Issue 16 November 2014

Focus on: Profile: Peter Müller-Barna: Neuromodulation Joseph Broderick TeleStroke units Page 10 Page 12 Page 16 ESCAPE trial permanently halted and declared positive Stemming from the positive results of the (we used ASPECTS, designed go from CT to groin puncture in MR CLEAN trial presented at World Stroke Congress to exclude patients with a large under 60 minutes, and from CT (22–25 October, Istanbul, Turkey) the ESCAPE trial core). We included patients with to reperfusion in under 90 min- has been permanently halted and declared positive, a proximal anterior circulation utes—and I can tell you that we instigating a “domino effect” on other similar trials blocked artery—the intracranial have done that, we have achieved including REVASCAT and SWIFT-PRIME. internal carotid artery (ICA) or an average median picture to the M1-MCA (middle cerebral puncture time of 51 minutes, and he news about the Speaking at the meeting artery). And finally, we assessed an average picture to reperfusion permanent halting via Skype, ESCAPE princi- the collateral circulation using time of 84 minutes in the data Tof ESCAPE broke at pal investigator Michael Hill multiphase CTA. Patients had to that we know so far. We were the Society of Vascular and confirmed that after discus- fulfil all three criteria of a small in fact very quick and that has Interventional Neurology sions with the Data and Safety core (favourable ASPECTS contributed substantially to the meeting (SVIN, 6–9 Novem- Monitoring Board (DSMB) score), a blocked large proximal outcome that we have today,” ber, Hollywood, Florida, on 6 November, it was agreed artery in the anterior circulation Hill explained. USA) where the atmosphere to permanently halt ESCAPE Michael Hill on CTA and good collaterals Step three of the process was was abuzz with the positive and declare it a positive trial. shown by multiphase CTA,” Hill to use the modern technology results of MR CLEAN and the He further reported that the open-label with blinded said. to get the artery open safely and subsequent effect on similar investigators remain blinded outcome evaluation, parallel He added that once physiology efficiently, where in this trial, as trials. MR CLEAN com- and that exact details are not group trial. The intervention was determined, the next step in has been the case in others, “sten- pared endovascular treatment known. Seventy-two patients was endovascular mechanical the trial was to act very fast— trievers are a game-changing (intra-arterial thrombolysis, continue to be followed and thrombolysis (with any off- “the imaging has a shelf-life, it is tool”. mechanical treatment or both) full results of the trial can be the-shelf device, but stentriev- a snapshot of time”. Therefore, As for how these results should with no treatment, against a expected in the New Year. ers were favoured), while the he reported, the vast majority of affect practice, Hill said that at background of optimal medical ESCAPE (Endovascular control group had best stand- cases were done endovascularly his site in Calgary, Canada, “we management, with or without treatment for small core and ard of care, including t-PA and with conscious sedation only. are recommending the use of intravenous alteplase. The anterior circulation proximal stroke unit care. The patient was taken straight the ESCAPE criteria to select results have reportedly shown occlusion with emphasis on “The first step in the selec- to the cath lab and procedures patients for now, and as more data endovascular treatment to be minimising CT to recanaliza- tion of patients was to measure optimised. “We set some very become available from the MR favourable. tion times) is a randomised, the physiology by imaging it aggressive targets. We wanted to Continued on page 2

all be coiled, but I think if you look at it Surgery versus endovascular honestly, there are problems with treating these wide necked aneurysms endovascu- larly. In terms of thromboembolic events, treatment for middle cerebral artery parent artery coil herniation can happen and branch occlusion is a real issue. Coil compaction and aneurysm regrowth are aneurysms: Debate rages on also real issues,” Lavine warned. As the debate of surgery versus endovascular treatment for MCA aneurysms, he is a passionate His advice to the delegates was “do middle cerebral artery (MCA) aneurysms continues, specialists supporter of the surgical point of view. not do something just because you around the world continue to ask the question: are MCA “Obviously we have two very good can—the end result is not always going aneurysms better to be clipped or coiled, and how are the techniques for treating aneurysms— to turn out well”. emerging endovascular technologies paving the way forward? coiling is outstanding, as well as clip Turning to the available literature ligation, but in the MCA, even with for surgical therapy, Lavine pointed elegates at the European Hospital, Ankara, Turkey) on the types my experience, I still have a strong out that it is very limited and largely Society of Minimally Invasive of treatment for middle cerebral artery personal bias that this should be treated old. Many of the studies look at the DNeurological Therapy annual aneurysms. With available literature surgically in most cases,” he said. techniques of treatment, but the actual meeting (ESMINT; 4–6 September, and personal preference as their refer- He added that when it comes to surgical outcomes have not been evalu- Nice, France) heard the expert opinion ence, Lavine and Cognard argued for MCA aneurysms, once there is a good ated. of Sean Lavine (Department of Neuro- surgical and endovascular treatment, surgical team, it is very difficult to When comparing existing MCA logical Surgery, Columbia University respectively, while Saatci discussed argue that with 100% of the aneurysm endovascular treatment studies, Lavine Medical Centre, New York, USA), the place of the newer endovascular gone and preservation of the branch, noted that complete occlusion rates are Christophe Cognard (Department of techniques. you could possibly get a better result disappointing (around 50%). He further Diagnostic and Therapeutic Neuro- Lavine, acknowledging that his with endovascular treatment than with pointed to the near complete, residual radiology, Hôpital Purpan, Toulouse, practice has evolved over the years to microsurgery. aneurysm and aborted embolisation France) and Isil Saatci (Radiology become more endovascular oriented, “Why not coil all MCA aneurysms? rates—36%, 7% and 10%, respectively. Department, Hacettepe University maintained that for the treatment of I am sure we will be told that they can Continued on page 4

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at four centres and a pre-planned analysis has similarly been affected by the MR ESCAPE trial permanently will take place soon. CLEAN data, and enrolment has been “There is going to be a pre-planned in- halted temporarily following the DSMB halted, declared positive terim analysis that has already been crossed consideration that equipoise has been Continued from page 1 (174 patients). We are going to look at the lost. CLEAN study and from our own study REVASCAT data before that and see whether the DSMB The study seeks to determine if patients in the New Year, we will better be able Also affected by the positive results of MR will consider stopping the trial based on experiencing an acute ischaemic stroke to analyse and think about the subgroups CLEAN and the halting of ESCAPE is the pre-planned criteria if the treatment effect is due to large vessel occlusion, treated that we should and should not treat and REVASCAT trial, which continues to enrol consistent with other trials,” Jovin said. with combined IV t-PA and Solitaire FR so on. But at the moment, we do not have patients but will undergo a pre-planned He added that one of the major consider- within six hours of symptom onset have those data and we cannot know that at analysis in the near future. ations of continuing to enrol is the fact that less stroke-related disability than those this time.” REVASCAT (Endovascular revascu- the MR CLEAN and ESCAPE data have patients treated with IV t-PA alone. Commenting on the affect of the find- larization with Solitaire device versus best yet to be published, “and we felt that that is Commenting on the decisions to ings on the future of stroke treatment, medical therapy in anterior circulation not sufficient evidence. Once these studies continue the trial and to halt enrolment Hill told NeuroNews: “The situation that stroke within eight hours) is a prospective, are published, things may change, and if made in REVASCAT and SWIFT- the stroke community finds itself in today multicentre, randomised, controlled, open, there is loss of equipoise we will conclude PRIME, respectively, Jovin said, “I is one where multiple endovascular treat- blinded-endpoint trial with a sequential that the trial cannot continue. In REVAS- think both decisions are reasonable ment trials are ongoing. When one trial design. The randomisation employs a 1:1 CAT the loss of equipoise was not assumed and defensible. I think these are issues reports significantly positive findings, it ratio of mechanical embolectomy with the and the indication from the DSMB is that it that are very difficult to judge for sure is ethically appropriate that other trials stentriever Solitaire FR (Covidien) versus is ok to continue the trial.” and there is no right or wrong answer consider their own design and current medical management alone. here, and I think both positions can be status. The outcome could be to prema- Giving a brief update on REVASCAT SWIFT-PRIME justified.” turely stop a trial or to keep going. In this at SVIN, study chair Tudor Jovin reported SWIFT-PRIME (Solitaire FR as primary Up to press time, no MR CLEAN or situation the details really matter.” that 192 patients have been enrolled so far treatment for acute ischemic stroke) ESCAPE data were published. MR CLEAN: expert opinion Since the first presentation of data at the World Stroke Congress, the MR CLEAN trial has sent a ripple across the entire neurointerventional arena, raising questions about the future of stroke treatment and the fate of similar trials, some of which have already been halted.

t the Society of Vascular and basically a stent retriever trial. The Interventional Neurology average time from onset to t-PA was Ameeting (SVIN) the as yet under 90 minutes, but the average time unpublished MR CLEAN (Multicentre from onset to randomisation was 200 randomised clinical trial of endovas- minutes. Because there was 110 min- cular treatment for acute ischaemic utes between t-PA start and randomisa- stroke in the Netherlands) results were tion, they ended up with t-PA failure discussed by an expert panel. The patients. Onset to groin puncture was panel, including Jeffrey Saver, Tudor 60 minutes faster than some of the Jovin, Osama Zaidat, Italo Linfante, prior studies. Serious adverse events Raul Nogueira, and Dileep Yavagal, were not greatly different between focused on the effect of the trial the two groups. In terms of results, in results on other trials and where that the onset to randomisation, whether leaves clinical practice going forward. patients were randomised early or late, MR CLEAN is a pragmatic phase within the first two hours or beyond III multicentre randomised clinical the first two hours, they benefited, so trial with blinded outcome assessment. two hours is not a key cut point.” Jeffrey Saver Tudor Jovin Endovascular treatment (intra-arterial thrombolysis, mechanical treatment or Way forward panel maintained that care must be process’.” both) was compared with no treat- The question was then raised: with taken. Following on from Jovin, Raul ment, against a background of optimal MR CLEAN and similar trials such as Tudor Jovin cautioned, “We must Nogueira stated, “Equipoise is medical management, with or with- ESCAPE and EXTEND IA declared remember that these results are in non- not what we [personally] think, it out intravenous alteplase. With the positive, what is the next step? “Are we published form; we do not know how is about what the whole medical enrolment of 500 patients complete, done with our trials; can we just go into these results are going to look in their community thinks, and we do not the results presented at World Stroke clinical practice and not have to worry definitive form. The same applies to know if things are going to change, Congress were in favour of interven- about anything yet?” ESCAPE. Before ESCAPE we could and stopping before things change tional treatment. Saver responded that just looking at have said that this could be an outlier, would be a mistake. We have duties Jeffrey Saver, who was present at the results of MR CLEAN, the answer but to me, the fact that ESCAPE was to the patient in front of us and to the World Stroke Congress, gave a is no. He pointed to the fully able to stopped due to crossing pre-defined the whole community of patients we brief summary of MR CLEAN: “MR return to work/non-disabled outcome efficacy boundaries tells me that this will see for the rest of our lives. It CLEAN had a very broad design. which reportedly showed that 88% of probably is the kind of treatment effect is a complicated ethical dilemma, I They could enrol patients who were patients in the intervention arm are that we are looking at. So I suspect think we need to measure the degree getting t-PA or not getting t-PA as the still unable to return to work and 97% the data are real and because of that of equipoise in the whole community, background therapy up to six hours of patients still have symptoms from I have no reason to believe that other and I think the trials should probably after onset. They had broad clini- their stroke. “So there is still a huge ongoing trials are not going to go the be put on hold as opposed to stopped.” cal criteria—NIHSS score of two or need for additional therapies. We have same direction. The question to me is Up to time of publication of this higher. Patients had to have an occlu- had a major step forward but we need less ‘should the trials be stopped’, and issue of NeuroNews, the ESCAPE sion in the terminal ICA, in the M1 to keep doing better, and so we need more, ‘should consenting be changed’, trial has been permanently halted, M2 or in the A1 A2. Even though they to move on to the next generation of because for all of these reasons you the SWIFT-PRIME trial has were broadly inclusive and started trials.” can make a good argument that trials been temporarily halted, and the in the pre-stent retriever era, most of As for the process of making should not be stopped. The question REVASCAT trial continues to enrol, the patients (97%) were treated with decisions for other trials based on data is ‘how do we incorporate this kind with a scheduled pre-planned analysis retrievable stents, so MR CLEAN is that are yet to be published, the expert of information into the consenting due in the near future.

