Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Body temperature is considered crucial in the management of acute stroke patients. Recently hypothermia applied as a therapy for stroke has been demonstrated to be feasible and safe in acute stroke patients. In the present study, we investigated the predictive role of admission body temperature to the long-term mortality in stroke patients. METHODS: We studied 390 patients with acute stroke admitted within 6 hours from stroke onset. Admission clinical characteristics (age, sex, admission stroke severity, admission blood glucose, cardiovascular risk factor profile, and stroke subtype) were recorded for patients with hypothermia (body temperature < or =37 degrees C) versus patients with hyperthermia (body temperature >37 degrees C). Univariately the mortality rates for all patients were studied by Kaplan-Meier statistics. To find independent predictors of long-term mortality for all patients, Cox proportional-hazards models were built. We included all clinical characteristics and body temperature as a continuous variable. RESULTS: Patients with hyperthermia had more severe strokes and more frequently diabetes, whereas no difference was found for the other clinical characteristics. For all patients mortality rate at 60 months after stroke was higher for patients with hyperthermia (73 per 100 cases versus 59 per 10 cases, P=0.001). When body temperature was studied in a multivariate Cox proportional-hazards model, a 1 degrees C increase of admission body temperature independently predicted a 30% relative increase (95% CI, 4% to 57%) in long-term mortality risk. For 3-month survivors we found no association between body temperature and long-term survival when studied in a multivariate Cox proportional hazard model (hazards ratio, 1.11 per 1 degrees C; 95% CI, 0.82 to 1.52). CONCLUSION: Low body temperature on admission is considered to be an independent predictor of good short-term outcome. The present study suggests that admission body temperature seems to be a major determinant even for long-term mortality after stroke. Hypothermic therapy in the early stage in which body temperature is kept low for a longer period after ictus could be a long-lasting neuroprotective measure.

Manual and oral apraxia in acute stroke, frequency and influence on functional outcome: The Copenhagen Stroke Study.

OBJECTIVES: To determine the frequency of manual and oral apraxia in acute stroke and to examine the influence of these symptoms on functional outcome. DESIGN: Seven hundred seventy six unselected, acute stroke patients who were admitted within seven days of stroke onset with unimpaired consciousness were included. If possible, the patients were assessed for manual and oral apraxia on acute admission. Neurologic stroke severity including aphasia was assessed with the Scandinavian Stroke Scale, and activities of daily living function was assessed with the Barthel Index. All patients completed their rehabilitation in the same large stroke unit. RESULTS: Six hundred eighteen patients could cooperate with the apraxia assessments. Manual apraxia was found in 7% of subjects (10% in left and 4% in right hemispheric stroke; chi2 = 9.0; P = 0.003). Oral apraxia was found in 6% (9% in left and 4% in right hemispheric stroke; chi2 = 5.4; P = 0.02). Both manual and oral apraxia were related to increasing stroke severity, and manual, but not oral, apraxia was associated with increasing age. There was no gender difference in frequency of apraxia. Patients with either type of apraxia had temporal lobe involvement more often than patients without. When analyzed with multiple linear and logistic regression analyses, neither manual nor oral apraxia had any independent influence on functional outcome. CONCLUSION: Apraxia is significantly less frequent in unselected patients with acute stroke than has previously been assumed and has no independent negative influence on functional outcome.

Potentially reversible factors during the very acute phase of stroke and their impact on the prognosis: is there a large therapeutic potential to be explored?

In the Copenhagen Stroke Study, we evaluated the combined impact on stroke outcome of potentially treatable factors such as acute body temperature, blood glucose, and stroke in progression. The patients were stratified into two groups: (1) patients with 'good' prognostic parameters (body temperature on admission < or = 37.0 degrees C and plasma glucose on admission < or = 6.5 mmol/l and who did not develop stroke in progression) and (2) patients with correspondingly 'poor' prognostic parameters. A poor outcome was observed in 4% of the patients with good prognostic parameters versus in 49% of the patients with poor prognostic parameters (p < 0.01). In the multivariate analysis which also included stroke severity, blood glucose contributed significantly to poor outcome with an odds ratio (OR) of 1.2/1.0 mmol/l increase, body temperature with an OR of 2.2/1 degrees C increase, and stroke in progression with an OR of 2.9. However, the combined effect of all three factors was more than additive with an OR of 10.0 (95% CI 1.5-56; p < 0.01). We have shown that in human stroke a strong and more than additive association exists between potentially reversible parameters and outcome. Intervention trials can prove whether these marked relations are causal.

