Pub Date : 2024-09-18DOI: 10.1136/bmjno-2024-000792
Andrew G L Douglas, Alexander G Thompson, Martin R Turner, Kevin Talbot
Background C9orf72 hexanucleotide repeat expansions are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in European populations. Variable disease penetrance between families presents a challenge for genetic counselling of at-risk relatives and reduces the predictive utility of testing asymptomatic relatives. We have developed a novel model for estimating penetrance in individual families affected by C9orf72 using available family history information, allowing the calculation of personalised risk estimates.Methods Published aggregated age-of-onset data for C9orf72-related ALS/FTD were used to generate age-related cumulative relative risks for at-risk relatives within pedigrees. Age-related relative risks are combined with a priori chance of individuals carrying an expansion based on known pedigree information. Penetrance is calculated as a number of affected individuals divided by the sum of cumulative age-related risks of relatives being affected by 80 years.Results This method allows family-specific penetrance to be estimated from family history and at-risk relatives’ personalised age-related ALS/FTD risks to be calculated and illustrated graphically. Penetrance reduces as the number and age of at-risk unaffected relatives increases.Conclusions Family history remains the best indicator of penetrance in C9orf72 expansion carriers. Calculating family-specific penetrance can aid genetic counselling by allowing at-risk relatives a more accurate understanding of their individual risk.
{"title":"Personalised penetrance estimation for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia","authors":"Andrew G L Douglas, Alexander G Thompson, Martin R Turner, Kevin Talbot","doi":"10.1136/bmjno-2024-000792","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000792","url":null,"abstract":"Background C9orf72 hexanucleotide repeat expansions are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in European populations. Variable disease penetrance between families presents a challenge for genetic counselling of at-risk relatives and reduces the predictive utility of testing asymptomatic relatives. We have developed a novel model for estimating penetrance in individual families affected by C9orf72 using available family history information, allowing the calculation of personalised risk estimates.Methods Published aggregated age-of-onset data for C9orf72-related ALS/FTD were used to generate age-related cumulative relative risks for at-risk relatives within pedigrees. Age-related relative risks are combined with a priori chance of individuals carrying an expansion based on known pedigree information. Penetrance is calculated as a number of affected individuals divided by the sum of cumulative age-related risks of relatives being affected by 80 years.Results This method allows family-specific penetrance to be estimated from family history and at-risk relatives’ personalised age-related ALS/FTD risks to be calculated and illustrated graphically. Penetrance reduces as the number and age of at-risk unaffected relatives increases.Conclusions Family history remains the best indicator of penetrance in C9orf72 expansion carriers. Calculating family-specific penetrance can aid genetic counselling by allowing at-risk relatives a more accurate understanding of their individual risk.","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1136/bmjno-2024-000767
Kevin Young Xu, Fábio A Nascimento, Binx Yezhe Lin, Tae Woo Park, Donovan T Maust, Hillary Samples, Greta A Bushnell
Background Characterising benzodiazepine (BZD) prescribing to individuals with psychogenic non-epileptic seizures (PNES) is important for optimising PNES outcomes, but existing data is lacking.Methods Using a nationwide administrative claims database (2016–2022), incident PNES was defined as an International classification of diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis in an inpatient or outpatient healthcare encounter after a 1-year period with no documented diagnosis. We described clinical characteristics of adults with incident PNES and estimated the prevalence of outpatient BZD treatment in the baseline year and 30-day follow-up period, with secondary analyses stratifying by baseline ES, anxiety and/or insomnia diagnoses, representing common indications for BZD receipt. We used logistic regression to evaluate predictors of post-PNES BZD receipt.Results Among 20 848 adults with incident PNES diagnosis, 33.1% and 15.1% received BZDs in the year and month prior to PNES diagnosis, respectively, and 18.1% received BZDs in the month following a PNES diagnosis; 5.4% of those without prior BZD prescriptions received BZDs after diagnosis. The median days’ supply was 30 days, with clonazepam, alprazolam and lorazepam representing the most common BZDs prescribed after PNES. Most people who received BZDs in the month prior to PNES diagnosis remained on BZDs in the month after PNES diagnosis (62.9%), with similar findings in the subcohorts without ES, anxiety and/or insomnia. Baseline BZD receipt and anxiety disorders, but not baseline ES diagnoses, were strong independent predictors of post-PNES BZD receipt.Conclusions While new BZD initiation is rare after PNES, most individuals with BZD scripts 1 month before PNES continue scripts after diagnosis.
