Pub Date : 2024-11-01Epub Date: 2024-10-23DOI: 10.1002/acn3.52180
Larysa Benistant, Damien Reita, Maleka Schenck, Vincent Castelain, Hélène Cebula, Benoît Lhermitte, Laura Bender
Diffuse midline gliomas present a particularly intricate and challenging clinical scenario. This rare case involves a patient with comutant H3F3A and FGFR diffuse midline glioma with a clinical presentation of fulminant leptomeningitis. A 22-year-old male presented with fatal and fulminant diffuse leptomeningitis. Next-generation sequencing of plasma and cerebrospinal circulating tumour DNA revealed diffuse midline gliomas with H3F3A and FGFR mutations. Methylome analysis of meningeal tissue collected during autopsy confirmed the diagnosis. Liquid biopsy plays a crucial role in the diagnosis of diffuse midline gliomas, mainly those with exclusively leptomeningeal presentations.
{"title":"Fulminant leptomeningeal disease diagnosed as comutant H3F3A and FGFR diffuse midline glioma.","authors":"Larysa Benistant, Damien Reita, Maleka Schenck, Vincent Castelain, Hélène Cebula, Benoît Lhermitte, Laura Bender","doi":"10.1002/acn3.52180","DOIUrl":"10.1002/acn3.52180","url":null,"abstract":"<p><p>Diffuse midline gliomas present a particularly intricate and challenging clinical scenario. This rare case involves a patient with comutant H3F3A and FGFR diffuse midline glioma with a clinical presentation of fulminant leptomeningitis. A 22-year-old male presented with fatal and fulminant diffuse leptomeningitis. Next-generation sequencing of plasma and cerebrospinal circulating tumour DNA revealed diffuse midline gliomas with H3F3A and FGFR mutations. Methylome analysis of meningeal tissue collected during autopsy confirmed the diagnosis. Liquid biopsy plays a crucial role in the diagnosis of diffuse midline gliomas, mainly those with exclusively leptomeningeal presentations.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"3037-3041"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-22DOI: 10.1002/acn3.52201
Robert Stowell-Campos, Erin Lawrence, Elisabeth Breese Marsh, Dawn Merbach
Objective: Strokes involving sensory pathways can result in contralesional pain syndromes often refractory to pharmacologic interventions. Scrambler therapy (ST) is a noninvasive electroanalgesia device used to treat pain caused by peripheral neuropathy; however, data are scarce regarding its use in conditions secondary to central nervous system pathology. We evaluate the efficacy of ST to treat poststroke pain.
Methods: Twenty patients with a history of prior stroke resulting in contralesional pain were randomized to receive ST or Sham as an adjunct to their stable medication regimen. Participants underwent 5 consecutive daily 40-min sessions. The study was blinded to patient and assessor. Pain scores (0-10) were recorded at baseline, pre- and postsession, and 4 weeks after final treatment. Student's t-tests compared differences in the mean change in pain score between groups immediately post-treatment #5, and at 4-weeks. The chi-squared analysis compared the proportion of patients in each group with >50% pain reduction.
Results: Participants randomized to ST had a mean change in pain score of -3.73 (SD 2.85) postintervention and -2.57 (SD 2.07) at 4 weeks, while the Sham group had a mean change in score of -0.94 (SD 1.36) and -0.25 (SD 0.84) (p between groups = 0.012, 0.004, respectively). Significantly more participants treated with ST reported a >50% reduction in pain immediately postintervention compared to Sham (70% vs. 10%, p = 0.006), but not at follow-up (30% vs. 10%, p = ns).
Interpretation: ST may effectively decrease poststroke pain compared to Sham. Larger studies are needed to evaluate confounders such as stroke location, time from stroke, and concomitant treatment with medications.
