Potential effects of a mobile stroke unit on time to treatment and outcome in patients treated with thrombectomy or thrombolysis: A Danish-German cross-border analysis.

BACKGROUND AND PURPOSE: A mobile stroke unit (MSU) reduces delays in stroke treatment by allowing thrombolysis on board and avoiding secondary transports. Due to the beneficial effect in comparison to conventional emergency medical services, current guidelines recommend regional evaluation of MSU implementation. METHODS: In a descriptive study, current pathways of patients requiring a secondary transport for mechanical thrombectomy were reconstructed from individual patient records within a Danish (n = 122) and an adjacent German region (n = 80). Relevant timestamps included arrival times (on site, primary hospital, thrombectomy centre) as well as the initiation of acute therapy. An optimal MSU location for each region was determined. The resulting time saving was translated into averted disability-adjusted life years (DALYs). RESULTS: For each region, the optimal MSU location required a median driving time of 35 min to a stroke patient. Time savings in the German region (median [Q1; Q3]) were 7 min (-15; 31) for thrombolysis and 35 min (15; 61) for thrombectomy. In the Danish region, the corresponding time savings were 20 min (8; 30) and 43 min (25; 66). Assuming 28 thrombectomy cases and 52 thrombolysis cases this would translate to 9.4 averted DALYs per year justifying an annual net MSU budget of $0.8M purchasing power parity dollars (PPP-$) in the German region. In the Danish region, the MSU would avert 17.7 DALYs, justifying an annual net budget of PPP-$1.7M. CONCLUSION: The effects of an MSU can be calculated from individual patient pathways and reflect differences in the hospital infrastructure between Denmark and Germany.

[Improvement of the treatment of patients with spastic movement disorder after stroke]. / Verbesserung der Versorgung von Patientinnen und Patienten mit spastischer Bewegungsstörung nach Schlaganfall.

BACKGROUND: Spastic movement disorder (SMD) develops in up to 43% of cases as a sequela of stroke. In the event of a functionally relevant or daily life impairing SMD or to avoid an impending complication, the medicinal treatment of a focal, multifocal and segmental increase in muscle tone with botulinum neurotoxin A (BoNT-A) is recommended; however, treatment data reveal a lack of guideline-conform treatment with BoNT­A in Germany. OBJECTIVE: The aim of the reported expert meeting was to discuss solutions to the incorrect treatment and undertreatment of patients with SMD and to formulate consensus recommendations to improve the care situation. METHODS: At a consensus meeting held in April 2022, eight experts from the fields of neurology, physical medicine and rehabilitation discussed the causes for the incorrect treatment and undertreatment and formulated consensus solution approaches. RESULTS: Possible reasons for the current incorrect treatment and undertreatment in SMD management in Germany include insufficient awareness of SMD among physicians, a lack of treatment capacities, a lack of information transfer in discharge management as well as staff shortages in the specialized inpatient and outpatient SMD treatment centers. The committee therefore recommended a patient pathway in which affected patients with SMD are provided with correctly implemented BoNT­A treatment in combination with physical measures. CONCLUSION: The recommended treatment pathway for use in stroke patients is intended to close gaps in care and thus ensure guideline-conform treatment of post-stroke SMD.

Preserved Corticospinal Tract Revealed by Acute Perfusion Imaging Relates to Better Outcome After Thrombectomy in Stroke.

BACKGROUND: The indication for mechanical thrombectomy (MT) in stroke patients with large vessel occlusion has been constantly expanded over the past years. Despite remarkable treatment effects at the group level in clinical trials, many patients remain severely disabled even after successful recanalization. A better understanding of this outcome variability will help to improve clinical decision-making on MT in the acute stage. Here, we test whether current outcome models can be refined by integrating information on the preservation of the corticospinal tract as a functionally crucial white matter tract derived from acute perfusion imaging. METHODS: We retrospectively analyzed 162 patients with stroke and large vessel occlusion of the anterior circulation who were admitted to the University Medical Center Lübeck between 2014 and 2020 and underwent MT. The ischemic core was defined as fully automatized based on the acute computed tomography perfusion with cerebral blood volume data using outlier detection and clustering algorithms. Normative whole-brain structural connectivity data were used to infer whether the corticospinal tract was affected by the ischemic core or preserved. Ordinal logistic regression models were used to correlate this information with the modified Rankin Scale after 90 days. RESULTS: The preservation of the corticospinal tract was associated with a reduced risk of a worse functional outcome in large vessel occlusion-stroke patients undergoing MT, with an odds ratio of 0.28 (95% CI, 0.15-0.53). This association was still significant after adjusting for multiple confounding covariables, such as age, lesion load, initial symptom severity, sex, stroke side, and recanalization status. CONCLUSIONS: A preinterventional computed tomography perfusion-based surrogate of corticospinal tract preservation or disconnectivity is strongly associated with functional outcomes after MT. If validated in independent samples this concept could serve as a novel tool to improve current outcome models to better understand intersubject variability after MT in large vessel occlusion stroke.

