Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials.

BACKGROUND AND OBJECTIVES: The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs. METHODS: We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK. RESULTS: Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed. DISCUSSION: Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.

Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Health Research and Education during and after the COVID-19 Pandemic: An Australian Clinician and Researcher Perspective.

Introduction: The COVID-19 pandemic had an unprecedented global effect on teaching and education. This review discusses research, education and diagnostics from the perspectives of four academic clinicians and researchers across different facilities in Australia. Materials and methods: The study adopted a literature review and an Australian researcher's perspective on the impact of the COVID-19 pandemic on health education, research and diagnostics. Results: At the start of the pandemic, medical facilities had to adhere urgently to major work restrictions, including social distancing, mask-wearing rules and/or the closure of facilities to protect staff, students and patients from the risk of COVID-19 infection. Telemedicine and telehealth services were rapidly implemented and adapted to meet the needs of medical education, the teaching of students, trainee doctors, nursing and allied health staff and became a widely accepted norm. The impact on clinical research and education saw the closure of clinical trials and the implementation of new methods in the conducting of trials, including electronic consents, remote patient assessments and the ability to commence fully virtual clinical trials. Academic teaching adapted augmented reality and competency-based teaching to become important new modes of education delivery. Diagnostic services also required new policies and procedures to ensure the safety of personnel. Conclusions: As a by-product of the COVID-19 pandemic, traditional, face-to-face learning and clinical research were converted into online formats. An hybrid environment of traditional methods and novel technological tools has emerged in readiness for future pandemics that allows for virtual learning with concurrent recognition of the need to provide for interpersonal interactions.

Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial.

BACKGROUND: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). METHODS: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. FINDINGS: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84). INTERPRETATION: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. FUNDING: Australian National Health and Medical Research Council and Stryker USA.

Clinical outcomes following reperfusion therapy in acute ischemic stroke patients with infective endocarditis: a systematic review.

Background: Acute ischemic stroke (AIS) is a common and fatal complication of infective endocarditis (IE); however, there is a lack of understanding regarding treatment efficacy. This systematic review aimed to evaluate the safety and efficacy of intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) in IE patients experiencing AIS. Objectives: The aim of this study was to perform a systematic review investigating the outcomes of AIS in IE patients receiving IVT and/or EVT as a treatment method and to evaluate the safety and efficacy of these methods of reperfusion therapy. Design: A systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was conducted. Data Sources and Methods: The EMBASE, Cochrane, and PubMed databases were searched for literature published between 2005 and 2021 investigating outcomes of reperfusion therapy post-AIS in IE and non-IE patients. Descriptive statistics were used to describe the overall frequency of clinical outcomes, and groupwise comparisons were performed using Fisher's exact test to assess the significance of groupwise differences. Results: Three studies were finally included in the systematic review. A total of 13.5% of IE patients compared to 37% of non-IE patients achieved a good functional outcome (modified Rankin Scale score≤ 2) (P < .001). Furthermore, a larger percentage of the IE cohort achieved good functional outcomes after EVT (22.0%) compared to IVT (10.4%) (P = .013). The IE cohort also had a higher 3-month postreperfusion mortality rate (48.8%) compared to the non-IE cohort (24.9%) (P < .001). The rate of intracranial hemorrhage (ICH) postreperfusion was also significantly higher in the IE cohort (23.5%) than in the non-IE cohort (6.5%) (P < .001). Conclusion: AIS patients with IE, treated with IVT, EVT, or a combination of the two, experience worse clinical and safety outcomes than non-IE patients. EVT yielded better functional outcomes, albeit with higher postreperfusion ICH rates, than IVT.

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.

Functional outcomes of an integrated Parkinson's Disease Wellbeing Program.

