Clinical-diffusion Mismatch Research Articles

Plasma mid-regional pro-adrenomedullin: A biomarker of the ischemic penumbra in hyperacute stroke.

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n=119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5h of onset. MR-proADM levels in HAIS were compared to healthy controls (n=1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p < 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (rs =0.09, p=0.348), they were higher in HAIS with CDM (n=34; 0.81 vs. 0.61 nmol/L, p < 0.001) or MDM (n=26; 0.83 vs. 0.62 nmol/L, p=0.002). These differences remained significant after adjusting baseline factors (adjusted odds ratio, 4.06 [95% CI, 1.31-12.55], p = 0.015 and 4.65 [1.35-16.11], p = 0.015, respectively). Plasma MR-proADM is elevated in HAIS, especially in those with a substantial penumbra, suggesting potential as a blood biomarker in this region.

Clinical Outcomes of Endovascular Treatment for Carotid Artery Dissection Without Intracranial Large Vessel Occlusion in Patients With Cerebral Ischemia Presentation.

Background and PurposeWe describe the clinical characteristics and outcomes (including the long-term patency of endovascular treatment [EVT]) of patients with acute ischemic strokes (AISs) featuring carotid artery dissection (CAD) but not intracranial large vessel occlusion.MethodsWe retrospectively reviewed patients who underwent EVT for spontaneous or post-traumatic AISs with CAD over a 13 year period from September 2005 to November 2018. The indications for EVT in patients with AIS-related CAD were a pretreatment diffusion-weighted imaging-Alberta Stroke Program early computed tomography (ASPECT) score > 6 and, clinical-diffusion mismatch. But, if the patients showed fluctuated ischemic symptoms, the joint decision by a stroke neurologist and neurointerventionist was done according to the onset-to-door time, symptoms, patient data, and the initial neuroimaging findings whether indicated that EVT was appropriate.ResultsTwenty-two dissected carotid arteries underwent balloon angioplasty and/or stent placement. The patients were 6 women and 16 men of median age 46 years. Twelve lacked any trauma history. Recombinant tissue plasminogen activator was prescribed for two (9.1%) patients. Four developed symptomatic intracranial hemorrhages (18.2%) but 86.4% exhibited modified Rankin scores ≤ 2.ConclusionsAlthough attention to the hemorrhagic complication is required, EVT for selective patients with cerebral ischemia associated with CAD may be safe and acceptable treatment strategy for reconstruction of luminal patency, with good clinical outcomes. Prospective large-scale randomized studies are required to optimize EVT for CAD patients.

Clinical-Diffusion Mismatch Is Associated with Early Neurological Improvement after Late-Window Endovascular Treatment

Background: Clinical-diffusion mismatch (CDM) and perfusion-diffusion mismatch (PDM) are used to select patients for endovascular thrombectomy (EVT) in the late-window period. As CDM well reflects true penumbra, we hypothesized that patients with CDM and PDM would respond better to EVT than those with PDM only at the late-window period. Methods: Acute ischemic stroke patients who received EVT 6–24 h after stroke onset were included. PDM (perfusion-/diffusion-weighted image (DWI) lesion volume >1.8) was used to select candidates for EVT in this time-period in our center. CDM was defined according to the DAWN trial criteria. Response to EVT was compared between patients with and without CDM. Early neurological improvement (ENI) was defined as improvement >4 points on National Institutes of Health Stroke Scale (NIHSS) score 1 day after EVT. Multivariable analysis was performed to investigate independent factors associated with ENI. The correlation between DWI lesion volume and NIHSS score was investigated in those with and without CDM. Results: Among 94 patients enrolled, all patients had PDM and 44 (46.3%) had CDM. Forty-eight patients (51.1%) showed ENI. The prevalence of hypertension, initial NIHSS score, improvement in NIHSS score after EVT, and prevalence of ENI were greater in patients with CDM than those without. ENI was independently associated with onset-to-door time (odds ratio [95% confidence interval]: 0.998 [0.997–1.000]; p = 0.042), complete recanalization (23.912 [2.238–255.489]; p = 0.009), initial NIHSS score (1.180 [1.012–1.377]; p = 0.034), and the presence of CDM (5.160 [1.448–18.386]; p = 0.011). The correlation between DWI lesion volume and initial NIHSS score was strong in patients without CDM (r = 0.731) but only moderate in patients with CDM (r = 0.355). Conclusion: Patients with both CDM and PDM had a better response to late-window EVT than those with PDM only.