Glyoxal in hyperglycaemic ischemic stroke - a cohort study.

BACKGROUND: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke. METHODS: In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested. RESULTS: Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid Nδ-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids Nε-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal. CONCLUSIONS: The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke.

Explicit Diagnostic Criteria for Transient Ischemic Attacks Used in the Emergency Department Are Highly Sensitive and Specific.

BACKGROUND: Making a correct diagnosis of a transient ischemic attack (TIA) is prone to errors because numerous TIA mimics exist and there is a shortage of evidence-based diagnostic criteria for TIAs. In this study, we applied for the first time the recently proposed explicit diagnostic criteria for transient ischemic attacks (EDCT) to a group of patients presenting to the emergency department of a large German tertiary care hospital with a suspected TIA. The aim was to determine the sensitivity and specificity of the EDCT in its clinical application. METHODS: A total of 128 patients consecutively presenting to the emergency department of the University Hospital of Lübeck, Germany, under the suspicion of a TIA were prospectively interviewed about their clinical symptoms at the time of presentation. The diagnosis resulting from applying the EDCT was compared to the diagnosis made independently by the senior physicians performing the usual diagnostic work-up ("gold standard"), allowing calculation of sensitivity and specificity of the EDCT. RESULTS: EDCT achieved a sensitivity of 96% and a specificity of 88%. When adding the additional criterion F ("the symptoms may not be better explained by another medical or mental disorder"), specificity significantly increased to 98%. CONCLUSIONS: The data show that the EDCT in its modified version as proposed by us are a highly useful tool for clinicians. They display a high sensitivity and specificity to accurately diagnose TIAs in patients referred to the emergency department with a suspected TIA.

Elevation of intracranial pressure affects the relationship between hemoglobin concentration and neuronal activation in human somatosensory cortex.

During neuronal activation, a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) occurs which is the basis of functional brain imaging with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Elevated intracranial pressure (eICP) has been shown to impair functional deoxy-Hb changes. This study investigated this effect and its relation to the underlying neuronal activity in the human primary somatosensory cortex (SI). Functional near-infrared spectroscopy (fNIRS) during somatosensory evoked potentials (SEP) monitoring was performed on 75 subjects during conditions of median nerve stimulation (MNS) and resting state, combined with normal breathing (NB) and eICP by escalating breathing maneuvers (breath holding [BH], Valsalva maneuver with 15 mmHg [V15] and 35 mmHg expiratory pressure [V35]). During NB, fNIRS revealed a typical oxygenated hemoglobin concentration (oxy-Hb) increase with deoxy-Hb decrease during MNS enabling SI brain mapping. Breathing maneuvers associated eICP produced a known global change of oxy-Hb and deoxy-Hb with and without MNS. When subtracting measurements during resting state from measurements during MNS, neither functional oxy-Hb nor deoxy-Hb changes could be recovered while SEPs remained unchanged. In conclusion, Valsalva-induced eICP prevents oxy-Hb and deoxy-Hb changes during neuronal activation in SI. This finding raises questions on the validity of oxy-Hb- and deoxy-Hb-based brain imaging (e.g., BOLD-fMRI) during eICP.

ICHD-3 is significantly more specific than ICHD-3 beta for diagnosis of migraine with aura and with typical aura.

