Lars Thomassen

Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke

BACKGROUND The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions. METHODS In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet‐only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24‐month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on imaging. RESULTS We enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow‐up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet‐only group (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.62; P=0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet‐only group (22 patients [5.7%] vs. 20 patients [11.3%]; relative risk, 0.51; 95% CI, 0.29 to 0.91; P=0.04), but the incidence of silent brain infarction did not differ significantly between the study groups (P=0.97). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet‐only group (P=0.22). Serious device‐related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure. CONCLUSIONS Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894.)

IL‐6: an early marker for outcome in acute ischemic stroke

Objectives –  Inflammation plays an important role in the pathophysiology of stroke. We correlated interleukin (IL)‐6, IL‐10, C‐reactive protein (CRP) and T‐lymphocyte subtype levels in acute ischemic stroke patients with stroke volume and clinical outcome.

Health-Related Quality of Life Among Young Adults With Ischemic Stroke on Long-Term Follow-Up

Background and Purpose— We sought to compare health-related quality of life (HRQoL) in young adults with ischemic stroke on long-term follow-up with controls and to evaluate HRQoL in clinically relevant patient subgroups. Methods— HRQoL was determined with the use of the 8 subscales of the Short-Form General Health Survey (SF-36). Subgroups of patients were defined by sex, age, functional status (modified Rankin Scale), marital status, education, depression (Montgomery-Åsberg Depression Rating Scale), and fatigue (Fatigue Severity Scale). SF-36 scores among patients were compared with SF-36 scores among age- and sex-matched controls and SF-36 scores available from the general Norwegian population. Results— SF-36 scores were obtained after a mean follow-up of 6.0 years among 190 young adults with ischemic stroke during 1988–1997 and among 215 responding controls (55%). The difference in HRQoL between patients, controls, and the general Norwegian population was restricted mainly to the 3 subscales physical functioning, general health, and social functioning (P<0.001). Subgroup analysis showed significantly reduced scores for all SF-36 items among patients who were depressed, suffered from fatigue, or unemployed. Linear regression analysis showed that fatigue and depression were major independent variables correlated with low HRQoL. Conclusions— Compared with controls and the general Norwegian population, low level of HRQoL among young adults with ischemic stroke was most pronounced in regard to physical functioning. Early identification and treatment of depression, fatigue, and physical disability may potentially improve HRQoL among stroke patients.

Fatigue at Long-Term Follow-Up in Young Adults with Cerebral Infarction

Background: To study the impact of fatigue in young ischaemic stroke patients. Methods: The Fatigue Severity Scale score was obtained in 192 patients (mean time 6.0 years after the stroke) and 212 controls. Results: Fatigue was associated with cerebral infarction in a multivariate analysis of patients and controls (p = 0.002). Fatigue was independently associated with unfavourable functional outcome (p = 0.001), depression (p < 0.001), and basilar artery infarction through interaction with the modified Rankin Scale score (p = 0.047) in patients. Conclusion: Fatigue is frequent in young adults with cerebral infarction. Stroke-related factors independently associated with fatigue include functional outcome. Stroke location may influence fatigue.

Risk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969–1993

We investigated the cancer risk of patients hospitalized for schizophrenia in a nationwide cohort study. All 22766 adults admitted for schizophrenia, ICD-8 295, in Denmark between 1969 and 1993 were followed up for cancer through 1995. The incidence of site-specific cancers was compared with national incidence rates, adjusted for sex, age and calendar time. The risk for cancer was increased for both men and women during the first year of follow-up. When the first year of follow-up was excluded, the risk for all tobacco-associated cancers and for prostate and rectal cancers was reduced for male patients with schizophrenia. The standardized incidence ratio (SIR) of lung cancer was marginally reduced (SIR, 0.86; 95% CI: 0.65, 1.02) for male patients with schizophrenia; this was due, however, to a reduction in risk for older patients. An increased risk for breast cancer found for female patients with schizophrenia (SIR, 1.20; 95% CI: 1.05, 1.38) should be interpreted with caution, given the high proportion of nulliparous women with schizophrenia in Denmark. The data might support reduced risks for prostate and rectal cancer among male patients with schizophrenia, whereas a changing smoking pattern might explain the reduced risk for tobacco-related cancers.

Long‐term outcome of cerebral infarction in young adults

Objectives – We analysed the long‐term outcome of 232 young adults aged 15–49 years with first‐ever cerebral infarction in 1988–1997 in western Norway.

Incidence and Short-Term Outcome of Cerebral Infarction in Young Adults in Western Norway

Background and Purpose— We sought to determine the incidence and short-term outcome of people aged 15 to 49 years with first-ever cerebral infarction in 1988–1997 in Hordaland County, Norway. Methods— Cases were found from computer search of hospital registries and detailed review of patient records. Stroke subtype was classified according to the major intracranial artery affected. Short-term outcome was evaluated by the modified Rankin Scale (mRS). Results— A total of 96 women and 136 men met the inclusion criteria. The average annual incidence was 11.4/100 000. Women outnumbered men among those aged <30 years (P =0.059); men predominated among those aged ≥30 years (P =0.004). A total of 148 patients had anterior circulation infarction (64%), and 84 had posterior circulation infarction (36%) (P <0.001). Patients with posterior circulation infarction had better mRS score at discharge (P =0.005). Eighty percent had favorable outcome (mRS score ≤2). The 30-day case fatality rate was 3.4%. The recurrence rate in hospital was 2.2%. Conclusions— The incidence was in the lower range compared with other reports from western Europe. Although men predominated, there was a strong trend toward more women among patients aged <30 years. Short-term outcome was generally good. Patients with posterior circulation infarction had significantly better short-term outcome.

Glutathione S-transferases as risk factors in prostate cancer.

Glutathione S-transferases are enzymes involved in the metabolism of carcinogens and in the defence against reactive oxygen species. Genetic polymorphisms have been detected in glutathione S-transferases M1, T1 and P1, and some of these polymorphisms have been associated with an increased risk of cancer. In a case-control study (153 cases and 288 controls) the effect of these genetic polymorphisms on the risk of prostate cancer was investigated. Homozygote deletion of either GSTM1 or GSTT1 was not associated with a statistically significant increased risk, odds ratio (OR) 1.3; 95% confidence intervals (CI) 0.9-1.9 and 1.3; 0.8-2.2, respectively. Deletion of both GSTM1 and GSTT1 gave a near-significant increased risk (OR 1.7; 95% CI 0.9-3.4). Two allelic variants of GSTP1 (codon 105) have been reported. This polymorphism was not linked to an increased risk (OR 0.8; 95% CI 0.5-1.1). Smokers that lack either GSTM1 or GSTT1 activity had a slightly higher risk of prostatic cancer than smokers expressing the genes, OR 1.4 (95% CI 0.6-3.3) and 1.6 (0.6-3.9), respectively. Our results show that differences in enzymes involved in the metabolism of carcinogens slightly modify prostate cancer risk, especially in people exposed to carcinogens that are detoxified by these enzymes.

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.

Etiology of first‐ever ischaemic stroke in European young adults: the 15 cities young stroke study

Risk factors for IS in young adults differ between genders and evolve with age, but data on the age‐ and gender‐specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers.