NeuroNews Issue 31 by BIBA Publishing

Sept

Issue

18 31 Steven Levine

To treat or not to treat? Page 14

Urs Fischer

Profile

Page 12

Page 19 17

SCENT trial leads to first ever indication of flow diverter to treat challenging aneurysms The results of the Surpass intracranial aneurysm embolization system pivotal trial to treat large or giant wide neck aneurysms (SCENT trial) showed that the device is successful in treating challenging aneurysms. The results led to the device becoming the first flow diverter to be indicated by the US Food and Drug Administration to treat large and giant posterior communicating artery aneurysms.

he Surpass flow diverter (Stryker) is the only flow diverter to be indicated to treat large and giant posterior communicating artery aneurysms and only the second flow diverting stent to gain US FDA approval. In the SCENT trial, the Surpass Streamline device achieved a technical success rate of 97.8% (176/180), with an average of 1.1 devices being used per patient. The technical success rate was defined as the proportion of patients in whom the Surpass flow diverter was delivered to cover the aneurysm neck and indicates that the device is manageable by a broad range of operators. Philip M Meyers, professor of Radiology and Neurological Surgery at New York Presbyterian/Columbia University Medical Centre, New York, USA, and co-principal investigator of the study, presented the findings at the Society of NeuroInterventional Surgery 15th annual meeting (SNIS; 23–27 July, San

Francisco, USA). Commenting on the results, Meyers said, “The technical success rate was remarkable, given that there were 26 sites with many operators.” The SCENT trial was a multicentre, prospective, non-randomised trial that aimed to evaluate the safety and effectiveness of the Surpass flow diverter compared to a historical control in the treatment of large or giant wide neck intracranial aneurysms. The investigational device exemption (IDE) study was conducted in accordance with good clinical practice. The trial design extended the region of the internal carotid artery from the petrous segment to the carotid terminus. The trial of another flow diverter device (Pipeline [Medtronic] for Uncoilable or Failed Aneurysm) only tested the device from the petrous segment to the ophthalmic segment. The design of the Surpass device means that it has greater radial force and opens more evenly, even over long

Surpass deployed in vessel

lengths, Meyers explained. The trial was conducted across 26 centres, 25 in the USA and one outside the USA. The required sample size was 180 patients with up to three rollin (training) cases per site, meaning a total of 213 patients were treated, though the results only included those in the intention-to-treat group. In the SCENT trial only patients with

large or giant intracranial aneurysms with a wide neck in which patients were implanted with the Surpass flow diverter. Current common therapies, such as endovascular coiling and surgical clipping, are often not able to treat large or giant intracranial aneurysms with wide necks. The risk of rupture, failed occlusion, and complications during endovascular or surgical treatment for these types of aneurysms is high and treatment options for these aneurysms are extremely limited. Therefore, the longterm success rate for these intracranial aneurysms is low. “Patients suffering from unruptured wide-neck aneurysms are at high risk of neurological event and death. It is important that there are effective and safe options to treat these patients, as if left alone there is a likelihood of these patients experiencing a rupture and haemorrhage is high,” explained Meyers. He continued, “Trying to occlude aneurysms in these complex locations is difficult. These results help to validate the use of the Surpass flow diverter in these aneurysm types. Overall, the majority of patients Continued on page 2

Evidence in favour of DRG stimulation builds with new study Recent research carried out by Huygen and colleagues in view to being published in Neuromodulation confirms that dorsal root ganglion (DRG) stimulation can significantly reduce the severity of patients’ pain and improve their quality of life through 12-months post-implant.

echnological advances have recently led to the development of a spinal cord stimulation system—that can specifically target the dorsal root ganglion (DRG) of the spinal level associated with the painful anatomic area—enabling treatment of chronic neuropathic pain. In previous studies, DRG stimulation has been demonstrated to be safe and effective. A recent randomised, controlled, comparative effectiveness trial of DRG stimulation in patients with chronic neuropathic pain due to CRPS I and CRPS II found that DRG stimulation resulted in superior treatment success compared to tonic dorsal column stimulation

at all follow-up assessments through 12 months. Yet, research surrounding this mode of spinal cord stimulation system is still fresh. The authors write, “To further characterise outcomes, this report presents data from the first postmarket, prospective, observational clinical study of DRG stimulation.” As the investigators aimed to provide real-world evidence for DRG stimulation, the inclusion criteria were particularly broad to emulate the typical clinical environment. Sixty-six patients were recruited (with an average age of 52 years ±11.5) from three investigators’ pain management practices in the Netherlands, during 2012 and 2013. Each

patient had to have intractable pain for at least six months prior to the study, with a minimum baseline pain rating on 60mm on the VAS (visual analogue scale) in the primary region of pain. Regarding the intervention itself, the Axium neurostimulation system (Abbott) was used to place electrodes at the target DRGs. At baseline, the regional distribution of each patients’s primary pain area, including intensity, was mapped. Measures of functioning, quality of life and mood were also assessed. Follow-ups were conducted at one, three, six and 12 months’ post-permanent implant; Continued on page 19

Sept

SCENT trial leads to first ever indication of flow diverter to treat challenging aneurysms Continued from page 1

experienced complete aneurysm occlusion without clinically significant parent artery stenosis or the need for retreatment. This was accomplished with a low rate of observed serious neurological events and mortality associated with the Surpass flow diverter.” The primary effectiveness endpoint was the percentage of patients with 100% occlusion of the aneurysm without clinically significant stenosis (defined as less than or equal to 50% stenosis) of the parent artery based on core lab evaluation of the 12-month follow-up angiogram and without any subsequent treatment of the target aneurysm at the 12-month follow-up visit. The primary safety endpoint was the percentage of patients with neurological death or major ipsilateral stroke through 12 months, which was determined by an independent Clinical Events Committee (CEC). The trial was considered a

Issue

18 31

Intracranial aneurysms

success if the primary effectiveness endpoint rate was statistically more than 50% and the primary safety endpoint rate was statistically less than 20%. The location of the primary effectiveness endpoint shows a majority (69% vs. 31%) of intradural aneurysms vs. extradural, which is different to other studies. Of the study group, 62.8% of patients met the primary

to the FDA requiring four patients who had been CEC adjudicated as not having device related safety failures to be included in the primary safety rate. This increased the safety rate from 8.3% to 10.6%. There was a 2.2% (four of 180 patients) risk of rupture at 12 months compared to around a 50% risk of rupture over five years if left untreated. At 12 months, 89.4% patients were free from neurological event or death. The trial cohort has an average age of 61 years, with the ethnicity demographics

cerebral diseases. To be included in the trial, patients needed to be 19 years or older, have unruptured large or giant saccular or fusiform aneurysm (greater than or equal to 10mm) with wide neck (neck width ≥4mm or dome-to-neck ratio <2) and the petrous segment to the carotid terminus arising from a parent vessel. Artery diameters needed to be 2.5–5.3mm.

Trying to occlude aneurysms in these complex locations is difficult. These results help to validate the use of the Surpass flow diverter in these aneurysm types. effectiveness endpoint, 65.8% of whom with aneurysms located in the posterior communicating artery. There was an 8.3% rate of new or worsening stroke which went up, due

closely mirroring real-world experience. There also was a high percentage of smokers (20% current smokers and 44% had previously been a smoker), which represented a higher risk factor for

Philip M Meyers

Aneurysms treated with hydrogel coils have a significantly reduced recurrence rate when compared to bare platinum coils The use of bare platinum coils resulted in aneurysm recurrence in 15.4% of cases compared to just 4.4% (p>0.001) when hydrogel coils were used. Changes in the Raymond-Roy scale were used to judge aneurysm recurrence, with any progression counting as recurrence.

he preliminary results of the new generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT) were announced at the Society of NeuroInterventional Surgery 15th Annual Meeting (SNIS; 23–26 July, San Francisco, USA). Speaking about the results, principal investigator Bernard R Bendock (Mayo Clinic, Phoenix, USA) said, “Hydrogel second generation coils showed a significant effect in reducing recurrence for 3–14 mm aneurysms.” The study looked at the second generation of hydrocoils (HydroFrame, HydroFill and HydroSoft; MicroVention)

to see if they safely reduced recurrence. compared to the bare platinum coil (5% It was a random, investigator initiated vs. 8%). Adverse events, such as mortality study with an 18–24-month follow-up and rebleeding were similar between the time and based on a nulltwo groups. hypothesis that there was no The trial was carried out at 46 difference in recurrence between sites in the USA and Canada and bare platinum and hydrogel 600 patients were enrolled and coils in treating 3–14mm brain Hydrocoil assigned on a 1:1 basis between aneurysm up to 24 months after the platinum and hydrogel group. treatment. The primary endpoint In the platinum cohort the was that any progression along coiling procedure stipulated that the Raymond scale was considered as only bare platinum coil could be used and recurrence. any bare platinum coil could be used and Although the study was not powered in the hydrogel group the cohort needed to look at retreatment, this also showed to be treated with at least 90% hydrogel better results in the hydrogel coil group coils. In both cohorts, assist devices such

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as balloons and stents could be used. The preliminary packing density was 24.8% for bare platinum coils and 33% for hydrogel coils. There has been a number of approaches over the last few decades on how to prevent aneurysm recurrence. These have included the improved design of platinum coils, bioactive coils, flow diversion and gel coils. The first generation of gel coils was found in animal models to be of benefit but were limited by early swelling and stiffness, limited repositioning time and preparation prior to use, Bendlock explained. The study was entirely funded by MicroVention, but the sponsor had no role in study design, data collection, data analysis or data interpretation, the writing of the report.

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THIS DOCUMENT IS INTENDED SOLELY FOR THE USE OF HEALTHCARE PROFESSIONALS. A physician must always rely on his or her own professional clinical judgment when deciding whether to use a particular product when treating a particular patient. Stryker does not dispense medical advice and recommends that physicians be trained in the use of any particular product before using it in a procedure. The information presented is intended to demonstrate the breadth of Stryker product offerings. A physician must always refer to the package insert, product label and/or instructions for use before using any Stryker product. Products may not be available in all markets because product availability is subject to the regulatory and/or medical practices in individual markets. Please contact your Stryker representative if you have questions about the availability of Stryker products in your area. The Stryker products listed above are CE marked according to the Medical Device Directive 93/42/EEC.

Sept

Issue

18 31

Intracranial aneurysms

Greater obliteration and less in-stent stenosis after ATLAS stent coiling as compared to LVIS Jr According to research published in the Journal of NeuroIntervential Surgery, Atlas stent-assisted coiling outperformed LVIS Jr in terms of greater obliteration rates and lower in-stent stenosis rates for aneurysms treated. The study was carried out at the University of Pittsburgh Medical Center, Pittsburgh, USA, by Bradley A Gross and colleagues.

ntracranial stent designs that facilitate aneurysm coiling are continuing to evolve. Both Atlas (Stryker Neurovascular) and LVIS Jr (MicroVention) are amongst the new group of stents that have emerged to be compatible with smaller delivery; 0.0165 inch microcatheters, facilitating access to daughter branches with more supple microcatheters. The current literature discusses the advantages of delivery via the ‘coil catheter,’ however, omits important potential limitations of both the Atlas and LVIS Jr stents. Gross et al’s research sought to clinically compare the two stents, with an emphasis on comparative rates of both technical success and complications. The study reviewed a prospectively maintained endovascular database, finding 27 patients undergoing deployment of the LVIS Jr, and 37 undergoing Atlas stent placement for aneurysm coiling. There was no significant difference in patient age, sex, previous aneurysm treatment, mean aneurysm size, or aneurysm location. Of five previously treated aneurysms in the Atlas cohort, two had previously ruptured, whilst, of eight previously treated in the LVIS Jr cohort, four had previously ruptured (more than one year before). Otherwise, all were unruptured.

