Ning Li, Jia Zhang, Yang Du, Jing Li, Anxin Wang, Xingquan Zhao
Objective: The association between gait speed and adverse outcomes after stroke has not been fully illustrated. This study aimed to explore the association of gait speed on long-term outcomes in minor stroke or transient ischemic attack (TIA).
Methods: We performed a longitudinal study with acute minor stroke or TIA based on a subgroup of the Third China National Stroke Registry data. The gait speed was evaluated using a 10-meter walking test at discharge and 3 months after the stroke onset. The primary outcomes were poor functional outcomes at 1 year, defined by a modified Rankin Score (mRS) of 2-6. Additional outcomes included all-cause death, ambulate dependency (mRS score 4-6), cognitive impairment (Montreal Cognitive Assessment <26), stroke recurrence, and composite vascular events.
Results: The study sample included a total of 1542 stroke patients with a median age of 60 (53-68). At 1-year follow-up, 140 (9.20%) patients experienced poor functional outcomes. Faster gait speed at discharge was associated with lower incidence of poor functional outcome (OR = 0.89; 95% CI, 0.84-0.94), cognitive impairment (OR = 0.93; 95% CI, 0.89-0.96), ischemic stroke recurrence (HR = 0.92; 95% CI, 0.87-0.98), and composite vascular events (HR =0.94; 95% CI, 0.89-0.99) at 1 year. Faster gait speed at 3 months was associated with lower incidence of poor functional outcome (OR = 0.90; 95% CI, 0.85-0.95), ambulate dependency (OR = 0.86; 95% CI, 0.77-0.97), and cognitive impairment (OR = 0.92; 95% CI, 0.88-0.95) at 1 year.
Interpretation: Our findings indicated that slow gait speed after minor stroke or TIA may be an independent predictor for long-term poor outcomes. Gait speed may be considered as a vital sign during follow-up in post-stroke patients.
{"title":"Gait speed after mild stroke/transient ischemic attack was associated with long-term adverse outcomes: A cohort study.","authors":"Ning Li, Jia Zhang, Yang Du, Jing Li, Anxin Wang, Xingquan Zhao","doi":"10.1002/acn3.52222","DOIUrl":"https://doi.org/10.1002/acn3.52222","url":null,"abstract":"<p><strong>Objective: </strong>The association between gait speed and adverse outcomes after stroke has not been fully illustrated. This study aimed to explore the association of gait speed on long-term outcomes in minor stroke or transient ischemic attack (TIA).</p><p><strong>Methods: </strong>We performed a longitudinal study with acute minor stroke or TIA based on a subgroup of the Third China National Stroke Registry data. The gait speed was evaluated using a 10-meter walking test at discharge and 3 months after the stroke onset. The primary outcomes were poor functional outcomes at 1 year, defined by a modified Rankin Score (mRS) of 2-6. Additional outcomes included all-cause death, ambulate dependency (mRS score 4-6), cognitive impairment (Montreal Cognitive Assessment <26), stroke recurrence, and composite vascular events.</p><p><strong>Results: </strong>The study sample included a total of 1542 stroke patients with a median age of 60 (53-68). At 1-year follow-up, 140 (9.20%) patients experienced poor functional outcomes. Faster gait speed at discharge was associated with lower incidence of poor functional outcome (OR = 0.89; 95% CI, 0.84-0.94), cognitive impairment (OR = 0.93; 95% CI, 0.89-0.96), ischemic stroke recurrence (HR = 0.92; 95% CI, 0.87-0.98), and composite vascular events (HR =0.94; 95% CI, 0.89-0.99) at 1 year. Faster gait speed at 3 months was associated with lower incidence of poor functional outcome (OR = 0.90; 95% CI, 0.85-0.95), ambulate dependency (OR = 0.86; 95% CI, 0.77-0.97), and cognitive impairment (OR = 0.92; 95% CI, 0.88-0.95) at 1 year.</p><p><strong>Interpretation: </strong>Our findings indicated that slow gait speed after minor stroke or TIA may be an independent predictor for long-term poor outcomes. Gait speed may be considered as a vital sign during follow-up in post-stroke patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Stölting, Colin Vanden Bulcke, Serena Borrelli, Céline Bugli, Renaud Du Pasquier, Vincent van Pesch, Pietro Maggi
Objective: Previous studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity.
