Olli Häppölä

Off-Label Thrombolysis Is Not Associated With Poor Outcome in Patients With Stroke

Background and Purpose— Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. Methods— All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. Results— One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age >80 years (n=159), mild stroke National Institutes of Health Stroke Scale score <5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time >3 hours (n=95), blood pressure >185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age >80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. Conclusions— Off-license thrombolysis was not associated with poorer clinical outcome, except for age >80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.

Door to thrombolysis: ER reorganization and reduced delays to acute stroke treatment

The authors reorganized the emergency room (ER) by moving CT to the ER and streamlining triage by prenotification by emergency medical services (EMS), which reduced in-hospital delays and enhanced access to stroke thrombolysis. CT delay dropped from 1 hour 3 minutes ± 14 minutes in 1999 to 7 ± 2 minutes in 2004 (p < 0.0001). Door-to-needle time dropped from 1 hour 28 minutes ± 7 minutes to 50 ± 3 minutes (p < 0.001), while symptom-to-needle time dropped from 2 hours 44 minutes ± 6 minutes to 2 hours 5 minutes ± 4 minutes (p < 0.0001). From 23 patients in 1999, thrombolysis access was increased to 100 patients in 2004 and 183 patients in 2005.

Cognitive and Neurophysiological Outcome of Cardiac Arrest Survivors Treated With Therapeutic Hypothermia

Background and Purpose— Cognitive deficits are common in survivors of cardiac arrest (CA). The aim of this study was to examine the effect of therapeutic hypothermia after CA on cognitive functioning and neurophysiological outcome. Methods— A cohort of 70 consecutive adult patients resuscitated from out-of-hospital ventricular fibrillation CA were randomly assigned to therapeutic hypothermia of 33°C for 24 hours accomplished by external cooling or normothermia. Neuropsychological examination was performed to 45 of the 47 conscious survivors of CA (27 in hypothermia and 18 in normothermia group) 3 months after the incident. Quantitative electroencephalography (Q-EEG) and auditory P300 event-related potentials were studied on 42 patients at the same time point. Results— There were no differences between the 2 treatment groups in demographic variables, depression, or delays related to the resuscitation. No differences were found in any of the cognitive functions between the 2 groups. 67% of patients in hypothermia and 44% patients in normothermia group were cognitively intact or had only very mild impairment. Severe cognitive deficits were found in 15% and 28% of patients, respectively. All Q-EEG parameters were better in the hypothermia-treated group, but the differences did not reach statistical significance. The amplitude of P300 potential was significantly higher in hypothermia-reated group. Conclusions— The use of therapeutic hypothermia was not associated with cognitive decline or neurophysiological deficits after out-of-hospital CA.

Community-Based Thrombolytic Therapy of Acute Ischemic Stroke in Helsinki

Background and Purpose— Thrombolysis with alteplase is used in acute ischemic stroke within 3 hours after symptom onset in many stroke centers, but experience remains limited in Europe. Methods— Using eligibility and management criteria similar to those published by the American Heart Association, we treated 75 consecutive patients aged 21 to 83 years (mean age, 63.6 years; median Scandinavian Stroke Scale score, 32/58) with hemispheric infarction with alteplase in 1998–2001. Their neuroradiological findings (ischemic and hemorrhagic changes) and functional outcome at 3 months were evaluated. Results— Sixty-one percent of the patients had recovered functional independence (Barthel Index 95 to 100) at the 3-month follow-up. On the modified Rankin Scale (mRS), 37% (28/75) of patients had no or minimal symptoms (mRS 0 to 1), while 17% (13/75) remained dependent (mRS 4 to 5) and 5% (4/75) died. Cerebral parenchymal hematomas occurred in 8% (6/75) and hemorrhagic transformation in 8% (6/75) of the patients. Low initial diastolic blood pressure and administration of intravenous antihypertensive medication were associated with unfavorable outcome (mRS 3 to 6). Conclusions— We conclude that our management protocol for thrombolytic therapy is safe. These rates of functional outcome, case fatality, and hemorrhagic cerebral events compare favorably with those of other published series of stroke thrombolysis with similar time windows and management guidelines. Associations between blood pressure and its treatment during thrombolysis with functional outcome deserve further analysis.

