DWI-ASPECTS as a Predictor of Dramatic Recovery After Intravenous Recombinant Tissue Plasminogen Activator Administration in Patients With Middle Cerebral Artery Occlusion
Background and Purpose—In patients with middle cerebral artery trunk occlusion we investigated whether the diffusion-weighted imaging- the Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) predicts short-term neurological recovery after intravenous recombinant tissue plasminogen activator administration, and investigated how DWI-ASPECTS relates to clinical outcome.
Methods—Dramatic recovery was defined as a ≥10-point reduction or a total National Institutes of Health Stroke Scale score of 0 to 1 at 24 hours and 7 days. Early recanalization was defined as recanalization within 1 hours after intravenous recombinant tissue plasminogen activator. Favorable outcome at 3 months was defined as a modified Rankin Scale score of 0 to 2.
Results—Sixty-six patients (median age [interquartile], 79 [70–85] years, male; 34 [52%]) were enrolled. DWI-ASPECTS was 6 (5–9). Dramatic recovery was seen in 16 (24%) and 26 (39%) patients at 24 hours and on day 7, respectively. Early recanalization occurred in 22 (33%) patients. DWI-ASPECTS ≥7 was an independent predictor of dramatic recovery at 24 hours (odds ratio, 100.85; 95% confidence interval, 4.29–2371.40; P=0.004) and 7 days (odds ratio, 14.15; 95% confidence interval, 2.21–90.48; P=0.005). Although the favorable outcome rate was not significantly different between patients with DWI-ASPECTS ≥7 with and without early recanalization (60% versus 31%; P=0.228), it was statistically more frequent in patients with DWI-ASPECTS <7 with early recanalization than those without early recanalization (38% versus 0%; P=0.017).
Conclusions—DWI-ASPECTS predicted short-term recovery in patients with middle cerebral artery trunk occlusion receiving intravenous recombinant tissue plasminogen activator. In patients with lower DWI-ASPECTS, there may still be benefit from early recanalization.
Diffusion-weighted imaging–the Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) can predict clinical outcome in patients treated with intravenous recombinant tissue plasminogen activator (IV-tPA).1 However, the role of DWI-ASPECTS in patients with large arterial occlusions has not been established. We investigated whether DWI-ASPECTS can serve as an independent predictor of short-term neurological recovery and whether DWI-ASPECTS is related to clinical and radiological outcomes after IV-tPA in patients with the middle cerebral artery trunk occlusion (M1-MCAO).
Consecutive patients between October 2005 and March 2012 were prospectively enrolled. IV-tPA therapy was administered based on the Japanese Guideline for the Management of Stroke.2 Acute stroke patients with unknown stroke onset time were also treated with IV-tPA based on DWI/fluid-attenuated inversion recovery (FLAIR) mismatch.3 Only patients with M1-MCAO on magnetic resonance angiography were enrolled. DWI-ASPECTS on admission was assessed by 1 expert vascular neurologist (K.K.) who was blinded to clinical information. Infarct volumes on initial DWI and FLAIR at 7 days were calculated using National Institutes of Health-image. Proximal M1-MCAO was defined as occlusion from the proximal half of the M1-MCAO. Recanalization was defined as new appearance of at least one of the distal middle cerebral artery branches assessed within 1 hour of IV-tPA (early recanalization) and 24 hours after IV-tPA. Dramatic recovery (DR) included a ≥10-point reduction or a total National Institutes of Health Stroke Scale (NIHSS) score of 0 to 1 at 24 hours and on day 7. At 3 months, the presence of a favorable outcome (a modified Rankin Scale [mRS] score of 0–2) was assessed.
Sixty-six patients (median age [interquartile], 79 [70–85] years; 34 [52%] males; NIHSS score, 18 [14–23]) were enrolled. No patients were treated with an intra-arterial intervention. None had symptomatic intracerebral hemorrhage. DWI-ASPECTS was 6 (5–9). DR was seen in 16 (24%) and 26 (39%) patients at 24 hours and on day 7, respectively. Early recanalization occurred in 22 (33%) patients. The online-only Supplemental Tables 1 and 2 show the clinical characteristics of patients with and without DR at 24 hours and 7 days, and Figure 1 shows the association of DR at 24 hours and 7 days as well as clinical outcome at 3 months with DWI-ASPECTS.
