Stroke Treatment Update | Dr. Victor C. Urrutia

Aug 26, 2023

Stroke Treatment Update | Dr. Victor C. Urrutia

In this installment of the Sheikh Khalifa Stroke Institute (SKSI) webinar series, Victor C. Urrutia, M.D., discusses treatments and new imaging techniques for acute ischemic stroke. He also reviews the benefits of organizing stroke care.

Content

0.89 -> >> Victor: Hello, my name is Dr. Victor Urrutia.

3.23 -> I'm an Associate Professor of Neurology

5.28 -> at Johns Hopkins University

7.02 -> and I am the director of the Comprehensive Stroke Center

10.53 -> at the Johns Hopkins Hospital.

13.2 -> I'm gonna talk about acute treatment of stroke

16.47 -> and give an update of the current state

20.32 -> of acute stroke treatment.

32 -> So, my objectives today are,

34.52 -> to discuss the treatments of acute ischemic stroke,

37.43 -> discuss new imaging techniques

40.209 -> in evaluating acute ischemic stroke patients

42.9 -> and review the benefits and principles

44.68 -> of organizing stroke care.

48.02 -> So, the treatment of stroke has gone a long way

50.68 -> in the last 23 years.

54.15 -> Since the publication of the NINDS IV tPA trial

59.82 -> for acute ischemic stroke in 1995,

63.68 -> through the extension of the time window from three hours

67.67 -> to four and a half hours

69.62 -> and then the demonstration of the benefit

73.62 -> of thrombectomy in 2015,

77.78 -> with the publication of five clinical trials

80.35 -> that showed benefit without a doubt.

83.97 -> In 2017 and 18, the window was extended to 24 hours

89.24 -> with advanced imaging by the DAWN and DEFUSE-3 study.

97.14 -> Intravenous thrombolysis is still

100 -> the only FDA-approved drug treatment for a stroke

106.84 -> and it's still recommended that every patient

111.68 -> that qualifies for this treatment, should receive it.

115.78 -> And the rationale for this is that,

120.15 -> it's a treatment that is quick and easy to administer.

125.04 -> It can be administered in more hospitals

127.72 -> than, for example, thrombectomy can be administered.

131.29 -> And as I'm gonna show you in a slide, next,

135.61 -> is that most patients are actually stroke patients

140.64 -> that don't have large-artery occlusion.

143.55 -> Now, very little has changed

145.96 -> in intravenous thrombolysis since 1996,

150.34 -> when it was approved by FDA,

152.15 -> except for the time window which was extended from zero

155.55 -> to three, to four and a half hours.

159.26 -> And the other thing that has changed,

163.32 -> is that there's been a recognition that patients

166.24 -> that have mild symptoms,

169.24 -> also have a 30% chance of having disability

173.75 -> and therefore deserve treatment.

176.32 -> So a task force was created

179.03 -> to try to define what are the patients

183.2 -> that have a low severity of stroke symptoms

189.33 -> that would be most likely to continue to be disabled

192.77 -> and therefore, warrant treatment with acute intervention

198.39 -> like IV tPA.

201.46 -> And what the taskforce found,

203.96 -> was that you could summarize it in three items,

209.75 -> which include complete hemianopia, or severe aphasia.

216.04 -> These patients often have a NIH scale two or three.

220.44 -> and if you went by strokes of 30,

224.93 -> they might be considered for not being treated.

227.86 -> However, these have been identified

231.25 -> as significant symptoms causing disability

235.37 -> and therefore, those patient's merit treatment.

239.73 -> Having visual or sensory extinction,

242.48 -> is another condition

244.25 -> that would portend a high risk of disability,

247.77 -> so it will require treatment.

250.53 -> Having any weakness,

251.9 -> limiting sustained effort against gravity,

254.93 -> is also considered a significant deficit.

258.4 -> And in this one, you also have to consider

261.07 -> what the patient's baseline is.

262.64 -> If you have a patient that works with their hands,

265.45 -> any weakness in their hand,

267.42 -> that is gonna affect dexterity,

269.42 -> is gonna be a source of disability in the future

272.06 -> and should be considered for treatment.

274.42 -> And any deficits leading to a total NIH stroke scale

277.19 -> of five or above,

278.62 -> should be a deficit that needs to be treated.

281.42 -> At the end, it also is recommended

285.61 -> that the physician considers the overall goals of care

289.84 -> of the patient.

