Baseline NIH Stroke Scale Score Research Articles

Intravenous TPA for Very Old Stroke Patients

Background: Although thrombolysis in patients with advanced age is considered more risky, some may benefit from TPA treatment. We studied safety and recanalization/recovery in patients older than 80 years treated with TPA and compared them with younger stroke patients. Methods: We studied patients treated with intravenous TPA and divided them into younger (<80 years) and older (≧80 years) groups for comparison. Diagnostic transcranial Doppler was completed before bolus, and patients were consequently monitored for up to 2 h when feasible. Clinical data included NIH Stroke Scale score, symptomatic intracranial hemorrhage (ICH) and discharge disposition. Results: We studied 127 younger (mean 63 years, range 31–79) and 56 older patients (mean 84 years, range 80–93). Median baseline NIH Stroke Scale score was higher in the older group (18 vs. 14 points, NS). Occlusion locations, onset to needle time (median 130 vs. 120 min) as well as improvement at 24 h (median 5 vs. 4 points) were similar in both groups. Transcranial Doppler monitoring showed similar partial or complete recanalization rates (66 vs. 66%), onset to recanalization time (median 160 vs. 158 min) and reocclusion rates (26 vs. 25%). Symptomatic and fatal ICH was not higher in the older group (7.1 and 3.5% vs. 6.3 and 3.9%, NS). There was higher mortality among older patients (20 vs. 11%, NS). At discharge, 23% of older patients went home, 41% underwent rehabilitation and 16% were transferred to skilled nursing facilities, compared with 31, 43 and 15% respectively, in the younger group. Conclusion: After intravenous TPA treatment, patients over 80 years of age have similar recanalization, short-term improvement and symptomatic ICH rates compared with younger patients. However, older patients tend to have higher in-hospital mortality.

Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion

Background: Edaravone has potent free radical quenching and antioxidant actions. The agent has been recently in commercial use for acute ischemic stroke patients. In this study, we investigated the therapeutic effect of edaravone on severe carotid-territorial stroke. Methods: Stroke patients with internal carotid artery occlusion and baseline NIH Stroke Scale Score ≥15 were treated for 14 days with drip intravenous infusion of edaravone ( n=30) and were compared with a historical control cohort of similar patients ( n=31). Glycerol was also administered to all patients in both groups. Results: Infarct volume ( P<0.02) and midline shift ( P<0.02) on CT performed on day 2 of the patients treated with edaravone were smaller than those without edaravone. For patients with edaravone, infarct volume ( P<0.0001) and midline shift ( P<0.0001) on days 5–7 were greater than those on day 2. Hemorrhagic transformation of infarcts on day 2 was less severe in patients with than without edaravone ( P<0.03). Within 14 days after the onset of stroke, 6 patients with edaravone (20%) and 14 without edaravone (45%) died directly of stroke ( P<0.03). Among all patients, only two treated with edaravone were independent without any assistance 8 weeks after the onset. Conclusions: Edaravone was associated with delayed evolution of infarcts and edema in patients with severe carotid-territorial stroke and decreased mortality during the acute stage. The agent, however, failed to prevent evolution of infarcts and edema on later days, and did not significantly improve functional outcome among the surviving patients.

線溶療法 発症３時間以内の虚血性脳血管障害に対するＧＭＫ‐５２７（アルテプラーゼ）静注療法臨床試験の結果

Treatment of acute ischemic stroke with alteplase, an intravenous recombinant tissue plasminogen activator (rt-PA) has been approved in 40 countries, but not yet in Japan. To assess the clinical applicability of this therapy in Japan, we conducted a single dose open label multicenter trial (Japan Alteplase Clinical Trial, J-ACT).Inclusion and exclusion criteria in this study were almost the same as NINDS rt-PA Stroke Study, except that excluded were patients with early ischemic changes>1/3 of the MCA territory on the pretreatment CT, mild stroke defined as the pretreatment NIH Stroke Scale (NIHSS) score 4 or less, and patients with coma. Patients received alteplase at dose of 0.6 mg/kg. The dose was chosen because of the results of a study for patients with acute myocardial infarction and the duteplase study for embolic stroke patients both carried out earlier in Japan. The modified Rankin Scale (mRS), NIHSS, and Barthel Index scores at 3 months from stroke onset were evaluated for outcome measures. Adverse events and symptomatic intracranial hemorrhage (s-ICH) were assessed within the initial 3 months.A total of 103 patients (78% for cardioembolic stroke) were enrolled. The baseline NIHSS scores were comparable to those in the NINDS trial. The incidence of s-ICH within 36 hours from treatment, and the ratio of good outcome (mRS 0-1) and mortality at 3 months were consistent with those in the NINDS trial. In con-clusion, the efficacy and safety of alteplase at 6.0 mg/kg in J-ACT was comparable to that at the 0.9 mg/kg in the NINDS trial.

Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter?

The National Institute of Neurological Disorders and Stroke (NINDS) trial reported that stroke subtype (e.g., large-artery atherothrombosis, cardioembolism, and lacunae) does not affect response to IV thrombolytic treatment. However, these conclusions were based upon stroke subtypes determined prior to extensive diagnostic evaluation. Because such initial diagnoses are frequently inaccurate, the efficacy of IV recombinant tissue plasminogen activator (rt-PA) based upon verified specific stroke subtypes remains uncertain. The records of consecutive acute stroke patients treated with IV rt-PA at two regional stroke centers were retrospectively reviewed. The final stroke subtype after complete diagnostic evaluation was determined. The relationship between final stroke subtype and response to thrombolytic therapy was then investigated and compared with the results reported in the NINDS trial. Ninety consecutive patients were studied. After adjusting for baseline NIH Stroke Scale scores, no significant difference in final outcome based on confirmed stroke mechanism was identified. These data are consistent with those of the NINDS trial that reported that the efficacy of IV thrombolysis within the 3-hour time window is similar between different stroke subtypes. Based upon these data, allocating treatment of stroke patients with IV rt-PA based upon presumed stroke mechanism may be unnecessary. Such testing may result in time delays that could compromise the efficacy of treatment.

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial.

Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased (p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.

Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage

It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.

Rebleeding leads to poor outcome in ultra-early craniotomy for intracerebral hemorrhage.

A modest benefit was previously demonstrated for hematoma evacuation within 12 hours of intracerebral hemorrhage onset. Perhaps surgery within 4 hours would further improve outcome. Adult patients with spontaneous supratentorial intracerebral hemorrhage were prospectively enrolled. Craniotomy and clot evacuation were commenced within 4 hours of symptom onset in all cases. Mortality and functional outcome were assessed at 6 months. This group of patients was compared with patients treated within 12 hours of symptom onset using the same surgical and medical protocols. The study was stopped after a planned interim analysis of 11 patients in the 4-hour surgery arm. Median time to surgery was 180 minutes; median hematoma volume was 40 mL; median baseline NIH Stroke Scale score was 19 and Glasgow Coma Scale score was 12. Six-month mortality was 36% and median Barthel score was 75 in survivors. Postoperative rebleeding occurred in four patients, three of whom died. A relationship between postoperative rebleeding and mortality was apparent (p = 0.03). Rebleeding occurred in 40% of the patients treated within 4 hours, compared with 12% of the patients treated within 12 hours (p = 0.11). There was a clear correlation between improved outcome and smaller postsurgical hematoma volume (p = 0.04). Surgical hematoma evacuation within 4 hours of symptom onset is complicated by rebleeding, indicating difficulty with hemostasis. Maximum removal of blood remains a predictor of good outcome.