目的:涉及感觉通路的中风可导致对侧疼痛综合征,而药物治疗往往难以奏效。Scrambler 疗法(ST)是一种非侵入性电镇痛设备,用于治疗由周围神经病变引起的疼痛;然而,有关其在继发于中枢神经系统病变的病症中的应用的数据却很少。我们评估了 ST 治疗中风后疼痛的疗效:方法:20 名既往中风导致对侧疼痛的患者随机接受 ST 或 Sham 作为稳定药物治疗的辅助治疗。参与者每天连续接受 5 次治疗,每次 40 分钟。该研究对患者和评估者均不设盲区。疼痛评分(0-10 分)在基线、疗程前和疗程后以及最终治疗后 4 周进行记录。学生 t 检验比较了治疗后 5 周和 4 周时各组疼痛评分平均变化的差异。卡方分析比较了各组疼痛减轻>50%的患者比例:随机接受 ST 治疗的患者在干预后疼痛评分的平均变化为-3.73(标准差为 2.85),4 周后疼痛评分的平均变化为-2.57(标准差为 2.07),而接受 Sham 治疗的患者在干预后疼痛评分的平均变化为-0.94(标准差为 1.36),4 周后疼痛评分的平均变化为-0.25(标准差为 0.84)(组间 p 分别为 0.012、0.004)。与 Sham 相比,接受 ST 治疗的患者在干预后疼痛立即减轻 50% 以上的人数显著增加(70% vs. 10%,P = 0.006),但在随访时没有增加(30% vs. 10%,P = ns):与 Sham 相比,ST 可有效减轻中风后疼痛。需要进行更大规模的研究,以评估中风位置、中风时间和同时接受药物治疗等混杂因素。
{"title":"Scrambler therapy for treatment of poststroke pain.","authors":"Robert Stowell-Campos, Erin Lawrence, Elisabeth Breese Marsh, Dawn Merbach","doi":"10.1002/acn3.52201","DOIUrl":"10.1002/acn3.52201","url":null,"abstract":"<p><strong>Objective: </strong>Strokes involving sensory pathways can result in contralesional pain syndromes often refractory to pharmacologic interventions. Scrambler therapy (ST) is a noninvasive electroanalgesia device used to treat pain caused by peripheral neuropathy; however, data are scarce regarding its use in conditions secondary to central nervous system pathology. We evaluate the efficacy of ST to treat poststroke pain.</p><p><strong>Methods: </strong>Twenty patients with a history of prior stroke resulting in contralesional pain were randomized to receive ST or Sham as an adjunct to their stable medication regimen. Participants underwent 5 consecutive daily 40-min sessions. The study was blinded to patient and assessor. Pain scores (0-10) were recorded at baseline, pre- and postsession, and 4 weeks after final treatment. Student's t-tests compared differences in the mean change in pain score between groups immediately post-treatment #5, and at 4-weeks. The chi-squared analysis compared the proportion of patients in each group with >50% pain reduction.</p><p><strong>Results: </strong>Participants randomized to ST had a mean change in pain score of -3.73 (SD 2.85) postintervention and -2.57 (SD 2.07) at 4 weeks, while the Sham group had a mean change in score of -0.94 (SD 1.36) and -0.25 (SD 0.84) (p between groups = 0.012, 0.004, respectively). Significantly more participants treated with ST reported a >50% reduction in pain immediately postintervention compared to Sham (70% vs. 10%, p = 0.006), but not at follow-up (30% vs. 10%, p = ns).</p><p><strong>Interpretation: </strong>ST may effectively decrease poststroke pain compared to Sham. Larger studies are needed to evaluate confounders such as stroke location, time from stroke, and concomitant treatment with medications.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2904-2911"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The single-center retrospective cohort study investigated underlying pathogenic mechanisms and clinical significance of patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), in the presence/absence of gray-white matter abnormalities (usually called "blurring"; GMB) in ipsilateral temporopolar region (TPR) on MRI.
Methods: The study involved 105 patients with unilateral TLE-HS (60 GMB+ and 45 GMB-) who underwent standard anterior temporal lobectomy, along with 61 healthy controls. Resected specimens were examined under light microscope. With combined T1-weighted and DTI data, we quantitatively compared large-scale morphometric features and exacted diffusion parameters of ipsilateral TPR-related superficial and deep white matter (WM) by atlas-based segmentation. Along-tract analysis was added to detect heterogeneous microstructural alterations at various points along deep WM tracts, which were categorized into inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and temporal cingulum.
Results: Comparable seizure semiology and postoperative seizure outcome were found, while the GMB+ group had significantly higher rate of HS Type 1 and history of febrile seizures, contrasting with significantly lower proportion of interictal contralateral epileptiform discharges, HS Type 2, and increased wasteosomes in hippocampal specimens. Similar morphometric features but greater WM atrophy with more diffusion abnormalities of superficial WM was observed adjacent to ipsilateral TPR in the GMB+ group. Moreover, microstructural alterations resulting from temporopolar GMB were more localized in temporal cingulum while evenly and widely distributed along ILF and UF.