291.6 -> And as I mentioned before,

293.14 -> if a patient has mild hand weakness,

295.65 -> but hand function and dexterity is intricate

299.84 -> for their livelihood,

302.35 -> that is something that should be considered.

303.93 -> The other part of this is,

305.19 -> not only the patients that present with symptoms

307.84 -> that are mild, but also patients

310.597 -> that present with more severe symptoms

312.9 -> and then improve to a level

315.56 -> where they're mild, those patients should be treated.

321.191 -> The benefits of treating with IV tPA,

323.51 -> are higher than the harm.

326.19 -> And in this slide,

327.2 -> you can see that from zero to three hours,

330.077 -> the numbers needed to treat to get a benefit, is eight.

335.07 -> And from three to four and a half hours,

336.837 -> the numbers needed to treat is 14.

338.87 -> What that means is that,

339.79 -> you need to treat 14 people for one to benefit.

342.83 -> If you compare that with coronary intervention,

346.51 -> so PCI for acute MRI,

349.16 -> which has the numbers needed to treat a 34,

351.5 -> according to some studies,

352.79 -> the treatment with tPA is actually highly effective.

357.12 -> Now, if you look at the bar graph,

359.81 -> you can see that time is definitely brain

362.27 -> and the earlier that you treat the patients,

364.227 -> the more benefit you're gonna derive.

367.07 -> And here the zero to 90-minute window,

369.73 -> you have a 27.8% chance of excellent outcomes

374.15 -> and you have a 1.5 chance of poor outcome.

378.28 -> So the poor outcome risk increases over time,

382.46 -> although not at the level of the benefit,

385.943 -> it's still beneficial after you get to four

388.67 -> and a half hours.

389.85 -> And after that, then you lose the benefit.

396.92 -> This is what I was referring to before.

400.97 -> This is a bar graph of the NIH stroke scale on the x-axis,

407.6 -> and the percent of patients presenting as an acute stroke.

411.557 -> And you can see that most patients,

414.36 -> are presenting with an NIH stroke scale less than 10

417.74 -> and definitely less than six.

421.31 -> So what that means is that,

424.1 -> most patients are gonna be patients

425.8 -> that don't have a large-artery occlusion and therefore,

428.47 -> IV tPA is gonna be the only treatment

430.91 -> that you're gonna be able to offer

432.66 -> to increase their ability to recover.

439.33 -> Mechanical thrombectomy has definitely been a revolution

443.3 -> after 2015, where it was shown

445.76 -> that the numbers needed to treat was four.

448.4 -> So if you remember the tPA numbers,

450.65 -> the numbers needed to treat

451.8 -> for zero to three hours was eight,

453.44 -> and from three to four and a half hours was 14.

456.57 -> For thrombectomy, which are the

458.71 -> large-artery occlusion patients,

460.4 -> which are the patients with the highest mortality

463.78 -> and risk for disability,

465.907 -> the numbers needed to treat

468.66 -> to get somebody back to independence, is four.

472.01 -> So, one out of four patients are gonna be back

474.61 -> to independence in 90 days.

476.51 -> And with the new studies,

478.11 -> we are able to extend the time window to 24 hours

483.37 -> if we do advanced imaging.

488.1 -> So the Hermes is a pull-down analysis

490.26 -> of the five endovascular trials.

492.12 -> And you can see

493.09 -> that there were 634 intervention cases, 653 controls,

499.16 -> the median time to treatment was three hours and 16 minutes.

501.84 -> So, you can get the sense

504.01 -> that the patients are being treated

506.71 -> very fast in these trials.

508.48 -> 71% recalculation,

511.57 -> numbers needed to treat to reduce one point

513.84 -> in your ranking score, in this score of disability, was 2.6.

518.88 -> And the overall numbers needed to treat was four.

524.54 -> In terms of detecting patients

526.66 -> that are beyond the four-and-a-half-hour window,

529.32 -> there are two approaches that have been successful.

531.77 -> One is to try to determine

533.96 -> if the stroke is truly within

536.29 -> the four-and-a-half-hour window

537.56 -> and this is the approach

539.65 -> that has been taking in the MR-Witness,

542.47 -> which is a clinical trial from the US

544.86 -> that was published some time ago

547.22 -> and the Wake-Up stroke,

548.55 -> which is a clinical trial from Germany,

551.98 -> in which they use the paradigm of DWI-FLAIR mismatch.