{"title":"Benzodiazepine receipt in adults with psychogenic non-epileptic seizures in the USA","authors":"Kevin Young Xu, Fábio A Nascimento, Binx Yezhe Lin, Tae Woo Park, Donovan T Maust, Hillary Samples, Greta A Bushnell","doi":"10.1136/bmjno-2024-000767","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000767","url":null,"abstract":"Background Characterising benzodiazepine (BZD) prescribing to individuals with psychogenic non-epileptic seizures (PNES) is important for optimising PNES outcomes, but existing data is lacking.Methods Using a nationwide administrative claims database (2016–2022), incident PNES was defined as an International classification of diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis in an inpatient or outpatient healthcare encounter after a 1-year period with no documented diagnosis. We described clinical characteristics of adults with incident PNES and estimated the prevalence of outpatient BZD treatment in the baseline year and 30-day follow-up period, with secondary analyses stratifying by baseline ES, anxiety and/or insomnia diagnoses, representing common indications for BZD receipt. We used logistic regression to evaluate predictors of post-PNES BZD receipt.Results Among 20 848 adults with incident PNES diagnosis, 33.1% and 15.1% received BZDs in the year and month prior to PNES diagnosis, respectively, and 18.1% received BZDs in the month following a PNES diagnosis; 5.4% of those without prior BZD prescriptions received BZDs after diagnosis. The median days’ supply was 30 days, with clonazepam, alprazolam and lorazepam representing the most common BZDs prescribed after PNES. Most people who received BZDs in the month prior to PNES diagnosis remained on BZDs in the month after PNES diagnosis (62.9%), with similar findings in the subcohorts without ES, anxiety and/or insomnia. Baseline BZD receipt and anxiety disorders, but not baseline ES diagnoses, were strong independent predictors of post-PNES BZD receipt.Conclusions While new BZD initiation is rare after PNES, most individuals with BZD scripts 1 month before PNES continue scripts after diagnosis.","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1136/bmjno-2024-000670
Nevin John, Yingtong Li, Floriana De Angelis, Jonathan Stutters, Ferran Prados Carrasco, Arman Eshaghi, Anisha Doshi, Alberto Calvi, Thomas Williams, Domenico Plantone, Thanh Phan, Frederik Barkhof, Jeremy Chataway, , Sebastien Ourselin, Marie Braisher, Tiggy Beyene, Vanessa Bassan, Alvin Zapata, Siddharthan Chandran, Peter Connick, Dawn Lyle, James Cameron, Daisy Mollison, Shuna Colville, Baljean Dhillon, Moira Ross, Gina Cranswick, Allan Walker, Lorraine Smith, Gavin Giovannoni, Sharmilee Gnanapavan, Richard Nicholas, Waqar Rashid, Julia Aram, Helen Ford, Sue H Pavitt, James Overell, Carolyn Young, Heinke Arndt, Martin Duddy, Joe Guadagno, Nikolaos Evangelou, Matthew Craner, Jacqueline Palace, Jeremy Hobart, Basil Sharrack, David Paling, Clive Hawkins, Seema Kalra, Brendan McLean, Nigel Stallard, Roger Bastow
Background The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.Methods We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial ( NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression.Results 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0–6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW.Conclusion Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS.Trail registration number NCT01910259.
