Nimodipine Dose Reductions in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The incidence of cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) is reduced by oral nimodipine but acute effects of the drug may include a significant decrease in mean arterial blood pressure (MAP). A dose reduction or discontinuation of the drug is recommended if recurrent MAP drops occur. The aim of our study was to evaluate the frequency and clinical significance of nimodipine dose modifications in patients suffering from aSAH. METHODS: 270 patients were included in our retrospective analysis of consecutively collected data of patients suffering from aSAH. The local treatment protocol was in accordance to national and international guidelines. Nimodipine was intended to be applied orally with a dosage of 60 mg every 4 h. RESULTS: Only 43.6 % of patients eligible for vasospasm prophylaxis with nimodipine received the full daily dose of 60 mg every 4 h. In 28.6 %, the dose had to be reduced by 50 % due to a significant reduction in blood pressure after administration and/or high dose of catecholamines. In 27.7 % of patients, oral administration of the drug was discontinued for the same reason. Dose reduction and discontinuation occurred with a significantly higher frequency in patients in poor clinical condition. Application of the full nimodipine dosage decreased the risk of unfavorable clinical outcome in multivariate analysis (OR 0.895, p = 0.029). CONCLUSIONS: Our results show that dose reduction or discontinuation of nimodipine due to changes in MAP occur frequently in clinical routine and may be associated with unfavorable clinical outcome.

Memorability of photographs in subjective cognitive decline and mild cognitive impairment: Implications for cognitive assessment.

INTRODUCTION: Impaired long-term memory is a defining feature of mild cognitive impairment (MCI). We tested whether this impairment is item specific, limited to some memoranda, whereas some remain consistently memorable. METHODS: We conducted item-based analyses of long-term visual recognition memory. Three hundred ninety-four participants (healthy controls, subjective cognitive decline [SCD], and MCI) in the multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs. RESULTS: We observed consistent memorability for images in healthy controls, SCD, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set. DISCUSSION: Individuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.

A novel score to predict shunt dependency after aneurysmal subarachnoid hemorrhage.

OBJECTIVE Feasible clinical scores for predicting shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The chronic hydrocephalus ensuing from SAH score (CHESS) was introduced in 2015 and has a high predictive value for SDHC. Although this score is easy to calculate, several early clinical and radiological factors are required. The authors designed the retrospective analysis described here for external CHESS validation and determination of predictive values for the radiographic Barrow Neurological Institute (BNI) scoring system and a new simplified combined scoring system. METHODS Consecutive data of 314 patients with aSAH were retrospectively analyzed with respect to CHESS parameters and BNI score. A new score, the shunt dependency in aSAH (SDASH) score, was calculated from independent risk factors identified with multivariate analysis. RESULTS Two hundred twenty-five patients survived the initial phase after the hemorrhage, and 27.1% of these patients developed SDHC. The SDASH score was developed from results of multivariate analysis, which revealed acute hydrocephalus (aHP), a BNI score of ≥ 3, and a Hunt and Hess (HH) grade of ≥ 4 to be independent risk factors for SDHC (ORs 5.709 [aHP], 6.804 [BNI], and 4.122 [HH]; p < 0.001). All 3 SDHC scores tested (CHESS, BNI, and SDASH) reliably predicted chronic hydrocephalus (ORs 1.533 [CHESS], 2.021 [BNI], and 2.496 [SDASH]; p ≤ 0.001). Areas under the receiver operating curve (AUROC) for CHESS and SDASH were comparable (0.769 vs 0.785, respectively; p = 0.447), but the CHESS and SDASH scores were superior to the BNI grading system for predicting SDHC (BNI AUROC 0.649; p = 0.014 and 0.001, respectively). In contrast to CHESS and BNI scores, an increase in the SDASH score coincided with a monotonous increase in the risk of developing SDHC. CONCLUSIONS The newly developed SDASH score is a reliable tool for predicting SDHC. It contains fewer factors and is more intuitive than existing scores that were shown to predict SDHC. A prospective score evaluation is needed.

Multicenter Resting State Functional Connectivity in Prodromal and Dementia Stages of Alzheimer's Disease.

