July 2020 | Issue 38 Thrombectomy proved efficacious in Latin America Page 10
Richard P Klucznik:
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COVID-19 causes “widespread disruption” to neuroendovascular research around the globe “Widespread disruption of neuroendovascular trials occurred because of COVID-19,” conclude the investigators of a survey-based study examining the impact of the pandemic. Now, as sites begin to resume clinical research, first author Ansaar T Rai of West Virginia University, Rockefeller Neuroscience Institute (Morgantown, USA), and colleagues throughout the USA call for steps to mitigate similar challenges that may arise in the future.
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he study, recently published in the Journal of NeuroInterventional Surgery (JNIS), focused on randomised controlled trials (RCTs) and singlearm studies for acute ischaemic stroke and cerebral aneurysms. The survey was developed by a group of senior neurointerventionalists, subsequently sent to sites identified through the clinical trials website, study sponsors, and physician investigators. “The survey was sent to 101 institutions, with 65 responding,” state Rai et al, as they added that stroke RCTs were (prior to the pandemic) being conducted at 40 sites, aneurysm RCTs at 22 sites, stroke single-arm studies at 37 sites, and aneurysm single-arm studies at 43 sites. However, following COVID-19, the authors report that enrolment was suspended at 51 (78%) sites; completely at 21, and partially at 30. Moreover, missed trial-related clinics, imaging follow-ups and protocol deviations were reported by 27, 24, and 27 sites, respectively. Negative reimbursements were reported at 17 sites. The majority of sites, Rai and colleagues note, were forced to put new trials on hold. The team found that many study coordinators (63%) worked from home, and 31% reported a personal financial impact. While remote consent was possible for some studies at 34 sites, only five sites reported that remote consent presented a viable option for all studies underway. Regarding the 51 sites with suspended trials, endovascular treatment without enrolment occurred at 61% of sites for stroke, and 45% of sites for aneurysms. Rai and the team found that this resulted in a total of 277 patients with acute ischaemic stroke, and a further 184 patients with cerebral aneurysms being treated Ansaar without consideration for Rai
Continued on page 2
Non-invasive vagus nerve stimulation may provide clinical benefit to patients with COVID-19
An article accepted into the journal Neuromodulation has concluded that, based on two case reports, non-invasive vagus nerve stimulation (nVNS) might provide clinical benefits in patients with COVID-19 via “multiple mechanisms”. WHILE MOST COVID-19 cases are mild, the authors, Peter Staats (electroCore, Basking Ridge, USA) and colleagues acknowledge that a minority of patients develop moderate to severe respiratory symptoms, which they say appear to be due to a hyperimmune
reaction—otherwise known as a “cytokine storm”. “While the search for an antiviral, or a vaccine effective for SARS-CoV-2, the virus causing COVID-19, remains a priority, we also need to put resources and an effort to solving this cytokine
storm,” Staats tells NeuroNews. As VNS has been demonstrated to block production of cytokines in sepsis in animal models and in many other medical conditions (including PTSD, Sjogrens disease, rheumatoid arthritis, and stroke), Staats and his team hypothesised that nVNS might provide clinical benefits in patients with respiratory symptoms, such as those exhibited in the novel coronavirus. The information on the two case reports was obtained via email correspondence and phone interviews with the patients. According to the authors, in case 1, the patient used nVNS to aid his recovery at home after hospital discharge, and was subsequently able to discontinue use of opioids and cough suppressant medications. In case 2, the
patient experienced reliable relief from chest tightness and dyspnea within five minutes of using the stimulation. He also observed an improved ability to clear his lungs when he used nVNS to manage his symptoms at home. “Avoidance of ventilator dependence in both cases and lack of hospitalisation in case 2 cannot be causally attributed to nVNS, but it is reasonable to speculate that nVNS therapy may have been a supporting factor, via either bronchodilation or inhibition of cytokine release,” argue Staats and colleagues. They add, given the concerns about number of intensive care unit beds and ventilators amid the pandemic, that it is “imperative to consider all viable therapeutic options”. Thus, they put forward that “the well-established safety Continued on page 16
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August 2020 | Issue 38
COVID-19
COVID-19 causes “widespread disruption” to neuroendovascular research around the globe Continued from page 1
trial enrolment. Discussing the justification for the investigation, the team state that while modifications for emergency treatment and safety procedures to accommodate those with COVID-19 have been widely agreed on and adopted, “the impact of COVID-19 on clinical research efforts has been less clear. “Disruption of clinical research infrastructure has implications for patient enrolment, study timing, sponsorship, and advances in clinical care and disease understanding. At the time of writing, fears of resurgent or re-emergent disease remain prominent,” add the authors.
continue. This could have added cost implications and change what the researchers had initially set out to achieve. One in five (18%) research projects had team members redeployed to front line NHS work, for example as neurologists, physiotherapists, and occupational therapists. Given these data, Rubina Ahmed, research director at the Stroke Association, comments in the statement: “Our work has laid the foundations for one of the most successful public health awareness campaigns in England, the Act FAST campaign. We also funded early research into the new emergency stroke treatment, thrombectomy. “But a lack of funding for research is now a ticking time bomb. If we do not act now, the coronavirus pandemic could set back stroke research for years to come. The research community will struggle to get projects back up and running, but it is vital for every stroke survivor and their loved ones that we do.”
“Long-term threat” to stroke research in the UK
Recommendations for the future
News in brief
The latest stories from the neuro world
n STROKE RISK HIGHER WITH COVID-19 THAN INFLUENZA: A higher rate of stroke has been reported in adults with COVID-19 compared to a cohort of patients with influenza. As the authors Alexander E Merkler and colleagues, New York, USA, call for additional studies to confirm these findings, they also provide an explanation for the discrepancy in the rate of stroke due to COVID-19 that has been creeping into recent literature.
For more on this story go to page 4
Though respondents of the survey in the The Stroke Association, the leading stroke USA indicated widespread disruption charity in the UK, has issued a statement of neurovascular clinical research, as announcing that almost three quarters well as research infrastructure, amid (74%) of its stroke research projects have the pandemic, the authors suggest that been suspended in light of the pandemic. it reveals opportunities for “increased As the charity anticipates a shortfall of Rubina Ahmed infrastructural strength and pliability”. £1.5 million in its funding programme this This includes the increased use of virtual year to resume current research and support vital new access for consent and follow-up, as well as the benefits projects, it warns of a “catastrophic knock-on effect” for of platform trial design at times when flexibility and stroke research, which could delay access to treatments. responsiveness are key advantages. The Stroke Association explain that despite stroke “Many questions remain to be answered,” Rai and being a leading cause of adult disability, research colleagues believe. For example, they query how the remains underfunded in the UK. In 2016, the charity field will incorporate COVID-19 screening into trial revealed that just £48 is spent on stroke research per criteria. patient, compared to £241 on cancer research. This, they The team write that, in the survey, 40% of the argue, has now been compounded by the devastation responding sites did not have any protocols in place that COVID-19 has had on the charity’s fundraising for remote consent. In light of this, they say that capabilities and researchers’ abilities to continue their study sponsors, local institutional review boards, and work. federal authorities regulating these trials will have to Findings from a survey conducted by the Stroke demonstrate creativity in modernising these procedures. Association also reveal the broader impacts that the “Harnessing emerging virtual technologies that allow pandemic has had on stroke researchers in the UK: for face-to-face interactions with legally authorised One in five researchers (22%) will need more funding. representatives, electronic exchange of documents, Two-thirds (66%) of researchers have said they need and digital signatures, represents a clear opportunity,” to make changes to their studies for their projects to add the authors. However, Rai and the team conclude that, based on expert predictions of the disease course, “disruptions due to COVID-19 will continue”. They argue that trials conducted in this “restrictive environment” will need to evolve. “Decisions about how to maintain enrolment during the current pandemic and in the event of future similar disruptions must be prioritised.”
n THROMBECTOMY PROVED EFFICACIOUS IN LATIN AMERICA: After receiving a standing ovation when presented at the European Stroke Organisation Conference last year, the final results of RESILIENT have now been published in The New England Journal of Medicine. The trial aims to bring about life-changing stroke treatment to over 80% of Brazilians that cannot currently afford private health insurance.
For more on this story go to page 10
n “STOICISM KILLS” The Stroke Association has revealed that a “concerning” new trend is causing preventable stroke deaths. The most at-risk groups are least likely to call for an ambulance due to not wanting to “burden the already busy emergency services”. However, according to the charity, these acts of altruism are causing people to die at home.
For more on this story go to page 15
A lack of funding for research is now a ticking time bomb.”
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July 2020 | Issue 38
COVID-19
Stroke risk higher in patients with COVID-19 than influenza A higher rate of stroke has been reported in adults with COVID-19 compared to a cohort of patients with influenza. A retrospective study published in JAMA Neurology concludes that around 1.6% of adults with COVID-19 who visited the emergency department or who were hospitalised experienced an ischaemic stroke.
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he authors, Alexander E Merkler and colleagues, from Weill Cornell Medicine, New York, USA, call for additional studies to confirm these findings, and write: “Clinicians should be vigilant for symptoms and signs of acute ischaemic stroke in patients with COVID-19, so that timesensitive interventions can be instituted if possible to reduce the burden of long-term disability.” They add that in the meantime, further elucidation of thrombotic mechanisms in patients with COVID-19 may “yield better strategies” to prevent disabling thrombotic complications like stroke. Discussing the rationale behind comparing cohorts of patients with COVID-19 and influenza, Merkler and the team note that while recent publications from China, France, and New York point to the possibility that COVID-19 may increase the risk of ischaemic stroke, the studies lacked appropriate control groups. “To evaluate whether COVID-19 is associated with a higher rate of ischaemic stroke than would generally be expected from a respiratory infection, we compared
the likelihood of acute ischaemic stroke in patients with COVID-19 with patients with influenza, a known risk factor,” the investigators state. This retrospective cohort study was conducted at two academic hospitals in New York, and included adult patients with emergency department visits or hospitalisations with COVID-19 from 4 March 2020 through to 2 May. The comparison cohort included adults with emergency department visits or hospitalisations with influenza A/B from 1 January 2016 to 31 May 2018 (spanning moderate and severe influenza seasons). A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. “We used logistic regression to compare the proportion of patients with COVID-19 with ischaemic stroke versus the proportion among patients with influenza,” note Merkler and colleagues. They reported that among 1,916 patients with emergency department visits or hospitalisations with COVID-19, 31 (1.6%; 95% CI, 1.1–2.3) had an acute ischemic stroke. The median age of
patients with stroke was 69 years, and 18 (58%) were men. Stroke was the reason for hospital presentation in eight cases (26%). In comparison, three of 1,486 patients with influenza (0.2%; 95% CI, 0.0–0.6) had an acute ischaemic stroke. According to the authors, the findings demonstrated that after adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3–25.2). “The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission,” Merkler and team add.
We compared the likelihood of ischaemic stroke in patients with COVID-19 with patients with influenza, a known risk factor.” However, they report: “Our understanding of the neurological complications of COVID-19 is limited.”
Discrepancies in the rate of stroke
Merkler and colleagues write that among 214 patients hospitalised with COVID-19
Incidence of stroke due to COVID-19 lower than previously reported, study says A recently published study has shown fewer people than previously reported have had strokes as a result of COVID-19; however, strokes that accompany the novel coronavirus appear to be more severe. The analysis by Shadi Yaghi and colleagues from New York University School of Medicine, New York, USA, was published online ahead of print in Stroke. THE STUDY FOUND that, of the 3,556 hospitalised patients with a diagnosis of COVID-19, fewer than 1% (32 patients) had a stroke. This, according to the authors, contrasts with the rates reported recently in small studies in China and Italy, which ranged from 2% to 5%. However, the investigation also demonstrated that patients with both conditions were younger, had worse symptoms, and were at least seven times more likely to die than stroke victims who were not infected. “When compared with contemporary controls, COVID-19positive patients had higher National Institutes of Health Stroke Scale [NIHSS] scores on admission and higher peak D-dimer levels,” the authors write, adding that when compared to historical controls, COVID-19positive patients were also more likely to be younger men with elevated troponin, higher NIHSS scores, and higher erythrocyte sedimentation rates. Additionally, Yaghi and his team reported that patients with COVID-19 and stroke had significantly higher mortality than both historical and contemporary controls. During the study period, 63% died, compared with 9% for those without the virus and 5% of pre-
pandemic stroke patients. The investigators conducted a retrospective cohort study with ischaemic stroke patients who were hospitalised between 15 March, 2020, and 19 April, 2020. Through the use of medical records, clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 were compared to patients without the disease (contemporary controls), and to a cohort of patients with stroke already discharged (historical controls). “Our findings provide compelling evidence that widespread blood clotting may be an important factor that is leading to stroke in patients with COVID-19. The results point to anticoagulant, or blood thinner therapy, as a potential means of reducing the unusual severity of strokes in people with the coronavirus,” states the study’s senior investigator, Jennifer Frontera (NYU Langone Medical Center, New York, USA), in a press release from her institution. Yaghi also highlights that the study is the largest of its kind among COVID-19 stroke victims and adds valuable insight into the poorly understood complications of
infection in Wuhan, China, 3% had a stroke. Yet, among 13 patients with COVID-19 infection who underwent brain magnetic resonance imaging (MRI) in France, 23% had an ischaemic stroke. More recently, Merkler and team say, investigators found that of the 3,556 patients hospitalised with COVID-19 in New York, 0.9% had an ischaemic stroke, while among the 1,916 patients in this study with emergency department visits or hospitalisations with COVID-19 infection, 1.6% received a diagnosis of ischaemic stroke. They add: “The rate of ischaemic stroke among patients hospitalised with COVID-19 in this study was 1.8%, which is similar to that observed in the Wuhan cohort, but higher than that observed in the study by Yaghi et al in New York.” In their paper, Merkler and the team proceed to discuss reasons for these discrepancies in the rate of stroke. First, they write, the method of stroke ascertainment varied across studies, and thus some patients with ischaemic stroke may have been missed. Secondly, the team acknowledged that many hospitalised patients with COVID-19 infection are severely ill, which makes acquiring brain imaging challenging and at times impractical. “As a consequence,” they state, “the threshold to obtain brain imaging may have varied between institutions.” Lastly, the team highlights that the demographic composition of patients included in these cohorts varied, and data suggest that races of colour appear to be at heightened risk for severe disease.
