Computed tomography angiography in the diagnosis of brain death: Implementation and results in Germany.

BACKGROUND: Computed tomography angiography (CTA) has been investigated as a confirmatory study (CS) for the diagnosis of brain death (BD). International consensus regarding its use, study parameters, and evaluation criteria is lacking. In the German BD guideline, a CTA protocol was first introduced in 2015. METHODS: The authors obtained a comprehensive dataset of all BD examinations in adults from the German organ procurement organization to investigate implementation, results, and impact of CTA on BD determination during the first 4 years. RESULTS: In 5152 patients with clinically absent brain function, 1272 CTA were reported by 676 hospitals. Use of CTA increased from 17.2% of patients in the first year to 29.7% in the final year. CTA replaced other CS such as electroencephalography without increasing overall CS frequency. Technical failure was rare (0.9%); 89.3% of studies were positive. Negative results (9.8%) were more frequent with secondary brain injury, longer duration of the clinical BD syndrome, or unreliable clinical assessment. Median time to diagnosis was longer with CTA (2.6 h) versus other CS (1.6 h). CTA had no differential impact on the rate of confirmed BD and did not improve access of small hospitals to CS for BD determination. CONCLUSIONS: CTA expands the range of available CS for the diagnosis of BD in adults. Real-world evidence from a large cohort confirms usability of the German CTA protocol within the guideline-specified context.

[Diagnosis of brain death in Germany-Implementation of the guidelines of the German Medical Association]. / Feststellung des irreversiblen Hirnfunktionsausfalls in Deutschland ­ Umsetzung der Richtlinie der Bundesärztekammer.

BACKGROUND: The 4th update of the guidelines of the German Medical Association on the diagnosis of irreversible loss of brain function (brain death, BD) has introduced important new regulations regarding the required qualification of the examiners, approved procedures for ancillary testing, and a clarification regarding the sequencing of diagnostic steps. OBJECTIVE: Investigation of the implementation and practical effects on the diagnosis of brain death. METHOD: Descriptive evaluation of the routine documentation of the German Organ Procurement Organization, comparing the periods July 2011-June 2015 (3rd update) and July 2015-June 2019 (4th update). RESULTS: Patient numbers decreased from 6100 to 5403. The largest decrease affected hospitals without neurosurgery. Children were not affected. With the 4th update, clinical diagnostics were increasingly performed during on-call hours by external neurologists. Of the patients 83.8% now received ancillary tests compared to 80.1% previously. Computed tomography angiography (CTA), first introduced in the 4th update, was applied in 23.2% and established complete loss of cerebral circulation in 89.4%. The time between first documentation of the clinical signs of BD and certification of BD increased from 7.0 ± 12.7 h to 8.2 ± 14.2 h. The diagnosis was slightly less frequent with 95.3% compared to 96.6%. CONCLUSION: The updated standards were implemented in accordance with the guidelines. The demand for external consulting neurologists and neurosurgeons as well as the time required for BD assessment have increased. Negative effects on pediatric BD diagnostics were not apparent. CTA is widely and successfully used in adults as a new ancillary diagnostic procedure.

[Diagnostics of irreversible brain death : Limitations and potential for improvement from the perspective of transplantation officials]. / Diagnostik des irreversiblen Hirnfunktionsausfalls : Limitationen und Verbesserungspotenziale aus Sicht der Transplantationsbeauftragten.

BACKGROUND: In Germany, postmortem organ donation requires a diagnosis of irreversible brain death (BD) in strict compliance with the guidelines of the German Medical Association. OBJECTIVE: Identification of factors that have a limiting effect on the initiation and execution of BD diagnostics. Identification of potential for improvement. MATERIAL AND METHODS: Anonymous survey of transplantation officials in hospitals in Berlin, Brandenburg and Mecklenburg-Western Pomerania. RESULTS: There is considerable heterogeneity with respect to the frequency of BD diagnostics and hospital-specific procedures, including the use of an existing consultation service. The local availability of qualified doctors and of suitable ancillary diagnostic tests has a structurally limiting effect. This is especially true for pediatric patients. Potential for improvement was seen in the identification of affected patients, the motivation of staff and the role of transplantation officials. CONCLUSION: According to the recently amended German Transplantation Act, a centrally organized consultation service for BD diagnostics must be implemented as soon as 2021. Recommendations can be derived from the present survey and from the experience of the regionally established consultation service. In addition to neurological and neurosurgical expertise, qualified pediatricians and mobile ancillary instrumental diagnostics should also be provided. Expert advice from neurointensive care physicians should be available at an early stage in order to identify potentially affected patients. The highly variable participation of hospitals in organ donation, despite the availability of an expert diagnostic service free of charge, points to an important role of additional factors, some of which may be nonmedical in nature.

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

AIMS: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. METHODS AND RESULTS: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively. CONCLUSION: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

A Narrative Review of Nonvitamin K Antagonist Oral Anticoagulant Use in Secondary Stroke Prevention.

The prevalence of atrial fibrillation (AF), the most common cardiac arrhythmia, increases with age, predisposing elderly patients to an increased risk of embolic stroke. With an increasingly aged population the number of people who experience a stroke every year, overall global burden of stroke, and numbers of stroke survivors and related deaths continue to increase. Anticoagulation with vitamin K antagonists (VKAs) reduces the risk of ischemic stroke in patients with AF; however, increased bleeding risk is well documented, particularly in the elderly. Consequently, VKAs have been underused in the elderly. Alternative anticoagulants may offer a safer choice, particularly in patients who have experienced previous stroke. The aim of this narrative review is to examine available evidence for the effective treatment of patients with AF and previous cerebral vascular events with non-VKA oral anticoagulants, including the most appropriate time to start or reinitiate treatment after a stroke, systemic embolism, or clinically relevant bleed. For patients with AF treated with oral anticoagulants it is important to balance increased protection against future stroke/systemic embolism and reduced risk of major bleeding events. For patients with AF who have previously experienced a cerebrovascular event, the use of oral anticoagulants alone also appears more effective than low-molecular weight heparin (LMWH) alone or LMWH followed by oral anticoagulants. Available data suggest that significant reduction in stroke, symptomatic cerebral bleeding, and major extracranial bleeding within 90 days from acute stroke can be achieved if oral anticoagulation is initiated at 4-14 days from stroke onset.

[New Challenges: Diagnosis of Brain Death in Newborn, Children and Adolescents]. / Neue Herausforderungen: Feststellung des irreversiblen Ausfalls der Hirnfunktion bei Neugeborenen, Kindern und Jugendlichen.

BACKGROUND: According to the current update of the German guideline on brain death (BD), participation of paediatricians is now mandatory for the examination of BD in patients younger than 14 years. The present analysis focuses on the previous practice and highlights the challenges that arise from the current update. METHODS: Retrospective evaluation of the patient registry of the German organ procurement organisation (north-eastern bureau) between January, 2001 and December, 2010 with specified paediatric age groups according to the 4th update of the German guideline on BD from the 1st of July 2015. RESULTS: 133 patients (0-17 years) received at least one BD examination. Secondary brain damage was most frequent within the first 6 months of life whereas traumatic and other causes of primary brain damage were predominantly observed thereafter. The number of patients who received BD examination by paediatricians or were treated on neonatal/paediatric intensive care units declined with increasing age. In more than two-third of all paediatric patients, no paediatrician was involved in BD diagnostics. DISCUSSION: After enforcement of the 4th update of the German guideline on BD, the participation of qualified paediatric physicians must be increased significantly compared to previous practice. Advancements in the specialist training of paediatric physicians, adjustments in patient-centered paediatric care and interdisciplinary diagnostic teams may be solutions to meet this demand.

Use of Observational Periods or Ancillary Tests in the Determination of Brain Death in Germany.

BACKGROUND: In the absence of primary infratentorial brain lesions, the German guideline on brain death (BD) permits diagnosis based on two clinical assessments separated by a defined observational period or by one clinical assessment and an ancillary test. METHODS: Retrospective analysis of patients fulfilling the clinical criteria of BD registered with the organ procurement organization of northeastern Germany during a 10-year period. RESULTS: 2,745 patients were included. Compared to clinical observations, ancillary tests led to the confirmation of BD more frequently (98.7 vs. 78.7%) and after a considerably shorter diagnostic duration (median 1.4 vs. 16.5 h). Organ donation was more frequent with inclusion of ancillary tests (69.3 vs. 34.7% of diagnosed patients). The rate of fatal circulatory failure increased with longer observation. Nonconfirmatory results of the first ancillary test were more frequent with primary infratentorial lesions (14.3%) and hypoxic brain damage (7.9%) compared to primary supratentorial lesions (2.9%). CONCLUSION: When used as an alternative to clinical reassessment, ancillary studies increase the rate of BD determination and organ donation. An increased rate of initially negative ancillary studies with infratentorial brain lesions or hypoxic brain damage supports the use of different diagnostic pathways for these patients, as defined by the current German guideline.

Brain death determination in patients with veno-arterial extracorporeal membrane oxygenation: A systematic study to address the Harlequin syndrome.

PURPOSE: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. MATERIALS AND METHODS: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. RESULTS: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). CONCLUSIONS: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

Measurement of cerebral circulation times using dynamic whole-brain CT-angiography: feasibility and initial experience.

The objective of the study was to use 320-detector row 4D CT angiography (CTA) for measuring cerebral circulation times (CCT) and to assess early venous drainage (EVD) and shortening of CCT in arteriovenous malformations (AVM) and to compare with DSA. CCT of 12 physiological patients and five AVM patients were acquired using a 4D CTA protocol by recording cerebrovascular bolus passage time. In the AVM patients EVD time (EVDT) was measured. Identical measurements were performed on DSA for the AVM patients. It was found that the physiological CCTs were 5.8 ± 1.4 s (M ± SD). EVD was seen in all AVMs and resulted in a shortened CCT of 3.4 ± 1.1 s (p = 0.01). There was no significant difference for CCT and EVDT values derived from DSA and 4D CTA. Thus, the CCTs can be measured non-invasively using clinical 4D CTA. Early venous drainage with shortened CCTs was observed by 4D CTA in all five patients with AVMs.

Neuroimaging by 320-row CT: is there a diagnostic benefit or is it just another scanner? A retrospective evaluation of 60 consecutive acute neurological patients.

320-row CT enables dynamic CT angiography (4D CTA) of the entire intracranial circulation and whole-brain perfusion imaging (CTP). Sixty acute patients with neurological symptoms underwent various 320-row CT-specific protocols, including combined 4D CTA and CTP. Clinical and neuroradiological records were assessed for presumptive diagnoses, final diagnoses, supplementary and follow-up imaging studies. Additional diagnostic benefits delivered by 320-row CT were noted. Out of 60 procedures, 59 were accomplished successfully. Ischemia (n = 19), intracerebral hemorrhage (n = 7) and transient ischemic attacks (n = 10) were the major final diagnoses. Except one small cortical and two small subcortical infarctions all ischemias were diagnosed. All hemorrhages were diagnosed together with their underlying vascular pathology in five atypical cases. In conclusion, 320-row CT is a technically robust procedure being suitable for comprehensive neuroimaging of acute patients. It can provide dynamic angiographic and perfusion data of the whole brain and can deliver additional diagnostic information not available by standard CT.

Low ankle-brachial index predicts cardiovascular risk after acute ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: A low ankle-brachial blood pressure index (ABI) is an established risk marker for cardiovascular disease and mortality in the general population, but little is known about its prognostic value in individuals with acute ischemic stroke or transient ischemic attack (TIA). METHODS: An inception cohort of 204 patients with acute ischemic stroke or TIA was followed up for a mean of 2.3 years. At baseline, patients underwent ABI measurement and were assessed for risk factors, cardiovascular comorbidities, and cervical or intracranial artery stenosis. The association between low ABI (

Transesophageal echocardiography in patients with cryptogenic cerebral ischemia.

BACKGROUND: In about one third of all patients with cerebral ischemia, no definite cause can be identified (cryptogenic stroke). In many patients with initially suspected cryptogenic stroke, however, a cardiogenic etiology can eventually be determined. Hence, the aim of this study was to describe the prevalence of abnormal echocardiographic findings in a large number of these patients. METHOD: Patients with cryptogenic cerebral ischemia (ischemic stroke, IS, and transient ischemic attack, TIA) were included. The initial work-up included a neurological examination, EEG, cCT, cMRT, 12-lead ECG, Holter-ECG, Doppler ultrasound of the extracranial arteries, and transthoracic echocardiography. A multiplane transeophageal echocardiography (TEE, including i.v. contrast medium application [Echovist], Valsalva maneuver) was performed in all patients RESULTS: 702 consecutive patients (380 male, 383 IS, 319 TIA, age 18-90 years) were included. In 52.6% of all patients, TEE examination revealed relevant findings. Overall, the most common findings in all patients were: patent foramen ovale (21.7%), previously undiagnosed valvular disease (15.8%), aortic plaques, aortic valve sclerosis, atrial septal aneurysms, regional myocardial dyskinesia, dilated left atrium and atrial septal defects. Older patients (> 55 years, n = 291) and patients with IS had more relevant echocardiographic findings than younger patients or patients with TIA, respectively (p = 0.002, p = 0.003). The prevalence rates of PFO or ASD were higher in younger patients (PFO: 26.8% vs. 18.0%, p = 0.005, ASD: 9.6% vs. 4.9%, p = 0.014). CONCLUSION: A TEE examination in cryptogenic stroke reveals contributing cardiogenic factors in about half of all patients. Younger patients had a higher prevalence of PFO, whereas older patients had more frequently atherosclerotic findings. Therefore, TEE examinations seem indicated in all patients with cryptogenic stroke - irrespective of age - because of specific therapeutic consequences.