{"title":"Brain reserve and physical disability in secondary progressive multiple sclerosis","authors":"Nevin John, Yingtong Li, Floriana De Angelis, Jonathan Stutters, Ferran Prados Carrasco, Arman Eshaghi, Anisha Doshi, Alberto Calvi, Thomas Williams, Domenico Plantone, Thanh Phan, Frederik Barkhof, Jeremy Chataway, , Sebastien Ourselin, Marie Braisher, Tiggy Beyene, Vanessa Bassan, Alvin Zapata, Siddharthan Chandran, Peter Connick, Dawn Lyle, James Cameron, Daisy Mollison, Shuna Colville, Baljean Dhillon, Moira Ross, Gina Cranswick, Allan Walker, Lorraine Smith, Gavin Giovannoni, Sharmilee Gnanapavan, Richard Nicholas, Waqar Rashid, Julia Aram, Helen Ford, Sue H Pavitt, James Overell, Carolyn Young, Heinke Arndt, Martin Duddy, Joe Guadagno, Nikolaos Evangelou, Matthew Craner, Jacqueline Palace, Jeremy Hobart, Basil Sharrack, David Paling, Clive Hawkins, Seema Kalra, Brendan McLean, Nigel Stallard, Roger Bastow","doi":"10.1136/bmjno-2024-000670","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000670","url":null,"abstract":"Background The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.Methods We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial ( NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression.Results 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0–6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW.Conclusion Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS.Trail registration number NCT01910259.","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1136/bmjno-2024-000770
Sameen Haque, Karen Crawley, Deborah Schofield, Rupendra Shrestha, Ryan Davis, Carolyn M Sue
Background Mitochondrial diseases often follow a chronic, multimorbid disease course in adults. Like other chronic conditions, mitochondrial diseases present a challenge to public and community health models and patients are potentially at higher risk of social isolation and loneliness. However, there is lack of data on social provisions in mitochondrial diseases.Methods We performed a cross-sectional observational study on patients with a confirmed genetic or clinical diagnosis of mitochondrial disease, recruited between September 2018 and December 2021. Participants completed the Social Provisions Scale (SPS) as a measure of social support. Designated carers similarly completed the SPS in carer-specific questionnaires.Results 95 mitochondrial disease patients and 24 designated carers completed the SPS. Social provisions were met for all six subscales of SPS in the mitochondrial disease cohort: (1) guidance 90.5% (n=86), (2) reassurance of self-worth 82.8% (n=77), (3) social integration 88.4% (n=84), (4) attachment 83.2% (n=79), (5) opportunity of nurturance, 61.1% (n=58) and (6) reliable alliance 95.8% (n=91). All social provisions were also met in the carer cohort.Conclusion Patients with mitochondrial diseases and their carers demonstrate a high perceived level of social support in the setting of a tertiary referral centre specialised in mitochondrial disease despite the burden of chronic disease.
{"title":"Social provisions in patients with mitochondrial diseases","authors":"Sameen Haque, Karen Crawley, Deborah Schofield, Rupendra Shrestha, Ryan Davis, Carolyn M Sue","doi":"10.1136/bmjno-2024-000770","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000770","url":null,"abstract":"Background Mitochondrial diseases often follow a chronic, multimorbid disease course in adults. Like other chronic conditions, mitochondrial diseases present a challenge to public and community health models and patients are potentially at higher risk of social isolation and loneliness. However, there is lack of data on social provisions in mitochondrial diseases.Methods We performed a cross-sectional observational study on patients with a confirmed genetic or clinical diagnosis of mitochondrial disease, recruited between September 2018 and December 2021. Participants completed the Social Provisions Scale (SPS) as a measure of social support. Designated carers similarly completed the SPS in carer-specific questionnaires.Results 95 mitochondrial disease patients and 24 designated carers completed the SPS. Social provisions were met for all six subscales of SPS in the mitochondrial disease cohort: (1) guidance 90.5% (n=86), (2) reassurance of self-worth 82.8% (n=77), (3) social integration 88.4% (n=84), (4) attachment 83.2% (n=79), (5) opportunity of nurturance, 61.1% (n=58) and (6) reliable alliance 95.8% (n=91). All social provisions were also met in the carer cohort.Conclusion Patients with mitochondrial diseases and their carers demonstrate a high perceived level of social support in the setting of a tertiary referral centre specialised in mitochondrial disease despite the burden of chronic disease.","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30eCollection Date: 2024-01-01DOI: 10.1136/bmjno-2024-000796
Jiyoung Gwak, Jinse Park
Introduction: This study aimed to evaluate the efficacy of acceptance and commitment therapy (ACT) in reducing the fear of falling (FOF) and promoting physical activity in individuals diagnosed with Parkinson's disease (PD).
