NeuroNews issue 45 – US

March 2022 | Issue 45

www.neuronewsinternational.com

Featured in this issue:

8

Radial access Is it here to stay?

Thrombectomy shown to restore more function than medication alone following severe stroke A new study from Japan has produced randomised controlled trial (RCT) evidence demonstrating the effectiveness of mechanical thrombectomy procedures, or endovascular therapy (EVT), alongside standard medical care in restoring function for patients who have suffered a severe ischaemic stroke due to extensive cerebral infarction. These late-breaking data— which also showed an increased occurrence of intracranial haemorrhage (ICH) among patients who underwent EVT—were presented at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA) and have since been published in the New England Journal of Medicine.

T

Profile Michael Chen

he respective senior and lead authors of this research, Takeshi Morimoto and Shinichi Yoshimura (Hyogo College of Medicine, Nishinomiya, Japan), told NeuroNews that their results offer evidence in favour of EVT for patients with extensive cerebral infarction in Japan—and may help to establish more global evidence when combined with findings from other, similar studies currently underway.

“Of course, there are limitations, such as the effect of race and the fact that the imaging evaluation method used in the majority of patients was MRI [magnetic resonance imaging],” they added, “but we believe it is significant that the results of a high-quality RCT showed the effectiveness of EVT in extensive cerebral infarction.”

And, moving on to discuss future directions for research in this space, they said: “We think it is important to estimate the number of patients and set the endpoints based on the

page 16

EVT group:

Ability to walk without assistance/none-tomoderate residual disability 90 days

31%

Major, early neurological improvement 48 hrs

31%

Intracranial haemorrhage 48 hrs

58%

page 23

Standard care group:

Ability to walk without assistance/none-tomoderate residual disability 90 days

13%

Major, early neurological improvement 48 hrs

9%

Intracranial haemorrhage 48 hrs

31%

quality registry, and then set up an RCT study plan using these estimates. This study was conducted only in Japan—and we believe that we should now aim for generalisation by recruiting patients throughout Asia and the rest of the world.”

EVT for severe stroke patients

In 2018, the American Heart Association (AHA) updated its stroke treatment guidelines to recommend EVT—involving mechanical clot removal via a thrombectomy—for select stroke patients, with a view to improving their odds of functional recovery. According to the AHA, effectiveness of the approach had previously been established in patients whose large-vessel clots disrupted blood flow to fewer areas of the brain. However, prior clinical evidence was mixed regarding patients with more severe strokes whereby a clot in one or more large brain arteries interrupts blood flow to a greater area of the brain.

“I have often encountered a dramatic improvement in a patient just after the mechanical clot removal procedure, even when the infarction area was large,” said Yoshimura.

Continued on page 2

Let’s go beyond.

Together, we can break new ground in neurovascular care.

Marc Russo The bright future of neuromodulation

NeuroMODULATION

Late-breaking data presented at NANS 2022

Physicians from across the globe gathered at the recent North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA) to hear multiple key pieces of research in neuromodulation and pain medicine presented for the first time.

DATA FROM LARGE CLINICAL trials assessing high-frequency spinal cord stimulation (SCS) for painful diabetic neuropathy and non-surgical refractory back pain were disclosed by Erika Petersen (Little Rock, USA) and Leonardo Kapural (Winston-Salem, USA), respectively.

Elsewhere, Guilherme Santos Piedade (Düsseldorf, Germany) offered new findings relating to optimising outcomes with dorsal root ganglion stimulation, while a novel approach using multiple-modality SCS therapy for chronic pain was presented

by Mark Wallace (San Diego, USA).

Several plenary sessions across the three-day conference saw pressing issues in neuromodulation—including the topic of telehealth, discussed

by Vwaire Orhurhu (Williamsport, USA)—feature prominently as well.

To read coverage of these NANS 2022 highlights, and much more from the world of neuromodulation, turn to page 21.

UC202212596 EN 2022 Medtronic.

Medtronic, Medtronic logo, and Engineering the extraordinary are trademarks of Medtronic.

All other brands are trademarks of a Medtronic company. 9775 Toledo Way, Irvine, CA 92618

March 2022 | Issue 45

2

Thrombectomy shown to restore more function than medication alone following severe stroke Continued from page 1

“Yet, patients sometimes also experienced severe haemorrhagic transformation after the artery was reopened. So, in Japan, our stroke physicians are always cautious about EVT when the infarction area is large.”

As the authors informed NeuroNews, concerns relating to an increased risk of a potentially fatal postoperative ICH in severe stroke patients following these procedures have somewhat limited clinical use of, and research into, EVT for strokes with a large ischaemic region.

They therefore conducted an RCT in which 203 stroke patients (average age=76 years; 44% women) were treated across 45 hospitals in Japan. Imaging via an MRI or computed tomography scan revealed clots blocking a large artery in the brain—either the internal carotid artery, proximal middle cerebral artery, or both—in all patients, and their strokes were rated as severe (median National Institutes of Health Shinichi Stroke Scale [NIHSS] score of 22) and Yoshimura involved disrupted blood flow to large areas of the brain (about 7/10 regions).

The patients were randomly selected to receive either standard medical care for stroke—consisting of providing intravenous fluids, controlling blood pressure and other risk factors, and administering clot-busting medications for select patients—or standard medical care plus EVT performed within an hour of imaging.

Due to bleeding concerns, intravenous thrombolysis was administered sparingly across the study (27%), and in a similar proportion between both treatment groups.

Fresh RCT data

Comparing the 100 patients in the EVT group with the 102 patients receiving standard care alone, the researchers found that patients who received EVT were 2.43 times more likely (31% vs 13%) to be able to walk without assistance and to have a residual disability rated as none-to-moderate (score of 0–3 on modified Rankin Scale [mRS]) after 90 days. In addition, at 90 days, more patients (14% vs 8%) in the EVT group were considered functionally independent, meaning they were 1.79 times more likely to either be able to carry out all their pre-stroke activities or have a slight disability that did not require daily assistance (score of 0–2 on mRS).

At 48 hours post-treatment, more patients (31% vs 9%) who received EVT also had a major, early neurological

improvement—defined as an increased ability to talk and move their limbs, or ≥8 points on NIHSS. “Our findings confirm that anyone who suffers from stroke should be transferred to a medical facility capable of EVT as soon as possible,” said Morimoto, who presented these data at ISC 2022. “The benefit of EVT is not limited by the severity or region of a stroke. These patients may have the chance to more fully recover, and go back to their previous lives and activity levels.”

In the study, several outcomes were compared in order to evaluate the safety of adding EVT to the current standard of care for severe stroke, with imaging inside 48 hours revealing more patients experienced bleeding within the brain in the EVT group compared to those who received standard medical care (58% vs 31%).

However, the number of patients who experienced other adverse outcomes—including need for decompressive craniectomy within the first week (10% vs 14%), and death (18% vs 23.5%) or recurrence of ischaemic stroke (5% vs 7%) within 90 days—was similar across the two treatment groups.

The researchers stated that the finding of more intracranial bleeding in patients who received EVT is “very important”.

“Because ICHs were significantly more common in the EVT group, the treating physician should strictly manage postoperative blood pressure and antithrombotic medications to Takeshi prevent these from becoming severe Morimoto haemorrhages,” they told NeuroNews.

However, they also noted that, while symptomatic ICHs (i.e. negatively impacting neurological status [worsening ≥4 points on NIHSS]) within 48 hours were more common in the EVT group compared to the standard

The benefit of EVT is not limited by the severity or region of a stroke.” Takeshi Morimoto

News in brief

The latest stories from the neuro world

n TENECTEPLASE DEMONSTRATES POTENTIAL TO INCREASE TIME WINDOW FOR ISCHAEMIC STROKE TREATMENT: This year’s International Stroke Conference saw Xin Cheng present data from a phase 2a clinical trial, the results of which indicate the effectiveness of tenecteplase (a bioengineered variant of alteplase) in safely restoring blood flow 4.5-to-24 hours from time last seen well in ischaemic stroke patients.

For more on this story go to page 4. n WORLDWIDE TCAR ANALYSIS PROVIDES “ROADMAP” TO EVALUATE FUTURE TRAINING APPROACHES: An analysis of worldwide experiences with transcarotid artery revascularisation (TCAR) has produced key objective proficiency metrics and an analytic framework to assess adequate training for the procedure—as per a report published in the Journal of Vascular Surgery by Brajesh Lal and colleagues.

For more on this story go to page 11.

medical care group (9% vs 5%) as well, the difference here was not statistically significant.

Moving on to summarise their findings in full, they added that the results—which demonstrate EVT could improve patients’ functional outcomes at 90 days for more severe strokes with a large ischaemic region— were “extremely close” to their pre-study predictions.

The researchers further stated that, although usage of intravenous thrombolysis was low due to stroke severity in the study, outcomes were not significantly different between the EVT and recombinant tissue-plasminogen activator (rt-PA) combination groups. They are now performing subanalyses of their results to assess the impact of rt-PA use, ischaemic volume, and other factors.

n STUDY DATA SUPPORT SAFETY AND EFFECTIVENESS OF CONTOUR DEVICE: Fresh data from the CERUS study, the first multicentre clinical trial evaluating safety and effectiveness outcomes with the Contour neurovascular system, have indicated “encouraging results” in the treatment of unruptured intracranial bifurcation aneurysms.

For more on this story go to page 14.

www.neuronewsinternational.com Editor-in-chief:

Prof Philip M Meyers

Publisher:

Roger Greenhalgh

Content director: Urmila Kerslake

Editor:

Jamie Bell jamie@bibamedical.com

Contributing writers:

Sarah Croft, Jocelyn Hudson and Anthony Strzalek

Design:

Published by:

Advertising:

BIBA Medical, Europe, 526 Fulham Road, Fulham, London, SW6 5NR, United Kingdom Tel: +44 (0) 20 7736 8788

Terry Hawes, Wes Mitchell and David Reekie Michael Broughton michael@bibamedical.com

Subscriptions:

subscriptions@bibamedical.com

Please contact the NeuroNews team with news or advertising queries Tel: +44 (0)20 7736 8788

facebook.com/neuronews

BIBA Publishing, which is a subsidiary of BIBA Medical Ltd

Buxton Press

https://www.linkedin.com/company/neuronews/

© BIBA Medical Ltd, 2022.

All rights reserved.

Write to us!

BIBA Medical, North America, 155 North Wacker Drive – Suite 4250, Chicago, IL 60606, United States Tel: +1 708-770-7323

Printed by:

Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the United Kingdom address.

If you have comments on this issue or suggestions for upcoming editions write to jamie@bibamedical.com

Make sure you get your copy of

Next issue May @NN_publishing

2022

March 2022 | Issue 45

Stroke Care

Newer clot-busting medication demonstrates potential to increase time window for ischaemic stroke treatment In a phase 2a clinical trial in China, the clot-busting medication tenecteplase has been shown to be effective in restoring blood flow to the brain without symptomatic brain bleeding—as per a late-breaking presentation at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA). Blood flow was safely restored to a small group of ischaemic stroke patients with large vessel occlusion (LVO) at 4.5-to-24 hours from time last seen well using tenecteplase in the trial. The researchers say their findings indicate that tenecteplase may someday extend the window for stroke treatment from 4.5 to 24 hours, but also note that larger, direct comparison clinical trials to validate this approach are now needed.

“T

he stroke burden continues to grow across the world, and particularly in China where stroke is the leading cause of death,” said Xin Cheng (Huashan Hospital of Fudan University/ National Center for Neurological Disorders, Shanghai, China), the lead author of the study. “There are two major limitations in thrombolysis with alteplase: the restricted time window of 4.5 hours, and a low rate of success in re-opening arteries and restoring blood flow when a large brain vessel is blocked.”

If ischaemic stroke patients obtain medical care more than 4.5 hours after their symptoms are noticed, it is too late to receive alteplase—the standard clot-busting medication. However, tenecteplase, a bioengineered variant of alteplase, has been subject to ongoing trials to determine its safety, efficacy and treatment parameters for ischaemic stroke, and previous studies have found that it may be non-inferior to alteplase and could even be superior for treating LVO strokes.

To evaluate tenecteplase’s potential in LVO stroke, Cheng and colleagues studied 86 patients with ischaemic strokes treated at 13 different hospitals in China. The patients had brain imaging between 4.5 and 24 hours after they were last known to be free of stroke symptoms. On imaging, all study participants were found to have large affected brain areas that could potentially be salvaged, if blood flow was re-established, and a few small areas that were unlikely to benefit Xin Cheng

American Academy of Neurology provides ethical guidance on stroke consent THE AMERICAN ACADEMY OF Neurology (AAN) has issued a position statement for neurologists on how to navigate consent issues for people who have experienced acute ischaemic stroke. The statement is published in an online issue of Neurology and was developed by the Ethics, Law and Humanities Committee—a joint committee of the AAN, American Neurological Association and Child Neurology Society.

This new guidance from January 2022

from treatment. Study participants were randomly assigned to two groups, with 43 patients (average age=68 years; 58.1% male) receiving a lower (0.25mg/ kg) dose of tenecteplase and 43 patients (average age=67 years; 72.1% male) receiving a higher (0.32mg/kg) dose.

The researchers had determined a pre-established, combined, positive outcome of effectiveness and safety if there was major restoration of blood flow without symptomatic brain bleeding 24–48 hours after treatment. If more than seven of 43 patients met the positive outcome criteria, that dose of tenecteplase would be deemed of sufficient promise to warrant further study. In addition to tenecteplase, some patients underwent a mechanical thrombectomy to remove their clot—at the treating physician’s discretion.

The researchers found that, at the lower dose of tenecteplase, 14 of 43 patients (32.6%) achieved the designated positive outcome criteria, while at the higher dose 10 of 43 patients (23.3%) achieved the designated positive outcome criteria. Among all study participants evaluated three months after treatment, more than half (53.5%) of the patients were no more than slightly disabled—not able to carry out all previous activities but did not require daily assistance—and 38.4% of the participants either had no significant symptoms of

replaces the AAN’s 1999 position paper as well as a 2011 policy statement.

“Stroke treatments that are effective in preserving brain function can only help if administered quickly, sometimes within just a few hours, yet consent for such treatments must often happen when the person who has had a stroke lacks the ability to make decisions and when those who could make decisions for them may be unavailable,” said position statement author Justin Sattin (University of Wisconsin, Madison, USA). “This position statement provides ethical guidance for neurologists on how to navigate the decision-making process for stroke patients when time is of the essence.”

The statement says that, when a stroke patient is unable to give consent for treatment, advance healthcare directives may provide guidance on their wishes. However, it says such directives, like living wills, are often

residual neurological deficits or had mild symptoms but could return to pre-stroke activities of daily living.

“Tenecteplase appears to be safe and potent in reestablishing blood flow through blocked, large brain vessels, thereby preventing damage to brain tissue at risk of dying,” Cheng said. “Using perfusion imaging to assess patients with larger areas of potentially salvageable brain tissue and smaller areas that have already been lost to stroke, it seems feasible that with tenecteplase we may be able to extend the time window for treatment to 24 hours after the time the patient was last known to be well. However, we still need more data from randomised controlled trials before practice changes to routinely include tenecteplase.”

In the subset of patients who received tenecteplase and underwent thrombectomy, fewer patients (three of 34 [8.8%]) reached the primary outcome measure of restoring blood flow without symptomatic brain bleeding, compared to those who received only tenecteplase (21 of 52 [40.4%]). “In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Cheng added. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”

Cheng and colleagues have identified the limitations of this study—including its lack of a control group and the fact the results may not be generalisable to other, non-Chinese populations. Nevertheless, their main focus was to assess whether treatment with tenecteplase is safe and effective enough to proceed to a larger clinical trial with more participants, and to determine potential medication doses appropriate for further research. And, based on their results, the lower tenecteplase dose is now being evaluated in a nationwide phase 2b study in China to compare its effectiveness and safety versus standard treatment.

Tenecteplase appears to be safe and potent in reestablishing blood flow through blocked, large brain vessels, thereby preventing damage to brain tissue at risk of dying.”

overly specific or too vague, addressing terminal conditions, but not debilitating conditions like stroke. Another form of advance directive that can be used is a power of attorney—while next of kin may also be authorised to serve as a surrogate decision-maker.

The position statement explains that a surrogate decision-maker may not be adequately prepared for representing a stroke patient’s wishes. As such, neurologists may need to guide them, giving priority to a patient’s preferences, if documented, or, if not, determining what the patient would want based on their beliefs. When beliefs are unknown, decisions should be made based on their best interests, the guidance says.

When a stroke patient needs emergency treatment and has no advance directive or surrogate decisionmaker, the position statement says treatments may be provided based on ethical presumptions of consent—what

a person would consent to if they could be asked. It adds that, when there is a generally accepted treatment like clotbusting drugs, neurologists may proceed with treatment on the presumption of consent, if necessary.

When treatments require more consideration of risks versus benefits, such as for an endovascular procedure to remove a clot, the guidance says decisions on whether to proceed should be informed by how closely a person’s case matches what is recommended in current treatment guidelines. And, when there are treatments for which evidence is lacking, it advises that neurologists should develop treatment protocols alongside their medical institutions.

Finally, the position statement says regarding stroke research that laws on consent by surrogates vary between US states, but the federal Common Rule—a rule of ethics in research—allows lawful surrogates to provide consent.

Image credit: Huashan Hospital of Fudan University

4

Issue 45 | March 2022

Stroke Care

Worldwide stroke rates dip slightly over time, but overall numbers remain high THE WORLDWIDE INCIDENCE and mortality rates for stroke decreased slightly from 1990 to 2019, but the overall numbers remain high—especially in high- and middleincome countries—according to a study published in an online issue of Neurology. The study focused specifically on ischaemic stroke, which is caused by blood clots and makes up 85% of stroke cases, according to a press release from the American Academy of Neurology.

“The decrease is likely due to better medical services available in high-income countries, which may offer earlier detection of stroke risk factors and better control of these risk factors,” said study author Liyuan Han (University of the Chinese Academy of Sciences, Ningbo, China). “But, even in these countries, the total number of people with strokes is increasing due to population growth and ageing, and worldwide stroke is the leading cause of death and a major cause of disability for adults.”

For the study, researchers analysed data from 1990 to 2019 from the Global Health Data Exchange. During that time, the average age-adjusted incidence rate of stroke decreased by 0.43%, from a rate of 105 strokes per 100,000 people to

95 strokes per 100,000 people. The rate was also higher in middle- and highmiddle-income countries than in other areas.

At a regional level, the highest rates were in East Asia, with 144 per 100,000, and North Africa, the Middle East and Eastern Europe, with rates of 135 per 100,000. The lowest region was Australasia at 44 strokes per

Stroke rate per 100,00 people Highest Lowest

Image credit: AHA

Serious disability is six times more likely to be the result three months after stroke among children whose large-vessel stroke was not treated with a mechanical thrombectomy procedure, according to preliminary late-breaking research presented at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA). n Australian study analysed severe strokes that occurred in a large artery or blood vessel in the brain in children. The typical treatment for these types of large-vessel clots in adults involves a mechanical thrombectomy procedure.

However, although mechanical thrombectomy is known to improve stroke recovery in adults, children

America at 16, Australasia at 17 and high-income Asia Pacific at 18.

“Since ischaemic stroke is highly preventable, it is essential that more resources be devoted to prevention, especially in low- and middle-income countries where economic development is leading to changes in diet and lifestyle that may increase people’s risk factors for stroke,” said Han. “It has been estimated that at least half of all strokes may be preventable if effective changes were made to common lifestyle factors, such as high blood pressure, obesity, smoking and inactivity.”

