Stroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have ...demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH).
This observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008-2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Patients' radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures.
Overall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median IQR NLR 5.8 3.0-10.0 for mRS score 0-2 vs NLR 8.3 4.5-12.6 for mRS score 3-6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR 95% CI 1.014 1.001-1.027; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden's index = 0.211; mRS score 3-6: 94/153 61.4% for NLR ≥ 7.05 vs 67/166 40.4% for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score-matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3-6 at 3 months: NLR ≥ 7.05 82/133 61.7% vs NLR < 7.05 62/133 46.6%; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 27.8% vs NLR < 7.05 27/133 20.3%; p = 0.131).
Among aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.
OBJECTIVETo evaluate the association of perihemorrhagic edema (PHE) evolution and peak edema extent with day 90 functional outcome in patients with intracerebral hemorrhage (ICH) and identify ...pathophysiologic factors influencing edema evolution.
METHODSThis retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. ICH and PHE volumes were studied using a validated semiautomatic volumetric algorithm. Multivariable logistic regression and propensity score matching (PSM) accounting for age, ICH volume, and location were used for assessing measures associated with functional outcome and PHE evolution. Clinical outcome on day 90 was assessed using the modified Rankin Scale (0–3 = favorable, 4–6 = poor).
RESULTSA total of 292 patients were included. Median age was 70 years (interquartile range IQR 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2). Besides established factors for functional outcome, i.e., ICH volume and location, age, intraventricular hemorrhage, and NIH Stroke Scale score on admission, multivariable logistic regression revealed peak PHE volume (odds ratio OR 0.984 95% confidence interval (CI) 0.973–0.994) as an independent predictor of day 90 outcome. Peak PHE volume was independently associated with initial PHE increase up to day 3 (OR 1.060 95% CI 1.018–1.103) and neutrophil to lymphocyte ratio on day 6 (OR 1.236 95% CI 1.034–1.477; PSM cohort, n = 124). Initial PHE increase (PSM cohort, n = 224) was independently related to hematoma expansion (OR 3.647 95% CI 1.533–8.679) and fever burden on days 2–3 (OR 1.456 95% CI 1.103–1.920).
CONCLUSIONOur findings suggest that peak PHE volume represents an independent predictor of functional outcome after ICH. Inflammatory processes and hematoma expansion seem to be involved in PHE evolution and may represent important treatment targets.
BACKGROUND AND PURPOSE—Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital ...stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH.
METHODS—This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na <135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality.
RESULTS—The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients <48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05–4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1–10.6; P<0.001); thereafter, mortality rates were similar.
CONCLUSIONS—Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.
Stroke-associated immunosuppression and inflammation are increasingly recognized as factors that trigger infections and thus, potentially influence the outcome after stroke. Several studies ...demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes in patients with ischemic stroke. However, little is known about the impact of NLR on short-term mortality in intracerebral hemorrhage (ICH).
This observational study included 855 consecutive ICH-patients. Patient demographics, clinical, laboratory, and in-hospital measures as well as neuroradiological data were retrieved from institutional databases. Functional 3-months-outcome was assessed and categorized as favorable (modified Rankin Scale mRS 0-3) and unfavorable (mRS 4-6). We (i) studied the natural course of NLR in ICH, (ii) analyzed parameters associated with NLR on admission (NLROA), and (iii) evaluated the clinical impact of NLR on mortality and functional outcome.
The median NLROA of the entire cohort was 4.66 and it remained stable during the entire hospital stay. Patients with NLR ≥4.66 showed significant associations with poorer neurological status (National Institute of Health Stroke Scale NIHSS 18 9-32 vs. 10 4-21; p < 0.001), larger hematoma volume on admission (17.6 6.9-47.7 vs. 10.6 3.8-31.7 mL; p = 0.001), and more frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 74.2% vs. 275/428 64.3%; p = 0.002). Patients with an NLR under the 25th percentile (NLR <2.606) - compared to patients with NLR >2.606 - presented with a better clinical status (NIHSS 12 5-21 vs. 15 6-28; p = 0.005), lower hematoma volumes on admission (10.6 3.6-30.1 vs. 15.1 5.7-42.3 mL; p = 0.004) and showed a better functional outcome (3 months mRS 0-3: 82/214 38.3% vs. 185/641 28.9%; p = 0.009). Patients associated with high NLR (≥8.508 = above 75th-percentile) showed the worst neurological status on admission (NIHSS 21 12-32 vs. 12 5-23; p < 0.001), larger hematoma volumes (21.0 8.6-48.8 vs. 12.2 4.1-34.9 mL; p < 0.001), and higher proportions of unfavorable functional outcome at 3 months (mRS 4-6: 173/214 vs. 418/641; p < 0.001). Further, NLR was linked to more frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; p = 0.001, sepsis: 78/214 vs. 116/641; p < 0.001), and increased c-reactive-protein levels on admission (p < 0.001; R2 = 0.064). Adjusting for the above-mentioned baseline confounders, multivariable logistic analyses revealed independent associations of NLROA with in-hospital mortality (OR 0.967, 95% CI 0.939-0.997; p = 0.029).