4 Controversy November 2014 Surgery versus endovascular treatment for middle cerebral artery aneurysms: Debate rages on

Continued from page 1 He said that the recanalisation rate The question to consider con- (15–20%) and the retreatment rate (7%) cerning the debate of clipping are significant. Lavine acknowledged that the rate of favourable outcomes versus coiling, is whether MCA (95%) is very good, but noted that re-bleeds occurring afterwards is an aneurysms should be consid- unacceptable result. ered differently versus all other “There is one study that has directly compared clipping and coiling in MCA aneurysms. aneurysms. Unfortunately, it was a small series, but they did look at the mostly complex with an integrated consequence might be asymptomatic complete occlusion rates for surgery important vessel, she noted that there occlusion of the critical trunk while versus endovascular, and overtime used to be limitations for endovascular the aneurysm is getting occluded. The endovascular therapy had a worse out- treatment. However, “with the intro- fourth scenario is remodelling of the come. In the endovascular group over- duction of stenting, flow diverters and aneurysm sac with the patency of all all versus the surgery group, there were intrasaccular flow modifiers, endo- bifurcation vessels preserved,” she more complications in the endovascular vascular treatment has started to offer said. group, and there were significantly a solution for difficult aneurysms as In terms of relevant literature, Saatci higher retreatment rates. Interestingly, well, and the limitations have started referenced her own experience of there were improved outcomes in the to fade away”. treating MCA aneurysms with flow endovascular group for the ruptured According to Saatci, stenting with diverters. The published study looks at aneurysms, although it is a small series Sean Lavine coiling became much more easily the first 25 MCA aneurysms treated at of ten patients versus nine patients, applicable with the Solitaire device her centre. so it is hard to draw any meaningful the complications… you can see that (Covidien) and Enterprise device (Cod- “Regarding the results, we do not conclusions there. But certainly it does you have more ruptures in the MCA man), and has become efficient and have mortality, we have one per- not bode well for endovascular therapy location and this is statistically signifi- widely used. manent morbidity and late transient in that small trial,” he said. cant,” he said. Further, she noted that with the symptoms in three patients in this Lavine concluded stating, “MCA an- Cognard also drew attention to the introduction of mini-stents, stenting group. In two, MRI did not show any eurysms are best treated with surgery lack of relevant literature on the sub- has become more widely used and ischaemic injury; it showed oedema as it has a better effect on durability ject, noting that none of the large stud- more easily applicable. “With the in one, a large one. Regarding the and a better effect on the natural his- ies have any real comparison between confidence on the smaller profile mi- efficiency and the patency of the tory, particularly with respect to un- the MCA and other locations. However, crocatheters, we then started to make branches, we have complete occlu- ruptured aneurysms. One issue that is he pointed out that, “In all the litera- loops with the deployment microcath- sion in 87% of the aneurysms and the significant and real is whether or not ture, we do not have evidence to say eter itself that we use with mini-stents remaining four have flow remodelling you have a surgeon who is skilled and that surgery could be better, and that so we do not need exchange manoeu- with no branch occlusion. In the entire who has a low complication rate for endovascular treatment is more risky in vres which sometimes may be the rea- series, 18 of the branches were patent, treating MCA aneurysms. I think un- the MCA and that clipping is less risky son for complications, and we started which means that 60% of the branches fortunately, the number of well-trained in the MCA.” to treat even more complex aneurysms stay open, and the remaining 40% ei- and well-practised surgeons that clip Cognard said that in all locations, the with no limitation of many exchange ther reduce in calibre, which may end aneurysms is decreasing, particularly problem is that there are so many new procedures,” she said. up in occlusion in the longer follow- in the USA.” devices becoming available, that it is Additionally, Saatci said that up period, and in 20% the branches With an opposite viewpoint to La- difficult to know what technique is the minicerebral stents have the advantage got occluded.” vine, Christophe Cognard maintained best at the moment. of being less traumatic in terms of “So the controversy of surgery that the middle cerebral artery location He concluded, giving his personal stent placement, and this therefore has or endovascular treatment in MCA by itself is not at all a reason for doing preference: “For me there are three increased the spectrum of aneurysms bifurcation aneurysms is still going on, surgery. Instead, he says that MCA types of aneurysms, the easy to coil which can be treated with endovascular however, with certain MCA aneurysms, aneurysms can be divided into three that should be coiled; the difficult to therapy. On the other hand, she said, flow diverters really provide a good categories: those that are easy to coil, coil that can be treated with stenting “the disadvantage of mini-stents is that solution,” Saatci maintained. with a small neck; those that are dif- (unruptured), or surgery (ruptured); and they have less flow diversion effect Finally, in terms of the use of ficult to coil and maybe easier to clip; the very difficult to coil and to clip, in despite the fact that you do wide stent- intrasaccular flow modifiers, Saatci and those that are very difficult to coil which you could do complex clipping ing. Our experience has been that even said that “the introduction of a single and to clip. or bypass. For me, when they are easy if you do wide stenting, you had better layer device has made it much easier to Cognard said that the questions to to coil with a small neck, I do not see still pack as much as possible”. navigate and they are softer and they consider are whether MCA aneurysms any reason to do surgery.” Turning to flow diverters, Saatci are efficient as well”. are different from all aneurysms in maintained that they ushered in a big She used the example of a ruptured other locations, and concerning the de- New endovascular change regarding aneurysm treat- aneurysm where an intrasaccular device bate of clipping versus coiling, whether techniques ment where the vessels are coming off offered a good solution using the Web MCA aneurysms should be considered Presenting a synopsis of the place of from the sac. “This inspired us to use device (Sequent Medical) with no anti- differently versus all other aneurysms. the new endovascular techniques in this technique for MCA aneurysms in aggregation, and played the next day Referring to a study done in France the treatment of MCA aneurysms, Isil selected situations (not in regular MCA MRI angiography showing no filling of seven years ago, he pointed to the Saatci looked at stenting, flow divert- aneurysms).” the aneurysm. differences between MCA aneurysms ers and intrasaccular flow modifiers. Posing the question of whether flow Saatci said that was an accept- versus other locations. “If you look at Explaining that MCA aneurysms are diverters can be used in the treatment able result, noting, however, that the of all aneurysms in the MCA territory, long-term follow-up for these patients One issue that is significant and Saatci referred to the four possible must be seen “because we know that complications of using flow diverters in intrasaccular devices will not get con- real is whether or not you have a bifurcation. tacted in the follow-up and will remain “When you use flow diverters in as they are, but we need to see if there surgeon who is skilled and who bifurcation the possible consequences is a regrowth”. has a low complication rate for are: one, it may keep all the bifurcation She concluded noting that, “Overall, vessels patent with the aneurysm occlu- the techniques are evolving in the en- treating MCA aneurysms. sion. The second possible consequence dovascular territory and there are new is that the branch may get hypoplastic, endovascular devices for the treatment reduced in calibre. The third possible of MCA aneurysms.”

6 Updates November 2014 CANOPY results support carotid artery stenting The most recent CANOPY data, presented as a late breaker at Vascular Interventional in the trial, which was well within the 95% confidence Advances (VIVA; 4–7 November, Las Vegas, USA), provide further support for carotid interval and statistically significantly better than the artery stenting as an alternative treatment in patients with obstructive carotid artery performance goal,” he reported. disease who are at standard risk of adverse events from carotid endarterectomy. Comparing CANOPY to CREST, Metzger pointed out that the patients in both trials were very similar, with urther to that, it was reported that the CANOPY National Institute of Health Stroke Scale and Modified the only notable difference being the number of symp- data show that the stroke rates in symptomatic Rankin Scale, stroke adjudication by a clinical events tomatic patients in CREST, which enrolled symptomatic Fand asymptomatic patients were consistent with committee, new neurological events, and device and patients only for the first half of the trial. stroke results of similar patients treated in the CREST procedure-related adverse events at all follow-up visits In terms of death and stroke rate, Metzger reported randomised trial. (24 hours, 30 days and one, two and three years). similar findings in the two trials, with slightly Investigators in the CREST trial found that among To be included in the study, patients had to be better results in the CANOPY trial (death patients with symptomatic or asymptomatic carotid at standard risk for carotid endarterectomy, and all stroke: CANOPY, 3.4% versus stenosis, the risk of the composite primary outcome of with a single lesion in the internal carotid CREST, 4.4%). stroke, myocardial infarction, or death did not differ sig- artery, with or without involvement of the Concluding, Metzger maintained that the nificantly in the group undergoing carotid artery stenting common carotid artery. CANOPY data “provide further support and the group undergoing carotid endarterectomy. Metzger explained that the primary end- of carotid stenting as a potential alterna- CANOPY is a multicentre, non-randomised single- point (composite of death and stroke through tive treatment in patients with obstructive arm, FDA-mandated real-world post-approval follow-up 30 days post-procedure, and ipsilateral carotid artery disease who are at standard study enrolling patients similar to those enrolled in the stroke up to one year) was compared risk of adverse events from carotid endar- CREST trial. It is the only contemporary and adjudicat- to a performance goal based on terectomy.” ed post-market carotid artery stenting study in standard the CREST and carotid Commenting further during a risk carotid endarterectomy patients. artery stenting literature discussion after his presentation, Presenting the one-year CANOPY results, principal data, considering a Metzger said, “This was truly investigator D Christopher Metzger (Wellmont CVA mix of symptomatic a real-world study, so these Heart Institute, Kingsport, USA) said that CANOPY and asymptomatic results are encouraging as provides prospective additional insights into carotid patients. He we left it to the operator or artery stenting clinical outcomes based on symptomatic added that the the site principal investiga- status and age. He added that the purpose of the FDA performance tor to really control things. mandate was to see if the favourable results of standard- goal was estab- The breakdown will be risk patients in CREST could be duplicated in a real- lished as 8.4% published later, but about world setting in similar patients. based on a point 60% of the operators had The objective of the CANOPY study was to evaluate predictor value 100 carotid stent procedures the continued safety and efficacy of the RX Acculink of 5.4% plus a 3% under their belt, so there stent and embolic protection system (Abbott Vascular), delta. were a lot of experienced used by a wide range of physicians in standard-risk “The results of the doctors in the trial, and we are patients. The primary endpoint was a composite of death CANOPY trial for com- going to see if there are enough and stroke through 30 days post-procedure, and ipsilat- posite of death and stroke at data to show experience versus eral stroke up to one year. Between October 2011 and 30 days and ipsilateral stroke outcomes.” September 2013, 1,203 patients were enrolled at 97 cen- at one year: the primary endpoint tres. Post-procedure assessment included Independent occurred in 4.4% of the patients D Christopher Metzger Neuromodulation procedures safe in outpatient setting

Jennifer Padwal (University of California, San Diego, La Jolla, paddle placed via a mini-laminectomy In terms of complications, two (8%) USA) and others in the Journal of NeuroInterventional Surgery in the epidural space at the desired patients presented with evidence of report that “with sufficient clinical skills and knowledge, level, were attached to a generator lead migration, lower than the reported trained interventional neuroradiologists may safely perform which was then placed in a prepared rate in the literature of 11-21%. Three [neuromodulation procedures] in an outpatient setting.” subcutaneous pocket, usually located patients (13%) went on to have infec- in the buttocks. tions necessitating the removal of the he retrospective study, examin- loss-of-resistance technique. An electri- The trials were conducted in an device, which was higher than the ing patient charts and medical cal lead was then manipulated under outpatient clinic (34) or in hospital rate reported in the literature of 4.5%. Trecords over a four-year period, fluoroscopic guidance up the T7–8 outpatient settings (11). Of the 45 However, as the authors explain, “one involved a total of 45 patients with a level. In cases of cervical epidural lead trials, 27 progressed to permanent patient was found to be an intravenous median age of 47 years. The selected placement, the entry point to the epi- implantation—a trial-to-implant ratio drug abuser who developed an infection patients had failed all types of con- dural space was around the T1–2 level, of 60%. Four of the implants were after six months of the implantation, servative treatment for chronic back or and the leads were usually advanced up subcutaneous and 23 were epidural. and another patient who developed neck pain, including physical therapy, to the level of the C2 vertebra. An interventional neuroradiologist an infection after three months was spinal injections and pain medication All but three patients required a performed 17 implantations, while found to have previously undiscovered therapy. The primary diagnoses for the second lead to ensure adequate cover- spine surgeons performed 10. Of the leukaemia.” There was one case of un- study included 23 cases of failed back age of painful areas, which was placed 18 patients to fail the trial process, 17 controllable bleeding during placement or neck surgery syndrome, 12 cases parallel or staggered in relation to the reported less than 50% pain relief and of one of the trial leads, resulting in the of spinal stenosis, four cases of axial first lead. The leads were then connect- one patient did not like the feeling of removal of the lead and the continua- pain, three cases of reflex sympathetic ed to an external pulse generator. In the the leads in his back. tion of the trial with one lead. dystrophy, one case of peripheral trial period, the patient manipulated The main mechanism of action was Padwal et al write: “Limitations of vascular disease, one case of phantom the different programmes and recorded based on the original work described the study include a relatively small limb and one case of post-concussion their pain level, activity and use of pain by the gate control theory of the relief sample size, the retrospective nature syndrome and occipital neuralgia. medications. At the end of the trial, a of pain proposed by Melzack and of the study and the fact that it was The trial period of the study ranged discussion was held with the patient Wall in 1965. The authors said that performed in a single-centre setting.” from three days to one week. The regarding these three points. the trial-to-implant ratio of their study Despite this, the authors believe that, epidural space was usually accessed A trial was deemed to be successful is “only slightly below the average given the lack of prior studies of this at the L1–2 level, angling steeply up if it saw a reduction in the patient’s trial-to-implant ratio reported in the nature, this study will “provide an from below the vertebral body using a pain level of ≥50%, calculated on a literature of 65–83%. With a larger appropriate foundation for the design 14G Touchy needle. The location of the visual analogue scale. In this event, sample size, the trial-to-implant ratio and implementation of future con- epidural space was assessed using the the electrical leads, or an electrical would most likely rise.” trolled prospective studies.”

8 Flow diverter therapy November 2014

bidity rates were 7.3% or less in the studied timeframe. Potential complica- Flow diverter technology tions mostly included early or delayed haemorrhagic (ICH and SAH) and ischaemic strokes. Not unexpectedly, more complications were noted in pos- for intracranial aneurysms terior circulation aneurysms compared to anterior circulation. Among others, of 110–250µm. There are other devices our recently published paper (Toth et currently in clinical trials. The Surpass al, J Neurointerv Surg. 2014 Jul 1. pii: (Stryker) is made of cobalt-chromium neurintsurg-2014-011281. doi: 10.1136/ GABOR TOTH strands with interwoven platinum/ neurintsurg-2014-011281) also discuss- tungsten wires, 30% metal surface es the difficulties and increased flow area coverage, and 20–32 pores/mm2. diverter treatment risks in posterior The FRED device (Microvention) has fossa aneurysms. Particular challenges COMMENT & ANALYSIS a dual-layer design with woven inner are fusiform basilar aneurysms, and the and outer stents; the inner low-porosity abundance of small perforators. stent has 48 braided nitinol wires, the There are several trials ongoing to Gabor Toth writes for NeuroNews about the flow diverters that are outer high-porosity stent has 16 wires compare the efficacy and safety of flow currently available and the ongoing clinical trials that could have and serves as a scaffold. diversion with surgical, conventional or the potential to extend the indications of flow diverter therapy to The early results with flow divert- other endovascular management options smaller and more aneurysm types in different locations. ers have been promising. Short-term, (FIAT, EVIDENCE, LARGE, MARCO six-month occlusion rates ranged from POLO, COCOA). Some of the studies ue to their unique characteristics, diseased aneurysmal segment. This is 82–94% in the initial Pipeline studies are looking at the possibility to extend flow diverters were originally considered a paradigm shift compared to (Lylyk et al, Neurosurg 2009; Szikora the indications of flow diverter therapy Dintended to provide a reconstruc- prior endovascular methods, which pre- et al, AJNR 2010; Nelson PK et al, to smaller and more aneurysm types in tive treatment option for atypical cerebral dominantly aimed at providing treatment AJNR 2011), and one year occlusion different locations. aneurysms which previously had no from inside the aneurysm sac. Another rates were as high as 86.8% in the Based on currently available evidence, feasible management alternatives, failed important consideration is that the poros- PUFS trial (Becske et al, Radiol- flow diverter therapy appears relatively safe prior therapy, or conventional endovas- ity of these stents is designed to allow ogy 2013). There were no significant and feasible for large, dysplastic, wide neck cular methods (coiling, stent-assisted small perforators to be preserved due to aneurysm recurrences in any of these anterior circulation aneurysms. Results coiling, balloon-assisted coiling, liquid flow demand. Early studies demonstrated studies. Major complication (stroke with smaller aneurysms are promising, embolic agents) showed suboptimal involution or regression of the aneurysm or death) rate with Pipeline was in the but will require additional confirmation results or increased recurrence. These sac with decreased mass effect on the 5–6% range. Initial case series with the in randomised trials. Posterior circula- devices are metal mesh tubes, which on surrounding parenchyma in many flow Silk device reported up to 5% mortal- tion, bifurcation and previously stented first glance may resemble conventional diverter cases, which would be difficult ity and 15% morbidity rates (Wagner aneurysms have had less optimal outcomes. stents. However, significant differences to achieve with previous endovascular et al, Neuroradiology 2012; Velioglu New flow diverter stents, and second and are noted in that they have higher surface techniques. et al, Neuroradiology 2012; Lubicz et third generation versions of the currently metal coverage and lower porosity than The first two available devices were al, Stroke 2010). Complete occlusion available devices are being developed to previously available vascular reconstruc- the Pipeline (ev3/Covidien), FDA rates with Silk were ranging 68-87% improve flexibility, durability, deliver- tion devices. As the name suggests, the approved in the USA in 2011, and the at 6-17 months of mean follow-up. ability and performance. Further data and primary goal of flow diverters is to redi- Silk (SFD, Balt Extrusion), approved Recent meta-analyses of multiple flow extended follow-up are needed to better rect blood flow toward the normal route in Europe around 2008. The Pipeline diverter studies including Pipeline understand the long-term risks and benefits in the parent vessel, leading to throm- device is a 25% platinum and 75% and Silk devices (Brijinki et al, Stroke of this rapidly evolving technology. bosis and obliteration of the aneurysm nickel-cobalt-chromium alloy with 2013; Arrese et al, Neurosurg 2013) lumen. They also provide a scaffolding approximately 30–35% metal surface also demonstrated over 75% overall Gabor Toth is an assistant professor at for later neoendothelial proliferation, area coverage. Silk is a nickel-titanium occlusion rate of treated aneurysms, but the Cleveland Clinic Lerner College of and vessel wall healing. Flow diverters (nitinol) alloy with platinum micro- mean follow-up times were less than Medicine, and staff neurointerventional- practically create a new, artificial lumen filaments providing a 35–55% metal one year. The overall early mortality ist at the Cleveland Clinic Cerebrovascu- inside the parent vessel, bridging the surface area coverage with a pore size rates appeared 4% or less, and mor- lar Center in Cleveland, USA

Fellowship Director at Lyerly Neurosur- case performed in gery and Baptist Health Jacksonville, Europe using the Update: SCENT study USA. The National co-principal Surpass Streamline Text submitted by Stryker Neurovascular investigator is Philip Meyers, Flow Diverter was professor of Radiology and performed on 2 October The SCENT study (Surpass intracranial aneurysm embolization Neurological Surgery and 2014 by Joost de Vries, system pivotal trial to treat large or giant wide neck aneurysms), clinical co-director of head of the Neurovascular sponsored by Stryker Neurovascular, is a multicentre, prospective, Neuroendovascular Working Group, Depart- non-randomised IDE trial designed to evaluate safety and Services at New York ments of Neurosurgery, Neuroradiol- effectiveness of the Surpass™ Flow Diverter as compared to Presbyterian Hospi- ogy, Neurology and Intensive Care, a historical control in the treatment of large or giant wide-neck tal, USA. Radboud University Nijmegen, intracranial aneurysms. The Surpass™ The Netherlands. The first Flow Diverter SCENT case performed in Large aneurysms are defined as having an into the parent artery across the neck of an received CE the USA using the Surpass aneurysm diameter ≥10mm and <25mm, aneurysm to divert blood flow away from mark Streamline Flow Diverter was giant aneurysms are defined as having an the aneurysm. Since effective endovascular approval performed on 7 November 2014 aneurysm diameter ≥25mm, and wide-neck treatment of large and giant wide-neck in De- by Demetrius Lopes, associate aneurysms are defined as having a neck brain aneurysms remains a challenge, the cember professor of the Departments ≥4mm or a dome to neck ratio <2 or aneu- Surpass Flow Diverter is undergoing evalu- 2010. The of Neurological Surgery and rysms with no discernible neck. ation in the SCENT study as an alternative Surpass™ Stream- Radiology and Director of Endo- The Surpass™ Flow Diverter (Stryker treatment option. line™ Flow Diverter vascular Surgery at Rush University Neurovascular) is a new generation of flow Patient enrolment is currently ongoing at (the Surpass Flow Diverter with the next Medical Center, Chicago, USA. diverter that was designed to treat unrup- 22 US clinical sites and one clinical site in generation delivery system designed to A Japanese study of the Surpass Stream- tured sidewall large and giant intracranial The Netherlands. The National principal enable recapture and repositioning of the line Flow Diverter that was designed to be aneurysms that are not amenable to surgical investigator for the SCENT trial is Ricardo implant) received CE mark approval in similar to the SCENT Study also was initi- or current standard endovascular treat- Hanel, director of the Stroke and Cer- September 2014, and is currently commer- ated in August 2014 and patient enrolment ment. The device is designed to be placed ebrovascular Center and Cerebrovascular cially available in Europe. The first SCENT is ongoing.

10 Neuromodulation November 2014 Focus on: Neuromodulation Over the past decade, who are uninformed on it. There is no reason why it should not be a routine neuromodulation has procedure for the right indications, grown into a wide but right now it is believed that and varied field with barely 5–10% of patients who need or approvals for additional qualify for this therapy actually get access to it. The commentary on com- applications increasing plications is that we need both device every year. NeuroNews and procedure related complications now speaks to four Image courtesy of St Jude Medical to come down. In the field of cardiac rhythm management they are a frac- thought-leaders in the tion of what they are in neuromodu- neuromodulation arena lation. That speaks to the younger about the research history of the specialty and the lower priorities, challenges absolute volumes of production. Konstantin Slavin: Challenges and and potential areas for complications of neuromodulation growth. are related to several things that have to do with clinical, technological and Neuromodulation is being theoretical aspects of this non-destruc- tested as a potential tive and minimally invasive approach. treatment for various The main issue remains proper patient different diseases and selection, as individual responses to ailments. In your view our neuromodulation procedures vary what are the research from person to person. The second priorities in the area of major challenge is in relative shortage neuromodulation, and of basic science research that could why? better explain the mechanisms of ac- Timothy Deer: The priorities can be tion of our interventions and perhaps classified into three separate groups: urinary incontinence, heart failure, What are the challenges aid in development of new technologi- we need to complete the current ran- arrhythmias, rheumatoid arthritis, and and complications cal breakthroughs. Finally, the tech- domised prospective comparative stud- gastrointestinal disorders. associated with nology itself presents a challenge as a ies on new waveforms and spinal cord Marc Russo: The key research priori- neuromodulation? large part of neuromodulation compli- targets. These studies will improve ties are to document the efficacy of Ali Rezai: One challenge impacting cations and unsatisfactory outcomes the validity of the field and provide neuromodulation in the different indi- the growth of neuromodulation is the may be explained by device-related a framework for future use. Sec- cations it has found success in and to cost of the implantable devices and issues; here the hope is in ongoing ondly, we need to consider the role of then additionally document cost-effec- limitations in reimbursement, thus progress in material science, develop- neuromodulation in disease manage- tiveness and healthcare cost utilisa- limiting access for patients who can ment of indication-specific hardware, ment. Early work in heart failure and tion compared to the alternatives. We benefit from these therapies. In addi- and emphasis on individually-tailored vascular disease is very promising. In need an evidence base that is second tion, improvements in patient selec- interventions. the spine and brain, work for many to none in the medical device industry tion criteria, guidelines, development diseases could become the standard of field. of registries, and objective biomarkers What are the key care. Lastly, the replacement of drugs Konstantin Slavin: There should be applications are needed, as well as things to keep in mind with electrical current could be a valu- two priorities, in my opinion—(a) studies of cost-effectiveness and qual- when developing able cost-effective option for inflam- strengthening of the body of evidence ity of life with neuromodulation. standards of practice in matory diseases, and other systemic for existing indications and (b) devel- Marc Russo: The challenge is to neuromodulation? illnesses. opment of new indications. Stronger effectively disseminate knowledge Ali Rezai: Key features for develop- Ali Rezai: Research that advances our evidence of efficacy (and cost- about neuromodulation to the large ing standards of practice in neuro- understanding of the neural networks effectiveness) is needed to maintain number of physicians and surgeons modulation are strong neuroscience and circuitry underlying various brain the access to neuromodulation for our disorders is fundamentally impor- patients with chronic pain, movement tant for guiding new applications of disorders, epilepsy and other currently targeted neurostimulation. Important approved indications. As evidence- areas of opportunities for discovery in based medicine is gaining momentum, brain neuromodulation involve deep many of our approaches that were brain stimulation studies in patients never properly tested have been ques- with cognitive and behavioural disor- tioned and sometimes denied by pay- ders such as depression, anxiety, ad- ors and insurers—very often despite dictions, Alzheimer’s disease, eating several decades of positive experi- disorders, and traumatic brain injury, ence. At the same time, development as well as stroke motor recovery. An- of new indications—such as various other area of significant opportunity pain conditions (headaches, back pain, for translational research is autonomic fibromyalgia), cardiovascular, gastro- nervous system neuromodulation. This intestinal and genitourinary disorders, has expanded the scope of neuromod- dementia, depression, post-stroke ulation by bringing in various other neurological deficits—will ensure specialists such as urologists, cardi- continuous growth of neuromodula- ologists, otolaryngologists and others. tion modalities and, subsequently, Clinical trial applications encompass further improvement of quality of life migraine and cluster headaches, for our patients. Timothy Deer Ali Rezai November 2014 Neuromodulation 11 and scientific rationale guiding new Konstantin Slavin: There are many clinical applications and clinical trial recent developments that are expected design. Patient selection standards are to change our practice of neuromodula- also crucial variables. Patient selec- tion within next several years—these tion should take into account accurate include development of new stimulation diagnosis, disease progression and paradigms (such as paraesthesia-free chronicity, medication intractable stimulation for pain), new stimulation nature, medication side effects and the principles (such as closed-loop or adap- use of other available treatment op- tive stimulation), new stimulation targets tions prior to consideration of neuro- (dorsal root ganglia, cerebral, spinal and modulation. Furthermore, patient and peripheral neural structures), new tech- family clarity about outcome expecta- nological developments (rechargeability, tions, limitation of benefit, and clear larger number of stimulation electrodes, understanding of the side effects has directional stimulation, simultaneous to be carefully considered. stimulation and recording, MRI-com- Marc Russo: The biggest improve- patibility, miniaturisation). Personally, ments in medicine come not from I was most impressed very recently by pushing up the top 1%, they come a development of an implanted device from pulling up the bottom 20%— that was powered by the body itself— Atul Gawande showed this clearly in earlier this year, there was a report of a his book. The field needs to ensure new pacemaker that is powered by the the practice standards it has pro- patient’s heart; I am sure there will be Marc Russo duced (NACC and PACC guidelines neuromodulation devices that are pow- as well as national guidelines) are ered by the body temperature, electrical investigational studies worldwide. graine headaches, and other pain condi- well disseminated and then, most signals of the nervous system, or some Several key studies of peripheral tions are being explored. With matura- importantly, followed. This comes other activity of the patient. and autonomic nerve stimulation are tion of this technology, applications for through audit both within and out- evaluating new applications of neu- many other areas will be forthcoming. side of one’s own practice. The In- Where are the key rostimulation technology for urinary Marc Russo: Not every new tech- ternational Neuromodulation Society opportunities for growth incontinence, migraine and cluster nology will turn out to be a winner. is leading the way in coordinating within the area of headaches, heart failure, asthma, and There will be a natural selection of this around the world. neuromodulation? rheumatoid arthritis. The use of high what really does make a difference Timothy Deer: Improved public aware- frequency spinal cord stimulation and and ‘moves the needle’ rather than What has the most ness is critical. Many patients feel that dorsal root ganglion stimulation is of being simply incremental. Two areas important development/ oral opioids are the only option for interest with several studies looking in I am looking at with excitement right breakthrough in severe chronic pain. Family physicians chronic pain patients. Additional spinal now are Sti mwave Technologies neuromodulation been? also are often unaware of the options for cord stimulation studies are evaluating which can eliminate the need for an Timothy Deer: In the past 40 years the their patients. In addition to these issues the potential for movements and gait implanted battery via microwave advancements were incremental and we should strive for improvements in improvements in those with spinal cord transponder technology, and down slow to develop. In the past few years globalisation to address pain in patients injuries. Deep brain stimulation is be- the line, Nicta which are develop- advancements in current delivery and in regions of the world where advanced ing investigated in Alzheimer’s, eating ing a feedback loop sensing system new targets have given us potential therapies are limited or unavailable. disorders, addictions, and traumatic for optimised spinal cord electrical changes in the field that could lead to Konstantin Slavin: I feel that the big- brain injury. Additionally, brain im- activation. dramatic improvements in patient ef- gest opportunity in neuromodulation plants are being used for chronic neural ficacy and safety. is in better penetration of the market recording for brain machine interface Timothy Deer is clinical professor of applications in patients with spinal cord Anaesthesiology at West Virginia Uni- Key features for developing and brain injury. versity, USA Marc Russo: In the pain arena we are Ali Rezai is Stanley D and Joan H standards of practice in neuro- now moving into healthcare cost- Ross chair in Neuromodulation at the effectiveness. That is paramount in a Ohio State University, Wexner Medical modulation are strong neurosci- dollar constrained healthcare world. Center, Columbus, USA ence and scientific rationale guiding new Outside of this area there are impor- Marc Russo is a fellow of the Australian tant trials being conducted in chronic and New Zealand College of Anaesthe- clinical applications and clinical trial de- headache, chronic angina and conges- tists and director of the Hunter Pain tive heart failure, for example, as indi- Clinic, Newcastle, Australia sign. Patient selection standards cations of organ system optimisation. Konstantin Slavin is chief of Stereotactic are also crucial variables. and Functional Neurosurgery Section, What new techniques/ Department of Neurosurgery, University – Ali Rezai technologies are you of Illinois at Chicago, USA keeping an eye on? Ali Rezai: One breakthrough in neu- related to currently existing indication: Timothy Deer: I am keeping my eye romodulation has been the visible and even by best estimates, neuromodula- on several new technologies: new clear success of deep brain stimulation tion today is used in less than 5-15% methods of stimulating the sacral for movement disorders, resulting in of patients depending on indication. nerves to treat incontinence and pelvic over 100,000 deep brain stimulation I do believe that one day we will see disorders; new methods of treating implants worldwide. Another is the a situation when every candidate for congestive heart failure with spinal use of implantable infusion pumps and neuromodulation procedure will be cord stimulation; brain machine inter- their safety and reliability for delivery at least given an option of having it: faces; and electrical pharmaceuticals of baclofen to treat spasticity and for similar to what is happening now when to treat systemic diseases. morphine and other medications for it comes to cardiac pacemakers. In ad- Ali Rezai: Recent technological chronic pain. dition to this, new indications (head- advances are allowing for the use of Marc Russo: This would have to be the aches, depression, dementia, low back micro-implantable neuromodulation introduction of multiple medical device pain) may eclipse by volume all current devices that are miniature, minimally companies into the field and the innova- neuromodulation uses due to very high invasive, and not attached with con- tion and competition they have brought prevalence of these potentially treatable necting wires to pacemaker batteries. as a result. Without that, the field would conditions. These micro-stimulators are remotely have stultified. As it is, it is a vibrantly powered and managed via hand held growing and advancing field with a rate What are the key ongoing external systems analogous to smart of change that is unparalleled in my 20 studies? phone-like devices. Applications for plus years in the field. Ali Rezai: There are many ongoing urinary incontinence, cluster and mi- Konstantin Slavin 12 Interview November 2014 Profile Joseph Broderick

Joseph Broderick, professor of neurology and director of the Neuroscience Institute at the University of Cincinnati, Cincinnati, USA, has focused much of his career on the treatment and underlying causes of stroke. He speaks to NeuroNews about the future of neurology and his research, in particular, his role as principal investigator for NIH StrokeNet—a network slated to be the engine for all new US National Institute of Neurological Disorders and Stroke-funded trials for stroke prevention, acute therapy, and recovery.

How did you come to choose medicine a normal neurological exam. Her serology (Lyme serol- as a career and, in particular, what ogy was just being developed at that time) eventually drew you to neurology and stroke confirmed Lyme disease, and she returned to college. treatment? I had a heck of time getting my case of tertiary Lyme My father is a wonderful role model as a person and disease published because reviewers would not accept physician, but I thought strongly about psychology and the concept without an actual spirochete. Changing lives pastoral counselling in college where my major was is what we do with acute stroke therapy and this was my classical studies and my minor was philosophy. I did not first taste of this experience which I saw again and again decide to pursue medicine until the end of junior year while treating stroke patients with t-PA for the first time and I had to take organic chemistry across summer to in the 1980s. make requirements for my medical school application. I planned to be a psychiatrist when I entered medical What innovations have changed school but found that psychiatrists in those days rarely neurology and in particular, stroke laid hands on patients which did not fit my vision of care, in the last 10 years? a physician. I then considered internal medicine like I think that the standardisation and my father, but my first rotation in internal medicine at expansion of neurocritical care units the beginning of third year was painful. I finally came and training have improved neurologi- to consider neurology, which combined the thought cal outcomes, although this is hard to processes and patient care of internal medicine with measure. I think that this is one reason my fascination of how the brain works. In residency, I underlying the decrease in mortality considered many potential subspecialties, but was drawn due to SAH over the past 20 years. The to stroke because of several role models: one who was a aggressive approach to medical stroke tremendous teacher and one who was a thoughtful clini- prevention—better blood pressure cal researcher. control, statins, smoking cessation, diet, antithrombotic medications, etc—has Who were your mentors in the field proven to be a match for interventional and what do you still remember from approaches to reduce stroke in patients their wisdom? with major extracranial and intracranial Burt Sandok was the chair of Neurology at the Mayo atherosclerosis. We have some excellent Clinic and ran a wonderful cerebrovascular teaching options instead of warfarin for patients conference. He became a role model for me as a stroke with atrial fibrillation. Endovascular physician and educator. Jack Whisnant, the former technology is changing the treatment of chair of Neurology at Mayo, was another important role both ischaemic and haemorrhagic stroke, model from whom I learnt the tools of clinical research, but demonstrating the subgroups of pa- research writing, and a critical approach to data that set tients most likely to benefit from its me on my path as a clinical researcher. use requires much more study.

What was your most memorable case As chair of the and why? American Heart The most memorable patient is from my earliest days Association Stroke as a senior neurology resident. I admitted a 19-year-old Council, what would college student who had progressive language problems you say are the and confusion over several weeks. She had aphasia benefits of becoming and apraxia upon examination and had a history of a a member? How do hospitalisation for aseptic meningitis, bilateral facial members help to weakness and possible rash at the age of 13 which shape the future of resolved completely with prednisone. Her cerebrospinal stroke care? fluid showed 15 white cells (lymphocytic) and nor- The AHA/ASA has been my mal glucose. At that time, neurological presentations entree into the world of stroke for Lyme disease had just been described (CDC first and cardiovascular science monitored the disease in 1985), but her classic presenta- and education. My career tion was six years earlier. I empirically treated her with may have been quite different intravenous penicillin for what I thought could be the without it. My very first grant first reported case of tertiary Lyme disease, although was an American Heart As- my attending physician was sceptical. She continued sociation Grant-in-Aid award that to worsen over two weeks despite antibiotics and was eventually led to our longstanding discharged to her home town. Two months later, I got population-based study of stroke in a call from the neurologic attending to come quickly to Greater Cincinnati/Northern Ken- his office because he wanted to show me something. To tucky. The ISC meetings are where my surprise, there was the young woman who now had I have been witness to the many major November 2014 Interview 13

Fact File

advances in stroke research over the past 25+years and We must do a much better job with transitions of care where I have developed some of my best collaborations in both neurology and stroke. Our current systems are and friendships within medicine, not just in North Amer- too fragmented and not as patient/family-centred as ica but around the world. Members of the AHA/ASA get they need to be. I believe that the great advances in the to help shape the strategic direction of science, next century will be in the area of neuro-recovery and education and advocacy to decrease the rehabilitation and that future advances in acute stroke burden of stroke and heart disease. therapy will ultimately be limited by the constraints of time and biology within the next 25 years or so. This has How do you see the already happened for the most part in the treatment of field of neurology acute myocardial infarction. and stroke care Current position developing in the What are your current areas of Professor of Neurology and Rehabilitation Medi- future? research focused on? cine, University of Cincinnati College of Medicine My current research areas include new and director of the University of Cincinnati Neuro- medical and interventional approaches science Institute, Cincinnati, USA to acute ischaemic stroke; triage of acute stroke patients; the improved design, Education organisation and delivery of clinical 1978 Honours Bachelor of the Arts, summa trials; and the genetics of intracranial cum laude with distinction aneurysm. One of my most exciting 1982 Medical doctor areas of research is my role as principal 1987 Fellow in cerebrovascular disease investigator of the national coordinating centre for the new NIH StrokeNet. This Appointments network will be the engine for all new 1986–1987 Instructor, Mayo Clinic NINDS-funded stroke trials for preven- 1987–1993 Assistant professor of Neurology, tion, acute therapy, and recovery. We University of Cincinnati hope that this infrastructure will allow us 1987–1993 Staff Attending Physician, Veter- to make progress in the prevention and ans Administration Medical Center treatment of stroke more rapidly and are 1988–1994 Director of Neurology Residency planning to link this network with other Training Program national stroke networks to do stroke 1993–1996 Associate professor of Neurology trials that are too big for one country in a 1997–2007 Director, Vascular Neurology Fel- reasonable time frame. lowship 1996–2010 Tertiary Neurosurgery Appoint- What recent publications ment have caught your eye? 2000–2013 Chairman, Department of Neurol- The publications in New England Journal ogy University of Cincinnati of Medicine (NEJM) this year regarding 2006–2013 Academic/Research Director of increased detection of atrial fibrillation University of Cincinnati Neurosci- with more prolonged monitoring are ence Institute interesting and probably will change 1987–present Staff attending physician, Univer- practice, although their true impact sity of Cincinnati on stroke prevention requires longer 1989–present Courtesy staff, 15 Community term study. I am looking forward to Hospitals the results of the MR CLEAN trial 1996–present Professor of Neurology which tests endovascular therapy as 2014–present Director, UC Neuroscience Institute compared to standard care in acute ischaemic stroke. And finally as a Honours (selected) neurologist, I was delighted to see 2000 Samuel Kaplan Visionary Research that a British-American scientist and Award—American Heart Association a pair of Norwegian researchers were 2003 William B Feinberg Award for Excellence awarded this year’s Nobel Prize in in Clinical Stroke—Stroke Council of the Physiology or Medicine for discov- American Heart Association ering “an inner GPS in the brain” 2007 University of Cincinnati Distinguished that enables virtually all creatures, Research Professorship award including humans, to navigate their 2010 Daniel Drake award for outstanding surroundings. Still left unsolved is achievements in biomedical science as why men do not like to ask for direc- evidenced by major significant contribu- tions. tions to medical research 2011 American Heart Association Clinical What are your interests Research Prize outside of medicine? My wife and four children, and a very Research (selected) large extended and close-knit family are the n Principal investigator, National Clinical Coordi- centre of my personal life. I am an avid college nating Center for NIH StrokeNet basketball fan and sports fan in general; I have n Principal investigator, SPOTRIAS very eclectic musical tastes and play the piano, and read n Principal investigator, IMS III broadly and often. And sometimes sleep. n Co-investigator, THERAPY 14 Traumatic brain injury November 2014 The changing face of traumatic brain injury: Life beyond the guidelines

ANDRÁS BÜKI ANDREW I R MAAS

COMMENT & ANALYSIS

Traumatic brain injury is one of the major challenges in health ed by routine MRI and that such injury logical significance. This precludes ef- care, representing the third most frequent cause of death can result in long-term functional ficient design of clinical trials simply worldwide. In Europe, 2.5 million people suffer a traumatic brain consequences. It is also documented because patient populations cannot be injury each year, of whom one million are admitted to hospital that morphometric and functional narrowed on the basis of pathobiology and 75,000 die. MRI may identify subtle alterations driven inclusion criteria, such as the in victims of minor traumatic brain application of biomarkers and other espite considerable efforts sity of the care at this specific patient injury despite negative CT and routine disease and patient specific endpoints. both in basic and clinical population might be influenced by a MRI exams. While a recent system- The above recognitions and the Dresearch, we have not seen a lack of enthusiasm about purported atic review indicates that premorbid inseminating work of the taskforce of major breakthrough in the care of the outcome—as a self-fulfilling proph- mental health is the most important the Common Data Elements—study head injured in the last three dec- ecy—leading to worse morbidity and determinant of outcome after mild group set the stage for novel research ades. Substantial hope was associated mortality figures. To this end, every brain injury, the “jury is still out” on initiatives aiming at the re-character- with the introduction of scientific effort should be made to provide state- how we should identify those patients isation of the disease itself applying evidence-based guidelines, however of-the-art care for the elderly sub- who are at risk after minor traumatic novel enrolment strategies no longer contemporary data on the epidemiol- group of traumatic brain injury victims brain injury and what measures should based on the ill-defined injury-severity ogy did not prove any alteration in the with early rehabilitation, as multiple be employed in their case. linked classification systems. This mortality figures of traumatic brain data indicate that such measures A major drawback hindering our novel approach is reflected in the injury. While some associate this with could actually lead to similar outcome better understanding of traumatic Int-BIR collaboration and its Euro- the lack-, or low rate of guideline- results observed in the young and mid- brain injury is associated with the pean part, the CENTER TBI project compliance, others, including the dle aged population. “one size fits all” approach that has supported by the FP-7 framework authors, primarily explain it as a result A considerable novel problem dominated the field of therapeutic programme of the European Union. of insufficient understanding of the In this work, more than 5,000 underlying pathobiology and inappro- Another factor that is slowing patients will be enrolled into three priate stratifications of the disease. strata such as patients taken care of at In order to provide proper answers down our understanding of trau- the emergency room (admitted to the to this challenge we have to under- floor), or to the intensive care unit. This stand the changing face of traumatic matic brain injury is derived from study does recognise the heterogeneity brain injury. More importantly, we the fact that our criteria used for the of care reflected in the application of should consider traumatic brain injury the principles of comparative effective- as a global problem. To this end, while stratification of traumatic brain ness research. Expected data will not in the western world the incidence of only help us to describe and character- traumatic brain injury is decreasing, injury are (at best) superficial or ise traumatic brain injury in a novel, and the preponderance of falls in com- ill-defined and outdated. far more comprehensive way, but also parison to motor vehicular accidents is include biosamples for biomarker and increased, in developing countries the primarily, but not exclusively, affect- trials as well as clinical care. This genetic analysis, as well as information growing motorisation and the con- ing the aged population, is the more approach is primarily based on the from physiological monitoring also tinuous baby boom leads to increased frequent occurrence of altered haemo- premise established in the experimen- serving the purpose of legacy research. incidence among the young, active stasis due to vitamin K antagonist and tal laboratory settings that we should It is of note that funding for the population primarily related to road antiplatelet drugs. Recent studies es- standardise every parameter of the in- above programmes is only a fraction traffic accidents. tablished a direct association between jury and investigate alterations in one compared to the social and economic A general problem for the more platelet inhibitors and poor outcome in single measure—than apply the results burden head injures are associated developed societies is the growing pre- traumatic brain injury. Novel oral an- to every patient. This approach simply with worldwide, however, this ambi- ponderance of the geriatric population ticoagulants—direct thrombin and Xa does not recognise that head injury is tious project and its international sis- among head injured. Due to comor- factor-inhibitors—represent a major a complex disease affecting the most ter programmes should represent the bidities and side effects of medications challenge as their therapeutic effect is complex organ of man, also disregard- first step towards a better understand- causing reduced function of the sensory hard to monitor and there is no proven ing the extreme heterogeneity of the ing and care for the silent epidemic organs and dizziness, the elderly have therapy to revert their action. head injured population as well as the represented by traumatic brain injury. higher tendency to fall; this subpopula- Contemporary scope of traumatic substantial—and well documented— tion is also characterised with signifi- brain injury research has been substan- regional differences in health care András Büki is professor and chair- cantly reduced physiological reserve tially altered by recent data from the systems. Another factor slowing down man, Department of Neurosurgery, capacity and reduced scavenge mecha- Track-TBI collaborative group leading our understanding of traumatic brain Pécs University, Pécs, Hungary nisms of oxidative stress. to the recognition that our apprecia- injury is derived from the fact that Caregivers should face new chal- tion of mild brain injury (mTBI) might our criteria used for the stratification Andrew I R Maas is professor and lenges with increasing proportion be wrong and even a single episode of of traumatic brain injury are (at best) chairman, Department of Neurosur- of the elderly population; recently CT-negative mTBI may lead to struc- superficial or ill-defined and outdated, gery, University Hospital Antwerp, published data indicate that the inten- tural damage in the brain demonstrat- most of them lacking any pathobio- Antwerp, Belgium

16 Telemedicine November 2014

was already good at the beginning but still improved over the last 10 years, as illus- TeleStroke Units improve stroke trated by the growing percentage of stroke patients admitted to hospitals with a Tel- eStroke Unit (from 19% to 78%). A Stroke care in underserved areas Unit admission rate of 78% in a rural area Units. The median time between a patient’s is high, but indeed it is not satisfactory. The arrival until thrombolysis was administered goal should be close to 100%. To achieve fell from 80 minutes to 40 minutes; exceed- this aim, in 2013 we started to set up ing American Heart Association/American further TeleStroke Units in administrative PETER MÜLLER-BARNA Stroke Association’s “Target: Stroke” goal districts so far lacking a (Tele-)Stroke Unit. of treating at least 50% of patients within All regions without direct access to a 60 minutes. The median time between Stroke Unit (or primary stroke centres) onset of stroke symptoms and receiving are candidates for a TeleStroke Unit. If COMMENT & ANALYSIS thrombolysis decreased from 150 minutes sufficient local stroke expertise is available, to 120 minutes. From 2003 to 2012, the a Stroke Unit can be run without telemedi- n rural areas inhabitants often do not including evaluation of brain imaging and proportion of patients transferred to stroke cine. However, TeleStroke Units can be have direct access to specialised Stroke patient examination via videoconferencing centres from regional hospitals fell from established within a short time, supported IUnits. But in fact, it is well known when needed. In addition to teleconsulta- 11.5% to 7%. by telemedical and educational expertise that Stroke Unit care improves prognosis tions, TEMPiS TeleStroke Units are also Therefore, we concluded that Telemedi- of tertiary stroke centres and provide of stroke patients and is therefore recom- supported by stroke centres in terms of cine improved and sustained high-quality high-standard Stroke Unit care to all local mended to all patients with stroke. It is education and quality management. In stroke care in rural Germany for patients stroke victims. For sure, network structures a major public health challenge to bring 2003, TeleStroke Units were introduced to without prompt access to specialised stroke always have to be adapted to regional stroke expertise to underserved areas. The 12 regional hospitals lacking neurology and centres. circumstances. use of telemedicine to ensure 24/7 access neurosurgery departments. Telemedicine The maximum time period of a Tel- In the hospitals with TeleStroke Units to consultation and care in rural areas is link them with two neurological stroke eStroke project observed prior to our study there are no neurosurgery departments one of the major recommendations of centres with vascular neurologists and is less than three years. There are reports available. The Telemedicine network is a the American Stroke Association in their other neurological experts. By 2012, there from South Carolina, USA (REACH great option to accelerate the emergency policy statement on systems of care. were 15 TeleStroke Units that had provided MUSC, 1,085 teleconsultations), Northern transfer of patients in need of neurosurgery. In our article (Müller-Barna et al, Stroke 31,864 consultations. Alberta, Canada (210 teleconsultations) At the same time, telemedicine helps to 2014) we present data about the largest Between the first year of implementa- and Finland (106 teleconsultations). Over avoid unnecessary transfers, because expert and longest evaluation of telemedicine for tion and the end of 2012, the percentage of the ten-year period, a total of 31,864 vascular neurologists serving as telecon- stroke. It is about the TeleMedical Project patients with stroke or transient ischaemic teleconsultations were performed in the sultants are involved in remote patient for Integrative Stroke Care (TEMPiS) in attack of the rural area served, who were TEMPiS network. assessment by video-examination and rural Bavaria, Germany. With the tel- treated at hospitals with TeleStroke Units The most important point was to get interpretation of CT-scans. emedically linked Stroke Units (TeleStroke rose from 19 to 78%. The number of acceptance of the TeleStroke Units by Units), patients in regional hospitals have patients receiving intravenous thrombolysis the emergency services and the general Peter Müller-Barna is at the Department around-the-clock access to consultations increased from 2.6 to 15.5% of all ischae- physicians, but also by the population and of Neurology, Krankenhaus Agatharied, with vascular neurologists at stroke centres, mic strokes admitted to these TeleStroke political representatives. The acceptance Norbert-Kerkel-Platz, Hausham, Germany November 2014 ADVERTORIAL 17

16 LINNC SEMINAR 2015 - A new course not to be missed November 2014 The LINNC SEMINAR takes form! LINNC Seminar is a LINNC extension, a new concept with the same spirit

Jacques Michel Laurent Moret, E. Mawad, Spelle, MD MD MD SEMINAR US EDITION COURSE DIRECTORS What was the motivation interaction and knowledge. This second application of these systems as well as general; specific AVMs such as of those for developing this new point led us to build the scientific pro- the clinical benefits of their use. of the marrow (spine and spinal cord), gram of LINNC Seminar – US edition spinal dural AVMs; the management of concept? around pre-recorded cases. complications, cerebral stroke, and also Within a specialty as vibrant and in How will you stimulate These cases, which will come from the the possible discussion on percutaneous constant evolution as our own, one of debate and discussion with Neuri Center Beaujon in Paris - France, techniques. As always, we are dedicated greatest challenges is to keep abreast of the St. Luke’s Episcopal Hospital, Hous- attendees? to offering an educational experience changes in information, technique and Beyond the choice of subjects and their ton - TX and the UPMC Stroke Institute, that can have an immediate and positive practice which seem to occur every presentation to the participants, using Pittsburgh - PA, have been carefully impact on the daily practice of physi- week. Working together, the L INNC pre-recorded cases also offers something chosen to create illuminating discussions cians. Thus the idea of creating this new community has responded to this which is inestimable – the actual expe- using the widest selection of patients and “seminar” is in keeping with our overall challenge with the creation of unique rience and presence of the operator who indications as well as the largest variety commitment to provide the highest pedagogical tools specially designed performed the case. You will have the of technical equipment in use today. quality of clinical and theoretical knowl- to reflect the state of the art in interven- specialists themselves, discussing their edge and information in a forum that tional neuroradiology and neurosurgery. every therapeutic gesture and act with emphasizes interactivity and encourages In 2015, in addition to the annual LINNC What are the advantages attendees. We cannot emphasize how participation. PARIS COURSE (which will be held on offered with pre-recorded valuable and essential the contribution of June 22-24, 2015 in Paris, Carrousel du cases? attendees is to this new LINNC Seminar. We look forward to seeing interventional Louvre) we propose today the latest fruits • By being pre-recorded, the presenter It is the participation, the willingness neuroradiologists and neurosurgeons in of our efforts with a new educational can lead the discussion where it needs to to share with us their own cases and New York in the spring of 2015 for a new tool: the LINNC SEMINAR. go, sensing and following the needs of concerns is one of the foundations of educational adventure. The first one, the US edition will be the audience as they arise. our pedagogy. At the LINNC Seminar held in New York City on Friday, March • This is also true for pre-recorded cases – US edition, this interaction will be 27th and Saturday, March 28th, 2015. An showing exceptional or rare situations underlined each day with the presentation LINNC SEMINAR 2015 - exciting new course born out of the same where the success of the treatment has of the best cases submitted by, the US EDITION attendees. We urge them to submit their spirit of innovation and experience that been shown to be effective… offering cases now (www.linnc.com) and become • Dates: March 27-28, 2015 characterizes LINC Houston, LINNC participants the possibility of sharing an important part of the program! • Meeting Location: Husdon Paris and LINNC online. clinical expertise. Theatre at Millennium Confe- • The careful choice of these cases allow rence Center. Why call it a seminar? us to present situations where complica- What are the main topics There is no accident in our choice of tions and the way they are handled can that will be discussed and • Accommodation: Millennium Broadway Hotel. terms and the architecture of this new be most effectively illustrated, regardless your learning objectives? course leaves nothing to chance…. of whether the chosen approach was the This, of course, has required a certain • Address: Times Square except the challenge of interaction and correct or incorrect way to handle the degree of preparation and for months we 45 West 44th St, New York, NY participation. In choosing to create a clinical problem; all is part of a creative have been working on identifying those • Early Bird Registration: January seminar, we look towards two goals: first, and open learning experience. cases that best fit the stringent require- 18th, 2015 to ensure the quality of exchange be- • Carefully choosing cases in advance ments of our pedagogy. These recorded tween the lecturers and the participants using the most sophisticated imaging case sessions will include discussion by Registration & Information: and second, to ensure the presentations systems available allow us to demon- an expert panel concentrating on specific www.linnc.com lend themselves to the highest quality of strate in the greatest detail the practical topics such as: aneurysms; AVMs in

LINNC SEMINAR - US EDITION SEMINAR March 27-28, 2015 US EDITION

New York City, NY, USA LINNC Seminar is a LINNC extension Millennium Conference Center a New Concept with the Same Spirit !

Live Interventional Neuroradiology & Neurosurgery Course www.linnc.com 18 Research November 2014 New electroencephalogram electrode set for emergency care developed in PhD study As part of his PhD study at the University of Eastern Finland, Pasi Lepola has developed a new, easy-to-use, disposable electroencephalogram (EEG) electrode set for the measurement of electrical activity in the brain. Lepola speaks to NeuroNews about this new EEG technology which uniquely allows the electrode set to be attached to the patient quickly, without any treatment to the skin.

How is the EEG electrode patient’s movements or patient transfer. set developed in your In addition, the EEG electrode allows research different to other record EEG recording without skin electrode sets currently in abrasion, which is a time-consuming use? procedure and may cause pain. Although the clinical importance of emergency EEG is widely recognised, How was your EEG there are still impediments to the routine electrode set developed use of EEG in emergency medicine. One and produced? What does it major obstacle is related to impracti- consist of? cal electrode solutions available on the Electrodes (16, 2xREF, 2xGND, 2xEOG, market. The attachment of traditional Fp1, Fp2, Af7, Af8, F7, F8, Sp1, Sp2, EEG electrodes according to the 10−20 T9 and T10) and conduction traces were EEG electrode set electrode system is a difficult and time- printed with silver directly to a flexible consuming process. polyester film in a flat-bed sheet silk EEG abnormalities were 83% and 100%, the conventional 10−20 electrode setup Unlike in the traditional EEG method, screen printing unit. The encapsula- respectively. The sophisticated screen- is not available or feasible, particularly the EEG electrode set is placed below tion was printed with insulation paste printed electrode structure with adhesive emergency use (Emergency Rooms, the hairline. Short setting time is a major with the same screen printing unit. The hydrogels enables stepwise attachment of ambulances etc). In addition, based on advantage in emergency situations where electrode positions of the screen-printed electrode set within a few minutes. The the present results, this EEG electrode time matters. The flexible polyester EEG electrode set were covered with an screen printing technology allows low-cost set might become a potential first-line body of the screen-printed electrode set adhesive hydrogel membrane to improve mass production of disposable electrode screening tool for non-convulsive status follows smoothly the surface and move- contact with the skin. Skin attachment sets. MRI and CT images did not suffer epilepticus. Because it is much easier and ments of the skin. The adhesive hydrogel was secured with non-conductive foam from clinically significant artifacts arising faster to attach than traditional meth- electrodes achieve a tight contact to the surrounding the hydrogel circles, which from the EEG electrode set, even when ods, we strongly believe in its potential. skin, which can significantly reduce the also prevents the gel from drying out. The equipped with a silver-shielding layer. Further, interest in the electrode set has motion artifacts usually caused by the final outshaping was performed with a However, further official standard tests exceeded all expectations. laser cutting technique to the pre-designed will be needed to guarantee the true MRI shape to allow a good fit onto the face. compatibility and safety. Going forward, what The shielding layer, particularly silver is the next step in the What were the results of ink, printed on the front side of the EEG development of this EEG your research? How was it electrode set effectively reduced interfer- electrode set and in your carried out? ence pick-up from external electromag- research? In the thesis, a disposable EEG netic fields. Therefore, it is easy to rec- Currently, further study with a larger electrode set for emergency use was suc- ommend the use of silver shielding in all number of patients is in progress. We cessfully developed. Its performance and screen printed electrodes. This is further will publish the results in peer-reviewed suitability for emergency use were inves- emphasised when measuring microvolt journals as soon as possible. Of course, tigated through electrical performance scale signals in interfering conditions. we have also a few other new research tests, EMC tests, CT and MR imaging, topics related to the EEG electrode set, and clinical EEG recordings. What potential does your but they are not public. On the other The EEG electrode set achieved good device have to change hand, because the Mega Electronics Ltd performance in signal quality tests even current practice? What do (Kuopio, Finland) acquired the rights without skin abrasion. The clinical question you think are the best uses to the invention [now commercialised could be answered based solely on record- of the device? as BrainStatus], they have the primary ings with EEG electrode set in most cases. The disposable EEG electrode set may responsibility for the further development Pasi Lepola The average sensitivity and specificity for be a solution for EEG registrations when of the EEG electrode set. Covidien begins enrolment in two neurovascular clinical trials ovidien has announced the start of enrolment in two unruptured, small and medium wide-necked intracranial rent endovascular stroke device in the USA is the Solitaire clinical trials designed to further underscore the aneurysms. 2 revascularisation device. Csafety and effectiveness of the company’s neurovas- “There is a need for an effective and sustained treat- “The STRATIS Registry will assess mechanical cular solutions. ment option for patients with wide neck small or medium thrombectomy as a treatment option in patients who cannot Baptist Medical Center in Jacksonville, USA, treated the intracranial aneurysms,” says Ricardo Hanel, neurovascu- get access to or are not eligible for IV t-PA,” says Curtis first patient enrolled in the PREMIER prospective study, lar surgeon with Lyerly Neurosurgery at Baptist Medical Given, co-director of neurointerventional services at Baptist an international Investigational Device Exemption (IDE) Center. “Redirecting blood flow away from the aneurysm Health Lexington. “It is very important to provide registry clinical study to evaluate the Pipeline embolisation device with the Pipeline device has been shown to reduce aneu- data to not only demonstrate the safety of a mechanical in smaller unruptured intracranial aneurysms. Separately, rysm recurrence and the need for retreatment in large and thrombectomy procedure on these patients, but also to track Baptist Health Lexington in Kentucky, USA, enrolled giant internal carotid artery aneurysms. This study will the outcomes, so we can compare the results to historical the first patient in the STRATIS registry for endovascular provide valuable clinical evidence in a new population of IV-tPA data. In some states, insurance carriers are refusing stroke devices, which will evaluate the use of all Covidien aneurysms.” to reimburse mechanical thrombectomy procedures, so it market-released stroke devices. The STRATIS registry is a prospective, multicentre, non- is vital that we collect the data to show not only safety, but The PREMIER study will enrol up to 141 patients in randomised, observational registry designed to evaluate efficacy, in order to ensure that we can continue to provide 20 global sites and is designed to assess the safety and the use of Covidien endovascular stroke devices in patients care to these patients that would otherwise not be offered effectiveness of the Pipeline device in the treatment of diagnosed with an acute ischaemic stroke. Covidien’s cur- any treatment for their stroke.” November 2014 Small-vessel disease 19