A limitation of the study the researchers identified was that quality and accuracy of data from some underdeveloped countries cannot be guaranteed, as many did not have reliable information on deaths and strokes.

220 200 180

Macedonia = 187

Jordan = 181

160

Children with severe stroke may fare better if treatment includes mechanical thrombectomy

A

100,000 people. At a country level, the highest rates were in the United Arab Emirates at 208, Macedonia at 187 and Jordan at 181, while the lowest rates were in Ireland at 36, Nepal at 37 and Switzerland at 38 strokes per 100,000 people. Egypt (1.4%) and China (1.1%) had the most pronounced increases in stroke rates, the researchers also report.

Similarly to the stroke occurrence rate, the rate of death from stroke decreased slightly over the three decades assessed (1.6%)—but the overall numbers were high. The death rate decreased from 66 deaths per 100,000 people to 44 deaths per 100,000 people. The highest death rates were in Eastern Europe, with a rate of 100 per 100,000, as well as Central Asia at 79 and Central Europe at 67. The lowest rates were in high-income North

5

United Arab Emirates = 208

140 120 100 80 60 40 20

Ireland = 36

Nepal = 37

Switzerland = 38

0

have not been included in previous mechanical thrombectomy were more than research—and as such the study in 3.5 times more likely to have significantly question compared post-stroke disability worse outcomes at three months after the between children who received the stroke. procedure and those who did not to explore “We were surprised by how common whether mechanical clot removal may be large vessel blockage is in children with beneficial for children after severe stroke. stroke and how much worse the disabilities The study included 166 children Kartik Bhatia were among the children who did not (average age=six years; 65% boys) treated receive mechanical clot removal, compared for stroke at different hospitals throughout New South to those who did,” said lead researcher Kartik Bhatia Wales in Australia from 2010 to 2019. Slightly less (Sydney Children’s Hospital Network, Westmead, than one quarter of the children (n=39) had a blockage Australia). “Now that we know how poor recovery is in a large blood vessel, or a severe stroke, which is for these children who did not receive endovascular similar to the rate found in adults. Thirteen children therapy, it is much easier to justify treatment options with this type of stroke received mechanical bloodlike clot removal for children with a large blood clot removal, while 26 did not. vessel stroke.”

The 26 children who did not receive mechanical In addition, the study found that about 80% of the blood-clot removal had greater physical disability children with a large vessel stroke met the Australian compared to the other two groups—the 13 children and US requirements—other than age—for adult who did receive mechanical thrombectomy, and eligibility for mechanical clot removal. “Our health the 127 children whose stroke was not caused by systems also need improvement so children with a blockage in a large blood vessel. Specifically, severe stroke are able to receive mechanical clot researchers found: removal more easily,” Bhatia added. “These children Children with a large blood vessel blockage who should be offered treatments to clear the blockages, did not receive blood-clot removal were six times just like we offer for adults.” more likely to have moderate-to-severe disability The study’s researchers note that it had several after three months compared to those who received limitations that may have affected the results, the procedure. including that it is a retrospective study relying on Compared to children with an ischaemic stroke medical records to identify the levels of disability, that was not in a large vessel, children with a and there was not a standard process of selection for large blood vessel blockage who did not receive treating patients.

6

March 2022 | Issue 45

Mechanical Thrombectomy

Global EXCELLENT study “shows how much stroke thrombectomy has advanced” The mechanical removal of blood clots reduced post-stroke disability in nearly half of “all-comer” real-world stroke patients in a global study, according to preliminary late-breaking research presented at this year’s International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA).

“THIS STUDY SHOWS HOW much stroke thrombectomy has advanced,” said lead study author Raul Nogueira (University of Pittsburgh School of Medicine, Pittsburgh, USA). “We saw a wide range of cases, including patients who, not too long ago, would not be considered good candidates for thrombectomy based on older age, pre-existing disability or large size of the stroke on presentation.

Our findings in this study expand thrombectomy to be considered for more stroke patients.”

Previous studies have found that stroke patients who received mechanical clot removal had less disability after three months than those who did not.

However, according to an American Heart Association press release, these studies were performed in carefully

selected centres and employed strict clinical and imaging inclusion criteria— which decreases the generalisability of their findings.

To examine the effectiveness of blood-clot removal across a wide range of stroke patients seen in routine daily care, i.e. outside of a clinical trial, the EXCELLENT (Embotrap extraction and clot evaluation and lesion evaluation for neurothrombectomy) trial enrolled 1,000 adult ischaemic stroke patients (average age=70, 52% female) at 36 sites worldwide, from September 2018 to March 2021. The sites were a mix of thrombectomy-capable and comprehensive stroke centres. Patients were treated with a specific mechanical thrombectomy device called Embotrap (Cerenovus) in an unlimited timeframe in the trial.

03-2022_Perflow-advertentie neuro news_225x153mm_DEF.indd 4

The study was designed to collect The study also found blood clots that real-world treatment and did not were rich in red blood cells and low exclude patients based on pre-stroke in platelets resulted in less disability independence level, severity of stroke, than blood clots composed of less red location of the occlusion, or blood cells, or those rich time between onset of stroke in red blood cells and high and treatment, researchers in platelet content. In this said. As per current study, only 10% of patients guidelines, mechanical whose clots had a higher thrombectomy treatment composition of red blood can be used within 24 cell count and a lower hours of symptom onset in composition of platelets died select patients. In addition, within 90 days, compared to Raul Nogueira the study analysed the 24% of patients whose clots characteristics of the removed blood had a lower composition of red blood clots and how that impacted stroke cells and platelets. Among patients with recovery. higher red blood cell content, 63% with The EXCELLENT trial found that lower platelet content had either slight most of the patients required only or no disability, compared to 51% with one attempt to remove the blood clot. higher platelet content.

However, it is common to require “We knew that fibrin was associated multiple attempts to completely remove with more difficult clot removal. the clot. In nearly half of all patients, However, this novel observation that clot removal resulted in slight/minimal platelets may modify clot properties is disability (able to look after own affairs very intriguing,” Nogueira added. “The without assistance or no worsening from results may have potential implications their pre-stroke condition)—as gauged for technique and device selection when by a standard scale measuring level of removing clots and the development of disability 90 days after stroke. better blood-clot removal strategies.”

The results may have potential implications for technique and device selection when removing clots and the development of better bloodclot removal strategies.”

10/03/2022 09:03

Issue 45 | March 2022

Aneurysm Treatment

Image credit: Biomodex

Preprocedural 3D simulations help optimise aneurysm embolisation strategy ENDOVASCULAR NEUROSURGERY rehearsals using 3D-printed, patient-specific aneurysm models have demonstrated the ability to optimise embolisation strategy, as per the findings of a study published in the Journal of Neuroradiology. This optimisation resulted in shorter procedure duration and cumulative fluoroscopy time, translating to reduced radiation exposure compared to procedures performed without preprocedural 3D simulation, the authors state.

François Eugène (Rennes University Hospital, Rennes, France) and colleagues note that, while the use of preprocedural computer simulations can help to improve treatment planning and mitigate some challenges associated with giant or wideneck aneurysm embolisation, it fails to address an “important criterion” of haptic feedback—which is directly linked to the handling of endovascular devices during challenging navigation.

However, they believe that EVIAS (Endovascular intracranial aneurysm system; Biomodex), a recently

developed technology deploying accurate, patientspecific, 3D-printed models to mimic the navigation experience and provide precise haptic feedback during such procedures, offers promise in this regard. The researchers therefore set out to assess the effect of preprocedural 3D simulation with EVIAS on procedural and clinical outcomes for wide-neck EVIAS aneurysm embolisation.

In an unblinded, non-randomised, prospective, multicentre study, dubbed ‘3D SIM’ and conducted from November 2018 through December 2020, 21 patients with complex intracranial aneurysms (neck >4mm or ratio <2) were treated with a Woven EndoBridge (WEB; Microvention) device or a Pipeline flow diverter (Medtronic). Prior to these procedures, in vitro simulations were performed by three senior neurointerventionists on patient-specific aneurysm models created using EVIAS. The primary endpoint of the study was 3D-printed model accuracy, evaluated using concordance between simulation and procedure. This was assessed using choice of implantable device. Secondary endpoints relating to embolisation outcomes—including complications and mortality rate, procedure times, and radiation dose—were also assessed via comparisons with a retrospective cohort of WEB cases.

Twenty-one patients (mean age=56 years; 67% women) were treated in the study—76% of cases with

Pushing the boundaries of aneurysm detection, monitoring and care with artificial intelligence Alejandro Spiotta Comment & Analysis Alejandro Spiotta (Medical University of South Carolina, Charleston, USA) outlines what he believes could be the next frontier in cerebral aneurysm care—artificial intelligence (AI).

ENDOVASCULAR TREATMENTS for brain aneurysms and other cerebrovascular diseases have significantly improved over the past few decades, and continue to progress at a very fast pace. From advances in techniques to improved medical devices, to growing expertise, the future looks promising for aneurysm patients and physicians providing their care.

AI integration holds great promise to be perhaps the biggest disruptor in recent medical history. Emerging technologies, such as AI-based image interpretation tools, are spurring further this rapid progression. These technologies are well-established in helping physicians save time and improve patient care by automating the clinical and operational aspects of ischaemic stroke management, and will soon be applied to aneurysm management as well.

Unruptured intracranial aneurysm remains a major public health concern.

Accurate, early diagnosis is critical and, unfortunately, misdiagnosis or delays in

diagnosis occur in up to one quarter of patients when initially seeking medical attention—making these advancements all the more important.

AI technologies can support and augment the process of identifying and monitoring intracranial aneurysms by increasing sensitivity of detection, as well as standardising quality across centres, so that every patient benefits from the highest possible diagnostic yield. Magnetic resonance angiography and computed tomography angiography (CTA) scans paired with integrated AI tools can enhance physicians’ ability to find aneurysms, as a recent study demonstrated. The study found that AI capabilities helped junior radiologists match the performance of more senior radiologists in identifying the most challenging aneurysms (<5mm) on CTA, and AI incorporation improved workflows by reducing time to diagnostic reporting.

From an operational standpoint, these technologies are showing tremendous promise in helping hospital teams

7

WEB and 24% with a flow diverter stent, according to Eugène and colleagues. Concordance between post-simulation and real procedure efficiency was 0.85 (0.69–1) for device selection and 0.93 (0.79–1) for wall-apposition/aneurysm neck closure.

The authors also note that geometrical accuracy of the 3D-printed model showed a mean absolute shift of 0.11mm.

Regarding safety, they detail that two complications occurred, neither of which were deemed to hold any major clinical impact, and mean post-procedure modified Rankin Scale (mRS) scores were identical to mean pre-procedure mRS scores.

“This study on a small number of patients underlines the potential of in vitro patient-specific simulations with the EVIAS system for optimal preoperative planning,” Eugène and colleagues write. “The results showed a potential improvement in terms of implantation failure (9.5% post-simulation vs 25.5% in the historic cohort, p=0.34), adequate device selection, radiation dose and cumulative fluoroscopy duration compared to a historic cohort in which device selection was based on conventional measurements.”

The authors also note several study limitations, including its design not allowing adequate evaluation of clinical outcome for benefit from in vitro simulation with multiple rehearsals, and its basis in two centres with a small number of practitioners and patients.

eliminate workflow inefficiencies and manage a higher capacity of case volume by taking over tedious tasks, and streamlining and standardising processes. The goal of these tools is to reduce communication breakdowns by connecting multidisciplinary staff involved in managing aneurysm patients. Effective workflow applications should also be able to advance communication among doctors and nurses by allowing them to update each other in real-time through text messaging and automated status updates—minimising the number of phone calls. Although reducing workflow inefficiencies in the emergency department is far from easy, integrating machine learning platforms can offer relief and ultimately result in more consistent, quality care.

Given the great promise to improve detection and workflows for monitoring and treating aneurysms, what is preventing widespread adoption of AI among the healthcare community?

First—and of utmost importance—the data supporting its use, including transparent sensitivities and specificities at various anatomical locations and in various conditions (for example, in the presence of subarachnoid haemorrhage), must be made available to promote physician trust in the technology.

Another barrier is a lack of resources.

Implementing new technologies requires time, training, and budget.

There must be tangible, widespread results on improvements to patient outcomes, care times, cost savings, and positive physician feedback to ensure a successful return on investment. These metrics are often challenging to prove upfront to garner the necessary support from hospital administration. There is also clinician resistance, or hesitation, towards emerging technologies. Many times, physicians remain faithful to

legacy systems and have difficulty modernising. It is critical to reinforce the fact emerging technologies will not replace physicians, but rather help them do their jobs more effectively and efficiently to better serve their patients.

Although every aneurysm case reveals its own unique set of clinical and operational challenges, emerging technologies have the power to offer significant improvements to care. As hospitals more widely deploy modern solutions, the healthcare ecosystem as a whole will benefit as it continues to advance into new territories. Health systems should actively seek out new solutions to recurring problems and not be skittish to push the boundaries of innovation. I believe the coming wave of AI-based technological improvements will profoundly and forever more alter the way we as physicians interpret images, communicate across large healthcare systems and interact with patients, and ultimately treat diseases.

Advancements like these are being supported by the Stroke Thrombectomy and Aneurysm Registry (STAR) collaboration—a multicentre initiative designed to track, and ultimately improve, treatment outcomes using large patient cohorts and global expertise.

References: References for this article are available online and can be viewed at neuronewsinternational.com/aneurysmdetection-monitoring-care-artificial-intelligence/.

Alejandro Spiotta is a professor of Neurosurgery and Neuroendovascular Surgery, and division director of Neuroendovascular Surgery, in the Department of Neurosurgery at the Medical University of South Carolina (MUSC) in Charleston, USA. Disclosures: Spiotta has received

research grants from or provides consulting for Medtronic, Penumbra, RapidAI, Siemens, Stryker and Terumo.

8

March 2022 | Issue 45

Radial Access

THIS ADVERTORIAL IS SPONSORED BY MEDTRONIC

Radial access is not just a new toy—it has come to stay Upon gaining CE-mark approval in September of last year, the Rist radial access system (Medtronic) became the first dedicated technology on the European market providing interventionists with the option of accessing their patients’ neurovasculature via the radial artery pathway for haemorrhagic stroke indications. Alejandro Tomasello (Vall d’Hebron Hospital, Barcelona, Spain) was one of the first physicians in all of Europe to use Rist for neurovascular procedures. Here, he sits down with NeuroNews to discuss his experiences of the system, as well as the benefits offered by transradial access and the likely place for this approach within existing treatment protocols.

T

o date, Tomasello and his team discharge following acute cases may allow at Vall d’Hebron Hospital have rehabilitation to begin sooner. completed more than 50 cases with He goes on to state that there are logistical the Rist radial access system throughout advantages to using radial access systems a period of several months. As per the like Rist too. From the patient’s perspective, indications Rist is currently approved for it carries increased levels of comfort, as they Alejandro in the European Union, the majority of do not have to lie completely flat during the Tomasello these cases have involved haemorrhagic procedure, and the radial artery is also less stroke-related procedures with flow diverters and affected by patient movement during the intervention other intrasaccular devices used to treat intracranial than the femoral artery—something Tomasello feels aneurysms. These cases have also been a mix of is especially relevant for post-procedure agitated elective and acute cases, Tomasello reports. patients, as well as for nursing teams.

“We are really happy with [Rist], because the behaviour of the catheter is wonderful and the Progress requires cautious, evidencenavigability is so good—and, in my experience, it is based approach also extremely user-friendly,” he says. Tomasello and In spite of this apparent glut of positives favouring his colleagues have also used Rist more sporadically radial access, Tomasello believes that “we are yet to for alternative indications beyond haemorrhagic fully understand the clinical benefits of radial access” stroke—including in select carotid artery stenting in the neurovascular space, adding that, beyond the (CAS) procedures and interventions requiring known reduction in complications, further research and multiple accesses, such as arteriovenous malformation experience will still be key in elucidating the specific (AVM) and dural arteriovenous fistula (AVF) patients it is suitable for. And, while comparisons treatments—and he believes these are areas in which between the two are necessary, he warns that directly radial access holds further promise. pitting radial and femoral approaches against one another may be a “mistake”—not least because the Benefits of radial access with Rist latter is an established and well-accepted method for According to Tomasello, one of the more significant accessing the neurovasculature quickly, and safely. benefits offered by the transradial approach is a Tomasello also emphasises the need to incorporate reduction in complications as compared to more Rist, a relatively new technology, into clinical established transfemoral access protocols. For one, practice based on existing evidence and common he says, deploying radial access means that it is sense, and warns that this process should be done not necessary to cross the ascending aorta—which methodically. “In neurointervention specifically, is known to play a role in the development of this is vital, because the risks in our space are even arteriosclerosis. In addition, the aggressive dual greater than in other types of surgery,” he says. “I antiplatelet therapy used alongside femoral access think it is important, despite the positive effect of procedures leads to an overall complication rate of up radial access, that we move slowly, and do so based to 10%, with major complications and retroperitoneal on the evidence we have.” Another major factor in bleeding being seen in around 2% and 0.4–0.5% of the implementation of radial access within healthcare cases, respectively, as well. “But, when you move systems is education. “You have to properly train your to the radial approach,” Tomasello claims, “there team,” Tomasello continues. “And, when it comes are almost zero complications, and this really is to radial access, you have to think about the whole something remarkable.”

“We also understand that the use of radial access affects the whole procedure process,” he continues.

“For example, you are often able to discharge the patient sooner.” Tomasello points to specific procedures like diagnostic arteriographies and CAS interventions whereby radial access can enable the patient to be discharged on the same day. “The impact of radial access is incredible—especially in countries where they keep the patient in the hospital for multiple days,” he says. “You will save a lot of money if you discharge your patient sooner Rist™ Radial and, in our experience, you can probably discharge Access system elected patients one or two days earlier compared to femoral access.” In addition to this positive economic impact, Tomasello notes that earlier patient

team, not just the physician, because it requires more work logistically inside the angio suite. All changes like this—even if they offer something better—have a learning curve.”

The current literature on radial access, which is derived largely from the cardiology space, has indicated that roughly 70 cases are needed to build up skillsets and offer radial access as a safe, effective option to the patient. “However, my understanding is that this may depend on the level of training the physician has,” Tomasello claims. “If you have a well-trained neurointerventionist with decades of experience, they will probably only need 10 or 20 cases.” He also reiterates here that radial access training is “extremely important”, and will continue to be so if the approach is expanded to ischaemic stroke indications, and thrombectomy procedures, in the future, owing to the ‘time is brain’ mantra and the fact these interventions must be completed quickly.

Accessing the future

“Radial access is not a new toy—it has come to stay, in my opinion,” Tomasello states, but tempers this by adding that it will not replace the femoral access approach completely. “Logic dictates that the two will coexist, and the choice will be made based on operator skill, healthcare centre protocols and, of course, benefit to the patient and their anatomic parameters,” he continues. Discussing potential next steps for Rist and radial access technologies more generally, Tomasello notes that a future increase in the variety of diameters available for these catheters may open up new possibilities in terms of appropriate patient anatomies and indications, and expand their adoption.