BACKGROUND: Alterations of intrinsic networks from resting state fMRI (rs-fMRI) have been suggested as functional biomarkers of Alzheimer's disease (AD). OBJECTIVE: To determine the diagnostic accuracy of multicenter rs-fMRI for prodromal and preclinical stages of AD. METHODS: We determined rs-fMRI functional connectivity based on Pearson's correlation coefficients and amplitude of low-frequency fluctuation in people with subjective cognitive decline, people with mild cognitive impairment, and people with AD dementia compared with healthy controls. We used data of 247 participants of the prospective DELCODE study, a longitudinal multicenter observational study, imposing a unified fMRI acquisition protocol across sites. We determined cross-validated discrimination accuracy based on penalized logistic regression to account for multicollinearity of predictors. RESULTS: Resting state functional connectivity reached significant cross-validated group discrimination only for the comparison of AD dementia cases with healthy controls, but not for the other diagnostic groups. AD dementia cases showed alterations in a large range of intrinsic resting state networks, including the default mode and salience networks, but also executive and language networks. When groups were stratified according to their CSF amyloid status that was available in a subset of cases, diagnostic accuracy was increased for amyloid positive mild cognitive impairment cases compared with amyloid negative controls, but still inferior to the accuracy of hippocampus volume. CONCLUSION: Even when following a strictly harmonized data acquisition protocol and rigorous scan quality control, widely used connectivity measures of multicenter rs-fMRI do not reach levels of diagnostic accuracy sufficient for a useful biomarker in prodromal stages of AD.

CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume.

INTRODUCTION: We examined the association between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, neural novelty responses, and brain volume in predementia old age. METHODS: We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Seventy-six participants completed task functional magnetic resonance imaging and provided CSF (40 cognitively unimpaired, 21 experiencing subjective cognitive decline, and 15 with mild cognitive impairment). We assessed the correlation between CSF biomarkers and whole-brain functional magnetic resonance imaging novelty responses to scene images. RESULTS: Total tau levels were specifically and negatively associated with novelty responses in the right amygdala and right hippocampus. Mediation analyses showed no evidence that these associations were dependent on the volume of hippocampus/amygdala. No relationship was found between phosphorylated-tau or Aß42 levels and novelty responses. DISCUSSION: Our data show that CSF levels of total tau are associated with anatomically specific reductions in novelty processing, which cannot be fully explained by atrophy.

The Barrow Neurological Institute Scale Revisited: Predictive Capabilities for Cerebral Infarction and Clinical Outcome in Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: In 2012, a new computed tomography (CT) grading scale was introduced by the Barrow Neurological Institute group ("BNI scale") to predict angiographic and symptomatic vasospasm in aneurysmal subarachnoid hemorrhage. OBJECTIVE: To address the question of whether BNI grading is reliable in the prediction of cerebral infarction and clinical outcome and to compare BNI scores to existing radiographic and clinical models of outcome prediction. METHODS: Consecutive data of 260 patients with aneurysmal subarachnoid hemorrhage was retrospectively analyzed with respect to radiographic and clinical parameters. RESULTS: Patients presenting with more severe BNI grades were older ( P = .002), displayed lower Glasgow Coma Scale scores at admission ( P < .001) and were more often diagnosed with intraventricular hemorrhage ( P < .001). An increasing BNI grade was associated with higher rates of severe angiographic vasospasm ( P = .007), the occurrence of new cerebral infarction ( P < .001), and poor patient outcome ( P < .001). In contrast, analysis according to the Fisher grading system did not show a significant relationship to any outcome parameter. Multivariate analysis combining radiographic and clinical parameters showed significant results for clinical scores (Hunt and Hess and World Federation of Neurosurgical Societies) with radiographic information losing its predictive capability. CONCLUSION: The BNI scale is easily applicable and superior to the original Fisher scale regarding prediction of angiographic vasospasm, new cerebral infarction, and patient outcome. Presence of intraventricular hemorrhage and intracerebral hemorrhage are additional radiographic factors with outcome relevance that are not part of the BNI scale. Established clinical scores like World Federation of Neurosurgical Societies and Hunt and Hess grading were more relevant for outcome prediction than any radiographic information.