Interpretation: Temporopolar GMB could signify more severe and widespread microstructural damage of white matter rather than a focal cortical lesion in TLE-HS, affecting selection of surgical procedures.
{"title":"Temporopolar blurring signifies abnormalities of white matter in mesial temporal lobe epilepsy.","authors":"Yuming Li, Peiwen Liu, Qiuxing Lin, Wei Li, Yingying Zhang, Jinmei Li, Xiuli Li, Qiyong Gong, Heng Zhang, Luying Li, Xiutian Sima, Danyang Cao, Xiang Huang, Kailing Huang, Dong Zhou, Dongmei An","doi":"10.1002/acn3.52204","DOIUrl":"10.1002/acn3.52204","url":null,"abstract":"<p><strong>Objective: </strong>The single-center retrospective cohort study investigated underlying pathogenic mechanisms and clinical significance of patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), in the presence/absence of gray-white matter abnormalities (usually called \"blurring\"; GMB) in ipsilateral temporopolar region (TPR) on MRI.</p><p><strong>Methods: </strong>The study involved 105 patients with unilateral TLE-HS (60 GMB+ and 45 GMB-) who underwent standard anterior temporal lobectomy, along with 61 healthy controls. Resected specimens were examined under light microscope. With combined T1-weighted and DTI data, we quantitatively compared large-scale morphometric features and exacted diffusion parameters of ipsilateral TPR-related superficial and deep white matter (WM) by atlas-based segmentation. Along-tract analysis was added to detect heterogeneous microstructural alterations at various points along deep WM tracts, which were categorized into inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and temporal cingulum.</p><p><strong>Results: </strong>Comparable seizure semiology and postoperative seizure outcome were found, while the GMB+ group had significantly higher rate of HS Type 1 and history of febrile seizures, contrasting with significantly lower proportion of interictal contralateral epileptiform discharges, HS Type 2, and increased wasteosomes in hippocampal specimens. Similar morphometric features but greater WM atrophy with more diffusion abnormalities of superficial WM was observed adjacent to ipsilateral TPR in the GMB+ group. Moreover, microstructural alterations resulting from temporopolar GMB were more localized in temporal cingulum while evenly and widely distributed along ILF and UF.</p><p><strong>Interpretation: </strong>Temporopolar GMB could signify more severe and widespread microstructural damage of white matter rather than a focal cortical lesion in TLE-HS, affecting selection of surgical procedures.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2932-2945"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-07DOI: 10.1002/acn3.52207
Rezan Ashayeri Ahmadabad, Kim H Tran, Yiran Zhang, Mahesh P Kate, Sachin Mishra, Brian H Buck, Khurshid A Khan, Jeremy Rempel, Gregory W Albers, Ashfaq Shuaib
Background: Early diagnosis of large vessel occlusion (LVO) in acute stroke often requires CT angiography (CTA). Automated CT perfusion (CTP) software, which identifies blood flow abnormalities, enhances LVO diagnosis and patient selection for endovascular thrombectomy (EVT). This study evaluates the sensitivity of automated CTP images in detecting perfusion abnormalities in patients with acute ischemic stroke (AIS) and LVO or medium vessel occlusion (MeVO), compared to CTA.
Methods: We screened acute ischemic stroke patients presenting within 24 h who underwent CT, CTA, and CTP as per institutional protocol. RAPID AI software processed CTP images, while neuroradiologists reviewed CTA for intracranial arterial occlusions. Sensitivity, specificity, and accuracy of automated CTP maps in detecting occlusions were assessed.
Results: Of 790 screened patients, 31 were excluded due to lack of RAPID CTP data or poor-quality scans, leaving 759 for analysis. The median age was 71 years (IQR: 61-81), with 47% female. Among them, 678 had AIS, and 81 had AIS ruled out. CTA identified arterial occlusion in 562 patients (74%), with corresponding CTP abnormalities in 537 patients (Tmax > 6 sec). In the 197 without occlusion, CTP was negative in 161. Automated CTP maps had a sensitivity of 95.55% (CI 95: 93.50-97.10%), specificity of 81.73% (CI 95: 75.61-86.86%), negative predictive value of 98.22% (CI 95: 97.39-98.79%), positive predictive value of 63.54% (CI 95: 56.46-70.09%), and overall accuracy of 85.18% (CI 95: 82.45-87.64%).
Conclusions: Automated CTP maps demonstrated high sensitivity and negative predictive value for LVOs and MeVOs, suggesting their usefulness as a rapid diagnostic tool, especially in settings without expert neuroradiologists.
{"title":"Utility of automated CT perfusion software in acute ischemic stroke with large and medium vessel occlusion.","authors":"Rezan Ashayeri Ahmadabad, Kim H Tran, Yiran Zhang, Mahesh P Kate, Sachin Mishra, Brian H Buck, Khurshid A Khan, Jeremy Rempel, Gregory W Albers, Ashfaq Shuaib","doi":"10.1002/acn3.52207","DOIUrl":"10.1002/acn3.52207","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of large vessel occlusion (LVO) in acute stroke often requires CT angiography (CTA). Automated CT perfusion (CTP) software, which identifies blood flow abnormalities, enhances LVO diagnosis and patient selection for endovascular thrombectomy (EVT). This study evaluates the sensitivity of automated CTP images in detecting perfusion abnormalities in patients with acute ischemic stroke (AIS) and LVO or medium vessel occlusion (MeVO), compared to CTA.</p><p><strong>Methods: </strong>We screened acute ischemic stroke patients presenting within 24 h who underwent CT, CTA, and CTP as per institutional protocol. RAPID AI software processed CTP images, while neuroradiologists reviewed CTA for intracranial arterial occlusions. Sensitivity, specificity, and accuracy of automated CTP maps in detecting occlusions were assessed.</p><p><strong>Results: </strong>Of 790 screened patients, 31 were excluded due to lack of RAPID CTP data or poor-quality scans, leaving 759 for analysis. The median age was 71 years (IQR: 61-81), with 47% female. Among them, 678 had AIS, and 81 had AIS ruled out. CTA identified arterial occlusion in 562 patients (74%), with corresponding CTP abnormalities in 537 patients (Tmax > 6 sec). In the 197 without occlusion, CTP was negative in 161. Automated CTP maps had a sensitivity of 95.55% (CI 95: 93.50-97.10%), specificity of 81.73% (CI 95: 75.61-86.86%), negative predictive value of 98.22% (CI 95: 97.39-98.79%), positive predictive value of 63.54% (CI 95: 56.46-70.09%), and overall accuracy of 85.18% (CI 95: 82.45-87.64%).</p><p><strong>Conclusions: </strong>Automated CTP maps demonstrated high sensitivity and negative predictive value for LVOs and MeVOs, suggesting their usefulness as a rapid diagnostic tool, especially in settings without expert neuroradiologists.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2967-2976"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-24DOI: 10.1002/acn3.52202
Ahmad A Toubasi, Jarrod J Eisma, Jiacheng Wang, Habeeb F Kazimuddin, Bryan Hernandez, Taegan Vinarsky, Caroline Gheen, Zachary Rohm, Carynn Koch, Margareta A Clarke, Rachael Cheek, John Kramer, James Eaton, Manus J Donahue, Francesca Bagnato
Objective: Paramagnetic rim lesions (PRLs) are a biomarker of chronic active lesions (CALs), and an important driver of neurological disability in multiple sclerosis (MS). The reason subtending some acute lesions evolvement into CALs is not known. Here we ask whether a relatively lower oxygen content is linked to CALs.
Methods: In this prospective cross-sectional study, 64 people with multiple sclerosis (PwMS), clinically isolated syndrome and radiologically isolated syndrome underwent a 7.0 Tesla (7 T) brain magnetic resonance imaging (MRI). The scanning protocol included a T2-w fluid-attenuated inversion recovery (FLAIR), and a single echo gradient echo from which susceptibility-weighted imaging (SWI) was derived. WM lesions were identified on the T2-w-FLAIR whilst PRLs were identified on the SWI sequence. T2-lesions were classified as PRLs and rimless lesions (PRLs-). We registered a universal vascular atlas to each subject's T2-w-FLAIR and classified each T2-lesions according to its location into watershed- (ws), non-watershed- (nws), and mixed-lesion (m). Ws-lesions were defined as lesions that were fully located in a region between the territories of two major arteries.
