Issue 22 May 2016

BrainBrain to Is IV t-PA Profile: dead? Jacques Moret Page 6 Page 14 Page 19 Mechanical thrombectomy Paraesthesia treatment: When does the may increase clock run out? attention to Is there a time after symptom onset at which acute ischaemic stroke patients should pain, study finds no longer be eligible for mechanical thrombectomy? This has become one of the most important questions now that the safety and efficacy of mechanical thrombectomy has A study recently published in the journal been established. Neuromodulation has concluded that using spinal cord stimulation devices, ccording to Tudor Jovin We are all after penumbral salvage, that it is the collaterals that paraesthesia are not necessary for pain (University of Pittsburgh but we need to understand that this determine this rate of growth. relief and may actually increase attention ASchool of Medicine, Pitts- is a time dependent process, and “It was worked out after IMS III to pain. burgh, USA) we should be asking with time, the core grows and the by Khatri et al, that every 30 minute the question, “Should there be a penumbra shrinks until the entire delay in reperfusion is associated ntil recently, Medicine, Cleveland, time window at all? And should we territory that is supplied by the with a 10% relative reduction in paraesthesia USA) and others even be concerned about time in occluded vessel has infarcted and at probability of good clinical outcome Uand spinal cord sought to evaluate the acute stroke interventions?” Jovin that point, any attempts to recanalise (mRS 0–2). If we look at the modern stimulation have come relative effectiveness weighed in on the subject at the the vessel are futile or even endovascular trials, we need to revise hand-in-hand. That was of conventional, International Stroke Conference detrimental,” Jovin explained. the Khatri curve. I think we are until the development subthreshold high- (ISC; 17–19 February, Los Angeles, What is perhaps less well dealing perhaps with different patient of paraesthesia-free density, and sham USA). His main point was that there understood, according to Jovin, is populations in the most recent trials. spinal cord stimulation stimulation on pain are two types of stroke patients to that this process occurs at different In MR CLEAN there is still a curve using high-density intensity and quality consider—“fast progressors” and speeds in different individuals. and it is significant, but it is only parameters. The study of life. “slow progressors”—and there is This was illustrated with data from 5% relative reduction in probability investigators, Jennifer To conduct the study, a need for fast workflows and fast DEFUSE 2 (a study that required of good clinical outcome. Why is Sweet (University Sweet et al screened 15 recanalisation overall. an MRI scan prior to endovascular that? Perhaps in MR CLEAN even Hospitals Case patients with response to He pointed out that recent trials therapy) where there was a range though there were no requirements Medical Center, Case conventional stimulation have shown that the purpose of of patients who had similar infarct for eliminating patients with large Western Reserve (60Hz/350μsec) with a intervention is to prevent infarct growth and widely different time infarcts, based on the fact that median University School of Continued on page 19 growth and to end up with a small points—“fast progressors” and ASPECTS score was 9, maybe MR infarct at the end of the procedure “slow progressors”. He explained CLEAN enrolled patients who had because there is a very strong better collaterals than IMS III,” he correlation between infarct volume said. Similarly, in REVASCAT, the and good clinical outcomes. It was “Should there be Khatri curve mirrors that seen in MR shown in IMS III and replicated in a time window CLEAN—5% reduction for every SWIFT PRIME that patients with 30-minute delay. small infarcts have a much higher at all? And ESCAPE, Jovin went on, required chance of doing well than those should we even inclusion only of patients who had patients with small infarcts. good collaterals, and the Khatri “We know that when a vessel is be concerned curve in ESCAPE patients is almost occluded we are dealing with two about time in flat, indicating that every 30-minute compartments: core and penumbra delay in reperfusion is associated (core being dead brain and acute stroke with a 0.5% relative reduction in penumbra tissue that is functionally interventions?” probability of good clinical outcome. impaired but structurally intact). Continued on page 2

neuronewsinternational.com facebook.com/neuronews @NN_publishing NN App 2 Acute ischaemic stroke May 2016 Mechanical thrombectomy treatment: When does the clock run out?

Continued from page 1 very attenuated or not detectable, whereas as selection criteria. Mismatch on diffusion Jovin reported a deeper analysis of the if we take a less strictly selected segment and perfusion is the same as the DEFUSE REVASCAT data, detailing all patients that of the acute stroke population such as those definition—core ˂70mL, mismatch ratio were subjected to endovascular therapy, enrolled in IMS III and (to a lesser extent) >1.8 and mismatch volume ≥15cc. not only the ones who reperfused. He said MR CLEAN and REVASCAT we are going Concluding, Jovin stated, “Time that it was found that from symptom onset to deal with a higher percentage of ‘fast dependency of favourable outcomes in to reperfusion there was a 26% reduction progressors’ and that is where we are going patients with large vessel occlusion in the in probability of good outcome with every to encounter a steep curve,” Jovin said. anterior circulation is most pronounced 30-minute delay. But from symptom onset As for what happens if these patients in those with poor collaterals—that does to imaging, there is no association with time; are treated, Jovin explained that data not mean that in patients who are ‘slow the curve is in fact driven by the imaging from DEFUSE 2 suggest that if there is progressors’ (those with good collaterals) to reperfusion interval. When it comes to mismatch and good collaterals, whether we have a justification to take our time. patients who had poor collaterals, ie. those a patient is treated beyond six hours or We need to have fast workflows and with low ASPECTS scores, there is a very within six hours what really counts is fast recanalisation even in the ‘slow steep curve—that is where there is a strong whether they reperfuse, and not the time progressors’ because there could be other relationship between time to reperfusion and window at which they are treated. benefits that current outcome measures good outcome. On the other hand, in patients “What does this mean? Should we treat are too insensitive to detect when who have good ASPECTS scores, ie. good patients with large vessel occlusions and we open up vessels very fast in these collaterals, this association does not exist. mismatch beyond six hours without any Tudor Jovin ‘slow progressors’. A non-insignificant He added that in DEFUSE 2, which enrolled time limit in routine clinical practice? proportion of patient with large vessel patients with good collaterals evidenced Not necessarily. Do we need any other To answer these questions, there are now occlusion stroke in the anterior circulation by a median baseline infarct volume of proof? Yes, we do need proof because the two large randomised trials ongoing— (estimated at about 20–30%) presenting 16cc, the Khatri curve is actually in the problem is that we have absolutely no idea DAWN and DEFUSE 3. DAWN is a single in the beyond six-hour time window have opposite direction and there is absolutely no what the behaviour is of the patients who device trial (Trevo embolectomy device) substantial mismatch (‘slow progressors’). association between time to symptom onset have mismatch and good collaterals but do sponsored by Stryker Neurovascular, Contrary to popular belief, it has been and good outcome. not get treated with endovascular therapy. with a time window of six to 24 hours, shown that whether they are wake-up or “How do I make sense of all these data? Because they have good collaterals it enrolling patients with proximal anterior witnessed onset does not make a difference I think we are looking at different patient may be that their stroke will never grow circulation occlusions (M1, ICA T), with a in terms of their response to endovascular populations here. In ESCAPE and in and therefore they may do well without core and clinical mismatch type selection therapy. In this patient population, DEFUSE 2 we are looking at an enriched intervention. The challenge is to figure out paradigm where age is also a factor. Nearly endovascular treatment appears to be patient population with respect to good who are those people with good collaterals 100 patients have been enrolled to date feasible and safe, but because we do not collateral status, we are looking at ‘slow who are going to experience growth of in this world-wide trial. DEFUSE 3 is an know anything about the natural history of progressors’, that is why this curve is much core with persistent vessel occlusion and NIH-funded, prospective, randomised, these ‘slow progressor’ patients we need flatter or the association between time of devise strategies for the treatment of those multicentre, adaptive blinded endpoint trial to complete a randomised trial to establish stroke onset to reperfusion and outcome is patients,” he maintained. that uses diffusion and perfusion mismatch the clinical efficacy of this approach”. Data support “careful” use of mechanical thrombectomy in non-top tier evidence criteria ELVO patients Investigators have found that with strict adherence to top tier evidence criteria, half and discharge NIHSS scores); sICH, defined as per of ischaemic stroke patients with emergent large vessel occlusion (ELVO) may not be the SITS-MOST definition; serious haemorrhage considered for mechanical thrombectomy even though according to their data, there is (defined as life-threatening systemic haemorrhage no increased risk of symptomatic intracerebral haemorrhage (sICH) and higher mortality requiring transfusion); time from groin puncture is largely linked to occlusions in the basilar artery and patients treated at an extended to recanalisation; post-recanalisation TICI grade; time window. endovascular procedural complications; and 90-day mortality and mRS score.” ohini Bhole (Stroke Team, Methodist from the American Heart Association/American A total of 126 ELVO patients treated with University Hospital, University of Stroke Association). mechanical thrombectomy were included in the RTennessee Health Science Center, Memphis, The authors conducted a retrospective analysis. Of them, 64 patients fulfilled top tier Tennessee, USA) and others state in the Journal of observational study of consecutive acute ischaemic evidence criteria (mean age 64±15 years; 47% NeuroInterventional Surgery that this study comes stroke patients registered in their centre’s database men; median pretreatment NIHSS score 16 (IQR in response to the recent guidelines for endovascular that were treated with mechanical thrombectomy 14–18)), and 62 patients did not meet top tier management of ELVO which award top tier evidence between January 2012 and June 2015. All cases evidence criteria (mean age 62±13 years; 52% men; to the selective criteria that was implemented in were coded as either meeting or not meeting top median pretreatment NIHSS score 14 (IQR 7–18)). the five positive trials (MR CLEAN, EXTEND-IA, tier evidence recommendations based on their The authors state: “Charateristics not meeting top ESCAPE, SWIFT PRIME, REVASCAT) in favour of conformance to the following criteria presented tier evidence for mechanical thrombectomy in the mechanical thrombectomy for the treatment of acute in the new guidelines: pre-stroke modified Rankin comparision group included six (10%) patients with ischaemic stroke. Scale (mRS) score 0–1; acute ischaemic stroke with a pretreatment NIHSS score of ˂6, 4 (6.5%) patients The study’s aim then, was to understand how receipt of IV t-PA within 4.5 hours of symptom onset; with an ASPECT score ˂6, 17 (27%) patients with guideline adherence would have impacted treatment causative occlusion of the internal carotid artery of a premorbid mRS score ≥2, 6 (10%) patients with numbers and outcomes in a cohort of patients from proximal (M1) middle cerebral artery (MCA); age M2 occlusions, 20 (32%) patients with posterior a comprehensive stroke centre. The investigators 18 years or older; National Institute of Health Stroke circulation occlusions, and 36 (58%) patients with compared disability and functional outcomes in Scale (NIHSS) score of ≥6; Alberta Stroke Program symptom to groin puncture time >6 hours. Twenty- patients that underwent mechanical thrombectomy Early CT (ASPECT) score of ≥6 and; treatment that six (42%) patients had two or more characteristics at one comprehensive stroke centre, according can be initiated (groin puncture) within six hours of removing them from the top tier evidence group.” to whether these patients met the top tier criteria symptom onset. They report that IV t-PA was given to 92% of for endovascular treatment set forth in the new Further, “Prospectively collected outcome patients in the top tier group, versus 40% (p˂0.001) guidelines (2015 AHA/ASA focused update of the and process data were used in this retrospective in the non-top tier group, primarily due to late arrival 2013 guidelines for the early management of patients cohort study as the following dependent variables: after symptom onset. Similarly, patients in the top tier with acute ischaemic stroke regarding endovascular neurological improvement during hospitalisation group had shorter symptom onset to groin puncture treatment: a guideline for healthcare professionals (defined as the difference between pretreatment Continued on page 13

4 Research May 2016 There is a “place” for MR imaging in acute stroke Magnetic resonance (MR) imaging may have advantages over other imaging modalities The reason is you are using cerebral blood volume in later time windows when it comes to selecting patients for endovascular treatment or cerebral blood flow to determine your core on CT of acute ischaemic stroke. That is according to Gregory Albers (Stanford University perfusion; your core is going to give you an answer for Medical Center, Stanford, USA). He made this assessment during a presentation at the what the cerebral blood volume or the cerebral blood International Stroke Conference (ISC; 17–19 February, Los Angeles, USA). flow is at the moment of your scan, it gives you no history. So if you had critical ischaemia a couple hours aking the case for MR imaging over computed ago, you will not see it—after reperfusion the cerebral tomography (CT), Albers explained that in blood flow is normal, after reperfusion the cerebral Mthe SWIFT PRIME trial, patients could be blood volume is normal, maybe even elevated, so we are selected using either MR imaging or CT. While the still at the advantage with diffusion weighted imaging in majority of patients were selected using CT, of the that situation,” Albers argued. patients selected using MR imaging in SWIFT PRIME, At his own centre in Stanford, the acute stroke 63% had a good outcome in the endovascular arm imaging protocol is rapid MR imaging for acute stroke selected by MR, and 33% in the control group, with a transfers. If they are told that the patient is coming, the 30% difference. MR technician is pre-notified, the MR is then open by Further, Albers reported, in the Rankin shift the time the patient arrives, and they are taken straight primary analysis of SWIFT PRIME, in the MR down to the MR, and with the six minute MR protocol, selected subgroup (34 patients) the control group had seven minutes after the patient gets onto the scanner, the mRS (modified Rankin Scale) 4 at 90 days, and the team gets the results. thrombectomy group had mRS of 2 (p=0.022). Infarct “But I must admit that we do not do that when they volume at 27 hours was 61ml in the control group and roll into the emergency room because if we have very 24ml in the thrombectomy group (p=0.052). There was little pre-notification, even at Stanford, we cannot get an no difference in CT perfusion versus MR group in age, instant MRI scan. We can get a CT much faster, so our NIHSS (National Institutes of Health Stroke Scale), or CT/CTA/CT perfusion rapid processing is two minutes,” door to randomisation time (median 67 min vs. 68.5 Albers conceded. min). The door to randomisation was only 90 seconds Another possible advantage for MR, he added, is the longer in these patients. late time window. He explained that this can be attributed to the fact that “Time is brain, that is our mantra, and what it says many of these patients were “drip and ship” or transfer is that when you reperfuse a patient at eight hours, patients—therefore, the hospitals were aware of them the good outcome rate is not terrific. In the recent and were able to have the MR ready upon their arrival. studies 30% of the patients had a good outcome if the “Why choose MR imaging over CT? Diffusion reperfusion occurred at eight hours. Think about this, weighted imaging is the gold standard for estimating what if we had a way to identify that 30% and that was ischaemic core, it may have some greater advantages Gregory Albers the only 30% that you took to your cath lab, what would in later time windows: it always gives you full brain your good outcome rate be at eight hours? It would be coverage and it detects smaller lesions. So if your In the recently initiated DEFUSE 3 (a prospective, pretty good,” Albers pointed out. patient comes in and their hemiplegia is because of a randomised, multicentre trial of patients with an acute As for the way forward, Albers maintained that, medial medullary infarct, which technique is going to ischaemic stroke who can be treated between six and 16 at least in the later time window, there is a need for show you that? Not the CT,” Albers maintained. hours of stroke onset) he explained, there is a six minute sophisticated imaging. The following trials are currently The caveat however, Albers said, is that MR imaging MR imaging protocol with 45 seconds of automated using a combination of CT perfusion and/or MR should not delay acute stroke therapy. He acknowledged processing, “so if you have scanner availability, you perfusion and will help to determine if endovascular that this is likely the reason most stroke teams do not should be able to get those images quickly”. therapy improves functional outcome in stroke patients use it because it would delay acute stroke therapies, but “CT perfusion has some limitations for core. If with favourable clinical and imaging characteristics: reiterated that if the hospital is prepared for the patient you had bad ischaemia a few hours ago and now it is DEFUSE 3 (6–16 hours), DAWN (6–24 hours), and has a system that can do the MR, the MR can be resolved, you will not see the core on CT perfusion, POSITIVE (6–12 hours), EXTEND (4.5–9 hours) and done very quickly. but you will see it on diffusion weighted imaging. ECASS 4 (4.5–9 hours) is using MR only.

