Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis

In recent years, new antibodies have been discovered which mediate autoimmune encephalitis. This immunological response can be triggered by an infection or a tumor. Classical onconeuronal antibodies are directed against intracellular neuronal agents but recently, a novel group of antibodies to neuronal cell-surface and synaptic antigens associated with different CNS-syndromes, has been discovered. Interestingly, the syndromes in this group can be successfully treated with immunotherapy and frequently do not have underlying tumors. The aim of this review is to describe the current state of knowledge about autoimmune encephalitis, in order to provide clinicians with a concise, up-to-date overview. Thus, a comprehensive literature search was performed in medical databases. The literature was carefully studied and new findings focusing on the symptoms, diagnosis and treatment were summarized and interpreted. Even though it might be challenging in some cases, the awareness of certain symptom constellations and demographic information, in combination with laboratory- and MRI-results, allows clinicians to make the diagnosis of probable autoimmune encephalitis at an early stage. Treatment can therefore be initiated faster, which significantly improves the outcome. Further investigations could define the underlying pathogenic mechanisms. Randomized controlled trials, paired with increasing clinical experience, will be necessary to improve the identification of affected patients, treatment strategies, and outcomes in the years to come

Susceptibility induced gray–white matter MRI contrast in the human brain

AbstractMR phase images have shown significantly improved contrast between cortical gray and white matter regions compared to magnitude images obtained with gradient echo sequences. A variety of underlying biophysical mechanisms (including iron, blood, myelin content, macromolecular chemical exchange, and fiber orientation) have been suggested to account for this observation but assessing the individual contribution of these factors is limited in vivo.For a closer investigation of iron and myelin induced susceptibility changes, postmortem MRI of six human corpses (age range at death: 56–80years) was acquired in situ. Following autopsy, the iron concentrations in the frontal and occipital cortex as well as in white matter regions were chemically determined. The magnetization transfer ratio (MTR) was used as an indirect measure for myelin content. Susceptibility effects were assessed separately by determining R2* relaxation rates and quantitative phase shifts. Contributions of myelin and iron to local variations of the susceptibility were assessed by univariate and multivariate linear regression analysis.Mean iron concentration was lower in the frontal cortex than in frontal white matter (26±6 vs. 45±6mg/kg wet tissue) while an inverse relation was found in the occipital lobe (cortical gray matter: 41±10 vs. white matter: 34±10mg/kg wet tissue). Multiple regression analysis revealed iron and MTR as independent predictors of the effective transverse relaxation rate R2* but solely MTR was identified as source of MR phase contrast. R2* was correlated with iron concentrations in cortical gray matter only (r=0.42, p<0.05).In conclusion, MR phase contrast between cortical gray and white matter can be mainly attributed to variations in myelin content, but not to iron concentration. Both, myelin and iron impact the effective transverse relaxation rate R2* significantly. Magnitude contrast is limited because it only reflects the extent but not the direction of the susceptibility shift

Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage: results of the Austrian Stroke Prevention Study

BACKGROUND AND PURPOSE: Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the most important risk factors. We assessed the association between MARCD and sequence alterations in the promoter region of the angiotensinogen (AGT) gene. METHODS: We studied 410 randomly selected community-dwelling individuals aged 50 to 75 years. MARCD was defined as early confluent or confluent white matter hyperintensities or lacunes on a 1.5-T MRI. The AGT promoter was analyzed by temporal temperature gradient gel electrophoresis and automated sequencing. RESULTS: We detected 4 polymorphic sites, at positions -6, -20, -153, and -218. They created 5 haplotypes, which we coded as A (-6:g, -20:a, -153:g, -218g), B (-6:a, -20:c, -153:g, -218:g), C (-6:a, -20:c, -153:a, -218:g), D (-6:a, -20:a, -153:g, -218:g), and E (-6:a, -20:a, -153:g, -218:a). MARCD was seen in 7 subjects (63.6%) carrying 2 copies of the B haplotype (B/B), in 12 subjects (38.7%) carrying 1 copy of the B haplotype in the absence of the A haplotype (B+/A-), but in only 70 subjects (19.0%) in the remaining cohort (P:<0.001). The odds ratios for the B/B and the B+/A- genotypes were 8.0 (95% CI, 2.1 to 31.1; P:=0.003) and 1.8 (95% CI, 0.8 to 4.2; P:=0.14) after adjustment for possible confounders. CONCLUSIONS: The B haplotype of the AGT promoter in the absence of the wild-type A haplotype might represent a genetic susceptibility factor for MARCD

Are morphologic features of recent small subcortical infarcts related to specific etiologic aspects?

Background: Recent small subcortical infarcts (RSSIs) mostly result from the occlusion of a single, small, brain artery due to intrinsic cerebral small-vessel disease (CSVD). Some RSSIs may be attributable to other causes such as cardiac embolism or large-artery disease, and their association with coexisting CSVD and vascular risk factors may vary with morphological magnetic resonance imaging (MRI) features. Methods: We retrospectively identified all inpatients with a single symptomatic MRI-confirmed RSSI between 2008 and 2013. RSSIs were rated for size, shape, location (i.e. anterior: basal ganglia and centrum semiovale posterior cerebral circulation: thalamus and pons) and MRI signs of concomitant CSVD. In a further step, clinical data, including detailed diagnostic workup and vascular risk factors, were analyzed with regard to RSSI features. Results: Among 335 RSSI patients (mean age 71.1 ± 12.1 years), 131 (39%) RSSIs were >15 mm in axial diameter and 66 (20%) were tubular shaped. Atrial fibrillation (AF) was present in 44 (13.1%) and an ipsilateral vessel stenosis > 50% in 30 (9%) patients. Arterial hypertension and CSVD MRI markers were more frequent in patients with anterior-circulation RSSIs, whereas diabetes was more prevalent in posterior-circulation RSSIs. Larger RSSIs occurred more frequently in the basal ganglia and pons, and the latter were associated with signs of large-artery atherosclerosis. Patients with concomitant AF had no specific MRI profile. Conclusion: Our findings suggest the contribution of different pathophysiological mechanisms to the occurrence of RSSIs in the anterior and posterior cerebral circulation. While there appears to be some general association of larger infarcts in the pons with large-artery disease, we found no pattern suggestive of AF in RSSIs

Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke

Objectives From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients. Methods In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke. Results Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections. Conclusions LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections

Off Equilibrium Study of the Fluctuation-Dissipation Relation in the Easy-Axis Heisenberg Antiferromagnet on the Kagome Lattice

Violation of the fluctuation-dissipation theorem (FDT) in a frustrated Heisenberg model on the Kagome lattice is investigated using Monte Carlo simulations. The model exhibits glassy behaviour at low temperatures accompanied by very slow dynamics. Both the spin-spin autocorrelation function and the response to an external magnetic field are studied. Clear evidence of a constant value of the fluctuation dissipation ratio and long range memory effects are observed for the first time in this model. The breakdown of the FDT in the glassy phase follows the predictions of the mean field theory for spin glasses with one-step replica symmetry breaking.Comment: 4 pages, 4 figure

Results From the Austrian Stroke Unit Registry

Evaluation of: Gattringer T, Ferrari J, Knoflach M et al. Sex-related differences of acute stroke unit care results from an Austrian stroke unit registry. Stroke 45, 1632–1638 (2014). The authors analyzed data from 47,209 patients diagnosed with ischemic stroke or transient ischemic attack from January 2005 to December 2012. In this study, epidemiological data, stroke type, diagnostics and clinical scores were analyzed for age-adjusted preclinical and clinical characteristics as well as quality of acute stroke care. Moreover, outcome at 3 months was included in a multivariate model corrected for demographic and clinical confounders. While there were no reported sex differences in stroke care and thrombolysis rates, males more often received magnetic resonance imaging (MRI) brain scans. From follow-up data, a worse functional outcome was observed for females in univariate and multivariate analysis. In fact, females were less likely to be prescribed statins and more likely to receive antiplatelet therapy. A..

Planning of stroke care and urgent prehospital care across Europe : Results of the ESO/ESMINT/EAN/SAFE Survey

Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SA is co-PI of the RACECAT trial. VC received grants and speaker fees from BI. UF is consultant for Stryker, Medtronic and CSL Behring; Research grant from the Swiss National Science Foundation, Swiss Heart Foundation and Medtronic. DAS, TG, FF, AK, IZ, MG and VF have no disclosures. Funding Information: The authors are grateful to all ?ESO/ESMINT/EAN/SAFE Survey on Stroke Care in Europe? collaborators. We are also in debt to Bo Norrving, Didier Leys, Kennedy Lees and Turgut Tatlisumak for their useful comments regarding the questionnaire, data collection methodology and policy implications of this paper. Publisher Copyright: © European Stroke Organisation 2019.Introduction: Adequate planning and implementation of stroke systems of care is key to guarantee a rapid healthcare response and delivery of specific reperfusion therapies among candidates. We assessed the availability of stroke care plans in Europe, and evaluated their impact on rates of reperfusion therapies for stroke. Patients: Based on the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN), and the Stroke Alliance for Europe (SAFE) survey, we analysed specific prespecified items in the questionnaire regarding availability and adequacy of stroke care plans, organised prehospital care and their potential impact on rates of delivery of reperfusion therapies for stroke at the country level. Results: Of 44 participating European countries, 37 have stroke care plans that operate at national and/or regional levels. Most stroke care plans take responsibility for the organisation/implementation of stroke systems of care (86%), quality of care assessment (77%), and act as a liaison between emergency medical systems and stroke physicians (79%). As for stroke systems of care, the focus is mainly on prehospital and in-hospital acute stroke care (Code Stroke systems available in 37/44 countries). Preferred urgent transport is via non-medicalised ambulances (70%). Presence of stroke care plans, stroke registry data, transport of urgent stroke patients via non-medicalised ambulances, and drip-and-ship routing of acute patients showed higher reperfusion treatment rates. Discussion: Availability of stroke care plans, still absent in some European countries, as well as some features of the stroke systems of care are associated with higher reperfusion treatment rates. Conclusion: Stroke is not yet a priority everywhere in Europe, which is a barrier to the spread of reperfusion therapies for stroke.publishersversionPeer reviewe

Sparse Decomposition and Modeling of Anatomical Shape Variation

Recent advances in statistics have spawned powerful methods for regression and data decomposition that promote sparsity, a property that facilitates interpretation of the results. Sparse models use a small subset of the available variables and may perform as well or better than their full counterparts if constructed carefully. In most medical applications, models are required to have both good statistical performance and a relevant clinical interpretation to be of value. Morphometry of the corpus callosum is one illustrative example. This paper presents a method for relating spatial features to clinical outcome data. A set of parsimonious variables is extracted using sparse principal component analysis, producing simple yet characteristic features. The relation of these variables with clinical data is then established using a regression model. The result may be visualized as patterns of anatomical variation related to clinical outcome. In the present application, landmark-based shape data of the corpus callosum is analyzed in relation to age, gender, and clinical tests of walking speed and verbal fluency. To put the data-driven sparse principal component method into perspective, we consider two alternative techniques, one where features are derived using a model-based wavelet approach, and one where the original variables are regressed directly on the outcome