Methods and analysis: This is a prospective, multicentre, rater-blinded and randomised controlled trial. Patients with PD and a history of falls will be randomly assigned to either an 8-week ACT intervention group or a control group receiving standard care. The primary outcomes measured will include FOF assessment using the Falls Efficacy Scale-International and physical activity levels measured via wearable sensor devices. Secondary outcomes will encompass the assessment of motor function, balance and fall frequency using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Berg Balance Scale and Timed Up and Go test. Objective measures of balance and physical activity will be obtained through static posturography and wearable sensors over a 3-day period, both before and after the intervention. Data will be analysed using mixed-effects models to evaluate the impact of ACT on FOF and physical activity.
Ethics and dissemination: We hypothesised that ACT would lead to a significant reduction in FOF and an increase in physical activity levels compared with standard care. Additionally, this study will also examine the relationship between reduced FOF and improvements in balance and motor function. Our results will provide valuable evidence to support the effectiveness of ACT in reducing FOF and promoting physical activity among patients with PD, and if validated, ACT could be recommended as a beneficial intervention to enhance the quality of life and reduce fall-related morbidity in patients with PD.
{"title":"Effect of acceptance and commitment therapy on fear of falling and physical activity in Parkinson's disease: a randomised controlled trial.","authors":"Jiyoung Gwak, Jinse Park","doi":"10.1136/bmjno-2024-000796","DOIUrl":"10.1136/bmjno-2024-000796","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the efficacy of acceptance and commitment therapy (ACT) in reducing the fear of falling (FOF) and promoting physical activity in individuals diagnosed with Parkinson's disease (PD).</p><p><strong>Methods and analysis: </strong>This is a prospective, multicentre, rater-blinded and randomised controlled trial. Patients with PD and a history of falls will be randomly assigned to either an 8-week ACT intervention group or a control group receiving standard care. The primary outcomes measured will include FOF assessment using the Falls Efficacy Scale-International and physical activity levels measured via wearable sensor devices. Secondary outcomes will encompass the assessment of motor function, balance and fall frequency using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Berg Balance Scale and Timed Up and Go test. Objective measures of balance and physical activity will be obtained through static posturography and wearable sensors over a 3-day period, both before and after the intervention. Data will be analysed using mixed-effects models to evaluate the impact of ACT on FOF and physical activity.</p><p><strong>Ethics and dissemination: </strong>We hypothesised that ACT would lead to a significant reduction in FOF and an increase in physical activity levels compared with standard care. Additionally, this study will also examine the relationship between reduced FOF and improvements in balance and motor function. Our results will provide valuable evidence to support the effectiveness of ACT in reducing FOF and promoting physical activity among patients with PD, and if validated, ACT could be recommended as a beneficial intervention to enhance the quality of life and reduce fall-related morbidity in patients with PD.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121052","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 : 2024-08-30DOI: 10.1136/bmjno-2024-000789
Samuel Gibbon, Fergus Doubal, Francesca Chappell, Joanna M Wardlaw, Baljean Dhillon, Thomas MacGillivray
Objective To test for associations between optic disc pallor and two clinical variables: ischaemic stroke subtype (cortical and lacunar) and cerebral small vessel disease (SVD) scores in a cohort of hospital patients admitted with mild stroke (Mild Stroke Study 1).Methods We used previously validated software, PallorMetrics, to quantify optic disc pallor in colour fundus photographs of patients diagnosed as having either cortical (n=92) or lacunar (n=92) stroke. We used logistic regression to assess the relationship between stroke type and disc pallor in several zones and ordinal logistic regression to assess the relationship between disc pallor and total SVD score. The left and right eyes were analysed separately.Results In the right eye, independent of age, sex, disc area, hypertension and diabetes, increased optic disc pallor was significantly associated with lacunar stroke in all zones (for global pallor: OR per SD increase=1.55, 95% CI 1.11 to 2.17, p=0.011) and total SVD score in the temporal superior (standardised β=0.36, SE=0.15, p=0.020) and nasal-inferior zones (standardised β=0.44, SE=0.15, p=0.004) in the right eye. Weaker trends were observed in the left eye; however, these did not reach statistical significance.Conclusion Optic disc pallor may be associated with SVD severity and lacunar stroke, which may reflect vascular damage to the optic nerve or its pathways. Our findings underscore the utility of colour fundus photography to learn more about SVD pathology.