“I am convinced that radial access offers a lot of benefits for the patient—but we have to prove this to more physicians and the neurointerventional world in order to move the market towards radial access,” he adds. “If you select patients for Rist properly, it is extremely safe, and the possibility of having a complication relating to the radial access approach itself is limited to very few cases.” Citing these benefits once more, and owing to the fact the financial costs of implementing both approaches into daily practice are “completely equivalent”, Tomasello concludes that radial and femoral access techniques

If you select patients for Rist properly, it is extremely safe, and the possibility of having a complication relating to the radial access approach itself is limited to very few cases.” will likely feature side-by-side in many hospitals moving forward—but that, once the role of radial access has been fully established in the coming years, more than half of all neurointerventions could be performed via this approach.

Alejandro Tomasello is the head of the Interventional Neuroradiology Unit at Vall d’Hebron Hospital in Barcelona, Spain.

Disclaimer: The data and content included in this

presentation express only the clinical perspective of the presenter. They are completely independent and do not necessarily reflect the opinions of Medtronic.

Issue 45 | March 2022

Radial Access

The pros and cons of radial access in neurointerventional surgery Pascal Jabbour Kareem El Naamani Comment & Analysis As the adoption of transradial access across the world of neurointervention begins to pick up pace, Pascal Jabbour and Kareem El Naamani (Thomas Jefferson University, Philadelphia, USA) take a look at both sides of the coin in this relatively new alternative to the transfemoral access approach.

T

he neurointervention field has witnessed immense technological advancements in the treatment of neurovascular diseases since the introduction of the Guglielmi detachable coils in 1991. One revolutionary milestone was the introduction of the radial access, which gained popularity in the neurointerventionist community— especially after several cardiology studies proved its safety and overall reduced morbidity and mortality.

Although the radial access site has inherent limitations, the decreased risk of access site and periprocedural complications demonstrated in the cardiac literature prompted neurointerventionists to pursue a “radial-first” strategy in their practice.

With the introduction of radial access, many studies were conducted in the neurovascular field to assess its efficacy, safety profile, and feasibility, and compare these parameters to those of the conventional femoral access in order to address the limitations, push for more advancements, and ensure that patient safety remains the top priority.

Advantages of radial access Radial access provides several advantages at the anatomical, safety, financial and feasibility levels. First, the radial artery is more superficial than the femoral artery, and is not in close proximity to any critical structures that are susceptible to injury during the procedure. Moreover, because of the dual blood supply to the hand, direct injury to the radial artery, such as thrombosis or dissection, is less detrimental to the patient. The transradial approach is particularly advantageous in complex arch anatomies. In patients with bovine arches, the common origin of the innominate artery and the left common carotid artery (CCA) allows direct navigation of the left CCA without the need to form the Simmons catheter in the aortic arch.

Also, in other cases, where the navigation of elongated and tortuous aortic arches (type II or III) poses a

challenge to the femoral approach, transradial confers a technically favourable, alternative direct catheterisation without the need for reforming. Compared to the femoral approach, the radial approach also provides a more straightforward access to the posterior circulation, which reduces time to revascularisation in the setting of vertebrobasilar strokes. In our recent large, single-centre case series involving diagnostic and interventional neuroendovascular procedures via radial access, we showed that there was no significant difference in access site complications between transradial and transfemoral approaches—which signifies that complex treatments can be effectively carried out via radial access.

Another advantage of radial access is that haemostasis can be achieved without the need for a vascular closure device. As patient comfort is pivotal, and taking into consideration the current climate in which patients have the benefit of choosing among many treatment options, radial access has gained a strong patient preference due to the ability of patients to ambulate directly after the procedure compared to post-femoral access procedures, which require bedrest for an extended period of time. Because of this, patients require less postprocedural nursing care and shorter hospital stay, which in turn reduces hospital costs. Other high-risk patients, such as the elderly, patients on blood thinners, pregnant patients, the severely obese, and patients with iliofemoral atherosclerotic disease, may also benefit from radial access due to reduced radiation exposure and fewer access site complications.

Left transradial access and distal transradial access are also additional refinements that expanded our armamentarium for unique anatomical limitations. The left vertebral artery is left-dominant in most patients and subclavian tortuosity has higher incidence on the right side. The left radial approach provides easier and more advantageous access in these cases. As for distal transradial access,

studies have not only shown that this approach is associated with lower rates of radial artery occlusion and hand ischaemia, but also—because hand supination is not required for these procedures—left-sided access becomes more comfortable with the hand draped across the body in a neutral position.

Disadvantages of radial access

Although low risk, several complications are associated with the transradial access, such as radial artery spasm (RAS), occlusion and perforation, which may result in forearm haematoma or compartment syndrome. Rarer complications include pseudoaneurysm, arteriovenous fistula formation or sterile abscess formation.

RAS has been reported to occur in 4–20% of transradial procedures, with risk factors including small radial artery diameter, repetitive friction and manipulation, patient pain and anxiety, and guidewire entrance into a side branch. When RAS manifests at the beginning of a procedure, it prevents further access, which results in a transfemoral conversion or procedure failure. On the other hand, if RAS occurs post-cannulation, vasodilators are administered through the sheath or guide.

When it comes to radial artery occlusion (RAO), the incidence varies between 1% and 6% of procedures, and is associated with female gender, low body mass index, high sheath to radial artery diameter ratio, diabetes and occlusive haemostasis—depending

Although transfemoral catheterisation... remains the primary access route for most patients, interest in radial access is growing.” on compression time and pressure.

Although RAO is asymptomatic due to the aforementioned dual blood supply, persistence of RAO may render the radial artery unviable for future radial access procedures. Other limitations for radial access are anatomical in nature and range from radial artery anomalies, tortuosity, arteria lusoria, and subclavian tortuosity, to aortic arch types.

One radial artery anomaly is highbifurcation radial origin, which requires the interventionist to navigate an elongated, smaller radial artery diameter, increasing the risk for RAS. Another anomaly is a radial artery loop, which may be accompanied by a recurrent radial artery branch at its apex, increasing the risk of perforation if a wire was advanced into the recurrent radial artery. Although subclavian tortuosity poses a challenge, using

9

the left radial access overcomes such obstacles.

Another challenge is an aberrant right subclavian artery, also known as arteria lusoria, which has an incidence of 0.6–1.4%, and causes repetitive entry of the guidewire into the descending aorta. While mentioned previously that the radial approach provides easier access in patients with type III aortic arch, in some cases—where the brachiocephalic artery is too inferior— selecting the descending aorta may be challenging, and reforming the catheter in the CCA or ascending aorta may be necessary. Lastly, some other concerns regarding radial access include the lack of familiarity with a novel technique, increased radiation exposure in operators in the beginning of their learning curve, and lack of devices designed specifically for radial artery dimensions.

The future of radial access

Although transfemoral catheterisation for neuroendovascular procedures remains the primary access route for most patients, interest in radial access is growing. The two landmark studies in cardiac literature—the RIVAL and MATRIX studies of more than 7,000 patients—showed that radial access is associated with a 60% reduction in vascular complications, as well as significant decreases in all-cause mortality and net adverse clinical events.

As for the neurointervention community, radial access has proven to be safe, effective, feasible and, most importantly, preferred by patients. Many centres around the USA, like ours, have introduced radial access training in their fellowship programmes to ensure that future neurosurgeons are transradial- and transfemoral-trained. Also, our centre was the first in the country to perform a transradial robotic-assisted carotid stenting. This not only proves that the scope of radial access is expanding, but also that the transradial approach is here to stay. However, along the journey, it is of utmost importance to address the limitations of radial access via technological advancements, learning curves, and randomised controlled trials—since the main goal of any medical revolution is patient care and safety.

References: References for this article are available online and can be viewed at neuronewsinternational.com/radial-accessneurointerventional-surgery-pros-cons/.

Pascal Jabbour is the head of the Division of Neurovascular and Endovascular Neurosurgery in the Department of Neurological Surgery at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, USA. Kareem El Naamani is a postdoctoral research fellow in the Department of Neurosurgery at Thomas Jefferson University Hospital in Philadelphia, USA. Disclosures: Jabbour is a consultant for

Balt, Cerenovus, Cerus Endovascular, Medtronic, Microvention and Q’Apel.

March 2022 | Issue 45

10 Carotid Interventions

Expedited carotid artery surgery after index event “probably safer” than expedited stenting A systematic review and metaanalysis of 71 studies suggests that, at present, carotid endarterectomy (CEA) is safer than carotid artery stenting (CAS) when performed within two or seven days of the index event. “The findings of this analysis will guide clinical practice when deciding on the type of intervention in the symptomatic patient with severe carotid stenosis,” authors Andreia Coelho (Centro Hospitalar Universitário de Porto, Porto, Portugal) et al write in the European Journal of Vascular and Endovascular Surgery (EJVES), where the findings were published as an Editor’s choice paper.

Coelho et al stress that the ideal timing of performing CAS in symptomatic patients, when indicated against CEA, is not yet defined.

E

uropean Society for Vascular Surgery guidelines advise that CEA or CAS should be performed within 14 days of symptom onset, the authors communicate. However, they note that the evidence would suggest there has been a drive towards performing interventions well within 14 days, especially in Europe. In addition, they write that a temporal trend towards a progressive decrease in delays from index event to undergoing CEA or

CAS has been reported in several national registries. days), they note, was associated with no difference However, mixed findings about the impact of in stroke rate but statistically significantly higher intervening within 48 hours of index event have been mortality rate (OR, 2.76; 95% CI, 1.39–5.5). reported, Coelho et al stress.

Coelho and colleagues write that there were In order to analyse the timing of carotid inconsistent findings regarding timing and outcomes in interventions after index event, as well as 30-day CAS patients. They elaborate: “In patients undergoing outcomes at varying time periods within 14 days of CAS ≤2 days of the index event (vs 3–14), there symptom onset, the investigators initiated a systematic was no apparent difference in 30-day stroke or MI review and meta-analysis of the available data. [myocardial infarction] but there was a statistically Coelho and colleagues first performed a systematic significantly higher risk of death. Conversely, there review, involving an online search of the Medline and were no differences in 30-day outcomes between Cochrane databases. Endpoints included procedural CAS performed ≤7 days (vs 8–14).” The authors stroke and/or death stratified by delay from hypothesise that the pathophysiology of the index event and surgical technique, they procedural stroke may differ with expedited, The convey. versus delayed, interventions in line with investigators acute changes in atherosclerotic plaque The investigators included 71 studies with 232,952 symptomatic vulnerability, which have been included patients. They detail that the associated with an increased risk 71 studies consisted of 34 of embolism and neurological retrospective databases, and events after CAS. nine prospective, three The investigators also randomised controlled, address some limitations of three case-control, and 22 the studies included in their retrospective, studies. analysis, including the fact symptomatic Writing in EJVES, that the studies analysed are studies Coelho et al report that CAS of moderate-to-low quality. patients was associated with higher 30In addition, they state that day stroke (odds ratio [OR], 0.7; “probably one of the main biases” 95% confidence interval [CI], 0.58–0.85) in the study was introduced in the election and mortality rates (OR, 0.41; 95% CI, for CAS/CEA, with fit patients treated by CEA 0.31–0.53) compared with CEA when while high-risk patients were treated by CAS. performed within two days of symptom The data suggest that, at the current onset. time, CEA is “probably safer” than CAS The research team analysed patients when performed within two or seven undergoing CEA/CAS in different time days after symptom onset, the authors frames: ≤2 vs 3–14 and ≤7 vs 8–14 conclude. Considering the wider days, which revealed that expedited topic area, they add that no studies CEA (vs 3–14 days) presented a have published outcome data for sampled 30-day stroke rate of 1.4%; transcarotid artery revascularisation 95% CI, 0.9–1.8 vs 1.8%; 95% CI, when used in the first 14 days after 1.8–2, with no statistically significant symptom onset as of yet, and that these Andreia difference. Expedited CAS (vs 3–14 data are “keenly awaited”.

Coelho

Women face increased risk of stroke and readmission after carotid interventions A RECENT STUDY HAS pointed to an increased risk of stroke in both asymptomatic and symptomatic female patients, as well as readmission in asymptomatic female patients following carotid endarterectomy (CEA) or carotid artery stenting (CAS). These findings were published online ahead of print in the Journal of Vascular Surgery (JVS).

Authors Steven Goicoechea (Loyola University Medical Center, Chicago, USA) and colleagues write that, historically, CEA has illustrated a higher rate of perioperative adverse events for female patients. Despite this, they note that recent research portrays evidence to suggest similar outcomes following CEA between female and male patients. In contrast, however, they stress that few studies have examined sex differences in CAS. In order to address this gap in the literature, Goicoechea et al prospectively collected contemporary data from

the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, and performed a retrospective crosssectional review.

The research team collected data from adult patients (n=106,658) who had undergone CEA (n=104,412) or CAS (n=2,156) in the period 2005– 2017, they communicate in JVS. The study’s primary outcomes of interest were 30-day postoperative adverse outcomes in asymptomatic versus symptomatic patients, and female versus male patients, who had undergone CEA or CAS. Among the asymptomatic group—in which nearly 60% of patients were male—female sex was associated with significantly higher rates of cerebrovascular accident (CVA; 32%, p=0.034), bleeding complication (203%, p=0.001), and urinary tract infection (70%, p=0.011) compared to male sex, the authors write.

71 232,952

Goicoechea and colleagues add that female sex was also associated with a lower rate of pneumonia (39%, p=0.039) and that female patients less than 75 years old illustrated increased rates of CVA (21%, p=0.001) and readmission (15%, p<0.001) compared to male patients, whereas this was not the case in female patients aged 75 years and older. Lastly, in both asymptomatic and symptomatic patients who received CEA, female patients had significantly higher rates of CVA (13%, p=0.006 and 31%, p=0.044); however, the same trend was not found in patients undergoing CAS. In the discussion of their findings, Goicoechea et al write that the current study highlights sex disparities

Women and ethnic minorities have historically been underrepresented in vascular surgery randomised controlled trials.”

in vascular surgery, including discrepancies in postoperative outcomes and complications that have previously been established. They detail that women and ethnic minorities have historically been underrepresented in vascular surgery randomised controlled trials (RCTs), especially in non-governmental and single-centre trials, commenting that this underrepresentation leads to under-reporting of potentially significant differences in outcomes between male and female patients.

Also in their discussion, the authors note that their study is limited by certain factors, including the use of retrospective data from an administrative dataset with potentially missing information, and difficulty identifying causes of discrepancies in female versus male outcomes due to a “lack of granularity” in a large database such as NSQIP. In concluding, Goicoechea et al stress that the present study emphasises the importance of understanding sex disparities in the surgical management of cerebrovascular disease, and stress that RCTs must ensure adequate representation of female patients in order to better understand these differences.

Issue 45 | March 2022

Carotid Interventions 11

Study highlights need to extend scope of cerebrovascular health disparities research A new research letter in Stroke outlines use of the novel National Institutes of Health (NIH) ‘All of Us’ research programme dataset of diverse participant data to identify factors that increase the risk of carotid artery stenosis and those who undergo revascularisation. The study, authored by Daniela Renedo (Yale School of Medicine, New Haven, USA) and colleagues, includes electronic health record data from over 200,000 US patients.

“IT IS INCREASINGLY recognised that underrepresented groups defined by factors other than race and ethnicity also carry a disproportionate burden of cardiovascular disease,” the authors begin. In order to test the hypothesis that the burden of carotid artery stenosis and the proportion of persons who undergo carotid revascularisation differ in broadly defined, underrepresented groups, the researchers utilised data collected via the ‘All of Us’ research programme.

According to the NIH website, the ‘All of Us’ research programme is inviting one million people from across the USA “to help build one of the most diverse health databases in history”, welcoming participants from all backgrounds. “Researchers will use the data to learn how our biology, lifestyle, and environment affect health”, with the ultimate aim of finding ways to treat and prevent disease, the website adds.

The team performed a cross-sectional study including ‘All of Us’ participants with available electronic health records

data, considering underrepresented groups defined by factors other than race and ethnicity, including education (less than high school degree); income (less than US$35,000); and gender identity/sexual orientation.

Of the 203,813 patients included in the study, the average age was 51.5 years and the majority (61%) were female. The authors relay that the prevalence of carotid artery stenting was 2.7% (n=5,420) and the proportion of patients who underwent carotid revascularisation was 7.3% (n=395).

Writing in Stroke, Renedo et al report a key finding that persons with income of less than US$35,000 were more likely to have both carotid artery stenosis and undergo revascularisation, detailing that income of less than US$35,000 was associated with higher odds of carotid artery stenosis (odds ratio [OR], 1.15 [95% confidence interval (CI), 1.07–1.24; p=0.001] and carotid revascularisation (OR,

1.38 [95% CI, 1.04–1.83]; p=0.024).

The investigators also found that, when evaluating underrepresented groups defined by race and ethnicity, Black (OR, 0.87 [95% CI, 0.78–0.96], p=0.006) and Hispanic (OR, 0.83 [95% CI, 0.73–0.94] participants had a lower prevalence of carotid artery stenosis, which they note is consistent with prior reports.

Moreover, the authors communicate that Black participants with carotid artery stenosis (OR, 0.41 [95% CI, 0.24–0.68]; p=0.001) had lower estimates of carotid revascularisation.

This could be explained by lower rates of high-grade stenosis, they remark, but stress that other factors should be explored further, including the potential presence of care access bias.

Renedo and colleagues acknowledge that their study may be subject to volunteer bias, leading to an increased number of healthy people enrolled.

In addition, they note that not all participants chose to share their electronic health records.

“These results highlight the need to extend cerebrovascular health disparities research beyond groups defined by race/ethnicity,” the researchers conclude, adding that this goal will be “significantly facilitated” by the newly established ‘All of Us’ research programme.

Speaking to Vascular News, Renedo conveyed the key takeaway

Worldwide TCAR analysis provides “roadmap” to evaluate future training approaches

Daniela Renedo

message from the study, that more attention should be given to the present healthcare disparities in this condition.

“Clinicians should be aware of these disparities, and offer patient-centred recommendations to prevent, mitigate and manage carotid artery stenosis across diverse populations,” she elaborated.

The first author also advised that, in the near future, the ‘All of Us’ research programme will provide access to genetic data from the participants.

Renedo is part of a lab team at Yale headed by Guido Falcone that is

Clinicians should offer patient-centred recommendations to prevent, mitigate and manage carotid artery stenosis across diverse populations.” focused on genetic epidemiology, and the team will therefore use the data from this study “to better understand the interaction between social determinants of health and biological factors that ultimately lead to carotid stenosis, and its consequences”.

Charles Matouk, also of Yale, jointly supervised the work with Falcone.

asymptomatic carotid stenosis, and had more prior experience with transfemoral carotid stenting, the researchers specify.

Writing in JVS, the authors report that the over 24-hour composite clinical adverse event rate (1%; 95% confidence interval [CI], 0.8–1.3%) and composite technical adverse event rate (6%; 95% An analysis of the worldwide experience of transcarotid artery revascularisation CI, 5.4–6.6%) did not differ significantly by training (TCAR) has produced key objective proficiency metrics and an analytic framework mode. In addition, they relay that the proficiency to assess adequate training for the procedure. “Training on cadavers or synthetic measures of cadaver-trained and synthetic modelmodels achieved clinical outcomes, technical outcomes and proficiency measures trained physicians “were not inferior to those for for subsequently performed TCAR procedures similar to those achieved with training the proctored physicians”. The team identified four using traditional proctoring on live cases,” Brajesh Lal (University of Maryland, key proficiency measures for TCAR, namely the Baltimore, USA) and colleagues conclude in the Journal of Vascular Surgery (JVS). mean contrast volume used during the procedure, the fluoroscopy time required for imaging, the CAR is a new hybrid approach to rates between the procedures performed duration of carotid artery flow reversal, and carotid artery revascularisation,” the by physicians after undergoing the three the total skin-to-skin time. authors begin. They note, however, training modes and tested whether the The authors recognise certain limitations that proctored training on live cases is an “effort-, proficiency measures achieved during TCAR of the present study. The retrospective nature time-, and resource-intensive approach to learning after training on cadavers and synthetic of the analysis was subject to selection bias, new procedures”. Against this backdrop, Lal et al models were non-inferior to proctored they acknowledge. However, they stress analysed the worldwide experience with TCAR training. that the clinical and technical composite Brajesh Lal to develop objective performance metrics for the Lal et al communicate that, in the period outcomes were similar to those reported procedure and compared the effectiveness of training 3 March 2009 to 7 May 2020, 1,160 from prospective studies. Another limitation physicians using cadavers or synthetic models to physicians underwent proctored (19.1%), cadaverthey highlight was the fact that trainees were not traditional in-person training on live cases. based (27.4%) and synthetic model-based (53.5%) randomised to the three study groups, nor to a noThe researchers describe how physicians TCAR training and subsequently performed 17,283 training control group. underwent one of three mandatory training TCAR procedures. “The present study is one of the Lal and colleagues conclude that the analytic programmes: in-person proctoring on live TCAR largest to analyse the clinical and technical outcomes approach outlined in their paper provides a procedures; supervised training on human cadavers; stratified by training mode,” the authors note in the “roadmap” to evaluate the effectiveness of training and supervised training on synthetic models. Lal discussion of their findings. The proctored physicians approaches for new technologies and surgical and colleagues then compared the adverse event treated younger patients and more patients with techniques in the future.

“T

Issue 45 | March 2022

Robotics 13

Few cases and short timeframe required to overcome learning curve with robot-assisted carotid artery stenting A RETROSPECTIVE ANALYSIS OF A prospectively maintained database has found that robot-assisted carotid artery stenting (CAS) is both safe and effective. Writing in Neurosurgical Focus, the analysis’ authors also state that the learning curve for robotic procedures was overcome within a short period of time and with relatively few cases at their highvolume cerebrovascular centre.

Fadi Al-Saiegh (Thomas Jefferson University Hospital, Philadelphia, USA) and colleagues undertook this research to evaluate the operational learning curve for CAS procedures with the CorPath GRX roboticassisted system (Corindus/Siemens Healthineers).

Their analysis was conducted at a single institution—Thomas Jefferson University Hospital— from December 2019 to June 2021 and identified 14 consecutive patients who underwent CAS over this time period. The metrics for proficiency they used were total fluoroscopy and procedure times, contrast volume

used, and radiation dose. And, in an effort to evaluate operator progress, patients were divided into three groups based on the study period.

All 14 patients received balloon angioplasty and stent placement, and their median degree of stenosis was 95%, the authors report. Ten of these patients (71%) were operated on via the transradial approach and four (29%) underwent a transfemoral approach— with all of the procedures ultimately being completed successfully. No procedural (technical- or access siterelated) complications were observed, and the median length of hospital stay was 4.5 days.

Discussing their results, Al-Saiegh et al state that the median contrast volume used was 80ml and the median radiation dose was 38,978.5mGy/cm2. The overall median fluoroscopy and procedure times were 24.6 minutes and 70.5 minutes, respectively. The authors also note that subgroup analysis showed a significant decrease in these times from 32 minutes and 86 minutes, respectively, in group one and to 21.9 minutes and 62 minutes, respectively, in group three.

“As with any new technology or technique, there is a learning curve to overcome,” they add. “Our results showed a statistically significant decrease in fluoroscopy time between the first five robot-assisted carotid artery stents and the last five. A similar, statistically significant decrease in procedure time was noted as well.”

The authors further note that a trend towards reduced

Why robotics holds the key to the future of stroke treatment Vitor Pereira Nicole Cancelliere Comment & Analysis Vitor Pereira and Nicole Cancelliere (St Michael’s Hospital, Toronto, Canada) outline recent breakthroughs in the deployment of robotics for neurointerventional procedures and discuss future use indications for these technologies within stroke treatment.

ALTHOUGH USE OF ROBOTICS in surgery is not a new concept, its application in neurointerventional surgery is very recent. On 1 November 2019, our team (Pereira et al) performed the first robotic-assisted neurosurgical procedure in the world, and we have since built the largest case series globally. The one-year follow-up imaging and clinical results from the initial case series was recently published in the Journal of NeuroInterventional Surgery—demonstrating the safety and efficacy of the system for intracranial aneurysm treatment.

Regarding the benefits of the current system, it is incredibly precise, and the operator can comfortably perform the procedure from a seated position without the need for a heavy X-ray protective suit and with a close-up view of the screens enhancing visualisation of the anatomy.

The team is using a robotic system called the CorPath GRX (Corindus/Siemens

Healthineers), which is currently the only robotic system clinically approved for neurovascular interventions.

The operator controls the robot from a controller in a lead-shielded cockpit or from the angio control room, while the bedside team—with a specialised robotic technologist—exchange devices into the robot and manage the patient. The system allows for millimetric control of one microcatheter and one microwire.

Although this is sufficient to perform most of the intracranial steps of an aneurysm repair, such as a stent-assisted coiling or flow diverter placement, the system will need to be developed further before it can be used in acute ischaemic stroke.

Endovascular treatments for acute ischaemic stroke In 2015, the results of five randomised controlled trials showed that a mechanical thrombectomy, or

radiation dose and contrast volume—albeit not a statistically significant one—was seen, signifying quicker procedures and a favourable learning curve that can be overcome with continued use. They emphasise the importance of incorporating CorPath GRX into neuroendovascular fellowship training “whenever possible”, due to its numerous advantages, but add that future studies are key to consolidating these findings.

Speaking to NeuroNews following publication of this study, Al-Saiegh pointed out that robotics could play a major role in the future of endovascular surgery—particularly in remote stroke care, where timely procedures like mechanical thrombectomies can be performed robotically by an off-site operator.

“Technical difficulties and regulatory challenges have yet to be overcome; however, this is the first step to remote, robotic-assisted stroke care,” he added.

Technical difficulties and regulatory challenges have yet to be overcome; however, this is the first step to remote, robotic-assisted stroke care.”

endovascular therapy (EVT), is the most effective treatment for large vessel occlusions causing acute ischaemic stroke. Across all trials, the single-most important indicator for good patient outcomes was time between symptom onset to reperfusion. The faster a patient receives EVT to remove the blood clot in the brain, the better the chance of survival and good neurological outcomes—hence “Time is Brain”.

Comprehensive stroke centres, which provide this life-saving procedure, are typically located in urban centres as highly specialised expertise is available.

It is virtually impossible to have a fully trained neurointerventionist team in all remote hospitals. For this reason, there is a large inequity in access to stroke care for patients living in rural communities.

More than half of the people living in North America do not have timely access to EVT, and thus are at a significantly higher risk of neurological impairment or death if they have a stroke.

Remote robotics and equal stroke care access for rural communities

Our team is working towards building a future where the operator in an urban city like Toronto will be able to perform an EVT procedure for stroke in a rural Canadian city using telerobotics.

There will certainly be challenges, but that is what makes the work we do so exciting. As part of the robotic research programme at the RADIS Lab, we have led over 200 experiments to develop the techniques and approaches used for robotic intracranial aneurysm procedures performed today.

Various themes will need to be addressed to make the leap from the current system to remote robotic stroke treatment. Although the CorPath GRX system has been used to perform long distance telerobotic-assisted

percutaneous coronary interventions, a newer generation of the robot—which gives the operator complete control from the access site to the brain—will need to be developed to make this goal of remote stroke treatment a success.

There has previously been some uncertainty expressed towards remote stroke treatment but, to allay these concerns, we are preparing the landscape well in advance. From system hardware, software, and connectivity, to legal and ethical concerns, we are considering it all. We believe it is not a matter of ‘if’ but rather ‘when’ it will happen. The problem is huge, and the benefits are massive. We will have to do the same as we did with stroke EVT treatment— show the benefit, and that will drive the change.

References: References for this article are available online and can be viewed at neuronewsinternational.com/roboticsneurointerventional-surgery-stroke-treatment-future/.

Vitor Pereira is a neurosurgeon and professor of Medical Imaging and Surgery at the University of Toronto in Toronto, Canada. He is specialised in endovascular neurosurgery, and treating complex neurovascular diseases of the head and spine. His research group, the RADIS Lab, at St Michael’s Hospital, is working to create innovative approaches in the field of neurointervention.

Nicole Cancelliere is the neurovascular research programme manager at St Michael’s Hospital in Toronto, Canada, and works as a medical radiation technologist specialised in neurointerventional and robotic-assisted procedures. She is also co-lead of the RADIS Lab, together with Pereira, at the St Michael’s Li Ka Shing Knowledge Institute.

Disclosures: The authors declared no

relevant disclosures.

March 2022 | Issue 45

14 Flow Diverters

INNOVATION

Latest data reinforce evidence on safety and effectiveness of Contour intra-aneurysmal flow diverter Fresh data from the CERUS study—the first multicentre clinical trial evaluating safety and effectiveness outcomes with the Contour neurovascular system (Cerus Endovascular)—have indicated “encouraging results” in the treatment of unruptured intracranial bifurcation aneurysms.

R

eporting these results in the journal Neurosurgery, Thomas Liebig (Ludwig Maximilian University of Munich, Munich, Germany) and colleagues also note that the latest Contour findings compare favourably to existing studies on intrasaccular devices—especially those involving conventional therapies for wide-neck bifurcation aneurysms (WNBAs).

The authors begin by noting that endovascular procedures have become the standard of care in certain anatomic locations and geometries, with the Contour device recently joining the Woven EndoBridge (WEB; Microvention) and LUNAAED (Medtronic) technologies on the list of intrasaccular flow disruptors used in these procedures.

However, they add, an important distinction here is that Contour is a planar braid entirely positioned at the neck of the aneurysm, while WEB and LUNA have spherical braids that fill the aneurysm dome.

CERUS study

The CERUS study is a single-arm, prospective, multicentre clinical trial designed to evaluate the procedural, short-term and midterm safety and effectiveness of Contour in unruptured saccular bifurcation aneurysms. In light of positive sixmonth follow-up results from the study, which were presented at the 2020 ABC-WIN seminar (13–17 January; Val-d’Isère, France), the device was granted European CE-mark approval in 2020.

The study was conducted at six European sites in Austria, Denmark and Germany. Inclusion criteria were as follows: untreated; 18–80 years of age; aneurysm unruptured; 2–8mm neck; and no adjunctive devices (except bailout). Primary endpoints of the CERUS study included technical success, occlusion at six months, and death or disabling stroke within 30 days and at six months, while occlusion at 12 months, instrumentation time, number of deployment attempts, and retreatment rate, were among its secondary endpoints.

Liebig and colleagues report that procedures in the study were performed under general anaesthesia on biplane angiosuites through a transfemoral approach, with a total of 34 patients (mean age=58 years; 19 males [55.9%]) being recruited for treatment with Contour between October 2018 and July 2019.

Recapping initial procedural data, they state that technical success was achieved in 32 of these patients (94%)—while two patients in the study’s intentionto-treat group were not implanted with the Contour device and excluded from follow-up after 30 days.

In 21 patients (66%), the device was implanted and detached at the first attempt and, in 11 patients (34%), it was deliberately retrieved and redeployed or

replaced with a different size. Instrumentation time ranged from five to 67 minutes (mean time=19.8 minutes), they add.

Twelvemonth data

The primary safety endpoint of death or disabling stroke within 30 days/at six months was met in two patients in the study’s intention-to-treat group, and in one patient in the per-protocol group. At 12 months, 30 of 32 patients in the per-protocol analysis had a modified Rankin Scale (mRS) score of zero. One patient entered into the study with an mRS score of two, and remained stable throughout, and another patient with an mRS score of zero at six months had no entry for the 12-month follow-up, Liebig and colleagues report.

Contour

SAFETY AND EFFICACY OUTCOMES mRS score of zero at

12 months (per-protocol analysis)

Complete occlusion at

12 months

Adequate occlusion at last available follow-up

94% of patients

69% of patients

84% of patients

Discussing these findings further, the authors note two procedural serious adverse events in the study, both of which were unrelated to Contour but instead attributed to the general risk of treatment.

They also observed two Thomas Liebig treatment-related minor strokes for which symptoms were resolved at the next follow-up visit. As such, Liebig and colleagues write: “Overall, the safety profile of the Contour is acceptable and most likely comparable with other endovascular treatment options.”

Regarding efficacy outcomes, complete occlusion was seen in 14 of 32 patients (44%) at six months and 22 of 32 (69%) at 12 months. Adequate occlusion, measured as one or two on Raymond-Roy occlusion classification, was reached in 84% of patients at the last available follow-up. The authors note that these results are “comparable with multicentre trials on WEB and thus superior to those of conventional therapies for WNBAs”. In the CERUS study, one patient from the intention-to-treat group and one from the per-protocol group received additional treatment during follow-up, they add.

Wider implications

Liebig and colleagues also provide a number of key pieces of context in their report, including the fact that 30 patients were imaged at six months, compared to 21 at 12 months, with patients who were unavailable to perform the 12-month follow-up having their six-month occlusion status carried forward. In addition, they note that completeness of follow-up was interfered with by the COVID-19 pandemic, as some 12-month follow-up visits fell within the first lockdown period and could only be performed by remote interview.

The authors report that there was no lead-in phase for the trial—meaning none of the operators had previously used the Contour device in a patient—and patient selection was performed without interference from Cerus Endovascular. “This has to be kept in

Overall, the safety profile of the Contour is acceptable and most likely comparable with other endovascular treatment options.” mind, especially when comparing the results with those of other studies,” they add.

The main limitations of the CERUS study, Liebig and colleagues write, are its small sample size, nonrandomised nature, and the fact patients were not excluded because of poor pretreatment clinical status or partial aneurysm thrombosis. However, there was also no case selection process in place, according to the authors, which they suggest represents a more realistic scenario and might make the results reproducible outside of a study setting.

“Further systematic evaluation is warranted in light of possible future iterations of the study device [Contour] and to better understand its full potential,” they conclude.

March 2022 | Issue 45

16 Interview

PROFILE

Michael Chen Michael Chen—a neurointerventionist and professor of Neurology, Neurosurgery and Radiology at Rush University Medical Center in Chicago, USA—speaks to NeuroNews to provide insight on his career, the ever-evolving world of neurointervention, and also his role in ongoing efforts to optimise USA-wide stroke triage and transport protocols as president of the Society of NeuroInterventional Surgery (SNIS).

My father was an obstetrician-gynaecologist (OBGYN), so I saw first-hand the life of a physician who takes call from an early age. Neurology fascinated me because each patient seemed like a mystery to be solved. Success depended on attention to detail, knowledge, and being thoughtful. I was taught early on that an accurate diagnosis was one of the most important things you could do to help a patient. But, what neurointervention also offers is a chance to directly provide therapies using your own abilities as a technician—to, at times, profoundly improve the lives of patients. Hence, neurointervention to me represented a series of worthwhile, fascinating and challenging mysteries.

Who have your mentors been and how have they impacted your career?

I have been blessed to have trained alongside inspiring teachers, including the late Lawrence Brass while I was at Yale, Louis Caplan while I was at Beth Israel Deaconess, and Philip Meyers, John Pile-Spellman and Sean Lavine while at Columbia. Being able to observe specific ways each of them practiced medicine influenced my mindset, habits and values in a profound way that has persisted after many years. Now, I am also fortunate to continually learn from my many colleagues on the board of SNIS and the Journal of NeuroInterventional Surgery, as well as my partners, Webster Crowley and Stephan Munich.

What has your experience been as the president of the Society of NeuroInterventional Surgery?

The experience so far has been one of paying attention, lots of phone calls/meetings, and really just a greater appreciation for all the enthusiasm, hard work and dedication among the staff, board of directors and active members. As such, I have felt, this year as president, a real responsibility to serve SNIS with leadership that is thoughtful, growth-oriented and patient-focused. It is a unique experience— not something I feel completely at ease with, but something that I am committed to, passionate about and fortunately I have many colleagues on the board to help with the more difficult decisions.

How have you attempted to advance minimally invasive surgery and endovascular stroke care during your tenure as SNIS president?

By balancing the competing needs of multidisciplinary growth with the essential principles of prioritising patient care. There have been a few recently published retrospective studies showing self-adjudicated outcomes to be similar regardless of one’s training background, with the over-reaching extrapolation being that cardiologists and interventional radiologists should be performing stroke thrombectomy. This type of analysis misses the point. The importance of one’s training background, which recedes further back every year, pales in comparison to the importance of

whether one is, in fact, well-trained. Being well-trained requires a knowledge base, practice and takes time.

Shortcuts in training are short-changing the patient.

Hence, one of my main priorities in this role has been trying to steer these conversations away from being too preoccupied about one’s speciality and more towards what it takes to be a truly effective, patientfocused neurointerventionist. This is not easy, but the more the community can work together to achieve this—instead of worrying so much about one’s training background—the faster we can progress as a field.

Why is the Get Ahead of Stroke campaign needed, and what are its main goals?

Get Ahead of Stroke is a national public education and advocacy campaign designed to improve systems of care for stroke patients in the USA. Founded in 2016 by SNIS, today the campaign is supported by a coalition of organisations with the goal of securing the best possible outcomes for stroke patients by driving policy change and public awareness nationwide.

Specifically, the campaign’s focus has been, at a state level, on facilitating legislation that improves severe stroke triage to hospitals that perform thrombectomy, as well as educating first responders on the most relevant principles and concepts that guide stroke triage.

Our understanding of how to efficiently triage, treat and measure outcomes is now going through more rapid changes after a long period of stagnation.”

What do you feel has been the most important development in the field of neurointervention during your career?

I have been in practice for 15 years. The only proven treatment for acute stroke when I first started was alteplase. So much investment by different organisations went into hospital certifications, very strict rules (e.g. long list of inclusion and exclusion criteria) and certain preconceived notions that, in and of themselves, served as an impenetrable barrier to thinking about and developing new therapies.

Fortunately, we are seeing the gradual but steady dissolution of these now obsolete concerns, such as the role of elapsed time and even computed tomography perfusion (CTP) as a surrogate marker for salvageable brain. The same goes for using 90-day modified Rankin Scale (mRS) as a universal outcome measure.

Our understanding of how to efficiently triage, treat and measure outcomes is now going through more rapid changes after a long period of stagnation. This paradigm change is so essential to the progress in acute stroke therapies our patients need.

alisonlang.com

What initially attracted you to medicine, and the field of neurointervention specifically?

What is the most significant unmet need in neurointervention right now?

Large vessel ischaemic stroke affects an order of magnitude more people than all other conditions treated with neurointervention. Yet, most patients, despite blood flow restoration with thrombectomy, end up with significant disability and/or death. Therefore, the most significant unmet need is optimising access to thrombectomy, much like trauma, such that first responders can accurately and efficiently determine stroke severity and triage them to hospitals that can perform thrombectomy. Meaningful improvement in access to thrombectomy would be the single most effective measure to reduce the burden of emergent large vessel ischaemic stroke. This is not an easy problem to solve—but doing so would be extremely powerful in meaningfully reducing the burden of stroke on society.