COVID-19 disease. He notes: “Our study suggests that stroke is an uncommon yet important complication of coronavirus given that these strokes are more severe when compared with strokes occurring in patients who tested negative for the virus.” However, the authors acknowledge that their findings should be interpreted with caution due to a number of “important limitations”. Yaghi and colleagues write that the study was a relatively small, retrospective, observational study with potential for selection bias, while the study may not be representative of all patients with stroke in their New York healthcare system, such as those who were critically ill. Moreover, as their report focused on ischaemic stroke, they state “these complications in the setting of COVID-19 need further study”. In addition to investigating anticoagulant therapy, Yaghi and the team plan to continue the study to confirm if the findings are sustained through the end of the year. In their paper, they allude to the PROTECT COVID trial, a randomised trial of anticoagulation strategies in COVID-19, which they say aims to examine the safety and efficacy of therapeutic versus prophylactic anticoagulation in patients with COVID-19 and mild to moderate elevation in D-dimer levels. SARS-CoV-2, the virus that causes COVID-19
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July 2020 | Issue 38
ESO clinical trial results
Routine use of fluoxetine after acute stroke not recommended
The final results of EFFECTS (Efficacy of fluoxetine: A randomised controlled trial in stroke) have been presented by Erik Lundström, Uppsala University, Uppsala, Sweden, during a large clinical trials webinar hosted jointly by the European Stroke Organisation (ESO) and the World Stroke Organisation (WSO), on 13 May.
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luoxetine once daily, six-months after an acute stroke, did not improve functional outcome. While the drug reduced depression, it increased the incidence of fractured bones and hyponatraemia. Taking these factors into account, Lundström concluded: “We do not recommend the routine use of fluoxetine after acute stroke.”
Why test fluoxetine?
He told the viewers that the idea was to take a known drug, “used by millions”, and try it for a new indication. Otherwise known as Prozac, fluoxetine is a commonly prescribed antidepressant. After looking into a meta-analysis of animal stroke studies, the team found that fluoxetine improves neurobehavioural outcome by over 50%. Lundström speculated that this was most likely due to increasing neuroplasticity within the brain. “There is evidence for neurogenesis; there is evidence for neuroprotection, and there is evidence that it influences the adrenergic system,” he said. But, according to Lundström, what really ignited the team’s interest in fluoxetine was the FLAME trial, published in The Lancet Neurology in 2011. “In this randomised controlled trial of 118 ischaemic stroke patients with hemiparesis, 17% more of the patients allocated to 20mg fluoxetine were independent at three
Endovascular therapy fails to outperform best medical management in basilar artery occlusion stroke Final results of the Basilar artery international cooperation study (BASICS) have been reported by Wouter J Schonewille (University Medical Centre Utrecht, Utrecht, the Netherlands) during a large clinical trials webinar hosted jointly by the European Stroke Organisation (ESO) and the World Stroke Organisation (WSO), on 13 May. CONCLUDING BASICS—WHICH set out to assess the efficacy and safety of endovascular therapy (EVT) plus best medical management, versus best medical management alone, <6 hours of estimated time of basilar artery occlusion (BAO), Schonewille said— “We found a limited risk difference of 6.5% after
months, compared to the placebo [group].” He also alluded to a Cochrane review of selective serotonin reuptake inhibitors (SSRIs) for stroke recovery published in 2012. While the review demonstrated that SSRIs reduce neurological impairment, anxiety and depression after stroke, Lundström acknowledged there was heterogeneity between the studies. “Large, well-designed trials were needed to determine whether SSRIs should be given routinely to patients with stroke. “This led us to develop a family of three trials, with a similar core protocol that was slightly tailored to national settings: FOCUS in the UK, EFFECTS in Sweden, and AFFINITY in Australia, New Zealand and Vietnam,” he added. The three trials together have recruited a total of 5,907 patients. The findings of FOCUS, which turned out to be neutral, were published in December, 2018, Lundström said.
Wouter Schonewille
endovascular therapy in BAO, mainly due to a better than expected outcome after best medical management alone.” However, though acknowledging that the trial was underpowered, he alluded to some interesting findings. “Patients over 70 years tended to do slightly better after endovascular therapy than the younger patients. Most interesting, we found a significant difference in outcome favouring EVT in patients with moderate to severe stroke, or NIHSS [National Institutes of Health Stroke Scale] ≥10 or more, while there was a trend towards a better outcome after IV thrombolysis in patients with minor deficit, or NIHSS <10. There was also a signal that patients did better after EVT if they were pretreated with IV thrombolysis.” Schonewille also reported that EVT was “remarkably” safe, as only 4% of patients in the intervention arm had a symptomatic intracranial haemorrhage within three days of treatment (0.7% in the control arm). He also noted that mortality at 90 days was slightly lower in the EVT arm (38.2% vs. 43.2% for best medical management), but the difference
EFFECTS: The findings
Fluoxetine daily for six-months after an acute stroke did not improve functional outcome. “The common odds ratio was 0.96 [95% CI 0.78, 1.13; p=0.41], so no benefit of fluoxetine,” Lundström said. Nevertheless, the results pointed to the fact that fluoxetine was safe in the stroke population, as Lundström reported that there was no treatment-related death, mortality was low, and there were no differences (between fluoxetine and placebo) in acute coronary events, epileptic seizures, and bleeding events. While the number of new depression was reduced by just under 4%, the number of fractured bones increased by 2.2%, and hyponatraemia by 1.34%. In terms of the inclusion criteria, patients 18 years or over were included in the trial. Those with either ischaemic stroke or intracerebral haemorrhage were randomised two to 15 days after onset. Lundström highlighted that patients needed to have persisting focal neurological deficit present at the time of randomisation severe enough to warrant treatment from both the physicians and the patients perspective. The “important” exclusion criteria he alluded to included: epilepsy, depression, previous drug overdose or attempted suicide, allergy or contraindication to fluoxetine, and life-threatening illness that would make 12-month survival unlikely. “Both groups were well balanced, with a median age of 71 years,” Lundström told the viewers. Around 98% of the population were independent before stroke. Eightyeight per cent had an ischaemic stroke. The median National Institutes of Health Stroke Scale (NIHSS) score was 3.
was not significant.” BASICS was a multicentre, international, controlled trial, with randomised treatment-group assignments, open-label treatment and blinded outcome assessment. Patients were assigned in a 1:1 ratio, and stratified according to randomising centre, use of IV thrombolysis, and NIHSS score (<20 vs. ≥20). Schonewille told viewers that the calculated sample size was 300 patients, assuming a favourable outcome in 46% with EVT plus best medical management, and 30% with best medical management alone, giving an absolute risk reduction of 16%. However, in the intervention arm, 44.2% had a favourable outcome as compared to 37.7% in the control arm, yielding an absolute risk reduction of 6.5%, which, according to Schonewille, was considerably lower than the expected risk reduction calculated of 16%. Of the 300 randomised patients, 154 were randomised to the intervention arm, and 146 received best medical management alone (the control arm). No patients were lost to follow-up at three months. “The demographics were well balanced, with the average age around 67 in both arms. Close to 80% of patients were treated with IV thrombolysis, and the median NIHSS score was just above 20 in both treatment arms,” Schonewille said. In terms of the secondary outcomes, the BASICS collaborators did not find a significant difference in excellent outcome (mRS 0–2) at day 90, as there
was only an absolute risk reduction of 5%. Additionally, no significant difference of modified Rankin Scale scores on shift analysis was observed. The inclusion criteria Schonewille highlighted were: EVT had to be feasible within six hours of estimated time of BAO, and, if indicated, IV thrombolysis had to be started within 4.5 hours of BAO. In contrast, patients were excluded if they had intracranial haemorrhage, extensive brainstem ischaemia, and cerebellar mass effect or acute hydrocephalus. He also acknowledged that the team, during their interim analyses, used sequential monitoring with a triangular test, each with 25 patients included. On the last interim analysis (n=252), the Data Safety Monitoring Board (DSMB) recommended to continue the trial to completion (n=300). Most patients were randomised in the Netherlands (n=200), followed by Brazil (n=42), Germany (n=31), France (n=12), Italy (n=10), Switzerland (n=4), and Czech Republic (n=1).
We found a significant difference in outcome favouring EVT in patients with moderate to severe stroke.”
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July 2020 | Issue 38
New technology
Novel AI technology a better predictor of stroke than traditional methods An artificial intelligence (AI) technology has demonstrated a more than 70% improvement in the accuracy of stroke prediction compared with a stenosis-based approach to riskstratification over a six-year time period. THESE INTERIM RESULTS from the CRISP (Carotid risk prediction) Consortium study were presented virtually during Scientific Session 9 at the Society for Vascular Surgery’s conference, SVS Online Summer 2020 (22 June–2 July). The study, led by Brajesh Lal, director of both the University of Maryland’s Center for Vascular Diagnostics and the NIH Vascular Imaging Core Facility, with participation by the Cleveland Clinic, Weill-Cornell and Case Western, sought to improve prediction of major adverse neurological events (MANE; stroke, transient ischaemic attack, and amaurosis fugax) by applying AI to traditional carotid imaging using the Elucid Bio vascuCAP software. Lal reported that colleagues from four participating centres contributed CT angiography imaging on patients with asymptomatic carotid stenosis. Lal’s NIH Vascular Imaging Core at the University of Maryland processed and analysed the images using vascuCAP for histologically validated plaque geometry and tissue composition from the CT angiogrpahy images. Using the imaging data, the investigators tested several high-performance multivariate models for the response variable of MANE. Testing differing sets of predictors, the investigators identified the model that optimised the area under
the receiver operating characteristic curve (area under the curve [AUC]) for the probability of MANE within six years. The best predictor (a combination of morphologic and patient features) was compared with the current standard of care (percent diameter stenosis) for MANE. Additionally, the ranked importance of individual morphologic features in the final model was determined.
AI algorithms for risk stratification in carotid atherosclerosis are a better predictor of stroke than stenosis assessment alone.” The combination of morphologic and patient features created a model with an AUC of 0.86 predication probability. This model significantly outperformed the prediction probability of the commonly used clinical parameter of percent stenosis (using the North American Symptomatic Carotid Endarterectomy Trial criteria:
stenosis only, AUC of 0.45). This resulted in a more than 70% improvement in the investigators’ ability to predict MANE in patients with asymptomatic carotid stenosis, Lal concluded at the SVS conference. “These study results demonstrate that the vascuCAP’s AI algorithms for risk stratification in carotid atherosclerosis are a better predictor of stroke than stenosis assessment alone,” stated Lal in Elucid Bio’s news release. “Implementing this predictive model on asymptomatic patients in the clinical setting could help identify and inform treatment for those at high-risk for future major adverse neurologic events.” The CRISP study was an all-comers design, adjusted for demographic factors. However, subjects without visible plaque within the carotid artery, or subjects with insufficient CT angiography image quality (defined strictly as documented in the vascuCAP Reading Manual) were excluded from the investigation. On the rationale behind advancing stroke prediction, the company acknowledge that current risk assessment for patients with carotid atherosclerosis relies primarily on assessing the degree of stenosis. More reliable risk stratification, Elucid Bio argues, has the potential to improve patient selection for more aggressive treatment for MANE by incorporating a combination of carotid plaque geometry, plaque tissue composition, patient demographics and clinical insights. The Elucid Bio technology is currently in clinical use and may have applications for informing risk for COVID-19 patients who have been experiencing strokes at a significantly higher rate, the medical technology company said. The software can identify endothelial damage—a subtle, but serious effect of COVID-19 that can cause blood clotting that leads to stroke, the company added.
First clinical study using patient-specific brain aneurysm models for pre-procedural rehearsals published The findings of the first clinical study to use the EVIAS (Biomodex) 3D printing models to plan aneurysm treatment using endovascular robotics and novel flow diverters have been published in the Journal of NeuroInterventional Surgery (JNIS).
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he authors, Vitor Nagai Yamaki of Universidade de São Paulo (São Paulo, Brazil) and colleagues, concluded that pre-procedural rehearsal using patient-specific 3D models provides precise procedural planning, which they say “can potentially lead to greater operator confidence, decreased radiation dose and improvements in patient safety, particularly in first inhuman experiences”. The study included eight patients with their respective EVIAS 3D aneurysm models. Pre-operative simulation was performed for the first in-human robotic-assisted neurovascular interventions (n=2) and new generation flow-diverter stents (n=6). According to the authors, aneurysms were located in both the anterior (n=5) and posterior (n=3) circulation and were on average 11.0±6.5mm in size. “We found reliable reproduction
of the aneurysm features and similar dimensions of the parent vessel anatomy between the 3D models and patient anatomy,” Yamaki et al write. The team also state that information learned from pre-surgical in vitro simulation are described in detail within the publication, including an improved patient treatment plan, which contributed to successful first in-world procedures with no intraprocedural complications. A Biomodex press release states that all rehearsals and procedures were performed by Vitor Mendes Pereira, a neurosurgeon and neuroradiologist at Toronto Western Hospital (Toronto, Canada) and senior author of the study. “This technology has the potential to increase operator confidence and improve patient outcomes, particularly in first in-human experiences using new devices and robotics. The rehearsals were instrumental in our recent successful
completion of the world’s first inhuman robotic-assisted neurovascular intervention,” Pereira comments. Biomodex’s 3D training models were created based on each patient’s unique CT angiography scans and printed using a Stratasys J750 Digital Anatomy 3D Printer. Biomodex Invivotech material
This technology has the potential to increase operator confidence and improve patient outcomes.”
was used to simulate the biomechanics of the aneurysm and the surrounding tissue. The models are made with various flexible photopolymers which, unlike single material models like silicone, allow control of the pliability of the target area, providing critical tactile feedback. The models are connected to the EVIAS station which includes a hydraulic system to replicate blood flow. The research study, led by RADIS lab’s clinical research technologist, Nicole Cancelliere (also lead co-author of the study), found the models to be a reliable and accurate reproduction of the aneurysm features and the parent vessel anatomy. “The rehearsals allowed the operator to address issues, such as device sizing, and practice challenging manoeuvres, for example: how to open flow diverter stents,” notes Cancelliere.
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July 2020 | Issue 38
Stroke trials
RESILIENT final results prove thrombectomy efficacious in Latin America After receiving a standing ovation when presented at the European Stroke Organisation Conference (ESOC; 22–24 May, Milan, Italy) last year, the final results of RESILIENT have now been published in The New England Journal of Medicine. THE TRIAL SHOWED that among patients in the public healthcare system of Brazil who were treated within eight hours after a stroke due to a proximal occlusion in the anterior circulation, 90-day functional outcomes were better with thrombectomy plus standard care than with standard care alone. Specifically, the percentage of patients with a score on the modified Rankin Scale (mRS) 0–2 was 35.1% in the thrombectomy group, and 20% in the control. Regarding safety outcomes, asymptomatic intracranial haemorrhage occurred in 51.4% of the patients in the thrombectomy group and 24.5% of those in the control group, while symptomatic intracranial haemorrhage occurred in 4.5% of the patients in each group. “All previous randomised clinical trials of mechanical thrombectomy were performed in high-income countries, and for that reason, have minimal to no impact over the public healthcare policies of lowand mid-income countries,” Raul Nogueira, (Grady Memorial Hospital, Atlanta, USA) principal investigator of the trial, tells NeuroNews. He adds that across the entirety of Latin America, there is only one thrombectomy-capable programme (in Santiago, Chile), currently being funded by a federal government. “This is the same reality of most of the developing countries around the world; thrombectomy is only available to those who can afford paying for private insurance or the treatment itself,” he says. However, despite the highly positive results of the previous thrombectomy trials published in 2015, Nogueira disclosed that the Brazilian Government
Direct mechanical thrombectomy alone deemed non-inferior to its combination with alteplase Investigators of the DIRECT-MT trial, who evaluated Chinese patients with acute ischaemic stroke from large-vessel occlusion, concluded that endovascular thrombectomy alone was non-inferior in terms of functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset.
I
n the findings, published in The New England Journal of Medicine (NEJM), authors Pengfei Yang, Department of Neurosurgery, Changhai Hospital, Shanghai, China, and colleagues report that endovascular
deemed the cost of thrombectomy too high, and its costeffectiveness unproven. Yet, the country agreed to fund a clinical trial to assess whether incorporation of the treatment into the Brazilian Universal Public Healthcare System would be beneficial. “The RESILIENT investigators hope that their study will now bring a life-changing treatment to the over 80% of Brazilians who cannot afford private health insurance,” Nogueira adds, as he tells the newspaper
The investigators hope that the study will bring a life-changing treatment to the over 80% of Brazilians that cannot afford private health insurance.”
in a 1:1 ratio to receive standard care plus mechanical thrombectomy (thrombectomy group) or standard care alone (control group). The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. In total, 300 patients were enrolled, including 79 who had undergone thrombectomy during an open-label roll-in period. Approximately 70% in the two groups received intravenous alteplase. According to the authors, the trial was stopped early because of efficacy when 221 of a planned 690 patients had undergone randomisation (111 to the thrombectomy group and 110 to the control group). The common odds ratio for a better distribution of scores on mRS at 90 days was 2.28 (95% confidence interval [CI], 1.41 to 3.69; p=0.001), favouring thrombectomy. Again, the percentage of patients with an mRS score 0–2, signifying an absence of or minor neurologic deficit, was 35.1% in the thrombectomy group and 20% in the control group (difference, 15.1 percentage points; 95% CI, 2.6 to 27.6).
that he hopes the findings will influence governmental decisions across many other countries facing similar challenges in their public healthcare system. The trial itself studied the safety and efficacy of thrombectomy in 12 public hospitals in Brazil. Patients with a proximal intracranial occlusion in the anterior circulation that could be treated within eight hours after the onset of stroke symptoms were randomly assigned
therapy alone was also associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4%) and overall successful reperfusion (79.4%) compared with the combined-therapy group (7% and 84.5%, respectively). Moreover, mortality at 90 days was 17.7% in the thrombectomy-alone group, and 18.8% in the combination-therapy group. DIRECT-MT was conducted at 41 academic tertiary care centres in China. According to Yang et al, patients with acute ischaemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone, or endovascular therapy preceded by alteplase, at a dose of 0.9mn per kilogram of body weight, within 4.5 hours after symptom onset. The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval (CI) of the adjusted common odds ratio ≥0.8. Additionally, the investigators assessed various secondary outcomes, including death and reperfusion of the ischaemic area. Of 1,586 patients screened initially, the investigators enrolled 656 patients from February 2018 through to July 2019: 327
assigned to thrombectomy-alone and of thrombectomy without alteplase 329 assigned to the combination-therapy pretreatment to thrombectomy alone.” group. “The baseline characteristics of In addition, Albers acknowledges the the patients were similar in the treatment improvements in reperfusion from the groups,” the authors write, adding addition of intravenous thrombolysis, that the median age was 69 but questions why they did not (interquartile range: 61–76), translate into clinical benefit. and 56.4% of patients “One possibility,” he says, “is were male. that the brief time in this trial In a corresponding between the administration editorial also published of alteplase and the initiation in NEJM, Gregory Albers of thrombectomy did not from the Stanford Stroke allow adequate time for the Center, Palo Alto, USA, intravenous effect to alludes to the fact that while Gregory Albers be expressed non-inferiority of direct “The mismatch between mechanical thrombectomy was the high percentages of patients with established, the margins used to declare reperfusion and the much smaller non-inferiority were “generous”. “The percentages of patients with clinical confidence intervals did not exclude recovery in thrombectomy studies a benefit of approximately 20% in the suggests that a substantial volume of combination-therapy group,” he writes, brain tissue is already irreversibly injured adding: “In fact, a similar Japanese trial in many patients by the time reperfusion did not establish the non-inferiority occurs,” he adds. Albers speculates that to improve outcomes in future stroke trials, adjunctive therapies like thrombolytic or neuroprotective agents might be started early, either at the primary stroke centre or in the prehospital setting. Regardless, he cautions: “Until more data are available, it is appropriate to follow current guidelines that recommend that all eligible patients receive alteplase before thrombectomy.”
Until more data are available, it is appropriate to follow current guidelines.”
Issue 38 | July 2020
Transradial access
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Transradial access may be safer than transfemoral access for flow diversion to treat cerebral aneurysms Transradial, as opposed to transfemoral access, may be a safer approach for flow diversion procedures to treat cerebral aneurysms at a wide range of locations. This conclusion was reached by Yangchun Li from the University of Miami Miller School of Medicine (Miami, USA) and colleagues, as their retrospective study, published online in the Journal of NeuroInterventional Surgery (JNIS), found that both access site complication rate and overall complication rate were lower for transradial access flow diversion.
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he investigators used a large multicentre registry to retrospectively analyse flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with a 95% confidence interval (CI) to account for results from multiple centres. Access site complication rates and overall complication rates were compared between the two approaches. Of the 2,285 patients included in the study who underwent flow diversion, 135 (5.85%) were treated with transradial access, and 2,151 (94.14%) via transfemoral access. Li and
the team reported that the two groups shared similar patient and aneurysm characteristics. “There were no access site complication in the transradial access group,” highlight the authors. However, they write that the rate of access site complications for the transfemoral approach was 2.48% (95% CI, 2.4– 2.57%, vs. 0%; p=0.039). Of note, one death resulted from a femoral access site complication. The overall complication rate was also higher in the transfemoral group (9.02%; 95% CI, 8.15–9.89%) compared with the transradial group (3.73%; 95% CI, 3.13–4.28%; p=0.035).
Why the authors are advocating for transradial access
These findings, Li et al say, help alleviate the apparent lack of neurointerventional literature directly comparing complication rates between the two approaches. Whilst the field of cardiology has conducted large randomised trials that have shown lower morbidity and mortality, as well as higher patient preference and cost reduction associated with transradial access, the same depth of investigation has yet to be applied to neuroendovascular medicine. Moreover, Li and colleagues write: “Reducing access site complications is relevant to flow diversion for two reasons. First, flow diversion employs larger bore access systems, which may increase the likelihood of access arterial injury, bleeding or occlusion. Second, prolonged dual antiplatelet therapy is administered to patients undergoing endovascular flow diversion along
with heparin, which increases the risk of access site bleeding. Additionally, the smaller diameter of the radial artery raises the question of whether a transradial access approach is uniformly feasible for flow diverting procedures.” The investigators state that the current study is “the largest series to date comparing transradial and transfemoral access for this type of neuroendovascular procedure”. Additionally, they argue that the study demonstrates a significant safety benefit with transradial access flow diversion, alongside the feasibility of treating both ruptured and unruptured aneurysms via transradial access at a wide range of locations. Lastly, the team surmise: “Combining both these findings with other benefits of transradial access, including high patient preferences, elimination of postprocedural bed rest and decreased cost, we continue to advocate for the transition to a radial-first approach for endovascular flow diversion.”
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July 2020 | Issue 38
Interview
Profile
Richard P Klucznik
Richard P Klucznik currently serves as the president of the Society of NeuroInterventional Surgery (SNIS) and the director of interventional neuroradiology at The Methodist Hospital (Houston, USA). Here, he talks to NeuroNews about his experience treating stroke throughout COVID-19, how the society has had to quickly adapt to deliver education, and the lessons learnt from the pandemic. Despite the upheaval in healthcare during this time, Klucznik argues that the future for the field of neurointerventional medicine, in general, looks bright. “There will be a world where no aneurysm cannot be treated by using minimally invasive techniques, and no thrombus will stay inside a blood vessel causing a stroke,” he says.
What first attracted you to the field of neuroradiology?
It was during my radiology residency when magnetic resonance imaging (MRI) first came to the forefront of imaging and we could see brain and spine like we never could before. The radiology residency programme was affiliated with the University of California at San Francisco and we were invited to the Thursday neuroradiology conferences. It was at that time that I was first introduced to interventional neuroradiology where Grant Heishima was giving grand rounds; I knew from then that I was interested in interventional neuroradiology.