Intravenous Thrombolysis of Basilar Artery Occlusion Predictors of Recanalization and Outcome

Background and Purpose— Basilar artery occlusion has a high mortality rate (85% to 95%) if untreated. We describe a large single-center cohort treated mostly with intravenous alteplase and heparin. Methods— The cohort included 116 patients with angiography-verified basilar artery occlusion. We studied baseline characteristics, frequencies of recanalization and symptomatic intracranial hemorrhage, and 3-month outcome (modified Rankin Scale [mRS]). Results— Thirty patients (25.9%) had mRS 0 to 2, 42 patients (36.2%) had moderate outcome (mRS, 0–3), 26 patients (22.4%) required daily help (mRS, 4–5), and 48 patients (41.4%) died. Eighteen patients (15.7%) developed symptomatic intracranial hemorrhage. In patients with post-treatment angiogram available (n=91), 59 patients (64.8%) had a complete or partial recanalization. Radiological location of basilar artery occlusion was known in 55 of 91 instances, and recanalization was associated directly with clot location at the top-of-basilar (odds ratio, 4.8 [1.1–22]; P=0.048). Independent outcome (mRS 0-2) was associated with lower age and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Age, nil or minimal recanalization, and symptomatic intracranial hemorrhage were independently associated with fatal outcome. Sixteen of 71 patients (22.5%) who presented with coma eventually reached moderate outcome, and additional 8 patients (11.3%) progressed to mRS 4. Conclusions— Whereas recanalization after intravenous thrombolysis strongly predicts survival and moderate outcome, therapeutic techniques should concentrate on clot location. Although most adverse baseline variables, age, symptom severity, but also coma are beyond control, it should not preclude thrombolysis, which may permit independent survival.

Outcome by Stroke Etiology in Patients Receiving Thrombolytic Treatment. Descriptive Subtype Analysis

Background and Purpose— Treating ischemic stroke with thrombolytic therapy is effective and safe, but limited data exist on its efficacy and safety in different etiologic subtypes. Methods— Patients with acute ischemic stroke treated with intravenous thrombolysis between 1995 and 2008 at our hospital were classified according to the Trial of ORG 10172 in Acute Stroke Treatment criteria based on diagnostic evaluation. Clinical outcome of the stroke subtypes by 3-month modified Rankin Scale was compared by multivariate logistic regression. A good outcome was defined as modified Rankin Scale ≤2. Symptomatic intracranial hemorrhage was defined according to both National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study criteria. Results— Of the 957 eligible patients, 41% (389) had cardioembolisms, 23% (217) large-artery atherosclerosis, and 11% (101) small-vessel disease (SVD). A good outcome was more common in SVD than in the other subtypes. Patients with SVD were more often male (64% versus 54%), had a lower baseline National Institutes of Health Stroke Scale score, lower mortality rate, and experienced no symptomatic intracranial hemorrhage. Patients with SVD had a prior stroke more often (20% versus 11%), whereas hypertension, diabetes, hypercholesterolemia, and transient ischemic attacks were equally distributed in all subtypes. Patients with SVD had a better outcome even after adjusting for baseline National Institutes of Health Stroke Scale and glucose level, age, and hyperdense artery sign (OR, 1.81; 1.01 to 3.23). In the adjusted multivariate model, other etiologic groups showed no significant correlation to good outcome. Conclusions— Patients with SVD were spared from bleeding complications and had the best outcome even after adjustment for confounding factors.

Stroke Mimics and Intravenous Thrombolysis

STUDY OBJECTIVEnThe necessity for rapid administration of intravenous thrombolysis in patients with acute ischemic stroke may lead to treatment of patients with conditions mimicking stroke. We analyze stroke patients treated with intravenous thrombolysis in our center to characterize cases classified as stroke mimics.nnnMETHODSnWe identified and reviewed all cases with a diagnosis other than ischemic stroke in our large-scale single-center stroke thrombolysis registry. We compared these stroke mimics with patients with neuroimaging-negative and neuroimaging-positive ischemic stroke results.nnnRESULTSnAmong 985 consecutive intravenous thrombolysis-treated patients, we found 14 stroke mimics (1.4%; 95% confidence interval 0.8% to 2.4%), 694 (70.5%) patients with neuroimaging-positive ischemic stroke results, and 275 (27.9%) patients with neuroimaging-negative ischemic stroke results. Stroke mimics were younger than patients with neuroimaging-negative or -positive ischemic stroke results. Compared with patients with neuroimaging-positive ischemic stroke results, stroke mimics had less severe symptoms at baseline and better 3-month outcome. No differences appeared in medical history or clinical features between stroke mimics and patients with neuroimaging-negative ischemic stroke results. None of the stroke mimics developed symptomatic intracerebral hemorrhage compared with 63 (9.1%) among patients with neuroimaging-positive ischemic stroke results and 6 (2.2%) among patients with neuroimaging-negative ischemic stroke results.nnnCONCLUSIONnStroke mimics were infrequent among intravenous thrombolysis-treated stroke patients in this cohort, and their treatment did not lead to harmful complications.

