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Research Interests: Cardiology, Magnetic Resonance Imaging, Medicine, Stroke, Prospective studies, and 15 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Aged, Middle Aged, Longitudinal Studies, Neurosciences, Transient Ischemic Attack (TIA), Predictive value of tests, Cognition disorders, Neuropsychological Tests, Diffusion magnetic resonance imaging, and Cardiovascular medicine and haematology
Research Interests: Medicine, Canada, Humans, Female, Male, and 15 moreBrain Ischemia, Clinical Sciences, Aged, Middle Aged, Adult, Prognosis, Intracerebral Hemorrhage, Asymptomatic, Cerebral Hemorrhage, Neurosciences, Predictive value of tests, Cohort Studies, modified Rankin Scale, Cardiovascular medicine and haematology, and cerebral arteries
Background: Early infarct growth after endovascular therapy (EVT) may lead to unfavorable outcomes despite successful reperfusion. The REPERFUSE-NA1 study replicated the preclinical NA1 experiment by investigating the effect of NA1 on... more
Background: Early infarct growth after endovascular therapy (EVT) may lead to unfavorable outcomes despite successful reperfusion. The REPERFUSE-NA1 study replicated the preclinical NA1 experiment by investigating the effect of NA1 on early DWI infarct growth in acute ischemic stroke patients receiving EVT. Methods: REPERFUSE-NA1 was a sub-study of the randomized controlled trial ESCAPE-NA1 (ClinicalTrialGov NCT02930018). Patients received MRI within 5 hours and 24 hours of EVT. The primary outcome was early diffusion weighted (DWI) infarct growth. The secondary outcome was region-specific DWI infarct growth in the white matter, cortical grey matter and basal ganglia. Results: A total of 71 patients was included, of whom 67 had sufficient MR imaging at 5h and 24h post-EVT. For patients who received NA1 compared to placebo, the median age (68.8 v 67.5), baseline NIHSS (15.5 v 16), time from symptom onset to reperfusion (161 v 167 minutes) and mTICI 2b-3 (94.4% v 94.3%) were statistically not different. Median DWI volumes post-EVT (5h) were 13.0 mL (IQR, 5.9-28.1) in NA1 and 13.3 mL (IQR, 3.1-27.0) in placebo. At 24h median DWI volumes increased to 22.6 mL (IQR, 11.2-63.4) in the NA1 group and 22.4 mL (IQR, 7.4-52.3) in the placebo group, equating to a 48.4% DWI volume growth in the NA1 group and a 66.0% growth in the placebo group. Median DWI volume growth was 55.1% for NA1 patients who received alteplase compared to 41.3% for NA1 patients who did not receive alteplase (p=0.65). In terms of region-specific infarct volumes, absolute growth was 2.27mL (IQR, 0.70-6.19) in the white matter, 3.93 mL (IQR, 0.18-12.40) in cortical grey matter, and 1.20 mL (IQR, 0.31-2.62) in basal ganglia in the overall cohort. Between the NA1 and the placebo groups, lesion growth in the white matter (1.96 mL v 2.77mL), cortical gray matter (3.93 mL v 4.07 mL) and basal ganglia (1.62 mL v 0.89 mL) did not differ significantly. Conclusion: There was substantial infarct growth early after EVT, with the largest absolute growth in cortical grey matter. No significant effect of NA1 on early infarct growth was observed.
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Background The relationship between duration of transient neurological events and presence of diffusion‐weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic... more
Background The relationship between duration of transient neurological events and presence of diffusion‐weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion‐weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For...
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Background: Cognitive reserve may protect against the effects of brain pathology, but few studies have looked at whether cognitive reserve modifies the adverse effects of vascular brain pathology. Objective: We determined if cognitive... more
Background: Cognitive reserve may protect against the effects of brain pathology, but few studies have looked at whether cognitive reserve modifies the adverse effects of vascular brain pathology. Objective: We determined if cognitive reserve attenuates the associations of vascular brain lesions with worse cognition in persons with subjective concerns or mild impairment. Methods: We analyzed 200 participants aged 50–90 years from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. Cognition was measured using the Montreal Cognitive Assessment and a neuropsychological test battery. High vascular lesion burden was defined as two or more supratentorial infarcts or beginning confluent or confluent white matter hyperintensity. Cognitive reserve proxies included education, occupational attainment, marital status, social activities, physical activity, household income, and multilingualism. Results: Mean age was 72.8 years and 48% were female; 73.5% had mild c...
