Influence of Time to Achieve Target Systolic Blood Pressure on Outcome After Intracerebral Hemorrhage: The Blood Pressure in Acute Stroke Collaboration.

OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage. METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect. RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events. CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

Functional outcomes of patients with ischaemic stroke with known atrial fibrillation not on therapeutic anticoagulation.

BACKGROUND: Anticoagulation significantly reduces the risk of ischaemic stroke in patients with atrial fibrillation (AF). There are a proportion of patients with known AF who remain off anticoagulation. Aims This study aims to retrospectively compare the baseline characteristics, treatments and functional outcomes between patients with ischaemic stroke and known AF based on their anticoagulation status. METHODS: A single-centre, retrospective review of consecutive patients with an ischaemic stroke and a known history of AF was conducted. RESULTS: Two hundred four patients with an ischaemic stroke had documented AF prior to the index admission, of which 126 were anticoagulated. Median admission National Institutes of Health Stroke Scale score was lower for anticoagulated patients, though not statistically significant (5.1 vs 7.0, P = 0.09). Median baseline modified Rankin score (mRS) did not significantly differ. Nonanticoagulated patients were more likely to have large vessel occlusions (37.2% vs 23.8%, P = 0.04) and more likely to receive intravenous thrombolysis (15.4% vs 1.6%, P < 0.01). There was no difference in rates of endovascular clot retrieval between groups (P > 0.05). Unfavourable functional outcome at 90 days (mRS ≥ 3) did not significantly differ between groups (P = 0.51). A total of 38.5% of nonanticoagulated patients had no documented reason for this. Of the patients who survived the index admission, 81.5% of patients who were not anticoagulated on admission received anticoagulation. CONCLUSIONS: Baseline anticoagulation was associated with milder stroke severity in ischaemic stroke patients with known AF. There was no significant difference in functional outcomes at 90 days between groups. Larger observational studies are required to further assess this cohort.

Optimal CT perfusion thresholds for core and penumbra in acute posterior circulation infarction.

Background: At least 20% of strokes involve the posterior circulation (PC). Compared to the anterior circulation, posterior circulation infarction (POCI) are frequently misdiagnosed. CT perfusion (CTP) has advanced stroke care by improving diagnostic accuracy and expanding eligibility for acute therapies. Clinical decisions are predicated upon precise estimates of the ischaemic penumbra and infarct core. Current thresholds for defining core and penumbra are based upon studies of anterior circulation stroke. We aimed to define the optimal CTP thresholds for core and penumbra in POCI. Methods: Data were analyzed from 331-patients diagnosed with acute POCI enrolled in the International-stroke-perfusion-registry (INSPIRE). Thirty-nine patients with baseline multimodal-CT with occlusion of a large PC-artery and follow up diffusion weighted MRI at 24-48 h were included. Patients were divided into two-groups based on artery-recanalization on follow-up imaging. Patients with no or complete recanalisation were used for penumbral and infarct-core analysis, respectively. A Receiver operating curve (ROC) analysis was used for voxel-based analysis. Optimality was defined as the CTP parameter and threshold which maximized the area-under-the-curve. Linear regression was used for volume based analysis determining the CTP threshold which resulted in the smallest mean volume difference between the acute perfusion lesion and follow up MRI. Subanalysis of PC-regions was performed. Results: Mean transit time (MTT) and delay time (DT) were the best CTP parameters to characterize ischaemic penumbra (AUC = 0.73). Optimal thresholds for penumbra were a DT >1 s and MTT>145%. Delay time (DT) best estimated the infarct core (AUC = 0.74). The optimal core threshold was a DT >1.5 s. The voxel-based analyses indicated CTP was most accurate in the calcarine (Penumbra-AUC = 0.75, Core-AUC = 0.79) and cerebellar regions (Penumbra-AUC = 0.65, Core-AUC = 0.79). For the volume-based analyses, MTT >160% demonstrated best correlation and smallest mean-volume difference between the penumbral estimate and follow-up MRI (R 2 = 0.71). MTT >170% resulted in the smallest mean-volume difference between the core estimate and follow-up MRI, but with poor correlation (R 2 = 0.11). Conclusion: CTP has promising diagnostic utility in POCI. Accuracy of CTP varies by brain region. Optimal thresholds to define penumbra were DT >1 s and MTT >145%. The optimal threshold for core was a DT >1.5 s. However, CTP core volume estimates should be interpreted with caution.

Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting.

