NeuroNews Issue 35 US New

September 2019 | Issue 35

RESILIENT trial set to shape stroke systems of care in developing countries

Georgios Matis:

“Disruptive” social media

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The final results of the first thrombectomy trial in a developing country convey the “overwhelming efficacy of mechanical thrombectomy”. Given that 35% of the treatment arm achieved a modified Rankin Scale (mRS) score of 0–2 compared to just 20% of controls, Raul G Nogueira (Grady Memorial Hospital, Atlanta, USA) says, “We have overcome financial, logistical and political barriers, [and] by doing so, we have had the opportunity to impact and influence many other countries that share our same reality.”

These data from the RESILIENT (Randomisation of endovascular treatment with stentretriever and/or thromboaspiration versus best medical therapy with acute ischaemic stroke due to large vessel occlusion) trial were first presented by Nogueira and Sheila Martins (Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil) at the European Stroke Organisation Conference (ESOC; 22–24 May, Milan, Italy). Now, Martins exclusively speaks to NeuroNews to provide an update on the RESILIENT team’s plan of action following the trial’s positive results.

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The clinical utility of evoked compound action potentials is echoed by data from Evoke and Avalon New data from both the Evoke and Avalon studies reiterate the importance of objective neurophysiological measures and clinically meaningful outcomes.

These studies evaluated the performance of the first closed-loop spinal cord stimulation (SCS) system (Evoke; Saluda Medical) that objectively measures the spinal cord’s response to stimulation and both studies have in turn demonstrated improvements in pain, function, sleep, and quality of life.

The RESILIENT team at ESOC

“A

fter presenting the results in May, we have had discussions with the Ministry of Health in Brazil about the results of the study and the cost-effectiveness analyses. Our plan is to start with 20 public hospitals, which were evaluated during the RESILIENT trial for around 18 months. After this, we are planning to evaluate other centres,” stated Martins, highlighting that, “We learned from the trial that you need to evaluate the quality of both the stroke centre and the quality of training for neurointerventionalists, because they need to be trained in thrombectomy before they can start to perform the procedures.”

Expanding on the first steps, Martins tells NeuroNews that the next stage is for the Ministry of Health to approve only these 20 centres initially.

Following this, she says, “We will write a policy for

these centres, detailing how to be a comprehensive stroke centre in Brazil, to guide the Ministry of Health with these approvals. The Ministry likes the results and the first cost-effectiveness outcomes; it is possible that it might approve it this year, or early next year.”

When questioned on whether Brazil has the capacity to accommodate the inevitable rise in thrombectomy treatment that will result, Martins posits, “We have 62 private stroke centres already performing thrombectomy in Brazil. But it is the public stroke centres that have a higher number of hospitals. Most likely, we will need more interventionalists, so some centres are opening a fellowship programme for neurointerventionalists to have more experts help cover the country. I think when we have hundreds of hospitals, or more, we will need more help. Right now, Continued on page 2

“FOR THE FIRST time, we use physiology to guide our decisions. When employing evoked compound action potentials [ECAPs] to control a feedback mechanism—providing more precise spinal cord activation—the results elicit superior clinical outcomes,” surmised Lawrence Poree (University of California, San Francisco, USA) while presenting the Evoke study during the International Neuromodulation Society (INS) 14th World Congress (25–30 May, Sydney, Australia).

The Evoke study is a prospective, multicentre, randomised, double-blind pivotal study comparing ECAP controlled closed-loop SCS with open-loop (fixed output). Providing the rationale behind the novel Evoke System, Poree put forward, “We know that the epidural space is a dynamic environment, and that the region of the spinal cord that is targeted may not always receive the stimulation we program as the spinal cord position within the electric field is constantly in motion due to cardiac pulsations, respiration, coughing, positional changes and so on. At this time, commercially available spinal cord stimulation devices are incapable of detecting and accommodating for most of these variables.”

Ultimately, Poree stated that the primary question that needed answering was whether analgesia and Continued on page 23

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September 2019 | Issue 35

RESILIENT

RESILIENT continues to shape stroke systems of care in developing countries Continued from page 1

we do not have enough neurointerventionalists.

“We discussed training with the government too. We have a partnership with the Society of Neurointerventionalists, and we have a plan to train more and more neurointerventionalists in this first year with Brazilian experts, some of whom are based in the USA, such as Raul Nogueira—a fellow principal investigator in the trial. Together, we want to create a strong hands-on teaching course to train neurointerventionalists.”

Discussing the importance of RESILIENT’s clinical implications worldwide, Martins said: “I think what is happening in Brazil is very important to other developing countries. I have participated in several meetings in other countries, encouraging them to implement endovascular treatment for stroke. For example, I went to Costa Rica, and I am headed to Argentina to talk about the idea of having a huge network to help other countries make plans to implement.”

According to Martins, the RESILIENT team is promoting the Global Stroke Alliance meeting (http:// globalstroke2020.com), which will take place in March 2020 in Brazil. It will include several experts and policy-makers from other developing countries, to help discuss how to implement stroke systems of care. It is expected that several countries in Latin America will participate, and that representatives from the Ministry of Health will consider how to make thrombectomy more available in other countries.”

RESILIENT: The rationale and results

Addressing the ESOC audience in May, Nogueira stated: “It took exactly 17 years for the government [of Brazil] to begin paying for tPA [tissue plasminogen activator] in the public heathcare system; this is the reality of healthcare outside of first-world countries. The issue is that, although we are dealing with the second cause of death and the main cause of disability, the cost of thrombectomy was judged to be too expensive for the country.”

Nogueira further explained to the audience why thrombectomy outcomes might differ in countries with lower resources, and specifically why the current study was likely to elicit negative results.

He said that in the prehospital setting, delays in diagnosis, transfer, and patient triage are common, while he added, “Our population is also a lot more

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patients for a 10% treatment effect difference, on 3 March earlier this year, the Data and Safety Monitoring Board (DSMB) recommended that the trial should be terminated due to a “clear crossing of the boundary for efficacy at the first interim analysis” after 174 patients had completed 90day follow-up.

Thus, in total, 221 patients with “similar baseline characteristics” were randomised over the course of 25 months: Raul Nogueira and Sheila Martins presenting RESILIENT at ESOC 111 to mechanical thrombectomy and 110 vulnerable in terms of nutritional, socio-economic controls (average age: 64, mean NIHSS: 18±5, 65% and educational status.” Regarding the hospital received tPA, 18% with ICA occlusions). infrastructure itself, he speculated that “different training In terms of patient presentation and procedural of neurointerventionalists, a difference in available duration, symptom onset-to-needle time was below angiosuite technology, postprocedural treatment, and a three hours in both groups: 170 (range: 132–213) lack of access to rehabilitation” all further contribute to minutes for thrombectomy and 161 (115–219) minutes suboptimal thrombectomy outcomes. for controls. Door-to-needle times were 34 (25–53) and 33 (25–50) minutes for thrombectomy and controls, respectively, while door-to-puncture time was 116 (90–159) minutes. Finally, symptom-to-recanalisation times were around five hours, taking an average of 317 (273–390) minutes.

Turning to the ESOC audience, Martins said that the ordinal analysis for the modified mRS score at 90-days displayed superiority for thrombectomy (adjusted OR: 2.28; 95% CI: 1.41, 3.7; p=0.001). The secondary outcomes examining functional independence (mRS Despite these limitations encountered in the Brazilian ≤2) at 90-days showed favourable results, as 35% of the public healthcare system, the Ministry of Health thrombectomy arm achieved mRS 0–2, with only 20% agreed to sponsor a thrombectomy trial. Co-chaired by of controls achieving the same result. This meant that Nogueira and Martins, the study investigators carried the number needed to treat for one additional 90-day out a multicentre, prospective, randomised, open, independent outcome was 6.6. blinded endpoint, controlled trial in 20 stroke centres In terms of safety outcomes, Martins reported the in Brazil. incidence of symptomatic intracranial haemorrhage The patient population (n=690) consisted of those as low, at around 6–7% for patients that received with acute ischaemic stroke with large vessel occlusion thrombectomy, and 5–6% for controls. “The mortality (ICA and/or MCA-M1) no more than eight hours was similar in both groups, with severe dependency from onset. Specifically, patients had a disability of [mRS 5–6] at 90-days higher in the clinical treatment modified Rankin Scale ≤1, while further key inclusion arm: 46% versus 31% for the treatment arm,” added criteria included National Institutes of Health Score Martins. Only 12 patients underwent procedural (NIHSS) ≥8 and Alberta stroke program early CT score complications.

(ASPECTS) ≥6 at baseline.

Summarising the study’s findings, Martins said, “The Patients were randomised 1:1 to either Solitaire overwhelming efficacy of mechanical thrombectomy (Medtronic) and/or Penumbra plus medical persists despite the many limitations encountered in the management, or medical management alone. Follow-up public healthcare system of a developing country,” and took place after 24 hours, at discharge and on day 90. added, “Mechanical thrombectomy should be available Although the sample size was set to achieve 690 to many more patients, globally.”

We have a plan to train more and more neurointerventionalists in this first year with Brazilian experts.”

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September 2019 | Issue 35

Treatment choices

Transradial access is safe and effective for neuroendovascular procedures

In the largest cohort study to date, new research from Jefferson (Philadelphia University and Thomas Jefferson University, Philadelphia, USA) demonstrates that transradial surgery, done via the wrist, is safe and effective for a broad range of neuroendovascular procedures, and gives patients faster recovery with less procedural risk. Neurointerventionalists most commonly use a transfemoral approach, threading instruments through arteries in the groin.

“D

espite improved safety shown in large cardiology trials, transradial brain surgeries via the wrist are much less common,” says senior author of the study and neurosurgeon Pascal Jabbour (Jefferson, Philadelphia, USA). “Neurosurgeons tend to prefer the transfemoral approach on which many of us were trained. But our research demonstrates that all kinds of neurological procedures can be done effectively and even more safely via the wrist.”

Transradial access has been widely adopted by interventional radiologists across a range of procedures, with many advocating for its use due to its positive clinical outcomes and patient satisfaction measures.

Jabbour and his team, including first author Omaditya Khanna, retrospectively examined the medical

records of 223 patients who underwent via transradial access. Periprocedurally, 233 consecutive neuroendovascular only two patients had symptomatic radial interventions via radial artery access artery spasm, and there were no instances at Jefferson. The procedures included of iatrogenic complications (such as vessel diagnostic angiograms, mechanical dissection, stroke, and haemorrhage). thrombectomies, arteriovenous In 10 cases (4.3%), the intended malformation (AVM)/ arteriovenous procedure could not be completed via a fistulae (AVF) embolisations, coiling, transradial approach, and, thus, femoral stent-assisted-coiling, Woven EndoBridge artery access had to be pursued instead.

(WEB) intracranial aneurysm device Ten patients complained of minor placement and flow-diversion treatments postprocedural complications, although Pascal Jabbour of cerebral aneurysms, and carotid stent none required therapeutic intervention. placement.

Jabbour and colleagues conclude: A subset of 66 patients who had undergone both “Radial artery catheterisation is a safe and durable transfemoral and transradial surgeries were selected to alternative to perform a wide range of neuroendovascular complete a satisfaction survey to assess their preference. procedures, with a low rate of complications. On As published in Stroke, the majority of patients—94%— the whole, patients prefer transradial compared with said they preferred surgery through the transradial route. transfemoral access.”

In addition, patients overall reported shorter recovery times with transradial access. It is easier to ensure a blood Transradial access in acute ischaemic vessel in the wrist has clotted, and so patients can go stroke interventions home shortly after surgery, rather than laying horizontally Jabbour was one of the first neurosurgeons to perform for four to six hours after transfemoral surgery. The brain surgery via the wrist and has continued to teach mean procedure time was also shorter for diagnostic others this technique. angiograms performed via transradial versus transfemoral In 2016, Diogo Haussen (Emory University School access (18.8±15.8 vs. 39.5±31.1 minutes; p=0.025). of Medicine and Grady Memorial Hospital Marcus “Lying flat after certain kinds of brain surgery should Stroke and Neuroscience Center, Atlanta, USA) and be avoided in cases with high intracranial pressure, colleagues set out to describe the feasibility and safety and yet it is the best way to prevent groin and internal of transradial access in the interventional management bleeds,” comments Jabbour. “For these cases surgery via of acute ischaemic stroke. Publishing their findings the wrist is by far the safest option.” in the British Medical Journal (BMJ), they concluded One of the most compelling reasons to change practice, that failure of transfemoral access in the endovascular says Jabbour, is that it eliminates the risk of rare but treatment of acute ischaemic stroke is uncommon, “but potentially dangerous complications of post-surgical leads to unacceptable delays in reperfusion and poor bleeds in the groin and retroperitoneal area, which can be outcomes. Standardisation of benchmarks for access difficult to detect. The overall incidence of perioperative switch could serve as a guide for neurointerventionalists. and postprocedural complications was investigated, and Transradial access is a valid approach for the was found to be low across all procedures performed endovascular treatment of acute ischaemic stroke.”

Practice area and physician experience among top factors influencing choice to treat A survey investigating the factors associated with the decision-making for endovascular thrombectomy (EVT) procedures found that such decisions differed significantly between regions and specialities depending on their local resources, but not under assumed ideal conditions. At the Society of NeuroInterventional Surgery’s (SNIS) annual meeting (22–25 July, Miami, USA), Mayank Goyal from the University of Calgary, Canada, lead author of the study, said that the most important factors influencing EVT decisions are the National Institutes of Stroke Scale (NIHSS) scores (34.9%), the level of evidence (30.2%), ASPECTS or ischaemic core volume (22.4%), patients age (21.6%) and clinicians’ experience in EVT procedures (19.3%).

“PHYSICIANS OF DIFFERENT specialties and practicing in different geographic regions make decisions based on different external variables,” said Goyal, adding that, “While it is promising to see acceptance of EVT as the standard of care for patients with acute ischaemic stroke, it is clear that more work needs to be done to standardise decision-making for the benefit of all patients.”

Goyal and colleagues took 22 casescenarios from 38 countries to form the contents of the survey. Then, each survey included 10 scenarios at random, each questioning “How would you treat it, and how do you think it should be treated?

“If you think about it, many factors, including patient demographics, the clinical presentation, as well as physician factors and local access factors all come into play collectively to decide whether the patient gets treated or not,” surmised Goyal.

Now speaking to NeuroNews, he discusses the results.

Did any of the results surprise you?

Overall, most of the results matched our expectations. We were pleasantly surprised to see most physicians decided to offer endovascular treatment regardless of patient age, co-morbidities, etc, and even in those case-scenarios for which no clear guideline recommendations for EVT exist.

Did you find any gender disparities in EVT decisionmaking?

We did not find any significant differences in treatment decision-making between female and male physicians.

However, the resources gap was higher for females compared to males (8% vs. 2%). In other words: 8% of female physicians wanted to perform EVT but could not due to external limitations, while the number for male physicians was lower (2%). We assume that this is because female physicians were mostly neurologists, and as opposed

to neurosurgeons or interventional neuroradiologists, they often work in smaller hospitals with limited access to endovascular treatment. However, we can only speculate about the reasons for this observation since it did not reach statistical significance.

How does decision-making vary geographically? Were there any unexpected resulting pertaining to this?

We found vast variations in EVT decision-making among different regions of the world. As expected, the resources gap in some countries—in South America and South Asia, for instance—was larger.

However, there were a few unexpected findings, too: the United Kingdom, for instance, despite being a relatively wealthy “first-world country”, had a dramatic resources gap of 33%. That means UK physicians cannot perform endovascular treatment in on out of three patients due to external limitations, although they would want to.

Is there a knowledge gap?

What can we do in the future to close this?

We indeed found a small knowledge gap in our study: under ideal conditions (i.e. when assuming there are no external restraints), the decision rate for casescenarios with level 1A evidence for EVT should ideally be 100%, since the guidelines clearly recommend EVT in these cases. But the decision rate we observed was lower (90.6%). This means physicians decided not to offer EVT in almost one out of 10 cases in which it was clearly indicated. This is what we called a “knowledge gap” in our study, but there are several explanations: one is that physicians are not aware of the guidelines (“real” knowledge gap), but it might as well be that they know the guidelines but do not personally agree with them and deliberately decided not to follow them.

We think that it is important to better understand the reasons of this presumed knowledge gap in order to increase guideline adherence and EVT rates further.

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September 2019 | Issue 35

Physician wellbeing

The burden of a stroke call: 56% of US neurointerventionalists meet criteria for burnout Fifty-six per cent of US neurointerventionalists meet criteria for burnout. This statistic, presented by Kyle Fargen from Wake Forest Baptist Health in Winston-Salem (USA) at the Society of NeuroInterventional Surgery’s (SNIS) annual meeting (22–25 July, Miami, USA), was based on a recent survey examining burnout and professional satisfaction among US neurointerventionalists.

A

multivariate regression revealed that feeling underappreciated by departments or institutions are independent predictors of burnout, while additional payments for stroke call is protective against burnout. Moreover, Fargen reported that physicians that covered more than one hospital on call had a two times higher odds of burnout compared to those that covered a single hospital while on call.

Addressing the SNIS audience, Fargen reiterated the unfortunate statistics associated with the topic: “Suicide is a leading cause of death in male residents and the second leading cause in female residents. Ten per cent of medical students report suicidal ideation [and] about 400 doctors commit suicide every year. As a population, we are about twice as likely as the general population to do so.” He added, “Whether you believe in [burnout] or not, it has become a huge talking point in the medical community.”

While burnout is associated with poor quality of life, depression, alcoholism, and suicidal ideation in the physician, it also carries negative implications for patients.

According to Fargen, physicians meeting criteria for burnout are more likely to make medical errors, and are 17% more likely to face malpractice lawsuits. “So we wanted to look at burnout for our population, and the impetus for doing so was the ever increasing burden of stroke,” he said.

Referring to a previous investigation, Fargen acknowledged that in 2016, a thrombectomy procedure occurred every five days, whereas in 2017 they rose to one every three days. “Now, after DAWN and DEFUSE 3, our unpublished research shows that a thrombectomy procedure occurs more frequently than one every two days.

This means that two hours a day—124 minutes—is spent on stroke.

“This is why physician representatives and leaders of all three neurointerventional organisations were involved in the development and dissemination of the survey.”

The 39 question online survey was comprised of 17 demographic, career or personal questions, and 22 from the Maslach Burnout Inventory Human

In terms of the risk factors for burnout, he noted, “There is no difference based on training background, no difference on practice setting, or based on years of independent practice. Interestingly, there was also no difference based on stroke call frequency. Obviously, we predicted that people taking calls every day or every other day would be at higher risk—but that is not the case.”

Yet, of importance, he told the SNIS audience that survey extracted some worrying figures: “It seems that half of us are taking a call every day or every other day, which seems excessive, and probably a problem.”

Reiterating the “protective” nature of additional compensation, Fargen said that 45% of neurointerventionalists report getting additional compensation for every 24-hour call. Interestingly,

your colleagues, and look out for your trainees. There is resiliency and mindfulness training for those that are concerned. Burnout should be a shared responsibility between physicians and health care systems, but realistically, until healthcare systems do their share, own it and be vigilant about it.”

Providing further insight on the matter, Philip M Meyers, associate professor of Radiology and Neurological Surgery, Columbia University, College of Physicians and Surgeons, New York, USA, speaks to NeuroNews and echoes the importance of the topic.

“Burnout has become a common theme in modern industrial society, and physicians are not exempt”, he says. “While the practice of medicine has often been referred to as a noble calling, physicians have demanding

Kyle Fargen

Kyle Fargen presenting the results at SNIS

Services Survey (MBI-HSS) for medical personnel. It elicits scores pertaining primarily to three domains: emotional exhaustion, depersonalisation and personal accomplishment.

Findings from the US survey

Fargen described the survey as a having an excellent response rate, explaining that the 321 responses represent a third of all US neurointerventionalists. “As a whole, 56% of our respondents met criteria for burnout, which falls right into the 50–60% range [for all physicians].” He added, “I thought that maybe we would see a higher personal accomplishment score in our specialty compared to others, but that was not the case.”

Alluding to some good news, he highlighted that even though 55% of neurointerventionalists meet criteria for burnout, life and career satisfaction scores within the field are high. “On a scale of one to 10, most people rate their career choice and happiness overall anywhere from seven to nine,” he said.

Half of us are taking a call every day or every other day, which seems excessive, and probably [is] a problem.” he also commented that at each step up of pay, there is a reduction in odds (of meeting burnout criteria) by 0.4. “This data is available in our publication,” he told delegates, adding that he used this data to argue for additional call compensation after the study was complete.

Concluding his talk, he called for attendees to further their awareness and understanding of the issue at hand.

“This is something that is here to stay.

Pay attention to your work environment,

jobs, requiring dedication, time, and personal sacrifice. Medscape conducted its annual report on physician burnout, depression and suicide in 2019, identifying burnout in 44% of more than 15,000 US physicians surveyed, particularly in those working more than 70 hours per week, often affecting their interactions with family, patients, staff, and colleagues. More than one physician commits suicide per day in the USA, a rate higher than any other profession. The majority of physicians do not seek help.

“Following the success of numerous stroke trials, the demand for emergency stroke care has increased dramatically. More than half of the 321 neurointerventionalists surveyed are oncall for neurological emergencies every other night. Moreover, the requisite 30-minute response time and stringent stroke practice metrics take their toll on physician wellbeing.

“Covering multiple hospitals simultaneously and feeling underappreciated were strong, independent predictors of burnout in Kyle Fargen’s model. Fewer than half of respondents receive additional compensation for their efforts. Fargen called for greater awareness and proactive measures to combat burnout among neurointerventionalists. As the need for neurointerventional services expand, a new balance between skilled work-force training and the demand for medical services must be met.”

Issue 35 | September 2019

Advertorial

7

ADVERTORIAL SPONSORED BY CERENOVUS

Advanced engineering improves rates of revascularisation through the first-pass effect In acute ischaemic stroke, fast and complete recanalisation of the occluded vessel is associated with improved outcomes. While morbidity and mortality in these patients can be high, achieving complete or near-complete reperfusion has been associated with significant clinical benefit and reduced adverse effects. Here, Professor Vincent Costalat, head of the department of Interventional Neuroradiology at Gui de Chauliac University Hospital, Montpellier, France, speaks to NeuroNews about how evolving technologies are permitting improved rates of revascularisation and clinical outcomes through achieving the first-pass effect.

What is the first-pass effect and how is this driving innovation in the treatment of acute ischaemic stroke?

The first-pass effect is the clinical benefit induced by a quick and fast recanalisation after the first-pass of a thrombectomy device. We know now that when we repeat the attempt in a patient, we are increasing the risk of collateral infarction, of vessel dissection and, in addition to this, we are increasing the time of the treatment. A recent publication from the Embotrap ARISE 2 study found that, independent of the time and the complication rate, opening the vessel immediately after one pass shows clear benefit to the patients.

What is its impact on patient outcomes and mortality rates?

The mortality rate in stroke management depends on the severity of the stroke that you are managing.

So, the severity of the patient at presentation would be the strongest prognostic factor. The success of recanalisation will dramatically reduce the mortality rate of the patients, and achieving a first-pass is a guarantee of reducing the final infarct core.

What are the usual success rates?

The usual success rates for recanalisation will depend on both operator and centre experience. From what we can see in the literature, the first data published in 2014 were around 60% of thrombolysis in cerebral infarction (TICI) 2b/3, in the context of low experience.

In more recent literature testing the latest technology, recanalisation rates are now around 85% of TICI 2b/3.

What are the different mechanisms currently used to remove a clot in the first pass?

The technique to remove a clot in the first pass will also vary depending on the operator and centre experience. But, in Montpellier for example, we tend to use a maximalist approach, using a balloon guide catheter, an intermittent catheter, and next-generation stents—like the Embotrap for example. This allows us to achieve more complete recanalisation after only one pass.

Why would you choose to use the Embotrap II device?

An advantage of Embotrap II is the basket end at the tip of the device, which may be used to grab some fragment of the clot during the retrieval manoeuvre. This Professor Vincent makes the Embotrap II a little different Costalat from the other stents today. Regarding the in silico study we did in our department using Embotrap II, we have carried out up to 150 In terms of real-world cases using consecutive thrombectomy cases that demonstrate that Embotrap II, could you describe the device has the ability to reduce the rate of collateral a typical patient’s status preinfarction compared to other devices and increase the intervention? complete recanalisation rate. This was an in silico study In general, the patients that present with a large artery of course, and while it did not reach full significance, occlusion have an average NIHSS (National Institutes the results were in favour of a trend. From what we of Health Stroke Scale) score of around 17. The experienced, the device performed really well at safely average necrotic core may vary a lot between patients. removing the thrombus in one pass. In addition, the With Embotrap you can treat any patient, from almost outcome of the Embotrap II ARISE 2 study was very promising, one of the best in the literature to date. We also have to understand that there is a learning curve, where the later studies tend to show better results than the earlier studies because of the learning curve in the community using the thrombectomy devices. But, we have to admit that the Embotrap II trial results were Embotrap II very encouraging, and Embotrap II is now one of our three major stentrievers used daily in the department.

Thrombectomy fails to find a benefit in the older population with low ASPECTS and large core infarct volume

The low Alberta stroke program early CT score (ASPECTS) of 4–5 has been deemed the threshold for mechanical thrombectomy, with no benefit elicited in those with ASPECTS 0-3. Moreover, the clinical outcome in low ASPECTS may be age dependent, with negligible benefit achieved in those above 75 years of age. These conclusions, presented by Osama Zaidat (Mercy Health, St Vincent Medical Center, Toledo, USA) at the Society of NeuroInterventional Surgery’s (SNIS) annual meeting (22–25 July, Miami, USA), are indicative of the low ASPECTS subgroup identified through the STRATIS registry.

“STRATIS HAS PROVIDED an opportunity to look at the patients that were enrolled outside the guidelines, patients with low ASPECTS. And, the good thing about CT ASPECTS from this registry is that they were core lab adjudicated,” said Zaidat.

He highlighted that ASPECTS 0–5 was associated with a lower functional outcome, while ASPECTS 0–3 have even lower rates of good outcome (10%), with a 60% rate

any location. The device is one size in diameter and length, and will allow you to treat vessels from M2 (of the middle cerebral artery) up to the carotid.

of mortality. Further, patients within the ASPECTS 4–5 group had a good clinical outcome of 33%, with a mortality rate (MR) of 23%. In terms of the intersection between age and low ASPECTS, patients above the age of 75 experienced little benefit (mRS 0–2: 0%, MR: 58%).

Describing the STRATIS patient population, he said that 984 were enrolled in the STRATIS Registry, 763 patients had a core lab ASPECTS read for their CT

scan, and 57 (7.5%) had an ASPECTS of 0–5. “So it is a small sample size, reflecting that many neurointerventionalists are following the guidelines and do not treat many patients with ASPECTS less than six.

However, this subgroup analysis provides an opportunity to explore the clinical outcome of these patients.”

He noted that the investigators further dichotomised these patients into ASPECTS scores of 0–3 and 4–5, with 10 and 47 patients in each group, respectively, to identify the threshold below which MT may be futile.

Zaidat said: “High ASPECTS patients were more likely to be younger, and they probably do not have as many collaterals.

Diabetics are more common with low ASPECTS scores.”

He added, “The stroke at baseline was more severe (average NIHSS of 22 for ASPECTS 0–3 vs. 17 for ASPECTS 6–10), meaning they were more likely to have general anaesthesia. And, there is a delay in groin-to-puncture times which may be related to the anaesthesia, the general management, or the severity of stroke [for low APSECTS patients]. You would think that a severe stroke would present early, but for some reason they presented late, which could be related to being more likely

wake up strokes.” Moreover, patients with ASPECTS 0–5 were more likely to have an internal carotid artery occlusion compared to those with higher scores (ASPECTS 0–3: 50%; ASPECTS 4–5: 40.4%; ASPECTS 6–10: 22%).

Ultimately, Zaidat surmised that ongoing prospective randomised controlled trials will address this specific group of patients.

Alluding to those currently underway, he pointed to the TESLA (Thrombectomy for emergent salvage of large anterior circulation ischaemic stroke) USA and EU trial, where patients (n=300) with ASPECTS 2–5 within 24 hours are to be selected and randomised to endovascular therapy plus medical management, or the latter alone.

Second, he noted that the TENSION (Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window) trial will include patients with ASPECTS 3–5, within zero to 12 hours from last known well or an unknown time onset. Finally, while the LASTE trial has not yet started recruiting, Zaidat said that it intends to evaluate acute mechanical revascularisation in an ASPECTS 0–5 patient population with large vessel occlusion within seven hours after stroke onset or last known well.

8

Device update

Three-year outcomes of the Surpass system confirm its safety and efficacy Three-year outcomes of the Surpass intracranial aneurysm embolisation system pivotal trial to treat large or giant wide neck aneurysm (SCENT trial) confirm the safety and efficacy of the device. Referring to the significant progression of aneurysm occlusion, Ricardo Hanel (Baptist Stroke & Cerebrovascular Center, Jacksonville, USA) said “the efficacy improves over time”, while the 12-month to three-year adverse eventrate with the Surpass device (Stryker) was found to be very low.

DURING HIS PRESENTATION of the data at the Society of NeuroInterventional Surgery’s (SNIS) annual meeting (22–25 July, Miami, USA), Hanel acknowledged that the trial’s 12 month results— presented at SNIS two years ago—led to the Surpass

September 2019 | Issue 35 device becoming the first flow diverter with sickle cell disease who had stopped to be indicated by the US Food and Drug taking antiplatelet agents, specifically Administration (FDA) to treat large and aspirin, and the other was a posterior giant posterior communicating artery circulation ischaemic stroke that, aneurysms. according to Hanel, “was not related to the “Its premarket approval enables its device and not in the territory of the index use for unruptured or giant saccular or procedure”. fusiform aneurysms (≥10mm diameter), In relation to the efficacy of the as well as wide neck, or those within the Surpass device, Hanel said there was an petrous segment to the terminus arising improvement from baseline occlusion from a parent vessel—for artery diameters rates. Clinically speaking, the percentage of 2.5–5.3mm,” said Hanel, adding that of modified Rankin Scale (mRS) scores Ricardo Hanel patients above the age of 18 with a single that had improved from the last visit was internal carotid artery aneurysm were 24.7% at 12 months, and 11.2% at 36 eligible for enrolment in the SCENT trial. months, while the percentage of those that had remained Moreover, he reported, “If you compare this SCENT stable was 64.5% and 75% at 12 and 36 months, trial with previously published prospective trials, it respectively. was mostly an intradural aneurysm trial, as 69% of the aneurysms were intradural, and 31% extradural—mostly cavernous aneurysms.”

Alluding to the decrease in the patient population over the past two years, he acknowledged that, “over time, we lose patients to follow-up”. Though the investigators began with a modified intention-to-treat number of 180, 42 were lost due to withdrawal or death, leaving the three-year outcomes representative of 138 patients.

Hanel surmised, “In total, 94.9% [131/138] patients Pointing to the effectiveness outcomes, Hanel reported, completed clinical follow-up at 36-months, while 81.2% “There is not much difference between parent stenosis [112/138] completed clinical and angiogram follow-up or implant stenosis at one year compared to three years.” at 36 months.”

Further, in terms of the complete aneurysm occlusion In terms of the safety results, he said, “When the rates, which increased from 68.3% at 12 months to 12-month data ware presented here before at SNIS, new 78.3% at 36 months, he noted that they represent “a or worsening ipsilateral stroke occurred in 8.3% [15/180] progression of the occlusion of the aneurysm as expected of the patient population, while 2.2% incurred an from one-year follow-up results to 36 months”, telling aneurysm rupture, and 0.6% had to undergo retreatment the SNIS audience: “You can see this represented in at 12 months.” a different way, between Raymond Class Grade 1, 2, Furthermore, Hanel pointed to data indicating that or 3. At 12-month follow-up, Raymond 1 was 66.1% only two new ischaemic events occurred beyond 12 and increased to 78.3% at 36 months, so a dramatic months. One involved an ischaemic stroke in a patient improvement in the occlusion rate at three years.”

[We saw] a dramatic improvement in the occlusion rate at three years.”

Issue 35 | September 2019

Research

9

Poll favours interventional radiologists to perform mechanical thrombectomy in lieu of neurointerventionalists

According to a BIBA MedTech survey, 52% of neurointerventionalists believe that they are the only specialists who have the relevant skills and experience to perform interventional stroke procedures (e.g. mechanical thrombectomy). However, of those who believe other specialities—with the appropriate training—could potentially perform such procedures, 58% propose interventional radiologists.

Previous discussions about other specialists performing interventional stroke procedures have focused on interventional cardiologists.

MECHANICAL THROMBECTOMY is now an established treatment for patients with emergent large vessel occlusion, but who should perform this procedure is controversial.

A 2016 multisociety consensus document—published in the Journal of NeuroInterventional Surgery—states that “physicians providing intra-arterial treatment for acute stroke are required to have appropriate training and experience for the performance of neuroangiography and interventional neuroradiology”. However, some believe that restricting interventional stroke procedures (specifically, mechanical thrombectomy) to neurointerventionalists may limit the number of patients who are able to access the therapy, given the lack of relevant operators in some areas. For example, in the 2019 Vascular and Endovascular Challenges Update, cardiologist Jan Kovac writes that “collaboration of various interventional specialists is desirable to deliver this therapy to a wider population”.

A previous poll on this issue, conducted at the 2019 Charing Cross Symposium (15–18 April, London, UK), indicated that 57% of respondents were against mechanical thrombectomy being restricted to neurointerventionalists. However, these respondents were predominantly vascular and endovascular surgeons.

Therefore, BIBA MedTech sought to understand how practising neurointerventionalists felt about the issue.

Of 54 neurointerventionalists surveyed, 52% agreed that “only neurointerventionalists should perform interventional stroke therapy” vs.

48% who did not agree. Of those who did not agree (26), 58% replied “interventional radiologists” in response to the question “who else (with appropriate training) do you feel might be able to perform interventional stroke procedures?”. Of note, only 15% said interventional cardiologists.

See Figure 1.

In his chapter in the 2019 Vascular and Endovascular Challenges Update, Kovac proposes interventional cardiologists as suitable alternative specialists to perform interventional stroke procedures. He states that cardiologists are “no strangers to stroke care”, commenting that “cardiologists have traditionally played an important role in stroke prevention by providing both comprehensive medical and interventional management of cardiovascular risk factors [for stroke] including atrial fibrillation.” He adds: “It appears reasonable to complement the existing workforce of neurointerventional radiologists by interventional cardiologists being properly trained in mechanical thrombectomy, joining the

Source: BIBA MedTech

interdisciplinary stroke teams led by neurologists”. However, Kovac does stress that there is “absolutely no doubt that a fully trained neurointerventionalist,

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BIBA Briefings is an online platform (www.bibamedtech.com/bibabriefings) that gives in-depth analysis of the latest market intelligence from BIBA MedTech Insights (www.bibamedtech.com). It also reviews the latest industry news and pipeline developments.

For editorial enquiries, please contact Dawn Powell: dawn@bibamedical.com For sales enquiries (including BIBA MedTech Insights), please contact Merveille Anderson: merveille@bibamedical.com

New study reveals independent predictors of the first-pass effect

Non-internal carotid artery (non-ICA) site of occlusion, the use of a balloon-guided catheter, and better collateral grade were all independent predictors of the first-pass effect.

Ashutosh Jadhav, University of Pittsburgh, Pittsburgh, USA, presented these findings from the STRATIS registry at the Society of NeuroInterventional Surgery’s (SNIS) annual meeting (22–25 July, Miami, USA).

D

uring his presentation, he defined the first-pass effect (FPE) as “having achieved complete revascularisation after a single attempt with mechanical thrombectomy”, and acknowledged that FPE has been “associated with good clinical outcomes in patients presenting with large vessel occlusion”.

The STRATIS registry was a non-randomised registry of 984 patient treated at 55 sites. “It afforded us several advantages over the previous NASA registry,” asserted Jadhav. “It was prospective, with core lab imaging, and included a larger population of patients.” Results of the study showed that a first-pass effect was achieved in 40% of patients and that rates of mortality at 90 days were lower in the FPE group compared to the non-FPE group (12% vs.

with audited practice outcomes, and adequate skill maintenance, is the optimal provider of mechanical thrombectomy for stroke patients”.

19%, respectively).

He said that in patients with FPE versus a non-FPE, characteristics were comparable across most of the baseline features. However, the presence of an ICA occlusion was much more frequent in the non-FPE population.

“If we look at procedural characteristics, there were no significant differences in the utilisation of IV tPA, onset to arrival, and onset to puncture. But, as you would expect, puncture to reperfusion was significantly faster in patients who achieved a first-pass effect,” reported Jadhav.

However, he addressed an important bias in the firstpass literature, “When you compare FPE versus non-FPE populations, you may be looking at patients who did not achieve complete recanalisation. We know that complete

recanalisation is a very strong predictor of good outcome.”

Pointing to a table of outcomes, he posited, “The first-pass effect continues to be a strong predictor of good outcome and lower mortality, even when compared to patients who achieved good recanalisation after multiple passes.”

Delving into the multivariate predictors of an FPE, he said that certain patient specific features favour achieving it, such as good collaterals, as well as M1 or M2 as the site of occlusion instead of ICA as the site of occlusion. “So, the more distal you go with your occlusion, the less clot burden, and the higher the likelihood of a first-pass effect,” Jadhav put forward.

“To summarise, the STRATIS registry shows similar improvements in outcome with an FPE as found in NASA, but it is a much more rigorous study design.” He added that the effect continues to be associated with better outcomes— even when compared to patients who achieved technical successful outcomes based on recanalisation. Moreover, patient outcomes overall have improved since NASA, which Jadhav attributed to improved devices and techniques.

Finally, he concluded that “by understanding more about the factors that influence a good clinical outcome, we can reach our goal of helping all stroke patients survive and thrive”, as he called for further studies “to maximise the FPE and continue these trends”.

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September 2019 | Issue 35

Robotics

A robotic future for the neurovascular field is deemed feasible Does the shift away from open surgical vascular procedures towards percutaneous interventions favour a rise in the use of robotics? Gavin Britz (Houston Methodist Hospital, Houston, USA) argues yes, telling the delegates at the Society of NeuroInterventional Surgery’s (SNIS) annual meeting that the shift has resulted in “faster, safer and more effective treatments”, and has been facilitated by the fact that the underlying disease process “lies within the vascular tree and affords direct access by minimally invasive means”.

FOLLOWING HIS PRESENTATION of the first study to demonstrate the feasibility of a robotic-assisted platform for intracranial neurovascular interventions at the SNIS annual meeting (22–25 July, Miami, USA), Britz spoke to NeuroNews about the findings of the trial and what the advent of robotic-assisted interventions may mean for the field.

What are the advantages of using robotics for neurovascular procedures?

Firstly, robotic-assisted interventions will decrease the radiation dose for the surgeon as the surgeon sits away from the direct radiation. Secondly, remote surgery will be possible, including remote stroke. This

will decrease the workforce needs, as a well-trained neurointerventionalist surgeon will be able to perform surgery from miles away. This is very important aspect. Next, remote proctoring is possible with robotics, and will allow a more senior surgeon to remotely help with the cases done by a junior surgeon. And lastly, automation of dangerous aspects of procedures will make them safer by decreasing human error.

What did you set out to achieve?

Despite advances in robotic-assisted technology for cardiac and peripheral vascular interventions, a robotic-assisted platform for neurovascular intervention is not yet available. The goal of this preclinical study was to evaluate the feasibility of the CorPath GRX robotic-assisted platform (Corindus) for neurovascular interventions.

What were the findings of the study?

The robotic system was tested for its ability to accurately navigate a variety of common neurovascular instruments in an in vitro flow model and in a live, anaesthetised pig, under conditions and following procedures appropriate for clinical intervention. An access catheter was introduced manually at the equivalent of the common carotid artery in both models. Endovascular wires and catheters were navigated through

Remote surgery will be possible, while automation of dangerous aspects of procedures will make them safer by decreasing human error.” the external and internal carotid artery and posterior cerebral vasculature under robotic assistance, using 0.014 inch guidewires, 2.4F/1.7F microcatheters, bare-metal stents, and embolic coils.

All procedures in both the flow and pig models, including navigation, wiring, and deployment of the stent and coils, were performed successfully with no technical complications. There was no evidence of extravasation, dissection, thrombosis, or other vascular injury when angiography was compared before and after the live-animal procedure. This is the first study to demonstrate that the use of a robotic-assisted platform is feasible for intracranial neurovascular intervention.

The robotic system was successful at navigating and deploying the small-gauge instruments specific to neurovascular procedures. Given the potential benefits of robotic-assisted surgery for the patient and the surgeon, further investigation is warranted for this indication, while the technology will continue to evolve and get better.

Issue 35 | September 2019

Combining reperfusion with neuroprotection: The main reasons to reappraise the concept “The main reason to reappraise the concept of neuroprotection in acute stroke is the [advent] of effective thrombectomy, which de facto has led to the development of a reversible middle cerebral artery (MCA) occlusion model in humans. By reliably combining neuroprotection with reperfusion in patients undergoing thrombectomy we can finally replicate previously succeseful animal models in human clinical trials,” concluded Tudor Jovin, of the Cooper Neurological Institute and Cooper Medical School of Rowan University, Camden, USA) at the Live Interventional Neuroradiology & Neurosurgery Course (LINNC; 3–5 June, Paris, France).

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ntroducing the unfortunate story of neuroprotection so far, Jovin said, “Neuroprotection has been the graveyard of acute stroke trials. None of the many hundreds of neuroprotectant agents, with proven efficacy in animal models, could be shown to be effective in human trials. While he acknowledged that previously, the lack of this MCA occlusion model in humans was the main reason for the “disconnect” between preclinical animal models of neuroprotection and human clinical trials, he outlined an array of issues that continue to hinder the replicability of animal models.

“In the animal model, we used to look at the primary endpoint being infarct size, but in clinical trials in humans, we measure the effect of the treatment with clinical outcome measures. Preclinical models have to take into account more behavioural and clinical outcomes as well, not just infarct size,” said Jovin.

Moreover, he acknowledged that stroke is most prevalent in elderly people, whereas most preclinical studies have tested young animals. Due to the fact that stroke is more prevalent in people with comorbidities, Jovin argued that preclinical models of healthy, young animals fail to capture the complex nature of the human population.

Alluding to certain biases that are present in preclinical versus clinical studies, he said, “All of these reasons explain the disappointing story of neuroprotection in stroke. But now”, he reiterated, “we have a reversible model of MCA occlusion in humans; this is the number one reason for why we should reappraise the concept”.

“What are the goals of neuroprotectants?” Jovin asked the LINNC audience, answering that, “They either protect the brain from cell death or enhance recovery.

One of the most important potential consequences of neuroporotection is extension of the therapeutic window for reperfusion.”

“If you have good collaterals, you are going to be a slow progressor, but if you have bad collaterals, you are going to be a fast progressor—meaning that, in the presence of large vessel occlusion, you are going to grow your infarct faster than the slow progressor. That is one prime target in neuroprotection. In my opinion, if we give it [the drug] early enough, ideally in the field—as soon as the stroke occurs—then we can transform fast progressors into slow progressors,” he added.

Referring to data from REVASCAT, he said that in this trial, patients who were all randomised within six hours of symptoms onset were considered to be slow versus fast progressors based on their ASPECTS scores; those with an ASPECTS score of less than eight were considered “fast progressors” while those with a score of eight and above were considered “slow progressors”.

“In the latter, there is no relationship between time to treatment and outcome. But, in fast progressors, you find a very strong relationship, they are obviously very sensitive to time. So if we can treat them with neuroprotection, early, we can transform them into slow progressors and expand the time window for which reperfusion can still be effective.”

However, Jovin also told the LINNC audience that the ischaemic cascade is a “complex phenomenon”, and “comprises many mechanisms”. With this in mind, he put forward that any neuroprotectant drugs should be tailored and administered at the time points where certain mechanisms come into play. The drugs administered early, he said, should address excitotoxicity, which is when neuronal injury occurs. “Inflammation and apoptosis kick in a bit later. So, you have to give these drugs at the right time, according to the mechanisms that they address,” he surmised.

Acknowledging the importance of the treatment setting, Jovin said, “The most exciting setting for transforming fast progressors into slow progressors is the

The most exciting setting for transforming fast progressors into slow progressors is the prehospital setting, especially with drugs that work on excitotoxicity.”

prehospital setting, especially with drugs that work on excitotoxicity or collateral enhancing drugs.”

Ultimately, Jovin referred to hyperthermia as “the mother of all neuroprotective strategies”. He said that it has been shown to work in virtually “every stage of the ischaemic cascade, whether acute or subacute”.

Moreover, according to Jovin, it has been shown to be effective in adults with cardiac arrest and in neonates with ischaemic hypoxic encephalopathy. “But, it has failed in brain trauma and moreover, in human ischaemic stroke, the results have been disappointing,” he added, attributing this to the fact that “we have not

Neuroprotection

11

figured out the right time window, duration, depth of hypothermia, and the right complication prevention strategies.

Further, Jovin touched on the existing trials examining neuroprotection.

“The most exciting in my opinion is the ESCAPENA1 trial, because it Tudor Jovin is a trial that is almost ready to be completed.

NA1 is a drug that works in the early stage of the ischaemic cascade on excitotoxicity, and it has very good preclinical as well as clinical data. It has been shown to reduce ischaemic lesions in patients undergoing aneurysm coiling where patients who received NA1 had a lower burden of ischaemic lesions on MRI.” He added that regardless of its outcome, the trial, which has currently enrolled over 1,000 patients, is “going to make a big difference in the way we look at neuroprotection and reperfusion”.

In terms of other promising approaches, Jovin put forward that uric acid has been shown to be safe in a randomised trial of reperfusion (predominantly tPA) patients. While he said that the corresponding trial did not meet its efficacy endpoint, he pointed to its intriguing results in a prespecified subanalysis of the trial in which patients undergoing thrombectomy had better clinical outcomes if treated with uric acid (treatment group) compared to those who only underwent thrombectomy (control group). Additionally—according to Jovin— the oral-antidiabetic, glyburide, prevents oedema formation. Alluding to trials that have shown that this drug significantly reduces oedema in patients with large strokes, he said, “It works best early and has been shown to reduce mortality in these giant strokes,” and put forward that the drug represents “an interesting approach before thrombectomy, as an anti-oedema agent” as it may transform fast progressors into slow progressors.

Lastly, Jovin explained a novel neuroprotective strategy that aims to increase collaterals. Recently published in The Lancet, the study involved stimulating the sphenopalatine ganglion by inserting an electrode in the soft palate under CT guidance. “The trial showed that in patients with cortical infarcts, there was a 10% difference in improvement beyond expectation in patients with acute stroke. The trial missed its endpoint, but was

very close to significance,” he said, and remarked, “This is another neuroprotective strategy that aims to increase collaterals, and I think that there will be some interesting applications in patients with large vessel occlusion, before, or even after thrombectomy.”

Concluding his talk, Jovin said, “I think that neuroprotection is not ready for prime time yet, but there is a new era in reperfusion therapies for stroke, and the reversible model of MCA occlusion in humans justifies the reappraisal of the concept of neuroprotection combined with reperfusion. So stay tuned, there will be some exciting developments in the near future.”

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September 2019 | Issue 35

ASTER 2

Combining contact aspiration with stent retriever techniques elicits no superiority

The first randomised controlled trial (RCT) to directly compare the efficacy of the combined use of contact aspiration and stent retriever against a stent retriever alone has found no superiority for the former.

“We detected an 8% difference in favour of the combined strategy, but it was not significant,” announced Bertrand Lapergue (Stroke Center, Hôpital Foch, Suresnes, France) while presenting data from the ASTER 2 trial at the European Stroke Organisation Conference (ESOC; 22–24 May, Milan, Italy).

SPEAKING TO THE ESOC audience, Lapergue said that ASTER 2 (Combined use of contact aspiration and the stent retriever technique versus stent retriever alone for recanalisation in acute cerebral infarction) was based on the strong relationship between recanalisation and disability. “The definition of successful recanalisation is thrombolysis in cerebral infarction (TICI) grade 2c/3, which is important to understand, because if you look at the rate of modified Rankin Scale (mRS) score 0–2 after TICI 2b compared to TICI 3, there is a huge difference in terms of disability.”

Moreover, given that a recent HERMES collaboration elicited a rate of modified TICI 2c/3 in 31.4% of patients, Lapergue argued that “this is not enough,” and suggested

that there may be a potential benefit to recanalisation of a combined contact aspiration and stent retriever approach.

In a previous interview, Lapergue told NeuroNews, “The advantages of the combined stent-aspiration technique include the potential synergistic effect of the technique when used simultaneously, as well as the use of a flexible large-bore catheter in a triaxial system—which provides stability for the stent-retriever.”

He added, “Whatever the first-line strategy chosen by the interventionalist, the rate of TICI 2c/3 remains low.

The choice of the first-line endovascular procedure is a critical issue given that the number of passes is correlated with higher per procedure complications and lower favourable outcome.”

Carried out at 11 centres in France from October 2017 to May 2018, ASTER 2 was a prospective, randomised, multicentre, open-label, blinded endpoint clinical trial.

Patients admitted with suspected anterior circulation

In the future, we will be able to detect a specific group [...] and choose the type of endovascular therapy.” ischaemic stroke secondary to large vessel occlusion, with onset of symptoms <8 hours, were randomly assigned to treatment with combined catheter aspiration and stent retriever, or stent retriever alone in a 1:1 ratio.

The primary outcome was the rate of “perfect reperfusion,” defined by a modified TICI score of 2c or 3 at the end of the endovascular procedure. Using a twosided test (alpha=5%, power=80%) while anticipating rate of spontaneous recanalisation and catheterisation failures of 20%, Lapergue and colleagues estimated that a sample

size of 408 patients would be necessary to detect an absolute difference of 15% in primary outcome.

Regarding the results, Lapergue announced, “In terms of complete recanalisation at the end of treatment—we detected an 8% difference in favour of the combined strategy, but it was not significant.” Specifically, 131 patients (64.5%) in the combined strategy group achieved TICI 2c/3 and 117 (57.9%) patients in the stent retriever alone group achieved the same level of recanalisation (p=0.17).

In relation to safety, he posited, “There was no difference in safety concerns between the two arms, in terms of embolisation in a new territory, arterial perforation, arterial dissection, and vasospasm. Even regarding symptomatic intracerebral haemorrhage, or new infarct.”

“It was interesting because when we look at the prespecified subgroup and at the ICA [internal carotid artery] occlusion, there is a high burden of clot, and there is strong data supporting the combined approach. So in the future, we may adapt our strategy according to the site of occlusion or the type of clot.

When further questioned on whether these data from subgroup analyses can support individualised treatment approaches during an ESO interview, he put forward, “We need more data on this, but the main result is that we do not support any maximalist [combined] approach for all patients, so whatever strategy is used, choose the one you trust.”

Shedding light on what the future holds following ASTER 2, Lapergue surmised, “Probably, in the future, we will be able to detect a specific group, such as patients with ICA occlusion or according to the type of clot, and choose the type of endovascular therapy.

The first thing is to increase the rate of complete recanalisation now using modern approaches. In the future, we could adapt the strategies to achieve complete recanalisation. I think there is a new era of research on this issue.”

Issue 35 | September 2019

Advertorial

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AP-002718

ADVERTORIAL SPONSORED BY STRYKER

Getting it right the first time: Commit to a first-pass effect with full-length visibility and flow control with the TRAP technique

While the treatment paradigm for stroke continues to evolve, even a quick review of the current literature will point to how complete reperfusion after a single thrombectomy pass is a predictor for favourable outcomes. During the Society of NeuroInterventional Surgery’s (SNIS) annual meeting (22–25 July, Miami, USA), NeuroNews caught up with some of the field’s key leaders, Raul Nogueira (Grady Memorial Hospital, Atlanta, USA), Ajit Puri (UMass Memorial Medical Center, Worcester, USA) and Demetrius Lopes (AdvocateAurora Health, Chicago, USA) about why stent retriever choice matters, how flow control can improve outcomes, and maximising the TRAP technique.

T

revo Stentriever allows for full-length visibility combined with 360 degrees of consistently large cells, providing real-time visual feedback for additional control. “I use the full-length visibility of the Trevo device to help me through several steps of the thrombectomy procedure. Having full visibility of the device gives you real-time feedback; not only tactile, but visual feedback on the degree of opening you achieve for every step of the deployment technique,” noted Nogueira.

“Often, you will see that the device is pinched. If the device is pinched, it means that you are dealing with one of two situations; either a high fibrin content clot, or intracranial atherosclerotic carotid disease.” If the latter is the reason for the occlusion, Nogueira proposed that he would immediately give the patient intravenous or intra-arterial tirofiban to prevent reocclusion and observe the lesion to decide whether or not to stent it. “In these cases, having the visual picture where I can see the Trevo device and the entire lesion, really helps me pick the right size and length for my angioplasty balloon or stent.”

He further explained, “Let us say if my device is stretching—it is not fully opposing the vessel wall—I know I have

to push the wire a little more as opposed to letting the microcatheter relax. Good wall opposition means a more complete opening of the device. This is where the data shows the active deployment technique is very important. Having full visibility is very helpful in making all of this possible” In terms of optimising flow control, Puri posited, “There is overwhelming evidence for the use of a balloon guide catheter for anterior circulation

Raul Nogueira

Ajit Puri

thrombectomy. [For example] preclinical studies which were published in Stroke in 2013, the NASA, STRATIS, and TRACK registries, and meta-analyses that all say that the use of a balloon guide catheter is an independent predictor of good clinical outcomes.”

Alteplase at 0.6mg/kg for stroke with unknown time of onset is deemed safe, but not effective Although an acceptable safety profile was demonstrated for MRIguided thrombolysis with alteplase at 0.6mg/kg for stroke with unknown time of onset, the latter approach was found comparable to standard medical treatment at 90-days. The results from the THAWS (Thrombolysis for acute wake-up and unclear onset strokes with alteplase at 0.6mg/kg) trial were presented by Masatoshi Koga (National Cerebral and Cardiovascular Center, Osaka, Japan) at the European Stroke Organisation Conference (ESOC; 22–24 May, Milan, Italy).

KOGA ALLUDED TO the fact that both the WAKE-UP and EXTEND trials have recently revealed the efficacy of imagingbased intravenous thrombolysis with alteplase at 0.9mg/kg in acute ischaemic stroke patients with unknown time of onset. He said that in Japan, alteplase at 0.6mg/kg is available, based on a singlearm multicentre trial.

Given this, Koga and colleagues set out to test whether alteplast at 0.6mg/kg is

safe and effective in patients with wake-up stroke or stroke with unknown onset who had diffusion-weighted imaging (DWI)FLAIR mismatch.

THAWS was an investigator-initiated, multicentre, randomised, open-label, blinded endpoint trial. Patients had a time window of more than 4.5 hours since last-known-well (wake-up stroke). They were randomly assigned (1:1) to receive alteplase at 0.6mg/kg or standard medical

He added, “That being said, it comes down to what we really care about; we want a good modified Rankin score at 90-days for our patients. And, over and over again, these studies have shown that you can achieve a better modified first-pass efficacy, shorter times to recanalisation, and eventually, better clinical outcomes with balloon guide catheters.”

Providing a balance of trackability and support, the FlowGate² balloon

Demetrius Lopes

guide catheter offers proximal flow control and a stable platform to facilitate the insertion and guidance of intravascular catheters. Speaking on the Trevo aspiration proximal flow control technique—coined TRAP—Lopes told NeuroNews, “I believe TRAP is the treatment if MRI showed acute ischaemic lesion on DWI and no remarkable corresponding hyperintensity on FLAIR. Following the early stop and positive result of the WAKE-UP trial, Koga said that the THAWS trial was prematurely terminated on 10 July 2018, with 131 of an anticipated 300 patients (55 women, mean age: 74.5±12.2 years, median National Institutes of Health Stroke Scale [NIHSS]: 7, IQR: 4–13).

At this point, the primary outcome modified Rankin Scale [mRS] 0–1 at 90 days was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%) (RR: 0.97; 95% CI: 0.68 to 1.41; p=0.892).

However, safety outcomes were found to be very similar, as symptomatic intracranial haemorrhage within 22–36 hours occurred in 1/71 (1.4%) and 0/60 (0%; RR, infinity; 95% CI: 0.06 to infinity; p=1.0), respectively. Further, death at 90 days occurred in 2/71 (2.8%) and 2/60 (3.3%; RR: 0.85; 95% CI: 0.06 to 12.58; p=1.0), respectively.

In light of these findings, Koga later stated in an ESO interview, “We managed to show an acceptable safety profile for alteplase for patients with wakeup stroke, but we could not show the

optimal approach for thrombectomy, mainly because of clot control. We never know what kind of clot we are going to be dealing with, so having a technique that addresses the majority of cases and allows for a first-pass success; it achieves the goal we all want.”

“My set-up for TRAP is a short 8F sheath, followed usually by the FlowGate2 with a VTK catheter. The inner catheter that comes with the FlowGate2 has improved and is very capable of getting to vertebral arteries and the right carotid artery. I have to say, I am very excited about the possibility of exchanging, for example, deploying the Trevo, removing the microcatheter and going up with a CAT 6 or 7, depending on the anatomy.”

Lastly, Lopes said, “I challenge operators to keep trying to incorporate TRAP into their workflow and practice it, because once you get the hang of it, it becomes extremely intuitive. Once you build the set-up for TRAP, you are ready for anything. You can do a carotid or intracranial stent, and distal clots as well as proximal clots, probably with the highest first-pass recanalisation that you can achieve with any technique.”

Raul Nogueira, Ajit Puri, and Demetrius Lopes are paid consultants of Stryker. difference in favourable outcome between rtPA [recombinant tissue plasminogen activator] and the controls.”

Providing an explanation as to why the trial was neutral in comparison to the WAKE-UP trial’s positive result, he speculated, “It could be due to the early initiation of antithrombotics, it could be by chance or because of a difference in dose.”

When asked if he would have preferred to have continued the trial to achieve the target sample size, Koga posited, “While funding is limited, we are working with the WAKE-UP group and the EXTEND group and we are planning to conduct a meta-analysis on individual patient data soon, so we decided to terminate the trial.”

In the same interview, Manabu Inoue (National Cerebral and Cardiovascular Center, Osaka, Japan), an investigator of THAWS, said, “We definitely think there is room for more research in this area. For instance, we only had a small number of patients and in collaboration with other similar trials we will expand the numbers [which] of course, will really magnify the impact of this trial.

“In future, we might think of another tPA, such as tenecteplase. That might be another option for all these wake-up trials as well.”

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September 2019 | Issue 35

Large clinical trials

Antiplatelet therapy shows “reassuring effects” on the risk of recurrent intracerebral haemorrhage “Starting antiplatelet therapy after intracerebral haemorrhage associated with antithrombotic drug use demonstrated reassuring effects on the risk of recurrent haemorrhage,” said Rustam Al-Shahi Salman (University of Edinburgh, Edinburgh, UK) while concluding the results of the RESTART trial at the European Stroke Organisation Conference (ESOC; 22–24 May, Milan, Italy).

SPECIFICALLY, HE STATED that of the 537 participants randomised, 12 (4%) that were allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage, compared to 23 (9%) of those allocated to avoid antiplatelet therapy (adjusted hazard ratio 0.51 [95% confidence interval [CI]: 0.25, 1.03]; p=0·060). Moreover, 18 (7%) of participants allocated to the former experienced major haemorrhagic events, compared with 25 (9%) participants allocated to avoid antiplatelet therapy.

With these findings in mind, he later acknowledged in an ESO interview, “I think this is a reassuring and permissive finding for clinical practice. I think it would be good for this result to be replicated in other randomised controlled trials [RCTs] that are underway.

And, I think that it would also be interesting to pursue the hypothesis that the underlying cause of recurrent brain haemorrhage may be thrombosis in the first instance, by doing a much larger RCT, imaging, and other mechanistic studies.”

The Restart or stop antithrombotics randomised trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial carried out between May 2013 and November 2018.

The study investigators recruited adults who were taking antithrombotic (either antiplatelet or anticoagulant) therapy for the prevention

of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived 24 hours.

“RESTART was addressing a common question nowadays about survivors of stroke due to brain haemorrhage. About a third to a half of these patients in high-income countries are taking antithrombotic drugs at the time they have a brain haemorrhage because of a past history of a heart attack or ischaemic stroke,” said Al-Shahi Salman. He added, “In our clinical practice, we usually stop these drugs as soon as intracerebral haemorrhage is diagnosed. In survivors, we are left with the uncertainty about whether we should start an antiplatelet drug, or whether to avoid it. The RESTART trial was an RCT at 122 hospitals in the UK that set out to answer this question.”

By using a computerised randomisation system that incorporated minimisation and allocated participants 1:1 to start or avoid antiplatelet therapy, Al-Shahi Salman and team were able to follow participants to assess the difference in: Rustam Al-Shahi Salman

Enhanced paramedic assessment does not increase the rate of thrombolysis “An enhanced paramedic assessment process does not facilitate thrombolysis,” concluded Christopher Price, University of Newcastle (UK), presenting the results of the Paramedic acute stroke treatment assessment (PASTA) trial at the European Stroke Organisation Conference (ESOC; 22–24 May, Milan, Italy).

Irrespective of this neutral clinical finding, Price said that cost savings were associated with the intervention, regarding both hospital costs and social care.

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n relation to the rate of thrombolysis, Price reported that PASTA did not increase the proportion of patients receiving thrombolysis. Moreover, the intervention group showed significantly longer paramedic scene to needle times, as the mean difference between groups was 8.5 minutes (98.1 minutes vs. 89.6 for standard care; p=0.01). Yet, he explained that a small non-significant QALY (quality-adjusted life year) gain for PASTA was observed at day 90, while the intervention was found to cost less than standard care by -£1,105 (95% CI: -£2,256 to -£60). Specific factors contributing to these cost savings included the decreased rate of thrombolysis, length of index stay, rehabilitation, and social care.

“We undertook a study that looked at

an enhanced paramedic role to see if it could improve the rate of thrombolysis delivery across 15 hospitals in the UK,” Price explained. The study involved 1,214 patients, 500 of whom received the additional PASTA pathway, consisting of additional prehospital information on IV thrombolysis eligibility, systematic pre-notification, structured handover, and assistance with simple tasks at hospital.

Those with confirmed stroke who were assessed by a study paramedic within four hours of onset were recruited for the trial. Comparatively, controls received standard stroke care. According to Price, this multicentre, randomised controlled trial (RCT) took place in the setting of three regional NHS ambulance services and 15 hyper-acute stroke units across

primary outcome (recurrent symptomatic intracerebral haemorrhage), secondary outcomes (all major vascular events), and other serious adverse events for up to five years. Participants were recruited a median of 76 days following intracerebral haemorrhage onset and followed for a median of two years subsequent to this. Al-Shahi Salman analysed treatment effects using intention-totreat analyses and Cox proportional hazards regression, adjusted for minimisation covariates.

In terms of major adverse events, Al-Shahi Salman reported that 39 (15%) of participants allocated to avoid antiplatelet therapy had major occlusive vascular events, compared to 38 (14%) allocated to no antiplatelet therapy (1.02 [0.65–1.60]; p=0.92).

Now, we raise the hypothesis that antiplatelet therapy might reduce the risk of recurrent intracerebral haemorrhage.”

He put to the audience: “So, in summary […], the effect we observed was much lower than the increase in risk expected. Now, we raise the surprising hypothesis that antiplatelet therapy might reduce the risk of recurrent intracerebral haemorrhage. Any risk encompassed by the upper 95% confidence interval of the adjusted hazard ratio (1.03) seems too small to exceed the established effect of antiplatelet therapy.”

Al-Shahi Salman noted, because the trial was small, that “We need to carry on recruiting to ongoing trials [such as RESTART-Fr in France and STATICH in the Nordic countries] and test the hypothesis that antiplatelet therapy helps these patients in a larger definitive trial.

both England and Wales. group. So, on health-economic grounds, Secondary outcomes included stroke it was a positive study, although still severity and complications following neutral in terms of its clinical endpoint.

IVT, as well as mortality and dependency We can only speculate on the mechanism at 90 days, QUALYs, and health and for this result, but it may relate to how the social care costs. enhanced paramedic assessment process On further discussion of the influenced the selection of patients for findings, Price explained in an ESO thrombolysis treatment.” interview, “There was actually less In relation to the lessons learnt from frequent thrombolysis in the the PASTA trial, fellow intervention group, which was principal investigator Gary a novel finding. This was not Ford (John Radcliffe Hospital, consistent with previous work University of Oxford, UK) that has been done around surmised, “This intervention is improving thrombolysis quite important when looking delivery. [However], when we at the future if we question went on to look at the health of how we are going to get people patients 90 days later, we found into drip and ship models that there was no significant Christopher Price assessed and then moved on to difference between the comprehensive stroke centres, intervention and the control group. So, that as that will involve paramedics staying non-significant reduction in thrombolysis with the patient. So, even though this had no impact on their health. And, when [trial] has been neutral—in fact it has we looked at the costs of care, we found slowed down the time to thrombolysis that there were significant cost savings by a small amount—it is very important associated with the intervention. This in terms of how we design our pathways was not simply because they got less and paramedics for doing the secondary thrombolysis, [it was] costs in the length transfers. of stay at hospital, in rehabilitation, and “We need to use this experience to think the costs of people needed following about how we use paramedics so we do [patients’] care after hospital. not slow down, for example, the transfer “Even if you included additional of people with large artery occlusion. I paramedic time for providing the think there are a lot of learnings from intervention, then the study showed what we have done. I do not think that the significant cost saving. This implies that assessment is of no value, it shows that actually the patients were in a better paramedics work quite rigidly, it is hard in state even though they had not received that respect to speed things up if they are thrombolysis as much as the control asked to do more check-lists.”

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September 2019 | Issue 35

Interview

Profile

Patrick Brouwer

Patrick Brouwer speaks to NeuroNews about what he considers to be the most important developments in the neurointerventional field to date. As president of the European Society for Minimally Invasive Neurological Therapy (ESMINT), Brouwer touches on the society’s long-term goals within the context of global expansion, and tells us about his most memorable case, what motivates him, and offers some honest advice to those beginning their neuro-career.

What initially drew you to medicine, and later, to neurointerventional radiology?

When I was around nine years old I heard some stories about lobotomies and psychosurgery which I thought it was interesting, and I was intrigued. I had two teddy bears that I was poking with needles all the time and I told my grandma that I wanted to do that as a doctor when I grew up.

I only started medicine at the age of 22 after a very poor school career with only music and jobs on the side. After my graduation from medical school, I worked as an emergency physician for almost 1.5 years in Amsterdam. If there would have been a formal training for this specialty, I would have taken it. Since my neurosurgical colleagues operated only one day a week, I chose the field that would give me as much hands-on time possible: interventional radiology. During my radiology training I met Rene van den Berg at Leiden University Medical Center and because of his enthusiasm, and the fact that it came full circle to poking the brain, I elected to work in neurointervention.

Have you had any important mentors throughout your career? What have they taught you?

The person that made me change my perspective on “being a physician” was an ENT surgeon in Amsterdam—Freerk van der Meulen. He was my supervisor during extracurricular research work at the Laser Center at the Academic Medical Center in Amsterdam where we worked on photodynamic therapy in oncology and AIDS related diseases.

The countless examples of the compassionate way he treated patients is something I will never forget, always being respectful and seeing things through their eyes.

I spent a number of summer holidays house-sitting for him when he went away with his family, so I got to know him as the family man he was, exactly the same.

This man never put up an act and always listened to the input and opinions of others but defended what he thought was right. He is my hero and great example both in and outside of medicine.

What has been the most important development in the neurointerventional field during your career?

It is very easy to say that stroke treatment is the most important one, as simply, it has the biggest impact on patient wellbeing and makes up the majority of procedures we perform. However, from both a technical and personal perspective, I would say that the introduction of the flow diverter made a real difference.

The reasons behind this are not totally altruistic. Being the worlds first SILK (Balt) user created an opportunity to present and proctor around the world, which in turn allowed me to meet some of the key opinion leaders in the field.

On the contrary, what has been the biggest disappointment?

Personally I found it very disappointing that some niche products were taken off of the market and were

not developed into the useful products that they could currently be. Examples are the trispan, symbiot stent, ascent balloon and the enzo microcatheter. Furthermore, most of the larger companies are focusing too much on “me too products”, which arrive on the market too late, and not on new technology which may put them in the lead again. Start-up companies are obviously the future since the large companies cannot take the financial risk.

This, unfortunately, shows the differences in motivation and incentive between industry and physicians in our field.

What are your current research interests?

I am currently involved in the TENSION study, which is a European Union Horizon 2020 sponsored initiative which looks into the thrombectomy effect in patients with extended lesions and extended time windows. This study will give us information on the patients that were not included in the original thrombectomy trials. Besides that, there are a number of projects I am working on such as the SURMOUNT Registry, BRAVO early evaluator study and so on.

As president of ESMINT, what are your goals for the society?

I personally feel that the course of the society should not be too dependent on the president. The definition of a society should imply that it is a concerted action for the benefit of the members and without egos deciding.

Some of the goals I set myself for this term is to structure the society in a way that it will continue to function no matter who will take the lead. This means that the goals for the next five years are set, in collaboration with our 20 executive committee chairs.

Obviously, in this day and age, our society also needs to focus on the organisation of care in Europe and define who should and, more importantly, who should not do neurointerventional treatments. We have a responsibility locally and therefore we established theoretical courses, the ECMINT and the EXMINT, and facilitate practical fellowships for young colleagues to build their portfolio.

Furthermore, the certification, accreditation and credentialing needs to be done in a way that will help local governments, hospitals, health inspectorates and insurance companies to determine which physicians are up to par.

We started a pilot project to see how we can help local governmental bodies implement our standards and guidelines. Due to the differences in the local organisation, language and culture, it is important to see what works best for that country. Personally, I really want the society to be professionalised and run by a fulltime dedicated office, which will enable us to account to our industrial sponsors for what we do and how we do it.

Finally, ESMINT receives a lot of requests from areas that are not covered by a society, such as the MiddleEast and Northern Africa, to help with training and guidance. With industry having EMEA as a region, it would make sense to make ESMINT supportive of those regions too.

We focus a lot on thrombectomy treatment as being the mainstay, but I think that we will gradually move to other focuses.”

What are the themes and highlights of this year’s meeting?

This year’s congress is organised by Anne-Christine Januel from Toulouse, France. Her motto, a quote

by Mark Twain, is very interesting: “They didn’t know that it was impossible, so they did it.” She has, in collaboration with the European Stroke Organisation (ESO), the European Association of Neurosurgical Societies (EANS) and the Society of NeuroInterventional Surgery (SNIS) built a programme that is enticing and I look forward to seeing it. This year we will honour another honourary member, James Byrne, who was one of the founders of the society.

A new addition in this edition is the “Amy Walters Foundation lecture”. Amy Walters worked in industry for a long time, and even sang with the ESMINT band on the beach in Nice (France) a couple of years ago, but sadly she suffered a major stroke during a congress two

Issue 35 | September 2019

Interview

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Fact File

and peripheral intervention, is currently using all kinds of units of measurement to describe our materials (eg. inches, French, 18-system, centimetres). Mistakes are made and it is unclear what device fits in what other device with the current naming. To start a potential revolution we wrote a paper on how this should be changed, and based on an collaborative initiative of SNIS and ESMINT we created a taskforce, with our industrial partners, that will look into creating a comprehensive metrical system for all companies and all products. Obviously there are legal and regulatory implications and the process will take time, but this initiative is something I consider very important.

Could you tell us about a particularly memorable case you have had, and what you learned from it?

The worst case in my life is that of a teenage patient that suffered a hemorrhage from an arteriovenous malformation. Initial targeted embolisation went well, but the follow up surgery was pushed forward because of family pressure. The mother was in the endstage of an oncological disease and she wanted to know that her child would be “cured” before she died. Although the surgery seemed to have gone technically well and the patient woke up the day after, the child died of a re-hemorrhage on day two and the mother the day thereafter. They were buried together. It showed me that no matter how much you try to help the patient and his family with their valid treatment related requests, it may still be wrong and we should stick with our proven regimen, irrespective if it would have changed the outcome in this case.

From your research and experience, what motivates you?

years ago. SNIS and ESMINT have started a foundation to be able to host a patient to our congress in order for them to have a presentation in which they let us see their experience through their own eyes. I recommend that all colleagues listen to Amy’s story, it is very impactful.

My main motivation lies in getting answers. I am a person that questions everything, even my own thoughts and opinions, and want to get to the underlying answers and motivations. With research it is the same; why do people claim that one treatment is better than the other, even if there is no clear evidence. I have detected similar biases in my own thinking and I love it when people confront me, even though it may take a while to admit it.

It shows me that I am not yet where I want to be.

What technological advances do you see shaping stroke treatment over the next 10 years, or beyond?

What advice would you give to physicians at the beginning of their neuro-career?

We focus a lot on the thrombectomy treatment as being the mainstay, but I think that we will gradually move to other focuses. The neuroprotective agents are moving in and I very much look forward to the results of the NA-1 study that will be analysed in December and presented afterwards. Drugs of this type may protect the brain in the early stage and thus have an even larger impact for the stroke patient. A second focus will be on the clot properties. Once we know what type of clot it is, we can tailor the treatment with drugs that either address fibrin, von Willebrand factor or neutrophil extracellular traps.

That is where I think the real progress can be found.

What recent publications have caught your eye?

At the risk of getting blamed for quoting my own paper, I do think that we collaboratively should work to standardisation of measurements in our field. We published a paper in the Journal of NeuroInterventional Surgery this year called “Size matters… but how do I know what size it is?”. Our field, as well as cardiology

Do not look up to key opinion leaders and do not believe everything you hear without checking the validity. Try to stay away from people badmouthing other colleagues and putting their egos first, and try to surround yourself with people that bring out the best in you and be that person for your colleagues. Most of all, be honest to your family regarding the time that is involved with this specialty and do not think that it will get better.

Outside of medicine, what are your hobbies and interests?

I have too many and actually need to stop working to maintain them. I love running, cycling, and sailing, but my main hobby is playing and writing music, which actually became a job too. I started a music production company, together with my son, writing film music and songs for artists, as well as producing and mixing. Both my daughter, who studies singing at the conservatory, and my son are gifted musicians and I am very happy that they found a life in the performing arts, rather than medicine. If I only could do it all over again…

Clinical and scientific appointments:

2019–Present: Leiden University Medical Center, the Netherlands - Neurointerventionalist 2014–2019: Karolinska University Hospital, Stockholm, Sweden - Neurointerventionalist 2010–2014: Neurovascular Network NorthSea Neurointerventionalist 2001–2010: Leiden University Medical Center Neurointerventionalist

Society positions:

2018–Present: President of ESMINT 2017–Present: Member at large for the World Federation of Interventional and Therapeutic Neuroradiology (WFITN) board 2016–Present: National representative for Sweden in the UEMS section of Neuroradiology 2016: ESMINT annual congress president

Teaching activities:

n EXMINT stroke course n ECMINT course n Examiner for annual ECMINT and EXMINT diploma n Proctor for SILK and Surpass flow diverters in more than 100 cases

Current research (selected):

SURMOUNT - Principal investigator SPERO trial - Principal investigator TENSION - Swedish project coordinator and coordinator for Work Package on training and guidelines BRAVO - Steering committee member Emboline study - Clinical events committee member and DSMB Percutaneous Laser Disc Decompression for Sciatica - Principal investigator, PhD-thesis Publications: 70+, four book chapters

Professional education:

1987–1996 Medical Degree ‘Cum Laude’, Free University Medical School, Amsterdam, The Netherlands 1997–2003 Residency in Radiology, KG Haarlem and Leiden University Medical Center, The Netherlands 2003–2004 Masters in Neurovascular Diseases, University Bicetre Paris/Mahidol Chiang Mai

Issue 35 | September 2019

Optimising stroke care

New AI tool for detecting cerebral aneurysms enhances clinicians’ accuracy Through developing a deep learning model to automatically detect clinically significant intracranial aneurysms on computed tomography (CT) angiography, clinicians’ sensitivity, accuracy, and interrater reliability were found to improve when compared to detection on original CT angiography scans. The corresponding study, published in The Journal of the American Medical Association, details the application of a convolutional neural network used to augment CTA aneurysm interpretation—whereby clinicians were provided with the models’ predictions in the form of regions of interest segmentations directly overlaid on top of CT angiography examinations.

ALTHOUGH CT ANGIOGRAPHY augmentation elicited no statistically significant change in mean specificity and time to diagnosis compared to unaugmented CT angiography, the authors, Allison Park and colleagues from Stanford University (Stanford, USA), write: “If integrated into the standard workflow, this diagnostic tool could substantially decrease both cost and time to diagnosis, potentially leading to more efficient treatment and more favourable outcomes.”

In their paper, Park et al allude to the importance of an automated detection tool, given the potential catastrophic outcome of a missed aneurysm at risk of rupture, alongside the significant variability that remains among clinicians when diagnosing aneurysms. The latter,

they say, is typically attributed to a lack of experience, subspecialty neuroradiology training, complex neurovascular anatomy, or the labour-intensive nature of identifying aneurysms.

Furthermore, the authors posit that the tools that are currently used to improve clinician aneurysm detection on CT angiography are labour- and timeintensive. Acknowledging the recent success of deep learning applications in clinical image-based recognition tasks, the authors point to studies that have displayed the superiority of a 2D convolutional neural network in detecting intracranial haemorrhage and other acute brain findings. Yet Park et al put forward, “Prior to this study, deep learning had not been applied to CT angiography, which

is the first-line imaging modality for detecting cerebral aneurysms.”

In light of this, the study investigators aimed to develop and apply a neural network segmentation model, known as the HeadXNet model, which was able to generate precise voxel-by-voxel predictions of intracranial aneurysms on head CT angiography imaging to augment clinicians’ intracranial aneurysm diagnostic performance. Park and team developed the 3D convolutional neural network architecture using a training set of 611 head CT angiography examinations to generate aneurysms segmentations.

Subsequently, a test set of 115 examinations from these segmentation outcomes were given to the participating clinicians. Through a crossover design that used a randomised order and a 14-day washout period, eight clinicians diagnosed the presence of aneurysm on the test set, both with and without model augmentation.

The authors note that head and neck examinations that were performed between January 2003 and May 2017 (at a single academic medical centre) were used to train, validate, and test the model.

Examinations positive for aneurysm had at least one clinically significant, nonruptured intracranial aneurysm.

In contrast, those with haemorrhage, ruptured aneurysm, post-traumatic or infectious pseudoaneurysm, arteriovenous malformation, surgical clips, coils, catheters, or other surgical hardware were excluded, while all other CT angiography examinations were considered controls.

In total, the dataset included 818 examinations from 662 unique patients, with 328 CT angiography

Type of stent denotes degree of complete occlusion following stent-assisted coiling of cerebral aneurysms

A study comparing three different stents used during stent-assisted coiling of cerebral aneurysms revealed that the type of stent used affects a patient’s immediate and long-term health outcomes, while a significant difference in the rate of complete occlusion among the stents was found. Maxim Mokin (University of South Florida, Tampa, USA) presented these data at the Society of NeuroInterventional Surgery’s annual meeting (SNIS; 22–25 July, Miami, USA).

T

he multicentre analysis of radiographic and clinical outcomes in 659 patients with 670 cerebral aneurysms compared the angiographic and clinical outcomes of endovascular coiling using three types of stents—Neuroform (NEU; Stryker), Enterprise (EP; Codman Neuro, part of the DePuy Synthes Companies of Johnson & Johnson), and Low-profile Visualized Intraluminal Support (LVIS; MicroVention Terumo).

The majority (73%) were anterior circulation aneurysms, 19% were ruptured and 89% of treated aneurysms were considered wide neck, while 58% were medium sized aneurysms (5–15mm). According to Mokin, a variety of treatment approaches were used, as well as different configurations of devices, with “jailing” and “coil-through” being the most common stent deployment techniques, used 39% and 38% of the time, respectively. Coiling first and then deploying the stent was administered 10% of the time, while balloonassisted coiling followed by stenting was used 13% of the time.

Yet, he said, “The weakest part of the study was that we had no core lab adjudication. Each centre adjudicated their own results.” Regardless, Mokin reiterated that dependent on the type of stent—there was a significant difference between the type of stent used and the degree of occlusion at immediate post-procedural outcome as well as at follow-up, with LVIS demonstrating superior angiographic results (p=0.0004).

The significant difference seen in the type of stent and degree of occlusion remains in both ruptured and unruptured aneurysms.”

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examinations (40.1%) containing at least one intracranial aneurysm and 490 examinations (59.9%) without intracranial aneurysms. The group of clinicians reading the test set were composed of six board-certified practicing radiologists, one practicing neurosurgeon, and one radiology resident, with their experience ranging from two to 12 years.

In the current study, augmenting CT angiography with artificial intelligenceproduced segmentation predictions elicited an increase of 0.059 (95% confidence intervel [CI]: 0.028, 0.091;

Prior to this study, deep learning had not been applied to CT angiography.” adjusted p=0.01) in clinicians’ mean sensitivity, while mean accuracy increased by 0.038 (95% CI: 0.014, 0.062; adjusted p=0.02) and mean interrater agreement increased by 0.060, from 0.799 to 0.859 (adjusted p=0.05).

“The [data] suggest that integration of an artificial intelligence-assisted diagnostic model may augment clinicians’ performance with dependable and accurate predictions and thereby optimise care,” write Park and colleagues.

Moreover, in terms of moving forward, the team postulate, “Future work should investigate the performance of this model prospectively and in application of data from other institutions and hospitals.”

“At follow-up, 84% of those treated with LVIS elicited a Raymond-Roy Grade Scale (RRGS) of 1. In comparison, 78% of patients treated with Neuroform and 68% of those treated with Enterprise achieved the same grade,” he said.

Furthermore, because the sample size was so large, the investigators were able to carry out subgroup analyses for both ruptured and unruptured aneurysms.

“The significant difference seen in the type of stent and degree of occlusion; it remains in both ruptured and unruptured aneurysms when analysed separately,” Mokin remarked, adding that for unruptured aneurysms, the investigators also noticed that there was a significant association between the type of stent and procedural-related complications, such as intraprocedural rupture and in-stent thrombosis, which was higher in the LVIS group. However, he noted that there was no association in post-procedural complication rates of aneurysm recurrence, stroke, or stent stenosis based on stent type (p=0.76).

Lastly, Mokin alluded to whether there were any differences in the patterns of treatment at the six participating centres. “The data for this were highly significant. Every variable that we looked at elicited a p-value of <0.05. These included the type of stents used, the approach to stent-assisted coiling as well as angiographic outcomes—they were quite variable.

It makes you wonder [...] when you see the single centre studies or multicentre joint efforts, there is high variability between how each centre performs, and this should be accounted for.”

With this in mind, Mokin concluded by saying that randomised prospective trials comparing the different types of stents are warranted, and would be “a good next step to further improve clinical outcomes and safety”.

Issue 35 | September 2019

A stroke trial update from SNIS 2019 From tissue plasminogen activator (tPA) augmentation and stroke systems of care through to the rise of neuroprotective investigations, Santiago Ortega-Gutiérrez, University of Iowa (Iowa City, USA) kick started the Society of NeuroInterventional Surgery (SNIS) annual meeting (22–25 July, Miami, USA) by outlining an array of ongoing stroke trials. “Everybody here in this room has witnessed an amazing 10 years of building something together that has made a huge difference. However, the more we progress, the more we realise we have many more things to do.”

A

lluding to the studies that address tPA augmentation, Ortega-Gutiérrez first detailed the MOST (Multi-arm optimisation of stroke thrombolysis) trial. “It is a phase 3, large vessel occlusion (LVO) and non-LVO stroke trial with a complex design that includes five arms. The control arm will be IV recombinant tissu plasminogen activator [rtPA] only. With the other four arms, the synergistic effect of Argatroban or Eptifibatide in both low and high doses in addition to IV rtPA will be assessed.” The primary outcome consists of a utility function modified Rankin Scale (mRS) at 90 days, with the sample size set to reach 1,500. Enrolment is due to begin in the next few months.

The second tPA augmentation trial he outlined was the TRUST (Aureva transcranial ultrasound device with tPA in patients with acute ischaemic stroke) trial.

Patients with LVO ischaemic stroke, receiving IV tPA, as well as being transferred to an endovascular therapy centre are going to be randomised to the intervention group: tPA plus ultrasound frame (placed in the patient for 90–120 minutes), versus tPA with sham ultrasound frame. He commented, “In this case, the primary outcome is complete recanalisation by modified Arterial Occlusive Lesion [mAOL] on the first catheter angiogram. The planned sample size is around 556 patients.”

Moving on to the development of the best systems of care for endovascular therapy in LVO, he said, “We are having a huge debate over what is the best approach. Our current systems are developed for IV tPA delivery, but not for LVO treatment. And, because of this, the trial results coming up are very important.”

The RACECAT (Direct transfer to an endovascular centre compared to transfer to the closest stroke centre in acute stroke patients with suspected LVO) trial is a prospective cluster randomised controlled trial currently underway in Barcelona. Patients are being selected by emergency medical services in the field based on the RACE scale. If it is more than 4, and once they identify the patients as potential LVO, they will be randomised to direct transfer to a comprehensive stroke centre, or to the closest local stroke centre. The outcome is 90 day mRS and the sample size is 1,754 patients. “I was speaking with [the lead principal investigator] Marc [Ribo] this morning, and I can tell you that they have enrolled well over 1,000 patients,” confirmed Ortega-Gutiérrez.

Addressing another important issue, he asks the SNIS audience: “Do we really need tPA in these patients with LVO?”. SWIFT DIRECT (Bridging thrombolysis versus direct mechanical thrombectomy in acute ischaemic stroke) is aiming to answer that very question. Patients with anterior circulation of LVO stroke that are IV tPA eligible within four hours and 15 minutes are going to be randomised to treatment with Solitaire (Medtronic) stent-retriever thrombectomy versus Solitaire with IV tPA. The target sample size is 404 patients.

“In terms of imaging selection, we all know that imaging allows us to, especially in the late window, have a better selection of patients, everything adds time. And, if we look outside Europe and the USA, this technology is not available everywhere. There is a

group from The Netherlands that is applying the same inclusion criteria, but now to the late window, 6–24 hours,” said Ortega-Gutiérrez. The corresponding study, MR CLEAN-LATE (Multicentre randomised clinical trial of endovascular treatment of acute ischaemic stroke in The Netherlands for late arrivals), randomises patients to endovascular therapy plus medical management, or the latter alone.

He pointed to another study outside of the USA, the BEST (Acute basilar artery occlusion: Endovascular interventions versus standard medical treatment) trial, a randomised trial for basilar occlusion within eight hours. “With a projected sample size of 344, these results were presented at the Society of Vascular and Interventional Neurology (SVIN) last year in October, but unfortunately this trial was stopped ahead of time because there was a lot of crossover from the medical management group to the treatment group, meaning the analysis was not valid.

Santiago Ortega-Gutiérrez

Our current systems are developed for IV tPA delivery, but not for LVO treatment. Because of this, the trial results coming up are very important.”

“However, we [now] have an ongoing basilar artery occlusion Chinese endovascular trial.” Led by Tudor Jovin and Xunming Ji, the investigators are randomising patients with basilar occlusion or bilateral vertebral artery occlusion at 6–24 hours. In terms

Ongoing stroke trials

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of selection, MR or CT based posterior circulation ASPECTS (Alberta Stroke Program Early CT Score) is being used. The sample size is 318 with the primary outcome 90 day mRS (0–4).

“But what about anaesthesia? […] Lately, we have some single centre European studies that have shown no inferiority of conscious sedation compared to general anaesthesia when the blood pressure was controlled,” noted Ortega-Gutiérrez. SEGA (Sedation versus general anaesthesia for endovascular therapy in acute ischaemic stroke) is a USA based multicentre trial aiming to randomise patients with symptom onset at 0–16 hours to conscious sedation (the control), with very strictly controlled blood pressure, versus general anaesthesia. The primary outcome is mRS at 90 days, with a target sample size of over 200 patients.

“Currently, about 40 patients have been enrolled in this study,” he added.

“There is also a lot of emphasis on how far we can push thrombectomy,” remarked Ortega-Gutiérrez.

“And, we treat patients with large core, and we treat patients with very low NIHSS. For this, there are several studies coming up. One of them is in Europe, called the TENSION trial.”

TENSION (Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window) will include LVO acute ischaemic stroke patients with ASPECTS 3–5, from zero to 12 hours from last known well or an unknown time onset.

Ortega-Gutiérrez added, “The sample size is going to be 714 patients, stratified on time from symptom onset (early or late window) and stroke severity (NIHSS ≤18, or NIHSS ≥18).

Moreover, in the USA, the TESLA (Thrombectomy for emergent salvage of large anterior circulation ischaemic stroke) trial will commence next month.

Patients with ASPECTS 2–5 within 24 hours are to be randomised to endovascular therapy plus medical management, or the latter alone, with the sample size estimated to be 300 patients.

“We also have a slightly more complex large core study; SELECT 2. In addition to selecting patients using CT, CT perfusion will also be applied.

Patients will be divided into six different groups [and], to assess whether patients may benefit from thrombectomy when they have large core, the investigators will examine the prospective concordance of CT perfusion and CT to measure large core infarct.” The primary aim of SELECT 2 is to investigate whether endovascular therapy is superior to medical management alone.

The penultimate trial he pointed to was the ENDOLOW trial. “This is a prospective phase 2 trial, which can be converted to phase 3. Patients will have NIHSS 0–5, with an ASPECTS of more than six.

They will be randomised to medical therapy versus endovascular therapy using the Embotrap device.”

Finally, Ortega-Gutiérrez said, “We will see a lot of neuroprotective studies coming up, but it is worth mentioning the one that has almost finished enrolment: ESCAPE-NA1 [Safety and efficacy of NA-1 in subjects undergoing endovascular thrombectomy for stroke].” Designed as an RCT, patients with large vessel occlusion, small core and good collaterals are being randomised to an IV dose of NA-1 (2.6mg/ kg) 10±1 minutes in addition to thrombectomy, or a placebo dose, with the outcome set as the proportion of favourable outcome 0–2 mRS at three months. “I am sure we will hear about these results very soon,” he concluded.

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Issue 35 | September 2019

The clinical utility of evoked compound action potentials is echoed by data from Evoke and Avalon Continued from page 1

other patient quality of life measures could be improved using an individual’s evoked compound action potentials to control the output of the SCS device in a closed-loop fashion.

Providing further explanation, he said, “Every individual patient has an individual ECAP signal that corresponds to their pain control. This represents their therapeutic window, the threshold, the maximum, and the comfort level. Once this therapeutic window is set, then the decision is made as to whether the patient will make all the adjustments to the stimulator to maintain the appropriate current output to maintain optimal analgesia (open loop) or if the primary control is turned over to the computer in the SCS implantable pulse generator to maintain a constant ECAP response (closed-loop) in much the same way automobiles equipped with cruise control can maintain a constant speed regardless if the vehicle is going uphill or downhill.

“When we give it to the computer, it uses that information in real-time to feedback and decide whether the output of the device should be lower or higher depending on the precise response of the individuals evoked compound action potential immediately before each stimulus,” Poree noted.

In terms of the study’s methodology, he said that an important aspect was that the ECAPs were collected and analysed

in all patients, not only those receiving closed-loop stimulation and the in-office programming to determine the individual therapeutic window was the same for both the open and closed loop groups. In addition, he highlighted that the decision about which group each patient was being allocated to was made after the surgical placement of the leads and determination of the therapeutic window.

“The primary objective was to demonstrate non-inferiority, and then test for superiority. The endpoint was a 50% reduction in overall trunk and limb pain as determined by VAS,” said Poree.

Describing the characteristics of the population, he noted that overall, around 63% of patients in both groups were taking opioids. Ages were similar, as well as duration of pain; between 11 and 13 years, and pre-operative VAS scores were the same.

Moreover, Poree emphasised that a variety of other measures were kept constant between the groups, such as the programming time of the patients and frequency range and pulse width. Additionally, lead location and the length of the trial were also kept constant.

Also presented at the INS World Congress were long-term data from the Avalon study. Charles Brooker (Royal North Shore Hospital, Sydney, Australia), one of the study’s principal investigators, revealed the 18 month outcomes from

The first wireless spinal cord stimulator system elicits a high response rate and significantly reduces disability A study evaluating different waveforms within a wireless spinal cord stimulator (SCS) device (Stimwave) has found high response rates for patients receiving both high and low frequency waveforms. These data from the SURF trial were presented

by Robert Bolash of Cleveland Clinic (Cleveland, USA) at the International Neuromodulation Society (INS) 14th World Congress (25–30 May, Sydney, Australia).

SPECIFICALLY, THE VISUAL Analogue Scale (VAS) indicated that sustainable pain reduction was achieved in 77% of patients in the high frequency arm, and 64% in the low frequency arm at the sixmonth endpoint. According to Bolash, these results “met or exceeded those of previously reported randomised controlled trials (RCTs) with implantable

this Australian prospective, single-arm study. As the effective relief of pain and associated symptoms were weighed against the same system, Evoke, the findings from both studies are outlined below.

Evoke and Avalon: The findings

The key three-month results of the Evoke pivotal study include how the closed-loop arm met all the pre-specified endpoints, and demonstrated statistically superior back and leg pain relief (with no increase in pain medications) compared to controls, with over 80% (82.5%; 51/62) of closed-loop subjects achieving greater than or equal to 50% pain relief (control: 60.3%; 38/63).

Furthermore, Poree reported that

Study results suggest that pain relief continues to improve over time.” more than half of closed-loop subjects (58.1%; 36/62) were high responders, as they achieved greater than or equal to 80% reduction in back and leg pain (control: 42.9%; 27/63). In addition, the investigators observed that closed-loop maintained spinal cord activation within the therapeutic window 1.5 times that of the control group (91.1% of the time with closed-loop vs. 59.5% for controls).

The findings from the Avalon trial only reiterate these successful outcomes.

At 18 months, 69.4% (25/36) of participants implanted with the Evoke system experienced more than 80% pain

relief, while 83.3% (30/36) experienced a clinically meaningful improvement in quality of life. Brooker also reported that disability was reduced, with 72.2% (26/36) of patients having only minimal to moderate disability compared to 18% at baseline.

In terms of a reduction in opioid medication, Brooker said that more than two out of three patients (67.9%; 19/28) reduced or eliminated their intake in the Avalon study, and lastly, he told the INS audience that spinal cord activation was maintained within the therapeutic window 97.5% of the time.

In light of these findings, Brooker told the INS, “With Evoke, study results suggest that pain relief continues to improve over time, which is not typically observed with fixed-output systems.

With the capability of neurophysiology measurements, such as percentage time in the therapeutic window, we can now start to understand a complex condition objectively in addition to patient reported outcomes, an important advancement to the field of pain management.”

Furthermore, Steven M Falowski, director of functional neurosurgery at Neurosurgical Associates of Lancaster (Lancaster, USA), and an investigator in the Evoke Study, commented on the data, “Both studies provide evidence supporting the novel design of the device where ECAPs are measured to monitor therapy delivery in real time. The technology provides an objective measure based on a neurophysiological response to control therapy delivery and provides insight into the mechanism of action. There were a plethora of talks featuring ECAPs at this congress and they highlight the potential clinical utility of this new technology.”

pulse generators (IPGs)”. Moreover, he interesting thing is that the miniaturised reported that 92% of patients receiving computer circuit board, which would high frequency stimulation achieved the typically be placed in the implantable primary endpoint of a 50% reduction pulse generator, has been miniaturised, in pain; achieved by 82% of the patient and placed within the lead itself,” Bolash population in the low frequency group. said, and suggested that, “This is the The SURF RCT study, a prospective, brains behind the spinal cord stimulator randomised, multicentre clinical trial was for this particular device.” the first ever pivotal study conducted He further highlighted that the device utilising a wirelessly powered SCS does not require the patient to have an system comparing a variety of waveform implantable pulse generator. “Therefore, options without a separate trialling what is absent in the study, is the device. According to Bolash, the study placement of a percutaneous lead, the participants were able to optimise their removal of a percutaneous lead a week pain relief outcomes and dial in the or two weeks later, and then returning to appropriate waveform and frequency Robert Bolash the procedure room to place a permanent customised to their unique pain relief device. With this device you can place the needs. device all in one step.”