disease on the brain than do the individual Total small-vessel disease score: a new MRI features separately. It is a simple and pragmatic visual quantification of cerebral and pragmatic way to assess the full small vessel disease that can easily be performed in clinical practice. For research purpose, the total SVD score could be help- impact of small-vessel disease on the brain ful for baseline stratification or as a surrogate the Edinburgh research group tested in marker for small vessel disease in prevention a large ischaemic stroke sample (n=461 and therapeutic trials. In clinical practice, patients) whether the SVD score was as- it could be used to identify subjects at risk sociated with previously described vascular of stroke, cognitive decline and physical JULIE STAALS risk factors for individual SVD features. We impairments, although further studies for also tested whether SVD score was higher refinement and validation of the score are in patients with lacunar (small vessel) stroke needed. We hope that the implementation compared to cortical (large vessel) stroke. of the SVD score will contribute to a better COMMENT & ANALYSIS Our results were recently published in understanding of cerebral small-vessel Neurology. disease, in the end leading to better treat- erebral small-vessel disease (SVD) tensities, perivascular spaces in the basal We showed that higher total SVD score ment strategies. is a prevalent age-related disease ganglia, and cerebral microbleeds. They was associated with age, male sex, hyperten- Cof the brain. It is a common cause are considered ‘MRI markers’ for cerebral sion, smoking and lacunar stroke subtype. Julie Staals worked with the Brain Re- of ischaemic (lacunar) stroke and deep small vessel disease (Figure). Furthermore, lacunar stroke patients had search Imaging Centre, Edinburgh, UK, haemorrhagic stroke. It may also lead to One of the reasons for the insufficient higher ratings of SVD burden compared and is currently at the Department of gait disturbances, cognitive impairment knowledge about cerebral small-vessel with cortical stroke patients. Neurology and Cardiovascular Research and even dementia. It has growing impact disease is that research always focused on The score provides a more complete Institute Maastricht at Maastricht Uni- on the ageing society and health care sys- individual radiological features, ignoring overall view of the impact of small-vessel versity Medical Center, the Netherlands tem worldwide. Age and hypertension are the co-occurrence of these features. We considered the most important risk factors. think that an imaging scale that integrates all There are multiple gaps in our knowl- four MRI features of cerebral small-vessel edge about the pathogenesis and even the disease would better capture the overall ‘standard’ vascular preventive treatments burden and impact of the disease and would have no convincing proven benefit for improve the assessment of disease severity. cerebral small-vessel disease. Recently, the Maastricht neurovascular Radiologically, the cerebral small ves- research group proposed a simple method sels cannot be visualised. The structural to assess the overall burden of cerebral consequences on the brain parenchym small-vessel disease: one point is assigned are therefore used to study the underly- for the dichotomised presence of each of Total SVD score is composed of 4 MRI markers: (from left to right) FLAIR MR image ing small vessel disease. These structural the four MRI markers, adding up to a 0 to 4 showing lacunes and white matter hyperintensities; T2 MR image showing perivascu- features that can be seen on conventional composite SVD score. lar spaces in basal ganglia and white matter hyperintensities; FFE MR image showing MRI are: lacunes, white matter hyperin- To further validate this total SVD score, cerebral microbleeds. 20 Updates November 2014

and actively discourages this practice; however, it is reasonably commonly used that way. Indeed, the Impact Factor is not Impact“ful” moments without controversy. In December of 2012 calendar years 2011 and 2012 was cited the San Francisco Declaration on Research twice in calendar year 2013, the 2013 Im- Assessment (DORA) took form. In es- pact Factor of our newly created journal sence, DORA takes issue with the use of would be two. In reality, the calculation is the Impact Factor as a method of evaluating JOSHUA A HIRSCH more complicated than this. For example, the merit of an individual scientist; a role, the 2013 Impact Factor is published in one could argue, that the Impact Factor was 2014. Moreover, not all materials printed never intended to assume. The Declaration, in a journal are included in the analysis which was published in May of 2013, has COMMENT & ANALYSIS that determines Impact Factor, just articles achieved fairly a reasonable measure of that are termed “citable items.” (See M support from a broad constituency. Once a year, in almost ritualised fashion, the editors of peer- E McVeigh, S J Mann, JAMA, 302 (10): One thing is for certain, 2015 will reviewed journals anxiously await publication of the Thomson 1107-9, 2009.) likely not be different than 2014 or to Reuters Impact Factor. Journals in the “neuro” space are no Review articles tend to be the most often prior years as editors and publishers of exception to this rule. In this commentary, Joshua A Hirsch cited type while case reports are least cited. journals “ritually” await publication of provides a background on the meaning of “impact factor”. This can have a number of distinct influ- the prior year’s Impact Factor. ences on publications found in journals. n 1955, Eugene Garfield proposed derived. Since 1975, using these citation The importance attached to the Impact Joshua A Hirsch is the director of Inter- the idea of an impact factor to figures, Impact Factors have been calcu- Factor likely varies by environment. It is by ventional Neuroradiology/Endovascular Iidentify the most significant journals lated for the academic journals covered its nature not designed to evaluate the im- Neurosurgery at Massachusetts General in a given field; originally, the measure by the former ISI, now officially known portance of an individual article or author, Hospital, Boston, USA was intended as an aid to librarians for as the Intellectual Property & Science and Thomson Reuters expressly disavows building and maintaining their journal business of Thomson Reuters. collections. Impressively, he founded the In selecting journals for indexing (and, American Journal of Neuroradiology 3.675 Institute of Scientific Information (ISI) in ultimately, for an Impact Factor calcula- Interventional Neuroradiology 0.773 Philadelphia, USA prior to receiving his tion), specialists in journal coverage at doctorate in Structural Linguistics from Thomson Reuters follow a methodology Journal of Neuroimaging 1.818 the University of Pennsylvania in 1961. of evaluation that has been described at Journal of NeuroInterventional Surgery 2.495 ISI’s flagship product, and another Gar- http://sciencewatch.com/articles/connect- Journal of Neurology, Neurosurgery and Psychiatry 5.58 field innovation, was the Science Citation ing-dots-it-all-starts-data. Once a journal Index (SCI), which, at the time, collected is selected, Impact Factors are calculated Journal of Neurosurgery 3.15 publication and citation data on roughly once per annum for those journals, and Neurology 8.25 4,000 journals. Today, the SCI’s online the figures are reported in the Thomson Neuroradiology 2.374 descendant, the Web of Science, covers Reuters Journal Citation reports. more than 12,000 journals. In addition to How is the Impact Factor calculated? A Neurosurgery 3.031 providing current awareness on topics in journal’s impact factor represents the aver- Stroke 6.018 the journal literature to ISI’s customers, age number of citations for each paper that the SCI generated the citation data from had been published in the prior two years. Recent Thomson Reuters Impact Factors of various journals in the “neuro” space. Data which the Impact Factor was (and still is) For example, if each article published in was gathered from the World Wide Web

Neuravi receives US patents The EmboTrap received CE mark ap- for neurovascular clot proval in 2013 and is not yet available for capture and retrieval use in the United States. Product News Neuravi has announced that the US Patent Office has approved two patents covering FDA and CE mark approval its therapeutic platform for the endovascu- for new CoverEdge surgical Codman Neuro launches first “The dual irrigation design is ideal for lar treatment of acute ischaemic stroke. leads disposable forceps with dual working with arteriovenous malforma- The granting of US Patent #8,852,205 Boston Scientific has received US Food irrigation tions and vascular tumours as they keep “Clot Retrieval Device for Removing and Drug Administration (FDA) and CE Codman Neuro has announced the launch the tips and vessels moist enhancing their Occlusive Clot from a Blood Vessel” and mark approval for the CoverEdge 32 of Spetzler Malis dual irrigating dispos- non-stick properties, and the transparent US Patent #8,777,976 B2 “Clot Capture and CoverEdge X 32 surgical leads. able non-stick bipolar forceps, the first fine tubing provides better visualisa- Systems and Associated Methods” expands Accoridng to a company release, the disposable dual irrigating forceps for tion,” says neurosurgeon Robert Spetzler, Neuravi’s US granted portfolio to 33 pat- world’s first 32-contact surgical leads are neurosurgery. director, Barrow Neurological Institute ents. These new patents disclose unique de- designed to blanket the spinal cord for Spetzler Malis dual irrigating forceps in Phoenix, Arizona, USA. “The Spetzler sign elements intended to enable both clot unprecedented pain coverage. Designed is the first disposable device to have Malis disposable bipolar forceps line has disengagement and capture and so facilitate for use with the Precision Spectra spinal irrigation channels inside both of its been designed to be non-stick, low pro- the protected removal of hazardous clot cord stimulator system, the CoverEdge branches, offering precise delivery of flu- file, and provide great tactile feedback.” from the brain. The CE-marked Embotrap surgical leads are powered by the Illumi- id through each forceps tip for improved According to Codman Neuro, the dual revascularisation system incorporates these na 3D software, a proprietary, anatomy- and uninterrupted visualisation. The irrigating forceps is the latest addition to advanced features into its design. based computer model for precise pain device also provides the same non-stick the Spetzler Malis forceps product line, The Embotrap revascularisation device targeting. coagulation performance as the industry following the launch of Spetzler Malis takes an inside-out approach to rapidly and Previous surgical leads have deliv- leading standard version of the Spetzler slim non-stick bipolar forceps earlier safely restoring blood flow to the affected ered pain therapy with a maximum of Malis disposable bipolar forceps. this year. Spetzler Malis slim forceps brain tissue. The device is designed to trap 16 independent contacts. By offering 32 have the slimmest profile available on the clot inside a proprietary structure that contacts – each powered by a dedicated the market and provide access to nar- the company calls a Stent-Trap while the power source – CoverEdge surgical leads row surgical fields. Standard Spetzler device restores blood flow to the brain. are designed to deliver more focused Malis disposable forceps have been The Stent-Trap structure is engineered to coverage of the spinal cord for more available since 2006. This family of retain the clot during the retrieval process, pain relief. Available in two configura- forceps features an ergonomic design and features a multi-dimensional fragment tions, the CoverEdge 32 surgical lead that provides excellent visualisation and protection zone. Physicians have observed features 32 tightly spaced contacts in control, which is especially important that minimising distal and new territory four columns for precise pain targeting. when operating on deep-seated tumours embolisation during endovascular stroke The CoverEdge X 32 surgical lead offers or vascular structures, and during skull- therapy may play an important role in the broadest span on the market among Spetzler Malis forceps based neurosurgery. patient outcomes. multi-column paddles. November 2014 Market watch 21

