Late lesion growth following endovascular therapy: is 24 hours too early to assess acute infarct size including the effects of secondary injury?

Introduction Stroke lesion volume on MRI or CT provides objective evidence of tissue injury as a consequence of ischemic stroke. Measurement of "final" lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome. The goals of this study were to quantify lesion growth during the first week after treatment, identify early predictors, and explore the association with clinical outcome. Methods This is a prospective study of stroke patients at two centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, and iii) had 3T MRI post-EVT at 24hr and 5-day. We defined "Early" and "Late" lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively. Complete reperfusion was defined as >90% reduction of the volume of tissue with perfusion delay (Tmax>6sec) between pre-EVT and 24hr post-EVT. Favorable clinical outcome was defined as modified Rankin scale (mRS) of 0-2 at 30 or 90 days. Results One hundred twelve patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 66% with M1 occlusion, and median baseline DWI volume 21.2mL. Successful recanalization was achieved in 87% and 68% had complete reperfusion, with an overall favorable clinical outcome rate of 53%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.3mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (64%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (87%: 46% mTICI 2b/ 41% mTICI 3). Late lesion growth patients had a 27.4mL change in Late lesion volume and 30.1mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome. Conclusion Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Most patients with no Early lesion growth had no Late lesion growth. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally, it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.

Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain.

Post-ischemic hyperemia following endovascular therapy for acute stroke is associated with lesion growth.

A substantial proportion of acute stroke patients fail to recover following successful endovascular therapy (EVT) and injury to the brain and vasculature secondary to reperfusion may be a contributor. Acute stroke patients were included with: i) large vessel occlusion of the anterior circulation, ii) successful recanalization, and iii) evaluable MRI early after EVT. Presence of hyperemia on MRI perfusion was assessed by consensus using a modified ASPECTS. Three different approaches were used to quantify relative cerebral blood flow (rCBF). Sixty-seven patients with median age of 66 [59-76], 57% female, met inclusion criteria. Hyperemia was present in 35/67 (52%) patients early post-EVT, in 32/65 (49%) patients at 24 hours, and in 19/48 (40%) patients at 5 days. There were no differences in incomplete reperfusion, HT, PH-2, HARM, severe HARM or symptomatic ICH rates between those with and without early post-EVT hyperemia. A strong association (R2 = 0.81, p < 0.001) was found between early post-EVT hyperemia (p = 0.027) and DWI volume at 24 hours after adjusting for DWI volume at 2 hours (p < 0.001) and incomplete reperfusion at 24 hours (p = 0.001). Early hyperemia is a potential marker for cerebrovascular injury and may help select patients for adjunctive therapy to prevent edema, reperfusion injury, and lesion growth.

Good outcome associated with blood-brain barrier disruption and lower blood pressure after endovascular therapy.

OBJECTIVES: To evaluate the association between post-endovascular thrombectomy (EVT) blood-brain barrier (BBB) disruption on MRI or CT and average systolic blood pressure (SBP) with favorable 90-day functional outcome. Observational studies have found elevated SBP associated with worse outcomes post-EVT, while recent randomized trials found no difference in targeted BP reduction. There may be a subgroup of patients who benefit from targeted BP reduction post-EVT. METHODS: This is a single-center study of 1) anterior large vessel occlusion stroke patients treated with EVT from 2015 to 2021, 2) achieved mTICI grade 2b or 3. Hyperintense acute reperfusion marker (HARM), hemorrhagic transformation (HT), and midline shift at 3 h post-EVT and 24 h imaging were assessed independently by multiple raters. Binary logistic regression models were used to determine the association of post-EVT SBP with outcomes. BBB disruption was defined as HT or HARM on 3h post-EVT imaging. RESULTS: Of 103 patients, those with SBP 100-129 versus SBP 130-160 found no significant difference in favorable 90-day outcome (64% vs. 46%, OR 2.11, 95% CI 0.78-5.76, p=0.143). However, among 71 patients with BBB disruption, a significant difference in favorable outcome of 64% in SBP 100-129 vs. 39% in SBP 130-160 group (OR 5.93, 95% CI 1.50-23.45, p=0.011) was found. There was no difference in symptomatic ICH, 90-day mortality, midline shift (≥5 mm), and hemicraniectomy, between BP or BBB groups. CONCLUSIONS: BBB disruption on 3h post-EVT imaging and lower SBP was associated with favorable outcome. This imaging finding may guide targeted BP therapy and suggests need for a randomized control trial.