Methods: In 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D-FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D-EPI phase. Using T1 relaxation time maps, lesions were categorized in long-T1 and short-T1. Lesion age was calculated from time of first gadolinium enhancement (N = 84 lesions). Results on clinical scores were validated in an extended cohort of 167 patients using normalized T1w-MPRAGE lesion values.
Results: Rim visibility (VCLS analysis) was associated with increasing lesional T1 (P/PFDR < 0.001). Of 1680 analyzed lesions, 427 were categorized as PRL. Long-T1 PRL were older than short-T1 PRL (average 0.8 vs. 2.0 years, P/PFDR = 0.005/0.008), and featured larger lesional volume (P/PFDR < 0.0001) and multi-shell diffusion-measured axonal damage (P/PFDR < 0.0001). The total volume of long-T1-PRL versus PRL showed 2× predictive power for both higher MS disability (EDSS; P/PFDR = 0.003/0.005 vs. P/PFDR = 0.042/0.057) and severity (MSSS; P/PFDR = 0.0006/0.001 vs. P/PFDR = 0.004/0.007). In random forest, having ≥1 long-T1-PRL versus ≥4 PRL showed 2-4× higher performance to predict a higher EDSS and MSSS. In the validation cohort, long-T1 PRL outperformed (~2×) PRL in predicting both EDSS and MSSS.
Interpretation: PRL show substantial heterogeneity in terms of intralesional tissue damage. More destructive, likely older, long-T1 PRL improve the association with MS clinical scales. This PRL heterogeneity characterization was replicated using standard T1w MRI, highlighting its potential for clinical translation.
{"title":"Clinical relevance of paramagnetic rim lesion heterogeneity in multiple sclerosis.","authors":"Anna Stölting, Colin Vanden Bulcke, Serena Borrelli, Céline Bugli, Renaud Du Pasquier, Vincent van Pesch, Pietro Maggi","doi":"10.1002/acn3.52220","DOIUrl":"https://doi.org/10.1002/acn3.52220","url":null,"abstract":"<p><strong>Objective: </strong>Previous studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity.</p><p><strong>Methods: </strong>In 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D-FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D-EPI phase. Using T1 relaxation time maps, lesions were categorized in long-T1 and short-T1. Lesion age was calculated from time of first gadolinium enhancement (N = 84 lesions). Results on clinical scores were validated in an extended cohort of 167 patients using normalized T1w-MPRAGE lesion values.</p><p><strong>Results: </strong>Rim visibility (VCLS analysis) was associated with increasing lesional T1 (P/P<sub>FDR</sub> < 0.001). Of 1680 analyzed lesions, 427 were categorized as PRL. Long-T1 PRL were older than short-T1 PRL (average 0.8 vs. 2.0 years, P/P<sub>FDR</sub> = 0.005/0.008), and featured larger lesional volume (P/P<sub>FDR</sub> < 0.0001) and multi-shell diffusion-measured axonal damage (P/P<sub>FDR</sub> < 0.0001). The total volume of long-T1-PRL versus PRL showed 2× predictive power for both higher MS disability (EDSS; P/P<sub>FDR</sub> = 0.003/0.005 vs. P/P<sub>FDR</sub> = 0.042/0.057) and severity (MSSS; P/P<sub>FDR</sub> = 0.0006/0.001 vs. P/P<sub>FDR</sub> = 0.004/0.007). In random forest, having ≥1 long-T1-PRL versus ≥4 PRL showed 2-4× higher performance to predict a higher EDSS and MSSS. In the validation cohort, long-T1 PRL outperformed (~2×) PRL in predicting both EDSS and MSSS.</p><p><strong>Interpretation: </strong>PRL show substantial heterogeneity in terms of intralesional tissue damage. More destructive, likely older, long-T1 PRL improve the association with MS clinical scales. This PRL heterogeneity characterization was replicated using standard T1w MRI, highlighting its potential for clinical translation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: We evaluated the effect of CHA2DS2-VASc score and prior use of oral anticoagulants (OACs) on endovascular treatment (EVT) in patients with acute ischemic stroke and atrial fibrillation (AF).
Methods: Patients with AF who received EVT in 353 centers in Japan (2018-2020) were included. The outcomes were symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, functional independence, and successful and complete reperfusion. The effects of CHA2DS2-VASc score, its components, and prior use of OACs were assessed via a multiple logistic regression model.
