Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
ABSTRACT: IgG4-related disease (IgG4-RD) is a rare and often misdiagnosed disorder with limited l... more ABSTRACT: IgG4-related disease (IgG4-RD) is a rare and often misdiagnosed disorder with limited literature that highlights the different neurological presentations of this treatable disease. The diagnosis of IgG4-RD could be challenging, while imaging is fundamental for the diagnosis, biopsy is considered the gold standard. Most cases respond well to steroids and immunosuppressive therapy. This is a case series study that illustrates the varied neurological presentations of IgG4-RD through three different patients that were followed at the Montreal Neurological Institute. This paper takes you through the diagnostic strategy that we followed to accurately diagnose and treat those patients.
Background and Purpose: Cellular adhesion molecules may play a critical role in the inflammatory ... more Background and Purpose: Cellular adhesion molecules may play a critical role in the inflammatory process leading to atherosclerosis. The purpose of this study was to determine whether soluble intercellular adhesion molecule-1 (sICAM-1) is a predictor of future ischemic events in high-risk individuals and also whether it is associated with carotid artery stenosis. Methods: We conducted a prospective study of sICAM-1 concentration in 3 groups: (1) subjects with recent (<7 days) ischemic stroke or TIA, (2) asymptomatic subjects with carotid stenosis ≧ 50% and (3) asymptomatic individuals with vascular risk factors. Subjects were followed for a minimum of 3 years. sICAM-1 levels were compared between the groups and correlated with the risk of ischemic events and the degree of carotid artery stenosis. Results: We studied 275 subjects. Mean sICAM-1 levels were significantly higher in those with recent ischemic stroke or TIA compared to those with risk factors alone. During follow-up, i...
IMPORTANCE Some patients have poor outcomes despite small infarcts after endovascular therapy (EV... more IMPORTANCE Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes. OBJECTIVE To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome. DESIGN, SETTING, AND PARTICIPANTS This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included. EXPOSURES Small FIV (volume Յ25th percentile) and large FIV (volume Ն75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score Ն3 despite small FIV or those with mRS scores Յ2 despite large FIV) and nondiscrepant cases. MAIN OUTCOMES AND MEASURES Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression-derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score. RESULTS Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, Յ25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, Ն75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (continued) Key Points Question Why do some patients have poor outcomes despite small infarcts after endovascular therapy, while others with large infarcts fare better? Findings In this cohort study of 1091 patients who received endovascular therapy as part of a randomized clinical trial, discrepancies between infarct volume and functional outcome were associated with prespecified pretreatment factors, such as age, cancer, and vascular risk factors, as well as posttreatment factors, such as infarct in new territory, stroke progression, intracerebral hemorrhage, recurrent stroke, pneumonia, and heart failure. Models including these factors performed similar to those derived from stepwise regressions. Meaning In this study, discrepancies between outcome and infarct volume were associated with pretreatment and posttreatment factors, including complications related to index stroke evolution, secondary prevention, and quality of stroke unit care.
BACKGROUND Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is... more BACKGROUND Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING Canadian Institutes for Health Research, Alberta Innovates, and NoNO.
Objective: To determine whether serum levels of soluble intercellular adhesion molecule-1 (sICAM)... more Objective: To determine whether serum levels of soluble intercellular adhesion molecule-1 (sICAM) differ between individuals with recent acute ischemic stroke (AIS) or transient ischemic attack (TIA) and control subjects. Methods: sICAM levels were measured in ...
Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neu... more Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neuropathy predominantly affecting the legs. This met clinical and electrophysiological criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Nerve biopsies showed a variety of abnormalities, none of which clearly distinguished between diabetic polyneuropathy and CIDP. The patients were treated with combinations of corticosteroids, azathioprine, plasmapheresis and intravenous immune globulin;
Journal of Stroke and Cerebrovascular Diseases, 1997
Intra-arterial Doppler sonography may complement arteriography by providing immediate physiologic... more Intra-arterial Doppler sonography may complement arteriography by providing immediate physiological evidence of hemodynamic adequacy and by obviating unnecessary angioplastic dilation. We used a Doppler-tipped guidewire in 16 patients and obtained velocity measurements at the site of stenosis immediately before and after carotid artery stenting (CAS) in 10 patients. Intra-arterial Doppler sonography confirmed hemodynamic improvement immediately after stent placement and correlated well with post-CAS duplex Doppler sonography results. Thus, intra-arterial Doppler sonography can be feasibly incorporated into CAS procedures for hemodynamic evaluation and can provide anatomic information that complements information provided by angiography.