The coil technique—jailing—was similar in both cohorts. The authors note that, whilst the closed-cell design of the LVIS Jr allows for improved retrieval ability and visibility, the open-cell design of the Atlas eliminates foreshortening and allows for better predictability of the proximal landing point of the stent (denoted by the marker). Available in 4mm and 4.5mm diameters, Atlas stents are advantageous in their use for the internal carotid artery (ICA) and vertebral aneurysms; with only one ICA branch aneurysm treated with LVIS Jr, compared with 10 treated with the Atlas. Otherwise, basilar apex and anterior communication artery were the most frequently treated aneurysms in both cohorts. During the procedure, incomplete stent expansion was seen in both cohorts (7% for LVIS Jr, 3% for Atlas), but stent thrombus formation was more frequent after deployment of LVIS Jr (11% of cases vs 0% for Atlas). In this study, all cases of in-stent clot formation were asymptomatic—a phenomenon which has led this finding to likely be unreported within previous studies. Initial clinical results showed that periprocedural ischaemic complications were seen in four patients after LVIS Jr stent deployment (15%) and in one patient after

Atlas stent deployment for coiling (3%). Post-treatment MRI scans were obtained in 23 Atlas patients and 21 LVIS Jr patients. Among the 23 patients with Atlas stents, 35% had DWI lesions; 13% of patients had single punctate lesion and 22% had multiple lesions. Among the 21 patients with LVIS Jr stents, 38% had diffusion-weighted imaging (DWI) lesions; 19% had single punctate lesions, and 19% had multiple lesions. Rates of DWI lesions after treatment did not significantly differ between the two groups. Clinical follow-up was available for all the 37 patients undergoing Atlas stent coiling over a mean period of 12.7 months, and available for 26/27 patients undergoing LVIS Jr stent placement over a mean period of 17 months. In both cohorts, no patients displayed clinical evidence of delayed ischaemic events or sustained aneurysm rupture in follow-up. Only one patient that underwent LVIS Jr stent placement had to be re-treated. Direct comparison between the two cohorts showed a significantly greater rate of aneurysm dome filling among patients treated with the LVIS Jr stent at the last angiographic follow-up (19% vs 0% for Altas, p=0.04). Additionally, there was a significantly greater rate of in-stent stenosis among patients that underwent stenting with

LVIS Jr (19% vs 0% for Altas, p=0.04). Improvement in aneurysm occlusion in patients with initial Raymond 2 or 3 occlusion after LVIS Jr coiling has previously been attributed to a potential ‘flow diverting’ property of the stent. Yet, according to the authors, given similar rates of improvement seen for the Atlas stent, it is difficult to consider that the improvement occurred as a result of a hypothetical ‘flow diverting’ property of the stent itself. The most intriguing result remains the significant difference in rates of in-stent stenosis at follow-up. This finding is less likely to be influenced by biased and may more directly reflect a clinically relevant difference in stent design and resultant performance. Regardless, a larger, multicentre and more representative sample, with a randomised comparison of the two stents, and a longer follow-up period would be preferable for future explorations of stent-assisted aneurysm coiling.

Atlas stent

Wide neck bifurcation aneurysms treated safely in WEB trial The treatment of wide neck bifurcation aneurysms is more incomplete and dangerous than you think, says Adam Arthur (professor of Neurosurgery, University of Tennessee Health Sciences Center, Semmes-Murphey Neurologic and Spine Clinic, Memphis, USA). Talking at the 15th annual meeting of the Society of NeuroInterventional Surgery (SNIS; 23–27 July, San Francisco, USA), he highlighted the unmet clinical need of wide neck bifurcation aneurysms and how the Web Intrasaccular Therapy (WEB-IT) study is helping to address this.

ide neck bifurcation aneurysms account for a large patient population, around 30–40% of all aneurysms, and, due to their complex physiology, they are difficult to treat and often need to be treated surgically. This means that research on other options, like intrasaccular flow disruption, is important. The safety rates for treating wide neck aneurysms vary greatly from 2.7–9.4% and the same is true for occlusion rates. Data from the WEBCAST trial shows complete occlusion in 56% of cases, with 85% of cases having adequate occlusion compared to 29% of aneurysms achieving complete occlusion and 82% achieving adequate occlusion in the CERECYTE (coils) trial. Simulation device training can help physicians prepare and practise their technique with a new device before treating patients. In the WEB-IT study a neurovascular replicator (Vascular Simulation) was used. This allowed physicians to learn how to size and use the Woven Endobridge (WEB, MicroVention) intrasaccular device correctly, as the study had zero roll-in cases. The WEB-IT study is a prospective, multicentre, single arm study looking at the efficacy of the WEB intrasaccular device in treating wide/challenging neck bifurcation aneurysms. Enrolment began in August 2014 and was completed in March 2016. The device is

designed so that they highest density/lowest porosity of mesh is in the area of highest flow. A paper, published in the Journal of NeuroInterventional Surgery, looked at the feasibility of training physicians taking part in the WEB-IT trial using a simulator, with positive results. “The level of safety achieved during procedures was directly comparable to that observed within a group of experienced European physicians,” wrote Arthur, et al. The implementation of the replicator-based training programme involved an initial skill building session where physicians deployed devices in several aneurysms. These aneurysms had varying levels of complexity and allowed investigators to become more comfortable with the procedure and communication with supervising protocol. This was followed by the replication of patient specific anatomy and pre-case rehearsal under the guidance of both supervisors and experienced clinical specialists. Experience obtained during the surgical rehearsal on patient-specific anatomy, which was modelled from imaging data from a patient in the trial, helped operators to anticipate potential challenges with respect to access, device sizing, and device deployment. The ability to perform patient-specific replicated cases within the operator’s angiography suite—on their

own angiography equipment and with their assistants and full surgical team participating—provided a unique opportunity for the entire team to gain experience and familiarity with the WEB device and procedure. “One particularly helpful aspect of this interaction was that it allowed the team to establish a lexicon of terms to optimise communication during the actual cases,” state the authors. “In our experience, conventional catheter-based rotational three-dimensional angiography provided the best possible data from which to construct a stereolithographic file that most accurately depicted the anatomy.” When computed tomographic angiography or magnetic resonance angiography data were used, they found that the replicated anatomy was less reliable. The use of the system provides the operator with an opportunity to use actual devices within a validated physiological system, but it is important to acknowledge that this benefit comes at a financial expense as numerous catheters, wires, and implants are required for the completion of a comprehensive replicator training. While basic procedural metrics can be compared with those of similar trials, there was no prospective intent, nor ability, to prove the effect of this replicator-based training programme within the US WEB-IT trial.

Consistently smooth deployment and stability, for the high performance you expect. Target™ Detachable Coils

Neuroform Atlas™ Stent System Excelsior ™ SL-10™ and XT-17™ Microcatheters

Smooth and stable. THIS DOCUMENT IS INTENDED SOLELY FOR THE USE OF HEALTHCARE PROFESSIONALS. A physician must always rely on his or her own professional clinical judgment when deciding whether to use a particular product when treating a particular patient. Stryker does not dispense medical advice and recommends that physicians be trained in the use of any particular product before using it in a procedure. The information presented is intended to demonstrate the breadth of Stryker product offerings. A physician must always refer to the package insert, product label and/or instructions for use before using any Stryker product. Products may not be available in all markets because product availability is subject to the regulatory and/or medical practices in individual markets. Please contact your Stryker representative if you have questions about the availability of Stryker products in your area. The Stryker products listed above are CE marked according to the Medical Device Directive 93/42/EEC. Copyright © 2018 Stryker AP002131 v1.0

Australian Sponsor Address Stryker Australia Pty Ltd 8 Herbert Street St Leonards, NSW 2065 Australia AUS

Stryker Neurovascular 47900 Bayside Parkway Fremont, CA 94538 strykerneurovascular.com Date of Release: MAY/2018 EX_EN_IL

Sept

Issue

18 31

Research

Smart flow diverter system could reduce need for monitoring

Less than a third of acute ischaemic stroke patients in Europe receive IV-PA therapy

Data from BIBA MedTech Neurovascular Monitor indicate that during first quarter of this year (1 January–31 March), only 20% of patients presenting with acute ischaemic stroke at a hospital in Western Europe received intravenous tissue plasminogen activator (IV-tPA) therapy.* Furthermore, only 7% underwent thrombectomy. This means that most patients (73%) receive conservative therapy. The data do not provide the reasons why so many patients are treated conservatively, but patients typically receive such therapy because they present outside the specified time window for IV-tPA or (on imaging) have contraindications for IV-tPA/thrombectomy.

According to the BIBA MedTech Neurovascular Monitor, conservative treatment is also the main approach for managing patients who present with intracranial aneurysms (being used in 75% of such patients). Of patients not treated with conservative therapy, 5% undergo surgical clipping and 20% receive endovascular therapy (14.7% aneurysm coiling, 2.6% stent-assisted coiling, 1.8% flow-diverters, and 0.9% intrasaccular devices). However, the estimates for these data are based on extrapolations from a select number of physician specialities and, therefore, may not be wholly representative of the overall market. * = Physicians interviewed were from Italy, France, Germany, Spain, or the UK (the top five countries with the largest healthcare markets in Western Europe)

Woon-Hong Yeo (The George W Woodruff School of Mechanical Engineering, Georgia Tech, Atlanta, USA) and colleagues have developed, according to a press release, a “highly flexible and stretchable sensor”. The sensor is designed to be integrated into a flow diverter for carotid aneurysms, to monitor haemodynamics via capacitance changes without conventional diagnostic procedures. Woon-Hong Yeo An animal in vitro study, published in ACS Nano, indicates that the sensor accurately measures blood flow. Yeo et al now aim to develop a wireless system that would allow them to test the sensor in vivo.

Money boost will help Viz.ai to expand their product portfolio

Viz.ai—developer of the only US FDA-approved artificial intelligence cloud-based platform for diagnosing large vessel occlusions—has raised US$21 million in Series A Funding. Led by Kleiner Perkins, with participation from GV (formerly, Google Ventures), the money will be used for market expansion and for Viz.ai to extend their product portfolio beyond stroke. Chris Mansi, who founded Viz.ai in 2016 with David Golan, comments: “In stroke, every minute matters. Our goal is to fundamentally change healthcare, making it proactive rather than reactive. By integrating Viz, we believe healthcare systems can increase access to proven life-saving therapy and reduce the time to treatment across their referral network. AI-assisted triage has the potential to save lives and reduce disability.”

BIBA Briefings

Source: BIBA MedTech Neurovascular Monitor Q1 2018

BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America. The platform also reviews data and news. For more information about BIBA Briefings or BIBA MedTech, please contact Shilpa Suthar: shilpa@bibamedical.com

ESO and SAFE launch stroke action plan for Europe: 2018–2030 The action plan provides a clear road map and suggests recommendations and targets for 2030 as an aide to governments. It has the aim of improving stroke care and reverse the expected trend of a 34% increase in strokes by 2035, as well as a 45% increase in the number of stroke deaths and 25% increase in the number of stroke survivors living with the effects of stroke.

he action plan was presented for the first time at the European Stroke Organisation Conference (ESOC; 16–18 May 2018, Gothenberg, Sweden). Organised by ESO with cooperation from Stroke Alliance for Europe (SAFE) with input from the World Health Organisation’s Regional Office for Europe. Building on previous Helsingborg Declarations (1995 and 2006), this update reviews the current situation in Europe and focuses the targets on areas with room for improvement as highlighted in the ESO/SAFE Burden of Stroke report. The document contains two news areas within the action plan, primary prevention and life after stroke, as well as the existing five (stroke organisation services, acute stroke management, secondary prevention, rehabilitation, evaluation of quality and outcomes). The collaborative initiative aims to define the priorities for stroke care and research across Europe over the next decade, and provide guidance for European and national plans

encompassing the chain of care from primary prevention to rehabilitation and life after stroke. Over 100 people were involved in the formulations of the action plan and a consensus conference was held in March 2018 to finalise the strategy. There are four overarching targets for 2030. The first is to reduce the absolute number of strokes in Europe by 10%. Commenting on this target, Bo Norrving, chair of the Stroke Action Plan for Europe steering committee (Lund University, Lund, Sweden) said, “What is effecting the absolute number of strokes is the risk of having a stroke and this is related to the population growth and to the ageing of the population. We know that it is possible to reduce the risk of stroke. In Sweden in the last eight years we have seen a 40% reduction in the number of strokes and from this we know that this can be achieved everywhere.” The second target is to treat 90% or more of all patients with stroke in Europe in a stroke unit as the first level of care.

Norrving said, “This is a basic requirement. Patients need to come to the right department from the beginning so they get the right care. We know that presently in Europe less than half of all patients are treated in stroke units, despite having the knowledge that everyone should get this type of care.” The third target of the action plan is to have national plans for stoke encompassing the entire chain of care from primary prevention through to life after stroke. Norrving explained, “We have seen the importance of having a national plan for stroke. We have seen in the UK, for instance, that it made a big change when there was government support and a national plan. It really develops the stroke services.” The fourth target is to fully implement national strategies for multi-sectorial public health interventions promoting and facilitating a health lifestyle, and reducing environmental, socioeconomical and educational risk factors that increase the risk of stroke. “Stroke has an enormous potential to have a better outcome. We can limit the disease; we need to reduce the number of stroke in the population otherwise the healthcare system for stroke will simply flood. The next stop [for the action plan] is to join hands with politicians and governments to see that this will be accomplished,” concluded Norrving.