BACKGROUND: In the emergency room, distinguishing between a migraine with aura and a transient ischemic attack (TIA) is often not straightforward and mistakes can be harmful to both the patient and to society. To account for this difficulty, the third edition of the International Classification of Headache disorders (ICHD-3) changed the diagnostic criteria of migraine with aura. METHODS: One hundred twenty-eight patients referred to the emergency room at the University Hospital of Lübeck, Germany with a suspected TIA were prospectively interviewed about their symptoms leading to admission shortly after initial presentation. The diagnosis that resulted from applying the ICHD-3 and ICHD-3 beta diagnostic criteria was compared to the diagnosis made independently by the treating physicians performing the usual diagnostic work-up. RESULTS: The new ICHD-3 diagnostic criteria for migraine with aura and migraine with typical aura display an excellent specificity (96 and 98% respectively), and are significantly more specific than the previous ICHD-3 beta classification system when it comes to diagnosing a first single attack (probable migraine with aura and probable migraine with typical aura). CONCLUSIONS: The ICHD-3 is a highly useful tool for the clinical neurologist in order to distinguish between a migraine with aura and a TIA, already at the first point of patient contact, such as in the emergency department or a TIA clinic.

Valsalva-induced elevation of intracranial pressure selectively decouples deoxygenated hemoglobin concentration from neuronal activation and functional brain imaging capability.

During neuronal activation, neurovascular coupling leads to a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) and thus forms the basis of many functional brain mapping methods. In animals, an elevated intracranial pressure (ICP) can attenuate or even reverse this deoxy-Hb signaling. To study the effect of an elevated ICP on functional brain imaging in humans, we used different breathing tasks to modify ICP and analyzed the resulting effect on neurovascular coupling in the motor cortex. Functional near-infrared spectroscopy (fNIRS) was performed on 45 subjects during alternating conditions of finger tapping and resting state combined with four different breathing maneuvers (normal breathing (NB), breath holding without Valsalva maneuver (BH), Valsalva maneuver with 15 mm Hg forced expiratory pressure against resistance (V15) and Valsalva maneuver with 35 mm Hg forced expiratory pressure against resistance (V35)) in randomized order. With escalation of breathing tasks the median amplitude of the functional deoxy-Hb decrease during finger tapping became smaller. In contrast, functional oxygenated hemoglobin concentration (oxy-Hb) and total hemoglobin concentration (total-Hb) responses did not show a significant alteration. The functional oxy-Hb map evoked by finger tapping withstood Valsalva challenges while the functional deoxy-Hb map identified the correct motor cortex in normal breathing conditions only and did not reveal a functional contrast during Valsalva maneuvers. In summary, we conclude that during ICP elevation, deoxy-Hb is not a reliable basis for functional brain imaging. This suggests that the validity of BOLD fMRI during increased ICP might be impaired.

[Singultus - Diagnostic Workup and Therapy]. / Singultus ­ Diagnostik und Therapie.

A hiccup is a reflex movement with diffusely distributed afferents and efferents in the thorax; its functional relevance is controversial. In its physiological form, it is mostly a minor complaint that stops spontaneously and rarely leads to medical consultation. However, prolonged agonizing hiccups represent serious deterioration of quality of life. Chronic hiccups by definition last for more than 48 h, with gastroesophageal reflux being the frequent underlying disease. Various other causes affect multiple organ systems, some with serious underlying diseases. A hiccup may be the only symptom at the first manifestation of some neurological disorders. In neuroimaging a lesion of the medulla oblongata is often seen. A NMO and an ischemic stroke with Wallenberg syndrome are 2 frequently underlying neurological diseases, but other inflammatory and vascular diseases and tumors of the central nervous system may be present. No optimal evidencebased recommendations for diagnosis and management of chronic hiccups are available. The search for the underlying disease often requires an interdisciplinary approach by internists, neurologists, and otolaryngologists. Symptomatic treatment may be necessary even before diagnosis. Persistent hiccups, a common problem in oncological palliative care, are often challenging. Proton pump inhibitor or prokinetics are used for treating underlying gastroesophageal reflux and baclofen with or without gabapentin in other cases. Anticonvulsants, antipsychotics, antidepressants, and calcium channel blockers represent other alternative treatment possibilities. In therapy-refractory cases, invasive procedures such as the selective phrenic nerve block are available. More studies are needed to help deal with the diagnostic and therapeutic challenge that hiccups present for neurologists.

Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome after experimental stroke.

