Neurointerventionists ‘can rarely recover payment’ under US No Surprises Act
page 7
Stroke thrombectomy: How far can we go?
page 10
Every hour saved between stroke onset and thrombectomy could equate to 25% greater odds of functional independence
A systematic review and meta-analysis of five studies and more than 11,000 patient records has indicated that each hour saved between acute ischaemic stroke symptom onset and initiating a mechanical thrombectomy procedure is associated with a 22–25% increase in the odds of achieving functional independence.
The review and analysis in question—dubbed ‘SWIFTEVT’—has been published in the Journal of Stroke and Cerebrovascular Diseases by Brittney Legere (University of Guelph, Guelph, Canada) and colleagues.
“While other systematic reviews have similarly analysed previous onset to EVT [endovascular therapy] time effects on patients, SWIFT-EVT provides a more recent and thorough analysis evaluating good and excellent functional independence,” Legere et al note. “Quantifying this substantial time-dependent benefit, relevant during the entire first six hours post-acute ischaemic stroke onset, may be useful to inform patient-specific and systems planning decisions.”
The researchers initially state that data through 2014 from the HERMES meta-analysis demonstrated that—particularly over the first six hours post-acute ischaemic stroke—the rapid administration of thrombectomy treatment “markedly improves outcomes”. However, while subsequent analyses and studies have further elucidated how ‘time to thrombectomy’ affects outcomes, “no recent systematic reviews have quantified patient outcomes based on time intervals, and the time-saving benefit of EVT”. Against this backdrop, SWIFT-EVT set out to calculate precise, patient-centred outcome benefits for incremental pre-
thrombectomy time savings within six hours of stroke onset—a “broadly accepted” and guideline-based window for prioritising EVT timings in large vessel occlusion (LVO) stroke patients.
The investigators’ aim was to provide “an updated metric summarising latest estimates for modified Rankin scale [mRS] improvements accrued by streamlining time to EVT”.
Legere et al’s review and analysis considered eligible studies to be those reporting a time-benefit slope with times from stroke onset/time last known normal to thrombectomy commencement, whereby ‘onset-to-groin-puncture’ time was the predictor. They
“Quantifying the benefit of faster time to EVT is of critical importance for design and improvement of stroke systems of care.”
Continued on page 4
Profile Thanh N Nguyen
page 12
GBD analysis elucidates global stroke trends
page 17
Nick Hopkins, 1943–2024: Neurointerventional community mourns pioneer and “force of nature” in endovascular care
LEO NELSON (NICK) Hopkins, a world-renowned surgeon, researcher and innovator who played a pioneering role in modern neurosurgery’s shift from open- to endovascular-first techniques, has died aged 81. Hopkins passed away on 5 October at the Gates Vascular Institute in Buffalo, USA—a centre that he created and which “embodied his vision of all vascular specialists working together collaboratively”. Hopkins was professor and chairman of neurosurgery, and professor of radiology, at the University at Buffalo’s (UB) Jacobs School of Medicine and Biomedical Sciences (Buffalo, USA) from 1989–2013. In 2013, he was awarded State University of New York (SUNY) distinguished professorship in neurosurgery and radiology—the SUNY system’s highest faculty rank. In addition to founding Kaleida Health’s Gates Vascular Institute and serving as its chairman of the board for many years, Hopkins co-founded Toshiba’s Canon Stroke and Vascular Research Center in 1991, instilling a multidisciplinary approach to exploring and improving
Continued on page 2 OBITUARY
Nick
Hopkins, 1943–2024: Neurointerventional community
mourns pioneer and “force of nature” in endovascular care
Continued from page 1
stroke therapies, and established the Jacobs Institute (JI) in 2008 as a hub for innovation in vascular medicine.
Hopkins is credited with being among the first neurosurgeons to truly embrace minimally invasive techniques as a means for treating stroke and other neurovascular diseases. In a tribute posted online, JI chief executive officer Adnan Siddiqui (Buffalo, USA) has described Hopkins as “a unique, unrelenting and powerful force of nature” whose efforts “moved endovascular technology to the forefront of neurosurgery and neurointervention”.
A lifetime in neurosurgery
He completed a surgical internship at Case Western Reserve University (Cleveland, USA) in 1970, and then neurology and neurosurgical residencies at UB in 1971 and 1975, respectively, upon returning to Buffalo.
Hopkins was an active member of the neurosurgical community in the USA and globally, serving on the board of directors of the American Association of Neurological Surgeons (AANS) and the executive committee of the Stroke Council of the American Heart Association (AHA). He has served as scientific and annual meeting chair for both the AANS and the Congress of Neurological Surgeons (CNS). Hopkins was also chair of the AANS/CNS Joint Section on Cerebrovascular Surgery from 1994–1996, and president of the American Academy of Neurological Surgery in 2006.
Hopkins
Hopkins led the UB Department of Neurosurgery as chairman for almost 25 years, transforming it into one of the foremost neurosurgical centres in the world and ultimately training many members of the current generation of neurointerventional thought leaders—with his mentees being fondly referred to as the ‘Buffalo Mafia’.
“Today, the neurosurgical community mourns the loss of a giant who gifted the world the specialty of neuroendovascular surgery,” said Elad Levy, the L Nelson Hopkins endowed chair of neurosurgery at UB (Buffalo, USA). “His legacy of disciples across the world continues to advance the field he started.”
“By virtue of his unique personality, strong desire for innovation, and going against the grain, he developed partnerships with budding entrepreneurs in the MedTech space, building lasting relationships and founding multiple successful companies which have helped millions of people around the world,” added Siddiqui, who also recently joined the Charing Cross (CX) Symposium executive board for 2025.
Hopkins—a proud Buffalo native—completed his undergraduate studies at Rutgers University (New Brunswick, USA) in 1965 before earning a cum-laude Doctor of Medicine (MD) degree from Albany Medical College (Albany, USA) in 1969.
In addition, as a researcher, Hopkins was the principal investigator for a number of clinical trials evaluating minimally invasive treatments for neurovascular diseases and authored more than 300 medical publications.
One of the most recent and most prominent examples of his significant contributions to endovascular neurosurgery was the role he played in the international SWIFT PRIME trial, which was published in the New England Journal of Medicine in 2015, and helped to establish mechanical thrombectomy as a safe and effective procedure for ischaemic stroke. Upon the release of these findings, Hopkins accurately predicted that “we are at the dawn of a new era in stroke”.
Hopkins’ achievements and legacy were recognised via numerous awards throughout his career. In 2019, he received the 2019 Chancellor Charles P Norton Medal, which is seen as UB’s highest honour. In 2021, he was inducted into the Buffalo Business First Business Leadership Hall of Fame. Hopkins also received the Kaleida Health Lifetime Spirit Award on two separate occasions and,
Today, the neurosurgical community mourns the loss of a giant who gifted the world the specialty of neuroendovascular surgery.”
Elad Levy
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in 2023, his “intense dedication to multidisciplinary collaboration and mentorship in medicine” was recognised via the Cardiovascular Research Foundation’s Pulse-Setter Champion Award. Last year, he was the honoured guest of the CNS annual meeting, where the ‘Hopkins Symposium’ featured a full programme celebrating his career.
Global homages
The news of Hopkins’ death was met online with hundreds of tributes and messages of condolence from across the globe.
“Folks like me practise our craft in the shade of the tree that he planted and nurtured for decades,” said Charles Matouk (New Haven, USA). “We will visit him often in the pantheon of neurosurgical heroes.”
“[This is] a sad day for our field—a true innovator, visionary and a great human being is gone,” wrote Pascal Jabbour (Philadelphia, USA). “He will remain alive, and his legacy will continue through his disciples and the many lives he saved.”
Hopkins was described by Adam Arthur (Memphis, USA) as “a truly great man, and one of the most impactful leaders and innovators in the entire history of medicine”, with Hal Rice (Southport, Australia) calling him “a true pioneer and gracious legend” and Alejandro Spiotta (Charleston, USA) stating simply that “there will never be another”.
“He made us all believe changing the world was possible by the power of his example,” said Alexander Khalessi (San Diego, USA). “He made his passion for neurovascular disease personal by opening his home, and always being there for his mentees and friends. His life was a true inspiration and gift to us all.”
In addition, as highlighted by Stephen Lownie (Halifax, Canada), Hopkins was the only neurosurgeon in a small, initial group of physicians that helped drive development of the Guglielmi detachable coil (GDC). Lownie also described Hopkins as a “role model” for collaboration alongside interventional neuroradiologists, as demonstrated by his work with Grant Hieshima.
Mohamed Aggour (London, UK) commented that Hopkins was “a legend who marked the lives of many—and not only his patients”, also calling him a “genuine human, humble scientist and leader”, while Michael Lawton (Phoenix, USA) hailed Hopkins as a “father of neuroendovascular surgery” and “a warrior who fought to realise this specialty”.
Current AANS president Jacques Morcos (Houston, USA) also paid tribute, commenting that Hopkins “dared to chase what others could not even see”, and that “his example transcends those he taught, for his appeal is universal”.
Hopkins is survived by his wife of 59 years, Bonnie; his sister, Jane; his three children, Bob, Margie and Betsy; and his eight grandchildren.
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Every hour saved between stroke onset and thrombectomy could equate to 25% greater odds of functional independence Continued from page 1
included five studies; four large, national/international registries—the 2017 STRATIS, 2018 MR CLEAN-R, 2018 Trevo Retriever and 2019 Get With The Guidelines (GWTG)-Stroke registries—as well as the 2020 Triveneto registry from a single Italian region. In combination, these studies comprised data from 11,343 patients. The researchers’ primary endpoint was the rate of functional independence (mRS 0–2) at 90 days, while rates of 90-day ‘excellent function’ (mRS 0–1) and mortality, and level of occlusion, were among key secondary endpoints.
Their results ultimately revealed an increased chance of a good functional outcome, defined as mRS 0–2, with each hour of pre-EVT time savings—a trend that
was present within an earlier time window of 0–270 minutes (odds ratio [OR], 1.25) and a later timeframe of 271–360 minutes (OR, 1.22). Legere et al report that, for each hour saved within the earlier timeframe, the odds of achieving functional independence improved by 25%, with these odds only diminishing slightly to 22% in the later window. In addition, within those studies assessing excellent function, the authors go on to note that comparable trends were observed at timeframes of both 0–270 minutes (OR, 1.34) and 271–360 minutes (OR, 1.20), as the odds of achieving mRS 0–1 were found to increase by 34% and 20%, respectively, with each hour saved. Legere et al also detail that—across their primary and secondary endpoint results on mRS 0–2 and mRS 0–1—“Cochrane’s Q, a reassuring Galbraith graph, and fixed-effects modelling, provided support for a finding that heterogeneity was not present to a degree precluding generation of a pooled effect estimate”.
In addition, the authors state that their analysis was ultimately unable to demonstrate an effect of time savings on mortality, with this being noted for both the early (p=0.68) and late (p=0.71) timeframes. However, they do relay that three included studies reported on the level of occlusion in relation to time savings, with sensitivity analyses to determine any alteration of their overarching findings when including only these studies
Patient empathy and avoiding the trap of depersonalisation
Blaise Baxter
In a guest piece for NeuroNews, Blaise Baxter (San Francisco, USA) discusses empathy and compassion in the working life of a neurointerventionist, and highlights the integral importance of maintaining positive doctor-patient relationships.
The day is off to a familiar start. A code ‘Stroke’ just fired and there is an emergent large vessel occlusion (ELVO) being transferred with an estimated time of arrival (ETA) of 45 minutes. The subarachnoid haemorrhage (SAH) that finally arrived in the intensive care unit (ICU) at midnight has had an external ventricular drain (EVD) placed and needs to be squeezed in between the elective aneurysm and the dural fistula embolisation. With the volume of work and the hectic nature of each day, it becomes easier to begin to think in terms of cases rather than the patients themselves. Additionally, the US Health Insurance Portability and Accountability Act (HIPAA) has made it easier for us to convince ourselves that we detach to protect our patient’s identity. However, if we are to be honest, there is an element of depersonalisation associated with performing high-intensity medical
procedures, day in and day out. For me personally—and I am sure it is true for all operators in our field—our patients and their families are the reason we do what we do. So, if our patients are of primary importance, how do we avoid the trap of depersonalisation?
As medical professionals, we enter into a unique and privileged relationship with a patient and their family. At a showstopping moment in someone’s life, when they are experiencing a life-threatening medical crisis, we show up, and a rapid and deep bonding process begins. Within minutes, family members must make critical life and death decisions regarding a loved one—based on the information we give them. They must quickly decide to put their complete trust in a stranger who has outlined a plan that, for most, is completely foreign. Regardless of where this journey leads, the intimate doctorpatient/family relationship has begun.
revealing that heterogeneity remained acceptable (27.45 %) and each hour saved was estimated to be associated with increased survival (OR, 1.35).
“Quantifying the benefit of faster time to EVT is of critical importance for design and improvement of stroke systems of care,” Legere et al write, discussing their results in greater detail. “Many patients who experience stroke are not near EVT-capable hospitals— over a third of the US population has EMS [emergency medical services] transport time of greater than one hour to a comprehensive or EVT-capable stroke centre.
“Our systematic review and meta-analysis estimated that—within the initial six hours—for every 20 cases of 60-minute reduction in time from LVO acute ischaemic stroke symptom onset to EVT start time, there was one additional case of functional independence.
“Importantly, our findings were based on calculations using a denominator of all EVT cases, so SWIFT-EVT estimations can be broadly useful in application to triage and transfer decisions that are necessarily made without full knowledge (or foreknowledge) of variables such as advanced imaging results or reperfusion success. While not definitive, SWIFT-EVT’s calculations may be useful for systemwide organisation and planning of medical care, as well for those making individual patient triage decisions.”
To develop this relationship in a healthy manner, we must purposefully think about our human kindness and interpersonal skills during these typically brief encounters. It can be easy to give in to the time pressures we feel, but being hurried often leaves a family feeling like they were shortchanged in terms of a clear and understandable explanation. More importantly, being in a rush often leaves an impression that they are not dealing with someone who truly cares.
Honing great communication and interpersonal skills is something that is overlooked all too often in the medical school course curriculum. Empathy, compassion, kindness, patience and being a great listener are all essential skills to cultivate the doctor-patient relationship. We frequently have to build on the limited training we receive in these skillsets by observing others as they interact with patients and their families.
Neurovascular procedures are high stakes and not without risk. These inherent challenges can also factor in to depersonalising the procedural work we perform. We are forced to develop our own coping mechanisms to deal with the inevitable losses that occur when dealing with such devastating disease states. There is a delicate balance between
There is a delicate balance between becoming over attached or over familiar, and remaining professional but not uncaring.”
becoming over attached or over familiar, and remaining professional but not uncaring. Regardless of the difficulty, we must strive to find that balance so that we can more effectively treat our patients and support their families.
To ‘re-personalise’ the relationships we have with patients and families, the Society of NeuroInterventional Surgery (SNIS) introduced the Amy Walters Patient Lectureship award in 2019. This award is given annually at the SNIS meeting to highlight a patient and their family’s journey after suffering a neurovascular crisis. The namesake for the award, Amy Walters, is a dear friend and colleague in the neurovascular community who suffered a major stroke while attending the SNIS annual meeting in 2017. Amy, working with Adam Arthur and Marie Williams, created the award to focus on the journey our patients and their families embark upon on their road to recovery.
Readjusting our perspective by concentrating on patients and families is just one way that we can ensure that our goal remains to serve and walk with those individuals who cross our paths at the most vulnerable moments of their lives.
As stated in the Hippocratic Oath: “I will remember that there is art to medicine as well as science, and that warmth, sympathy and understanding may outweigh the surgeon’s knife or the chemist’s drug.”
Blaise Baxter is an interventional neuroradiologist at Sutter Health’s California Pacific Medical Center (CPMC) Van Ness Campus in San Francisco, USA. He is also a past president of the SNIS and the current chair of the SNIS Foundation. In addition, Baxter was an associate professor and chair of radiology at the University of Tennessee College of Medicine in Chattanooga, USA for several years.
Point of View
Endovascular BCI technology achieves positive results in US COMMAND study
Synchron has announced positive results from the COMMAND study evaluating the safety and efficacy of the company’s Stentrode brain-computer interface (BCI) device in six patients over a 12-month period.
THE STUDY RESULTS WERE presented at the 2024 Congress of Neurological Surgeons (CNS) annual meeting (28 September–2 October, Houston, USA) by Elad Levy (Jacobs Institute/University at Buffalo, Buffalo, USA). Levy is a co-principal investigator for the COMMAND study alongside David Lacomis (University of Pittsburgh, Pittsburgh, USA) and David Putrino (Mount Sinai Health System, New York, USA).
“The COMMAND study results represent a major medical milestone, confirming the safety of the Stentrode BCI with no neurologic safety events reported during the 12-month study
period,” said Levy. “This minimally invasive approach has the potential to unlock BCI technology at scale for the millions of patients with paralysis and other mobility challenges.”
With support from the National Institutes of Health (NIH) BRAIN initiative, COMMAND was conducted at three US clinical sites and enrolled six patients with severe chronic bilateral upper-limb paralysis who were unresponsive to therapy, all of whom received the BCI implant.
All six patients successfully met COMMAND’s primary endpoint of no device-related serious adverse events resulting in death or permanent
Novel BCI technology allows ALS patient to communicate intended speech
A new brain-computer interface (BCI) developed at University of California (UC) Davis Health (Sacramento, USA) has allowed a man with severely impaired speech due to amyotrophic lateral sclerosis (ALS) to communicate by transforming his brain activity into text— which is then read aloud by a computer.
ACCORDING TO UC DAVIS HEALTH, THIS novel device translates brain signals into speech with up to 97% accuracy, making it “the most accurate system of its kind”. A study now published in the New England Journal of Medicine (NEJM) details how researchers implanted sensors into the patient’s brain, and he was able to communicate his intended speech “within minutes” of activating the system.
“Our BCI technology helped a man with paralysis to communicate with friends, families and caregivers,” said David Brandman (UC Davis Health, Sacramento, USA), co-principal investigator and co-senior author of the study. “Our paper demonstrates the most accurate speech neuroprosthesis [device] ever reported.”