Comparative evaluation of 64-slice CT angiography and digital subtraction angiography in assessing the cervicocranial vasculature.

BACKGROUND: Noninvasive 64-slice computed tomography angiography (64-MSCTA) closely approximates conventional catheter angiography (DSA) in terms of detail resolution. OBJECTIVE: Retrospective evaluation of cervicocranial (cc) 64-MSCTA in comparison with DSA in patients with presumptive cc vascular disorders. MATERIAL AND METHODS: Twenty-four 64-MSCTA studies (32 mm detector width, slice thickness 0.5 mm, 120 kv, 150 mAs, pitch 0.75) of patients with presumptive cc vascular pathology (13 men, 11 women, mean age 38.3 +/- 11.3 yrs, range 19-54 yrs) were assessed in comparison with DSA studies without abnormal findings in age-matched patients (11 men, 13 women, mean age 39.7 +/- 11.9 yrs, range 18-54 yrs). Study readings were performed in a blinded manner by two neuroradiologists with respect to image quality and assessibility of various cc vascular segments by using a five-point scale. Radiation exposure was calculated for 64-MSCTA. RESULTS: Each reader assessed 384/528 different vessel segments (64-MSCTA/DSA). Superior image quality was attributed to DSA with respect to the C1 ICA-C6 ICA, A3 ACA, and P3 PCA segments as well the AICA and SCA. 64-MSCTA was scored superior for C7 ICA and V4 VA segments. A significantly increased number ofnonassessable V2- and V3 VA segments in DSA studies was noted. The effective dose for 64-MSCTA amounted to 2.2 mSv. CONCLUSIONS: 64-MSCTA provides near-equivalent diagnostic information of the cc vasculature as compared with DSA. According to our results, DSA should be considered primarily when peripheral vessels (A3/P3) or ICA segments close to the skull base (C2-5) are of interest, such as in primary angiitis or stenoocclusive ICA disease, respectively.

Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke.

BACKGROUND AND PURPOSE: The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume. We hypothesized that patients with type 2 diabetes mellitus taking sulfonylurea agents both at the time of stroke and during hospitalization would have superior outcomes. METHODS: We reviewed medical records of patients with diabetes mellitus hospitalized within 24 hours of onset of acute ischemic stroke in the Neurology Clinic, Charité Hospital, Berlin, Germany, during 1994 to 2000. After exclusions, the cohort comprised 33 patients taking a sulfonylurea at admission through discharge (treatment group) and 28 patients not on a sulfonylurea (control group). The primary outcome was a decrease in National Institutes of Health Stroke Scale of 4 points or more from admission to discharge or a discharge National Institutes of Health Stroke Scale score of 0. The secondary outcome was a discharge modified Rankin Scale score < or =2. RESULTS: No significant differences, other than stroke subtype, were observed among baseline variables between control and treatment groups. The primary outcome was reached by 36.4% of patients in the treatment group and 7.1% in the control group (P=0.007). The secondary outcome was reached by 81.8% versus 57.1% (P=0.035). Subgroup analyses showed that improvements occurred only in patients with nonlacunar strokes and were independent of gender, previous transient ischemic attack, and blood glucose levels. CONCLUSIONS: Sulfonylureas may be beneficial for patients with diabetes mellitus with acute ischemic stroke. Further investigation of similar cohorts and a prospective randomized trial are recommended to confirm the present observations.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - Endorsed by the European Academy of Neurology.

The current proposal for cerebral venous thrombosis guideline followed the Grading of Recommendations, Assessment, Development, and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews of all available evidence and writing recommendations and deciding on their strength on an explicit and transparent manner, based on the quality of available scientific evidence. The guideline addresses both diagnostic and therapeutic topics. We suggest using magnetic resonance or computed tomography angiography for confirming the diagnosis of cerebral venous thrombosis and not screening patients with cerebral venous thrombosis routinely for thrombophilia or cancer. We recommend parenteral anticoagulation in acute cerebral venous thrombosis and decompressive surgery to prevent death due to brain herniation. We suggest to use preferentially low-molecular weight heparin in the acute phase and not using direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations due to very poor quality of evidence concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that in women who suffered a previous cerebral venous thrombosis, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular weight heparin should be considered throughout pregnancy and puerperium. Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of cerebral venous thrombosis.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death.

PURPOSE: We investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). MATERIALS AND METHODS: We retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. RESULTS: Intracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (-8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. CONCLUSIONS: Brain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow.