will be compared in the study arms with targeting that is designed to manage es- cal business as part of its Neurovascular and without cerebral protection. sential tremor symptoms effectively and product line in the Medical Devices seg- improve patient quality of life.” ment. Annualised dilution is not expected Medina Medical announces “The Vercise deep brain stimulation to be material. CE mark for its embolisation system features multiple independent Reverse Medical is currently commer- coil current control, which gives clinicians cialising its vascular embolisation plugs, Medina Medical has received CE mark the ability to control stimulation precisely MVP Micro Vascular Plug System and authorisation for its Embolisation Fram- for a neural target to help minimise un- UNO Neurovascular Embolisation Sys- ing Coil for commercial distribution in wanted side effects,” says Timmermann. tem. MVP and UNO are self-expanding the European Union. “The 25 year battery life may also help vessel occlusion devices, which close CoverEdge surgical leads The Medina Embolisation Framing reduce the frequency of surgical interven- blood vessels for vascular embolisation. Coil is used to treat brain aneurysms tions to replace depleted batteries.” A number of clinical applications require “I see the CoverEdge surgical leads using minimally-invasive techniques, and occlusion of the vasculature to rapidly, as a game changer for patients,” says is delivered like other embolisation coils Medtronic acquires Sapiens effectively and safely provide blood flow Giancarlo Barolat, medical director of through a micro-catheter that has been Steering Brain Stimulation cessation. Barolat Neuroscience in Denver, USA. threaded through blood vessels into the Medtronic has acquired Sapiens Steering Other Reverse Medical products “Because it provides greater coverage aneurysm. The novel Medina Embolisa- Brain Stimulation (Sapiens SBS) for include ReVerse Microcatheter for device of the spinal cord, I believe this product tion Framing Coil is designed to occupy approximately US$200 million in an all- delivery and Barrel Vascular Reconstruc- will give patients, especially those with space efficiently within an aneurysm. cash transaction. tion Device (VRD), a self-expandable low back pain or pain in multiple areas, a Sapiens SBS, located in Eindhoven, bifurcation aneurysm bridging device. better opportunity for relief.” EBS expands commerciali- The Netherlands, is developing a deep All the devices have received CE Mark The combination of the CoverEdge sation of Next Wave non- in- brain stimulation system that features an approval and are commercially avail- surgical leads with the Precision Spectra vasive electrical brain stimu- advanced lead with 40 individual stimu- able in Europe. Additionally, MVP-3 and spinal cord stimulator system and Illu- lation device lation points. This system is designed MVP-5 are 510(k) cleared in the USA. mina 3D Software is designed to deliver EBS Technologies has opened its first to allow more precise stimulation of spinal cord stimulation in new ways. For ophthalmologic clinical site in Germany the intended target in the brain and may CE mark for new Asahi example, a key challenge in spinal cord that is offering the use of the EBS Next potentially result in reduced procedure Intecc neurovascular guide stimulation therapy is stimulating the Wave brain stimulation device designed time and fewer stimulation-induced side wires neural target without stimulating unde- to expand the visual field of patients with effects. Asahi Intecc has received CE certifica- sired areas. By taking into account the impaired vision caused by glaucoma, Employees at the Eindhoven facility tion of neurovascular guide wires: Asahi conductivity of 3D anatomical structures stroke and other neurological diseases. will continue to work toward bringing Chikai 008, Asahi Chikai black, and and physician placement of the spinal EBS announced that a clinical study this technology to market. In the future, Asahi Chikai black 18 and is initiating cord stimulator leads, the Illumina 3D (“Brain functional connectivity network the site will serve as a global research sales in Europe. Software is designed for simple point- breakdown and restoration in blind- and development centre for Medtronic’s According to the company, the above and-click pain targeting. ness”) published in the journal Neurology Neuromodulation business. wires join the currently marketed Asahi validates non-invasive brain stimulation Medtronic and Sapiens SBS will work Chikai and Asahi Chikai 10 in incor- First patient treated in US for restoring partial vision to an impaired to finalise product development and porating Asahi Intecc’s unique Actone pivotal trial evaluating eye; the company’s Next Wave system is begin clinical research to integrate these technology, which provides improved cerebral protection during a non-invasive brain stimulation device technologies into an expanded portfolio torque performance, shape retention and TAVI that is designed to expand the visual field of deep brain stimulation products within support. One of the new wires, Asahi Claret Medical has announced that the of patients with impaired vision caused Medtronic’s Neuromodulation business. Chikai 008 is designed to deliver the flow first patient has been successfully treated by glaucoma, stroke or other neurological directed microcatheters that are used for in its SENTINEL trial in the United disorders. Next Wave is approved for sale Covidien acquires Reverse the arterial venous malformation treat- States, a multicentre pivotal trial of the in Europe. Medical Corporation ment. Asahi Chikai black 18 is designed Sentinel Cerebral Protection System Covidien has announced that it has to deliver microcatheters for stent assist (CPS). The landmark SENTINEL trial CE mark for Vercise deep acquired Reverse Medical Corporation, procedures, flow diverters, stroke devices is the first prospective, randomised, brain stimulation system for a privately held medical device company and other devices that require large in- controlled, blinded trial in the USA to patients with tremor focused on expanding the management of ner lumen diameter catheters. The third evaluate the role of cerebral protection Boston Scientific has received CE mark vascular disease. Financial terms of the wire, Asahi Chikai black is a 0.014 inch during transcatheter aortic valve implan- approval for the Vercise deep brain transaction were not disclosed. workhorse wire for neuro endovascular tation (TAVI). stimulation system for the treatment of “Covidien is focused on technolo- procedures. Unlike the Asahi Chikai, the The first patient was treated at New tremor, including the most common form gies that deliver improved patient care Chikai black has a polymer jacket over York and Presbyterian Hospital/Co- of this movement disorder known as es- through clinically relevant and economi- the spring coils to facilitate enhanced lumbia University Medical Center by sential tremor. cally valuable solutions,” says Brett Wall, lubricity. Susheel Kodali, a national co-principal Experts say essential tremor may be president, Neurovascular, Covidien. Masahiko Miyata, president and chief investigator for the trial. The SENTINEL as much as 20 times more prevalent than “The acquisition of Reverse Medical is executive officer of Asahi Intecc com- trial will evaluate up to 284 patients at up Parkinson’s disease. The Vercise deep complementary to our existing portfolio ments, “Developing and manufacturing to 15 centres nationwide. brain stimulation system is the first sys- and will allow us to leverage existing various sizes and designs of the neuro- The primary endpoints for the SEN- tem designed to offer precise neural tar- vascular technologies to compete in the vascular wires in response to the neuro TINEL Trial are the reduction in total geting, allowing physicians to customise worldwide vascular embolisation market, interventionalists’ needs will contribute new lesion volume as determined by therapy for patients with essential tremor. which is growing at a double digit rate.” to the expansion of neuro endovascular diffusion-weighted magnetic resonance It also features a rechargeable battery that Covidien will report the Reverse Medi- therapy and ultimately benefit patients.” imaging (DW-MRI) and major adverse can last up to 25 years. cardiac and cerebrovascular events One of the first commercial implanta- (MACCE). A number of secondary tions of the Vercise deep brain stimula- endpoints, such as neurocognitive and tion system for essential tremor was histopathological outcomes during TAVI, performed at the University Hospital Cologne, Germany, by a team of physi- cians, led by Veerle Visser Vandewalle, head of the Department of Stereotaxy and Functional Neurosurgery, and Lars Tim- mermann, neurologist and professor of Neurological Movement Disorders. “Essential tremor can be very de- bilitating for patients in their day-to-day activities such as writing and eating,” says Vandewalle. “The Vercise deep brain stimulation system provides advanced Vercise tremor care through precise neural Chikai black 22 Market watch November 2014

NeuroNews Product News team

Editor-in-chief: Stryker Neurovascular launches is the softer and smaller Trevo Retriever, Dr Andrew Platts three new technologies in with softer radial force compared to Prof Philip M Meyers Europe Trevo XP 4x20mm (n=3) and Solitaire FR Stryker Neurovascular has announced the 6x20mm and 4x20mm (n=5) and smaller Publisher: launch of three new technologies designed diameter (3mm, as labelled) compared to the Stephen Greenhalgh to improve physician experience in aneu- diameter of the Trevo XP 4x20mm (4mm, as rysm and acute stroke interventions. labelled). A company release adds that the Revive SE thrombectomy device Head of Publishing: According to the company, the Surpass Trevo XP Marcio Brito Streamline flow diverter with its streamlined ProVue 3x20mm is a softer retriever de- The Revive SE Device is designed to ease delivery system is the only flow diverter signed specifically for right sizing in smaller navigation through small and tortuous blood Editor: that can be repositioned both proximally vessels. vessels and arteries in the cerebral vascula- Amanda Nieves and distally. It features the Pilot technol- ture. The new device enables rapid restora- [email protected] ogy, which can be used to precisely place Revive SE thrombectomy tion of blood flow to the brain during an the flow diverter and is designed to enhance acute ischaemic stroke. device approved in China, Editorial contribution: vessel apposition. It is designed to: recap- “We are pleased to offer the Revive SE de- South Korea and Taiwan David Brennan ture, reposition, redeploy. Codman Neuro has announced regulatory vice in these countries, which have a high in- The Surpass Streamline flow diverter has approval from the China Food and Drug cidence of stroke and an increasing need for Design: CE mark approval, but is not available for Administration (CFDA), South Korea’s new and advanced treatment options,” says P David Reekie sale in the United States. Ministry of Food and Drug Safety (MFDS), Laxmin Laxminarain, worldwide president of Secondly, the Target Nano detachable and the Taiwan Food and Drug Administra- Codman Neuro. “Codman Neuro continues coils, according to Stryker, offer the softest tion (TFDA) for the company’s Revive SE to expand its presence throughout the world Layout: coiling technology with advanced micro- Thrombectomy Device, a next-generation with existing and new solutions that fill clini- Tim Parker catheter stability and are now available in 2, self-expanding clot removal device intended cal needs and improve patient care.” 2.5, 3, 3.5mm sizes. to restore blood flow in patients with acute The Revive SE Thrombectomy Device is Advertising: Additionally, Stryker has launched the ischaemic stroke secondary to intracranial not currently approved for distribution in the Shilpa Suthar Trevo XP ProVue Retriever 3x20mm. This occlusive vessel disease. United States. [email protected]

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