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48 Background: In patients eligible for thrombolytic therapy, the TIBI grading system defines residual transcranial Doppler (TCD) flow signals at the site of clot location. In addition, TIBI flow grades correlate with angiography and... more
48 Background: In patients eligible for thrombolytic therapy, the TIBI grading system defines residual transcranial Doppler (TCD) flow signals at the site of clot location. In addition, TIBI flow grades correlate with angiography and predict short-term improvement following TPA therapy. The aim of this study was to develop a valid and reliable instrument to assess how accurately health professionals determine TIBI flow grades. Methods: Two expert sonographers developed a 60 question computerized examination of the 6 TIBI flow grades. Gold standard interpretation was determined by a consensus interpretation by a pool of expert sonographers. All items were equally weighted and written in a standard format. A computerized TIBI grading tutorial and standard interpretation rules were available for all test-takers. To assess content validity and reliability, a blinded panel of 3 experts independently took the examination. Inter-rater agreement was determined among experienced sonographers...
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IntroductionVascular disease is a common cause of dementia, and often coexists with other brain pathologies such as Alzheimer's disease to cause mixed dementia. Many of the risk factors for vascular disease are treatable. Our... more
IntroductionVascular disease is a common cause of dementia, and often coexists with other brain pathologies such as Alzheimer's disease to cause mixed dementia. Many of the risk factors for vascular disease are treatable. Our objective was to review evidence for diagnosis and treatment of vascular cognitive impairment (VCI) to issue recommendations to clinicians.MethodsA subcommittee of the Canadian Consensus Conference on Diagnosis and Treatment of Dementia (CCCDTD) reviewed areas of emerging evidence. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assign the quality of the evidence and strength of the recommendations.ResultsUsing standardized diagnostic criteria, managing hypertension to conventional blood pressure targets, and reducing risk for stroke are strongly recommended. Intensive blood pressure lowering in middle‐aged adults with vascular risk factors, using acetylsalicylic acid in persons with VCI and covert brain inf...
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Background Patients with proximal arterial M2-segment of the Middle Cerebral Artery (M2-MCA) occlusions were largely excluded from endovascular stroke trials. Current American Stroke guidelines are conservative in recommending... more
Background Patients with proximal arterial M2-segment of the Middle Cerebral Artery (M2-MCA) occlusions were largely excluded from endovascular stroke trials. Current American Stroke guidelines are conservative in recommending thrombectomy for such patients. We sought to assess the natural history of medically- treated M2-MCA occlusion patients. Methods This is a prospective multi-central international cohort study of all acute ischemic stroke patients with intracranial occlusions on baseline imaging. Patients with M2-MCA occlusions were identified on baseline CT angiography and non-endovascular-treated patients were included. The M2-MCA segment was defined as the first-order branch of the proximal MCA, excluding the anterior temporal artery. The M2-MCA was further classified according to its visually-assessed diameter relative to the M1-MCA into: M1-equivalent (>90% of the diameter of the M1-MCA), Major (50%–90%), Minor (<50%). Follow-up CTA 4 hours from baseline imaging was used to assess recanalization using the revised arterial occlusive lesion (rAOL). Results Out of 575 patients in the entire study, there were a total of 184 M2-MCA occlusions seen. Of those, 104 patients were NOT treated with endovascular therapy: 90 patients (86.5%) received IV TPA and 14 (23.5%) patients conservative management. Among those, 23.1% (24/104) M1-equivalent, 66.4% (69/104) major, and 9.6% (10/104) minor M2-MCA. The median age was 76 years (interquartile range 19 years). The median (IQR) baseline NIHSS score of the cohort was 9 (9): M1-equivalent 12(10), major 9 (9), minor 7 (8). The median baseline ASPECTS was 9 overall and in all M2 groups. Successful recanalization was observed in 44.2% (46/104) of the medical M2 occlusion cohort overall. TPA group was 47.8% (43/90) and conservative group 21.4% (3/14). With IV TPA successful recanalization occurred in 30% (6/20) of M1-equivalent, 50% (31/62) of major, and 75% (6/8) of minor M2-MCA occlusions. In conservative management group successful recanalization occurred in 25% (1/4) of M1-equivalent, 14.3% (1/7) of major, and 