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study.

To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct. A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct. Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population. Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct. This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.

Impact of MRI Selection on Triage of Endovascular Therapy in Acute Ischemic Stroke: The MRI in Acute Management of Ischemic Stroke (MIAMIS) Registry

Background: The recently published multicenter randomized DAWN trial confirmed greater outcome benefit of endovascular therapy (ET) for anterior circulation large vessel occlusion ischemic stroke from 6 to 24 h from symptom onset compared to medical management in patients selected by advanced imaging with MRI or perfusion CT to identify mismatch between clinical deficit and infarct volume, which represents salvageable penumbra. The debate of CT over MRI is usually the potentially increase time consumption and the difficulty in establishing an adequate standardized workflow utilizing MRI during the hyperacute phase. Purpose: While CT-based selection of patients is the current standard of care, we sought to determine the time impact of the alternative approach of MRI selection in the 0–12 h window. Methods: In the MRI in Acute Management of Ischemic Stroke (MIAMIS) registry, we retrospectively analyzed 89 consecutive patients from January 2008 to January 2010 who presented with acute stroke symptoms with a National Institutes of Health Stroke Scale score ≥5 or aphasia within 0–12 h from symptom onset. The presence of penumbra was determined by MR perfusion-diffusion mismatch or clinical diffusion mismatch. Patients were stratified based on the presence of mismatch and clinical outcomes in patients who received ET. Imaging times were recorded. Results: The MRI turnaround time was 95.5 ± 48.5 min. The total MRI time was 27.7 ± 12.8 min. Seventeen (19.1%) patients were found to have nonvascular etiology. Mismatch was found in 35 (48.6%) patients with acute ischemic stroke (AIS). Patients with nonvascular etiology were younger (55.7 vs. 65.6 years, p < 0.02), without any vessel occlusion or mismatch noticed in this group. We dichotomized the 39 AIS patients with vessel occlusion into two subgroups: these with mismatch and these without. Patients without mismatch were older (76.7 vs. 64.4 years, p < 0.05), more likely to have congestive heart failure (71.4 vs. 22%, p < 0.03), a higher total serum cholesterol level (196 vs. 156 mg/dL, p < 0.04), and medium to large lesions on diffusion-weighted imaging (DWI) (85.7 vs. 37.5%, p < 0.04). Conclusions: Multimodality MRI screening for AIS symptoms for ET is feasible. Optimizing each center’s protocol and the utilization of MRI with DWI only may be a time-saving alternative.

Abstract WP28: Safety and Feasibility of Angioplasty and Stenting in Symptomatic Internal Carotid Artery Occlusive Disease

Introduction: Symptomatic internal carotid artery occlusion (ICAO) can lead to subsequent neurologic decline, recurrent stroke, and mortality. We sought to evaluate safety and feasibility of endovascular revascularization for ICAO without tandem intracranial large vessel occlusion (LVO). Methods: This is a retrospective cohort analysis of all patients presenting to a single academic center with ischemic stroke and ipsilateral, cervical ICAO from November 2003 through April 2016. Patients were excluded if pre-procedural angiography demonstrated tandem LVO or if patients were known to have chronic ICAO. Study endpoints included discharge neurologic exam, post-procedural infarct burden, 3-month functional outcomes, and treatment durability. Results: A total of 107 patients with symptomatic, angiographically confirmed cervical ICAO without tandem LVO were identified. Median admission NIHSS was 8 (IQR 11). Baseline radiographic stroke severity was assessed by ASPECT score (median 9; IQR 2), perfusion mismatch (present in 93%), and clinical-diffusion mismatch (42%). Median time from symptom onset to treatment was 25 hours (IQR 61). Successful revascularization was achieved in 92% of patients. At discharge, 83% had stable or improved NIHSS, while at 3-months 65% achieved functional independence (mRS ≤2). The most common complication was distal embolization (22%) of which 16% required intra-arterial treatment. Rate of significant restenosis (≥70%) was 15% at 1-year. Conclusions: Stenting in selected patients at risk of neurological deterioration due to symptomatic ICAO can be performed with high rates of technical success and good clinical outcomes. Because of significant peri-procedural risks and high rates of restenosis, randomized studies are necessary to understand the benefit of this approach.

Clinical diffusion mismatch better discriminates infarct growth than mean transit time–diffusion weighted imaging mismatch in patients with middle cerebral artery–M1 occlusion and limited infarct core

Background and purposeOur purpose was to compare clinical diffusion mismatch (CDM) and mean transit time (MTT)-diffusion mismatch as predictors of infarct growth in patients with proximal middle cerebral artery (MCA)...

