TOAST stroke subtype classification in clinical practice: implications for the Get With The Guidelines-Stroke nationwide registry

IntroductionThe TOAST (Trial of ORG 10172 in Acute Stroke Treatment) is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National Get With The Guidelines-Stroke (GWTG-Stroke) registry. However, stroke diagnostics have advanced substantially since the TOAST classification was designed 30 years ago, potentially making it difficult to apply reliably.MethodsIn this prospective diagnostic accuracy study, we analyzed consecutive ischemic stroke patients admitted to a Comprehensive Stroke Center between July–October 2021. Clinical practice TOAST classification diagnoses rendered by the stroke team in the electronic medical record (EMR) at discharge were retrieved from GWTG-Stroke registry and compared to a reference (“gold”) standard diagnosis derived from agreement between two expert raters after review of the EMR and patient imaging.ResultsAmong 49 patients; age was 72.3 years (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1–11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE ± TEE in 92%; and TCD emboli evaluation in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-39%, OTH-10%, UND-M (more than one cause)-20%, and UND-C (cryptogenic)-10%. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 30/49 (61%). Among the 6 subtype diagnoses, specificity was generally high (84.8%–97.7%), but sensitivity suboptimal for LAA (33%), OTH (60%), UND-M (10%), and UND-C (20%). Positive predictive value was suboptimal for 5 of the 6 subtypes: LAA (13%), SVD (58%), OTH (75%), UND-M (50%), and UND-C (50%).DiscussionClinical practice TOAST classification subtype diagnoses entered into the GWTG-Stroke registry were accurate in only 61% of patients, a performance rate that, if similarly present at other centers, would hamper the ability of the national registry to provide dependable insights into subtype-related care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic embedded in electronic medical records, is desirable

Abstract WP174: A Large-Scale Perfusion Imaging Atlas of Subacute Ischemia in MCA Atherosclerotic Stenosis

Background: Impaired perfusion may be an important determinant of outcomes in intracranial atherosclerotic disease (ICAD). CT and MRI perfusion imaging patterns of stenosis due to MCA ICAD have not been studied in detail. We characterized CT and MRI perfusion imaging measures of subacute ischemia subjects with MCA stenosis to create a novel atlas and define specific blood flow parameters. Methods: A retrospective, 5-year, analysis of consecutive ICAD patients evaluated with CT or MRI perfusion imaging for recent TIA or stroke (0-7 days) due to sub-occlusive (50-99%) MCA stenosis was conducted. CT/MRI volumes of core and hypoperfusion (>5 ml) were extracted with RAPID (iSchemaView, Inc.) and analyzed with respect to clinical variables. Descriptive statistics were used to quantify and map patterns of impaired perfusion. Results: 194 (median age 71, range 30-102 years; 53% women) patients with subacute ischemia were evaluated with MRI (n=161) or CT (n=33) perfusion imaging. Median initial NIHSS was 5 and median inpatient length of stay (LOS) was 4 (1-42) days. Hypoperfusion with Tmax>4s delay volumes (median 66.5 ml, mean 107.5 ml) were noted in 162 (84%) patients, Tmax>6s delay volumes (median 11.0 ml, mean 41.5 ml) in 118 (61%), Tmax>8s delay volumes (median 0 ml, mean 23.4 ml) in 81 (42%) and Tmax>10s delay volumes (median 0 ml, mean 16.9 ml) in 61 (31%). Hypoperfusion intensity ratios (Tmax>10s/Tmax>6s) were median 0.08 and mean 0.24. Ischemic core volumes on MRI (ADC6s hypoperfusion was unrelated to initial NIHSS (r=0.17, p=NS) or LOS (r=0.11, p=NS). Conclusions: Hypoperfusion is common in recently symptomatic ICAD patients with MCA stenosis. Tmax delay volumes and hypoperfusion intensity ratios are distinct from acute MCA occlusion. Mapping and understanding these specific patterns of perfusion will be instrumental in planning future ICAD trials

Impaired Distal Perfusion Predicts Length of Hospital Stay in Patients with Symptomatic Middle Cerebral Artery Stenosis

Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients. This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and <4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs. <7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS. One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max >6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244). In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings

Abstract P575: Impaired Distal Perfusion Predicts In-Hospital Outcome in Patients With Symptomatic Middle Cerebral Artery Stenosis

Background: Perfusion imaging is increasingly used to risk stratify patients with symptomatic intracranial stenosis. Length of hospital stay (LOS) in patients with ischemic stroke is a surrogate marker of increased morbidity. We aim to determine the association between perfusion delay on T max ( 6 sec) on perfusion weighted imaging and LOS in patients with symptomatic middle cerebral artery (MCA) stenosis. Methods: We included consecutive patients with left MCA stenosis admitted with ischemic stroke or TIA 6 sec delay, mismatch volume ≥ 15 mL based on T max 4-6 sec delay, and neither of the above mismatch patterns. The primary outcome was LOS, both as a continuous variable and categorical (≥ 7 days (prolonged LOS) vs. 6 sec and 31.3% had a mismatch volume ≥ 15 mL based on T max 4-6 sec and the median (IQR) LOS was 4 days (2-8). After adjusting for age and NIHSS, T max > 6 sec mismatch definition was associated with prolonged LOS (OR 2.90 95% CI 1.06-8.18; p=0.039) but T max 4-6 sec definition was not (OR 1.45 95% CI 0.46-4.58, p=0.528), without any interaction based on perfusion imaging modality (p interaction = 0.568). We found similar associations when LOS was considered as a continuous variable for T max > 6 sec (β coefficient=2.01, 95% CI 0.05-3.97, p=0.044) and T max 4-6 sec (β coefficient=1.24, 95% CI -0.85-3.34, p=0.244). In receiver operating curves, the optimal mismatch volume for T max > 6 sec was 10 mL (sensitivity 0.61 and specificity 0.63) whereas for T max 4-6 sec it was 39 mL (sensitivity 0.61 specificity 0.56). Conclusion: In patients with recently symptomatic MCA stenosis, the T max > 6 sec definition for mismatch, but not T max 4-6 sec, is associated with prolonged LOS. Prospective studies are needed to validate our findings and define the optimal mismatch threshold in patients with symptomatic MCA stenosis

Abstract P314: Mechanisms of Intracranial Atherosclerotic Disease Drive Hypoperfusion Patterns

Background: In patients with symptomatic intracranial atherosclerotic disease (ICAD), borderzone infarct pattern and perfusion mismatch have each been shown to independently predict recurrent strokes, which may reflect the shared underlying mechanism of hypoperfusion distal to the intracranial atherosclerosis. As such, we hypothesized that perfusion volumes and patterns may correlate with various ICAD subtypes. Methods: A retrospective, 5-year analysis of consecutive ICAD patients with perfusion imaging for acute strokes (0-24 hours) due to sub-occlusive (50-99%) stenosis was conducted. The following subtypes were assigned based on the infarct pattern seen on the diffusion-weighted imaging (DWI): perforator, borderzone, and thromboembolic. Core volume on MRI and perfusion parameters on CT or MR perfusion, obtained concurrently or within 12 hours of MR DWI, were studied in each group. Results: 42 patients (57% women, mean age 71±13 years old) with acute strokes received MRI imaging upon initial presentation. 15 were found with borderzone, 12 perforator, and 15 with thromboembolic pattern on DWI. Across all ICAD subtypes, median core volume (ADC 4s and Tmax >6s delay volumes was significantly higher in the thromboembolic and borderzone infarct patterns compared to the perforator subtype ( Figure 1 ). The volume difference between Tmax >4s and Tmax >6s (Δ Tmax>4s - Tmax>6s) was higher in the borderzone subtype compared to thromboembolism when analyzed pairwise. Conclusion: Core volume in ischemic strokes secondary to symptomatic ICAD is minimal. TMax>4 and TMax>6 parameters vary across the different ICAD patterns, with significantly large Tmax>4 delay volumes in the borderzone profile. Perfusion mapping may further elucidate hemodynamic mechanisms underlying ICAD

Intracranial atherosclerotic disease mechanistic subtypes drive hypoperfusion patterns