The study enrolled 99 patients (mean age: 58) at seven Thus, Bolash reported that after an initial 30-day centres in the USA. The high frequency patients received trial period with the permanent implanted device, and 10kHz SCS and the lower frequency patients received throughout a six-month follow-up, treated patients a number of different waveforms. Inclusion criteria experienced statistically significant improvement in VAS required patients to have predominantly back and/or scores in both arms of the study. back and leg pain associated with post-laminectomy Concluding the study, he highlighted that the syndrome, for at least 12 months. However, patients investigators observed a significant reduction in who had had previous SCS in the past were excluded, disability, meaning that patients were able to go out, including devices that had be explanted. “These really enjoy certain activities and spend time with their were de novo patients, who had never been exposed to families. “This was much more reassuring to me than SCS. And, we did exclude patients who would require seeing some of the data that are more objective,” Bolash MRI during the period of the study, although the device emphasised. Finally, he alluded to the high patient does carry MRI conditionality,” Bolash explained. satisfaction rate they experienced with the device, and “The wireless cord stimulator device used in this trial noted that patients were “certainly satisfied with the has very similar characteristics to a lead that you would analgesia they received and their ability to avoid an place with a conventional spinal cord stimulator. The implantable battery.”

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September 2019 | Issue 35

Disruptive innovation in neuromodulation: What can we learn from #SocialMedia disrupting our communication style?

(27% of patients comment or post about health) and social (30% of patients view other patients’ related experience). Plus, they are decision-makers; 77% use search engines before making an appointment and 40% report that information from social media affects their choice of doctor, hospital or medical facility.

Looking specifically at the

physicians increase visibility in the neuromodulation community (boosted Twitter profile, engagement with key opinion leaders), get referrals, and save costs by utilising industry resources to build educational materials. On the other hand, industry builds strong collaborations with hospitals, increases the number of implants, and recruit’s patient ambassadors.

On the whole, the potential of social in neuromodulation is tremendous. Patients can achieve autonomy, empowerment, self-efficacy and support. For example, patients with rare diseases may feel less isolated, while patients with fecal incontinence can access information about sacral neuromodulation without embarrassment. Professionals can make healthcare decisions aligned with patients’ or families’ priorities.

Medical knowledge, attitudes and skills (e-learning modalities) are also improved.

Moreover, social media helps clinical trial recruitment and patient follow-up.

The promotion of awareness campaigns (CRPS), fundraising and dissemination of news and research, including journals, societies, conferences and trials, are all advantages. Furthermore, it can enhance professional networking and telementoring (e-mentorship), increase a doctor’s credibility as a thought leader and open doors to other medical leaders in the field.

Also, with social media providing some empowerment for professional development and recognition, new voices are pushing to influence an old status quo. Over the last years many women (and men) spent time and energy on social media to support professional development of underrepresented women physicians in medicine. Lastly,

involvement of physicians, 24% of doctors use social media daily or many times daily to conduct medical research; 88% to research pharmaceutical, biotech, and medical devices. Interestingly, 60% of physicians believe social media improves the quality of care delivered to patients.

Social media channels leverage marketing efforts through reach, provision of a platform to develop or reinforce an authoritative voice, and a relatively minimal material investment.

In the commercial sphere, in Germany, 85% of healthcare companies currently use social media marketing compared to 58% in 2012. The scenario makes sense. A mutually beneficial partnership (physicians/industry) emerges. The

but certainly not least, it seems social media could benefit academic careers.

For example, the number of tweets can predict highly cited articles within the first three days of article publication and corresponding “tweetation metrics” have been proposed.

In medicine, practitioners must bear in mind contraindications to any modality.

Likewise, it is responsible to anticipate the downsides to social media and always proceed with caution. For instance, concerns have been raised about the quality and reliability of information (“echo-chamber effect”: following content that agrees with established viewpoints), medicolegal liability (personal opinions, no medical advice), and confidentiality/privacy (preserving

Georgios Matis Comment & Analysis Twenty-four per cent of doctors are using social media daily to conduct medical research, and 85% of healthcare companies now implement social media marketing, says Georgios Matis. Although calling for patients and practitioners alike to “proceed with caution” when using social media for medical purposes, he elaborates on the benefits of these platforms, such as how new voices are beginning to emerge to challenge the status quo within the medical community.

C

ommunication can be hard; as G B Shaw once said, “The single biggest problem in communication is the illusion that it has taken place.” Communication is also the core element of social media, and is defined as a two-way process of reaching mutual understanding, in which participants not only exchange (encode-decode) information, news, ideas and feelings but also create and share meaning. The challenge of clearly conveying meaning takes on new dimensions in social media, a world of human interactions driven by content and supported by use of technology.

Meanwhile, the importance of its growing reach and clout was noted in 2006 when Time Magazine chose an unconventional “Person of the Year”: the readers; you, me, all of us.

The number of active social media users worldwide was estimated in 2018 as over 3.1 billion (42% of the total population) with 448 million in Europe.

There are likely several reasons active users contribute to SM. Perhaps out of a sense of altruism? Or maybe because of “anticipated reciprocity”; receiving valuable information in return. Or aiming for increased recognition or community? Maybe it is for all these reasons. In any case, social media is a disruptive innovation, and it’s here to stay. And, “disruptive innovation” is not a buzzword. It is reality. Social media enables a whole new population of consumers: patients, physicians, industry, to use this service for “communication”.

This new mode of communication directly impacts patients’ activities and outlook. Patients today are informed (80% of internet users have searched for health information online), engaged

professional boundaries between patients and physicians; accepting a patient´s friend request allows access to potentially personal content, whereas extending a friend request to a patient may pose pressure due to the inherent power differential). Moreover, social media activity could become an end in itself and distract from the learning process.

The internet is about content and conversation. Social media channels are only as evidence-based as the content they reference and any information stream is only as good as what you let in.

These imperatives benefit from a dedicated focus, with a web presence and social media activity being hallmarks of modern organisations. Many years ago the International Neuromodulation Society recognised the importance of social media in transforming the neuromodulation field and hired a consultant, Nancy Garcia, to penetrate the social media market and expand its journal’s influence.

In closing, using this medium responsibly requires always keeping principled values foremost. To be provocative, one might ask: Do we need less social media? Do we need less marketing in neuromodulation? I would say no. However, enthusiasm for neuromodulation as a field must not veer toward deceptive marketing. In the era of “alternative facts” we should underline the necessity of eliminating misrepresentation of facts about company products, procedures and studies.

Misleading patients and physicians about capabilities of specific products must be also a no go. As author C S Lewis wrote, “Don´t use words too big for the subject.

Don´t say ´infinitely´ when you mean `very`; otherwise you’ll have no word left when you want to talk about something really infinite”. Companies, healthcare professionals and key opinion leaders all bear responsibility.

In this light, best practices and codes of ethics are urgently needed and more than welcome. The bottom line in how the potentially disruptive mode of social media communication is approached should all be about credibility and trust.

As Robert Levy (INS President) once commented: “We need to evaluate what really drives us and ensure that these are reasonable, appropriate and necessary values and if so, then we must take back our culture and convince others of the value of our mission”. We owe this to ourselves and our patients because we love what we are doing. And, with the following words of Gaudí, “To do things right, first you need love, then technique,” I would like to extend an invitation to join us for the 15th INS World Congress in Barcelona, Spain (1–6 May, 2021)! A great future lies ahead!

Georgios Matis is an INS Public Education committee member and a senior consultant at the Department of Stereotactic & Functional Neurosurgery, University Hospital of Cologne, Cologne, Germany.

The author would like to thank Nancy Garcia, INS Public Education and Website Manager, for her editorial assistance.

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Issue 35 | September 2019

Similar success rates for anatomic and targeted lead placement for spinal cord stimulation “Anatomical lead placement is a viable alternative to targeted lead placement for spinal cord stimulation,” concluded Jason E Pope, Evolve Restorative Center, Santa Rosa, USA, while presenting data from the DELIVERY trial, which evaluated anatomic versus targeted lead placement for BurstDR therapy during the trial evaluation period. “Anatomical leads offer more predictable trial and surgery times, while there is a greater preference from physicians, and there was no statistical difference in clinical outcomes or patient satisfaction,” he added.

THE CORRESPONDING RESULTS were presented during the International Neuromodulation Society (INS) 14th World Congress (25–30 May, Sydney, Australia). The study was a prospective, randomised, single-blinded, multicentre international study. Pope said that the purpose of the study was to compare the trial success rate between the two lead placement techniques for spinal cord stimulation (SCS) using a nonlinear burst stimulation pattern.

In terms of those who were enrolled, patients were deemed eligible if they had had back and/or leg pain, with a Numeric Rating Scale (NRS) score of more than or equal to six, who had not undergone previous SCS. Pope reported that a total of 270 patients were randomised in a 1:1 ratio to each treatment group.

In the anatomic lead placement group, one lead tip was placed at the mid-body of T8, and the other at the superior endplate of T9. In contrast, for patients

in the paraesthesia-mapped group, physicians confirmed coverage of the patient’s primary pain location.

According to Pope, the investigators measured the trial success using a composite of the following endpoints: ≥50% patient-reported pain relief at the end of the minimum three-day trial period, physician’s recommendation and patient’s interest in a permanent implant.

In relation to the results, trial success for the anatomic lead placement group was 84.4%, only slightly higher than the paraesthesia-mapped lead placement group at 82.3%. Yet, Pope acknowledged that procedural times for the placement of two leads were 31% shorter in the anatomic lead placement group (p<0.0001).

The decrease in the mean NRS pain score was also found to be similar

When you ask physicians about their preference, about 70% chose the anatomic group.”

Placebo-controlled RCTs of spinal cord stimulation are on the rise, but their reporting and replicability is poor Important methodological aspects of clinical trials of spinal cord stimulation (SCS) using a placebo are consistently being poorly reported, says a recent systematic review. Within the context of the fast-evolving field that is neuromodulation, the authors, Rui V Duarte from Liverpool Reviews and Implementation Group (University of Liverpool, Liverpool, UK) and colleagues’ express concern about the validity and replicability of the current literature.

W

ithin their appraisal, published in Neuromodulation, Duarte et al allude to the important aspects that need to be clearly reported, including the reporting of stimulation programming parameters, patient position during perception threshold measurement, management of the patient handheld programmer, frequency of recharging, as well as the assessment of the fidelity of blinding.

Throughout the medical literature, high-quality randomised controlled trials (RCTs) are considered to be the “gold standard” to evaluate the effectiveness of a treatment. Yet, the authors acknowledge that “in contrast to drug therapies, providing an appropriate placebo control in clinical trials of healthcare procedures involving a medical device is often much more challenging.”

Nevertheless, Duarte and colleagues point to the advent of a new “comparator arm” for RCTs to investigate the effectiveness of SCS. Despite blinding difficulties, they write that a number of small studies have managed to compare conventional or paraesthesia producing SCS to sham stimulation.

Thus, by systematically reviewing the current evidence base of RCTs regarding SCS placebo/sham trials alongside critiquing the corresponding literature, Duarte and his team developed a checklist for the design and reporting of future RCTs. In order to carry out this task, they searched electronic databases from inception until

January 2019, while any RCTs that included only an active comparator were excluded. Ultimately, 12 eligible RCTs were identified. The modalities that were assessed included: paraesthesia stimulation, subthreshold, burst and Rui Duarte high-frequency SCS, which were predominantly conducted on patients with failed back surgery syndrome, complex regional pain syndrome, and refractory angina.

The authors write, “The quality and transparency of reporting of the methods of placebo stimulation, blinding of patients, clinicians, and researchers varied markedly across studies. In the 12 RCTs identified in this systematic review, the placebo varied from simply switching off the SCS device to more complex approaches such as intermittent switch on of low current stimulation or programming a current leak during the placebo periods so that the recharging time and frequency were equivalent during the different crossover periods.”

In light of such shortcomings, Duarte et al propose that authors of future SCS placebo-controlled studies should consider a number of specific aspects of the design and reporting of any subsequent trials.

between groups; 53.2% for the anatomic lead placement group, and 53.8% for the paraesthesia-mapped group; p=0.79).

Pope also reported that trial success for patients who went on to an extended trial with tonic stimulation was 50% (5/10), compared with 79% (11/14) for anatomical lead group and paraesthesiamapped group, respectively (p=0.2).

He continued, “this may suggest the importance of paraesthesia mapping for those patients that fail paraesthesia free waveforms, requiring extended trials, in an effort to promote durable outcomes. “ Moreover, Pope highlighted, “When you ask physicians about their preference associated with using an anatomically placed lead versus a paraesthesia-mapped lead, about 70% of [physicians] chose the anatomic group.”

Commenting on adverse events, he reported that a total of 13 adverse events were observed (4.5%), the majority of which were due to lead migrations and pain around implant site, with no difference between groups.

Concluding the study, Pope maintained how there was no difference between groups regarding the trial success rate, reiterating that the current trial was the first study to show that there was an 80% responder rate with conversion using this burst nonlinear waveform.

Regarding studies using non-rechargeable devices, the authors point to the importance of programming parameters for the active and sham arm, as well as how the patient handheld programmer is managed and, if a handheld programmer is provided to the patients, to think about how blinding is ensured. For studies utilising subthreshold programming as a comparator, Duarte and colleagues note that these investigations should “specify the position(s) in which the threshold was measured in and whether a feedback loop/position adjustment was utilised to modulate current intensity”.

In terms of rechargeable devices, the authors maintain that the use of a placebo is further compounded by a number of factors, including the need for the patients in both arms to experience a similar recharging burden.

The quality and transparency of reporting across studies varied markedly.”

“Accordingly,” they add, “the frequency and duration of recharging should be reported. This is important in both cross-over and parallel design studies.”

In addition, they emphasise that the management of both patient handheld programmers and patient rechargers needs to be specified. And, for the latter, particularly where the recharger contains a feedback screen that allows the subject to assess IPG (implantable pulse generator) charge.

“There are several possibilities to manage sensations related to placebo responses depending on the nature of the active comparator. These include devices that cyclically switch on to deliver a short burst of suprathreshold stimulation, devices that deliver subthreshold current of very low intensity continuously or intermittently [and] devices that are fully switched off,” write the authors. Yet they highlight, “Only this [latter] strategy avoids the risk that stimulation might be therapeutic, even when the dose is minimal. Use of a full switch off strategy against a paraesthesia stimulation comparator risks unblinding participants.”

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September 2019 | Issue 35

Clinical ProductNews News

Stimwave announces completion of enrolment for the Tsunami placebocontrolled double-blind randomised trial of wireless DRG stimulation for chronic back pain

Stimwave has announced completion of patient enrolment and preliminary results of the first-of-its-kind Tsunami study. The Tsunami placebo-controlled double-blind randomised controlled trial (RCT) is the first ever placebocontrolled double-blind RCT in the chronic pain relief neuromodulation industry. This study is also the first study evaluating the delivery of a high frequency waveform acting on sensory fibres at the dorsal root ganglion (DRG) and dorsal horn portions of the dorsal column.

The Tsunami study has now completed enrolment with 50 chronic low back pain subjects. Subjects underwent a small procedure with a one-stage implant, and the electrodes are placed using a novel technique at the T9 level and the exiting nerve root. Patients were randomised to either active therapy or sham and implanted without general anaesthesia. Patients in the sham arm did not receive any therapeutic stimulation for at least one month, and were never active at any point while blinded. If patients were reporting less than 50% pain reduction, they were unblinded and sham patients were crossed over to the treatment arm.

