So now we'll move on to our abstracts, a late-breaking abstract presentation. Complete six-month primary endpoint results from a prospective INSPIRE study of the investigational neurospinal scaffold in acute thoracic complete spinal cord injury by K. Stewart Lee. Thank you, Ryan. I promise that this talk will not be nearly as exciting as the last one. Thank you for allowing us to present the results of the INSPIRE trial. Disclosures are shown here. The neurospinal scaffold is a device developed by Dr. Robert Langer for implantation into the spinal cord at the site of spinal cord injury. The device itself is a small porous structure made of polyglycolic acid, essentially vicryl suture, and polylysine. These, polylysine in particular, has been shown to enhance neural sprouting. In rat contusion models of acute spinal cord injury, the placement of the scaffold has been shown to decrease the size of a residual cavity, spare white matter tracks, and promote an environment of remodeling of tissue. The INSPIRE trial was designed to determine if the scaffold is safe, and also whether there's any efficacy in the patients who have acute thoracic spinal cord injuries, complete injuries, when the device is implanted within 96 hours of injury. The primary endpoint was AIS conversion by six months, and the objective performance criterion was that 25% of the patients in the study would convert an AIS grade, go from complete to incomplete within six months. Large natural history registries and databases would suggest that in complete thoracic spinal cord injury, only about 12 to 16% of patients would convert at six months. The key eligibility criteria are shown. All these patients were complete. They had a T2 to T12 neurological level of injury. They had to have a visible contusion on an MRI, so that we hoped that the contusion would lead to a cavity within the cord. All of these patients were already undergoing stabilization surgery within 96 hours of injury. There were no incomplete patients included, no penetrating injuries, no cord transections by MRI. Patients who had significant traumatic brain injury were excluded, because all these patients required a very detailed INSCE exam before surgery, so if they had a significant brain injury, obviously they could not participate in the INSCE exam. Patients with significant neurologic comorbidities, such as prior stroke, MS, were excluded. And these seem pretty simple, but as we all know, these patients usually have significant multiple injuries, and they're quite sick, and so this actually proved to be a very difficult trial in which to enroll patients. The procedure itself, at the time of stabilization surgery, a decompressible laminectomy is done at the site of injury. Ultrasound is used to determine the maximum site of contusion. The dura is opened. A myelotomy is performed if necessary. Most of these patients did have a myelotomy. There were a few who had open injuries in the cord, and at the time the dura was opened, the cord itself was open. General irrigation is done to remove the necrotic debris and expose the cavity. The scaffold comes in two and three millimeter diameters, and is a centimeter long. Could be trimmed, if necessary, lengthwise, but the correct scaffold size was decided upon, and the scaffold is implanted lengthwise, as you see here. One side note of the INSPIRE trial is that this gave us an opportunity to look at the pathology of acute human spinal cord injury, something that's generally done at autopsy. Not surprisingly, it's very similar to animal models of acute spinal cord injury. This patient was operated on at 40 hours post-injury. The left slide's a little blurry because it was taken from a video in the operating room, but you see the arrow, which shows, at the time the myelotomy's made, this debris exudes out from the cord. That was collected, and not surprisingly, shows significant disruption of the neuropil, acute hemorrhage, acute inflammation, and they're already at 40 hours axonal retraction bulbs. So this was a side note. We did get pathology in most of the patients. 19 patients had a scaffold implanted at 11 sites across the US. Neurologic outcomes, there were really no predictors of who was going to convert at six months. Seven of 16 patients, or 44%, converted at six months. Three patients who were AISB at six months actually had late conversions at either 12 or 24 months to AISC. Three patients died within two weeks of scaffold implantation. It was determined that neither their spinal surgery nor the scaffold itself were related to their deaths. Again, all these patients had significant other injuries. In an effort to try to compare the INSPIRE group to the natural history, a study called the Contempo study was done. This was actually presented by Dr. Jim Guest from Miami at the Spine Summit recently. But three natural history databases were queried in an effort to get a similar group of patients to those in the INSPIRE trial. So they were all injured between 2006 and 2016. They were all complete, T2 to T12 injuries. They had to have a baseline INSKE exam and an INSKE exam at six months. And actually, many of the patients in these registries do not have INSKE exams. The conversion rate of the INSPIRE group is shown on the left graph in blue, and the conversion rates of the patients in the other series are