Novel combination technique prevents distal embolisation during thrombectomy In a study evaluating the safety and feasibility of a combination of proximal internal aspiration and balloon occlusion of the proximal internal carotid artery occlusion using a balloon catheter and distal aspiration through an carotid artery. After the thrombectomy the balloon was intermediate catheter in stroke patients treated with mechanical thrombectomy with deflated and angiographic runs were performed to control a stent retriever, the investigators report that there was no macroscopic thrombus flow restoration. In cases of persistent occlusion the migration to a new vascular territory. procedure was repeated. Stampfl et al report: “In all patients the ini- he study, carried out by Sibylle Stampfl (Depart- loon guide catheter was placed within the proxi- tial TICI was 0. A TICI score of ≥2b was ment of Neuroradiology, University Hospital mal internal carotid artery of the affected side. achieved in 96.8%. No new thrombo- THeidelberg, Heidelberg, Germany) and colleagues, After angiographic visualisation of the thrombus, the embolic complications occurred. The included patients with an occlusion in the anterior circula- intermediate catheter was advanced through the Cello median NIH Stroke Scale score was 19 tion who were treated with thrombectomy using a balloon catheter and navigated as close to the thrombus as at admission and 4.5 at discharge. After catheter for proximal flow arrest, and an intermediate possible. The thrombus was then passed with the mi- three months 51.6% of the patients had a catheter for distal aspiration. Pre- and post-interventional crowire/microcatheter. The microwire was removed favourable clinical outcome (modified Rankin thrombolysis in cerebral infarction (TICI) scores were and a stent retriever was deployed by Scale score 0–2) and 19.3% had died. assessed. Clinical presentation at admission and discharge withdrawing the microcatheter. “In our study of 31 patients the combination and after three months was evaluated and complications Subsequently, the Cello of proximal internal carotid artery occlusion via were recorded. balloon was inflated using a balloon catheter and distal aspiration through the The devices used were an 8F Cello balloon catheter a 2.5ml syringe filled with SOFIA intermediate catheter was a safe and efficient complement (Covidien/Medtronic) and a SOFIA catheter (Soft torque- a mixture of contrast me- to mechanical thrombectomy with stent retrievers. The able catheter optimised for intracranial access; Micro- dium and normal saline. procedure was technically successful in a large number vention). The stent retrievers used were the Solitaire Prior to thrombectomy, as- of cases. No macroscopic thrombus migration into a new (Medtronic) and Trevo (Stryker Neurovascular). piration was applied through vascular territory occurred,” the authors conclude. They The study authors retrospectively identified 31 patients the intermediate catheter go on to caution, however, that “the rate of favourable from their prospectively collected stroke database who lumen using a 20mL or 60mL outcome after three months was not higher than 50%.” met the inclusion criteria. The procedure was carried out syringe. Thrombectomy was then The study was published in the Journal of as follows: Using transfemoral access, the 8F Cello bal- performed under continuous distal NeuroInterventional Surgery (JNIS).

6 Debate May 2016

BrainBrain IV thrombolysis to in acute stroke treatment is dead

It has now been universally accepted that mechincal thrombectomy for the treatment of patients with acute ischaemic stroke with large vessel occlusions is the future. But what does that mean for long-time gold standard treatment of intravenous (IV) thrombolysis? In this Brain to Brain debate, Keith W Muir and Urs Fischer weigh in on whether stroke patients should still be receiving IV thrombolysis at all. Is IV thrombolysis dead? Far from it Keith W Muir endovascular treatment in SYNTHESIS question that a clinician ought to consider significant proportion of patients, and can were not different compared to IV throm- is whether the totality of evidence truly even be brought to geographically remote ndovascular mechanical thrombec- bolysis alone, and a probable reason for indicates a different risk:benefit balance areas with telemedicine. tomy is an important advance for this lies in the additional delay incurred in that individual compared with those In conclusion, IV thrombolysis is an Ethose patients with large artery in starting endovascular procedures. who fall within licence. In a great many effective treatment that should be initi- occlusive, anterior circulation stroke, Devices and team organisation have ated in all eligible patients as rapidly but all that we know about this treat- improved since SYNTHESIS but “better” as possible, irrespective of whether ment modality is built on a foundation of recanalisation may yet fail if it is not also subsequent eligibility for additional highly efficient provision of intravenous “faster”. endovascular treatment is determined. thrombolysis—this applies equally to the Contrary to a frequently repeated claim Endovascular treatment in IV thrombol- 90% of participants in recent endovascular that “IV thrombolysis does not work” for ysis-ineligible patients appears to be a trials who had received IV thrombolytic some categories of patient, recent trials reasonable option based on a very limited drugs as part of standard care, but also report higher rates of recanalisation with amount of data, but grounds for ineligi- to the 10% of trial participants who were IV therapy alone, even for large vessel bility need to be considered carefully, and considered ineligible for IV thrombolysis, and high clot burdens,4 than were docu- future evolution of IV thrombolytic treat- since these patients benefitted from the mented in older studies. In EXTEND-IA, ments may well modify the risk:benefit same streamlined assessment process for 11% of eligible patients had already balance. Is IV thrombolysis dead? Far selection. Median stroke onset to start of largely recanalised prior to angiography.5 from it: it is the basis for providing endo- IV thrombolysis times in the recent trials The same proportion in SWIFT PRIME vascular care for the small proportion of were superior to all previously published either could not have endovascular patients who require it, and ongoing trials data on routine thrombolytic treatment (as treatment (because of vascular access are likely to reinvigorate it. short as 85 minutes in the MR CLEAN issues or imaging misinterpretation) or References trial,1 and overall median 100 minutes no longer needed it because recanalisa- 1. Berkhemer OA, Fransen PS, Beumer D, et al. A Rand- 2 6 omized Trial of Intraarterial Treatment for Acute Ischemic across all five published trials ). tion had occurred. Intention to treat Stroke. The New England Journal of Medicine 2015; 372(1): In order to justify omission of an with endovascular approaches neither 11–20. 2. Goyal M, Menon BK, van Zwam WH, et al. Endovascular established and effective treatment—IV guarantees that this is feasible, or neces- thrombectomy after large-vessel ischaemic stroke: a meta- thrombolysis—very robust evidence sary. The rapidly declining benefit of IV Keith W Muir analysis of individual patient data from five randomised trials. Lancet 2016. should be demanded. This presently is thrombolysis over the first hours7 does 3. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. The New England Journal not available. not concur with the time scale for loss of cases there is no evidence of greater risk of Medicine 2013; 368(10): 904–13. While individual patient data meta- viable tissue on imaging,8 and therefore or lower benefit, and IV thrombolysis 4. Demchuk AM, Goyal M, Yeatts SD, et al. Recanalization and clinical outcome of occlusion sites at baseline CT angiography analysis of the five trials included in the may reflect modification of clot charac- should be considered. Trials investigating in the Interventional Management of Stroke III trial. Radiology HERMES collaboration, including the teristics that make successful lysis less alternative doses of alteplase, alternative 2014; 273(1): 202–10. 5. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular 188 patients deemed ineligible for IV likely. Earlier delivery of IV therapy al- thrombolytic agents, and combination therapy for ischemic stroke with perfusion-imaging selec- thrombolysis, yields a point estimate for ters the landscape for IV therapy as well therapies, all promise to alter the land- tion. The New England Journal of Medicine 2015; 372(11): 1009–18. effect very similar to those who received as for endovascular treatment, and it is scape for IV therapy in the near future, 6. Saver JL, Goyal M, Bonafe A, et al. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke. IV alteplase, the small sample means wrong to assume that figures from studies with the prospect of safer and more effec- The New England Journal of Medicine 2015. that confidence intervals are wide and conducted many years ago reflect today’s tive IV therapy.11 7. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous encompass the possibility that the true reality as door to needle times shorten. Finally, and perhaps most importantly, thrombolysis with alteplase for acute ischaemic stroke: a effect may differ.2 Randomised trial IV therapy itself does not stand still, but endovascular treatment is currently inap- meta-analysis of individual patient data from randomised trials. Lancet 2014; 384(9958): 1929–35. data that are now unfashionable—the continues to evolve. Data already indicate propriate, inaccessible or unavailable 8. Cheripelli BK, Huang X, McVerry F, Muir KW. What is the re- SYNTHESIS expansion trial3—indicate both safety and efficacy of IV alteplase in for most stroke patients even in those lationship among penumbra volume, collaterals, and time since onset in the first 6 h after acute ischemic stroke? International that bypassing the established IV throm- many of the patient groups excluded from high-income countries where pockets of Journal of Stroke 2016; 11(3): 338–46. 9. Meretoja A, Putaala J, Tatlisumak T, et al. Off-label throm- bolysis pathway in favour of a “more ef- clinical trials and thus the current alteplase expertise exist—worldwide it represents bolysis is not associated with poor outcome in patients with fective” endovascular approach may not licence.9,10 When faced with a patient who a tiny fraction of activity. IV throm- stroke. Stroke 2010; 41(7): 1450–8. 10. Frank B, Grotta JC, Alexandrov AV, et al. Thrombolysis in be in the patient’s interest: outcomes of falls out of the licence criteria, the first bolysis can, in contrast, be delivered to a stroke despite contraindications or warnings? Stroke 2013; 44(3): 727–33. 11. Ramani L, Huang X, Cheripelli B, Muir KW. Intravenous thrombolysis for acute stroke: current standards and future Is IV thrombolysis dead? Far from it: it is the basis for directions. Current Treatment Options in Cardiovascular providing endovascular care for the small proportion of Medicine 2015; 17(4): 373. Keith W Muir is SINAPSE professor of patients who require it, and ongoing trials are likely to Clinical Imaging & consultant neurolo- gist at the Institute of Neuroscience & reinvigorate it. Psychology, University of Glasgow, – Keith W Muir Queen Elizabeth University Hospital, Glasgow, UK May 2016 Debate 7 Acute endovascular stroke treatment: “To bridge or not to bridge, that is the question!” IV treatment before mechanical thrombectomy is of no benefit Urs Fischer the middle cerebral artery (MCA). transfer to a comprehensive stroke centre „„ IV rt-PA may facilitate embolectomy and for embolectomy.9 The unanswered question may result in fewer stent retriever passes.9 „„ IV rt-PA causes some rare side effects such In 1996 the US Food and Drug Administra- „„ IV rt-PA may help to recanalise thrombi in as life-threatening orolingual angioedema.8 tion approved intravenous thrombolysis with small vessels and in the microvascular struc- recombinant tissue plasminogen activator ture, inaccessible for endovascular devices.8 Current evidence (IV rt-PA) for treatment of acute ischaemic On the other hand, rt-PA has several impor- Several studies compared IV rt-PA eligible stroke based on the results of the National tant limitations:9 patients treated with mechanical thrombec- Institute of Neurological Disorders and „„ IV rt-PA may increase the risk of intrac- tomy with IV rt-PA ineligible patients: The Stroke (NINDS) trial.1 In the meantime, IV erebral haemorrhage (ICH) and any other proportion of functionally independent rt-PA has become the “holy grail” of acute bleeding complications.8 Kidwell et al patients at 90 days were similar across stud- stroke treatment and is currently the standard found that intravenous or intra-arterial ies ranging 48–68% in the IV rt-PA plus me- treatment of care for all eligible stroke rt-PA resulted in a greater breakdown of chanical thrombectomy group and 42–59% patients presenting within 4.5 hours after the blood-brain barrier compared with in the mechanical thrombectomy alone symptom onset. embolectomy or no treatment. group.12,13,14,15 These data were confirmed in Urs Fischer However, the field of intravenous throm- „„ IV rt-PA is ineffective in the majority of the above-mentioned meta-analysis of indi- bolysis has been stagnant for the last 20 patients with large thrombi and in patients vidual patient data from the five randomised questions in acute stroke treatment 400 years years. The major breakthrough in modern with large vessel occlusions. trials.7 However, in all these studies patients after the death of William Shakespeare is: “To stroke treatment came in 2015, when five „„IV rt-PA may result in migration of thrombi treated with mechanical thrombectomy bridge or not to bridge. That is the question!” randomised controlled trials consistently from proximal into distal vessels, where alone had contraindications for IV rt-PA, Acknowledgments showed that endovascular clot retrieval in thrombectomy is no longer possible. which makes a direct comparison of these Prof. Dr. Jeffrey L. Saver, UCLA Comprehensive Stroke Center, Los Angeles, USA addition to best medical treatment (± IV „„ Immediate administration of antiplatelet different patient groups difficult. Prof. Vitor Mendes Pereira, Department of Surgery Toronto rt-PA) improves outcome in acute anterior agents and heparin are contraindicated for Only recently, two studies compared Western Hospital, Toronto, Canada Prof. Jan Gralla, Department of Diagnostic and Interventional circulation stroke patients with proximal 24 hours after IV rt-PA, but potentially clinical and radiological outcomes of pa- Neuroradiology, Bern, Switzerland vessel occlusion.2,3,4,5,6 Interestingly enough, beneficial after endovascular intervention tients treated with IV rt-PA in combination References a meta-analysis of individual patient data and clearly indicated when stents have to be with mechanical thrombectomy to IV rt- 1. Tissue plasminogen activator for acute ischemic stroke: the Na- 8 tional Institute of Neurological Disorders and Stroke rt-PA Stroke from these five randomised trials did not placed during the endovascular procedure. PA eligible patients treated with mechani- Study Group. N Engl J Med. 1995;333(24):1581–7. show any difference in outcome in patients „„ The therapeutic window for IV rt-PA is cal thrombectomy alone directly referred 2. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, 8,16 Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treat- who received alteplase and those who were narrow with a rapidly increasing number to comprehensive stroke centres. In ment for acute ischemic stroke. N Engl J Med. 2015;372:11–20. ineligible for IV rt-PA. needed to treat.8 both studies, outcome in patients treated 3. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-Retriever Thrombectomy after Intravenous t-PA vs. Whether treatment with IV rt-PA prior to „„ IV rt-PA has a considerable impact on with bridging thrombolysis and those with t-PA Alone in Stroke. N Engl J Med. 2015;372:2285–95. 4. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, mechanical thrombectomy is of any benefit healthcare costs: IV rt-PA, which is mechanical thrombectomy alone did not Thornton J, et al. Randomized assessment of rapid endovascular has currently become an important unan- eventually not beneficial in these patients differ, but rates of haemorrhages tended treatment of ischemic stroke. N Engl J Med. 2015;372:1019–30. 5. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov swered question in acute stroke treatment. would unnecessarily increase the cost of to be higher in bridging patients than in L, Yassi N, et al. Endovascular therapy for ischemic stroke with treatment in patients presenting with prox- those, treated with mechanical thrombec- perfusion-imaging selection. N Engl J Med. 2015;372:1009–18. 6. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Ro- Pros and cons of bridging imal vessel occlusion, if stent retriever tomy alone. vira A, et al. Thrombectomy within 8 Hours after Symptom Onset thrombectomy alone is equally effective in Ischemic Stroke. N Engl J Med. 2015;372:2296–306. therapy 7.Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, There are several arguments for and against as IV rt-PA followed by stent retriever Relevance Demchuk AM, Dávalos A, Majoie CB, van der Lugt A, de Miquel 9 MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van administering IV rt-PA in acute stroke thrombectomy. Critics argue that the proportion of patients den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, patients with a proximal vessel occlusion in „„ Many patients with severe strokes and treated with endovascular treatment is only Millán M, Davis SM, Roy D, Thornton J, Román LS, Ribó M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge the anterior circulation: large vessel occlusions have absolute or relevant for a small minority of patients in RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. „„IV rt-PA can be started earlier than me- relative contraindications for IV rt-PA (ie. advanced healthcare systems, and therefore Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised chanical thrombectomy and may produce wake-up strokes, borderline coagulation the question whether patients should be trials. Lancet. 2016 Feb 18. pii: S0140-6736(16)00163-X recanalisation and reperfusion, avoiding status, high blood pressure and glucose treated with IV rt-PA is irrelevant.17 How- 8. Broeg-Morvay A, Mordasini P, Bernasconi C, Bühlmann M, Pult F, Arnold M, Schroth G, Jung S, Mattle HP, Gralla J, Fischer U. 9 the need for embolectomy. However, in levels, etc.) putting them at an increased ever, recent positive trials have boosted the Direct Mechanical Intervention Versus Combined Intravenous and 8 Mechanical Intervention in Large Artery Anterior Circulation Stroke: the recent landmark trials, reperfusion risk of ICH. proportion of patients treated with thrombec- A Matched-Pairs Analysis. Stroke. 2016 Apr;47(4):1037–44 prior to embolectomy occurred in only „„ IV rt-PA prior to endovascular clot retriev- tomies in many countries. In well-estab- 9. Chandra RV, Leslie-Mazwi TM, Mehta BP, et al. Does the use of IV tPA in the current era of rapid and predictable recanalization 5–10% of patients. Reperfusion rates al might even delay endovascular therapy, lished comprehensive stroke centres with a by mechanical embolectomy represent good value? J. Neuroint- depend on the site of vessel occlusion especially in centres where patients can be large network of stroke units, up to 20% of erv. Surg. Jan 12 2016. 10. Kidwell CS, Latour L, Saver JL, et al. Thrombolytic toxicity: with very low rates in internal carotid quickly moved to the endovascular suite. stroke patients referred to a comprehensive blood brain barrier disruption in human ischemic stroke. Cerebro- artery (ICA) occlusions and with higher „„ Initial triage to a primary stroke centre stroke centre are currently treated with me- vasc Dis 2008;25:338–43. 11. Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele rates in occlusions in the M2 segment of for administration of IV rtPA may delay chanical thrombectomy (unpublished data R, Deuschl G, Jansen O. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke from the Bernese stroke registry). depends on thrombus length. Stroke. 2011;42:1775–7. 12. Davalos A, Pereira VM, Chapot R, et al. Retrospective multi- center study of Solitaire FR for revascularization in the treatment Outlook of acute ischemic stroke. Stroke. Oct 2012;43(10):2699–2705. IV rt-PA will remain the standard of care 13. Pereira VM, Gralla J, Davalos A, et al. Prospective, multi- center, single-arm study of mechanical thrombectomy using for all patients presenting within 4.5 hours Solitaire Flow Restoration in acute ischemic stroke. Stroke. Oct after symptom onset with peripheral vessel 2013;44(10):2802–7. 14. Leker RR, Pikis S, Gomori JM, Cohen JE. Is Bridging Neces- occlusion. However, current evidence sary? A Pilot Study of Bridging versus Primary Stentriever-Based Endovascular Reperfusion in Large Anterior Circulation Strokes. J. suggests that direct mechanical interven- Stroke Cerebrovasc. Dis. Jun 2015;24(6):1163–7. tion may be equally effective compared 15. Guedin P, Larcher A, Decroix JP, et al. Prior IV Thrombolysis Facilitates Mechanical Thrombectomy in Acute Ischemic Stroke. to bridging thrombolysis in patients with J. Stroke Cerebrovasc. Dis. May 2015;24(5):952–7. large anterior circulation stroke and there is 16. Weber R, Nordmeyer H, Hadisurya J, et al. Comparison of outcome and interventional complication rate in patients with acute equipoise that calls for a randomised trial. stroke treated with mechanical thrombectomy with and without A randomised trial comparing mechanical bridging thrombolysis. J. Neurointerv. Surg. Feb 22 2016. 17. Muir K. No space left for intravenous thrombolysis in acute thrombectomy alone with bridging therapy stroke: CONS. Intern Emerg Med. 2016 Apr 15 in patients directly referred to a compre- TICI: Thrombolysis in cerebral infarction; sICH: symptomatic intracerebral hemorrhage; aICH: asymptomatic intracerebral hensive stroke centre, where immediate Urs Fischer is professor for Acute Neurol- hemorrhage; Any ICH: sICH plus aICH; mRS: modified Rankin scale reperfusion is possible could solve this ogy and Stroke and co-director of the Table 1 Outcome in bridging patients (mechanical thrombectomy and IV rt-PA) versus question and is currently planned. Clinical Trial Unit at the University of patients with mechanical thrombectomy alone without contraindications for IV rt-PA. Therefore, one of the relevant unanswered Bern, Switzerland 8 Stroke treatment May 2016 Inside the NIH StrokeNet The National Institutes of Health (NIH) StrokeNet, which was tals with the central IRB at the Univer- Regional Center to decide whether this is initiated in 2013, currently involves 288 hospitals across the sity of Cincinnati, and the development possible. Hospitals can also participate in United States and is designed to serve as the infrastructure and and submission of new trials. The NIH future NIH Stroke Trials even if they are pipeline for new potential treatments for patients with stroke and StrokeNet centres currently participate in not part of the network, if there is a need those at risk of stroke, according to the User’s Guide published the CREST 2, MISTIE III, iDEF Trial, for centres beyond the NIH StrokeNet and in the journal Stroke. POINT, Rhapsody, and SHINE trials as they can demonstrate the ability to recruit well as other NIH funded stroke trials. Two into a specific type of clinical trial. euroNews now speaks to Joseph trials which have come directly from the Broderick (Department of Neurol- NIH StrokeNet investigators include the Can you explain the educa- N ogy and Rehabilitation Medicine, TeleRehab Trial (just started this autumn) tion platform provided by University of Cincinnati Neuroscience Insti- and DEFUSE 3 which is just starting. A StrokeNet? What are its tute, Cincinnati, USA), principal investigator large number of trials have been submitted benefits? of the National Coordinating Center for the for review or will be submitted for review The platform provides a year of support NIH StrokeNet, about the ins and outs of the by June 2016. for trainees to learn about stroke research. network and its progress thus far. These trainees (including neurologists, as What are the subgroups well as physicians from other specialties, Why was the NIH StrokeNet within the NIH StrokeNet and pharmacists and physical therapists among established? what roles do they play? others) have access to an extensive series The NIH StrokeNet was established There are three working groups (Acute of scientific and professional educational primarily to facilitate Phase II and Phase Treatment, Prevention, and Recovery/ presentations, the opportunity to present III Trials of acute stroke treatment, stroke rehabilitation) who help investigators as- their research at national meetings, local prevention, and recovery after stroke. Joseph Broderick sess their trial design and feasibility. Some and national mentorship for trainees, and Having an infrastructure already in place of the proposed trials have sprung out of interaction with their peers and stroke substantially decreases the time for new tion Hospitals as well as Children’s Hospi- these working groups. There are two major leadership across the USA. stroke trials to get started and the infra- tals. The National Coordinating Center is Cores: the Educational Core and the Imag- structure can be immediately focused on based at the University of Cincinnati and ing Core. The latter Core plays a major Are there any plans to link other trials when a trial is completed or the National Data Management Center is role in assessing the imaging components this network with national stopped early. A second goal of the NIH based at the Medical University of South of proposed trials. There are also advisory stroke networks in other StrokeNet is to train the next generation of Carolina. The NIH StrokeNet represents a groups (Minority Recruitment, Endovas- countries? If so, what would clinical researchers in stroke with at least close collaboration with the NINDS who cular, Paediatric) who provide input as the implications of that be? one new fellow at every of the 25 regional provide significant input and oversight to needed on proposed trials. Yes. Our leadership has been meeting with stroke centres every year. Industry col- the activities of the network. newly developing stroke networks in other laboration is encouraged. How would new hospitals go countries for the past 12+ months. These Since its initiation in 2013, about joining StrokeNet and other networks may decide to participate What is its organisational how has StrokeNet been what are the key benefits of in some of our ongoing trials. They may structure? performing? doing so? be able to support their local stroke infra- The NIH StrokeNet is composed of 25 All parts of the network were not funded Hospitals can contact one of the Regional structure and thus help facilitate quicker Regional Stroke Centers in the USA. Each until mid-2014, and the first year and a half Center principal investigators (this infor- completion of trials. Networking also can regional centre includes a number of hos- was focused on setting up the infrastructure mation can be found on NIH StrokeNet allow for planning of similar trials in other pitals and/or additional academic hospitals. and contracts, reliance agreements at each website) to see if they would qualify as countries which facilitates pooling of data These Regional Centers include Rehabilita- regional centre and participating hospi- a satellite site. However, it is up to the when the trials are completed. Thrombectomy in clinical practice: what we can expect It must be accepted that mechanical thrombectomy the largest response rate also had routine we will treat patients who for the treatment of acute ischaemic stroke in clinical the best placebo response, there would not have made it into a routine will not have the same “excellent” results was a 31% absolute difference,” clinical trial. For example, think as in the trial environment. That being said, the use he reported. of someone who has Parkin- of mechanical thrombectomy in clinical routine will As for how that will compare son’s disease, and because of his give patients who could not meet trial inclusion with clinical routine, Hacke Parkinson’s he has a mRS of 2. He criteria a chance at an improved outcome. explained that the broader the can never get into a stroke trial, inclusion criteria are and the less but saving him to remain with hat is according to Werner tissue at risk or RAPID). complex the imaging criteria are the mRS 2 instead of going down Hacke (University Hospital Hacke pointed out that the (plain CT, exclusion of very large to a mRS 4 because now he had Tof Heidelberg, Heidelberg, factors influencing the treatment early infarct and bleed only), the a stroke, that is what medicine Werner Hacke Germany) who spoke at the Inter- effects are time to recanalisation more patients will qualify for is about, but it is not reflected in national Stroke Conference (ISC; (or, more frequently assessed, time thrombectomy. As a result, more clinical trials. So let us not be dis- in most it will not,” Hacke stated. 17–19 February, Los Angeles, to groin) and level of recanalisa- patients with a lower likelihood to appointed when our local registries Giving advice for how patients USA). tion. “But the level of imaging show superiority to standard treat- show higher mortality rates and should be designated in registries In the recent thrombectomy requirements for patient selection ment will be treated, including M2 lesser percentages of excellent out- from now on, Hacke suggested trials there were many common also varied between the trials. In occlusion, milder stroke (NIHSS come because this reflects clinical that patients should be classified features: These were mostly MR CLEAN (plain CT, AS- ˂10), long time windows and reality with broad inclusion. So let as ideal candidates and last chance moderate to severe strokes, in PECTS post hoc) there was 14% extended early infarcts. us accept that there will be a higher candidates prospectively, and then mostly proximal occlusions (ICA, absolute difference between the With very broad inclusion, as number of treatment failures with the results can be benchmarked M1); predominant use of modern endovascular treatment group and will be the case in clinical routine, broad inclusion. for the ideal patients and operators stent retriever devices; and the the control group; in REVASCAT he added, it is unrealistic for “We will treat patients that we must accept that the non-ideal majority of patients were treated (plain CT and ASPECTS) there stroke teams to expect to generate know are probably not the best patients will dilute the results. on top of t-PA. The differences was 16% absolute difference; in outcomes like in SWIFT PRIME candidates (very old, more than “Even if we get very broad with among the trials were seen in the ESCAPE (all ASPECTS >5) there or even EXTEND-IA. Rather, eight hours after onset, tandem the inclusion, we may include time to recanalisation and in the was 24% absolute difference; he said, the mRS 0–2 outcome occlusions) because we know we patients who will not benefit and type of imaging selection (imaging in SWIFT PRIME (ASPECTS, will probably be closer to that in will give them a chance with the may have a risk, but independently almost exclusively CT-based; some RAPID) there was a 21% ESCAPE and hopefully a little treatment, and as long as we do of that we will never lose the good CT-selection varied from plain absolute difference; and finally, in better than in MR CLEAN or not hurt them with giving them a ones, they will always qualify, the CT over ASPECTS, estimation of EXTEND-IA (all RAPID), which REVASCAT. chance this is absolutely appropri- broader the inclusion may be,” collaterals to automatic analysis of had the best treatment effect and “But let us accept that in clinical ate. In some the miracle will work, Hacke concluded.