INTRODUCTION: There is growing evidence that exercise provides benefit in treating motor and non-motor symptoms in Parkinson's disease (PD). OBJECTIVES: The aims of this study were to determine (a) whether a 5-week PD-specific program resulted in sustained physical and psychosocial benefits, and (b) the relationship between patient characteristics, exercise, falls and physical and psychosocial parameters. DESIGN: Single-centre prospective observational study. METHODS: A total of 135 consecutive patients with mild-to-moderate PD underwent a 5-week PD-specific education and exercise program from August 2013 to March 2015. Gait, mobility and psychosocial measures were compared at baseline, 6 weeks and 12 months. RESULTS: Significant improvements in physical (walking distance in 2 minutes, number of "Sit To Stands" in 30 seconds, time in seconds taken to "Timed Up and Go," fast gait velocity over 10 m, Berg Balance Scale [BBS]) and psychosocial (quality of life (QoL) [PDQ-39], depression and anxiety [DASS-21], and fatigue [PSF-16]) measures were seen at 6 weeks (all P < .01) with physical improvements sustained at 12 months (all P < .001). The number of patients at 12 months with ≥1 fall reduced from 66% to 33%, and the number not exercising reduced from 42% to 21%. A lack of exercise correlated with ≥1 fall at 12 months (OR 3.39, 95% CI 1.36-8.39, P = .009). It was also associated with poorer balance and psychosocial parameters at 12 months (all P < .05). CONCLUSIONS: Patients recruited into a 5-week Parkinson's disease education and exercise program achieved significant 12-month benefits in physical but not psychosocial measures. Patients with ≥1 fall post-treatment were less likely to have been exercising at 12-month follow-up.

Impact of small vessel disease on severity of motor and cognitive impairment in Parkinson's disease.

BACKGROUND: Subcortical small vessel disease and vascular risk factors are associated with motor and cognitive impairment. In this study we examined the relationship between these factors and the severity of motor impairment and dementia in pathologically-confirmed Parkinson's disease (PD). METHODS: The extent and severity of small vessel disease (SVD) was assessed pathologically in 77 patients with PD. The severity of motor impairment was determined using a cumulative index derived from longitudinal measures of Hoehn and Yahr score. The presence of dementia was scored using the Clinical Dementia Rating. The presence or absence of vascular risk factors and stroke were also recorded. Interactions were assessed using stepwise multiple regression analyses. RESULTS: Significant correlations were demonstrated between perivascular pallor in the globus pallidus interna and the Hoehn and Yahr stage and between increasing Braak PD stage, the number of vascular risk factors and dementia. Among the vascular risk factors, hypertension was the only variable to independently correlate with dementia. SVD pathology did not correlate with dementia in our cohort. CONCLUSIONS: This study demonstrates an association between SVD and motor impairment, and between vascular risk factors, particularly hypertension, and dementia in PD and highlights the need to manage vascular co-morbidities in PD patients.

Factors Associated with Stroke Misdiagnosis in the Emergency Department: A Retrospective Case-Control Study.

BACKGROUND: Failure to recognise acute stroke may result in worse outcomes due to missed opportunity for acute stroke therapies. Our study examines factors associated with stroke misdiagnosis in patients admitted to a large comprehensive stroke centre. METHODS: Retrospective review comparing 156 consecutive stroke patients misdiagnosed in emergency department (ED) with 156 randomly selected stroke controls matched for age, gender, language spoken and stroke subtype for the period 2014-2016. RESULTS: There were 141 ischemic and 15 hemorrhagic misdiagnosed strokes (median age: 77 years, male:female = 1.3: 1). Symptom resolution, altered mental status, nausea/vomiting, dizziness and vertigo favored misdiagnosis (p < 0.05). Hemiparesis and dysarthria favored an accurate diagnosis (p < 0.05). Misdiagnosed patients were more commonly triaged into a lower ED category (62 vs. 42%, p = 0.001), clinically assessed as Face, Arm, Speech and Time (FAST) - negative (78 vs. 22%, p < 0.001) and underwent delayed CT imaging (median 4.1 vs. 1.5 h, p < 0.001). Misdiagnosed patients were more likely to have posterior circulation stroke (PCS; 39 vs. 22%, p = 0.01) and be admitted under non-neurological services (35 vs. 11%, p < 0.001) with worse discharge outcomes including increased mortality. CONCLUSIONS: Patients with stroke misdiagnosis were commonly FAST-negative with nonspecific symptoms including altered mental status, dizziness and nausea/vomiting often associated with PCS. Improved diagnostic accuracy may increase access to acute therapies.

Frequency, Aetiology, and Outcome of Small Cerebellar Infarction.

BACKGROUND AND PURPOSE: Strokes due to small (<2 cm) cerebellar infarction are under-recognised, and their profile and aetiology have not been well characterised. We aimed to determine the frequency, clinical features, aetiology, and outcome of small as compared to large cerebellar infarction. METHODS: This study is a retrospective analysis of clinical and imaging features of a prospectively assessed series of 108 consecutive patients with acute cerebellar infarction admitted to Liverpool Hospital, Sydney, NSW, Australia, during 2011-2015. RESULTS: The mean age of the patients was 67 years, and 33 (31%) had small cerebellar infarction. Compared to large cerebellar infarction, those with small cerebellar infarction had a comparable distribution of vascular risk factors but significantly less nausea and vomiting, gait disturbance, limb ataxia, and dysarthria. The posterior (n = 22, 67%) lobe was most commonly affected, followed by the anterior (n = 9, 27%) and flocculonodular (n = 2) lobes. Dizziness, limb ataxia, and nystagmus were significantly more common in patients with anterior lobe infarction. Vertebrobasilar disease was the presumed aetiology in 40 patients (37%), and was less commonly seen in small as compared to large cerebellar infarction. Cardioembolism affected 37% of the patients, irrespective of the size or topography of the cerebellar infarction, and there was no relation of supratentorial white matter lucencies (WMLs) to the size of cerebellar infarction. At 3 months, 65% of the patients were functionally independent (according to modified Rankin Scale scores of 0-2), and having a poor outcome was significantly related to moderate-to-severe supratentorial WML and large cerebellar infarction. CONCLUSIONS: Small cerebellar infarction accounted for one-third of the ischaemic strokes in this location, most often involved the posterior lobe, causing fewer clinical features, and had a better clinical outcome than large cerebellar infarction. Patients with small cerebellar infarction require appropriate vascular management including investigation for a cardioembolic source.

Can head trauma trigger adult-onset Rasmussen's encephalitis?

Rasmussen's encephalitis (RE) is a rare unilateral inflammatory brain disorder that causes progressive neurocognitive deterioration and refractory epilepsy including epilepsia partialis continua (EPC). We describe a patient with a unique presentation, where right upper limb EPC due to RE began within 2weeks of a concussive left frontal head injury, in a 36-year-old female without other identifiable etiology, no prior neurological deficit nor suggestion of intracranial pathology or infection, and no preceding seizures. The diagnosis of RE followed extensive investigation, excluding confounding diagnoses, with supportive histopathology, and her EPC has proven refractory to treatment. In the absence of a satisfactory alternative etiology and exclusion of differential diagnoses, the most likely cause or precipitant of this patient's RE was head trauma.

Cerebellar Infarction and Factors Associated with Delayed Presentation and Misdiagnosis.

BACKGROUND AND PURPOSE: The diagnosis of cerebellar infarction (CBI) is often challenging due to non-specific or subtle presenting symptoms and signs. We aimed to determine whether a common syndromic cluster of symptoms, signs or vascular risk factors were associated with delayed presentation or misdiagnosis to an Emergency Department (ED). The degree of misdiagnosis between ED and neurology physicians and the influence of delayed presentation or misdiagnosis on outcome were also investigated. METHODS: A prospective study of CBI patients at a large tertiary-referral hospital with a comprehensive stroke service. Data are reported with OR and 95% CIs. RESULTS: Of 115 consecutive CBI patients (mean age ± SD 66 ± 14 years, 51% male), infarction was isolated to the cerebellum in 46%; the remainder had additional vascular territory involvement ('mixed CBI'). Most patients (n = 79, 69%) had a mild stroke (National Institute of Health Stroke Scale score ≤4), and tended to present late to ED (>4.5 h; p = 0.05). Dysarthria (OR 3.9, 95% CI 1.6-9.6, p = 0.003) and prior history of atrial fibrillation (AF; OR 3.0, 95% CI 1.02-9.1, p = 0.047) predicted early presentation (<4.5 h; in 52%). Neurological signs (as determined by neurology physicians) were more commonly absent in patients with isolated CBI (OR 4.0, 95% CI 1.2-13.3, p = 0.03) who were also less likely to receive acute stroke therapy (p = 0.03). ED physicians detected fewer neurological signs than neurology physicians (mean 1 vs. 2 signs, p < 0.001), and 34% of CBI patients were misdiagnosed, with peripheral vestibulopathy being the most common alternative diagnosis. Nausea and vomiting (OR 2.3, 95% CI 1.01-5.5, p = 0.046), absence of neurological signs as determined by ED physicians (OR 3.5, 95% CI 1.5-8.0, p = 0.003) and isolated CBI (OR 2.2, 95% CI 1.01-4.8, p = 0.047) correlated with misdiagnosis. Vascular territory involvement did not correlate with time to presentation or misdiagnosis. At 3 months, 65% of patients were functionally independent (modified Rankin Scale (mRS) score 0-2). History of hypertension (p = 0.008), AF (p = 0.012), mixed CBI (p = 0.004) and in-hospital stroke-related complications (p < 0.001) were associated with patients having a poor outcome (mRS ≥3). At 3 months, mortality was 16%, and AF was the only predictor of death (OR 3.2, 95% CI 1.1-8.9, p = 0.03). Late presentation to ED and misdiagnosis did not significantly influence 3-month functional outcome. CONCLUSIONS: Late ED presentation and misdiagnosis are common for CBI. Timely diagnosis of CBI may increase opportunity for acute stroke therapies and reduce risk of stroke-related complications.

