Comparison of Stroke Care Costs in Urban and Nonurban Hospitals and Its Association With Outcomes in New Zealand: A Nationwide Economic Evaluation.

BACKGROUND: Although geographical differences in treatment and outcomes after stroke have been described, we lack evidence on differences in the costs of treatment between urban and nonurban regions. Additionally, it is unclear whether greater costs in one setting are justified given the outcomes achieved. We aimed to compare costs and quality-adjusted life years in people with stroke admitted to urban and nonurban hospitals in New Zealand. METHODS: Observational study of patients with stroke admitted to the 28 New Zealand acute stroke hospitals (10 in urban areas) recruited between May and October 2018. Data were collected up to 12 months poststroke including treatments in hospital, inpatient rehabilitation, other health service utilization, aged residential care, productivity, and health-related quality of life. Costs in New Zealand dollars were estimated from a societal perspective and assigned to the initial hospital that patients presented to. Unit prices for 2018 were obtained from government and hospital sources. Multivariable regression analyses were conducted when assessing differences between groups. RESULTS: Of 1510 patients (median age 78 years, 48% female), 607 presented to nonurban and 903 to urban hospitals. Mean hospital costs were greater in urban than nonurban hospitals ($13 191 versus $11 635, P=0.002), as were total costs to 12 months ($22 381 versus $17 217, P<0.001) and quality-adjusted life years to 12 months (0.54 versus 0.46, P<0.001). Differences in costs and quality-adjusted life years remained between groups after adjustment. Depending on the covariates included, costs per additional quality-adjusted life year in the urban hospitals compared to the nonurban hospitals ranged from $65 038 (unadjusted) to $136 125 (covariates: age, sex, prestroke disability, stroke type, severity, and ethnicity). CONCLUSIONS: Better outcomes following initial presentation to urban hospitals were associated with greater costs compared to nonurban hospitals. These findings may inform greater targeted expenditure in some nonurban hospitals to improve access to treatment and optimize outcomes.

Complications of Intravenous Tenecteplase Versus Alteplase for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent. METHODS: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www. CLINICALTRIALS: gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase. RESULTS: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I2=0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I2=0%), 0.77 ([95% CI, 0.53-1.14]; I2=0%), and 2.31 ([95% CI, 0.69-7.75]; I2=40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I2=0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I2=1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I2=52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents. CONCLUSIONS: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.

Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.

BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

End the confusion: general anaesthesia improves patient outcomes in endovascular thrombectomy.

Expert physiological and pharmacological care by anaesthetists is required in all stroke endovascular thrombectomy cases. RCTs show clinical benefits in recanalisation rates and functional recovery after endovascular thrombectomy with general anaesthesia compared with sedation. Many stroke centres will require wholesale reorganisation of stroke pathways to ensure anaesthesia services are available for all cases. Anaesthetists have an integral role in improving clinical outcomes in large vessel occlusion stroke.

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. METHODS: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90. RESULTS: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (P=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], P=0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], P=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], P=0.46). CONCLUSIONS: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.

Impact of Body Temperature Before and After Endovascular Thrombectomy for Large Vessel Occlusion Stroke.

Background and Purpose- In ischemic stroke, body temperature is associated with functional outcome. However, the relationship between temperature and outcome may differ in the intraischemic and postischemic phases of stroke. We aimed to determine whether body temperature before or after endovascular thrombectomy (EVT) for large vessel occlusion stroke is associated with clinical outcomes. Methods- Consecutive EVT patients were identified from a prospective registry. Temperature measurements within 24 hours of admission were stratified into pre-EVT (preprocedural and intraprocedural) and post-EVT measurements, which served as surrogates for the intraischemic and postischemic phases of large vessel occlusion stroke, respectively. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0, 1, or 2 at 3 months. Secondary outcomes included the ordinal shift of modified Rankin Scale scores at 3 months, symptomatic intracerebral hemorrhage, and mortality at 3 months. Results- Four hundred thirty-two participants were included (59% men, mean±SD age 65.6±15.7 years). Multivariable logistic regression demonstrated that higher median pre-EVT temperature (per 1°C increase) was an independent predictor of reduced functional independence (odds ratio [OR], 0.66 [95% CI, 0.46-0.94]; P=0.02), poorer modified Rankin Scale scores (common OR, 1.42 [95% CI, 1.08-1.85]; P=0.01), and increased mortality (OR, 1.65 [95% CI, 1.02-2.69]; P=0.04). Peak post-EVT temperature (per 1°C increase) was a significant predictor of elevated modified Rankin Scale scores (common OR, 1.39 [95% CI, 1.03-1.90]; P=0.03) and higher mortality (OR, 1.66 [95% CI, 1.04-2.67]; P=0.03). Conclusions- In patients with large vessel occlusion stroke treated with EVT, higher body temperatures during both the intraischemic and postischemic phases were associated with poorer clinical outcomes. Future research investigating the maintenance of normothermia or therapeutic hypothermia in patients needing to be transferred from primary to EVT-capable stroke centers could be considered.

Vertebrobasilar Artery Calcification and Outcomes in Posterior Circulation Large Vessel Occlusion Thrombectomy.

Background and Purpose- Intracranial carotid artery calcification is associated with worse outcome in anterior circulation stroke patients who undergo endovascular thrombectomy. We investigated the association between vertebrobasilar artery calcification (VBAC) and outcome in patients undergoing endovascular thrombectomy for posterior circulation large vessel occlusion. Methods- Consecutive patients treated for posterior circulation large vessel occlusion from a prospective single-center registry were studied. VBAC was manually segmented on computed tomography brain scans. The associations between VBAC and VBAC volume, functional independence (90-day modified Rankin Scale score of 0-2), and 90-day mortality were assessed using propensity score-adjusted logistic regression. Results- Sixty-four posterior circulation large vessel occlusion patients were included. Twenty-five (39.1%) patients had VBAC, and of these, the median (interquartile range) VBAC volume was 19.8 (6.65-23.4) mm3. VBAC was associated with reduced functional independence (OR, 0.19 [95% CI, 0.04-0.78]; P=0.03) and increased mortality (OR, 9.44 [95% CI, 2.43-36.62]; P=0.005). Larger VBAC volumes were a significant predictor of reduced functional independence and increased mortality. Conclusions- VBAC is an independent predictor of outcome in patients undergoing endovascular thrombectomy for posterior circulation large vessel occlusion. Considering the presence of VBAC might improve prognostication and shared treatment decision-making between patients, families, and physicians.

Neurochemical balance and inhibition at the subacute stage after stroke.

Stroke is a leading cause of death and disability worldwide with many people left with impaired motor function. Evidence from experimental animal models of stroke indicates that reducing motor cortex inhibition may facilitate neural plasticity and motor recovery. This study compared primary motor cortex (M1) inhibition measures over the first 12 wk after stroke with a cohort of age-similar healthy controls. The excitation-inhibition ratio and gamma-aminobutyric acid (GABA) neurotransmission within M1 were assessed using magnetic resonance spectroscopy and threshold hunting paired-pulse transcranial magnetic stimulation respectively. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Patients with a functional corticospinal pathway had motor-evoked potentials on the paretic side and exhibited better recovery from upper limb impairment and recovery of function than patients without a functional corticospinal pathway. Compared with age-similar controls, the neurochemical balance in terms of the excitation-inhibition ratio was greater within contralesional M1 in patients with a functional corticospinal pathway. There was evidence for elevated long-interval inhibition in both ipsilesional and contralesional M1 compared with controls. Short-interval inhibition measures differed between the first and second phases, with evidence for elevation of the former only in ipsilesional M1 and no evidence of disinhibition for the latter. Overall, findings from transcranial magnetic stimulation indicate an upregulation of GABA-mediated tonic inhibition in M1 early after stroke. Therapeutic approaches that aim to normalize inhibitory tone during the subacute period warrant further investigation.NEW & NOTEWORTHY Magnetic resonance spectroscopy indicated higher excitation-inhibition ratios within motor cortex during subacute recovery than age-similar healthy controls. Measures obtained from adaptive threshold hunting paired-pulse transcranial magnetic stimulation indicated greater tonic inhibition in patients compared with controls. Therapeutic approaches that aim to normalize motor cortex inhibition during the subacute stage of recovery should be explored.

Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). INTERPRETATION: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. FUNDING: None.

Ethnic Differences in Access to Stroke Reperfusion Therapy in Northern New Zealand.

BACKGROUND: In New Zealand, Maori and Pacific people have higher age-adjusted stroke incidence rates, younger age at first stroke, and higher mortality at 12 months than other ethnic groups. We aimed to determine if access to acute stroke reperfusion therapy with intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT) is equitable among ethnic groups. METHODS: Data were obtained from the Northern Region component of the New Zealand Stroke Registry over the 21 months between January 1, 2018 and September 30, 2019. Data recorded included demographic details, self-identified ethnicity, treatment times, and clinical outcomes. National hospital discharge coding of patients admitted with ischemic stroke and stroke unspecified was used to determine the proportion of patients treated by ethnic group. RESULTS: There were 537 patients normally resident in the Northern Region who received reperfusion therapy: 281 received IVT alone, 123 received EVT after bridging IVT, and 133 received EVT alone. Of the 537 patients treated with IVT or EVT, there were 81 (15.1%) Maori, 78 (14.5%) Pacific, 57 (10.6%) Asian, and 341 (63.5%) NZ European/other ethnicity patients. There were no ethnic differences in treatment process times. When compared with NZ European/others, Maori and Pacific people were younger, and Maori had worse neurological impairment at admission. A higher proportion of Maori were treated with EVT with a trend to higher proportion treated with IVT. Day 90 modified Rankin Scale (mRS) for EVT-treated patients was similar apart from Asian patients who had worse outcome when compared with NZ European/others (mRS 3 vs. 2; p = 0.03). CONCLUSIONS: This study has shown equitable access to acute stroke reperfusion therapies and largely similar outcomes in different ethnic groups in northern New Zealand.

Trends in stroke reperfusion treatment and outcomes in New Zealand.

BACKGROUND: Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) can help reverse stroke symptoms in selected patients but are both time sensitive interventions. AIMS: To report current stroke reperfusion rates and quality measures as well as trends over time in New Zealand. METHOD: Since 2015 New Zealand treatment centres have been mandated to enter prospectively all IVT and EVT patients into a low-cost National Stroke Register. Data were cleaned, and missing data added where possible through contact with individual hospitals. Main outcomes include treatment delays, vital status at day 7 and complications. RESULTS: In 2018, there were 719 of 7173 (10.0%) patients with ischaemic stroke or stroke unspecified treated with IVT, up from 389 of 5963 (6.5%) patients in 2015 (P < 0.001), with no change in day 7 mortality (P = 0.63) or sICH rate (P = 0.22). Median (interquartile range (IQR)) door-to-needle times decreased from 65 (47-89) min in 2017 to 59 (40-84) min in 2018 (P = 0.022), and patients treated within 60 min increased from 40 to 51% (P < 0.001). In 2018, there were 243 (3.4%) patients treated with EVT up from 134/6859 (1.9%) in 2017 (P < 0.0001), with no change in 7-day mortality (P = 0.39) or intracerebral haemorrhage (sICH) (P = 0.78). There was no significant change in onset-to-needle (P = 0.21), arrival-to-groin (P = 0.28) or onset-to-reperfusion time (P = 0.32). CONCLUSION: Stroke reperfusion rates in New Zealand are continuously rising with no associated increase in complications. More patients are being treated faster upon hospital arrival but there remains room for further improvement in reducing onset to treatment delays.

Chronic Kidney Disease and Outcome Following Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is present in 20% to 35% of acute ischemic stroke patients and may increase the risk of poor functional outcome or death. We aimed to determine whether CKD was associated with worse outcome in stroke patients treated with endovascular thrombectomy (EVT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Consecutive EVT patients were identified from a prospective registry and dichotomized into patients with and without CKD, defined as an eGFR of less than 60 mL/min/1.73m2. The primary outcome was 3-month mortality following EVT. Secondary outcomes included symptomatic intracerebral hemorrhage (defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study), early neurological recovery (defined as change in National Institutes of Health Stroke Scale [NIHSS] score of ≥8 at 24 hours or an NIHSS of 0-1 at 24 hours) and functional independence (defined as a modified Rankin Scale [mRS] score of 0, 1 or 2) at 3 months. RESULTS: 378 EVT patients (223 men; mean ± SD age 65 ± 15 years) were included. The median (IQR) admission eGFR was 71 (58-89) mL/min/1.73 m² and 117 (31%) patients had CKD. Multiple logistic regression adjusted for potential confounders demonstrated that CKD was a significant predictor of lower rates of functional independence (OR = .54, 95% CI, .31 to .90, P = .02), higher mRS scores (common OR = 1.78, 95% CI, 1.14 to 2.81, P = .01), and increased mortality (OR = 2.19, 95% CI, 1.16 to 4.12, P = .01). There was no association between CKD and early neurological recovery (OR = .92, 95% CI, .55 to 1.49, P = .71) or symptomatic intracerebral hemorrhage (OR = 1.18, 95% CI, .38 to 3.69, P = .77). CONCLUSIONS: CKD was a significant predictor of worse functional outcome and mortality in stroke patients treated with EVT. The presence of CKD should not preclude patients from proceeding to EVT, but may help with prognostication and improve shared decision-making between patients, families and physicians.

Platelet-Reactive Antibodies in Patients after Ischaemic Stroke-An Epiphenomenon or a Natural Protective Mechanism.

Ischaemic brain damage induces autoimmune responses, including the production of autoantibodies with potential neuroprotective effects. Platelets share unexplained similarities with neurons, and the formation of anti-platelet antibodies has been documented in neurological disorders. The aim of this study was to investigate the presence of anti-platelet antibodies in the peripheral blood of patients after ischaemic stroke and determine any clinical correlations. Using a flow cytometry-based platelet immunofluorescence method, we detected platelet-reactive antibodies in 15 of 48 (31%) stroke patients and two of 50 (4%) controls (p < 0.001). Western blotting revealed heterogeneous reactivities with platelet proteins, some of which overlapped with brain proteins. Stroke patients who carried anti-platelet antibodies presented with larger infarcts and more severe neurological dysfunction, which manifested as higher scores on the National Institutes of Health Stroke Scale (NIHSS; p = 0.009), but they had a greater recovery in the NIHSS by the time of hospital discharge (day 7 ± 2) compared with antibody-negative patients (p = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets (p = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% (p < 0.001), suggesting the potential to interfere with thrombus formation. In conclusion, platelet-reactive antibodies can be found in patients soon after ischaemic stroke and correlate with better short-term outcomes, suggesting a potential novel mechanism limiting thrombosis.

Contrast-Associated Acute Kidney Injury in Endovascular Thrombectomy Patients With and Without Baseline Renal Impairment.

Background and Purpose- In ischemic stroke, baseline renal impairment is present in 20 to 35% of patients and may increase the risk of contrast-associated acute kidney injury (CA-AKI). We aimed to determine whether endovascular thrombectomy (EVT) patients with baseline renal impairment are at increased risk of CA-AKI. Methods- Consecutive EVT patients were identified from a prospective database. Patients were stratified by estimated glomerular filtration rate. The primary outcome was CA-AKI assessed at 24 to 72 hours following EVT, defined as an increase in serum creatinine of ≥26.5 µmol/L or 1.5× baseline serum creatinine. Secondary outcomes included requirement for renal replacement therapy and 3-month mortality. Results- Three hundred thirty-three EVT patients (201 men; mean±SD age 63.9±15.8 years) were included. The mean±SD iohexol contrast volume used in diagnostic and EVT imaging was 236±77 mL per patient. CA-AKI occurred in 11 (3.3%) patients; none required renal replacement therapy, but 4 of 11 (36.4%) had died by 3 months. Propensity score-adjusted logistic regression showed that estimated glomerular filtration rate <30 mL/(min·1.73 m2) was a significant predictor of CA-AKI (odds ratio, 19.93; 95% CI, 2.33-170.74; P=0.006). The dose of contrast was not associated with an increased risk of CA-AKI (P>0.05). Multiple logistic regression adjusted for potential confounders demonstrated that CA-AKI was independently associated with increased mortality (odds ratio, 4.68; 95% CI, 1.05-20.97; P=0.04). Conclusions- There is utility in obtaining baseline creatinine levels to identify patients at risk of CA-AKI and to establish a diagnosis of CA-AKI in patients with subsequent creatinine rises. However, contrast-requiring diagnostic imaging and EVT should not be delayed by waiting for the results of baseline renal function.