Estimating Perfusion Deficits in Acute Stroke Patients Without Perfusion Imaging.

BACKGROUND: Perfusion weighted imaging (PWI) is critical for determining whether stroke patients presenting in an extended time window are candidates for mechanical thrombectomy. However, PWI is not always available. Fluid-attenuated inversion recovery hyperintense vessels (FHVs) are seen in patients with a PWI lesion. We investigated whether a scale measuring the extent FHV could serve as a surrogate for PWI to determine eligibility for thrombectomy. METHODS: The National Institutes of Health (NIH) FHV score was developed to quantify the burden of FHV and applied to magnetic resonance imaging scans of stroke patients with fluid-attenuated inversion recovery and perfusion imaging. The NIH-FHV was combined with the diffusion weighted image volume to estimate the diffusion-perfusion mismatch ratio. Linear regression was used to compare PWI volumes and mismatch ratios with estimates from the NIH-FHV score. Receiver operating characteristic analysis was used to test the ability of the NIH-FHV score to identify a significant mismatch. RESULTS: There were 101 patients included in the analysis, of whom 78% had a perfusion deficit detected on PWI with a mean lesion volume of 47 (±59) mL. The NIH-FHV score was strongly associated with the PWI lesion volume (P<0.001; R2=0.32; ß-coefficient, 0.57). When combined with diffusion weighted image lesion volume, receiver operating characteristic analysis testing the ability to detect a mismatch ratio ≥1.8 using the NIH-FHV score resulted in an area under the curve of 0.94. CONCLUSIONS: The NIH-FHV score provides an estimate of the PWI lesion volume and, when combined with diffusion weighted imaging, may be helpful when trying to determine whether there is a clinically relevant diffusion-perfusion mismatch in situations where perfusion imaging is not available. Further studies are needed to validate this approach.

Association of Multiple Passes during Mechanical Thrombectomy with Incomplete Reperfusion and Lesion Growth.

INTRODUCTION: Despite complete recanalization by mechanical thrombectomy, abnormal perfusion can be detected on MRI obtained post-endovascular therapy (EVT). The presence of residual perfusion abnormalities post-EVT may be associated with blood-brain barrier breakdown in response to mechanical disruption of the endothelium from multiple-pass thrombectomy. We hypothesize that multiple-pass versus single-pass thrombectomy is associated with a higher rate of residual hypoperfusion and increased lesion growth at 24 h. MATERIALS AND METHODS: For this analysis, we included patients presenting to one of two stroke centers between January 2015 and February 2018 with an acute ischemic stroke within 12 h from symptom onset if they had a large vessel occlusion of the anterior circulation documented on magnetic resonance angiography or CTA, baseline MRI pre-EVT with imaging evidence of hypoperfusion, underwent EVT, and had a post-EVT MRI with qualitatively interpretable perfusion-weighted imaging data at 24 h. MRI Tmax maps using a time delay threshold of >6 s were used to quantitate hypoperfusion volumes. Residual hypoperfusion at 24 h was solely defined as Tmax volume >10 mL with >6 s delay. Complete recanalization was defined as modified treatment in cerebral infarction visualized on angiography at EVT completion. Hyperintense acute reperfusion injury marker was assessed on post-EVT pre-contrast fluid-attenuated inversion recovery at 24 h. Major early neurological improvement was defined as a reduction of the admission National Institutes of Health Stroke Scale by ≥8 points or a score of 0-1 at 24 h. Good functional outcome was defined as 0-2 on the modified Rankin Scale on day 30 or 90. RESULTS: Fifty-five patients were included with median age 67 years, 58% female, 45% Black/African American, 36% White/Caucasian, median admission National Institutes of Health Stroke Scale 19, large vessel occlusion locations: 71% M1, 14.5% iICA, 14.5% M2, 69% treated with intravenous recombinant tissue plasminogen activator. Of these, 58% had multiple-pass thrombectomy, 39% had residual perfusion abnormalities at 24 h, and 64% had severe hyperintense acute reperfusion injury marker at 24 h. After adjusting for complete recanalization, only multiple-pass thrombectomy (odds ratio, 4.3 95% CI, 1.07-17.2; p = 0.04) was an independent predictor of residual hypoperfusion at 24 h. Patients with residual hypoperfusion had larger lesion growth on diffusion-weighted imaging (59 mL vs. 8 mL, p < 0.001), lower rate of major early neurological improvement (24% vs. 70%, p = 0.002) at 24 h, and worse long-term outcome based on the modified Rankin Scale at 30 or 90 days, 5 versus 2 (p < 0.001). CONCLUSIONS: Our findings suggest that incomplete reperfusion on post-EVT MRI is present even in some patients with successful recanalization at the time of EVT and is associated with multiple-pass thrombectomy, lesion growth, and worse outcome. Future studies are needed to investigate whether patients with residual hypoperfusion may benefit from immediate adjunctive therapy to limit lesion growth and improve clinical outcome.

