Two-Hour Improvement of Patients in the National Institute of Neurological Disorders and Stroke Trials and Prediction of Final Outcome

Abstract

Background Ongoing clinical trials are using early response to IV tPA to stratify patients into endovascular therapies. Little is known about the likelihood of early recovery and its correlation with final stroke outcome. Methods We analyzed the NINDS t-PA dataset for patients with early improvement (EI), a change of ≥4 or score 0 on the 2-hour NIHSS, to predict good 90-day outcome. We adjusted for multiple confounders and divided the patients by baseline NIHSS 0–10, 11–20, >20 and stroke type to analyze if EI predicted good outcome across stroke severities and types. We analyzed different EI thresholds to identify the best level of NIHSS change to predict good 90-day outcome using a Receiver Operator Characteristic (ROC). Results In total 183/624 (29.3%) patients had EI, 112/312 (35.9%) in the tPA and 71/312 (22.7%) in the placebo groups (p<0.0001). Smokers (p=0.012) and patients treated under 90 minutes (p=0.008) were more likely; diabetics (p=0.023) less likely to show EI. The baseline NIHSS (mean±SD) of patients with EI was 16.1±6.5 versus 14.3±7.4 (p=0.001). A 90-day mRS of 0–1 was achieved in 68/112 (60.7%) tPA treated patient with EI and 65/200 (32.5%) without (placebo groups 30/71 (42.3%) versus 53/241 (22.0%)). The adjusted odds ratio for good outcome was 1.71 (95% CI: 1.1,2.6, p=0.011) for t-PA treatment and 7.69 (4.63, 12.76, p<0.0001) for early improvement. EI predicted good outcome in patients with cardioembolic (13.6(3.6–51.5)) and small vessel (6.98(2.86–17.03), but not large vessel stroke (1.82(0.38–8.59). The ROC showed that a threshold of 4 on the NIHSS for prediction of good outcome had a sensitivity of 84% and 36% specificity. Conclusion Early improvement was more common in t-PA treated patients and associated with good 90 day outcome. While 32.5% of non-responders after t-PA had a good 90 day outcome, the use of EI to predict stroke outcome shows value.

Drip and Ship Thrombolytic Therapy for Acute Ischemic Stroke

“…Early improvement after tPA was well documented in the original National Institute of Neurological Disorders and Stroke (NINDS) tPA trial. 17 For patients treated by the drip and ship method, the captured NIHSS score is usually at the receiving hospital, post-tPA infusion, likely underestimating true baseline severity. This bias does not exist for front-door patients.…”

“…В связи с тем, что медиана времени от момента развития симптомов до поступления в клинику GWTG была в 4,8 раза боль-ше (249 минут vs 51 минута) у пациентов группы «drip and ship», вполне вероятно, что клиническое улучше-ние у значительного числа пациентов группы «drip and ship» произошло после раннего введения ТАП в клини-ке, осуществляющей перевод. Раннее улучшение после введения ТАП было четко подтверждено в оригиналь-ном испытании ТАП, проведенном Национальным институтом неврологических расстройств и инсульта (NINDS) [17]. Для пациентов группы «drip and ship» оценку по NIHSS, как правило, проводили в прини-мающей клинике после введения ТАП, и она, ско-рее всего, не отражала истинной исходной тяжести инсульта.…”

Timing of Neurological Improvement after Acute Ischemic Stroke and Functional Outcome

“…The effect of early neurological improvement on outcome has been mostly studied in clinical trials with thrombolytic treatment [12,13,14,15]. They focused on the immediate clinical response with recanalization after thrombolysis.…”

“…Most studies on thrombolytic treatment have adopted the definition of neurological improvement requiring a change of ≥4 points or ≥8 points in the NIHSS score [12,13,14]. Patients with a low baseline NIHSS score may be less likely to meet these criteria of neurological improvement unless they reach a NIHSS score of 0.…”

Wireless Accelerometry is Feasible in Acute Monitoring of Upper Limb Motor Recovery after Ischemic Stroke

“…IV-tPA improves clinical outcomes after acute ischemic stroke [1,2], but requires rapid and cohesive management of patients to maximize benefit. It is recognized that the acute clinical course after thrombolysis predicts longer-term functional status [3]. Between 18 and 35% of patients demonstrate rapid motor recovery within 2 h of IV-tPA, leading to a high proportion of good outcomes at 3 months [3,4,5].…”