Revascularization in Acute Ischemic Stroke Based on Clinical-Diffusion Mismatch (REVASC): A Planned Phase I Trial (P1.134)

Revascularization in Acute Ischemic Stroke Based on Clinical-Diffusion Mismatch (REVASC): A Planned Phase I Trial (P1.134)

Clinical-diffusion mismatch and short-term clinical outcomes among patients with acute ischemic stroke

To explore the law of clinical-diffusion mismatch (CDM) among patients with acute ischemic stroke (AIS) and analyze the relationships between CDM and short-term clinical outcomes. A prospective study was conducted for 56 patients with AIS admitted into our hospital within 72 hours from March 2011 to March 2012. And brain magnetic resonance imaging (MRI) examinations were completed within one week. All cases were diagnosed with infarction in the area of middle cerebral artery (MCA). The diffusion-weighted imaging (DWI) volume was calculated by semi-automatic method. Also the scores of National Institutes of Health stroke Scale (NIHSS) and modified Rankin Scale (mRS) were scored at baseline, days 7, 15, 30 post-admission respectively. The non-parametric variables were analyzed by Spearman's rank correlation. And the differences for non-parametric variables between CDM and non-CDM groups were analyzed by Mann-Whitney rank-sum test. A total of 16/56(28.6%) patients showed CDM. The CDM ratios of the patients undergoing MRI within 72 hours after onset and those beyond 72 hours after onset were 36.3% and 17.4% respectively. Also 50.0% of those with CDM had favorite neurological outcomes. While for the other group without CDM, only 6.7% did so. The differences were significant (P = 0.001). The correlations for all AIS patients between NIHSS scores and DWI volume were strong (rs = 0.721, P = 0.009). Specifically, the correlations for without CDM group (rs = 0.847, P = 0.000) were stronger than those of with CDM group (rs = 0.610, P = 0.012). No significant inter-group differences existed in favorite clinical outcome, mortality case or neurological deterioration. CDM still occurs within 1 week after onset among patients with AIS. Although no significant differences exist in favorite clinical outcome between patients with CDM and without CDM, the CDM group may improve more in NIHSS scores and have better neurological outcomes.

Abstract W P40: Assessing Criteria for Intra-Arterial Therapy: Inter-Rater Reliability of Clinical-Diffusion Mismatch Among Stroke Clinicians

Background: Optimal patient selection strategy for intra-arterial therapy (IAT) in acute ischemic stroke remains uncertain. Clinical-diffusion mismatch (CDM) and perfusion-diffusion mismatch (PDM) on MRI are two selection methods used in practice. PDM can be radiologically defined and its analysis automated but this requires additional time and contrast administration. CDM is less technically challenging, however, there is variation in its definition and its inter-rater reliability has not been reported. Hypothesis: CDM has a higher inter-rater variability than PDM among vascular neurologists. Methods: Fellowship-trained vascular neurologists from our high-volume stroke center were surveyed on ten cases. For each case, they were first shown diffusion-weighted and apparent diffusion coefficient imaging and NIHSS score components and were asked if they felt a CDM existed. Based on the CDM alone, they were next asked if they would pursue IAT in the presence of a persistent large vessel occlusion. A perfusion image was then shown and the participants were asked if they felt a PDM existed. A final slide was shown giving the age, co-morbidities and pre-morbid disability, and location of arterial occlusion, after which they were again asked if they would pursue IAT. Kappa statistics were used to assess agreement. Results: Ten vascular neurologists participated in this study. The average inter-rater kappa for CDM was 0.35, 95% CI (0.28, 0.43) across the 10 cases. The average inter-rater kappa to take a patient for IAT based on CDM alone was 0.37, 95% CI (0.28, 0.46). The average inter-rater kappa for PDM was 0.61, 95% CI (0.53, 0.69). The average inter-rater kappa for final decision to take the patient to IAT was 0.30, 95% CI(0.22,0.37). The rate of IAT over the 10 cases varied from 10% to 70% among the vascular neurologists. Conclusions: This study suggests that vascular neurologists have a marginal inter-rater reliability for determining CDM. Inter-rater reliability for PDM was good although this did not have an effect on the reliability of final decision to take a patient for IAT. Further multi-center studies are needed to assess the variability of decision making for IA therapy.

Prolonged ictal aphasia presenting as clinical-diffusion mismatch in a patient with acute ischemic stroke.

Prolonged ictal aphasia presenting as clinical-diffusion mismatch in a patient with acute ischemic stroke.

Abstract TP32: ‘ABC/2’ Method for Stroke Measurement has Excellent Intra-Class Correlation for Different Modalities and Raters

BACKGROUND: The ‘Revascularization in Stroke Based on Clinical-Diffusion Mismatch’ study will evaluate the safety of endovascular therapy for stroke patients beyond 8 hours from onset. The inclusion criteria include diffusion weighted magnetic resonance imaging (DW-MRI) stroke lesion volume &lt;/=25 mL3. To apply this criterion in practice, measurement techniques easily performed by any clinician, such as the ‘ABC/2’ formula for intracerebral hemorrhage (ICH), are needed. This has been validated against planimetry for middle cerebral artery (MCA) infarction on DW-MRI. We sought to evaluate the inter-rater reliability between raters and the correlation between different ABC/2 formulas for lesions on DWI-MRI and CT. METHODS: CTs and DWI-MRIs of stroke and hemorrhage patients were screened to select a sample of lesions in the cerebral cortex, subcortex, basal ganglia, brainstem, and cerebellum for each group (CT hemorrhage, CT stroke, DW-MRI stroke). Three raters then measured lesion volume as follows: (AxBxC)/2, where A= largest linear lesion diameter in centimeters (cm) on a single slice; B=largest linear diameter perpendicular to A (cm); C=counts between lesion slices multiplied by slice thickness in cm. The ‘adjusted ABC/2’ formula for ICH weights each scan slice by proportion of hemorrhage to the index slice. To evaluate differences between these techniques, a single rater evaluated each lesion using each of the formulas. Measurements were examined through the intraclass correlation (ICC) statistic, to give a composite score of intra-observer and inter-observer variability. The ICC was tested for being significantly different from 0 yielding the reported p-value (1 indicates good ICC). RESULTS: CONCLUSION: The ABC/2 method has excellent ICC on DW-MRI and CT for different examiners, lesions, and locations as well as minimal variability between different formulas. This may be an alternative to computer planimetry for triage of stroke patients in future studies.

Abstract WP43: ‘Clinical-Diffusion Mismatch’ Triage Criteria at 8-24 Hours from Symptom Onset Identifies 4% of Stroke Patients for Potential Intervention

Background: ‘Clinical-diffusion mismatch’ (CDM) criteria may identify ischemic stroke (IS) patients with salvageable penumbra, and is intended for triage in a planned prospective trial of acute stroke intervention for patients presenting between 8 and 24 hours. For this study, CDM is defined as a National Institutes of Health Stroke Scale Score (NIHSSS) ≥8 and diffusion weighted imaging (DWI) stroke volume of ≤25 mL3 using a modified ‘ABC/2’ criteria, which has previously been validated against planimetric imaging and shown to have excellent inter-rater reliability. We sought to determine the percentage of potential patients who may be screened for enrollment on this basis in 2 urban teaching hospitals which each receive &gt;200 stroke patients per year. Methods: We identified all IS admissions from our Get with the Guidelines database from 1/1/10-12/31/10. We then abstracted those arriving within 8 to 24 hours of symptom onset and then, of this subset, those who had an initial NIHSSS ≥8. To determine those meeting radiographic criteria, we measured stroke volume on the admission head computed tomogram (CT) using the unadjusted ABC/2 formula. As CT is known to have a 60% sensitivity for IS compared with DWI within 12 hours, we estimated that only 60% of the patients from the above calculation might still have lesion volumes ≤25mL3 on DWI. Results: A total of 588 IS patients were admitted in 2010. Of these, 162 patients presented within 8-24 hours. NIHSSS were ≥8 in 41 of whom 28 had lesions ≤25mL3. Considering 60% of these would remain valid on DWI, would leave approximately 17 patients (2.6%). Incomplete data led to attrition at each step; applying the same percentages at each recruitment step to those lost yields 9 patients, for an overall potential recruitment of 26 (4.4%, table). Conclusion: We conservatively estimate that in 1 year, 4% of IS patients within 8-24 hours demonstrate a CDM. These data are important for trialists and funding agencies planning studies using CDM criteria.

O-003 Temporal distribution of stroke volumes and clinical-diffusion mismatch in patients with proximal arterial occlusions

Background and PurposePrevious studies have demonstrated that the benefit of reperfusion therapy declines over time. The Clinical-Diffusion Mismatch (CDM) model has been suggested as surrogate for salvable tissue in acute...

