To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Cervico-cephalic arterial dissections (CeAD) are an important cause of stroke in young patients. This study aimed to determine the frequency and predictors of recanalization in spontaneous CeAD and to study the effect of recanalization on functional outcomes.
We identified patients presenting with acute ischemic stroke secondary to CeAD from the CT angiography (CTA) database of the Calgary Stroke Program. Dissections were diagnosed based on standard clinical and imaging findings. At the discretion of treating stroke Neurologists, the patients were either treated with single antiplatelet or dual antiplatelet or triple therapy. Follow-up imaging with CTA, magnetic resonance imaging, and DSA was completed, and a Modified Rankin scale (mRS) was performed to determine the outcome.
Fifty-six patients with CeAdD were studied. Thirty-four patients (18 VAD; vertebral artery dissection and 16 CAD; carotid artery dissection) were followed up for recanalization. Complete recanalization was observed in 27 subjects; 13 patients with VAD recanalized in comparison to 14 with CAD (p = 0.40). All non-recanalized patients had hypertension. A good clinical outcome (mRS ≤ 2) was observed in 47 patients. Interestingly, the likelihood of a good neurological outcome was not influenced by recanalization status. There was no difference in clinical outcome for different sites in VAD, whereas patients with intracranial CAD had severe strokes (NIHSS > 21).
CeAD has good recanalization rates and neurological outcomes, with recanalization seen even in vessels with initial complete occlusion. The presence of hypertension may influence recanalization. The efficacy of dual antiplatelets and heparin for early recanalization needs to be assessed in future clinical trials.
Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.
We examined the return on investment (ROI) from the Endovascular Reperfusion Alberta (ERA) project, a provincially funded population-wide strategy to improve access to endovascular therapy (EVT), to inform policy regarding sustainability.
We calculated net benefit (NB) as benefit minus cost and ROI as benefit divided by cost. Patients treated with EVT and their controls were identified from the ESCAPE trial. Using the provincial administrative databases, their health services utilization (HSU), including inpatient, outpatient, physician, long-term care services, and prescription drugs, were compared. This benefit was then extrapolated to the number of patients receiving EVT increased in 2018 and 2019 by the ERA implementation. We used three time horizons, including short (90 days), medium (1 year), and long-term (5 years).
EVT was associated with a reduced gross HSU cost for all the three time horizons. Given the total costs of ERA were $2.04 million in 2018 ($11,860/patient) and $3.73 million in 2019 ($17,070/patient), NB per patient in 2018 (2019) was estimated at −$7,313 (−$12,524), $54,592 ($49,381), and $47,070 ($41,859) for short, medium, and long-term time horizons, respectively. Total NB for the province in 2018 (2019) were −$1.26 (−$2.74), $9.40 ($10.78), and $8.11 ($9.14) million; ROI ratios were 0.4 (0.3), 5.6 (3.9) and 5.0 (3.5). Probabilities of ERA being cost saving were 39% (31%), 97% (96%), and 94% (91%), for short, medium, and long-term time horizons, respectively.
The ERA program was cost saving in the medium and long-term time horizons. Results emphasized the importance of considering a broad range of HSU and long-term impact to capture the full ROI.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada.
Methods and Results:
Over a 3-year period (April 2015–March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI −2.74–14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94–20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time.
We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.
In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting <3 hours from stroke onset and achieving ultra-early reperfusion (<45 minutes from CTP) are reported. CTP thresholds that predict follow-up infarction vary based on time to reperfusion: Tmax >20 to 23 seconds and cerebral blood flow <5 to 7 ml/min−1/(100 g)−1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.