BACKGROUND: Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. METHODS: Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. RESULTS: During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8-77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9-58.3], P<0.001). No difference was observed between specificities of NCCT+CTA and NCCT+CTA+CTP (98.7% [95% CI, 98.5-100] versus 98.7% [95% CI, 96.9-99.6], P=0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1-77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5-2.7mL). CONCLUSIONS: Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.

Cerebrovascular Disease Profiles of Culturally and Linguistically Diverse Communities in South Western Sydney and New South Wales.

INTRODUCTION: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). METHODS: This was a 10-year retrospective analysis (2011-2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. RESULTS: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. DISCUSSION/CONCLUSION: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Early lowering of blood pressure after acute intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

OBJECTIVE: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH). METHODS: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect. RESULTS: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth. INTERPRETATION: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent. PROSPERO REGISTRATION NUMBER: CRD42019141136.

A Multicentre Study Comparing Cerebrovascular Disease Profiles in Pacific Islander and Caucasian Populations Presenting with Stroke and Transient Ischaemic Attack.

INTRODUCTION: In a multicentre study, we contrasted cerebrovascular disease profiles in Pacific Island (PI)-born patients (Indigenous Polynesian [IP] or Indo-Fijian [IF]) presenting with transient ischaemic attack (TIA), ischaemic stroke (IS) or intracerebral haemorrhage (ICH) with those of Caucasians (CSs). METHODS: Using a retrospective case-control design, we compared PI-born patients with age- and gender-matched CS controls. Consecutive patients were admitted to 3 centres in South Western Sydney (July 2013-June 2020). Demographic and clinical data studied included vascular risk factors, stroke subtypes, and imaging characteristics. RESULTS: There were 340 CS, 183 (27%) IP, and 157 (23%) IF patients; mean age 65 years; and 302 (44.4%) female. Of these, 587 and patients presented with TIA/IS and 93 (13.6%) had ICH. Both IP and IF patients were significantly more likely to present >24 h from symptom onset (odds ratios [ORs] vs. CS 1.87 and 2.23). IP patients more commonly had body mass indexes >30 (OR 1.94). Current smoking and excess alcohol intake were higher in CS. Hypertension, diabetes, and chronic kidney disease were significantly higher in both IP and IF groups in comparison to CS. IP patients had higher rates of AF and those with known AF were more commonly undertreated than both IF and CS patients (OR 2.24, p = 0.007). ICH was more common in IP patients (OR 2.32, p = 0.005), while more IF patients had intracranial arterial disease (OR 5.10, p < 0.001). DISCUSSION/CONCLUSION: Distinct cerebrovascular disease profiles are identifiable in PI-born patients who present with TIA or stroke symptoms in Australia. These may be used in the future to direct targeted approaches to stroke prevention and care in culturally and linguistically diverse populations.

Creutzfeldt-Jakob Disease in South West Sydney 2014-2020: An Unusually High Incidence of a Rare Disease.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD), a spongiform encephalopathy, caused by a transmissible misfolded cellular prion protein, is a rapidly progressive, debilitating neurodegenerative disorder with no effective treatment. The estimated global incidence is at 1/million inhabitants. This retrospective study examined the incidence of CJD in South Western Sydney Local Health District (SWSLHD) from 2014 to 2020. BACKGROUND: SWSLHD had an estimated population of 1,038,534 in 2020, with CJD data being limited. METHODS: The New South Wales (NSW) Health Information Exchange (HIE) database, for all admissions with CJD diagnoses in SWSLHD, between 2014 and 2020, was reviewed according to the WHO diagnostic criteria, consistent with the Australian national CJD registry. Only probable CJD cases were included. Incidence was calculated based on the projected SWSLHD population. RESULTS: Thirty-five patients, diagnosed with CJD, were identified. Each was evaluated by 2 independent investigators, including clinical presentation, MRI, EEGs, 14-3-3, and RT-QuIC results, before assigning CJD-probable status. Four failed the CJD criteria and were excluded. Of the 31 CJD-probable cases, most (59%) were male and older (37%, range 61-70 years). The incidence rate peaked at 9/million in 2017 and was above 2/million, throughout the 7 years, with an average of 4.859/million/year. CONCLUSIONS: The incidence of CJD, in SWSLHD, exceeds the national average of 1/million. Cost-effective, adequate diagnostic and screening tools, implementable over a large population, will become increasingly essential.

Intravenous Thrombolysis Is Associated with Less Disabling Stroke and Lower Mortality in Multiple-Pass Endovascular Thrombectomy.

