Henrik Stig Jørgensen

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°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 t0=36.8°C to t6=35.5°C (P <0.001), and hypothermia was present until 4 hours after therapy (t0=36.8°C versus t10=36.5°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.

Who Benefits From Treatment and Rehabilitation in a Stroke Unit? A Community-Based Study

BACKGROUND AND PURPOSEnThe 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.nnnMETHODSnThis 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.nnnRESULTSnThe 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 patients 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.nnnCONCLUSIONSnA 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.

Prediction of walking function in stroke patients with initial lower extremity paralysis: The Copenhagen Stroke Study

OBJECTIVESnThe majority of stroke patients with initial leg paralysis do not regain independent walking. We characterize the minority who, despite initial leg paralysis, regained independent walking.nnnDESIGNnConsecutive and community based.nnnSETTINGnA stroke unit receiving all stroke patients from a well-defined community.nnnPATIENTSnA total of 859 acute stroke patients; 157 (15%) initially had leg paralysis.nnnMAIN OUTCOME MEASURESnScandinavian Stroke Scale (SSS) and Barthel index (BI) on admission and weekly during rehabilitation. Univariate and multivariate statistics were considered.nnnRESULTSnOf the 157 patients with initial leg paralysis, 84 (60%) died; 73 (40%) survived. Fifteen (21%) survivors regained walking function (the walking group), and 58 (79%) did not (the nonwalking group). The BI on admission was the only factor of significant predictive value (p < .03). Mean admission BI was 50 in the walking group versus 3 in the nonwalking group (p < .001). Age, gender, lesion size, total SSS score, and comorbidity had no predictive value. Within the first week, the walking group gained 3.2 points in the SSS subscore for leg strength versus 0.5 points in the nonwalking group (p < .02).nnnCONCLUSIONnOnly 10% of stroke patients with initial leg paralysis regained independent walking. In these patients, BI on admission was high and leg strength improved quickly in the first week.

Predicted impact of intravenous thrombolysis on prognosis of general population of stroke patients: simulation model

Alteplase (recombinant tissue plasminogen activator) can be used to dissolve blood clots and achieve reperfusion in some stroke patients. Three randomised controlled trials have studied its clinical effect.1–3 A US trial studied patients who were treated within three hours of onset of stroke and reported a 32% (95% confidence interval 1% to 70%) relative increase in the proportion of patients with full recovery but no effect on overall mortality.1 This led to approval of alteplase for stroke patients in the United States. A European trial of patients treated within six hours of stroke onset was negative,2 and a second trial, published recently, reported no significant positive effect.3 An application for European approval of alteplase treatment within three hours of stroke onset is being considered. Alteplase often leads to bleeding and should be given only by …

Increasing Incidence of Hospitalization for Stroke and Transient Ischemic Attack in Young Adults: A Registry‐Based Study

Background Studies have reported increasing incidence of ischemic stroke in adults younger than 50 to 55 years. Information on temporal trends of other stroke subtypes and transient ischemic attack (TIA) is sparse. The aim of this study was to investigate temporal trends of the incidence of hospitalizations for TIA and stroke including sex‐ and subtype‐specific trends in young adults aged 15 to 30 years. Methods and Results From the Danish National Patient Register, we identified all cases of first‐ever stroke and TIA (age 15–30 years) in Denmark, who were hospitalized during the study period of 1994 to 2012. Incidence rates and estimated annual percentage changes (EAPCs) were estimated by using Poisson regression. During the study period, 4156 cases of first‐ever hospitalization for stroke/TIA were identified. The age‐standardized incidence rates of hospitalizations for stroke increased significantly (EAPC 1.83% [95% CI 1.11–2.55%]) from 11.97/100 000 person‐years (PY) in 1994 to 16.77/100 000 PY in 2012. TIA hospitalizations increased from 1.93/100 000 PY in 1994 to 5.81/100 000 PY in 2012 and after 2006 more markedly in men than in women (EAPC 16.61% [95% CI 10.45–23.12%]). The incidence of hospitalizations for ischemic stroke was markedly lower among men, but increased significantly from 2006 (EAPC 14.60% [95% CI 6.22–23.63%]). The incidences of hospitalizations for intracerebral hemorrhage and subarachnoid hemorrhage remained stable during the study period. Conclusions The incidence rates of first‐time hospitalizations for ischemic stroke and TIA in young Danish adults have increased substantially since the mid 1990s. The increase was particularly prominent in the most recent years.