Fluid-Attenuated Inversion Recovery Hyperintense Ischemic Stroke Predicts Less Favorable 90-Day Outcome after Intravenous Thrombolysis.

INTRODUCTION: The absence of an ischemic lesion on MRI fluid-attenuated inversion recovery (FLAIR) is helpful in predicting stroke onset within 4.5 h. However, some ischemic strokes become visible on FLAIR within 4.5 h. We hypothesized that the early lesion visibility on FLAIR may predict stroke outcome 90 days after intravenous (IV) thrombolysis, independent of time. MATERIALS AND METHODS: We analyzed data from acute ischemic stroke patients presenting over the last 10 years who were screened with MRI and treated with IV thrombolysis within 4.5 h from onset. Three independent readers assessed whether ischemic lesions seen on diffusion-weighted imaging were also FLAIR positive based on visual inspection. Multivariable regression analyses were used to obtain an adjusted odds ratio of favorable clinical and radiological outcomes based on FLAIR positivity. RESULTS: Of 297 ischemic stroke patients, 25% had lesion visibility on initial FLAIR. The interrater agreement for the FLAIR positivity assessment was 84% (κ = 0.604, 95% CI: 0.557-0.652). Patients with FLAIR-positive lesions had more right hemispheric strokes (57 vs. 41%, p = 0.045), were imaged later (129 vs. 104 min, p = 0.036), and had less frequent favorable 90-day functional outcome (49 vs. 63%, p = 0.028), less frequent early neurologic improvement (30 vs. 58%, p = 0.001), and more frequent contrast extravasation to the cerebrospinal fluid space (44 vs. 26%, p = 0.008). CONCLUSIONS: Early development of stroke lesion on FLAIR within 4.5 h of onset is associated with reduced likelihood of favorable 90-day outcome after IV thrombolysis.

Prevalence of Imaging Targets in Patients With Minor Stroke Selected for IV tPA Treatment Using MRI: The Treatment of Minor Stroke With MRI Evaluation Study (TIMES).

OBJECTIVE: To determine the IV tissue plasminogen activator (tPA) treatment rate of patients with minor acute ischemic stroke (mAIS) at our centers and compare the frequency of MRI targets by treatment stratification and clinical severity, we evaluated clinical characteristics and baseline MRIs for tPA-treated and untreated patients. METHODS: Patients with ischemic stroke from 2015 to 2017 with admit NIH Stroke Scale (NIHSS) <6 were considered. The treated cohort received standard IV tPA and was screened with baseline MRI. The untreated cohort received no acute intervention and baseline MRI was <4 hours from onset. Patients were stratified into "clearly" and "not clearly" disabling deficits by NIHSS elements. Baseline MRI was evaluated by independent raters for AIS targets, with frequencies compared between groups. RESULTS: Of 255 patients with mAIS ≤4.5 hours from onset, 140 (55%) received IV tPA, accounting for 46% of all IV tPA patients (n = 305). Eighty-five percent (n = 119) were screened with baseline MRI and had significantly more frequent imaging targets compared to those untreated (n = 90). Of this treated cohort, 75% (n = 89) were not clearly disabling. Except for perfusion-diffusion mismatch (81% clearly disabling vs 56% not clearly disabling [p = 0.036]), there were no significant differences in the frequency of imaging targets across the treated cohort stratified by clinical severity. CONCLUSIONS: In MRI-screened mAIS, imaging targets were more frequently seen in patients treated with IV tPA, with similar frequencies even in those without clearly disabling deficits. MRI targets could be used to guide thrombolytic therapy in patients with mAIS; however, a randomized trial is needed to demonstrate efficacy.

