Design and Validation of a Novel Method to Measure Cross-Sectional Area of Neck Muscles Included during Routine MR Brain Volume Imaging

Low muscle mass secondary to disease and ageing is an important cause of excess mortality and morbidity. Many studies include a MR brain scan but no peripheral measure of muscle mass. We developed a technique to measure posterior neck muscle cross-sectional area (CSA) on volumetric MR brain scans enabling brain and muscle size to be measured simultaneously.We performed four studies to develop and test: feasibility, inter-rater reliability, repeatability and external validity. We used T1-weighted MR brain imaging from young and older subjects, obtained on different scanners, and collected mid-thigh MR data.After developing the technique and demonstrating feasibility, we tested it for inter-rater reliability in 40 subjects. Intraclass correlation coefficients (ICC) between raters were 0.99 (95% confidence intervals (CI) 0.98-1.00) for the combined group (trapezius, splenius and semispinalis), 0.92 (CI 0.85-0.96) for obliquus and 0.92 (CI 0.85-0.96) for sternocleidomastoid. The first unrotated principal component explained 72.2% of total neck muscle CSA variance and correlated positively with both right (r = 0.52, p = .001) and left (r = 0.50, p = .002) grip strength. The 14 subjects in the repeatability study had had two MR brain scans on three different scanners. The ICC for between scanner variation for total neck muscle CSA was high at 0.94 (CI 0.86-0.98). The ICCs for within scanner variations were also high, with values of 0.95 (CI 0.86-0.98), 0.97 (CI 0.92-0.99) and 0.96 (CI 0.86-0.99) for the three scanners. The external validity study found a correlation coefficient for total thigh CSA and total neck CSA of 0.88.We present a feasible, valid and reliable method for measuring neck muscle CSA on T1-weighted MR brain scans. Larger studies are needed to validate and apply our technique with subjects differing in age, ethnicity and geographical location

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbased ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting

Response to symptoms of stroke in the UK: a systematic review

<p>Abstract</p> <p>Background</p> <p>The English National Stroke Strategy suggests that there is a need to improve the response of patients and witnesses to the symptoms of acute stroke to increase rapid access to specialist care. We wished to review the evidence base regarding the knowledge, attitudes and behaviours of stroke patients, witnesses and the public to the symptoms of stroke and the need for an urgent response at the onset of symptoms.</p> <p>Methods</p> <p>We conducted a systematic review of UK articles reporting empirical research on a) awareness of and response to the symptoms of acute stroke or TIA, and b) beliefs and attitudes about diagnosis, early treatment and consequences of acute stroke or TIA. Nine electronic databases were searched using a robust search strategy. Citations and abstracts were screened independently by two reviewers. Data were extracted by two researchers independently using agreed criteria.</p> <p>Results</p> <p>11 studies out of 7144 citations met the inclusion criteria. Methods of data collection included: postal survey (n = 2); interview survey (n = 6); review of hospital documentation (n = 2) and qualitative interviews (n = 1). Limited data reveal a good level of knowledge of the two commonest stroke symptoms (unilateral weakness and speech disturbance), and of the need for an emergency response among the general public and at risk patients. Despite this, less than half of patients recognised they had suffered a stroke. Symptom recognition did not reduce time to presentation. For the majority, the first point of contact for medical assistance was a general practitioner.</p> <p>Conclusions</p> <p>There is an assumption that, in the UK, public knowledge of the symptoms of stroke and of the need for an emergency response is lacking, but there is little published research to support this. Public awareness raising campaigns to improve response to the symptoms of stroke therefore may not produce an increase in desired behaviours. Further research is needed to understand why people who experience or witness stroke symptoms frequently do not call emergency services.</p

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomised controlled trials of vasoactive drugs in acute stroke: the Blood pressure in Acute Stroke Collaboration, stage-3 (BASC-3)

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains, particularly for ischaemic stroke. The ‘Blood pressure in Acute Stroke Collaboration’ (BASC) commenced in the mid 1990s focusing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, BASC planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, encompassing both intracerebral haemorrhage and ischaemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on haemodynamic variables. Methods and design Individual patient data from randomised controlled trials of blood pressure management in participants with ischaemic stroke and/or intracerebral haemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 hours), acute (<48 hours) and sub-acute (<168 hours) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in prespecified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, haemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration