Patents who experience an ischemic stroke and who have a large-vessel occlusion but only mild symptoms are at "substantial" risk for early neurologic deterioration after thrombolysis, a new study shows.
However, the findings also suggest that those with the highest risk can be easily identified with two simple parameters obvious on imaging, which may help to select the best candidates for additional thrombectomy.
Dr Pierre Seners
"Our results show that in patients with a minor stroke but who are found to have a large-vessel occlusion on imaging, those who have a longer thrombus and a proximal location of the thrombus have a much higher risk of early deterioration after thrombolysis alone," lead author Pierre Seners, MD, Institut de Psychiatrie et Neurosciences, Université de Paris, Paris, France, told Medscape Medical News.
"Based on these results, we have developed and validated a clinical score which can be used to identify these higher-risk patients who might then be considered for transfer for thrombectomy," he added.
The study was published online in JAMA Neurology on January 11.
Patients who experience an acute ischemic stroke and who have mild deficit, defined as National Institutes of Health Stroke Scale (NIHSS) score <6, but who are found to have a large-vessel occlusion on imaging present quite a dilemma as to how they should be treated, Seners explained.
At present, thrombolysis alone is the recommended strategy for these patients, who represent around 10% of stroke patients with a large-vessel occlusion. Thrombectomy after thrombolysis is reserved for patients with more severe symptoms on presentation (NIHSS score >6), he noted.
"The problem is that some of these patients with mild symptoms and a large-vessel occlusion can have a sudden deterioration in the first 24 hours, and by then, it is often too late to get the benefits of thrombectomy," Seners commented.
Some centers transfer these patients for early thrombectomy to avoid this scenario, but there are no good data on whether or not this is the best strategy. "Thrombectomy is not without risk, so we don't want to be performing it unnecessarily," he added.
For the current study, Seners and colleagues assessed the frequency of early neurologic deterioration caused by ischemia (defined as an increase of 4 or more points on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause) in these patients with mild symptoms but who had a large-vessel occlusion and who were treated with thrombolysis alone. They also sought to identify parameters that may predict which of these patients would experience early neurologic deterioration.
They evaluated 729 patients who had experienced a large-vessel occlusion stroke and whose median NIHSS score was 3.
Results showed that early neurologic deterioration occurred in 96 patients (13.2%). For 88 patients (12.1%), this was attributable to ischemia.
Patients with early deterioration due to ischemia had a significantly poorer 3-month outcome (Modified Rankin Scale [mRS] shift analysis) than those without early deterioration (common odds ratio [OR], 7.37; P < .001).
The rate of excellent functional outcome, defined as an mRS score <2, was 34% among patients who experienced early deterioration and 77.5% among those who did not experience early deterioration (P < .001).
Among the patients with early deterioration caused by ischemia, 56% underwent rescue thrombectomy. These patients had a better 3-month outcome than those who did not undergo rescue thrombectomy (common OR, 3.72; P = .001).
The rate of excellent functional outcome was 48% among those with early neurologic deterioration who received rescue thrombectomy, vs 16% for similar patients who did not receive rescue thrombectomy (P = .002).
But among patients who experienced early deterioration and who received rescue thrombectomy, rates of excellent functional outcome were lower than for patients who did not experience early deterioration (48% vs 77.5%; P < .001).
Key Parameters Signaling High Risk
The researchers also found that two imaging variables were strongly associated with early deterioration. The first was a proximal location of the occlusion, in particular, the carotid or M1 artery.
"In patients with an M2 occlusion, only around 5% had an early neurological deterioration, compared with 20% of those with a proximal M1 occlusion and 50% of those with a carotid occlusion," Seners reported.
The second variable associated with early deterioration was length of thrombus.
"This can easily be measured on MRI/CT imaging, and we found that the longer the thrombus, the higher the risk of an early deterioration. This is because long thromboses tend not to dissolve well with thrombolysis," Seners noted.
The researchers developed a 4-point score derived from these variables — 1 point for thrombus length, and 3 points for occlusion site — which showed good discriminative power for early neurologic deterioration (C statistic = 0.76).
This score was successfully validated in a second cohort of 347 patients. In both cohorts, the probability of early neurologic deterioration due to ischemia was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2, and 3–4, respectively.
"We are suggesting that this score can be used to inform about risk and to identify patients for whom thrombolysis alone may not be sufficient as treatment and could be candidates for early thrombectomy after thrombolysis," Seners commented.
He pointed out that although patients with higher scores are known to have higher risk for early deterioration after thrombolysis alone, it is still not known for sure whether thrombectomy after thrombolysis improves their outcomes. This would require randomized clinical trials comparing the two strategies.
Two such trials are currently underway ― the MOSTE trial, which is being conducted in France, Spain, and the United States, and the ENDOLOW trial, which is being conducted in Canada, the United States, and Germany. Results are expected in 3 to 5 years.
Seners is urging clinicians to enroll appropriate patients in these trials. Until the results are available, he recommends that those centers that cannot enroll patients in these trials use this new score and consider thrombectomy after thrombolysis for patients with higher scores.
"The score is very easy to calculate at brain imaging on admission, with only information on location and length of thrombus required," he said.
In their article, the researchers conclude that the "straightforward score" derived from the associations seen in this study, which were successfully validated in an independent cohort, affords good discriminative power for predicting early neurologic deterioration due to ischemia, which may eventually help clinical decision making.
Seners has disclosed no relevant financial relationships.
JAMA Neurol. Published online January 11, 2021. Abstract
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