The system introduced by UC Davis Health functions by interpreting brain signals when the user tries to speak and turning those signals into text that is subsequently read aloud by a computer. To evaluate their system, the team enrolled Casey Harrell, a 45-year-old man with ALS, in the BrainGate clinical trial. Harrell had tetraparesis and dysarthria at the time of his enrolment, and required others to help interpret his speech. In July 2023, Brandman implanted the investigational BCI device, placing four microelectrode arrays designed to record brain activity from 256 cortical electrodes into the patient’s left precentral gyrus.
A UC Davis Health press release notes that prior efforts to enable communication via BCI technologies have been slow and prone to errors, because the
increased disability during the one-year post-implant evaluation period.
Additionally, the results have reported that patients had no serious adverse events (SAEs) related to the brain or vasculature during the 12-month study period.
As stated in a press release from Synchron, the study also demonstrated that brain signals related to motor intent can be consistently captured and
Stentrode BCI implant
transformed into digital motor outputs (DMOs)—allowing participants to successfully perform a range of digital tasks.
In 100% of cases, the Stentrode device was accurately deployed, demonstrating a median deployment time of 20 minutes and achieving target
machine-learning programmes used to interpret brain signals have required large amounts of time and data.
“Previous speech BCI systems had frequent word errors,” Brandman commented. “This made it difficult for the user to be understood consistently and was a barrier to communication. Our objective was to develop a system that empowered someone to be understood whenever they wanted to speak.”
ALS patient Harrell has used the system in both prompted and spontaneous conversational settings. In both cases, speech decoding occurred in real time, with continuous system updates ensuring that it kept working accurately. The decoded words were shown on a screen and even read aloud in a voice that sounded like Harrell’s before he had ALS, having been composed using software trained with existing audio samples of his pre-ALS voice.
At the first speech data training session, the system took 30 minutes to achieve a word accuracy rate of 99.6% across a 50-word vocabulary. In the second session, the size of the potential vocabulary increased to 125,000 words. With just an additional 1.4 hours of training data, the BCI achieved a word accuracy of 90.2% within this greatly expanded vocabulary. And, following continued data collection, the BCI has been able to maintain an accuracy of 97.5%.
The NEJM study reports on 84 data collection sessions over a period of 32 weeks. Harrell used the speech BCI in self-paced conversations for a total of more than 248 hours, communicating in person and via video chat.
“At this point, we can decode what Casey is trying to say correctly about 97% of the time, which is better than many commercially available smartphone applications that try to interpret a person’s voice,” Brandman said. “This technology is transformative because it provides hope for people who want to speak but can’t.”
Our objective was to develop a system that empowered someone to be understood whenever they wanted to speak.”
David Brandman
motor cortex coverage in the brain for all six patients.
“The users were able to generate DMOs with the BCI. These are simple, thought-derived expressions of intent, converted into digital actions on computers,” said Tom Oxley, Synchron’s chief executive officer and founder. “Making the DMOs easy to use, stable over time, and generalisable across technology platforms, will unlock layers of independence and autonomy for patients.”
The COMMAND study is the first US Food and Drug Administration (FDA)-approved investigational device exemption (IDE) trial of a permanently implanted BCI, according to Synchron. The company’s BCI is implanted in the blood vessel on the surface of the brain’s motor cortex via the jugular vein, utilising a minimally invasive endovascular procedure. Once implanted, it is designed to detect and wirelessly transmit motor intent out of the brain with the goal to restore the capability for severely paralysed people to control personal devices through hands-free, ‘point-and-click’ techniques.
UK hospital completes “world’s first” human graphene-based BCI procedure
INBRAIN NEUROELECTRONICS HAS announced the “world’s first” human procedure involving its cortical brain-computer interface (BCI) in a patient undergoing brain tumour resection. According to a press release, the company’s BCI technology was able to differentiate between healthy and cancerous brain tissue with micrometre-scale precision.
This milestone represents a significant advancement in demonstrating the ability of graphene-based BCI technology—beyond decoding and translating brain signals—to potentially becoming a reliable tool for use in precision surgery in diseases like cancer, and in neurotechnology more broadly, Inbrain claims.
The study in question was conducted at Salford Royal Hospital in the UK. It was led by chief clinical investigator David Coope (Manchester Centre for Clinical Neuroscience, Manchester, UK), and chief scientific investigator and Inbrain co-founder Kostas Kostarelos (University of London, London, UK).
“We are capturing brain activity in areas where traditional metals and materials struggle with signal fidelity,” stated Coope, who performed the recently announced first procedure in the trial. “Graphene provides ultra-high density for sensing and stimulating, which is critical to conduct high-precision resections while preserving the patient’s functional capacities, such as movement, language or cognition.”
“After extensive engineering development and preclinical trials, Inbrain’s first-in-human study will involve 8–10 patients, primarily to demonstrate the safety of graphene in direct contact with the human brain,” Kostarelos added. “The study will also aim to demonstrate graphene’s superiority over other materials in decoding brain functionality in both awake and asleep states.”
The present study—primarily funded by the European Commission’s Graphene Flagship project— is being powered by Inbrain’s graphene-based Intelligent Network Decoding and Modulation (BCI-Tx) platform.
New ESMINT and SNIS presidents among women “making history” in neurointervention
Interventional neuroradiologist Anne-Christine Januel (Toulouse University Hospital, Toulouse, France) has been elected as the new president of the European Society of Minimally Invasive Neurological Therapy (ESMINT)—and, alongside several other physicians, including recently appointed Society of NeuroInterventional Surgery (SNIS) president Johanna T Fifi (Mount Sinai Hospital, New York, USA), is part of a group of women currently “making history” in the neurointerventional space.
THE RECENT ESMINT congress (4–6 September 2024, Marseille, France) saw Januel succeed Zsolt Kulcsár (University Hospital of Zürich, Zürich, Switzerland) as the organisation’s president.
“I am deeply honoured to serve as the new president of ESMINT—a society dedicated to advancing neurointerventional care across Europe and beyond,” Januel told NeuroNews “Building on the excellent foundations laid by my predecessors, particularly Dr Kulcsár, we will continue to focus on education and research, building networks and strengthening our outreach to improve patient outcomes.
“In addition, I intend to promote diversity within our society, ensuring that neurointerventional care benefits
from the strength of varied perspectives and inclusive collaboration. I am incredibly proud to be part of this historic moment for women in neurointerventions, as we work together to shape the future of our field.”
Other significant changes on the ESMINT executive board include the appointments of Christian Taschner (University Hospital Freiburg, Freiburg, Germany) as general secretary and Luca Valvassori (San Carlo Borromeo Hospital, Milan, Italy) as treasurer— and ESMINT 2024 also saw Ivan Vukasinovic (University Clinical Centre of Serbia, Belgrade, Serbia) and Kamil Zeleňák (Comenius University, Bratislava, Slovakia) replace Alessandra Biondi (Besançon University Hospital, Besançon, France) and Elisa Ciceri
(IRCCS Foundation ‘Carlo Besta’ Neurological Institute, Milan, Italy) as congress presidents for the coming year.
In a social media post during the 2024 ESMINT congress, SNIS—having elected Fifi as its president following this year’s annual meeting (22–26 July, Colorado Springs, USA)— acknowledged that Januel is part of a group of female physicians who are currently “making history”.
For the first time, the post adds, four major neurointerventional professional organisations are now being led by a woman. In addition to ESMINT and SNIS’ recent appointments, Thanh N Nguyen (Boston University School of Medicine, Boston, USA) is currently serving as the first ever female president of the Society of Vascular and Interventional Neurology (SVIN), while Stavropoula Tjoumakaris (Thomas Jefferson University, Philadelphia, USA) is presently chair of the joint Cerebrovascular Section of the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS).
Sinai’s Icahn School of Medicine— succeeds Mahesh Jayaraman (Rhode Island Hospital, Providence, USA) as SNIS president, and will lead the society in its pursuit to advance the field and improve patient outcomes in the neurointerventional surgery specialty, according to a press release.
“I’m eager to lead SNIS at a time when our field is advancing rapidly and discovering new ways to apply neurointerventional medicine in areas like paediatrics and oncology,” said Fifi. “Being a member of SNIS pushes us to be better neurointerventionists and advocates. Learning alongside global practitioners within our field is critical, because it ensures that we all continue to grow and innovate for the benefit of our patients.”
Fifi—an interventional neurologist, and professor of neurosurgery, neurology and radiology at Mount
Neurointerventionists ‘can rarely recover payment’ for out-of-network thrombectomy
under US No Surprises Act
A new study has found that neurointerventionists have “essentially no financially viable access to payment recovery” through the US No Surprises Act (NSA) for professional mechanical thrombectomy out-of-network (OON) claims. The study—led by the Harvey L Neiman Health Policy Institute (HPI; Reston, USA) and recently published in the Journal of NeuroInterventional Surgery (JNIS)—generated its findings based on 1,000 simulated years of OON thrombectomy claims.
AS NOTED IN A RECENT PRESS RELEASE from Neiman HPI, patients suffering a stroke or any other condition characterised by an occlusive blood clot do not have time to select their care provider based on their insurance network—and the federal NSA was enacted to protect patients from surprise medical bills when circumstances were beyond patients’ control.
However, “in effect, insurers decide what to pay based on what they consider the typical in-network rate”, the release continues, adding that physician practices have one channel through which to recoup payments from unfair insurance underpayment: the independent dispute resolution (IDR) process. And, while the process comes with “hefty fees”, batching multiple OON claims together can serve to spread out those fees.
Against this backdrop, the recently published JNIS study evaluated the likelihood that neurointerventionists can—given their stroke centre’s case volume—‘batch’ thrombectomy claims in order to spread out IDR costs and make the process financially viable.
Researchers found that, regardless of stroke centre size, the IDR process “was not viable for a vast majority of even global thrombectomy claims”, including both professional and facility costs. Specifically, only 13.2%, 6.1% and 3.3% of claims for
large, medium and small stroke centres, respectively, were shown to recover payments that would exceed IDR fees, according to the modelled data. The researchers also found no opportunity for batch claims covering only professional costs to reach a sufficient quantity to at least recover IDR costs.
“The expected cost of the IDR process is US$235 if only one claim is submitted, and US$281 if multiple claims are submitted in the same batch,” stated Jonathan Grossberg (Emory Healthcare, Atlanta, USA), first author of the study. “Hence, it is financially unwise for a neurointerventionist to submit OON claims to the IDR process unless they expect payment recovery will be at least as much as the costs of entering the IDR process. This means they would need to batch at least four professional claims or at least two global claims before they can expect payment recovery [that is] more than IDR costs.
“Our 1,000 simulated years found that, for large stroke centres, 87% of OON claims could not be batched with another claim given the 30-business-day batching rules. For the 13.2% of claims that could be batched with another claim, in no instance did these batches have more than two claims. While a batch of two global claims is financially viable for entering the IDR process, the reality is that a batch of four or more claims is required to make entering the IDR process
Further changes on the SNIS board of directors include the appointments of Guilherme Dabus (Baptist Health Miami Cardiac and Vascular Institute, Miami, USA) as president elect, Peter Kan (University of Texas Medical Branch, Galveston, USA) as vice president, Justin Fraser (University of Kentucky, Lexington, USA) as treasurer, and Maxim Mokin (University of South Florida, Tampa, USA) as secretary.
financially viable for professional claims.”
The most crucial assumption in the study’s simulation model was the OON rate, the Neiman HPI release notes. The study used an OON rate of 1.1% of commercial claims based on a recent study and, to examine the sensitivity of the results relative to this OON rate, the authors evaluated the results assuming various OON rates from 2–10% of claims.
“Even when we assumed a 10% OON rate, only 11.6% of claims could be batched with four or more claims for neurointerventionists working in a large stroke centre,” said Joshua Hirsch (Massachusetts General Hospital, Boston, USA). “This is the bestcase scenario. For medium and small stroke centres, this percentage is only 3.8% and 0.7%, respectively. Likewise, assuming a 5% OON rate, these percentages are 2%, 0.9%, and 0%, for large, medium and small stroke centres, respectively.
“The NSA process was designed to protect patients from unexpected bills following non-elective medical services. Rulemaking provided insurers with lopsided power, resulting in potential diminution of in-network providers. Given the nature of many neuroendovascular cases, the field is at particular risk of under-reimbursement from commercial health insurance companies and is frequently without access to IDR in a cost-effective manner, as our study shows.”
Rulemaking [has] provided insurers with lopsided power, resulting in potential diminution of in-network providers.”
Joshua Hirsch
Anne-Christine Januel
Johanna T Fifi
HEAL coating holds potential to “alleviate some of the biggest concerns” around neurovascular stenting
While intracranial stents are among the devices most commonly used by neurointerventionists, one challenge that hampers their utilisation in routine practice is thrombogenicity. However, HEAL (Acandis)—a novel coating technology applied to the surface of these devices—has emerged as a means for improving overall treatment safety. Here, NeuroNews speaks to Tomáš Riedel (Czech Academy of Sciences, Prague, Czechia), a scientist who played a leading role in developing the technology, and Hannes Nordmeyer (Solingen Municipal Hospital, Solingen, Germany), a physician with firsthand experience using and studying HEAL, to discuss its potential.
HEAL is an innovative, non-eluting surface modification technology that consists of a fibrin mesh with bound heparin. This unique combination mimics the last step of haemostasis, leading to anti-thrombogenic, anti-inflammatory and endothelialisation-promoting properties, creating the potential to quickly occlude aneurysms and reduce complications associated with endovascular treatment.
“The HEAL coating is a groundbreaking technology designed specifically for neurovascular stents, incorporating several innovative features that enhance its performance and safety,” Riedel says. “It addresses the inherent challenges associated with stent implantation, such as the risk of thrombosis, inflammation, and delayed healing.” A key characteristic of HEAL is its combination of two separate endogenous components: fibrin and heparin.
rates of long-term complications. Owing to these characteristics as well as its biomimetic design and non-eluting, localised action, Riedel believes that HEAL “sets itself apart” from other coatings.
“HEAL stands out because it directly covers all these critical aspects related to neurovascular stent treatment at once,” he states, adding that the majority of current surface modification technologies target either thrombogenicity or endothelialisation—but typically fail to address both simultaneously.
“The fibrin network is produced through a process that closely mimics the final stage of haemostasis, replicating the natural formation of fibrin during the wound healing process,” Riedel explains. “This biomimetic approach ensures that the fibrin has very low thrombogenicity, and provides an excellent scaffold for endothelial cells, thereby creating an environment conducive to vessel repair—which is critical for long-term stent success. And, to further reduce thrombogenicity of the coating, heparin is covalently crosslinked within the fibrin matrix. This ensures that the heparin remains firmly attached to the fibrin coating, making it stable and more resistant towards fibrinolysis while providing a localised effect without being released into the bloodstream. By immobilising heparin in this way, HEAL creates a strong anti-thrombogenic cover at the stent site, reducing the risk of thrombosis while avoiding the potential complications of systemic anticoagulation. In this way, fibrin and heparin work synergistically in the HEAL coating, with both components helping to reduce inflammation and create an environment that is crucial for restoring the integrity of the vessel lining.”
Standing out from the crowd
According to Riedel, HEAL has the capacity to provide a “highly effective and safe solution for neurovascular stenting”, with its effects having been confirmed via “extensive” in-vitro and in-vivo studies. Through its anti-thrombogenic, anti-inflammatory and endothelialisation-promoting characteristics, HEAL offers benefits that directly target “crucial” challenges associated with neurovascular stent placement. The technology’s anti-thrombogenicity eases a “major concern” associated with neurovascular procedures by reducing the risk of blood clot formation; its anti-inflammatory properties help minimise vessel wall inflammation, which can lead to complications like restenosis; and, by promoting growth of healthy endothelial cells over the stent, it can be seen to facilitate natural vessel healing and potentially reduce
“HEAL provides a balanced solution by tackling both immediate and long-term challenges,” he notes. “Its combined, comprehensive approach offers significant advantages over other commercially available coatings, as well as mitigating the need for prolonged dual antiplatelet therapy [DAPT], which is a common requirement with stents. In fact, existing studies suggest HEAL can be effectively used under single antiplatelet therapy [SAPT], lowering risks of bleeding complications and enhancing the patient’s quality of life.”
The study Riedel cites here was published earlier this year by Uysal et al in the American Journal of Neuroradiology, detailing initial experiences treating brain aneurysms with the DERIVO® 2heal® Embolisation Device (Acandis) under standard or reduced-dose SAPT. The authors observed an absence of permanent, periprocedural neurologic deficits and favourable occlusion rates, indicating HEAL’s potential to increase the safety and efficacy of flow diversion.
SAPT versus DAPT
“Nowadays, we’re facing more and more emergency situations that demand DAPT— for example, in rescue stenting or in aneurysm treatment,” Nordmeyer says. Regarding the former example, he highlights ischaemic stroke cases where recanalisation cannot be achieved via first-line thrombectomy, leading the operator to place a stent instead. “These patients are not prepared for stenting, because they are usually not on DAPT beforehand,” he adds. “We need to put them on aggressive therapy and, in an emergency setting, we need fast-acting medications to keep the stent open.”
situations”, according to Nordmeyer. HEAL’s potential benefits recently moved closer to being more widely realised, as the DERIVO 2heal Embolisation Device’s instruction for use (IFU) has been updated to give physicians the choice of implanting the device alongside SAPT—when no other treatment option is deemed suitable and it is justified due to, for example, heightened risks of haemorrhagic complications.
Clinical experiences
Nordmeyer and his team in Solingen implanted their first HEAL-coated devices in 2021—and, today, their experiences with the coating comprise a large series of both ischaemic and haemorrhagic cases. Here, Nordmeyer highlights multiple instances of strokes and brain aneurysms in which HEAL has enabled his team to treat patients using devices like the DERIVO 2heal Embolisation Device, or the CREDO® heal Stent (Acandis), while also transitioning them to a monotherapy and ultimately making their antiplatelet strategy “less aggressive”.
A multicentre study published recently in Clinical Neuroradiology by Dorn, Nordmeyer et al constitutes the largest clinical evaluation of the CREDO heal Stent to date. In 81 patients receiving postthrombectomy rescue stenting to treat intracranial stenosis, the device was found to be safe and effective, with final modified thrombolysis in cerebral infarction (mTICI) 2b–3 achieved at a rate of 95.1% after a median of two thrombectomy manoeuvres plus stenting, and just four periprocedural complications resulting in clinical deterioration being observed.
However—similarly to Uysal et al—the authors conclude that more data are needed to define optimal antithrombotic regimes in these cases. Nordmeyer adds that sufficient antiplatelet therapy will likely remain “mandatory” in rescue stenting until further studies have established the real-world advantages of implanting the CREDO heal Stent under SAPT.
“Apart from HEAL’s reduced thrombogenicity that, of course, has to be proven in larger trials like RECHRUT, we have to evaluate the reduction of inflammatory reactions and endothelialisation,” he continues. “As per the literature, we expected a 15–20% rate of in-stent restenosis in these cases—but, in those evaluated with follow-up DSA [digital subtraction angiography], we found much lower in-stent restenosis numbers due to neointimal hyperplasia. This may be attributed to the reduced inflammatory effects and more natural endothelial healing enabled by HEAL.”
Alluded to here by Nordmeyer, RECHRUT is an ongoing study evaluating post-thrombectomy rescue stenting with the CREDO heal Stent. Recently presented interim results show “technical and clinical success in line with the literature on rescue stenting”, with a 100% rate of mTICI 2b–3 recanalisation and no recurrent occlusions in the first 18 patients enrolled.
Such patients have likely undergone a complex recanalisation procedure that carries the risk of bleeding-related complications—a risk exacerbated by the medications required during rescue stenting. “What we need in these cases are products that could enable us to treat them under mono-prasugrel or mono-clopidogrel therapies,” Nordmeyer explains. He goes on to state that a similar concept applies to haemorrhagic diseases, including acute aneurysm cases that cannot be successfully treated with coils or intrasaccular devices, thus requiring stent usage and creating “the same problem” of bleeding risks. As such, coated stents “would be a gamechanger in these
“I think the potential of such a coating is really significant, once we have data that give us the confidence to really change our antiplatelet regimens, because it opens the door to treat more patients— including in the acute setting, in patients with a high haemorrhagic risk who have to be treated under SAPT,” Nordmeyer concludes. “It could also enable us to apply these products to more processes inside smaller vessels where very subtle intimal hyperplasia can lead to severe and haemodynamically relevant in-stent restenosis. So, overall, HEAL could alleviate some of the biggest concerns around putting implants into the neurovasculature.”
Tomáš Riedel
Hannes Nordmeyer
Ten years of MR CLEAN: Stroke thrombectomy’s evolution and ongoing challenges
Charles Majoie Diederik Dippel
This year, 25 October marks a full decade since the initial presentation of results from the MR CLEAN randomised controlled trial (RCT), which—along with multiple other RCTs—instigated the rapid expansion of mechanical thrombectomy in the treatment of acute ischaemic stroke. Here, two of MR CLEAN’s leading clinical investigators, Charles Majoie (Amsterdam, The Netherlands) and Diederik Dippel (Rotterdam, The Netherlands), reflect on the impact of the study and outline remaining areas for improvement regarding thrombectomy treatments.
Within a decade, the landscape of acute stroke treatment has changed drastically. Looking back now, to when it all began at the 9th World Stroke Congress (WSC; 22–25 October 2014, Istanbul, Türkiye), shows that much has been done and changed, and many patients have benefitted—but we are not finished yet!
Here, we present a historical summary and also a global overview of the availability of this highly effective treatment for ischaemic stroke.
Evolution of EVT
Before 2014, thrombectomy—or endovascular therapy (EVT)—was performed in selected cases, mostly under research protocols or in major stroke centres. The MR CLEAN trial helped to change that by providing high-quality evidence, prompting rapid adoption in clinical practice. By 2015, after MR CLEAN and subsequent trials, EVT became part of routine stroke care guidelines, resulting in significant global growth.
The pivotal MR CLEAN trial was first presented at WSC on 25 October 2014, marking a turning point in the treatment of ischaemic stroke. This groundbreaking study highlighted the benefits of EVT for large vessel occlusion (LVO) strokes, and it paved the way for global changes in stroke management.
MR CLEAN was published in the New England Journal of Medicine in January 20151, followed by publication of six other landmark trials: ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, THRACE and PISTE, and an individual patient data metaanalysis.2 These trials confirmed the efficacy of EVT in treating acute ischaemic stroke, solidifying its place
access to thrombectomy, reinforcing the need for further expansion efforts.
Global access disparity
The number of interventions performed worldwide has skyrocketed—but disparities in access remain. While developed regions benefit from widespread implementation of EVT, many lower-resource countries still face challenges in providing this life-saving treatment. Such a gap calls for increased efforts in infrastructure development and training to make EVT more universally available.
Developed regions—including North America, Western Europe, Australia and parts of Asia like Japan and South Korea—have seen a more uniform increase in thrombectomy rates due to established infrastructure, access to stroke care centres, and trained interventionists. In contrast, many low- and middle-income regions and countries still have limited access to EVT, despite growing recognition of its importance. This leads to considerable variation in thrombectomy availability across the world.
procedures, combined with the critical urgency of stroke care, has underscored the need for better workforce support, including improved work-life balance, team expansion, and mental health resources.
In addition, with expanding indications, there is a growing need for refined patient selection to ensure that EVT is used optimally. The MR PREDICTS tool represents a promising selection algorithm that could help clinicians identify patients most likely to benefit from thrombectomy, potentially improving outcomes and streamlining decision-making.5,6 Looking ahead, the key focus must be on increasing EVT availability, particularly in underrepresented regions and countries. Initiatives should focus on building capacity, training more interventionists, and enhancing stroke care infrastructure, including prehospital triage and stroke unit care in underserved areas to ensure that all patients—regardless of location—can access this life-saving treatment and benefit from it in a sustainable way.
References:
as the standard of care. The profound impact of these studies is evidenced by widespread citations and recognition in stroke literature.
Over the past decade, the indications for EVT have expanded significantly. Initially limited to LVO within 0–6 hours of stroke onset, it now encompasses treatment windows extended to 24 hours, and patients with small to large infarcts.3 Treatment is no longer confined by age or certain preexisting conditions, making EVT a viable option for a broader range of stroke patients.
The expanded eligibility criteria for EVT—including patients presenting up to 24 hours after stroke onset and those with more extensive infarcts—has dramatically increased the number of potential candidates for the procedure. This has also contributed to the surge in thrombectomy numbers worldwide.
In recent years, China and India have made efforts to scale up thrombectomy services, given their large populations and increasing burden of stroke. This can be seen with the increased number of thrombectomies in China, rising from 20,000 in 2019 to 72,000 in 2023. But, although growth has been rapid, these countries are still catching up in terms of the ratio of thrombectomy procedures relative to stroke incidence. In 2023, in India, only 4,500 out of 375,000 patients who qualified for stroke intervention received this lifesaving treatment.
Further challenges
In 2016, roughly 30,000–40,000 thrombectomies were performed across the globe. By 2020, this number grew substantially to more than 100,000 annual procedures, driven by better access, expanded treatment windows, and the broadening criteria for patient eligibility. For 2022–2023, estimates suggest over 150,000 EVT procedures globally per year, with regions like North America and Europe accounting for a large proportion of these numbers.4
However, despite this remarkable growth, the lack of adequate facilities and trained professionals in many regions continues to hinder global
The success of acute thrombectomy has highlighted the need for adequate post-intervention stroke unit care and basic rehabilitation, in order to make the effect of the treatment sustainable. Stroke unit care benefits more patients, and its overall health impact—on a population level— is at least as significant as the effect of thrombectomy.
The increasing demand for thrombectomies has also placed a significant burden on interventional teams, leading to an increased risk of burnout. The intensive nature of EVT
1. Berkhemer O A, Fransen P S, Beumer D et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015; 372(1): 11–20.
2. Goyal M, Menon B K, Van Zwam W H et al Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016; 387(10029): 1723–31.
3. Nguyen T N, Abdalkader M, Fischer U et al Endovascular management of acute stroke. Lancet 2024; 404(10459): 1265–78.
4. Rai A T, Link P S, Domico J R. Updated estimates of large and medium vessel strokes, mechanical thrombectomy trends, and future projections indicate a relative flattening of the growth curve but highlight opportunities for expanding endovascular stroke care. J Neurointerv Surg. 2023; 15(e3): e349–55.
Charles Majoie is a professor of neuroradiology at the Amsterdam University Medical Centers (UMC) in Amsterdam, The Netherlands.
Diederik Dippel is a neurologist and professor of neurovascular diseases at the Erasmus Medical Center (MC), and co-director of the Erasmus MC Stroke Centrum, in Rotterdam, The Netherlands.
The success of acute thrombectomy has highlighted the need for adequate postintervention stroke unit care and basic rehabilitation, in order to make the effect of the treatment sustainable.”
Point of View
Stroke thrombectomy: Limitless potential or a success story nearing its final chapter?
Mechanical thrombectomy has gone from strength to strength in the treatment of acute ischaemic stroke over the past decade—progressing beyond early-window large vessel occlusions (LVOs) to patients presenting >6 hours post-symptom onset and those with occlusions located in the posterior circulation. The latest frontier thrombectomy appears to have conquered is those cases characterised by more extensive infarcts on imaging, generally referred to as ‘large-core’ strokes. However, as alluded to by both Wim van Zwam (Maastricht University Medical Center, Maastricht, The Netherlands) and Joseph Broderick (University of Cincinnati College of Medicine, Cincinnati, USA) in recent interviews with NeuroNews, a number of important questions remain.
Earlier this year, the LASTE trial became the latest addition to an ever-growing list of published randomised controlled trials (RCTs) indicating the safety and clinical benefit of mechanical thrombectomy in ischaemic strokes with large ischaemic cores. Outlining their results in the New England Journal of Medicine (NEJM), the LASTE investigators report that thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone, but also led to a higher incidence of symptomatic intracerebral haemorrhage (sICH), across a population of acute stroke patients with a large infarct of unrestricted size presenting within seven hours of symptom onset.
The past three years have seen a number of similar RCTs presented to the world, starting with the Japanbased RESCUE-Japan LIMIT trial in early 2022, which established the notion that thrombectomy may be safe and more effective than the existing standard of care for these large-core stroke patients. This has since been followed by the Chinese ANGELASPECT and global SELECT2 trials, and the largely European TENSION study, all of which met their primary endpoint and echoed prior indications of the benefits to treating large-core patients endovascularly. TESLA—a solely USA-based RCT—very marginally missed its three-month primary endpoint for demonstrating thrombectomy’s effectiveness versus medical care, but generated a more successful finding at one-year follow-up.
While these studies are being grouped together as ‘the large-core trials’, they all differ from one another in a handful of subtle yet meaningful ways. Notably, where RESCUE-Japan LIMIT, ANGEL-ASPECT and SELECT2 all primarily defined a ‘large core’ as one characterised by an Alberta stroke programme early computed tomographic score (ASPECTS) of 3–5, TESLA included a wider range of core volumes (ASPECTS 2–5). In addition, a point that TESLA and TENSION have prided themselves on is their use of more pragmatic imaging protocols, solely utilising non-contrast CT scans to define core volumes. ANGEL-ASPECT and SELECT2, on the other hand, have integrated CT perfusion or diffusion-weighted magnetic resonance imaging (DW-MRI) into their assessments of infarct sizes. And, continuing this trend, ASPECTS ranges and imaging protocols are among the minutiae upon which LASTE appears to have broken new ground.
“A unique feature of our trial was the lack of restriction on the upper limit of the infarct size,” the LASTE authors write. “Consequently, 56% of the patients in our trial had a baseline infarct size (ASPECTS value ≤2) that would have precluded their enrolment in other trials that included patients with a large core. Furthermore, the median baseline infarct
volume of 135ml in our trial was larger than that in other trials, which may explain why the percentages of patients who died or had severe disability were higher than those in other trials. Nonetheless, the effect favouring thrombectomy was similar in magnitude to that seen in other thrombectomy trials, including those that only enrolled patients with a small or moderately sized baseline infarct; however, no direct comparisons with other trials can be made because of differences in trial designs and patient populations.”
TESLA in context
One point that Van Zwam is keen to address when homing in on the results of these studies is the perception of TESLA and its findings; having missed its three-month primary endpoint, the trial is more likely than any of its large-core contemporaries to be thought of as a ‘negative’ research endeavour. However, Van Zwam points out that a key driver of this outcome was the triallists’ use of Bayesian statistical analyses—as opposed to a more conventional approach, which would have seen the trial reach its primary endpoint and likely come to be viewed in an even more positive light.
“They had to present it as a ‘neutral’ trial that missed the threshold of its primary endpoint,” Van Zwam comments. “But, for me, it’s a positive trial. If you compare it with the other trials, the treatment effect is just as large, so it’s a matter of how you interpret the data.”
As mentioned previously, the TESLA trial also came to reach its primary success measure upon evaluation of the 12-month follow-up data, and has since been joined by both SELECT2 and TENSION in achieving positive results in the long term. The apparent uptick in thrombectomy’s clinical benefits from three months to one year led TESLA’s presenting authors to conclude that—in addition to highlighting the importance of continued follow-up and rehabilitation—their findings point to the better recovery and overall improvement in functional outcome enabled by thrombectomy. Van Zwam agrees with this conclusion, adding that the observed effect is demonstrative of the fact that, over a longer period of time, patients in control groups receiving only standard medical care without thrombectomy do even worse versus those who are treated interventionally, resulting in a more noticeable divergence in functional outcomes between the two.
“It’s something that we’ve also seen with the MR CLEAN-LATE trial. We didn’t see a difference in mortality [between thrombectomy and controls] after three months, but there was a difference after two years,” he continues, stating that a similar trend appears to be present in patients with large-core strokes—a group that, in general, already experiences
worse outcomes versus those with smaller infarcts. “That is the mechanism we see with longer followup. We saw it in REVASCAT as well; after one year, the treatment benefit is still there, and mortality is increasing in the control group. And it makes sense that the treatment effect in larger cores will be even stronger after a longer period, because the control groups in these low-ASPECTS trials do very badly.”
Truly defining ‘large core’
According to Van Zwam, the fact that TESLA initially missed its primary endpoint makes the results of LASTE “even more spectacular, because around 50% of its patients had an ASPECTS of 0–3, with the other half being ASPECTS 4–5”.
“In LASTE, we were afraid that those very severe, very low-ASPECTS patients would dilute the effect of thrombectomy and it would not produce significantly positive results—but it was positive [at the six-month follow-up], even though it had that large cohort with very low ASPECTS,” he explains.
While LASTE has been lauded as the latest in a long line of momentous breakthroughs with stroke thrombectomy, the neurointerventional community is still faced with a handful of unresolved challenges. And, in Broderick’s view, despite the overwhelming positivity surrounding them, the published trials in this space do carry their own limitations—with one of these being a degree of “overlap” in how each of them defines large core.
“First of all, I think almost all of them started with patients who really had no disability or minimal disability to begin with, meaning they’re a very pristine group—they’re not people who already have some functional disabilities, brain injuries or a lot of prior strokes. So, that’s one thing you’re taking out,” Broderick states. “In addition, I think our data on large-core patients with ASPECTS ≥3 are pretty good, but data on ASPECTS 0–2 are still very limited. And, also, when you get to large cores as defined by perfusion studies, we don’t have a lot of data beyond the 100cc range. We also don’t have a lot of data on the very old. So, there are a lot of questions that still have to be answered.”
Van Zwam and Broderick are in agreement about another area requiring further clarity: potential discrepancies between a patient’s ASPECTS and the true ‘core size’ of an ischaemic stroke. While a low ASPECTS has become something of a proxy for general stroke severity, Van Zwam notes that ASPECTS primarily indicates early signs of ischaemia and reduced perfusion, but does not provide conclusive information on the extent to which areas of brain tissue are already ‘dead’ or unsalvageable. This is because some of the damage may in fact be reversible if the affected blood vessel can be reopened and reperfused once more. According to Van Zwam, this notion has been confirmed via studies looking at final infarcts in which stroke severity has turned out to be lower than anticipated based on ASPECTS.
“There is a lot of research in progress right now, and these trials help enormously, but a single item like large core on perfusion CT or like ASPECTS probably does not define whether a patient should receive
L-R: Wim van Zwam, Joseph Broderick
thrombectomy or not, or their chance of a good outcome,” Van Zwam explains, also highlighting areas of demarcated hypodensity on imaging as potentially being a better indicator of ‘real core’ that is truly unsalvageable. However, even this metric is unable to account for the convergence of numerous variables— brain frailty, old age, atrophy, hyperglycaemia and hypertension as well as time last known well—that all play into thrombectomy-related decision-making.
“We should, in fact, be very liberal in treating patients with all of those early signs of infarction because, even in the late window, those signs don’t define anything beyond the severity of the symptoms when the patient enters the hospital. ASPECTS shows the area that is affected but it doesn’t tell us what tissue is still salvageable. I think, when you have ASPECTS 1–2—especially in the very early window—the patient can still do very well if you treat them [with thrombectomy] very quickly. In the later window, you may have to be a bit more selective, but we still suspect that ASPECTS is not a good discriminator between who will benefit from treatment and who will not.”
In addition, the early signs of ischaemia on imaging are often very subtle, with several factors contributing to their appearance, meaning the determination of ASPECTS can also be highly subjective.
“There are whole discussions going on right now regarding those baseline CT scans,” Broderick adds. “How dark is dark on ASPECTS? What’s the measurable water content in the brain? One term I’ve heard used recently is that, while there’s the ‘dark brain’ that’s pretty much dead, maybe there’s the ‘dusty brain’ that might not be dead yet but is getting close. So, again, there’s a lot of variability in definitions and a lot of variability in the populations being studied, and it’s going to be important for us to work out—with these larger areas of damage—who best qualifies for treatment, as well as being realistic about the benefit itself.”
The timing of ASPECTS measurement is also thought to hold some relevance, as earlier imaging— either on CT or MRI—is a less clear indicator of ‘dead brain’ as compared to imaging performed in the later time window. On this point, Broderick highlights the fact that LASTE required ASPECTS imaging to be done within 6.5 hours.
Another point he makes is that determining ASPECTS based on CT imaging or MRI is not the only way that a large core can be defined. An alternative approach is via diffusion-weighted changes, which Broderick says gives a clearer indication of tissue that is likely to be unsalvageable versus parts of the brain that are not yet ‘dead’ despite appearing to have diminished blood flow. However, this discussion is something of a balancing act because, while DW-MRI—as compared to baseline CTs—is likely to be a more accurate and less ambiguous indicator of irreversible brain damage, CT imaging offers a significantly more pragmatic and easy-to-use solution that is far more widely available and utilised at a greater proportion of centres.
“I don’t think MRI is going to end up being the standard imaging tool for stroke patients in the emergency department, at least for a while,” Broderick speculates. “It is in some places, where they have it set up and they have very good programmes—but
CT is just so fast, and it provides a lot of information to help make initial decisions, so I don’t see its role being usurped by MRI at this moment in time.
“The other thing is that, in some places, they go right to the angio suite and do a ‘poor man’s’ CT—but a reasonable CT—with the equipment they have there. Again, this saves time, and time really is brain. It’s been a frequent refrain for many, many years, but it’s true, so anything that can get you the key information that you need to help make the best decisions is going to be the predominant way that we treat patients.”
New frontiers
Looking back to 2013, when three RCTs—IMS III, MR RESCUE and SYNTHESIS—were published, and suggested unanimously that thrombectomy should not be considered an appropriate treatment for LVO acute ischaemic stroke, the situation stands in stark contrast to the groundswell of enthusiasm surrounding the intervention today. Patient inclusion criteria, treatment time windows, imaging protocols and the quality of thrombectomy devices all hampered those earlier studies, before being optimised ahead of the five positive RCTs published just two years later.
It may therefore come as little surprise that greater refinement in each of these areas, in addition to an improved understanding of the mechanisms behind the procedure and ever-growing levels of operator experience, has led to positive results in subsequent trials seeking to expand thrombectomy’s range further still. LASTE and the other large-core RCTs, as well as the 2018 DAWN and DEFUSE-3 studies extending the appropriate therapeutic window to 6–24 hours, and the more recent ATTENTION and BAOCHE trials supporting the endovascular treatment of basilar-artery
The recent largecore trials are a step forward [...] but there are still a lot of unanswered questions.”
occlusions (BAOs), are all notable examples. As Van Zwam quips, “nowadays, it seems that whatever trial we do will be positive, because the treatment effect is so significant”. Nonetheless, in the minds of both Van Zwam and Broderick, further studies will add critical information to the neurointerventional community’s current knowledge base. Here, Van Zwam highlights stroke patients with very mild symptoms and low National Institutes of Health stroke scale (NIHSS) scores as a noteworthy area of interest moving forward, with strokes caused by more distal or medium-vessel occlusions (D/MeVOs) being another.
However, on the latter front, he advises a degree of caution, citing the fact that many skilled physicians already routinely operate on more distally located occlusions—and have done for many years following the positive LVO stroke trials of 2015—despite a multitude of RCTs specifically investigating these cases still being in progress right now. A second area where some discrepancy remains is the aforementioned basilar artery: while the successes of the Chinese ATTENTION and BAOCHE alleviated some concerns in this location following more mixed results from BASICS and BEST, one of the drivers of this was their decision to focus solely on BAO patients with more severe deficits.
“We sometimes become overenthusiastic and think that all treatments will be beneficial, which is ‘nearly true’,” Van Zwam opines. “Most of the trials we do now are positive, but there are a few exceptions. I
don’t think we should always treat the BAOs with very mild symptoms endovascularly. And the more distal occlusions with mild symptoms—maybe not, but we have to wait for the trial results. Even at conferences, you see that companies often offer dedicated devices for very distal occlusions, and physicians present cases where they go very distal with a tiny device and show that they can open the vessel. But I don’t know if, in general, this is a good thing to do. We have to wait.”
The bottom line
“I think we’re going to find that there are limits to thrombectomy [in the brain], like there are in the heart—they have the same issue with myocardial infarction and we’re about 10 years behind them,” Broderick adds. “We have slightly different situations in terms of what causes the strokes and even the devices we use to treat them. The recent large-core trials are a step forward, and we have a lot of data to work with, but there are still a lot of questions that are unanswered.”
In addition, while LASTE has created an air of excitement around the idea that thrombectomy’s effect may not be curtailed by even the largest infarct sizes, Broderick believes it is important for interventionists to remain realistic and reasonable regarding the benefits they expect to see with endovascular treatment versus best medical care.
“We have to take into account the patient’s functional status and what the family’s wishes are,” he says. “What do you do in the case of somebody who already has a major deficit and experiences a large-core stroke? The best you can hope for is to get them back to the same deficit or, more probably, a less functional state than before.
“I also think that, while there’s been a lot of excitement about large core, there has been some pushback from the interventional community, because people just don’t like to take care of patients who— even if you open up their artery and they do a little bit better—are still going to be pretty affected by their stroke. People prefer to take the patients who are younger and, when you reopen their vessel, they’re able to walk again and talk again. A lot of the more severe large-core stroke patients still die or have a very bad outcome, even though we’ve moved the needle in the right direction with endovascular treatment.”
Broderick comments that it will likely take time for physicians to become more comfortable with the existing data and how they relate to routine practice, and—as he puts it—this continued angst over whether or not to treat certain patients proves that, “even among the interventional community, it’s not all smiles and rainbows”.
“However, I think the main message is that, for patients who appear to have a reasonable amount of brain injury, some of them can still have an [acceptable] outcome—they don’t all return to full functional ability but, if you look at a scale of how well they function, there is some improvement compared to those who did not get any kind of intervention,” he continues. “And the bottom line is that, as long as we’re doing good, randomised trials, and we’re being as inclusive as possible, we’ll gain more and more information about who best qualifies and who doesn’t qualify for thrombectomy. It’s about getting the best data from the scientific trials and then applying them to the individual situation, and the individual patient.”
To conclude, Broderick draws attention to an upcoming statement being worked on by the American Heart Association (AHA) that will “provide a lot more clarity” when it comes to the large-core trials— adding that, “while we’ve made a lot of progress, that statement will really help to illustrate what we know and what we don’t know”.
THANH N NGUYEN
As one of six women currently leading major neurointerventional societies across the globe, Thanh N Nguyen (Boston, USA) is proudly playing a key role in challenging the medical field’s history of underrepresentation. In addition to her present tenure as president of the Society of Vascular and Interventional Neurology (SVIN), Nguyen is also professor of neurology, neurosurgery and radiology at Boston University Chobanian and Avedisian School of Medicine, as well as director of Interventional Neuroradiology and Interventional Neurology, and attending physician in the Vascular Neurology Service, at Boston Medical Center. Here, Nguyen speaks to NeuroNews about her neurointerventional mentors, ongoing efforts to boost gender equity in the field, and the most impactful clinical studies she has contributed to, among other topics.
What initially attracted you to medicine, and the field of neurology specifically?
I was drawn to medicine by my father, who was a primary care physician. The interest was to help people, understanding it would be a great privilege to learn and think about patient symptoms and physical signs.
I became interested in neurology during medical school when I had the chance to learn, from my neurologist teacher Colin Chalk at McGill University (Montreal, Canada), how to perform a history and physical exam. Fascinated with the nervous system, it was then that I knew this is what I wanted to study.
Who have your most valued mentors been and how have they impacted your career?
I have been fortunate to have many mentors, foremost of whom are my piano teacher Luba Zuk, as well as neurointerventional mentors Jean Raymond, Alexander Norbash, Osama Zaidat and Raul Nogueira. Luba taught me the importance of a work ethic with daily piano practice and how to communicate music with an audience.
Jean Raymond, Daniel Roy, Alain Weill and Francois Guilbert—my fellowship teachers—were instrumental in teaching me the simplicity, rigour and art of the neurointerventional field. I also learned about scientific writing and the importance of pragmatic trials from Jean. He believed that randomisation should be part of our clinical practice and that, with or without funding, it was our imperative to find the answers of how best to treat our patients through randomisation. My first papers with Jean were a sea of red lines. Jean was my harshest and toughest critic, which has helped me build to how I write today.
Osama Zaidat gave me my first multicentre research project from the NASA registry, from which my confidence in research sprouted.
Raul Nogueira was my senior resident, from whom I drew inspiration and guidance in neurointerventional research.
You are currently midway through your tenure as SVIN president—could you outline your experiences to date and your future aspirations in this role?
It has been a terrific journey and learning experience to serve as SVIN president. I have been fortunate to have a great team with our SVIN officers, board of directors, and committee chairs and vice-chairs. During my time as president, we have learned the
importance of governance to empower our colleagues and our youth to succeed, lead and grow in synergy. I have had the pleasure to meet and work with a broad array of volunteers from our society, committee leaders, and the community at large. Our SVIN volunteers and our committee leaders are our bedrock. They drive the many missions of our society forward.
Some of these experiences to date including the development of the SVINStroke Interventional Lab Certification (SILC) initiative, in conjunction with Mission Thrombectomy. We acknowledge the importance of recognising and advocating for SILC labs globally. Fawaz Al-Mufti, our SVIN Mission Thrombectomy chair, has done a terrific job representing SVIN at the United Nations. We have had a terrific streak of educational platforms via the ‘WebNIRs’ and Virtual Stroke Academy, led by Krishna Amuluru and Amanda Jagolino-Cole.
Over the next few months, we are rolling out brief practice updates and SVIN guidelines— you can be on the lookout for these in Stroke: Vascular and Interventional Neurology, our SVIN journal! And, the best is yet to come, as our annual meeting (20–22 November 2024, San Diego, USA) is around the corner, led by Alexandra Czap with a stellar lineup of speakers and innovation.
You are the first woman president of SVIN in its 18-year history. What impact do you think this will have?
Our field has an underrepresentation of women. We are now at an inflection point, with six neurointerventional societies being led by women—SVIN, the Society of NeuroInterventional Surgery (SNIS), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the AsianAustralasian Federation of Interventional Therapeutic Neuroradiology (AAFITN), the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Cerebrovascular Section, and the Argentine College of Neurointerventionists (CANI). It is our collective hope that this will draw more women to our field.
In addition, under the leadership of Robin Novakovic-White, the multisociety women’s group—where we forge common areas of discussion, collaboration and communication between women leaders across multiple societies—was initiated this past year. Dr Novakovic-White has also developed a women’s speaker registry so that conference
FACT FILE
CURRENT APPOINTMENTS
2023–present: President, SVIN
2019–present: Professor, Neurology, Neurosurgery and Radiology, Boston University Chobanian and Avedisian School of Medicine
2007–present: Director, Interventional Neuroradiology and Interventional Neurology, Boston Medical Center
EDUCATION
2005–2007: Fellow, Interventional Neuroradiology, University of Montreal Hospital Center
2004–2005: Fellow, Stroke and Neurocritical Care, Massachusetts General Hospital (MGH)/Brigham and Women’s Hospital
2001–2004: Resident, Neurology, MGH/Brigham and Women’s Hospital
2000–2001: Intern, Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
2000: Doctor of Medicine (MD), McGill University Faculty of Medicine
HONOURS (SELECTED)
2022: Paper of the Month Award (JAMA Neurology publication), World Stroke Academy/ World Stroke Organization
2018: Fellow, American Heart Association (FAHA)
2017: 2019–2023: Top Doctor, Boston Magazine
2012: Fellow, SVIN (FSVIN)
2004: Senior Neurology Resident Teacher of the Year Award, MGH/Brigham and Women’s Hospital
organisers can refer to a list of women speakers, along with their area of expertise, as they plan their meetings.
Why is it necessary for neurologists, neurosurgeons, radiologists and other relevant specialties to cooperate and work together effectively, and how can this be achieved?
The advancement of our field draws from the collective strengths of the expertise and knowledge that each of our colleagues bring across multiple disciplines. This can be achieved by encouraging a collaborative environment of equity and sharing, whether it be from our shared advocacy efforts, educational outreach, or research collaborations.
What do you feel has been the most important development in the field of neurology during your career?
As many would agree, the most important advancement in the field of neurology has been the development and implementation of mechanical thrombectomy to decrease disability in patients with acute stroke secondary to large vessel occlusion. The abilities to embolise an aneurysm or pseudoaneurysm with coils, or embolise a dural fistula or chronic subdural haematoma without having to do open surgery, have also been remarkable innovations for our field.
Which of the studies you have been involved with do you believe has had the greatest impact on neurointerventional care?
I have been fortunate to be involved in many innovative and high-impact trials and projects, including ABBA, ACTION-CVT, ADJUVANT, ANGEL-ASPECT, ANGELREBOOT, ANGEL-TNK, ARAMIS, ASSETIT, ATTENTION, ATTENTION-IA, BASIS, BRIDGE-TNK, CLASS, CLEAR, ESCAPEMeVO, Global COVID SVIN Registry, MARVEL, PICASSO, PLATO, POST-TNK, POST-UK, REACT, RESCUE-BT, RESCUEICAS, SELECT2, SUMMIT MAX, SVIN Registry, TATUM, TEAM, TESLA, TOBAS, and TRIMIS.
I believe that the CLEAR (Computed tomography [CT] for late endovascular reperfusion) study has had an impact on neurointerventional care, based on anecdotal feedback I’ve received, as it has enabled sites—particularly those with no access to perfusion imaging—to have data to show that treatment of patients with thrombectomy in the late window, as selected by non-contrast CT and CT angiography (CTA), conferred equally good outcomes compared to patients selected with advanced CT perfusion or magnetic resonance imaging (MRI).1
And, we recently showed, with data published in the journal Neurology, that treating these patients with non-contrast CT and CTA selection had twice the odds of good outcomes compared to the medical management of these patients.2
Besides your own work, what is the most interesting piece of stroke research you have seen in the past year?
I was intrigued by the TRACE III trial, wherein patients with an arterial occlusion presenting in the 4.5-to-24-hour window who had no access to thrombectomy but had salvageable tissue were shown to have better outcomes when treated with intravenous tenecteplase compared to those who were medically managed.
This offers a ray of hope for treating patients where systems of care or their economic circumstances do not permit thrombectomy access.
Looking ahead, which technologies or studies do you feel are likely to have the most significant impact on the treatment of neurovascular diseases?
There are many exciting innovations that are under development or in clinical trials.
The Cerevasc endovascular shunt developed by Carl Heilman and Adel Malek
is a novel way to divert cerebrospinal fluid into the venous system for patients with communicating hydrocephalus, without having to place a ventriculoperitoneal shunt.
Brain-computer interfaces have the potential to restore function to patients affected by amyotrophic lateral sclerosis, stroke or spinal cord injury.
Nanoparticles developed by Euphrates are a novel way to break up distal clots that may not be amenable to treatment with current endovascular techniques.
What advice would you give to people embarking on a career in the field of neurology?
It is important to keep an open mind and continue to learn the broad specialties of medicine—even if you know that you want to go into neurology. There are many intersections between medicine and neurology, so learning broadly will serve as a strong foundation base upon which you build your clinical skills.
"The advancement of our field draws from the collective strengths of the expertise and knowledge that each of our colleagues bring across multiple disciplines.”
What are your interests outside of the field of medicine?
Playing piano, playing tennis, and spending time with my daughters. Also, in my earlier years, marathon running—but my knees gave out after the seventh marathon—and crosscountry skiing.
What is your favourite song to play on the piano?
Ballade No. 1, Opus 23, by Frédéric Chopin.
References:
1. Nguyen T N, Abdalkader M, Nagel S et al. Non-contrast computed tomography versus computed tomography perfusion or magnetic resonance imaging selection in late presentation of stroke with large vessel occlusion. JAMA Neurol. 2022; 79(1): 22–31. DOI: 10.1001/jamaneurol.2021.4082.
2. Nguyen T N, Nogueira R G, Qureshi M M et al. Non-contrast computed tomography-selected thrombectomy versus medical management for late-window anterior large vessel occlusion. Neurology. 2024; 102(10): e209324. DOI: 10.1212/ WNL.0000000000209324.
Flow diverters “particularly effective” but also associated with “non-negligible” complication
rate in distal ACA aneurysms
An analysis presented at this year’s European Society of Minimally Invasive Neurological Therapy (ESMINT) congress (4–6 September, Marseille, France) has indicated that flow diverters are “particularly effective” in the treatment of unruptured, distal anterior cerebral artery (ACA) aneurysms, while also highlighting the potential risk of ischaemic complications associated with this approach.
THE ANALYSIS IN QUESTION was delivered by Luca Scarcia (Henri Mondor Hospital, Créteil, France) on behalf of investigators for CRETA—a retrospective and prospective registry evaluating the clinical and radiological outcomes of endovascular treatment for distal ACA aneurysms that has enrolled 512 patients from 39 hospitals across 14 countries to date, and was developed alongside co-principal investigators Andrea Alexandre (Gemelli Hospital, Rome, Italy) and Adam Dmytriw (Massachusetts General Hospital, Boston, USA).
“Distal aneurysms—especially distal ACA aneurysms—are very poorly represented in [current] series of flow diverters,” the speaker initially noted, highlighting the backdrop to the present study.
Scarcia and colleagues’ analysis of CRETA included adult patients with unruptured ACA aneurysms located beyond the anterior communicating artery who underwent flow-diverter treatment from January 2018–December 2022. Their primary endpoint was complete occlusion of the target aneurysm at final follow-up, as per classification on the O’Kelly-Marotta (OKM) grading scale. Key secondary endpoints included the rate of adequate occlusion on OKM as well as the incidence and types of complications, radiological outcomes of covered branches, mortality, and modified Rankin scale (mRS) scores.