Results: Out of 1,975 T2-lesions, 88 (4.5%) were PRLs. Ws-regions had a higher number (p = 0.005) and proportion (p < 0.001) of PRLs- compared to nws-regions. Ws-PRL- were larger compared to nws-ones (p = 0.009). The number (p = 0.043) and proportion (p < 0.001) of PRLs was higher in ws-regions compared to nws-ones. Ws-PRLs were not significantly larger than nws-ones (p = 0.195).
Interpretation: We propose the novel concept of a link between arterial vascularization and chronic activity in MS by demonstrating a preferential localization of CALs in ws-territories.
{"title":"Chronic active lesions preferentially localize in watershed territories in multiple sclerosis.","authors":"Ahmad A Toubasi, Jarrod J Eisma, Jiacheng Wang, Habeeb F Kazimuddin, Bryan Hernandez, Taegan Vinarsky, Caroline Gheen, Zachary Rohm, Carynn Koch, Margareta A Clarke, Rachael Cheek, John Kramer, James Eaton, Manus J Donahue, Francesca Bagnato","doi":"10.1002/acn3.52202","DOIUrl":"10.1002/acn3.52202","url":null,"abstract":"<p><strong>Objective: </strong>Paramagnetic rim lesions (PRLs) are a biomarker of chronic active lesions (CALs), and an important driver of neurological disability in multiple sclerosis (MS). The reason subtending some acute lesions evolvement into CALs is not known. Here we ask whether a relatively lower oxygen content is linked to CALs.</p><p><strong>Methods: </strong>In this prospective cross-sectional study, 64 people with multiple sclerosis (PwMS), clinically isolated syndrome and radiologically isolated syndrome underwent a 7.0 Tesla (7 T) brain magnetic resonance imaging (MRI). The scanning protocol included a T<sub>2</sub>-w fluid-attenuated inversion recovery (FLAIR), and a single echo gradient echo from which susceptibility-weighted imaging (SWI) was derived. WM lesions were identified on the T<sub>2</sub>-w-FLAIR whilst PRLs were identified on the SWI sequence. T<sub>2</sub>-lesions were classified as PRLs and rimless lesions (PRLs-). We registered a universal vascular atlas to each subject's T<sub>2</sub>-w-FLAIR and classified each T<sub>2</sub>-lesions according to its location into watershed- (ws), non-watershed- (nws), and mixed-lesion (m). Ws-lesions were defined as lesions that were fully located in a region between the territories of two major arteries.</p><p><strong>Results: </strong>Out of 1,975 T<sub>2</sub>-lesions, 88 (4.5%) were PRLs. Ws-regions had a higher number (p = 0.005) and proportion (p < 0.001) of PRLs- compared to nws-regions. Ws-PRL- were larger compared to nws-ones (p = 0.009). The number (p = 0.043) and proportion (p < 0.001) of PRLs was higher in ws-regions compared to nws-ones. Ws-PRLs were not significantly larger than nws-ones (p = 0.195).</p><p><strong>Interpretation: </strong>We propose the novel concept of a link between arterial vascularization and chronic activity in MS by demonstrating a preferential localization of CALs in ws-territories.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2912-2922"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-15DOI: 10.1002/acn3.52178
Nisa Vorasoot, Yahya J Abdulrahman, Farrah Mateen, James P Fryer, Vyanka Redenbaugh, Jessica A Sagen, Abdu K Musubire, Sarah M Jenkins, Amy P Gorsh, John J Chen, Anastasia Zekeridou, Andrew McKeon, Eoin P Flanagan, John R Mills, Sean J Pittock
Objective: This study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin-4-IgG (AQP4-IgG) testing.
Methods: Prospective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live-cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4-IgG detection between DBS and serum (gold standard) was compared.
Results: Among 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92-0.99). AQP4-IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74-0.95) and 100% specificity (95% CI: 0.96-1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43-0.84) and 95.2% specificity (95% CI: 0.76-0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47-0.87) and 98.4% specificity (95% CI: 0.91-0.99). The stability of DBS in detecting AQP4-IgG persisted over 24 months for most cases.