NLR represents an independent parameter associated with increased mortality in ICH patients. Stroke physicians should focus intensely on patients with increased NLR, as these patients appear to represent a population at risk for infectious complications and increased short-mortality. Whether these patients with elevated NLR may benefit from a close monitoring and specially designed therapies should be investigated in future studies.
BACKGROUND AND PURPOSE—This study determined the influence of concomitant antiplatelet therapy (APT) on hematoma characteristics and outcome in primary spontaneous intracerebral hemorrhage (ICH), ...vitamin K antagonist (VKA)- and non–VKA oral anticoagulant-associated ICH.
METHODS—Data of retrospective cohort studies and a prospective single-center study were pooled. Functional outcome, mortality, and radiological characteristics were defined as primary and secondary outcomes. Propensity score matching and logistic regression analyses were performed to determine the association between single or dual APT and hematoma volume.
RESULTS—A total of 3580 patients with ICH were screened, of whom 3545 with information on APT were analyzed. Three hundred forty-six (32.4%) patients in primary spontaneous ICH, 260 (11.4%) in VKA-ICH, and 30 (16.0%) in non–VKA oral anticoagulant-associated ICH were on APT, and these patients had more severe comorbidities. After propensity score matching VKA-ICH patients on APT presented with less favorable functional outcome (modified Rankin Scale score, 0–3; APT, 48/202 23.8% versus no APT, 187/587 31.9%; P=0.030) and higher mortality (APT, 103/202 51.0% versus no APT, 237/587 40.4%; P=0.009), whereas no significant differences were present in primary spontaneous ICH and non–VKA oral anticoagulant-associated ICH. In VKA-ICH, hematoma volume was significantly larger in patients with APT (21.9 7.4–61.4 versus 15.7 5.7–44.5 mL; P=0.005). Multivariable regression analysis revealed an association of APT and larger ICH volumes (odds ratio, 1.80 1.20–2.70; P=0.005), which was more pronounced in dual APT and supratherapeutically anticoagulated patients.
CONCLUSIONS—APT does not affect ICH characteristics and outcome in primary spontaneous ICH patients; however, it is associated with larger ICH volume and worse functional outcome in VKA-ICH, presumably by additive antihemostatic effects. Combination of anticoagulation and APT should, therefore, be diligently evaluated and restricted to the shortest possible time frame.
Objective
Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to ...determine whether the max‐ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long‐term outcomes after ICH.
Methods
This multicenter validation study compared the prognostication of the max‐ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German‐wide studies (RETRACE I + II; anticoagulation‐associated ICH only) conducted at 22 participating centers, one German prospective single‐center study (UKER‐ICH; nonanticoagulation‐associated ICH only), and 1 US‐based prospective longitudinal single‐center study (MGH; both anticoagulation‐ and nonanticoagulation‐associated ICH), treated between January 2006 and December 2015.
Results
Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% 440 of 2,377; MGH: 31.0% 577 of 1,283). Validation of long‐term functional outcome prognostication by the max‐ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve AUROC, German cohort: 0.81 0.78–0.83 vs 0.74 0.72–0.77, p < 0.01; MGH: 0.85 0.81–0.89 vs 0.78 0.74–0.82, p < 0.01), and for the entire cohort (AUROC, German cohort: 0.84 0.82–0.86 vs 0.80 0.77–0.82, p < 0.01; MGH: 0.83 0.81–0.85 vs 0.77 0.75–0.79, p < 0.01). Both scores showed no evidence of poor calibration. The clinical utility investigated by decision curve analysis showed, at high threshold probabilities (0.8, aiming to avoid false‐positive poor outcome attribution), that the max‐ICH Score provided a clinical net benefit compared with the ICH Score (14.1 vs 2.1 net predicted poor outcomes per 100 patients).
Interpretation
The max‐ICH Score provides valid and improved prognostication of functional outcome after ICH. The associated clinical net benefit in minimizing false poor outcome attribution might potentially prevent unwarranted care limitations in patients with ICH. ANN NEUROL 2021;89:474–484
This observational study was performed to show the impact of complications and interventions during neurocritical care on the outcome after aneurysmal subarachnoid hemorrhage (SAH).
We analyzed 203 ...cases treated for ruptured intracranial aneurysms, which were classified regarding clinical outcome after one year according to the modified Rankin Scale (mRS). We reviewed the data with reference to the occurrence of typical complications and interventions in neurocritical care units.
