Maximilian I. Sprügel

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

Background and Purpose: 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). Methods: 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. Results: 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). Conclusions: 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.

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves

Aims Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time‐window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results We pooled individual patient‐data (n = 2504) from a nationwide multicentre cohort‐study (RETRACE, conducted at 22 German centres) and eventually identified MHV‐patients (n = 137) with anticoagulation‐associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no‐TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity‐score matching and multivariable cox‐regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no‐TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no‐TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate‐ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67‐35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA‐timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33‐21.37; P < 0.01). The hazard for the composite—balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10‐5.70; P = 0.03). Conclusion Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing—between least risks for thromboembolic and haemorrhagic complications—provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk. Figure. No Caption available.

Association of prothrombin complex concentrate administration and hematoma enlargement in non–vitamin K antagonist oral anticoagulant–related intracerebral hemorrhage

To investigate parameters associated with hematoma enlargement in non–vitamin K antagonist oral anticoagulant (NOAC)‐related intracerebral hemorrhage (ICH).

Factors associated with occurrence and outcome of super-refractory status epilepticus

PURPOSE Super-refractory status epilepticus (SRSE) represents a challenging medical condition with high morbidity and mortality. In this study, we aimed to establish variables related to SRSE development and outcome. METHODS We retrospectively screened our databases for refractory SE (RSE) and SRSE episodes between January 2001 and January 2015. Baseline demographics, SE characteristics, and variables reflecting the clinical course were compared in order to identify factors independently associated with SRSE occurrence. Within the SRSE cohort, predictors of in-hospital mortality as well as good functional outcome in survivors to discharge were established through univariate and multivariable analyses. RESULTS A total of 131 episodes were included, among those 46 (35.1%) meeting the criteria of SRSE. Comparison of RSE and SRSE episodes revealed a lower premorbid mRS score (odds ratio (OR) per mRS point, 0.769; p=0.039) and non-convulsive SE (NCSE) in coma (OR, 4.216; p=0.008) as independent predictors of SRSE. SRSE in-hospital mortality was associated with age (OR, 1.091 per increasing year; p=0.020) and worse premorbid functional status (OR, 1.938 per mRS point; p=0.044). Good functional outcome in survivors was independently related to shorter SRSE duration (OR, 0.714 per day; p=0.038). CONCLUSION Better premorbid functional status and NCSE in coma as worst seizure type indicate a role of acute underlying etiologies in the development of SRSE. In-hospital mortality in SRSE is determined by nonmodifiable factors, while functional outcome in survivors depends on seizure duration underscoring the need of achieving rapid seizure termination.

Influence of Prior Nicotine and Alcohol Use on Functional Outcome in Patients after Intracerebral Hemorrhage

BACKGROUND The influence of prior nicotine or alcohol use (legal drug use [LDU]) on outcome measures after intracerebral hemorrhage (ICH) is insufficiently established. We investigated drug-specific associations with (1) neuroradiologic and clinical parameters and (2) functional long-term outcome after ICH. METHODS This observational cohort study analyzed consecutive spontaneous patients with ICH (n = 554) from our prospective institutional registry over a 5-year study period (January 2010 to December 2014). We compared no-LDU patients with LDU patients, and patients using only nicotine, only alcohol, or both. To account for baseline imbalances, we reanalyzed cohorts after propensity score matching. RESULTS Prevalence of prior LDU was 197 of 554 (35.6%), comprising 94 of 554 (17.0%) with only nicotine use, 33 of 554 (6.0%) with only alcohol use, and 70 of 554 (12.6%) with alcohol and nicotine use. LDU patients were younger (65 [56-73] versus 75 [67-82], P <.01), less often female (n = 61 of 197 [31.0%] versus n = 188 of 357 [52.7%], P <.01), had more often prior myocardial infarction (n = 29 of 197 [14.7%] versus n = 24 of 357 [6.7%], P <.01), and in-hospital complications (sepsis or systemic inflammatory response syndrome: n = 95 of 197 [48.2%] versus n = 98 of 357 [27.5%], P <.01; pneumonia: n = 89 of 197 [45.2%] versus n = 110 of 357 [30.8%], P <.01). Except for an increased risk of pneumonia (odds ratio 2.22, confidence interval [1.04-4.75], P = .04) in patients using both nicotine and alcohol, we detected no significant differences upon reanalysis after propensity score matching of neuroradiologic or clinical parameters, complications, or long-term outcome between patients with and without LDU (mortality: n = 48 of 150 [32.0%] versus n = 45 of 150 [30.0%], P = .71; favorable outcome [modified Rankin Scale 0-3]: n = 56 of 150 [37.3%] versus n = 53 of 150 [35.3%], P = .72). CONCLUSIONS Prior nicotine use, alcohol use, and their combination were associated with significant differences in baseline characteristics. However, adjusting for unevenly balanced baseline parameters revealed no differences in functional long-term outcome after ICH.