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

Pedersen PM, J/orgensen HS, Kammersgaard LP, Nakayama H, Raaschou HO, Olsen TS: Manual and oral apraxia in acute stroke, frequency and influence on functional outcome: the Copenhagen Stroke Study. Am J Phys Med Rehabil 2001;80:685–692. 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; &khgr;2= 9.0;P = 0.003). Oral apraxia was found in 6% (9% in left and 4% in right hemispheric stroke; &khgr;2= 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.

Impaired Orientation in Acute Stroke: Frequency, Determinants, and Time-Course of Recovery

Orientation is an indicator of general intellectual function and is defined as the ability to report time, place, and personal data. Our knowledge of orientation in acute stroke is sparse. We examined the frequency of impaired orientation in acute stroke, its determinants, and recovery in 653 consecutive patients with acute stroke who were not unconscious and who were without severe aphasia. Prospective assessments of orientation and stroke severity were done by the Scandinavian Neurologic Stroke Scale at the time of acute admission and hereafter weekly until the end of rehabilitation. Impaired orientation was found in 23% of the patients on acute admission and in 12% of the survivors after completed rehabilitation. A stationary level of orientation was achieved by 80% of the patients within 2 weeks and by 95% within 6 weeks. A multiple linear regression analysis found neurological score (B = 0.027, SE(B) = 0.003), age (B = –0.013, SE(B) = 0.003), and comorbidity (B = –0.023, SE(B) = 0.078), but not sex, prior stroke, handedness, or side of stroke lesion to be significant independent determinants of orientation score on acute admission. Lesions involving the anterior and medial thalamus and/or any of the cerebral lobes were associated with impaired orientation. In conclusion, impaired orientation is frequent in acute stroke and the time-course of recovery is similar to what has been found in other neuropsychological impairments with the major part of recovery early after stroke onset.

An Insertion/Deletion polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene is associated with plasma levels but not with stroke risk in the elderly.

The purpose of the present study was to examine the effects of an insertion/deletion (ins/del) polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene on plasma PAI-1 antigen and activity levels and on stroke risk in the elderly. The ins/del genotype and PAI-1 antigen and activity plasma levels were determined in 177 patients with ischemic stroke (mean age, 75 years) and 93 healthy elderly subjects (mean age, 74 years). There was no difference in the frequencies of the ins and del alleles between stroke patients and healthy elderly subjects. The del/del genotype was associated with the highest plasma PAI-1 antigen levels in the healthy subjects: those with the ins/ins genotype had 36% lower plasma PAI-1 antigen levels than those with the del/del genotype (effect of genotype, P=0.3). In contrast, the ins/del genotype was not associated with plasma PAI-1 antigen and activity levels in 89 patients who had a stroke less than 10 days before blood sampling. However, an association of ins/del genotype with plasma PAI-1 activity levels could be demonstrated in 88 other patients more than 5 months after the stroke. This may suggest that PAI-1 metabolism is temporarily perturbed after a stroke. The present data suggest that an ins/del polymorphism in the PAI-1 promoter region affects plasma PAI-1 levels but has little or no effect on stroke risk in the elderly.

Tissue plasminogen activator is elevated in women with ischemic stroke.

A recent study suggests that a high plasma level of tissue plasminogen activator (t-PA antigen) is a risk factor for stroke in men. Whether t-PA antigen is a risk factor for stroke in women is unknown. We measured plasma levels of t-PA antigen in 302 nonselected patients with acute ischemic stroke and in 138 healthy control subjects. In a subgroup of the patients, plasma t-PA antigen was remeasured 6 months after the stroke. Women with acute ischemic stroke (n=171) had median plasma t-PA antigen that was 39% higher than the healthy female control subjects (n=86): 10.3 (8.0 to 13.7) versus 7.4 (6.1 to 9.1) ng/mL (median [interquartile range]), P=.0001. At the reexamination of the patients after 6 months, plasma t-PA antigen was unchanged in the female patients. This suggests that the difference in plasma t-PA antigen between the female patients and the healthy control subjects did not result from an acute phase reaction. In a multivariate regression analysis, high t-PA antigen was an independent risk factor for stroke, and high plasma level of t-PA antigen was associated with severe stroke in women. The current data suggest that plasma t-PA antigen is elevated in women with ischemic stroke.