Michaela K. Bode

Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study.

Background and Purpose— Warfarin use has rapidly increased with the aging of the population. We investigated the temporal trends in the incidence and outcome of warfarin-related intracerebral hemorrhages (ICHs) in a defined population. Methods— We identified all subjects with first-ever primary ICH during 1993 to 2008 among the population of Northern Ostrobothnia, Finland. The number of warfarin users was obtained from the national register of prescribed medicines kept by the Social Insurance Institution of Finland. We calculated the annual incidence of warfarin-related ICHs, 28-day case fatality, and deaths from the primary bleed. Results— The proportion of warfarin users among the population increased 3.6-fold from 0.68% in 1993 to 2.28% in 2008. Of a total of 982 patients with ICH, 182 (18.5%) had warfarin-related ICH. One-year survival rate after onset of stroke was 35.2% among warfarin users and 67.9% among nonusers. The annual incidence (P=0.062) and 28-day case fatality of warfarin-related ICHs (P=0.002) decreased during the observation period. Warfarin users were older (mean difference 6.6; 95% CI, 5.0 to 8.1; P<0.001) than nonusers. Admission international normalized ratio values above the therapeutic range (2.0 to 3.0) decreased through the observation period, suggesting improved control of anticoagulant therapy over time. Conclusions— The annual incidence and case fatality of warfarin-related ICHs decreased, although the proportion of warfarin users almost quadrupled in our population.

White matter in autism spectrum disorders – evidence of impaired fiber formation

Background Diffusion tensor imaging (DTI) enables measurements and visualization of the microstructure of neural fiber tracts. The existing literature on autism spectrum disorders (ASDs) and DTI is heterogenous both regarding methodology and results. Purpose To compare brain white matter of high-functioning individuals with ASDs and controls. Material and Methods Tract-based spatial statistics (TBSS), a voxel-based approach to DTI, was used to compare 27 subjects with ASDs (mean age 14.7 years, range 11.4–17.6 years, 20 boys, 7 girls) and 26 control subjects (mean age 14.5 years, range 11.7–17.3 years, 17 boys, 9 girls). Mean fractional anisotropy (FA) image (skeleton) was created and each subjects aligned FA data were then projected onto this skeleton. Voxelwise cross-subject statistics on the skeletonized FA data, mean diffusivity (MD), and measures of diffusion direction were calculated. Importantly, the data were corrected across the whole image instead of using ROI-based methods. Results The ASD group showed significantly greater FA (P < 0.05, corrected) in the area containing clusters of optic radiation and the right inferior fronto-occipital fasciculus (iFOF). In the same area, λ3 (representing transverse diffusion) was significantly reduced in the ASD group. No age-related changes were found. Conclusion The results suggest that the reduced transverse diffusion within the iFOF is related to abnormal information flow between the insular salience processing areas and occipital visual areas.

Ultrasonography and Core Needle Biopsy in the Differential Diagnosis of Fibroadenoma and Tumor Phyllodes

Background: The diagnosis of phyllodes tumors of the breast is challenging due to many similarities with common fibroadenomas. Purpose: To determine the diagnostic accuracy of core needle biopsy in diagnosing phyllodes tumors and to analyze the ultrasonographic (US) features of phyllodes tumors and fibroadenomas. Material and Methods: From 1999 to 2003, 1010 breast lesions underwent imaging-guided core needle biopsy. Of these, 57 fibroadenomas and 12 phyllodes tumors were removed surgically. The US and needle biopsy results of a total of 64 lesions (52 fibroadenomas and 12 phyllodes tumors) were further analyzed, compared, and correlated with surgical histological results. Results: The median sonographic sizes of the phyllodes tumors and the fibroadenomas were 3.2 cm and 1.6 cm, respectively. At US, 58% of the phyllodes tumors (7/12) were classified as equivocal or suspicious of malignancy and 42% (5/12) as probably benign, while 54% of the fibroadenomas (28/52) were classified as probably benign and 46% (24/52) as equivocal. The sensitivity, specificity, and positive and negative predictive values of core needle biopsy histology regarding tumor phyllodes were 83%, 92%, 71%, and 96%, respectively. Conclusion: Imaging-guided core needle biopsy was accurate in differentiating between fibroadenomas and phyllodes tumors. US classification was unreliable due to considerable overlap in the findings. Combined use of US feature analysis and needle biopsy may help to avoid the misinterpretation of phyllodes as fibroadenoma.

Potential of diffusion imaging in brain tumors: a review:

Diffusion magnetic resonance imaging (MRI) is a method for quantifying the microscopic random motion of water molecules in tissues. Diffusion imaging provides indirect structural information of a kind not available on basic MRI sequences of many pathological conditions. Lately, especially brain tumors have been under active investigation, with numerous papers already published, and their number continues to increase. This review summarizes the heterogeneous and complex research data on diffusion imaging of brain tumors.

Predictors for Recurrent Primary Intracerebral Hemorrhage A Retrospective Population-based Study

Background and Purpose— Underlying comorbidities, previous strokes, and medication may increase the risk for primary intracerebral hemorrhage (PICH) and its recurrence. The aim of this study was to determine the independent predictors for recurrent PICH. Methods— We identified 961 subjects with first-ever PICH from 1993 to 2008 among the population of Northern Ostrobothnia, Finland. Hospital and death records were reviewed and data on drug use were obtained from the national register of prescribed medicines. Kaplan–Meier survival curves and Cox proportional hazards models were used to demonstrate predictors for recurrence of PICH. Results— Total follow-up time of the 961 patients was 3481 person-years. During the follow-up time, 58 subjects had altogether 68 recurrent PICHs. The annual average incidence of first recurrence was 1.67%. Cumulative 5- and 10-year incidence rates were 9.6% and 14.2%, respectively. In univariable analysis, history of ischemic stroke, diabetes mellitus, and aspirin use were associated with a higher recurrence rate. In multivariable analysis, only previous ischemic stroke (adjusted hazard ratio, 2.22; 95% confidence interval, 1.22–4.05; P=0.009) independently predicted PICH recurrence. Diabetes mellitus tended to increase (adjusted hazard ratio, 2.38; 95% confidence interval, 0.98–5.80; P=0.056), whereas treated hypertension tended to decrease (0.45, 0.20–1.01; P=0.054) the risk for fatal recurrent PICH. Conclusions— Previous ischemic stroke independent of confounding factors may increase the risk for PICH recurrence.

Ultrasonography-Guided Core Needle Biopsy in Differential Diagnosis of Papillary Breast Tumors

Background: Papillary lesions of the breast are considered diagnostically challenging for various reasons. A relatively high malignancy rate in final pathological analysis has in many cases necessitated excision of these lesions, regardless of core needle biopsy (CNB). Purpose: To assess mammographic, sonographic, and CNB findings of papillary lesions, and to correlate them with final histology obtained by surgical excision. Material and Methods: From 2000–2006, 29 benign and 19 malignant papillary tumors examined with CNB were surgically removed. Mammographic, sonographic, and CNB results were analyzed and correlated with final histology. Results: On ultrasonography (US), 69% (20/29) of the benign lesions were solid and 31% (9/29) were cystic, and 47% of the malignant lesions (9/19) were solid and 53% (10/19) were cystic. The mammographic findings were nonspecific, although most of the malignant tumors (67%, 12/18) were categorized as BI-RADS 4 lesions. The sensitivity, specificity, and positive predictive value of the core needle biopsy histology was 32% (6/19), 100% (29/29), and 100% (6/6), respectively, for papillary carcinoma. A negative predictive value of 91% (21/23) for malignancy and 48% (11/23) for either atypia or malignancy was shown. Of the lesions with CNB diagnosis of benign papillary lesion with atypia, 58% (11/19) turned out to be malignant and 11% (2/19) were benign on surgery. Conclusion: The probability of malignancy is low when the CNB result shows a benign papillary lesion with no atypia. However, the only way to reliably diagnose atypical papillary lesions is to surgically remove all papillary tumors, irrespective of the CNB result. Differentiation between benign and malignant lesions or malignant noninvasive and invasive tumors is not possible based on sonographic or mammographic appearance.

Improved survival of patients with warfarin-associated intracerebral haemorrhage: a retrospective longitudinal population-based study

Background Warfarin-associated intracerebral haemorrhage carries poor outcome due to rapid haemorrhage growth. Reversal of warfarin anticoagulation with prothrombin complex concentrate has been implemented as an acute treatment option for these subjects. Aim We investigated whether survival of subjects with warfarin-associated intracerebral haemorrhage had improved after implementation of reversal of warfarin anticoagulation with prothrombin complex concentrate. Methods We identified all subjects with warfarin-associated intracerebral haemorrhage during 1993–2008 among the population of Northern Ostrobothnia, Finland. From 2004 onwards, prothrombin complex concentrate was used in Oulu University Hospital, the only hospital treating intracerebral haemorrhage subjects in the region, to counteract the effect of warfarin in subjects with warfarin-associated intracerebral haemorrhage. We compared the outcomes of subjects admitted during 1993–2003 and 2004–2008 and those treated and not treated with prothrombin complex concentrate. We also explored the predictors for one-year survival of the warfarin-associated intracerebral haemorrhage subjects. Results We identified altogether 181 subjects who had intracerebral haemorrhage while on warfarin. One-year survival was significantly (P = 0·031) higher for the 60 subjects admitted during 2004–2008 (43·3%) than for the 121 admitted before 2004 (30·6%). In multivariable analysis, prothrombin complex concentrate treatment reduced one-year case fatality (hazard ratio 0·52, 95% confidence interval 0·29–0·93). Thromboembolic complications did not occur more frequently among those treated with prothrombin complex concentrate. Conclusion The survival of warfarin-associated intracerebral haemorrhage subjects among the population of Northern Ostrobothnia has improved likely because of introduction of prothrombin complex concentrate.