Interpretation: The DBS represents a viable alternative for detecting AQP4-IgG in resource-limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point-of-care testing.
{"title":"Dried blood spot improves global access to aquaporin-4-IgG testing for neuromyelitis optica.","authors":"Nisa Vorasoot, Yahya J Abdulrahman, Farrah Mateen, James P Fryer, Vyanka Redenbaugh, Jessica A Sagen, Abdu K Musubire, Sarah M Jenkins, Amy P Gorsh, John J Chen, Anastasia Zekeridou, Andrew McKeon, Eoin P Flanagan, John R Mills, Sean J Pittock","doi":"10.1002/acn3.52178","DOIUrl":"10.1002/acn3.52178","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin-4-IgG (AQP4-IgG) testing.</p><p><strong>Methods: </strong>Prospective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live-cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4-IgG detection between DBS and serum (gold standard) was compared.</p><p><strong>Results: </strong>Among 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92-0.99). AQP4-IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74-0.95) and 100% specificity (95% CI: 0.96-1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43-0.84) and 95.2% specificity (95% CI: 0.76-0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47-0.87) and 98.4% specificity (95% CI: 0.91-0.99). The stability of DBS in detecting AQP4-IgG persisted over 24 months for most cases.</p><p><strong>Interpretation: </strong>The DBS represents a viable alternative for detecting AQP4-IgG in resource-limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point-of-care testing.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2855-2865"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-30DOI: 10.1002/acn3.52206
Davide Ranucci, Fabrizia Falco, Valerio Nicolella, Cristina Di Monaco, Laura Migliaccio, Federica Lamagna, Federica Caracciolo, Martina Eliano, Maria Petracca, Marcello Moccia, Vincenzo Brescia Morra, Antonio Carotenuto, Roberta Lanzillo
Objective: People with multiple sclerosis (MS) might experience symptoms that are usually underestimated. Dysphagia should be evaluated within the Expanded Disability Status Scale (EDSS), but clinicians often do not assess it properly. The objectives of this study are as follows: To assess the prevalence of dysphagia in patients with MS utilizing the Swallowing Disturbance Questionnaire (SDQ); to examine the correlation with the EDSS; to investigate the relationship between dysphagia and clinico-demographic characteristics of MS.
Methods: In total, 177 MS patients underwent evaluations with EDSS, SDQ, cognitive functions, anxiety, depression, fatigue, and sleep quality tests. We compared clinico-demographic data of patients with and without dysphagia and native-EDSS to SDQ-EDSS.
Results: Out of the 177 MS patients, 56% of individuals were identified having dysphagia according to the SDQ with 41 patients exhibiting mild dysphagia, 31 showing moderate dysphagia and 27 patients having severe dysphagia. Only 6 patients had dysphagia recorded in the EDSS. SDQ-EDSS scores were significantly higher than native scores. Dysphagia was associated with depressive symptoms and sleep quality.
Interpretation: Dysphagia affects up to 56% of MS patients. The SDQ questionnaire is useful for identifying dysphagia, which can help in capturing disease progression and preventing complications like aspiration pneumonia. The SDQ-EDSS was higher than the native-EDSS, reflecting the poor ability of the native-EDSS to evaluate certain symptoms such as dysphagia. The SDQ correlated with depressive symptoms, which are associated with a greater perception of MS symptoms, and poor sleep quality, which could be associated with the triggering of pathogenic mechanisms responsible for disease progression.