50% (1/2) of minor M2-MCA occlusions. Good functional outcome (mRS 0–2) at 90 day was observed in 62.1% (64/104) of the cohort overall. Among those with successful recanalization, 76.1% (35/46) achieved good outcome. With IV TPA, the proportion of patients achieving independent functional outcome was 45% (9/20) with M1-equivalent, 70.5% (43/61) of major, and 62.5% (5/8) of minor M2-MCA occlusions. In the conservative management group, the proportion of patients achieving independent functional outcome at 90 day was 25% (1/4) with M1-equivalent, 71.4% (5/7) of major, and 50% (1/2) of minor M2-MCA occlusions. In logistic regression analyses, successful recanalization predicted independent functional outcome (OR 2.9, 95% CI 1.02 to 8.1, p 0.046). Age (OR 0.89, 95% CI 0.84 to 0.94, p<0.001) and baseline NIHSS (OR 0.90, 95% CI 0.83 to 0.97, p 0.009) were negative predictors of good outcomes. Conclusion While over one half of medically-treated patients with M2-MCA segment occlusions achieve independent outcome, a subset of patients suffers poor functional outcomes at 90 days. Successful recanalization are associated with higher odds of independent functional outcome. Disclosures B. Menon: None. M. Najm: None. F. Al-Ajlan: None. M. Almekhlafi: None. J. Puig: None. M. Castellanos: None. D. Dowlatshahi: None. A. Calleja: None. S. Sohn: None. S. Ahn: None. A. Poppe: None. R. Mikulik: None. N. Asdaghi: None. T. Field: None. A. Jin: None. T. Asil:None. J. Boulanger: None. E. Smith: None. S. Coutts: None. P. Barber: None. S. Bal: None. S. Subramanian: None. S. Mishra: None. A. Trivedi: None. S. Dey: None. M. Eesa: None. T. Sajobi: None. M. Goyal: None. M. Hill: None. A. Demchuk: None.
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Rationale Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce... more
Rationale Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. Aim The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume—Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. Methods and design REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will ...
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Background A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. Aims Infarct growth may occur even after successful recanalization and could... more
Background A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. Aims Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials. Methods Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic stroke patients. Sample sizes per arm (90% power, 30% effect size) for diffusion-weighted imaging lesion growth between initial and 24 h, early change in the National Institutes of Health Stroke Scale between pre- and 24 h, National Institutes of Health Stroke Scale at 24 h, and diffusion-weighted imaging lesion volume at 24 h were estimated to power a placebo-controlled stroke therapy trial. Results For patients with poor recanalization (modified thrombolysis in cerebral infarction <2 a; modified ...
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The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no... more
The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co‐exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials. There is a growing need for non‐pharmacological interventions and infrastructural support from governments to encourage psychosocial and behavioral interventions. Secondary prevention trials need to be redesigned based on the risk profile of individual subjects, which require the use of validated and standardized clinical, biological, and neuroimaging biomarkers. Multi‐d...
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Neuroimaging has improved our understanding of the evolution of stroke at discreet time points helping to identify irreversibly damaged and potentially reversible ischemic brain. Neuroimaging has also contributed considerably to the basic... more
Neuroimaging has improved our understanding of the evolution of stroke at discreet time points helping to identify irreversibly damaged and potentially reversible ischemic brain. Neuroimaging has also contributed considerably to the basic premise of acute stroke therapy which is to salvage some portion of the ischemic region from evolving into infarction, and by doing so, maintaining brain function and improving outcome. The term neurovascular unit (NVU) broadens the concept of the ischemic penumbra by linking the microcirculation with neuronal-glial interactions during ischemia reperfusion. Strategies that attempt to preserve the individual components (endothelium, glia and neurons) of the NVU are unlikely to be helpful if blood flow is not fully restored to the microcirculation. Magnetic resonance imaging (MRI) is the foremost imaging technology able to bridge both basic science and the clinic via non-invasive real time high-resolution anatomical delineation of disease manifestati...
