Kirsi Rantanen

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.

Two years of Finnish Telestroke Thrombolysis at spokes equal to that at the hub

Background: Official guidelines on stroke promote the use of telemedicine via bidirectional videoconferencing equipment, which provides a valid and reliable means of facilitating thrombolysis delivery to patients in distant or rural hospitals. Methods: The present prospective cohort study describes the characteristics and 3-month outcome of the thrombolysis patients treated in 5 community hospitals served by the Helsinki University Central Hospital (HUCH) in a telestroke network during 2007 to 2009. The characteristics and outcome of telestroke thrombolysis patients are compared with consecutive thrombolysis patients (n = 985) treated at HUCH. Results: A total of 106 consecutive telestroke consultations in 2 years led to IV thrombolysis in 61 patients (57.5%). The median NIH Stroke Scale score was 10 (range 3–26), onset to treatment time 120 minutes (interquartile range [IQR] 49), length of consultation 25 minutes (IQR 18) if the consultation led to thrombolysis and 15 minutes (IQR 10) if not (p = 0.032). The rate of symptomatic intracranial bleedings was 6.7% (4/60) according to the National Institute of Neurological Disorders and Stroke definition. Half (28/57) of the thrombolysis patients with complete follow-up data had a favorable outcome (modified Rankin Scale [mRS] 0–2) and a third (17/57) had an excellent recovery (mRS 0–1). Thus the patients treated with thrombolysis based on teleconsultation had similar outcome with those treated at HUCH (mRS 0–2: 49.1% vs 58.1%, p = 0.214 and mRS 0–1: 17/57 [29.4%] vs 352/957 [36.8%], p = 0.289). Conclusions: A special feature of the Finnish pilot is the high percentage of consultations leading to thrombolytic treatment with features and results very similar to on-site thrombolysis at the neurologic emergency room of HUCH.

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.

Post-Thrombolytic Hyperglycemia and 3-Month Outcome in Acute Ischemic Stroke

Background: Treating hyperglycemia in acute ischemic stroke may be beneficial, but knowledge on its prognostic value and optimal target glucose levels is scarce. We investigated the dynamics of glucose levels and the association of hyperglycemia with outcomes on admission and within 48 h after thrombolysis. Methods: We included 851 consecutive patients with acute ischemic stroke treated with intravenous thrombolysis in the Helsinki University Central Hospital during 1998–2008. Outcome measures were unfavorable 3- month outcome (3–6 on the modified Rankin Scale), death, and symptomatic intracerebral hemorrhage (sICH) according to NINDS criteria. Hyperglycemia was defined as a blood glucose level of ≧8.0 mmol/l. Four groups were identified based on (a) admission and (b) peak glucose levels 48 h after thrombolysis: (1) persistent normoglycemia (baseline plus 48-hour normoglycemia), (2) baseline hyperglycemia (48-hour normoglycemia), (3) 48-hour hyperglycemia (baseline normoglycemia), and (4) persistent hyperglycemia (baseline plus 48-hour hyperglycemia). Results: 480 (56.4%) of our patients (median age 70 years; onset-to-needle time 199 min; National Institutes of Health Stroke Scale score 9), had persistent normoglycemia, 59 (6.9%) had baseline hyperglycemia, 175 (20.6%) had 48-hour hyperglycemia, while persistent hyperglycemia appeared in 137 (16.1%) patients. Persistent and 48-hour hyperglycemia independently predicted unfavorable outcome [odds ratio (OR) = 2.33, 95% confidence interval (CI) = 1.41–3.86, and OR = 2.17, 95% CI = 1.30–3.38, respectively], death (OR = 6.63, 95% CI = 3.25–13.54, and OR = 3.13, 95% CI = 1.56–6.27, respectively), and sICH (OR = 3.02, 95% CI = 1.68–5.43, and OR = 1.89, 95% CI = 1.04–3.43, respectively), whereas baseline hyperglycemia did not. Conclusions: Hyperglycemia (≧8.0 mmol/l) during 48 h after intravenous thrombolysis of ischemic stroke is strongly associated with unfavorable outcome, sICH, and death.

Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms.

Background Thrombolysis of ischemic stroke patients presenting with mild symptoms is controversial. Aim We aimed to describe the clinical outcome and frequency of infarcts and symptomatic intracerebral hemorrhages on follow-up imaging of such thrombolysis-treated patients. Methods Our cohort included 1398 consecutive ischemic stroke patients treated with intravenous thrombolysis at the Helsinki University Central Hospital, years 1995–2010. We analyzed the patients according to baseline National Institutes of Health Stroke Scale: ≤2, 3–4, 5–6, and >6. In our institution, visualization of an artery occlusion or perfusion deficit is required for thrombolysis with National Institutes of Health Stroke Scale ≤ 2. We used univariate and multivariable methods to describe the cohort and study associations between the variables. Excellent three-month outcome was defined as modified Rankin Scale 0–1. Results Fifty-eight (4·1%) patients were treated with National Institutes of Health Stroke Scale ≤ 2, another 194 (13·6%) with 3–4 points, and 236 (16·5%) with 5–6 points. With National Institutes of Health Stroke Scale ≤ 2, 45 (78%) of the patients had excellent three-month outcome, achieved in 116 (59%) patients with National Institutes of Health Stroke Scale 3–4, in 130 (55%) with National Institutes of Health Stroke Scale 5–6, and in 241 (26%) with National Institutes of Health Stroke Scale > 6. Frequencies of symptomatic intracerebral hemorrhage (European Cooperative Acute Stroke Study-2) were 0%, 2·6%, 2·1%, and 8·1%, and visible infarcts on follow-up imaging 48%, 43%, 48%, and 74%, respectively. In patients with baseline National Institutes of Health Stroke Scale ≤ 6, poor outcome was associated with previous stroke, diabetes, elevated admission blood glucose, and development of intracerebral hemorrhage. Conclusions Half of patients presenting with National Institutes of Health Stroke Scale 0–6 developed an infarction despite thrombolysis, and 40% had poor outcome, which was associated with glucose metabolism and hemorrhagic complications. Managing thrombolysis candidates with mild symptoms warrants individual consideration often supported by multimodal imaging.

Undetermined stroke with an embolic pattern—a common phenotype with high early recurrence risk

Abstract Introduction. Undetermined strokes with an embolic pattern (USEP) represent a common phenotype. We assessed their frequency and compared USEP with cardioembolic stroke with a known source and non-cardioembolic stroke etiology. Methods. Study patients were 540 consecutive ischemic stroke patients admitted to Helsinki University Hospital with primary end-point of recurrent stroke in a 21-month follow-up. Cox regression adjusting for CHA2DS2-VASc and anticoagulation estimated the risk of USEP on recurrent stroke. Results. A total of 229 (42.4%) patients had a non-cardioembolic stroke etiology, 184 (34.1%) had a cardioembolic stroke with a known source, and 127 (23.5%) were classified as USEP. USEP patients had less diabetes and prior TIA, with more severe symptoms than the non-cardioembolic stroke cases. They were younger, had fewer comorbidities, and less severe symptoms than the cardioembolic stroke patients. Cumulative risk of recurrent stroke was 10.0% (95% CI 4.1%–15.9%) for USEP, 5.0% (1.1%–8.9%) for cardioembolic strokes, and 5.0% (3.0%–7.0%) for non- cardioembolic strokes (P = 0.089). USEP associated with a higher risk of recurrent stroke compared to non-cardioembolic strokes (hazard ratio 2.36, 95% CI 1.02–5.47; P = 0.046) and cardioembolic stroke with a known source (1.83, 1.07–3.14; P = 0.028). Conclusions. Despite their younger age and more favorable risk factor profile compared with other phenotypes, USEP exhibited a high risk of stroke recurrence.