Archives of Physical Medicine and Rehabilitation, 2002
Mayo NE, Wood-Dauphinee S, Côté R, Durcan L, Carlton J. Activity, participation, and quality of l... more Mayo NE, Wood-Dauphinee S, Côté R, Durcan L, Carlton J. Activity, participation, and quality of life 6 months poststroke. Arch Phys Med Rehabil 2002;83:1035-42.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
ABSTRACT: IgG4-related disease (IgG4-RD) is a rare and often misdiagnosed disorder with limited l... more ABSTRACT: IgG4-related disease (IgG4-RD) is a rare and often misdiagnosed disorder with limited literature that highlights the different neurological presentations of this treatable disease. The diagnosis of IgG4-RD could be challenging, while imaging is fundamental for the diagnosis, biopsy is considered the gold standard. Most cases respond well to steroids and immunosuppressive therapy. This is a case series study that illustrates the varied neurological presentations of IgG4-RD through three different patients that were followed at the Montreal Neurological Institute. This paper takes you through the diagnostic strategy that we followed to accurately diagnose and treat those patients.
Background and Purpose: Cellular adhesion molecules may play a critical role in the inflammatory ... more Background and Purpose: Cellular adhesion molecules may play a critical role in the inflammatory process leading to atherosclerosis. The purpose of this study was to determine whether soluble intercellular adhesion molecule-1 (sICAM-1) is a predictor of future ischemic events in high-risk individuals and also whether it is associated with carotid artery stenosis. Methods: We conducted a prospective study of sICAM-1 concentration in 3 groups: (1) subjects with recent (<7 days) ischemic stroke or TIA, (2) asymptomatic subjects with carotid stenosis ≧ 50% and (3) asymptomatic individuals with vascular risk factors. Subjects were followed for a minimum of 3 years. sICAM-1 levels were compared between the groups and correlated with the risk of ischemic events and the degree of carotid artery stenosis. Results: We studied 275 subjects. Mean sICAM-1 levels were significantly higher in those with recent ischemic stroke or TIA compared to those with risk factors alone. During follow-up, i...
IMPORTANCE Some patients have poor outcomes despite small infarcts after endovascular therapy (EV... more IMPORTANCE Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes. OBJECTIVE To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome. DESIGN, SETTING, AND PARTICIPANTS This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included. EXPOSURES Small FIV (volume Յ25th percentile) and large FIV (volume Ն75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score Ն3 despite small FIV or those with mRS scores Յ2 despite large FIV) and nondiscrepant cases. MAIN OUTCOMES AND MEASURES Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression-derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score. RESULTS Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, Յ25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, Ն75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (continued) Key Points Question Why do some patients have poor outcomes despite small infarcts after endovascular therapy, while others with large infarcts fare better? Findings In this cohort study of 1091 patients who received endovascular therapy as part of a randomized clinical trial, discrepancies between infarct volume and functional outcome were associated with prespecified pretreatment factors, such as age, cancer, and vascular risk factors, as well as posttreatment factors, such as infarct in new territory, stroke progression, intracerebral hemorrhage, recurrent stroke, pneumonia, and heart failure. Models including these factors performed similar to those derived from stepwise regressions. Meaning In this study, discrepancies between outcome and infarct volume were associated with pretreatment and posttreatment factors, including complications related to index stroke evolution, secondary prevention, and quality of stroke unit care.
BACKGROUND Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is... more BACKGROUND Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING Canadian Institutes for Health Research, Alberta Innovates, and NoNO.
Objective: To determine whether serum levels of soluble intercellular adhesion molecule-1 (sICAM)... more Objective: To determine whether serum levels of soluble intercellular adhesion molecule-1 (sICAM) differ between individuals with recent acute ischemic stroke (AIS) or transient ischemic attack (TIA) and control subjects. Methods: sICAM levels were measured in ...
Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neu... more Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neuropathy predominantly affecting the legs. This met clinical and electrophysiological criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Nerve biopsies showed a variety of abnormalities, none of which clearly distinguished between diabetic polyneuropathy and CIDP. The patients were treated with combinations of corticosteroids, azathioprine, plasmapheresis and intravenous immune globulin;
Journal of Stroke and Cerebrovascular Diseases, 1997
Intra-arterial Doppler sonography may complement arteriography by providing immediate physiologic... more Intra-arterial Doppler sonography may complement arteriography by providing immediate physiological evidence of hemodynamic adequacy and by obviating unnecessary angioplastic dilation. We used a Doppler-tipped guidewire in 16 patients and obtained velocity measurements at the site of stenosis immediately before and after carotid artery stenting (CAS) in 10 patients. Intra-arterial Doppler sonography confirmed hemodynamic improvement immediately after stent placement and correlated well with post-CAS duplex Doppler sonography results. Thus, intra-arterial Doppler sonography can be feasibly incorporated into CAS procedures for hemodynamic evaluation and can provide anatomic information that complements information provided by angiography.
Archives of Physical Medicine and Rehabilitation, 2002
Mayo NE, Wood-Dauphinee S, Côté R, Durcan L, Carlton J. Activity, participation, and quality of l... more Mayo NE, Wood-Dauphinee S, Côté R, Durcan L, Carlton J. Activity, participation, and quality of life 6 months poststroke. Arch Phys Med Rehabil 2002;83:1035-42.
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Papers by Liam Durcan