Contrast-enhanced sonothrombolysis in acute ischemic stroke patients without intracranial large-vessel occlusion.

BACKGROUND: Contrast-enhanced sonothrombolysis (CEST) leads to a more rapid recanalization in acute ischemic stroke caused by intracranial large-vessel occlusion (LVO). Animal studies have shown that CEST also may be safe and efficient in treating the ischemic microcirculation in the absence of LVO. The exact mechanism behind this treatment effect is not known. We aimed to assess safety and efficacy of CEST in acute ischemic stroke patients included in the Norwegian Sonothrombolysis in Acute Stroke Study (NOR-SASS) without LVO on admission CT angiography (CTA). METHODS: NOR-SASS was a randomized controlled trial of CEST in ischemic stroke patients treated with intravenous thrombolysis within 4.5 hours after stroke onset. Patients were randomized to either CEST or sham CEST. In this study, patients were excluded if they had partial or total occlusion on admission CTA, ultrasound-resistant bone window, had received CEST with incorrect insonation as compared to stroke location on Magnetic resonance imaging (MRI), or were stroke mimics. RESULTS: Of the 183 patients included in NOR-SASS, a total of 83 (45.4%) patients matched the inclusion criteria, of which 40 received CEST and 43 sham CEST. There were no patients with symptomatic intracranial hemorrhage (sICH) in the CEST group. Rates of asymptomatic ICH, microbleeds, and mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days were similar in both groups. CONCLUSION: CEST is safe in ischemic stroke patients without intracranial LVO. There were no differences in clinical outcomes between the treatment groups.

Elevated body temperature in ischemic stroke associated with neurological improvement.

OBJECTIVES: Some studies suggest that high body temperature within the first few hours of ischemic stroke onset is associated with improved outcome. We hypothesized an association between high body temperature on admission and detectable improvement within 6-9 hours of stroke onset. MATERIALS AND METHODS: Consecutive ischemic stroke patients with NIHSS scores obtained within 3 hours and in the interval 6-9 hours after stroke onset were included. Body temperature was measured on admission. RESULTS: A total of 315 patients with ischemic stroke were included. Median NIHSS score on admission was 6. Linear regression showed that NIHSS score 6-9 hours after stroke onset was inversely associated with body temperature on admission after adjusting for confounders including NIHSS score <3 hours after stroke onset (P<.001). The same result was found in patients with proximal middle cerebral occlusion on admission. CONCLUSIONS: We found an inverse association between admission body temperature and neurological improvement within few hours after admission. This finding may be limited to patients with documented proximal middle cerebral artery occlusion on admission and suggests a beneficial effect of higher body temperature on clot lysis within the first three hours.

Mild stroke: safety and outcome in patients receiving thrombolysis.

OBJECTIVES: The aim of this study was to compare the short-term clinical outcome of patients with acute cerebral ischemia and mild symptoms receiving rt-PA with that of patients with acute cerebral ischemia and mild symptoms not treated with rt-PA, and to investigate the frequency of symptomatic intracranial hemorrhage (sICH) in these patients. MATERIALS AND METHODS: All patients with confirmed ischemic stroke/TIA and mild symptoms were included. Mild symptoms were defined as NIHSS score≤5 on admission. Functional outcome was assessed with modified Rankin Scale (mRS) at day 7 or at earlier discharge. Excellent outcome was defined as mRS=0. sICH was defined according to both NINDS and ECASS III criteria. RESULTS: Of 2753 patients with confirmed ischemic stroke/TIA admitted between February 2006 and February 2013, 966 (35.3%) were excluded because of having admission NIHSS>5. A total of 1791 patients presented with mild symptoms on admission (NIHSS≤5), of which 158 (8.8%) patients received rt-PA. Treatment with rt-PA and early admission were independently associated with excellent outcome. Higher NIHSS score on admission and prior ischemic stroke were independently associated with poor outcome. Three (1.9%) sICH were diagnosed in rt-PA-treated patients and one (0.1%) in patients not receiving rt-PA. CONCLUSIONS: This study highlights the efficacy of rt-PA in patients with acute cerebral ischemia presenting with mild symptoms and confirms the low-risk profile of this treatment.

Diffusion-weighted lesions in acute ischaemic stroke patients with migraine.

OBJECTIVES: There is increasing knowledge about an association between migraine and ischaemic stroke. Cortical spreading depression (CSD) is the probable biological substrate of migrainous aura. To investigate the influence of CSD on the apparent stroke - migraine association, we hypothesized that magnetic resonance (MR) diffusion weighted images of acute ischaemic stroke patients would reveal an association between small cortical infarctions and migraine. METHODS: We included all patients admitted to the Bergen stroke unit between 2006 and 2012 with verified acute ischaemic stroke by MR imaging. Patients were grouped in a migraine and a no-migraine group. Baseline data and clinical characteristics were analysed between the groups. Imaging data were analysed with respect to infarct location and size. Multivariate analyses were performed to adjust for confounders and provide risk estimates for observed associations. RESULTS: A total of 1703 subjects were enrolled, 787 subjects were excluded due to uncertain or unobtainable migraine diagnosis, leaving 196 and 720 subjects in the migraine and no-migraine group, respectively. The migraine group was younger and included a higher proportion of females. There were more infarctions due to cardio-embolism (P=0.015) and fewer due to small vessel disease (P=0.018) in the migraine group. A higher rate of patients in the migraine group presented symptoms from the posterior circulation (P=0.008). Migraine was associated with cortical infarctions (OR 1.8 CI: 1.3-2.5, P=0.001). Migraine was also associated with small infarctions (OR 1.9 CI: 1.04-3.5, P=0.038). CONCLUSIONS: Migraine was associated with small cortical infarctions. This association may be due to cortical spreading depression.

Is smoking associated with favourable outcome in tPA-treated stroke patients?

BACKGROUND: Smoking has been associated with improved outcome in thrombolysed patients with myocardial infarction and higher recanalization rates in stroke patients treated with tissue plasminogen activator (tPA). We hypothesized a positive association between smoking and favourable outcome in stroke patients treated with tPA and no such association in acute stroke patients not treated with tPA, suggesting a beneficial effect of smoking on thrombolysis with tPA. METHODS: Stroke patients treated with tPA and stroke patients not treated with tPA, but presenting within 6 h after stroke onset, were included in two separate groups. Three groups were defined according to smoking habits: current smoking, previous smoking and no smoking. Functional outcome by modified Rankin Scale (mRS) was assessed after 1 week or at discharge, if discharged earlier. Favourable outcome was defined as mRS 0 or 1. RESULTS: A total of 399 patients were treated with tPA (94 current smokers, 148 previous smokers and 157 non-smokers), whereas 424 patients were not treated with tPA (90 current smokers, 164 previous smokers and 170 non-smokers). Current smoking was independently associated with favourable outcome in patients treated with tPA when adjusted for confounders (OR 2.08, 95% CI 1.09-3.95, P = 0.025). There was no such association in acute stroke patients not treated with tPA (OR 1.26, 95% CI 0.67-2.36, P = 0.472). CONCLUSION: Our study showed an association between current smoking and favourable short-term outcome in stroke patients treated with tPA, but not in acute stroke patients not treated with tPA. This may indicate a more effective thrombolysis with tPA in smokers.

Body temperature and major neurological improvement in tPA-treated stroke patients.

BACKGROUND: Major neurological improvement (MNI) at 24 hours represents a marker of early recanalization in ischaemic stroke. Although low body temperature is considered neuroprotective in cerebral ischaemia, some studies have suggested that higher body temperature may promote clot lysis in the acute phase of ischaemic stroke. We hypothesized that higher body temperature was associated with MNI in severe stroke patients treated with tPA, suggesting a beneficial effect of higher body temperature on clot lysis and recanalization. METHODS: Patients with ischaemic stroke or transient ischaemic attack (TIA) treated with tPA between February 2006 and August 2012 were prospectively included and retrospectively analysed. Body temperature was measured upon admission. MNI was defined by a ≥8 point improvement in NIHSS score at 24 hours as compared to NIHSS score on admission. No significant improvement (no-MNI) was defined by either an increase in NIHSS score or a decrease of ≤2 points at 24 hours in patients with an admission NIHSS score of ≥8. RESULTS: Of the 2351 patients admitted with ischaemic stroke or TIA, 347 patients (14.8%) were treated with tPA. A total of 32 patients (9.2%) had MNI and 56 patients (16.1%) had no-MNI. Patients with MNI had higher body temperatures compared with patients with no-MNI (36.7°C vs 36.3°C, P = 0.004). Higher body temperature was independently associated with MNI when adjusted for confounders (OR 5.16, P = 0.003). CONCLUSION: Higher body temperature was independently associated with MNI in severe ischaemic stroke patients treated with tPA. This may suggest a beneficial effect of higher body temperature on clot lysis and recanalization.