Characteristics and Outcome of Ischemic Stroke Patients Who Are Free of Symptoms at 24 Hours following Thrombolysis

Background: A part of ischemic stroke patients score 0 on the National Institutes of Health Stroke Scale (NIHSS) within 24 h following thrombolysis. Their clinical characteristics and long-term outcome are poorly studied. We report a single-center assessment of such patients. Methods: The cohort comprises 874 consecutive patients from the Helsinki Stroke Thrombolysis Registry, out of whom 113 scored 0 on 24-hour NIHSS. We analyzed their baseline demographic, clinical and radiological characteristics and 3-month outcome (modified Rankin Scale, mRS). Associations between the study parameters were tested by multivariate analysis. Results: Patients with a 24-hour NIHSS score = 0 (n = 113) were younger than the rest of the population (n = 761; median: 65.6 vs. 71.5 years; p < 0.001), their NIHSS score on admission was lower (median: 5 vs. 10; p < 0.001), as was their glucose level (median: 6.2 vs. 6.7 mmol/l; p = 0.02). The onset-to-treatment time was similar in both groups (median: 120 vs. 115 min; p = 0.89). Patients with a 24-hour NIHSS score = 0 more often achieved an excellent outcome (mRS scores: 0–1; 81 vs. 31%; p < 0.001) and had lower mortality (1.8 vs. 11.8%; p < 0.01). One third of these patients had a brain infarction visible on 24-hour imaging. Lower baseline NIHSS score and younger age were independently associated with 24-hour NIHSS score = 0, which, in turn, was independently associated with excellent 3-month outcome. Conclusions: Patients with an NIHSS score = 0 at 24 h following thrombolysis are younger, have milder symptoms and have a lower glucose level on admission. They achieve more often excellent outcome and lower mortality. Still, 8% of them required help in daily activities or were dead at 3 months (mRS scores: 3–6).

Antithrombotic Treatment in the Prevention of Ischemic Stroke

Approximately 5.7 million people died from stroke in 2005 [1]. According to World Health Organization estimates, figures are predicted to increase to 23 million first-ever strokes, 77 million stroke survivors, 61 million disability adjusted life years (DALYs) and 7.8 million deaths in the next 20 years [2]. Heart disease and stroke are leading causes of DALYs lost and deaths worldwide [3]. Over 70 % of ischemic strokes are first events, which makes primary prevention immensely important. The treatments for acute ischemic stroke have emerged during the last decade and there is growing evidence of efficacy and importance of secondary prevention. We foresee that patients at high risk of vascular events could reduce their risk by 75 to 80 % through optimal prevention strategies including a combination of lifestyle changes and medical therapy [4]. In this review, we will focus on the aspects of antithrombotic treatment of ischemic stroke (IS) in the primary and secondary prevention.

Secondary prevention of ischemic stroke.

Stroke strikes often suddenly, causes long-term disability and death, and is a huge economical burden for the society, not to mention the human tragedy for the patient and the family. At least 15% of stroke survivors will have a second stroke during the next five years, quarter of which prove out to be fatal within four weeks. Secondary prevention of ischemic stroke (IS) targets at reducing stroke recurrence by means of 1) detection and modification of risk factors, 2) antithrombotic or anticoagulant treatment, and 3) surgical interventions for selected patient subgroups. In this review we will discuss these issues in detail and also offer our personal suggestions for treatment choices. Detecting and treating the modifiable risk factors is the major challenge of secondary prevention of IS.

Valsalva maneuver as migraine inducer: a case report of a woman with patent foramen ovale and an ischemic stroke.

The association between patent foramen ovale, ischemic stroke, and migraine with aura is well known. It is, however, complicated and generates a considerable debate about the features and clinical consequences of the phenomenon. We report a case of a woman for whom patent foramen ovale has possibly acted as an inducer of both migraine attacks and ischemic stroke.