Temporal Changes in CSF Cell Parameters After SAH: Comparison of Ventricular and Spinal Drain Samples.

BACKGROUND: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)-derived and lumbar spinal drain-derived samples. METHODS: We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain-derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling. RESULTS: We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4-5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64-618 × 106). The cell ratio and index peaked at 8-9 days (0.90% [IQR 0.35-1.98%] and 2.71 [IQR 1.25-6.73], respectively). In spinal drain-derived samples, the leucocyte count peaked at days 6-7, reaching a median of 238 × 106 (IQR 60-396 × 106). The cell ratio and index peaked at 14-15 days (4.12% [IQR 0.63-10.61%]) and 12-13 days after aSAH (8.84 [IQR 3.73-18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain-derived samples at days 6-17, and the cell ratio as well as the cell index was significantly higher in spinal drain-derived samples compared to EVD samples at days 10-15. CONCLUSIONS: CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.

Effect of antiplatelet and anticoagulant medication use on injury severity and mortality in patients with traumatic brain injury treated in the intensive care unit.

BACKGROUND: Antiplatelet and anticoagulant medication are increasingly common and can increase the risks of morbidity and mortality in traumatic brain injury (TBI) patients. Our study aimed to quantify the association of antiplatelet or anticoagulant use in intensive care unit (ICU)-treated TBI patients with 1-year mortality and head CT findings. METHOD: We conducted a retrospective, multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted to four university hospital ICUs during 2003-2013. The patients were followed up until the end of 2016. The national drug reimbursement database provided information on prescribed medication for our study. We used multivariable logistic regression models to assess the association between TBI severity, prescribed antiplatelet and anticoagulant medication, and their association with 1-year mortality. RESULTS: Of 3031 patients, 128 (4%) had antiplatelet and 342 (11%) anticoagulant medication before their TBI. Clopidogrel (2%) and warfarin (9%) were the most common antiplatelets and anticoagulants. Three patients had direct oral anticoagulant (DOAC) medication. The median age was higher among antiplatelet/anticoagulant users than in non-users (70 years vs. 52 years, p < 0.001), and their head CT findings were more severe (median Helsinki CT score 3 vs. 2, p < 0.05). In multivariable analysis, antiplatelets (OR 1.62, 95% CI 1.02-2.58) and anticoagulants (OR 1.43, 95% CI 1.06-1.94) were independently associated with higher odds of 1-year mortality. In a sensitivity analysis including only patients over 70, antiplatelets (OR 2.28, 95% CI 1.16-4.22) and anticoagulants (1.50, 95% CI 0.97-2.32) were associated with an increased risk of 1-year mortality. CONCLUSIONS: Both antiplatelet and anticoagulant use before TBI were risk factors in our study for 1-year mortality. Antiplatelet and anticoagulation medication users had a higher radiological intracranial injury burden than non-users defined by the Helsinki CT score. Further investigation on the effect of DOACs on mortality should be done in ICU-treated TBI patients.

One-Year Survival of Ischemic Stroke Patients Requiring Mechanical Ventilation.

BACKGROUND: The outcome of patients with acute ischemic stroke who require mechanical ventilation has been poor. Intubation due to a reversible condition could be associated with better 1-year survival. METHODS: All adult patients treated in Helsinki University Hospital in 2016-2020 who were admitted because of an ischemic stroke (either stroke or thrombosis seen on imaging) and needed mechanical ventilation were included in this retrospective cohort study. Data on demographics, medical history, index stroke, and indication for intubation were collected. The primary outcome was 1-year mortality. Secondary outcomes were modified Rankin Scale (mRS) score at 3 months and living arrangements at 1 year. RESULTS: The mean age of the cohort (N = 121) was 66 ± 11 (mean ± SD) years, and the mean admission National Institutes of Health Stroke Scale score was 17 ± 10. Forty-four (36%) patients were male. The most common indication for intubation was unconsciousness (51%), followed by respiratory failure or airway compromise (28%). One-year mortality was 55%. Three-month mRS scores were available for 114 (94%) patients, with the following distribution: 0-2, 18%; 3-5, 28%; and 6 (dead), 54%. Of the 1-year survivors, 72% were living at home. In the multivariate analysis, only age over 75 years and intubation due to unconsciousness, respiratory failure, or cardiac arrest remained significantly associated with mortality. CONCLUSIONS: The indication for intubation seems to significantly affect outcome. Functional outcome at 3 months is often poor, but a great majority of 1-year survivors are able to live at home.

Characteristics and Outcomes of Thrombolysis-Treated Stroke Patients With and Without Saccular Intracranial Aneurysms.