Clinical implications of increased use of MRI in TIA.

BACKGROUND: Transient ischemic attack has been redefined as a tissue-based diagnosis and MRI recommended as the preferred imaging modality. We aimed to investigate whether an increased use of MRI leads to a decrease in the proportion of TIA as compared to cerebral infarction. We also sought to see whether DWI-positive patients with transient ischemic symptoms <24 h differ from DWI-negative TIA patients in terms of performed diagnostic investigations and clinical characteristics. METHODS: Patients admitted with cerebral infarction or TIA in the period 2006-2011 were prospectively registered. The use of MRI in patients with transient ischemic symptoms <24 h and proportion of TIA were annually recorded. DWI-positive and DWI-negative patients with transient ischemic symptoms <24 h were compared in univariate analyses regarding baseline data, diagnostic investigations, and etiology. Multivariate analyses were performed to identify predictors of DWI lesions. RESULTS: The use of MRI increased from 65.0% in 2006-2008 to 89.0% in 2009-2011 (P < 0.001). The proportion of TIA as compared to cerebral infarction decreased from 12.2% in 2006-2008 to 8.3% in 2009-2011 (P = 0.002). DWI-positive patients were more often examined with 24-h Holter monitoring (P < 0.001) and echocardiography (P < 0.001). Lower age (P < 0.001) and prior myocardial infarction (P < 0.029) were independently associated with DWI lesions in patients with transient ischemic symptoms <24 h. CONCLUSIONS: An increased use of MRI and a tissue-based TIA definition resulted in a decrease in the proportion of TIA at discharge as compared to cerebral infarction. DWI-positive patients had a more extensive cardiac work-up and were associated with lower age and prior myocardial infarction.

Safety of off-label stroke treatment with tissue plasminogen activator.

BACKGROUND: Many patients with acute ischaemic stroke do not receive intravenous thrombolysis due to contraindications. We aimed to assess safety, short-term clinical development, short-term outcome and mortality in patients treated off-label with tissue plasminogen activator (tPA). METHODS: Stroke patients treated with tPA within 4.5 h after symptom onset during 2006-2011 were prospectively included. Patients with contraindications to tPA according to national guidelines were compared to patients without any of these contraindications. Separate analyses were performed on patients who had compatible contraindications and did not receive tPA. Primary outcome was rate of symptomatic intracerebral haemorrhage (SICH). Secondary outcomes were short-term clinical development, short-term outcome and 30-day mortality. RESULTS: Of the 265 patients who received tPA, 135 patients (50.9%) had formal contraindications and 130 patients (49.1%) had no such contraindications. Rates of SICH were similar for patients with or without contraindications (P = 0.305). Patients with contraindications to tPA had a similar rate of clinical improvement (P = 0.504), a trend of less favourable outcome (P = 0.052) and higher mortality (P = 0.005) than patients without contraindications. Logistic regression analysis showed no association between presence of contraindications to tPA and short-term outcome or mortality when adjusted for age, sex and admission National Institute of Health Stroke Scale score. Short-term outcome and mortality were similar in patients with contraindications who received tPA and patients with contraindications who did not receive tPA (n = 134). CONCLUSIONS: Intravenous thrombolysis with tPA may be safe and efficient in stroke patients with a number of formal contraindications to tPA. Prospective randomized trials are imperative to clarify the need for a re-evaluation of the current contraindications to tPA.