10 Intracranial aneurysms May 2016 Real-world experience confirms safety and efficacy of WEB in wide-necked aneurysms The real-world experience of a centre in Germany has confirmed the overall promising (10%), with a new permanent deficit in one patient. results in feasibility, safety and effectiveness of the WEB device (Woven Endobridge; Re-rupture after WEB treatment was detected in Sequent Medical) reported in other studies. two aneurysms (4.3%), which had both initially presented with subarachnoid haemorrhage. Overall, n the largest single-centre experience published time of follow-up using the modified Rankin Scale angiographic follow-up revealed adequate occlusion to date, Christin Clajus (Helios General Hospital (mRS). According to the WEBCAST trial, morbidity in 68 of 90 aneurysms (75.6%), with complete IErfurt, Erfurt, Germany) and others analysed an was defined as an mRS >2. Follow-up imaging and occlusion in 52 aneurysms (57.8%) and a neck all-inclusive cerebrovascular database of patients clinical examinations have been performed—and remnant in 16 aneurysms (17.8%). In 22 aneurysms treated with the WEB device between October 2010 will continue to be—at six months, 12 months and (24.4%) residual aneurysm filling was noted. and May 2015. The database included 108 patients five years post-intervention. Aneurysm occlusion Fifteen aneurysms (16.7%) required retreatment. with 114 saccular aneurysms treated was graded as either “adequate” (complete Finally, the study authors write, permanent with the WEB. occlusion, neck remnant) or “aneurysm morbidity and mortality in all patients who received The WEB is a self-expanding remnant” (if filling of the aneurysm a WEB device and follow-up angiography were intra-aneurysmal flow disruptor beyond the neck was noted). 5.3% and 8.5% (five and eight patients of 94 consisting of compliant braided Of the 114 aneurysms patients involved), respectively. nitinol mesh. The device is treated, 47 aneurysms were The authors conclude, “Intra-aneurysmal flow currently available in Europe. ruptured (41.2%). After disruptors represent an emerging endovascular In terms of procedure in a mean of 13.4 months, treatment strategy for wide-necked bifurcation their series, the authors 86 patients received aneurysms, with the main advantages of not requiring report that following angiographic and clinical permanent anti-platelet therapy and allowing the WEB placement, post- follow-up. One hundred and treatment of many of these aneurysms during a interventional control ten of the 114 WEB devices technically straightforward, efficient, single-step angiography was (96.5%) were deployed procedure. From the results of the WEBCAST, the performed to evaluate the successfully. French Observatory and our series, we think that the degree of initial aneurysm As it relates to adverse WEB device can become the treatment of choice for occlusion. Clinical status events, the authors report that many cerebral aneurysms.” was assessed immediately post- thromboembolic complications The study was publishing the Journal of procedure, at discharge, and at the WEB occurred in 11 of 110 interventions NeuroInterventional Surgery. New aneurysm device acts as both flow disruptor and diverter

The Contour Neurovascular System (Cerus Endovascular) will offer a new option for treating intracranial aneurysms. According to Kyriakos Lobotesis, Principle Clinical Advisor at Cerus, “the objective of the device is to treat the neck of the aneurysm, thus avoiding protracted manoeuvres and manipulation within the aneurysm, which can be experienced while using other available devices”.