Have you had important mentors throughout your career? What have they taught you? One of my first mentors was Dr Samuel Wolpert, who epitomised the word gentleman. He received a gold award for his work in the field of neuroradiology. He knew the vascular anatomy of the brain better than anyone I have ever met. Other teachers I have had include Drs Eddie SK Kwan and Michel Mawad. My partner Dr Orlando Diaz is a mentor to many and I have learnt a lot from him, and I believe him to be one of the smartest neurointerventionalists. I consider him a good friend, partner, and mentor. Other members have not only taught me a skill set that is necessary for interventional neuroradiology, but how to treat patients properly as human beings and their family members who are so intimately involved in their care.
What has your experience as president of SNIS been like amid COVID-19?
My experience as president of SNIS amid the COVID-19 pandemic has been quite interesting. Since all travel was banned, I was not able to represent the SNIS at other meetings across the world, and everything became web-based. We learnt quickly how to adapt with webinars and the upcoming annual meeting will also be web-based. We naturally could not hold an in person board meeting as well. Sadly, it is the personal relationships that have been sacrificed because it is important to make lasting friendships and to pass the torch to the incoming president and vice president.
How has the pandemic changed the society’s approach to delivering education?
The pandemic has certainly changed the society’s approach to delivering education. We have become totally web-based and are now giving weekly webinars for our society members. We do not know when we will have an in person meeting in the future, hopefully next year at the Broadmoor Hotel in Colorado Springs.
Can you tell us about your experience practising as a physician during
COVID-19? Have you had to make any difficult clinical decisions?
During the pandemic we have learnt how to wear personal protective equipment (PPE) that we never had to wear before with multiple layers, facemasks, and N95 masks. It seems we learnt that stroke patients may not be making it into the hospital for fear of the virus and we have begun a programme to reach out to patients to reassure them that we are here to treat them. Early on we were not sure which patients may have the virus so we were treating all incoming strokes as if they were infected. We have now learnt with more testing that we do not have to go to a full extent on a daily basis unless we know that they are infected.
What positives do you see coming from the pandemic in terms of lessons learnt?
One positive I can see from the pandemic is the fact that we have adapted to a new world and learnt to treat infected patients while ensuring we ourselves, and our staff, are safe. We were in the process of building a new hospital with new angiographic equipment and new rooms. We now have to re-examine those plans and instead of routine interventional rooms we must plan for negative pressure rooms in order to deal with the virus in the future.
We have adapted to a new world and learnt to treat infected patients while ensuring we ourselves, and our staff, are safe.” I think telehealth is also one of the big winners of this pandemic. Already our neurologists were “seeing” stroke patients from other hospitals via telemedicine and all of us are working to “see” patients and consult via the web. As far as other things we have learnt from the pandemic, I think masks will be the new norm for quite some time. We are also learning more about how to fight the virus; some medications seem to be working, such as steroids and maybe remdesivir. However, we need to start returning to normal soon, as patients may not be treated for stroke or heart attack; cancer screening is down and there is a toll that is not being talked about concerning a rise in suicide and drug abuse, as well as spousal or family abuse.
What has been the most important development in the neurointerventional field during your career? I have seen the neurointerventional field grow from its infancy, not just in devices but in personnel. Of
course, the most important development of all was the development of platinum coils that can be placed in aneurysms; now they can be treated using minimally invasive techniques instead of craniotomy. One of the newest developments is the devices for the removal of clots in emergent large vessel occlusions (ELVO). These have drastically changed the landscape, not just for the people who perform the procedures, but also for the millions of patients that we can now help on a daily basis by treating their acute stroke in a timely manner and then allowing them to recover. The use of new devices such as these has truly revolutionised the treatment of stroke.
On the contrary, what has been the biggest disappointment?
Before the advent of the thrombectomy devices, the biggest disappointment was the devices that came before and did not work, but now that has been completely changed.
Issue 38 | July 2020
Interview
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Fact File
Present positions:
Director, Interventional Neuroradiology, Endovascular and Therapeutic Neuroradiologist, The Methodist Hospital, Houston, USA Clinical Associate Professor, Weill Medical College, Cornell University, New York, USA Director, Texas Neurovascular Center, CoDirector, Methodist Brain Aneurysm Center Consulting Radiologist, M.D. Anderson Cancer Center Associate Professor of Clinical Radiology, Institute for Academic Medicine, Houston Methodist Hospital, Houston, USA
Society membership:
American Society of Neuroradiology (Senior Member) Society of Neurointerventional Surgery (Senior Member) The Radiological Society of North America American College of Radiology
Active clinical trials:
Pivotal Trial of the Neuroform Atlas Stent for Treatment of Anterior Circulation Aneurysms: One-Year Outcomes
Recent publications:
What technological advances do you see shaping stroke treatment over the next 10 years, or beyond?
The technological advances in stroke treatment will come through new devices that allow us to get to the clot quicker, as well as more distal devices. The advent of stem cell treatments for stroke will also be a game-changer.
What advice would you give to those beginning their neuro career?
My advice for those beginning their career in the neurointerventional field would be to learn from the past and look to the future, as it is very bright. There will be a world where no aneurysm cannot be treated by using minimally invasive techniques, and no thrombus will stay inside a blood vessel causing a stroke. There may be a need for some specialisation for those to only perform stroke treatments due to the volume, and not necessarily do the rest of
neurointerventional procedures.
Outside of medicine, what are your hobbies and interests?
Outside of medicine, my hobbies include downhill skiing, trying to learn how to play golf, and shooting. Since my father fought in World War II in North Africa and Italy, my son has developed an interest in World War II history, and we have begun collecting firearms from the war, such as an M1 rifle that we can take to the range and actually fire at targets. It is amazing that our soldiers in the past carried weapons that not only were heavy but had a heckuva kick and only had eight rounds. We owe all of our veterans of World War II a great deal of thanks. I am also reading the Bible for the first time in my life thanks to the influence of my wife, Nina. We also love to travel but obviously due to the pandemic that has been put on hold.
A case of cerebral vasculitis due to neurobartonellosis Society of NeuroInterventional Surgery recommendations for the care of emergent neurointerventional patients in the setting of COVID-19 A joint statement from the Neurointerventional Societies: Our position on operator experience and training for stroke thrombectomy Impact of balloon guide catheter use on clinical and angiographic outcomes in the STRATIS stroke thrombectomy registry
Education:
1979-1983: Doctor of Medicine, Tufts University School of Medicine, Boston, USA 1984-1988: Diagnostic Radiology Resident, David Grant Medical Center, Travis Air Force Base Fairfield, USA 1988-1990: Fellowship in Neuroradiology, Tufts - New England Medical, Boston, USA 1994-1996: Fellowship in Interventional Neuroradiology, Methodist Hospital, Baylor College of Medicine Houston, USA
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July 2020 | Issue 38
Treatment techniques and training
CX 2020 LIVE: The conversation on challenges in acute stroke continues Despite COVID-19, CX 2020 LIVE came to life online, attracting over 6,000 registrants from over 120 countries. The penultimate session focused on challenges surrounding acute stroke, and promising technologies such as intracranial stenting and virtual simulation were placed under the spotlight. CX chair Roger Greenhalgh (London, UK) introduced Hugh Markus (Cambridge, UK), who chaired the session alongside moderator Ross Naylor (Leicester, UK), who took live questions from participants joining the session from around the world. Arguing that “intracranial stenting for stenosis is not dead”, Andrew Clifton (London, UK) compared results from the SAMMPRIS trial, which did not favour stenting with the WingSpan device (Boston Scientific), and the WEAVE trial, to refute the “traditional dogma” that best medical treatment should be the favoured approach. Clifton outlined the limitations of the SAMMPRIS trial, with specific reference to the minimum requirement of operator experience. “A minimum of three WingSpan stent cases were required for the operators. It is, if you have not used it, quite a complicated device,” he said. This is in contrast, he explained, to the WingSpan
stent system post-market surveillance (WEAVE) trial, where interventionalists were “required to be genuinely experienced”. He highlighted that operators with greater than 50 WingSpan cases before enrolment in WEAVE had a 0% (out of 69) periprocedural stroke and death rate. Thus, Clifton proposed that findings from WEAVE indicate that the poor clinical outcomes observed in SAMMPRIS were not necessarily due to the stent, but more likely due to the inexperience of the interventionalists, as well as poor patient selection and underdeveloped standards in intracranial stenting. “We need to proceed to a careful randomised controlled trial,” he told the CX 2020 LIVE audience. The discussion saw Naylor question the relevance of such a trial when a more generalisable set of interventionalists will have to perform the procedures in the long run. Clifton replied: “When you are looking at a patient who has had a stroke, particularly the subsets—AfroCaribbean or Asian—that have a high incidence of intracranial stenosis, you need to select them carefully
The apprenticeship model [for training] cannot stand alone, and simulation cannot stand alone.” [and] perhaps refer them on to a centre that does a lot of these; not every centre should do them.” Clarifying that the technology and medical treatment have improved since the SAMMPRIS trial, Clifton reiterated: “The centre’s experience is very important when it comes to managing these patients, as is the experience of the interventionalist (usually a neurointerventionalist), who has got the numbers under their belt, and the audit to prove they can do it safely.”
A new reality for mechanical thrombectomy
On the subject of ensuring the safety of stroke procedures, Lars Lönn (Copenhagen, Denmark) discussed validation studies of virtual reality simulation performance metrics for mechanical thrombectomy. “Despite the proven effectiveness [of mechanical thrombectomy],” he began, “access is limited, and one
New Embolus retriever with interlinked cages provides “equivalent results” to conventional stent retrievers A large multicentre registry has found that through the use of propensity score matching, the Embolus retriever with interlinked cages (ERIC; Microvention) device has yielded equivalent angiographic and clinical results to conventional stent retrievers.
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he authors, Célina Ducroux (Fondation Ophtalmologique Adolphe de Rothschild, Paris, France) and colleagues write in the Journal of NeuroInterventional Surgery that ERIC is one of the latest devices for performing thrombectomy. “It has several architectural features that are supposed to enhance its ability to remove clots and prevent distal emboli,” they note. The team, on behalf of the ETIS
(Endovascular treatment of ischaemic stroke) investigators, set out to compare ERIC with standard stent retrievers. The clinical and radiological data of all consecutive patients treated with ERIC or standard US Food and Drug Administration (FDA)-approved stent retrievers were collected from a prospective multicentre registry. The team compared procedural outcomes (recanalisation rates and procedural
Clockwise from top left: Roger Greenhalgh, Hugh Markus, Ross Naylor, Peter Schneider, Andrew Clifton, and Lars Lönn.
of the reasons is a shortage of operators trained for the procedure. One approach is to enhance the learning experience and train doctors to do the procedure using metric-based virtual simulation.” A group of senior interventional experts at the ASSERT centre, University College Cork, Cork, Ireland, in conjunction with Mentice, have created the training simulation method. “We set out to determine whether a simulator could distinguish between novice interventional neuroradiologists and experts,” he explained. The team found that experienced practitioners, when compared to “rookies”, were 47% faster and had 97% fewer errors. During the discussion that followed, Naylor queried whether Lönn’s team has considered training consultant cardiologists or physicians from other disciplines to do mechanical thrombectomy, given the shortage of neurointerventionalists. Refusing to be drawn into the politics around specialty, Lönn replied: “A proctor in the simulator gives you tips and tricks in a structured way, so you train everyone in the same manner, which is a good thing. We can also test this to see if they have reached a certain level. If they have, then of course they have proficiency, regardless of their initial speciality. But they have to train.” An incoming question from Argentina touched on whether stimulation should be obligatory in training programmes. Clifton shared his “strong opinions on this”, arguing that stimulation is a great adjunct, but not a replacement for traditional apprenticeships. Lönn agreed: “The apprenticeship model cannot stand alone, and simulation cannot stand alone.” Greenhalgh noted that voting from CX 2019 supported the belief that, as long as adequate training was undertaken, the interventionalist need not be a neuroradiologist. The debate on whether neuroradiology training is a prerequisite for performing stroke interventions therefore prevails.
complications) and clinical outcomes (modified Rankin Scale [mRS] and mortality at three months). “A total of 1,230 were included,” Ducroux and colleagues report. They write that in both the propensity scorematched cohort (195 ERIC patients, 630 stent retriever patients) and the inverse probability of treatment weighting propensity-adjusted cohort (206 ERIC patients, 1,024 stent retriever patients) there was no difference in terms of successful recanalisation, good clinical outcome (mRS: 0–2 or equal to pre-stroke mRS), or mortality at three months. “Patients treated with first-line ERIC had a higher rate of complete recanalisation (mTICI 3); however, they also required more passes and more frequent rescue therapy than the stent retriever patient group,” add the investigators. Given the results, the ETIS investigators conclude that the ERIC device may be “as safe and effective as current FDA-approved stent retrievers for endovascular thrombectomy of acute
ischaemic strokes with an emergent large vessel occlusion.” Alluding to what is required in terms of further research, Ducroux et al say that it should focus on “a tailored approach” based on the clot imaging or biological characteristics. This, they write, “may identify patients more likely to benefit from one technique/device over another”. Of note, the team state that ERIC was initially designed to try to overcome both structural and functional limitations of standard stent retrievers. “Architecturally,” they say, “the ERIC device consists of several interlinked spherical cages. Compared with the tubular design of standard stent retrievers, the interlinked structure of the ERIC [device] is supposed to improve clot capture and decrease clot fragmentation (and thus distal emboli). “The structure of ERIC may also enhance deployment along curved segments of arteries and reduces interaction with arterial walls, thereby limiting endothelial damage.”