In total, 168 patients with 168 unruptured, distal ACA aneurysms treated with a flow diverter (74.4% female; median age, 61 years) were available for analysis. The vast majority of these cases were saccular (91.7%) as opposed to fusiform (8.3%) aneurysms, and
the median parent vessel diameter across the cohort was 1.9mm. Regarding treatment results, Scarcia noted that a single flow diverter was implanted in 162 cases (96.4%), with the most frequently used devices being the Silk Vista Baby (Balt; 47%) and the Pipeline Shield (Medtronic; 26.1%). In addition, adjunctive coiling was performed in 11 aneurysms (6.5%) while only one patient included in the analysis received single antiplatelet therapy (SAPT).
Arriving at the crux of the analysis, Scarcia reported that complete occlusion (OKM D) at final radiological follow-up—which took place at a median timepoint of 16.5 months—was seen in 118 cases (70.2%), and adequate occlusion (OKM C–D) was observed in 138 cases (82.1%). Immediate occlusion rates were as follows: 8.9% OKM D; 10.7% OKM C; and 80.4% OKM A–B. The analysis also saw just two patients undergo retreatment (1.2%), with both cases involving adjunctive flow-diverter treatment. Scarcia then relayed the analysis’ clinical outcomes, noting that 18 periprocedural thromboembolic complications occurred (10.7%), with 16 of these ultimately resulting in the patient being asymptomatic at the final clinical followup. There were also seven cases of haemorrhagic complications (4.2%)—of which five were intraparenchymal haemorrhages, and one resulted in an mRS shift of 4. Covered side-branch occlusion occurred in 10.1% of cases. The speaker went on to highlight a “very, very low” mortality rate of 0.6%, with the one and only death seen in the analysis ultimately adjudged to have been unrelated to the
Tiny ‘magnetic robot armies’ could be used to treat aneurysmal brain bleeds
Researchers have created nanoscale robots that could be used to manage bleeds in the brain caused by aneurysms, potentially enabling a more precise and relatively low-risk treatment approach.
A STUDY PUBLISHED RECENTLY
in the journal Small “points to a future where tiny robots could be remotely controlled to carry out complex tasks inside the human body” in a minimally invasive way, according to a team fronted by clinician researchers from the University of Edinburgh’s School of Engineering (Edinburgh, UK) and the Shanghai Sixth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (Shanghai, China).
Such tasks include targeted drug delivery and organ repair, the researchers suggest.
“Nanorobots are set to open new frontiers in medicine, potentially allowing us to carry out surgical repairs
with fewer risks than conventional treatments and target drugs with pinpoint accuracy in hard-to-reach parts of the body,” said Qi Zhou (University of Edinburgh, Edinburgh, UK), who coled the study. “Our study is an important step towards bringing these technologies closer to treating critical medical conditions in a clinical setting.”
The research team engineered magnetic nanorobots about a 20th of the size of a human red blood cell comprising blood-clotting drugs encased in a protective coating that are designed to melt at precise temperatures. In lab tests, several hundred billion of these robots were injected into an artery and then remotely guided as a ‘swarm’— using magnets and medical imaging—to
flow-diversion procedure. Overall, 85.7% of patients had an mRS score of 0 at final follow-up, Scarcia added.
“The high rate of occlusion suggests that flow diverters are particularly effective in treating aneurysms in this location, probably due to their ability to reconstruct the parent artery and promote endothelialisation over the aneurysm neck, as suggested by other studies,” he also stated, discussing the results of the present analysis.
Scarcia further noted that traditional coiling “often struggles” when it comes to aneurysms that are located in challenging anatomical regions like the distal ACA.
“Despite good efficacy, the use of flow diversion in distal ACA aneurysms in our series was associated with a non-negligible rate of complications [10.7%], with thromboembolic events being the most frequent—although most were asymptomatic,” he continued. “These findings are similar to those reported in a recent meta-analysis, which found a complication rate of 12.5% for distal ACA aneurysms treated with flow diversion. The neurological morbidity rate observed in our study [2.8%] was also comparable to other studies.”
Scarcia concluded by alluding to potential limitations of the analysis: its retrospective design; the fact there was no standardisation regarding antithrombotic therapies among participating centres; and the lack of centralised core lab imaging analyses or independent clinical outcome assessments.
However, he also pointed to the analysis’ multicentre nature, large number of cases and relatively long follow-up periods as being among its strengths—before reiterating that, overall, this study underscores the efficacy of flow diverters in treating unruptured, distal ACA aneurysms while also drawing attention to potential associated risks of ischaemic complications.
the site of a brain aneurysm.
Magnetic sources outside the body then cause the robots to cluster together inside the aneurysm and be heated to their melting point, releasing a naturally occurring blood-clotting protein, which blocks the aneurysm to prevent or stem bleeding into the brain.
The international research team successfully tested their devices in model aneurysms in the lab and in a small number of rabbits. The researchers say that nanorobots show potential for transporting and releasing drug molecules to precise locations in the body without risk of leaking into the bloodstream—a key test of the technology’s safety and efficacy.
The researchers also believe the study could pave the way for further development towards trials in people.
Their advance could ultimately improve on current treatments for brain
Nanorobots are set to open new frontiers in medicine.”
aneurysms, whereby doctors typically thread a tiny microcatheter tube along a patient’s blood vessels before using it to insert devices that either stem the aneurysmal blood flow or divert the bloodstream in the artery.
The researchers posit that their new technique could decrease the risk that the body will reject implanted materials, and curb reliance on anti-blood-clotting drugs, which can cause bleeding and stomach problems.
In addition, this new method avoids the need for doctors to manually shape a microcatheter to navigate a complex network of small blood vessels in the brain in order to reach the aneurysm— which is described by the researchers as a “painstaking task” that may take hours during surgery. Larger brain aneurysms—which can be particularly difficult to stem quickly and safely using metal coils or stents—could potentially be treated using the new technique too, the researchers believe.
The study recently published in Small was led by a team from the UK and China who have also developed nanorobots to remove blood clots, meaning they hold potential in the treatment of stroke.
Luca Scarcia
Endovascular treatment of brain aneurysms—
is under 5mm a ‘go’ or ‘no-go’ area?
Victor Volovici
Point of View
In light of recently presented and generally positive findings from the COAST study, which deemed coiling to be safe in the treatment of small (<5mm) intracranial aneurysms, Victor Volovici (Rotterdam, The Netherlands) outlines existing clinical data, and weighs up the real-world pros and cons of this approach.
During a well-represented, highstakes meeting on the treatment of intracranial aneurysms, a US physician once stated: “Coiling aneurysms under 5mm is like voting for Trump—nobody says they do it, and everybody does it”.
The question of whether aneurysms under 5mm should undergo treatment at all, and whether it is safe to do it, has been lingering in the minds of researchers and clinicians for at least the past two decades. The COAST study has made an important step towards a better understanding of the consequences of such a treatment. In order to better put
these results in perspective, however, we should take into consideration the natural history of intracranial aneurysms, look at ruptured and unruptured aneurysms separately, and discuss blood blisterlike aneurysms as well. One of the most often-heard arguments in favour of treatment when discussing small aneurysms is the discrepancy between natural history studies, showing a low longitudinal risk of haemorrhage from small aneurysms, on one hand, and retrospective analyses showing a preponderance of small aneurysms in large subarachnoid haemorrhage (SAH) series on the other.
TOBAS analysis finds low event rate with conservative care of unruptured AVMs
Patients with unruptured brain arteriovenous malformations (AVMs) who are allocated to conservative management, or ‘observation’, experience a low rate of neurological events, according to a TOBAS registry analysis presented by Jean-Christophe Gentric (Cavale Blanche Hospital, Brest, France) at the 2024 European Society of Minimally Invasive Neurological Therapy (ESMINT) congress (4–6 September, Marseille, France).
GENTRIC DELIVERED AN INTERIM REPORT on a total of 434 patients evaluated within the TOBAS registry, noting that the analysis included some patients with ruptured AVMs but primarily consisted of unruptured AVM cases (87%), with a roughly even split of low- and high-grade AVMs across the entire cohort. A mean follow-up period of 3.3 years resulted in a total of more than 1,300 patient years within the analysis. Its primary endpoint was an AVM-related modified Rankin scale (mRS) score >2 at any time—although, for patients with an initial mRS score >2 at enrolment, the primary endpoint shifted to an mRS point increase ≥1. He went on to report that 23 out of 434 patients
These facts make researchers conclude that, ‘small aneurysms do bleed, and the risk of haemorrhage may be much higher than expected’. On the one hand, natural history studies are, primarily, highly selected longitudinal registries of Japanese patients not selected for treatment. The aneurysms perceived morphologically to pose a higher risk were treated and were thus not eligible for follow-up. This state of affairs makes natural history data heavily confounded by indication and likely an underestimation of the true risk in a non-representative population. On the other hand, epidemiologically, smaller aneurysms are the larger group—their prevalence is much higher. Therefore, their higher prevalence in SAH studies should not come as a surprise and may purely reflect the mathematical distribution of aneurysm size in general. The truth probably lies somewhere in the middle, with natural history studies likely underestimating the true risk of rupture, but not to the extent suggested by these retrospective studies.
The COAST study included 300 patients from 15 centres in the USA over a timespan of about five years. In terms of the ruptured aneurysms included, these were ‘ISAT-type aneurysms’, in which coiling was proven beneficial— and it is good to see that, even for the smallest aneurysms on this spectrum, ‘simple’ coiling is feasible and should remain the go-to treatment. In terms of the unruptured aneurysms, this is where the discussion makes a turn into a greyer area. The abstract and the presentation of COAST do not give sufficient detail about the types of patients and the characteristics of the aneurysms included.
(5.3%) reached the analysis’ primary endpoint, and that seven of these patients had a low-grade AVM compared to 16 with high-grade AVMs. These numbers correspond to an incidence of death or new/ worsened dependency of 1.7 per 100 patient years (95% confidence interval [CI], 1.1–2.5) for all patients in the study, and to an even lower incidence of 0.6 per 100 patient years (95% CI, 0.2–1.7) for low-grade, unruptured AVMs specifically. Additionally, poor outcomes were found to be more frequent in ruptured AVMs and infratentorial AVMs, and in patients aged 55 years or older. Regarding instances of intracranial haemorrhage (ICH), Gentric detailed that 38 patients (9%) experienced a new ICH, with 35 of these being major. The overall incidence of any new ICH was therefore found to be 2.8 per 100 patient years. Among patients with low-grade AVMs, the incidence of any new, major ICH was 1.3 per 100 patient years, and major AVM rupture occurred in 4% of these patients with one (0.6%) being fatal. Some of the finer points of Gentric et al’s analysis revealed that new, major haemorrhages were more frequent in patients with a history of previous AVM rupture; in high-grade AVMs or those that were large in size; and in AVMs with deep venous drainage. The speaker stated that the rate of all serious adverse events (SAEs)—including haemorrhages—was 3.6 per 100 patient years across the entire cohort. Among low-grade, unruptured AVMs, this incidence decreased
Death or new/ worsened dependency
1.7 per 100 patient years across the entire study
0.6 per 100 patient years solely in low-grade, unruptured AVMs
Such a treatment can only be considered safe when its safety profile outweighs the lifelong bleeding risk. As such, whether a disability and mortality rate of ‘just’ 2.4% makes the treatment safe is debatable. The treatment is preventive; therefore, it can only be justified in aneurysms in which the lifelong bleeding risk is higher. Treatment is perhaps also justifiable for relatively young patients without comorbidities, and less so for older patients. One important aspect of this treatment, nevertheless, is patient preference. Often—especially in the USA—patients have a very strong treatment preference, substantiated by the wealth of online information found on reputable websites. Many patients may be more than willing to accept the 49-to-1 odds of a negative outcome. In addition, no mention is made in the abstract or the presentation about blood blister-like aneurysms. While certain people do not agree with this terminology, and there are debates over whether these aneurysms truly ‘exist’ as a separate pathological entity, some reports suggest a more fragile aneurysmal wall and thus a greater risk of periprocedural rupture. The optimal strategy regarding blood blister-like aneurysms remains incompletely assessed. All aspects considered, the COAST is not clear yet— but most rooms have been confirmed to be enemy-free by the interventional team.
Victor Volovici is a cerebrovascular and skull-base neurosurgeon, methodologist, and clinical epidemiologist—and co-director of the Center for Complex Microvascular Surgery—at Erasmus University Medical Center in Rotterdam, The Netherlands.
to 1.8 per 100 patient years. Overall, SAEs were found to have been more common in ruptured, high-grade and infratentorial AVM types. In terms of major, non-haemorrhagic neurological events, Gentric noted an incidence of 0.6 per 100 patient years across the full cohort, and highlighted the fact that 26 patients (6%) were treated during the follow-up period, including 11 with lowgrade, unruptured AVMs. In roughly half of these cases—14 out of 26 and 6 out of 11, respectively—treatment was in response to a major neurological event. Providing a closer examination of these findings, Gentric reiterated that—across a follow-up period of three years—the analysis showed low risks of death or new/worsened disability (1.7% per year), but that new, major ICHs were the main driver among patients who did experience these negative outcomes (2.6% per year). Gentric also noted that these results “are in line with previous studies that have almost universally identified rupture status, deep venous drainage, and infratentorial location, as risk factors for future haemorrhages and poor clinical outcomes”. The speaker further highlighted absolute risks of major ICH in the analysis as being “very similar” to those in the existing literature as well, at 2–3% per year for unruptured and 4–8% per year for ruptured AVMs.
“In conclusion, observation was proposed to nearly half of the patients recruited in TOBAS, and patients observed over a mean of 3.2 years suffered from a relatively low rate of neurological events,” he added.
Revisiting unruptured aneurysm risk and the UK ROAR study
Diederik Bulters
A lack of overall understanding regarding rupture risks is one of the most notable challenges impeding the successful treatment and management of brain aneurysms—and therefore also represents one of the most pressing unmet needs faced by these patients. In a guest piece for NeuroNews, Diederik Bulters (Southampton, UK) lays out the scope of this challenge and outlines how the UK Risk of Aneurysm Rupture (ROAR) study is attempting to provide some much-needed answers.
Deciding with your patient whether or not to treat an unruptured intracranial aneurysm remains one of the most common clinical scenarios faced by neurovascular specialists. It is unlikely to have a single, uniform answer applicable to everyone, and it is therefore not a question that can be addressed by a randomised trial—even in the unlikely event that sufficient buyin could be found, from both patients and clinicians, to undertake one.
As such, it is likely that, for most of our careers, treatment decisions will continue to be made based on our understanding of the natural history of aneurysms.
On the face of it, there is a lot known about this, and studies like ISUIA and PHASES were step changes in our understanding of how to manage the condition. Despite this, there remain many uncomfortable contradictions in the available data that are difficult to reconcile and difficult to explain to patients.
Existing evidence
When we first started thinking about this problem, we took things back to basics and asked: what is it that patients want from our risk prediction models? And does our existing evidence satisfy these requirements? Our conclusion was that they want three things: models that are accurate, personalised, and long term (ideally lifetime).
If we assess what we have, it is hard to claim that we are sure our risk predictions are accurate, when the available studies all give conflicting estimates. At the extremes, we have the ISUIA and Finnish studies. ISUIA showing a 0% risk of a small aneurysm rupturing is in stark contrast to the Finnish data showing a 26% rupture
methodology, and therefore PHASES does not really resolve the issue that we do not know which estimates are accurate for our patients.
In addition to questions about accuracy, it is also questionable to what degree our estimates are personalised. Most of the studies have provided risk estimates based on a couple of factors—mostly aneurysm size and location. This is largely due to power limitations posed by low event rates. Even PHASES only considers six features, and does not consider things like family history or aneurysm shape. It is very difficult to persuade a patient with two first-degree relatives who have had a subarachnoid haemorrhage (SAH) that this should not be weighed up when deciding whether or not to treat their aneurysm!
for National Statistics (ONS). In the UK, almost all patients found to have aneurysms will be discussed with a neurosurgeon—and we have used this to collect detailed baseline clinical data on more than 20,000 patients with unruptured aneurysms.
We are also fortunate to have a single national database of admissions and deaths. While the level of detail on these is limited, the data are perfect for detecting events of SAH that will always lead to hospital admission or death. If used as a screening tool for aneurysm rupture, we have demonstrated they can help to detect 95.8% of events, rising to 98.2% when used in combination with neurosurgical records, and can be used to follow up patients indefinitely.
risk at 30 years.
Whichever study we opt to use, we must make significant assumptions. Using ISUIA, we have to assume that the 72% of patients treated—including the ones that did not enter the trial’s conservative management arm—were treated at random. That is to say there was no selection based on features that may alter rupture risk that were not accounted for in the analysis (for example, aneurysmal blebs or family history). The Finnish data are subject to essentially no treatment or followup bias, and they are therefore very attractive to adopt—even if they came from only 142 patients. However, to use these data, we have to assume there are no differences in rupture risk between populations.
It is worth mentioning that there is also a third source of data. This comes from Japan and actually provides the largest dataset by some margin. It also has higher rates of rupture than ISUIA. This is particularly unfortunate given Japan is also the only country other than Finland hypothesised to have different rupture rates from the rest of the world. It leaves clinicians outside of Japan and Finland with the difficult decision of whether to use the most representative population (ISUIA), the data with the least bias (Finland), or the largest dataset (Japan).
The PHASES meta-analysis, in many ways, set out to resolve this. However, in choosing to include Finland or Japan, or neither, as one of the predictors, it has made the assumption that the differences in rupture risk are due to differences in populations, and not study methodology and consequent biases. In truth, we do not know whether the differences are due to differences in populations or
And perhaps the biggest issue is that of long-term risk. A typical female patient presenting at 50 years of age has a life expectancy of nearly 40 years. The median length of follow-up in PHASES was just one year. To use this, we need to extrapolate. This assumes risk is constant over time—however, we simply do not know if this is the case. Some clinicians believe aneurysms are most at risk early after diagnosis, whereas PHASES suggests that they are riskier in older age. Even if the risk of rupture does not change over time, just tiny differences in one-year risk make huge differences in lifetime estimates. There are real, practical barriers to
We hope, in time, to be able to provide what our brain aneurysm patients need: accurate, personalised lifetime estimates of rupture risk.”
resolving these issues. To study rupture risk, you need a large study population consisting of thousands of patients, due to low event rates. To personalise estimates, you need to increase sample sizes much further, to tens of thousands of patients. You then need to find ways to follow up such a large cohort in the long term while also minimising follow-up biases.
ROAR study
We designed the ROAR study to overcome these barriers and address those three fundamental requirements that we identified at the outset: that data are accurate, personalised and long term.
We have done this by linking local neurosurgical records, and national databases of hospital admissions and deaths from NHS Hospital Episode Statistics (HES) and the UK Office
We have been very lucky to initially obtain funding from local charities—including Smile4Wessex and the Polycystic Kidney Disease (PKD) charity—to pilot this work and subsequently secure funding from the Royal College of Surgeons and National Institute for Health and Care Research (NIHR) in the UK for the full study.
We have baseline data on over 20,000 patients. We have linked the first 10,000 patients to HES/ONS data, and the remaining 10,000 are currently undergoing linkage by NHS England. Over the next year, all cases of aneurysm rupture will be manually validated before—hopefully—we are able to report first results in autumn 2025.
Going forward, we hope to secure recurrent funding to search the cohort against HES/ONS data every five years, in order to update our evidence base with rupture risk timeframes of increasing lengths. We also want to link to the three systems of general practitioner (GP) records used in the UK to study time-dependent variables—including medication, blood pressure and hormones—and we are pulling magnetic resonance imaging (MRI) scans from the cohort for image analysis. Furthermore, with the assistance of Hereditary Brain Aneurysm (HBA) Support and the International Stroke Genetics Consortium, we are making applications to obtain saliva samples from the cohort, to aid with DNA extraction and genotyping.
We therefore hope, in time, to be able to provide what our brain aneurysm patients need: accurate, personalised lifetime estimates of rupture risk.
Diederik Bulters is a consultant neurosurgeon and professor of neurosurgery at University Hospital Southampton in Southampton, UK. He also served as president of the British Neurovascular Group from February 2019 to November 2021. Bulters is the chief investigator for the ROAR study—a UK-based, multicentre research project aiming to enhance the current understanding of brain aneurysm rupture risks.
Point of View
Roughly half of all healthy life lost to stroke is caused by haemorrhagic subtype, new study suggests
The latest analysis of the Global Burden of Disease, Injuries and Risk Factors study (GBD), assessing data ranging from 1990–2021, has indicated that roughly half of all healthy years of life lost due to stroke worldwide are caused by haemorrhagic stroke— despite it being almost half as common as ischaemic stroke.
The analysis revealed that, with 81 million healthy years of life having been lost, haemorrhagic strokes were responsible for half of all strokerelated disability and lives lost globally in 2021. The most affected people were found to be those aged 70 years and younger—as well as those living in lowincome countries, where the proportion of strokes characterised by intracerebral haemorrhage (ICH) is double compared to high-income countries (37% vs 18%, respectively). In addition, regarding the major drivers of stroke across the globe, the GBD analysis’ investigators report that—“for the first time”—their study suggests ambient particulate matter air pollution is a top risk factor for subarachnoid haemorrhage (SAH), currently contributing to 14% of the death and disability caused by this stroke subtype at a rate that is comparable to smoking.
More broadly, the researchers conclude that the worldwide stroke burden has undergone a rapid rise since 1990, with ageing and growing populations as well as a significant increase in people’s exposure to environmental and behavioural risk factors being among the key drivers escalating stroke’s prevalence today. These findings were recently published in The Lancet Neurology and subsequently presented at the 2024 World Stroke Congress (WSC; 23–26 October, Abu Dhabi, United Arab Emirates).
Rapid rise of stroke burden
Although stroke is now considered a highly preventable and treatable condition, this newly published GBD analysis provides evidence that there has been a notable uptick in the global burden of the condition over the past three decades.
Across the globe, the number of people having a new stroke rose to 11.9 million in 2021—a 70% increase from 1990. The number of stroke survivors rose to 93.8 million (up 86% versus 1990) and stroke-related deaths rose to 7.3 million (up 44% versus 1990), making the condition the third most common cause of death worldwide in 2021, behind ischaemic heart disease and COVID-19. More than three quarters of those affected by stroke live in low- and middle-income countries (LMICs), the GBD analysis also found. The number of disability-adjusted life years (DALYs) lost to stroke was observed to have increased by 32% between 1990 and 2021, with the estimated amount of healthy life lost growing from 121.4 million years to 160.5 million years—making stroke the fourth leading cause of worldwide health loss after COVID-19, ischaemic heart disease, and neonatal disorders.
Investigators for the GBD analysis conclude that the burden of stroke is rising due in no small part to population growth and the prevalence of ageing populations across the globe. However, they also identify a number of preventable environmental, metabolic and behavioural risk factors that have “increased substantially” and contributed to rising stroke numbers from 1990 to 2021. Examples include an 88% increase in high body mass index (BMI), a 72% increase in high temperatures, and a 32% increase in high blood sugar rates. And, while accounting for the impact of demographics via ‘age standardisation’ revealed that there was a trend towards lower worldwide rates of stroke incidence (down 22%), prevalence (down 8%), deaths and DALYs (both down
39%) across almost every level of country income between 1990 and 2021, the investigators ultimately found that improvements in global incidence rates have “stagnated” since 2015. In addition, age-standardised rates of stroke incidence and prevalence, as well as stroke-related death and DALYs, have worsened across Southeast Asia, East Asia and Oceania, and also in people younger than 70 years of age.
“The global growth of the number of people who develop stroke—and died from or remain disabled by stroke—is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” said lead author Valery Feigin (Auckland University of Technology, Auckland, New Zealand). “New proven-effective, population-wide and motivational, individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk—as recommended in the recent Lancet Neurology Commission on Stroke— should be implemented across the globe urgently.”
Discrepancies and risk factors
The present study has revealed that, in 2021, there were “striking differences” in the overall stroke burden between world regions and national income levels. In high-income areas in North America and Australasia, and middle-income parts of Latin America—regions with the lowest stroke burden—the agestandardised rates of incidence and prevalence were lowest in New Zealand (67.8 and 707.4 per 100,000 people, respectively); death rates were lowest in Canada (20.4 per 100,000 people); and DALY rates were lowest in Australia (435 per 100,000 people). In contrast, in low- and middle-income regions of East and Central Asia, and also sub-Saharan Africa, the rates of incidence, prevalence, death and DALYs were between two and 10 times higher (more than 248, 1,458, 190 and 4,320 per 100,000 people, respectively) in 2021.
“Stroke-related health loss disproportionately impacts many of the most disadvantaged countries in Asia and sub-Saharan Africa due to the growing burden of uncontrolled risk factors, especially poorly controlled high blood pressure, and rising levels of obesity and type 2 diabetes in young adults, as well as the lack of stroke prevention and care services in these regions,” explained co-author Catherine Johnson (Institute for Health Metrics and Evaluation [IHME], Seattle, USA). “The shift in stroke burden towards younger populations is likely to continue unless effective
preventive strategies are implemented urgently.” The investigators found that metabolic risk factors— especially high BMI, high systolic blood pressure and high low-density lipoprotein (LDL) cholesterol— contributed to the greatest level of stroke burden across all country income levels, ranging from 66–70%, in 2021. This was followed by environmental risk factors collectively—including air pollution, low/high ambient temperature and lead exposure—in LMICs, ranging from 35–53%. Overall, in 2021, the five leading global risk factors for stroke were high systolic blood pressure, particulate matter air pollution, smoking, high LDL cholesterol, and household air pollution, with considerable variation by age, sex and location. Alongside their finding that ambient particulate matter air pollution is now a leading risk factor for SAH, the investigators report that “substantial progress” has been made in reducing the overall global stroke burden from risk factors linked to poor diet, air pollution, and smoking, suggesting that strategies to reduce exposure to these risk factors over the past three decades—such as clean air zones and public smoking bans—have been successful.
Opportunities for progress
NEW STROKES
Among other key findings from the GBD analysis is an estimation that the global number of stroke-related DALYs, attributable to a total of 23 different risk factors, has risen from 100 million years of healthy life lost in 1990 to 135 million in 2021—presenting “a public health challenge and an opportunity for action”. The largest proportions of these risk factors are found in Eastern Europe, Asia, and sub-Saharan Africa. “With 84% of the stroke burden linked to 23 modifiable risk factors, there are tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Johnson added. “Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated. And, with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes. Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis.”
The authors believe that, through implementing and monitoring evidence-based recommendations set out in the 2023 World Stroke Organization-Lancet Neurology Commission on Stroke, there is an opportunity to “drastically reduce” the global burden of stroke in this decade and beyond.
According to Feigin, “additional and more effective” stroke prevention strategies “must be urgently implemented across all countries”—including task-shifting from doctors to nurses and health volunteers; wider use of evidencebased mobile and telehealth platforms; pragmatic solutions to address critical gaps in stroke service delivery; workforce capacity building; and epidemiological surveillance systems.
Experts align on ‘outdated’ nature of two-week CEA target for symptomatic carotid patients
Gianluca Faggioli (University of Bologna, Bologna, Italy) and Gert J de Borst (UMC Utrecht, Utrecht, The Netherlands) went head-to-head at the 2024 European Society for Vascular Surgery (ESVS) annual meeting (24–27 September, Kraków, Poland) to debate a motion that the two-week carotid endarterectomy (CEA) target for symptomatic patients is ‘outdated’, and that evidence-based treatment is now achievable.
FAGGIOLI’S MAIN ARGUMENT, OPENING the debate, was that both clinical and anatomic factors should be used to determine the timing of intervention rather than a set threshold.
The presenter first addressed the origin of the two-week CEA target. “It’s come from the fact that the risk of recurrent stroke usually happens within 15 days,” he informed ESVS attendees. Early intervention, Faggioli continued, is supported by a paper from Rantner et al, in which performing CEA within seven days is shown to reduce the risk of subsequent stroke. However, Faggioli stressed that to fully answer the question at hand, it is important to understand that neurological symptoms in symptomatic patients are highly varied and must be categorised into stable and unstable, with stable symptoms being far more common.
Citing a review of the literature on patients with stable symptoms, Faggioli relayed that stroke and death rates among patients operated within 48 hours actually appear to be higher than those in patients operated later on, but not significantly so. Regarding transient ischaemic attack (TIA), the presenter continued, the literature and the guidelines suggest ascertaining the cause of the TIA before intervening.
“After that,” he said, “you can intervene without a significant recommendation regarding the timing of the intervention”. Faggioli also noted that intervening within 48 hours after a stroke incurs a far greater risk of complication than intervening later on.
However, the presenter stressed that there is a wide variety of data on this topic, adding also that in patients with more severe strokes and extended ischaemic lesions, the risks associated with
SVS Vascular Quality Initiative launches Carotid Care Quality Champion programme
The Society for Vascular Surgery Vascular Quality Initiative (SVS VQI) clinical registry has announced the Carotid Care Quality Champion recognition programme.
THE PROGRAMME HONOURS healthcare organisations across the USA dedicated to improving the safety and effectiveness of vascular care through participation in the VQI’s carotid artery stenting and endarterectomy registries.
intervening quickly “are very much increased”.
“We have to consider not only the presence of the cerebral lesions but also their size and the clinical appearance of these strokes,” Faggioli emphasised.
Furthermore, the presenter noted that there is a “significant” difference in outcomes for patients with large ischaemic lesions treated before and after four weeks. Finally, in patients with more significant ischaemic lesions, Faggioli continued, European guidelines recommend deferring carotid intervention, while US guidelines advise against treatment.
“Symptomatic carotid patients can present with a variety of clinical and anatomical situations,” Faggioli said in his conclusion, emphasising that these must be central to any treatment decision.
“Timing of revascularisation should be decided according to both clinical and anatomical factors.”
De Borst was in agreement that the two-week threshold is ‘outdated’. Where his argument differed from Faggioli’s related to the available evidence, with the presenter highlighting its heterogeneity.
“First of all,” de Borst began, “I think it’s crucial that we discuss stable symptoms—that’s where the greatest benefit can be achieved.”
With this in mind, the presenter gave an overview of the available literature, starting with the oldest. He highlighted a high natural-cause risk apparent here. “In the past,” he explained, “relatively early surgery was considered to be associated with very high perioperative risk, and that was why CEA was delayed on purpose—to six weeks or more.”
This changed with an analysis from Rothwell et al, de Borst noted. “Not everybody is aware where this 14-day threshold actually came from—it’s from this
Select facilities across the country have been recognised as Carotid Care Quality Champions. These organisations engage the SVS VQI infrastructure to monitor the quality of care for their vascular patients and help them comply with the latest societal and governmental guidelines, including the change in carotid artery stenting coverage reflected in the Centers for Medicare and Medicaid Services’ (CMS) recent national coverage decision (NCD) 20.7.
As part of the CMS NCD 20.7 reimbursement modifications, the organisation requires centres to establish a quality monitoring programme and maintain institutional and physician standards. Registry participation provides a robust and user-friendly approach to CMS compliance. A press release notes that the SVS VQI carotid artery stent registry is the gold standard for
analysis,” he pointed out.
Here de Borst remarked: “If Rothwell would have chosen 10 days or 20 days, all of us would have been discussing that time frame.” On the two-week threshold, he continued: “It’s absolutely an arbitrary threshold.” De Borst commented that “it’s not bad to do a surgery at 15 days from symptoms—it’s only bad if you do surgery at 15 days and you have a very high perioperative stroke risk, and then you’re not providing any benefit to your patients”.
Since the Rothwell analysis, de Borst continued, a meta-analysis from Sweden of 12 studies including more than 230,000 patients—which the presenter noted “caused a lot of noise in our field”—revealed “very high and alarming” stroke and mortality rates resulting from operating within the first two days post-index operation. “This is astonishing, this should not be true,” he said. Following this meta-analysis, de Borst noted that several subsequent studies “showed a completely different picture”.
Referencing four randomised controlled trials on symptomatic patients, de Borst highlighted that stroke and death rates both within and beyond seven days show that surgery is safe in both time frames, while rates with stenting are “alarmingly high”.
Citing some of the most recent data, de Borst put forward a central component of his argument: “In my view, the most critical point is that within studies there’s a very heterogeneous definition of the index event—this should be standardised so we can speak the same language.”
Here he reiterated the “arbitrary” nature of the twoweek cut-off, aligning with the view put forward by Faggioli, while going on to stress that “there’s still no strong evidence to change policy today”.
Within studies there’s a very heterogeneous definition of the index event—this should be standardised so we can speak the same language.”
Gert J de Borst
developing a carotid quality assurance programme, with registry participation enabling centres to ensure the safety of their patients and adhere to the CMS coverage decision.
“We are proud to launch the Carotid Care Quality Champion programme to honour organisations across the country that are demonstrating their commitment to exceptional patient care by maintaining a robust quality programme,” says Jens EldrupJorgensen (Maine Medical Center, Portland, USA), SVS Patient Safety Organization (PSO) medical director.
“By harnessing the power of data with benchmarked reports from over 900 centres, these centres have access to the best resources available for quality assurance and focused quality improvement efforts.”
Since the SVS VQI’s inception, clinical data gathered from participating centres has dramatically impacted
patient care, leading to scientific discoveries that have changed the way in which care is delivered. Participating centres include academic medical centres, teaching hospitals, community hospitals and office-based labs.
A press release details that VQI participation enables centres to:
● Track provider and centre performance and compare to national benchmarks;
● Identify areas for quality improvement, including patient outcomes and length of stay;
● Participate in a robust quality improvement programme, with access to quality improvement toolkits, quality charters, webinars and one-on-one mentoring for members;
● Network with other participating centres to review outcomes data, foster collaboration and spark further clinical innovation.
Carotid endarterectomy ‘remains useful and relevant’ in era of improving medical therapy
Findings from a retrospective analysis presented at the recent European Society for Vascular Surgery (ESVS) annual meeting (24–27 September, Kraków, Poland) provide evidence that—for symptomatic carotid artery stenosis patients—endarterectomy “remains a useful and relevant intervention in the era of improving medical therapy”.
DELIVERING THESE DATA
at ESVS 2024, Sashini Iddawela (University College London Hospital NHS Trust, London, UK) initially noted that urgent carotid endarterectomy (CEA) is currently the first-line recommendation for symptomatic, significant carotid artery stenosis. There is also speculation, however, that presentation with symptomatic stenosis could be substantially reduced thanks to today’s advancements in optimal medical therapy and anti-major cardiovascular event (anti-MACE) medications.
As such, Iddawela and her colleague Daryll Baker—also of the University
College London Hospital NHS Trust—undertook a study in an effort to determine whether or not patients undergoing CEA were already on optimal medical therapy prior to their index admission.
They performed a retrospective analysis of patients receiving urgent CEA following development of a stroke or transient ischaemic attack (TIA) at a regional hub in Northwest London between 2021 and 2023, collecting data on these patients’ index presentation of symptomatic stenosis features at a healthcare facility.
The researchers recorded data on comorbidities and medication history—
including antiplatelets, anticoagulants, antihypertensives, and diabetic control. Medications at discharge were also recorded as well as any reasons for alteration.
Proportions of patients on antiplatelets, antihypertensives and statins—both pre- and post-CEA— were compared using the chi-squared test. Optimal medical therapy was defined via the standard set by ESVS 2023 guidelines for asymptomatic stenosis: antiplatelets and statins as a minimum, with an antihypertensive added on where appropriate.
A total of 124 patients were consecutively analysed. Hypertension and hyperlipidaemia were found to be the most common pre-CEA morbidities recorded (64% and 42%, respectively), followed by diabetes mellitus (36%) and ischaemic heart disease (23%).
In addition, the majority of patients were on an antihypertensive agent or statin at index presentation (64% and 60%, respectively), and a 36% rate of antiplatelet use was also demonstrated across the cohort—with 77% of these patients being on aspirin monotherapy and the remainder being on clopidogrel/ticagrelor/prasugrel.
Carotid intervention linked to improved survival versus medical management in symptomatic patients
New study data suggest that the interventional treatment of symptomatic carotid artery disease may result in an improved rate of age-adjusted overall survival compared to medical management. However, the same study—which was presented at this year’s ESVS annual meeting—also indicates a relatively low future ipsilateral stroke risk among patients who were not offered carotid intervention, highlighting medical management’s importance as a standalone strategy in patients deemed to be ‘high risk’ if treated via intervention.
FINDINGS FROM THE STUDY IN QUESTION were delivered by Eric T A Lim (Waikato Hospital, Hamilton, New Zealand), on behalf of Manar Khashram (Waikato Hospital, Hamilton, New Zealand) and other investigators, in an abstract presentation at ESVS 2024.
“There is Level 1 evidence around the management of symptomatic carotid artery stenosis, with superiority of intervention compared to medical therapy for stroke prevention,” Lim and colleagues state in their abstract. “While, long term, the efficacy of carotid intervention has been clearly documented, the natural history on symptomatic patients with ipsilateral carotid stenosis has not been well described in the contemporary era—when best medical therapy has evolved. With an ageing population and increase in frailty, information on medical management alone should be discussed with patients to assist in clinical decision-making.”
disease referrals at the centre being included, but cases with no carotid imaging or in which the patient subsequently underwent carotid surgery within six weeks of referral being excluded. Lim and colleagues performed Kaplan-Meier analyses to assess ipsilateral stroke-free and age-adjusted Cox proportional hazard models, and ultimately determine all-cause survival.
During the study period, a total of 280 patients were referred with symptomatic carotid disease. The majority of these patients (63.7%) underwent carotid endarterectomy (CEA), while 1.3% underwent carotid artery stenting (CAS) and 35% were managed medically. In the 84 patients managed medically—or ‘conservatively’—the median age was 73.6 years.
On this basis, Lim et al’s prospective, observational study—undertaken in a single vascular tertiary referral centre in New Zealand—aimed to assess the outcomes of symptomatic carotid artery stenosis cases that were managed non-operatively.
The study was carried out from June 2019 to January 2024, with all symptomatic carotid artery
Lim et al found that the three most common reasons for selecting conservative management were the patient being below the threshold for the consideration of intervention (43.2%); internal carotid artery (ICA) occlusion/near occlusion (25%); and poor neurological recovery post-stroke (11.4%).
Out of the 10 patients with poor neurological recovery post-stroke, only two went on to receive a delayed carotid intervention, the investigators report. However, there were five patients (6%) who developed a further ipsilateral stroke or transient ischaemic attack
Overall, 36 patients (29%) were on a combination of an antiplatelet, antihypertensive and statin during their index presentation with symptomatic carotid stenosis.
According to the researchers, there was no significant difference between the proportion of patients on antiplatelets, antihypertensives or statins pre- versus post-CEA. However, patients with ischaemic heart disease, diabetes or hypertension were observed as being significantly more likely to be on an antiplatelet (odds ratio [OR], 1.9; p<0.01), statin (OR, 1.25; p<0.01) or antihypertensive (OR, 1.76; p<0.01) at the point of their first presentation to a healthcare facility.
These findings led to the conclusions that patients undergoing CEA are generally multimorbid and are also more likely to be on cardiovascular risk-modifying therapy at their index presentation with symptomatic carotid artery stenosis. And, on this basis, the researchers aver that—even within the context of recent improvements in medical therapy for carotid disease—CEA should still be considered a useful and relevant intervention in these patients.
(TIA) following conservative management during the follow-up period. The majority of patients (65.5%) were commonly managed with dual antiplatelet therapy (DAPT) and statins, Lim et al relay.
According to the investigators, patients who underwent carotid intervention had a 0.25 (0.17–0.5) hazard ratio of survival compared to patients managed conservatively—when adjusted for age. The overall survival rates at one and four years were 88% and 57%, respectively, and corresponding ipsilateral stroke-free survival rates at both one and four years were 97% in the medically managed patient group.
“These data support [the finding] that patients who were not offered intervention for symptomatic carotid artery disease, and were managed medically, had lower age-adjusted overall survival compared to patients undergoing carotid intervention,” Lim and colleagues conclude.
“However, the risk of future ipsilateral stroke was relatively low compared to the landmark trials, highlighting the importance of medical therapy as a standalone strategy for those patients deemed high risk for carotid intervention. Further, larger cohorts are warranted to assess the long-term outcomes comparing surgical intervention to nonoperative management in symptomatic carotid artery disease.”
Further, larger cohorts are warranted to assess the long-term outcomes comparing surgical intervention to nonoperative management in symptomatic carotid artery disease.”
Manar Khashram (L) and Eric T A Lim
Evasc announces treatment milestone alongside Eclips data presentation at ESMINT 2024 Evasc Neurovascular recently announced a “landmark achievement” during the 2024 European Society of Minimally Invasive Neurological Therapy (ESMINT) congress (4–6 September, Marseille, France), reporting that more than 300 patients have been successfully treated with the company’s Eclips device.
As per a recent Evasc press release, this milestone further underscores the efficacy and safety of the “unique and revolutionary” Eclips remodelling system in treating cerebral bifurcation aneurysms—and marks a pivotal point in the company’s mission to enhance outcomes for patients with complex cerebrovascular conditions.
The 2024 ESMINT congress saw Leif Sørensen (Aarhus University Hospital, Aarhus, Denmark) detail comprehensive multisite experiences with the Eclips implant for the endovascular treatment of bifurcation aneurysms.
Sørensen’s findings—through a follow-up period of 38 months— included a 1% neurologic mortality rate, 1.8% catheter-induced stroke rate and 4.3% repeat procedure rate. Sørensen also reported an absence of post-procedural thromboembolic events, a complete occlusion rate (Raymond-Roy occlusion classification [RROC] 1) of 85%, and a satisfactory occlusion rate (RROC 1–2) of 96%, reaffirming that Eclips implants exhibit a robust safety profile and sustained efficacy, according to Evasc.
The release goes on to note that Evasc’s EESIS-France trial is “progressing well” and is on schedule for completion by the end of this year. The core lab-adjudicated results from the EESIS-France study—which the company anticipates will be presented next year—are expected to provide further validation of the Eclips device’s performance. This trial also builds on the positive outcomes witnessed in the initial core lab-controlled EESIS trial and the low aspect ratio score trial, “paving the way for broader clinical acceptance”.
“Looking ahead, Evasc Neurovascular is optimistic about the Eclips device’s potential to become the preferred treatment option for bifurcation aneurysms, especially with its newest version, the EBFD [Eclips bifurcation flow diverter]—a flow diverter that can be used at a bifurcation without adjuvant coiling,” the release adds.
Hyperfine shares promising interim findings on portable, ultra-low-field MRI system
Hyperfine has announced the presentation of interim data supporting the role portable, ultra-low-field magnetic resonance imaging (MRI) can
play in acute stroke workup within a hospital emergency department setting.
Findings from the study, titled “Interim analysis from singlecentre observational study of ultralow-field portable MRI in acute stroke diagnostic workup”, were presented by Keith Muir (University of Glasgow, Glasgow, UK) during a scientific session at the 2024 European Society of Neuroradiology (ESNR) annual meeting (18–22 September, Paris, France).
This study—which includes a subset of patients from phase one of the prospective, international, multi-site ACTION PMR study— analysed images from Hyperfine’s portable, ultra-low-field Swoop MR brain imaging system to assess its performance in acute care stroke workup versus the current standard of care. The analysis compared timeto-scan, diagnostic performance, specificity and patient experience between ultra-low-field MRI, conventional MRI, and head computed tomography (CT).
As stated in a company press release, key findings showed that the Swoop system was dramatically faster than conventional MRI, with a median time-to-scan of 2.5 hours compared to 27.7 hours. The data also demonstrated reliability in acute stroke diagnosis, with comparable diagnostic performance compared to head CT and good specificity when compared to routine clinical MRI (1.5T). Further, nearly all patients reported a positive experience with the Swoop system.
“This interim analysis demonstrates that the portable [ultra-low-field] MRI system is a promising tool for the acute stroke diagnostic workup in an emergency department setting,” the study’s conclusion states. “The improved time to imaging compared to routine MRI could facilitate quicker decision-making in acute stroke management. Additionally, the high tolerance rate among patients underscores its potential usability in a clinical environment. The findings suggest that portable [ultra-low-field] MRI could enhance stroke diagnosis accessibility and efficiency— particularly in settings where conventional MRI availability is limited.”
InspireMD receives IDE approval from US FDA for CGUARDIANS II pivotal trial InspireMD has announced US Food and Drug Administration (FDA) approval of the company’s investigational device exemption (IDE) application to initiate the CGUARDIANS II pivotal study of its CGuard Prime 80cm carotid stent system during transcarotid artery revascularisation (TCAR) procedures.
A company press release describes this approval as “an important milestone and a significant step forward” in InspireMD’s mission to serve “the broadest range of physician and patient needs with a comprehensive set of tools that can deliver [its] bestin-class carotid stent system, CGuard Prime, for both carotid artery stenting and TCAR procedures”. “In parallel, we continue to advance development of our comprehensive, next-generation TCAR neuroprotection system, SwitchGuard NPS,” the release adds.
In February 2024, InspireMD also announced that Patrick Geraghty (Washington University School of Medicine, St Louis, USA) and Patrick Muck (Good Samaritan Hospital, Cincinnati, USA) had agreed to act as lead investigators for the CGUARDIANS II pivotal study.
London-based hospital becomes first in Europe to use Emboguard balloon guide catheter
The Royal London Hospital (London, UK) has become the first in Europe to use an innovative balloon guide catheter (BGC) called Emboguard (Johnson & Johnson MedTech Neurovascular) for mechanical thrombectomy procedures in clinical practice.
service has been able to expand without additional infrastructure investment, reducing health inequalities across the region by providing timely access to life-saving stroke care for areas like Kent and Medway.
Since its expansion in 2020, the service has experienced a 300% increase in patient numbers, performing 256 thrombectomy procedures in 2021 alone. Over 22,000 suspected stroke cases have been processed, with a “remarkable” increase in thrombectomy success across the region, the announcement adds.
“We’re committed to using the latest technology to maximise outcomes for our patients,” Makalanda commented. “The introduction of Emboguard is a major step forward in stroke care, allowing us to deliver even better results for those we treat.”
Initial studies have suggested that, during mechanical thrombectomies, the Emboguard BGC may be able to achieve faster and more effective clot removal compared to the standard base catheters that are usually deployed in these procedures.
Oxford Heartbeat completes patient recruitment in trial evaluating PreSize software
Oxford Heartbeat has announced that the clinical impact trial of its artificial intelligence (AI)-powered PreSize Neurovascular software has successfully completed patient recruitment.
“Timely and effective treatment of stroke patients is critical to reducing lifelong disability or dependency,” said Levansri Makalanda (Barts Health NHS Trust, London, UK). “We are big believers in using the most modern and evidence-based technology for patient-specific care. For us here at Barts Health, and others within the specialty, the benefits of BGCs are recognised for their ability to maximise patient outcomes. The Emboguard is a gamechanger—with its large bore and flexible design allowing better access to intracranial circulation. This significantly improves the chances for patients to live a functional and fulfilling life post-stroke.”
As stated in a recent announcement from Barts Health NHS Trust, the Royal London Hospital’s Stroke Mechanical Thrombectomy Network is the largest 24/7 service of its kind in the UK, serving more than eight million people across South and East England. And, despite the challenges posed by the COVID-19 pandemic, the
A company press release describes this as a “huge milestone” as the trial—which is funded by the UK’s National Institute for Health and Care Research’s (NIHR) prestigious AI in Health and Care Award—is the first of its kind for decision-support software in the field. The trial therefore “sets a standard of evidence generation” regarding the use of AI software to support clinical decisionmaking in neurovascular surgery and beyond, the release adds.
The registered and ethics-approved prospective, multicentre trial is being independently run by Imperial Clinical Trials Unit (London, UK), with the aim of quantifying the benefits of using PreSize in clinical practice. In order to achieve this, 100 patients for whom PreSize was used to inform their treatment were recruited into the trial. Overall, there was participation from nine centres across the UK and a total of 25 surgeons. Patients included in the trial were diagnosed with a cerebral aneurysm and scheduled to be treated minimally invasively via placement of a flow-diverting stent into the affected blood vessel, to divert blood away from the aneurysm and minimise the risk of it rupturing.
Oxford Heartbeat’s recent release notes that choosing the best-fit device
Levansri Makalanda
for each patient is challenging, and suboptimal choices resulting from current planning methods can lead to device wastage, surgical inefficiencies and patient complications. However, PreSize allows real-time, virtual rehearsal of treatment scenarios so that the clinical team can determine the optimal device before starting the procedure. The software is CE-mark certified—meaning it is compliant with safety/performance requirements for medical software— and has undergone rigorous testing, as published studies have shown that it can be reliably used to inform clinical decisions with high levels of accuracy and can positively impact clinical decision-making.
The recently completed trial is comparing the clinical decision-making between traditional methods, without PreSize, versus with PreSize. When PreSize is used to support the selection of implants, information is collected on surgical efficiency metrics—such as devices used in the procedure and duration of surgery. It is the only such trial in the field where data are prospectively collected to demonstrate objective and measurable benefits that the use of software can bring to patients and clinical teams in a real-world setting, Oxford Heartbeat claims.
Now that the study recruitment has been completed, the Imperial Clinical Trials Unit statistics team will analyse the dataset and the full results will be published in due course, the company’s recent release also states.
Penumbra announces completion of enrolment in THUNDER IDE study
Penumbra has announced the completion of enrolment in its THUNDER investigational device exemption (IDE) clinical study for patients with acute ischaemic stroke.
THUNDER is evaluating the safety and efficacy of the company’s latest computer-assisted vacuum thrombectomy (CAVT) technology— the Penumbra system with Thunderbolt aspiration tubing—for the removal of blood clots in the brain. This multicentre, single-arm study is evaluating patients with acute ischaemic stroke secondary to intracranial large vessel occlusion (LVO) who are eligible for mechanical thrombectomy, and its primary efficacy endpoint includes revascularisation of the occluded target vessel immediately post-procedure.
A recent Penumbra press release describes this completion of enrolment as a “critical milestone”, with the THUNDER study set to provide the dataset needed to evaluate the company’s Thunderbolt technology effectively. As stated in the release, the Penumbra system with Thunderbolt aspiration tubing uses an advanced CAVT software algorithm to generate proprietary, modulated aspiration, reducing friction between the clot and reperfusion catheter, and facilitating a more rapid and complete removal of
blood clots in the brain. Thunderbolt aspiration tubing has been designed for use with the Penumbra Engine and Red reperfusion catheters, the release adds.
Rapid completes interim safety analysis of DISTALS study evaluating Tigertriever 13 device
Rapid Medical has announced completion of the interim safety analysis from the multicentre, pivotal DISTALS study, reporting no safety concerns in medium vessel occlusions at the 2024 European Society of Minimally Invasive Neurological Therapy (ESMINT) congress (4–6 September, Marseille, France).
“We are pleased that the DSMB [data safety monitoring board] found that the safety profile of Tigertriever 13 allows us to continue randomisation,” said DISTALS study principal investigator David Fiorella (Stony Brook University Medical Center, Stony Brook, USA).
“This reflects its unique design, which facilitates thrombectomy procedures smaller vessels given its low profile and adjustability.”
Per protocol, all safety data— including the rate of symptomatic intracerebral haemorrhage (sICH)— were analysed for 82 patients by the DSMB, which includes Joshua Hirsch, Robert Regenhardt (both Massachusetts General Hospital, Boston, USA), Thabele LeslieMazwi (University of Washington, Seattle, USA), and Scott Hamilton (Stanford Medicine, Stanford, USA). The data were also adjudicated by the imaging core lab and the clinical event committee.
As stated in a Rapid press release, Tigertriever 13’s adjustability engages the clot and then relaxes to minimise vessel traction upon removal. Published data indicate distal stroke treatment performed with the device can lead to higher revascularisation success and post-treatment patient outcomes, with 78% recanalisation success compared to 42% with medical management.
aged 18–85 years with LHI. In May 2024, Remedy conducted prespecified subgroup analyses, along with posthoc analyses examining the impact of lesion volume on outcomes, which revealed significant improvements in functional outcomes on the modified Rankin scale (mRS) at 90 days. Remedy’s recent release states that further post-hoc analyses have now been performed and show that the odds ratio (OR) for achieving an mRS score of 0–3 across 118 patients with a lesion volume <125ml was 4.1 in favour of Cirara (p<0.01). In addition, within a modified intention-to-treat EVT population with a lesion volume <125ml, consisting of 34 patients, the OR for achieving an mRS score of 0–3 was 18.5 in favour of Cirara (p=0.03), indicating an even more dramatic improvement in functional outcomes, particularly in the ability to ambulate independently.
Remedy reports trial data indicating Cirara’s potential in large hemispheric infarction Remedy Pharmaceuticals recently announced promising new data from the phase-three CHARM clinical trial of Cirara (intravenous glyburide) in patients with large hemispheric infarction (LHI)—a serious form of ischaemic stroke characterised by large-volume lesions that can lead to malignant brain swelling, severe disability, and death.
The analysis revealed significant and clinically meaningful improvements in patients’ ability to ambulate independently following administration of Cirara, particularly when used in combination with endovascular therapy (EVT), as per a company press release.
The CHARM clinical trial was a multicentre, multinational, doubleblind, randomised, placebo-controlled phase-three study involving patients
impact” on thrombectomy procedures, adding that the first use of the Toro 88 SuperBore catheter in Japan marks a “critical step” towards realising this vision. The company believes that its devices will offer physicians an improved first-line stroke treatment, possibly delivering faster and more effective results.
Toro’s catheters have the potential to significantly elevate the standard of stroke care and expand access to stroke therapy in developing regions, the release further notes. However, this is subject to regulatory approvals, as the company’s Toro 88 SuperBore aspiration catheter is currently not commercially available for use in any country.
Toro Neurovascular announces first treatment in SuperBore aspiration catheter study Toro Neurovascular has announced the successful treatment of the first patient using its Toro 88 SuperBore aspiration catheter as part of a first-in-man clinical study. The procedure—performed by Nobuyuki Sakai and his staff at Seijinkai Shimizu Hospital in Kyoto, Japan—marks “a key milestone in Toro’s mission to transform stroke treatment through cuttingedge technology”, as stated in a company press release.
“Toro 88’s performance was exceptional, particularly in accessing the intricate anatomy of the cerebral vasculature,” Sakai commented. “Its ability to efficiently remove large clot burden and navigate challenging conditions is impressive. I am pleased to be part of this study, which has the potential to significantly enhance stroke treatment and improve patient outcomes.”
Toro’s innovative catheter technology is poised to establish a new standard for navigating complex neurovascular anatomy, the company further claims. Featuring MicroFlex technology—a reinforced microwire design—the Toro 88 catheter was engineered from the ground up for enhanced control and navigation through tortuous, challenging conditions. Its advanced support profile is designed to provide exceptional manoeuvrability, precision and efficient access to the M1 segment of the middle cerebral artery (MCA). With a vessel-matched 0.088-inch lumen, Toro 88 aims to enable complete clot ingestion, potentially transforming patient outcomes, the company’s recent release adds.
Toro states that it is driven by the potential to make a “profound
New Viz.ai data indicate fewer futile transfers and substantial cost savings in stroke Viz.ai has announced clinical data validating the impact of Viz LVO in the management and outcomes of patients with large vessel occlusion (LVO) ischaemic stroke. Viz LVO— part of the Viz Neuro suite of artificial intelligence (AI)-powered solutions— automatically detects and triages suspected LVO patients to reduce delays in acute stroke treatment.
A real-world study now published in the journal Interventional Neuroradiology evaluated the clinical impact of Viz LVO on the rate of transfers resulting in endovascular thrombectomy and associated costs before and after implementation of an AI-based software. The study found that the Viz LVO software significantly increased computed tomography angiography (CTA) use and led to a 14% rise in transfers treated with thrombectomy—with an associated increase in spoke revenue and potentially lower payer costs.
“Our findings highlight the efficacy and practical application of AI in a clinical setting,” said James Bonner (Inspira Medical Center Mullica Hill, Harrison Township, USA). “We are proud to partner with Viz.ai and utilise their innovative solutions to continue advancing the management of patients with LVOs where every minute counts. The care that the spoke hospitals can deliver has been significantly enhanced by real-time, actionable data that Viz.ai has delivered for us.”
A recent press release from Viz.ai notes that the transfer of an ischaemic stroke patient with suspected LVO who does not undergo thrombectomy at a comprehensive stroke centre (CSC)—a ‘futile transfer’—is taxing on providers, costly to healthcare systems, and displaces patients from their families. This study demonstrated the impact of implementing the company’s AI-based system, which allowed the care team at the hub and spokes to quickly and reliably access, review, and comment on, both non-contrast and contrast CT scans with automated alerts for suspected LVO.
Tigertriever 13
Nobuyuki Sakai
Borvo Medical gains US FDA 510(k) clearance for minimally invasive SDH drainage system Borvo Medical has announced US Food and Drug Administration (FDA) 510(k) clearance of the Borvo Endoport Vacuum-Assisted Collection (EVAC) system—an advanced alternative to traditional subdural haematoma (SDH) drainage methods. In addition, Borvo recently presented its innovative technology at the 17th World Federation of Interventional and Therapeutic Neuroradiology (WFITN) congress (6–10 October, New York, USA).
Designed to address the limitations of existing devices, Borvo EVAC leverages state-of-the-art fabrication techniques, improved materials science, and ergonomic designs, to provide a modernised, efficient and less invasive solution. That is according to a recent press release from the company, which also states that EVAC “meets the evolving needs of an ageing population, and individuals requiring SDH drainage due to head injuries and other causes”.
“It’s clear that the current SDH drainage systems need an upgrade, especially as the demand for better minimally invasive options increases with the rise of middle meningeal artery (MMA) embolisation,” said Adam Arthur (University of Tennessee/Semmes Murphey Clinic, Memphis, USA). “Borvo presents an opportunity to enhance both safety and effectiveness, which have been limited by the outdated existing options. As a more efficient, imaging-compatible alternative, I am optimistic that Borvo EVAC holds promise to significantly improve neurosurgical practices for patients.”
Borvo EVAC stands poised to fill current gaps in care and transform SDH drainage solutions, according to the company. With advanced technology that reduces artifacts on postoperative computed tomography (CT) scans, it delivers clearer, more reliable followup imaging for medical teams. And, unlike existing options, Borvo EVAC is magnetic resonance imaging (MRI)compatible, providing a broad range of imaging and monitoring options without performance interference.
The EVAC system is anticipated to be available in early 2025, as per Borvo’s recent press release.
Boston Scientific closes acquisition of Silk Road Medical Boston Scientific has announced the close of its acquisition of Silk Road Medical—a medical device company that has pioneered a new approach for stroke prevention and the treatment of carotid artery disease through the minimally invasive transcarotid artery revascularisation (TCAR) procedure.
Boston Scientific initially announced that it had entered into an agreement to acquire Silk Road back in June 2024.
As detailed in a recent press release, the acquisition includes a purchase price of US$27.50 per share, reflecting an enterprise value of approximately US$1.18 billion. The impact to Boston Scientific adjusted earnings per share is expected to be immaterial in 2024 and 2025, and accretive thereafter. The impact to generally accepted accounting principles (GAAP) earnings per share is expected to be less accretive—or dilutive, as the case may be—due to amortisation expense and acquisition-related net charges.
Cerevasc secures US FDA Breakthrough Device designation for eShunt system
Cerevasc has announced that it has received Breakthrough Device designation from the US Food and Drug Administration (FDA) for its eShunt system, which is intended for the treatment of normal-pressure hydrocephalus (NPH).
system represents a new class of technology that should simplify neurosurgical procedures and provide patients a chance at more favourable outcomes.”
The Neuroblade system is made up of three components: the Neuroblade, a single-use multifunctional neuroendoscope; the Neuropad, a reusable medical-grade tablet; and Clearpath, a disposable transparent access sheath. This system is designed to improve the efficiency and outcomes of minimally invasive neurosurgical procedures.
The Breakthrough Device designation was supported by data generated during pilot clinical studies of the device, according to a recent press release from Cerevasc. The company notes that this recent designation will enable priority review and enhanced communication with the US FDA during the clinical trial and premarket review process.
In addition, Cerevasc was recently granted an investigational device exemption (IDE) for its STRIDE pivotal study evaluating the eShunt system for the treatment of NPH, with enrolment on track to begin in the second half of 2024.
Clearmind Biomedical announces US FDA clearance and initial Neuroblade case
Clearmind Biomedical has received US Food and Drug Administration (FDA) 510(k) clearance for its Neuroblade system—a novel neuroendoscopy system that enables minimally invasive procedures with integrated features like visualisation, illumination, irrigation, suction, coagulation, and powered debridement.
The company has also announced the successful completion of the first US surgery using the Neuroblade, performed by Christopher Kellner at Mount Sinai Hospital in New York, USA.
“The Neuroblade system offers a valuable new tool for the surgical management of intracerebral haemorrhage,” Kellner said. “Its minimally invasive design streamlines the operating room setup and integrates essential functions into a single handpiece, potentially improving patient outcomes. The Neuroblade
In the initial US case, Kellner employed the Neuroblade system during an urgent procedure to evacuate a haemorrhagic stroke. The Clearpath sheath allowed precise access to the target area, while the Neuroblade provided an all-inone instrument with real-time visualisation and integrated tools for suction, irrigation, powered debridement, and coagulation, according to a Clearmind press release.
Contego receives US FDA approval for Neuroguard IEP system Contego Medical has announced the US Food and Drug Administration’s (FDA) premarket approval (PMA) of the Neuroguard Integrated Embolic Protection (IEP) system for carotid revascularisation.
The company shares in a press release that clinical studies of the Neuroguard IEP system, including the PERFORMANCE I trial and PERFORMANCE II investigational device exemption (IDE) trial, have consistently recorded “unprecedented” low event rates—including zero major strokes, zero neurologic deaths, and no stent thrombosis, at 30 days and one year.
“FDA approval confirms the results of the clinical studies,” stated William Gray (Main Line Health, Wynnewood, USA), co-national principal investigator of the PERFORMANCE II trial. “The innovative Neuroguard IEP system performs exceptionally well with the lowest one-year stroke rates ever shown for any type of carotid revascularisation, thereby establishing a new standard of care for meaningfully reducing the risk of procedural and long-term stroke among patients with carotid artery disease.”
The Neuroguard IEP system utilises Contego’s IEP technology, featuring a 40-micron filter integrated on a 6Fr delivery catheter. The size of the integrated filter can be adjusted by the operator to custom fit each patient’s unique anatomy, and the pores on the filter are 3–4 times smaller than those on traditional filters, the company claims, improving protection against stroke and cognitive impairment. According to Contego, the newestgeneration closed cell stent is highly
conformable and shows remarkable short- and long-term durability, with no thromboses, no clinically driven targetlesion revascularisation, and very low restenosis rates, at one year.
Cerenovus and Biosense Webster among brands newly incorporated into J&J MedTech
Johnson & Johnson (J&J) recently shared that its medical technology businesses— including Cerenovus and Biosense Webster, as well as Abiomed, DePuy Synthes, and Ethicon—will now go by the name ‘Johnson & Johnson MedTech’.
This move “underscores J&J’s leadership in medical technology with a focus on cardiovascular, orthopaedic, surgery and vision solutions”, according to a company press release, and is the next step of J&J’s updated brand and visual identity—which was originally announced in September 2023.
Moving forward, Cerenovus will be referred to as ‘Johnson & Johnson MedTech Neurovascular’, while Biosense Webster’s brand name has been updated to ‘Johnson & Johnson MedTech Electrophysiology’.
However, the announcement has no impact on the medical technology products and solutions currently offered to customers, the release adds—also stating that, “while Ethicon, DePuy Synthes, Biosense Webster, Abiomed and Cerenovus will now go by Johnson & Johnson MedTech, we will continue to honour the legacies of these brands by maintaining the products, services and approach to collaboration that made them some of the most trusted names in healthcare”.
RapidAI and Alaska Stroke Coalition partner to overcome treatment barriers
RapidAI and the Alaska Stroke Coalition (ASC) have announced their partnership on the ‘Rapid AK’ project—a three-year initiative focused on advancing health equity for Alaskans affected by stroke.
As part of the effort, six hospitals across the US state have implemented RapidAI’s artificial intelligence (AI)-powered core stroke imaging and workflow products to help overcome challenges associated with rural care, joining an additional four Alaskan hospitals already leveraging the technology to improve stroke identification and treatment in their regions.
Rapid NCCT stroke solution
Christopher Kellner
Through partnership with healthcare providers, stroke survivors, and community stakeholders, the ASC aims to reduce the impact of stroke on individuals and families by enhancing prevention, treatment, and rehabilitation efforts, with the ultimate goal of achieving better stroke outcomes and quality of life for residents in every region of Alaska.
“Alaska is certainly unique in its vast size and rural landscape. In fact, a patient might need to travel nearly the same distance as from Dallas to New York just to reach thrombectomy services at either Providence Alaska Medical Center or Alaska Regional Hospital, the state’s only comprehensive stroke centre,” said Lucy He (Anchorage Neurosurgical Associates, Anchorage, USA), physician sponsor of the ASC. “We can’t control the distance or weather that stands in the way of timely treatment but, by leveraging this technology, we’re learning that we can directly impact the number of stroke patients we detect and how fast we treat them, resulting in more equitable care for residents across the state.”
While rural hospitals in particular face a host of challenges in prompt diagnosis and treatment of stroke— including limited technology, distance from surgery-capable centres, and a lack of specialised, multidisciplinary teams—a recent press release details that RapidAI will attempt to combat these challenges by offering clinical context on computed tomography (CT) scans, as well as a centralised patient workflow through mobile and web applications.
Route 92 announces US$50 million Series F extension equity financing
Route 92 Medical has announced a new US$50 million extension to its previously announced, oversubscribed Series F financing, bringing the total raised to US$82 million.
Novo Holdings joined returning investors US Venture Partners, Norwest Venture Partners, InnovaHealth Partners, and The Vertical Group, in supporting the round. In connection with the investment, Noel Jee—a partner in Growth Investments at Novo Holdings US—will join the Route 92
Conference calendar
20–22 November 2024
Society of Vascular and Interventional Neurology (SVIN) Annual Meeting San Diego, USA W: svin.org/i4a/pages/index. cfm?pageID=3645
23–24 November 2024
LINNC SeminarChina Edition Beijing, China W: linnc.com/Course-information/ LINNC-Seminar-2024-China-Edition
board of directors, bringing more than 10 years of experience in life-science investing and consulting.
Proceeds from the financing will be used to accelerate the global commercialisation of the company’s neurovascular intervention portfolio, and to pursue regulatory authorisations in new geographies, according to a press release.
Route 92 claims to have streamlined neurovascular intervention by creating a suite of reperfusion and access systems leveraging unique designs—all featuring the patented Tenzing delivery catheter. These products are designed to work harmoniously as complete systems to improve the efficiency of endovascular thrombectomy procedures, enabling clinicians to quickly restore blood flow to a patient’s brain following acute ischaemic stroke.
BrainPath device
combining Sim&Cure’s cutting-edge simulation technology with Siemens Healthineers’ advanced imaging systems, the collaboration will offer healthcare professionals state-of-the-art tools to enhance diagnosis, treatment planning, and patient outcomes, the release adds.
Both companies are committed to maintaining the highest standards of quality and compliance, the release continues, and—through coordinated efforts—will demonstrate the significant benefits of their solutions for brain aneurysm treatment. Their common activities will be led jointly, ensuring consistency and alignment with each company’s brand and regulatory requirements.
Earlier this year, Route 92 completed enrolment in its SUMMIT MAX clinical trial, which is evaluating the safety and effectiveness of the company’s HiPoint 88 and HiPoint 70 reperfusion catheters as part of the Monopoint reperfusion system.
Sim&Cure and Siemens Healthineers partner to advance brain aneurysm treatment Sim&Cure and Siemens Healthineers have announced a strategic partnership aimed at enhancing patient care and advancing brain aneurysm treatment.
A recent press release from the two companies notes that “immediate medical intervention is crucial for ruptured aneurysms”, while “proactive management of unruptured aneurysms can prevent future health crises”. The release also states that detection and treatment of brain aneurysms remain critical to preventing potential ruptures and associated health issues.
As such, their partnership will attempt to bring together the expertise and technology leadership of both companies to create and promote innovative solutions designed to improve the precision and effectiveness of brain aneurysm interventions. By
1–5 December 2024
Radiological Society of North America (RSNA) Annual Meeting Chicago, USA W: rsna.org/annual-meeting
2–4 December 2024
Barts Research and Advanced Interventional Neuroradiology (BRAIN) Conference London, UK W: brainconference.co.uk/ event/2024/summary
This collaborative approach will help to effectively communicate the advantages of the combined technologies to healthcare providers worldwide.
Stryker completes acquisition of Nico Corporation
Stryker has announced that it has completed the acquisition of Nico Corporation—a company attempting to provide a systematic approach to minimally invasive surgery for tumour and intracerebral haemorrhage (ICH) procedures.
As noted in a recent company press release, this acquisition further strengthens Stryker’s commitment to neurotechnology through tumour and stroke care.
The release adds that Nico’s BrainPath and Myriad products enable a treatment option for ICH— a deadly form of stroke associated with high morbidity and a 30-day mortality rate ranging from 40–50%— that provides improved functional outcomes compared to guideline-based medical management alone, the current standard of care.
Microvention officially rebrands to Terumo Neuro
Microvention, a wholly owned subsidiary of Terumo Corporation,
9–13 December 2024
The European Course in Minimally Invasive Neurological Therapy (ECMINT) 5.4 Oxford, UK W: esmint.eu/ecmint
28–31 January 2025
12th ESO-ESMINT-ESNR Stroke Winter School Bern, Switzerland W: strokewinterschool.ch
has announced its official rebranding to Terumo Neuro, effective as of September 2024.
This name change signifies a new chapter in the company’s evolution while maintaining its unwavering commitment to the creation and commercialisation of groundbreaking innovations in neurovascular care, as stated in a press release.
Founded in 1997 and acquired by Terumo Corporation in 2006, Microvention has been at the forefront of developing technologies that support neurovascular surgeons in preserving and restoring brain health. As Terumo Neuro, the company is poised to continue its legacy of innovation with an enhanced focus on driving impactful growth and leveraging Terumo’s global resources and reputation, the release continues.
Carsten Schroeder, president and chief executive officer of Terumo Neuro, commented on the rebranding: “This transformation reflects our growth as a company and Terumo’s confidence in our future. For eighteen years, we have maintained independent branding as Microvention and now, as Terumo Neuro, we’re combining the best of Microvention with the full strength and support of the Terumo family. Our culture, speed of innovation, focus on game-changing technologies, and close collaboration with physicians, will remain unchanged.
“What will evolve is a deeper partnership with Terumo, a new visual brand, and a more defined brand identity under our new name and slogan—‘Terumo Neuro: gamechanging impact’. Our strategy is expanding beyond our core focus on haemorrhagic and ischaemic stroke and access solutions to encompass the neurovascular patient care continuum.”
As Terumo Neuro, the company says that it will continue its close collaboration with leading physicians worldwide, translating clinical insights into technologies that enhance patient outcomes.
Schroeder also emphasised that the company’s DNA remains rooted in innovation for ischaemic stroke, haemorrhagic stroke, and access, while expanding into broader areas of neurovascular care.
30 January–1 February 2025
North American Neuromodulation Society (NANS) Annual Meeting Orlando, USA W: neuromodulation.org/annualmeeting.html
5–7 February 2025
International Stroke Conference (ISC) Los Angeles, USA W: professional.heart.org/en/ meetings/international-strokeconference
17–19 February 2025
WFITN Neurovascular Anatomy in Stroke Course Naples, Italy W: wfitn.org/events/wfitnneurovascular-anatomy-strokecourse-2025
23–24 February 2025
6th International Brain Stimulation Conference Kobe, Japan W: elsevier.com/events/ conferences/all/international-brainstimulation-conference