Results: Of the 6984 patients, 780 (11.2%) used warfarin and 1168 (16.7%) used direct oral anticoagulants (DOACs) before EVT. Based on the CHA2DS2-VASc score, 6046 (86.6%) presented a high risk (≥2 for males and ≥3 for females) while 938 (13.4%) had intermediate to low risks. Higher CHA2DS2-VASc scores were associated with increased sICH, in-hospital mortality, and decreased functional independence, regardless of prior OACs. For patients with a high-risk category, prior DOACs increased the odds of successful and complete reperfusion (adjusted odds ratio [95% confidence interval (CI)], 1.27 [1.00-1.61] and 1.30 [1.10-1.53]). For those with integrated intermediate to low risks, neither prior warfarin nor DOAC affected the outcomes. Regardless of total CHA2DS2-VASc scores, patients with congestive heart failure or left ventricular dysfunction, hypertension, age >75 years, or female benefited similarly from prior DOAC use.
Interpretation: Prior DOAC use for patients with high- and selected intermediate-risk CHA2DS2-VASc scores increased prevalence of successful and complete reperfusion. These findings may provide supplemental evidence to introduce preventive DOAC for patients with AF.
{"title":"CHA<sub>2</sub>DS<sub>2</sub>-VASc score and prior oral anticoagulant use on endovascular treatment for acute ischemic stroke.","authors":"Yukihiro Imaoka, Nice Ren, Soshiro Ogata, Hirotoshi Imamura, Yasuyuki Kaku, Koichi Arimura, Shogo Watanabe, Eri Kiyoshige, Kunihiro Nishimura, Syoji Kobashi, Masafumi Ihara, Kenji Kamiyama, Masafumi Morimoto, Tsuyoshi Ohta, Hidenori Endo, Yuji Matsumaru, Nobuyuki Sakai, Takanari Kitazono, Shigeru Fujimoto, Kuniaki Ogasawara, Koji Iihara","doi":"10.1002/acn3.52217","DOIUrl":"https://doi.org/10.1002/acn3.52217","url":null,"abstract":"<p><strong>Objective: </strong>We evaluated the effect of CHA<sub>2</sub>DS<sub>2</sub>-VASc score and prior use of oral anticoagulants (OACs) on endovascular treatment (EVT) in patients with acute ischemic stroke and atrial fibrillation (AF).</p><p><strong>Methods: </strong>Patients with AF who received EVT in 353 centers in Japan (2018-2020) were included. The outcomes were symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, functional independence, and successful and complete reperfusion. The effects of CHA<sub>2</sub>DS<sub>2</sub>-VASc score, its components, and prior use of OACs were assessed via a multiple logistic regression model.</p><p><strong>Results: </strong>Of the 6984 patients, 780 (11.2%) used warfarin and 1168 (16.7%) used direct oral anticoagulants (DOACs) before EVT. Based on the CHA<sub>2</sub>DS<sub>2</sub>-VASc score, 6046 (86.6%) presented a high risk (≥2 for males and ≥3 for females) while 938 (13.4%) had intermediate to low risks. Higher CHA<sub>2</sub>DS<sub>2</sub>-VASc scores were associated with increased sICH, in-hospital mortality, and decreased functional independence, regardless of prior OACs. For patients with a high-risk category, prior DOACs increased the odds of successful and complete reperfusion (adjusted odds ratio [95% confidence interval (CI)], 1.27 [1.00-1.61] and 1.30 [1.10-1.53]). For those with integrated intermediate to low risks, neither prior warfarin nor DOAC affected the outcomes. Regardless of total CHA<sub>2</sub>DS<sub>2</sub>-VASc scores, patients with congestive heart failure or left ventricular dysfunction, hypertension, age >75 years, or female benefited similarly from prior DOAC use.</p><p><strong>Interpretation: </strong>Prior DOAC use for patients with high- and selected intermediate-risk CHA<sub>2</sub>DS<sub>2</sub>-VASc scores increased prevalence of successful and complete reperfusion. These findings may provide supplemental evidence to introduce preventive DOAC for patients with AF.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saeed Jahromi, Margherita A.G. Matarrese, Lorenzo Fabbri, Eleonora Tamilia, M. Scott Perry, Joseph R. Madsen, Jeffrey Bolton, Scellig S.D. Stone, Phillip L. Pearl, Christos Papadelis
Objective
Interictal biomarkers are critical for identifying the epileptogenic focus. However, spikes and ripples lack specificity while fast ripples lack sensitivity. These biomarkers propagate from more epileptogenic onset to areas of spread. The pathophysiological mechanism of these propagations is elusive. Here, we examine zones where spikes and high frequency oscillations co-occur (SHFO), the spatiotemporal propagations of spikes, ripples, and fast ripples, and evaluate the spike–ripple onset overlap (SRO) as an epilepsy biomarker.