Routine use of FLAIR-negative MRI in the treatment of unknown onset stroke.

BACKGROUND: Treatment of FLAIR-negative stroke in patients presenting in an unknown time window has been shown to be safe and effective. However, implementation can be challenging due to the need for hyper-acute MRI screening. The purpose of this study was to review the routine application of this practice outside of a clinical trial. METHODS: Patients presenting from 3/1/16 to 8/22/18 in a time window <4.5 h from symptom discovery but >4.5 h from last known normal were included if they had a hyper-acute MRI performed. Quantitative assessment based on the MR WITNESS trial and qualitative assessment based on the WAKE-UP trial were used to grade the FLAIR images. The MR WITNESS trial used a quantitative assessment of FLAIR change where the fractional increase in signal change had to be <1.15, whereas the WAKE-UP trial used a visual assessment requiring the absence of marked FLAIR signal changes. RESULTS: During the study period, 136 stroke patients presented and were imaged in the specified time window. Of these, 17 (12.5%) received IV tPA. Three patients had hemorrhage on 24-h MRI follow up; none had an increase in NIHSS ≥4. Of the 119 patients who were screened but not treated, 18 (15%) were eligible based on FLAIR quantitative assessment and 55 (46%) were eligible based on qualitative assessment. In all cases where patients were not treated, there was an identifiable exclusion based on trial criteria. During the study period, IV tPA utilization was increased by 5.6% due to screening and treating patients with unknown onset stroke. CONCLUSIONS: Screening stroke patients in an unknown time window with MRI is practical in a real-world setting and increases IV tPA utilization.

MRI-based thrombolytic therapy in patients with acute ischemic stroke presenting with a low NIHSS.

OBJECTIVE: Treatment of patients with stroke presenting with minor deficits remains controversial, and the recent Potential of rtPA for Ischemic Strokes with Mild Symptoms (PRISMS) trial, which randomized patients to thrombolysis vs aspirin, did not show benefit. We studied the safety and efficacy of thrombolysis in a population of patients with acute stroke presenting with low NIH Stroke Scale (NIHSS) scores screened using MRI. METHODS: The NIH Natural History of Stroke database was reviewed from January 2006 to December 2016 to identify all patients with an initial NIHSS score ≤5 who received thrombolysis within 4.5 hours of symptom onset after being screened with MRI. The 24-hour postthrombolysis MRIs were reviewed for hemorrhagic transformation. Primary outcomes were symptomatic intracranial hemorrhage (sICH) and favorable 90-day outcome modified Rankin Scale score 0-1. Subgroup analysis was performed on patients who would have been eligible for the PRISMS trial, which enrolled patients with a nondisabling neurologic deficit. RESULTS: A total of 121 patients were included in the study with a median age of 65 and an NIHSS score of 3; 63% were women. The rate of any hemorrhagic transformation was 13%, with 11% of them being limited to petechial hemorrhage. The rate of sICH was <1%. Sixty-six patients had 90-day outcome data; of those, 74% had a favorable outcome. For the subgroup of 81 PRISMS-eligible patients, none experienced sICH. Fifty of these patients had 90-day outcome data; of these, 84% had a favorable outcome. CONCLUSIONS: Thrombolytic therapy was safe in our patients with stroke with minor deficits who were initially evaluated by MRI. Future studies of this population may benefit from MRI selection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with acute ischemic stroke and NIHSS ≤5 screened with MRI, IV tissue plasminogen activator is safe.

Rapid Apparent Diffusion Coefficient Evolution After Early Revascularization.

