June
Issue
18 30
App
Dylan N Wolman
Profile
and Jeremy J Heit
Neuroimaging for EVT
Mayank Goyal
Page 8
Page 12
Page 17
WAKE-UP trial shows that thrombolysis can benefit certain stroke patients with unknown time of onset In patients with unknown symptom onset stroke with magnetic resonance imaging (MRI) pattern of diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch, treatment with alteplase resulted in better functional outcome than placebo. These benefits were consistent across all categories of outcome and major clinical secondary endpoints.
T
he effect size of MRI-guided thrombolysis in unknown symptom onset stroke is comparable to the effect size of thrombolysis <4.5 hours. The study set out to prove efficacy and safety of MRI-based thrombolysis on patients with unknown time of onset. This is common, with around 25% of stroke patients having an unknown time of onset. Patients often wake-up with stroke, making it impossible to say when onset was. As a result of the WAKE-UP trial these patients can now benefit from intravenous thrombolysis. The WAKE-UP trial results were presented at European Stroke Organisation Conference (ESOC; 16–18 May 2018, Gothenburg, Sweden) by lead investigator Götz Thomalla, University Medical Centre, Hamburg, Germany. The European Union–funded study was also published online simultaneously in the New England Journal of Medicine. “This is the first positive trial of IV thrombolysis in stroke with unknown time of onset and will lead to a paradigm change,” Thomalla said. “It will make a big impact on clinical practice as about 25%
of stroke patients have undetermined time of onset, and approximately one third to one half of these will now qualify for the treatment based on these imaging criteria.” To see whether treatment with alteplase would improve functional outcomes in patients with an unknown time of stroke onset and a mismatch between diffusionweighted imaging and fluidattenuated inversion recovery (FLAIR) findings on MRI, the researchers conducted a randomised controlled trial. The patients enrolled had an ischaemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on FLAIR, suggesting that the stroke had occurred within the previous 4.5 hours. Patients who had planned thrombectomies were excluded. For the study, researchers screened 1,362 patients ischaemic stroke of unknown time of onset to identify those with an ischaemic lesion visible on diffusion-weighted MRI but no parenchymal hyperintensity on fluid-
attenuated inversion recovery (FLAIR). Of these patients, 503 had suitable imaging results and were randomly assigned to alteplase or placebo. Most patients had mild to moderate strokes. The primary endpoint was favourable outcome, as defined by a score of 0 or 1 on the mRS, at 90 days. This occurred in 53.3% of the alteplase group and 41.8% of the placebo group (adjusted odds ratio, 1.61; 95% CI, 1.09–2.36; p=0.02). The secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale compared with placebo. The shift analysis also showed benefit with alteplase: the median mRS score at 90 days was one in the alteplase group and two in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 – 2.23; p=0.003). There was a trend toward increased mortality in the alteplase group, with 10 deaths (4.1%) in patients receiving alteplase vs. 3 (1.2%) in the placebo group (odds
ratio, 3.38; 95% CI, 0.92–2.52; p=0.07). In the alteplase group, four deaths were attributed to symptomatic intracranial haemorrhage and one to recurrent ischaemic stroke. The other five deaths were attributed to noncerebral causes unrelated to the initial stroke or treatment. The rate of symptomatic intracranial haemorrhage was 2% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57–42.87; p=0.15). Addressing the risk-benefit ratio, senior author, Christian Gerloff, University Medical Center, Hamburg, pointed out that results from the shift analysis suggested that the benefits of treatment outweighed the harms. “The shift analysis was even more significant than the primary endpoint. This includes all categories, including death—so the mortality data do not weaken the overall benefit,” he commented. The researchers hope that the results of WAKE-UP will have an immediate impact on clinical practice and guidelines of stroke treatment and that MRI-based thrombolysis will become the standard of care.
ReActiv8 results: Neurostimulation safe and effective treatment for chronic low back pain
Following implantation of a restorative neurostimulation system significant improvements were observed in pain, disability and quality of life compared to baseline in patients with chronic refectory low back pain.
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he ReActiv8-A trial was a prospective single arm clinical trial that collected performance and safety data on a new implantable restorative neurostimulation system for patients with chronic refractory low back pain. The results were presented by Vivek Mehta, St Bartholomew’s Hospital, London, UK, at the World Congress of the World Institute of Pain (WIP; 9–12 May 2018, Dublin, Ireland).
Bilateral stimulation of the medial branch of the L2 dorsal ramus elicits episodic contractions of the lumbar multifidus and reactivation of lumbar multifidus motor control and restoration of dynamic stability has been a hypothesised mechanism of action facilitating recovery. The trial enrolled 53 patients (age 44±10 years, pain duration 14±11 years) who were implanted at nine centres in Europe and Aus-
tralia. Selection criteria included disabling chronic refractory low back pain despite 90-days of medical management, no indications for spine surgery and no prior surgery. Patients administered 30 minute stimulation sessions twice daily for a minimum of 90 days. Measures recorded were numerical rating scale (NRS) for pain, Oswestry Disability Index (ODI) for disability, EQ-5D for quality of life and treatment satisfaction.
Utilising matched data, significant improvements (p<0.001) were observed in pain, disability, and quality of life compared to baseline. NRS (6.8±0.2 at baseline) improved 35%±5% at 90-days (n=52), 32%±5% at six months (n=51) and 33%±6% at one year (n=47). The proportion of patients with a clinically important improvement one or more of the numerical rating scale, the Oswestry Disability Index and
EQ-5D were 94%, 86% and 87% respectively. Similarly, 89%, 84% and 81% reported being satisfied or very satisfied with the treatment. There were no unanticipated adverse events and no serious therapy related adverse events. The study concluded that neurostimulation to contract the lumbar multifidus appears to be a safe and effective treatment option for these patients with chronic refractory low back pain.