Sept

Issue

18 31

Stroke

ADVERTORIAL

NeVaTM is not just another stent retriever Effective thrombectomy requires the complete removal of the clot. Vesalio’s NeVa™ combines innovative product design with cutting-edge technique, allowing all types of clots to be captured and retained. Dr Juan Macho, interventional neuroradiologist and head of the angio-radiology department, Hospital Clinic Barcelona, Spain, talks to NeuroNews about his experience.

In our first-in-man patients we have first pass success in more than 70% of cases, with TICI 3 in practically all these cases.

What is your experience to date with the NeVa thrombectomy device?

We [Hospital Clinic de Barcelona, Spain] have been participating in the first in man study of the NeVa device, which treated around 10 patients from our centre. We worked very closely with the Hospital Vall d’Hebron in Barcelona and together we have over 20 cases.

Does this aide in the removal of difficult clots, such as hard clots?

What could you tell us about NeVa?

For sure, thanks to the capability of including bigger volumes of thrombus, whatever their consistency.

NeVa has unique features, when compared with the other devices in the market. It has a higher radial force and is designed with two completely open zones, rotated 90 degrees, which allows for complete incorporation of the clot in the device.

How has the existence of Drop Zones affected your retrieval technique?

In the first group of included patients we modified our technique in only the last few patients. Once we understood the engineering of the device, we adapted our technique to this design. In our case, the results did not change as dramatically in these last few cases as in other centres, but we really feel that now we understand what we do better, and we participate more actively in the procedure.

open, the step-wise retrieval movement of the Drop Zone Technique, helps the thrombus to be completely included inside the device and decrease the probability of partial or complete migration of the thrombus throughout the retrieval manoeuvre.

Do you observe or feel a difference in your procedural results? NeVaTM thrombectomy device design with mulifunctional zones

How does the NeVa Drop Zone Retrieval Technique differ from others?

NeVa has completely open areas, which serve as clot entrance points, designed for including and retaining the harder clots more effectively. You can move and rotate the device to make the clot drop in the next open zone.

How does it help clot extraction?

Instead of waiting several minutes with the stent retriever

It is still too early to say, but when we use this device we like to use this active process not only in the placement, which needs to be slightly more distal, but also in the retrieval, which as I had already mentioned, should not be continuos but in steps. It is not one more retriever in our armaments, but a different concept in design that reveals its potential with a different retrieving technique. In our first-in-man patients we have first pass success in more than 70% of cases, with TICI 3 in practically all of them. These are very promising results. We are expecting the full analysis of clinical results to be available in September.

Researchers find major inequalities in acute stroke treatment across Europe

Every year, up to 1.3 million people in Europe suffer a first stroke. Acute stroke treatment strategies such as acute treatment of patients in a stroke unit, intravenous thrombolysis and endovascular treatment significantly improve the outcome for patients with ischaemic stroke and thus reduce its socioeconomic burden. However, reliable data on access to and delivery of acute stroke treatment strategies throughout Europe are lacking.

he European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN) and the patient organisation Stroke Alliance for Europe (SAFE) have therefore surveyed stroke experts from 44 of 51 European countries on the best available information regarding national access to and delivery rates of acute stroke unit care, intravenous thrombolysis, and endovascular treatment. The results of this survey identify major inequalities in acute stroke treatment, with many countries reporting rates that were far below highest country rates. This article shows in which countries patients still have no or obviously inadequate access to appropriate acute stroke treatment. According to Urs Fischer, Professor of Acute Neurology and Stroke at the University Hospital Bern, Switzerland, up to 226,662 additional patients could be treated with intravenous thrombolysis and an additional 67,347 with endovascular treatment each year. “Many stroke

victims in Europe still have no access to acute stroke treatment,” he said. “If stroke unit care, intravenous thrombolysis and endovascular therapy would be routine practice throughout Europe, many more victims could survive their stroke without a major handicap”. According to Fischer, these inequalities not only have a major impact on the patients, but also on their families and the socioeconomic burden. “Recent studies have shown, that acute stroke treatment is highly cost effective—if you treat your patients right, you will not only improve the quality of life of the patient and his family, you will also save money for your society”, he said. Therefore, efforts have to be done to increase the number of stroke units, intravenous thrombolysis and endovascular stroke therapy. “We have to talk to governments, politicians, health care specialists and stroke physicians in order to set up and improve the system in regions, where acute stroke treatment is lacking!” In May 2018, ESO and SAFE presented the Stroke Action Plan for Europe to set achievement goals for stroke care by 2030. This survey already provided

important insights for the Stroke Action Plan authors. The findings from this

survey are relevant for future health-care planning in Europe and beyond.

Sept

Issue

18 31

Stroke intervention

How to treat ischaemic stroke fast: Getting the correct patient to the correct hospital “The single biggest challenge going forward is the organisation of stroke care,” said Mayank Goyal (University of Calgary, Canada). He dissected the arguments at the Live Interventional Neuroradiology & Neurosurgery Course (LINNC; 11–13 June, Paris, France).

evisiting the denominator fallacy, Goyal explained that if 100 people come to the hospital within 30 minutes of stroke onset, 90% of them will have favourable imaging and 60% of them will have good outcomes. “Compare this to 100 patients that come to the hospital six hours after stroke onset, where only 10 of them have favourable imaging and six go on to have good outcomes,” Goyal noted. This, he added, shows that just by reducing the time between stroke and hospital admission there is the potentially to have a 400% effect size. “That is the single biggest problem we face right now: getting these patients to come to us earlier,” Goyal said. “Going to the wrong hospital is like going to a black hole and coming out, on average you lose two hours just by going to the wrong hospital.” How do we create a system here the patient goes to the correct hospital first time? Goyal, who is an advocate of big data, has been working on an updated model that inputs data such

as the time it takes to get to primary care centre or comprehensive care centre. From this model, he and his research group found that unless a patient with significant stroke symptoms lives in the “middle-of-nowhere”, it is always best to go straight to the comprehensive stroke centre, not just a facility offering alteplase. The models show that only if the primary care centres are able to administer alteplase within 30 minutes of hospital arrival is it better to go there instead of to a comprehensive care centre. When the door-toneedle time at the primary care centre is longer, the “Drip ‘n Ship” option is likely to be beneficial only for those primary care centres that are further away from the comprehensive care centres. The predicted probability of good outcomes declines as the distance to the comprehensive care centres increases. An additional benefit of the model is that it can adapt to changing circumstances and can be updated based on data. Goyal said, “It is quite possible that the efficacy of endovascular thrombectomy improves with

improvements in technique, training and technology resulting in improved outcomes; these improved outcomes can immediately be plugged into the model.” Goyal is hoping to make the model “live”, enabling the model to adapt to local conditions such as traffic and weather. This shows the need of centralised planning regarding the placement of comprehensive stroke centres. Goyal said, by doing this, the time from stroke onset to optimal treatment can be greatly reduced, moving more patients into the optimal outcome group. Highlighting this issue, Goyal explained, “Nobel Laureate Amartya Sen and his work on famines showed that famine is not about lack of food but about the distribution of food. This can be compared to stroke care: at a basic level it is dependent on the distribution of neurointerventionalists skill sets as opposed to the total number of fellows that are trained.” He continued, “There is a risk that as we train fellows there will be more and more neurointerventionalists in the big cities, such as New York and Chicago, but that they still do not provide service to the areas that need it. We need to create a plan for services so there is a reasonable distribution of interventionalists.”

New stroke imaging technology could reduce potential for patient brain damage A study found that new stroke imaging technology could decrease delays in care by up to 60 minutes, giving patients a better chance at making a full recovery. The results were presented at the Society of NeuroInterventional Surgery’s 15th annual meeting (SNIS; 23–26 July, San Francisco, USA).

he study, titled “New Multiple computed tomography (CT) Assessment of Acute Stroke Patients: Are We Ready for Prime Time?”, shows that recent advances in imaging software in the angiosuite give neurointerventionalists the essential details required to diagnose a patient with large vessel occlusion for an endovascular thrombectomy. The study suggests that in the future, stroke patients can bypass the CT scan or emergency department and go directly to the angiosuite for imaging and proper care.

“By using this technology in the angiosuite, hospitals can reduce intra-facility transfer delays and hence the time of stroke symptom onset to treatment, which will significantly reduce brain damage and improve outcomes for patients,” said Nicole Cancelliere, lead author of the study and an interventional clinical research technologist at Toronto Western Hospital, Canada. The time required to transfer a patient from their CT scan to the operating room could delay endovascular thrombectomy by as long as 60 minutes.

Preliminary results show that the cone beam imaging software compares favourably with baseline and follow-up CT scans. The imaging allows accurate detection of haemorrhage, occlusion site, ischaemic core, and tissue at risk, suggesting that baseline imaging can be performed in the angiosuite using cone beam imaging. The lead prinicpal investigator on this study, Vitor Mendes Pereira, concluded by saying, “By reducing intra-facility transfer times, patients can receive endovascular thrombectomy treatment sooner, which can significantly impact patient outcomes”. The study compared the capability of new cone beam CT protocols to standard CT. The inclusion criteria were patients with acute ischaemic stroke who received endovascular mechanical thrombectomy treatment and

Stroke imaging technology

underwent standard CT and CT perfusion imaging within 90 minutes of arrival to the angiosuite. Once the patients arrived at the angiosuite, three different cone beam CT scans were carried out: non-enhanced XperCT (MASK scan); Initial IV contrast enhanced XperCT (“early-phase” scan) and delayed IV contrast enhanced XperCT (“late-phase” scan). Three subtractions were then used to understand better perfusion of the brain. The first was MASK with the “early-phase” subtracted, which shows the early phase of perfusion, then the “late-phase” minus MASK to see the late perfusion of the brain and finally, “late-phase” minus the “earlyphase”, which showed the delayed fill into the brain. The imaging was then evaluated by an experienced interventional neuroradiologist, who compared them to non-contrast CT scans, CT perfusion imaging and to 24-hour follow-up imaging. The evaluation was done using a fivepoint quality assessment questionnaire which looked at nine different areas, including core definition and comparisons to other imaging methods such as RAPID and follow-up CT. These were ranked from “very good” to “poor”. For the study 13 cases were performed, of which nine patients were included. Five patients were excluded due to lack of comparative CT perfusion imaging, intense patient movement and poor revascularisation. The results showed that in some of the areas, such as occlusion or stenosis detection, cone beam CT performed very well but in others, such as core definition compared to baseline CT, it fell below average. Speaking about the results, Cancelliere said “It is important to note that, overall, the images were good enough to use and allowed for more rapid patient treatment.”

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Stroke

Time is “money”, not just brain Thrombectomy is a highly effective way to treat ischaemic large vessel occlusion stroke. “Time is brain” remains crucial as the thrombectomy benefit is highly time-dependent. Speaking at the 15th annual meeting of the Society of NeuroInterventional Surgery (SNIS; 23-27 July, San Francisco, USA), Wolfgang G Kunz, (assistant professor of Radiology at LMU Munich, Germany) presented results from the HERMES collaboration on the lifetime health and cost consequences of treatment delays in thrombectomy for stroke. The data illustrate that not only is time brain, time also is money.

hrombectomy is expected to reduce the financial impact that stroke has in many countries, including the USA, UK, Australia and Sweden, said Kunz. In a letter he co-wrote with Myriam G Hunink (Erasmus University Medical Center, Rotterdam, the Netherlands) and published in Stroke in 2017, he reinforced that the use of thrombectomy will lead to long-term cost-savings, not just in the US insurance-based system but also in the UK’s free at point of use system. Knowing this means that it is imperative to implement thrombectomy and to reduce time to treatment—for the patients as well as to reduce the financial burden of stroke in ageing societies. There are many delays in the stroke treatment workflow. Even before the patient gets to the hospital there can be delays in symptom recognition, contacting emergency services and getting the patient

to a hospital that provides thrombectomy. Once a patient reaches the correct hospital, the workflow often is not optimised for stroke triage with serial instead of parallel task processing and imaging protocols that can add up to a 20-minute delay (Goyal et al. Radiology 2016). Quality-adjusted life years (QALY) represent quality of life over time. The quality of life ranges from 1.0 representing a perfect quality of life, to 0.0 representing no quality of life. The stroke patients’ quality of life is closely related to their modified Rankin Scale (mRS): mRS of 0 typically leads to very high quality of life while patients with an mRS of 5 reported on average 0.0 quality of life, as evident from questionnaires across multiple large patient cohorts. In a cost analysis of the SWIFT-PRIME trial, a thrombectomy procedure cost on average US$15,000 with the long-term care costs ranging from

US$10,569 annually for patients with an mRS of 1, to US$64,327 annually for patients with an mRS of 5. Mayank Goyal, senior author of the study, neurointerventionalist at the University of Calgary in Canada, and chair of the HERMES collaboration, co-designed the analysis with Kunz. They applied data from all seven participating trials of HERMES and used 90-day mRS outcome stratified by time to puncture as main input for the health economic model calculations. They found that for every minute delay in treatment there was a loss of four days of disability-free life. Considering life with functional independence (mRS 0–2), a one-minute delay even resulted in a loss of 10 days on average. The net monetary benefit is an indicator of the economic value of care, and was highest when the time to puncture was shortest. The analysis showed that the median loss in net monetary benefit of thrombectomy per minute was US$1,059— expediting treatment with thrombectomy by 10 minutes in the USA on a national level would lead to a financial benefit of US$249 million annually. By reducing time to treatment, streamlining workflow, and improving thrombectomy technique there is a vast potential, not only to save and improve patients’ lives, but also to reduce the economic burden of stroke.