Background and Purpose- In this era of endovascular therapy (EVT) with early, complete recanalization and reperfusion, we have observed an even more rapid apparent diffusion coefficient (ADC) normalization within the acute ischemic lesion compared with the natural history or IV-tPA-treated patient. In this study, we aimed to evaluate the effect of revascularization on ADC evolution within the core lesion in the first 24 hours in acute ischemic stroke patients. Methods- This retrospective study included anterior circulation acute ischemic stroke patients treated with EVT with or without intravenous tPA (IVT) from 2015 to 2017 compared with a consecutive cohort of IVT-only patients treated before 2015. Diffusion-weighted imaging and ADC maps were used to quantify baseline core lesions. Median ADC value change and core reversal were determined at 24 hours. Diffusion-weighted imaging lesion growth was measured at 24 hours and 5 days. Good clinical outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Results- Twenty-five patients (50%) received IVT while the other 25 patients received EVT (50%) with or without IVT. Between these patient groups, there were no differences in age, sex, baseline National Institutes of Health Stroke Scale, interhospital transfer, or IVT rates. Thirty-two patients (64%) revascularized with 69% receiving EVT. There was a significant increase in median ADC value of the core lesion at 24 hours in patients who revascularized compared with further ADC reduction in nonrevascularization patients. Revascularization patients had a significantly higher rate of good clinical outcome at 90 days, 63% versus 9% (P=0.003). Core reversal at 24 hours was significantly higher in revascularization patients, 69% versus 22% (P=0.002). Conclusions- ADC evolution in acute ischemic stroke patients with early, complete revascularization, now more commonly seen with EVT, is strikingly different from our historical understanding. The early ADC normalization we have observed in this setting may include a component of secondary injury and serve as a potential imaging biomarker for the development of future adjunctive therapies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Molecular signature of penumbra in acute ischemic stroke: a pilot transcriptomics study.

We aimed to characterize peripheral blood gene expression profile of penumbra defined as MRI perfusion-diffusion mismatch (PD MM) in peripheral blood of patients with acute ischemic stroke. We studied 23 patients. Perfusion-diffusion mismatch volume was observed to be associated and significantly correlated with the expression of 34 genes including those related to inflammation, SUMOylation, and coagulation; while lipopolysaccharide inhibition was identified to be a candidate upstream regulator of these processes (z-score -2.38, P = 0.04). Penumbral volume is correlated with a specific gene expression profile in the peripheral blood characterized by overlap of inflammatory and neuroprotective pathways that are regulated by lipopolysaccharide inhibition.

Recurrent thrombolysis of a stuttering lacunar infarction captured on serial MRIs.

Lacunar strokes account for about a fourth of all ischemic strokes. Pontine infarcts often present with stuttering symptoms, referred to as pontine warning syndrome (PWS). Patients presenting with fluctuating symptoms can appear to have rapidly improving symptoms and thus often go untreated despite the risk of recurrent deficits. MRI carries a higher sensitivity in detecting posterior circulation strokes compared to computed topagraphy, but does not always indicate irreversible injury. Here we present the first description of a stuttering lacune, captured radiographically on serial magnetic resonance imaging (MRI), that was initially averted with the administration of intravenous (IV) tissue plasminogen activator (tPA), only to return a month later and progress on imaging despite re-administration of tPA. During the first admission, our patient had spontaneous resolution of symptoms with complete reversal on restricted diffusion soon after IV tPA administration. On the second admission, the stuttering symptoms returned as did the same pontine lesion. Although his stuttering lesions lasted for several days, and the pontine lesion did ultimately progress to partial infarction on MRI, he was discharged home without neurologic deficits. Our case suggests that tPA may be of benefit in patients with lacunar pontine strokes even if symptoms rapidly improve or resolve.

Mortality After Pediatric Arterial Ischemic Stroke.

OBJECTIVES: Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS). METHODS: Neonates (0-28 days) and children (29 days-<19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry. Death during hospitalization and cause of death were ascertained from medical records. Logistic regression was used to analyze associations between risk factors and in-hospital mortality. RESULTS: Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were stroke-related, with remaining deaths attributed to medical disease. In multivariable analysis, congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI]: 1.23-12.29; P = .021), posterior plus anterior circulation stroke (OR: 5.36; 95% CI: 1.70-16.85; P = .004), and stroke presentation without seizures (OR: 3.95; 95% CI: 1.26-12.37; P = .019) were associated with in-hospital mortality for neonates. Hispanic ethnicity (OR: 3.12; 95% CI: 1.56-6.24; P = .001), congenital heart disease (OR: 3.14; 95% CI: 1.75-5.61; P < .001), and posterior plus anterior circulation stroke (OR: 2.71; 95% CI: 1.40-5.25; P = .003) were associated with in-hospital mortality for children. CONCLUSIONS: In-hospital mortality occurred in 2.6% of pediatric AIS cases. Most deaths were attributable to stroke. Risk factors for in-hospital mortality included congenital heart disease and posterior plus anterior circulation stroke. Presentation without seizures and Hispanic ethnicity were also associated with mortality for neonates and children, respectively. Awareness and study of risk factors for mortality represent opportunities to increase survival.

An MRI Hyperintense Acute Reperfusion Marker Is Related to Elevated Peripheral Monocyte Count in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke. METHODS: We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan. RESULTS: Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011). CONCLUSION: Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke.

Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale.

BACKGROUND AND PURPOSE: It is increasingly recognized that time is one of the key determinants in acute stroke outcome when interventional stroke therapy is applied. With increasing device efficacy and understanding of imaging triage options, reducing pre-treatment time loss may be a critical component of improving interventional stroke outcomes for the population at large. Time sensitive procedures such as organ harvest have transported physicians to the patient site to improve time to procedure. Applying this same principle to interventional stroke management may be a valid paradigm. METHODS: Previous logistical deliberation with hospital and Medevac companies was carried out to provide the rationale and funding for helicopter transfer of a neurointerventionalist to an in-network hospital with an on-site angiographic suite. An appropriate patient with large vessel occlusion and an NIH Stroke Scale score >8 was identified. MRI was performed, then the Medevac transport system was activated and the intervention was carried out. Times were collected during the case and assessed for time efficiency. RESULTS: The proof of concept case was identified and Medevac was consulted at 12:13 after verifying that no in-house emergencies would prevent physician departure. Weather clearance was obtained and stroke intervention confirmed as a go at 12:24. Groin puncture occurred at 13:07 and the intervention was completed at 13:41. The total time from decision-to-treat to groin puncture was 43 min and groin closure was completed at 77 min from decision-to-treat. CONCLUSIONS: This proof of concept case is presented for logistical, financial and use-case analysis. As it is a first case, times can likely be improved. We assert that this model may be another option in the spoke-and-hub design of stroke systems of care.

Effects of increasing IV tPA-treated stroke mimic rates at CT-based centers on clinical outcomes.

OBJECTIVE: To determine to what degree stroke mimics skew clinical outcomes and the potential effects of incorrect stroke diagnosis. METHODS: This retrospective analysis of data from 2005 to 2014 included IV tissue plasminogen activator (tPA)-treated adults with clinical suspicion for acute ischemic stroke who were transferred or admitted directly to our 2 hub hospitals. Primary outcome measures compared CT-based spoke hospitals' and MRI-based hub hospitals' mimic rates, hemorrhagic transformation, follow-up modified Rankin Scale (mRS), and discharge disposition. Secondary outcomes were compared over time. RESULTS: Of the 725 thrombolysis-treated patients, 29% were at spoke hospitals and 71% at hubs. Spoke hospital patients differed from hubs by age (mean 62 ± 15 vs 72 ± 15 years, p < 0.0001), risk factors (atrial fibrillation, 17% vs 32%, p < 0.0001; alcohol consumption, 9% vs 4%, p = 0.007; smoking, 23% vs 13%, p = 0.001), and mimics (16% vs 0.6%, p < 0.0001). Inclusion of mimics resulted in better outcomes for spokes vs hubs by mRS ≤1 (40% vs 27%, p = 0.002), parenchymal hematoma type 2 (3% vs 7%, p = 0.037), and discharge home (47% vs 37%, p = 0.01). Excluding mimics, there were no significant differences. Comparing epochs, spoke stroke mimic rate doubled (9%-20%, p = 0.03); hub rate was unchanged (0%-1%, p = 0.175). CONCLUSIONS: Thrombolysis of stroke mimics is increasing at our CT-based spoke hospitals and not at our MRI-based hub hospitals. Caution should be used in interpreting clinical outcomes based on large stroke databases when stroke diagnosis at discharge is unclear. Inadvertent reporting of treated stroke mimics as strokes will artificially elevate overall favorable clinical outcomes with additional downstream costs to patients and the health care system.

Perfusion Deficits and Association with Clinical Outcome in Patients with Anterior Choroidal Artery Stroke.

BACKGROUND AND PURPOSE: Anterior choroidal artery (AChA) strokes have a varied pattern of tissue injury, prognosis, and clinical outcome. It is unclear whether perfusion deficit in AChA stroke is associated with the clinical outcome. This study aims to determine the frequency of perfusion abnormalities in AChA stroke and association with clinical outcome. METHODS: The study cohort was derived from ischemic stroke patients admitted to 2 stroke centers between July 2001 and July 2014. All patients received an acute magnetic resonance imaging (MRI) scan. Patients with ischemic stroke restricted to the AChA territory were included in the study. Lesion size was measured as the largest diameter on diffusion-weighted imaging (DWI) or apparent diffusion coefficient and divided into 2 groups (<20 mm or ≥20 mm). Group comparisons were performed among patients with and without perfusion abnormalities and based on diffusion diameter. Favorable clinical outcome was defined as discharge to home. RESULTS: A total of 120 patients were included in the study. Perfusion deficits were identified in 67% of patients. The admission National Institutes of Health Stroke Scale (NIHSS) was higher in patients with perfusion abnormalities (P = .027). Diameter lesion size on DWI was larger among patients with a perfusion deficit median [interquartile range], 1.63 [1.3-2.0], as compared with those without, 1.18 [1.0-1.7], P < .0001. Patients with a perfusion deficit were less likely to be discharged to home than those without (36% versus 60%, P = .013). CONCLUSIONS: Two thirds of patients with an AChA stroke have a perfusion deficit on MRI, higher admission NIHSS, and larger DWI lesion size at presentation.

Diffuse Fluid-Attenuated Inversion Recovery Hyperintensity in Subarachnoid Space Following Cerebral Angiography and Intravenous Thrombolysis.

OBJECTIVE: Transient cortical blindness (TCB) is a relatively rare but well-recognized complication following cardiovascular and cerebral angiography. METHODS: A 68-year-old male developed TCB following cerebral angiography along with punctate diffusion lesion evident on emergent magnetic resonance imaging (MRI). The patient received intravenous tissue plasminogen activator (IV-tPA) for suspected stroke. RESULTS: Follow-up MRI revealed diffuse hyperintensities in subarachnoid space in fluid-attenuated inversion recovery (FLAIR) sequence mostly in bilateral occipital lobes. CONCLUSION: The finding on the FLAIR as described in this case is an indication of diffuse disruption of the blood-brain barrier perhaps secondary to cerebral angiography, high blood pressure, and IV-tPA. To the best of our knowledge, this is the first reported case of TCB with diffuse postcontrast FLAIR changes.

Screening with MRI for Accurate and Rapid Stroke Treatment: SMART.

OBJECTIVE: The objective of this study was to demonstrate the feasibility of timely multimodal MRI screening before thrombolysis in acute stroke patients. METHODS: Quality improvement processes were initiated in 2013 to reduce door-to-needle (DTN) time at the 2 hospitals where the NIH stroke team provides clinical care. Acute ischemic stroke (AIS) patients who received IV tissue plasminogen activator (tPA) ≤4.5 hours from last known normal were identified. Demographic and clinical characteristics and timing metrics were analyzed comparing the time periods before, during, and after the quality improvement processes. RESULTS: There were 157 patients treated with IV tPA for AIS during 2012-2013, of whom 135 (86%) were screened with MRI. DTN time was significantly reduced by 40% during this period from a median of 93 minutes in the first half of 2012 to 55 minutes in the last half of 2013 (p < 0.0001) with a significant 4-fold increase in the proportion of treated patients with DTN time ≤60 minutes from 13.0% to 61.5%, respectively (p < 0.00001). Improvement in DTN time was associated with reduced door-to-MRI time, and there were no differences in demographic or clinical characteristics (p = 0.21-0.76). CONCLUSIONS: It is feasible and practical to consistently and rapidly deliver IV tPA to AIS patients within national benchmark times using MRI as the routine screening modality. The processes used in the SMART (Screening with MRI for Accurate and Rapid Stroke Treatment) Study to reduce DTN time have the potential to be widely applicable to other hospitals.