Methods
We retrospectively analyzed intracranial EEG data from 41 patients with drug-resistant epilepsy. We mapped propagations of spikes, ripples, and fast ripples, and identified their onset and spread zones, as well as SHFO and SRO. We then estimated the SRO prognostic value in predicting surgical outcome and compared it to onset and spread zones of spike, ripple, and fast ripple propagations, and SHFO.
Results
We detected spikes and ripples in all patients and fast ripples in 12 patients (29%). We observed spike and ripple propagations in 40 (98%) patients. Spike and ripple onsets overlapped in 35 (85%) patients. In good outcome patients, SRO showed higher specificity and precision (p < 0.05) in predicting resection compared to onset and zones of spikes, ripples, and SHFO. Only SRO resection predicted outcome (p = 0.01) with positive and negative predictive values of 82% and 57%, respectively.
Interpretation
SRO is a specific and precise biomarker of the epileptogenic zone whose removal predicts outcome. SRO is present in most patients with drug-resistant epilepsy. Such a biomarker may reduce prolonged intracranial monitoring and improve outcome.
{"title":"Overlap of spike and ripple propagation onset predicts surgical outcome in epilepsy","authors":"Saeed Jahromi, Margherita A.G. Matarrese, Lorenzo Fabbri, Eleonora Tamilia, M. Scott Perry, Joseph R. Madsen, Jeffrey Bolton, Scellig S.D. Stone, Phillip L. Pearl, Christos Papadelis","doi":"10.1002/acn3.52156","DOIUrl":"10.1002/acn3.52156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Interictal biomarkers are critical for identifying the epileptogenic focus. However, spikes and ripples lack specificity while fast ripples lack sensitivity. These biomarkers propagate from more epileptogenic onset to areas of spread. The pathophysiological mechanism of these propagations is elusive. Here, we examine zones where spikes and high frequency oscillations co-occur (SHFO), the spatiotemporal propagations of spikes, ripples, and fast ripples, and evaluate the spike–ripple onset overlap (SRO) as an epilepsy biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed intracranial EEG data from 41 patients with drug-resistant epilepsy. We mapped propagations of spikes, ripples, and fast ripples, and identified their onset and spread zones, as well as SHFO and SRO. We then estimated the SRO prognostic value in predicting surgical outcome and compared it to onset and spread zones of spike, ripple, and fast ripple propagations, and SHFO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We detected spikes and ripples in all patients and fast ripples in 12 patients (29%). We observed spike and ripple propagations in 40 (98%) patients. Spike and ripple onsets overlapped in 35 (85%) patients. In good outcome patients, SRO showed higher specificity and precision (<i>p <</i> 0.05) in predicting resection compared to onset and zones of spikes, ripples, and SHFO. Only SRO resection predicted outcome (<i>p</i> = 0.01) with positive and negative predictive values of 82% and 57%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>SRO is a specific and precise biomarker of the epileptogenic zone whose removal predicts outcome. SRO is present in most patients with drug-resistant epilepsy. Such a biomarker may reduce prolonged intracranial monitoring and improve outcome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2530-2547"},"PeriodicalIF":4.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386584","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}
Odile Feys, Vincent Wens, Sophie Schuind, Estelle Rikir, Benjamin Legros, Xavier De Tiège, Nicolas Gaspard
Introduction
Cortico-cortical evoked potentials (CCEPs) were described as reproducible during trains of single-pulse electrical stimulations (SPES). Still, few studies described a variability of CCEPs that was higher within the epileptogenic zone (EZ). This study aimed at characterizing the relationship of CCEP variability with the occurrence of interictal/ictal epileptiform discharges at the temporal vicinity of the stimulation, but not during the stimulation, by effective connectivity modifications.
Methods
We retrospectively included 20 patients who underwent SPES during their stereo-electroencephalography (SEEG). We analyzed the variability of CCEPs by using the post-stimulation time course of intertrial standard deviation (amplitude) and the timing of peak amplitude signal of CCEP epochs (latency). Values were corrected for the Euclidian distance between stimulating/recording electrodes. Receiver operating characteristics curves were used to assess the relationship with the EZ. The link between CCEP variability and interictal discharges occurrence, seizure frequency prior to the SEEG recording, and number of seizures during SEEG recording was assessed with Spearman's correlations.