The preliminary results with 38 subjects show a positive outlook for this unique therapy. Sixty-three per cent of active subjects reported a reduction in pain greater than 50%. Comparatively, only 16% of the sham subjects reported 50% pain reduction thus demonstrating a statistically significant (p=0.007) in favour of the active therapy. At the time of this report, all sham patients were unblinded and now 77% of all patients are reporting greater than 50% pain reduction.

NIH study to utilise NeuroPace RNS system for research on the brain’s reward system

NeuroPace has announced that the company’s RNS system, a closed-loop neuromodulation technology approved to treat adults with medically refractory focal onset epilepsy, will be used in a clinical investigation that will examine whether neuromodulation could be effective as a means of managing loss-

Product News of-control eating for patients with a body mass index (BMI) of 45–60 kg/ m2 for whom medication and gastric bypass surgery have not been effective treatments, and for whom loss-ofcontrol eating is a contributing factor.

There is evidence to suggest that long-term alterations in brain function, particularly in the reward and impulse control circuitry, occur with eating disorders, including loss-of-control eating. In addition, there is growing evidence to suggest that there are discrete changes in brain activity, or biomarkers, which immediately precede loss-of-control eating events.

“We have long known that the neural recording and personalised interventional capability of the RNS system provides an unprecedented window to the brain, resulting in an effective treatment that works by identifying the precursors of seizures and treating them immediately and automatically,” said NeuroPace chief medical officer Martha Morrell.

“We are pleased to support this new research, which will be among the first to explore additional applications of the RNS system beyond epilepsy. This may help lead to the treatment of other conditions where there may be signals or biomarkers that can be identified and used to time therapy delivery, and where there is also a real clinical need.”

The five-year study will be conducted at Stanford University School of Medicine (Stanford, USA). The study will use NeuroPace’s first-of-its-kind closed-loop neurostimulation system to interrupt brain activity patterns in the nucleus accumbens, a key component of the brain’s reward circuit and a region believed to be involved in loss-of-control eating. The study is supported by a grant from the National Institutes of Health’s (NIH) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative,

a public-private research enterprise supporting research to revolutionise the understanding of the human brain.

“Obesity is a disease with many contributing factors,” said Tara Skarpaas, principal scientist at NeuroPace and one of the study’s researchers. “This study will evaluate whether neurostimulation can automatically respond to the signals that occur immediately before a loss-ofcontrol eating episode to help patients regain control.

“The RNS system’s ability to continuously monitor brain activity and respond with therapy when these biomarkers are detected makes the system an ideal fit for this research.”

The first non-invasive, adaptive neuromodulation digital treatment for migraine receives CE mark Neurolief, a developer of digital therapeutics brain neuromodulation technology, has announced that it has received CE mark for its Relivion non-invasive, adaptive digital treatment for migraine. The CE mark allows Neurolief to market, sell, and distribute the Relivion device as an over-the-

loop, interchangeable, multi-channel neuromodulation results in a better outcome compared to single-nerve neuromodulation,” said Eran Schenker, Neurolief’s chief medical innovation officer. “We hypothesise that the disruptive technology synergistic neuromodulatory effect elicited by concurrent activation of both the occipital and trigeminal neural pathways contributes to the superior therapeutic results shown.”

Relivion neuromodulation system

counter therapy within the European Union and countries that participate with Agreements on Mutual Recognition of Conformity Assessment.

The Relivion is the first noninvasive, adaptive, multi-channel brain neuromodulation technology that offers a highly effective therapy, without the risks and costs associated with invasive procedures and without the side effects related to medications. This type of therapy was previously possible only with implanted devices. The Relivion system is simple and safe for patients to self-administer at home at a fraction of the cost of surgical implants.

Neurolief’s Relivion is comprised of a comfortable and adjustable headset that provides precise modulated pulses simultaneously to six branches of the occipital and trigeminal nerves via several adaptive output channels around the patient’s head. The sophisticated cloud-enabled device connects to a proprietary mobile phone app and learns over time to deliver personalised treatment for each patient.

The CE mark was granted based on data from a randomised, double-blind, placebo-controlled clinical trial which showed very high efficacy and safety of the Relivion in the treatment of migraine headache. Seventy-six per cent of the participants achieved headache relief after only one treatment while no serious adverse effects were observed. Full results of the trial will be presented at the American Headache Society’s 61st Annual Scientific Meeting on 13 July, 2019 in Philadelphia, USA. “Clinical data demonstrate that the Relivion’s confined, closed-

Amit Dar, Neurolief’s co-founder and chief technology officer, added, “Future generations of Neurolief’s innovative technology will include embedded artificial intelligence and machine learning algorithms, which will provide powerful capabilities to analyse the data collected from each user and from multiple users along with accurate migraine prediction.

“This will integrate in a seamless fashion to enable updates of the closedloop personalised brain neuromodulation treatment that improves over time, providing a tailored, precise treatment for each patient.”

EVER Pharma launches patient-friendly subcutaneous pump for Parkinson’s disease

EVER Pharma, a company specialising in neurological diseases, has announced the launch of its D-mine Pump. This portable micro-infusion device recently received European CE approval and is currently being launched in several European countries. It was specifically designed to provide precise continuous subcutaneous drug delivery for Parkinson´s patients in a compact, simple-to-use and patient-friendly package.

Parkinsons patients often have difficulty coordinating movement.

So, the ease of handling, safety, and intuitive use were the primary goals for the D-mine Pump development.

Leveraging special micro-rotary pump technology, minimal buttons and a bespoke menu screen interface, the device is conveniently compact and

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Issue 35 | September 2019 easy to use. It also features automatic drug filling, multiple languages, data storage, and does not require complex flow rate calculations.

“CE approval of the D-mine Pump and the launch, is an important milestone for our product portfolio in Parkinson´s disease. EVER Pharma is now able to deliver an enhanced and comprehensive package of care with its Parkinsons disease medication Apomorphine and its own medical devices”, explains Dominic Benning, head of dopaminergic therapy at EVER Pharma.

Axonics announces FDA approval for the use of full-body MRI for pivotal study patients

commented, “Allowing full-body MRI scans for our clinical study patients means that none will have to undergo an explant of their neurostimulator device should they require an MRI. “We view this as a very positive step by the FDA that underscores the quality of data that Axonics has submitted to the agency. Given this approval, we are confident that this capability will be included as part of the Axonics SNM system premarket approval, which is anticipated in the second half of 2019.”

Saluda Medical secures debt financing from Medtronic

Saluda Medical has announced that it has Axonics has announced secured a four-yearthat the Food and Drug term loan agreement Administration (FDA) with Medtronic, to fund approved the use of full-body continued development of magnetic resonance imaging its Evoke ECAP-controlled, (MRI) using 1.5 Tesla MRI closed-loop spinal cord scanners for clinical study stimulation (SCS) system patients implanted with the for the treatment of chronic Axonics System. intractable pain of the D-mine Pump The approval was a result trunk and limbs. Additional of a supplement filed by Axonics with terms of the loan agreement were not the FDA under the investigational disclosed. device exemption (IDE) regarding the Medtronic is an existing shareholder company’s ARTISAN-SNM (sacral of Saluda Medical, having participated neuromodulation) 129-patient pivotal in two previous financing rounds. clinical study. The FDA concluded that “We are pleased to once again Axonics provided sufficient data to partner with Medtronic in this support full-body MRIs. financing,” said John Parker, CEO of Raymond W Cohen, CEO of Axonics, Saluda Medical. “This funding provides

Axonics’ neuromodulation system

us with the financial flexibility to accelerate further development of our closed-loop SCS system and prepare for commercialisation.”

Saluda Medical raises US$75 million equity financing from Boston Scientific and Redmile Group Following the announcement of the debt financing with Medtronic, Saluda Medical has announced that it has secured US$75 million in equity financing from Boston Scientific and Redmile Group. The latter investment is set to fund the final stages of development through commercialisation of its Evoke ECAP-controlled, closed-loop spinal

cord stimulation (SCS) system for the treatment of chronic intractable pain of the trunk and limbs.

“This equity financing in combination with our recent debt transaction strategically positions us to fund the final developmental stages of the Evoke SCS system through global commercialisation,” said John Parker, CEO of Saluda Medical.

“Evoke has the potential to be the first closed-loop spinal cord stimulation system introduced to the market— which we believe has immense potential for radically improving the way pain is treated. The US pivotal clinical study met the pre-specified endpoints, including significant evidence of pain relief.”

Issue 35 | September 2019

Market watch

Product News Perfuze’s Millipede Clot Ingestion System receives breakthrough device designation from FDA

Perfuze, a medical device company developing next-generation catheterbased technology to treat acute ischemic stroke, has been granted breakthrough device designation by the US Food and Drug Administration (FDA) for its Millipede Clot Ingestion System (CIS) technology.

Millipede CIS comprises a catheter technology that is designed to remove clots from the brain following an acute ischaemic stroke. The designation recognises the novelty of the Millipede technology and its potential to offer significant advantages over existing alternatives for treatment of acute ischaemic stroke.

Medtronic partners with Viz.ai to accelerate adoption of new AI software Medtronic and Viz.ai have partnered to accelerate the adoption of Viz.ai’s new technology, which helps synchronise stroke care and decrease time to treatment, potentially improving outcomes for patients.

Viz.ai’s technology uses artificial intelligence (AI) to identify suspected

large vessel occlusion (LVO) strokes and automatically notify specialists.

The Viz.ai software connects to hospital computed tomography (CT) scanners and alerts stroke specialists within minutes that a suspected LVO stroke has been identified, sending the radiological images directly to their smart phones where they can be viewed.

Viz.ai enables a physician to provide the patient with the treatment they need as quickly as possible.

“The combination of AI powered alerts, mobile image viewing, and HIPAA compliant communication facilitates synchronisation of stroke care with great potential to impactfully reduce door-to-needle time and help an increased number of patients,”said Elad Levy, chairman in the Department of Neurosurgery with the University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences and medical director of Neuroendovascular Services

at Gates Vascular Institute.

Every two minutes someone in the USA has an LVO, but only an estimated 15% receive a potentially lifesaving mechanical thrombectomy, a minimallyinvasive procedure that removes blood clots. A Viz.ai study in two centres showed that in 95.5% of true positive cases, its technology alerted the stroke specialist earlier than the standard of care, saving an average of 52 minutes.

Through this agreement, Medtronic will distribute Viz.ai’s existing LVO detection and triage software services, which are currently permitted for marketing in the USA. It was the first clinical decision support software designed to analyse CT results that may notify providers of a potential stroke in their patients cleared by the US Food and Drug Administration (FDA). The technology is available in over 200 hospitals, with the goal of making Viz.ai available to every stroke centre in the country.

Penumbra introduces latest stroke thrombectomy aspiration technology at SNIS 2019 Penumbra announced commercial availability of the Penumbra JET 7 reperfusion catheter with XTRA FLEX technology, at the Society of NeuroInterventional Surgery (SNIS) 16th Annual Meeting in Miami, USA. Penumbra JET 7 with XTRA FLEX technology is used with the Penumbra ENGINE in the fully integrated

29

Penumbra System—an aspiration-based mechanical thrombectomy system that enables physicians to extract thrombus in acute ischaemic stroke patients.

The Penumbra JET 7 reperfusion catheter with XTRA FLEX technology is the latest advancement in the Penumbra System JET–ENGINE family of products, which was launched last September. As the Penumbra System’s eighth generation reperfusion catheter for proximal large vessel occlusions, the catheter is designed for advanced trackability and navigation, and maintains the large 0.072” lumen.

Penumbra JET 7 with XTRA FLEX technology, together with the power of the Penumbra ENGINE, are designed to maximise thrombus removal force.

Corindus announces regulatory approval of CorPath GRX for neurovascular intervention in Australia and New Zealand CorPath GRX CorindusCorindus Vascular Robotics has announced that it received approval from the Australian Therapeutic Goods Administration to commercialise its CorPath GRX System for neurovascular interventions in Australia and New Zealand. The CorPath GRX System is already approved for percutaneous coronary and peripheral vascular interventions in the region.

In March 2019, Corindus received CE mark to commercialise CorPath GRX for neurovascular interventions in 33

30

September 2019 | Issue 35

Events

Product News countries in Europe and the company plans to initiate clinical cases with select partners in Europe as early as this summer.

RAPID imaging platform expands options for speedy stroke treatment at Atlantic Health System Neuroscience Recognising how vital it is that stroke neurosurgeons and neurologists receive timely information about the type of stroke a person is having so they can decide on the best treatment, Atlantic Health System Neuroscience recently introduced a system-wide rollout of a cutting-edge technology called RAPID. RAPID allows experts to swiftly discern whether a patient has reduced blood flow to the brain and other signs of brain injury. The technology enables them to treat a greater number of patients within the newly expanded 24hour post-stroke onset window during which surgery and other therapies can be helpful.

The platform is noteworthy for its ability to shave time from the treatment decision-making process: Images are transmitted from patients’ CTA (computed tomography angiography) and CTP (computed tomography perfusion) to hospital systems and physicians’ smart phones within just minutes.

Following the pilot roll out of RAPID at Overlook Medical Center, Atlantic Health System hospitals Morristown, Newton and Chilton medical centres also implemented the software for use

RAPID Imaging Platform

by their comprehensive and primary stroke centre teams.

“This speed is key when it comes to treating patients,” said John M Hanna, medical director, Comprehensive Stroke Center, Overlook Medical Center.

“Before, processing of the CTA into clinically meaningful images took 15 to 20 minutes. This did not account for the time it took to upload the images into our system. With RAPID, after the CTA is complete, it takes two minutes to send the key images to our phones.”

Atlantic Health System Neuroscience has been a leader in embracing technology to treat stroke patients with its earlier adoption of the TeleStroke platform, which is in use throughout Atlantic Health System. TeleStroke enables EMTs and paramedics to communicate directly with a neurologist while the patient is still being transported by ambulance, facilitating any preparations that need to be made before his or her arrival. Once the patient is in the emergency department, a TeleStroke robot—comprised of a camera and monitor—lets the neurologist see and assess the patient remotely. Based on the success of TeleStroke, acquiring RAPID was the next natural step

toward streamlining the diagnosis and treatment process for stroke patients at Atlantic Health System.

Vesalio obtains additional CE approval for new products with NeVa clinical data published Vesalio has announced that it has obtained its second CE approval spanning multiple new NeVa product designs and technology. The new generation NeVa devices expand on the Drop Zone and Smart Marker technologies while also introducing first-to-market features such as a distal filter. A controlled launch of the new technology will begin in June in Europe with expected full commercial release in Q4 of this year.

“The new technology looks very promising based on early feedback from several physician key opinion leaders. The positive clinical results that were recently published from our first generation NeVa devices, has led to an increased market interest in NeVa. The expansion of the NeVa platform should provide an excellent opportunity for Vesalio to gain additional market share,” commented Steve Rybka, CEO of Vesalio.

Calendar of events 4–6 September ESMINT: European Society of Minimally Invasive Neurology Therapy Annual Meeting Nice, France

27–28 September 1st Annual International Congress on the Future of Neurology New York, USA www.1st-international-

21–24 October WFITN: World Federation of Interventional and Therapeutic Neuroradiology Naples, Italy

www.esmint-2019

congress-on-the-future-of-

www.wfitn2019.com

neurology

19–22 September ESNR: European Society of Neuroradiology Annual Meeting Oslo, Norway www.esnr.org

September

Profile: Istvan Szikora

Issue 19

ious Brain Is consc safe?

Brainto sedation

30 September– 2 October SLiCE: Stroke Live Course Nice, France

20–23 November SVIN: Society of Vascular and Interventional Neurology annual meeting Atlanta, USA

www.slice-online.com

www.svin.org

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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23–26 January NANS: North American Neuromodulation Society 23nd Annual Meeting Las Vegas, USA

11–14 March Global Stroke Alliance Rio de Janeiro, Brazil

conference

https://neuromodulation.org

3–5 December UK Stroke Forum Conference Telford, UK

18–21 February ISC: International Stroke Conference Los Angeles, USA

www.stroke.org.uk

https://professional.

12–15 May ESO-WSO: Joint European Stroke Organisation and World Stroke Organisation Conference Vienna, Austria

heart.org/professional/

eso-stroke.org/events/eso-

EducationMeetings

wso-conference-2020

globalstroke2020.com/

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