Issue 38 | July 2020
COVID-19
“Stoicism kills”: A “concerning” trend is causing preventable stroke deaths A “concerning” new trend has been revealed by the Stroke Association. The charity states that the most at risk groups are least likely to call for an ambulant due to not wanting to “burden the already busy emergency services”. These acts of altruism, however, are causing people to die at home.
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espite the National Health System (NHS) and Government advice that the NHS is “open for business”, new survey results released on behalf of the Stroke Association have found that despite being most at risk, over 65s are most likely to put off calling 999 for non-COVID life threatening conditions. They report the main reason is not wanting to “burden the already busy emergency services”. The charity warns, in accordance with their successful stroke campaign, that those that see signs of stroke need to act fast and call 999. Public Health England have reported that hospital admissions are still down from what is expected at this time of year. Moreover, the Office for National Statistics (ONS) has reported that deaths at home attributed to stroke during the coronavirus period in England are much higher than the previous five-year average, rising by 54%. Martin James, clinical director of the King’s College London Stroke Programme and consultant stroke
Deaths at home have risen by
54%
physician at the Royal Devon & Exeter Hospital, Exeter, comments: “On my acute stroke unit in Exeter and across the country stroke specialists have seen striking reductions in the number of people coming into hospital with the symptoms of stroke during the coronavirus pandemic. But our hospitals remain well equipped and ready to treat stroke patients safely and so we would say to the Great British public, despite everything else that is going on, stroke is still a medical emergency.” Chief Executive of the Stroke Association, Juliet Bouverie, adds that “stoicism kills”. She maintains that the British sense of ‘keep calm and carry on’ does not saves lives: “It is really worrying to see that the people most at risk of stroke are most likely to die at home because they were too frightened
of bothering the emergency services— your life matters. Stroke is a brain attack.
When you see the signs of stroke, you need to raise the alarm right away by calling 999.” Key findings collated by the Stroke Association include that deaths at home have risen by 54% based on the rolling five-year average, while hospital admissions in England are down 38% from what is expected at this time of
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year, according to Public Health England. Moreover, the charity states that over a third of older people (35%) say they were less likely to contact emergency services with non-COVID symptoms due to the pandemic, and 51% of older people stated, when asked on their reason for not attending hospital, that they did not want to burden the emergency services.
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July 2020 | Issue 38
Non-invasive vagus nerve stimulation may provide clinical benefit to patients with COVID-19 Continued from page 1
and tolerability of nVNS therapy make it a particularly attractive treatment modality that merits immediate study”.
exploration of this pathway.
Underlying mechanisms
Staats and his team believe there is a strong scientific and clinical foundation for the hypothesis that nVNS can improve disease outcomes in patients with COVID-19. They reiterate that the established safety and tolerability of the modality strengthens the case for additional investigation and use of nVNS to fight the pandemic. According to the investigators, an Emergency Use
In terms of how VNS can help patients with respiratory distress brought on by COVID-19, Staats and colleagues allude to two main mechanisms. They write that when the body’s inflammatory response is dysregulated, bronchoconstriction can occur, which limits the flow of air to and from the lungs. “VNS may inhibit this airway constriction through a parasympathetic-sympathetic reflex arc, whereby stimulation of an afferent vagal nerve causes an efferent sympathetically mediated release of catecholamines that results in smooth muscle relaxation,” posit the authors. Secondly, they argue, based on available evidence, that the cholinergic anti-inflammatory pathway (CAP) is believed to be the vagus nerve-based arm of the inflammatory reflex. “The use of CAP to regulate the inflammatory response has been investigated broadly using varying forms of VNS for more than 20 years, [and] the use of nVNS to target neural pathways to treat inflammatory diseases represents the most recent
A future for nVNS in the setting of COVID-19
nVNS therapy may have been a supporting factor [in patient recovery], via either bronchodilation or inhibition of cytokine release.”
New study shows significant positive impact of vagus nerve stimulation therapy for treatment-resistant bipolar depression Adding vagus nerve stimulation (VNS) therapy to treatment as usual has been demonstrated to improve outcomes in patients with treatment-resistant bipolar depression (TRBD). In a recent news release, LivaNova announces the publication of a new study in the International Journal of Bipolar Disorders, and details its findings.
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he study examined patients from a five-year prospective registry and found 63% of TRBD patients treated with adjunctive VNS therapy in addition to treatment as usual had a significant reduction in depressive symptoms, as measured by a 50% or greater reduction in the Montgomery– Åsberg Depression Rating Scale (MADRS), compared with 39% of patients in the TAU alone group. The study also showed that TRBD patients treated with adjunctive VNS Therapy experienced both a more durable anti-depressant effect and a significantly greater mean reduction in suicidality score than for patients receiving treatment as usual alone (p < 0.001). “Given the significant unmet need with regard to the management of bipolar depression patients, it is critical that alternative treatment options for patients with TRBD are explored,” said A John Rush of Duke-National University of Singapore, Singapore. “This study’s
findings that adjunctive use of VNS can significantly improve depressive symptoms and reduce suicidal ideation while also increasing the durability of antidepressant effect, promises to transform the lives of patients with difficult-to-treat bipolar depression for the better.” According to the company’s news release, bipolar patients are symptomatic nearly half of the time and the majority of their symptoms are depression-related, yet safe, effective, long-term treatment options are scarce. Similar to patients with difficult-to-treat depression (DTD), this TRBD subpopulation struggles to get well and stay well with 30% remaining depressed at 12 months despite initiation of antidepressant treatment. A significant fraction of the disease burden in bipolar disorder is suicide-related and it is estimated that between 25% and 60% of individuals with bipolar disorder will attempt suicide at least once in their lives and between 4% and 19% will
Authorization application was submitted to the US Food and Drug Administration (FDA) on 2 April 2020, which aims to facilitate use and further study of nVNS amid COVID-19. Meanwhile, randomised controlled trials are being initiated at multiple sites in both the USA and Europe. While, according to Staats, enrolment has been slower than anticipated, given the impact the pandemic has had on clinical trials, he tells NeuroNews that there is now an international consortium investigating whether VNS can have a positive effect that meets once a week.
Peter Staats
complete suicide. The study was conducted with a patient population of 156 TRBD patients with 97 in the adjunctive VNS therapy group and 59 in the treatment as usual group. Before treatment, subjects in the adjunctive VNS therapy group had, on average, suffered from 20.7 lifetime episodes of depression, had approximately three lifetime suicide events and had been treated with nine different therapies, including an antidepressant at some point. In comparison to the treatment as usual group and prior to the study, patients in the adjunctive VNS therapy group had experienced more episodes of depression, psychiatric hospitalisations, lifetime suicide attempts, along with a higher suicidality score and more severe symptoms based on MADRS and other scales at baseline. The study concluded that VNS therapy as an adjunctive treatment to treatment as
usual was more effective than the latter alone in reducing depressive symptoms and suicidal ideation. In addition, patients who received adjunctive VNS therapy had a more rapid onset of response and more durable antidepressant effects. The study drew the conclusion that adjunctive VNS therapy is an efficacious antidepressant treatment for patients with TRBD.
Patients who received adjunctive VNS therapy had more durable antidepressant effects.”
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Issue 38 | July 2020
Burst spinal cord stimulation improves psychosocial outcomes and reduces opioid usage at one year A study investigating chronic pain sufferers treated with burst spinal cord stimulation (B-SCS) has concluded that improvements were observed among all psychological measures at one year. The largest impact of the therapy was on catastrophising and depression. “These pain-related beliefs and behaviours, and not pain intensity, have been shown to put patients at greatest risk of a poor prognosis and quality of life,” write the authors, Steven Falowski, Neurosurgical Associates of Lancaster, Lancaster, USA, and colleagues.
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ublished in Neuromodulation, the study sought to investigate the effect of B-SCS on psychosocial functioning and its influence on pain and quality of life. The rationale of the research pertains to the fact that B-SCS has previously been shown to reduce neuronal firing in the anterior cingulate cortex through selective modulation of the medial pain pathway tract. Those with chronic, intractable pain of the trunk, and/or lower limbs were eligible for enrolment in the study. Of the 269 patients that were enrolled at 22 centres around the USA, trial success
rate was 90%. Once deemed successful, patients received a permanent implant and returned for follow-up at six and 12 months. Falowski and his team report significant improvements in pain, physical, mental, and emotional functioning, observed from baseline to the six and 12-month follow-up. “Overall, patients had improved quality of life, became more active, and the negative impact of pain on daily life was decreasing,” write the authors. Specifically, at one year, 81% of subjects were satisfied or very satisfied with their
therapy. Additionally, subjects showing the benefits of optimising clinical settings significant improvements on mental for B-SCS. health outcomes reported enhanced pain However, they write that because relief and quality of life scores compared the study had broad inclusion criteria, with subjects with continued impaired the internal pulse generator (IPG) mental health at follow-up. systems and electrode configurations Regarding reduced opioid were used according to usage, the team found that at physician preference. “Our one year, 89% of subjects who study represents real-world were taking opioids at baseline outcomes, illustrating the decreased, or stayed at the effectiveness of B-SCS same level of opioid use, and to address the affective 19% stopped taking opioids component of pain in a altogether. representative population Discussing the importance rather than a tightly controlled of these findings, Falowski Steven Falowski environment,” Falowski and et al state that chronic pain team surmise. affects approximately 30% of adults worldwide, and is constantly associated Moving the field forward with psychological disorders across all The team speculate that future research geographies. “Patients seek medical should seek to refine programming and care for pain, not only for diagnostic stimulation configurations in the field of evaluation and symptom relief, but neuromodulation. also because pain interferes with daily Speaking with NeuroNews, Falowski activities, causes worry and emotional comments: “We are moving away from distress, and undermines confidence,” subjective and largely inaccurate pain they note. scores for patients. It is more important The team also highlight that expanding to deliver functional improvements and the literature on quality of life outcomes quality of life to our patients. will provide clinicians with additional “This study has shown that not only data to better educate patients about the can we improve pain scores, but we can benefits of SCS and set comprehensive now truly improve patient outcomes goals for treatment outcomes. with objective measures that are more Pointing to a particular caveat, correlative to their outcomes. Perhaps Falowski and colleagues acknowledge the most impactful is that this realthat, as the current investigation is a realworld study was able to improve pain world study, stringent programming and catastrophising in our patients to be cycling guidelines could not be imposed, in line with or better than a normal even as recent research has demonstrated population.”
Up to 13% of patients could have their spinal cord stimulator removed by five years According to a study published in Neuromodulation, five years after implantation, spinal cord stimulators have been explanted in 13.5% of patients. Furthermore, about 10% of these explants are for non-infections reasons. Predictors of non-infected explants include being younger, using tobacco, and having certain psychiatric conditions. MARK C DOUGHERTY (University identified 252 patients who underwent of Iowa Hospitals and Clinics, Iowa City, spinal cord stimulation implantation. USA) and colleagues report that therapeutic Of these, within the available followfailure for spinal cord stimulator “remains up time (mean 2.6 years), 17 patients remarkably common”. As a consequence of (6.7%) underwent explantation with this failure, the authors add, “a substantial 11 (4.4%) undergoing explantation for number of have their devices removed, or non-infectious reasons. In a Kaplanexplanted”. Meier analysis, excluding the patients The lack of data in this area prompted who underwent explantation for a Dougherty et al to perform survival non-infectious reason, Dougherty analysis and multivariate regression et al predicted “an explantation rate analysis to describe timing and predictors Mark Dougherty of approximately 10% at five years of spinal cord stimulator removal. “We after implantation for non-infectious hypothesised that certain baseline patient characteristics reasons”. The rate increased to 13.5% if infected would be able to predict risk of future device removal. explants were included in the analysis. We further hypothesised that, although most explants A multivariate analysis of the potential predictors would happen within one to two years of implantation, of explant indicated that age, tobacco use, and “other removals would continue to occur years later,” they mental health disorders” were all significant factors. comment. However, the authors note that “other mental health Using a private insurance database, the authors disorders” are “difficult to define precisely” and,
therefore, explored the factor in more detail. “Eight of the 11 [non-infected] explant patients had a diagnosis corresponding to ‘other’ mental health disorders. In all but one patient, the diagnosis was either 1) adjustment disorder with depressive and/or anxiety symptoms or 2) pain disorder with related psychological factors. The last patient had a personality disorder,” Dougherty et al comment. The investigators write that although the current study is neither the largest insurance data base study on spinal cord stimulation explantation, nor the first survival analysis for the modality’s explanation, it represents the first study combining these approaches. They also acknowledge the importance of distinguishing between explants that were done for infection, and those carried out for other reasons, such as device failure or patient satisfaction, as “device infection does not necessarily suggest a lack of device efficacy”. Concluding their research, Dougherty and the team state that spinal cord stimulator removal is less likely to occur in “older non-smokers without certain psychiatric disorders. “Ultimately, while spinal cord stimulation is helpful for many patients, there is still much room for improvement in the treatment of refractory chronic pain of the spine and limb,” they add. Speaking to NeuroNews, Dougherty says: “While certain patient characteristics seem to suggest a higher likelihood of failure and explantation down the road, we are not yet at a point where we can predict these outcomes with enough accuracy to determine—prior to surgery—whether a patient will benefit or not. “Hopefully, at some point in the future we will have sufficiently accurate predictive tools, meaning that we can avoid placing spinal cord stimulators that will not be beneficial, thus avoiding pointless surgeries. We also still need better ways to treat chronic pain in patients that do not benefit from spinal cord stimulation.”
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July 2020 | Issue 38
Dorsal root ganglion stimulation “safe, effective, and durable” for treating neuropathic pain
For neuropathic pain caused by peripheral nerve injuries (PNIs), dorsal root ganglion (DRG) stimulation has been found to be a safe, effective, and durable treatment option. Through three years, the authors, Marcus A Schwarz and colleagues (SRH Wald-Klinikum Gera, Strasse des Friedens, Germany) found that patients experienced a significant pain relief, with mental and physical function showing “immediate and sustained improvements”.
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n their paper published in Neuromodulation, Schwarz and the team also write: “The treatment allows cessation of often ineffective pharmacotherapy (including opioid misuse) and significantly improves quality of life.” Traumatic PNIs often result in severe neuropathic pain, which typically becomes chronic and is associated with sleep disturbances, anxiety, and depression, the authors note. They also acknowledge that pharmacological treatments proven to be effective against neuropathic pain are not well tolerated due to side effects. However, they say that neuromodulation techniques such as peripheral nerve or spinal cord stimulation (SCS) have yielded mixed results so far and may be limited in therapeutic benefit due to their reduced somatotopic specificity. Schwarz and team therefore set out to investigate whether DRG stimulation may be more effective in this aetiology. Of the 27 patients who were initially tested with a DRG neuromodulation system for PNI, trial success was reported at 85%; 23 patients received a permanent stimulator. However, due to explants occurring in two patients, 36-month outcome data was
Asleep surgery improves the therapeutic window for deep brain stimulation Evidence in support of the notion that asleep surgery improves the therapeutic window for deep brain stimulation (DBS), when compared to awake surgery, has been published in the journal Neuromodulation. “Our study provides first evidence for improvement of the therapeutic window by asleep surgery, […] which can be strengthened further by directional DBS,” write the authors of the study, Farhad Senemmar and colleagues from HeinrichHeine University Düsseldorf, Düsseldorf, Germany. THE AUTHORS ARGUE that the effect of anaesthesia type in terms of asleep versus awake DBS surgery on the therapeutic window of the modality has not been investigated so far, and remains an unmet need. Thus, they sought to examine whether asleep DBS surgery of the subthalamic nucleus improves the
available for 21 patients (12 females; median age of 53 years) Compared to baseline, the investigators observed a significant pain relief (p<0.001) at three (58%), 12 (66%), 18 (69%), 24 (71%), and 36 (73%) months. They also reported that opioid dosage “reduced significantly” at three (30%), 12 (93%), 18 (98%), 24 (99%), and 36 months (99%), and 20 out of 21 patients were opioid free after 36 months. Schwarz et al note that there were five lead migrations, two electrode fractures, and one wound infection that was conservatively managed. While the team posit that DRG stimulation “may be a valuable option for patients suffering from otherwise intractable pain”, they acknowledge several limitations to the current study. First, it was a single-centre investigation analysing outcomes from one provider and approach. The retrospective nature of the design, where the data relied on accurate patient information, also limits the validity of the findings, they note. However, though stating that their observations may be “limited”, Schwarz and the team write: “Our outcomes data, in terms of improvements in efficacy
therapeutic window for both directional and omnidirectional DBS stimulation in a large single-centre population. A total of 104 consecutive patients (75 male) with Parkinson’s disease undergoing subthalamic nucleus DBS surgery (80 asleep; 24 awake) were compared in terms of therapeutic window, therapeutic threshold, side effect threshold, improvement of Unified Parkinson’s disease Rating Scale motor score (UPDRS-III), and degree of levodopa equivalent daily dose (LEDD) reduction. Senemmar and colleagues report that asleep DBS led to a “significantly wider therapeutic window” compared to awake surgery, for both directional and omnidirectional DBS. “However,” they note, “directional DBS further increased the therapeutic window compared to omnidirectional in the asleep group only.” They add that clinical efficacy regarding improvement in UPDRSIII and LEDD reduction did not differ between groups. Though the investigators acknowledge that the focus of the study was the therapeutic window, which takes into account stimulation-induced side effects; providing a more suitable outcome measure compared to a pure motor scoring system, they write that the advantages of a wider therapeutic window for real-life programming still needs to be confirmed in further longterm studies.
Explaining the difference
Discussing their findings, Senemmar and team state that “at first sight, this
over time, are remarkable in comparison to SCS therapy.” Expanding on this, the authors argue that a recent review has revealed that in 20–40% of SCS patients, the initial effectiveness declines, due to central nervous system tolerance. “This loss of efficacy is the leading reason for eventual system explantation,” they say. Schwarz and colleagues posit that the more novel DRG stimulation has “emerged as a promising therapy”, especially with regards to targeting the primary sensory neurons of the DRG, which are involved in the pathophysiologic changes that lead to neuropathic pain. “Results from this retrospective chart review contribute to the growing body of evidence to support DRG simulation as an effective, targeted treatment option for patients suffering from PNI-induced neuropathic pain,” the authors conclude. They maintain that chronic pain is multifaceted;
DRG stimulation has emerged as a promising therapy.” an emotional, social, and economic burden for those living with it. “Depression, reduced quality of life, absenteeism from work, and a lower household income are positively correlated with chronic pain,” write Schwarz et al. Thus, they suggest that physicians should work with patients and support them through goal-orientated follow-up to assist in alleviating pain, as well as to reduce medication consumption.
Directional DBS further increased the therapeutic window compared to omnidirectional in the asleep group only.” result may be surprising”. They propose that awake surgery usually allows for intraoperative testing of both therapeutic threshold and side effect threshold, which should lead to optimal therapeutic window postoperatively. Thus, the authors note that several aspects need to be taken into
consideration explaining the difference between both groups. “First of all, asleep DBS may lead to higher accuracy with regard to the preoperative image-based targeting. It is proposed that higher precision in asleep surgery may be achieved by reduction of brain shift.” They add that they feel it is also important to mention that, in contrast to other centres, their team in Germany also use microelectrode recording in asleep surgery after reduction of anaesthesia, which is similar to a controlled general anaesthesia technique. They write: “It is possible that, in our patients, microelectrode recording and clinical testing for capsular side effects were already sufficient to determine the optimal target for implantation and further clinical testing had no additional impact. Moreover, given the fact that the therapeutic window was smaller in the awake group, clinical testing could have even had a negative impact. “One has to take into account that adequate clinical evaluation of slight changes of muscle tone, oculomotor function, or speech […] in the operation room—with the patient off medication for more than 12 hours—can be challenging even for an experienced neurologist specialised for clinical monitoring of DBS surgery. “Finally”, they assert, “the mere fact that the patient undergoes clinical testing in the awake state can already lead to placebo effects leading to better intraoperative clinical outcome that may not be confirmed postoperatively.”
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Issue 38 | July 2020
Decision-making in intrathecal drug delivery devices “life-threatening” amid COVID-19
Amid the COVID-19 pandemic, the need to prevent the spread of disease and manage critical hospital resources has never been more critical. In a letter to the editor of Neuromodulation, Philip Kim (Center for Interventional Pain & Spine, Bryn Mawr, USA) and Timothy Deer (The Spine and Nerve Center of the Virginias, Charleston, USA) stress that decision-making in intrathecal drug delivery devices can be “life-threatening” and medical judgement should be used on a case per case basis. THROUGH UTILISING multiple combinations of off-label and onlabel preparations, Kim and Deer acknowledge that these intrathecal drug delivery devices are “lifechanging” in providing relief for intractable pain and spasticity that is not responsive to systemic analgesics. “Holding off on these therapies and asking patients to return to oral medication alternatives including opioids can lead to concerns of opioid addiction, dependence, and diversion,” they add. In terms of the “many” patients receiving a combination of therapies, Kim and Deer argue that sudden and severe withdrawal reactions could occur. Alluding to a specific example,
they write that abrupt cessation of intrathecal baclofen can result in life-threatening multi-organ failure and death.
Treating COVID-positive or high-risk patients The authors urge, “if possible”, to delay refill of the intrathecal drug delivery devices, as well as reprogramming for two weeks. However, if this is not possible, home visits should be considered, preferably at Philip the end of the Kim day to minimise exposure to staff and allow
Educational curriculum for spinal cord stimulation developed to fill “unmet need” A spinal cord stimulation (SCS) training curriculum has been developed by a multidisciplinary taskforce of the North American Neuromodulation Society’s (NANS) education committee. It aims to standardise educational requirements across multiple training paths to SCS service, and defines Accreditation Council for Graduate Medical Education (ACGME) milestones for basic and advanced learners, as well as practitioners, meaning it can be adopted by programmes, hospitals, or other entities. An article detailing the development of the curriculum, written by Alaa Abd-Elsayed, University of Wisconsin School of Medicine and Public Health (Madison, USA), and colleagues throughout the USA, has been published in Neuromodulation. ACCORDING TO THE authors, SCS is the most widely used neuromodulation therapy, which is offered to tens of thousands of patients every year in the USA alone. Despite the first use in humans in 1967, no specifically defined SCS training or expertise standards are available nor have been developed. The urgent need for such a curriculum, AbdElsayed et al acknowledge, is further underscored by the large number of SCS implantations performed. They write that many different medical specialities participate in aspects of neuromodulation trials: patient
selection, implantation, and followup. This means that SCS knowledge and training may “differ widely among specialties”. Importantly, the NANS committee also highlight the link between patient outcomes and physician expertise, referring specifically to the physician’s choice of patient selection, surgical technique, and follow-up care. Given the fast-evolving data and expansion in indications, techniques, and hardware, the authors write, “This increased complexity and utilisation of the technology mandates proper training of physicians in their
further decontamination.
Treating COVID-negative or low-risk patients
Ensuring minimal patient movement and abiding by social distancing rules during the initial assessment is the top priority, according to Kim and Deer. The patient should also be encouraged to wear a mask, while the healthcare provider should wear a mark, eye glass protection, and a surgical gown and gloves. If possible, N95 masks should be used, and the healthcare worker should utilise the plastic covers of the programmer, note the authors. They also allude to the routine aseptic technique, and—though acknowledging that the Center for Disease Control and Prevention (CDC) or the World Health Organisation (WHO) have not issued instructions about how to clean face masks—Kim and Deer urge workers to safely remove and dispose of gloves, masks and material.
Timothy Deer
application.” The taskforce, represented by multiple specialties, established the educational curriculum for SCS over periodic conferences. After being peer-reviewed at two different levels; the educational committee of NANS and the society’s board members, the curriculum was approved in August of 2019. “The curriculum was divided under the rubrics of patient care and procedural skills, systems-based practice, medical knowledge, interpersonal skills and communication, practice-based learning, and professionalism,” the authors note. They add that it acknowledges the differences in residency versus fellowship programmes for these specialties, and where along the training continuum the individual would be exposed to SCS therapies. “The goal is to establish the necessary competence to offer to take part in the implementation of neuromodulation therapies regardless of one’s individual specialty,” AbdElsayed and colleagues surmise. They maintain that there was an “unmet need” to establish a continuum of education and goals, as well as the ability to track completion through formal assessments. Finally, they note that the curriculum denotes a standard by which “an accepted competency could be met”, and provides guidance towards eventual accreditations and certifications.
Oral pain medications not associated with intrathecal opioid dose escalation According to a retrospective study published in Neuromodulation, the use of antiepileptics, antidepressants, or low oral opioid dose, was not associated with attenuation of intrathecal dose escalation. Instead, the authors, Jason Hale (Center for Anesthesiology Education, Cleveland Clinic Foundation, Cleveland, USA) report that intrathecal opioid dose escalation was observed to occur similarly, regardless of baseline oral analgesics simultaneously employed. WHILE PATIENTS TREATED with intrathecal therapy frequently require opioid dose increases to maintain analgesic effects, Hale and colleagues note that the kinetics surrounding intrathecal opioid dose escalation “are poorly understood”. “We hypothesised that antidepressant use, antiepileptic use, and lower baseline oral opioid intake prior to intrathecal pump implantation will be protective against intrathecal dose escalation,” they write. In order to carry out the retrospective analysis, the team used targeted drug delivery medication doses that were collected from patients who had an intrathecal pump implanted between 2007 and 2016. From the acquired sample size of 136 patients, Hale and his team assessed the association between antidepressant, antiepileptic, and oral opioid use with intrathecal dose escalation using statistical models. Regarding the results, they report that individuals using an antiepileptic had an estimated ratio of means (97.5% confidence interval [CI]) of opioid consumption of 0.91 (97.5% CI, 0.48–1.73, p=0.74) at six months, 0.83 (CI, 0.43–1.58, p=0.51) at 12 months, and 0.77 (CI, 0.40–1.45, p=0.36) at 24 months. Moreover, patients prescribed antidepressants had an estimated ratio of means (97.5% CI) of 1.43 (CI, 0.77–2.65, p=0.19) at six months, 1.41 (CI, 0.76–2.63, p=0.22) at 12 months, and 1.33 (CI, 0.70–2.51, p=0.31) at 24 months. “In our secondary analysis of pre-implant oral opioid use, patients treated with high oral opioid doses had a similar pattern of intrathecal dose escalation when compared to patients using low doses of oral opioids,” Hale and team surmise. Discussing their research interests moving forward, the investigators write: “Analysis of efficacy resultant from the use of intrathecal therapy over an extended follow-up period also remains an area of parallel interest. We therefore advocate for future characterisation of this population including long-term follow-up over years.”
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July 2020 | Issue 38
Market watch
be evaluated by the operating physician.
Balt receives IDE approval to begin the STEM trial
Industry News Avicenna.AI secures FDA clearance for its CINA Head neurovascular imaging AI tool
Avicenna.AI has announced it has received 510(k) clearance from the US Food and Drug Administration (FDA) for its CINA Head triage AI solution for neurovascular emergencies. The FDA’s decision covers CINA’s automatic detection capabilities for both intracranial haemorrhage (ICH) and large vessel occlusion (LVO) from CTscan imaging. Using a combination of deep learning and machine learning technologies, CINA Head automatically detects and prioritises acute ICH and LVO cases within 20 seconds, alerting the radiologist within their existing systems and workflow. CINA’s ICH detection capability was validated using data from 814 cases conducted at more than 250 imaging centres across the USA, with 96% accuracy, 91.4% sensitivity and 97.5% specificity. The product’s LVO detection capability was validated based on 476 cases, with 97.7% accuracy 97.9% sensitivity and 97.6% specificity. CINA Head is the first in a family of AI tools for emergency radiology being developed by Avicenna.AI. Subsequent products spanning the trauma and vascular fields are expected to be unveiled in the next 12 months.
Balt receives CE mark for its Silk Vista flow diverter
Balt has received CE mark approval for its Silk Vista flow diverting stent to treat patients with unruptured intracranial aneurysms, in turn enabling commercialisation in over 30 countries in and around the European Union. Flow diverters are intended to divert blood flow away from an aneurysm, allowing the aneurysm to heal and reducing the risk of aneurysm rupture. According to the news release, the Silk Vista device is designed for predictable and accurate deployment, as well as high visibility under angiography. It joins the lower profile Silk Vista baby flow diverter, which received CE mark in 2018. “Balt introduced the Silk Vista baby two years ago, a flow diverter device for the treatment of distal aneurysms with the benefits of excellent visibility and device deployment,” said Vitor Mendes Pereira, an endovascular neurosurgeon and professor of Medical Imaging and Surgery at the University of Toronto (Toronto, Canada). “Now, with Silk Vista, Balt has provided physicians the same outstanding deliverability and
visibility for the treatment of aneurysms arising off of neurovascular vessels 3.5mm and larger, while managing to keep the device compatible with a very low profile .021” microcatheter.” Pereira performed the first-in-man case of Silk Vista in Toronto in June.
Rapid ASPECTS receives CADx clearance from the FDA
RapidAI has announced that Rapid ASPECTS has received US Food and Drug Administration (FDA) clearance as the first neuroimaging analysis device in the CADx (computer-assisted diagnostic software) category. Rapid ASPECTS is the only neuroimaging product shown to improve physicians’ interpretations of non-contrast CT scans using a standardised ASPECT score. Validated through the rigorous FDA process, the use of Rapid ASPECTS automated score combined with the physician’s review of the scan, improves the accuracy of the ASPECT score calculation which is particularly important for less experienced readers. Based on the Alberta Stroke Program Early CT Scoring (ASPECTS) system, Rapid ASPECTS uses a validated machine-learning algorithm to automatically identify the ASPECTS regions of the brain and generate an ASPECT score to indicate early signs of brain infarction on non-contrast CT scans—helping physicians identify areas of irreversible brain injury. The company state that by automating and standardising this process, Rapid ASPECTS helps stroke teams across hospital sites and referral networks quickly assess patient eligibility for thrombectomy—enabling faster triage and transfer decisions that facilitate better patient outcomes. The press release goes on to list three key advantages of the technology. In addition to Rapid ASPECTS automatically delivering a standardised ASPECT score, in turn assisting physicians’ decisions, it utilises a machine-learning algorithm that has been validated in clinical research studies. While the algorithm delivers fast measurements, RapidAI write that the system also supports collaboration between hospitals and specialists, increasing the speed of triage and transfer decisions of patients.
MIVI Neuroscience receives IDE approval to study the Q aspiration catheter
MIVI Neuroscience has announced that the US Food and Drug Administration (FDA) has approved an investigational device exemption (IDE) for the initiation of a human clinical study of the MIVI Q aspiration catheter in the USA. EVaQ is
Balt has received investigational device exemption (IDE) approval from the US Food and Drug Administration (FDA) to begin the Squid trial for the a prospective, multicentre, single-arm embolisation of the middle meningeal study of the Q revascularisation system artery (STEM) for the treatment of for neurointervention in acute ischaemic chronic subdural haematoma. stroke. A recent Veterans Affairs (VA) study According to the company, the study of chronic subdural haematoma found will assess the Q catheter’s ability to a prevalence rate of 79.4 per 100,000 remove thrombus that causes large persons. The authors predicted that vessel occlusions in the arteries of the the incidence rate of chronic subdural brain. Patient enrolment is planned at haematoma in USA in the ageing VA up to 12 clinical centres in the USA and and civilian populations will reach 121.4 additional sites in the European Union. and 17.4 cases per 100,000 persons, Principal investigators for the EvaQ respectively, by 2030. By this time, study are Lucas Elijovich, with the approximately 60,000 cases will occur Semmes Murphy Clinic in Memphis, each year in the USA. USA; Brian Jankowitz, with Cooper “We are excited to have the University Health Care in Camden, opportunity to investigate the Squid USA; and professor Christophe Liquid Embolic Device as a minimally Cognard, with Purpan University invasive treatment option,” stated Hospital in Toulouse, France. David Fiorella (Stony Brook University Medical Center, New York, USA) in the phenox announces company’s news release. European launch of its new Co-primary Investigators Adam thrombectomy devices Arthur (Semmes-Murphey Neurologic phenox has announced the full and Spine Institute and University of European launch of the pRESET 5–40 Tennessee Health Sciences Center) and pRESET LUX 4–20 thrombectomy and David Fiorella have worked to devices after receiving CE mark design a prospective, randomised, approval last year. The pRESET device controlled, multicentre trial with the is a stentriever which is used for objective of demonstrating the safety mechanical thrombectomy in patients and effectiveness of middle meningeal with acute ischaemic stroke, due to large artery (MMA) embolisation with the vessel occlusion. SQUID Liquid Embolic Device for Over the past few the management of chronic subdural years, safety and haematoma in both surgical and nonefficacy using mechanical surgical patients. thrombectomy has Arthur commented, “This is been proven in patients a disease which affects a large with large vessel number of people. Current occlusion in four major treatment options are not randomised controlled trials well-studied and often (MR CLEAN1, SWIFT-PRIME2, require invasive surgeries pRESET LUX 4–20 EXTEND-IA3, ESCAPE4). and prolonged stays in the thrombectomy The pRESET thrombectomy intensive care unit.” device device was evaluated in the Patients often present with ARTESp study (prospective, focal neurological symptoms, multicentre, single-arm post-market non-focal cognitive symptoms clinical follow-up study) and or generalised dysfunction. “The demonstrated its safety and efficacy: STEM study will enable us to learn a TICI (Thrombolysis in cerebral tremendous amount about how to help infarction) 2b/3: 84,4% and mRS (0–2) these patients and how best to treat a at 90 days: 62.5%. major reversible cause of dementia and According to the company, the disability in the elderly,” added Arthur. development of the new pRESET 5–40, Fiorella went on to state, “We have addresses the trend towards the use of seen some dramatic radiological and longer thrombectomy devices, which clinical improvement using liquid may have the capability to remove an embolic agents to treat patients with even larger clot mass in fewer attempts. chronic subdural haematoma, both as The 5–40 product line extension inherits an adjunct to surgical treatment and as a the principal pRESET design, including standalone therapy. a low-profile 0.021” delivery platform. “We are hopeful that this randomised In addition to the 5–40 line extension, controlled trial will provide definitive the pRESET product family is evidence that embolisation of the middle broadened with the new pRESET LUX meningeal artery with Squid will not technology, which adds full radiopacity only improve surgical outcomes but to the proven stentriever design. will also provide a minimally invasive A recent news release also states that endovascular treatment option for a noble alloy coating (NAC) has been patients who do not require urgent applied to the full length of the device, or emergent open cranial surgery. so that it can be fully seen under X-ray. Improving outcomes for this large group By maximising the device’s visibility, of patients would represent a significant the exact positioning and opening can advance.”
Issue 38 | July 2020
Market watch
Industry News Cerus Endovascular’s 021 Contour neurovascular system approved in Europe
021 Contour Cerus endovascularCerus Endovascular has received CE Mark approval for its 0.021-inch Contour neurovascular system, compatible with smaller commercially available 021 microcatheters for the treatment of saccular intracranial aneurysms. According to the company, the Contour neurovascular system is a fine
mesh braid that is deployed across the neck of the aneurysm sac and provides a combination of flow diversion and flow disruption through a single device implant. This new, lower profile system will allow physicians to access more distally challenging vascular anatomies.
Brilinta significantly reduced the rate of the composite of stroke and death in patients who had an acute ischaemic stroke: Results from the phase III THALES trial
Results from the positive phase III THALES trial showed AstraZeneca’s Brilinta (ticagrelor) 90mg used twice daily and taken with daily aspirin for 30 days, reduced the rate of the primary composite endpoint of stroke and death by 17% (HR 0.83 [95% CI: 0.71, 0.96], p=0.02), compared to aspirin alone in patients who had an acute ischemic stroke or transient ischemic attack (TIA). These findings have been published in The New England Journal of Medicine. The company note that this was a statistically significant and clinically meaningful reduction. Furthermore, aspirin plus Brilinta significantly reduced the rate of the first secondary endpoint of ischaemic stroke by 21%, compared to aspirin alone up to day 30. The risk for severe bleeding events was 0.5% in the aspirin plus Brilinta group and 0.1% in the aspirin group. The results were in line with the known safety profile of Brilinta. Clay Johnston, lead investigator for the THALES trial and Dean of the Dell Medical School at The University of Texas in Austin, USA, said: “About one in four stroke survivors go on to experience a second stroke, and the risk is particularly high within the first month after the initial event. Early treatment is important to prevent a subsequent stroke.” Mene Pangalos, executive vice president, BioPharmaceuticals R&D, added: “Results from the Phase III THALES trial confirm that aspirin plus Brilinta has the potential to be a new effective treatment option for these high-
risk patients and we look forward to continuing discussions with regulatory authorities.” The company also state that currently, Brilinta is approved in more than 110 countries for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ACS) and in more than 70 countries for the secondary prevention of cardiovascular events among high-risk patients who have experienced a heart attack. In May 2020, the US Food and Drug Administration (FDA) approved a label update for Brilinta in the USA to include the reduction of the risk of a first heart attack or stroke in high-risk patients with coronary artery disease.
American Academy of Neurology recommends PFO closure for selected stroke patients
New guidance from the American Academy of Neurology (AAN) recommends the closure of a patent foramen ovale (PFO) for some people who have had a stroke. The updated practice advisory has been published online in Neurology. Previous guidance concluded there was not enough evidence to support routine PFO closure to prevent a second stroke. The new guidance states that PFO closure may be considered for some people under age 60 to help prevent a second stroke, according to the practice advisory, which is endorsed by the American Heart Association/ American Stroke Association, the Society for Cardiovascular Angiography and Interventions and the European Academy of Neurology. It updates a 2016 advisory, which said that there was not enough evidence to support routine PFO closure to prevent a second stroke. However, since then, new studies reported that for people with stroke due to a PFO, closure in addition to taking medication to prevent blood clots, reduced the risk of future strokes better than medication alone. Therefore, the new guidance recommends that when considering PFO closure in people who have had a stroke, that doctors with expertise in stroke to first rule out causes other than the PFO—such as hardening or a tear of the blood vessels—to ensure that PFO is the most likely cause of stroke; it does not recommend PFO closure if another higher risk cause of stroke is identified. Furthermore, the guidance states that for people younger than 60 years’ old who have had a stroke thought to be caused by a PFO and no other cause, doctors may recommend closure of
the PFO after discussing the potential benefits. These benefits include a 3.4% reduction in the risk of a second stroke in five years, as well as the potential risks, such as a 3.9% chance of procedural complications and an increased risk of an abnormal heart rhythm called atrial fibrillation of 0.33% per year. Lead author Steven R Messé (Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA), says: “While there is generally a very low risk of stroke in patients with PFO, in younger people who have had a stroke without any other possible causes identified, closing the PFO may reduce the risk of having another stroke better than medication alone.”
CereVasc gains financing to support eShunt system to treat hydrocephalus
CereVasc, a company focused on the treatment of patients with hydrocephalus, announced the closing of an expanded Series A financing that raised US$43.9 million. The financing was led by the Perceptive Xontogeny Venture Fund and ATON Partners. According to CereVasc, the capital will be used to support the first-inhuman clinical trial of the eShunt system, as well as clinical studies to support regulatory approvals. The first study is expected to begin enrolment during the second half of 2020. The eShunt system, which is CereVasc’s lead product, is an endovascularly implanted cerebrospinal fluid (CSF) shunt and delivery technology for the treatment of hydrocephalus. The device is implanted through a percutaneous femoral venous approach under X-ray guidance in an angiography suite using local anaesthesia. The device is designed to avoid the need for invasive surgery, extended hospitalisation, and post procedure pain management associated with the current surgical treatment. The news release notes that the eShunt implant may also significantly reduce failures associated with ventriculoperitoneal shunt systems such as treatment infection, catheter obstruction, and over drainage.
phenox launches p64 MW Flow modulation device with HPC coating technology
phenox has announced the European launch of the new p64 MW Flow modulation device, intended for the treatment of intracranial aneurysms. The device received CE mark in January 2020 and is available with the proprietary HPC (hydrophilic polymer coating) surface modification. The p64 MW Flow modulation device
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phenox p64 MW Flow modulation device
is a next-generation stent-like device, implanted across the neck of a cerebral aneurysm, and is intended to divert blood flow away from the aneurysm. Over the course of several months, the diseased vessel is then reconstructed, permanently occluding the aneurysm from blood flow. In addition to the novel HPC coating, the new p64 MW device includes new design features which improve deliverability, including a moveable wire and drawn filled tube construction for complete visibility under fluoroscopy. According to the company, the p64 MW is also 0.021” microcatheter compatible, making it the lowest profile 64-wire flow diverter available today. phenox state that all p64 MW implants are available as a bare version as well as an HPC-coated version that provides additional safety in patients by mimicking the intact vessel wall. “HPC significantly reduces the thrombogenicity of our devices, by imitating the natural vessel wall without altering in vivo tissue response,” says Ing Hermann Monstadt, managing partner and founder of phenox. The company’s release also notes that surface modification of stents with HPC may also enable mono-antiplatelet therapy (MAPT) in patients for whom DAPT (double-antiplatelet therapy) is unsuitable.
Cerus Endovascular receives CE mark for its Neqstent Coil Assisted Flow Diverter Cerus Endovascular has announced that it has received CE mark approval for its Neqstent Coil Assisted Flow Diverter device. The flow diverter is designed to treat intracranial aneurysms and a range of morphologies, including wide-necked bifurcation and bifurcation aneurysms. Neqstent is an adjunctive intrasaccular flow diverter device that provides stable aneurysm neck coverage for the placement of embolisation coils within the sac and long-term occlusion of the aneurysm. According to the company’s press release, commercial sales, via a controlled market release across the European Union, are expected to begin during the fourth quarter of 2020. “Many physicians already have firsthand experience using embolisation coils, and the Neqstent will serve as an intrasaccular flow diverting device, which will work in combination with embolisation coils,” stated Stephen Griffin, president of Cerus Endovascular. “Our goal is to offer a breath of solutions for the treatment of these aneurysms. Physicians who have used the Neqstent comment on its ease of use through its controlled deliverability and deployment.”
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July 2020 | Issue 38
Market watch
Clinical News
Vitality Smartcable Vagus Nerve Stimulator
Vagus nerve stimulation clinical trial begins enrolment of COVID-19 patients
An interventional clinical trial has begun enrolling COVID-19 patients at Hospital Virgen del Carmen in Zarate, Argentina to evaluate the therapeutic effect of transcutaneous auricular vagus nerve stimulation (TAVNS) in patients with pneumonia associated with the disease. Hospital Virgen del Carmen, the first health centre in South America to conduct such a study, will use Vitality Smartcable taVNS devices supplied by Nemechek Technologies, according to a
press release. Some COVID-19 patients have an excessive inflammatory immune response known as a “cytokine storm.” Vagus nerve stimulation is shown to suppress inflammatory reactions and may be useful in controlling the hyperimmune response that can lead to lung failure and death. Stimulation of vagus nerve fibres in the ear activates what is known as the “inflammatory reflex.” Much like the baroreflex that controls blood pressure, the inflammatory reflex signals the body to naturally regulate its immune response. Hospitalised study participants will receive TAVNS for five minutes four times a day. After patient consent, stimulation will be given to adults with moderate or severe pneumonia not requiring mechanical ventilation, or critical pneumonia requiring a mechanical ventilator. Study patients will continue to receive standard of care treatment. Patients who choose not to receive TAVNS therapy will continue to receive standard care treatment. The results obtained in patients treated with TAVNS plus standard treatment and patients with standard treatment alone will be compared. In a press release, neuroscience researcher and Nemecheck Technologies
co-founder Patrick Nemechek (Tucson, Arizona), stated: “Resource-limited healthcare systems desperately need a cost-effective treatment to limit the progress of COVID-19 in seriously ill patients.”
requires several unique technologies including our breakthrough mini-CT stimulator and SNAP accessories, proprietary LTE current management, and the simple and powerful ElectraRx portal.”
Soterix wins IDE for depression treatment trial
RECOVER trial design evaluating vagus nerve stimulation for treatmentresistant depression published
Soterix Medical has announced that it received US Food and Drug Administration (FDA) investigational device exemption (IDE) to launch a trial of its non-invasive transcranial direct current simulation-limited total energy (tDCS-LTE) neuromodulation system. The system is an at-home platform intended for those suffering from major depressive disorder (MDD). According to a company press release, the proprietary technology is designed to support the home-based tDCS, including the single-use SNAPpad electrodes and the ElextraRx digital healthcare platform. Amid the COVID-19 pandemic, Soterix says there is an even more urgent need for reliable at-home intervention for patients with MDD. With the IDE trial, it is setting out to benefit those patients whose access to depression therapy has been limited as a result of the pandemic. “The home-based tDCS-LTE therapy continues our commitment to lead in the creation of innovative non-invasive neuromodulation treatments,” Soterix chief technology officer Abhishek Datta said in the release. “Reliable home-use
LivaNova has announced a publication in Contemporary Clinical Trials, which details the design for a prospective, multicentre, randomised controlled blinded trial demonstrating the safety and effectiveness of vagus nerve stimulation (VNS) therapy system as adjunctive therapy versus a no stimulation control in subjects with treatment-resistant depression, or the RECOVER clinical study. RECOVER is currently underway as part of a Coverage with Evidence Development framework of the US Centers for Medicare & Medicaid Services’ (CMS) National Coverage Determination process. “VNS Therapy for treatment-resistant depression has proven to be a safe and effective adjunctive treatment that significantly improves patients’ response and remission rates in this chronically ill population that is difficult to treat,” said Charles R Conway, director of the Washington University Resistant Mood Disorders Center, who serves as principal investigator for RECOVER.
Issue 38 | August 2020
Market watch
Product News Axonics receives FDA approval for 3T full-body MRI scans
Axonics, a company that has developed and is commercialising novel implantable sacral neuromodulation (SNM) devices for the treatment of urinary and bowel dysfunction, has announced that it has received US Food & Drug Administration (FDA) approval under a premarket approval supplement for 3T full-body magnetic resonance imaging (MRI) conditional labelling for the Axonics r-SNM System. In September 2019, the FDA approved the Axonics r-SNM System with full-body conditional labelling for 1.5T MRI scanners. “With this incremental approval for 3T scans, the Axonics device continues to be the only SNM system available in the USA that is MRI compatible for both 1.5T and 3T full-body scans,” the company states in a press release.
FDA approves Percept PC neurostimulator with BrainSense technology
Medtronic has announced it received US Food and Drug Administration (FDA) approval for the Percept PC deep brain stimulation (DBS) system. BrainSense technology makes Percept the first and
only DBS neurostimulation system with the ability to chronically capture and record brain signals while delivering therapy to patients with neurologic disorders associated with Parkinson’s disease, essential tremor, dystonia, epilepsy or obsessive-compulsive disorder (OCD). Physicians can now track patient brain signals and correlate these with patientrecorded actions or experiences, such as symptoms, side-effects, or medication intake. This enables more personalised, data-driven neurostimulation treatment. Mayo Clinic in Rochester, USA, will be the first in the USA to implant the newly approved device. “Our goal is for patients to regain independence, and we know that DBS can significantly improve motor function in people with Parkinson’s disease compared to standard medication alone,” said Bryan Klassen, neurologist, Mayo Clinic. “We can now more precisely tailor therapy to the individual needs of each patient based on data from neuronal activity.”
Mainstay Medical announces FDA approval of ReActiv8 neurostimulation system for chronic low back pain Mainstay Medical has announced that
Medtronic Percept PC neurostimulator
the US Food and Drug Administration (FDA) has approved the company’s premarket approval (PMA) application for ReActiv8, its implantable neurostimulation system to treat intractable chronic low back pain. “ReActiv8 is designed to be a restorative treatment and represents a new option for patients suffering with chronic low back pain. This disease affects millions of people around the world, and our clinical data demonstrates that ReActiv8 therapy provides progressive improvements in pain and disability over time, both in magnitude of effect and the proportion of patients who benefit from the treatment. This therapy has the potential to improve quality of life for the most severely-affected patients, and we look forward to making it available to US patients and physicians beginning in the first half of 2021,” commented Jason Hannon, CEO of Mainstay, in a
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company press release. Chris Gilligan, principal investigator of the ReActiv8-B study, added: “ReActiv8 fills an unmet clinical need of patients suffering from chronic low back pain. Patients indicated for ReActiv8 therapy have generally tried numerous other treatments, including physical therapy and pain medications, and many are on long-term opioids to manage their pain. “I have seen ReActiv8 provide durable improvements in back pain, the disabling effects of back pain, and quality of life.” Robert Levy, a neurosurgeon and president of the International Neuromodulation Society (INS), commented: “The use of neuromodulation to target underlying functional and motor-control issues in patients with musculoskeletal back pain can address a large unmet clinical need. ReActiv8 does not compete with other forms of neuromodulation such as spinal cord stimulation. These patients are difficult for clinicians to treat with current therapy options, which is why so many of them take opioids to manage their pain.” The FDA approval of ReActiv8 is primarily based on results from the ReActiv8-B clinical study, a pivotal 204-patient, international, multicentre, prospective, randomised, active shamcontrolled, blinded trial with oneway cross-over, conducted under an investigational device exemption (IDE) from FDA.
Calendar of events 4–7 August SNIS: Society of NeuroInterventional Surgery 17th Annual Meeting Virtual www.snisonline.org
26–29 August The World Institute of Pain (WIP) 10th World Congress Rome, Italy (also offered virtually) wip-rome2020.org/
9–11 September 12th ESMINT Congress 2020 Nice, France www.esmint.eu/
5–7 October SLiCE: Stroke Live Course Montpellier, France www.slice-worldwide.com/
7–11 October 11th World Congress for Neurorehabilitation Virtual www.wcnr-congress.org/
23–25 October International Neuromodulation Society Interim Meeting Mumbai, India
7–9 November ESO-WSO: Joint European Stroke Organisation and World Stroke Organisation Conference Virtual
eso-stroke.org/events/eso-wsoconference-2020
www.neuromodulation.com/interimmeeting
Event details correct at time of publication. Please check www.neuronewsinternational.com/events for updates in the wake of COVID-19.
September
2019 | Issue
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8–10 November LINNC: Live Interventional Neuroradiology & Neurosurgery Course Paris, France LINNC-Paris-2020
2021 19–20 March LINNC Seminar 2021 – Americas Edition Miami, USA
LINNC-Seminar-2021-AmericasEdition
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