001) and presented with higher stroke severity (median National Institutes of Health Stroke Scale (NIHSS) 17 vs 14; p<0.001). They also experienced shorter ATP (158 vs 174 min; p=0.006). Patients requiring interpreters equally exhibited shorter ATP times (152 vs 170 min; p=0.01) and higher stroke severity. There was no significant disadvantage hailing from the LOTE group in OTA times and in any time metrics for subgroup analyses stratified by primary presenter status. However, LOTE patients had poorer 3-month outcomes (mRS ≤2: 46.5% vs 55.4%; p=0.021), which was associated with higher baseline NIHSS and diabetes in adjusted analyses.
Conclusion: LOTE patients in SWS undergoing EVT were not disadvantaged in hospital time metrics. Poorer 3-month functional outcomes in LOTE patients highlight the need for targeted strategies addressing risk factors, such as diabetes mellitus.
背景:急性缺血性卒中(AIS)的血管内血栓切除术(EVT)以及文化和语言多样性(CALD)人群的结果差异尚未得到充分研究。西南悉尼(SWS)的特点是CALD人群的高患病率,为探索这些差异提供了理想的环境。这项研究旨在评估是否出生在英语不是主要语言的国家(“英语以外的语言”;LOTE)影响急性缺血性卒中的EVT获取和预后,同时也确定影响卒中严重程度和预后的人口统计学危险因素。方法:对2018年至2023年在悉尼利物浦医院连续接受EVT治疗的AIS患者进行回顾性队列研究。参与者根据原产国澳大利亚/新西兰/英国或LOTE进行分类。主要结局包括时间指标——从发病到到达(OTA)和到达到穿刺(ATP),以及3个月的修正Rankin评分(mRS)。统计分析包括多变量逻辑回归来评估功能结局的预测因素。结果:在911例EVT转诊中,纳入721例患者。LOTE患者(50.3%)更容易患糖尿病(30% vs 16%;结论:在接受EVT治疗的SWS患者中,LOTE患者在住院时间指标上并不处于劣势。LOTE患者3个月的功能预后较差,这表明需要针对糖尿病等危险因素采取有针对性的策略。
{"title":"Time to endovascular thrombectomy for acute ischaemic stroke in language other than English (LOTE) communities in South-Western Sydney.","authors":"Vivek Pidugun, Daniel Wardman, Peter Thomas, Helen Badge, Jing Ji, Chushuang Chen, Timmy Pham, Andrew K Cheung, Nathan Manning, Christopher Blair, Cecilia Cappelen-Smith, Longting Lin, Suzanne J Hodgkinson, Alan McDougall, Mark Parsons, Dennis Cordato","doi":"10.1136/bmjno-2025-001114","DOIUrl":"10.1136/bmjno-2025-001114","url":null,"abstract":"<p><strong>Background: </strong>Access to endovascular thrombectomy (EVT) for acute ischaemic stroke (AIS) and the outcome disparities in culturally and linguistically diverse (CALD) populations are understudied. South-Western Sydney (SWS), characterised by high prevalence of CALD populations, provides an ideal setting to explore these disparities. This study aimed to assess whether being born in a country where English is not the primary language ('language other than English'; LOTE) affects access to EVT and outcomes for acute ischaemic stroke while also identifying demographic risk factors influencing stroke severity and outcomes.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on consecutive patients with AIS who underwent EVT at Liverpool Hospital, Sydney, from 2018 to 2023. Participants were categorised based on country-of-origin Australia/New Zealand/United Kingdom or LOTE. Primary outcomes included time metrics-onset-to-arrival (OTA) and arrival-to-puncture (ATP)-and 3-month modified Rankin Score (mRS). Statistical analyses included multivariate logistic regression to evaluate predictors of functional outcomes.</p><p><strong>Results: </strong>Of 911 EVT referrals, 721 patients were included. LOTE patients (50.3%) were more likely to have diabetes mellitus (30% vs 16%; p<0.001) and presented with higher stroke severity (median National Institutes of Health Stroke Scale (NIHSS) 17 vs 14; p<0.001). They also experienced shorter ATP (158 vs 174 min; p=0.006). Patients requiring interpreters equally exhibited shorter ATP times (152 vs 170 min; p=0.01) and higher stroke severity. There was no significant disadvantage hailing from the LOTE group in OTA times and in any time metrics for subgroup analyses stratified by primary presenter status. However, LOTE patients had poorer 3-month outcomes (mRS ≤2: 46.5% vs 55.4%; p=0.021), which was associated with higher baseline NIHSS and diabetes in adjusted analyses.</p><p><strong>Conclusion: </strong>LOTE patients in SWS undergoing EVT were not disadvantaged in hospital time metrics. Poorer 3-month functional outcomes in LOTE patients highlight the need for targeted strategies addressing risk factors, such as diabetes mellitus.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 1","pages":"e001114"},"PeriodicalIF":2.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}