{"title":"Association between optic disc pallor and lacunar stroke","authors":"Samuel Gibbon, Fergus Doubal, Francesca Chappell, Joanna M Wardlaw, Baljean Dhillon, Thomas MacGillivray","doi":"10.1136/bmjno-2024-000789","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000789","url":null,"abstract":"Objective To test for associations between optic disc pallor and two clinical variables: ischaemic stroke subtype (cortical and lacunar) and cerebral small vessel disease (SVD) scores in a cohort of hospital patients admitted with mild stroke (Mild Stroke Study 1).Methods We used previously validated software, PallorMetrics, to quantify optic disc pallor in colour fundus photographs of patients diagnosed as having either cortical (n=92) or lacunar (n=92) stroke. We used logistic regression to assess the relationship between stroke type and disc pallor in several zones and ordinal logistic regression to assess the relationship between disc pallor and total SVD score. The left and right eyes were analysed separately.Results In the right eye, independent of age, sex, disc area, hypertension and diabetes, increased optic disc pallor was significantly associated with lacunar stroke in all zones (for global pallor: OR per SD increase=1.55, 95% CI 1.11 to 2.17, p=0.011) and total SVD score in the temporal superior (standardised β=0.36, SE=0.15, p=0.020) and nasal-inferior zones (standardised β=0.44, SE=0.15, p=0.004) in the right eye. Weaker trends were observed in the left eye; however, these did not reach statistical significance.Conclusion Optic disc pallor may be associated with SVD severity and lacunar stroke, which may reflect vascular damage to the optic nerve or its pathways. Our findings underscore the utility of colour fundus photography to learn more about SVD pathology.","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1136/bmjno-2024-000800
Valeriya Kuznetsova, Harsh Oza, Hannah Rosenfeld, Carmela Sales, Samantha van der Linde, Izanne Roos, Stefanie Roberts, Fiore D’Aprano, Samantha M Loi, Mark Dowling, Michael Dickinson, Tomas Kalincik, Simon J Harrison, Mary Ann Anderson, Charles B Malpas
Introduction Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely.Methods and analysis This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint.Ethics and dissemination This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145).
简介:免疫效应细胞相关神经毒性综合征(ICANS)是嵌合抗原受体 T 细胞(CAR-T)疗法的一种常见副作用,症状从轻微到偶尔危及生命不等。ICANS 的神经、认知、精神和社会心理后遗症多种多样,定义不清,给诊断和管理带来了挑战。该综合征的康复轨迹尚不确定。在这一人群中,很少有患者在治疗前接受检查,这就为确定仅与 CAR-T 治疗相关的症状增加了一层复杂性。我们提出了一项前瞻性纵向研究方案,研究对象是在澳大利亚一家血液科接受 CAR-T 治疗的成年患者。该研究将描述 ICANS 特有的神经认知特征,描述潜在综合征的特征,捕捉恢复情况,识别不同输注后结果的预测因素,并确定一套必要的认知工具,以便对患者进行急性监测。 方法与分析 这是一项前瞻性纵向研究,包括 CAR-T 治疗前、治疗后急性期、输注后 28 天、6 个月和 12 个月的神经心理学和神经学检查。数据将来自客观心理测量、临床检查、精神病理学自我报告问卷以及主观认知症状的描述。本研究的结果将通过在同行评审期刊上发表和在科学会议上演讲的方式传播。所有涉及人类受试者/患者的程序均已获得彼得-麦克卡勒姆癌症中心人类研究伦理委员会(Peter MacCallum Cancer Centre Human Research Ethics Committee)的批准(21/145)。
{"title":"Neuropsychological outcomes of patients with haematological malignancies undergoing chimeric antigen receptor T-cell therapy: protocol for a prospective study","authors":"Valeriya Kuznetsova, Harsh Oza, Hannah Rosenfeld, Carmela Sales, Samantha van der Linde, Izanne Roos, Stefanie Roberts, Fiore D’Aprano, Samantha M Loi, Mark Dowling, Michael Dickinson, Tomas Kalincik, Simon J Harrison, Mary Ann Anderson, Charles B Malpas","doi":"10.1136/bmjno-2024-000800","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000800","url":null,"abstract":"Introduction Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely.Methods and analysis This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint.Ethics and dissemination This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145).","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21eCollection Date: 2024-01-01DOI: 10.1136/bmjno-2024-000765
Alexandra Astner-Rohracher, Alyssa Ho, John Archer, Fabrice Bartolomei, Milan Brazdil, Melita Cacic Hribljan, James Castellano, Irena Dolezalova, Martin Ejler Fabricius, Mercedes Garcés-Sanchez, Kahina Hammam, Akio Ikeda, Kristin Ikeda, Philippe Kahane, Giridhar Kalamangalam, Gudrun Kalss, Mays Khweileh, Katsuya Kobayashi, Patrick Kwan, Joshua Andrew Laing, Markus Leitinger, Samden Lhatoo, Julia Makhalova, Aileen McGonigal, Iona Mindruta, Mary Margaret Mizera, Andrew Neal, Irina Oane, Prachi Parikh, Piero Perucca, Francesca Pizzo, Rodrigo Rocamora, Philippe Ryvlin, Victoria San Antonio Arce, Stephan Schuele, Andreas Schulze-Bonhage, Ana Suller Marti, Alexandra Urban, Vincente Villanueva, Laura Vilella Bertran, Benjamin Whatley, Sandor Beniczky, Eugen Trinka, Georg Zimmermann, Birgit Frauscher
Introduction: Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions.