Can you describe the the neck of the aneurysm, it is not Contour Neurovascular limited to specific aneurysm location System? or morphology, therefore it can be used The Contour Neurovascular System to treat a wide range of intracranial is an innovative, intrasaccular, self- aneurysms. Its ease of deliverability anchoring, embolisation device targeting and accurate positioning allow it to the aneurysm neck. address even difficult to treat wide- necked bifurcation aneurysms and How is it different aneurysms with branches arising from from existing devices their side wall. As mentioned above, for the treatment of being intrasaccular, its use does not intracranialaneurysms, necessitate dual antiplatelet therapy. such as coils, intrasaccular It hence can be used for the treatment flow disruptors and flow of both ruptured and unruptured diverters? intracranial aneurysms. The device, due to its unique placement Contour Neurovascular System across the neck of the aneurysm, acts What were the results of the as both a flow disrupter and diverter. How does the device work device has consistently demonstrated first-in-man study? Unlike other intrasaccular devices and what are the objectives? high rates of complete occlusion of First-in-man studies have confirmed the Contour Neurovascular System The objective of the device is to treat the aneurysm, which were sustained device stability at six months and is not as limited by aneurysm size or the neck of the aneurysm, thus avoiding over a period of time. Thrombosis steady aneurysm occlusion during this shape. Its unique stabilising design protracted manoeuvres and manipulation and neointimal growth across the period. The patients all maintained architecture prevents it from migrating within the aneurysm, which can be neck were repeatedly confirmed their pre-treatment status and most or compacting into an aneurysm experienced while using other available histopathologically. Deliverability, importantly there were no adverse post-deployment. The device mesh devices. The aim is to offer consistent positioning and device stability were events. The patients will of course provides a uniform scaffold distributed neck coverage and stability to reduce also excellent throughout. These continue to be followed-up. across the neck of the aneurysm the risk of compaction/recanalisation/ results, and other testing performed, for the establishment of neointimal retreatment. The device works by a provided the confidence to move What is planned in terms of development and unlike devices placed combination of diversion and disruption forward into first human use. future trials? in the parent vessel, is not dependent of flow in the aneurysm sac. The first trial has been approved and on the use of dual antiplatelet therapy. What types of intracranial is already recruiting patients. A second Hence it can be used for the treatment What were the results of the aneurysms can the Contour multicentre trial is currently seeking of both ruptured and unruptured animal studies? device be used to treat? approval and will start enrolling intracranial aneurysms. Over a number of animal studies, the Because the Contour System addresses patients shortly.

12 Aspiration May 2016 Long-term experience confirms ADAPT as effective treatment for stroke A study of the long-term use of the ADAPT technique for the tion was achieved in 180 (94.2%) patients, time for recanalisation was 37.3min. TICI treatment of acute ischaemic stroke has confirmed that it is TICI 2C or better was achieved in 157 2B or better recanalisation was achieved in an efficient method to achieve good clinical and angiographic (82.2%) patients, and TICI 3 was achieved 180 (94.2%) patients. Ninety-eight patients outcomes, with 82.2% of patients achieving TICI 2C or better in 85 patients (44.5%). Recanalisation was (54.1%) had an mRS of 0–2 at 90 days. recanalisation and 90-day mRS scores of 0–2 in 54.4%. unsuccessful in two cases. In one patient Of note, ADAPT was successful in who suffered a basilar occlusion from achieving final recanalisation in 145 of an Vargas (Medical University of South operators. Ninety-one patients were women extensive atherosclerotic plaque, recana- cases, and 43 cases required the additional Carolina, Charleston, USA) and col- (47.6%), and the average age was 67 (range lisation was not achieved (TICI 0) due to use of a stent retriever. Eight direct aspira- Jleagues sought to report their centre’s 27–93 years, ±14 years). A total of 171 abortion of the procedure secondary to tion only cases had lesions in more than ongoing experience with the ADAPT (89.5%) ischaemic strokes occurred in the intraprocedural basilar artery rupture. In one vessel, compared with four in the direct technique, which has been used as the anterior circulation and 20 (10.5%) in the a second patient, multiple attempts were aspiration with adjunctive devices. In two primary revascularisation technique at that posterior circulation. Patients presented made to recanalise a completely occluded cases, recanalisation was not achieved. institution since 2012. with a mean NIHSS score of 15.4 (range right internal carotid artery, ultimately Additionally, the authors highlight, “Mean A retrospective analysis of a prospective- 0–36, ±7), and 71 (37.2%) patients received resulting in partial revascularisation. The time to recanalisation was significantly ly maintained database was performed to IV t-PA. The average time from onset to ACE 64 catheter (Penumbra) was used in faster for direct aspiration only cases, with identify all patients undergoing thrombecto- puncture was 7.8 hours (range 20min to >36 seven cases, all of which achieved a TICI revascularisation achieved in 30.12min my for large vessel occlusion with ADAPT hours, ±6.1 hours). Twenty-three patients score of 2C or better (100%). The 5 MAX (range 7–150min, ±29.56) compared at that institution using an institutional (12%) presented as wake up strokes. The ACE (Penumbra) was used in 101 cases, with 61.4min (range 8–160min, ±35.85) review board approved protocol. Patients average length of stay was 9.3 days (range of whom 78 (77.2%) achieved TICI 2C or (p=0.00000201). There were no significant undergoing thrombectomy between De- 0–193, ±16.9 days). Twelve (6.3%) patients better. The 5 MAX catheter (Penumbra) differences in likelihood of achieving a cember 2012 and April 2015 were included. had tandem lesions noted during treat- was used in 33 cases, of whom 30 (90.2%) 90-day mRS of 0–2 (57.7% for direct aspi- Specific parameters captured included age, ment. In 10 cases, the occlusion was in the achieved TICI 2C or better. The likelihood ration only vs. 43.2%; p=0.12) or mortality gender, National Institutes of Health Stroke internal carotid artery, with tandem distal of achieving TICI 2C or better recanalisa- rates among the two groups (13.9% for Scale (NIHSS) score at presentation, and lesions in ipsilateral branches of the middle tion was not significant for the ACE 64 direct aspiration only vs. 18.2%; p=0.47).” time to presentation from last normal. Of cerebral artery. There were no cases of (p=0.35), 5 MAX ACE (p=0.087), or 5 Vargas et al conclude that in their long- significance, angiograms were blindly grad- emboli to new territory following aspira- MAX (p=0.21) catheters.” term experience, “ADAPT is an efficient ed by an independent neurointerventionalist tion thrombectomy. In two cases of basilar As it relates to complications, they write method to achieve good clinical and angio- to assess pre- and post-revascularisation artery occlusion, the patients had additional that there were four intraprocedural compli- graphic outcomes, with 82.2% of patients using both the Thrombolysis in Cerebral Is- occlusion of left sided middle cerebral cations. Further, 13 (6.8%) patients suf- achieving TICI 2C or better recanalisation chaemia (TICI; with scores of 0, 1, 2A, 2B, artery branches, one of which was felt to be fered clinically significant post-procedural and 90-day mRS scores of 0–2 in 54.4%. and 3) flow post procedure and the modified a chronic thrombus and was not aspirated. parenchymal haematomas; one patient These results are comparable with recent 2C TICI grading scale (including scores of The authors report, “The average time (0.57%) had a retroperitoneal haematoma; randomized trials that demonstrate the ben- 0, 1, 2A, 2B, 2C, and 3). for recanalisation was 37.3min (range and seven patients (3.7%) suffered post- efit of intra-arterial thrombectomy.” They According to the data, from Decem- 7–160min, ±29.6) across all cases. There procedural gastrointestinal bleeds. add that ADAPT as a first line strategy for ber 2012 to June 2015, 191 consecutive were no differences among operators. In terms of outcome, Vargas et al achieving revascularisation in the setting patients who suffered an acute ischaemic Independent adjudicated angiographic report that the average time from onset to of acute large vessel occlusion should be stroke were treated with ADAPT by four outcomes of TICI 2B or better recanalisa- puncture was 7.8 hours and the average further studied in a randomised trial. May 2016 Data sharing 13 The double-edged sword of clinical data sharing set than can be explored by the people He thus calls for universal open access that are collecting it. Moreover, there are from publishing houses. many more practitioners in the field of Fiorella goes on to point out that the medicine with ideas than there are with ICMJE is creating an unfunded mandate JOSHUA A HIRSCH the ability to generate large, randomised for clinical researchers to create the mecha- datasets. He points to potential research nisms by which this data sharing occurs. partners in private practice, who lack a He points out that the ICMJE does not offer strong research infrastructure. So-called any insight or suggestions in how to fund COMMENT & ANALYSIS “research parasites” might allow greater these requests. realisation of this academic potential Fiorella’s final argument relates to The Journal of NeuroInterventional Surgery (JNIS) recently through broader collaboration. industry sponsorship of clinical trials in featured a point/counterpoint regarding sharing clinical trial Hirsch’s final argument related to neurointervention. He imagines a situation data. In fact, the participants were two of the journal’s founding the moral imperative at work in clini- in which industry sponsors would choose editors. cal trials as exemplified by ischaemic not to allow the publication of medical stroke. Neurointerventional practition- research in peer-reviewed journals, but t the heart of the discussion was for data sharing as a component of clinical ers asked their vulnerable patients and simply submit to regulatory bodies and a proposal from the International trial registration. This plan would include families suffering from strokes caused then use the data as they see fit to construct ACommittee of Medical Journal where the researchers will house the data by large vessel occlusion to participate marketing materials. In these cases, such Editors (ICMJE) that was published in and how other interested parties will be in endovascular trials despite the fact studies would then never be subject to the multiple lead journals entitled “Sharing provided access to the data. The ICMJE that many lacked “personal” equipoise scrutiny of peer review and publication Clinical Trial Data—A Proposal from proposes a one-year delay in implement- and believed that randomisation away for public consumption. This IPD sharing the International Committee of Medical ing the proposal to minimise disruption to from treatment put patients in harm’s mandate, he thus argues, could also provide Journal Editors. ” current efforts. way. In fact, the trials proved that this is a powerful overarching disincentive to The ICMJE describes itself as a “small The editors of the New England Journal the case. Going against our own beliefs industry to enter into collaborative clinical working group of general medical journal of Medicine (NEJM) have written a we withheld what might have been life research initiatives with physicians. editors, whose participants meet annually contemporaneous commentary that has saving treatment by promoting partici- Both authors recognise the legitimacy and fund their own work on the Recom- received quite a bit of attention. Drs Dan pation in the trials. In the article, Hirsch of each other’s point of view and are mendations for the Conduct, Reporting, Longo and Jeffrey Drazen raise concerns states that neurointerventional scientists delighted that the JNIS provides a forum Editing and Publication of Scholarly Work that people who were not involved in and clinicians honour that sacrifice by for robust discussion. We are hopeful that in Medical Journals”. The premise of this the generation and collection of the data publicly sharing trial data to facilitate however this ICMJE proposal plays out, proposal is that the editors believe there is may not understand the choices made in further study and commentary. remora, oxpecker’s and orchids are made an ethical responsibility, indeed, “obliga- defining the parameters. Doubling down, Dr David Fiorella takes a different to feel welcome. tion”, to share clinical trial data, because they raise the notion that a new class of point of view with respect to the ICMJE References trial participants in a tangible way have research person could emerge; people they proposal. He asks, “Is clinical data shar- 1. Taichman DB, Backus J, Baethge C, Bauchner H, de Leeuw PW, Drazen JM, Fletcher J, Frizelle FA, Groves been placed in potential harm’s way. termed “research parasites.” ing the future of clinical trials?” Reading T, Haileamlak A, James A, Laine C, Peiperl L, Pinborg A, The proposal is that investigators Dr Joshua Hirsch supported the propos- through his response, it is fair to say that Sahni P, Wu S. Sharing Clinical Trial Data--A Proposal from the International Committee of Medical Journal would be required to share de-identified al and took aim at the notion of “research Fiorella believes the answer to be a firm Editors. N Engl J Med. 2016 Jan 28;374(4):384-6. doi: individual-patient data (IPD), underly- parasites”. He noted that Longo and Dra- and resounding no. 10.1056/NEJMe1515172. Epub 2016 Jan 20. No abstract available. PMID: 26786954 ing the results presented in an article zen use of this inherently negative term With brilliant flair, Fiorella turns the 2. Longo DL, Drazen JM. Data Sharing. N Engl J Med. 2016 Jan 21;374(3):276-7. doi: 10.1056/NEJMe1516564. published in a member journal. This to make a point. Hirsch thought it would question back on the journals and editors 3. Hirsch JA. The future of clinical trials: data shar- requirement would include tables, figures, be helpful to remember that remora, that make up the ICMJE. He points out ing. J Neurointerv Surg. 2016 Apr 15. pii: neurint- surg-2016-012434. doi: 10.1136/neurintsurg-2016-012434. and appendices or supplementary material oxpeckers and orchids have been, at times that the cost of open access publication is [Epub ahead of print] No abstract available. PMID: and be required to happen no later than inaccurately described as parasites as well high and passed on to authors. If authors 27084961 4. Fiorella D. Is data sharing the future of clinical trials? six months after publication. The data when in fact they provide commensal or do not accept this cost, readers often J Neurointerv Surg. 2016 Apr 21. pii: neurint- underlying the results are defined as the symbiotic relationships to their hosts. He need to pay a high fee in order to read the surg-2016-012435. doi: 10.1136/neurintsurg-2016-012435. [Epub ahead of print] No abstract available. IPD required to reproduce the article’s believes the metaphor is helpful in think- article. Fiorella posits that a moral obli- PMID:27102199 findings, including necessary metadata. ing through clinical data sharing. gation to study participants might include Notably, the ICMJE proposal will require Hirsch goes on to further argue that allowing the papers to be more broadly Joshua A Hirsch is at Massachusetts a specific indication of the author’s plan there are more ideas within each data studied than the present model allows for. General Hospital, Boston, USA Data support “careful” use of mechanical thrombectomy in non-top tier evidence criteria ELVO patients

Continued from page 2 similar at 8% in the top tier group, compared with 10% in multivariate analysis.” times (234 min (IQR 177–291) vs. 381 min (IQR 268–454) the non-top tier group (p=0.731). Patients in the top tier Overall, the study showed that despite lacking top tier p˂0.001), but the median door to puncture times between group also achieved greater neurological improvement evidence for mechanical thrombectomy, “33% of cases the two groups were not significantly different (151 min during hospitalisation (10 points (IQR 6–14)) compared treated outside these recommendations attained an mRS (IQR 115–190) vs. 149 min (IQR 115–237), p=0.628). with the patients in the non-top tier group (5 points (IQR score of ≤2 by three months, and that nearly half of the Further, they write that median ASPECT scores were 1–10); p=0.006) in initial univariate analyses. Mortal- mechanical thrombectomy cases would have been denied also higher in patients meeting top tier criteria compared ity was significantly lower in the top tier evidence group mechanical thrombectomy if top tier evidence criteria were with those not meeting top tier criteria (10 (IQR 10–10) at 26% compared with 45% in other cases (p=0.044), upheld in clinical practice. Additionally, the data indi- vs. 9 (IQR 8–10), p=0.001). Additionally, cases not whereas favourable outcome (mRS ≤2) at three months cated no increased risk of sICH or serious haemorrhagic meeting top tier evidence included 20 (32%) basilar artery was similar at 46% in the top tier evidence group versus complications in the group that lacked top tier evidence for occlusions, and of these, 11 (55%) died, while five (25%) 33% non-top tier evidence group (p=0.158). mechanical thrombectomy, demonstrating that a sizeable achieved mRS ≤2 at the three-month follow-up. They explain, “After adjusting for potential imbalances percentage of patients not meeting top tier criteria may still Finally, the investigators report that rates for sICH were between the two groups, including baseline ASPECT have a good outcome with mechanical thrombectomy.” 8% in each group, and serious haemorrhage rates were score, IV t-PA pretreatment, intubation and time elapsed Finally, commenting on the devices used for mechani- from symptom onset to groin cal thrombectomy, the authors add, “Despite guidelines puncture, associations between endorsing stent retrievers as the technology of choice for endovascular mechanical thrombectomy, our data showed that in clinical practice, thrombectomy in top tier evi- aspiration and a combination of technologies (aspiration dence cases and others did not and stent retrievers) played a greater role in the treatment Trevo-XP ProVue Retriever (Stryker Neurovascular) reach statistical significance in of ELVO.” 14 Interview May 2016 Profile Jacques Moret

As the course director of the Live Interventional Neuroradiology and Neurosurgery Course (LINNC; 23–25 May, Paris, France) Jacques Moret talks about the importance of a live course and about the highlights of the 2016 meeting. He also shares the advice that he hopes his mentees will always follow and addresses three questions in interventional neuroradiology that are still in need of an answer.