Early infection and prognosis after acute stroke: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Infection is a frequent complication in the early course of acute stroke and may adversely affect stroke outcome. In the present study, we investigate early infection developing in patients within 3 days of admission to the hospital and its independent relation to recovery and stroke outcome. In addition, we identify predictors for early infections, infection subtypes, and their relation to initial stroke severity. METHODS: In the community-based Copenhagen Stroke Study, 1,156 unselected patients were examined for early infection. Stroke severity was assessed with the Scandinavian Stroke Scale (SSS) on admission and at discharge. Multiple logistic and linear regression analyses were used to determine independent relations to early infection. Relevant stroke risk factors, admission stroke severity, and body temperature were included in the analysis. RESULTS: Of the subjects studied, 19.4% developed early infection. In women, 68% of the early infections were urinary tract infections, and in men, 49% of the early infections were pneumonias. Independent predictors of early infection were advanced age (OR per 10 years, 1.24; 95% CI, 1.02-1.64), female gender (OR, 2.0; 95% CI, 1.3-3.0), and decreased SSS score on admission (OR per 10 points, 0.69; 95% CI, 0.62-0.78). The presence of early infection prolonged hospital stay by a mean of 9.3 days (P < .0001) but not death during hospital stay (P = .78), stroke severity at discharge (P = .32), or rate of discharge to nursing home (P = .17). CONCLUSION: Advanced age, female gender, and increased stroke severity independently predict development of early infection. The present study indicates that early infection does not influence outcome in acute stroke patients per se, but it delays patient discharge from the hospital.

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. METHODS: We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the "forced air" method, a surface cooling method that uses a cooling blanket with a flow of cool air (10 degrees C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. RESULTS: Body temperature decreased from t(0)=36.8 degrees C to t(6)=35.5 degrees C (P:<0.001), and hypothermia was present until 4 hours after therapy (t(0)=36.8 degrees C versus t(10)=36.5 degrees C; P:=0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (P:=0. 50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (P:=0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. CONCLUSIONS: Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the "forced air" method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.

[Treatment and rehabilitation in an apoplexy unit increases the 5-year survival]. / Behandling og rehabilitering på apopleksiafsnit øger 5-års-overlevelsen.

Treatment of stroke patients in specialised stroke units has become more frequent, but the longterm effect of this treatment has not been determined. In this prospective, community-based study of 1241 unselected acute stroke patients we compared outcome between patients geographically randomised to treatment in a stroke unit or in a general neurological/medical ward, from the time of acute admission to the end of rehabilitation. Baseline characteristics were comparable between the two treatment groups regarding age, sex, marital status, pre-stroke residence, and stroke severity. Patients treated in the stroke unit had higher comorbidity with regard to hypertension and diabetes. Multivariate linear and logistic regression analyses were applied to estimate the independent influence of stroke unit treatment on outcome. Stroke unit treatment significantly reduced not only initial mortality, but also mortality within five years from stroke onset. The relative risk of dying within the first five years from stroke was reduced by 40%, p < 0.01. Treatment and rehabilitation of unselected stroke patients in a stroke unit reduces initial mortality, discharge rate to nursing home, reduces cost of treatment, and improves longterm survival up to five years after stroke.

Who benefits from treatment and rehabilitation in a stroke Unit? A community-based study.

BACKGROUND AND PURPOSE: The beneficial effects of treatment and rehabilitation of patients with acute stroke in a dedicated stroke unit (SU) are well established. We wanted to examine if these effects are limited to certain groups of patients or if they apply to all patients independent of age, sex, comorbidity, and initial stroke severity. METHODS: This was a community-based study of outcome in 1241 consecutive stroke patients from 2 communities in Copenhagen: In one (Frederiksberg), treatment and rehabilitation were given in general neurological and medical wards (GW), and in the other (Bispebjerg) in one single large SU. Outcome measures were initial, 1-year, and 5-year mortality rates, a poor outcome (initial death or discharge to a nursing home), and length of hospital stay (LOHS). Multivariate regression analyses were used to examine the independent effect of SU treatment on the various subgroups. RESULTS: The relative risks of initial death, poor outcome, and 1-year and 5-year mortality rates were reduced by 40% on average in patients treated in the SU compared with the GW. A beneficial effect of SU treatment was observed regardless of the patient's age, sex, comorbidity, and initial stroke severity. Those who benefited most appeared to be the patients with the most severe strokes (poor outcome: OR 0.17; 95% CI 0.05 to 0.58). Those who benefited least were patients with mild or moderate strokes (poor outcome: OR 0.66; 95% CI 0.41 to 0.98) and patients <75 years of age (poor outcome: OR 0.66; 95% CI 0.36 to 1.19). LOHS was reduced by 2 to 3 weeks in all who had their treatment in the SU except in patients with the most severe strokes. LOHS in these patients was similar to LOHS in the GW. CONCLUSIONS: A beneficial effect of treatment in a SU is achieved in completely unselected patients independent of their age, sex, comorbidity, and stroke severity. Those who had the most severe strokes appeared to benefit most. All patients with acute stroke should therefore have access to treatment and rehabilitation in a dedicated SU.