{"title":"Dysphagia assessment in patients with multiple sclerosis - an additional piece to disability burden.","authors":"Davide Ranucci, Fabrizia Falco, Valerio Nicolella, Cristina Di Monaco, Laura Migliaccio, Federica Lamagna, Federica Caracciolo, Martina Eliano, Maria Petracca, Marcello Moccia, Vincenzo Brescia Morra, Antonio Carotenuto, Roberta Lanzillo","doi":"10.1002/acn3.52206","DOIUrl":"10.1002/acn3.52206","url":null,"abstract":"<p><strong>Objective: </strong>People with multiple sclerosis (MS) might experience symptoms that are usually underestimated. Dysphagia should be evaluated within the Expanded Disability Status Scale (EDSS), but clinicians often do not assess it properly. The objectives of this study are as follows: To assess the prevalence of dysphagia in patients with MS utilizing the Swallowing Disturbance Questionnaire (SDQ); to examine the correlation with the EDSS; to investigate the relationship between dysphagia and clinico-demographic characteristics of MS.</p><p><strong>Methods: </strong>In total, 177 MS patients underwent evaluations with EDSS, SDQ, cognitive functions, anxiety, depression, fatigue, and sleep quality tests. We compared clinico-demographic data of patients with and without dysphagia and native-EDSS to SDQ-EDSS.</p><p><strong>Results: </strong>Out of the 177 MS patients, 56% of individuals were identified having dysphagia according to the SDQ with 41 patients exhibiting mild dysphagia, 31 showing moderate dysphagia and 27 patients having severe dysphagia. Only 6 patients had dysphagia recorded in the EDSS. SDQ-EDSS scores were significantly higher than native scores. Dysphagia was associated with depressive symptoms and sleep quality.</p><p><strong>Interpretation: </strong>Dysphagia affects up to 56% of MS patients. The SDQ questionnaire is useful for identifying dysphagia, which can help in capturing disease progression and preventing complications like aspiration pneumonia. The SDQ-EDSS was higher than the native-EDSS, reflecting the poor ability of the native-EDSS to evaluate certain symptoms such as dysphagia. The SDQ correlated with depressive symptoms, which are associated with a greater perception of MS symptoms, and poor sleep quality, which could be associated with the triggering of pathogenic mechanisms responsible for disease progression.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2958-2966"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-28DOI: 10.1002/acn3.52195
Shu-Huai Lin, Jun-Hao Xie, Jun-Yi Jiang, Xin-Yu Yan, Chao-Yin Hong, Wan-Jin Chen, Ning Wang, Xiang Lin
FARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77, is a rarely neurodegenerative disease. Here, we reported two affected siblings in an autosomal recessive spastic paraplegia family with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2. Both patients gradually developed altered gaits and weakness in both lower limbs. In our literature review, spastic paraplegia type 77 shows high heterogeneity in clinical manifestations. Our study broadens the scope of pathogenic mechanisms of SPG77 resulting from compound heterozygous mutations in FARS2 and provides strong evidence that deletion in FARS2 due to recombination event mediated by Alu element.
{"title":"A pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2 causing spastic paraplegia 77.","authors":"Shu-Huai Lin, Jun-Hao Xie, Jun-Yi Jiang, Xin-Yu Yan, Chao-Yin Hong, Wan-Jin Chen, Ning Wang, Xiang Lin","doi":"10.1002/acn3.52195","DOIUrl":"10.1002/acn3.52195","url":null,"abstract":"<p><p>FARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77, is a rarely neurodegenerative disease. Here, we reported two affected siblings in an autosomal recessive spastic paraplegia family with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2. Both patients gradually developed altered gaits and weakness in both lower limbs. In our literature review, spastic paraplegia type 77 shows high heterogeneity in clinical manifestations. Our study broadens the scope of pathogenic mechanisms of SPG77 resulting from compound heterozygous mutations in FARS2 and provides strong evidence that deletion in FARS2 due to recombination event mediated by Alu element.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"3019-3024"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-02DOI: 10.1002/acn3.52198
Michael Eyre, Michael Absoud, Omar Abdel-Mannan, Sarah Crichton, Yael Hacohen, Thomas Rossor, Sarah Rudebeck, Gavin Giovannoni, Ming Lim, Cheryl Hemingway
It is unknown if cognition is impaired before clinical onset of paediatric acquired demyelinating syndromes. We conducted a matched cohort study using prospectively collected educational data in multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) patients (n = 60) and controls (pooled n = 449,553). Academic performance at ages 10-11 was impaired in MOGAD (-1.27 adjusted z-score [95% CI: -1.81 to -0.73], P < 0.001) and preclinical MS (-0.40 [-0.80 to -0.0003], P = 0.0498). Moderate/high-efficacy MS treatment was associated with better final academic performance (0.92 [0.28-1.57], P = 0.005). After clinical onset MS patients missed 8.7% of school (controls 2.9%, P < 0.001) and MOGAD patients 11.9% (controls 2.0%, P < 0.001).