Decompressive craniectomy (odds ratio 21.77 / 6.17 ; p < 0.0001 / p = 0.013), sepsis (odds ratio 14.67 / 6.08 ; p = 0.037 / 0.033) and hydrocephalus (odds ratio 3.71 / 6.46 ; p = 0.010 / 0.00095) were significant predictors for poor outcome and death after one year beside "World Federation of Neurosurgical Societies" (WFNS) grade (odds ratio 3.86 / 4.67 ; p < 0.0001 / p < 0.0001) and age (odds ratio 1.06 / 1.10 ; p = 0.0030 / p < 0.0001) in our multivariate analysis (binary logistic regression model).
In summary, decompressive craniectomy, sepsis and hydrocephalus significantly influence the outcome and occurrence of death after aneurysmal SAH.
Using flat-detector CT (FD-CT) for stroke imaging has the advantage that both diagnostic imaging and endovascular therapy can be performed directly within the Angio Suite without any patient transfer ...and time delay. Thus, stroke management could be speeded up significantly, and patient outcome might be improved. But as precondition for using FD-CT as primary imaging modality, a reliable exclusion of intracranial hemorrhage (ICH) has to be possible. This study aimed to investigate whether optimized native FD-CT, using a newly implemented reconstruction algorithm, may reliably detect ICH in stroke patients. Additionally, the potential to identify ischemic changes was evaluated.
Cranial FD-CT scans were obtained in 102 patients presenting with acute ischemic stroke (n = 32), ICH (n = 45) or transient ischemic attack (n = 25). All scans were reconstructed with a newly implemented half-scan cone-beam algorithm. Two experienced neuroradiologists, unaware of clinical findings, evaluated independently the FD-CTs screening for hemorrhage or ischemic signs. The findings were correlated to CT, and rater and inter-rater agreement was assessed.
FD-CT demonstrated high sensitivity (95-100%) and specificity (100%) in detecting intracerebral and intraventricular hemorrhage (IVH). Overall, interobserver agreement (κ = 0.92) was almost perfect and rater agreement to CT highly significant (r = 0.81). One infratentorial ICH and 10 or 11 of 22 subarachnoid hemorrhages (SAHs) were missed of whom 7 were perimesencephalic. The sensitivity for detecting acute ischemic signs was poor in blinded readings (0 or 25%, respectively).
Optimized FD-CT, using a newly implemented reconstruction algorithm, turned out as a reliable tool for detecting supratentorial ICH and IVH. However, detection of infratentorial ICH and perimesencephalic SAH is limited. The potential of FD-CT in detecting ischemic changes is poor in blinded readings. Thus, plain FD-CT seems insufficient as a standalone modality in acute stroke, but within a multimodal imaging approach primarily using the FD technology, native FD-CT seems capable to exclude reliably supratentorial hemorrhage. Currently, FD-CT imaging seems not yet ready for wide adoption, replacing regular CT, and should be reserved for selected patients. Furthermore, prospective evaluations are necessary to validate this approach in the clinical setting.
Purpose
The three-dimensional digital subtraction angiography (3D DSA) technique is the current standard and is based on both mask and fill runs to enable the subtraction technique. Artificial ...intelligence (AI)-based 3D angiography (3DA) was developed to reduce radiation dosage because only one contrast-enhanced run of the C‑arm system is required for reconstruction of DSA-like 3D volumes. The aim was the evaluation of this algorithm regarding its diagnostic information.
Methods
3D DSA datasets without pathologic findings were reconstructed both with subtraction technique and with the AI-based algorithm. Corresponding reconstructions were evaluated by 2 neuroradiologists with respect to image quality (IQ), visualization of major segments of the circle of Willis (ICA = C4-C7; OphA; ACA = A1-A2, MCA = M1-M2; VA = V4; BA; AICA; SUCA; PCA = P1-P2), identifiability of perforators (lenticulostriate/thalamoperforating arteries) and vessel diameters (ICA = C4; MCA = M1; BA; PCA = P1).
Results
In total 15 datasets were successfully reconstructed as 3D DSA and 3DA with diagnostic image quality. All major segments of the circle of Willis and perforators were comparably visualized with 3DA. Quantitative analysis of vessel diameters in 3D DSA and 3DA datasets was equivalent and did not show relevant differences (
r
ICA
= 0.901,
p
= 0.001;
r
M1
= 0.951,
p
= 0.001;
r
BA
= 0.906,
p
= 0.001;
r
P1
= 0.991,
p
= 0.001).
Conclusions
The use of 3DA demonstrated reliable visualization of cerebral vasculature with respect to quantitative and qualitative parameters. Therefore, 3DA is a promising method that might help to reduce patient radiation.
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