Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.

BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. FINDINGS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). INTERPRETATION: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. FUNDING: Australian National Health Medical Research Council; Boehringer Ingelheim.

Diabetes mellitus and stroke: A clinical update.

Cardiovascular disease including stroke is a major complication that tremendously increases the morbidity and mortality in patients with diabetes mellitus (DM). DM poses about four times higher risk for stroke. Cardiometabolic risk factors including obesity, hypertension, and dyslipidaemia often co-exist in patients with DM that add on to stroke risk. Because of the strong association between DM and other stroke risk factors, physicians and diabetologists managing patients should have thorough understanding of these risk factors and management. This review is an evidence-based approach to the epidemiological aspects, pathophysiology, diagnostic work up and management algorithms for patients with diabetes and stroke.

Progressive multifocal leukoencephalopathy masquerading as cerebellar infarction.

Progressive neurological signs and symptoms, in immunocompromised individuals, could be due to progressive multifocal leukoencephalopathy (PML). We report the case of a patient who present a stroke unit with symptoms that were consistent initially with a posterior circulation stroke. Prior chemotherapy with Rituximab, for a lymphoma, had predisposed the patient to infection with the JC virus. Physicians need to be aware of the condition, and patients need to aware of these risks of chemotherapy.

Cerebral misery perfusion diagnosed using hypercapnic blood-oxygenation-level-dependent contrast functional magnetic resonance imaging: a case report.

INTRODUCTION: Cerebral misery perfusion represents a failure of cerebral autoregulation. It is an important differential diagnosis in post-stroke patients presenting with collapses in the presence of haemodynamically significant cerebrovascular stenosis. This is particularly the case when cortical or internal watershed infarcts are present. When this condition occurs, further investigation should be done immediately. CASE PRESENTATION: A 50-year-old Caucasian man presented with a stroke secondary to complete occlusion of his left internal carotid artery. He went on to suffer recurrent seizures. Neuroimaging demonstrated numerous new watershed-territory cerebral infarcts. No source of arterial thromboembolism was demonstrable. Hypercapnic blood-oxygenation-level-dependent-contrast functional magnetic resonance imaging was used to measure his cerebrovascular reserve capacity. The findings were suggestive of cerebral misery perfusion. CONCLUSIONS: Blood-oxygenation-level-dependent-contrast functional magnetic resonance imaging allows the inference of cerebral misery perfusion. This procedure is cheaper and more readily available than positron emission tomography imaging, which is the current gold standard diagnostic test. The most evaluated treatment for cerebral misery perfusion is extracranial-intracranial bypass. Although previous trials of this have been unfavourable, the results of new studies involving extracranial-intracranial bypass in high-risk patients identified during cerebral perfusion imaging are awaited.Cerebral misery perfusion is an important and under-recognized condition in which emerging imaging and treatment modalities present the possibility of practical and evidence-based management in the near future. Physicians should thus be aware of this disorder and of recent developments in diagnostic tests that allow its detection.

Inclusion body myositis: an underdiagnosed myopathy of older people.

Inclusion body myositis (IBM), a condition characterised by progressive muscle weakness and inclusion bodies visible on muscle biopsy, is the most common type of myopathy in patients over 50 years of age. However, it is not only under diagnosed but frequently misdiagnosed as polymyositis and hence wrongly treated with steroids. In the evaluation of progressive weakness in older Caucasian males, IBM should be an important diagnostic consideration. Treatment-resistant 'polymyositis' in patients over 50 years of age is often IBM. If there is no histological confirmation, the diagnostic criteria allow for a category of 'possible IBM'. Sometimes, the diagnosis is missed because of the slow progression of the disease and a lack of suspicion on the part of physicians. The following case report and literature review will explore many of these issues.

Paraneoplastic limbic encephalitis--case report and review of literature.

We report a 77-year old man who presented with a sub-acute dementia associated with aggressive behaviour, ataxia, rapid progression and death. No cause for his illness could be detected in his lifetime, but at post mortem he was found to have paraneoplastic limbic encephalitis and a bronchogenic tumour. A diagnosis of paraneoplastic limbic encephalitis should be considered in the differential diagnosis of unexplained dementias and appropriate investigations performed to diagnose the condition.