NeuroNews Issue 37 - US Edition

April 2020 | Issue 37

COVID-19: Lessons learnt from Italy, China and the USA

Jesse Dawson:

Profile

A webinar hosted by the Society of NeuroInterventional Surgery (SNIS) on 2 April brought together neurointerventionalists and endovascular neurosurgeons from Italy, China, and the USA. Important questions such as who to treat, whether to intubate, and how to optimise post-care pathways in the setting of COVID-19 were raised, as each physician disclosed what they would have done two weeks prior, had they known of the pandemic’s devastating effects.

Page 10

Philip M Meyers and Arthur Wang: New York amid COVID-19

Page 4

New trial finds high responder rates for ECAP-controlled, closed-loop spinal cord stimulation

A randomised, double-blind trial finds ECAP-controlled closed-loop spinal cord stimulation (SCS) statistically superior for the treatment of chronic pain, compared to open-loop stimulation. At 12-months, >83% of closed-loop patients reached the ≥50% responder threshold and >56% reached the ≥80% high responder threshold in overall back and leg pain.

Presenting these results at the North American Neuromodulation Society’s (NANS) annual meeting (23–26 January, Las Vegas, USA), Timothy Deer, president and CEO of The Spine and Nerve Center of the Virginias, Charleston, USA, argued that these are “some of the best results seen within our field and any publication today”.

“C

OVID is devastating, but so is large vessel stroke,” declared J Mocco, endovascular neurosurgeon from Mount-Sinai Health System, New York, USA. “Stroke patients need an advocate.” Arguing that many procedures carried out in hospitals are elective or semi-elective, he added, “There is a lot of improving quality of life work, and procedures that can wait. Stroke is not one of them.

We are in the minority taking care of this highly timesensitive patient population. We need to advocate for them.”

Though in agreement, Michael Levitt, University of Washington (Seattle, USA) asserted, “For places that do not have the right personal protective equipment [PPE], now is not the time to go off the reservation and do things that are outside the scope of typical practice.”

Alluding specifically to COVID-endemic areas, Levitt said there is a continuum in terms of who to treat.

“The way I look at it is: What is the risk of COVID infection in the population? Is the risk of leaving something alone for two weeks greater than the risk of COVID infection for the population? If the answer

It is a false sense of security saying that intubated patients are safer.” is yes, then it is reasonable to do that case … But benign tumours, unruptured aneurysms or unruptured AVM—there is no reason to be doing those cases. You are actually subtracting from your healthcare system’s ability to handle things.”

Tao Hong of Xuanwu Hospital, Beijing, China, confirmed that in Beijing, non-emergency interventional procedures have been suspended. For cases like subarachnoid haemorrhage, which, according to Hong, now commonly present with fever, the team at Xuanwu Hospital awaits the results of the patient’s COVID-19 screening test before performing digital subtraction angiography (DSA) and embolising.

Continued on page 2

THE STUDY ALSO found that the median ECAP (evoked compound action potentials) amplitude with open-loop stimulation fell below the in-clinic target when patients were outside of the clinic. Yet the closed-loop group maintained the target level of activation. Moreover, Deer acknowledged that the time spent in the therapeutic range was almost double—and significantly different—with closedloop stimulation (95.2% vs. 47.9%), and the most frequent spinal cord activation level was six times greater in this cohort, compared to those receiving open-loop.

Speculating about the mechanics behind this spinal cord activation data, Deer said: “This would indicate to us that the activation of the ECAPs, and staying in the zone of activation, is an important issue. After nearly 50 years of not quite knowing the neural tissue response to SCS, this is the first time we can say we are activating ECAPs.” He added: “This leads to a lot more discussion for future research on the subject.”

Deer explained that the study was designed to preserve objectivity and minimise bias. Aspects Continued on page 15

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April 2020 | Issue 37

COVID-19

COVID-19: Lessons learnt from Italy, China and the USA Continued from page 1

Discussing how neurointerventional practice has changed in Beijing, Hong said that a chest CT scan has been added to the diagnostic workup of acute stroke patients, while the number of medical professionals in surgery itself is reduced. He added, “There is a lot of telemedicine now in China, after COVID-19, with a lot of consultants encouraged to provide services online, including our department.”

Hong told the audience of a lesson learnt in China.

“We had a neurosurgeon get infected, and the whole department was shut down. … To protect ourselves is to protect our ability to treat further patients.”

Reiterating the importance of self-protection, Leonardo Renieri, Careggi University Hospital, Florence, Italy, emphasised that not only has their practice changed in Italy, but their approach to patients.

“We used to think about the best approach for the patient, but now, we have to think first about how to protect ourselves, the personnel working with us, and the non-COVID patients admitted to the hospital. It means we have to wait for the swab [COVID-19 test] whenever possible.”

Renieri added that his hospital prefers performing stroke procedures under general anaesthetic once the patient is intubated, as it is safer, he said, and “should be considered more”.

Noting a difference in patient triage between Renieri’s practice in Florence and his own in Seattle, Levitt said they assume all patients are COVIDpositive, until proven otherwise. Moreover, on what he refers to as a highly debated topic: to intubate or not to intubate, Levitt speculates: “It is not that straightforward”, and emphasised that an intubated patient is not necessarily safer. Though acknowledging that if a patient is intubated somewhere else and bought in, they are on a closed circuit, meaning they are safer, he argued that anytime the circuit is disrupted—through suctioning, cuff leaks, manipulation or switching from a transport vent to a regular vent—an aerosolising event could occur.

“It is a false sense of security saying that intubated patients are safer,” Levitt continued. He urged his colleagues listening in to try and avoid intubating in the angiosuite prior to thrombectomy, while unplanned intraprocedural intubation should be avoided “at all costs”.

Expanding on these lessons learnt, Mocco proposed that areas expecting to become COVID-endemic should prepare for intensive care unit (ICU) expertise. He encouraged physicians to “start thinking beyond just

the neurointerventional suite, and the fact that you may be called on to provide ICU care.” He added that he had sent his own department at MountSinai Health System an email requesting all faculty to participate in a 90-minute course, as well as around eight hours of online training each for critical care and ICU support.

In addition, Mocco called for hospitals to prepare for employee shortage. “It is not just the doctors, but the hospital transporters, the clerks, the ward staff, and the nurses, who are all unbelievable in their dedication.” He added that it is also important to think about improving pathways for non-ICU recovery, yet acknowledged that “every institute has its own nuances”.

A question and answer session followed the speakers’ presentations, whereby a question was raised regarding what to do with the supplies that were used for a COVID-positive patient. Levitt replied: “You need to disinfect the outside of just about everything, with some kind of industrial cleaning wipe. If you have cabinets of equipment in your angiosuite that are closed, then you do not need to open them and wipe down every individual box, but you do need to wipe down the outside of the cabinet. If you are opening and closing the doors for your stroke equipment, that is when that kit goes outside [during the procedure].

To protect ourselves is to protect our ability to treat further patients.”

News in brief

The latest stories from the neuro world

n NEW YORK AMID THE CHAOS OF COVID-19: The coronavirus continues to wreak havoc in New York, with morgues reaching capacity and medical resources running short. Amid the chaos, Philip M Meyers and Arthur Wang explain how it is becoming increasingly difficult to care for both critically-ill COVID-19 sufferers and non-COVID patients simultaneously, and detail the challenges they face every day to optimise stroke care in a pandemic.

For more on this story go to page 4 n NEUROPROTECTION DEEMED POSSIBLE: The highly anticipated ESCAPE-NA1 trial has been presented at the recent International Stroke Conference by Michael Hill and Mayank Goyal.

Though nerinetide, the Michael Hill (left) and neuroprotectant drug, Mayank Goyal (right) was found not superior to placebo, effect modification by alteplase was observed, which lead the investigators to conclude that neuroprotection in humans is possible.

For more on this story go to page 6

“The jury is out on how long aerosolised particles may stay in a non-negative pressure environment,” Levitt added. “We think it is somewhere between 15–20 minutes, but it is important for cleaning staff going into an environment that has been recently aerosolised to wear full PPE,” he highlighted.

Lastly, Levitt explained that regarding PPE and safety measures, there is a point to be made about timing.

“All the time metrics are no longer important to me; the safety of the staff is the thing I think about.

“There are no true emergencies in a pandemic like this, there is no cutting corners. Everything will take longer, and we have to be okay with that. Because if you go down, nobody will be getting stroke care, so we have to think about the long term.”

n STROKE RECOMMENDATIONS DURING COVID-19: The Society of NeuroInterventional Surgery (SNIS) has published a set of recommendations for the care of emergent neurointerventional patients during the COVID-19 pandemic. Primarily covering the management of stroke thrombectomy, they emphasise the importance of safety measure for healthcare providers in the context of COVID-19.

For more on this story go to page 12

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April 2020 | Issue 37

COVID-19

New York City in the age of COVID-19: A neuroendovascular experience

reality has set in at Columbia Medical Center. It is increasingly difficult, if not impossible, to care for both the critically ill COVID-19 patients and non-COVID patients simultaneously. In response to growing demands, Columbia Medical Center has cancelled all elective and semi-elective surgeries in order to focus resources on the people, supplies, and physical space needed to care for COVID-19 patients. Our operating rooms and recovery rooms have been transformed into makeshift intensive care units (ICUs) housing upwards of six COVID-19 patients per operating room.

challenges in this age of COVID-19.

Every day, the neurointerventional team has to walk the line between caring for urgent neuroendovascular patients and the risk of exposing team members to COVID-19. This delicate balance is performed in the face of PPE scarcity. At Columbia, N-95 masks as well as surgical gowns are in short supply and are often rationed accordingly. To conserve PPE, only essential personnel scrub in the case and staff are given one mask at a time and often re-use masks throughout the week. This scarcity of PPE is compounded by the lack of point-of-care testing on the market. Without immediate test results, the bulk of PPE supply is rationed to the emergency department where physicians and nurses on the front lines desperately need protective gear.

The other immediate challenge is getting used to working with a skeleton crew of staff. No longer do we have the luxury of doing a case at any hour of the day, or with our specific neuroteam. All across the hospital, department chairmans, attendings, fellows, residents and nurses are actively being redeployed to other departments of the hospital, including the emergency department where the daily surplus of COVID-19 patients is outpacing the available man power. This is further compounded by nurses and technologists calling out sick.

To address the issue of triaging surgical cases, The Centers for Disease Control and Prevention (CDC) recently released a set of guidelines. Given the time sensitive nature of neuroendovascular procedures, many of our procedures do not fall under the purview of these guidelines. No procedure demonstrates this better than stroke thrombectomy where revascularising a patient’s vessel occlusion means the difference between

Physicians and nurses from different departments have been redeployed to the frontlines of these ICUs to help. As cases continue to rise, all in-patient beds have become occupied, corridors and administrative areas are slowly beginning to be lined with patients, some requiring non-invasive ventilation.

With the continuous stream of COVID-19 patients entering our hospital, it is easy to forget that physicians here at Columbia continue to treat other life-threatening conditions such as heart attacks and strokes. Since the COVID-19 outbreak, the division of neuroendovascular surgery at Columbia has continued to adapt our practice patterns to meet the ever growing

life and death and where success is measured in seconds and minutes.

While the technical aspects of performing thrombectomy cases has not changed, we are witnessing changes in our perioperative management of stroke patients as it relates to mitigating personnel exposure to potential COVID-19. Often, little is known about a stroke patient’s medical history when they roll into the angiosuite. This is because the time sensitive nature of the thrombectomy often precludes a thorough medical workup of the patient.

The uncertainty of a patient’s COVID-19 status on top of the already stressful task of successfully performing the procedure has grown taxing on everyone in the

Philip M Meyers Arthur Wang Comment & Analysis Amid the chaos of the pandemic, Philip Meyers and Arthur Wang describe how it is getting increasingly difficult, “if not impossible”, to care for both the critically ill COVID-19 sufferers and the nonCOVID patients simultaneously. Where seconds or minutes can mean the difference between life and death for a patient presenting with stroke, they outline challenges they never thought they would have to face.

T

he first confirmed case of COVID-19 in New York state was on 1 March, 2020. Since then, New York state and New York City in particular has seen a dramatic rise in COVID-19 cases. The outbreak is on the scale seen in Italy. Similarly, the New York metro area has now become the new epicentre for the COVID-19 outbreak in the USA. This has forced local, state, and federal government officials to issue a “shelter-in-place” order on 20 March for all non-essential workers in order to mitigate the spread of the virus.

With a population density of 26,000 people per square mile, New York City is the densest of all cities in the USA. Healthcare in the city is provided through 66 hospitals comprised of a mixture of private and public hospitals. At New York Presbyterian, Columbia Medical Center, we are the largest of the private medical campuses in the city. Since COVID-19 testing became readily available, our hospital has seen a surge in COVID-19 patients to the point that we are now pressed beyond our hospital’s capacity. If one were to walk through the emergency department, a common theme is noticed. Ninety-five per cent of the patients come in with fever and cough. They are immediately placed into isolation rooms away from their families.

Anxious physicians and nurses frantically search for an already limited supply of personal protective equipment (PPE) to protect themselves. On top of this, with a limited number of test kits and the delay between testing and receiving test results, many physicians are forced to work in the face of the unknown. Outside of the emergency department, large tents have been erected to add additional space to care for a long line of patients that extend around the block. Every patient has the same story: fever, cough, and shortness of breath.

As the steep upward rise of COVID-19 cases in New York continue, a grim

endovascular suite.

When faced with a thrombectomy patient, the endovascular team ranging from the interventionalist to anaesthesiologist to the nurse quickly risk stratifies the patient. The patient is assessed for fever, leukocytosis and other laboratory markers of COVID-19 infection. If family is present, information about travel and exposure history is ascertained. We check the patient’s chest X-ray, if available, or will look at the apical lung fields on the CT angiogram of the head and neck for radiographic clues of COVID-19.

With the current lack of point-of-care testing, we often have to go on clinical gut instinct and treat all thrombectomy patients as harbouring COVID-19.

To further mitigate exposure risk, our threshold for performing mechanical thrombectomy under general anaesthesia is much lower now. Knowing COVID-19 is spread through respiratory droplets and aerosolised particles, an intubated patient will hopefully keep the virus contained within the closed circuit of the anaesthesia machine. Ideally, intubation and extubation is performed in a negative pressure room if possible. While we feel a degree of control over protecting ourselves in this regard, it is sobering to realise that the challenges associated with other daily activities such as touching computers, pushing the button in an elevator, twisting the doorknob, eating lunch in the cafeteria is the real hidden danger.

After thrombectomy, we are encountering challenges finding ICU space in the neurological ICU for the patient where they are historically cared for. Because of the overwhelming number of COVID patients, our 18-bed neurological ICU has been transformed into a COVID-19 unit.

In the neurological ICU, a large white erase board has been erected. On the board, every ICU room number is listed.

A pattern quickly becomes apparent.

Next to each room number is written “COVID” in big red letters with the ventilator settings highlighted. Walking down the neurological ICU, we see intubated patient after intubated patient, all COVID-19 patients, all in acute respiratory distress syndrome, all with a multitude of intravenous medications.

From the exhausted and frightened look on a nurse’s face to the ICU resident’s shaky voice, you can see the enormous emotional toll the pandemic has already taken.

Reflecting on the past few weeks and looking into the future, we are faced with a jarring reality. As numbers continue to climb in NYC and through the rest of the USA, we will continue working through resource constraints, uncertainty and fear. Despite all that, the pursuit of clinical excellence continues, and our professional spirit marches on.

Philip M Meyers is a professor of radiology and neurological surgery at Columbia University Medical Center/ New York-Presbyterian Hospital, New York, USA, where Arthur Wang serves as his fellow.

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April 2020 | Issue 37

Neuroprotection

Neuroprotective drug elicits beneficial effects in the 40% of patients who did not receive alteplase The final results of the ESCAPE-NA1 trial have been presented and published contemporaneously in The Lancet. The study investigated the safety and efficacy of nerinetide—a neuroprotectant drug—in subjects undergoing endovascular thrombectomy.

At the International Stroke Conference (ISC; 19–21 February, Los Angeles, USA), Michael Hill and Mayank Goyal, University of Calgary, Calgary, Canada, concluded that nerinetide was not superior to placebo. However, effect modification by alteplase was observed.

“W

hen all patients were included; patients who received both alteplase and no alteplase, there was only a small effect size [2.1%],” explained Hill, adding that this demonstrates non-significance between modified Rankin Scale (mRS 0–2) scores at 90-days in nerinetide and placebo patients (61.3% vs. 59.2%, respectively).

Yet, evidence of a treatment effect modification was present, resulting in inhibition of treatment effect in patients receiving alteplase. Hill said that in around 40% of patients who did not receive the thrombolytic, nerinetide was associated with improved functional outcomes, a lower risk of mortality, and reduced infarct volume. “The overall effect size is quite large: 9.5% absolute risk difference [in mRS scores at 90-days]; the number needed to treat [NNT] around 11 patients, with an adjusted risk ratio of 1.18.

“We also, remarkably, see a mortality reduction,” Goyal added, alluding to the 7.5% absolute mortality benefit in the no alteplase stratum that received nerinetide. The latter finding corresponded with a reduction in infarct volumes (39.2 vs. 26.7mL reduction in the nerinetide and placebo group, respectively), which were measured blinded to outcome, he noted.

They speculated that the treatment effect appears to come about because of a “substantial” reduction in the available nerinetide in patients receiving alteplase.

“We have a small group of patients from which we got pharmacokinetic data. We think that there is clear biological evidence that the reason we saw no effect in the alteplase group was that the alteplase was activating proteases, which were chewing up the drug.”

In relation to the safety results of the current study, Hill reported that an equivalent number of serious adverse events occurred in each group: 35.7% in the placebo arm, with 33.1% for nerinetide patients.

The next steps for neuroprotection

It was these interactions that led Hill to conclude: “Neuroprotection in humans is possible”, as he asserted that further studies of nerinetide are needed to explore its effects.

In agreement, René Chapot, Department of Endovascular Therapy, Alfred-Krupp Hospital, Essen, Germany, tells NeuroNews: “The results of ESCAPENA1 open new perspectives and raise numerous questions.

“First, the ESCAPE-NA1 results will need to be replicated in subsequent studies before it becomes standard of care. Specifically, the NA-1 neuroprotective effect will have to be confirmed in patients treated by thrombectomy alone. If so, this will have a major impact on stroke treatment and further reduce the relevance of thrombolysis. It is likely that other neuroprotective drugs, that were considered to be inactive, may be tested again in combination to thrombectomy.”

Chapot proposes that ultimately, a choice will have

Michael Hill (left) and Mayank Goyal (right)

This evolution will trigger the development of distal thrombectomy” to be made for adjuvant treatment to thrombectomy: either alteplase or NA-1. “Considering the presumed low effect of alteplase in combination to thrombectomy, and the efficiency of NA-1 without time restriction for administration, it may be assumed that treatment of stroke will shift from IV thrombolysis to neuroprotection,” he adds.

Chapot speculates that this evolution will trigger the development of distal thrombectomy, as residual smaller peripheral clots after proximal thrombectomy will be expected to resolve without IV thrombolysis.

Ryan McTaggart, Department of Neurology and Neurosurgery, Rhode Island Medical Imaging, Providence, USA, further speaks to NeuroNews about the next steps going forward. “ESCAPE-NEXT is a trial dedicated to EVT patients that do not receive alteplase.

We anticipate this will be the first trial in history to show, unequivocally, that neuroprotection in humans is possible.”

He adds that a form of nerinetide resistant to cleaving by alteplase, known as NA-3, may be in Phase 1 trials within a year, which “could make this neuroprotection

mechanism relevant to all patients undergoing EVT, not just EVT patient’s ineligible for alteplase”.

Lastly, McTaggart says: “Our specialty has struggled to be meaningfully transparent and collaborative. Both Michael Hill and Mayank Goyal are indefatigable and masters at coordinating and engaging different stroke centres to answer important clinical questions about patients with large vessel occlusion stroke. The ESCAPE network is poised, right now, to answer important clinical questions about neuroprotection and expanding indications for EVT.”

Neuroprotection: The rationale

Discussing the study of neuroprotection in humans, Goyal told delegates at the ISC: “Over 1,000 compounds have been tested for neuroprotection and around 10% of those have been tested in humans.

But as of right now, no neuroprotectants have shown clinical benefit.

“Nerinetide, or NA-1, is a promising agent that has shown neuroprotection in cell cultures, rodents, primates, and in a phase 2 study—the ENACT study,” he added. Published in 2012 in The Lancet Neurology, ENACT included patients undergoing endovascular treatment for aneurysms. According to Goyal, it demonstrated the safety of nerinetide and showed a reduction in the degree of diffusion hits and volume in patients treated with nerinetide.

Prior work in primates was carried out using an ischaemic-reperfusion model. “A middle cerebral artery occlusion was produced, and after waiting for a certain period of time, the drug was given. After 30 minutes the clip was removed to maintain reperfusion. This was able to show a significant reduction in infarct volume in the primates who got NA-1, but more importantly, there was a significant clinical improvement as measured by the National Institutes of Health Primate Stroke Scale (NIHPSS), where the primates who received the drug performed better,” explained Goyal.

ESCAPE-NA1 aimed to recapitulate the primate model in community-onset ischaemic stroke, accounting for existing standards of care with alteplase.

It was a phase 3, multicentre, blinded, placebocontrolled, parallel group, single-dose design.

“We had the intention of enrolling 1,120 subjects, randomised 1:1 to nerinetide to placebo, stratified by alteplase use and by declared first choice of device,” said Goyal. All the patients had proximal vessel occlusion and underwent endovascular therapy, while ASPECTS ≥5 were allowed to be enrolled.

Goyal acknowledged that the inclusion criteria were “quite standard”. The five aspects he highlighted included: acute ischaemic stroke suitable for immediate endovascular treatment, age 18 or older, an onset time to randomisation within 12 hours, a baseline NIHSS greater than 5 at the time of randomisation, and prestroke independent functional status in activities of daily living with modified Barthel Index (BI) >90 (95 or 100). “The imaging criteria was similar to what was used in the ESCAPE trial, we just made it slightly more lenient as an ASPECTS 5 was allowed to be included.

“We used multiphase CT angiography to determine collaterals, and patients with moderate to good collaterals were necessary for the patient to be included.

Part of our thinking was that the collaterals were necessary to allow the study drug to reach the ischaemic issue,” noted Goyal.

Alluding to details of the intervention, Hill said it involved a single, 10-minute infusion of nerinetide. The weighted dose was 2.6mg/kg, which was administered “as soon as possible” in the whole process of treating the patient. “We had a target of randomisation to study drug infusion time within 30 minutes, which we achieved with only a median time of 11 minutes,” he confirmed.

According to Hill, ESCAPE-NA1 had 48 sites around the world, primarily in Canada and the USA. The investigators stopped the trial once 1,105 patients were enrolled, which took under just two years.

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April 2020 | Issue 37

ISC late-breaking trials

Fast treatment via mobile stroke unit found to reduced survivor disability Treating stroke patients in specialised ambulances speeds treatment and reduces patients’ disability, according to late-breaking science presented at the International Stroke Conference (ISC; 19–21 February, Los Angeles, USA).

DISCUSSING THE BERLIN prehospital or usual delivery (B_PROUD) trial, Heinrich J Audebert, Center for Stroke Research at Charité Universitätsmedizin, Berlin, Germany, told delegates: “Sixty per cent of patients assigned to the mobile stroke unit received clot-busting treatment with alteplase if a mobile stroke unit was available, compared to 48% of patients who received conventional treatment in the hospital.”

Further important findings he alluded to included that the time to treatment was shortened by an average of 20 minutes (50 vs. 70 minutes) when a mobile stroke unit was dispatched, and the use of a mobile stroke unit reduced the likelihood and severity of disability and death at three months by 26%. These patients had a positive shift in modified Rankin Scale (mRS) scores (p<0.001), with an mRS score 0-2 seen in 63% of the

Heinrich J Audebert

patients treated when a specialised unit was available, and 57% of those treated at other times.

“While we had anticipated better outcomes in the patients treated in the mobile stroke units, we are amazed by the magnitude of the effects,” said Audebert. “It is obvious that clot-busting treatment is most effective if it is applied in the ultra-early phase of stroke—ideally within the first or ‘golden hour’ of symptom onset.”

Since treatment within the first hour of symptom onset happens rarely in conventional care, Audebert urged healthcare providers to consider ways to optimise treatment so it can begin during transportation to the hospital. “Stroke treatment is more effective the earlier it starts,” he said. “Just waiting until the patient arrives at the hospital is not enough anymore.”

The B_PROUD trial investigated if prehospital treatment in a mobile stroke unit could improve patient outcomes compared to usual care, which was emergency transportation in a conventional ambulance and inhospital treatment.

A total of 749 patients (average age: 73; 46% female) were assigned to treatment based on the availability of three mobile stroke units in the metropolitan area of Berlin, Germany, and compared with patients

Trend toward benefit in using blood-clotting agent to treat intracerebral haemorrhage

Treatment with tranexamic acid, a common medication that reduces bleeding, has led to a non-statistically significant reduction in intracerebral haemorrhage (ICH) growth, both in binary and absolute terms, according to data from the STOP-AUST trial presented during the late-breaking session at the International Stroke Conference (ISC; 19–21 February, Los Angeles, USA).

D

iscussing STOP-AUST (Spot sign and tranexamic acid on preventing ICH growth— Australasia trial) at the meeting, Nawaf Yassi, Royal Melbourne Hospital, Melbourne, Australia, told delegates that the overall prevalence of ICH growth (48%) was higher in this <4.5 spot-sign selected trial compared to other trials, such as TICH-2 (27%), while he also noted: “Our work and others have shown that tranexamic acid is safe in primary ICH.” “Unfortunately, compared to ischaemic stroke, treatments for ICH are extremely limited,” Yassi said, speaking on the rationale behind the research. He added that ICH is estimated to affect 2 million people globally every year, with some reports of mortality up to 40% in the first 30 days.

One of the most consistent predictive factors for poor outcome after ICH, according to Yassi, is haematoma expansion. Haemostatic therapies have thus been identified as potential treatments for this condition. “One of

Mobile stroke unit

these agents is recombinant factor VIIIa [rFVIIIa], which has been shown in phase II and phase III trials, to reduce haematoma growth. But unfortunately this has not translated to improved outcomes and has been associated with increased thromboembolic events.”

Alluding to a meta-analysis of the SPOTLIGHT and STOP-IT trials, Yassi said rFVIIIa in spot-sign positive ICH patients did not significantly reduce ICH growth, although growth was small in both groups.

“We have been interested in tranexamic acid for some time. It is an antifibrinolyic agent with several attractive features.

It is a reversible direct inhibitor of plasminogen lysine binding sites, and prevents the activation of plasmin and degradation of fibrin,” Yassi enthused.

He said that its pharmacokinetic profile (as it is excreted unchanged in urine with 90% clearance in 24 hours) is favourable, adding that the medication crosses the blood-brain barrier, has no relevant interactions, and remains inexpensive.

STOP-AUST was a phase II

(n=794, average age: 74; 48% females) who received conventional care.

Commenting on the study, Mitchell SV Elkind from Columbia University, New York, USA, posited in an American Stroke Association (ASA) news release: “We have had therapies for acute stroke for several years now, but the big issue of course, has been getting the treatment to the patients as early as possible.

Thrombolytic therapy in the ambulance at the site is really a very exciting development.”

He added that in terms of prehospital stroke care, “there has not been a lot of head-to-head comparison of standard therapy allowing people to get to the emergency room and get treated there, versus treating them in the mobile stroke unit. What makes the B_ PROUD study so exciting is that they were able to do just that; a randomised trial. [It] was sort of a pseudorandomised design, because they treated one group who were able to get this treatment in the ambulance and the other group could not.”

However, Elkind acknowledged that there was not a lot of bias in determining which patients were enrolled in the two arms of B_PROUD, especially considered that they were patients in Berlin, where, according to Elkind, “they have had a longstanding programme to deliver mobile stroke unit therapy”.

Regardless of the trials success, Elkind pointed to the potential limitations of stroke treatment via a mobile stroke unit. He told the ASA that “mobile stroke units can be extremely expensive”, and explained that not only does the machine have to be purchased, but it has to be manned by staff who are available. “In some settings it may not be used 24/7, but at certain times of day.”

Importantly, he said there is a concern that mobile stroke units will lead to an increase in disparities; who can get treated and where.

investigator-initiated, Findings and randomised, double-blind, future directions placebo-controlled trial of Yassi highlighted that tranexamic acid in spot sign ICH growth (33% relative positive patients within 4.5 growth or 6mL absolute hours of ICH. From March growth) occurred in 44% of 2013 to August 2019, 100 the tranexamic acid group, patients were recruited from compared to 52% of the 13 centres in Australia, Nawaf Yassi placebo, which is an absolute Taiwan and Finland. It was risk reduction of 8%, but was hypothesised that these ICH patients not statistically significant. with CTA “spot sign” will have lower In terms of secondary outcomes, the rates of haematoma growth when treated absolute growth of the haematoma was with intravenous tranexamic acid within 1.9mL in the tranexamic group, compared 4.5 hours of stroke onset compared to to a median of 3.4 for placebo. There was placebo. The primary endpoint was no difference in intraventricular growth, growth of the haematoma between the or modified Rankin Scale scores. base CT scan and a CT scan at 24 hours, Major thromboembolic events occurred and the functional outcome was assessed in one patient in the tranexamic acid at 90 days. group, and in two patients in the placebo group, and there were no significant differences in this outcome, or in death within 90 days (13 vs. eight patients, respectively), Yassi reported.

In a post-hoc analysis, the investigators identified that the strongest trends towards reduction of haematoma growth were in those treated earliest, particularly in those treated in the ≤3hour and the ≤2hour window.

These results led Yassi and his coinvestigators to conclude that further “The baseline demographics were exploration of tranexamic acid therapy in fairly typical of an ICH cohort”, Yassi the ultra-early time window is warranted. said. “The onset to imaging time was Yassi confirmed: “We are doing this at approximately 1.5 hours in both groups, present in the STOP-MSU [Stopping and we managed to deliver treatment at a haemorrhage with tranexamic acid median time of approximately 50 minutes hyperacute onset presentation including after the baseline CT, resulting in an mobile stroke units] trial in mobile stroke onset to treatment time of around units and emergency departments across 2.5 hours.”

Australasia.”

Our work and others have shown that tranexamic acid is safe in primary ICH.”

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April 2020 | Issue 37

Interview

Profile

Jesse Dawson

“It is an amazing time to work in stroke medicine,” Jesse Dawson tells NeuroNews. Looking back at his career, he discusses the field’s biggest disappointment, and, in line with his own interests, believes the future of stroke treatment should embrace the importance of diet and exercise as preventative measures. As co-chair of the joint European Stroke Organisation and World Stroke Organisation Conference (ESO-WSO 2020) Planning Group and Programme Committee, he touches on the themes of the upcoming meeting, with implementing best practices globally and artificial intelligence representing hot topics.

What initially attracted you to medicine and stroke therapy in particular?

I have to admit I had no particular desire to be a doctor, it was just what you were encouraged to do when you got good grades at school. However, as soon as I started my studies, it was clear I made the right choice. I was particularly interested in research at a very early stage.

I lack the concentration span to stand for hours in an operating theatre and I find the idea of sticking my hands in someone’s guts rather sickening. So while I have the utmost respect for my surgical colleagues’ skills and abilities, it definitely is not for me.

Cardiology was my favourite subject, but I was not interested in intervention and when I trained it was the boom time for interventional cardiology. I am also five-foot-eight and not remotely macho, so it was not for me either (I am sure it is a bit different now). I liked neurology so stroke medicine was the logical choice.

A bit of cardiology and a bit of neurology but unlike “proper” neurology, I would not have to give everyone steroids.

It is an amazing time to work in stroke medicine. Real strides forward are being made and outcomes are getting better and better. My earliest memory of a hospital was seeing my grandmother who had a large stroke whilst visiting us when I was age 10 or 11. I still marvel at how she managed to return home and live independently for years and I think that stimulated my interest in recovery.

Who were your mentors and what impact have they had on your career?

I have been very lucky in the support I have had from a number of people. First and foremost my main mentor has been Professor Kennedy Lees. It is fair to say that my whole career and progress is thanks to his support and guidance. It was a great honour to train under him and an even greater honour to now lead the research group he set up. Although he spends proportionally more of his time at sea now, he is still available for advice and at times when I need it! Another friend and colleague is Professor Matthew Walters, who supervised all my early research projects and is still a great source of support.

More recently I was given the opportunity to join the CLEAR and MISTIE trials by Professor Daniel Hanley, and it was a real privilege to see the diligence and thoroughness with which he conducts his trials. I will measure all my future work on how close I can get to those standards. In the UK we are lucky to have an extremely supportive and thoughtful group of senior physicians and both Professor Gary Ford and Professor Phillip Bath have been sources of support.

In the wake of COVID-19, what impact has the decision to stop scheduling elective procedures had on the work of neurosurgeons, in your experience?

We have not yet seen any changes to neurosurgical work. In our unit, stroke care is classed as acute so it is proceeding fairly normally at the moment. We do expect that to change. We have begun a lot of remote consultations and we are much more circumspect

in deciding whether a test or consultation is really necessary.

What positives do you see coming from the COVID-19 pandemic in terms of lessons learnt?

I think these experiments with technology will help streamline our care in the future and we will emerge from this awful episode very deeply wounded, but overall a little stronger.

Throughout your career, what has been the biggest disappointment, i.e. something you thought would be practice-changing but was not?

I was very disappointed that the ESUS trials did not demonstrate superiority of anticoagulation over antiplatelets in people with embolic stroke of undetermined source. I thought it made sense and I really did think it would work. However, this serves as an excellent reminder that high quality trials are always needed to test ideas.

What technology are you currently keeping an eye on?

I think it is going to be fascinating to see how everyday technology such as wearables and phones can be used to predict risk, prevent and detect cardiovascular diseases such as stroke.

I think we will start to see people coming to our clinics in the next few years with their own data on blood pressure, heart rate and rhythm and we will need to act on them.

In terms of preventative treatment for stroke, should the field refine existing treatments or focus their efforts on researching novel approaches?

I am a bit of a fitness fanatic and I am increasingly convinced that we should be focussing on diet and exercise more and more. Sure, we can spend thousands of pounds on new drugs—we all like new stuff and spending money. But if we can find a way to help people move more and eat better, the benefits will be far greater.

You do not need to take my word for it, it is all on Netflix. Of course, this will work less well in secondary prevention in people with disability but for primary prevention and in a great many patients, it would be effective.

Could you tell us about the novel treatments for upper limb weakness after stroke that you are working on?

We are currently exploring whether use of vagus nerve stimulation paired with intensive upper limb rehabilitation is effective for improving arm function after stroke. We hope to conclude a phase 3 study in the next year or so. We are also exploring whether use of the Saebo Glove allows people with the most severe arm weakness to better engage with physiotherapy early after stroke.

We will emerge from this awful episode [COVID-19] very deeply wounded, but overall a little stronger.”

In your opinion, what are the highlights of the joint ESO-WSO 2020 meeting?

The main highlight of the joint meeting has been in bringing together the ideas from both societies. We have greatly increased the number of presentations giving investigators more chances to present their work.

We will have sessions on big data and artificial intelligence as well as sessions on the whole stroke care pathway. One of our key themes will be on

Issue 37 | April 2020

Interview

11

Fact File

Clinical and academic appointments: 2017–Present: Professor of Stroke Medicine, Institute of Cardiovascular and Medical Sciences at the University of Glasgow, UK

2014–2017: Clinical Reader in Medicine, Institute of Cardiovascular and Medical Sciences at the University of Glasgow, UK 2011–2015: Consultant in Stroke Medicine and in Hypertension Clinic, Western Infirmary Hospital, Glasgow, UK 2011–2014: C linical Senior Lecturer in Medicine, Institute of Cardiovascular and Medical Sciences at the University of Glasgow, UK 2007–2011: Clinical Lecturer in Medicine and Clinical Pharmacology in the Acute Stroke Unit/Institute of Cardiovascular and Medical Sciences at the University of Glasgow, UK. Specialist Registrar in Clinical Pharmacology and General Internal Medicine.

Society positions:

implementing best practices throughout the world. This year we will have more parallel sessions and have had over 3,400 abstracts submitted and over 500 of these will have a form of oral presentation. We have also had presentation of a number of large clinical trials confirmed.

From your research and experience, what motivates you?

I am motivated by trying to find solutions to problems.

And also the vanity of seeing one of my ideas make it into clinical practice.

What advice do you hope your PhD and MD students will follow?

Take the initiative. If there is a problem, confront it; find a solution and fix it. Do not just bring a problem to a senior or a colleague. Bring the problem and a suggestion for how to fix it.

The suggestion might not be the best solution but that does not matter.

What has been your most memorable case?

I think it was the first time I saw a patient in the stroke unit who was younger than me.

What are your interests outside of medicine?

My family and also, when I am not cycling, all I think about is cycling, and when I am cycling, all I think about is not cycling.

Do you have a fantasy experiment or study?

I would like to see us properly test lifestyle measures in people at risk of stroke; prescribing diets and exercise programmes rather than drugs and surgery.

2018–Present: Chair, European Stroke Organisation Conference and co-chair joint ESO-WSO congress.

2018–Present: Treasurer, Scottish Society of Physicians 2017–Present: Executive committee, Association of Physicians 2015–Present: Chair, MVLS Research Ethics Committee 2014–2019: Editorial Board for Stroke 2014–2018: Committee member, British Association of Stroke Physicians

Current research:

Altered extracellular vesicle microRNA expression in ischaemic stroke and small vessel disease Robotic therapy for upper limb recovery RATULS Allopurinol for the prevention of stroke XILO-FIST Vagus nerve stimulation paired with upper limb rehabilitation after chronic stroke: A blinded randomised pilot study

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April 2020 | Issue 37

COVID-19

SNIS releases recommendations for emergent neurointerventional patients during COVID-19 The Society of NeuroInterventional Surgery (SNIS) has published a set of recommendations for the care of emergent neurointerventional patients during the COVID-19 pandemic.

“ACUTE ISCHAEMIC STROKE patients are a high-risk patient cohort,” the authors write, adding that patients with a history of ischaemic stroke and/ or its risk factors are “particularly at risk” for the severe form of the coronavirus. The recommendations also acknowledge evidence that the disease can cause neurological signs, which have been reported in the brains of humans and in animal models.

Pointing to a study documenting neurological manifestations of hospitalised patients with COVID-19 in Wuhan, China, the society writes: “36.4% of SARS-CoV-2 [severe-acute respiratory syndromecoronavirus 2] respiratory distress patients demonstrated neurological symptoms, with 4.5% of severe patients suffering ischaemic stroke.”

Given this evidence, the SNIS recommendations state that in this setting, neurointerventionalists should expect to be involved in the care of COVID-19-positive patients, as well as those whose status is unknown.

The document specifically advises on the criteria for mechanical thrombectomy: “The presence of COVID-19 as a public health issue should not alter the inclusion and exclusion criteria for mechanical thrombectomy […] denial of this treatment likely creates a greater drain on healthcare resources.”

However, the authors urge that maximum safety precautions should be taken when a patient with COVID-19 positive documentation requires treatment.

The successful care of future COVID-19 patients will depend on the effective safety and prevention strategies for healthcare workers.”

If a patient’s COVID status is unknown, SNIS recommends that patients be treated as high risk for COVID-positive, provided institutional resources are available.

The document also details guidance on postthrombectomy principals during the pandemic. The society recommends transferring uncomplicated postthrombectomy patient’s out of the intensive care unit (ICU) “as soon as possible”, to maximise availability of ICU beds. Further, it advocates for COVID-19 testing of all acute ischaemic stroke patients on admission, if available, to allow preservation of personal protective equipment (PPE), and to “separate true COVID-19 positive patients to prevent nosocomial transmission.”

Due to how the cleaning of angiography equipment and suites will impact on the readiness of additional cases, SNIS advises that elective and non-urgent cerebrovascular cases be postponed until the pandemic’s peak has been reduced. Lastly, the society encourages the shift-based allocation of staff and physicians, to separate individuals with overlapping skillsets.

Given the number of identified COVID-19 patients is expected to increase, the authors underline the importance of safe delivery of care for both patients and providers. “If we fail to protect physicians, nursing staff, and ancillary providers, we will fail to meet the needs of future patients.

“The successful care of future COVID-19 patients will depend on the effective safety and prevention strategies for healthcare workers.”

As the COVID-19 pandemic continues to unfold, SNIS will consider revisiting these recommendations to match up-to-date information. Any such revisions will be provided as updates on the SNIS web page, the society advised.

Issue 37 | April 2020

ISC late-breaking trials

Non-inferiority for direct mechanical thrombectomy “could not be proven” Skipping IV thrombolysis and using mechanical clot removal alone for stroke was not shown to be non-inferior compared to the combination of both treatments, but was associated with a lower risk of intracerebral haemorrhage, according to late-breaking data presented at the International Stroke Conference 2020 (ISC; 19–21 February, Los Angeles, USA).

K

entaro Suzuki of Nippon Medical School Hospital (Tokyo, Japan), presented the results of the SKIP (Randomised study of endovascular therapy with versus without intravenous tissue plasminogen activator [IV tPA] in acute stroke with ICA and M1 occlusion) study at the conference.

At 90 days, favourable outcomes, based on disability level, were similar: 59% for those who received clot removal alone and 57% for those who received the combination approach. There was no difference in death rates between the two groups. Importantly however, he acknowledged that the rates of intracerebral haemorrhage within 36 hours were significantly lower for the mechanical clot removal group than for the combination treatment group (34% vs. 50%, respectively; p=0.02).

Alluding to the purpose and rationale of the current research, Suzuki said: “As you know, the recanalisation rate of IV thrombolysis in large vessel occlusion [LVO]

patients is low. As for the haemorrhagic risk, severe haemorrhagic risk of IV thrombolysis becomes three times as much [5.9% IVT vs. 1.7% for placebo].”

Addressing the ISC audience, he asked: “Do you think IV tPA in LVO patients is still beneficial?”

He explained that the SKIP study was conducted to answer this very question. Further benefits of eradicating tPA, Suzuki said, include a lower haemorrhagic risk to the patients, no prohibition of antithrombotic agents, and lower costs. He added: “We may be missing reperfusion opportunities and delaying the initial therapy.”

We may be missing reperfusion opportunities and delaying the initial therapy.”

Brain stent safe and effective for reducing recurrent stroke risk, study suggests A brain stent appears safe and effective for reducing the risk of recurrent stroke in patients with intracranial atherosclerotic disease (ICAD), according to late-breaking data presented at the International Stroke Conference (ISC; 19–21 February, Los Angeles, USA).

DISCUSSING THE ONE-YEAR because it only included on-label patients, results of the WOVEN (Wingspan oneand prior studies included both off-label year vascular events and neurological and on-label patients. “It is the largest outcomes) trial, Michael J Alexander, intracranial stent trial for atherosclerotic Cedars-Sinai Medical Center, Los disease performed according to the Angeles, USA, told delegates: US FDA [Food and Drug “The stroke and death Administration] indication rate (8.5%; n=129) was for the Wingspan stent,” substantially lower than Alexander confirmed. the one-year rate of 20% According to Alexander, in the stenting arm of the WOVEN was an investigatorSAMMPRIS trial and slightly initiated study, conducted at 12 better than the 12.2% stroke US centres from the original and death rate in the medical 24 WEAVE sites participating. arm of SAMMPRIS.” Michael Alexander The investigators presented He added that the re-stenosis follow up on 129 of the 152 rate was 16.8% in the patients stented patients who were treated with the on-label with the Wingspan stent, and Wingspan stent from the WEAVE trial. that 7/18 of these patients (38.9%) were Enrolling sites performed chart and symptomatic. “This was the primary image reviews of patients who were cause of delayed stroke within the first stented with the Wingspan stent under its year post-stenting,” Alexander noted. strict on-label usage. The investigators He explained that the trial is unique collected data on subsequent strokes

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Notably, he alluded to the fact that most patients with IVT in the HERMES collaboration included IVT ineligible patients, and subsequently highlighted the need for an RCT in eligible RCT patients.

Thus, the Japanese, multicentre, prospective, randomised trial was carried out at 23 sites and included 200 stroke patients (average age 74; 62% men) that were assigned to either mechanical clot removal alone or the combination of IV thrombolysis and mechanical clot removal.

While Suzuki pointed out that they could not prove non-inferiority of direct mechanical thrombectomy, as the frequency of favourable outcome did not differ between the two arms, he reiterated that any intracerebral haemorrhage was significantly less frequent in the direct mechanical thrombectomy group compared with those undergoing combination therapy.

However, in an American Heart Association/ American Stroke Association (AHA/ASA) news release, Mitchell SV Elkind, president elect of the AHA from Columbia University, New York, USA, stated: “Current recommendations from the AHA/ASA suggest using intravenous therapy within the 4.5 hour-time window and then treating with mechanical clot removal, if appropriate.

“The best strategy is usually to treat with [alteplase] … and then if the patient is eligible, the patient goes for endovascular therapy as well,” Elkind said. “But [we] do not skip that initial step because sometimes the endovascular therapy gets delayed or does not occur for some reason or another.”

Regardless, Suzuki noted that five ongoing trials, including the current study, will continue to investigate the optimal approach for stroke patients.

and deaths with respect to time from stenting and medications at the time of the index event, while follow-up imaging was assessed for incidence and severity of in-stent stenosis and the follow-up management of these patients.

WOVEN found that 16.8% of the 129 patients had restenosis of 70% or greater. Alexander reported that the mean time to restenosis was five months, and patients were managed medically, with angioplasty, stenting or some combination.

“ICAD represents a significant subset of stroke,” highlighted Alexander, as he told delegates that 8–10% of stroke in

the USA are due to ICAD. “The longterm results of the WOVEN study are important to determine if safer stenting practices and lower complication rates from the treatment itself resulted in improved patient outcomes at one-year,” he said. “Intracranial stenting could provide an alternative when medical therapy and other treatments have been unsuccessful,” he added.

He concluded by stating that the data strongly support further randomised clinical trials for ICAD between stenting and medical therapy for high-risk patients (with haemodynamic compromise) treated in an on-label fashion.

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April 2020 | Issue 37

ISC late-breaking trials

Wearable brain stimulation could safely improve motor function after stroke A new, non-invasive wearable magnetic brain stimulation device to improve recovery for stroke survivors has been deemed safe and effective. David Chiu, director of the Eddy Scurlock Stroke Center at Houston Methodist Hospital, Houston, USA, presented the preliminary late-breaking data at the International Stroke Conference (ISC; 19–21 February, Los Angeles, USA), and told delegates: “This technology would be the first proven treatment for recovery of motor function after chronic ischaemic stroke.”

IN AN INITIAL, randomised, doubleblind, sham-controlled clinical trial of 30 chronic ischaemic stroke survivors, a new wearable, multifocal, transcranial, rotating, permanent magnet stimulator, or TRPMS, has produced statistically

significant improvements on bloodoxygen-level-dependent (BOLD) fMRI as well as improvement on physical functioning measures.

According to Chiu, TRPMS affords simultaneous stimulation at six sites; four

ipsilesional and two contralesional, by using a non-invasive, portable, batteryoperated device that delivers focal stimulation, which is unaffected by head movement.

“The robustness of the increase

in physiological brain activity was surprising. With only 30 subjects, a statistically significant change was seen in brain activity,” said Chiu.

“If confirmed in a larger multicentre trial, the results would have enormous implications.”

He further explained that magnetic stimulation of the brain was previously investigated to promote recovery of motor function after stroke. Thus, as the stimulation held the possibility to change neural activity and induce reorganisation of circuits in the brain, researchers introduced a new wearable stimulator.

Chiu reported that stroke survivors who had weakness on one side of their body at least three months post-stroke were enrolled in a preliminary study to evaluate safety and efficacy of the device. Half of the patients were treated with brain stimulation administered in 20 40-minute sessions over four weeks. The rest underwent sham treatment, acting as controls. The team analysed physiologic brain activity before, immediately after and one month after treatment.

Specifically, patients in the treatment arm had a significantly greater increase in the number of active voxels on fMRI immediately after treatment compared to sham (p=0.038), one month after treatment (p=0.024) and a higher proportion of patients with ˃15% increase in active voxels (p=0.025).

MRI outcomes were found to correlate with functional outcomes, while active treatment patients displayed significant increase in gait velocity and numerical improvement in Fugl-Meyer upper extremity, action research arm test, grip strength and National Institutes of Health (NIH) stroke scale scores.

Though reporting that there was no improvement in pinch strength scores, the investigators found that treatment was well tolerated, and there were no device-related complications.

Additionally, Chiu emphasised that the treatment effect on the primary endpoint was not significantly influenced by

If confirmed in a large multicentre trial, the results would have enormous implications.” age, time after stroke, or cortical versus subcortical lesion location.

“Although the study does not prove that the transcranial stimulator improved motor function, numerical improvements were demonstrated in five of six clinical scales of motor function, as measured by a functional MRI test,” Chiu explained.

The team found that the treatment effects persisted over a three-month follow-up.

As Chiu strongly speculated that study results are a signal of possible improved clinical motor function after magnetic brain stimulation for patients after stroke, he highlighted the need for a large, multicentre trial to confirm them.

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Issue 37 | April 2020

New study finds high responder rates for ECAP-controlled, closedloop spinal cord stimulation Continued from page 1

of the design that were closely group. “Previous literature suggests monitored included both the number that if pain endures for over 10 years, and duration of clinic visits in both response to a fixed-loop system is groups, as well as lead location pretty low,” he remarked. Around and procedure time, while blinding 60% of patients in both groups were was maintained. “There were no on opioids. And, in terms of previous significant differences between back surgery, groups,” he posited, “which is very Deer said that important and can eliminate some of roughly 60% the confounds that can occur if one of patients group had a different programming had had or time spent with the patient in that back surgery, regard.” leaving In total, 134 patients were 40% of the randomised 1:1 to the closed-loop versus open-loop arms, with the latter being the control.

Fifty-nine patients in each arm remained at 12 months. Deer noted no significant differences in baseline characteristics between the two groups, yet pointed to the fact that the duration of pain in patients in both groups was long: 14 years in the closed-loop Timothy Deer group; 11 in the open-loop

BurstDR stimulation reduces negative psychological effects associated with chronic pain New quality of life and functional improvement data from both the BOLD and TRIUMPH studies echo the benefits of the Proclaim XR neurostimulation system (Abbott) for the treatment of chronic pain. Presenting the results at the North American Neuromodulation Society’s (NANS; 23–26 January, Las Vegas, USA) Annual Meeting, Timothy Deer, president and CEO of The Spine and Nerve Center of the Virginias, Charleston, USA, remarked: “BOLD found that BurstDR stimulation reduced the negative psychological effects associated with chronic pain by 62% at the six-month follow-up.”

T

he BOLD (BurstDR microdosing stimulation in de novo patients) trial is a prospective, multicentre investigation. It utilises patients’ pain catastrophising scale (PCS) scores in order to determine how pain affects the mental state of a person experiencing chronic pain.

Deer highlighted that 78% of patients had a baseline Oswestry Disability Index (ODI) score of “severe”, “crippling”, or “bed bound”. However, following treatment with the Proclaim XR

implant for six months, 71% of patients had “minimal or moderate ODI score”, with 29% having a “severe” or “crippling” ODI score.

“Chronic pain is a broad term that does not accurately capture the variety of issues and symptoms

population never having undergone surgery, “which could be important later on”, he noted.

In terms of opioid reduction over time, the closed-loop group had a baseline of 80 MMEs (morphine milligram equivalents), which decreased to 45 at 12 months.

According to Deer, a reduction in opioids was also observed in the open-loop group. “I think that is a very important result,” he said.

The investigators also looked at clinically important improvements in disability, quality of life, mental functioning and sleep.

A statistical difference in improvement was found for emotional functioning, assessed with Profile of Mood Stats (POMS), for the closed-loop group. This population also improved on the other aforementioned patientreported measures to a greater degree than patients receiving open-loop stimulation.

Speaking on what the future holds, Deer tells NeuroNews, “We keep seeing major innovations in the space at a very encouraging pace,” as he highlights that the need for collaboration and commitment to excellence in outcomes, which has “never been more critical”, he says. people experience as a result of it,” Deer proposed, adding that, “whether the individual is worrying about being bedridden or experiencing severe pain for the rest of their lives, we can share with them the science behind the [Proclaim XR] system to address physical and psychological aspects of pain”.

Further reinforcing these results, additional data were presented at NANS from the TRIUMPH study, a prospective, multicentre, singlearm, international study of 269 patients. The trial found significant improvements in physical, mental, and emotional function, which was sustained for up to one-year, postpermanent implant. Patients also reported a reduction in the impact of pain on daily life, which resulted in patients becoming more active when measured at one year.

Commenting on findings, Steven M Falowski, Neurosurgical Associates of Lancaster, USA, said: “We now have clinical evidence that Proclaim XR, using the BOLD dosing protocol, shows reductions in two standard measures of characterising pain. These improvements are critical factors in creating personalised care plans that help individuals feel better overall, as they help treat multiple aspects of pain.”

The improvements in these areas are critical factors in creating personalised care plans that help individuals feel better overall.”

First long-term vagus nerve stimulation implant in mice Data showing the effective use of a long-term vagus nerve implant in mice were presented at the North American Neuromodulation Society’s Annual Meeting (NANS; 23–26 January, Las Vegas, USA).

Ibrahim Mughrabi from The Feinstein Institutes for Medical Research at Northwell Health (New York, USA) reported the results, concluding: “The implants were functional for 60–90 days, [and] in regular test sessions, vagus nerve stimulation [VNS] delivered through the implant caused physiological effects indicative of vagus nerve activation.”

FURTHERMORE, MUGHRABI said that some mice were subjected to a final test of whether VNS delivered through the long-term implants can suppress acute inflammation.

The investigators found that when VNS was delivered through 60–90 days, it was successful at supressing inflammation in two out of four mice. “This provides a way forward for testing long-term VNS in chronic inflammatory conditions,” remarked Mughrabi.

On the rationale behind the research, he put forward that previous preclinical VNS studies have been limited to short-term stimulation (from minutes to hours), due to the surgical and technological challenges of implanting a stimulator small enough to fit a mouse nerve.

This led Stavros Zanos, assistant professor at the Institute of Bioelectronic Medicine to develop new techniques to deliver long-term electrical stimulation in mice— according to a press release.

In the study, a commercial bipolar cuff electrode was implanted around the left cervical vagus nerve of mice. The electrode functionality was evaluated over up to 90 days after implantation, and through electrocardiogram and breathing sensors researchers were able to measure real-time physiological responses to neurostimulation and adjust stimulation intensity accordingly.

By extending the research window of stimulation, from a single action to up to 90 days, a long-term vagus nerve implant provides “new opportunities” to thoroughly investigate the therapeutic potential of chronic VNS in a range of relevant diseases modelled in mice, noted Mughrabi.

“The ability to chronically stimulate the vagus nerve through a permanent implant has not been reported before in mice,” he added. “We are eager to continue to advance this new approach and look forward to the positive impact this implant will have on future bioelectronic research around the world.”

The research was conducted in collaboration with Robert Froemke, associate professor at New York University, New York, USA, and Cristin Welle, assistant professor at the University of Colorado, Boulder, USA.

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April 2020 | Issue 37

10kHz safe and effective for treating painful diabetic neuropathy, multicentre study finds A multicentre study across 18 centres finds 10kHz spinal cord stimulation (SCS) safe and effective for the treatment of painful diabetic neuropathy. Sensory improvements were observed in many patients who underwent stimulation with these parameters, as well improvements in quality of life measures. Erika Petersen, University of Arkansas for Medical Sciences, Little Rock, USA, presented these data at the North American Neuromodulation Society’s (NANS) Annual Meeting (23–26 January, Las Vegas, USA) and told delegates that the study is due to run through 24 months, with later evaluations of health economics and pain medication usage.

“OUR CLINICAL TRIAL is the largest randomised

controlled trial to date, involving 216 patients randomised 1:1 to conventional medical management [n=103] alone or conventional medical management plus high frequency 10kHz stimulation [n=113],” explained Petersen.

She added that all patients were evaluated by independent medical monitors before they were enrolled in the study, and were required to have at least ≥5 of 10cm of the visual analogue scale (VAS) as well as a BMI <45 to be included. When looking at the demographics of the two arms, Petersen said, “they are identical”; no significant differences were observed in terms of duration of diabetes, duration of time of painful diabetic neuropathy, gender, or other factors.

Lead location was T8–T11. Petersen posited that this is the “typical location for addressing lower limb and lower extremity pain”. She further emphasised that one of the endpoints of the study was safety. “For the stimulation group, 19 adverse events [occurred] in 15 patients, two of which were rated as a serious adverse event,” she acknowledged, adding that one arose due to infection, while the other was acquired at plantation.

“I want to highlight our infection rate,” Petersen said.

“People worry about diabetics having a higher risk of infection. But, what we can see for this population is a 1.8% rate, which is comparable to the majority of studies in the literature for this population.”

For the primary endpoint analysis, Petersen and her co-investigators looked at a composite of safety and effectiveness, in terms of pain reduction at three months. Those with ≥50% pain relief without a worsening neurological deficit from baseline were characterised as responders. Of the patients receiving SCS stimulation, 86% were considered responders at three months, compared to only 5% of patients in the conventional medicine management arm, reported Petersen, adding that the team observed a trial stimulation success rate of 94%.

She alluded to the reduction in VAS scores, which

10kHz spinal cord stimulation deemed safe and effective for treatment of chronic pelvic pain Data from a prospective, multicentre trial examining high-frequency spinal cord stimulation (SCS) at 10kHz for the treatment of chronic pelvic pain supports the safety and effectiveness of the therapy.

“A clinically meaningful improvement for pelvic pain was indicated through a responder rate of 77% and a remitter rate of 69% at three to 12-months follow-up,” reported Jordan Tate, Alliance Spine and Pain Centers (Atlanta, USA), whilst presenting the results at the North American Neuromodulation Society’s Annual Meeting (NANS; 23–26 January, Las Vegas, USA).

T

ate highlighted that the subjects felt no paraesthesia, “which is extremely important when treating chronic pelvic pain”, she said. The baseline visual analogue scale (VAS) score of 7.9 was reduced down to 2.3 at three months, which was sustained through to 12 months. “Overall, we are looking at a 70% pain relief,” Tate reported.

In terms of the Pain Disability Index (PDI), she noted that the patients exhibited significant functional improvements. Patients at baseline were reporting 45.2, which decreased, on average, to 16.2. According to Tate, this reduction was three times the minimally clinical important difference.

Discussing the rationale behind the research, Tate commented that current treatment options for the treatment of chronic pelvic pain are “limited or ineffective”. In addition to medications, such as antidepressants and opioids, Tate said that physicians will try interventional procedures, including pudendal nerve blocks and radiofrequency thermocoagulation, while many patients will have multiple surgeries. “They [physicians] might try some physical therapy. Specifically, pelvic floor training, which is actually a great treatment option. But, it is very expensive and has to be undertaken repetitively and for a long time.”

Furthermore, Tate mentioned that

decreased from 7.6 (lower limb VAS) at baseline to 2.4 at one month, and 1.7 at three months. “I hope to be able to show you this maintained at 24 months when we present those data in the future,” Petersen noted. Moreover, through looking at individual pain relief between the stimulator and the conventional management group, it was revealed that 77% of stimulation patients achieved pain relief, compared to only 5% of controls.

Part of the assessment was to have each investigator assess sensory changes within the patients, Petersen explained. The team had asked patients to draw out subjective diagrams of where they perceived numbness, both at baseline and three months. “We were able to perceive what seemed to be a change in sensation in the stimulator population in 72% of those patients,” Petersen confirmed.

“But pain relief is nothing without improving quality of life,” said Petersen, alluding to the fact that investigators examined three measures of sleep, each of which saw significant improvements. They also implemented a six-minute walking test as a means of achieving an objective measure of functional improvement. Compared to the conventional medical management group, the stimulator patients walked further in six minutes at the three-month time point.

“When you look at this by individuals,” Petersen discussed, “you can see that it is not across all patients, but the average and median change allows for a longer distance walked [of 39 metres; a 17% increase] in the same amount of time.”

In terms of impression of change, both patients themselves as well as the clinicians evaluating them were asked to assess their improvement. In total, 67% of the stimulator population said “they are better, a great deal better” than baseline, compared to a mere 2% of controls. These findings were reflected throughout a multitude of other functional indicator questionnaires, noted Petersen.

the evidence in the space of SCS has previously been lacking. “There have been several case reports and case series, [but] there has not been, to date, a consensus on optimal lead placement or frequency for this patient population.”

Nevertheless, she said that given the SENZA randomised controlled trial results, in addition to anecdotal experience in clinical practice, the study investigators felt that it would be a reasonable assumption that highfrequency 10kHz therapy would present as a good treatment option for chronic pelvic pain. The study included allcomers with chronic pelvic pain, with the most common diagnoses being complex regional pain syndrome. The patients had to have had pain for over three months, and a visual analogue scale (VAS) score above five. Patients who had previous neuromodulation experience, significant spinal stenosis, or mechanical spine instability were excluded.

In relation to the lead span, Tate remarked: “At the beginning of the study, we did not know where the sweet spot would be for the stimulation of chronic pelvic pain. We had a span at the top of T8, and the second lead reached to T12.

This was important to give us control.”

Patients had a mean baseline VAS score of 8, while 91% were female and 49 years of age, on average. In total, 13 patients were followed through to 12 months, with post-surgical complications predominating the field in terms of diagnoses.

In addition to VAS scores, the study investigators also looked at various components of pain interference, including continuous pain, intermittent pain, neuropathic pain and affective descriptors. “These were all decreased across the board in all patients carried out to 12 months”, Tate reported.

There were no sustained neurological deficits, added Tate, but 10 adverse events occurred, such as non-clinically significant lead migration and infection.

However, all adverse events resolved without sequelae.

“Overall, we were very impressed with the results. These are difficult patients, and we thought it would be a challenge.

I thought I would be very happy to see even a 40% reduction in even some of the patients. But, once again with 10kHz therapy, we saw similar results to other pathologies, and these patients really had profound outcomes.”

Lastly, Tate explained: “Ultimately, lead placement was predictable. The sweet spot is around the mid T10 vertebral body. We had very few patients who we needed to stimulate up into T8, [but] we did have some that needed stimulation at T12. So it is important to have the leads a little lower than your standard back protocol.

“The data indicate promising results using 10kHz SCS in chronic pelvic pain, which is a difficult-to-treat aetiology of chronic pain. We are excited to see what the next steps for chronic pelvic pain might be.”

17

Issue 37 | April 2020

Sheep model helps guide investigation of analgesia tolerance and reversal during opioid crisis Having been honoured with the Best Basic Science Abstract Award at the North American Neuromodulation Society’s (NANS) 2020 annual meeting (23–26 January, Las Vegas, USA), Denise Wilkes now speaks to NeuroNews about how the perception of opioid treatment has changed over the past decade, and the benefits or using a large animal model to investigate analgesia tolerance and reversal.

Could you tell us about the rationale behind your study?

Overall, the rationale was to compare the rate of tolerance formation between an ultra-low dose or microdose intrathecal (IT) infusion, with 1mg/day—an intermediate dose—and 3mg morphine representing a standard higher dose.

How has the perception regarding the use of opioids (as a treatment) changed within the field in recent years?

We have seen huge changes in our perception of opioids. Around 10–15 years ago we thought that tolerance,

so heavily studied in rat models, was not much of a problem clinically. If patients developed tolerance, the dose would simply be increased. Now, during the opioid crisis, we are trying to limit prescribed amounts because of overdose risks, pharmacy availability, and prescriber pill counts totals. There are many incentives to use the minimal dose.

How should IT opioid therapy be initiated?

Chronic pain patients on long-term opioid therapy are often transitioned to an intrathecal (IT) opioid route in order to improve analgesia. The method of transitioning patients from systemic to

intrathecal delivery has considerable variation among physicians. A survey showed 40% wean, 33% did not wean, while starting doses varied from 12.5 μg/ day to 1–2 mg/day.1,2,3 Microdose method is comprised of three phases: weaning of systemic opioids, an opioid-free period (4–6 weeks), and an IT microdose morphine dose (less than 1 mg/day).4,5

What are the benefits of using a sheep model?

The sheep model has a dose response curve that is much closer to opioid effects observed in humans, enabling measurement of effects of dose, duration of dose, and discontinuation. The size of the sheep allows us to be able to use commercially available devises such as IT infusion pumps.

What did you find regarding the morphine doseresponse?

Morphine tolerance is best measured by a change in slope of the morphine dose-response curve from pre- to postinfusions. We showed that there was a greater reduction in the slope with the 3mg/day than the 1mg/day. There was negligible development of tolerance with

We have seen huge changes in our perception of opioids.”

the microdose, or 0.2mg/day.

Did you draw any further conclusions from the results?

It is important to keep opioid doses low.

A higher dose will create more tolerance and then the opioids will be even less effective. We need to supplement medical management with interventions that can reduce pain even if it is only relatively short lived.

What do future studies need to take into account?

Future studies need to examine bolus doing and other infusion methods, while the systemic effects of microdose IT therapy also warrant further investigation.

We initially thought that IT mostly avoided these effects but high dose IT does produce systemic side-effects.

Unfortunately, those doses were high and we do not know what is the threshold.

References 1. Deer TR, Prager J, Levy R, Burton A, Buchser E, et al. Polyanalgesic Consensus Conference--2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel.

Neuromodulation 2012:15: 420-435; discussion 435.

2. Deer TR, Prager J, Levy R, Rathmell J, Buchser E, et al. Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation 2012:15: 436-464; discussion 464-436.

3. Wilkes DM, Orillosa SJ, Hustak EC, Williams CG, Doulatram GR, et al. Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

Pain Medicine 2017.

4. Hamza M, Doleys D, Wells M, Weisbein J, Hoff J, et al. Prospective study of 3-year follow-up of low-dose intrathecal opioids in the management of chronic nonmalignant pain. Pain Med 2012:13: 1304-1313.

5. Grider JS, Harned ME, Etscheidt MA. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician 2011:14: 343-35

18

April 2020 | Issue 37

Market watch

Industry News Enrolment completed early for Rapid Medical’s TIGER study for thrombectomy device

Rapid Medical has announced that it has completed enrolment in the TIGER (Treatment with Intent to generate reperfusion) study ahead of the planned scheduled. This is a USA-based, multicentre study of the performance of TIGERTRIEVER, the company’s thrombectomy device for the acute treatment of ischaemic stroke.

The TIGERTRIEVER is a fullyvisible, controllable stentriever that is adjusted to fit the dimensions of a blocked blood vessel causing acute ischaemic stroke. Jeffrey Saver, stroke neurology director at Ronald-ReaganUCLA Medical Center in Los Angeles, USA, and neurointerventionalist Rishi Gupta director, Neurocritical Care at WellStar Health System, Marietta, USA, are the principal investigators of the study.

TIGER is an investigational device exemption study evaluating the safety and effectiveness of Rapid Medical’s TIGERTRIEVER for treatment of ischaemic brain stroke. The study results will be used as part of the 510K submission of the device for US Food and Drug Administration (FDA) clearance.

The study was completed ahead of schedule and took place at 16 of the leading stroke centres throughout the US and one centre in Israel. The TIGERTRIEVER device has CE mark clearance and is commercially available in Europe; thousands of ischaemic stroke thrombectomy procedures are performed with the device every year.

COVID-19: European Commission agrees to postpone new MDR because of pandemic

The European Commission (EC) has adopted a proposal to postpone by one year the date of application of the new Medical Devices Regulation (MDR), which was due to come into force on 26 May this year. The postponement, a press release reports, is to allow Member States, health institutions and economic operators to prioritise “the fight against the coronavirus pandemic”. As previously reported, the announcement follows the EC college (video) meeting on 25 March in which EC spokesperson Stefan de Keersmaecker stated that the commission were looking to delay the “entry into force” of the new MDR because of the global coronavirus pandemic.

According to the press release, the decision to delay “takes into account the unprecedented challenges of the coronavirus pandemic and the need for an increased availability of vitally

important medical devices across the EU while continuing to ensure patient health and safety until the new legislation becomes applicable”. The proposal, therefore, delays the application of the MDR by one year (until 26 May 2021).

Additionally, the proposal also ensures that Member States and the Commission can address potential shortages of vitally important medical devices in the EU in a more effective manner through EU wide derogations.

However, the press release notes that the proposal would need the full support of the European Parliament and the Council through an accelerated codecision procedure.

CMSS “strongly urges action” to ensure all frontline healthcare professionals are protected

In a new statement published on 2 April 2020, all 45 societies represented by the US Council of Medical Specialty Societies (CMSS)—over 800,000 physicians—emphatically declare their belief that all frontline healthcare professionals must have access to personal protective equipment (PPE) and be able to speak publicly about the lack of PPE without retribution while pushing for adequate supply and distribution.

This statement comes days after reports emerged in mainstream media outlets of threats made to hospital staff who have spoken publicly about the difficulties they are confronting on the frontlines of the COVID-19 pandemic.

Among other cases, the story emerged of a Washington state emergency room physician who is said to have been fired after giving an interview to a newspaper on claims he had made about inadequate equipment and testing on his Facebook page, according to a report carried by Bloomberg News.

AHA commits US$2.5 million for fast-tracked COVID-19 heart and brain research The American Heart Association (AHA) has committed US$2.5 million to research efforts to better understand the novel coronavirus, COVID-19, and its interaction with the body’s

cardiovascular and cerebrovascular systems.

Specifically, the Association will be offering fast-tracked research grants for short-term projects that can turn around results within nine to 12 months to better understand the diagnosis, prevention, treatment and clinical management of COVID-19 as it relates to heart and brain health. There will also be additional funding made available to the Association’s new Health

clinical trials and product development

Technologies & Innovation Strategically Focused Research Centers to develop rapid technology solutions to aid in dealing with the COVID-19 pandemic.

Cerus Endovascular receives FDA Approval for its first microcatheter

Medtronic issues urgent field safety notice for some Pipeline Flex embolisation devices

Medtronic has issued an urgent field safety notice to warn on specific production lots of its Pipeline Flex embolisation devices due to the potential for device fracture.

The company initiated verbal communication about the issue last month after identifying the potential for device fracture at the distal section during use, due to a weakened bond in a subset of recently manufactured devices.

Use of the affected product could result in unintended separation, where the distal portion of the device delivery system remains in the patient, which could cause significant patient injury, including a prolonged procedure, ischaemic stroke, intracranial haemorrhage, neurological deficit and/ or death.

Medtronic has not received complaints related to the issue within the affected population, but the company is recalling the affected products due to the increased potential for fracture, according to the field safety notice.

If a Pipeline Flex embolisation device was already successfully implanted, there is no increased risk to patients due to the issue, and those patients can continue with their normal course of treatment. The affected lots include devices with a “use-before” date on or after 21 October 2022.

The company urged those affected by the issue to cease the use of any affected products and to remove and quarantine all unused devices in their inventory before returning them to Medtronic.

NeuroVasc secures US$34 million in funding to support

NeuroVasc Technologies has entered into a strategic partnership with the Wego Group that includes US$34 million in funding to support the company’s product portfolio development and global clinical trial programme.

With a focus on novel catheter-based technologies to treat neurovascular disease, NeuroVasc has developed a development strategy to bring differentiated tools to the interventional neuroradiology community to facilitate broader treatment options for patients suffering stroke and other neurovascular diseases, a company press release states.

The partnership marks a step forward for NeuroVasc Technologies in bringing a full neurovascular platform to market.

This treatment focus includes over 25.7 million cases of stroke globally each year. By 2025, the worldwide neurovascular devices market for stroke alone is expected to grow from US$2.5 billion to US$3.4 billion.

Cerus Endovascular receives US FDA approval for its first microcatheter. The 021 microcatheter will be offered with three different distal configurations, and commercial sales are expected to begin during the second quarter of 2020.

According to a press release, the company will be developing additional microcatheters of various dimensions to offer a comprehensive selection of instrumentation for the needs of interventional neuroradiologists.

Moreover, the company announced it has successfully completed its Series B financing that has raised a total of US$19 million from current and new institutional investors since the commencement of the round in July 2018.

Completion of the Series B financing will allow the company to execute on its go-to-market strategy and to complete the planned expansion of its product portfolio, including a smaller delivery platform for its recently CE marked Contour Neurovascular System, for the treatment of intracranial aneurysms.

Viz.ai adds new capabilities to its AI stroke platform

Viz.ai has launched the next generation of its synchronised care platform for stroke. Viz.ai incorporates cutting edge artificial intelligence with HIPAAcompliant communication to allow stroke teams to quickly and efficiently triage patients to time-sensitive care with the aim of reducing time to treatment and increasing access to endovascular intervention.

New capabilities allow the stroke care team to synchronise care from stroke code notification to the post-acute care period. Expanded functionality will empower the stroke team with quick, relevant, clinical and imaging information to support faster diagnosis and treatment decisions.

Issue April 2020 19 37 |Events

April 2020 | Issue 1937

Product Industry News NeuroPace RNS System receives FDA approval for MRI Labeling, allowing thousands more patients to benefit from personalised, data-driven epilepsy treatment

NeuroPace has announced that its RNS System has received US Food and Drug Administration (FDA) approval of MRI labelling for the RNS System, expanding treatment options for approximately one million patients in the USA living with seizures that do not respond to medication.

Individuals with focal onset seizures that also have brain anomalies that require monitoring, such as tuberous sclerosis, brain tumours or multiple sclerosis, as well as those with nonbrain MRI requirements, can now be offered the RNS System as a treatment option. This will also allow people to receive the RNS System before committing to an irreversible surgery such as laser ablation, while keeping

their future treatment options open.

“MRI conditional labelling opens up valuable medical imaging possibilities for our patients treated with the model RNS-320 neurostimulator, who can now receive full-body 1.5T magnetic resonance imaging (MRI) scans under appropriate conditions,” says Michael Favet, president and CEO of NeuroPace.

tablet with a colour touchscreen and an easy-to-use graphical interface, and expands on its user-friendly capabilities by streamlining and simplifying the patient programming process.

The Programmer offers a predictive programming algorithm that translates intra-operative responses and suggests how to programme the patient for optimum therapy, thereby reducing the need to adjust therapy postimplant. In addition, a fully wireless system that reduces time during surgery and simplifies post-implant device programming is available, according to a company press release.

FDA approval of Axonics’ enhanced neurostimulator programmer

Axonics announces FDA approval of an enhanced, second-generation programmer for its r-SNM system under a premarket approval (PMA) application supplement.

The new programmer is used to program the Axonics external trial neurostimulator as well as the implantable neurostimulator in both the procedure and post-operative environments.

The programmer is a custom-made

Medtronic launches Efficio software to help clinicians efficiently manage targeted drug delivery therapy with SynchroMed II

Medtronic announce the launch of Efficio, a cloud-based data management software for use with the SynchroMed II intrathecal drug delivery system, that will allow clinicians to more efficiently manage their targeted drug delivery

pump practices to treat patients with chronic pain, cancer pain and severe spasticity.

Efficio management software allows clinicians to manage patients’ pumps with greater efficiency and ease by consolidating, organising and providing visual summaries of patient data from the clinician programmer in a secure cloud environment accessible at anytime, anywhere. Efficio connects individual patient measures and dosing trends, which can help clinicians unlock powerful therapy management insights, a company press release states. Additional benefits include the ability to proactively schedule patient appointments, facilitate prescription drug order tracking for pump refills, and printing reports on-demand.

The company adds that with Efficio, clinicians can manage patient data without the use of spreadsheets and easily export data into their electronic medical records systems as appropriate.

According to the news release, Efficio software supports HIPAA compliance and is designed to safeguard protected health information. Data is protected using encryption and authentication.

Access restrictions and login time limits are also in place to help protect data.

Calendar of events 30 May–4 June ASNR: American Society of Neuroradiology 58th Annual Meeting Las Vegas, USA

6–8 July World Live Neurovascular Conference Washington DC, USA www.wlnc.org/

www.asnr.org/annualmeeting/

25–27 June 2nd Joint Congress of the INS European Chapters Paris, France

4–7 August SNIS: Society of NeuroInterventional Surgery 17th Annual Meeting San Diego, USA

www.neuromodec.com/

www.snisonline.org

events/

24–26 August LINNC: Live Interventional Neuroradiology & Neurosurgery Course Paris, France www. LINNC-Paris-2020

26–29 August The World Institute of Pain (WIP) 10th World Congress Rome, Italy www.wip-rome2020.org/

9–11 September 12th ESMINT Congress 2020 Nice, France www.esmint.eu/

5–7 October SLiCE: Stroke Live Course Nice, France www.slice-online.com/

7–10 October 11th World Congress for Neurorehabilitation Lyon, France www.wcnr-congress.org/

September

2019 | Issue

Georgios

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convey the nt ing country the treatme in a develop that 35% of 20% of ectomy trialectomy”. Given red to just the first thromb ical thromb 0–2 compa says, “We have the score of results of had of mechan , USA) The final we have efficacy l, Atlanta Scale (mRS) reality.” d Rankin Memorial Hospita [and] by doing so, “overwhelming our same stent, d a modifie l barriers es that share nt with arm achieve G Nogueira (Grady ic Raul al and politica other countri scular treatme controls, financial, logistic e many acute ischaem of endova e and influenc misation and Sheila an therapy with overcom to impact medical Nogueira NT (Rando opportunity from the RESILIE tion versus best first presented by Brazil) at the Europe exclusively oaspira on) trial were Alegre, These data do Sul, Porto Italy). Now, Martins and/or thromb occlusi action of Grande vessel retriever Milan, Rio plan large l do to May, NT team’s stroke due sidade Federance (ESOC; 22–24 on the RESILIE Martins (Univer ation Confere an update to provide Stroke Organis NeuroNews results. positive speaks to the trial’s following

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23–25 October International Neuromodulation Society Interim Meeting Mumbai, India www.neuromodulation.com/ interim-meeting

30–31 October LINNC Seminar 2020 – Americas Edition Miami, USA www. LINNC-Seminar-2020Americas-Edition

7–9 November ESO-WSO: Joint European Stroke Organisation and World Stroke Organisation Conference Vienna, Austria www.eso-stroke.org/events/ eso-wso-conference-2020 Event details correct at time of publication.

Please check www. neuronewsinternational. com/events for updates in the wake of COVID-19.

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