Stroke patients treated at a teaching hospital are less likely to be readmitted Stroke patients appear to receive better care at teaching hospitals with less chance of landing back in hospital during the early stages of recovery, according to new research from the University of Texas Health Science Centre at Houston (UTHealth), USA.

he study, published in JAMA Network Open, provides the first comprehensive nationwide analysis of 30-day readmission rates for both Medicare and privately insured patients with different types of stroke. It reveals that although readmissions have fallen by 3% a year on average between 2010 and 2014, patients discharged from nonteaching hospitals faced a significantly higher risk of readmission mainly due to having another stroke, related complications or septicemia, a serious blood infection.“The research is important because readmissions have become a focus for improving quality of care while in a hospital, as well as reducing costs, and very little has been published about stroke patients at this scale,” said the study’s lead author Farhaan Vahidy, assistant professor of neurology at McGovern Medical School at UTHealth. “Our findings help set national performance benchmarks for readmission levels among patients of all ages, types of stroke and insurance classes. This provides potential to identify specific groups for readmission reduction through targeted interventions that improve continued support for discharged patients, which should start before they leave the hospital doors.” The overall decline in readmissions

was not attributed to reduced stroke recurrence, which in fact increased in some cases, but more a result of a drop in readmission rates for other high volume conditions likely to affect stroke patients, who tend to be older and have additional health issues. Results revealed more than 90% of all 30-day stroke-related readmissions were unplanned and, depending on the stroke type, up to 13.6% were deemed potentially preventable. The greatest danger of readmission applied to patients with haemorrhagic stroke, a more serious form caused by a bleeding vessel in the brain, which carried a 13.7% likelihood. By contrast, patients with ischaemic stroke, caused by a blocked vessel, faced a 12.4% risk. “Many, but not all, patients with more severe stroke are transferred to an academic hospital, which were found to have a steady readmission rate regardless of how many stroke cases were admitted, suggesting superior care,” Vahidy said. “These patients are all inherently more vulnerable to stroke recurrence and associated conditions such as septicemia. Patients from nonacademic hospitals, however, seem to be even more prone to this happening as stroke patient volumes increase, indicating opportunities for improvement in pre-discharge patient care and

transitional follow-up.” Nonteaching hospital stroke patients accounted for around half (46.4%) of all patients and the disparity between readmission rates compared to teaching hospitals widened as the number of stroke patients treated at the nonteaching hospitals grew. “The difference started to become statistically significant at hospitals discharging 300 stroke patients annually. For instance, at the 500 patient mark the increased risk of readmission is about 1%, which may not sound much, but it is because we are talking about millions of patients,” Vahidy said. Greater adherence to quality-of-care metrics, use of telestroke technology and organisation of care delivery, as well as having adjoining outpatient clinics, were among the features common at teaching hospitals, which could

give these centres a competitive edge in patient care, the researchers wrote. The research therefore highlights a wealth of information which individual hospitals can use to identify issues and take measures to prevent secondary complications of stroke. “Our work emphasises the continued need for more robust approaches and planning strategies to further raise standards, minimise hospital readmissions and improve outcomes for all stroke patients,” said Vahidy. “Readmission reduction is a patientcentred outcome. Medicare provides publically available data for hospitals’ performance on readmission in stroke patients. However, additional analyses such as ours are needed to be incorporated, so patients and their families can better advocate for their care and make more informed choices.”

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Physician wellbeing

The truth about physician burnout Writing in the Journal of NeuroInterventional Surgery, Kyle M Fargen (Wake Forest University, Winston-Salem, USA) and Joshua A Hirsch (Massachusetts General Hospital, Boston, USA) shed light on the growing endemic of physician burnout, particularly within neurointerventionalists.

ental health is a significant concern for physicians. In the USA, there are 400 physician suicides a year; twice the suicide rate of the general American population. Death by suicide is the second leading cause of death among residents. Fifty-four per cent of doctors say they are burned out; 88% acknowledge they are moderately to severely stressed, and 59% of doctors say they would not recommend a career in medicine to their children. These statistics are the result of recent research by Tait Shanafelt (Mayo clinic; Stanford Medicine, Stanford, USA) and colleagues, where the investigators surveyed almost 7,000 physicians. The same study reveals that between 2011 and 2014, there was an increase in the percentage of physicians reporting burnout, and a decrease in the number of surgeons who believed they experienced a good work-life balance. Neurointerventional physicians are at high risk of burnout; in the survey around 50% of neurosurgeons and neurologists and over 60% of radiologists reported burnout. American psychologist Herbert Freudenberger defined burnout, which first appeared in print in a 1974 issue of the Journal of Social Issues, as, “A state of emotional, mental and physical exhaustion caused by excessive and prolonged stress. It is a chronic process of energy expenditure without appropriate periods of recovery.” With the release of the results of DAWN and DEFUSE 3 trials, and the increased candidacy for mechanical intervention, Fargan and Hirsch note that the demand on neurointerventionalists is increasing. With most consultations occurring (60%) outside working hours, meaning that the risk of emotional, mental and physical exhaustion is increasing. Michael Weinstein, a general surgeon at Thomas Jefferson University Hospital, Philadelphia, USA, wrote a first person account of his struggles with dysthymia, depression and suicidal ideation in the New England Journal of Medicine. Weinstein wrote: “I endured. I completed residency and fellowship and continued to endure for 16 years. Outside observers might have perceived me as ‘having it all’: a surgeon with leadership promise, with an amazing wife and two great kids, who’s paid more than I ever expected to earn. “But enduring is not thriving. I had heard of burnout but didn’t really comprehend it. And though I had mental illness, I still saw it as a weakness, a personal fault. I remember early in my career hearing of a colleague who took a leave of absence for a ‘nervous breakdown.’ I joked about it, said he was weak. Now it was my turn. “My work lost meaning; I was just going through the motions. I thought everything I tried to accomplish was a failure. I had trouble relating to patients and felt the urge to avoid encounters altogether. I cared less and less about anything I was doing. I didn’t

know it then, but I had long experienced classic signs of burnout: emotional exhaustion, depersonalisation, and low perceived personal achievement. But the burnout had been waxing and waning for 22 years; now I was in the worst episode of major depression of my life.” This recognition is crucial, Fargan and Hirsch explain: acknowledgement of

physician burnout saves lives, and is the first step to recovery. Academic medical centres are starting to pay more attention to physician burnout and suicide, but it is still rare for a practicing doctor to be as forthcoming as Weinstein, or for mental health issues to be given a platform. The myriad solutions to this problem revolve around understanding the causes of physician burnout. Writing in the Journal of Internal Medicine in June 2018, Colin West and co-authors claim that the “drivers of this epidemic are largely rooted within healthcare organisations and systems,” and include: “excessive workloads, inefficient

work processes, clerical burdens, workhome conflicts, lack of input or control for physicians with respect to issues affecting their work lives, organisational support structures and leadership culture.” Fargen and Hirsch conclude, “Experts argue that physician burnout is best combated by shared responsibility between healthcare systems and by individual physicians. Fair compensation, development of shared schedules, hiring of non-physician providers for clerical responsibilities, and improved efficiency with elective schedules are potential avenues to reduce the risk of burnout.”

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Interview

Profile

Urs Fischer

Urs Fischer is a clinical researcher with a particular interest in the diagnosis, management, treatment and outcome of patients with acute neurological diseases, especially of patients with acute ischaemic and haemorrhagic stroke. He is participating in multiple preventive, diagnostic and acute treatment trials and stroke registrie. Here, he speaks to NeuroNews about his current research, his wish list in terms of the development of stroke therapy and his interests outside of medicine.

What drew you to neurology and stroke therapy in particular?

When I was in high school, I found it challenging to focus on a specific area or field because my interests were just too broad—I studied languages, I loved science and the arts, I played the cello in various orchestras and chamber music ensembles, among other things. Medical school was therefore the perfect choice for an indecisive person like me, since I could postpone the dilemma of whether I should study science or the arts. In my second year at medical school, I began to attend lectures in neuroanatomy and I immediately knew that neuroscience was a sphere about which I wanted to discover much more. Neuroscience—the interface between science and the arts—was the ideal field to combine my interests. I wrote my medical doctoral thesis on neurophysiology and I realised that I wanted to work in a therapeutic rather than in a diagnostic domain of neurology. I then had the good fortune to meet Prof Heinrich Mattle, chair of the Stroke Center Bern (Switzerland), and a pioneer in endovascular stroke therapy. He offered me a position in his research group. This was in the early 2000s, when endovascular stroke therapy was still in its experimental stages and evidence from randomised trials was lacking. We prospectively analysed clinical and imaging predictors of outcome in stroke patients treated with endovascular procedures and we saw a tremendous impact of recanalisation on outcome—a finding that was later confirmed by the randomised trials after 2014.

Who were your mentors and what impact have they had on your career? I was luckily supported by several mentors. Prof Heinrich Mattle was probably the most influential person in my professional career. Together with his research partners and team (Prof Gerhard Schroth, Prof Marcel Arnold and many others), he taught me to pursue a research idea and to focus on relevant scientific questions. During my research fellowship at the Stroke Prevention Research Unit at the University of Oxford, I had the privilege to be supported by Prof Peter Rothwell, one of the leading scientists in the field of stroke. He taught me the basic skills in epidemiology and statistics and he was a great mentor. He always tried to find the most relevant factor in stroke prevention with the biggest impact on outcome. Further important mentors were—and still are—Prof Valeria Caso, past president of the European Stroke Organisation (ESO), and Prof Claudio Bassetti, chair of the Department of Neurology at the University Hospital in Bern.

You have been practising for a number of years. How have you seen the field of neurology change and develop over that time? Neurology has changed dramatically since I was in medical school: traditionally neurology was a diagnostic rather than a therapeutic domain. Today, many neurological diseases can be prevented and treated, and neurologists are working in emergency departments, on intensive care units, in acute neurological wards etc. The image of neurology has completely changed, and I strongly believe that neuroscience has become the “royal discipline” in medicine. However, there are more

challenges than ever with the ageing populations. Many diseases, especially neurodegenerative ones cannot be prevented and treated yet.

In your opinion, what has been the most practice-changing advance in terms of treatment options and devices?

The changes in neurology are tremendous; however, the biggest breakthrough was in acute stroke management, especially endovascular stroke therapy with stent retrievers. There is almost no other intervention in the history of medicine with such a big effect. You have to treat only two patients with acute stroke due to a large vessel occlusion to prevent one major disabling or fatal event. Further practicechanging advances were treatment of stroke patients on dedicated units (i.e. stroke units), urgent investigation and treatment of patients with transient ischaemic attacks (TIAs) and minor strokes (i.e. TIA clinics), as well as carotid endarterectomy and stenting. There have also been other major breakthroughs in neuroscience such as all the new treatment options for patients with multiple sclerosis, migraine, medical and surgical treatment of epilepsy, and deep brain stimulation in Parkinson’s disease to name but a few.

What has been the biggest disappointment—i.e. something that you thought would be practice-changing but was not?

In 2018, we still have no evidence-based treatment option for patients with intracerebral haemorrhage, a terrible condition that affects 15–20% of our stroke patients and is associated with a high morbidity and mortality. The outcomes of previous trials such as FAST, STICH I and II, INTERACT, TICH II, etc. were all negative and the major breakthrough in prevention and management of intracerebral haemorrhage is not yet in sight. Our pathophysiological understanding of the manifold causes of intracerebral haemorrhage and their prevention is still insufficient. Therefore, prevention and treatment of intracerebral haemorrhage should become one of the main priorities for stroke research over the coming years. And there are many other disappointments: e.g. all the dementia trials to remove cerebral amyloid in Alzheimer’s patients failed and we still have no treatment option for other neurodegenerative diseases.

What is on your wish list in terms of the future development of stroke therapy?

My wish list is long, but before starting to develop new things, we should focus on the implementation of the current effective therapies in clinical practice. The top three priorities on my wish list are implementation, individualised treatment solutions and prevention of secondary brain damage. Implementation: We have highly effective treatments for stroke patients with a very low number needed to treat, but, in many parts of the world, these treatments are still not available. This is why we have established the ESO ESMINT ESNR Stroke Winter School (www. strokewinterschool.ch) in order to train young physicians. We hope that, following the training, these young colleagues will implement acute stroke treatment strategies in their own hospitals. In 2019, we will organise the first Stroke Winter School in Asia. Individualised treatment approaches: Randomised trials

have shown the efficacy of interventions in well-defined populations. However, we are treating individuals. Further efforts should be made to establish more evidence for personalised treatment. As a clinician, I would like to be able to identify the patients who are most likely to benefit from a specific intervention, especially if the number needed to treat for that intervention is high and the number needed to harm is relevant. For instance, we should know, whether all patients with large vessel occlusion should be pretreated with intravenous thrombolysis prior to mechanical thrombectomy, or whether there is a subgroup (e.g. patients with carotid artery occlusion) which should better be treated with direct mechanical thrombectomy, given the low chances of recanalisation after thrombolysis and the relevant risk of bleeding complications. This is only one of many examples where we need more evidence, whether the same treatment strategy applies for all patients, or just for a certain subgroup. Population-based studies, randomised trials within cohorts, tailored randomised trials with stricter inclusion criteria and, eventually, advances in precision medicine should hopefully help to guide decisions on personalised treatment in the near future. Prevention of secondary brain damage: Even though recanalisation rates in previous trials were very high, only about 50% of patients have regained their independence after three months and we now have to establish strategies to prevent secondary brain damage after the first hit. The ESCAPE NA1 trial is currently pursuing this aim and I am

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very keen to know whether this and other neuroprotection strategies will help us to further improve the outcome in addition to recanalisation strategies. Finally yet importantly, many more efforts should be done to prevent strokes: it is much more (cost-) effective to prevent a stroke than to try to treat a stroke!

You are publishing a survey on stroke in Europe. What were the key findings?

Reliable data on access to and delivery of acute stroke treatment strategies (i.e. stroke unit treatment, intravenous thrombolysis [IVT] and endovascular stroke therapy[EVT]) throughout Europe are lacking. We therefore surveyed stroke experts from 44 of 51 European countries on rates of acute stroke unit care, IVT and EVT. We found major inequalities in acute stroke treatment, with many countries reporting rates that were far below the highest country rates. Another survey is currently underway assessing provision of secondary prevention services throughout Europe.

Were there any findings that were surprising or unexpected?

Even though I expected these inequalities, the numbers are alarming: more than 226,662 stroke patients in Europe could have been treated with IVT (339,929 instead of 113,267) and 67,347 with EVT (94,852 instead of 27,505), if best practice had been followed in all countries. Although these are still rather conservative estimates, this means that two-thirds of patients who would potentially be eligible for IVT and three-quarters of candidates for EVT did not receive adequate treatments in Europe. Globally these numbers could even be worse, but reliable data are lacking.

Interview

As part of the group who produced the Action Plan for Stroke in Europe 2018– 2030, what effect do you hope the action plan will have?

Fact File

The findings of our survey highlight the importance of the implementation of the current treatment options in clinical practice throughout Europe. The ESO, together with the patient organisation SAFE (Stroke Alliance for Europe) has therefore prepared a European Stroke Action Plan (www.esostroke.org/action-plan-stroke-europe-2018-2030-2) which has four overarching targets, namely: To reduce the absolute number of strokes in Europe by 10% To treat 90% or more of all patients with stroke in Europe in a dedicated stroke unit To have national plans for stroke encompassing the entire chain of care from primary prevention to life after stroke To fully implement national strategies for multisector public health interventions to promote and facilitate a healthy lifestyle, and reduce environmental, socioeconomic and educational factors that increase the risk of stroke.

What are your other current research interests?

I am passionate about all aspects of acute stroke management and the overarching “leitmotiv” of my research interests are the “unanswered questions” in acute stroke care, which I would like to answer with case–control studies and randomised controlled trials. Together with Prof Jan Gralla, chair of the Department of Neuroradiology, we are performing the SWIFT DIRECT trial (www.swift-direct.ch), addressing the impact of intravenous thrombolysis before thrombectomy in patients with large vessel occlusion. Furthermore, together with my colleagues from neurosurgery, we are currently analysing with the SWITCH trial, whether decompressive craniectomy improves the outcome in patients with intracerebral haemorrhage (www.switchtrial.ch). The ELAN trial addresses the question of when oral anticoagulation with novel oral anticoagulants can be restarted in ischaemic stroke patients with atrial fibrillation (www.elan-trial.ch). Lastly, we have started the EUROPEAN STROKE PROJECT, a prospective study to assess the status of stroke prevention and treatment within Europe.

What advice do you hope your mentees and students will always follow?

Good mentors feel responsible for the success of their mentees and empower them to develop their own strengths, beliefs and skills. I am very grateful for all the support I have received. Now that I am trying to become a good mentor myself, I realise how difficult a task this is. Apart from qualities such as knowledge, expertise and skills, you need a lot of time—time to analyse, time to listen, time to discuss, time to write and time to build trust, for example. I really hope that my students will focus their research projects on unanswered questions with a major impact on the outcome for our patients. I learned from Prof Peter Rothwell “Do the simple things first and right”, and I hope that my students and mentees will follow this advice as well.

What are your interests and hobbies outside of medicine?

Music has always been an important part of my life and I have been playing in the quartet “mit vier” for many years now. This offers a unique opportunity for me to dive into a completely different world and to meet people from outside the circle of medicine. And—most importantly—I love to spend as much time as possible with my family. Swimming in the river Aare in Bern in summer is a major highlight, which I try to do regularly with my wife and daughters after work! My kids love skiing with me and I go running on a regular basis. Spending time with friends is also very important. However, finding the right balance between family, friends, clinical and academic work is probably the biggest challenge.

Academic appointments

Chair Acute Neurological Inpatient Department, University Hospital, Bern Co-Chair Stroke Center, University Hospital, Bern Deputy-Director Clinical Trial Unit, University of Bern Head of the Neuro Clinical Trial Unit, University Hospital, Bern General Secretary, European Stroke Organisation

Awards

2015 Best Publication in Clinical Neurosciences 2015, Neurocentro della Svizzera Italiana 2011 Swiss Stroke Society poster prize 2011 Déjerine-Dubois prize (Jung S, et al; co-author) 2010 Swiss Stroke Society award for the best oral presentation 2010 Robert Huber prize (El-Koussy M, et al; co-author) 2008 Fellowship of the European Federation of Neurological Societies (EFNS)

Research

ELAN – principal investigator SWIFT DIRECT – co-principal investigator SWITCH – co-principal investigator BEYOND SWIFT – co-principal investigator INTERCAT 2 – local investigator

Professional training and career

2018 – Chair Acute Neurological Inpatient Department, Department of Neurology, University of Bern 2015 – Professor for Acute Neurology and Stroke (Extraordinarius), University of Bern 2015 – Co-Chair Stroke Center, Department of Neurology, University of Bern 2015 – Co-Director Clinical Trial Unit Bern 2014 – present Senior consultant (Leitender Arzt), Department of Neurology, University of Bern 2008 Research fellow, Stroke Prevention Research Unit, (Prof. P. Rothwell), Department of Clinical Neurology, University of Oxford, UK

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Stroke treatment

The dilemma: To treat or not to treat acute minor stroke with IV rt-PA? STEVEN LEVINE COMMENT & ANALYSIS There is a varied approach to treating minor stroke. Steven R Levine (SUNY Downstate Medical Center and Kings County Hospital Center, New York, USA) writes in NeuroNews about his research into the varying factors that influence physician decision making for these strokes.

he US Food and Drug Administration (FDA) updated the alteplase (Activase, Genentech); a type of recombinant tissue plasminogen activator (rtPA) package insert in February 2015. It requires greater stroke-treating physician judgment about several previous exclusion criteria. We therefore explored factors that may influence a physician’s decision to use IV alteplase, focusing on the more controversial area of treating minor stroke. An expert stroke panel, using the Delphi method of consensus building, selected seven factors to build a series of survey vignettes: National Institutes of Health Stroke Scale (NIHSS) level five: 1–5, NIHSS area of primary deficit (three levels: visual/language/weakness), baseline functional status (two levels: fully independent/mild-moderate disability), previous ischaemic stroke (three levels: yes, less than six weeks ago/yes, six or more weeks ago/no), previous intracerebral haemorrhage

(three levels: yes, less than six months ago/yes, six or more months ago/no), recent use of anticoagulation (three levels: yes, less than 48 hours ago/yes, 48 or more hours ago/no), and temporal pattern of symptoms in first hour of emergency department care (two levels: stable/improving). A total of 150 vignettes were constructed, with variation in each of the seven factors from vignette to vignette. Each survey participant was randomised to one of 10 parallel forms, each comprised of 15 vignettes. The sequence of presentation of vignettes within each form was randomised for each survey participant. For each vignette, participants were asked to supply a subjective likelihood of giving IV alteplase: never; rarely (10–30%); some of the time (30–50%); a good bit of the time (50–70%); most of the time (70–90%); always. Responses were rated 0–5 with categories anchored to probabilities of 0 (never), 0.2, 0.4, 0.6,

0.8 and 1.0 (always), respectively. For each vignette, participants were told to assume the patient is admitted to the emergency department within 60 minutes from stroke symptoms onset. Surveys were sent to email lists for investigators in multiple stroke and emergency clinical trials networks and other regional associations and consortiums. Reponses were returned from 194 patients satisfying inclusion criteria; 56 returned complete vignette data and were analysed. Three quarters of respondents were male; mean age 46 (range 27–76); 80% were trained in neurology; 20% in emergency medicine and 74% practiced in an urban environment, with 21% in suburban, and 5% rural environments. Ninteen per cent practiced in a community hospital, 55% in an academic institution, and 27% in a combination of both; 58% practiced in a comprehensive stroke centre, 38% in a primary stroke centre, and 3% in a facility without certification. Telestroke access was available to 67%. The probability of IV alteplase treatment ranged across all the vignettes from 6% to 95%. Four of the seven main effects account jointly for approximately 57% of total importance, with the top three (prior intracerebral haemorrage, recent anticoagulation, and NIHSS) all of a similar magnitude. The conjoint model accounted for 25% of the total observed response variance (R2=0.25); in contrast, a fully-crossed model accounted for 30% of the variance. We tried to understand how specific factors may influence treatment

decisions, focusing on minor stroke. The predictive power of the conjoint model was modest; only about 25% of variance was explained. The model including all possible interactions was not much better (30%). Further, the three main effects jointly account for a little less than half the explained variance, i.e. less than half of one-quarter of the total variance (approximately 1/8 of the variance). The data suggest major factors involved in the decisionmaking process were not included in the study vignettes or there are many factors (none major), each with limited impact on fluencing treatment. Despite utilising expert opinion, we were unable to identify the majority of what determines treatment decisions for minor stroke. Physician knowledge/beliefs about alteplase effectiveness for minor stroke, risk-benefit perception, risk tolerance, and degree of uncertainty are known to affect physician decision making; errors in risky decision-making do occur. The recent PRISMS results question use of IV rt-PA for minor, non-disabling stroke. Understanding the physician decisionmaking process is complex. Attempts to better understand the process may come from quantitative methods adapted from mathematics and economics as well as qualitative approaches using historical, philosophical, and psychological principles. Steven R Levine is distinguished professor of Neurology and Emergency Medicine; Executive Vice-Chair of Neurology at the State University of New York (SUNY), New York, USA.