Predictive value of C-reactive protein for the outcome after primary intracerebral hemorrhage

OBJECT Primary intracerebral hemorrhage (ICH) carries high morbidity and mortality rates. Several factors have been suggested as predicting the outcome. The value of C-reactive protein (CRP) levels in predicting a poor outcome is unclear, and findings have been contradictory. In their population-based cohort, the authors tested whether, independent of confounding factors, elevated CRP levels on admission (< 24 hours after ictus) are associated with an unfavorable outcome. METHODS The authors identified all patients who suffered primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland, and from the laboratory records they extracted the CRP values at admission. Independent predictors of an unfavorable outcome (moderate disability or worse according to the Glasgow Outcome Scale at 3 months) were tested by unconditional logistic regression in a model including all the well-established confounding factors and CRP on admission. RESULTS Of 961 patients, 807 (84%) had CRP values available within 24 hours of admission, and multivariable analysis showed elevated CRP at that point to be associated with an unfavorable outcome (OR 1.41 per 10 mg/L [95% CI 1.09-1.81], p < 0.01), together with diabetes mellitus (OR 1.99 [95% CI 1.09-3.64], p < 0.05), age (1.06 per year [95% CI 1.04-1.08], p < 0.001), low Glasgow Coma Scale score (0.75 per unit [95% CI 0.67-0.84], p < 0.001), hematoma size (1.05 per ml [95% CI 1.03-1.07], p < 0.001), and the presence of an intraventricular hemorrhage (2.70 [95% CI 1.66-4.38], p < 0.001). Subcortical location predicted a favorable outcome (0.33 [95% CI 0.20-0.54], p < 0.001). CONCLUSIONS Elevated CRP on admission is an independent predictor of an unfavorable outcome and is only slightly associated with the clinical and radiological severity of the bleeding.

Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study

OBJECT Patients receiving oral anticoagulants run a higher risk of cerebral hemorrhage with a poor outcome. Serotonin-modulating antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]) are frequently used in combination with warfarin, but it is unclear whether this combination of drugs influences outcome after primary intracerebral hemorrhage (PICH). The authors investigated case fatality in PICH among patients from a defined population who were receiving warfarin alone, with aspirin, or with serotonin-modulating antidepressants. METHODS Nine hundred eighty-two subjects with PICH were derived from the population of Northern Ostrobothnia, Finland, for the years 1993-2008, and those with warfarin-associated PICH were eligible for analysis. Their hospital records were reviewed, and medication data were obtained from the national register of prescribed medicines. Kaplan-Meier survival curves were drawn to illustrate cumulative case fatality, and a Cox proportional-hazards analysis was performed to demonstrate predictors of death. RESULTS Of the 176 patients eligible for analysis, 17 had been taking aspirin and 19 had been taking SSRI/SNRI together with warfarin. The 30-day case fatality rates were 50.7%, 58.8%, and 78.9%, respectively, for those taking warfarin alone, with aspirin, or with SSRI/SNRI (p = 0.033, warfarin plus SSRI/SNRI compared with warfarin alone). Warfarin combined with SSRI/SNRI was a significant independent predictor of case fatality (adjusted HR 2.10, 95% CI 1.13-3.92, p = 0.019). CONCLUSIONS Concurrent use of warfarin and a serotonin-modulating antidepressant, relative to warfarin alone, seemed to increase the case fatality rate for PICH. This finding should be taken into account if hematoma evacuation is planned.

Immediate, early and late seizures after primary intracerebral hemorrhage

BACKGROUND Seizures after primary intracerebral hemorrhage (PICH) are significant and treatable complications, but the factors predicting immediate, early and late seizures are poorly known. We investigated characteristics and outcome with special reference to occurrence and timing of a first seizure among consecutive subjects with PICH. METHODS A population-based study was conducted in Northern Ostrobothnia, Finland, in 1993-2008 that included all patients with a first-ever primary ICH without any prior diagnosis of epilepsy. Immediate (<24h after admission), early (1-14 days) and late (>2 weeks) seizures were considered separately. RESULTS Out of a total of 935 ICH patients, 51 had immediate, 21 early and 58 late seizures. The patients with seizures were significantly younger than the others and more often had a subcortical hematoma location (p<0.05). Lifestyle factors did not differ between the groups. The risk factors for immediate seizures in multivariable analysis were a low Glasgow coma scale score (GCS) on admission, subcortical location and age inversely (p<0.01). The only independent risk factor for early seizures was subcortical location (p<0.001), whereas subcortical location (p<0.001), age inversely (p<0.01) and hematoma evacuation (p<0.05) independently predicted late seizures. Immediate and early seizures predicted infectious complications (p<0.05). CONCLUSIONS Patients with subcortical hematoma and of younger age are at risk for immediate seizures after primary ICH irrespective of hematoma size. Patients with immediate and early seizures more often had infectious complications. Surgery increases the risk of a late seizure after ICH.