Rationale and design of Short-Term EXenatide therapy in Acute ischaemic Stroke (STEXAS): a randomised, open-label, parallel-group study.

INTRODUCTION: Both hyperglycaemia and hypoglycaemia in acute ischaemic stroke (AIS) are associated with increased infarct size and worse functional outcomes. Thus, therapies that can maintain normoglycaemia during stroke are clinically important. Glucagon-like peptide 1 (GLP-1) analogues, including exenatide, are routinely used in the treatment of hyperglycaemia in type 2 diabetes, but data on the usefulness of this class of agents in the management of elevated glucose levels in AIS are limited. Owing to their glucose-dependent mechanism of action, GLP-1 analogues are associated with a low risk of hypoglycaemia, which may give them an advantage over intensive insulin therapy in the acute management of hyperglycaemia in this setting. METHODS AND ANALYSIS: The Short-Term EXenatide therapy in Acute ischaemic Stroke study is a randomised, open-label, parallel-group pilot study designed to investigate the efficacy of exenatide at lowering blood glucose levels in patients with hyperglycaemia with AIS. A total of 30 patients presenting with AIS and blood glucose levels >10 mmol/L will be randomised to receive the standard therapy (intravenous insulin) or intravenous exenatide for up to 72 h. Outcomes including blood glucose levels within the target range (5-10 mmol/L), the incidence of hypoglycaemia and the feasibility of administering intravenous exenatide in this patient population will be assessed. A follow-up visit at 3 months will facilitate evaluation of neurological outcomes post-stroke. ETHICS AND DISSEMINATION: This study has been approved by the local Institutional Review Board (Northern Sydney Local Health District Human Research Ethics Committee). The study results will be communicated via presentations at scientific conferences and through publication in peer-reviewed journals. CONCLUSIONS: As GLP-1 analogues require elevated glucose levels to exert their insulin potentiating activity, the use of exenatide in the management of hyperglycaemia in AIS may reduce the incidence of hypoglycaemia, thereby conferring a benefit in morbidity and mortality for patients in the long term. TRIAL REGISTRATION NUMBER: ACTRN12614001189617.

Rapid access point of care clinic for transient ischemic attacks and minor strokes.

We present 24months of prospective data from a new model of care for transient ischemic attacks (TIA) and minor stroke, established at the Royal North Shore Hospital, a tertiary teaching hospital in Sydney, Australia. Prior to 2011, approximately 200 patients were admitted to our emergency department (ED) annually, following presentation with a suspected TIA. These patients had an average length of stay of 5.3days. Following the establishment of a twice weekly multidisciplinary, one stop, stroke prevention and hospital avoidance clinic, all patients with suspected TIA were investigated and treated as outpatients. There was an average time to clinic from the initial presentation in the ED of 3.9days. Symptoms that were highly suggestive of TIA were seen in 47% of patients, and an additional 14% had MRI-confirmed acute stroke. In total, 405 patients were referred to the clinic, saving 2146.5 inpatient bed days and approximately AUD$1,180,575. Our model of care for patients with suspected TIA provides early access for investigation, treatment and management of the risk factors. The rapid access TIA clinic is highly cost effective and provides a transferable model of care for other health districts with similar patient loads and cost structures.

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.).

No relationship of lipid-lowering agents to hematoma growth: pooled analysis of the intensive blood pressure reduction in acute cerebral hemorrhage trials studies.

BACKGROUND AND PURPOSE: Controversy persists over statins and risk of intracerebral hemorrhage. We determined associations of premorbid lipid-lowering therapy and outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). METHODS: The pooled data of INTERACT 1 and 2 (international, multicenter, prospective, open, blinded end point, randomized controlled trials of patients with intracerebral hemorrhage [<6 hours] and elevated systolic blood pressure) were analyzed with regard to associations of baseline lipid-lowering treatment and clinical outcomes of 3184 participants in a multivariate model. Associations of lipid-lowering therapy and hematoma growth (baseline to 24 hours) in computed tomographic substudies participants (n=1310) were estimated in ANCOVA. RESULTS: Among 204 patients (6.5%) with baseline lipid-lowering treatment, 90-day clinical outcomes were not significantly different after adjustment for confounding variables including region and age. In the computed tomographic substudy, 24-hour hematoma growth was greater in 124 patients (9%) with, compared with those without, prior lipid-lowering therapy. However, this association was not significant between groups (9.2 versus 6.8 mL; P<0.13), after adjustment for prior antithrombotic therapy. CONCLUSIONS: No independent associations were found between lipid-lowering medication and adverse outcomes in patients with intracerebral hemorrhage. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

Rapid Induction of COOLing in Stroke Patients (iCOOL1): a randomised pilot study comparing cold infusions with nasopharyngeal cooling.