BACKGROUND: Intravenous thrombolysis seems safe in acute ischemic stroke patients with saccular, unruptured intracranial aneurysms (UIAs), but little is known about the differences in cardiovascular risk factors and outcomes between intravenous thrombolysis-treated stroke patients with and without UIAs. We hypothesized that UIA patients would have a higher burden of cardiovascular risk factors and, therefore, a higher risk of an unfavorable outcome. METHODS: In this prospective cohort study conducted in Helsinki University Hospital, we identified intravenous thrombolysis-treated patients with concurrent saccular UIAs admitted to a comprehensive stroke center between 2005 and 2019 using 2 overlapping methods. For each UIA patient, a control patient was identified and matched (1:1) for age, sex, admission year, and stroke severity. The primary outcome was an unfavorable outcome at 3 months, defined as a modified Rankin Scale (mRS) score 3 to 6. The secondary outcomes were an excellent outcome (mRS score 0-1) at 3 months and mRS difference in shift analysis. RESULTS: In total, 118 UIA patients and 118 matched control patients were identified. The UIA patients were more often current smokers, and their admission systolic blood pressure was higher. The rate of hemorrhagic complications did not differ between the groups. UIAs were not associated with an unfavorable outcome in the conditional logistic regression analysis (odds ratio, 1.41 [95% CI, 0.79-2.54]; P=0.25). However, the UIA patients were less likely to have excellent outcomes (odds ratio for non-excellent outcome, 2.09 [95% CI, 1.13-3.85]; P=0.02). In shift analysis, UIAs were associated with higher mRS (odds ratio, 1.61 [95% CI, 1.03-2.49]; P=0.04). CONCLUSIONS: The intravenous thrombolysis-treated stroke patients with UIAs were more often current smokers and had higher systolic blood pressure than the matched patients without UIAs. They were as likely to have unfavorable outcomes at 3 months but seemed less likely to achieve excellent outcomes and were more likely to have higher mRS in shift analysis.

Trends in Mortality after Intensive Care of Patients with Aneurysmal Subarachnoid Hemorrhage in Finland in 2003-2019: A Finnish Intensive Care Consortium study.

BACKGROUND: Previous studies suggest that case mortality of aneurysmal subarachnoid hemorrhage (aSAH) has decreased during the last decades, but most studies have been unable to assess case severities among individual patients. We aimed to assess changes in severity-adjusted aSAH mortality in patients admitted to intensive care units (ICUs). METHODS: We conducted a retrospective, register-based study by using the prospectively collected Finnish Intensive Care Consortium database. Four out of five ICUs providing neurosurgical and neurointensive care in Finland participated in the Finnish Intensive Care Consortium. We extracted data on adult patients admitted to Finnish ICUs with aSAH between 2003 and 2019. The primary outcome was 12-month mortality during three periods: 2003-2008, 2009-2014, and 2015-2019. Using a multivariable logistic regression model-with variables including age, sex, World Federation of Neurological Surgeons grade, preadmission dependency, significant comorbidities, and modified Simplified Acute Physiology Score II-we analyzed whether admission period was independently associated with mortality. RESULTS: A total of 1,847 patients were included in the study. For the periods 2003-2008 and 2015-2019, the mean number of patients with aSAH admitted per year increased from 81 to 123. At the same time, the patients' median age increased from 55 to 58 years (p = 0.001), and the proportion of patients with World Federation of Neurological Surgeons grades I-III increased from 42 to 58% (p < 0.001). The unadjusted 12-month mortality declined from 30% in 2003-2008 to 23% in 2015-2019 (p = 0.001), but there was no statistically significant change in severity-adjusted mortality. CONCLUSIONS: Between 2003 and 2019, patients with aSAH admitted to ICUs became older and the proportion of less severe cases increased. Unadjusted mortality decreased but age and case severity adjusted-mortality remained unchanged.

Neurointensive care results and risk factors for unfavorable outcome in aneurysmatic SAH: a comparison of two age groups.