What drew you to medicine and knowledge of the disease, the knowledge of the vascular neuroradiology in particular? anatomy, the practical training (as any surgical procedures) I wanted to be a doctor since I was in college. I moved to and how to manage a complication. The discussion is open Interventional Neuroradiology (INR) because I had the “vi- all along, and the sessions are organised as a live forum, sion” that doing surgical procedures without opening the body which is fed by the flow of questions from the audience, could be the future. The beginning of Interventional Neurora- through the “app” of the course. It is a fantastic way to learn diology, which was promoted by Professor Réné Djindjan in and an incredible source of progress for everybody, just France, for spinal cord arteriovenous malformations treatment because an imprecise science needs gathering of multiple was the spark! experiences to become more and more reliable.

Who were your mentors and what wisdom What are the highlights of LINNC Paris did they impart to you? 2016? My mentors were Dr Jacqueline Vignaud and Professor This year the highlights will be first of all (as last year) the Dominique Doyon. They brought me a very important pa- “stroke treatment”: basically mechanical thrombectomy rameter for my career, which is more than a parameter, it is a (results, indications, new perspectives). In addition to real gift; they gave me their confidence and a full freedom. I stroke, we will focus on new liquid embolic materials for remember one very important sentence: “Jacques, maybe you brain arteriovenous are right or maybe you are wrong, but if this is what you want malformations to develop, do it”. treatment, as well as flow study, Which innovations in interventional computerised neuroradiology have shaped your career? virtual tools for Innovations are steps of development and will never stop, but aneurysm treatment it is not a “shaping tool”, at least for me. The shaping tool is mimicking real the concept of the so-called “minimally invasive surgery”. practice and “live The innovations are just the consequences of new therapeutic micro-vascular concepts. However, over the last 35 years, I recognise three anatomy” which is major technological innovations: the coils, the flow diverter the future for the stents and the phenomenal peri-operative imaging improve- coming five years. ment. As far as the concept is the way to progress, I recognise that clearance of cerebral artery using mechanical thrombec- What are tomy is the most important evolution for the quality of life of your current stroke patients over the last ten years. research interests? What was one of your most memorable Current research cases? is going towards One of my most memorable cases is of a one and a half year the screening of old baby I treated in 1990 in Beijing for a mural type of Vein the structure of the of Galen malformation. The procedure went ok and after it, arterial wall and the I requested to keep the baby quiet, with control of the blood structure of the clot. pressure and heparin treatment. When I came back the next “Live micro-vascular morning, the baby was playing with some other children anatomy” is one of the outside of his room, in a garden of the hospital, with no control highlights of the LINNC at all and no heparin treatment. Last year I got a picture of the 2016 course, but also one baby who is now a strong man in very good shape! of the research directions.

As the course director of LINNC for many You have been years, what do you think is the importance involved in many of a live course? studies into new Medicine is an imprecise science where being utterly neuro devices convinced is frequently perceived as a medical truth, despite throughout your the fact that there is no scientific basis! In medicine one can career. In your say anything and everything! During live courses lying is opinion, what has not possible! Having said that, live courses must respect the been the greatest patient and give them the best chance of success, that is the advancement, reason why during the LINNC course, the operator has no and how do you direct link with the audience, he cannot speak and answer see the field of questions at the time of the treatment. A doctor, from the interventional operator’s team in the conference room, speaks and answers neuroradiology in the name of the operator. These are our ethics and I stick to developing in it, without any exception. the future? The answer to this At LINNC, a lot of focus is placed on question is a kind delegate participation and interaction, why of melting pot of the is this important? above reported items. Interventional neuroradiology has four components: the I have no doubt that the May 2016 Interview 15

Fact File

greatest advancement comes from the five stroke studies that have been published in 2015. It is absolutely unique in the medical literature to have, over a one year period, five randomised studies, which all demonstrate the incredible positive result of mechanical thrombectomy versus thrombolysis. How do I see the field of interventional neurora- Current position diology developing in the future? Professor and honorary chairman of Interventional This is a difficult question because Neuroradiology, NEURI, the Brain Vascular Center, there are parameters that I do not Bicetre University Hospital, Paris, France master. What I clearly master is the tremendous potential of develop- Professional career: ment of interventional neuroradiol- „„Medical Doctor, (Thesis 1975) ogy in terms of concept evolution, „„Fellowship in Radiology 1974–1977 and technological innovations. What „„Fellow Department of Neuroradiology, Loma I do not master at all is the way this Linda University USA (1975) fast growing field will be organised „„Board of Radiology (1977) University René by the doctors and the healthcare Descartes, Paris, France authority. Interventional neuroradiol- „„Full Professor of Radiology, Baylor College of ogy is a tremendously attractive “cake” Medicine, Houston, USA (1989–1994) and it arouses a lot of keen interests. I „„Former chairman, Department of Interventional am afraid that those interests push the Neuroradiology, Foundation Rothschild discipline in a direction where the patients Hospital, Paris, France (1994–2010) will not be the full beneficiary! „„Former chairman, Department Of Interventional Neuroradiology, Beaujon University, Hospital You have mentored and Clichy, Paris, France (2011–2015) trained a number of „„Honorary chairman, Department of physicians throughout your Interventional Neuroradiology at Bicetre career. What advice do you University Hospital Le Kremlin Bicetre, Paris hope they will always follow? (2015–) I hope they will follow and feel my „„Professor of Neuroradiology, University Paris enthusiasm in doing and developing Vii, Faculty of Medicine “Bichat-Beaujon”, Paris, interventional neuroradiology, I hope France (1994–2015) they will share my happiness teach- ing them and by the way I hope they Medical Societies will reproduce it when teaching their „„Member of the Societe Francaise de own pupils. I hope they will behave as Neuroradiologie scientists being true and good medical „„Member of the European Society of doctors and becoming true “medical Neuroradiology leaders” instead of becoming “key „„Member of the American Society of opinion leaders” which is a pure Neuroradiology industrial concept and a hidden way to „„Member of European Society of Minimally say “best customers”. Invasive Neurological Therapy (ESMINT) „„Founding Member of ABC-W.I.N. (Working What three questions Group In Interventional Neuroradiology) in interventional neuroradiology are still in Distinctions need of an answer? „„President of ESMINT (2008–2010) 1. How to make the guidelines of the „„Doctor Honoris Causa of the University of Lund, WFITN a reality in the medical educa- Sweden (2005) tion and medical organisation. „„President of the Societe Francaise de 2. How to change the process of the Neuroradiologie (2000–2001) healthcare authority in the analysis of „„Co-president of the first congress of the World the services rendered to the patients Federation of Interventional and Therapeutic regarding the new devices in order to Neuroradiology, Zurich (1991) get the reimbursement in due time. „„Winner of the “Schneider Lecture” of the 3. How to regulate the distribution American Association of Neurological Surgeons of the interventional neuroradiology (Cushing Society) (1991) centres in big cities such as Paris, in „„Winner of the “Schering” Award of the Euro- order to serve a better medical quality pean Society of Neuroradiology (1988) for the patients, understanding that this „„Honorary Professor of the University Of Beijing quality is for a large part related to a (1986) large practice. 16 Guidelines May 2016 SVIN releases consensus criteria for standardising stroke infrastructure

The Society for Vascular and Interventional Neurology (SVIN) has lab capabilities at a time of rapid advance- To advance this goal, SVIN developed a developed Stroke Interventional Laboratory Consensus (SILC) ments in stroke treatment, including the use “7M” management approach for standardis- criteria to standardise stroke interventional laboratories for safe, of stent retrieval devices, vacuum suction ing stroke infrastructure and includes: effective, and timely stroke care worldwide. devices, and clot-busting drugs to save lives „„Manpower: personnel including roles and reduce long-term damage to the brain. of medical and administrative directors, rain attack care is now explod- “There is an unmet need to establish a new “Our hope is that these consensus criteria interventional technologists, interven- ing with new devices and national standard to provide optimal, timely will provide the roadmap for growth of high tional nurses, physician extenders, and all “Boptions, just as heart attack care stroke care to all patients suffering from quality stroke intervention labs worldwide the key stakeholders in the stroke chain grew rapidly in the 1990s,” says Tanzila acute ischaemic strokes.” similar to the growth of cardiac catheterisa- of survival; Shams, and lead author of a report on the The SILC criteria reflect the need to tion labs,” says SVIN past-president Tudor „„Machines: resources needed in terms criteria published Interventional Neurology. clearly distinguish stroke interventional Jovin, co-author of the report. of physical facilities, and angiography equipment; „„Materials: medical device inventory, medications, and angiography supplies; „„Methods: standardised protocols for stroke workflow optimisation; „„Metrics (volume): existing creden- tialing criteria for facilities and stroke interventionalists; „„Metrics (quality): benchmarks for qual- ity assurance; and „„Metrics (safety): radiation and proce- dural safety practices; “National efforts in the uniform organisa- tion, accreditation, and certification of stroke intervention practices are more important than ever,” says Vallabh Janardhan, and sen- ior author of the report. “For effective stroke therapy to reach millions of people, we need to have the right infrastructure in place.” “Standardising stroke interventional labs will increase treatment rates and help achieve SVIN’s Mission 2020 goal of 200,000 clot retrieval procedures worldwide by the year 2020,” says Dileep Yavagal, SVIN past-president, and co-author of the report. “We now have exciting new therapies for brain attacks, such as retrievable stents and vacuum suction devices that are similar to balloons and stents for heart attacks,” says Janardhan. “But these technology innova- tions need to be supported by the appropri- ate stroke interventional lab infrastructure so that patients receive timely care.” Currently, there are 1,476 primary stroke centres in the USA that can provide clot-busting medications, and more than 170 comprehensive stroke centres whose capabilities include neurosurgical and catheter interventional treatments as well as medications. “Although this tiered system of stroke centres has improved outcomes in the treatment of strokes, more emphasis is needed on the development and opera- tions of the stroke intervention lab within a stroke centre,” says Janardhan. For instance, standardisation is needed on emergency triage procedures for stroke patients, stroke interventional protocols and equipping, staffing and managing a stroke interventional lab. “As we enter a new era of stroke care, national standards are needed to direct patients, families and EMS to the right centre,” said Raul Nogueira, SVIN president. “We believe SVIN’s report on consensus criteria can provide a frame- work for developing those standards, leading to a higher level of care and better patient outcomes.” May 2016 Stroke treatment 17 Majority of Charing Cross audience disagrees that endovascular acute stroke treatment should be done only by neuroradiologists

During the inaugural Acute Stroke Challenges session at the Charing Cross Symposium (CX; 26–29 April, London, UK), 68.8% of the audience disagreed that neuroradiologists should be the only operators that perform intra-arterial treatment of acute ischaemic stroke. The issue has been a topic of contention since the results of five randomised controlled trials published in 2015 changed the face of acute ischaemic stroke treatment, providing overwhelming evidence in favour of mechanical thrombectomy for patients with emergent large vessel occlusions.

s is customary at the Charing Cross Symposium, ischaemic stroke should be done by clinicians experienced Posing the other side of the debate, Jos van den the issue became a subject for debate (“Only in the use of thrombolysis for stroke and interpretation of Berg maintained that there is sufficient evidence Aneuroradiologists should undertake intra- relevant imaging. The procedure should only be carried from the literature that acute stroke treatment can be arterial thrombectomy”) between two experts—in out by appropriately trained specialists with regular performed safely and successfully by a large range of this case, a neuroradiologist and an interventional experience in intracranial endovascular intervention specialists, including, interventional neuroradiologists, radiologist. Andrew Clifton (consultant neuroradiologist, with appropriate facilities and neuroscience support”. interventional radiologists, interventional St George’s University Hospitals NHS Foundation Finally, Clifton referred to the recently published neurologists, vascular surgeons, neurosurgeons. Trust, London, UK) spoke for the motion, facing off “Training Guidelines for Endovascular Ischaemic Stroke Van den Berg quoted from a study in journal against Jos van den Berg (interventional radiologist, Intervention: An International Multi-Society Consensus Cardiovascular Interventional Radiology, which Ospedale Regionale di Lugano, sede Civico Lugano, Document”, which according to the document “seeks to concludes that “a treatment strategy with general Switzerland) who spoke against the motion. define what constitutes adequate training for physicians interventional radiologists performing neurointerventional Starting his argument, Clifton acknowledged who can provide endovascular treatment for acute procedures in acute stroke patients with large vessel that there is growing pressure from patient groups ischaemic stroke patients. These training guidelines are occlusions can be achieved to the benefit of patients”. and the stroke community to roll out this therapy modelled after prior standards of training documents such Further, he referred to a study in the Journal of as soon as possible, but maintained that delivering as the training, competency and credentialing standards Vascular and Interventional Radiology which it with inexperienced operators may discredit the for diagnostic cerebral angiography, carotid stenting and concludes “peripheral interventional radiologists technique. While the results of the published trials cerebrovascular intervention and the performance and who use CT perfusion imaging for patient triage are convincing, he said, those excellent results were training standards for endovascular ischaemic stroke can have good neurological outcomes and provide achieved because the procedures were performed by treatment, written and endorsed by multispecialty groups. sustainable, safe and complete around-the-clock fellowship-trained neurointerventionalists practising In addition, the importance of organ specific training, coverage for endovascular stroke treatment”. in conjunction with stroke neurologists/physicians and rigorous quality improvement benchmarks, and minimum A common factor in the existing literature, neurointensivists at high volume centres. These results, volume requirements needed to maintain high quality van den Berg pointed out, is that there was Clifton cautioned, cannot be duplicated by physicians care has been extensively described for acute myocardial always a close collaboration with diagnostic with no training in interventional neuroradiology. infarction, an analogous time sensitive disease”. neuroradiologists and stroke neurologists. The ideal person to perform mechanical thrombectomy, Summarising his points, Clifton conceded that The key issue, he said, was that the mechanical he argued, is someone with adequate knowledge, in his opinion, mechanical thrombectomy in acute thrombectomy operator should have adequate training, experience and training, who is part of a high volume stroke should be performed by a trained neuro- as is made clear in the CIRSE guidelines: “Intra-arterial centre and therefore performs a great number of interventionalist who can be a neuroradiologist, stroke therapy requires imaging, clinical, cognitive, and interventional neuroradiology procedures. Further, he neurosurgeon, neurologist, cardiologist, or interventional extensive technical skills. It is our belief that there is a added, the stroke patients must be treated at a centre that radiologist, but a person who has had proper training. direct correlation between skill level and outcome for can provide good post-procedure care and stroke care. “Training leads to appropriate patient selection, faster intra-arterial stroke therapy. The unskilled must undergo To support his argument, Clifton quoted from the and safer procedures with fewer complications. Many will rigorous curriculum-based training in approved training National Institute of Health and Care Excellence (NICE) have read the misguided BMJ article which suggested institutions associated with an assessment of competence recommendations: “Current evidence on the safety and teams of cardiologists in DGH settings were best placed before performing these procedures. Reaccreditation efficacy of mechanical clot retrieval for treating acute to take on mechanical thrombectomy, however, such must be earned on a frequent basis. Patients deserve ischaemic stroke is adequate to support the use of this teams will need to acquire the necessary diagnostic appropriately trained expert endovascular specialists”. procedure provided that standard arrangements are in interventional and clinical decision making skills which Similarly, the Society for Interventional Radiology has place for clinical governance, consent and audit. Selection will require a significant period of training to gather the outlined three components of adequate training: of patients for mechanical clot retrieval for treating acute adequate knowledge and experience,” Clifton stated. 1. Formal training that imparts an adequate depth of cognitive knowledge of the brain and its associated pathophysiologic vascular processes, clinical syndromes, and the full array of ischaemic stroke presentations; 2. Procedural skill, including management of complications secondary to these endovascular/surgical procedures, that is achieved by repetitive supervised training in an approved clinical setting by a qualified instructor; 3. Diagnostic and therapeutic acumen, including the ability to recognise procedural/angiographic complications. Weighing in on the debate, panellist Tommy Andersson (AZ Groeninge Kortrijk, Belgium and Karolinska University Hospital, Stockholm, Sweden) said that when it comes down to it, it does not matter the specialty, as long as the individual possesses the adequate training. “It is not the background, but the training that counts. Why should we accept that untrained people do mechanical thrombectomy when we would not accept it for anything else?” he questioned. At the end of the debate, the consensus was clear from all sides that mechanical thrombectomy operators do not necessarily have to be neuroradiologists, but they must have the proper knowledge, experience and Charing Cross Symposium training as outlined in the respective guidelines.

May 2016

Burst stimulation “generally” more effective than tonic stimulation

A new study has concluded that burst spinal cord stimulation is “in general” more effective than tonic stimulation in patients already familiar with spinal cord stimulation.

arleen C Tjepkema-Cloostermans (Department of Clinical Neurophysiology, MMedisch Spectrum Twente Hospital, Enschede, The Netherlands) and others state in the journal Neuromodulation that it has been suggested that burst spinal cord stimulation (five pulses at 500 Hz, delivered 40 times per second) suppresses neuropathic pain at least as well as conventional tonic spinal cord stimulation, but without evoking paraesthesia. The aim of this study, therefore, was to evaluate the efficacy of paraesthesia-free high and low amplitude burst spinal cord stimulation for the treatment of neuropathic pain in patients who are already familiar with tonic spinal cord stimulation. The study included 40 patients receiving conventional (30–120 Hz) tonic spinal cord stimulation for at least six months. The authors report that all patients received high and low amplitude burst spinal cord stimulation, for a two-week period in a double blind randomised crossover design, with a two-week period of tonic stimulation in between. The investigators evaluated the average visual Image courtesy of St Jude Medical analogue scale (VAS) scores for pain during the last three days of each stimulation period, as well as quality significant additional pain reduction (>30% decrease in that “individual patients can highly benefit from of life (QoL) scores, and patient’s preferences. VAS for pain) during high and/or low amplitude burst burst stimulation”; but caution however, that “the They report that the “average VAS score for pain were stimulation. Eleven patients preferred tonic stimulation, therapeutic range of burst stimulation amplitudes lower during high (40, p=0.013) and low amplitude 15 high amplitude burst stimulation, and fourteen low requires individual assessment”. burst stimulation (42, p=0.053) compared with tonic amplitude burst stimulation”. The study, Effect of burst stimulation evaluated in stimulation (52). QoL scores did not differ significantly. The authors conclude that “burst stimulation is in patients familiar with spinal cord stimulation, was At the individual level, 58% of the patients experienced general more effective than tonic stimulation” and published online ahead of print in April 2016. Paraesthesia may increase Higher spinal cord attention to pain, study finds stimulation frequency may

Continued from page 1 high-density stimulation (p<0.05, one-week trial of subthreshold high- Student’s t-test). Sweet et al explain, reduce epileptic seizure density stimulation (1200Hz/200μsec/ “All subjects reported a positive The ability of spinal cord stimulation to affect spike-and-wave amplitude 90% paraesthesia threshold) impression of change for subthreshold discharges has been suggested as a means to mitigate epileptic and enrolled them if there was at least high-density stimulation compared seizures in recent literature. In an attempt to map the relationship a 50% reduction on visual analogue with conventional stimulation, and between spinal cord stimulation frequency and spike-and-wave scale (VAS) for pain. Patients were there was a trend toward greater discharges, researchers from Aalborg University (Aalborg, randomised into two groups and likelihood for response to subthreshold Denmark) measured their effects in rats. treated with four two-week periods of high-density stimulation in comparison conventional, subthreshold high-density, with sham stimulation (p=0.07, entylenetetrazole severity of seizures. wave spike power and and sham stimulation in a randomised Fisher’s exact test).” was used in These results were frequency were induced crossover design. Notably, Sweet and colleagues Pnine rats to measured against by 130 and 180Hz The study authors report that four of 15 further report that at the end of the induce spike-and- control intervals stimulation frequencies. patients responded to subthreshold high- trial, all of the patients enrolled elected wave discharges. Four without stimulation. The authors noted that density stimulation. “Mean VAS during to continue to receive subthreshold frequencies (30, 80, 130 The researchers the observed reductions conventional, subthreshold high-density, high-density stimulation rather than and 180Hz) of spinal observed significant “may indicate an and sham stimulation was 5.32±0.63, conventional stimulation. cord stimulation were increases in normalised anticonvulsive effect 2.29±0.41, and 6.31±1.22, respectively. The study therefore concluded that in delivered by means spike-and-wave spike of these spinal cord There was a significant difference in pain fact, “Paraesthesia are not necessary for of a cervical-level power and frequency stimulation frequencies, scores during the blinded crossover study pain relief using commercially available epidural electrode. when spinal cord whereas 30Hz spinal of subthreshold high-density stimulation spinal cord stimulation devices, and Electrocorticographic stimulation was cord stimulation induced versus sham stimulation (p<0.05, may actually increase attention to pain. and intracortical signals conducted at 30Hz, whilst the opposite effects Student’s t-test),” they state. Subthreshold high-density stimulation were analysed to derive no significant changes and, therefore, may be Further, a post hoc analysis revealed represents a viable alternative to normalised spike-and- were noted at 80Hz proconvulsive. that patients reported significantly greater conventional stimulation among wave discharges and stimulation. Conversely, The study was attention to pain during conventional patients who are confirmed to have a frequency—data which decreases in both published in the journal stimulation compared with subthreshold clinical response to it.” were used to project the normalised spike-and- Neuromodulation. 20 May 2016 Pulse frequency is “vital Transcranial direct current parameter” for successful spinal stimulation can boost cord stimulation therapy language comprehension, The importance of pulse frequency as a parameter in neurostimulation is well-known. Data published in Neuromodulation: Technology at the Neural Interface offer an analysis of the effects of pulse frequency Penn study finds alteration on stimulation thresholds, paraesthesia site coverage and patient sensation and satisfaction associated with spinal cord How the human brain processes the words we hear and stimulation. constructs complex concepts is still somewhat of a mystery to the neuroscience community. Transcranial easuring changes in perception perception, and at 650Hz for discomfort direct current stimulation (tDCS) can alter our language threshold, therapeutic threshold. Paraesthesia coverage was not processing, allowing for faster comprehension of M perception and discomfort observed to be significantly influenced meaningful word combinations, according to new research threshold, researchers stimulated fifty by pulse frequency. Unsurprisingly, from the department of Neurology the Perelman School of patients at 26 pulse frequency rates the authors noted that pulse frequency Medicine at the University of Pennsylvania, USA. The work between 40 and 1200Hz. Sustaining a significantly “affects patient sensation is published in the Journal of Neuroscience. pulse width of 300μsec, the researchers and satisfaction.” also observed the paraesthesia coverage Given the inverse relationship between ntegrating conceptual done using three separate brain of the painful area, as well as patient pulse frequencies, stimulation thresholds knowledge is one of stimulation sessions in 18 healthy satisfaction and sensation. and therapeutic perception, the authors “Ithe neural functions adults. Subjects donned the tDCS The researchers found a statistically recognise that pulse frequency is a fundamental to human stimulation cap equipped with significant (p<0.05) inversely proportional “vital parameter” to the achievement of intelligence,” says the study’s first electrodes that stimulated the left relationship between pulse frequency therapeutic success. According to these author Amy Price, a neuroscience angular gyrus or the right angular and stimulation threshold, with the data, the quality of paraesthesia and graduate student at Penn. “For gyrus, as well as applied a fake mean threshold decreasing for all patients’ individual sensory experience example, when we read or listen to form of stimulation known as sham three measures as the pulse frequency can be modified by pulse frequency. a sentence, we need to combine, or stimulation as a control. After each increased. “As pulse frequency increased Considering the implications of their integrate, the meaning of the words stimulation session, subjects were from 40 to 1200Hz, the mean threshold research, the authors suggest that “higher to understand the full idea of the presented with word pairs that decreases from 7.25 to 1.38 (perception pulse frequency may need to be set up sentence. We perform this process could to be semantically integrated threshold), 8.17 to 1.63 (therapeutic at subthreshold amplitude to achieve effortlessly on a daily basis but it is into coherent, or meaningful, perception) and 9.2 to 1.85 (discomfort positive response.” quite a complex process and little is combinations—such as “plaid threshold)”, the authors noted. Differences The study was carried out by David known about the brain regions that jacket” and another set of word became significant at 750Hz for Abejón (Hospital Universitario Quirón support this ability.” pairs that formed non-coherent, or perception threshold and therapeutic Madrid, Spain) and colleagues. Semantic memory is our stored non-meaningful combinations— knowledge about the world, such such as “fast blueberry.” as the meaning of words and This was followed by a letter task objects. “We sought to understand that served as a control for brain Electrical brain stimulation could how and in what part of the brain stimulation effects on vision and semantic representations are attention, in which subjects looked support stroke recovery integrated into more complex at non-pronounceable strings of ideas,” says senior author Roy letters—such as vsbsl vsbql—and Applying an electric current to the brain can help recovery from Hamilton, an assistant professor were asked to indicate whether or stroke, Oxford University researchers have found. Their research is in the departments of Neurology not the letter strings matched. published in Science Translational Medicine. and Physical Medicine & Results showed that stimulation Rehabilitation, and director of to the left angular gyrus resulted team from Oxford’s Nuffield Depart- motor skills were assessed using estab- the Laboratory for Cognition in a faster comprehension of ment of Clinical Neurosciences, led lished clinical measures to see how much and Neural Stimulation at meaningful relative to non- Aby Heidi Johansen-Berg and Char- they had improved. Penn. Recent findings from meaningful word pairs when lotte Stagg, studied the use of transcranial Johansen-Berg says, “The assessments functional MRI scans (fMRI) and compared with both sham and direct current stimulation (tDCS) to support before the training were used to establish magnetoencephalography (MEG) right angular gyrus stimulation. rehabilitation training. a baseline score for motor skills. Further have suggested the angular gyrus, This same effect was not produced In this case, the team used a variant called assessments could then be used to deter- a region of the brain known to in the letter-string task, showing ipsilesional anodal tDCS. Anodal stimula- mine what improvement there was above be involved in language, number that these findings cannot be easily tion has previously been shown to increase that baseline. processing and spatial cognition, attributed to non-specific effects the learning of motor skills in healthy “Three months after training, the group memory retrieval and attention, on attention, motor control or low- people. The hope was that this effect could that had received tDCS had improved as a potential hub for semantic level visual processing. also be demonstrated in stroke patients, more on our clinical measures than those memory integration, specifically “Our findings extend our using tDCS to reinforce training that helps in the control group. This showed that the left angular gyrus. knowledge about the angular patients relearn how to use their body. the patients who had received tDCS were Hamilton and team, which gyrus as a centre wherein the Heidi Johansen-Berg says, “For stroke better able to use their hands and arms for also included Jonathan Peelle, brain constructs higher-level patients, longer and more intensive training movements such as lifting, reaching and an assistant professor in the meaning from individual words leads to greater recovery. However, cost and grasping objects.” Department of Otolaryngology at during semantic comprehension staff availability limit what can be provided. Magnetic resonance imaging scans also the Washington University School and plays an important role in the That means that there is increasing interest showed that those who had had tDCS had of Medicine; Michael Bonner, fluent composition of meaning in therapies that can be used to boost the more activity in the relevant brain areas for a postdoctoral fellow in the in language,” Hamilton says. effects of training.” motor skills than the control group. Department of Psychology at Penn; “They are also consistent with The study included twenty-four vol- The research team conclude that there and Murray Grossman, professor the broader claim that the angular unteers who had had a stroke affecting is positive evidence for the use of tDCS of Neurology and director of the gyrus is a cortical semantic hub.” their hand and arm function, split into two to aid stroke recovery but caution that the Penn Frontotemporal Dementia This work was supported groups. Both groups were given nine days technique must be proved to have long term Center, looked at the role of the left by the National Institutes of of motor training. One group had tDCS benefits not only in clinical measurements angular gyrus in semantic memory Health (AG017586, AG032953, during the training sessions, while the other but also in the ability to carry out tasks im- by applying high definition tDCS in AG038490, NS044266, NS053488, group acted as a control. portant to daily life. Larger studies, they say, healthy adults to modulate neural AG00255), the Wyncote Before, and at various times up to three will be needed before this approach could activity and determine its effect Foundation, and the Jameson- months after the training, the volunteers’ enter routine clinical care. on semantic integration. This was Hurvich fund. May 2016 21