Ultraearly Thrombolysis in Acute Ischemic Stroke Is Associated With Better Outcome and Lower Mortality

Background and Purpose— Pooled analysis of major placebo-controlled trials suggests that the earlier thrombolysis is given after ischemic stroke, the better the outcome. We report a single-center assessment of the effect of ultraearly thrombolysis on the outcome of our patients. Methods— Between January 2003, and December 2008, a total of 878 patients with ischemic stroke received thrombolysis within 4.5 hours from the symptom onset at the Helsinki University Central Hospital. Using univariate methods and multivariable logistic regression, we assessed the association between onset-to-treatment time (OTT) and favorable 3-month outcome (modified Rankin Scale 0 to 2). Results— Median age was 70.5 years, median OTT 115 minutes, and median National Institutes of Health Stroke Scale (NIHSS) on admission 9. After adjustment for baseline stroke severity, more patients with OTT <70 minutes had a favorable outcome than those with OTT ≥70 minutes. Specifically, OR of 5.15 (1.50 to 27.5) was for the patients with NIHSS 7 to 12, and 2.74 (1.26 to 5.90) for those with NIHSS ≥13. Of the patients with OTT ≤90 minutes, those with NIHSS 7 to 12 had an OR of 1.72 (1.00 to 2.96) for a favorable outcome, and those with NIHSS ≥13 had lower mortality than the ones with OTT >90 minutes (16.4% versus 29.5%; P=0.01). Multivariable model showed an association of better outcome with lower baseline glucose level, younger age, lower baseline NIHSS, and OTT <70 minutes. Conclusions— Ultraearly thrombolysis was associated with better outcome of our patients with stroke with moderate or severe symptoms. The earlier the treatment was given, the higher the likelihood of favorable outcome.

Source estimation of spontaneous MEG oscillations in mild cognitive impairment.

Mild cognitive impairment (MCI) is a memory disorder often preceding Alzheimers disease (AD). AD has been shown to be associated with abnormal generation of spontaneous electromagnetic activity. We investigated whether the cortical generation of spontaneous brain oscillations in MCI shows changes resembling those observed in AD. A minimum current estimates algorithm was applied to identify cortical sources of magnetoencephalographic (MEG) spontaneous brain oscillations in male MCI patients with a clear memory disorder and in healthy elderly controls. This data was subsequently compared to a male subsample of AD patients from an earlier study. While there were clear oscillatory abnormalities in AD patients, there was no evidence of significant changes in the alpha source distribution in MCI patients as compared to healthy controls. Deficits in the distribution of oscillatory sources in the resting state are thus likely to occur at later stages of cognitive impairment than MCI.

Sequential analysis of pretreatment delays in stroke thrombolysis.

OBJECTIVESnThe aim was to determine if an intensive restructuring of the approach to acute stroke improved time to thrombolysis over a 3-year study period and to determine whether delay modifications correlated with increased thrombolytic intervention or functional outcome.nnnMETHODSnThe study examined the pretreatment process to define specific time intervals (delays) of interest in the acute management of 289 consecutive ischemic stroke patients who were transported by the emergency medical services (EMS) and received intravenous (IV) thrombolytic therapy in the emergency department (ED) of Helsinki University Central Hospital. Time interval changes of the 3-year period and use of thrombolytics was measured. Functional outcome, measured with the modified Rankin Scale (mRS) at 3 months, was assessed with multivariable statistical analysis.nnnRESULTSnDuring implementation of the restructuring program from 2003 to 2005, the median total time delay from symptom onset to drug administration dropped from 149 to 112 minutes (pu2009< 0.0001). Prehospital delays did not change significantly during the study period. The median delay in calling an ambulance remained at 13 minutes, and the total median prehospital delay stayed at 71 minutes. In-hospital delays decreased from 67 to 34 minutes (pu2009< 0.0001). The median call delay was 25 minutes in patients with mild symptoms (National Institute of Health Stroke Scale [NIHSS] scoreu2009<u20097) and 8 minutes with severe symptoms (NIHSSu2009> 15). In the multivariate model, stroke severity (odds ratio [OR]u2009= 0.83, 95% confidence interval [CI]u2009= 0.78 to 0.88, pu2009< 0.0001), age (ORu2009= 0.57, 95% CIu2009= 0.42 to 0.77, pu2009< 0.0001), and in-hospital delay (ORu2009= 0.47, 95% CIu2009= 0.22 to 0.97, pu2009= 0.04) were suggesting a good outcome.nnnCONCLUSIONSnRestructuring of the teamwork between the EMS personnel and the reorganized ED significantly reduced in-hospital, but not prehospital, delays. The present data suggest that a decreased in-hospital delay improves the accessibility of the benefits of thrombolysis.