Early decompressive hemicraniectomy in thrombolyzed acute ischemic stroke patients from the international ENCHANTED trial

Abstract Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Diagnostic and prognostic utility of computed tomography perfusion imaging in posterior circulation acute ischemic stroke : a systematic review and meta-analysis

Background: Computed tomography perfusion (CTP) imaging could be useful in the diagnosis of posterior circulation stroke (PCS) and in identifying patients who are likely to experience favorable outcomes following reperfusion therapy. The current study sought to investigate the diagnostic and prognostic capability of CTP in acute ischemic PCS by performing a systematic review and meta-analysis. Methods: Medline/PubMed and the Cochrane Library were searched using the terms: “posterior circulation”, “CT perfusion”, “acute stroke”, and “reperfusion therapy”. The following studies were included: (1) patients aged 18 years or above; (2) patients diagnosed with PCS; and (3) studies with good methodological design. Pooled sensitivity (SENS), specificity (SPEC), and area under the curve (AUC), computed using the summary receiver operating characteristic (SROC) curves, were used to determine diagnostic/prognostic capability. Results: Out of 14 studies included, a meta-analysis investigating diagnostic accuracy of CTP was performed on nine studies. Meta-analysis demonstrated comparable diagnostic accuracy of CTP to non-contrast computed tomography (NCCT) (AUCCTP: 0.90 [95% CI 0.87–0.92] vs. AUCNCCT: 0.96 [95% CI 0.94–0.97]); however, with higher pooled sensitivity (SENSCTP: 72% [95% CI 57%–83%] vs. SENSNCCT: 25% [95% CI 17%–35%]) and lower specificity (SPECCTP: 90% [95% CI 83%–94%] vs. SPECNCCT: 96% [95% CI 95%–98%]) than NCCT. Meta-analysis to determine prognostic capability of CTP could not be performed. Conclusions: CTP has limited diagnostic utility in acute ischemic PCS, albeit with superior diagnostic sensitivity and inferior diagnostic specificity to NCCT. Further prospective trials are required to validate the prognostic capability of CTP-derived parameters in PCS

Optimising the diagnosis of posterior circulation stroke

The aim of this thesis was to optimise the diagnosis of posterior circulation stroke (PCS), a less common stroke subtype with potentially devastating consequences to those patients with delayed or missed diagnosis. The first study investigated the frequency of delayed presentation and misdiagnosis of cerebellar infarction (CBI) in 115 consecutive patients presenting to the Emergency Department (ED) of a large comprehensive stroke centre. Most patients tended to present late (>4.5h, p=0.05). 34% were misdiagnosed, most commonly as having a benign peripheral vestibular disorder. Nausea and vomiting, the absence of neurological signs and isolated CBI significantly correlated with misdiagnosis (p<0.05). Only 10% of patients received acute intravenous thrombolysis and/or endovascular therapy. The study confirmed the need for an improved diagnostic paradigm to differentiate peripheral causes of dizziness and vertigo from PCS.The second study involving the same prospectively collected cohort demonstrated that patients with small CBI (<2cm, 33/108 [31%]) presented with fewer symptoms and signs compared to large CBI. Vertebrobasilar disease was the presumed aetiology in 37% of patients. Small CBI patients were less likely to have large vessel atheromatous vertebrobasilar disease. Cardioembolism affected 37% of patients, irrespective of CBI size or topography. The presence of moderate-severe small vessel white matter disease correlated with 3-month functional dependence, particularly in large CBI. The findings reinforced the importance of comprehensive vascular risk factor assessment including extensive cardioembolic work-up in patients with small CBI. The third study examined the diagnostic utility of non-invasive, quantitative vestibular function tests in differentiating between central (PCS) and peripheral (vestibular neuritis [VN]) causes of acute vestibular syndrome (AVS). Semicircular canal and otolith function tests were undertaken within 14 days of symptom onset in 22 patients with PCS and 22 with VN. Findings were compared to 40 normal controls. The study demonstrated that the vestibulo-ocular reflex gain and saccade characteristics obtained from video Head Impulse Testing (vHIT) were the most useful in separating VN and PCS. Vestibular function testing was also helpful in separating PCS from normal controls. These findings suggest that performing vHIT in AVS patients may help identification of the aetiology of AVS in emergency settings

Association of Lesion Topography with Functional Outcomes in Acute Ischemic Stroke Patients Considered for, or Receiving, Reperfusion Therapy: A Meta-Analysis

Background: The impact of lesion topography (LT), characterised by the Alberta Stroke Programme Early CT Score (ASPECTS), on outcomes after reperfusion therapy in acute ischemic stroke (AIS) is poorly elucidated. We investigated the prognostic accuracy of ASPECTS-based LT assessment and its association with clinical outcomes in AIS patients considered for reperfusion therapy or receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or none or both. Methods: Studies were identified from PubMed with additional studies added from Google Scholar. The prevalence of individual ASPECTS regions will also be determined. The association of individual ASPECTS regions with the functional outcome at 90 days will be assessed using random-effects modelling for various cut-offs, such as 6, 7 and 8. The association of continuous ASPECTS with the functional outcome at 90 days will also be undertaken. Forest plots of odds ratios (ORs) will be generated. Results: A total of 25 studies have been included in the final analysis, encompassing 11,404 patients. Pooled estimates indicate that the highest prevalence rates were in cases involving the insula and lentiform nucleus. Subgroup analysis for ASPECTS &lt; 6 (OR 6.10; 95% CI 2.50&ndash;14.90; p &lt; 0.0001), ASPECTS &lt; 7 (OR 4.58; 95% CI 1.18&ndash;17.86; p &lt; 0.0001) and ASPECTS &lt; 8 (OR 2.26; 95% CI 1.32&ndash;3.89; p &lt; 0.0001) revealed a significant association with poor functional outcome at 90 days. Decreasing ASPECTS significantly increased the odds of poor functional outcomes at 90 days (SMD &minus;1.15; 95% CI &minus;1.77&ndash;&minus;0.52; p &lt; 0.0001). Conclusions: Our meta-analysis demonstrates that decreasing ASPECTS is significantly associated with poor functional outcomes. Individual ASPECTS regions associated with the highest odds of poor functional outcomes were identified. Future studies on the association of LT and clinical outcomes specific to EVT are required

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921