Automated Measurement of Cerebral Atrophy and Outcome in Endovascular Thrombectomy.

Background and Purpose- Methods of identifying ischemic stroke patients with a greater probability of poor outcome following endovascular thrombectomy (EVT) might improve shared treatment decision-making between patients, families, and physicians. We used an objective, automated method to measure cerebral atrophy and investigated whether this was associated with outcome in EVT patients. Methods- Consecutive EVT patients from a single-center registry were studied. CT brain scans were segmented with a combination of a validated U-Net and Hounsfield unit thresholding. Intracranial cerebrospinal fluid (CSF) volume was used as a marker of cerebral atrophy and calculated as a proportion of total intracranial volume. The primary outcome was functional independence, defined as a 3-month modified Rankin Scale score of 0 to 2. Results- Three-hundred sixty EVT patients were included. Functional independence was achieved in 204 (56.7%) patients. The mean±SD CSF volume was 9.0±4.7% of total intracranial volume. Multivariable regression demonstrated that increasing CSF volume was associated with reduced functional independence (OR=0.65 per 5% increase in CSF volume; 95% CI, 0.48-0.89; P=0.007) and higher 3-month modified Rankin Scale scores (common OR, 1.59 per 5% increase in CSF volume; 95% CI, 1.05-2.41; P=0.03). Conclusions- Cerebral atrophy determined by automated measurement of intracranial CSF volume is associated with functional outcome in patients undergoing EVT. If validated in future studies, this simple, objective, and automated imaging marker could potentially be incorporated into decision-support tools to improve shared treatment decision-making.

Stroke Incidence by Major Pathological Type and Ischemic Subtypes in the Auckland Regional Community Stroke Studies: Changes Between 2002 and 2011.

BACKGROUND AND PURPOSE: Major pathological stroke types (ischemic stroke [IS], primary intracerebral hemorrhage [ICH], and subarachnoid hemorrhage) and IS subtypes, have differing risk factors, management, and prognosis. We report changes in major stroke types and IS subtypes incidence during 10 years using data from the ARCOS (Auckland Regional Community Stroke Study) III performed during 12 months in 2002 to 2003 and the fourth ARCOS study (ARCOS-IV) performed in 2011 to 2012. METHODS: ARCOS-III and ARCOS-IV were population-based registers of all new strokes in the greater Auckland region (population aged >15 years, 1 119 192). Strokes were classified into major pathological types (IS, ICH, subarachnoid hemorrhage, and undetermined type). Crude annual age-, sex-, and ethnic-specific stroke incidence with 95% confidence intervals was calculated. ISs were subclassified using TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria into 5 etiologic groups. Rate ratios with 95% confidence intervals were calculated for differences in age-standardized rates between the 2 studies. RESULTS: In ARCOS-IV, there were 1329 (81%) ISs, 211 (13%) ICHs, 79 (5%) subarachnoid hemorrhages, and 24 (1%) undetermined type strokes. The proportional distribution of IS subtypes was 29% cardioembolism, 21% small-vessel occlusion, 15% large-artery atherosclerosis, 5% other determined etiology, and 31% undetermined type. Between 2002 and 2011, age-standardized incidence decreased for subarachnoid hemorrhage (rate ratios, 0.73; 95% confidence intervals, 0.54-0.99) and undetermined type (rate ratios, 0.14; 95% confidence intervals, 0.09-0.22). Rates were stable for IS and ICH. Among IS subtypes, large-artery atherosclerosis and small-vessel occlusion rates increased significantly. The frequency of all risk factors increased in IS. Ethnic differences were observed for both stroke subtype rates and their risk factor frequencies. CONCLUSIONS: A lack of change in IS and ICH incidence may reflect a trend toward increased incidence of younger strokes. Increased rates of large-artery atherosclerosis and small-vessel occlusion are associated with increased smoking and high blood pressure. Ethnic differences in the proportional distribution of pathological stroke subtypes suggest differential exposure and susceptibility to risk factors.