在儿科获得性脱髓鞘综合征临床发病之前,认知能力是否会受损尚不清楚。我们利用前瞻性收集的教育数据,对多发性硬化症(MS)和髓鞘少突胶质细胞糖蛋白抗体病(MOGAD)患者(n = 60)和对照组(合计 n = 449,553 人)进行了一项匹配队列研究。多发性硬化症和髓鞘少突胶质细胞糖蛋白抗体病(MOGAD)患者 10-11 岁时的学习成绩受损(调整后 Z 评分为-1.27 [95% CI:-1.81 至-0.73],P<0.05)。
{"title":"Academic outcomes before and after clinical onset of acquired demyelinating syndromes in children: a matched cohort data linkage study.","authors":"Michael Eyre, Michael Absoud, Omar Abdel-Mannan, Sarah Crichton, Yael Hacohen, Thomas Rossor, Sarah Rudebeck, Gavin Giovannoni, Ming Lim, Cheryl Hemingway","doi":"10.1002/acn3.52198","DOIUrl":"10.1002/acn3.52198","url":null,"abstract":"<p><p>It is unknown if cognition is impaired before clinical onset of paediatric acquired demyelinating syndromes. We conducted a matched cohort study using prospectively collected educational data in multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) patients (n = 60) and controls (pooled n = 449,553). Academic performance at ages 10-11 was impaired in MOGAD (-1.27 adjusted z-score [95% CI: -1.81 to -0.73], P < 0.001) and preclinical MS (-0.40 [-0.80 to -0.0003], P = 0.0498). Moderate/high-efficacy MS treatment was associated with better final academic performance (0.92 [0.28-1.57], P = 0.005). After clinical onset MS patients missed 8.7% of school (controls 2.9%, P < 0.001) and MOGAD patients 11.9% (controls 2.0%, P < 0.001).</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"3025-3030"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-23DOI: 10.1002/acn3.52151
Andrea Pilotto, Alice Galli, Cinzia Zatti, Fabio Placidi, Francesca Izzi, Enrico Premi, Silvia P Caminiti, Luca Presotto, Andrea Rizzardi, Marcello Catania, Alessandro Lupini, Leandro Purin, Maria P Pasolini, Nicola B Mercuri, Agostino Chiaravalotti, Mariana Fernandes, Carmen Calvello, Silvia Lucchini, Francesco Bertagna, Barbara Paghera, Daniela Perani, Daniela Berg, Alessandro Padovani, Claudio Liguori
Methods: This study assessed data from two cohorts of patients with alpha-synucleinopathies (University of Brescia and University of Rome Tor-Vergata cohorts). Consecutive participants with video-polysomnography-confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I-FP-CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I-FP-CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls.
Results: The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age-matched controls. Individuals with iRBD were categorized as RBD-DAT- (n = 32) and RBD-DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD-DAT- showed an early involvement of the left insula, which increased in RBD-DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18-10.27].
Interpretation: In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non-pharmacological interventions.
{"title":"Insular monoaminergic deficits in prodromal α-synucleinopathies.","authors":"Andrea Pilotto, Alice Galli, Cinzia Zatti, Fabio Placidi, Francesca Izzi, Enrico Premi, Silvia P Caminiti, Luca Presotto, Andrea Rizzardi, Marcello Catania, Alessandro Lupini, Leandro Purin, Maria P Pasolini, Nicola B Mercuri, Agostino Chiaravalotti, Mariana Fernandes, Carmen Calvello, Silvia Lucchini, Francesco Bertagna, Barbara Paghera, Daniela Perani, Daniela Berg, Alessandro Padovani, Claudio Liguori","doi":"10.1002/acn3.52151","DOIUrl":"10.1002/acn3.52151","url":null,"abstract":"<p><strong>Methods: </strong>This study assessed data from two cohorts of patients with alpha-synucleinopathies (University of Brescia and University of Rome Tor-Vergata cohorts). Consecutive participants with video-polysomnography-confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and <sup>123</sup>I-FP-CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain <sup>123</sup> I-FP-CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls.</p><p><strong>Results: </strong>The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age-matched controls. Individuals with iRBD were categorized as RBD-DAT- (n = 32) and RBD-DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD-DAT- showed an early involvement of the left insula, which increased in RBD-DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18-10.27].</p><p><strong>Interpretation: </strong>In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non-pharmacological interventions.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":"2836-2845"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}