The Effect of Biofeedback as a Psychological Intervention in Multiple Sclerosis: A Randomized Controlled Study.

BACKGROUND: Relaxation, mindfulness, social support, and education (RMSSE) have been shown to improve emotional symptoms, coping, and fatigue in multiple sclerosis (MS). Biofeedback was trialed as a psychological intervention, designed to improve self-control, in two groups of patients with MS. Both groups received RMSSE, and one group additionally received biofeedback. METHODS: Forty people with relapsing-remitting MS were recruited from three sites in Sydney, Australia. The mean disability score (Expanded Disability Status Scale; EDSS) was 2.41 ± 1.46 (95% confidence interval [CI], 1.46-3.36); the mean age in years was 45.9 ± 12.42 (95% CI, 41.92-49.87). Participants were randomly assigned to two active treatment groups (n = 20 per group). All participants received one 1-hour session per week for 3 weeks of RMSSE, while biofeedback equipment measured breathing rate and muscle tension. Members of one group used biofeedback screens to regulate physiological response. RESULTS: Whole-group pre- and post-treatment scores demonstrated a reduction of 38% for anxiety and 39% for depression scores (P = .007 and P = .009, respectively). A post-treatment comparison failed to demonstrate any significant difference between the two active treatment groups in anxiety and depression scores. The biofeedback group showed significant pre- to post-treatment improvement or trends toward improvement in anxiety, fatigue, and stress (P = .05, .02, and .03, respectively). Comparison of pre-post treatment results between groups showed improvements for the biofeedback group in breathing rate and muscle tension (P = .06 and .09). CONCLUSIONS: For relapsing-remitting MS patients receiving biofeedback in addition to RMSSE, there was a demonstrable reduction in anxiety, fatigue, and stress. There was also a trend toward significant reduction of breathing rate and muscle tension in favor of biofeedback.

Rectal carbamazepine as effective long-acting treatment after cluster seizures and status epilepticus.

Carbamazepine (CBZ) is the gold standard antiepileptic drug (AED) for focal onset seizures. Despite CBZ being the benchmark AED, with readily available therapeutic drug monitoring, patients presenting with recurrent secondarily generalized tonic-clonic (or cluster) seizures or generalized tonic-clonic status epilepticus (SE) are primarily treated with other long-acting agents. The aim of the study was to examine the potential use of rectal (PR) CBZ as alternative long-acting treatment to parenteral AEDs following the termination of cluster seizures or SE with acute intravenous therapies. Oral CBZ syrup was given PR using 400-mg equivalent aliquots. Serum CBZ levels were requested after administration to confirm achievement of minimum therapeutic levels (total CBZ>20µmol·L(-1)). Where levels were subtherapeutic, the procedure was repeated using 400-mg CBZ bolus aliquots until therapeutic levels were achieved. Seven patients received PR CBZ to manage cluster seizures or SE following the initial termination of acute seizures with IV therapies including benzodiazepines. Six patients had no prior history of seizures, and 1 patient with a prior history was not taking AED therapy at the time of presentation. All patients subsequently remained seizure-free, and therapeutic CBZ levels were achieved in 6 of the 7 subjects within 5-10h of initial CBZ dosing. In conclusion, the present study reports 7 patients who were safely and effectively treated with PR CBZ, which proved to be a viable and safe alternative to parenteral AEDs for maintenance of seizure freedom.