In symptomatic intracranial atherosclerotic stenosis (ICAS), borderzone infarct pattern and perfusion mismatch are associated with increased risk of recurrent strokes, which may reflect the shared underlying mechanism of hypoperfusion distal to the intracranial atherosclerosis. Accordingly, we hypothesized a correlation between hypoperfusion volumes and ICAS infarct patterns based on the respective underlying mechanistic subtypes. We conducted a retrospective analysis of consecutive symptomatic ICAS cases, acute strokes due to subocclusive (50%-99%) intracranial stenosis. The following mechanistic subtypes were assigned based on the infarct pattern on the diffusion-weighted imaging: Branch occlusive disease (BOD), internal borderzone (IBZ), and thromboembolic (TE). Perfusion parameters, obtained concurrently with the MRI, were studied in each group. A total of 42 patients (57% women, mean age 71 ± 13 years old) with symptomatic ICAS received MRI within 24 h of acute presentation. Fourteen IBZ, 11 BOD, and 17 TE patterns were identified. IBZ pattern yielded higher total T > 4 s and T > 6 s perfusion delay volumes, as well as corresponding T  > 4 s and T  > 6 s mismatch volume, compared to BOD. TE pattern exhibited greater median T  > 6 s hypoperfusion delay in volume compared to BOD. In IBZ versus TE, the volume difference between T > 4 s and T > 6 s (Δ T  > 4 s - T  > 6 s) was substantially greater. ICAS infarct patterns, in keeping with their respective underlying mechanisms, may correlate with distinct perfusion profiles

Neurologic Improvement in Acute Cerebral Ischemia

Background and objectivesInvestigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period.MethodsWe analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post-emergency department (ED) arrival examinations and classified as moderate (2-3 point) or dramatic (4-5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale [mRS] score 0-1) and death by 90 days.ResultsAmong the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2); 45% were women; the median prehospital LAMS was 4 (interquartile range [IQR] 3-5); the median last known well to ED-LAMS time was 59 minutes (IQR 46-80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28-39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0-1) at 90 days 65.1% (246/378) vs 35.4% (302/852), p &lt; 0.0001; decreased mortality by 90 days 3.7% (14/378) vs 16.4% (140/852), p &lt; 0.0001; decreased symptomatic intracranial hemorrhage 1.6% (6/384) vs 4.6% (40/861), p = 0.0112; and increased likelihood of being discharged home 56.8% (218/384) vs 30.2% (260/861), p &lt; 0.0001.DiscussionU-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov. Unique identifier: NCT00059332

Los Angeles Motor Scale to Identify Large Vessel Occlusion

Background and purposePrehospital scales have been developed to identify patients with acute cerebral ischemia (ACI) because of large vessel occlusion (LVO) for direct routing to Comprehensive Stroke Centers (CSCs), but few have been validated in the prehospital setting, and their impact on routing of patients with intracranial hemorrhage has not been delineated. The purpose of this study was to validate the Los Angeles Motor Scale (LAMS) for LVO and CSC-appropriate (LVO ACI and intracranial hemorrhage patients) recognition and compare the LAMS to other scales.MethodsThe performance of the LAMS, administered prehospital by paramedics to consecutive ambulance trial patients, was assessed in identifying (1) LVOs among all patients with ACI and (2) CSC-appropriate patients among all suspected strokes. Additionally, the LAMS administered postarrival was compared concurrently with 6 other scales proposed for paramedic use and the full National Institutes of Health Stroke Scale.ResultsAmong 94 patients, age was 70 (±13) and 49% female. Final diagnoses were ACI in 76% (because of LVO in 48% and non-LVO in 28%), intracranial hemorrhage in 19%, and neurovascular mimic in 5%. The LAMS administered by paramedics in the field performed moderately well in identifying LVO among patients with ACI (C statistic, 0.79; accuracy, 0.72) and CSC-appropriate among all suspected stroke transports (C statistic, 0.80; accuracy, 0.72). When concurrently performed in the emergency department postarrival, the LAMS showed comparable or better accuracy versus the 7 comparator scales, for LVO among ACI (accuracies LAMS, 0.70; other scales, 0.62-0.68) and CSC-appropriate (accuracies LAMS, 0.73; other scales, 0.56-0.73).ConclusionsThe LAMS performed in the field by paramedics identifies LVO and CSC-appropriate patients with good accuracy. The LAMS performs comparably or better than more extended prehospital scales and the full National Institutes of Health Stroke Scale