of the responders discontinued their pain medication use during the pilot study. Product News First US commercial implants of Axium DRG system announced St Jude Medical has announced the US launch and first FDA clears Stimwave’s miniature peripheral nerve stimulator will minimise the need post-approval implants of the St Jude Medical Axium StimQ peripheral nerve stimulator for surgery in patients who already are suffering from Neurostimulator System for dorsal root ganglion pain. It has long been needed and now is finally a reality.” (DRG) stimulation to treat patients with chronic pain The technology uses a miniature device—which is that has been hard to control with traditional spinal less than 5% of the size of other standard implanted cord stimulation (SCS). First commercial implants of options—that delivers small pulses of energy, in a the device were performed at the Center for Pain Relief fully-selectable manner, to electrodes placed at a in Charleston, USA by Timothy Deer, and at the Sutter peripheral nerve. The implant is powered by a small, Santa Rosa Surgery and Endoscopy Center in Santa flexible and comfortable wearable external fabric Rosa, USA, by Jason Pope. patch unit. In the coming weeks, DRG implants will occur in The company previously received FDA clearance half the states in the United States. St Jude Medical for the Freedom-8A/4A spinal cord stimulation has already partnered with implanting chronic pain (SCS) system, which utilises the same technology specialists who will conduct more than 100 procedures specifically for back and leg pain based on placements in 59 centres nationwide in the first month after launch. only in the spinal column region for the device. Over the course of the year, the company expects to have more than 300 physicians across the country Neuros Medical completes interim trained to effectively deliver DRG therapy to patients analysis of pivotal study for post- in immediate need of targeted stimulation to alleviate amputation pain chronic pain resulting from moderate to severe chronic Stimwave intractable pain of the lower limbs in adult patients with Complex Regional Pain Syndrome (CRPS) types Stimwave has begun to market the StimQ peripheral I and II. nerve stimulator (PNS) system for the relief of severe “Although many chronic pain patients can find relief intractable chronic pain of peripheral origin. from a traditional spinal cord stimulation device, many The system is designed to provide relief to peripheral patients suffering from focal chronic pain including nerves with an implantable device that can be optionally CRPS I and II do not receive adequate pain relief placed through a needle-sized cannula to next to from spinal cord stimulation,” Deer says. “Adding peripheral nerve locations where the pain is originating. dorsal root ganglion stimulation with the Axium The StimQ PNS system, the world’s first wireless, neurostimulator system to my therapeutic arsenal is fully-programmable PNS (peripheral nerve an exciting step in the treatment of chronic intractable stimulator) neuromodulation device, also received US pain of the groin, knee and foot. I am impressed with Food and Drug Administration (FDA) 510k clearance the speed in which I am able to reach and stimulate this month. the dorsal root ganglion, something I was unable to do “By providing an alternative to opioids, our before the Axium neurostimulator system. For the first Freedom spinal cord stimulation (SCS) system time, I now have a device designed specifically for the helps minimise back and leg pain, and now our new large and growing number of under-treated chronic StimQ PNS System expands the treatment field Neuros Medical has announced that it has successfully pain patients I could not previously serve.” by pinpointing stimulation directly to the affected completed a planned interim analysis of its pivotal Stimulation of the DRG, a spinal structure peripheral nerves,” says Stimwave chairman and chief study. The study is designed to evaluate the Altius densely populated with sensory nerves that transmit executive officer, Laura Tyler Perryman. “The StimQ System High Frequency Nerve Block technology for information to the brain via the spinal cord, allows PNS System can be placed directly at the site of pain the management of post-amputation pain. physicians to treat the specific areas of the body at many peripheral nerve locations without wires and As part of the interim analysis, an independent where pain occurs. The St Jude Medical Axium bulky battery implants.” data monitoring committee conducted a statistical neurostimulator system is the only therapeutic The StimQ PNS System can be implanted through probability analysis focused on safety as well as approach of its kind designed to treat moderate to a standard needle size insert or small incision. efficacy factors for the first 20 patients enrolled. severe chronic intractable pain of the lower limbs According to a company release, this wireless Based on the results, the committee recommended in adult patients with CRPS. Patients with CRPS neuromodulation approach is expected to significantly continuation of the study. are often underserved by conventional medical reduce the lifetime cost of care for chronic pain “The interim analysis provides hope for this management and many interventional pain procedures. patients and offer a safe, viable and effective promising therapy and for a successful pivotal study. Many patients have tried multiple treatment options alternative to pain medications. The Neuros High Frequency Nerve Block therapy without receiving adequate pain relief. Sanjay Gupta, president of the American Pain is truly a paradigm shift in treating chronic pain, “Stimulation of the dorsal root ganglion is the Association and principal clinician at Atlantic Pain especially post-amputation pain, due to its on-demand and Wellness Institute, says “Our country is facing blocking effect,” says Leonardo Kapural, the study’s a horrible epidemic of drug overdose deaths, which principal investigator, from the Carolinas Pain Institute has led the American Pain Association to launch an in Winston-Salem, USA. awareness campaign. These wireless products provide “The successful completion of the interim analysis an alternative to opioids, which is much needed in the marks an important step in our goal of providing armamentarium for effective pain control.” a proven, safe, and effective therapy for patients This new indication will allow the use of wirelessly suffering from chronic pain,” states Jon J Snyder, powered, micro-technology neurostimulators to be president and chief executive officer of Neuros used for the treatment of various pain syndromes Medical, “And is a testament to the commitment of including, but not limited to: shoulder, upper our pivotal study principal investigators and clinical extremity neuropathies, mid and low back pain, chest research coordinators, as well as the team at Neuros.” wall pain, abdominal wall pain, hernia pain, pelvic The prospective, randomised, controlled pivotal pain, as well as lower extremity neuropathies at the clinical trial will consist of up to 130 patients at 15 knee, tibial, ankle, and foot. institutions to evaluate the safety and efficacy of “The major issue with peripheral nerve stimulators Neuros Medical’s Altius System. When completed, the in the past has always been the bulk and length of results will support a PreMarket Approval Application cables, connectors and pulse generators needed to to the FDA in order to market the device. The pivotal stimulate a small target that is often ‘out on a limb,’” study builds off of Neuros’ long-term pilot study, in says Richard North, consultant and retired professor which patients are nearing four years of device use and of Neurosurgery at John Hopkins University School over 4,300 uses to date, and patients continue to report of Medicine, Baltimore, USA. “A miniature wireless significant pain reduction. In addition, more than half 22 May 2016

eagerly awaited the approval of this lead for the Senza SCS system,” says Ashwini D Sharan, professor and program director of Neurosurgery at Thomas Jefferson Product News University, USA. “In my practice, I have already witnessed the significant advantages of HF10 therapy, which provides superior pain relief for chronic back and first therapy option designed specifically for patients Department of Neurosurgery at Yale University School leg pain patients. Now, with the ability to use surgical suffering from complex regional pain syndromes. of Medicine and principal investigator of the study. “The leads with the Senza SCS system, I look forward to This serious and traditionally challenging to treat FLARE study will help to determine whether patients providing Nevro’s therapy to a broader set of patients.” chronic pain condition can occur from complications may benefit from a minimally invasive procedure, such The Senza system is the only SCS system that to recovery from surgeries such as knee arthroscopy, as LITT. FLARE is designed to provide important delivers Nevro’s proprietary HF10 therapy, an SCS foot surgery or hernia surgery,” Pope says. “Having insight into the safety and efficacy of this approach and therapy that provides electrical pulses to the spinal cord a treatment option rooted in clinical evidence its potential impact on neurocognition and seizures. This to alleviate pain. The electrical pulses are delivered by fundamentally changes our approach to treating patients. study is an important step forward in evaluating a new small electrodes on leads that are placed near the spinal I am thrilled to be among the first in the United States to modality designed for medically refractory epilepsy.” cord and are connected to a compact, battery-powered offer previously underserved patients this revolutionary FLARE is designed to evaluate the generator implanted under the skin. technology.” performance of LITT using the HF10 therapy is the only SCS therapy indicated to According to the Institute of Medicine, chronic pain Monteris NeuroBlate System for provide pain relief without paraesthesia (a stimulation- affects more than 100 million Americans, an incidence the treatment of drug-refractory induced sensation, such as tingling or buzzing, which rate which outpaces heart disease, cancer and diabetes medial temporal lobe epilepsy is the basis of traditional SCS) and is also the first SCS combined. Neuropathic pain represents one of the most in appropriate candidates. The therapy to demonstrate superiority to traditional SCS for prevalent yet under-treated forms of chronic pain in the primary endpoint of the study is back and leg pain in a comparative pivotal study. United States, with an estimated one in every 10 adults to characterise the safety of laser over the age of 30 suffering from the condition. ablation surgery with the NeuroBlate Abbott to acquire St Jude Medical “Since the approval of dorsal root ganglion System in this patient population, stimulation with the Axium system in February 2016, including evaluation of adverse we have focused on a strategic rollout with a disciplined events and neuropsychological training program for physicians across the country. changes. Seizure outcome and We believe this approach ensures patient access to quality of life will be evaluated this highly effective new therapy to help manage their as secondary endpoints. Patients chronic pain,” says Allen Burton, medical director of enrolled in the study will undergo Neuromodulation and vice president of Medical Affairs laser ablation surgery and will at St Jude Medical. “The first Axium system implants then be followed for 24 months. in the United States reflect our ongoing commitment to Monteris Medical expects to initiate working with our physician partners to deliver on our FLARE in the second half of 2016 promise to transform the treatment of chronic pain.” and estimates that it will take Initial results from the ACCURATE IDE study, the approximately 3.5 years to complete largest study to date evaluating patients suffering from the study. neuropathic chronic intractable pain associated with “Refractory epilepsy represents a CRPS I and II or peripheral causalgia (PC), showed significant unmet medical need. The DRG stimulation provided patients with superior pain FLARE study will help increase relief over traditional tonic SCS. Approval of DRG our understanding of the potential Abbott is set to acquire St Jude Medical, expanding its stimulation with the Axium Neurostimulator System benefit the NeuroBlate System portfolio to cover cardiovascular markets such as atrial was based in part on the results of this study in which may have on the quality of life of fibrillation, structural heart and heart failure as well as patients were randomised to receive either DRG patients living with this serious and neuromodulation. The combined company will thus stimulation delivered by the Axium neurostimulator debilitating disease,” says Daryle produce devices across cardiovascular, diabetes, vision system or traditional tonic SCS therapy delivered by a Petersen, vice president, Clinical and neuromodulation markets. competitor’s system. Affairs at Monteris Medical. Miles D White, chairman and chief executive officer, Abbott, says, “The combined business will have a Monteris Medical receives IDE FDA approves new powerful pipeline ready to deliver next-generation approval from FDA to evaluate surgical leads for Senza medical technologies, and offer improved efficiencies NeuroBlate in patients with medically SCS System for health care systems around the world.” refractory epilepsy Nevro has announced that it has Michael T Rousseau, St Jude Medical president and Monteris Medical has announced that the US Food received US Food and Drug chief executive officer, says, “Our combined scale will and Drug Administration (FDA) has approved the Administration (FDA) approval expand the global reach, competitiveness and impact Investigational Device Exemption (IDE) to evaluate the for its surgical leads, which are of our medical device innovation for physicians and NeuroBlate System in medically refractory epilepsy. specifically designed for use with the hospitals.” With this approval, Monteris will initiate the Feasibility Senza Spinal Cord Stimulation (SCS) New medical devices planned for release across study on laser interstitial thermal ablation for the System delivering HF10 therapy. diverse markets by the combined company include: treatment of medically refractory epilepsy (FLARE). “Placement of surgical SCS leads „„St Jude Medical’s EnSite Precision next-generation This multicentre, open-label prospective study is is an important clinical option for cardiac mapping system, designed to allow physicians expected to enrol up to 45 patients at as many as eight many surgeons and their patients,” to visualise and navigate catheters in the heart during clinical sites in the USA, with the goal of evaluating says Michael DeMane, chairman ablation procedures; approximately 30 patients using laser interstitial thermal and chief executive officer of „„ MultiPoint pacing technology using quadripolar therapy (LITT) for neurosurgical applications. Nevro. “With the approval of technology, which is designed to provide additional Since obtaining initial FDA clearance in 2013, the Nevro surgical leads, we can options for cardiac resynchronisation therapy patients NeuroBlate System has been used by surgeons to now enable more surgeons to who are not responsive to other pacing options; destroy and coagulate neurosurgical soft tissue lesions. deliver on the promise of HF10 „„ Proclaim Elite recharge-free spinal cord stimulation The Centers for Disease Control and Prevention therapy. Consistent with the US system; and estimate that there are about 2.9 million people in the launch of HF10 therapy, the Nevro „„ Prodigy chronic pain system—a device used for USA with active epilepsy and that about one third of organisation is prepared to initiate a treating chronic pain which is MRI safe, upgradeable, these patients continue to experience seizures despite responsible and staged rollout to US featuring St Jude Medical’s proprietary Burst treatment with one or more anti-epileptic drugs. surgeons and the patients they serve technology. “Many refractory epilepsy patients in the USA to ensure we deliver the clinical „„ Abbott’s FreeStyle Libre, a sensor-based glucose are eligible for resection surgery treatment, but the outcomes that are the foundation of monitoring system; vast majority of patients and their doctors choose our therapy and company.” „„ Tecnis Symfony, a continuous range of vision not to undertake such an invasive procedure due to “My fellow surgeons and I have intraocular lens for the treatment of people with the underlying risks associated with traditional open cataracts; and brain surgery,” says Dennis Spencer, chair of the Nevro leads „„Absorb, a bioresorbable coronary stent.

24 Market watch May 2016

90 minutes… Our hypothesis is that we will deliver hospital-level standard of stroke care faster, equally safe, but with better outcomes due to the ability to Product News intervene much earlier,” says Alexandrov. “Our ‘time to treatment’ target is less than one hour.” The mobile stroke unit is funded through a public- NICE provides positive guidance First mobile stroke unit with advanced private collaboration for which more than US$3 mil- on gammaCore treatment for the CT imaging capabilities launched in lion has been raised, which will enable operation for prevention and acute treatment of Memphis, USA up to three years. The unit will operate 12 hours a day, migraine and cluster headache one week on and one week off beginning late April The UK’s National Institute of Health and Care 2016. Excellence (NICE) has published guidance that “The mobile stroke unit will be based in the heart of electroCore’s non-invasive vagus nerve stimulation a 10-mile, most critical needs areas of Memphis with treatment (gammaCore) for the prevention and acute the highest incidence of stroke, but can be deployed treatment of migraine and cluster headache is safe and within the entire metro region. We estimate that 300 can now be used in the NHS. patients will need to be treated by the Mobile Stroke The guidance issued by NICE showed that among Unit to prove its effectiveness over the course of three the five separate clinical trials of gammaCore they years,” says Alexandrov. “We believe this study will reviewed, many patients experienced substantial and help establish a baseline of results that medical com- meaningful benefit from the therapy. munities worldwide can use to develop and deploy Among cluster headache patients, this benefit similar programs to affect stroke outcomes.” included significantly fewer headache attacks, complete headache relief in some patients within Mobile stroke unit Toshiba partners with UC Irvine for minutes of using the device, supplementary headache study of cerebral microbleeds in high treatments were needed on fewer occasions, and there The University of Tennessee College of Medicine in school football players was an improved quality of life. Memphis, USA has introduced the world’s most com- As chronic traumatic encephalopathy stands in the In the migraine trials reviewed, NICE found that prehensive mobile stroke unit, designed to conduct and national spotlight for high impact sports, the Univer- there was pain relief in about half the patients and produce advanced quality imaging for stroke diagnosis sity of California, Irvine has partnered with Toshiba complete pain relief in around 20% of patients within and noninvasive computed tomography (CT) angiogra- America Medical Systems for a first-of-its-kind study two hours of using gammaCore. They also found that phy with a Siemens Somatom Scope CT scanner. of cerebral microbleeds in high school football players there was relief from sickness, sensitivity to light According to a press release, this is the first time CT as a potential precursor to chronic traumatic encepha- and noise in up to 50% of patients, recovery from capabilities of this magnitude have been available in lopathy. The study will utilise Toshiba’s Vantage Titan disability in about 30% of patient within two hours and a mobile setting. This is intended to create the ability 3T MR system as the key diagnostic tool, taking additional migraine treatments were only needed in to diagnose and launch treatments, including tissue advantage of its non-invasive capabilities. about half the patients two hours after treatment. plasminogen activator (tPA) treatment and nicardipine The study will investigate the use of non-contrast JP Errico, chief executive officer and founder of within the first hour, and select patients for endovascu- MRI as a safe and noninvasive way to examine youth electroCore commented, “We are very pleased that lar interventions, neurosurgery and neuro-critical care athletes and other patients for early signs of chronic with this guidance gammaCore can now be used directly from the prehospital arena. traumatic encephalopathy, a degenerative disease across the NHS which will open up this treatment to This unit is designed to prep a patient straight for the found in those who suffer head trauma and a well- more patients suffering from these very debilitating catheterisation laboratory, neuro intensive care unit or documented consequence of sub-concussive head conditions. While these five studies represent a hospital stroke unit, bypassing a stop in the emergency injury. This will include evaluations of local high significant number of patients, we have conducted and department entirely. school student volunteers, including 100 test subjects continue to conduct a number of additional clinical “We are thrilled to have this medical first in Mem- (football players) and 50 control subjects (non-football trials that will be used to update NICE to advance the phis. I want to stress that the mobile stroke unit is a players). Toshiba will provide application training to guidance available to patients and providers throughout product of worldwide industry leaders,” said David UCI researchers concerning the use of Toshiba’s MRI the UK.” Stern, the Robert Kaplan Executive Dean and Vice- equipment. The gammaCore device, which is CE marked, is Chancellor for Clinical Affairs for The University of “There have not been extensive studies of chronic widely used across the world and is available across Tennessee College of Medicine and The University of traumatic encephalopathy in younger populations to the UK at specialist headache clinics and through Tennessee Health Science Center. “The vehicle frame- date, so we see this as an important opportunity to neurologists. work is from Canada…the scanner was developed by examine if there are precursors or early signs that can The treatment is easily self-administered by a German company, the custom assembly took place lead to better diagnosis and treatment,” says Mark patients, by placing the gammaCore on the side of in New York, with the oversight and direction coming Fisher, UCI professor of Neurology and study lead the neck, over the vagus nerve (where the pulse from University of Tennessee College of Medicine in researcher. “Using Toshiba’s Titan 3T MR system, we is felt), and stimulating for two minutes. Multiple Memphis.” may have an effective way to examine how playing doses can be administered, with a typical treatment The Mobile Stroke Unit, weighing in at more than football is affecting these patients, and we hope to lasting between four and six minutes. The number 14 tons, includes features and capabilities such as: break new ground in diagnosing and treating head of treatments per day is dependent on the type of „„A hospital-quality CT scanner with advanced imag- trauma before it can potentially cause problems for headache and treatment regimen advised by the ing capabilities to not only allow brain imaging, but these athletes in the future.” treating clinician. also imaging of blood vessels in the brain. The Vantage Titan 3T MR was chosen for its ability According to electroCore, two of the benefits of „„A dedicated gantry automatically moves the patient to provide non-contrast neuro imaging. This includes gammaCore are, first, that there are no serious side to obtain images, providing the same number of elements such as a suite of advanced neuro-imaging effects, particularly compared to other headache slices in high resolution as obtained and expected in sequences and Pianissimo noise-reduction technology, treatments (a few patients experienced a local skin the hospital setting. and in particular its ability to determine the prevalence irritation at the site of stimulation, but that was „„ The unit is to be staffed with stroke fellowship- of cerebral microbleeds using the Flow Sensitive Black mild and transient), and second, that patients can trained, doctorally-prepared nurses certified as Blood sequence. take existing medications without any known drug advanced neurovascular practitioners. interaction side effects. This allows the patient to „„ It is the largest mobile stroke unit in the world, decrease the use of some of their existing medications complete with an internal power source designed to or to use combination treatments with minimal risk. match regular electrical outlet access. Nicholas Silver, consultant neurologist at the Walton „„ The unit should transport trainees and researchers Centre for Neurology and Neurosurgery said: “We as interested in the science of early stroke management. specialists very much welcome the emergence of new “We have a tremendous burden of stroke in Shelby therapies such as gammaCore that may potentially County, with a stroke rate per 100,000 population that provide safe, effective and reliable treatment, both to is 37% higher than the national average,” says Stern. prevent attacks of headache and also to treat attacks “The goal of the mobile stroke unit is to minimise mor- when they occur. In my view, electroCore are to be bidity and mortality, to have more patients walk out of congratulated on their innovation and the development the hospital fully functional.” of a high quality worldwide research program to find “If we eliminate the treatment delay getting to better treatments in these conditions.” and through the emergency room, we can save up to Vantage Titan 3T May 2016 Market watch 25

