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.

Bilateral Thalamic Stroke Arising From an Occlusion of the Artery of Percheron: Barriers to Diagnosis, Management, and Recovery.

A 90-year-old male patient presented with excessive somnolence, right-sided weakness, and left facial droop. CT and MRI scans of the head, taken several days after initial head CT proved to be non-revealing, demonstrated a bilateral thalamic stroke, a rare phenomenon. The infarct arose in the territory of the artery of Percheron, an anatomic variant in which a single artery supplies both sides of the thalamus and midbrain. When this artery becomes occluded, it results in severely dysregulated consciousness and alertness. This type of stroke proved challenging for the medical team, due to poor resolution of initial imaging, as well as the therapy teams, due to the constant need for sleep. This case report outlines how barriers in diagnosis and management make knowledge of the artery of Percheron and its occlusion crucial to patient care and recovery.

Sexual dysfunction after stroke-A biopsychosocial perspective.

OBJECTIVES: Poststroke sexual dysfunction (PSSD) is widespread and underrecognised, affecting over half of stroke patients with significant effects on a patients' quality of life. We reviewed the postulated factors contributing to PSSD and explore the underrecognition by presenting a questionnaire study as well as examining existing literature. METHODS: A literature search between January 1980 and December 2019 in electronic databases such as EMBASE, MEDLINE and PubMed was conducted. The questionnaire study involved all adult stroke patients attending the outpatient clinic over a 6-month period, containing multiple choice and open questions relating to prevalence, impact and provision provided for patients with PSSD. FINDINGS: Poststroke sexual dysfunction is unlikely attributed solely to the physical effects of stroke. We present a biopsychosocial model summarising the wide range of factors which can contribute to PSSD. Less than 10% of patients receive any advice despite 90% of patients hoping for advice relating to sexual dysfunction in stroke. INTERPRETATION AND IMPLICATIONS: A multidisciplinary, proactive involvement in screening and managing PSSD is required to successfully manage a commonly forgotten complication of stroke. As part of the wider theme of managing lifestyle factors poststroke (eg, smoking, driving advice, dietary advice, alcohol), the 'sexual function aspect' of patients' lives must not be ignored.

Meningovascular syphilis causing recurrent stroke and diagnostic difficulties: a scourge from the past.

We describe a case of a 49-year-old man who presented with recurrent strokes in the left middle cerebral artery territory, manifesting with dysphasia, higher cognitive deficits, motor deficits and subsequent infarcts in the right middle cerebral and anterior cerebral artery territories, manifesting with seizures, behavioural and social issues. A key issue of the case was the diagnostic difficulty faced by the physicians. 'Meningovascular syphilis' was subsequently confirmed and appropriate treatment was given but there was subsequent relapse with worsening of the symptoms. Multiple specialists were involved in the management, namely stroke team, neurologists, psychiatrists, infectious disease and multidisciplinary therapy teams. This case highlights the need to be vigilant to the resurgence of syphilis, a scourge from the past, as a cause of stroke, especially in individuals who have had exposure to affected people. It is easy to miss the diagnosis and mistake it for other conditions unless a detailed history is taken and appropriate investigations are conducted, with a low threshold for diagnosis.

Cerebral misery perfusion due to carotid occlusive disease.

PURPOSE: Cerebral misery perfusion (CMP) is a condition where cerebral autoregulatory capacity is exhausted, and cerebral blood supply in insufficient to meet metabolic demand. We present an educational review of this important condition, which has a range of clinical manifestations. METHOD: A non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease, using Pubmed and Sciencedirect. FINDINGS: Patients with CMP may present with strokes in watershed territories, collapses and transient ischaemic attacks or episodic movements associated with an orthostatic component. While positron emission tomography is the gold standard investigation for misery perfusion, advanced MRI is being increasingly used as an alternative investigation modality. The presence of CMP increases the risk of strokes. In addition to the devastating effect of stroke, there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease (COD) and misery perfusion. The evidence for revascularisation in the setting of complete carotid occlusion is weak. Medical management constitutes careful blood pressure management while addressing other vascular risk factors. DISCUSSION: The evidence for the management of patients with COD and CMP is discussed, together with recommendations based on our local experience. In this review, we focus on misery perfusion due to COD. CONCLUSION: Patients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many specialties. Early identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow, while avoiding potentially harmful treatment.

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.

Computer vision syndrome-A common cause of unexplained visual symptoms in the modern era.

OBJECTIVES: The aim of this study was to assess the evidence and available literature on the clinical, pathogenetic, prognostic and therapeutic aspects of Computer vision syndrome. METHODS: Information was collected from Medline, Embase & National Library of Medicine over the last 30 years up to March 2016. The bibliographies of relevant articles were searched for additional references. FINDINGS: Patients with Computer vision syndrome present to a variety of different specialists, including General Practitioners, Neurologists, Stroke physicians and Ophthalmologists. While the condition is common, there is a poor awareness in the public and among health professionals. INTERPRETATIONS AND IMPLICATIONS: Recognising this condition in the clinic or in emergency situations like the TIA clinic is crucial. The implications are potentially huge in view of the extensive and widespread use of computers and visual display units. Greater public awareness of Computer vision syndrome and education of health professionals is vital. Preventive strategies should form part of work place ergonomics routinely. Prompt and correct recognition is important to allow management and avoid unnecessary treatments.

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.

Fatigue after stroke: frequency and effect on daily life.

PURPOSE: An audit was conducted to assess the frequency of fatigue after stroke, to determine the impact on daily life, and whether it was discussed with clinicians. METHOD: Patients were recruited from Nottingham University Hospitals NHS Trust stroke service. Patients were interviewed about their fatigue, and the Fatigue Severity Subscale (FSS-FAI), Brief Assessment Schedule for Depression Cards (BASDEC), Barthel Index and Nottingham Extended Activities of Daily Living (EADL) Scale were administered. RESULTS: 64 patients were recruited, with a mean age 73.5 years (SD 14.0, range 37-94 years), 37 (58%) as in-patients and 27 (42%) as outpatients. There were 41 (64%) who reported significant levels of fatigue and 31 (48%) with significant fatigue on the Fatigue Severity Scale. Demographic and clinical variables were not significantly related to fatigue (p > 0.05), apart from gender, with women reporting significantly more fatigue than men (p = 0.006). There was a moderate correlation between the BASDEC and FSS (r(s) = 0.41, p = 0.002). Of the 41 participants who reported fatigue, 33 (81%) had not discussed this with their clinician. CONCLUSIONS: Fatigue was a common problem after stroke. There was a lack of awareness in both patients and clinicians and little advice being given to patients with fatigue.

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.