Outcomes for contact aspiration and stent retrievers shown to be similar according to the admission clot burden score The post-hoc analysis of the contact aspiration versus stent retriever for successful revascularisation (ASTER) trial showed that the clot burden score on admission was found to be a reliable indicator of 90-day clinical outcome. No difference was observed between contact aspiration and stent retriever use as first line strategies.

his confirms the results from the original ASTER data. It had previously been shown that there is a relationship between clot burden score and recanalisation success but mainly for intravenous thrombolysis. Novel thrombectomy techniques, such as contact aspiration, have diversified endovascular approaches and raised the question of what the best approach for treating acute ischaemic strokes with a large clot burden is. This study set out to comparatively assess and compare the efficiency of these two different techniques (contact aspiration and stent retriever) and evaluated the efficiency of mechanical thrombectomy according to the clot burden

score. Using the clot burden score provides physicians with an additional marker to help them predict clinical outcomes. The clot burden score is evaluated at admission on computed tomography (CT) or magnetic resonance image (MRI) and characterises the intracranial arterial thrombus extent. The study included 231 randomised patients, of which almost half of the patients (114) had a clot burden score of 0–6 and 117 had a clot burden score of 7 or more. The results showed a higher rate of reperfusion and 90day favourable outcome after mechanical thrombectomy

for small thrombus burden, defined as clot burden score of 7 or more. Similar angiographic and clinical outcomes were observed after the first-line strategy and at the end of all procedures with stent retriever and contact aspiration for both small and large thrombus burdens (clot burden score 0–6 and ≥7). Combined therapy with stent retriever and aspiration therapy in first line strategy will be evaluated in the ASTER 2 (Combined Use of Contact Aspiration and the Stent Retriever Technique Versus Stent Retriever Alone for Recanalisation in Acute Cerebral Infarction) trial, which has recently completed enrolment, aiming to show the superiority of combining the use of contact aspiration with a stent retriever, compared to using a stent retriever alone for the treatment of acute ischaemic stroke with an aimed study completion date of 2020. The findings were published in Stroke.

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Stroke

ADVERTORIAL

Q&A with Dr Mayank Goyal, University of Calgary, Canada Source: GE Healthcare Global

Why the world-renowned stroke care leader credits improved outcomes to workﬂow efficiencies

When a patient has a stroke, every minute matters. Dr Mayank Goyal1, director of imaging and endovascular treatment at the Calgary Stroke Program in Alberta, Canada, knows this. That is why, since the early 2010s, Dr Goyal has worked with the University of Calgary to reduce the intake-to-treatment window substantially—from a then-average of about 200 minutes to an imageto-reperfusion (of the affected brain) timeline of just an hour.2 That kind of efficiency takes a great deal of manpower, resources, and technology, but above all, it takes a keen eye on workﬂow optimisation at every juncture of a patient’s care—from the initial 911 call to imaging, treatment, patient/caregiver education, and discharge. “It might sound daunting, but it is doable”, Dr Goyal stresses. With a clear focus on improving outcomes, any centre, anywhere, can clean up their workﬂow for a smooth experience for all. NeuroNews caught up with the world- renowned stroke care leader, who also helped develop GE Healthcare’s FastStroke platform, to learn how to reach this goal.

The Calgary Stroke Program has a strong reputation for excellent acute stroke outcomes. How did you achieve such distinction? These things grow organically. Like with everything else, what happens is that people who are motivated and share a common cause come together for the beneﬁt of improving outcomes. Then, that creates a snowball effect and attracts other similar minds and then, from there, it keeps on growing.

What role did workﬂow efficiency and operations play in that growth?

It helps that we were among the early ones to realise the importance of workflow. Back in 2011, not a lot of people were talking that much about workflow, but we were really focused on it. We were working on all kinds of process changes to optimise workflow and train people. For example, one of the innovations that I created back in 2011 is what I call BRISK, Brisk Recanalisation Ischaemic Stroke Kit, which is a way of setting up your angio so that it is always ready to receive a stroke patient.

Did people from other centres start to take notice?

Yes, that was our intent. My colleague Michael Hill and I travelled to sites to spend time training them on all that we had learned to influence other sites as well. So not only were we trying to optimise workflow on our side; we were doing two other things, too. On one hand, we were publishing data to say why it makes sense, like our 2013 study that showed feasibility for a 60-minute imaging-to-reperfusion time.2 And secondly, we travelled to other sites within that trial to help them optimise their workflow, too.

What are all the milestones involved in shortening that window of

So if a patient is coming in, I can quickly get into the database and ﬁnd out the past history, whether they have a cardiac disease or not, whether they have had previous strokes or not, and what kind of medications they are on. Another thing you need is communication between the primary hospital and the tertiary hospital. Neither of those things is difficult to implement because the technology already exists.

So, it is just a question of implementing the technology we already have?

Absolutely. It is very different now compared to what it was six or seven years ago, because now we have data, policies, and good articles on how to do it. So, if someone wanted to do it, now they can put these things into play quite quickly because it is already known what all needs to be done. You do not have to reinvent the wheel.

Clinically speaking, what minimal CT scanning is needed to enable the post-processing analysis? Dr Mayank Goyal

treatment time?

One of the things we realised early was that ultimately, the faster we can open the vessel, the higher the likelihood of a good outcome. Once you realise that, then you ask: What is preventing us from opening the vessel fast, and how can we solve those challenges? If it is spending time on imaging to do an MRI, maybe you consider replacing the MRI with a CT scan, which is much faster. Or it could be focusing on shortening the time for other things, too—like setting up the IV line, or explaining things to the family. You focus on the various steps you can take and approach every one with a solution. And as different people come up with different ideas, you are able to inﬂuence those changes and move them forward.

What does it take to make those changes happen?

There are two components to it. Obviously, you need resources and the necessary manpower. But you also need a local champion who is going to advocate for improvement and pull everyone together, to get everyone to realise the importance of what you are doing.

How does staffing fit into all of that? Generally, we are strongly in favour of having a certain level of centralisation so that there is sufficient volume and everyone knows what they are doing: the overall machinery is well-oiled. But a vital piece of that is organisation at the prehospital level so that appropriate decisions are made in the field and the team at the hospital is notified of upcoming patients before they arrive.

And what about technology?

You need a few things. One is a centralised imaging and patient record database. Here in Alberta, we have a central database for the whole province of Alberta where every patient is in a central record.

At the very least, a patient with suspected stroke needs to have a non-contrast CT to rule out bleed and a CTA to detect the presence of large vessel occlusion. Additional information to detect viability of affected tissue is of course desirable and important. This can be done in different ways, such as ASPECTS, collaterals or CT perfusion.

And what role does advanced imaging analytics play in enabling a rapid and accurate diagnosis?

Stroke is highly time sensitive and there is a sense of urgency for decision making. Additionally there is the issue of instantaneous availability of expertise 24/7/365. This is where stroke analytics can play a major role and make it easier to interpret and make decisions, whether it is the diagnosis of large vessel occlusion or determination of brain viability.

In what ways have you worked with GE Healthcare to develop FastStroke, and how does that platform enable faster diagnostic and treatment decisions? What was your experience in helping develop FastStroke?

I worked with the GE Healthcare team to facilitate the design of FastStroke from the earliest stages of how the product should look and behave to finally testing the final product. The beauty of the product is its user-friendly intuitive interface while at the same time maintaining flexibility based on varying practice patterns at different institutions. In addition, the interface is modular that allows the addition of features and further analytics as the field progresses. References: 1. Mayank Goyal. The Hotchkiss Brain Institute. http:// www.hbi.ucalgary.ca/ profiles/dr-mayank-goyal. Accessed June 19, 2018. 2. Ultrashort imaging to reperfusion time interval arrests core expansion in endovascular therapy for acute ischemic stroke. Journal of NeuroInterventional Surgery. https://www.ncbi.nlm.nih.gov/pubmed/? term=Ultrashort+imaging+to +reperfusion+time+interval+arrests +core+expansion+in+endovascular+therapy+for+acute+ischemic +stroke. Accessed June 19, 2018.

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Treatment options

Multicentre study shows Derivo embolisation device to be safe and effective in treating unruptured intracranial aneurysms Endovascular treatment of unruptured intracranial aneurysms with the Derivo (Acandis) embolisation device is associated with high procedural safety and adequate occlusion rates. All procedures using the device were technically successful, with a morbidity rate of 2.4% and no mortality.

he study, published in the Journal of NeuroInterventional Surgery, retrospectively analysed all patients with unruptured intracranial aneurysms treated with the embolisation device between November 2015 and December 2017 at three German care centres. Procedural details, complications, and morbidity within 30 days after treatment, as well as the aneurysm occlusion rates after six months (O’Kelly–Marotta scale, OKM), were evaluated.

Implantation of the embolisation device was attempted in 42 patients with 42 aneurysms. All procedures were technically successful. Multiple embolisation devices were used in three aneurysms (7.2%; two embolisation devcies in two cases, three embolisation devices in one case) and adjunctive coiling was used in 11 (26.2%) cases due Derivo device to large aneurysm size. Secondary balloon angioplasty was necessary in four cases (9.5%) in order to ensure appropriate wall apposition of the embolisation device. Procedure-related complications occurred in four

cases (9.5%) including three thromboembolic events and one aneurysm perforation. The morbidity rate was 2.4% and there was no mortality. One patient suffered an ischaemic stroke with persistent aphasia at 30-day follow-up due to a thromboembolic infarct (modified Rankin Scale score 1). Among 33 patients (78.6%) available for angiographic follow-up, complete (OKM D) and favourable (OKM C+D) aneurysm occlusion was obtained in 72.7% (24/33) and 87.9% (29/33), respectively. The authors, from the University Hospital of Dusseldorf, University Hospital of Munich and University Hospital of Cologne, Germany, write: “Although the present study showed promising results regarding short-term safety and aneurysm occlusion rates, further studies with larger patient samples and longer follow-up periods will provide a definite conclusion about the safety and efficacy of the Derivo embolisation device.”

Empowering clinicians to diagnose neurological diseases THOMAS DEVLIN COMMENT & ANALYSIS Enabling more clinicians to assess cerebral blood flow characteristics and detect neurological diseases such as stroke using robotic ultrasound technology could enable more efficient patient triage and intervention. Thomas Devlin, (Erlanger Health System, Chattanooga, USA) looks at how expanding use of ultrasound could positively impact the diagnostic landscape for neurological diseases.

s a neurologist based in Tennessee, one of the eleven states in the stroke belt where stroke prevalence is significantly above the national rate, we see an average of over 2400 strokes per year. Stroke affects more than 795,000 people in the USA and every four minutes someone dies from stroke. Neurological diseases represent a significant cost burden to the healthcare system amounting to nearly US$800 billion annually, with stroke, traumatic brain injury, migraine and Alzheimer’s accounting for more than US$438 billion of that cost. Despite the high cost of stroke and the great strides in treatment over the past three years, there is still a great need for an accurate pre-hospital assessment tool for stroke. Most emergency medical services (EMS) screening tools do not

adequately assess stroke severity and demonstrate poor sensitivity in distinguishing patients with large vessel occlusion (LVO) stroke which is critical to determining the treatment facility to take a given patient. Less than 5% of stroke patients qualify for intervention because they are not brought in early enough. Transcranial Doppler ultrasound technology is an established method to detect neurological diseases such as acute ischaemic stroke. It is relatively inexpensive, and provides non-invasive real-time measurements of blood flow characteristics. One drawback, however, is that this assessment technique employs expert technicians (sonographers, who are currently understaffed, to globally support the volume of patients needed for rapid stroke detection and management. To address limitations in assessing

neurological diseases, we initiated a clinical study using a recently FDAcleared robotic ultrasound device, known as the Lucid Robotic System, to determine its efficacy in detecting neurological diseases. The Lucid Robotic System is a combination of the Lucid M1 Transcranial Doppler Ultrasound System, an all-in-one neurovascular ultrasound device designed to non-invasively measure and display brain blood flow information, and the NeuralBot, a robotically assisted headset which automatically adjusts orientation and position under the guidance of a healthcare professional. We presented results from the first phase of the study, at the 10th Annual Society of Vascular and Interventional Neurology meeting, which demonstrated that the technology platform was accurate with >94% area under the curve for early measurement of acute ischaemic stroke caused by LVO. The study was conducted on 107 patients either experiencing acute ischaemic stroke caused by LVO of the internal carotid artery or the middle cerebral artery as confirmed by CT angiography or were part of one of two control sets including an in-hospital and out of hospital group. Transcranial Doppler ultrasound scans in LVO patients were recorded in 30-second intervals across multiple depths for each brain hemisphere while patients were treated with a drug or awaited endovascular or surgical treatment. The data demonstrated the Lucid M1 System is capable of measuring and displaying LVO with 91% sensitivity and 85% specificity compared to the current standard of care