and outcome information to the database through Quentry, a web-based image sharing service, which employs advanced encryption and access-control Product News technologies to ensure that all sensitive medical information is secure. “Over the next two years, all 30 hospitals in the “This study presents an opportunity to determine distinguish it and provide a substantial advantage registry are expected to upload thousands more how Toshiba’s MRI equipment can be used by health- over its competitors.” patients,” says Jason Sheehan, Harrison Distinguished care providers to safely and effectively diagnose seri- Aviv Lotan, chief executive officer of Amnis Thera- Teaching Professor & Vice Chair, Department of ous brain trauma or chronic traumatic encephalopathy peutics, noted: “The results of the recent trials prove Neurological Surgery, University of Virginia Health earlier than ever before, which could ultimately impact that the product is safe and effective in thrombectomy System (Charlottesville, USA). “In an era of evidence- a patient’s quality of life in the future,” says Eugene in an animal model. Moreover, the results significantly based medicine, this SRS Registry offers the potential Mensah, director, Clinical Collaborations, Toshiba. support the company’s belief of the Golden Retriever’s to provide concrete guidelines and process benchmarks “We are proud to have the researchers using Toshiba’s superiority over its competitors, and our ability to of- that could change patient outcomes on a global scale.” Vantage Titan 3T MR system to establish these po- fer the market a product which was designed for neuro Current US sites providing patient data via Brainlab tential markers of chronic traumatic encephalopathy, thrombectomy and is better, safer, more effective and Quentry: which speaks to Toshiba’s commitment to partnering easier for use. Neuro thrombectomy is a large market, „„University of Colorado Hospital, Aurora with healthcare providers to identify the right imaging growing impressively each year, so an effective solu- „„ University of Virginia Health System, solutions to complex clinical situations.” tion is sure to be very attractive to target audiences and Charlottesville potential strategic partners alike.” „„ University of Southern California Norris Golden Retriever safe and effective in The company intends to continue the validation pro- Comprehensive Cancer Center, Los Angeles pre-clinical trials cess towards a clinical trial estimated in Q4 2016. „„ Mayfield Clinic—University of Cincinnati, The Golden Retriever is made of minuscule me- Cincinnati tallic strands, which open/deploy inside „„ Jefferson Hospital for Neuroscience, Philadelphia the blood clot and grip it strongly „„ Norton Cancer Institute, Louisville and it is expected to be the „„ Carolina Neurosurgery and Spine, Charlotte smallest in the market „„ Ronald Reagan UCLA Medical Center, Los Angeles compared to current „„ Penn State Hershey Medical Center, Hershey competition. Its size „„ Northwell Health, Great Neck (formerly North Golden Retriever and flexibility enable Shore LIJ) Amnis Therapeutics has announced successful quick and easy access By the end of the summer, five additional facilities in results in its pre-clinical trials, which tested the to blood clots, usu- the USA are set to begin uploading data to the SRS safety and efficacy of the Golden Retriever neuro ally located in middle cerebral artery in the brain. In Patient Registry: thrombectomy device. The safety trial was conducted addition, the device is capable of extracting large, long „„ Huntsman Cancer Institute, University of Utah, Salt in Israel, while the efficacy trial was conducted in a complex blood clots in a single procedure. Lake City US lab. Amnis Therapeutics will present the positive results „„ Yale New Haven Health System, New Haven According to a company press release, the safety at the Advanced Treatment in Neuro Therapeutics „„ University of Rochester Medical Center, Strong trial comprised catheterisations in two animals. The Meeting on 2 May in Tel Aviv, Israel. Memorial Hospital, Rochester effect of the product on the functioning of six blood ASTRO and AANS lead the Scientific Advisory vessels in which it was operated was tested and National Stereotactic Radiosurgery Committee charged with providing strategic oversight compared to a competing product. (SRS) patient registry gains for the registry. Analysis of the de-identified patient In the trial, both angiographic parameters momentum data will be scientifically published, and the fully (radiographic visualisation of blood vessels during the Brainlab has enrolled 11, to date, of the expected de-identified data elements will subsequently be made catheterisation) and histologic parameters (microscopic 30 hospitals and healthcare systems in the national available in the public domain. blood vessel structure) were tested. Stereotactic Radiosurgery (SRS) Patient Registry. The results of the trial showed the Golden Retriever Launched in partnership with The American Neuravi stent retriever platform not to have any significant side effects during the Association of Neurological Surgeons (AANS) receives new US patent catheterisation and the blood vessels to be altogether and the American Society for Radiation Oncology The US Patent and Trademark Office (USPTO) has undamaged and fully functional following a 30-day (ASTRO), the patient registry will gather important approved a patent providing additional coverage of follow-up period. On the other hand, the release patient data, aiming to define national patterns of care Neuravi’s therapeutic stent-retriever platform for the states, the competing product demonstrated significant in radiosurgery, with an eye to improving health care endovascular treatment of acute ischaemic stroke. pathological findings in the blood vessels walls after outcomes, supporting informed decision-making and Earlier this year, Neuravi also received a European 30 days (including trauma to artery layers and emboli) potentially lowering the cost of care for patients. patent grant for this platform. in two of the six treated vessels. Overall, this pre- To date, the SRS Patient Registry is gathering de- The Neuravi intellectual property estate now clinical trial demonstrated the high safety profile of the identified data on almost 400 patients at the diverse, extends to 63 US filings, 34 granted patents, one Golden Retriever compared to the competitor in the high-volume enrolled facilities. The registry logs the notice of allowance, and 28 pending applications. tested animal model. de-identified SRS treatment information of patients Outside the USA, Neuravi has multiple pending The efficacy trial comprised of 16 catheterisations, affected by brain metastases, benign brain tumours and applications with the European Patent Office, in each including the extraction of blood clots from arteriovenous malformations (AVMs). The SRS patient China and Japan, and internationally under the Patent various arteries. The blood clots were similar in their registry is set to prospectively collect data from 30 of Cooperation Treaty. qualities and size to those typically found in stroke the best hospitals in the USA over a three-year period, The design of Neuravi’s EmboTrap cases. The interventionalists succeeded in extracting and under the banner of quality, generate a large clinical Revascularisation device was informed by research 15 of the 16 blood clots, with 13 clots extracted at first database, unlike any other. on the wide range of different clot types that can attempt, one at the second attempt and one at the third “This level of detailed patient data analysis can cause ischaemic stroke. Insights from this research attempt. One catheterisation was deemed a failure. change the way we look at methods and patterns of care led to the enhancement of the proprietary design of Overall, the Golden Retriever achieved a score of from a both a population database and personalized both the EmboTrap and future Neuravi devices in 93.8% in the efficacy trial, as well as very positive medicine perspective,” says Brian Kavanagh, development, according to a company release. feedback regarding its effectiveness and ease of use Department of Radiation Oncology, University of The EmboTrap Revascularisation Device is (an accumulated score of 30 of 30), the company Colorado School of Medicine, Aurora, USA. “The more available in Europe to treat patients with acute release states. patients we upload into the registry, the closer we can ischaemic stroke. The EmboTrap is not currently The catheterisations were performed by the approach our ultimate goal of thoroughly understanding approved in the USA, where it is available for company’s consultants, Professor Ronit Agid, from SRS best practices so that we can help improve patient investigational use only in the ARISE II clinical trial. Toronto Western Hospital in Canada and Professor outcomes.” Adnan Siddiqui, director of the Neurosurgical Stroke Brainlab transfers Service, Kaleida Health in Buffalo, New York, USA. treatment Agid noted that, “The ease of using the device, its small size, which enables the fast and relatively easy access to the clot, as well as its flexibil- ity and effective grasp and grip of the clot, EmboTrap 26 Societies May 2016

of events Society News Calendar team

Editor-in-chief: American Association of from the University of Arkansas in 1978 2016 Prof Philip M Meyers Neurological Surgeons and his medical degree from the University names Frederick A Boop of Arkansas for Medical Sciences in 1983 20–23 May 3–5 October Publisher: president (both Fayetteville, USA). He completed WIP: World Institute SLICE: Stroke Live Roger Greenhalgh Frederick A Boop has been named his internship at The University of Texas of Pain Congress Course president of the American Association Health Science Center (Austin, USA); his New York, USA Nice, France Head of Publishing: of Neurological Surgeons (AANS). His residency at The University of Texas Health W: www.wip2016.kenes.com W: www.slice-online.com Marcio Brito appointment was announced during the Science Center; his neurology rotation at 84th AANS Annual Scientific Meeting (30 the Institute of Neurology, The National 23–25 May 16–19 November April–4 May, Chicago). Hospital, Queen’s Square, in London, UK; LINNC: Live SVIN: Society Editor: Named one of America’s top doctors by his paediatric neurosurgery rotation at Interventional of Vascular and Amanda Nieves US News and World Report in 2012, Boop The Hospital for Sick Children, Toronto, Neuroradiology and Interventional [email protected] is currently the JT Robertson professor and Canada; his epilepsy and functional neu- Neurosurgery Course Neurology Annual chairman of the department of neurosurgery rosurgery fellowship at the University of Paris, France Meeting Editorial contribution: at the University of Tennessee Health Sci- Minnesota (Minneapolis, USA); and his W: www.linnc.com Brooklyn, USA Katherine Hignett ence Center in Memphis, USA. Additionally, paediatric neurosurgery fellowship at the W: www.svin.org he works as the co-director of the LeBonheur University of Arkansas for Medical Sci- 27–29 May Design: Neuroscience Institute (Memphis, USA). ences. He received his American Board of WLNC: World 28–30 November David Reekie Aside from his leadership role within the Neurological Surgery certification in 1993, Live Neurovascular UK Stroke Forum AANS, Boop’s professional memberships his American Board of Pediatric Neurologi- Conference Conference Layout: include the American Board of Neurological cal Surgery certification in 1996 and his Shanghai, China Liverpool, UK Naomi Amorra Surgery (ABNS), the American Board of Gamma Knife certification in 2000. W: www.wlnc.net W: www.stroke.org.uk Pediatric Neurological Surgery (ABPNS), AANS has also announced the appoint- Advertising: the International Society of Pediatric Neu- ment of Alex B Valadka as president elect of 25–29 July Shilpa Suthar rosurgeons (ISPN) and NeurosurgeryPAC, the society. SNIS: Society of 2017 [email protected] where he served as president. In 2010, he In addition to Virginia Commonwealth NeuroInterventional received the Endowed Chair of Pediatric University’s (VCU) professor and chair of Surgery 13th Annual 19–22 January Neurosurgery at St Jude’s Children’s Re- the Department of Neurosurgery, Valadka Meeting & Fellows NANS: North Subscriptions: search Hospital (Memphis, USA). is also a director of the American Board of Course American Sue Couch “The AANS has been fortunate to have Neurological Surgery (ABNS) and, most Boston, USA Neuromodulation [email protected] a succession of vibrant, innovative leaders recently, served as the AANS Treasurer. He W: www.snisonline.org Society Annual Meeting over the past years, and I’ve enjoyed the has also served as chair of the Washington Las Vegas, USA Please contact the time I’ve served on the Executive Com- Committee for Neurosurgery. Prior to joining 4–8 September W: www.neuromodulation.org NeuroNews team with mittee. I spent three years as secretary and VCU, he served as chairman and chief ex- EANS: European As- news or advertising this past year as president-elect learning ecutive officer of the Seton Brain and Spine sociation of Neurosur- 22–24 February queries the organisation and its major initiatives, Institute in Austin, Texas; the largest and gical Societies Annual ISC: International Tel: +44 (0)20 7736 8788 which has helped prepare me for my new most comprehensive neuroscience program Meeting Stroke Conference role. The AANS continues to do amazing in Central Texas. Athens, Greece Houston, USA Published by: things for its membership, and I will keep the Valadka has a strong clinical and research W: www.eans2016.com W: www.heart.org BIBA Medical, momentum going during my tenure. From interest in neurotrauma and critical care, 526 Fulham Road, the NeurosurgeryPAC in Washington, DC as evidenced by his research funding and 8–10 September 27 May–1 June Fulham, London, (USA), working key legislation; to our own, publications. He has been an investigator ESMINT: European INS: International SW6 5NR, UK neurosurgeon-designed-and-defined data and co-investigator on 18 research grants, Society of Minimally Neuromodulation Tel: +44 (0) 20 7736 8788 collection group, NeuroPoint Alliance; to our including serving as initiating investigator on Invasive Neurological Society World Fax: +44 (0) 20 7736 8283 efforts to provide and fund top-notch educa- a US$33.7-million Department of Defense Therapy Annual Congress tional opportunities for the best medical can- research consortium on mild traumatic brain Meeting Edinburgh, UK Printed by: didates through the Neurosurgery Research injury. He is author or co-author on more Nice, France W: www.neuromodulation.com and Education Foundation; the AANS is the than a hundred scientific papers, as well as W: www.esmint.com Buxton Press voice of neurosurgery, and I’m proud to be dozens of book chapters. He co-edited the part of its legacy,” states Boop. textbook Neurotrauma: Evidence-based Reprint requests and all Boop received a Bachelor of Arts degree Answers to Common Questions. correspondence regarding the newspaper should be addressed to the editor at the above address.

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