557.94 -> And what the studies have shown is that,

562.62 -> the number of patients

563.73 -> that are gonna have an obvious lesion, in FLAIR,

567.32 -> which is the black bars here,

571.07 -> increases over time,

572.7 -> and the inflection point is really four and a half hours.

575.47 -> After four and a half hours,

576.68 -> most of the patients are going to have a FLAIR lesion.

580.95 -> Whereas before, most of the patients

583.26 -> are not gonna have a FLAIR lesion.

584.76 -> So, taking this in mind,

587.75 -> the idea is that, if you have a positive diffusion,

590.81 -> weighted image lesion,

592.35 -> like in this picture,

594.02 -> or in this picture,

595.74 -> and you compare it to the FLAIR and FLAIR is negative,

598.61 -> then that patient might actually be within

600.41 -> four and a half hours.

604.05 -> The bottom panel,

605.58 -> you can see that the DWI and the FLAIR are matched.

609.04 -> So with this paradigm, MR-Witness and Wake-Up,

612.15 -> demonstrated that you can treat patients

614.21 -> that had no knowledge of the time of onset

619.52 -> and they could be treated safely

621.29 -> with intravenous thrombolytics.

623.72 -> There's been other studies from the US.

626.27 -> Also, the Wake-Up study and the Ceylon study,

630.1 -> where the patients were treated with wake-up stroke,

635.34 -> based under their non-contrast head CT,

638.93 -> or based on the MRI deficient FLAIR mismatch.

643.64 -> Now, the concept of the perfusion imaging,

646.1 -> comes from this slide,

647.73 -> which was presented by Greg Albers

650.88 -> in the International Stroke Conference in 2013,

654.36 -> where the volume of the infarct

656.49 -> and the y-axis, compared to the time from stroke onset,

662.42 -> shows that in the first few hours of the stroke,

665.53 -> most of the patients are gonna have a low volume.

667.97 -> But there's going to be a few outliers

669.96 -> that have a large volume of stroke that is irreversible.

675.02 -> However, you would think

676.06 -> that all the patients in the later times,

678.56 -> are gonna have a high stroke volume.

682.3 -> But in essence, what studies have shown,

685.33 -> is that there's a significant number of people

688.1 -> that are gonna have a volume of stroke

690.44 -> that is less than 50 CCS,

692.69 -> even at 24 hours after the onset.

696.48 -> And using this paradigm of trying to identify

699.91 -> how much of the core which is irreversible is present,

705.59 -> has been successfully used by the DAWN study,

708.61 -> the DEFUSE-3 study, the EXTEND study

711.4 -> and the EXTEND IV study.

714.04 -> And that has led to really a revolution in treatment

718.11 -> of acute stroke with perfusion imaging

719.92 -> after 24 hours for large-artery occlusion.

723.78 -> These are the criteria for the DAWN study.

729.32 -> They divided patients in three groups,

732.53 -> by age and stroke scale.

734.45 -> In the DAWN study, it's really a study

738.452 -> of severity of stroke versus core.

741.75 -> So it's a severity-core mismatch

744.41 -> in which the core was determined by the CT perfusion.

748.23 -> So in Group A, patients that are 80 years of age and older,

753.21 -> with an NIH stroke scale that is 10 or more,

756.96 -> and the core that was exceedingly small,

760.38 -> less than 21 CCS, could be treated with thrombectomy.

764.61 -> In Group B, patients that were less than 80 years of age,

768.81 -> with NIH stroke scale equal more than 10,

770.98 -> with a core less than 31 CCS,

773.01 -> were treated with thrombectomy.

775.15 -> In group C, patients that were younger than 80 years of age,

778.53 -> NIH stroke scale of more than 20,

781.512 -> and core between 31 and 51 CCS

784.11 -> were treated with thrombectomy.

785.14 -> And then the findings of this trial showed that,

788.48 -> numbers needed to treat for better disability score was two

792.08 -> and for independence was 2.8.

794.77 -> Now, the reality is that this trial,

798.53 -> even though it shows a criteria for a core less than 31

803.39 -> for Group B,

804.45 -> and a core between 31 and 51 for Group C,

808.673 -> the median core size was less than 25.

813.26 -> So this trial identified patients with very small cores

817.71 -> and were treated effectively.