[Consensus statement: Management of oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation]. / Konsensuspapier: Schlaganfallprophylaxe bei Patienten mit nichtvalvulärem Vorhofflimmern.

With the introduction of edoxaban last year in Germany, four nonvitamin K antagonist oral anticoagulants are now available for stroke prevention in patients with nonvalvular atrial fibrillation. These novel oral anticoagulants (NOAC) represent an attractive new option compared to vitamin K antagonists (e.g., warfarin or phenprocoumon) due to simple use and fewer interactions with other drugs or food. Therefore, no INR monitoring and dosage adjustments are required for NOAC. The compelling clinical advantage of NOAC is the dramatic risk reduction of hemorhagic stroke and intracranial bleeding compared to current standard. In addition, total mortality is significantly reduced by 10 %. These effects are demonstrated for all four NOAC (dabigatran, rivaroxaban, apixaban and edoxaban). Therefore, current national and international guidelines recommend NOAC as the preferred option or at least as an attractive alternative compared to the former standard of vitamin K antagonists. The economic impact and reimbursement by Statutory Health Insurance (GKV) is of major importance for treatment in an outpatient setting. For apixaban and edoxaban, an additional benefit was granted by the institution of G­BA and IQWiG in this clinical setting, whereas dabigatran and rivaroxaban were not assessed due to market entrance prior to 2011 before the AMNOG procedure was initiated. The members of this consensus paper recommend NOAC as the preferred option for patients with nonvalvular atrial fibrillation who are currently not treated with anticoagulant drugs in spite of clear indication for anticoagulation. For new patients with nonvalvular fibrillation, it should be decided on an individual basis which treatment option is adequate for the patient with their respective comorbidities.

A "malignant" variant of status epilepticus.

BACKGROUND: Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined the term malignant SE for this most severe variant of SE. OBJECTIVE: To assess frequency, risk factors, and in-hospital outcome of malignant SE. DESIGN: Retrospective cohort study. SETTING: Neurologic intensive care unit of a large university hospital. Patients Sample of 35 episodes of SE not responding to first-line anticonvulsants in 34 patients. MAIN OUTCOME MEASURES: Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases with refractory SE and persistent epileptic activity after failure of first-line anticonvulsants. RESULTS: Status epilepticus that could not be controlled by first-line anticonvulsants resulted in malignant SE in 20% of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P = .03). Encephalitis was identified as an independent risk factor for malignant SE (P = .008). Outcome in malignant SE was poor, with significantly longer duration of seizure activity (P<.001), longer stay in the neurologic intensive care unit (P<.001) and in the hospital (P = .007), and more patients with functional dependency at discharge from the hospital (P = .04). CONCLUSIONS: Malignant SE is not rare after failure of first-line anticonvulsants. The patient at risk is typically young and suffers from encephalitis. Such patients should be treated aggressively early in the course of SE to prevent malignant SE.

Functional, cognitive and emotional long-term outcome of patients with ischemic stroke requiring mechanical ventilation.

Prognosis of patients with ischemic stroke requiring mechanical ventilation (MV) has been reported to be poor. However, longterm survival and functional outcome have scarcely been studied and nothing is known about the prevalence of cognitive impairment or depression in survivors and their quality of life (QoL). We identified all patients treated for acute ischemic stroke on a Neurological Intensive Care Unit during 3.5 years who required MV for more than 24 hours. Early mortality rate at 2 months and survival rates at 1 and 2 years were determined. Survivors were examined for functional outcome (modified Rankin Scale (mRS), Barthel Index), cognitive impairment (Mini Mental State Examination (MMSE)), depression (Beck Depression Inventory, BDI) and QoL (Short Form-36). Clinical characteristics on admission were analyzed for prognostic significance. Of 101 consecutive patients, 44% died within 60 days. Survival rates at 1 and 2 years were 40% and 33%, respectively. Age > 60 years (p = 0.002) and Glasgow Coma Scale score < 10 on admission (p = 0.002) were independent predictors of early and late mortality. History of myocardial infarction (p = 0.007) independently predicted late mortality at 2 years. Of 33 surviving patients, nine (27%) had a good functional outcome (mRS 0-2). Of 27 survivors who could be interviewed, 17 (63%) had no cognitive impairment (MMSE > 24) and 20 (74%) did not suffer from relevant depression (BDI < 19). In conclusion, longer-term survival of patients with ischemic stroke requiring MV was 33% and every fourth survivor resumed an independent life without dementia or depression. Older patients comatose on admission and with concomitant cardiovascular disease had the lowest probability of a favorable outcome.