[Vertigo from a neurological point of view]. / Schwindel aus neurologischer Sicht.

Vertigo has many different causal disorders, ranging from general dizziness and orthostatic regulation disorders to attacks of rotary vertigo. A targeted anamnesis and clinical examination can be used to narrow down the differential diagnosis. Questions about the type of dizziness, the duration and accompanying symptoms must be clarified. Various methods are used for differentiation in clinical examinations: the head impulse test, testing of the vertical divergence of the eyes, positioning maneuvers and the ability to stand and walk. But diagnostic imaging is also important. MRI can be used to confirm or rule out vascular causes (cerebral infarction or minor bleeding) and inflammatory lesions. Because the most serious misdiagnosis of dizziness is overlooking a stroke.

Spatial and temporal variation of routine parameters: pitfalls in the cerebrospinal fluid analysis in central nervous system infections.

The cerebrospinal fluid (CSF) space is convoluted. CSF flow oscillates with a net flow from the ventricles towards the cerebral and spinal subarachnoid space. This flow is influenced by heartbeats, breath, head or body movements as well as the activity of the ciliated epithelium of the plexus and ventricular ependyma. The shape of the CSF space and the CSF flow preclude rapid equilibration of cells, proteins and smaller compounds between the different parts of the compartment. In this review including reinterpretation of previously published data we illustrate, how anatomical and (patho)physiological conditions can influence routine CSF analysis. Equilibration of the components of the CSF depends on the size of the molecule or particle, e.g., lactate is distributed in the CSF more homogeneously than proteins or cells. The concentrations of blood-derived compounds usually increase from the ventricles to the lumbar CSF space, whereas the concentrations of brain-derived compounds usually decrease. Under special conditions, in particular when distribution is impaired, the rostro-caudal gradient of blood-derived compounds can be reversed. In the last century, several researchers attempted to define typical CSF findings for the diagnosis of several inflammatory diseases based on routine parameters. Because of the high spatial and temporal variations, findings considered typical of certain CNS diseases often are absent in parts of or even in the entire CSF compartment. In CNS infections, identification of the pathogen by culture, antigen detection or molecular methods is essential for diagnosis.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Sensory trick effect in craniofacial dystonia as one of the possible impacts of wearing face masks during the COVID-19 pandemic.

BACKGROUND: The report of a patient with blepharospasm during the COVID-19 pandemic suggested a potential ameliorating effect of wearing a face mask. OBJECTIVE: We prospectively evaluated a possible symptom change through wearing a face mask in all consecutive patients with craniofacial hyperkinesias in our botulinum toxin outpatient treatment cohort. METHODS: Patients with craniofacial hyperkinesia were asked to rate changes of symptoms between - 2 (markedly worsened), - 1 (slightly worsened), 0 (no change), + 1 (slightly improved) and + 2 (markedly improved). RESULTS: Of 101 patients (19 with blepharospasm [BSP], 54 with cervical dystonia [CD], 6 with oromandibular dystonia [OMD], and 22 with hemifacial spasm [HFS]) 81 (80%) rated no symptom change, 11 (11%) symptom improvement, and 9 (9%) symptom worsening. Improvements in 9 of the 82 dystonia patients (BSP, CD, OMD) consisted of a perceived decrease in dystonic activity. 33% of dystonia patients had previously noticed or used a sensory trick. Its presence turned out to be a significant predictor of improvement during mask wearing. Deteriorations were attributed from all patients to disturbing effects of the mask interacting with facial muscle overactivity. Improvements in HSF patients were attributed to the symptom-hiding nature of the mask and not to an effect on the spasm activity itself. CONCLUSIONS: Wearing a face mask did not affect self-perceived symptoms in 80% of patients with craniofacial hyperkinesis. 11% of patients reported an improvement, which occurred as sensory trick in dystonia patients and as a concealment of a stigmatizing facial expression in patients with HSF.

Neurocritical care complications and interventions influence the outcome in aneurysmal subarachnoid hemorrhage.

BACKGROUND: This observational study was performed to show the impact of complications and interventions during neurocritical care on the outcome after aneurysmal subarachnoid hemorrhage (SAH). METHODS: 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. RESULTS: 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). CONCLUSIONS: In summary, decompressive craniectomy, sepsis and hydrocephalus significantly influence the outcome and occurrence of death after aneurysmal SAH.

Comparative Analysis of the Euroimmun CXCL13 Enzyme-Linked Immunosorbent Assay and the ReaScan Lateral Flow Immunoassay for Diagnosis of Lyme Neuroborreliosis.

Diagnosis of Lyme neuroborreliosis (LNB) is challenging, as long as Borrelia-specific intrathecal antibodies are not yet detectable. The chemokine CXCL13 is elevated in the cerebrospinal fluid (CSF) of LNB patients. Here, we compared the performances of the Euroimmun CXCL13 enzyme-linked immunosorbent assay (CXCL13 ELISA) and the ReaScan CXCL13 lateral flow immunoassay (CXCL13 LFA), a rapid point-of-care test, to support the diagnosis of LNB. In a dual-center case-control study, CSF samples from 90 patients (34 with definite LNB, 10 with possible LNB, and 46 with other central nervous system [CNS] diseases [non-LNB group]) were analyzed with the CXCL13 ELISA and the CXCL13 LFA. Classification of patients followed the European Federation of Neurological Societies (EFNS) guidelines on LNB. The CXCL13 ELISA detected elevated CXCL13 levels in all patients with definite LNB (median, 1,409 pg/ml) compared to the non-LNB controls (median, 20.7 pg/ml; P < 0.0001), with a sensitivity of 100% and a specificity of 84.8% (cutoff value, 78.6 pg/ml; area under the receiver operating characteristic [ROC] curve, 0.93). Similarly, the CXCL13 LFA yielded elevated CXCL13 levels in 31 patients with definite LNB (median arbitrary value, 223.5) compared to the non-LNB control patients (median arbitrary value, 0; P < 0.0001) and had a sensitivity and specificity of 91.2% and 93.5%, respectively (cutoff arbitrary value, 22.5; area under the ROC curve, 0.94). The correlation between the CXCL13 levels obtained by ELISA and LFA was strong (Spearman correlation coefficient r = 0.89; P < 0.0001). The CXCL13 ELISA and the CXCL13 LFA are comparable diagnostic tools for the detection of CXCL13 in the CSF of patients with definite LNB. The advantage of the CXCL13 LFA is the shorter time to result.

Impact of Complications and Comorbidities on the Intensive Care Length of Stay after Aneurysmal Subarachnoid Haemorrhage.

In this observational study, we analysed a cohort of 164 subarachnoid haemorrhage survivors (until discharge from intensive care) with the aim to detect factors that influence the length of stay (LOS) in intensive care with multiple linear regression methods. Moreover, binary logistic regression methods were used to examine whether the time in intensive care is a predictor of outcome after 1 year. The clinical 1-year outcome was measured prospectively in a 12-month follow-up by telephone interview and categorised by the modified Rankin Scale (mRS). Patients who died during their stay in intensive care were excluded. Complications like pneumonia (ß = 5.11; 95% CI = 1.75-8.46; p = 0.0031), sepsis (ß = 9.54; 95% CI = 3.27-15.82; p = 0.0031), hydrocephalus (ß = 4.63; 95% CI = 1.82-7.45; p = 0.0014), and delayed cerebral ischemia (DCI) (ß = 3.38; 95% CI = 0.19-6.56; p = 0.038) were critical factors depending the LOS in intensive care as well as decompressive craniectomy (ß = 5.02; 95% CI = 1.35-8.70; p = 0.0077). All analysed comorbidities such as hypertension, diabetes, hypothyroidism, cholesterinemia, and smoking history had no significant impact on the LOS in intensive care. LOS in intensive care (OR = 1.09; 95% CI = 1.03-1.15; p = 0.0023) as well as WFNS grade (OR = 3.72; 95% CI = 2.23-6.21; p < 0.0001) and age (OR = 1.06; 95% CI = 1.02-1.10; p = 0.0061) were significant factors that had an impact on the outcome after 1 year. Complications in intensive care but not comorbidities are associated with higher LOS in intensive care. LOS in intensive care is a modest but significant predictor of outcomes after subarachnoid haemorrhage.