DWI-ASPECTS ≥7 was found to be the cut-off that could identify the DR at 24 hours and 7 days (sensitivity of 0.88 and 0.77, specificity of 0.64 and 0.70, and area under curve of 0.771 and 0.743, respectively, all P=0.001). Multivariate analysis revealed that DWI-ASPECTS ≥7 was an independent predictor of DR both at 24 hours and 7 days (Table). In patients with DWI-ASPECTS ≥7, early recanalization was associated with DR at 24 hours. In those with DWI-ASPECTS <7, early recanalization was related to DR at 7 days (Figure 1).
DWI and FLAIR infarct volumes were not different between patients with DWI-ASPECTS ≥7 with and without early recanalization (DWI, 0.6 [0.2–5.1] mL versus 3.1 [1.8–9.9] mL; P=0.159 and FLAIR, 11.0 [4.9–37.7] mL versus 31.7 [10.7–158.6] mL; P=0.100). Although DWI-measured volume was similar between patients with DWI-ASPECTS <7 with and without early recanalization (46.0 [33.2–59.6] mL versus 39.8 [21.3–75.4] mL; P=0.159), FLAIR-measured volume was significantly smaller in patients with DWI-ASPECTS <7 with early recanalization than those without early recanalization (97.5 [50.1–138.4] mL versus 231.7 [164.3–453.1] mL; P=0.001).
Favorable outcome was seen in 14 (26%) of 54 patients with a premorbid mRS of 0 to 2. The rate of favorable outcome in patients with DWI-ASPECTS ≥7 was not associated with early recanalization. To the contrary, out of all of the patients without early recanalization, none of the patients with DWI-ASPECTS <7 had a favorable outcome (Figure 2).
DWI-ASPECTS ≥7 was an independent predictor of short-term neurological recovery after an M1-MCAO. Limited DWI changes before IV-tPA have been reported as a predictor of neurological recovery.4 Presence of a clinical-DWI mismatch defined as DWI-ASPECTS ≥7 and an NIHSS score ≥8 has also been reported to be predictors of neurological recovery after IV-tPA.5 An advantage of our study is that the utility of DWI-ASPECTS was evaluated after adjusting for several established imaging and laboratory parameters.
Although early recanalization was associated with DR in patients with DWI-ASPECTS ≥7 and <7, its role regarding clinical and radiological outcomes depended on the initial DWI-ASPECTS. In patients with DWI-ASPECTS ≥7, the favorable outcome rate and follow-up infarct volume were not statistically different between patients with and without early recanalization. To the contrary, in patients with DWI-ASPECTS <7, favorable outcomes were only seen in patients with early recanalization. Early recanalization also led to smaller infarct volumes at day 7, despite that these infarcts were still large. These results indicate that in patients with lower DWI-ASPECTS there may be no benefit to delayed recanalization, whereas there may still be benefit from early recanalization. The combination of IV-tPA and intra-arterial intervention has attracted significant attention attributable to the resultant increase in the early recanalization rate. Administration of a free radical scavenger might also elevate the rate of early recanalization.6 Immediate combination of these therapies may provide better outcomes in patients with lower DWI-ASPECTS.
There are several limitations to the present study. The number of patients was small and most patients were older. A tPA dose of 0.6 mg/kg was used (based on the Japanese guideline), and patients with off-label use of IV-tPA were also enrolled. The rate of recanalization was high, possibly because recanalization was assessed using magnetic resonance angiography. Because the patients were simply divided into 2 groups based on the DWI-ASPECTS cut-off of 7, the exact relationship of DWI-ASPECTS with early recanalization regarding short-term recovery and clinical and radiological outcomes is unclear.
In conclusion, DWI-ASPECTS predicted short-term neurological recovery in patients with M1-MCAO after receiving IV-tPA. In patients with lower DWI-ASPECTS, early recanalization was associated with functional independence at 3 months after stroke.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.112.675470/-/DC1.
- Received August 29, 2012.
- Revision received October 13, 2012.
- Accepted October 24, 2012.
- © 2013 American Heart Association, Inc.
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