BACKGROUND: The mean age of actively treated subarachnoid hemorrhage (SAH) patients is increasing. We aimed to compare outcomes and prognostic factors between older and younger SAH patients. METHODS: A retrospective single-center analysis of aneurysmal SAH patients admitted to a neuro-ICU during 2014-2019. We defined older patients as ≥70 years and younger patients as <70 years. For every older patient, we identified three younger patients with the same World Federation of Neurological Surgeons (WFNS) grade. We only included patients receiving active aneurysm treatment. Favorable functional outcome, defined as a Glasgow Outcome Scale (GOS) of 4-5 at 12 months, was our primary outcome. We used logistic regression to compare prognostic factors between the groups. RESULTS: Ninety-five (85%) of 112 older patients and 317 (94%) of 336 younger patients received aneurysm treatment. Of the younger patients, 91% with a good-grade SAH (WFNS I-III) had a favorable outcome compared to 52% in the older good-grade SAH group. In poor-grade patients (WFNS IV-V), favorable outcome was seen in 51% of younger patients, compared to 24% of older patients. Acute hydrocephalus and intracerebral hemorrhage were associated with unfavorable outcome in the younger (OR 4.7, 95% CI 2.6-8.4, and OR 3.7, 95% CI 2.1-6.4), but not in the older patients (OR 1.8, 95% CI 0.8-4.2, and OR 1.3, 95% CI 0.5-3.1, respectively). CONCLUSIONS: In actively treated SAH patients, age was a major determinant of outcome. Factors reflecting increases in intracranial pressure associated with outcome only among younger patients.

Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage: Location, Distribution Patterns, Infarct Load, and Effect on Outcome.

BACKGROUND AND OBJECTIVES: Delayed cerebral ischemia (DCI) is one of the main contributing factors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Unsuccessful treatment can cause irreversible brain injury in the form of DCI-related infarction. We aimed to assess the association between the location, distribution, and size of DCI-related infarction in relation to clinical outcome. METHODS: Consecutive patients with SAH treated at 2 university hospitals between 2014 and 2019 (Helsinki, Finland) and between 2006 and 2020 (Aachen, Germany) were included. Size of DCI-related infarction was quantitatively measured as absolute volume (in milliliters). In a semiquantitative fashion, infarction in 14 regions of interest (ROIs) according to a modified Alberta Stroke Program Early CT Score (ASPECTS) was noted. The association of infarction in these ROIs along predefined regions of eloquent brain, with clinical outcome, was assessed. For this purpose, 1-year outcome was measured by the Glasgow Outcome Scale (GOS) and dichotomized into favorable (GOS 4-5) and unfavorable (GOS 1-3). RESULTS: Of 1,190 consecutive patients with SAH, 155 (13%) developed DCI-related infarction. One-year outcome data were available for 148 (96%) patients. A median overall infarct volume of 103 mL (interquartile range 31-237) was measured. DCI-related infarction was significantly associated with 1-year unfavorable outcome (odds ratio [OR] 4.89, 95% CI 3.36-7.34, p < 0.001). In patients with 1-year unfavorable outcome, vascular territories more frequently affected were left middle cerebral artery (affected in 49% of patients with unfavorable outcome vs in 30% of patients with favorable outcome; p = 0.029), as well as left (44% vs 18%; p = 0.003) and right (52% vs 14%; p < 0.001) anterior cerebral artery supply areas. According to the ASPECTS model, the right M3 (OR 8.52, 95% CI 1.41-51.34, p = 0.013) and right A2 (OR 7.84, 95% CI 1.97-31.15, p = 0.003) regions were independently associated with unfavorable outcome. DISCUSSION: DCI-related infarction was associated with a 5-fold increase in the odds of unfavorable outcome, after 1 year. Ischemic lesions in specific anatomical regions are more likely to contribute to unfavorable outcome. TRIAL REGISTRATION INFORMATION: Data collection in Aachen was registered in the German Clinical Trial Register (DRKS00030505); on January 3, 2023.

Midlife cardiovascular risk factors and late cognitive impairment.

Cardiovascular risk factors increase the risk of dementia in later life. The aims of the current study were to assess the effect of multiple midlife cardiovascular risk factors on the risk of cognitive impairment in later life, and to assess the validity of the previously suggested CAIDE Study risk score predicting dementia risk 20 years later. A total of 2,165 Finnish twins were followed and at the end of the follow-up their cognitive status was assessed with a validated telephone interview. The assessment of the risk factors at baseline was based on a self-report questionnaire. Relative risk ratios (RR) were calculated and receiver operating characteristic analyses performed. Midlife obesity (RR 2.42, 95 % CI 1.47-3.98), hypertension (RR 1.38, 95 % CI 1.01-1.88) and low leisure time physical activity (RR 2.52, 95 % CI 1.10-5.76) increased the risk of cognitive impairment after a mean follow-up of 22.6 ± 2.3 years. Hypercholesterolemia did not significantly increase the risk (RR 1.52, 95 % CI 0.92-2.51). Overweight individuals who gained more than 10 % weight between 1981 and 1990 had an increased risk of cognitive impairment (RR 4.27, 95 % CI 1.62-11.2). The CAIDE Study risk score combining various individual risk factors had an area-under-curve of 0.74 (95 % CI 0.69-0.79, n = 591), and there was a strong association between an increasing risk score and the risk of cognitive impairment. The results indicate that multiple midlife cardiovascular risk factors increase the risk of cognitive impairment in later life. Also, a risk score including easily measurable midlife factors predicts an individual's cognitive impairment risk well.