[Acute stroke treatment in old age]. / Schlaganfallakuttherapie im Alter.

In patients over 80 years old, 4 of the 5 evidence-based acute treatments of ischemic stroke, i.e. stroke unit treatment, antiplatelet therapy, intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are effective but with a higher morbidity than in younger patients. The indications for the more invasive forms of treatment, such as IVT and MT are given in principle but have to be oriented to the individual patient comorbidities. In the case of failure of these procedures a consistent therapeutic target change to palliative measures is appropriate. Decompressive craniotomy in space-occupying media infarction can be indicated up to the relative age limit of 60 years and absolute age limit of 70 years. Patients over 80 years often do not undergo IVT or MT. Although the German approval for alteplase within the framework of IVT over the age of 80 years suggests a careful and critical review of the indications, its use is generally recommended.

Dynamics of outcome after aneurysmal subarachnoid hemorrhage.

In this observational study, we analyzed and described the dynamics of the outcome after aneurysmal subarachnoid hemorrhage (SAH) in a collective of 203 cases. We detected a significant improvement of the mean aggregate modified Rankin Score (mRS) in every time interval from discharge to 6 months and up to 1 year. Every forth to fifth patient with potential of recovery (mRS 1-5) at discharge improved by 1 mRS point in the time interval from 6 month to 1 year (22.6%). Patients with mRS 3 at discharge had a remarkable late recovery rate (73.3%, p = 0.000085). Multivariate analysis revealed age ≤ 65 years (odds ratio 4.93; p = 0.0045) and "World Federation of Neurological Surgeons" (WFNS) grades I and II (odds ratio 4.77; p = 0.0077) as significant predictors of early improvement (discharge to 6 months). Absence of a shunting procedure (odds ratio 8.32; p = 0.0049) was a significant predictor of late improvement (6 months to 1 year), but not age ≤ 65 years (p = 0.54) and WFNS grades I and II (p = 0.92). Thus, late recovery (6 month to 1 year) is significant and independent from age and WFNS grade.

[Acute stroke treatment in old age]. / Schlaganfallakuttherapie im Alter.

In patients over 80 years old, 4 of the 5 evidence-based acute treatments of ischemic stroke, i.e. stroke unit treatment, antiplatelet therapy, intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are effective but with a higher morbidity than in younger patients. The indications for the more invasive forms of treatment, such as IVT and MT are given in principle but have to be oriented to the individual patient comorbidities. In the case of failure of these procedures a consistent therapeutic target change to palliative measures is appropriate. Decompressive craniotomy in space-occupying media infarction can be indicated up to the relative age limit of 60 years and absolute age limit of 70 years. Patients over 80 years often do not undergo IVT or MT. Although the German approval for alteplase within the framework of IVT over the age of 80 years suggests a careful and critical review of the indications, its use is generally recommended.

Association of Surgical Hematoma Evacuation vs Conservative Treatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage.

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH. Design, Setting, and Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015). Exposure: Surgical hematoma evacuation vs conservative treatment. Main Outcomes and Measures: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH. Results: Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02). Conclusions and Relevance: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.

[Management of refractory and super-refractory status epilepticus]. / Management des refraktären und superrefraktären Status epilepticus.

If status epilepticus continues despite the use of intravenous antiepileptic drugs or narcotics, it is called "refractory" or "super-refractory" status epilepticus (RSE, SRSE). Prolonged seizure activity is associated with neuronal damage, systemic complications and mortality rates of up to 50%, especially in generalized tonic clonic seizure types. In order to terminate the status, several rescue interventions with drugs and other measures are available. However, their evidence base is low because the effectiveness of the measures was almost exclusively derived from case reports and case series. In individual cases, a good outcome is possible even after several months of ongoing SRSE.

[Acute Disorders of Consciousness and Coma - Systematics, Differential Diagnosis and Management]. / Bewusstseinsstörungen und Koma.