Results
A relationship was demonstrated between the EZ and both the distance-corrected latency variation (area under the curve (AUC): 0.73–0.74) and the distance-corrected amplitude variation (AUC: 0.71–0.72) and both were related with the occurrence of seizures.
Conclusion
Seizures before/during SEEG impact the dynamics of effective connectivity within the epileptogenic network by reducing the variability of CCEP latency/amplitude when the seizure frequency increases. It suggests a strengthening of the epileptogenic network with the occurrence of many seizures. These findings stress the importance of early epilepsy surgery at a time when the network organization has not yet been complete.
{"title":"Variability of cortico-cortical evoked potentials in the epileptogenic zone is related to seizure occurrence","authors":"Odile Feys, Vincent Wens, Sophie Schuind, Estelle Rikir, Benjamin Legros, Xavier De Tiège, Nicolas Gaspard","doi":"10.1002/acn3.52179","DOIUrl":"10.1002/acn3.52179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cortico-cortical evoked potentials (CCEPs) were described as reproducible during trains of single-pulse electrical stimulations (SPES). Still, few studies described a variability of CCEPs that was higher within the epileptogenic zone (EZ). This study aimed at characterizing the relationship of CCEP variability with the occurrence of interictal/ictal epileptiform discharges at the temporal vicinity of the stimulation, but not during the stimulation, by effective connectivity modifications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively included 20 patients who underwent SPES during their stereo-electroencephalography (SEEG). We analyzed the variability of CCEPs by using the post-stimulation time course of intertrial standard deviation (amplitude) and the timing of peak amplitude signal of CCEP epochs (latency). Values were corrected for the Euclidian distance between stimulating/recording electrodes. Receiver operating characteristics curves were used to assess the relationship with the EZ. The link between CCEP variability and interictal discharges occurrence, seizure frequency prior to the SEEG recording, and number of seizures during SEEG recording was assessed with Spearman's correlations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A relationship was demonstrated between the EZ and both the distance-corrected latency variation (area under the curve (AUC): 0.73–0.74) and the distance-corrected amplitude variation (AUC: 0.71–0.72) and both were related with the occurrence of seizures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Seizures before/during SEEG impact the dynamics of effective connectivity within the epileptogenic network by reducing the variability of CCEP latency/amplitude when the seizure frequency increases. It suggests a strengthening of the epileptogenic network with the occurrence of many seizures. These findings stress the importance of early epilepsy surgery at a time when the network organization has not yet been complete.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2645-2656"},"PeriodicalIF":4.4,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379637","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}
Yuzhi Shi, Gehong Dong, Hua Pan, Hongfei Tai, Yi Zhou, An Wang, Songtao Niu, Bin Chen, Xingao Wang, Zaiqiang Zhang
Objective: To delineate the characteristics of stroke-like episodes (SLEs) in patients with adult-onset neuronal intranuclear inclusion disease (NIID) and to compare these characteristics with those of patients with MELAS.
Methods: Twenty-three adult-onset NIID patients who presented with acute or subacute brain disorders and 13 late-onset MELAS patients were enrolled in the study. Patients with NIID were categorized into the SLEs group and the encephalopathy-like episodes (ELEs) group according to the associated stroke-like lesions (SLLs) findings. Clinical characteristics were compared between the SLEs group and the ELEs group among NIID patients and between NIID patients with SLEs and MELAS patients.
Results: Eleven (47.8%) NIID patients who manifested acute or subacute brain disorders had detectable associated SLLs and were categorized into SLEs group. SLEs patients were more likely to report fever, headache, and seizures instead of sleep disorders than ELEs patients. Four (36.4%) NIID patients with SLEs absence of diagnostic or suggestive NIID imaging features. The clinical manifestations, laboratory test results, and neuroimaging and muscle biopsy histological features of NIID patients with SLEs majorly overlapped with those of late-onset MELAS patients. Older age at the first SLE (OR [95% CI], 1.203 [1.045-1.384]), symptoms of movement disorders on admission (OR [95% CI], 9.625 [1.378-67.246]), and white matter hyperintensity in corpus callosum (OR [95% CI], 16.00 [1.542-166.46]) associated with the NIID diagnosis in patients with SLEs.
Interpretation: NIID patients with SLEs exhibit evident features of mitochondrial disorders. Interventions aimed at mitochondrial dysfunction might be a promising therapeutic approach for treating this disease.