Issue 45 | March 2022

Interview 17

Besides your own work, what is the most interesting piece of neurointervention research you have seen in the past year?

The most important bottleneck currently in delivering thrombectomy to large vessel stroke patients is access to treatment. Artificial intelligence software that expedites the interpretation of a head computed tomography angiography (CTA) in a stroke patient holds so much promise to decrease the latency to thrombectomy treatment. You no longer have to wait for an emergency room physician or on-call radiologist to interpret the image and notify the thrombectomycapable hospital. Once the images are acquired, the rest is taken care of automatically. There has been widespread adoption of this technology, which is becoming more refined to improve accuracy and efficiency of stroke triage in large vessel occlusion.

What advice would you give to people embarking on a career in neurointervention?

Read all the time. Write often. Be humble. Learn from others, including patients and especially other neurointerventionists from different training backgrounds. Do not keep doing the same thing or hanging around the same type of people. Stay away from echo chambers and keep challenging what you think you already know. You may be faced with situations where you can exploit situations for your own financial or egotistical gain. Choosing what the patient needs over these competing forces takes real strength of character and a practised discipline of values. In the book, The Remains of the Day, Kazuo Ishiguro illustrates how butlers maintain focus on their jobs despite a variety of distractions, including insults, indiscretions, and attacks. He summarises by discussing the elite Hayes Society criteria for membership, which to me has relevance to careers in neurointervention. Ishiguro captures the essence of Hayes Society butlers in possessing ‘a dignity in keeping with his position’.

What are your interests outside of the field of medicine?

I am currently trying to recover from a shoulder injury, but I would normally most love to be playing tennis either with my daughter, who plays competitively, or friends. I drive my other daughter around a lot and cheer for her hockey team, the Chicago Young Americans. At home, I enjoy smoking meats— especially beef brisket for family and friends—along with too much red California wine from Hall, Scarecrow and Kosta Browne vineyards. I have also rediscovered the joys of reading good books, ranging from Jack Reacher novels to Michael Lewis, to Dostoyevsky.

Fact file Current appointments

Professor, Departments of Neurology, Neurosurgery and Radiology, Rush University Medical Center, Chicago, USA

Education

2005–2007: Fellowship, Interventional Neuroradiology, Columbia College of Physicians and Surgeons/New York Presbyterian Hospital, New York, USA

2004–2005: Fellowship, Stroke and Cerebrovascular Disease, Harvard Medical School/Beth Israel Deaconess Medical Center, Boston, USA 2000–2003: Residency, Neurology, Yale University School of Medicine, Yale New Haven Hospital, New Haven, USA 1995–1999: Doctor of Medicine, John A Burns School of Medicine, University of Hawaii, Honolulu, USA

Honours (selected)

2021–present: President, Society of NeuroInterventional Surgery 2021–present: Chair, Neurosurgery Research Committee, Rush University Medical Center 2013–present: Commissioning Editor, Journal of NeuroInterventional Surgery 2017–2021: Top Doctors Award, Chicago Magazine/Castle Connolly

Issue 45 | March 2022

Novel Techniques 19

Precise new form of brain surgery requires no incisions or scalpels UNIVERSITY OF VIRGINIA SCHOOL OF Medicine (UVA; Charlottesville, USA) researchers have developed a non-invasive way to remove faulty brain circuits that could allow doctors to treat certain debilitating neurological diseases without the need for conventional brain surgery.

The UVA team, together with colleagues at Stanford University (Stanford, USA), indicate that the approach—if successfully translated to the operating room—could revolutionise the treatment of some of the most challenging and complex neurological diseases, including epilepsy, movement disorders and more.

The approach uses low-intensity focused ultrasound waves combined with microbubbles to briefly penetrate the brain’s natural defences and allow the targeted delivery of a neurotoxin. This neurotoxin kills the culprit brain cells while sparing other healthy cells and preserving the surrounding brain architecture.

“This novel surgical strategy has the potential to supplant existing neurosurgical procedures used for the treatment of neurological disorders that do not respond to medication,” said researcher Kevin Lee (UVA, Charlottesville, USA). “This unique approach eliminates the diseased brain cells, spares adjacent healthy cells and achieves these outcomes without even having to cut into the scalp.”

INNOVATION

The new approach is called PING (precise, intracerebral, non-invasive, guided surgery), and it has already demonstrated exciting potential in laboratory studies, UVA claims. For instance, one promising application for PING could be in the surgical treatment of epilepsies that do not respond to medication.

Approximately one third of patients with epilepsy do not respond to anti-seizure drugs, and surgery can reduce or eliminate seizures for some of them. Lee and his team—along with their collaborators at Stanford— have shown that PING can reduce or eliminate seizures in two research models of epilepsy. These findings raise the possibility of treating epilepsy in a carefully targeted and non-invasive manner without the need for traditional brain surgery.

Another important potential advantage of PING is that it could encourage the surgical treatment of appropriate patients with epilepsy who are reluctant to undergo conventional invasive or ablative surgery.

In a new scientific paper in the Journal of Neurosurgery, Lee and his collaborators detail the ability of PING to focally eliminate neurons in a

Our hope is that the PING strategy will become a key element in the next generation of very precise, noninvasive, neurosurgical approaches to treat major neurological disorders.”

brain region while sparing non-target cells in the same area. In contrast, currently available surgical approaches damage all cells in a treated brain region.

Reporting their results, they write: “Focal neuronal loss was observed in targeted areas of blood-brain barrier opening, including brain regions that are prime objectives for epilepsy surgery. Notably, other structures in the area of neuronal loss, including axons of passage, glial cells, vasculature, and the ventricular wall, were spared with this procedure.”

A key advantage of the approach is its incredible precision, according to UVA. PING harnesses the power of magnetic resonance imaging (MRI) to let scientists peer inside the skull so that they can precisely guide sound waves and open the body’s natural blood-brain barrier exactly where needed. This barrier is designed to keep harmful cells and molecules out of the brain, but it can also prevent the delivery of potentially beneficial treatments.

The UVA group’s new paper concludes that PING allows the delivery of a highly targeted neurotoxin, cleanly wiping out problematic neurons without causing collateral damage. Another key advantage of the precision of this approach is that it can be used on irregularly shaped targets in areas that would be extremely difficult or impossible to reach through regular brain surgery. “If this strategy translates to the clinic,” the researchers write in their recent paper, “the non-invasive nature and specificity of the procedure could positively influence both physician referrals for and patient confidence in surgery for medically intractable neurological disorders.”

“Our hope is that the PING strategy will become a key element in the next generation of very precise, non-invasive, neurosurgical approaches to treat major neurological disorders,” added Lee.

New technology enables option for neurosurgeons to avoid pinning patients’ heads for brain surgery Following the introduction of its BrainPath navigation probe adapter at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA), medical device innovator NICO Corporation claims to have become the first and only provider to offer an adapter for electromagnetic navigation (EM) when performing minimally invasive parafascicular surgery—giving neurosurgeons the option to deploy a frameless brain surgery procedure.

THIS MEANS, ACCORDING to a NICO press release, that appropriate patients will no longer have to be pinned in a rigid headframe during the navigation process, providing a more compassionate, minimally invasive surgery option.

The BrainPath navigation probe adapter for the Medtronic StealthStation EM is used with specific navigation pointers during minimally invasive parafascicular surgery procedures.

This technology further differentiates NICO’s platform solution to provide surgeons more choices and efficiencies in the operating room based on what is

needed for each patient, the release adds.

“The simple and easy operating room setup with frameless stereotaxy and BrainPath helps us get the patient treated in a safe, fast and efficient way,” said Justin Singer (Spectrum Health, Grand Rapids, USA). “I have found this to be a great option for patients where pinning would not be indicated for subcortical tumour removal and beneficial in treating emergent haemorrhagic stroke patients.”

The BrainPath adapter is a sterile, single-use accessory that secures the position of the EM pointer during BrainPath cannulation. It is part of an integrated platform system for

brain surgery that NICO claims “did not previously exist”—providing safe subcortical access to all regions of the brain, automated removal of brain abnormalities, and simultaneous biological preservation of collected tissue for use in the delivery of novel therapeutics and potential implantation to the brain.

In its limited market evaluations, involving more than 20 cases, surgeons reported the navigation probe adapter as “ideal” for emergent intracerebral haemorrhages (ICH), traumatic ICH and subcortical tumours, citing seamless integration in the operating room and workflow efficiencies, the release also notes.

I have found this to be a great option for patients where pinning would not be indicated for subcortical tumour removal and beneficial in treating emergent haemorrhagic stroke patients.”

Issue 45 | March 2022

NeuroMODULATION New 18-month data show durability of high-frequency SCS for painful diabetic neuropathy

Erika Petersen presents at NANS 2022

This year’s North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA) saw 18-month data from SENZA-PDN—a randomised controlled trial (RCT) evaluating the safety and efficacy of high-frequency spinal cord stimulation (SCS) in painful diabetic neuropathy (PDN) patients—disclosed for the first time. Erika Petersen (University of Arkansas for Medical Sciences, Little Rock, USA) presented these findings, stating that they build on previously published data from the study and demonstrate the durability of this novel, paraesthesia-free treatment option for PDN.

P

etersen, who is also the principal investigator for the SENZA-PDN trial, began by alluding to prior data from this study, stating that six-month results were published in JAMA Neurology in April 2021 and 12-month results were recently published in Diabetes Care. She also referenced “relatively underwhelming” existing treatments for the millions of Americans currently living with PDN. With this in mind, an RCT was conducted prospectively across 18 US centres to evaluate high-frequency SCS with the Senza system (Nevro) in PDN patients. Petersen reported that 216 patients were enrolled and underwent 1:1 randomisation to receive either conventional medical management (CMM) or 10kHz stimulation plus CMM. On the study’s design, Petersen told the NANS audience that its primary endpoint was chronic pain reduction, as per visual analogue scale (VAS) scores, but that neurological function and quality of life measures were assessed too.

In SENZA-PDN, patients were also offered the option to cross over from one study arm to the other if they did not have a successful response to their assigned treatment at six months—with 77 patients (93% of those eligible) ultimately opting to move from CMM to 10kHz SCS plus CMM at six months due to being non-responders (<50% pain relief). Sixty of these crossover patients completed the 18-month followup, giving a “sizeable cohort” when combined with the 84 patients originally randomised into the stimulation group.

Reporting safety outcomes over 18 months, Petersen said there were no explants of the Senza device due to lack of efficacy in this time, but noted five explants were required due to infection, resulting in an infection explant rate of 3.2%—a figure that is comparable to those seen in published literature on SCS in patients without diabetes.

“Infection remains the most common adverse event that we see with SCS procedures,” she said, also relaying no stimulation-related neurological deficits at 18 months and three implantable

pulse generator revisions due to site-related pain.

Moving on to discuss pain reduction in the study, Petersen reported a “dramatic change” on this front, detailing a precipitous decline from baseline in patients in the original stimulation arm, which was maintained at 18 months. “As soon as they have access to SCS, the pain scores in our crossover population drop as well—and they do not drop at a different proportion,” she added. “They drop to exactly where our original stimulation arm drops to.” Petersen stated that, overall, there was an 85% responder rate (>50% pain relief), as well as the average rate of pain relief being 73% and the rate of remission—patients whose VAS pain score was less than three and stayed that way for six months, continuously— being 68%.

Petersen then noted that the number needed to treat in SENZA-PDN’s stimulation arm was 1.3, comparing favourably to the same measure in pharmacological studies involving PDN patients. “This is certainly an efficacy level that I think is worth considering due to some of the sideeffects that we see on medication,” she added.

In addition, Petersen said comparisons between the two study arms showed there were fewer hospital visits per 100 patients at both six months and 12 months in the stimulation arm, adding that “there is an indication here that this may be a cost-effective way to improve the quality of care for patients with refractory diabetic neuropathy”.

Petersen also noted, however, that further, large-scale analysis is required to confirm these early indications.

“In conclusion, this is the largest randomised controlled trial of SCS for PDN that has ever been performed,” she claimed. “Our primary endpoint at three months showed safety and efficacy, and what we show today is durability, as it remains safe and effective [at 18 months].”

Petersen added that the trial met seven of its eight secondary endpoints too, with data now being collected for the study’s 24-month endpoint as well.

There is an indication here that this may be a cost-effective way to improve the quality of care for patients with refractory diabetic neuropathy.”

21

NIH launches US$9.8 million competition to accelerate development of neuromodulation therapies THE NATIONAL INSTITUTES OF Health (NIH) has launched the first phase of the Neuromod Prize—a US$9.8 million competition to accelerate the development of neuromodulation therapies. The competition seeks scientists, engineers and clinicians to submit novel concepts and clinical development plans demonstrating solutions for precisely stimulating the peripheral nervous system to treat disease and improve human health.

The first phase of the competition will award up to US$800,000, and a judging panel will select as many as eight quarterfinalists to receive a share of this first-phase prize pool.

The NIH also plans to launch a second phase awarding up to US$4 million— anticipated to take place starting in 2022—and a third phase awarding up to US$5 million, subject to the availability of funds, expected to begin in 2023.

Phase-one quarterfinalists will be exclusively invited to participate in the second phase, which will translate their winning ideas into preclinical studies.

Semifinal winners will then be eligible to compete in the final phase, moving their preclinical work into advanced translational and clinical studies as a “critical step towards the regulatory approvals needed to bring new neuromodulation therapies to market”, according to an NIH press release.

“Through the Neuromod Prize, we are asking potential solvers to use the foundational knowledge and technologies that have come out of our SPARC [Stimulating Peripheral Activity to Relieve Conditions] programme, and take it to the next level with their innovative concepts and ideas,” said ​​ James Anderson, director of the Division of Program Coordination, Planning, and Strategic Initiatives, which oversees the NIH Common Fund. “This competition is an exciting opportunity to come up with tangible plans for harnessing the power of the body’s electrical system to help transform treatments for millions of people living with chronic or acute illnesses.”

Phase-one participants will submit concept papers describing proposed therapeutic approaches and plans for conducting proof-of-concept studies, rationales for therapeutic use, and expectations for clinical impact, with submissions due by 28 April 2022.

22

NeuroMODULATION

March 2022 | Issue 45

Lower frequencies may improve outcomes of pain treatment with dorsal root ganglion stimulation Lower frequencies of dorsal root ganglion stimulation (DRG-S) may be more effective in the treatment of neuropathic pain—as per a late-breaking presentation from Guilherme Santos Piedade (University of Düsseldorf, Düsseldorf, Germany) at this year’s North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA).

PIEDADE RELAYED THE RESULTS OF A randomised clinical trial in which several levels of DRG-S frequency, from 20Hz to 80Hz, were assessed in patients with various pain aetiologies. A number of measures including pain intensity, quality of life and depression were used by the investigators to evaluate the effectiveness of DRG-S therapy.

“In this study, lower stimulation frequency— as low as 20Hz—was able to treat patients with neuropathic pain more effectively,” Piedade told the NANS audience. “And, we are already doing [further] studies to record and document the effect of even lower stimulation frequencies. We think that it is very important to consider battery lifetime, but we are also excited by the idea that we can target different neurocomponents of the DRG with different stimulation frequencies.”

Piedade began with a nod to previous studies in this

Telehealth to play key role in improving patient access to neuromodulation therapies COVID-19 MAY HAVE HELD a defining role in the “rebirth” of telehealth and remote care models in the USA, but their utility in improving patient access to neuromodulation therapies looks set to extend far beyond the global pandemic. This was a key message delivered by Vwaire Orhurhu (University of Pittsburgh Medical Center, Williamsport, USA) at the 25th North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA).

Orhurhu began his presentation by noting that “healthcare is changing”— adding that this change was accelerated by the outbreak of COVID-19 and will most likely lead to greater variation in the delivery of care. However, he continued—while their usage was more limited prior to the global health crisis—telehealth and telemedicine have been around for decades, with prior research demonstrating that they can enable effective diagnoses and treatments to be performed remotely.

space, which have alluded to the effect DRG-S “It is very curious to see that, for patients frequency can have on therapy outcomes. As with a painDETECT questionnaire [PD-Q] such, he and his colleagues conducted what score lower than 12—meaning that they is—to the best of their knowledge—the first have a strong nociceptive component—the randomised, double-blinded trial to directly frequency had no real effect over stimulation assess this link regarding DRG-S. on pain intensity scores,” he continued.

They enrolled 19 patients (mean age=53 “Unfortunately, we only have five patients Guilherme years) who had already been receiving DRG-S in this situation, so we could not achieve Santos for a mean total of 17.2 months. Notable statistical significance here, but it is still a very Piedade pain aetiologies included complex regional interesting find.” pain syndrome (CRPS, n=7), postsurgical pain after In addition to the statistically significant difference arthroplasty (n=4) and postherpetic neuralgia (n=3). in pain intensity scores between 20Hz and 40Hz, Frequencies of 20Hz, 40Hz, 60Hz and 80Hz, as Piedade claimed that the same trend was seen in well as a sham stimulation protocol, were tested in the every other outcome measure used in the study. study, with stimulation lasting for four days prior to a “Higher frequencies led to worse quality of life, and two-day washout period. Each patient was followed for worse scores on McGill pain questionnaire and Beck a total of five weeks, using the visual analogue scale depression inventory,” he stated. “We must say that this (VAS) for pain intensity, the McGill pain questionnaire, effect was not always statistically significant—as seen quality of life measures, and the Beck depression in pain intensity scores—but the trend is surely there.” inventory, to assess DRG-S outcomes.

Speculating on the reasons behind these findings, Prior to disclosing results from the study, Piedade Piedade referred to the phenomenon of ‘phase locking’, also noted a couple of “very important” points, with which has been outlined in previous DRG-S literature, the first being the fact that DRG-S was amplitude and can only occur up to a frequency of 20Hz. corrected for each of the tested frequencies, so that Assessing the study itself in more depth, the speaker every patient was stimulated at a subthreshold level said that a washout period of two days was adequate each week. Secondly, he detailed that every patient was for assessing pain control, but not for autonomic undergoing DRG-S at a standard frequency of 20Hz symptoms, and future studies involving CRPS could before the study was initiated. therefore benefit from longer washout periods. He Piedade reported a baseline VAS score of 3.9— added that the study was strengthened by the fact which was similar to the mean score of 3.7 achieved it included multiple pain aetiologies—creating an with 20Hz in the study itself. He went on to note an inhomogeneous group—but it was “underpowered” increase in patient VAS scores at 40Hz, to 4.9. “And, to show a statistically significant difference between when you increase the frequency even more, to 60Hz PD-Q scores above and below 12. and 80Hz, you see that patients get worse and achieve Piedade concluded by noting that it would also be pain intensity scores of 5.8,” he added. Piedade noted “very interesting” to see if there are differences in a pain intensity score of 8.6 with sham stimulation, the effect of stimulation frequency over different pain which was close to the pre-implantation VAS score aetiologies like CRPS, and stated that larger studies in observed within retrospective patient data. this space would be valuable moving forward.

Orhurhu referred to existing medical literature in this space, reporting a 94% reduction in wait times, from 72 to four days, on average, when comparing telehealth to more established approaches involving visits to the clinic.

He also pointed to another benefit—a reduction in the number of steps needed to successfully deliver care to the patient—and the fact neuromodulation therapy outcomes for both pain and function have been shown to be comparable to those achieved with inperson models.

