Management of delirium in acute stroke patients: a position paper by the Austrian Stroke Society on prevention, diagnosis, and treatment.

Delirium is a common complication in acute stroke patients, occurring in 15-35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking. For this purpose, the Austrian Stroke Society, in cooperation with the Austrian Society of Neurology, the Austrian Society of Neurorehabilitation, and the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics has formulated an evidence-based position paper addressing the management of delirium in acute stroke patients. The paper outlines practical recommendations on the three pillars of care in stroke patients with delirium: (a) Key aspects of delirium prevention including stroke-specific delirium risk factors and delirium prediction scores are described. Moreover, a non-pharmacological delirium prevention bundle is presented. (b) The paper provides recommendations on timing and frequency of delirium screening to ensure early diagnosis of delirium in acute stroke patients. Moreover, it reports on the use of different delirium screening tools in stroke populations. (c) An overview of non-pharmacological and pharmacological treatment strategies in patients with delirium and acute stroke is presented and summarized as key recommendation statements.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

Background: 'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Objective: Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. Design and methods: This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. Results: We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Conclusion: Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Multiple sclerosis in the elderly: a retrospective cohort study.

BACKGROUND: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients. OBJECTIVE: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients. METHODS: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities. RESULTS: Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis. CONCLUSIONS: In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

Stroke risk factors and treatment variables in rural and urban Austria: An analysis of the Austrian Stroke Unit Registry.

BACKGROUND AND OBJECTIVES: Differences in stroke risk factors and treatment variables between rural and urban regions in Austria were analyzed retrospectively as European data on this topic are scarce. RESEARCH DESIGN AND METHODS: We performed statistical analysis using group comparisons and time series analysis of data of the Austrian Stroke Unit Registry between 2005 and 2016. 87411 patients were divided into three groups (rural, intermediate, urban) according to the degree of urbanisation classification of the European Commission/Eurostat. RESULTS: Patients in the rural group were significantly younger, more often female, had a lower pre-stroke disability, and were more frequently transported by an emergency physician. Vascular risk factors were significantly higher in urban patients, leading to a higher rate of microangiopathic etiology. Onset-to-door (ODT) and Onset-to-treatment times were significantly higher in the rural group, but ODTs decreased over time. Door-to-needle times and time to first vascular imaging were significantly lower in the rural group. Intravenous thrombolysis and rehabilitation rates were lower in urban patients. DISCUSSION AND IMPLICATIONS: Contrary to previous literature predominantly from outside of Europe, vascular risk factors were higher in Austrian urban patients. Further, rural patients had higher intravenous thrombolysis and rehabilitation rates maybe because of lower pre-stroke disability. ODTs in rural patients were generally higher, but they decreased over time, which might be a consequence of better education of the public in noticing early stroke signs, better transportation and education of emergency medical personnel, better advance notification to the receiving hospital and implementation of Stroke Units in rural areas.

Insights into Intrinsic Brain Networks based on Graph Theory and PET in right- compared to left-sided Temporal Lobe Epilepsy.

The human brain exhibits marked hemispheric differences, though it is not fully understood to what extent lateralization of the epileptic focus is relevant. Preoperative [(18)F]FDG-PET depicts lateralization of seizure focus in patients with temporal lobe epilepsy and reveals dysfunctional metabolic brain connectivity. The aim of the present study was to compare metabolic connectivity, inferred from inter-regional [(18)F]FDG PET uptake correlations, in right-sided (RTLE; n = 30) and left-sided TLE (LTLE; n = 32) with healthy controls (HC; n = 31) using graph theory based network analysis. Comparing LTLE and RTLE and patient groups separately to HC, we observed higher lobar connectivity weights in RTLE compared to LTLE for connections of the temporal and the parietal lobe of the contralateral hemisphere (CH). Moreover, especially in RTLE compared to LTLE higher local efficiency were found in the temporal cortices and other brain regions of the CH. The results of this investigation implicate altered metabolic networks in patients with TLE specific to the lateralization of seizure focus, and describe compensatory mechanisms especially in the CH of patients with RTLE. We propose that graph theoretical analysis of metabolic connectivity using [(18)F]FDG-PET offers an important additional modality to explore brain networks.

Prevention of poststroke cognitive decline: ASPIS--a multicenter, randomized, observer-blind, parallel group clinical trial to evaluate multiple lifestyle interventions--study design and baseline characteristics.

