Titto T. Idicula

Admission C – reactive protein after acute ischemic stroke is associated with stroke severity and mortality: The 'Bergen stroke study'

BackgroundThere is growing evidence that inflammation plays an important role in atherogenesis. Previous studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. It is not clear whether this is due a direct dose-response effect or rather an epiphenomenon. We studied the effect of CRP measured within 24 hours after stroke onset on functional outcome, mortality and future vascular events.MethodsWe prospectively studied 498 patients with ischemic stroke who were admitted within 24 hours after the onset of symptoms. CRP and NIH stroke scale (NIHSS) were measured at the time of admission. Short-term functional outcome was measured by modified Rankin scale (mRS) and Barthel ADL index (BI) 7 days after admission. Patients were followed for up to 2.5 years for long-term mortality and future vascular events data.ResultsThe median CRP at admission was 3 mg/L. High CRP was associated with high NIHSS (p = 0.01) and high long-term mortality (p < 0.0001). After adjusting for confounding variables, high CRP remained to be associated with high NIHSS (p = 0.02) and high long-term mortality (p = 0.002). High CRP was associated with poor short-term functional outcomes (mRS > 3; BI < 95) (p = 0.01; p = 0.03). However, the association was not significant after adjusting for confounding variables including stroke severity (p = 0.98; p = 0.88). High CRP was not associated with future vascular events (p = 0.98).ConclusionAdmission CRP is associated with stroke severity and long-term mortality when measured at least 24 hours after onset. There is a crude association between high CRP and short-term functional outcome which is likely secondary to stroke severity. CRP is an independent predictor of long-term mortality after ischemic stroke.

Inverse relationship of baseline body temperature and outcome between ischemic stroke patients treated and not treated with thrombolysis: the Bergen stroke study

Naess H, Idicula T, Lagallo N, Brogger J, Waje‐Andreassen U, Thomassen L. Inverse relationship of baseline body temperature and outcome between ischemic stroke patients treated and not treated with thrombolysis: the Bergen stroke study. 
Acta Neurol Scand: 2010: 122: 414–417.
© 2010 The Authors Journal compilation

Serum Albumin in Ischemic Stroke Patients: The Higher the Better

Background: Animal studies show a neuroprotective effect of serum albumin in ischemic stroke. The neuroprotective effect of albumin in ischemic stroke in humans is not well studied. This study was aimed to determine the association of serum albumin with outcome and mortality after ischemic stroke. Methods: In a prospective study, we included 444 patients with ischemic stroke. Serum albumin was measured at the time of admission. Stroke severity was measured at the time of admission with the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was measured with the modified Rankin scale (mRS) on day 7. Multiple logistic regression analysis was used to assess the independent association between variables and outcome. Survival was analyzed by Cox regression analysis after adjusting for age, sex and NIHSS score on admission. Results: The mean age (SD) of the patients was 70.4 (14.4) years. The median NIHSS score (interquartile range) on admission was 4 (1–8) and the median mRS score (interquartile range) on day 7 was 2 (1–3). Sixty patients (13%) died during a median follow-up period of 2 years. High serum albumin was independently associated with a better outcome (OR = 1.12, 95% CI = 1.05–1.20, p = 0.001). After adjusting for age, sex and NIHSS score on admission, high serum albumin was associated with lower mortality (OR = 0.88, 95% CI = 0.83–0.93, p < 0.0001). Conclusions: The current study indicates that high serum albumin is associated with better outcome and lower mortality in ischemic stroke patients. High serum albumin may be neuroprotective in ischemic stroke in humans.

Serum uri acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study

BackgroundA possible synergic role of serum uric acid (SUA) with thrombolytic therapies is controversial and needs further investigations. We therefore evaluated association of admission SUA with clinical improvement and clinical outcome in patients receiving rt-PA, early admitted patients not receiving rt-PA, and patients admitted after time window for rt-PA.MethodsSUA levels were obtained at admission and categorized as low, middle and high, based on 33° and 66° percentile values. Patients were categorized as patients admitted within 3 hours of symptom onset receiving rt-PA (rt-PA group), patients admitted within 3 hours of symptom onset not receiving rt-PA (non-rt-PA group), and patients admitted after time window for rt-PA (late group). Short-term clinical improvement was defined as the difference between NIHSS on admission minus NIHSS day 7. Favorable outcome was defined as mRS 0 - 3 and unfavorable outcome as mRS 4 - 6.ResultsSUA measurements were available in 1136 patients. Clinical improvement was significantly higher in patients with high SUA levels at admission. After adjustment for possible confounders, SUA level showed a positive correlation with clinical improvement (r = 0.012, 95% CI 0.002-0.022, p = 0.02) and was an independent predictor for favorable stroke outcome (OR 1.004; 95% CI 1.0002-1.009; p = 0.04) only in the rt-PA group.ConclusionsSUA may not be neuroprotective alone, but may provide a beneficial effect in patients receiving thrombolysis.