What determines good recovery in patients with the most severe strokes? The Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Even patients with the most severe strokes sometimes experience a remarkably good recovery. We evaluated possible predictors of a good outcome to search for new therapeutic strategies. METHODS: We included the 223 patients (19%) with the most severe strokes (Scandinavian Stroke Scale score <15 points) from the 1197 unselected patients in the Copenhagen Stroke Study. Of these, 139 (62%) died in the hospital and were excluded. The 26 survivors (31%) with a good functional outcome (Barthel Index >/=50 points) were compared with the 58 survivors (69%) with a poor functional outcome (Barthel Index <50 points). The predictive value of the following factors was examined in a multivariate logistic regression model: age; sex; a spouse; work; home care before stroke; initial stroke severity; blood pressure, blood glucose, and body temperature on admission; stroke subtype; neurological impairment 1 week after onset; diabetes; hypertension; atrial fibrillation; ischemic heart disease; previous stroke; and other disabling disease. RESULTS: Decreasing age (odds ratio [OR], 0.50 per 10-year decrease; 95% CI, 0.25 to 0.99; P=0.04), a spouse (OR, 3.1; 95% CI, 1.1 to 8. 8; P=0.03), decreasing body temperature on admission (OR, 1.8 per 1 degrees C decrease; 95% CI, 1.1 to 3.1; P=0.01), and neurological recovery after 1 week (OR, 3.2 per 10-point increase in Scandinavian Stroke Scale score; 95% CI, 1.1 to 7.8; P=0.01) were all independent predictors of good functional outcome. CONCLUSIONS: Patients with the most severe strokes who achieve a good functional outcome are generally characterized by younger age, the presence of a spouse at home, and early neurological recovery. Body temperature was a strong predictor of good functional outcome and the only potentially modifiable factor. We suggest that a randomized controlled trial be undertaken to evaluate whether active reduction of body temperature can improve the generally poor prognosis of patients with the most severe strokes.

Treatment and rehabilitation on a stroke unit improves 5-year survival. A community-based study.

BACKGROUND AND PURPOSE: We have previously reported a marked reduction in mortality up to 1 year after treatment and rehabilitation on a stroke unit versus on general neurological and medical wards in unselected stroke patients. In the present study we wanted to test the hypothesis that this mortality-reducing effect is not temporary but is long lasting. METHODS: We performed a community-based comparison of outcome in 1241 stroke patients from 2 adjacent communities in Copenhagen: in one (Frederiksberg), treatment and rehabilitation were provided on general neurological and medical wards, and in the other (Bispebjerg), treatment and rehabilitation were provided on a single large stroke unit. RESULTS: The 2 stroke populations were comparable regarding age, sex, initial stroke severity, lesion diameter on CT, and stroke subtype (hemorrhage/infarct), but patients treated on the stroke unit had a higher frequency of comorbidity and lower incomes. One-year mortality was 39% (general wards) versus 32% (stroke unit) (P=0.01). This difference was still present 5 years after stroke (71% versus 64%; P=0.02). In a multiple logistic regression model of 5-year mortality, treatment on a stroke unit reduced the relative risk of death by 40% (odds ratio, 0.60; 95% CI, 0.42 to 0.85; P<0.01), independent of age, sex, stroke severity, and comorbidity. CONCLUSIONS: The mortality-reducing effect of treatment and rehabilitation on a dedicated stroke unit is long lasting rather than temporary. Stroke unit treatment reduced the relative risk of death within 5 years after stroke by 40% in an unselected, community-based stroke population. These results emphasize the need for organization of treatment and rehabilitation of unselected stroke patients on dedicated stroke units.

Leukocytosis in acute stroke: relation to initial stroke severity, infarct size, and outcome: the Copenhagen Stroke Study.

UNLABELLED: Leukocytosis is a common finding in the acute phase of stroke. A detrimental effect of leukocytosis on stroke outcome has been suggested, and trials aiming at reducing the leukocyte response in acute stroke are currently being conducted. However, the influence of leukocytosis on stroke outcome has not been clarified. METHODS: In 763 unselected patients with stroke admitted within 24 hours from onset, we prospectively studied the relation between leukocyte count and outcome considering relevant confounders and predictors such as initial stroke severity, risk factor profile, body temperature, and infection. RESULTS: Univariate, leukocyte count on admission was significantly related to initial stroke severity (assessed by the Scandinavian Stroke Scale), lesion size on computed tomography, mortality, and outcome in survivors. However, multivariate regression analysis revealed that only the relation between leukocytosis and initial stroke severity was independent of other factors, whereas the relations found univariately between leukocytosis and lesion size, mortality, and outcome in survivors disappeared when initial stroke severity was included in the multivariate model. CONCLUSION: Leukocytosis on admission was related to initial stroke severity but not to outcome. Leukocyte count on admission seems merely to reflect initial stroke severity and is most likely a stress response with no independent influence on outcome. Our study may suggest that attempts aimed merely at lowering leukocyte count in peripheral circulating blood in the acute phase of stroke cannot be expected to improve outcome.