BACKGROUND: Cognitive impairment after stroke is a considerable burden to patients and their caregivers and occurs in one-third of stroke survivors. No strategy to prevent cognitive decline after stroke exists thus far. Established vascular risk factors have been associated with cognitive decline and may be a target for therapeutic interventions in stroke survivors. AIM: To test whether intensive multifactorial non-pharmacologic interventions based on lifestyle modification can reduce the risk of cognitive decline in patients who recently suffered ischemic stroke. METHODS: A randomized, controlled, multicenter, observer-blind trial was designed. The reference group obtains stroke care according to standard guidelines. The intervention group additionally receives intensive control and motivation for better compliance with prescribed evidence-based medication, regular blood pressure measurements, healthy diet, regular physical activity and cognitive training. Primary outcomes are the rate of cognitive decline at 24 months, assessed by a neuropsychological test battery and the cognitive subscale of the Alzheimer's Disease Assessment Scale. RESULTS: 202 patients (29% women), aged 62 ± 9 years, were recruited during 2010 to 2012. Stroke related impairment at inclusion was low (mean National Institutes of Health Stroke Scale: 1.9±1.8, median modified Rankin Scale: 1 (0-1)). At baseline, groups did not differ significantly in demographic, clinical or lifestyle characteristics. CONCLUSION: The recruitment was successful and the groups are balanced regarding potential confounding variables. The study will provide essential data about the feasibility and efficacy of lifestyle intervention after stroke in order to develop a new approach to prevent cognitive decline in patients with mild ischemic stroke.

Benefits of inpatient multidisciplinary rehabilitation in multiple sclerosis.

BACKGROUND: Rehabilitation is often recommended to MS-patients but data on its efficacy is limited. OBJECTIVE: To evaluate the benefit of inpatient multidisciplinary rehabilitation. METHODS: A rater-blinded, randomized, waiting list controlled exploratory study. 19 participants completed the study with ten allocated to the intervention and nine to the waiting list group. Assessment of outcome-parameters was done at baseline and after 3 months. Time Walking Tests (TWTs) and 9 Hole Peg Test were used to objectively assess the level of activity, Functional-Assessment-in-MS and MS-Self Efficacy-Scale to assess participation and quality of life and Expanded Disability Status Scale (EDSS) to assess bodily function. Additionally Rivermead Mobility Index, Berg Balance Scale, Tinetti-Test, MS-Functional Composite and a rater-blinded evaluation of a video-analysis on walking performance was done. RESULTS: Mean change scores of Timed 50 meter Walk (p = 0.014), walking speed (p = 0.034), 2- (p = 0.204) and 6-Minute Walk (p = 0.027) indicated an improvement favoring inpatient multidisciplinary rehabilitation. We could not demonstrate a benefit for upper limb function and some improvement was seen in other outcome-parameters without reaching statistical significance. EDSS remained unchanged. CONCLUSION: Inpatient multidisciplinary rehabilitation is effective in MS patients with positive impact on the level of activity as measured by TWTs covering both short and long distance ambulation.

Value of semiquantitative analysis for clinical reporting of 123I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)nortropane SPECT studies.

UNLABELLED: Clinical (123)I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) SPECT studies are commonly performed and reported using visual evaluation of tracer binding, an inherently subjective method. Increased objectivity can potentially be obtained using semiquantitative analysis. In this study, we assessed whether semiquantitative analysis of (123)I-FP-CIT tracer binding created more reproducible clinical reporting. A secondary aim was to determine in what form semiquantitative data should be provided to the reporter. METHODS: Fifty-four patients referred for the assessment of nigrostriatal dopaminergic degeneration were scanned using SPECT/CT, followed by semiquantitative analysis calculating striatal binding ratios (SBRs) and caudate-to-putamen ratios (CPRs). Normal reference values were obtained using 131 healthy controls enrolled on a multicenter initiative backed by the European Association of Nuclear Medicine. A purely quantitative evaluation was first performed, with each striatum scored as normal or abnormal according to reference values. Three experienced nuclear medicine physicians then scored each striatum as normal or abnormal, also indicating cases perceived as difficult, using visual evaluation, visual evaluation in combination with SBR data, and visual evaluation in combination with SBR and CPR data. Intra- and interobserver agreement and agreement between observers and the purely quantitative evaluation were assessed using κ-statistics. The agreement between scan interpretation and clinical diagnosis was assessed for patients with a postscan clinical diagnosis available (n = 35). RESULTS: The physicians showed consistent reporting, with a good intraobserver agreement obtained for the visual interpretation (mean κ ± SD, 0.95 ± 0.029). Although visual interpretation of tracer binding gave good interobserver agreement (0.80 ± 0.045), this was improved as SBRs (0.86 ± 0.070) and CPRs (0.95 ± 0.040) were provided. The number of striata perceived as difficult to interpret decreased as semiquantitative data were provided (30 for the visual interpretation; 0 as SBR and CPR values were given). The agreement between physicians' interpretations and the purely quantitative evaluation showed that readers used the semiquantitative data to different extents, with a more experienced reader relying less on the semiquantitative data. Good agreement between scan interpretation and clinical diagnosis was seen. CONCLUSION: A combined approach of visual assessment and semiquantitative analysis of tracer binding created more reproducible clinical reporting of (123)I-FP-CIT SPECT studies. Physicians should have access to both SBR and CPR data to minimize interobserver variability.