820.05 -> Same thing happened with the DEFUSE-3

821.65 -> which used a different paradigm

823.43 -> in which instead of using the severity-core mismatch,

829.45 -> they did a perfusion-core mismatch.

832.47 -> So, the criteria was ischemic stroke core

836.51 -> of less than 70 CCS,

838.69 -> a ratio of procedures deficit, versus score of 1.8 or more

844.88 -> and an absolute volume of potentially reversible ischemia

848.14 -> of 15 CCS, 15 milliliters or more.

852.72 -> And here, you can see an example

856.17 -> where the core is measured to be 23 CCS

860.35 -> and the perfusion deficit is much larger,

863.89 -> measured out to be 128 CCS

866.8 -> and the mismatch volume is 105,

868.94 -> which is greater than the 15 that is stated

872.14 -> in the mismatch range, so it's greater than 5.6

877.24 -> which is greater than 1.8.

878.44 -> So this patient qualifies for treatment.

881.26 -> Now, as I've mentioned before,

885.74 -> the DAWN study had a median core size of 7.6

890.36 -> with an interquartile range of two to 18.

894.92 -> DEFUSE-3 had a median core of 9.4,

900.189 -> with the interquartile range of 2.3 to 25.

904.69 -> So, you can see that most of the patients

907.08 -> did not have a high core even in the less than 70 CC range,

911.72 -> but it was very smaller cores.

914.61 -> However, the implementation of these two trials

917.44 -> in clinical practice, have been effective,

919.97 -> and we're currently using those criteria

921.8 -> for select patients with thrombectomy.

924.733 -> What the future holds,

925.87 -> is that this same approach of perfusion imaging,

930.47 -> is showing good results in intravenous thrombolysis.

935.13 -> And this trial reported efficacy

940.35 -> at nine hours from stroke onset.

942.99 -> Now, this draw was not significant enough

946.89 -> to provide change in practice,

949.88 -> but it's definitely a step in the right direction,

952.28 -> in terms of extending the time window

954.04 -> for intravenous thrombolytics.

957.24 -> Now, I'm gonna change the track a little

960.26 -> to talk about stroke units.

962.52 -> If there's a clear benefit for stroke patients

967.85 -> to the creation of stroke units,

970.34 -> they've been shown by several studies

972.9 -> and meta analysis,

974.5 -> including the Cochrane Database investigation,

978.8 -> that the stroke units reduce mortality

982.57 -> by about 20% and also disability.

987.016 -> The effect size is comparable to that of tPA.

990.01 -> What that means is that,

991.53 -> when you look at the numbers needed to treat,

994.43 -> to help patients with stroke get reduced disability,

1001.46 -> just by the basis of being in a stroke unit,

1004.01 -> versus not a stroke unit,

1005.9 -> the number is about 18 numbers needed to treat,

1010.23 -> which is very close to the 14 that you see

1012.39 -> in the three to four-and-a-half-hour window for tPA.

1017.37 -> What a stroke really represents,

1018.98 -> is really the determination of protocols

1022.37 -> that standardize the stroke care and stroke order sets,

1026.63 -> adherence to best practices,

1028.75 -> telemetry for 24 hours and then as needed

1031.78 -> and then vital signs and neurological assessments

1035.45 -> that are given by trained nurses.

1039.57 -> And one of the things that are more surprising,

1041.74 -> but very effective, is that the bedside swallow evaluation,

1046.27 -> glucose checks, DVT prophylaxis, temperature management,

1050.56 -> have demonstrated benefit,

1053.05 -> in terms of stroke survival and recovery.

1056.75 -> And here is what I was mentioning,

1058.85 -> the Cochrane Database Systematic Review,

1061.2 -> showing the numbers needed to treat of 18 for stroke units.

1065.24 -> And also this study from Canada,

1067.9 -> in which patients were randomized

1070.56 -> to centers that were offering swallowing, fever

1073.75 -> and blood glucose control, versus centers that were not,

1077.56 -> and there was a benefit in the functional outcome

1082.08 -> into patients that were randomized to the centers

1084.25 -> that were doing swallowing, screen fever control

1086.82 -> and blood glucose control

1088.43 -> with a numbers needed to treat of 6.4,

1090.74 -> which is better than tPA.