Methods and analysis: Non-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion.
Ethics and dissemination: Prospective multicentre validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences.
{"title":"Prognostic value of the 5-SENSE Score to predict focality of the seizure-onset zone as assessed by stereoelectroencephalography: a prospective international multicentre validation study.","authors":"Alexandra Astner-Rohracher, Alyssa Ho, John Archer, Fabrice Bartolomei, Milan Brazdil, Melita Cacic Hribljan, James Castellano, Irena Dolezalova, Martin Ejler Fabricius, Mercedes Garcés-Sanchez, Kahina Hammam, Akio Ikeda, Kristin Ikeda, Philippe Kahane, Giridhar Kalamangalam, Gudrun Kalss, Mays Khweileh, Katsuya Kobayashi, Patrick Kwan, Joshua Andrew Laing, Markus Leitinger, Samden Lhatoo, Julia Makhalova, Aileen McGonigal, Iona Mindruta, Mary Margaret Mizera, Andrew Neal, Irina Oane, Prachi Parikh, Piero Perucca, Francesca Pizzo, Rodrigo Rocamora, Philippe Ryvlin, Victoria San Antonio Arce, Stephan Schuele, Andreas Schulze-Bonhage, Ana Suller Marti, Alexandra Urban, Vincente Villanueva, Laura Vilella Bertran, Benjamin Whatley, Sandor Beniczky, Eugen Trinka, Georg Zimmermann, Birgit Frauscher","doi":"10.1136/bmjno-2024-000765","DOIUrl":"10.1136/bmjno-2024-000765","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions.</p><p><strong>Methods and analysis: </strong>Non-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion.</p><p><strong>Ethics and dissemination: </strong>Prospective multicentre validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences.</p><p><strong>Trial registration number: </strong>NCT06138808.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037716","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 : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1136/bmjno-2024-000738
Peter Dudley, Jan Paul Marquez, Fiona Farrell, Jennifer Benson, Fergus Rugg-Gunn, Meneka K Sidhu, Suzanne O'Sullivan, Matthew Walker, Mahinda Yogarajah
Abstract:
Objective: Identify the proportion of patients referred with putative functional seizures (FS) that were subsequently re-diagnosed as epileptic seizures (ES), or an alternative diagnosis, following video telemetry EEG (VTEEG). In addition, describe the characteristics of those seizures.
Methods: The VTEEG reports from patients admitted to the Chalfont Centre for Epilepsy between 2019 and 2022 were reviewed. Pre-VTEEG and post-VTEEG diagnoses were compared to identify whether a diagnostic revision was made from suspected FS to ES or another diagnosis. Diagnostic revision cases were then grouped into cohorts with associated features and reviewed to characterise and describe FS mimics.
Results: 444 VTEEG reports where patients had habitual events were identified. 4.7% of patients were referred with FS and were subsequently diagnosed with ES or another diagnosis. In this group, several cohorts could be identified including frontal lobe epileptic seizures, ES with functional overlay, insular or temporal lobe epileptic seizures associated with autonomic or marked experiential peri-ictal symptoms, and individuals who had both ES and FS but whose ES were revealed on medication withdrawal.
Conclusion: In patients referred to a tertiary epilepsy unit, a small minority of cases had seizures diagnosed as functional and reclassified as epileptic or an alternative diagnosis. It is clinically important to be aware of these FS mimics.
摘要:目的:确定因推测为功能性癫痫发作(FS)而转诊的患者中,经过视频遥测脑电图(VTEEG)检查后被重新诊断为癫痫发作(ES)或其他诊断的患者比例。此外,还要描述这些癫痫发作的特征:方法:对查尔丰癫痫中心在 2019 年至 2022 年期间收治的患者的 VTEEG 报告进行了审查。对 VTEEG 前和 VTEEG 后的诊断进行比较,以确定是否从疑似 FS 诊断修正为 ES 诊断或其他诊断。然后将诊断修正病例归入具有相关特征的队列,并对其进行审查,以确定和描述 FS 拟态的特征:结果:共发现 444 份患者有习惯性事件的 VTEEG 报告。4.7% 的患者因 FS 转诊,随后被诊断为 ES 或其他诊断。在这组患者中,可以识别出几个队列,包括额叶癫痫发作、有功能叠加的 ES、伴有自主神经或明显体验性发作周症状的岛叶或颞叶癫痫发作,以及同时患有 ES 和 FS 但 ES 在停药后显现的患者:结论:在转诊至三级医院癫痫科的患者中,少数病例的癫痫发作被诊断为功能性发作,并被重新归类为癫痫或其他诊断。在临床上,警惕这些功能性癫痫模拟者非常重要。
{"title":"Functional seizures and their mimics: a retrospective service review of cases from a tertiary video telemetry database.","authors":"Peter Dudley, Jan Paul Marquez, Fiona Farrell, Jennifer Benson, Fergus Rugg-Gunn, Meneka K Sidhu, Suzanne O'Sullivan, Matthew Walker, Mahinda Yogarajah","doi":"10.1136/bmjno-2024-000738","DOIUrl":"10.1136/bmjno-2024-000738","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Objective: </strong>Identify the proportion of patients referred with putative functional seizures (FS) that were subsequently re-diagnosed as epileptic seizures (ES), or an alternative diagnosis, following video telemetry EEG (VTEEG). In addition, describe the characteristics of those seizures.</p><p><strong>Methods: </strong>The VTEEG reports from patients admitted to the Chalfont Centre for Epilepsy between 2019 and 2022 were reviewed. Pre-VTEEG and post-VTEEG diagnoses were compared to identify whether a diagnostic revision was made from suspected FS to ES or another diagnosis. Diagnostic revision cases were then grouped into cohorts with associated features and reviewed to characterise and describe FS mimics.</p><p><strong>Results: </strong>444 VTEEG reports where patients had habitual events were identified. 4.7% of patients were referred with FS and were subsequently diagnosed with ES or another diagnosis. In this group, several cohorts could be identified including frontal lobe epileptic seizures, ES with functional overlay, insular or temporal lobe epileptic seizures associated with autonomic or marked experiential peri-ictal symptoms, and individuals who had both ES and FS but whose ES were revealed on medication withdrawal.</p><p><strong>Conclusion: </strong>In patients referred to a tertiary epilepsy unit, a small minority of cases had seizures diagnosed as functional and reclassified as epileptic or an alternative diagnosis. It is clinically important to be aware of these FS mimics.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908293","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: Erectile dysfunction (ED) and stroke share common risk factors, and symptoms of ED often precede the development of clinical cardiovascular disease (CVD). However, little is known about how ED is associated with cardiovascular (CV) risk factors in patients who had a stroke and if concomitant ED is a marker of more severe CVD.
Aims: We aimed to identify the prevalence of ED and CV risk factors in patients admitted with a stroke or transient ischaemic attack (TIA). Further, we wanted to test if self-reported ED associated with presence of CV risk factors, and if patients with ED had increased stroke severity compared with patients without ED.
Methods: This was a post hoc analysis of data retrieved in a cross-sectional survey from two non-comprehensive stroke units in Denmark. Multiple logistic regression adjusted for covariates was performed to investigate the association between CV risk factors and self-reported ED.