Abstract 3851: Temporal Distribution of Stroke Volumes and Clinical-Diffusion Mismatch in Patients with Proximal Arterial Occlusions

Background and Purpose: Previous studies have demonstrated that the benefit of reperfusion therapy declines over time. The Clinical-Diffusion Mismatch (CDM) model has been suggested as surrogate for salvable tissue in acute ischemic stroke (AIS) patients. We sought to describe the temporal behavior profile of infarct volumes and CDM in patients suffering AIS due to proximal arterial occlusion (PAO). Methods: We performed a retrospective analysis of consecutive AIS patients admitted to two large academic institutions fulfilling the following criteria: (1) Baseline NIHSS ≥8; (2) PAO defined as MCA-M1, intracranial ICA, or tandem cervical + ICA/MCA-M1 occlusion on admission CTA/MRA; and (3) MRI-DWI performed ≤8 hours from time of stroke onset/last seen well (TSO). CDM was defined as baseline NIHSS ≥8 and DWI volume ≤25cc (as proposed by Davalos et al). Linear regression analysis was performed to define the changes on DWI lesion volume on presentation over time. The observed TSO to MRI were broken down into quartiles to look for any differences in the distribution of the baseline variables over time. Results: A total of 132 consecutive patients were identified (mean age, 66±16.8 years; 57% females; mean baseline NIHSS 17.5±5.3; occlusion site: MCA-M1, 64%; intracranial-ICA, 29%; tandem, 5%, mean TSO to DWI, 269.5±105.48 minutes). The mean DWI stroke volume on presentation was 46.7±54.8 cc (range, 0.19-436.1) and 63 (46.7%) patients had CDM. There was no significant changes in age, gender, baseline NIHSS, or occlusion site amongst the different time quartiles. Median infarct volume (cc) increased (quartile #1=8.5; #2=30.1; #3=38.5; #4=29.4) and the chances of having a CDM decreased (p&lt;0.0001) across the different time quartiles. However, there was an overall poor correlation between DWI lesion volume on presentation and TSO to MRI (R-square=0.031, Figure ) and a significant proportion of the patients still had a CDM at later time epochs (#1=91.1%[20/22]; #2=47.8%[11/23]; #3=34.4%[21/61]; #4=42.3%[11/26]). Conclusions: Although infarct volume increases and the amount of penumbral tissue decreases over time, many patients with PAO will still have salvable penumbra at the later time epochs. This reflects individual differences in anatomic and physiological characteristics including the strength of collateral flow and highlights that selected patients may benefit from reperfusion therapy even at the later time windows. Figure : Relationship between Baseline DWI Volume (cc) and Time (minutes). Line is best fitted linear regression model.

Magnetic Resonance Angiography–Diffusion Mismatch Reflects Diffusion–Perfusion Mismatch in Patients with Hyperacute Cerebral Infarction

We evaluated whether clinical-diffusion mismatch (CDM) or magnetic resonance angiography (MRA)-diffusion mismatch (MDM) is useful in detecting diffusion-perfusion mismatch (DPM) in hyperacute cerebral infarction within 3 hours after stroke onset. Among patients with cerebral infarction who arrived within 3 hours after stroke onset at our hospital between May 2007 and December 2010, we included 21 patients (16 men and 5 women; mean age 70 ± 7.8 years) with cerebral infarction of the anterior circulation, and in whom magnetic resonance imaging (diffusion-weighted imaging)/MRA and computed tomograpic perfusion of the head were performed at the time of arrival. DPM-positive status was defined as a difference between DWI abnormal signal area and mean transit time prolongation area (≥ 20% on visual assessment). CDM-positive status was defined as a National Institute of Health Stroke Scale score ≥ 8 and DWI-Alberta Stroke Program Early CT Score (ASPECTS) ≥ 8. MDM-positive status was defined as a major artery lesion and DWI-ASPECTS ≥ 6. Ten of 21 patients had DPM. In all DPM-positive patients, MRA revealed a major artery lesion. Of the 10 DPM-positive patients, 6 were CDM-positive. CDM detected DPM with a sensitivity of 60% and a specificity of 64%. The positive likelihood ratio was 1.65. Of the 10 DPM-positive patients, all were MDM-positive. MDM detected DPM with a sensitivity of 100% and a specificity of 82%. The positive likelihood ratio was 5.5. In hyperacute cerebral infarction within 3 hours after onset, MDM, as compared with CDM, was able to detect DPM with higher sensitivity and specificity. This suggests that MDM is more reflective of DPM.

Early Biomarkers of Clinical–Diffusion Mismatch in Acute Ischemic Stroke

Clinical-diffusion mismatch (CDM; National Institutes of Health Stroke Scale score≥8 and diffusion-weighted imaging lesion volume<25 mL) has been suggested as a surrogate of ischemic brain at risk of infarction and might be used to recognize salvageable ischemic tissue. Our aim was to identify early biomarkers associated with the presence of CDM. We prospectively evaluated CDM in 226 patients (71.6±11.1 years, 58% men) with hemispheric ischemic stroke within 12 hours from symptom onset (median, 3.6 hours). Diffusion-weighted MRI lesion volume was measured by manual segmentation method. Serum levels of glutamate, aspartate, interleukin-10, tumor necrosis factor-α, interleukin-6, S100β, neuron-specific enolase, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, active matrix metalloproteinase-9, and cellular fibronectin were determined by immunoassay or high-performance liquid chromatography techniques in blood samples obtained at admission. CDM was found in 61 patients (26.9%). Patients with CDM had higher serum levels of interleukin-10, tumor necrosis factor-α, and glutamate and lower serum levels of neuron-specific enolase, interleukin-6, and active matrix metalloproteinase-9 (all P<0.0001). Binary logistic regression showed that tumor necrosis factor-α≥21 pg/mL (OR, 21), glutamate≥230 μmol/L (OR, 27), neuron-specific enolase≥23 ng/mL (OR, 0.05), interleukin-6≥10 pg/mL (OR, 0.06), and active matrix metalloproteinase-9≥21 ng/mL (OR, 0.28) were independent molecular predictors of CDM after adjustment for covariates. The association of interleukin-10≥23 pg/mL and glutamate≥230 μmol/L levels predicted CDM with a sensitivity of 96% and a specificity of 98%. High levels of interleukin-10, tumor necrosis factor-α, and glutamate as well as low levels of neuron-specific enolase, interleukin-6, and active matrix metalloproteinase-9 are associated with CDM.

O-002 Acute stroke treatment: without time limitations

BackgroundMany new stroke trials are evaluating the utility of perfusion imaging for patient selection within certain time constraints. There is evidence that patients with a delayed (>12 h) clinical–diffusion mismatch...

Significance of Clinical–Diffusion Mismatch in Hyperacute Cerebral Infarction

In recent years, patient selection for intravenous tissue plasminogen activator (t-PA) therapy based on clinical-diffusion mismatch (CDM) has been closely examined. We investigated the relationship between prognosis and CDM in patients with hyperacute cerebral infarction within 3 hours of onset and compared CDM with diffusion-perfusion mismatch (DPM). Of 122 patients with hyperacute cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and November 2008, 85 patients with cerebral infarction in the anterior circulation who underwent head magnetic resonance imaging diffusion-weighted imaging (DWI)/magnetic resonance angiography (MRA) (51 men and 34 women; average age, 74 ± 10 years) were enrolled. Seventeen of these patients underwent CT perfusion imaging. CDM-positive cases were those with a National Institute of Health Stroke Scale (NIHSS) score ≥ 8 and a DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≥ 8; CDM-negative cases were those with an NIHSS score ≥ 8 and an ASPECTS-DWI < 8. The other patients were classified as belonging to the NIHSS score < 8 group. Of the 32 CDM-positive cases, 10 received t-PA infusion. These patients had markedly higher modified Rankin Scale scores 90 days after onset compared with the 22 patients who did not receive t-PA infusion. The 8 CDM-positive cases included 4 DPM-positive cases and 4 DPM-negative cases, and a discrepancy was confirmed between CDM and DPM. In all DPM-positive cases, MRA confirmed lesions in major intracranial arteries. CDM may enable more accurate prediction of outcomes in patients with hyperacute cerebral infarction. In addition, the combination of CDM findings and MRA findings (stenosis or occlusion in major intracranial arteries) may be an alternative to DPM for determining the indications for IV t-PA therapy in patients with hyperacute cerebral infarction.

Clinical-Diffusion Mismatch and Benefit From Thrombolysis 3 to 6 Hours After Acute Stroke

Clinical-Diffusion Mismatch and Benefit From Thrombolysis 3 to 6 Hours After Acute Stroke