BACKGROUND AND PURPOSE: The benefit of bridging intravenous thrombolysis (IVT) in acute ischaemic stroke patients eligible for endovascular thrombectomy (EVT) is unclear. This may be particularly relevant where reperfusion is achieved with multiple thrombectomy passes. We aimed to determine the benefit of bridging IVT in first and multiple-pass patients undergoing EVT ≤6 h from stroke onset to groin puncture. METHODS: We compared 90-day modified Rankin Scale (mRS) outcomes in 187 consecutive patients with large vessel occlusions (LVOs) of the anterior cerebral circulation who underwent EVT ≤6 h from symptom onset and who achieved modified thrombolysis in cerebral ischaemia (mTICI) 2c/3 reperfusion with the first pass to those patients who required multiple passes to achieve reperfusion. The effect of bridging IVT on outcomes was examined. RESULTS: Significantly more first-pass patients had favourable (mRS 0-2) 90-day outcomes (68 vs. 42%, p = 0.001). Multivariate analysis showed an association between first-pass reperfusion and favourable outcomes (OR 2.25; 95% CI 1.08-4.68; p = 0.03). IVT provided no additional benefit in first-pass patients (OR 1.17; CI 0.42-3.20; p = 0.76); however, in multiple-pass patients, it reduced the risk of disabling stroke (mRS ≥4) (OR 0.30; CI 0.10-0.88; p = 0.02) and mortality (OR 0.07; CI 0.01-0.36; p = 0.002) at 90 days. CONCLUSION: Bridging IVT may benefit patients with anterior circulation stroke with LVO who qualify for EVT and who require multiple passes to achieve reperfusion.

Impact of interhospital transfer on patients undergoing endovascular thrombectomy for acute ischaemic stroke in an Australian setting.

OBJECTIVE: To assess the impact of interhospital transfer on the interplay between functional outcome, mortality, reperfusion rates and workflow time metrics in patients undergoing endovascular thrombectomy (EVT) for acute ischaemic stroke due to large vessel occlusion (LVO) in the anterior cerebral circulation. DESIGN SETTING AND PARTICIPANTS: This is an analysis of a prospective database of consecutive patients undergoing EVT for LVO presenting between January 2017 and December 2018 at a single Australian comprehensive stroke centre (CSC). Patients presented directly or were transferred to the CSC from 21 sites across New South Wales and the Australian Capital Territory. MAIN OUTCOME MEASURES: The main outcome measures were rate of good 90-day functional outcome (modified Rankin Scale 0-2), successful reperfusion (Thrombolysis in Cerebral Infarction scale grade 2b or 3), symptomatic intracerebral haemorrhage (sICH) and 90-day mortality. Key workflow time metric milestones were examined. RESULTS: 154 of 213 (72%) patients were interhospital transfers. There was no significant difference in baseline characteristics including age, National Institutes of Health Stroke Scale score, intravenous thrombolysis administration or procedure time between transferred and direct presenters (all p>0.05). Transferred patients had worse 90-day functional outcome (39.6% vs 61.0%, OR 0.42, 95% CI 0.23 to 0.78), higher mortality (25.3% vs 6.8%, OR 4.66, CI 1.59 to 13.70) and longer stroke onset to treatment (groin puncture) time (298 min vs 205 min, p<0.01). Successful reperfusion rates and sICH were similar between the cohorts (96.8% vs 98.3%, and 7.8% vs 3.4%). CONCLUSION: Interhospital transfer is associated with longer stroke onset to treatment, worse 90-day functional outcome and higher mortality compared with patients presenting directly to the CSC.

Cerebral venous thrombosis as a complication of intracranial hypotension after lumbar puncture.

BACKGROUND: Optic neuritis is recognised by the international classification of headache disorders as a painful cranial nerve lesion. A lumbar puncture may be performed in the investigation of optic neuritis. Postdural puncture headache (PDPH) due to intracranial hypotension is a frequent complication of this procedure. In contrast, cerebral venous thrombosis (CVT) is a rare but potentially fatal complication of dural puncture. A few studies have identified an association between iron deficiency anaemia and venous thrombosis. There are no reports linking CVT with lumbar puncture and iron deficiency anaemia. METHODS AND RESULTS: We present a 32-year-old woman with optic neuritis and iron deficiency anaemia complicated by a PDPH and CVT. CONCLUSION: CVT should be considered in a patient with persistent headache, recent lumbar puncture and iron deficiency anaemia. Early recognition and treatment of this condition are vital to avoiding mortality and morbidity.