Results: We included 287 male patients of which 116 (40.4%) had self-reported ED. Advanced age was significantly associated with self-reported ED (reference ≤60 years: OR 3.93, 95% CI 1.84 to 8.37 for men 71-80 years and OR 4.61, 95% CI 1.92 to 11.08 for men >80 years). Self-reported ED was not significantly associated with CV risk factors or stroke severity.
Discussion: Four in 10 men with acute stroke or TIA reported to have ED prior to their stroke, and this was associated with age rather than CV risk factors. Hence, self-reported ED was not restricted to the CVD load, nor was ED a risk marker for increased stroke severity. However, our population was of high age with well-established CVD, and the presence of ED may be a stroke risk marker in younger patients who had a stroke. Based on the prevalence, potential treatment of ED should be addressed in stroke recovery.
背景:勃起功能障碍(ED)和中风具有共同的风险因素,ED症状往往发生在临床心血管疾病(CVD)之前。目的:我们旨在确定中风或短暂性脑缺血发作(TIA)入院患者中 ED 和 CV 危险因素的发生率。此外,我们还想检验自我报告的 ED 是否与存在的 CV 危险因素有关,以及与无 ED 的患者相比,有 ED 的患者的中风严重程度是否更高:这是对丹麦两个非综合卒中单位的横断面调查数据进行的事后分析。结果:我们共纳入了 287 名男性患者,其中有 1.6% 的人患有 ED:我们纳入了 287 名男性患者,其中 116 人(40.4%)自述有 ED。高龄与自我报告的 ED 显著相关(参考值≤60 岁:71-80岁男性的OR值为3.93,95% CI为1.84-8.37;大于80岁男性的OR值为4.61,95% CI为1.92-11.08)。自我报告的ED与CV风险因素或中风严重程度无明显关系:讨论:每 10 位急性卒中或 TIA 患者中就有 4 位报告在卒中前有 ED,这与年龄而非 CV 风险因素有关。因此,自我报告的 ED 并不局限于 CVD 负荷,ED 也不是卒中严重程度增加的风险标志。然而,我们的研究对象年龄偏高,心血管疾病已得到确诊,ED 的存在可能是年轻中风患者的中风风险标志。根据发病率,在脑卒中康复过程中应注意对 ED 的潜在治疗。
{"title":"High prevalence of erectile dysfunction in male patients with acute stroke was associated with age but not to modifiable cardiovascular risk factors.","authors":"Christel Baagø Schjørring, Heidi Shil Eddelien, Jawad Haider Butt, Christina Kruuse","doi":"10.1136/bmjno-2024-000795","DOIUrl":"10.1136/bmjno-2024-000795","url":null,"abstract":"<p><strong>Background: </strong>Erectile dysfunction (ED) and stroke share common risk factors, and symptoms of ED often precede the development of clinical cardiovascular disease (CVD). However, little is known about how ED is associated with cardiovascular (CV) risk factors in patients who had a stroke and if concomitant ED is a marker of more severe CVD.</p><p><strong>Aims: </strong>We aimed to identify the prevalence of ED and CV risk factors in patients admitted with a stroke or transient ischaemic attack (TIA). Further, we wanted to test if self-reported ED associated with presence of CV risk factors, and if patients with ED had increased stroke severity compared with patients without ED.</p><p><strong>Methods: </strong>This was a post hoc analysis of data retrieved in a cross-sectional survey from two non-comprehensive stroke units in Denmark. Multiple logistic regression adjusted for covariates was performed to investigate the association between CV risk factors and self-reported ED.</p><p><strong>Results: </strong>We included 287 male patients of which 116 (40.4%) had self-reported ED. Advanced age was significantly associated with self-reported ED (reference ≤60 years: OR 3.93, 95% CI 1.84 to 8.37 for men 71-80 years and OR 4.61, 95% CI 1.92 to 11.08 for men >80 years). Self-reported ED was not significantly associated with CV risk factors or stroke severity.</p><p><strong>Discussion: </strong>Four in 10 men with acute stroke or TIA reported to have ED prior to their stroke, and this was associated with age rather than CV risk factors. Hence, self-reported ED was not restricted to the CVD load, nor was ED a risk marker for increased stroke severity. However, our population was of high age with well-established CVD, and the presence of ED may be a stroke risk marker in younger patients who had a stroke. Based on the prevalence, potential treatment of ED should be addressed in stroke recovery.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894859","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}