Research Interests: Neuroscience, Computer Science, Analytical Chemistry, Neuroimaging, Magnetic Resonance Imaging, and 12 moreMedicine, Sensors, Stroke, Humans, Ischemia, Blood brain barrier, Two Stroke Engine, Cerebral Blood Flow, Electrical And Electronic Engineering, Magnetite Nanoparticles, Contrast Media, and penumbra
An 81-year-old right handed man presented with bilateral leg weakness. The patient had been previously independent and was medicated with warfarin for atrial flutter. He had longstanding type 2 diabetes, controlled by oral hypoglycemic... more
An 81-year-old right handed man presented with bilateral leg weakness. The patient had been previously independent and was medicated with warfarin for atrial flutter. He had longstanding type 2 diabetes, controlled by oral hypoglycemic medication. At presentation, he reported sudden onset left sided weakness with accompanying neck pain at 22h00 the previous evening. Pertinent findings on neurological examination included a left pronator drift and profound left leg weakness with unsustained antigravity strength. Deep tendon reflexes were brisk throughout but absent at the ankles and there was a left extensor plantar response. Cranial nerve and sensory examinations were normal.
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Research Interests: Algorithms, Radiology, Nuclear medicine, Problem Based Learning, Medicine, and 15 moreSoftware Design, Humans, Cerebral Cortex, American, Artifacts, Brain Ischemia, Clinical Sciences, Image Enhancement, Observer Variation, Clinical Competence, Sensitivity and Specificity, Neurosciences, Reading Process, Acute Disease, and Diffusion magnetic resonance imaging
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Research Interests: Cognitive Science, Neurology, Medicine, Humans, Cerebral Cortex, and 15 moreFemale, Male, Brain Ischemia, Clinical Neurology, Clinical Sciences, Aged, Alberta, Mouth, Angioedema, Angiotensin Converting Enzyme Inhibitors, Neurosciences, Frontal Lobe, Bradykinin, Antihypertensive agents, and Drug synergism
OBJECTIVES Cerebral blood flow (CBF) measurements after endovascular therapy (EVT) for acute ischemic stroke are important to distinguish early secondary injury related to persisting ischemia from that related to reperfusion when... more
OBJECTIVES Cerebral blood flow (CBF) measurements after endovascular therapy (EVT) for acute ischemic stroke are important to distinguish early secondary injury related to persisting ischemia from that related to reperfusion when considering clinical response and infarct growth. METHODS We compare reperfusion quantified by the modified Thrombolysis in Cerebral Infarction Score (mTICI) with perfusion measured by MRI dynamic contrast-enhanced perfusion within 5 h of EVT anterior circulation stroke. MR perfusion (rCBF, rCBV, rTmax, rT0) and mTICI scores were included in a predictive model for change in NIHSS at 24 h and diffusion-weighted imaging (DWI) lesion growth (acute to 24 h MRI) using a machine learning RRELIEFF feature selection coupled with a support vector regression. RESULTS For all perfusion parameters, mean values within the acute infarct for the TICI-2b group (considered clinically good reperfusion) were not significantly different from those in the mTICI <2b (clinical...
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Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to... more
Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. Methods: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. Results: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Me...
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Research Interests: Geriatrics, Medicine, Humans, Female, Male, and 15 moreBrain Ischemia, Ischemic Stroke, Clinical Sciences, Aged, Middle Aged, Medicine and Health Sciences, Cerebral Hemorrhage, New England Journalof Medicine, Mechanical Thrombectomy, Endovascular Procedures, Combined Modality Therapy, modified Rankin Scale, Medical and Health Sciences, Intention to treat analysis, and collateral circulation
IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces... more
IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC w...
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21 Background CT scanning remains the fastest and easiest method of neuro-imaging in acute ischemic stroke. The ASPECT score has been shown to be useful in assessing acute CT scans and has demonstrated validity and reliability. Previous... more
21 Background CT scanning remains the fastest and easiest method of neuro-imaging in acute ischemic stroke. The ASPECT score has been shown to be useful in assessing acute CT scans and has demonstrated validity and reliability. Previous studies have not prospectively evaluated early CT ischemia using ASPECTS. Methods 115 CT scans from the CASES study have been reviewed to date. All baseline and 24–48h follow-up scans were examined by a panel of 3 reviewers. Rating was done by 1 neuroradiologist and 2 of 3 neurologists per session. Consensus was achieved by majority opinion (2 of 3) on each data point. Reviewers were aware of the symptom side but blind to other patient characteristics. Results 79% of CT scans showed some degree of early ischemic change (ASPECTS < 10). 4.3% of follow up scans were normal (ASPECTS=10) when the baseline ASPECT score was < 9. The baseline ASPECT score was highly associated with the follow-up score (p<0.001) (Figure) Discussion Early ischemic cha...