Endovascular therapy for ischemic stroke with perfusion-imaging selection.

BACKGROUND: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS: We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS: The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).

Proportional Recovery From Lower Limb Motor Impairment After Stroke.

BACKGROUND AND PURPOSE: In people with preserved corticospinal tract (CST) function after stroke, upper limb impairment resolves by ≈70% within 3 months. This is known as the proportional recovery rule. Patients without CST function do not fit this rule and have worse upper limb outcomes. This study investigated resolution of motor impairment in the lower limb (LL). METHODS: Patients with stroke and LL weakness were assessed 3 days and 3 months after stroke with the LL Fugl-Meyer. CST integrity was determined in a subset of patients using transcranial magnetic stimulation to test for LL motor-evoked potentials and magnetic resonance imaging to measure CST lesion load. Linear regression analyses were conducted to predict resolution of motor impairment (ΔFugl-Meyer) including factors initial impairment, motor-evoked potential status, CST lesion load, and LL therapy dose. RESULTS: Thirty-two patients completed 3-month follow-up and recovered 74% (95% confidence interval, 60%-88%) of initial LL motor impairment. Initial impairment was the only significant predictor of resolution of motor impairment. There was no identifiable cluster of patients who did not fit the proportional recovery rule. Measures of CST integrity did not predict proportional LL recovery. CONCLUSIONS: LL impairment resolves by ≈70% within 3 months after stroke. The absence of a nonfitter group may be because of differences in the neuroanatomical organization of descending motor tracts to the upper limb and LL. Proportional recovery of the LL is not influenced by therapy dose providing further evidence that it reflects a fundamental biological process.

Proportional Motor Recovery After Stroke: Implications for Trial Design.

BACKGROUND AND PURPOSE: Recovery of upper-limb motor impairment after first-ever ischemic stroke is proportional to the degree of initial impairment in patients with a functional corticospinal tract (CST). This study aimed to investigate whether proportional recovery occurs in a more clinically relevant sample including patients with intracerebral hemorrhage and previous stroke. METHODS: Patients with upper-limb weakness were assessed 3 days and 3 months poststroke with the Fugl-Meyer scale. Transcranial magnetic stimulation was used to test CST function, and patients were dichotomized according to the presence of motor evoked potentials in the paretic wrist extensors. Linear regression modeling of Δ Fugl-Meyer score between 3 days and 3 months was performed, with predictors including initial impairment (66 - baseline Fugl-Meyer score), age, sex, stroke type, previous stroke, comorbidities, and upper-limb therapy dose. RESULTS: One hundred ninety-two patients were recruited, and 157 completed 3-month follow-up. Patients with a functional CST made a proportional recovery of 63% (95% confidence interval, 55%-70%) of initial motor impairment. The recovery of patients without a functional CST was not proportional to initial impairment and was reduced by greater CST damage. CONCLUSIONS: Recovery of motor impairment in patients with intact CST is proportional to initial impairment and unaffected by previous stroke, type of stroke, or upper-limb therapy dose. Novel interventions that interact with the neurobiological mechanisms of recovery are needed. The generalizability of proportional recovery is such that patients with intracerebral hemorrhage and previous stroke may usefully be included in interventional rehabilitation trials. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ANZCTR12611000755932.