shown towards the right of that slide. And then on the right graph, you can see the patients at AIS grade at six months in the various registries. Conclusions, implantation of the scaffold is safe in the setting of acute complete thoracic spinal cord injury. There is no major morbidity directly related to the implantation of the scaffold. The primary endpoint of AIS conversion at six months was achieved in 44 of those patients available for followup, which was greater than the 25% objective performance criterion of the study. The 44% AIS conversion rate at six months was also greater than the approximately 20% conversion rate in the Contempo comparative group. So these results would encourage further investigation into the scaffold. Therefore, the FDA recently approved what is called INSPIRE 2.0. It's going to be a randomized trial in which 10 patients will be randomized to standard care, which is surgical stabilization, and the other 10 will be randomized to have stabilization plus the scaffold. We're hopeful that that trial can begin sometime later this summer or early fall. And finally, on behalf of all the investigators in the trial, we would like to thank our very courageous patients who agreed to participate in this study. As we all know, we added a significant potential complication by opening the Dura, and so we're very grateful for their participation. Thank you very much. This paper will now be discussed by Sanjay Dowell. I'd like to thank the AANS for allowing me to discuss this really exciting trial. Here are my disclosures. So as mentioned, this is a trial that basically focused on complete or AISA thoracic cord injuries. They essentially, what they did was they performed a durotomy, and for the most part, myelotomies. They're actually cutting the spinal cord open and placing the scaffold into the intramedullary cavities. Obviously, this is a very bold study and very unique. So the results have already been discussed. I think the most interesting part of the results is that there were those patients that, I think approximately three of them, who converted their neurologic status, a very severe certain neurologic injury, in a very delayed fashion. And that is quite unique for a thoracic injury, and it really invokes some questions about what is happening in the spinal cord at this later date. Now, there were some issues with the study. For example, if you look at the timing of surgery, it's quite variable. It ranged from nine hours to three and a half days, which is a huge range. At least in the abstract that I received, there wasn't any mention about ICU care, blood pressure goals, whether intraoperative monitoring was used, and the final question is, are these patients benefiting from a scaffold or from having their dura opened? So if you look at, first of all, the timing, we have, at UCSF, we have pretty robust data now that timing of surgery has a profound impact on the neurologic recovery after spinal cord injury. We've actually found that patients who have surgery within 12 hours have a significantly greater neurologic recovery. They actually will improve by more than one ASIA grade, and compared to the other conversion data that was just presented, 89% of our AISA patients will convert if they have surgery within 12 hours. Now, of course, this includes cervical patients and thoracic, so that is a bit of a confounder, but it's still a much, much higher conversion rate than in the literature. The other thing is evoked potential monitoring has grown in its value. We've been able to show that there's a dichotomy in complete patients. The patients that appear clinically complete with no motor function, no sensory function, no voluntary anal contraction, they're not all the same. There are patients that we take to the operating room and we do motor evoked potentials, and we actually are able to elicit an MEP, and those patients all went on to recover in our study as compared to patients without MEPs who tended not to recover. So finally, the other question that arises this study is unique because it asks the surgeon to open the dura, perform a myelotomy, place a scaffold, and then likely sew in a dural patch to close the dura back up again. Now, there's been really interesting work done in the UK on expansive duroplasty. They've been able to show that it improves cord profusion. Here are some images of a patient of ours that we performed this procedure on, and you can see the severe thoracic fracture dislocation, the durotomy that was performed, the very injured spinal cord, and then finally on the right, you can see a patch graft and you can see the intraspinal pressure monitor that's been placed. So this brings up the question, is the scaffold benefiting these patients or is the expansive duroplasty benefiting these patients? Nonetheless, I think Dr. Lee and the other authors and in vivo all really deserve congratulations on pursuing this very bold, very aggressive trial that I really absolutely applaud and I'm very excited by. I look forward to hearing more of their long-term data. I really hope that there'll be some consideration of a comparative study between duroplasty and duroplasty plus the scaffold. And thank you very much for your time. Thank you.

INSPIRE study

neurospinal scaffold

acute thoracic complete spinal cord injury

conversion rate

INSPIRE 2.0