Initiating anticoagulant therapy after ICH is associated with patient characteristics and treatment recommendations

BackgroundThe proportion of patients with intracerebral hemorrhage (ICH) and concomitant indication for oral anticoagulant (OAC) therapy is increasing. Although recent studies documented a favorable risk–benefit profile of OAC initiation, deciding whether, when, and which OAC should be started remains controversial. We investigated (1) OAC recommendations, its implementation, and adherence and (2) factors associated with OAC initiation after ICH.MethodsThis prospective observational study analyzed consecutive ICH patients (n = 246) treated at the neurological and neurosurgical department of the University-Hospital Erlangen, Germany over a 21-month inclusion period (05/2013–01/2015). We analyzed the influence of patient characteristics, in-hospital measures, and functional status on treatment recommendations and on OAC initiation during 12-month follow-up.ResultsIn-hospital mortality of 24.8% (n = 61/246) left 185 patients discharged alive of which 34.1% (n = 63/185) had OAC indication. In these patients, OAC initiation was clearly recommended in only 49.2% (n = 31/63) and associated with favorable [modified Rankin Scale (mRS) = 0–3] functional discharge status [OR 7.18, CI (1.05–49.13), p = 0.04], less frequent heart failure [OR 0.19, CI (0.05–0.71), p = 0.01], and younger age [OR 0.95, CI (0.90–1.00), p = 0.05]. OAC was more often started if clearly recommended [n = 19/31 (61.3%) versus (no recommendation) n = 4/26 (15.4%), p < 0.001; (clearly not recommended, n = 6)] and associated with younger age [67 (58–74) versus 79 (73–83), p < 0.001], favorable functional outcome [n = 10/23 (43.5%) versus n = 5/40 (12.5%), p = 0.01], decreased mortality [n = 6/23 (26.1%) versus n = 19/40 (47.5%), p = 0.06], and functional improvement [n = 13/17 (76.5%) versus n = 7/21 (33.3%), p = 0.01]. We observed no differences in rates of intracranial complications [thromboembolism, n = 3/23 (13.0%) versus n = 4/40 (10.0%), p = 1.00; hemorrhage, n = 1/23 (4.3%) versus n = 3/40 (7.5%), p = 1.00].ConclusionsClear treatment recommendations by attending stroke physicians significantly influence OAC initiation after ICH. OAC were more frequently recommended and started in younger patients with better functional recovery independent from intracranial complications. This might represent an important determinant of observed beneficial associations, hinting towards an indication bias which might affect observational analyses.

Peak Troponin I Levels Are Associated with Functional Outcome in Intracerebral Hemorrhage

Background: Troponin I is a widely used and reliable marker of myocardial damage and its levels are routinely measured in acute stroke care. So far, the influence of troponin I elevations during hospital stay on functional outcome in patients with atraumatic intracerebral hemorrhage (ICH) is unknown. Methods: Observational single-center study including conservatively treated ICH patients over a 9-year period. Patients were categorized according to peak troponin I level during hospital stay (≤0.040, 0.041–0.500, > 0.500 ng/mL) and compared regarding baseline and hematoma characteristics. Multivariable analyses were performed to investigate independent associations of troponin levels during hospital stay with functional outcome – assessed using the modified Rankin Scale (mRS; favorable 0–3/unfavorable 4–6) – and mortality after 3 and 12 months. To account for possible confounding propensity score (PS)-matching (1: 1; caliper 0.1) was performed accounting for imbalances in baseline characteristics to investigate the impact of troponin I values on outcome. Results: Troponin elevations (> 0.040 ng/mL) during hospital stay were observed in 308 out of 745 (41.3%) patients and associated with poorer status on admission (Glasgow Coma Scale/National Institute of Health Stroke Scale). Multivariable analysis revealed troponin I levels during hospital stay to be independently associated with unfavorable outcome after 12 months (risk ratio [95% CI]: 1.030 [1.009–1.051] per increment of 1.0 ng/mL; p = 0.005), but not with mortality. After PS-matching, patients with troponin I elevation (≥0.040 ng/mL) versus those without had a significant higher rate of unfavorable outcome after 3 and 12 months (mRS 4–6 at 3 months: < 0.04 ng/mL: 159/265 [60.0%] versus ≥0.04 ng/mL: 199/266 [74.8%]; p < 0.001; at 12 months: < 0.04 ng/mL: 141/248 [56.9%] versus ≥0.04 ng/mL: 179/251 [71.3%]; p = 0.001). Conclusions: Troponin I elevations during hospital stay occur frequently in ICH patients and are independently associated with functional outcome after 3 and 12 months but not with mortality.

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

Background: Data on clinical characteristics and outcome of patients with intracerebral hemorrhage (ICH) and concomitant systemic cancer disease are very limited. Methods: 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. Results: 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; p = 0.002), had more often prior renal dysfunction (19/83 [22.9%] vs.107/890 [12.0%]; p = 0.005), and smaller hemorrhage volumes (10.1 [4.8-24.3] vs. 15.3 [5.4-42.9] mL; p = 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%]; p = 0.368; mRS = 0-3: 28/81 [34.6%] vs. 52/158 [32.9%]; p = 0.797) and 12 months (mortality: 39/78 [50.0%] vs. 70/150 [46.7%]; p = 0.633; mRS = 0-3: 25/78 [32.1%] vs. 53/150 [35.3%]; p = 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. Conclusions: 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.