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P39 Background: Hyperacute neurovascular imaging has great potential to help clinicians better tailor stroke therapy. Future decisions to use intravenous and/or intra-arterial lytics may depend on site of MCA occlusion. TCD has not been... more
P39 Background: Hyperacute neurovascular imaging has great potential to help clinicians better tailor stroke therapy. Future decisions to use intravenous and/or intra-arterial lytics may depend on site of MCA occlusion. TCD has not been seriously considered as such a technique because of the misconception TCD is too operator dependent and not reliable. We evaluated if our acute stroke TCD service could accurately and reliably identify MCA occlusion. Methods: A series of acute stroke patients underwent TCD examination by 1 of 3 stroke physicians or 1 stroke nurse. MRA was also performed at a time closely corresponding to TCD exam. Blind to MRA findings and patient info except symptom side, all 4 sonographers independently interpreted the TCD exam for presence of MCA occlusion using previously established TCD criteria and evaluated TIBI flow grades (5 normal waveform, 4 stenotic, 3 dampened, 2 blunted, 1 minimal, 0 absent) at 65, 55, 45 mm MCA depths. This result was compared to blind...
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P40 Background: The hyperdense appearance of the middle cerebral artery is now a familiar early warning of large cerebral infarction, brain oedema and poor prognosis. Less well described, however, is the hyperdensity associated with... more
P40 Background: The hyperdense appearance of the middle cerebral artery is now a familiar early warning of large cerebral infarction, brain oedema and poor prognosis. Less well described, however, is the hyperdensity associated with embolic occlusion of branches of the middle cerebral artery seen in the sylvian fissure (MCA ”dot“ sign). The aim of this study was to define this sign, and to determine the incidence, its diagnostic value, and reliability. Methods: Computed tomographic (CT) scans performed on patients with acute ischemic stroke within 3 hours of symptom onset were analysed for signs of thromboembolic stroke and evidence of early CT ischemia. Two neuroradiologists and two stroke neurologists initially blinded to all clinical information, and then with knowledge of the affected hemisphere evaluated scans for the presence of a hyperdense MCA sign (HMCA), a hyperdense sylvian fissure MCA ”dot“ sign, and for early MCA territory ischemic changes. Results: Of 100 consecutive p...
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P183 Background T-PA is an effective treatment of acute ischemic stroke within 3 hours. However, the success of t-PA on reducing disability is dependent on it being accessible to more patients. We identified the reasons why patients with... more
P183 Background T-PA is an effective treatment of acute ischemic stroke within 3 hours. However, the success of t-PA on reducing disability is dependent on it being accessible to more patients. We identified the reasons why patients with ischemic stroke did not receive intravenous t-PA and assessed the community impact of the therapy in a large North American city. Methods Consecutive patients with acute ischemic stroke were identified in a prospective stroke registry at a teaching hospital between October 1996 and December 1999. Additional patients with ischemic stroke admitted to one of three other hospitals during the study period were identified. The Oxford Community Stroke Program Classification was used to record stroke type. Results Of 2165 stroke patients presenting to the emergency department 1179 (54.5%) were diagnosed with ischemic stroke, 31.7% with intracranial hemorrhage, and 13.8 % with transient ischemic attack. 84/339 (29%) patients were admitted within 3 hours of s...
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TIA and minor stroke have a high risk of early neurological deterioration. Many of these early deteriorations are from progression of the presenting event. It has previously been shown that patients with large early neurological... more
TIA and minor stroke have a high risk of early neurological deterioration. Many of these early deteriorations are from progression of the presenting event. It has previously been shown that patients with large early neurological improvement are at high risk of subsequent deterioration. In this study we prospectively generated a scoring system for assessing the most severe historical deficit. Methods: Consecutive patients presenting with TIA or minor stroke (NIHSS<4) were prospectively enrolled in the prospective CATCH imaging study, if a stroke neurologist assessed them and they had a CT/CTA (Aortic arch to vertex) completed within 24 hours of symptom onset. The Historical Stroke Severity Score (HSSS) was developed in advance of the study to allow measurement of the severity of a patients’ worst deficits. The HSSS was scored based upon the clinical history and ranged from 0-11 points and included assessment of: a. Level of consciousness (alert (0), drowsy (1), Unconscious (2)); b...
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P233 Background Large MCA ischemic stroke when associated with extensive mass effect can result in brain herniation and death. As yet there are no guidelines to aid the selection of patients for decompressive therapies, such as... more
P233 Background Large MCA ischemic stroke when associated with extensive mass effect can result in brain herniation and death. As yet there are no guidelines to aid the selection of patients for decompressive therapies, such as hemicraniectomy. Methods This was a multicentre retrospective study of large MCA infarction requiring neurocritical care. The repeat CT scans performed within 120 hours of stroke onset were assessed for horizontal displacement of septum pellucidum and pineal gland, the size of MCA infarction, involvement of other vascular territories and hydrocephalus. The primary outcome measure was death within 30 days. Results A total of 251 patients fulfilled entry criteria into the study of which 201 received conventional medical therapy alone. Univariate analysis identified the following predictors of early death: NIHSS >16 (P<0.03, OR 2.17 95% CI 1.12–4.2), anteroseptal shift >7 mm (P<0.001, OR 9.2 95% CI 4.1–20.63), pineal shift >3 mm (P<0.001, OR 12...
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Hippocampus atrophy is an early structural feature that can be measured from magnetic resonance imaging (MRI) to improve the diagnosis of neurological diseases. An accurate and robust standardized hippocampus segmentation method is... more
Hippocampus atrophy is an early structural feature that can be measured from magnetic resonance imaging (MRI) to improve the diagnosis of neurological diseases. An accurate and robust standardized hippocampus segmentation method is required for reliable atrophy assessment. The aim of this work was to develop and evaluate an automatic segmentation tool (DeepHarp) for hippocampus delineation according to the ADNI harmonized hippocampal protocol (HarP). DeepHarp utilizes a two-step process. First, the approximate location of the hippocampus is identified in T1-weighted MRI datasets using an atlas-based approach, which is used to crop the images to a region-of-interest (ROI) containing the hippocampus. In the second step, a convolutional neural network trained using datasets with corresponding manual hippocampus annotations is used to segment the hippocampus from the cropped ROI. The proposed method was developed and validated using 107 datasets with manually segmented hippocampi accord...
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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... 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.
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Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. Patients with M1-middle cerebral artery... more
Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within t...
Research Interests: Radiology, Medicine, Stroke, Prospective studies, Humans, and 13 moreFemale, Male, Brain Ischemia, Clinical Sciences, Aged, Middle Aged, Prognosis, X ray Computed Tomography, Neurosciences, Cerebral Angiography, Outcome assessment (Health care), Cardiovascular medicine and haematology, and Computed tomography angiography
Background and Purpose— Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized... more
Background and Purpose— Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Methods— The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I–III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days. Results— From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow...
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The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a... more
The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject's infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional statu...
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In 1977, Symon et al.1 adapted the term ischemic penumbra from astronomy to describe the region of susceptible brain between the necrotic core and normal brain (the umbra, or shadow) in a model of focal ischemia. The limits of the... more
In 1977, Symon et al.1 adapted the term ischemic penumbra from astronomy to describe the region of susceptible brain between the necrotic core and normal brain (the umbra, or shadow) in a model of focal ischemia. The limits of the ischemic penumbra were defined by the thresholds of electrical and membrane failure; neurons in the penumbra were defined as structurally intact, with their ultimate fate dependent on the duration of ischemia, thus uniting reduction in cerebral blood flow (CBF) and cerebral function and metabolism. Subsequent studies suggest a more complex process. During the initial few hours of vascular occlusion, different neuronal functions break down at widely varying CBFs. At declining flow rates, protein synthesis is first inhibited; this is followed by anaerobic glycolysis, the release of neurotransmitters, impaired energy metabolism, and finally membrane depolarization2; in ischemia models, this can precisely define, temporally and spatially, the penumbra. The imaging of the penumbra in humans can be performed by several techniques, but is challenging. PET first demonstrated the ischemic penumbra, defined by PET parameters of CBF,3 cerebral metabolic rate of oxygen (CMRO2), and …