INTRODUCTION: Induction methods for therapeutic cooling are under investigated. We compared the effectiveness and safety of cold infusions (CI) and nasopharyngeal cooling (NPC) for cooling induction in stroke patients. METHODS: A prospective, open-label, randomised (1:1), single-centre pilot trial with partially blinded safety endpoint assessment was conducted at the neurointensive care unit of Heidelberg University. Intubated stroke patients with an indication for therapeutic cooling and an intracranial pressure (ICP)/temperature brain probe were randomly assigned to CI (4°C, 2L at 4L/h) or NPC (60L/min for 1 h). Previous data suggested a maximum decrease of tympanic temperature for CI (2.1L within 35 min) after 52 min. Therefore the study period was 1 hour (15 min subperiods I-IV). The brain temperature course was the primary endpoint. Secondary measures included continuous monitoring of neurovital parameters and extracerebral temperatures. Statistical analysis based on repeated-measures analysis of variance. RESULTS: Of 221 patients screened, 20 were randomized within 5 months. Infusion time of 2L CI was 33 ± 4 min in 10 patients and 10 patients received NPC for 60 min. During active treatment (first 30 min), brain temperature decreased faster with CI than during NPC (I: -0.31 ± 0.2 versus -0.12 ± 0.1°C, P = 0.008; II: -1.0 ± 0.3 versus -0.49 ± 0.3°C, P = 0.001). In the CI-group, after the infusion was finished, the intervention no longer decreased brain temperature, which increased after 3.5 ± 3.3 min. Oesophageal temperature correlated best with brain temperature during CI and NPC. Tympanic temperature reacted similarly to relative changes of brain temperature during CI, but absolute values slightly differed. CI provoked three severe adverse events during subperiods II-IV (two systolic arterial pressure (SAP), one shivering) compared with four in the NPC-group, all during subperiod I (three SAP, one ICP). Classified as possibly intervention-related, two cases of ventilator failure occurred during NPC. CONCLUSIONS: In intubated stroke patients, brain cooling is faster during CI than during NPC. Importantly, contrary to previous expectations, brain cooling stopped soon after CI cessation. Oesophageal but neither bladder nor rectal temperature is suited as surrogate for brain temperature during CI and NPC. Several severe adverse events in CI and in NPC demand further studying of safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT01573117. Registered 31 March 2012.

An unusual cause of cerebellar hemorrhage in a young patient: essential thrombocythemia.

Essential thrombocythemia (ET) is a risk factor for ischemic stroke and, far more rarely, hemorrhage. We report the case of an untreated 32-year-old woman with a history of JAK2 V617F-positive ET with cerebellar and subarachnoid hemorrhages without evidence of sinus vein thrombosis. She was commenced on oral cytotoxic and antiplatelet therapy. This case report discusses the underlying mechanism of hemorrhagic thrombocythemia and the management dilemma presented by the recommended treatment implications.

Safety evaluation of nasopharyngeal cooling (RhinoChill®) in stroke patients: an observational study.

INTRODUCTION: New technologies for therapeutic cooling have become available. The objective of our study was to investigate the safety of nasopharyngeal cooling with the RhinoChill(®) device in stroke patients, focusing on systemic and neurovital parameters. METHODS: In this prospective observational study, consecutive patients with severe ischemic or hemorrhagic stroke who underwent intracranial pressure (ICP) and brain temperature monitoring have been enrolled. Ten patients who were treated with the RhinoChill(®) device were analyzed. Brain and bladder temperature and systemic and neurovital parameters were monitored continuously. Additional evaluations of safety included bleeding complications and otolaryngological examinations. RESULTS: Baseline brain temperature of 36.7 °C (SD 0.9) decreased by an average of 1.21 °C (SD 0.46) within 1 h, the effect of brain temperature decrease ranged from a maximum of 2 °C (patients 3 and 7) to a minimum of 0.6 °C (patient 4). Within the first several minutes after initiating RhinoChill(®) treatment, 3 of 10 patients experienced an increase in systolic arterial pressure by 30, 30, and 53 mmHg, respectively. Heart rate rose as well (mean 3 bpm, SD 2.9). ICP and oxygen saturation were unaffected by the treatment. We observed 1 bleeding complication in the control CT scan of patient 10. Rhinoscopical findings 3 days after nasopharyngeal cooling and at the follow-up (>6 months) and a 16-item smell test were normal. CONCLUSION: The RhinoChill(®) system cools the brain efficiently. However, steep increases in blood pressure raise serious concerns regarding the safety of its use in stroke patients.

Induction of cooling with a passive head and neck cooling device: effects on brain temperature after stroke.

BACKGROUND AND PURPOSE: Therapeutic hypothermia improves clinical outcome after cardiac arrest and appears beneficial in other cerebrovascular diseases. We conducted this study to investigate the relationship between surface head/neck cooling and brain temperature. METHODS: Prospective observational study enrolling consecutive patients with severe ischemic or hemorrhagic stroke undergoing intracranial pressure (ICP) and brain temperature monitoring. Arterial pressure, ICP, cerebral perfusion pressure, heart rate, brain, tympanic, and bladder temperature were continuously registered. Fifty-one applications of the Sovika cooling device were analyzed in 11 individual patients. RESULTS: Sovika application led to a significant decrease of brain temperature compared with baseline with a maximum of -0.36°C (SD, 0.22) after 49 minutes (SD, 17). During cooling, dynamics of brain temperature differed significantly from bladder (-0.25°C [SD, 0.15] after 48 minutes [SD, 19]) and tympanic temperature (-1.79°C [SD, 1.19] after 37 minutes [SD, 16]). Treatment led to an increase in systolic arterial pressure by >20 mm Hg in 14 applications (n=7 patients) resulting in severe hypertension (>180 mm Hg) in 4 applications (n=3). ICP increased by >10 mm Hg in 7 applications (n=3), led to ICP crisis >20 mm Hg in 6 applications (n=3), and a drop of cerebral perfusion pressure <50 mm Hg in 1 application. CONCLUSIONS: Although the decrease of brain temperature after Sovika cooling device application was statistically significant, we doubt clinical relevance of this rather limited effect (-0.36°C). Moreover, the transient increases of blood pressure and ICP warrant caution.