As well as noting that the outbreak of COVID-19 “precipitated the rebirth” of telehealth, Orhurhu pinpointed the expansion Vwaire of telehealth under the Orhurhu US Centers for Medicare & Medicaid Services (CMS) 1135 waiver in March 2020 as the moment when physicians began rethinking patient access, due to increased reimbursement and redefined complexity in the use of telehealth being offered under the waiver.

Orhurhu then outlined a number of leading models for implementing telehealth into medical practice: the largely clinical data-focused ‘store and forward’ approach; the more strippeddown ‘direct contact consultation’ model that attempts to drill down and

determine which patients truly require in-person consultations; and the ‘direct contact hub and spoke’ model in which clinicians can create networks of patients or fellow care providers, and directly engage with and impact them by deploying telehealth.

The fourth and final model he focused on is known as the ‘direct contact home base’ model—which is currently the most well-known and commonly used telehealth framework, and involves the clinician directly engaging with and advising their patients while they are at home.

“The reason I bring this up is because the other models are not as well-utilised, as people do not talk about them as much,” Orhurhu added. “But, when we talk about neuromodulation and how we can deliver care to our patients, I do think these models play a key role.”

In addition, he highlighted guidance from the American Academy of Pain Medicine that was released in 2020 and supplied information on which patients may be considered “red flags” that should not be considered as telehealth candidates. This guidance also indicated the most appropriate contexts in which telehealth could be appropriate, including coordination of referrals, discussions of imaging

results, non-controlled medication management, and post-procedure care, in established follow-up patients.

Orhurhu then provided a handful of tips for physicians wanting to implement any of the four major telehealth models into their neuromodulation practice. Crucially, he said, they should ensure their platform is Health Insurance Portability and Accountability Act (HIPPA)-compliant.

“Initially, when telehealth first got off the ground, there was a lot more leniency towards it because it was an emergency and patients had to be seen—but there are much stricter guidelines now,” he added.

Other pointers he relayed included the need to establish a process for using telehealth and ensuring medical teams understand that remote consultations are still clinical visits, and should be treated as such.

Orhurhu further highlighted the importance of maintaining good patient communication, as well as staying on top of the latest regulatory and reimbursement policies, which are everchanging.

“Every company out there with a neuromodulation platform is beginning to talk more and more about this,” Orhurhu concluded. “So, I always encourage my colleagues to reach out and see what else is out there that can be applied to their patient population at this time.”

NeuroMODULATION

Issue 45 | March 2022

Artificial intelligence, cost reductions and more represent bright future for neuromodulation industry Marc Russo Comment & Analysis On technological and commercial fronts alike, the neuromodulation space is one of the more rapidly evolving subsectors within the medical industry—and has undergone a remarkable period of growth in the past couple of decades. With this progress showing little sign of slowing any time soon, Marc Russo (Hunter Pain Specialists, Newcastle, Australia) assesses the current landscape in brain stimulation therapies, and provides a glimpse of what the future may yet hold.

W

hen I think back over the history of neuromodulation, I marvel at several things.

Firstly, how quickly theory became reality after the Gate Control Theory of Pain was published and Norman Shealy’s pioneering first implant.1,2 Secondly, how slowly things moved for a generation of physicians as incremental progress was made on adding contacts, shrinking batteries, decreasing device failures, and identifying responder patients. Thirdly, how progress has exploded over the last 15 years with the arrival of multiple new neuromodulation companies— spearheaded by Nevro Corporation, founded by Konstantinos Alataris in 2007—as well as sophisticated models of neural transmission that have

In spinal cord stimulation and deep brain stimulation, we are seeing complex waveforms better interface with the nervous system at the same time as the patient’s experience with their device interaction becomes much more seamless and naturally intuitive.”

informed waveform development. This process is continuing to play out.

As of 2022, we have companies in this space with multiple waveform patterns, waveforms to stimulate neurones and glial cells in concert, energy-efficient waveforms that allow primary cell pulse generators, closedloop monitoring of spinal cord electrical compound action potentials, ultralow frequency waveforms, ultra-high frequency waveforms, and battery-less pulse generators.3 There is not space to elaborate on all the potential and the deliverables that they offer patients.

The common theme from the above is a desire to understand the neurophysiology of pain, of spasticity, of gait disorders and of motor weakness, and to harness that knowledge into building waveforms and devices that efficiently and successfully interact with the nervous system to inhibit or augment nerve signalling to achieve the clinical ends. Where once we forced the nervous system to respond to tonic (repetitive and unvarying) square waves, because it was easy to see on an oscilloscope and easy to build into a pulse generator, we now accept and embrace complexity to achieve our targets.

In spinal cord stimulation (SCS) and deep brain stimulation, we are seeing complex waveforms better interface with the nervous system at the same time as the patient’s experience with their device interaction becomes much more seamless and naturally intuitive. I am glad that Apple and Google train so many engineers, because some of them end up in the neuromodulation space and bring their concepts of ‘lifestyle experience’ into the design ecosystem.

A second major development in this field is understanding where we are helping or hindering our patients by their adjuvant treatment. Nissen et al have shown that opioids (morphine

>40mg/day) increase the explant rate of SCS, while drugs that decrease central sensitisation (i.e. augment descending inhibition) decrease explant rates of SCS.4 The figure can swing from worst-case 30% explants to bestcase 0% explants depending on just these two factors. I think it likely that understanding how the endocannabinoid system interfaces with neuromodulation devices may refine this further.

We are also in the ongoing process of moving neuromodulation from its traditional cottage industry of relatively isolated practitioners doing low-volume implants to integrated high-volume centres of excellence with evaluation, implant, holistic optimisation, and functional rehabilitation, audit, research and publishing. This will yield improvements as big as (or more so) addressing the technology shortfalls.

The International Neuromodulation Society is very much engaged in this area through both Neurostimulation Appropriateness Consensus Committee (NACC) and Polyanalgesic Consensus Committee (PACC) articles, and Centers of Excellence development programme.5 Lastly, the elephant in the room for which we hold much promise in—machine learning or artificial intelligence being designed into devices.

Independent thinking software running the hardware (within defined limits) combined with input from the patient (in a bewildering variety of inputs, some non-intuitive) as well as with meta data analysis of thousands/millions of patient inputs and outputs held in the cloud; where will these lead to? That is hard to say, but the devices I cut my teeth on in the 1990s will be seen as the electronic version of rubbing two sticks together.

I have both high hopes for and great faith in what is to come for neuromodulation as we traverse the 2020s. Devices are improving at

Figure 1. Exponential growth of computing for 110 years

by Kurzweil (2010)

23

something beyond a linear rate. Medical provider and patient awareness of therapy is improving, albeit not as fast as we would like. Third-party payers are gradually seeing the cost-effectiveness data come through that they need to see to support the therapy (why did the field ignore this aspect for so long, I wonder?), and governmental and regulatory bodies are seeing the unique solutions that this therapy can provide across multiple refractory conditions.

Is there anything here that is the odd man out? Well, Moore’s Law reinterpreted by Ray Kurzweil states that cost should come down as computing power goes up over time.6 I think to a certain extent neuromodulation is a bit of a holdout in regards to that and I predict that, over time, we will see it follow Kurzweil’s graph (Figure 1) and cost reduction will be the next frontier to be crossed in our area.

References: 1. Melzack R, Wall P D. Pain mechanisms: a new theory.

Science. 1965; 150(3699):971-9.

2. Shealy C N, Mortimer J T, Reswick J B. Electrical Inhibition of Pain by Stimulation of the Dorsal Columns. Anesthesia & Analgesia. 1967; 46(4):489-91.

3. Provenzano D A, Heller J A, Hanes M C. Current Perspectives on Neurostimulation for the Management of Chronic Low Back Pain: A Narrative Review. Journal of Pain Research. 2021; 14:463-479.

4. Nissen M, Ikäheimo T M, Huttunen J, et al.

Gabapentinoids Associated With Lower Explantation Rate in 203 Patients With Spinal Cord Stimulation for Failed Back Surgery Syndrome. Neurosurgery. 2021; 89(4):626-634.

5. International Neuromodulation Society Committees. https://www.neuromodulation.com/ins-committees.

Accessed 7 February 2022.

6. Kurzweil R. The Age of Spiritual Machines: When Computers Exceed Human Intelligence. New York, Viking, 1999.

Marc Russo is the director of Hunter Pain Specialists in Newcastle, Australia and current president of the International Neuromodulation Society (INS).

Disclosures: The author declared no

relevant disclosures.

24

NeuroMODULATION

March 2022 | Issue 45

High-frequency SCS drives impactful outcomes for non-surgical refractory back pain patients Leonardo Kapural Comment & Analysis Following the recent introduction of key data supporting the use of high-frequency spinal cord stimulation (SCS) in the treatment of non-surgical refractory back pain (NSRBP), Leonardo Kapural (Carolinas Pain Institute, Winston-Salem, USA) details what these findings mean for a patient population that, up to now, has been largely undertreated.

A

cute back pain causes more disability around the world than any other condition1 and a quarter of US adults report they have experienced back pain within the past three months.2 NSRBP is particularly troubling, with more than 500,000 patients experiencing pain but few widespread treatment options.3 Beginning in the 1990s, efforts to improve pain management resulted in a four-fold increase in the rate of opioid prescribing, disregarding the addictiveness, low therapeutic ratio, and lack of documented effectiveness of opioids in the treatment of chronic pain.4 While a recent study by the American Medical Association (AMA) showed the prescription rate of opioids has declined over the last 10 years, the country is now facing a worsening drugrelated overdose and death epidemic.

This highlights several related things.

The number of patients living with chronic pain has not decreased, leading to the assumption that patients who have come to depend on opioids for their pain management are now turning to less-controlled medical and nonmedical pain management. Prioritising the outcomes, research and access to evidence-based pain management options is a viewpoint echoed by both the American Academy of Neurology and the AMA.

Chronic pain and SCS

An example of this is the welldocumented use of SCS to treat chronic pain. When CMM is not working, SCS should be considered. Of the 500,000 patients experiencing NSRBP, fewer than 5% have been offered SCS treatment.5 There are various SCS options on the market for various conditions, but multiple studies point to the efficacy of high-frequency SCS. In contrast to low-frequency (40–60Hz) SCS, high-frequency (10kHz) SCS is paraesthesia-independent and uniquely

has since been published in the Journal of Neurosurgery: Spine. Senza is now the only SCS system with specific labelling to treat NSRBP patients.

The SENZA-NSRBP RCT was designed to specifically study SCS therapy in the NSRBP population. Some 159 patients confirmed by neurosurgeon evaluation as non-surgical candidates and who failed medical management were randomised 1:1, undergoing CMM with and without utilisation of 10kHz SCS. The back pain responder rates were significant, with 78.2% of the 10kHz therapy subjects achieving ≥50% pain relief at 12 months. The average pain relief (percentage reduction of visual analogue scale [VAS] score from baseline) was 72.1%. In the crossover arm, 78.2% of participants reported pain relief of >50%, and the average pain relief was 70.4%, after using 10kHz therapy for six months.

Furthermore, a profound relief (>80%) was achieved in 50% of the subjects using 10kHz SCS therapy.

We also concluded that 10kHz SCS

What do these data mean?

This study provided key insight into the durability of high-frequency SCS therapy for these patients. We saw long-term improvements in pain level, opioid use and overall quality of life.

We also saw effective and sustained improvements in functional capacity, with 75% of subjects experiencing a more than 10-point Oswestry Disability Index (ODI) score reduction. Both initial 10kHz and crossover study groups’ reductions in disability remained stable through 12 months.

The data analysed in SENZA-NSRBP add to the growing body of clinical evidence of high-frequency SCS, and not only speaks to the durability of the pain relief and quality of life measures at 12 months but also provides the data input necessary for payers to expand coverage to this undertreated patient population.

In conclusion, these study data support high-frequency SCS in NSRBP patient populations, and additional studies validate its use in chronic back and leg pain6, and painful diabetic neuropathy.7 References: 1. Hoy D, March L, Brooks P et al. The Global Burden of Low Back Pain: Estimates from the Global Burden of Disease 2010 Study. Ann Rheum Dis. 2014; 73(6): 968–74.

2. Deyo R A, Mirza S K, Martin B I. Back Pain Prevalence and Visit Rates: Estimates from U.S. National Surveys, 2002. Spine (Phila Pa 1976). 2006; 31(23): 2724–7.

3. Sources: US Census Bureau; CLBP Market Research; CMS OP Hospital SAF Data 2012–2018. www.neuromodulation.com/failed-back-surgerysyndrome-definition.

4. Frieden T R, Houry D. Reducing the Risks of Relief— the CDC Opioid Prescribing Guideline. NEJM. 2016; 374: 1501–4.

5. Kapural L, Jameson J, Johnson C et al. Treatment of nonsurgical refractory back pain with high-frequency spinal cord stimulation at 10 kHz: 12-month results of a pragmatic, multicenter, randomized controlled trial. Journal of Neurosurgery: Spine. 2022. DOI: 10.3171/2021.12.SPINE211301.

6. Kapural L, Yu C, Doust M W et al. Comparison of 10-kHz High-Frequency and Traditional LowFrequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-month Results from a Multicenter, Randomized, Controlled Pivotal Trial.

Neurosurgery. 2016; 79(5): 667–77.

7. Petersen E A, Stauss T G, Scowcroft J A et al.

Durability of High-Frequency 10-kHz Spinal Cord Stimulation for Patients With Painful Diabetic Neuropathy Refractory to Conventional Treatments: 12-Month Results From a Randomized Controlled Trial.

Diabetes Care. 2022; 45(1): e3–e6.

Senza Omnia

provides direct neural inhibition to the dorsal horn.

I recently presented 12-month outcomes from the SENZA-NSRBP randomised controlled trial (RCT) at the 25th North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA), which documented the efficacy of highfrequency 10kHz therapy in subjects with NSRBP. One of the main drivers for this study was to collect validation for a specific NSRBP indication and coverage expansion—given that many eligible patients have access limitations due to commercial insurance barriers.

The study, which supported the US Food and Drug Administration (FDA) approval of expanded labelling for the high-frequency Senza system (Nevro),

opioid dose by half, and 28% eliminated opioid use completely. These data indicate that high-frequency SCS should be used as part of the NSRBP treatment algorithm.

These data indicate that high-frequency spinal cord stimulation should be used as part of the non-surgical refractory back pain treatment algorithm.” reduces and, at times, eliminates opioid requirements in NSRBP patients. Fifty percent of subjects reduced their daily

Leonardo Kapural is a partner and pain physician at the Carolinas Pain Institute in Winston-Salem, USA, and the Center for Clinical Research and BestOpinionDoctor.com. His interests include peripheral nerve stimulation, spinal cord stimulation, discogenic low back pain and visceral abdominal pain. He served as professor of anaesthesiology at the Cleveland Clinic Lerner College of Medicine of Case Western University (Cleveland, USA) and Wake Forest University (WinstonSalem, USA).

Disclosures: Kapural is a consultant to Biotronik, Medtronic, Nalu, Presidio and Saluda Medical, and leads clinical research with Biotronik, Gimer Medical, Medtronic, NeuraLace, Neuros Medical, Nevro and Saluda.

26

NeuroMODULATION

March 2022 | Issue 45

Multiple-modality spinal cord stimulation demonstrates sustained improvement in chronic pain outcomes A spinal cord stimulation (SCS) system capable of simultaneously delivering multiple treatment modalities has produced a sustained improvement in outcomes in a randomised controlled trial (RCT) involving chronic pain patients. Two-year findings from this study—the COMBO (Combining mechanisms for better outcomes; Boston Scientific) RCT—were presented by Mark Wallace (University of California San Diego [UCSD] Health System, San Diego, USA) at the North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA).

“N

o one experiences pain in the same way, which is why the ability to layer modalities and waveforms in different combinations and patterns can help providers comprehensively respond to each patient,” Wallace said, speaking to NeuroNews following NANS 2022.

“Also, a patient’s experience of pain may change over time, so the ability to evolve and adapt the SCS programming is vital when thinking about long-term management. The WaveWriter spinal cord stimulator [Boston Scientific] is capable of achieving this goal.”

Wallace noted that several published, preclinical SCS studies have shown stimulation of different neuronal targets—for example, the dorsal horn and the dorsal column—helps to more robustly modulate neural activity and, in turn, perception of pain. As such, he and his colleagues at UCSD hypothesised that therapeutic neurostimulation, configured in a manner that would allow for multiple simultaneous targets to be stimulated, via the combined usage of sub-perception- and supra-perception-based SCS modalities, may help to enhance pain relief outcomes.

They assessed this approach through the prospective, multicentre, parallel-group COMBO RCT, which saw 89 chronic pain patients (mean age=57.3 years; 65.2% females) randomised into either a combination therapy arm, or a monotherapy arm. Those randomised into the

former were subject to the Contour algorithm (Boston Scientific), which involves simultaneously delivered, customised sub-perception dorsal horn modulation plus conventional, paraesthesia-based, standard-rate dorsal column modulation. Those in the latter group received paraesthesia-based, standard-rate dorsal column modulation alone. The Spectra WaveWriter SCS system was deployed in both groups.

Providing further background on the COMBO RCT, Wallace reported that the study met its primary endpoint regarding responder rates (percentage of patients with ≥50% pain relief), as well as all its secondary endpoints, at three months—based on a prespecified, 89-patient cohort. Combination therapy using a novel field shape algorithm was therefore deemed to have enabled more chronic pain patients to achieve a successful outcome than monotherapy alone at the initial follow-up timepoint.

“The two-year results from the COMBO study showed us that the WaveWriter SCS system offers durable and effective relief, over the long term, using combination therapy,” Wallace added. “Specifically, there Mark Wallace was a high responder

Brain stimulation rapidly improves cognitive deficits in long-COVID patients In a new study, scientists have demonstrated that cognitive impairment in patients with long-COVID can be significantly improved in three-to-four days using alternating non-invasive brain stimulation (NIBS) therapy via microcurrents. They report their findings in two long-COVID patients in the journal Restorative Neurology and Neuroscience.

“COVID-19 INFECTION CAN induce delayed cognitive impairments that are quite serious in some patients,” explained the study’s lead investigator Bernhard Sabel (Otto-von-Guericke University Magdeburg, Magdeburg, Germany). “Common symptoms include fatigue, shortness of breath, and cognitive dysfunction, such as lower attention span and loss of short-term memory—all of which have a dramatic impact on everyday functioning. There is currently no effective treatment that improves visual and cognitive impairments resulting from COVID-19 in such a short time.”

Vascular problems throughout the retina and the brain are thought to be the probable cause of longCOVID symptoms. Because patients

report vision loss, these investigators hypothesised that NIBS treatment could help induce cognitive recovery. This assumption was based on prior success improving vision in most of their glaucoma patients using this treatment.

Two female long-COVID patients were treated for 10 and 13 days, respectively, with alternating current stimulation of the eyes and brain for 45 minutes daily. Both had vision problems and severe cognitive impairments, which resulted in them being unable to work or carry out daily tasks. While one patient (age=40 years) had been infected with COVID-19, the other (age=72 years) had developed symptoms following vaccination with ChAdOx1-S (Oxford/ AstraZeneca). Before and after therapy, cognition was assessed subjectively

rate of 85% for overall pain, and an improvement in disability, with 85% of patients reporting being ‘much’ or ‘very much’ better. However, these results include all patients—both those using combination therapy and those using paraesthesia-only therapy. This is due to COVID-19 delaying our ability to separate out the therapies at two years for analysis.”