Stroke-induced immunodepression (SIDS) is an essential cause of poststroke infections. Pharmacological inhibition of SIDS appears promising in preventing life-threatening infections in stroke patients. However, SIDS might represent an adaptive mechanism preventing autoreactive immune responses after stroke. To address this, we used myelin oligodendrocyte glycoprotein (MOG) T-cell receptor transgenic (2D2) mice where >80% of peripheral CD4(+) T cells express a functional receptor for MOG. We investigated in a murine model of middle cerebral artery occlusion the effect of blocking SIDS by inhibiting body's main stress axes, the sympathetic nervous system (SNS) with propranolol and the hypothalamic-pituitary-adrenal axis (HPA) with mifepristone. Blockade of both stress axes robustly reduced infarct volumes, decreased infection rate, and increased long-term survival of 2D2 and C57BL/6J wild-type mice. Despite these protective effects, blockade of SIDS increased CNS antigen-specific Type1 T helper cell (Th1) responses in the brains of 2D2 mice 14 d after middle cerebral artery occlusion. One month after experimental stroke, 2D2 mice developed signs of polyradiculitis, which were diminished by SIDS blockade. Adoptive transfer of CD4(+) T cells, isolated from 2D2 mice, into lymphocyte-deficient Rag-1KO mice did not reveal differences between SIDS blockade and vehicle treatment in functional long-term outcome after stroke. In conclusion, inhibiting SIDS by pharmacological blockade of body's stress axes increases autoreactive CNS antigen-specific T-cell responses in the brain but does not worsen functional long-term outcome after experimental stroke, even in a mouse model where CNS antigen-specific autoreactive T-cell responses are boosted.

Dysphagia in Patients with Acute Ischemic Stroke: Early Dysphagia Screening May Reduce Stroke-Related Pneumonia and Improve Stroke Outcomes.

BACKGROUND: Dysphagia is associated with poor outcome in stroke patients. Studies investigating the association of dysphagia and early dysphagia screening (EDS) with outcomes in patients with acute ischemic stroke (AIS) are rare. The aims of our study are to investigate the association of dysphagia and EDS within 24 h with stroke-related pneumonia and outcomes. METHODS: Over a 4.5-year period (starting November 2007), all consecutive AIS patients from 15 hospitals in Schleswig-Holstein, Germany, were prospectively evaluated. The primary outcomes were stroke-related pneumonia during hospitalization, mortality, and disability measured on the modified Rankin Scale ≥2-5, in which 2 indicates an independence/slight disability to 5 severe disability. RESULTS: Of 12,276 patients (mean age 73 ± 13; 49% women), 9,164 patients (74%) underwent dysphagia screening; of these patients, 55, 39, 4.7, and 1.5% of patients had been screened for dysphagia within 3, 3 to <24, 24 to ≤72, and >72 h following admission. Patients who underwent dysphagia screening were likely to be older, more affected on the National Institutes of Health Stroke Scale score, and to have higher rates of neurological symptoms and risk factors than patients who were not screened. A total of 3,083 patients (25.1%; 95% CI 24.4-25.8) had dysphagia. The frequency of dysphagia was higher in patients who had undergone dysphagia screening than in those who had not (30 vs. 11.1%; p < 0.001). During hospitalization (mean 9 days), 1,271 patients (10.2%; 95% CI 9.7-10.8) suffered from stroke-related pneumonia. Patients with dysphagia had a higher rate of pneumonia than those without dysphagia (29.7 vs. 3.7%; p < 0.001). Logistic regression revealed that dysphagia was associated with increased risk of stroke-related pneumonia (OR 3.4; 95% CI 2.8-4.2; p < 0.001), case fatality during hospitalization (OR 2.8; 95% CI 2.1-3.7; p < 0.001) and disability at discharge (OR 2.0; 95% CI 1.6-2.3; p < 0.001). EDS within 24 h of admission appeared to be associated with decreased risk of stroke-related pneumonia (OR 0.68; 95% CI 0.52-0.89; p = 0.006) and disability at discharge (OR 0.60; 95% CI 0.46-0.77; p < 0.001). Furthermore, dysphagia was independently correlated with an increase in mortality (OR 3.2; 95% CI 2.4-4.2; p < 0.001) and disability (OR 2.3; 95% CI 1.8-3.0; p < 0.001) at 3 months after stroke. The rate of 3-month disability was lower in patients who had received EDS (52 vs. 40.7%; p = 0.003), albeit an association in the logistic regression was not found (OR 0.78; 95% CI 0.51-1.2; p = 0.2). CONCLUSIONS: Dysphagia exposes stroke patients to a higher risk of pneumonia, disability, and death, whereas an EDS seems to be associated with reduced risk of stroke-related pneumonia and disability.

Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging.

BACKGROUND AND PURPOSE: Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation. METHODS: MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies. RESULTS: ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO. CONCLUSIONS: The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes.

The lesion core extent modulates the impact of early perfusion mismatch imaging on outcome variability after thrombectomy in stroke.

Introduction: Despite profitable group effects on functional outcomes after mechanical thrombectomy (MT) in large vessel occlusion (LVO), many patients with successful reperfusion show a non-favorable long-term outcome, highlighting the necessity to identify potential biomarkers predicting outcome variability. In this regard, the role of perfusion mismatch imaging for outcome variability in the early time window within 6 h after symptom onset is a matter of debate. We attempted to investigate under which conditions early perfusion mismatch imaging accounts for variability in functional outcomes after mechanical thrombectomy. Patients and methods: In a retrospective single-center study, we examined 190 consecutive patients with LVO who were admitted to the Medical Center Lübeck within 6 h after symptom onset, all of whom underwent MT. Perfusion mismatch was quantified by applying the Alberta Stroke Program Early CT score (ASPECTS) on CT-measured cerebral blood flow (CBF-ASPECTS) and subtracting it from an ASPECTS application on cerebral blood volume (CBV-ASPECTS), i.e., ASPECTS mismatch. Using multivariate ordinal regression models, associations between ASPECTS mismatch and modified Rankin Scale (mRS) after 90 days were assessed. Furthermore, the interaction between ASPECTS mismatch and the core lesion volume was calculated to evaluate conditional associations. Results: ASPECTS mismatch did not correlate with functional outcomes when corrected for multiple influencing covariables. However, interactions between ASPECTS mismatch and CBV-ASPECTS [OR: 1.12 (1.06-1.18), p-value < 0.001], as well as NCCT-ASPECTS [OR: 1.15 (1.06-1.25), p-value < 0.001], did show a significant association with functional outcomes. Model comparisons revealed that, profoundly, in patients with large core lesion volumes (CBV-ASPECTS < 6 or NCCT-ASPECTS < 6), perfusion mismatch showed a negative correlation with the mRS. Discussion and conclusion: Perfusion mismatch imaging within the first 6 h of symptom onset provides valuable insights into the outcome variability of LVO stroke patients receiving thrombectomy but only in patients with large ischemic core lesions.

Aß38 and Aß43 do not differentiate between Alzheimer's disease and cerebral amyloid angiopathy.

Differential diagnosis between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) using cerebrospinal fluid (CSF) biomarkers is challenging. A recent study suggested that the addition of Aß38 and Aß43 to a standard AD biomarker panel (Aß40, Aß42, t-tau, p-tau) to improve the differential diagnosis. We tested this hypothesis in an independent German cohort of CAA and AD patients and controls using the same analytical techniques. We found excellent discrimination between AD and controls and between CAA and controls, but not between AD and CAA. Adding Aß38 and Aß43 to the panel did not improve the discrimination between AD and CAA.

Early or late initiation of dabigatran versus vitamin-K-antagonists in acute ischemic stroke or TIA: The PRODAST study.

BACKGROUND: The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications. AIMS: In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA. METHODS: PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early (⩽ 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. RESULTS: Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10-2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00-13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints. CONCLUSIONS: The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate.

Characterizing mixed location hemorrhages/microbleeds with CSF markers.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. PATIENTS AND METHODS: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. RESULTS: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. CONCLUSION: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

Headache in the emergency room: the role of immigrant background on the frequency of serious causes and diagnostic procedures.

Headache is the most frequent neurological chief complaint in the emergency room (ER). During diagnostic workup, accurate history taking still is the mainstay for identification of patients with a serious underlying disorder. However, in patients with an immigrant background, language problems and cultural influences on pain perception and pain-associated behavior can pose serious challenges for physicians. Here, we have evaluated the epidemiological characteristics of the chief complaint headache in ER patients with a probable immigrant background. We performed a retrospective study on 4,132 consecutive neurological ER patients. Identification of patients with probable immigrant background was done by a name based algorithm. Epidemiological characteristics of ER headache patients with and without probable immigrant background were evaluated. Patients with a probable immigrant background had a higher frequency of headache as chief complaint compared to age- and sex-matched control patients (32 vs. 21%). In addition, headache patients with a probable immigrant background had a lower frequency of serious causes (5.2 vs. 16%). Approximately eight cranial imaging procedures and three lumbar punctures were performed for one serious diagnosis in patients with a probable immigrant background. In control patients, these ratios were three and one, respectively. Taken together, our data suggest that socio-cultural factors such as migrational status significantly affect pain-associated behavior of headache patients as well as the clinical workup in an ER. Culturally competent care may be optimized by interpreters, standardized headache questionnaires and easy access to cranial imaging when a benign etiology cannot be firmly established.

Acute Stroke and Atrial Fibrillation: Risk of Incorrect NOAC Dosage When Estimating Renal Function From Plasma Creatinine Only.

Background: Cardioembolic stroke (CS) due to atrial fibrillation (AF) bears a high risk of unfavorable outcome. Treatment with a non-vitamin K antagonist oral anticoagulant (NOAC) reduces this risk. NOAC dosage occurs on a thin line during the acute phase of the stroke unit when the patient is threatened by both recurrent CS and a hemorrhagic stroke. It is often adapted to renal function-usually glomerular filtration rate (GFR)-to prevent both under- and overdosing. This study investigates the hypothetical risk of incorrect NOAC dosage after acute stroke when relying on plasma creatinine alone in comparison to a more exact renal function assessment including urine collection. Methods: In a cohort study on consecutive 481 patients treated in a stroke unit with acute stroke and AF, the GFR estimated from plasma creatinine (eGFR) was compared to concurrent creatinine clearance measurement (CrCl) from urine collection regarding the hypothetically derived NOAC dosage. Results: The risk of incorrect dosage (mean, 95% confidence interval) was 6.9% (4.8-9.5), 26% (23-31), 38% (33-42), and 20% (16-23) for apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The overall risk for incorrect dosage of any NOAC was 23% (21-25). Thresholds for age and admission eGFR were optimized to achieve an overall risk below 5% by additional CrCl measurements in selected patients (apixaban <36 ml/min and any age, dabigatran <75 ml/min and >70 y, edoxaban >36 ml/min and >58 y, rivaroxaban <76 ml/min and >75 y, any NOAC <81 ml/min and >54 y). The resulting portion of patients requiring an additional CrCl measurement was 10, 60, 80, 55, and 65% for apixaban, dabigatran, edoxaban, rivaroxaban, and any NOAC, respectively. Conclusions: There is a considerable risk of incorrect NOAC dosage in patients with acute CS treated in a stroke unit that can be lowered by targeted CrCl measurements in selected patients.

On the quest for hidden ovarian teratomas in therapy-refractory anti-NMDA receptor encephalitis: a case report.

BACKGROUND: Anti-NMDA-receptor (anti-NMDAR) encephalitis is often associated with ovarian teratoma (OT). The best management of anti-NMDAR encephalitis patients with normal imaging studies (pelvic ultrasound/MRI) but clinically high risk of OT (e.g., female, adult, black) is unclear. We report on the surprising diagnostic quest in a young black woman with anti-NMDAR encephalitis, in whom invasive procedures could finally disclose two OTs that were hidden from the initial non-invasive diagnostics. CASE REPORT: The patient presented with a one-week history of psychotic symptoms, developing oro-facial dyskinesia, seizures and coma, eventually requiring mechanical ventilation. NMDA-receptor antibodies were positive in serum and cerebrospinal fluid. Pelvic MRI and transabdominal ultrasound were normal. Exploratory laparoscopy was also unremarkable at first, but due to a suspicious echogenic mass (15 mm) in the right ovary on perioperative transvaginal ultrasound, an ovarian incision was performed which led to the detection of a first OT and its removal via ovarian-preserving cystectomy. Following a severe therapy-refractory clinical course despite aggressive immunotherapy and tumor removal, 6 months later bilateral oophorectomy was performed as ultima ratio, disclosing a second micro-OT (6 mm) in the left ovary. Unfortunately, the patient has not improved clinically yet. CONCLUSIONS: In therapy-refractory anti-NMDAR encephalitis with high risk of OT, small and bilateral OTs hidden from primary non-invasive diagnostics should be considered, which may trigger further invasive diagnostic procedures.

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis.

BACKGROUND: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. METHODS: Beta-amyloid 1-40 (Aß40), beta-amyloid 1-42 (Aß42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. RESULTS: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. CONCLUSION: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.