Aneurysmal Subarachnoid Hemorrhage in Hospitalized Patients on Anticoagulants-A Two Center Matched Case-Control Study.

Objective-Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods-Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results-During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4-5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1-3) after 12 months. Conclusions-Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients.

One-Year Outcome After Aneurysmal Subarachnoid Hemorrhage in Elderly Patients.

BACKGROUND: The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) admitted to intensive care units (ICUs) has increased. We aimed to analyze the characteristics and outcomes of such patients in a tertiary university hospital during a 5-year period. METHODS: A retrospective single-center analysis was performed of patients with aSAH ≥70 years old admitted to a tertiary neuro-ICU during January 2014-May 2019 based on medical records and computed tomography scans. The primary outcome was functional outcome at 12 months. We used multivariable logistic regression to assess factors associated with unfavorable outcome (Glasgow Outcome Scale score 1-3 and institutionalized). RESULTS: Of 117 included patients, 49% had a favorable outcome at 12 months, and mortality was 41%. In multivariable analysis, poor-grade aSAH and intraventricular hemorrhage were predictors of poor outcome (odds ratio, 4.7, 95% confidence interval, 1.7-12.5 and odds ratio, 2.8, 95% confidence interval, 1.1-7.2, respectively). None of the patients with a Glasgow Coma Scale (GCS) motor score of 1-3 three days after admission was alive at 12 months. In contrast, 65% of those with a GCS motor score 6 had favorable outcome. CONCLUSIONS: Half of elderly patients with aSAH admitted to a neuro-ICU were able to live at home after 12 months. Mortality was significant, but the number of severely disabled patients was low. Clinical status at admission was the strongest predictor of outcome, whereas intraventricular hemorrhage increased the risk of poor outcome as well. GCS motor score 3 days after admission seemed to predict mortality and outcome.

Cerebral glucose metabolism in dizygotic twin pairs discordant for Alzheimer's disease.

Positron emission tomography (PET) with 2-deoxy-2[(18)F]-fluoro-D-glucose (FDG) can be used to estimate regional cerebral glucose metabolism (rCMRgluc). FDG-PET studies have shown rCMRgluc to be reduced especially in temporal and parietal cortices in Alzheimer's disease (AD). A previous study on monozygotic twins discordant for AD showed that the rCMRgluc of the non-demented twins is reduced significantly in the lateral temporal and parietal cortices compared to unrelated controls. In this study we examined 9 pairs of dizygotic twins discordant for AD with FDG-PET. The rCMRgluc of the demented twins was 16% lower in the prefrontal cortex (p = 0.04), 20% lower in the hippocampus (p = 0.002) and 15% lower in the lateral temporal cortex (p = 0.003) compared to controls. The non-demented twins showed no such reductions on any cortical region compared to unrelated control subjects. This implies that both genes and environment, and not genes alone, are causative in the pathogenesis of AD.

Midlife sleep characteristics associated with late life cognitive function.

STUDY OBJECTIVES: Previous studies with limited follow-up times have suggested that sleep-related traits are associated with an increased risk of incident dementia or cognitive decline. We investigated the association between midlife sleep characteristics and late life cognitive function. DESIGN: A follow-up study with a median follow-up time of 22.5 (range 15.8-25.7) years assessing the association between midlife sleep characteristics and later cognitive function. SETTING: Questionnaire data from 1981 were used in the assessment of sleep characteristics, use of hypnotics, and covariates at baseline. Between 1999 and 2007, participants were assigned a linear cognitive score with a maximum score of 51 based on a telephone interview (mean score 38.3, SD 6.1). Linear regression analyses were controlled for age, sex, education, ApoE genotype, and follow-up time. PARTICIPANTS: 2,336 members of the Finnish Twin cohort who were at least 65 years of age. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Baseline short (< 7 h/day) and long (> 8 h/day) sleepers had lower cognitive scores than participants sleeping 7-8 h/ day (ß = -0.84, P = 0.014 and ß = -1.66, P < 0.001, respectively). As compared to good sleep quality, poor or rather poor sleep quality was associated with a lower cognitive score (ß = -1.00, P = 0.011). Also, the use of hypnotics ≥ 60 days per year was associated with poorer cognitive function (ß = -1.92, P = 0.002). CONCLUSIONS: This is the first study indicating that midlife sleep length, sleep quality, and use of hypnotics are associated with late life cognitive function. Further confirmation is needed, but sleep-related characteristics may emerge as new risk factors for cognitive impairment.