Wallace noted that, despite this disruption to the COMBO RCT, data from two-year comparisons between the study groups are “forthcoming”. He also stated that the currently available results suggest customising a patient’s treatment through combination therapy can lead to a sustained reduction in pain and improvement in disability. In addition to a two-year responder rate of 85% (n=59), compared to 84% (n=79) at one year, Wallace reported improved outcomes for disability on the Oswestry Disability Index (25-point mean reduction [improvement of one disability level], and increased patient satisfaction of 85% as per the Patient Global Impression Change scale, at two-year follow-up. He further claimed that the two-year functional improvement results from COMBO compare favourably to those seen in previously published monotherapy RCTs using other SCS systems.

“The COMBO RCT continues— which is important, because we want to understand how patients respond to the device at long-term followup,” Wallace concluded. “We need to separate the patients using the combination therapy from those using paraesthesia-based stimulation alone and determine what percentage of the patients chose each therapy, as well as the outcomes. I am very encouraged by the data we have already presented, particularly when you consider the response rate and how people reported improvements in disability.”

by interview and visual fields were quantified with perimetry. One patient was also assessed via a cognitive test battery and a retinal dynamic vascular analyser (DVA)—a surrogate marker of vascular dysregulation in the brain.

In both patients, NIBS markedly improved cognition and partially reversed visual field loss within three-tofour days. The significant improvements in their cognitive abilities included less fatigue, better short-term memory, attention, and multitasking. Both were able to return to work too. The observations of blood vessels in the eye confirmed that the improvement may be explained by recovery from blood vessel constriction, which is a possible source of visual and cognitive decline. Formal

This is the first demonstration that cognitive impairment can be improved in such a brief period of time.”

cognitive tests confirmed recovery of up to 40–60% in cognitive subfunctions with perimetry results showing stable and visual field recovery even during follow-up. DVA also showed that NIBS reduced vascular dysregulation by normalising vessel dynamics (dilation/constriction), with particularly noticeable changes in the small venous and arterial microvessels.

The investigators propose that hypometabolic neurons are the probable biological cause of the neurological deficits manifested as long-COVID symptoms, and that NIBS reactivates these ‘silent’ neurons by reoxygenation, which is the presumed basis of recovery.

“This is the first demonstration that cognitive impairment can be improved in such a brief period of time,” added Sabel. “We believe that our treatment could benefit patients with long-COVID worldwide to improve cognitive impairment. Our results are compatible with our earlier proposal that residual neuronal reserves can be reactivated by behavioural training or NIBS, providing a biological substrate for restoration of central nervous system function in the eye and brain. While NIBS is now already being offered in the clinic, further clinical trials should be conducted to study the mechanisms of action in greater detail.”

Issue 45 | March 2022

Market Watch 27

NeuroMODULATION NEWS Medtronic announces FDA approval of SCS therapy for diabetic peripheral neuropathy

Medtronic has received US Food and Drug Administration (FDA) approval of its Intellis rechargeable neurostimulator and Vanta rechargefree neurostimulator for the treatment of chronic pain associated with diabetic peripheral neuropathy (DPN).

This new indication offers patients with DPN access to the company’s spinal cord stimulation (SCS) portfolio of rechargeable and recharge-free platforms—which include multiple programming options to personalise patient therapy and provide unrestricted magnetic resonance imaging access, and the Medtronic TYRX neuroabsorbable antibacterial envelope.

Independent studies have shown that patients with DPN achieve significant pain relief when treated with SCS compared to conventional treatments alone, and a recent meta-analysis showed a significant improvement in health-related quality of life in patients treated with SCS compared to those receiving only conventional treatments, Medtronic claims.

Valencia Technologies announces FDA approval of eCoin therapy for urinary urge incontinence

Valencia Technologies Corporation has announced that the US Food and Drug Administration (FDA) has granted premarket approval of its eCoin leadless tibial neurostimulator for the treatment of urinary urge incontinence (UUI)—which affects more than 60% of overactive bladder patients.

This FDA approval was supported by the efficacy and favourable safety profile seen in the eCoin pivotal trial, the results of which are published in the Journal of Urology.

The eCoin device is a nickel-sized tibial nerve stimulator implanted subcutaneously in the lower leg during a minimally invasive outpatient procedure that utilises a local anaesthetic. It contains a primary battery and, once programmed, automatically delivers intermittent stimulation to the tibial nerve to reduce UUI symptoms.

The device does not require ongoing patient management of a power source or a stepped programmer, and the therapy is clinically different from more invasive sacral neuromodulation

surgery, which typically requires general anaesthesia and continuous patient device management.

Dolphin vagus nerve stimulation receives Health Canada approval as COVID-19 treatment

Center for Pain and Stress Research has announced that its Dolphin vagus nerve stimulation (VNS) device has received breakthrough approval from Health Canada—making it Canada’s first VNS therapy specifically intended for treating COVID-19.

As per the Health Canada authorisation letter, Dolphin Neurostim applied as a non-invasive vagal nerve stimulator is authorised for emergency use in the acute treatment of adults with known or suspected COVID-19.

Specifically, it is intended to provide symptom relief for patients experiencing exacerbation of asthmarelated dyspnoea and reduced airflow, and patients in whom approved drug therapies are not tolerated or provide insufficient symptom relief as assessed by their healthcare provider.

“There are no safety or effectiveness issues with regards to this expanded use,” the authorisation letter notes.

Large real-world analysis deems Nerivio safe and effective in migraine treatment

Theranica has announced a real-world evidence study analysing the efficacy, safety and sustainability of remote electrical neuromodulation (REN) as a standalone, and medication-adjunct, treatment of migraine.

The study, published in Frontiers in Pain Research, concludes that REN—administered via Nerivio, the company’s wearable, digitally connected flagship product— performs well across all three of these parameters.

Results from more than 23,000 treatments across 19 months demonstrated the efficacy of REN. An analysis including 2,514 patients saw 32% of episodic migraine patients and 21% of chronic migraine patients achieve pain freedom two hours posttreatment in most of their treatments, and more than 65% experienced sustained pain relief post-two hours.

In the safety analysis, 59 of 12,368 participants (0.48%) reported any device-related adverse events. Fiftysix of these were mild, and no severe events were reported.

Mainstay Medical announces positive efficacy and safety outcomes from ReActiv8-B trial

eCoin

Mainstay Medical has announced the publication of two-year patient outcomes data from its pivotal ReActiv8-B clinical trial.

ReActiv8

The data, which are published in Neuromodulation: Technology at the Neural Interface, confirm the efficacy and safety of the company’s implantable ReActiv8 device in restorative neurostimulation, and also demonstrate long-term durability and improvement over time on key outcome measures in the treatment of intractable chronic low back pain.

On the vast majority of all key efficacy measures, the two-year data from 156 patients show improvements over data from their one-year visits, including 71% of patients reporting pain intensity (visual analogue scale [VAS] score) reductions of 50% or more from baseline at two years— compared to 64% at one year—and 60% of patients who were taking opioids at baseline voluntarily eliminating or reducing their opioid use at two years, versus 48% at one year.

The ReActiv8-B trial patient cohort continues to be evaluated to generate additional data on longer-term efficacy.

Abbott gains expanded MRI compatibility for Proclaim XR SCS system in USA

Abbott has announced that the US Food and Drug Administration (FDA) has approved new, expanded magnetic resonance imaging (MRI) compatibility for its Proclaim XR spinal cord stimulation (SCS) system with Octrode leads.

This new labelling lifts MRI restrictions for lead tip location and the amount of radiofrequency power that can be used as part of the normal operating mode of an MRI scan. The expanded labelling covers the majority of Proclaim XR patients, providing additional benefits to them and their healthcare providers.

It also means patients with a Proclaim XR SCS device—an implantable system designed to relieve chronic trunk/limb pain—can benefit from higher quality images with faster MRI scan times. The update will benefit existing Proclaim XR SCS patients with Octrode leads too, improving their access to MRI imaging.

First patient implanted in integrated spinal fusion and DRG stimulation proof-ofconcept study SynerFuse has announced the first implantation in its proof-ofconcept study assessing the outcomes of simultaneously implanting spinal fusion hardware and a dorsal root ganglion (DRG) neurostimulator in patients suffering from chronic lower back pain.

The first patient was implanted

by Michael Park and Rohan Lall

at M Health Fairview University of Minnesota Medical Center in Minneapolis, USA. The SynerFuse proof-of-concept study will evaluate the safety and tolerability of this integrated therapy.

Patients undergoing an initial spinal fusion, among other criteria, are eligible for the study, which is supporting the enrolment of up to 20 patients.

Nevro gains expanded FDA labelling to treat nonsurgical refractory back pain with high-frequency SCS system

Nevro Corporation has received US Food and Drug Administration (FDA) approval of expanded labelling for its Senza spinal cord stimulation (SCS) system in the treatment of non-surgical refractory back pain (NSRBP).

This approval is specific to highfrequency therapy using the company’s Senza system—which Nevro claims is now the only SCS system with specific labelling to treat NSRBP patients.

Publication of 12-month results from the SENZA-NSRBP randomised controlled trial played a key role in Nevro gaining this expanded labelling.

In the trial, NSRBP patients who received 10kHz therapy demonstrated improvements in pain relief, function, quality of life, awareness of positive change and reduction in daily opioid use versus conventional medical management at 12 months postimplant. The study’s participants will also continue to be followed out to 24 months.

Feinstein Institutes scientists develop “first-ofits-kind” neuromodulation device for research

Engineers and researchers at the Feinstein Institutes for Medical Research (Manhasset, USA) have developed a fully implantable, wireless, bidirectional vagus nerve stimulation (VNS) and sensing device for research in mice.

Details about the device and its capabilities—not only in applying VNS, but also in sensing physiological and neural signals—are published in Biosensors and Bioelectronics.

They outline a potential to “transform how bioelectronic medicine research is conducted in labs worldwide”, according to the Feinstein Institutes.

The new device is compatible with different types of electrodes and sensors, and could also be used for applications other than VNS, such as deep brain stimulation or pain relief, in the future.

Feinstein Institutes’ wireless device

March 2022 | Issue 45

28 Market Watch

Clinical News InspireMD announces inclusion of CGuard carotid stent in CREST-2 trial

InspireMD has announced that its CGuard embolic prevention stent system will be included as a device option for carotid stenting in the CREST-2 trial. Following the recent approval of the CREST-2 investigational device exemption (IDE) supplement application from the US Food and Drug Administration (FDA), the company states that it will be evaluating strategic sites to enable expedited access.

The study first enrolled patients in 2014, as two parallel, multicentre, randomised, observer blinded-endpoint clinical trials with the purpose being to determine the best way to prevent strokes in patients with high-grade carotid stenosis but no stroke symptoms related to the blockage.

The trial will enrol an estimated 2,480

CGuard

participants who will remain in the study for four years following the start of intervention.

“It is critical for any long-term study to remain aligned with evolving technology and relevant devices,” said Thomas Brott (Mayo Clinic, Jacksonville, USA), principal investigator of the National Institute of Neurological Disorders and Stroke (NINDS)-sponsored trial. “After examining the extensive clinical experience with the CGuard stent and the large body of evidence to its effectiveness, the study executive committee felt it appropriate to include this stent as a treatment option. Patients that agree to participate in the CREST-2 trial, depending on accessibility, and operator training and discretion, will now have access to this state-of-the-art carotid stent device.”

NeuroOne releases successful long-term recording data with novel electrode technology

NeuroOne Medical Technologies has announced that it has successfully completed initial preclinical, long-term testing of recording capabilities on its thin-film platform electrode technology.

In test procedures, the electrodes’ ability to record electrical activity

over five years was measured using an accelerated ageing test model, and the results demonstrated their reliability against environmental factors that may contribute to device failure or malfunction—a well-established challenge with thin-film electrode technology, according to the company.

These results support the potential expansion of utilisation with these electrodes for long-term recording in indications like epilepsy, Parkinson’s disease, chronic back pain due to failed back surgeries, and other related neurological disorders, as well as research applications.

The tests in question were accelerated soak tests, which NeuroOne claims are widely used in the field of neurotechnology, and allowed for comparison between its own electrodes and other approaches in academic and industry settings.

Bendit announces firstin-human use of Bendit21 catheter in USA

Bendit Technologies has announced the successful first use in the USA of its Bendit21 neurocatheter in a life-saving treatment. The case was completed at the University of Texas Southwestern (UTSW) Medical Center (Dallas, USA) and involved a 57-year-old female patient who had been suffering for years from an inoperable, symptomatic internal carotid artery aneurysm.

The Bendit21 steerable microcatheter is designed to allow access to hardto-reach vasculature locations with its

three-dimensional, clinician-controlled movement and independent control of catheter tip deflection. According to Bendit, these capabilities are intended to enable surgeons to navigate quickly and precisely through the neuro, peripheral and coronary vasculature.

John Barr (UTSW Medical Center, Dallas, USA) used the Bendit21 device under compassionate use granted by the US Food and Drug Administration (FDA). “We were pleased to be granted FDA approval for the compassionate use for this first case in the USA,” he said. “Previous access attempts had failed both here at UTSW, and at an outside facility, because the neck of the giant aneurysm could not be crossed using other catheters.”

Microvention announces treatment of first US patient with Fred X flow diverter Microvention, a subsidiary of Terumo, has announced the first US clinical case using its next-generation flow diverter, the Fred X device, at Thomas Jefferson University Hospital (Philadelphia, USA). The Fred X flow diverter features the company’s X technology—a proprietary nanopolymer surface modification designed to reduce material thrombogenicity on the device surface.

Building on the original Fred device—which received US Food and Drug Administration (FDA) premarket approval in 2019—the Fred X device uses a self-expanding braided nitinol mesh to help redirect blood flow and

Issue 45 | March 2022

Market Watch 29

Clinical News Fred X

promote aneurysm occlusion. This latest iteration gained premarket approval from the FDA in September 2021.

With the addition of X technology, Fred X is designed to reduce thrombogenicity and enhance blood vessel healing. It also offers “both the smallest and largest flow diversion systems available in the USA”, providing physicians with “the broadest range of options for treating their patients”, according to Microvention.

“Fred X represents an important advancement in flow diversion therapy. The X technology surface treatment applied to the Fred X device is designed to reduce material thrombogenicity and has further increased the deliverability of the Fred X,” said Stavropoula Tjoumakaris (Thomas Jefferson University Hospital, Philadelphia, USA), principal investigator of the FRED X [postapproval] study.

“We are excited to be the first centre in the USA to have clinical experience using the Fred X device and look forward to a clinical study on the benefits of X technology.”

Myopro shows clinically significant gains in motor function for chronic arm weakness

Myomo has announced that new research measuring the benefits of its Myopro myoelectric orthosis found “statistically significant improvements” in a number of motor function measurements.

The study, which is published in Frontiers in Neurology, followed 13 patients with chronic moderate-tosevere arm weakness from stroke or traumatic brain injury (TBI). Outcomes were collected from in-therapy sessions and home use. The study’s authors, lead investigator Svetlana Pundik (Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, USA) and colleagues, note that “statistically significant and clinically meaningful improvements were observed on Fugl-Meyer assessment (+7.5 points)”.

They add: “Gains were seen at week three, increased further through the in-clinic phase, and were maintained during the home phase. Statistically significant changes in modified Ashworth scale, range of motion, and Chedoke arm and hand activity inventory, were seen early during the in-clinic phase.

“The orthotic and prosthetic user’s survey demonstrated satisfaction with the device throughout study

participation. Both stroke and TBI participants responded to the intervention. Use of Myopro in motor learning-based therapy resulted in clinically significant gains with a relatively short duration of inperson treatment.”

Evasc Neurovascular announces enrolment of first patient in French eClips study

Evasc Neurovascular has announced enrolment of the first patient in its EESIS-FR study in France, which will be conducted with the objective of evaluating the technical feasibility, safety and efficacy of the company’s eClips products for the treatment of bifurcation aneurysms.

Up to 28 neurointerventional sites across France will enrol patients in this study. Procedural success with the second-generation eClips bifurcation remodelling system will be evaluated to determine its feasibility, while safety outcomes will be measured via major stroke or death within 30 days, or major territorial stroke or neurological death within one year. Additional endpoints will be evaluated in the study, and data are also set to be collected to assess procedural success and record efficacy information on other eClips products.

“I am pleased to have enrolled the first patient in this important clinical study to help further the clinical understanding of the real-world effectiveness of the second-generation eClips aneurysm treatment system,” said Raphaël Blanc (Rothschild Foundation Hospital, Paris, France), principal investigator of the study. “We have seen an enormous improvement in the second-generation eClips delivery system: stability and placement within eight minutes is a gamechanger in the neurointerventional practice.”

NovaGuide intelligent ultrasound found to improve right-to-left shunt detection

NovaSignal Corporation has announced the results of a multicentre, prospective, single-arm study indicating that the company’s autonomous NovaGuide intelligent ultrasound is three times more likely to detect right-to-left shunt (RLS)—a recognised risk factor for stroke—than standard-of-care transthoracic echocardiography (TTE).

These results were presented in a latebreaking session at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA).

“In the stroke population, RLS detection—especially due to a patent foramen ovale—is important to reduce the risk of future stroke,” said the study’s principal investigator Mark Rubin (University of Tennessee Health Science Center, Memphis, USA). “We have known for decades

that transcranial Doppler (TCD) is exquisitely sensitive for RLS detection, but expertise is scarce. NovaGuide broadens the availability of TCD, allowing any provider to help their patients benefit from the sensitivity of TCD for RLS detection. The BUBL study results underscore the potential for using this diagnostic capability to improve the management of ischaemic stroke patients.”

The BUBL clinical trial assessed use of NovaGuide compared to TTE for RLS diagnosis in adult patients, and its primary outcome was the percentage shunt detection rate of NovaGuide relative to standard-of-care TTE. Among 129 evaluable participants, RLS detection rate was 63.6% with NovaGuide (82 patients) and 20.9% with TTE (27 patients). Additionally, NovaGuide accurately identified 35 patients (27%) with intervenable shunts, while TTE identified 13 (10%) of these cases. With an adverse event rate of 0%, NovaGuide also met the study’s primary safety endpoint.

NovaGuide

CereVasc receives FDA nod to study eShunt system in normal-pressure hydrocephalus patients

CereVasc has announced that the US Food and Drug Administration (FDA) has approved its investigational device exemption (IDE) application to initiate a pilot trial of the eShunt system in patients with normal-pressure hydrocephalus (NPH).

“This is a very important stage in the ongoing development of this technology. We are committed to continuing the development of this alternative to conventional shunting for the thousands of patients suffering from disabling effects of NPH and other forms of adult hydrocephalus,” said Carl Heilman (Tufts Medical Center, Boston, USA).

Representing the first minimally invasive treatment for NPH, according to CereVasc, the eShunt device offers the potential to result in benefits over the current treatment—a dated procedure associated with frequent failure, infection risk and high costs.

First patient enrolled in pivotal EMAGINE trial of electromagnetic field therapy for stroke recovery BrainQ has announced that the first patient has been enrolled at MedStar National Rehabilitation Hospital

(Washington, USA) in the pivotal, randomised, double-blind, multicentre EMAGINE trial, which is evaluating its frequency-tuned electromagnetic field treatment in facilitating recovery in individuals with moderately severe ischaemic stroke.

The EMAGINE stroke recovery trial (the BQ5 study) provides a remote and decentralised care model, and will enrol 150 randomised subjects between four and 10 days following a stroke, with up to 19 academic sites expected to participate. The primary outcome measure for the study is score on the modified Rankin Scale for measuring post-stroke disability.

It is designed to allow participants to receive BrainQ’s BQ investigational therapy device—beginning during acute hospitalisation, and accompanying them to the inpatient rehab facility and eventually home.

The device is intended to extend the window of opportunity for reducing disability from the acute phase to the sub-acute phase in wider stroke populations.

“For many years, stroke rehabilitation has lacked novel technologies that change the treatment paradigm for patients,” said Pamela Duncan (Wake Forest School of Medicine, Winston-Salem, USA), a co-lead principal investigator for the pivotal trial. “There is a potential that BrainQ’s therapy, coupled with exercise training commencing within a few days of stroke and continuing for nine weeks, will optimise recovery and reduce stroke disability.”

Rebus Esper platform leveraged to create “cell atlas” of brain vasculature in new study

Rebus Biosystems has announced the publication of a study in Science highlighting its Rebus Esper platform’s ability to spatially resolve vascular cell diversity in the adult human brain.

This effort was led by researchers at the University of California San Francisco (UCSF; San Francisco, USA).

In collaboration with other institutions, teams from UCSF analysed cells present in subjects with arteriovenous malformations (AVMs)—which are caused by incorrectly formed blood vessels in the brain, and often lead to stroke.

The researchers compared these cells with samples from healthy adult brain blood vessels to determine which genes were being expressed in the differing samples. They then created a comprehensive cell atlas of the vascular system in the brain.

This research revealed that certain immune cells appear to weaken smooth muscle cells in the diseased brain vasculature of patients with AVMs, resulting in a stroke.

Rebus claims this particular immune cell subtype may serve as a new therapeutic target, while systematically defining other candidate targets for future investigation and therapeutic development.

March 2022 | Issue 45

30 Market Watch

Product News Cerenovus launches Emboguard balloon guide catheter for acute ischaemic stroke

Cerenovus—part of Johnson & Johnson Medical Devices Companies—has announced the launch of Emboguard, its next-generation balloon guide catheter intended for use in endovascular procedures, including those for patients with acute ischaemic stroke.

“Without timely and effective treatment of stroke, patients can suffer from lifelong disability or dependency,” said David Fiorella (Stony Brook University Hospital, New York, USA).

“The benefits of balloon guide catheters are becoming increasingly recognised for their ability to maximise patient outcomes. By adding this innovation to their stroke solutions portfolio, Cerenovus will be arming physicians with the tools they need to better serve our patients, potentially increasing

Emboguard

the chances to live a functional and fulfilling life post-stroke.”

Emboguard, which debuted at the recent International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA), is the latest addition to Cerenovus Stroke Solutions—a suite of technologies designed “with compatibility in mind” to assist physicians in performing mechanical thrombectomy procedures, according to the company.

Wallaby Medical launches Avenir coil system for haemorrhagic stroke treatment in Japan

Wallaby Medical has partnered with Japan Lifeline to bring its Pharmaceuticals and Medical Devices Agency (PMDA)-approved Avenir coil system to the Japanese market.

With stroke accounting for more than 125,000 deaths annually in Japan, the country represents “one of the most important markets to serve”, Wallaby claims.

Avenir is used in the intravascular embolisation of intracranial aneurysms and other neurovascular malformations, such as arteriovenous malformations and arteriovenous fistulas, as well as

arterial and venous embolisation of peripheral blood vessels.

According to Wallaby, the Avenir coil system is designed with three outstanding features, including “exceptional” complex framing— providing “excellent” wall apposition and implant distribution to facilitate dense packing—as well as “ultra-soft finishing, and an innovative, highly reliable instant detachment system”.

Rapid Medical receives FDA Breakthrough Device designation for vasospasm treatment

Rapid Medical has announced US Food and Drug Administration (FDA) Breakthrough Device designation for its Comaneci embolisation assist technology, which is intended to facilitate the treatment of cerebral vasospasm—a major complication and cause of morbidity from subarachnoid haemorrhage—following a haemorrhagic stroke.

“We just need better solutions for patients—no single treatment has been shown to be uniformly safe and effective in treating symptomatic vasospasm,” said Brian Jankowitz (University of Pennsylvania, Philadelphia, USA). “Comaneci is the first device to provide combination therapy to the brain with an adjustable diameter/radial force that may lower the risk of vessel injury.”

Comaneci is also available in Europe for vasospasm intervention and is showing “promising results”, Rapid claims. In a 30-patient, multicentre, retrospective analysis, 97% of patients showed an increase in vessel opening of at least 25%, with 80% of patients showing an increase of 50% or more.

Additionally, more than 10,000 procedures have been performed worldwide utilising Comaneci to assist in the coil embolisation of wide-neck intracranial aneurysms to date.

The device’s adjustable diameter, low delivery profile and excellent visibility have “drawn physicians around the globe to demand Comaneci”, according to Rapid. As a temporary device, it is designed to offer a treatment modality that may prevent the need for permanent devices implanted in the brain.

Viz.ai receives FDA 510(k) clearance for cerebral aneurysm detection algorithm

Viz.ai has received US Food and Drug Administration (FDA) 510(k) clearance for Viz Aneurysm—a new algorithm that uses artificial intelligence (AI) to detect suspected cerebral aneurysms.

Viz Aneurysm is designed to help hospital systems ensure that, once detected, patients are captured and the aneurysm workflow across an entire

health system is standardised, allowing Perfuze announced last year that the patients to receive the appropriate first acute ischaemic stroke patients follow-up care and creating financial had been treated with its CE-marked benefits for hospital systems and Millipede 088 clot aspiration catheter. payers.

A study at the University of Toronto Vena balloon distal access (Toronto, Canada) tested the accuracy catheter gains Health of Viz Aneurysm using 528 computed Canada medical tomography angiographies (CTAs) device licence with 674 aneurysms broadly distributed Vena Medical has announced the first across the cerebral vascular territories, Health Canada medical device licence encompassing anterior and posterior for its new product, the Vena balloon circulation. Viz.ai states that data distal access catheter, which combines analysis demonstrated 94% accuracy the balloon guide catheters and distal with the algorithm. access catheters that are currently used “Aneurysms can often be missed in thrombectomy procedures to remove because they require a very clots from the brains of methodical diagnostic stroke patients. approach,” said Vitor Vena claims that Pereira (University of combining these two devices Toronto, Toronto, Canada). allows the clinician to get “The Viz.ai aneurysm the balloon “much closer” algorithm was able to to the clot—improving detect cerebral aneurysms key metrics like first pass in consecutive CTAs. The success rate and leading model has demonstrated to significantly better that a deep learning AI patient outcomes, while algorithm can achieve also reducing the number clinically useful levels of devices required to treat of accuracy for clinical each patient and, therefore, decision support and will Viz Aneurysm procedural costs. help us to improve how we And, according to the help aneurysm patients.” company, “important regulatory The Viz Aneurysm module is clearances” such as this, coupled with additive to the wider Viz Intelligent key senior hires like the recent addition Care Coordination platform, alongside of Adam Karamath as Vena’s head of other AI-powered offerings including commercial operations, are allowing Viz LVO for suspected large vessel it to transition from a start-up to a occlusion detection and Viz ICH for scale-up. suspected intracerebral haemorrhage detection.

ClaroNav receives Chinese

Perfuze raises €22.5 million in Series A funding for novel acute ischaemic stroke treatment

Perfuze has closed a €22.5 million Series A investment round—the proceeds from which will be used to drive the next stage of a US clinical study and regulatory clearance of its Millipede system. The funds will also be used to support ongoing development of new products and to initiate commercialisation of this technology.

The funding round was led by new investors LSP and Seroba Life Sciences, and supported by SV Health Investors as well as existing investors Earlybird, HBM-MedFocus Fund, Enterprise Ireland, and a syndicate of Irish business veterans and stroke physicians.

With the closing of this Series A financing round, Anne Portwich, partner at LSP, and Daniel O’Mahony, partner at Seroba Life Sciences, will join the Perfuze board of directors, while Megan MacDonagh, senior associate at SV Health investors, will join as a board observer.

Perfuze’s next-generation, catheterbased aspiration technology for the treatment of large vessel occlusion stroke aims to provide improved clinical outcomes in shorter procedural times, resulting in safe, cost-effective therapy, according to the company.

regulatory clearance for Navient neuro-navigation system

ClaroNav Kolahi—a subsidiary of ClaroNav—has received regulatory clearance from the National Medical Products Administration (NMPA) to market and sell its Navient cranial model in China. Previously, the company has also received NMPA approval for its Navient ENT model.

Navient, an image-guided surgical navigation system, is akin to a global positioning system (GPS) enabling surgeons to navigate inside a patient’s skull, ClaroNav states, as it provides three-dimensional visualisation to assist surgeons with finding a way inside the skull and navigating their way safely to the diseased area.

With NMPA approval now secured, the company has received approval for its Navient product from “all major regulatory agencies”, including the US Food and Drug Administration (FDA), Health Canada, the Korean Ministry of Food and Drug Safety (MFDS), the Brazilian Agência Nacional de Vigilância Sanitária (ANVISA) and the FDA in Taiwan, as well as gaining European Conformitè Europëenne (CE) certification.

Imperative launches Zoom Pod aspiration tubing for use in stroke treatments Imperative Care has announced the launch of its Zoom Pod aspiration

Issue 45 | March 2022

Market Watch 31

Product News tubing, the company’s latest innovation in elevating stroke care. Zoom Pod is a sterile field clot filter device enabling faster time to clot capture during mechanical thrombectomies for ischaemic stroke patients.

It is integrated into the aspiration tubing, shortening the distance from aspiration to filtration while maintaining full aspiration power.

And—Imperative claims—because it is positioned within the sterile field, the physician can immediately see the clot as it is extracted from the patient, quickly confirming clot capture and giving them more control over the thrombectomy procedure.

“Stroke care is all about speed.

In order to achieve the best possible outcomes for patients, it is imperative to retrieve the clot from the brain quickly,” said Shahid Nimjee (The Ohio State University Wexner Medical Center, Columbus, USA). “The Zoom Pod will allow Zoom Pod physicians like

myself to visually confirm immediately, right within the sterile field, that the clot has been captured. Additionally, the ability to capture the clot in the Zoom Pod allows me to easily take the clot back to the pathology lab, break it down, and analyse it.”

This newly launched technology is the latest addition to Imperative’s Zoom stroke solution, which is an ischaemic stroke product portfolio also including the Zoom 88 large distal platform for neurovascular access, four Zoom aspiration catheters in various sizes, and the Zoom pump with accessories.

CyberKnife robotic radiosurgery system approved for treatment of trigeminal neuralgia in Japan

Accuray has received approval from the Japanese Ministry of Health, Labor and Welfare (Shonin) to market its CyberKnife robotic radiosurgery

Calendar of events

26–28 April Charing Cross (CX) Symposium London, UK and virtual

2–7 April American Academy of Neurology (AAN) Annual Meeting Seattle, USA

29 April–2 May American Association of Neurological Surgeons (AANS) Annual Scientific Meeting Philadelphia, USA

aan.com/events/annual-meeting

24–29 April AVM-WIN Joint Meeting Val d’Isère, France avm2022.org

trigeminal neuralgia globally, including in the USA, Europe, Africa, India and the Middle East.

Brainomix launches e-Stroke 11 to enhance network communications and workflow

Brainomix has announced the launch of e-Stroke 11, the latest version of its artificial intelligence (AI)powered stroke imaging platform, which is intended to enhance stroke network communications and optimise workflows—facilitating faster transfer and treatment decisions.

E-Stroke is a collection of AI algorithm-supported tools designed to provide real-time interpretation of brain scans, and allow physicians to quickly and securely access, review and share images and patient data, send messages, make calls directly from the e-Stroke mobile app, and flag patients eligible for thrombectomy.

“Brainomix has revolutionised the way that we are managing stroke patients,” said Paul Bhogal (Royal London Hospital, London, UK). “Its e-Stroke platform allows for fast, accurate and effective analysis of images and patient data across a stroke network—which is key for us, as we operate the largest stroke network in the UK, performing close to 300 thrombectomies a year.”

Please be advised that the events listed below are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

28–29 March LINNC Seminar—Americas Edition Miami, USA linnc.com/Course-information/LINNCSeminar-2022-Americas-Edition

system for the treatment of trigeminal neuralgia in Japan, giving more patients access to a precise radiosurgery treatment typically delivered during a single outpatient procedure.

“As a neurosurgeon, I have seen many people suffering from trigeminal neuralgia,” said Hiroshi Takahashi (Kasugai CyberKnife Rehabilitation Hospital, Yamanashi, Japan). “Some of them were worried about medication that worked initially and gradually became ineffective, and others were disappointed with the recurrence of pain despite choosing surgery as a potentially curative option.

“For these people, SRS [stereotactic radiosurgery] may be an extremely useful treatment method. I am very pleased about this recent CyberKnife approval. The system delivers SRS treatments with accuracy and precision, and with the potential for long-lasting results. I believe it will be an important option for our patients with trigeminal neuralgia.”

Data published in Neurosurgery indicate that SRS treatments delivered with the CyberKnife system result in rapid and long-lasting pain relief, with 93.5% of trigeminal neuralgia patients experiencing relief after three weeks and 76% maintaining stable pain control for three years after the first treatment, according to Accuray.

The system is currently used to treat

cxsymposium.com/cx2022

aans.org/meetings

4–6 May European Stroke Organisation Conference (ESOC) Lyon, France eso-stroke.org/meetings/esoconference-2022

14–18 May American Society of Neuroradiology (ASNR) Annual Meeting and Symposium Neuroradiologicum (SNR) New York City, USA asnr.org/annualmeeting

21–26 May International Neuromodulation Society (INS) World Congress Barcelona, Spain neuromodulation.com/ins-congress

30 May–1 June LINNC Paris Paris, France

linnc.com/Course-information/LINNCParis-2022

6–9 June Leipzig Interventional Course (LINC) Leipzig, Germany leipzig-interventional-course.com/visitors/ linc-2022

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

Sign up for a free print subscription* and e-newsletter subscription** www.neuronewsinternational.com *Available for US and EU readers only ** Available worldwide

POD400 & PAC400 ™

™

Designed for Efficient, Dense Packing One POD400 and one PAC400, 4 mm vessel

POD400

Distal Anchor Segment

5 mm POD400 PAC400 (×6)

POD400

Proximal Softer Packing Segment

PAC400

Designed to Seek Space for Dense Packing Available in lengths up to 60 cm

Vertebral Artery Sacrifice Dr. Erik Hauck Duke University, NC

Photographs taken by and on file at Penumbra, Inc. Bench test results may not be indicative of clinical performance. Image used with permission. Consent on file at Penumbra, Inc. Individual results may vary depending on a variety of patient-specific attributes and other factors.

Penumbra Coil System – Indication for Use The Penumbra Coil System is indicated for the embolization of: • Intracranial aneurysms. • Other neurovascular abnormalities such as arteriovenous malformations and arteriovenous fistulae.

• Arterial and venous embolizations in the peripheral vasculature.

Contraindications There are no known contraindications. Warnings The Penumbra Coil System should only be used by physicians who have received appropriate training in neuro-interventional techniques. Precautions • The device is intended for single use only. Do not resterilize or reuse. Resterilization and/or reuse may compromise the structural integrity of the device or increase the risk of contamination or infection leading to device failure and/ or cross-infection and potential patient injury, illness, or death.

• Do not use kinked or damaged devices. Do not use opened or damaged packages. Return all damaged devices and packaging to the manufacturer/distributor. • Use prior to the “Use By” date. • Use device in conjunction with fluoroscopic guidance. • Do not advance or retract the device against resistance without careful assessment

of the cause using fluoroscopy.

• Moving or torquing the device against resistance may result in damage to the vessel or device. • Maintain a constant infusion of an appropriate flush solution. Potential Adverse Events Possible complications include, but are not limited to, the following: acute occlusion; air embolism; allergic reaction and anaphylaxis from contrast media; aneurysm rupture; arteriovenous fistula; coagulopathy; coil herniation into parent vessel; death; device malfunction; distal embolization; emboli; embolic stroke and other cerebral ischemic events; false aneurysm formation; hematoma or hemorrhage at access site of entry; incomplete aneurysm occlusion; infection; intima dissection; intracranial hemorrhage; ischemia; myocardial infarction; neurological deficits including stroke; parent artery occlusion; peripheral thromboembolic events; post-embolization syndrome; premature device detachment; recanalization; renal failure; respiratory failure; revascularization; thromboembolic episodes; vessel spasm, thrombosis, dissection, or perforation.

POD System – Indication for Use For POD Coils with nominal sizes ≤ 6 mm The POD System is indicated for the embolization of: • Intracranial aneurysms. • Other neurovascular abnormalities such as arteriovenous malformations and arteriovenous fistulae. • Arterial and venous embolizations in the peripheral vasculature. Contraindications There are no known contraindications. Warnings The POD System should only be used by physicians who have received appropriate training in interventional techniques. Precautions • The device is intended for single use only. Do not resterilize or reuse. Resterilization and/or reuse may compromise the structural integrity of the device or increase the risk of contamination or infection leading to device failure and/ or cross-infection and potential patient injury, illness, or death.

• Do not use kinked or damaged devices. Do not use opened or damaged packages. Return all damaged devices and packaging to the manufacturer/distributor. • Use prior to the “Use By” date. • Use device in conjunction with fluoroscopic guidance. • Do not advance or retract the device against resistance without careful assessment of

the cause using fluoroscopy. If POD cannot be advanced or retracted, withdraw the device as a unit with the microcatheter. • Moving or torquing the device against resistance may result in damage to the vessel or device. • Maintain a constant infusion of an appropriate flush solution. Potential Adverse Events Possible complications include, but are not limited to, the following: acute occlusion; air embolism; allergic reaction and anaphylaxis from contrast media; aneurysm rupture; arteriovenous fistula; coagulopathy; coil herniation into parent vessel; death; device malfunction; distal embolization; emboli; embolic stroke and other cerebral ischemic events; false aneurysm formation; hematoma or hemorrhage at access site of entry; incomplete aneurysm occlusion; infection; intima dissection; intracranial hemorrhage; ischemia; myocardial infarction; neurological deficits including stroke; parent artery occlusion; peripheral thromboembolic events; post-embolization syndrome; premature device detachment; recanalization; renal failure; respiratory failure; revascularization; thromboembolic episodes; vessel spasm, thrombosis, dissection, or perforation.

Caution: Federal (USA) law restricts these devices to sale by or on the order of a physician. Prior to use, please refer to the Instructions for Use for complete product indications, contraindications, warnings, precautions, potential adverse events, and detailed instructions for use. Renderings for illustrative purposes only. Individual results may vary depending on a variety of patient-specific attributes and other factors. Image used with permission. Consent on file at Penumbra, Inc. Please contact your local Penumbra representative for more information.

Copyright ©2022 Penumbra, Inc. All rights reserved. The Penumbra P logo, POD, POD400, and PAC400 are registered trademarks or trademarks of Penumbra, Inc. in the USA and other countries. 22913, Rev. A 01/22 USA

22913A_LVC_Ad_USA_8Mar22_NeuroNews.indd 1

www.penumbrainc.com

3/8/22 11:38 PM