imaging in persons suspected of stroke. Findings from an ongoing study presented at the 23rd meeting of the European Society of Neurosonology and Cerebral Hemodynamics also demonstrated there was no statistical difference between ultrasound blood flow data collected with the system and data collected manually by an expert technician with the traditional ultrasound platform. The system allowed for easier facilitation of ultrasound on the brain, enabling trained clinicians to collect blood flow data and diagnose neurological disorders faster and more efficiently, potentially without the need for more invasive testing. This analysis can be performed in inpatient and outpatient settings. By making ultrasound imaging technology more accessible to clinicians in hospitals, referral centres and emergency medical service settings that were otherwise restrained from utilising the modality due to cost and complexity, we hope to see more stroke patients diagnosed and triaged for treatment in time. This technology has the potential to be implemented beyond stroke and is currently being studied in other neurological disease such as concussion and Alzheimer’s disease. Thomas Devlin is the executive medical director of Erlanger Neuroscience Institute and the co-medical director of the Southeast Regional Stroke Center in Chattanooga, USA References Center for Disease Control. Stroke Facts. https://www. cdc.gov/stroke/facts.htm. Accessed July 17, 2018 Robert L Dickson, et al. A Paradigm Shift in EMS Evaluation of Stroke. Journal of Emergency Medical Services. 2016 Christopher R Bernheisel, Jeffrey D Schlaudecker, Katelyn Leopold. Subacute Management of Ischemic Stroke. American Family Physician, 2011 Dec 15;84(12):13831388 Purkayastha S, Sorond F. Transcranial Doppler Ultrasound: Technique and Application. Seminars in neurology. 2012; 32(4):411-420. DOI: 10.1055/s-0032-1331812. Sarkar S, Ghosh S, Ghosh SK, Collier A. Role of transcranial Doppler ultrasonography in stroke. Postgraduate Medical Journal. 2007;83(985):683-689. doi:10.1136/ pgmj.2007.058602.

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Self-tuning brain implant could help treat patients with Parkinson’s disease A recent study describes the first fully implanted deep brain stimulation (DBS) system that uses feedback from the brain itself to fine-tune its signalling. The study was supported by the National Institutes of Health’s Brain Research through Advancing Innovative Technologies (BRAIN) Initiative and the National Institute of Neurological Disorders and Stroke (NINDS).

“T

he novel approach taken in this small-scale feasibility study may be an important first step in developing a more refined or personalised way for doctors to reduce the problems patients with Parkinson’s disease face every day,” said Nick B Langhals, program director at NINDS and team lead for the BRAIN Initiative. Traditional deep brain stimulation delivers constant stimulation to the basal ganglia to help treat the symptoms of Parkinson’s. However, this approach can lead to unwanted side effects, requiring reprogramming of the device. The new method described in this study is adaptive, so that the stimulation delivered is responsive in real-time to signals received from the patient’s brain. “This is the first time a fully implanted device has been used for closed-loop, adaptive deep brain stimulation in human Parkinson’s disease patients,” said Philip Starr, professor of neurological surgery, University of California, San Francisco, USA, and senior author of the study, which was published in the Journal of Neural Engineering. In a short-term feasibility trial, two

patients with Parkinson’s received a fully implanted, adaptive deep brain stimulation device (Activa PC + S, Medtronic). The device differs from traditional ones in that it can both monitor and modulate brain activity. In this work, sensing was done from an electrode implanted over the primary motor cortex, a part of the brain critical for normal movement. Signals from this electrode are then fed into a computer program embedded in the device, which determines whether to stimulate the brain. For this study the researchers taught the program to recognise a pattern of brain activity associated with dyskinesia as a guide to tailor stimulation. Stimulation was reduced when it identified dyskinesiarelated brain activity and increased when brain sensing indicated no dyskinesia to minimise deep brain stimulation-related side effects. Results of initial, short-term studies aimed at demonstrating feasibility and effectiveness of using adaptive deep brain stimulation to overcome the impediment to movement of Parkinson’s suggested that this adaptive approach was equally effective at controlling symptoms as traditional deep brain stimulation. Doctors saw

and patients noticed no differences in the improvement in movement under adaptive stimulation versus constant, open-loop stimulation set manually by the researchers. Because adaptive deep brain stimulation did not continuously stimulate the brain, the system saved about 40% of the device’s battery energy used during traditional stimulation. The short time periods over which movement was assessed did not

permit comparison of the two deep brain stimulation paradigms relative to incidence of dyskinesia, but it is hoped that the variable stimulation will also translate into a reduction in adverse effects when tested over longer time periods. “Other adaptive deep brain stimulation designs record brain activity from an area adjacent to where the stimulation occurs, in the basal ganglia, which is susceptible to interference from stimulation current” said Starr. “Instead, our device receives feedback from the motor cortex, far from the stimulation source, providing a more reliable signal.” Many patients with Parkinson’s disease who would benefit from deep brain stimulation are difficult to treat because too much stimulation can cause dyskinesia. Thus, finding the correct level of stimulation is like trying to hit a constantly moving target. An adaptive system like the one being tested here could offer an effective alternative and may also limit adverse effects of traditional deep brain stimulation, but considerable testing remains to be done. “Here we have demonstrated the feasibility of adaptive deep brain stimulation,” said Starr. “We are now planning larger, longer-term trials to determine how effective this system is in managing the symptoms of patients with Parkinson’s disease.”

Evidence in favour of DRG stimulation builds with new study

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repeating baseline assessments and evaluating patients for any adverse events. Outcomes at the end of the trial stimulation period were quantified by the percentage change in the VAS scores relative to baseline, to assess the change from baseline to each follow-up visit. Of the 66 subjects enrolled, failed back surgery syndrome, peripheral nerve injury, and complex regional pain syndrome formed the largest aetiologies. Permanent implants were placed in 56 of the subjects (86.2% of those originally recruited). After 12 months of treatment, the VAS scores indicated that average pain ratings in subjects’ primary area of pain decreased from 8.0cm at baseline to 4.1 (a mean percentage reduction of 48.8% (±3.27), and 49% of subjects had ≥50% reduction in pain. Furthermore, functional capacity was increased, and mood and quality of life improved. Importantly, improvement in quality of life was sustained over time; with the EQ-5D index scores (ranging from 0

to 1.0) having increased from 0.36 at baseline to 0.62 at 12 months, therefore almost doubling the subject’s ratings. Additionally, no confirmed lead migrations were observed, and there was a low rate of infection. In conclusion, the authors write: “These converging real-world clinical outcomes support the notion that DRG stimulation can provide safe and clinical significant pain relief.” Moving forward, the authors suggest how detailed quantitative and qualitative assessments may shed further light on the rehabilitative contribution of neuromodulaton and its personal impact. Additional investigation into partial responders to DRG stimulation is also necessary, as the mean reduction in pain score in this group never exceeded 30% in the current study.

DRG stimulation

Sept

Product News Abbott expands its directional deep brain stimulation therapy by offering new MR-conditional labelling

Parkinson’s disease and essential tremor patients can now benefit from upgraded functionality with Abbott’s Infinity DBS system. Abbott has announced US Food and Drug Administration (FDA) approval for an overthe-air software upgrade for all currently implanted Infinity DBS systems that delivers magnetic resonance (MR)-conditional labelling and innovative features. Prior to the latest Abbott approval, people new to deep brain stimulation (DBS) therapy or those living with older systems from other manufacturers may have experienced barriers in accessing the most advanced DBS therapy options because of the potential need for an MRI in the future. With its updated labeling, Abbott has addressed this challenge with the Infinity DBS system’s improved therapy platform—the first and only FDAapproved MR-conditional directional DBS system. This new approval allows existing implanted Infinity DBS systems to be upgraded via secure Bluetooth wireless technology without the need for surgery, giving full-body MRI conditional labeling to the entire Infinity DBS system, along with the suite of system upgrades. “The announcement of the newly released MRIcompatibility of the Infinity DBS system reflects Abbott’s continued commitment to patient-centric, cutting-edge care—where the patient’s options are expanded by the therapy instead of limited by it,” said Brian Kopell, a neurosurgeon and director of the Center for Neuromodulation at Mount Sinai Health System in New York City, USA.

Intellis is now licensed in Canada

Medtronic has announced in a press release that it has received a licence from Health Canada for its Intellis

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platform, which includes the world’s smallest implantable spinal cord stimulator (SCS) for the management of certain types of chronic intractable pain. Chronic pain is a debilitating condition that can negatively impact all aspects of a person’s life—relationships, work productivity and activities of daily living—yet it remains under-recognised and undertreated. Given the national crisis involving opioid abuse, it is more important than ever for Canadians suffering from chronic pain to have access to new non-opioid treatment options. “Persistent neuropathic pain is challenging to treat, and our goal should be to restore our patient’s mobility and improve their quality of life with effective long-term pain relief,” said Sean Christie, associate professor and director of research at Dalhousie University. “Considering the recommendations of Choosing Wisely Canada*, it’s more important than ever to find effective, long-term, non-opioid solutions. The availability of the Intellis spinal cord stimulator offers new possibilities for some patients struggling with debilitating pain.” “Chronic pain affects up to 19% of Canadians,” said Peter Tomashewski, senior director for Restorative Therapies at Medtronic Canada. “Intellis is an important innovation in the field of SCS for both physicians and patients alike. Transformative features and standardised guidance create a balanced approach enabling us to meet our goal of helping people with chronic pain have more freedom to do the things they love.”

Algovita SCS System implantations reach 2,000 in the USA

Nuvectra Corporation, a neurostimulation medical device company, has announced that the Company’s Al-

govita Spinal Cord Stimulation (SCS) system has been implanted in over 2,000 patients in the US. The Algovita SCS System utilises one of the most robust internal pulse generators used for spinal cord stimulation and patent-protected stretchable lead technology to deliver four unique stimulation modes to patients seeking nonpharmaceutical relief from chronic pain. Scott Drees, CEO of Nuvectra, said, “I am excited to recognise Nuvectra’s 2,000th US implant as another significant commercial milestone which further demonstrates our team’s continued success in driving adoption of our Algovita SCS system. This achievement represents a doubling of US implants in just over six months and reflects the world-class professional service provided by our sales force and the clinical efficacy of our system. We continue to receive positive clinical and patient feedback and look forward to accelerating our growth in the expanding SCS market.” Nuvectra is a neurostimulation company committed to helping physicians improve the lives of people with chronic conditions. The Algovita Spinal Cord Stimulation (SCS) System is our first commercial offering and is CE marked and FDA approved for the treatment of chronic intractable pain of the trunk and/or limbs.

Nuvectra’s Algovita neuromodulation system

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Market watch

Product News BRAVO flow diverter receives European regulatory approval

Cerenovus, part of the Johnson & Johnson Medical Devices Companies, announced it has received European CE mark approval for its BRAVO flow diverter. The device is approved for use in the treatment of patients suffering from intracranial aneurysms. The device will divert blood flow from the aneurysm and promote healing thereby reducing the risk of rupture. The BRAVO flow diverter marks Cerenovus’ entry into the flow diverter category, adding to its portfolio of devices used in endovascular treatment of haemorrhagic and ischaemic stroke. The design of the device aims to improve clinician ease of use, improve cost effectiveness and reduce length of procedure. “Flow diverters are now widely used and for many, have become the go to option for the treatment of complex aneurysms” explains Patrick Brouwer senior consultant Neurointerventionalist at Karolinska University Hospital, Sweden, and evaluator for BRAVO Flow Diverter. “I believe the design of the BRAVO Flow Diverter, particularly the proximal and distal expansion rings,

provides a fresh approach to treat aneurysms.” “The BRAVO flow diverter builds on our legacy of providing meaningful innovation to enable patients to live a life free from the burden of stroke” said Daniella Cramp, Cerenovus worldwide president. “Our entry into the flow diverter market demonstrates our commitment to push the boundaries of stroke treatment and marks a key step towards changing the trajectory of stroke”. Early evaluations are scheduled to take place across Europe ahead of European commercialisation. The device is currently not approved for use in the USA.

Rapid Medical receives CE mark approval for Tigertriever 13

Rapid Medical, a company focused on the development of next generation neurovascular devices, has announced that it has received CE mark approval for the Tigertriever 13. In addition, the first patients have been treated successfully with the device. Tigertriever, the first-ever adjustable, fully visible clot retriever is designed to treat ischaemic stroke patients. About 1,500 patients have

Vesalio launches the NeVa™ Thrombectomy System designed for first pass success with all clot types

esalio announces it has advanced into full commercial launch of the NeVa™ thrombectomy platform, designed for first pass success with all clot types. What distinguishes NeVa from other stent retrievers is the presence of multiple functional zones, including designated areas for clots to enter the device basket. Referred to as Drop Zone TechnologyTM, these clot pockets are engineered to improve first pass success by facilitating capture of more difficult, organised, fibrin-rich and hard NeVaTM thrombectomy device clots. The capability of capturing the entire spectrum of clot types with first pass success is a critical unmet need among physicians who perform neurothrombectomy. “We are extremely pleased with NeVa’s initial clinical results and the unprecedented first pass success rates we are observing” said Steve Rybka, CEO of Vesalio. He went on to explain that Vesalio has completed over 100 cases to date and is preparing to publish data from a multicentre first in man registry including 90-day follow up data. This feature is sponsored by Vesalio.

Tigertriever 13 deployed in the distal Pericallosal artery (a). Angiographic image of the device (b). Image of the Tigertriever 13 with the retrieved clot (c). Images courtesy of Prof Rene Chapot

been successfully treated with the Tigertriever so far, the Tigertriever 13 is the newest addition of the Tigertriever family. Its default profile is 83% smaller than any other device on the market and it is delivered through a neurovascular microcatheter with a soft distal outer diameter of 1.3F. It is designed to recanalise intracranial vessels of 1mm–2.5mm. These medium vessel occlusions (MVO) may account for up to 30% of ischaemic stroke patients and cannot be treated by any other device on the market. “Tigertriever 13 is a very important addition to the ischaemic stroke device market,” said René Chapot, Germany. “For the first time ever, we have a tool that is dedicated to more distal occlusions. These occlusions can have a dramatic disabling effect on patients and until now there was little to be done for them. Using the Tigertriever 13 we were able to retrieve clots from an MVO that was not treatable until now.” Jeffrey Saver, professor of neurology and director of the comprehensive stroke centre at the David Geffen School of Medicine of UCLA, USA, commented on the first clinical experience with the Tigertriever 13: “We know that endovascular therapy is the best option for large vessel occlusions. The Tigertriever 13 will further extend this powerful treatment for acute ischaemic stroke to patients with medium vessel occlusions (MVOs).” Rapid Medical will launch the Tigertriever 13 in Europe during Q3 2018.

First ischaemic stroke patients treated with EMBOTRAP II revascularisation device since commercial availability in US

Cerenovus have announced the first

patients have been treated with its new EMBOTRAP II revascularisation device since it became commercially available in the USA..EMBOTRAP II is a next stent retriever used to capture and remove life-threatening blood clots from the brain following an ischaemic stroke. The company received US Food and Drug Administration (FDA) clearance to market the mechanical clot removal, or thrombectomy, device in May. “The Embotrap II is an important new device for treating stroke patients and an important advancement in mechanical thrombectomy,” said Andrew DeNardo, an interventional neuroradiologist with Goodman Campbell Brain & Spine, who along with John Scott, Daniel Sahlein, and Richard Paulsen, recently performed thrombectomies with the device at Indiana University Health Methodist Hospital and St. Vincent Hospital in Indianapolis, USA. The device, with its proprietary dual-layer design, engages and grips stroke-inducing blood clots differently than other stent retrievers, allowing a doctor to maintain engagement and control of the clot with minimal compression during removal. It is indicated for use within eight hours of symptom onset. “Blood clots can originate in different parts of the body, resulting in different clot types,” said Scott. “These different clot types present unique retrieval challenges during mechanical thrombectomy. The design of the Embotrap II Device helps minimise these challenges and my early experience has been positive.” In the ARISE II (Analysis of Revascularisation in Ischaemic Stroke with Embotrap device) study published earlier this year in the journal, Stroke, neurointerventional stroke physicians restored blood flow in 80% of patients treated within three passes and in about half of patients within a single pass. At the 90-day follow-up, more than two-thirds were functionally independent. The study included 228 patients with large vessel occlusions and moderate to severe neurological deficits.

FDA clearance for SOFIA thrombectomy device

MicroVention has announced the US FDA clearance of a new clinical indication for the SOFIA Catheter (Soft torqueable catheter for intracranial access) to include contact aspiration technique for successful revascularisation among patients with acute ischaemic stroke, secondary to intracranial large vessel occlusive disease. When considered separately from other cardiovascular diseases, stroke ranks fifth among all causes of death in the US, with nearly 133,000 people’s lives lost every year. Someone in the US has a stroke about once every 40 seconds and stroke accounts for one out of every 19 deaths. (Source: American Stroke

Sept

Product News Association 2018) “In my clinical experience the unequaled tracking performance and the increased reperfusion capability of the SOFIA Catheter make a major difference when treating patients suffering from an ischaemic stroke. The SOFIA Catheter makes my practice less challenging, reducing navigation time and providing effective clot extraction,” said Markus Möhlenbruch, Section chief of interventional neuroradiology, Heidelberg University Hospital, Germany. The SOFIA Catheter has been approved in Europe (CE marked) for aspiration indication since 2015 and has been safely used in other parts of the world to treat acute ischaemic stroke. The unique design of the SOFIA Catheter allows for great trackability and a large inside lumen, to provide a fast and effective way to restore blood flow in stroke patients.

iSchemaView completes MDSAP audit—moves to expand worldwide adoption of RAPID imaging platform iSchemaView has announced that the company has completed the Medical Device Single Audit Program (MDSAP), with coming certification. iSchemaView is now applying for clearances and approvals of the RAPID imaging platform in all participating countries around the world. In 2014, the International Medical Device Regulators Forum (IMDRF) launched a global approach to auditing

and monitoring the manufacturing of medical devices, in an effort to improve safety and oversight on an international scale. The result was the creation of the MDSAP, a regulatory audit that serves as a critical step in satisfying the relevant requirements of international regulatory authorities. MDSAP participating countries include Australia, Brazil, Canada, Japan and the United States, with the World Health Organisation and European Union among official observers.

“With dozens of new stroke centers installing RAPID’s automated CTP, MR, CTA and ASPECTS solutions each month, we are seeing accelerating adoption this year,” said Don Listwin, CEO of iSchemaView. “Now that we have completed the MDSAP we are looking to ensure that patients to our North, and around the world, can take advantage of our unmatched imaging solutions. Our mission is to help health care systems address and treat more stroke patients than ever before, and this news moves us ever more swiftly down the path of success.” With MDSAP complete, iSchemaview will be pursuing approval for RAPID in all participating countries, with estimated clearance in Canada expected this summer. In lock-step with the process, iSchemaview is also announcing that Kevin Talmage of Yocan Medical Systems will partner with the company as a Canadian region representative. Talmage brings with him over twenty years of successful medical device marketing and sales experience across Canada.

Calendar of events 6–8 September

ESMINT: European Society of Minimally Invasive Neurological Therapy Annual Meeting

19–23 September

ESNR: European Society of Neuroradiology Annual Meeting Rotterdam, Netherlands W: www.esnr.org

Nice, France

W: www.esmint.eu

1st joint Congress of the INS European Chapters Nijmegen, The Netherlands W: www.ecm2018.eu

17–20 October

World Stroke Congress Montreal, Canada

W: www.world-stroke.org

1–3 November

14–17 November

SVIN: Society of Vascular and Interventional Neurology annual meeting San Diego, USA

W: www.svin.org

SLiCE: Stroke Live Course Nice, France

Seventh Annual Miami Neuro Symposium and Sixth Annual Miami Neuro Nursing Symposium

W: www.slice-online.com

Miami, USA

W: www.stroke.org.uk

14–16 October

net

1–3 October

19–22 September

4th World AVM Congress Montreal, Canada

W: www.avm2018.org

W: www.MiamiNeuro.BaptistHealth.

September

Profile: Istvan Szikora

e to or less: Tim 60 minutes in acute stroke reperfusion st be reduced mu y therap Page 6

has now ic stroke sed, ischaem nt of acute the brain is reperfu of sity faster for the treatme that the Tudor Jovin (Univerof the terial therapy w observed of intra-ar also been e. Therefore, says cy and workflo the The efficacy hed, but it has outcom the efficien around how of a good gravitate s to move the rgh, USA), been establis e, Pittsbu must now the chance minute be to reduce the higher School of Medicin stroke patientthat a time of 90 acute goal should ins Pittsburgh caring for the He mainta too long and the is still entire teamcan be made faster. puncture procedure door-to-groin less. patient from 60 minutes or to iolthat time

finds US study erior DRG sup tional to conven across stimulation ts all endpoin odulation

tional Neurom ss (INS; Congre al At the Interna ) princip 12th World Society’s Montreal, Canadapresented 6–11 June, Timothy Deer, FDA-defined investigator,onth data (the and for safety trial for the the three-m endpoint ATE primary dorsal root of the ACCUR efficacy) He reported that showed not first time. (DRG) stimulation superiority but also ganglion eriority, cord only non-inf tional spinal endpoint over convenacross all primary stimulation analyses.

ional Neurorad the Live Intervent (LINNC; 22–24 peaking at gery Course that it has been said ogy & Neurosur France) Jovin minutes delay from lthough DRG June, Paris, every 30 to about 10% stimulation d that roughly n translates discovere “It is clear is approved outcome. onset to reperfusio of a good time of symptoms in use in ip between the likelihood and has been for decrease in very strong relationsh we need to get Australia is a n and Europe and the United that there reperfusio as fast as in onset and e to reperfuse some time, symptoms stimulation to the angiosuit States DRG investitreatthese patients steps in the he said. ty remains under are critical possible,” that there the opportuni US-based teams have gation. The study is Jovin explained TE first medical in which stroke ACCURA ment process times, stemming from le, room arrival; these emergency the first large-sca n. to shorten on arrival; randomised reperfusio hospital the prospective and finally, contact at to develop of dorsal groin puncture; we have to start Axium clinical trial stimula. first image; critical steps our efficiency root ganglion nal “Around these we use to measure or picture-to roin conventio that ence The door-to-g tion versus some metrics picture-to-puncture They reflect stimulaIII was ongoing. median, which metrics are (Marcus NeurosciRaton ical metrics. spinal cord time IMS that the Very useful physiolog Boca with 2.7 hours were at the explains you establish Institute at n. These are , Registry was Boca tion for patients pain and largely from when reperfusio Hospital, in the Merci has mismatch were you spend to time RESCUE) is “very sobering” l Regional complex regional that the patient explained the time that treatment (IMS III, MR and periphera Jovin maintains 10% chance a small infarct, e physiology for Raton, USA) root syndrome metric previous trials lost represents a patient has has favourabl The other important why all the hours to that the dorsal 30 minutes causalgia. to take three that the patient a simple backthe brain. of a system negative. “Every therefore, if we ganglion is reperfuse there is no Giving some is that is the efficiency outcome, when you roin, then He the premise of a good that captures fast as possible, which roin spinal structure on page 16 from door-to-g Jovin said. ground into ganglion as is the metric Continued and door-to-g ” move the patient trials were negative,” to stroke teams to patient through -puncture of dorsal root these call Levy move the n, Robert Both picture-to correlated with outcome, surprise that as a wakeup roin. results stimulatio those door-to-g strongly to described shown to be he said, is together. recordhave been 2 task now, on page that were get their act tal side, the Continued roin times most Jovin said. On the pre-hospi the door-to-g he believes is the presented terms He in Registry, which how efficient ed in the Mercidataset that captures ular stroke tive treating endovasc representa US hospitals of treatment

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Honolulu, USA

W: www.heart.org

22–23 March

Telford, UK

Miami, USA

17–20 January

15 April

NANS: North American Neuromodulation Society 22nd Annual Meeting

W: www.linnc.com

CX Acute Stroke Controversies London, UK

W: www.cxsymposium.com

NeuroNews is a trusted, independent source of news and opinion in the neurointerventional and neurosurgical world.

2015

Page 16 Page 14

ISC: International Stroke Conference

LINNC Seminar 2019—US Edition

W: www.neuromodulation.org

ious Brain Is consc safe? Brainto sedation

6–8 February

UK Stroke Forum Conference

4–6 December

Las Vegas, USA

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