{"title":"Stroke-like episodes in patients with adult-onset neuronal intranuclear inclusion disease and patients with late-onset MELAS: A comparative study.","authors":"Yuzhi Shi, Gehong Dong, Hua Pan, Hongfei Tai, Yi Zhou, An Wang, Songtao Niu, Bin Chen, Xingao Wang, Zaiqiang Zhang","doi":"10.1002/acn3.52219","DOIUrl":"https://doi.org/10.1002/acn3.52219","url":null,"abstract":"<p><strong>Objective: </strong>To delineate the characteristics of stroke-like episodes (SLEs) in patients with adult-onset neuronal intranuclear inclusion disease (NIID) and to compare these characteristics with those of patients with MELAS.</p><p><strong>Methods: </strong>Twenty-three adult-onset NIID patients who presented with acute or subacute brain disorders and 13 late-onset MELAS patients were enrolled in the study. Patients with NIID were categorized into the SLEs group and the encephalopathy-like episodes (ELEs) group according to the associated stroke-like lesions (SLLs) findings. Clinical characteristics were compared between the SLEs group and the ELEs group among NIID patients and between NIID patients with SLEs and MELAS patients.</p><p><strong>Results: </strong>Eleven (47.8%) NIID patients who manifested acute or subacute brain disorders had detectable associated SLLs and were categorized into SLEs group. SLEs patients were more likely to report fever, headache, and seizures instead of sleep disorders than ELEs patients. Four (36.4%) NIID patients with SLEs absence of diagnostic or suggestive NIID imaging features. The clinical manifestations, laboratory test results, and neuroimaging and muscle biopsy histological features of NIID patients with SLEs majorly overlapped with those of late-onset MELAS patients. Older age at the first SLE (OR [95% CI], 1.203 [1.045-1.384]), symptoms of movement disorders on admission (OR [95% CI], 9.625 [1.378-67.246]), and white matter hyperintensity in corpus callosum (OR [95% CI], 16.00 [1.542-166.46]) associated with the NIID diagnosis in patients with SLEs.</p><p><strong>Interpretation: </strong>NIID patients with SLEs exhibit evident features of mitochondrial disorders. Interventions aimed at mitochondrial dysfunction might be a promising therapeutic approach for treating this disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Granger causal analysis (GCA) and amplitude of low-frequency fluctuation (ALFF) are commonly used to evaluate functional alterations in brain disorders. By combining the GCA and ALFF, this study aimed to investigate the effective connectivity (EC) changes in patients with acute ischemic stroke (AIS) and anterior circulation occlusion after mechanical thrombectomy (MT).
Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 43 AIS patients with anterior circulation occlusion within 1 week post-MT and 37 healthy controls. ALFF and GCA were calculated for each participant. Patients were further divided into groups based on prognosis and perfusion levels. The differences in ALFF and EC were compared between AIS patients and healthy controls and between subgroups of patients. Pearson correlations between EC, ALFF values, and clinical characteristics of patients were calculated.
Results: Compared to healthy controls, post-MT, AIS patients exhibited significant ALFF increases in the left precuneus and decreases in the left fusiform gyrus and right caudate. Increased EC from the contralesional lingual gyrus, contralesional putamen, ipsilesional thalamus, and contralesional thalamus to the contralesional caudate was obsrved, while decrease in EC were found for contralesional caudate to the ipsilesional thalamus and medial superior frontal gyrus. EC differences were particularly notable between perfusion groups, with significantly lower EC in the poorly perfused group. EC values were also positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores pre-MT.
Interpretation: In AIS patients, the caudate nucleus was central to the observed EC changes post-MT, characterized by decreased outputs and increased inputs. These changes indicate functional remodeling within the cortico-basal ganglia-thalamic-cortical pathway.
{"title":"Evaluating post-thrombectomy effective connectivity changes in anterior circulation stroke.","authors":"Jiaona Xu, Weiwei Chen, Guozhong Niu, Yuting Meng, Kefan Qiu, Tongyue Li, Luoyu Wang, Liqing Zhang, Yating Lv, Zhongxiang Ding","doi":"10.1002/acn3.52221","DOIUrl":"https://doi.org/10.1002/acn3.52221","url":null,"abstract":"<p><strong>Objective: </strong>Granger causal analysis (GCA) and amplitude of low-frequency fluctuation (ALFF) are commonly used to evaluate functional alterations in brain disorders. By combining the GCA and ALFF, this study aimed to investigate the effective connectivity (EC) changes in patients with acute ischemic stroke (AIS) and anterior circulation occlusion after mechanical thrombectomy (MT).</p><p><strong>Methods: </strong>Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 43 AIS patients with anterior circulation occlusion within 1 week post-MT and 37 healthy controls. ALFF and GCA were calculated for each participant. Patients were further divided into groups based on prognosis and perfusion levels. The differences in ALFF and EC were compared between AIS patients and healthy controls and between subgroups of patients. Pearson correlations between EC, ALFF values, and clinical characteristics of patients were calculated.</p><p><strong>Results: </strong>Compared to healthy controls, post-MT, AIS patients exhibited significant ALFF increases in the left precuneus and decreases in the left fusiform gyrus and right caudate. Increased EC from the contralesional lingual gyrus, contralesional putamen, ipsilesional thalamus, and contralesional thalamus to the contralesional caudate was obsrved, while decrease in EC were found for contralesional caudate to the ipsilesional thalamus and medial superior frontal gyrus. EC differences were particularly notable between perfusion groups, with significantly lower EC in the poorly perfused group. EC values were also positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores pre-MT.</p><p><strong>Interpretation: </strong>In AIS patients, the caudate nucleus was central to the observed EC changes post-MT, characterized by decreased outputs and increased inputs. These changes indicate functional remodeling within the cortico-basal ganglia-thalamic-cortical pathway.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α-Synuclein (α-Syn) species in plasma neuron-derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs).
Methods
Nanoscale flow cytometry was used to detect α-Syn-containing NDEVs in plasma.
Results
A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α-Syn, α-Syn aggregates, and phosphorylated α-Syn at Ser129 (pS129)-containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (p < 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α-Syn, pS129, and α-Syn aggregate-containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α-Syn aggregate-containing NDEVs exhibited a negative correlation with Sniffin’ Sticks olfactory scores (r = −0.351, p = 0.039). Smokers with iRBD exhibited lower levels of α-Syn aggregates and pS129-containing NDEVs in plasma compared to nonsmokers (pα-Syn aggregates = 0.014; ppS129 = 0.003).
Interpretation
The current study demonstrated that the levels of total α-Syn, α-Syn aggregates, and pS129-containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α-Syn species-containing NDEVs in plasma may serve as biomarkers for iRBD.
{"title":"α-Synuclein species in plasma neuron-derived extracellular vesicles as biomarkers for iRBD","authors":"Xuemei Wang, Yuanchu Zheng, Huihui Cai, Wenyi Kou, Chen Yang, Siming Li, Bingxu Zhu, Jiayi Wu, Ning Zhang, Tao Feng, Xiaohong Li, Fulong Xiao, Zhenwei Yu","doi":"10.1002/acn3.52200","DOIUrl":"10.1002/acn3.52200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α-Synuclein (α-Syn) species in plasma neuron-derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nanoscale flow cytometry was used to detect α-Syn-containing NDEVs in plasma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α-Syn, α-Syn aggregates, and phosphorylated α-Syn at Ser129 (pS129)-containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (<i>p</i> < 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α-Syn, pS129, and α-Syn aggregate-containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α-Syn aggregate-containing NDEVs exhibited a negative correlation with Sniffin’ Sticks olfactory scores (<i>r</i> = −0.351, <i>p</i> = 0.039). Smokers with iRBD exhibited lower levels of α-Syn aggregates and pS129-containing NDEVs in plasma compared to nonsmokers (<i>p</i><sub>α-Syn aggregates</sub> = 0.014; <i>p</i><sub>pS129</sub> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The current study demonstrated that the levels of total α-Syn, α-Syn aggregates, and pS129-containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α-Syn species-containing NDEVs in plasma may serve as biomarkers for iRBD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2891-2903"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265424","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}
This study aims to elucidate the cognitive underpinnings of language abnormalities in Alzheimer's Disease (AD) using a computational cross-linguistic approach and ultimately enhance the understanding and diagnostic accuracy of the disease.
Methods
Computational analyses were conducted on language samples of 156 English and 50 Persian speakers, comprising both AD patients and healthy controls, to extract language indicators of AD. Furthermore, we introduced a machine learning-based metric, Language Informativeness Index (LII), to quantify empty speech.