Cerebral diseases such as epileptic seizures, cerebral hemorrhages or meningoencephalitis are the primary cause of approximately 50 % of non-traumatic acute disorders of consciousness. For the differential diagnosis, history and other symptoms are important such as hemiplegia, signs of brain stem dysfunction, meningism or headache. Metabolic, endocrinologic, toxicologic or electrolytic causes of coma usually can be diagnosed by laboratory examinations. Anamnestic informations, body inspection, clinical neurological examination as well as laboratory and imaging findings have to be added and categorized by a multilevel composition to establish a conclusive diagnosis. Simultaneously therapeutic measures for suspected primary cerebral diseases must be initiated, for example a rapid antibiotic treatment in case of a possible bacterial meningitis. A fast and structured diagnostic approach is crucial for ensuring a good prognosis and helps to miss relevant diagnostic steps. Potential diagnostic and therapeutic pitfalls must be kept in mind.

Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage.

OBJECTIVE: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH. METHODS: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. RESULTS: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC. CONCLUSIONS: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Impact of Comorbidities and Smoking on the Outcome in Aneurysmal Subarachnoid Hemorrhage.

The intention of this observational study is to show the significant impact of comorbidities and smoking on the outcome in aneurysmal subarachnoid hemorrhage (SAH). During this observational study 203 cases of treatment of ruptured intracranial aneurysms were analyzed. We examined and classified prospectively the 12 month outcome according to the modified Rankin Scale (mRS) considering retrospectively a history of smoking and investigated prospectively the occurrence of early and delayed cerebral ischemia between 2012 and 2017. Using logistic regression methods, we revealed smoking (odds ratio 0.21; p = 0.0031) and hypertension (odds ratio 0.18; p = 0.0019) to be predictors for a good clinical outcome (mRS 0-2). Age (odds ratio 1.05; p = 0.0092), WFNS Grade (odds ratio 6.28; p < 0.0001), early cerebral ischemia (ECI) (odds ratio 10.06; p < 0.00032) and delayed cerebral ischemia (DCI) (odds ratio 4.03; p = 0.017) were detected as predictors for a poor clinical outcome. Significant associations of occurrence of death with hypertension (odds ratio 0.12; p < 0.0001), smoking (odds ratio 0.31; p = 0.048), WFNS grade (odds ratio 3.23; p < 0.0001) and age (odds ratio 1.09; p < 0.0001), but not with ECI (p = 0.29) and DCI (p = 0.62) were found. Smoking and hypertension seem to be predictors for a good clinical outcome after aneurysmal SAH.

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.

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

OBJECTIVE: To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH). METHODS: This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale. RESULTS: The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months. INTERPRETATION: In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor-related ICH. Ann Neurol 2018;83:186-196.

[Stroke Mimics and Stroke Chameleons: Differential Diagnosis of Stroke]. / Stroke Mimics und Stroke Chamäleons ­ Differenzialdiagnose des Schlaganfalls.

The analysis of misdiagnosis of stroke has become increasingly relevant because of the time pressure in the thrombolytic treatment of ischemic strokes. Within the narrow time window of thrombolysis, a false-positive stroke diagnosis can lead to a faulty and potentially dangerous thrombolysis. The terms "Stroke Mimic" (SM = false-positive stroke diagnosis) and "Stroke Chameleon" (SC = false-negative stroke diagnosis) have been introduced for misdiagnosis in this field. The rate of SM decreases during the treatment phases from approximately 50 % in the preclinical situation to approximately 2-10 % in the Stroke Unit indicating thrombolytic therapy. The complication rate for not indicated thrombolysis in SM is low with 0.5 % for intracranial bleeding and 0.3 % for orolingual edema. Thus, the net balance in favour of fast thrombolysis is maintained, even when a higher number of mis-indicated lyses occurs in SM. The rate of SC during the stages of treatment drops from about 50 % in the preclinical stage to about 2-5 % in stroke units. The rates of SM and SC are inversely linked: a reduction in the SM rate leads to a more critical diagnosis of stroke, thus increasing the number of underdiagnosed stroke cases as SC, and vice versa. While SM rarely lead to the legal consequences of treatment error, SC often give rise to accusations of medical errors.