Purpose: We measured anterior cerebral artery (ACA)-middle cerebral artery (MCA) and posterior cerebral artery (PCA)-MCA pial filling on single-phase computed tomography angiograms (sCTAs) in acute ischemic stroke and correlate with the CTA-based Massachusetts General Hospital (MGH) and digital subtraction angiography (DSA)-based American Society of Interventional and Therapeutic Neuroradiology (ASITN) score. Methods: Patients with acute stroke and M1 MCA±intracranial internal carotid artery occlusion on baseline CTA were included. Baseline sCTA was assessed for phase of image acquisition. An evaluator assessed collaterals using the Calgary Collateral (CC) Score (measures pial arterial filling in ACA-MCA and PCA-MCA regions separately), the CTA-based MGH score, and on DSA using the ASITN score. Infarct volumes were measured on 24- to 48-hour magnetic resonance imaging/ computed tomography. Results: Of 106 patients, baseline sCTA was acquired in early arterial phase in 9.9%, peak arterial in 50.7%, equilibrium in 32.4%, early venous in 5.6%, and late venous in 1.4%. Variance in ACA-MCA collaterals explained only 32% of variance in PCA-MCA collaterals on the CC score (Spearman’s correlation coefficient rho [rho]=0.56). Correlation between ACA-MCA collaterals and the MGH score was strong (rho=0.8); correlation between PCA-MCA collaterals and this score was modest (rho=0.54). Correlation between ACA-MCA collaterals and the ASITN score was modest (n=53, rho=0.43); and correlation between PCA-MCA collaterals and ASITN score was poor (rho=0.33). Of the CTA-based scores, the CC Score (Akaike [AIC] 1022) was better at predicting follow-up infarct volumes than was the MGH score (AIC 1029). Conclusion: Collateral assessments in acute ischemic stroke are best done using CTA with temporal resolution and by assessing regional variability. ACA-MCA and MCA-PCA collaterals should be evaluated separately.
We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA).
Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)±intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA.
A total of 104 patients (mean age 65.1±12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006).
Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree.
Lack of additional utility over non-contract computed tomography (NCCT) in decision making and delay in door to needle time are arguments used against routine computed tomographic angiography (CTA) use in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center.
We reviewed 850 stroke thrombolysis patients in a university hospital in Canada from April 1996 to December 2009. Time to treatment was divided into the following interval times: onset-to-door, door-to-needle and onset-to-needle. Patients were categorized into: Group 1 (April 1996-Dec 2002) (Non-contrast CT Scan based thrombolysis) n=297, Group 2 (Jan 2004-Dec 2009) (CTA based thrombolysis) n=504. The period from Jan to Dec 2003 (n=49) was considered a washout period as we had started the CTA protocol that year. Interval times were compared between the two groups.
Interval times in Group 1 and Group 2 were: median onset-to-door times in Group 1 [55 minutes (IQR 48),] and Group 2 [61 minutes (IQR 57)] (p=0.019); median door-to-needle times in Group 1 [67 minutes(IQR 43)] and Group 2 [62.5 minutes (IQR 52)] (p=0.519); median onset-to-needle times in Group 1 (139 minutes (IQR 73)] and Group 2 (141.5 min (IQR 109.5) (p=0.468). In multivariable linear regression analysis, age and onset-to-door time influenced the door-to-needle time. For every decade of age, door-to-needle times were 5.4 minutes faster.
CTA based thrombolytic approach for acute ischemic stroke does not significantly delay thrombolysis in routine clinical practice.
Hyperacute surgical evacuation of intracerebral hemorrhage is associated with a high rebleeding rate. The peri-operative administration of rFVIIa to patients with intracerebral hemorrhage may decrease the frequency of post-operative hemorrhage, and improve outcome.
Patients receiving recombinant activated factor VII (rFVIIA) therapy immediately prior to acute surgery were collected at two centres. The intracerebral hemorrhage (ICH) score and ICH Grading Scale were determined, as was long-term outcome using the modified Rankin Scale. Residual/ recurrent clot was evaluated by comparing pre-operative to post-operative CT scans.
Fifteen patients with intracerebral hemorrhage received 40-90 μg/kg of rFVIIa and underwent surgical hematoma evacuation at a median time of five hours following symptom onset. Median pre-operative clot volume was 60 ml, decreasing to 2 ml post-operatively. There were no thromboembolic adverse events. Thirteen patients survived, 11 (73%) were independent, and two (13%) had a moderate to severe disability. These outcomes were significantly better than expected based on the median ICH score (40% mortality) and based on median ICH Grading Scale (18% good outcome).
The pre or peri-operative administration of rFVIIa resulted in minimal residual or recurrent hematoma volume and may be an important adjunct to surgery in patients with intracerebral hemorrhage.
Intravenous rt-PA (IV rt-PA) for acute stroke has raised many concerns, including its inadvertent use in patients presenting with acute stroke-like symptoms as the expression of their somatoform disorder. Diagnosis of the somatoform disorder is often delayed, and thrombolytics in these patients for their stroke-like presentation subjects them to risk for hemorrhage.
The presentation, neurological findings, and the therapeutic decision making was audited in 85 patients who received IV rt-PA for a diagnosis of acute stroke. All the surviving patients were re-examined neurologically at least three months after IV rt-PA. Baseline and follow-up brain CT scans were re-reviewed by a neuroradiologist who was blinded to clinical presentation and outcome. Patients whose clinical presentation, brain CT and neurological outcome did not fit into known or expected anatomical and clinical patterns of stroke underwent psychological assessment using the Minnesota Multiphasic Personality Inventory-2.
In two patients three stroke-like presentations of somatoform disorder inadvertently were treated with IV rt-PA. This was primarily caused by abbreviated neurological examination and narrow differential diagnosis.
Patients with somatoform disorder may present with symptoms mimicking acute stroke. Under the time constraints of IV rt-PA use, a diagnosis of somatoform disorder can be missed, subjecting such patients to the potential complications of thrombolytics.
Sickle cell disease is a hemoglobinopathy occurring due to replacement of valine for glutamic acid at the sixth position of the beta globin chain. The altered hemoglobin structure makes it prone for polymerization during hypoxic and infective stress. Polymerization of the hemoglobin molecule leads to sickling of the red blood cells in the vessels causing thrombosisvasoocclusive crises. Although abdomen and extremities are more often involved, silent cerebral infarcts and stroke can occur in up to 25-29% of patients and is the major cause of morbidity and mortality.
The computed tomogram angiography (CTA) ‘spot sign’ describes foci of intralesional enhancement associated with hematoma expansion in primary intracerebral hemorrhage patients. A consistent radiological definition is required for two proposed recombinant Factor VIIa trials planning patient dichotomization according to ‘spot sign’ presence or absence. We propose radiological criteria for diagnosis of the CTA ‘spot sign’ and describe different morphological patterns.
Material and Methods:
A prospective cohort of 36 consecutive patients presenting with primary intracerebral hemorrhage (ICH) were enrolled in a multicenter collaborative study, and have been included for the present analysis. Three reviewers analyzed the CTA studies in a blinded protocol. Analysis of specific ICH and ‘spot sign’ features was performed including prevalence, number, size, location, morphology and Hounsfield unit density.
Twelve of thirty-six patients (33%) demonstrated a total of 19 enhancing foci consistent with the CTA ‘spot sign’. Mean maximal axial ‘spot sign’ dimension was 3.7±2.2 mm and mean density was 216±57.7 HU. No significant differences in age or blood pressure (p=0.7), glucose (p=0.9), INR/PTT (p=0.3 and 0.4) or hematoma location (p=0.3) were demonstrated between patients with or without the ‘spot sign’. Consensus definition and classification criteria for the CTA ‘spot sign’ are proposed.
The ‘spot sign’ is defined as spot-like and/or serpiginous foci of enhancement, within the margin of a parenchymal hematoma without connection to outside vessels. The ‘spot sign’ is greater than 1.5 mm in maximal dimension and has a Hounsfield unit density at least double that of background hematoma density.
Alteplase for acute ischemic stroke may be the first stroke intervention to have a significant public health impact. In February 1999, this therapy was conditionally licensed in Canada for acute ischemic stroke within three hours of symptom onset. However, considerable controversy exists regarding its safety, its wider applicability outside clinical trials, and its ultimate availability. In this article we review the thrombolytic literature, attempt to answer many of the concerns, provide new guidelines for its use, and cite the need for more information about whom we should and should not be treating with this therapy.
Accuracy of intracranial magnetic resonance angiography (MRA) and reliability of interpretation are not well established compared to conventional selective catheter angiography. The purpose of this study was to determine the accuracy of MRA in evaluation of intracranial vessels in acute stroke and transient ischemic attack (TIA) patients.
Twenty-nine patients (seven females, 22 males; median age 53) with acute stroke or TIA were enrolled into the study. All patients underwent both MRA using a 3 T clinical magnet and conventional angiography within 48 hours. Median time between MRA and angiography was 263 minutes. Conventional angiography preceded MRA in 15 cases. Fourteen patients received thrombolysis during MRA or angiography. National Institutes of Health Stroke Scale scores were obtained prior to the MR exam. One neuroradiologist rated all conventional angiograms, which were used as gold standard. Five observers, blinded to conventional angiography results and all clinical information except symptom side, rated the MR angiograms. Kappa statistics were used to assess reliability; contingency tables were used to assess accuracy of non-enhanced and enhanced MRA.
Two hundred and fifty two intracranial vessels were assessed. Agreement between raters was good for both non-enhanced (k=0.50) and gadolinium-enhanced (k=0.46) images. There were a total of 26 vessels occluded by DSA. Overall, the non-enhanced MRA showed sensitivity of 84.2% (95% CI 60.4-96.6) and specificity of 84.6% (95% CI 78.6-89.4). The enhanced MRA showed sensitivity of 69.2 (95% CI 38.6-90.9) and specificity of 73.6 (95% CI 65.5-80.7).
Magnetic resonance angiography is a good non-invasive screening tool for assessing intracranial vessel status in acute ischemic stroke. Angiography remains the gold standard for definitive assessment of the intracranial circulation.
Stroke thrombolysis is limited by the “last-seen well” principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were “last-seen well” at the time they went to bed implying an interval that is most often greater than three hours.
A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death.
Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10).
Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.
transient ischemic attack (tIA) and minor stroke have a high risk of early neurological deterioration, and patients who experience early improvement are at risk of deterioration. We generated a score for quantifying the worst reported motor and speech deficits and assessed whether this predicted outcome.
510 tIA or minor stroke (NIHSS>4) patients were included. the Historical Stroke Severity Score (HSSS) prospectively quantified the patient's description of the worst motor or speech deficits. the HSSS was rated at the time of first assessment with more severe deficits scoring higher. Motor HSSS included assessments of arm and leg motor power (score total 0-5). Speech HSSS assessed severity of dysarthria and aphasia (total 0-3). the association between motor and speech HSSS and symptom progression was assessed during the 90-day follow-up period.
the proportion of patients in each category of the motor HSSS was 0: 43% (216/510), 1: 22%(110/510), 2: 17% (89/510), 3: 7% (37/510), 4: 5% (28/510) and 5: 6% (30/510). Motor HSSS was associated with symptom progression (p=0.004) but not recurrent stroke. Speech HSSS was not associated with either progression or recurrent stroke. Motor HSSS predicted disability (p=0.002) and intracranial occlusion (p=0.012). Disability increased with increasing motor HSSS.
taking a detailed history about the severity of motor deficits, but not speech, predicted outcome in tIA and minor stroke patients. A score based on the patient's description of the severity of motor symptoms predicted symptom progression, intracranial occlusion and functional outcome, but not recurrent stroke in a tIA and minor stroke population.