C-reactive Protein and Homocysteine Predict Long-term Mortality in Young Ischemic Stroke Patients

BACKGROUND We investigated the relationship between C-reactive protein (CRP) and homocysteine on follow-up and subsequent mortality in young ischemic stroke patients in a population-based study. METHODS Young ischemic stroke patients were followed-up on average 6 years after the index stroke. CRP and homocysteine levels were measured and risk factors were recorded, including myocardial infarction, diabetes mellitus, hypertension, smoking, alcoholism, and cancer. Stroke outcome was measured using the modified Rankin Scale score. Subsequent survival was obtained by examining the official population registry. Cox regression analyses were performed. RESULTS In total, 198 patients were included in this study (82 [41%] women and 116 [59%] men). The mean age on follow-up was 47.8 years. In total, 36 (18.2%) patients died during the subsequent mean follow-up of 12.4 years. Cox regression analysis revealed that mortality was associated with CRP (hazard ratio [HR] 1.05; P=.001) and homocysteine levels (HR 1.04; P=.02) in patients without dissection. Kaplan-Meier curves grouped by dichotomized CRP (CRP≤1 v >1 mg/L) showed increasing separation between the survival curves, and likewise for dichotomized homocysteine (≤9 v >9 μg/L). CONCLUSIONS There is an independent association between CRP and homocysteine levels obtained several years after ischemic stroke in young adults and subsequent mortality, even when adjusting for traditional risk factors. This association seems to continue for at least 12 years after the measurements.

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial

BACKGROUND Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. METHODS This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. FINDINGS Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64-79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2-8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84-1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). INTERPRETATION Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase. FUNDING Research Council of Norway.

Clinical presentation and diffusion weighted MRI of acute cerebral infarction. The Bergen Stroke Study

BackgroundNo large study has compared the yield of diffusion-weighted imaging (DWI) with clinical examination in order to differentiate lacunar stroke from other stroke subtypes. This differentiation is important for guiding further investigations and treatment.MethodsConsecutive patients admitted with cerebral infarction were classified according to the Oxfordshire Community Stroke Project scale. Based on DWI and CT stroke was classified as lacunar (LI) and non-lacunar (NLI). Acute ischemic lesion <1.5 cm and located in subcortex or in brainstem were classified as LI. All other infarctions were classified as NLI.ResultsDWI was performed in 419 (69%) patients. Among patients with lacunar syndrome (LACS) 45 (40.5%) had NLI on DWI. All patients with total anterior syndrome (TACS) and 144 (88.3%) with partial anterior syndrome (PACS) had NLI on DWI.ConclusionDWI is important among patients presenting with clinical symptoms suggestive of lacunar syndrome to differentiate between LI and NLI. On the other hand, there is good correspondence between TACS or PACS and NLI on DWI.

The Effect of Physiologic Derangement in Patients with Stroke Treated with Thrombolysis

BACKGROUND Body temperature, blood glucose, and blood pressure (BP) may interfere with outcome in patients with acute ischemic stroke treated with thrombolysis. METHODS We prospectively studied 127 patients who received thrombolysis with tissue plasminogen activator for acute stroke in Bergen, Norway. Body temperature, blood glucose, and BP were measured before thrombolysis. Maximum body temperature and maximum blood glucose within the first 5 days after thrombolysis and maximum BP within the first 24 hours after thrombolysis were measured. The outcome was measured with modified Rankin scale score obtained at 3 months after stroke onset. Variables were tested using multiple logistic regression analysis after adjusting for National Institute of Health Stroke Scale score before thrombolysis and potential confounders. RESULTS The average age of the patients was 63 years and the median National Institute of Health Stroke Scale score was 13. On admission, diabetes mellitus was present in 6% of patients and hypertension in 51% of patients. High body temperature and high blood glucose after thrombolysis were associated with poor prognosis (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.29-6.25, P = .01; OR 1.33, 95% CI 1.02-1.74, P = .03). High body temperature and high blood glucose before thrombolysis were not associated with outcome (OR 0.79, 95% CI 0.39-1.58, P = .5; OR 1.04, 95% CI 0.75-1.20, P = .08). High systolic BP both before and after thrombolysis was associated with poor outcome (OR 1.27, 95% CI 1.03-1.52, P = .025; OR 1.22, 95% CI 1.00-1.44, P = .045). High diastolic BP both before and after thrombolysis was not associated with outcome (OR 1.03, 95% CI 0.97-1.36, P =.85; OR 1.16, 95% CI 0.99-1.46, P = .29). CONCLUSIONS The current study indicates that in patients with ischemic stroke, high body temperature and high blood glucose after thrombolysis are associated with poor prognosis. Frequent monitoring of these parameters and the appropriate treatment of it, if elevated, are important during the first few days after thrombolysis. High systolic BP both before and after thrombolysis was associated with poor outcome. This finding may support the practice of reducing systolic BP below 185 mm Hg both before and after thrombolysis.

Neurological complications and aspects of basilar artery occlusive disease.

A recent case of basilar artery occlusion (BAO) in a 62-year-old woman is presented, along with a review of the literature on the clinical aspects of the disorder and treatment options. Therapeutic modalities such as intravenous and intra-arterial thrombolysis may significantly improve outcomes for patients with this disease.

High Proportion of Lacunar Strokes at Night: The Bergen Stroke Study

The main objective of this study was to investigate the circadian distribution of subtypes of ischemic stroke. The time of onset of stroke in consecutive stroke patients was registered and categorized into the following time intervals: midnight-6 am, 6 am-noon, noon-6 pm, and 6 pm-midnight. Patients with unknown onset of stroke were categorized as woke up with stroke, found with stroke by others, and miscellaneous. Patients who woke up with stroke, were included in the midnight-6 am interval. Stroke subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria and as lacunar or embolic stroke based on diffusion-weighted magnetic resonance imaging (DWI). The study group comprised 1101 patients who sustained ischemic stroke between February 2006 and March 2008. The proportion of lacunar stroke, defined according to both the TOAST criteria and DWI findings, was significantly higher in the midnight-6 am interval compared with the other time intervals. In our study group, the prevalence of lacunar strokes was highest at night.