Results
Despite considerable disparities in surface structures between the two languages, we observed consistency across language indicators of AD in both English and Persian. Notably, indicators of AD in English resulted in a classification accuracy of 90% in classifying AD in Persian. The substantial degree of transferability suggests that the language abnormalities of AD do not tightly link to the surface structures specific to English. Subsequently, we posited that these abnormalities stem from impairments in a more universal aspect of language production: the ability to generate informative messages independent of the language spoken. Consistent with this hypothesis, we found significant correlations between language indicators of AD and empty speech in both English and Persian.
Interpretation
The findings of this study suggest that language impairments in AD arise from a deficit in a universal aspect of message formation rather than from the breakdown of language-specific morphosyntactic structures. Beyond enhancing our understanding of the psycholinguistic deficits of AD, our approach fosters the development of diagnostic tools across various languages, enhancing health equity and biocultural diversity.
方法我们对 156 位英语和 50 位波斯语使用者（包括阿尔茨海默病患者和健康对照者）的语言样本进行了计算分析，以提取阿尔茨海默病的语言指标。此外，我们还引入了一种基于机器学习的指标--语言信息度指数（LII）--来量化空洞的语音。结果尽管两种语言的表面结构存在相当大的差异，但我们观察到英语和波斯语中的AD语言指标具有一致性。值得注意的是，英语中的 AD 指标对波斯语中 AD 的分类准确率高达 90%。这种高度的可转移性表明，注意力缺失症的语言异常与英语特有的表面结构并无紧密联系。随后，我们假设这些异常源于语言产生的一个更为普遍的方面的障碍：即产生独立于所使用语言的信息的能力。与这一假设相一致的是，我们发现 AD 的语言指标与英语和波斯语的空洞言语之间存在显著的相关性。 本研究的结果表明，AD 的语言障碍源于信息形成的一个普遍方面的缺陷，而不是源于特定语言形态句法结构的破坏。除了加深我们对注意力缺失症心理语言障碍的理解之外，我们的研究方法还促进了各种语言诊断工具的开发，提高了健康公平性和生物文化多样性。
{"title":"Language abnormalities in Alzheimer's disease indicate reduced informativeness","authors":"Sabereh Bayat, Mahya Sanati, Mehrdad Mohammad-Panahi, Amirhossein Khodadadi, Mahdieh Ghasimi, Sahar Rezaee, Sara Besharat, Zahra Mahboubi-Fooladi, Mostafa Almasi-Dooghaee, Morteza Sanei-Taheri, Bradford C. Dickerson, Neguine Rezaii","doi":"10.1002/acn3.52205","DOIUrl":"10.1002/acn3.52205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to elucidate the cognitive underpinnings of language abnormalities in Alzheimer's Disease (AD) using a computational cross-linguistic approach and ultimately enhance the understanding and diagnostic accuracy of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Computational analyses were conducted on language samples of 156 English and 50 Persian speakers, comprising both AD patients and healthy controls, to extract language indicators of AD. Furthermore, we introduced a machine learning-based metric, Language Informativeness Index (LII), to quantify empty speech.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite considerable disparities in surface structures between the two languages, we observed consistency across language indicators of AD in both English and Persian. Notably, indicators of AD in English resulted in a classification accuracy of 90% in classifying AD in Persian. The substantial degree of transferability suggests that the language abnormalities of AD do not tightly link to the surface structures specific to English. Subsequently, we posited that these abnormalities stem from impairments in a more universal aspect of language production: the ability to generate informative messages independent of the language spoken. Consistent with this hypothesis, we found significant correlations between language indicators of AD and empty speech in both English and Persian.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The findings of this study suggest that language impairments in AD arise from a deficit in a universal aspect of message formation rather than from the breakdown of language-specific morphosyntactic structures. Beyond enhancing our understanding of the psycholinguistic deficits of AD, our approach fosters the development of diagnostic tools across various languages, enhancing health equity and biocultural diversity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2946-2957"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265420","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}
Monica Margoni, Paolo Preziosa, Elisabetta Pagani, Loredana Storelli, Mor Gueye, Lucia Moiola, Massimo Filippi, Maria A. Rocca
The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.
{"title":"Assessment of central vein sign and paramagnetic rim lesions in pediatric multiple sclerosis","authors":"Monica Margoni, Paolo Preziosa, Elisabetta Pagani, Loredana Storelli, Mor Gueye, Lucia Moiola, Massimo Filippi, Maria A. Rocca","doi":"10.1002/acn3.52208","DOIUrl":"10.1002/acn3.52208","url":null,"abstract":"<p>The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"3031-3036"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265426","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}
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