Intensive care therapy of space-occupying large hemispheric infarction

Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference

Supplementary Material for: Functional Long-Term Outcome after Left- versus Right-Sided Intracerebral Hemorrhage

<p><b><i>Background and Purpose:</i></b> Hemispheric location might influence outcome after intracerebral hemorrhage (ICH). INTERACT suggested higher short-term mortality in right hemispheric ICH, yet statistical imbalances were not addressed. This study aimed at determining the differences in long-term functional outcome in patients with right- vs. left-sided ICH with a priori-defined sub-analysis of lobar vs. deep bleedings. <b><i>Methods:</i></b> Data from a prospective hospital registry were analyzed including patients with ICH admitted between January 2006 and August 2014. Data were retrieved from institutional databases. Outcome was assessed using the modified Rankin Scale (mRS) score. Outcome measures (long-term mortality and functional outcome at 12 months) were correlated with ICH location and hemisphere, and the imbalances of baseline characteristics were addressed by propensity score matching. <b><i>Results:</i></b> A total of 831 patients with supratentorial ICH (429 left and 402 right) were analyzed. Regarding clinical baseline characteristics in the unadjusted overall cohort, there were differences in disfavor of right-sided ICH (antiplatelets: 25.2% in left ICH vs. 34.3% in right ICH; <i>p</i> < 0.01; previous ischemic stroke: 14.7% in left ICH vs. 19.7% in right ICH; <i>p</i> = 0.057; and presence/extent of intraventricular hemorrhage: 45.0% in left ICH vs. 53.0% in right ICH; <i>p</i> = 0.021; Graeb-score: 0 [0-4] in left ICH vs. 1 [0-5] in right ICH; <i>p</i> = 0.017). While there were no differences in mortality and in the proportion of patients with favorable vs. unfavorable outcome (mRS 0-3: 142/375 [37.9%] in left ICH vs. 117/362 [32.3%] in right ICH; <i>p</i> = 0.115), patients with left-sided ICH showed excellent outcome more frequently (mRS 0-1: 64/375 [17.1%] in left ICH vs. 43/362 [11.9%] in right ICH; <i>p</i> = 0.046) in the unadjusted analysis. After adjusting for confounding variables, a well-balanced group of patients (<i>n</i> = 360/hemisphere) was compared showing no differences in long-term functional outcome (mRS 0-3: 36.4% in left ICH vs. 33.9% in right ICH; <i>p</i> = 0.51). Sub-analyses of patients with deep vs. lobar ICH revealed also no differences in outcome measures (mRS 0-3: 53/151 [35.1%] in left deep ICH vs. 53/165 [32.1%] in right deep ICH; <i>p</i> = 0.58). <b><i>Conclusion:</i></b> Previously described differences in clinical end points among patients with left- vs. right-hemispheric ICH may be driven by different baseline characteristics rather than by functional deficits emerging from different hemispheric functions affected. After statistical corrections for confounding variables, there was no impact of hemispheric location on functional outcome after ICH.</p

Supplementary Material for: Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor for In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage

<p><b><i>Background and Purpose:</i></b> 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). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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]; <i>p</i> < 0.001), larger hematoma volume on admission (17.6 [6.9-47.7] vs. 10.6 [3.8-31.7] mL; <i>p</i> = 0.001), and more frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 [74.2%] vs. 275/428 [64.3%]; <i>p</i> = 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]; <i>p</i> = 0.005), lower hematoma volumes on admission (10.6 [3.6-30.1] vs. 15.1 [5.7-42.3] mL; <i>p</i> = 0.004) and showed a better functional outcome (3 months mRS 0-3: 82/214 [38.3%] vs. 185/641 [28.9%]; <i>p</i> = 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]; <i>p</i> < 0.001), larger hematoma volumes (21.0 [8.6-48.8] vs. 12.2 [4.1-34.9] mL; <i>p</i> < 0.001), and higher proportions of unfavorable functional outcome at 3 months (mRS 4-6: 173/214 vs. 418/641; <i>p</i> < 0.001). Further, NLR was linked to more frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; <i>p</i> = 0.001, sepsis: 78/214 vs. 116/641; <i>p</i> < 0.001), and increased c-reactive-protein levels on admission (<i>p</i> < 0.001; <i>R</i>² = 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; <i>p</i> = 0.029). <b><i>Conclusions:</i></b> 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.</p

Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.

Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells

Supplementary Material for: Presence of Concomitant Systemic Cancer is Not Associated with Worse Functional Long-Term Outcome in Patients with Intracerebral Hemorrhage

<p><b><i>Background:</i></b> Data on clinical characteristics and outcome of patients with intracerebral hemorrhage (ICH) and concomitant systemic cancer disease are very limited. <b><i>Methods:</i></b> Nine hundred and seventy three consecutive primary ICH patients were analyzed using our prospective institutional registry over a period of 9 years (2006-2014). We compared clinical and radiological parameters as well as outcome - scored using the modified Rankin Scale (mRS) and analyzed in a dichotomized fashion as favorable outcome (mRS = 0-3) and unfavorable outcome (mRS = 4-6) - of ICH patients with and without cancer. Relevant imbalances in baseline clinical and radiological characteristics were adjusted using propensity score (PS) matching. <b><i>Results:</i></b> Prevalence of systemic cancer among patients with ICH was 8.5% (83/973). ICH patients with cancer were older (77 [70-82] vs. 72 [63-80] years; <i>p</i> = 0.002), had more often prior renal dysfunction (19/83 [22.9%] vs.107/890 [12.0%]; <i>p</i> = 0.005), and smaller hemorrhage volumes (10.1 [4.8-24.3] vs. 15.3 [5.4-42.9] mL; <i>p</i> = 0.017). After PS-matching there were no significant differences neither in mortality nor in functional outcome both at 3 months (mortality: 33/81 [40.7%] vs. 55/158 [34.8%]; <i>p</i> = 0.368; mRS = 0-3: 28/81 [34.6%] vs. 52/158 [32.9%]; <i>p</i> = 0.797) and 12 months (mortality: 39/78 [50.0%] vs. 70/150 [46.7%]; <i>p</i> = 0.633; mRS = 0-3: 25/78 [32.1%] vs. 53/150 [35.3%]; <i>p</i> = 0.620) among patients with and without concomitant systemic cancer. ICH volume tended to be highest in patients with hematooncologic malignancy and smallest in urothelial cancer. <b><i>Conclusions:</i></b> Patients with ICH and concomitant systemic cancer on average are older; however, they show smaller ICH volumes compared to patients without cancer. Yet, mortality and functional outcome is not different in ICH patients with and without cancer. Thus, the clinical history or the de novo diagnosis of concomitant malignancies in ICH patients should not lead to unjustified treatment restrictions.</p