Los Angeles Motor Scale to Identify Large Vessel Occlusion

Background and purposePrehospital scales have been developed to identify patients with acute cerebral ischemia (ACI) because of large vessel occlusion (LVO) for direct routing to Comprehensive Stroke Centers (CSCs), but few have been validated in the prehospital setting, and their impact on routing of patients with intracranial hemorrhage has not been delineated. The purpose of this study was to validate the Los Angeles Motor Scale (LAMS) for LVO and CSC-appropriate (LVO ACI and intracranial hemorrhage patients) recognition and compare the LAMS to other scales.MethodsThe performance of the LAMS, administered prehospital by paramedics to consecutive ambulance trial patients, was assessed in identifying (1) LVOs among all patients with ACI and (2) CSC-appropriate patients among all suspected strokes. Additionally, the LAMS administered postarrival was compared concurrently with 6 other scales proposed for paramedic use and the full National Institutes of Health Stroke Scale.ResultsAmong 94 patients, age was 70 (±13) and 49% female. Final diagnoses were ACI in 76% (because of LVO in 48% and non-LVO in 28%), intracranial hemorrhage in 19%, and neurovascular mimic in 5%. The LAMS administered by paramedics in the field performed moderately well in identifying LVO among patients with ACI (C statistic, 0.79; accuracy, 0.72) and CSC-appropriate among all suspected stroke transports (C statistic, 0.80; accuracy, 0.72). When concurrently performed in the emergency department postarrival, the LAMS showed comparable or better accuracy versus the 7 comparator scales, for LVO among ACI (accuracies LAMS, 0.70; other scales, 0.62-0.68) and CSC-appropriate (accuracies LAMS, 0.73; other scales, 0.56-0.73).ConclusionsThe LAMS performed in the field by paramedics identifies LVO and CSC-appropriate patients with good accuracy. The LAMS performs comparably or better than more extended prehospital scales and the full National Institutes of Health Stroke Scale

Platelet FcγRIIa Expression in Ischemic Stroke: A Marker of Increased Platelet Reactivity

Background Platelet FcγRIIa amplifies platelet activation and, thus, increased expression identifies patients with increased platelet reactivity. Previous work has demonstrated that platelet FcγRIIa can identify patients at high and low risk of subsequent cardiovascular events after myocardial infarction (MI). This study was designed to compare platelet expression of FcγRIIa in patients with stroke and transient ischemic attack (TIA) with that in patients with a recent MI. Methods Patients were enrolled based on an admitting diagnosis of stroke/TIA, and the discharge diagnosis was used to categorize patients into stroke/TIA (n=99) and other causes of neurologic dysfunction (hemorrhagic, trauma, toxic, and seizure; n=14). Patients with stroke/TIA were divided into embolic (both cardioembolic and thromboembolic; n=32) and not embolic causes (n=67). Results were compared with platelet FcγRIIa expression in patients with recent MI from a previous study (n=197). Platelet expression of FcγRIIa (molecules of FcγRIIa/platelet) was quantified with the use of flow cytometry. Results are mean±SD. Results Platelet expression of FcγRIIa was similar in patients with ischemic (both embolic and nonembolic) stroke/TIA (11 332±4127), embolic (11 204±3889) and nonembolic (11 393±4263) causes, and MI (11 479±2405). Patients with other causes of neurologic dysfunction had modestly but not significantly lower platelet expression of FcγRIIa (9389±2883; P =0.13). Conclusions Platelet expression of FcγRIIa was similar in patients with stroke/TIA and recent MI. These results support future studies designed to determine whether platelet FcγRIIa expression can discriminate risk of subsequent stroke/TIA and its potential use as a precision tool capable of guiding individualized treatment decisions