1093.46 -> And that's a significant demonstration,

1096.96 -> that organizing a stroke center with protocols,

1101.187 -> the stroke unit has a definitive effect

1105.134 -> in the outcome of stroke patients.

1108.65 -> It's important for the stroke program

1110.48 -> to have skills in triage to detect stroke.

1116.12 -> And one of the most used and more effective one,

1119.31 -> is the BEFAST scale,

1121 -> which includes two parameters for procedure simulation,

1124.07 -> which are balancing eyes.

1125.68 -> So the V stands for balance, E stands for eyes

1130.67 -> which is double vision or loss of vision,

1133.23 -> F for face weakness,

1135.87 -> A for arm weakness,

1137.43 -> S for speech, either dysphasia your aphasia,

1140.12 -> and T for time.

1141.69 -> There are other scales,

1142.65 -> there's the RACE

1143.483 -> which is a modified NIH stroke scale,

1145.36 -> there's the LAMS, that is face, arm grip,

1149.07 -> and grip strength that is very predictive

1151.46 -> for large-artery occlusion.

1154.78 -> In the stroke center,

1156.93 -> in addition to what I've mentioned before,

1159.04 -> it's important to have a preset workflow

1163.59 -> for rapid assessment

1165.19 -> and evaluation of patients for both thrombolytic therapy

1168.76 -> and mechanical thrombectomy.

1169.98 -> And that includes a scale triage to detect the stroke

1176.42 -> in monitoring airway breathing circulation,

1179.39 -> and then breaking down to two windows,

1181.89 -> zero to four and a half hours,

1183.22 -> to four and a half to 24 hours

1184.82 -> which determines patients

1186.72 -> that could be treated within the four-and-a-half-hour,

1191.587 -> or patients can be treated

1193.34 -> with either thrombolytic therapy or thrombectomy.

1197.3 -> And those patients are gonna need to be evaluated

1199.66 -> by CT or CTA.

1203.61 -> In the four-and-a-half to three to four-hour window,

1206.14 -> patients are gonna be qualifying for thrombectomy

1210.22 -> if they have large-artery occlusion

1212.02 -> and will require perfusion either by CT, CTA,

1215.478 -> CTP perfusion, or MR-perfusion.

1220.15 -> Essentially, there's sort of two-time windows

1222.07 -> that I explained.

1224.693 -> IV thrombolytics in the four-and-a-half-hour window

1227.11 -> and patients that have large-artery occlusion

1229.6 -> can be selected for thrombectomy

1232.11 -> in the four-and-a-half to 24-hour window

1234.51 -> by doing perfusion imaging.

1237.86 -> And acute evaluation,

1239.48 -> and this is useful for the emergency department doctors,

1242.62 -> especially to present to the stroke neurologist

1247.19 -> or the neurologist,

1249.09 -> is that the critical aspect,

1251.63 -> is to have a sense of time from last known well,

1256.35 -> and then assess a brief HPI,

1259.32 -> a brief history of person illness, a quick exam,

1263.28 -> neurologic exam and physical exam,

1266.09 -> to do it in a stroke scale.

1267.58 -> And this is important.

1268.58 -> All emergency medicine doctors should be proficient

1271.49 -> in the NIH stroke scale,

1273.4 -> as well as the neurologists, of course.

1275.98 -> But it's good for the emergency medicine physician

1278.7 -> that, if they have the time of last known well,

1281.6 -> the HPI and exam and NIH stroke scale

1284.75 -> and they can go through an inclusion-exclusion form,

1289.58 -> then you can talk to a neurologist

1291.96 -> and expedite the decision to treat

1294.39 -> or not treat a patient with IV tPA or thrombectomy.

1299.13 -> And then documentation of this process is important.

1304.29 -> So in conclusion, in this day of multiple windows

1306.72 -> and treatments for acute ischemic stroke,

1309.32 -> logistics and organization of systems of care are vital.

1312.98 -> And creation of stroke units to that end,

1317.17 -> is a critical step.

1318.98 -> Increasing capacity and getting the right patient

1321.34 -> to the right place, for the first time, is key.

1324.33 -> The future of stroke is to make this treatments accessible

1327.3 -> to all patients.

1328.73 -> And organizing centers in the system is paramount.

1332.81 -> I hope you enjoyed this talk

1335.19 -> and look forward to having questions, thank you.

Source: https://www.youtube.com/watch?v=hdamv6YFTYo