Predictors of post-stroke delirium incidence and duration: Results of a prospective observational study using high-frequency delirium screening.

BACKGROUND: Post-stroke delirium (PSD) is a modifiable predictor for worse outcome in stroke. Knowledge of its risk factors would facilitate clinical management of affected patients, but recently updated national guidelines consider available evidence insufficient. AIMS: The study aimed to establish risk factors for PSD incidence and duration using high-frequency screening. METHODS: We prospectively investigated patients with ischemic stroke admitted within 24 h. Patients were screened twice daily for the presence of PSD throughout the treatment period. Sociodemographic, treatment-related, and neuroimaging characteristics were evaluated as predictors of either PSD incidence (odds ratios (OR)) or duration (PSD days/unit of the predictor, b), using logistic and linear regression models, respectively. RESULTS: PSD occurred in 55/141 patients (age = 73.8 ± 10.4 years, 61 female, National Institutes of Health Stroke Scale (NIHSS) = 6.4 ± 6.5). Age (odds ratio (OR) = 1.06 (95% confidence interval (CI): 1.02-1.10), b = 0.08 (95% CI = 0.04-0.13)), and male gender (b = 0.99 (95% CI = 0.05-1.93)) were significant non-modifiable risk factors. In a multivariable model adjusted for age and gender, presence of pain (OR < sub > mvar = 1.75 (95% CI = 1.12-2.74)), urinary catheter (OR < sub > mvar = 3.16 (95% CI = 1.10-9.14)) and post-stroke infection (PSI; OR < sub > mvar = 4.43 (95% CI = 1.09-18.01)) were predictors of PSD incidence. PSD duration was impacted by presence of pain (b < sub > mvar = 0.49 (95% CI = 0.19-0.81)), urinary catheter (b < sub > mvar = 1.03 (95% CI = 0.01-2.07)), intravenous line (b < sub > mvar = 0.36 (95% CI = 0.16-0.57)), and PSI (b < sub > mvar = 1.60 (95% CI = 0.42-2.78)). PSD (OR = 3.53 (95% CI = 1.48-5.57)) and PSI (OR = 5.29 (95% CI = 2.92-7.66)) independently predicted inferior NIHSS at discharge. Insular and basal ganglia lesions increased the PSD risk about four- to eight-fold. DISCUSSION/CONCLUSION: This study identified modifiable risk factors, the management of which might reduce the negative impact PSD has on outcome.

Splenic rupture and fungal endocarditis in a pediatric patient with invasive fusariosis after allogeneic hematopoietic stem cell transplantation for aplastic anemia: A case report.

Background: Invasive mold infections are a well-known and life-threatening condition after allogeneic hematopoietic stem cell transplantation (HSCT). While Aspergillus species are recognized as predominant pathogens, Fusarium species should also be considered due to their broad environmental distribution and the expected poor outcome of invasive fusariosis. Particularly, splenic rupture as a complication of disseminated disease has not been reported yet. Case presentation: Two weeks after allogeneic HSCT for severe aplastic anemia, a 16-year-old boy presented with painful, erythematous skin nodules affecting the entire integument. As disseminated mycosis was considered, treatment with liposomal amphotericin B and voriconazole (VCZ) was initiated. Invasive fusariosis was diagnosed after histological and previously unpublished polymerase chain reaction-based examination of skin biopsies. Microbiological tests revealed Fusarium solani species. Despite stable neutrophil engraftment and uninterrupted treatment with VCZ, he developed mold disease-associated splenic rupture with hypovolemic shock and fungal endocarditis. The latter induced a cardiac thrombus and subsequent embolic cerebral infarctions with unilateral hemiparesis. Following cardiac surgery, the patient did not regain consciousness because of diffuse cerebral ischemia, and he died on day +92 after HSCT. Conclusion: Invasive fusariosis in immunocompromised patients is a life-threatening condition. Despite antimycotic treatment adapted to antifungal susceptibility testing, the patient reported here developed uncommon manifestations such as splenic rupture and fungal endocarditis.

Prevalence of SARS-CoV-2 IgG antibodies among dental teams in Germany.

OBJECTIVES: During the corona pandemic, dental practices temporarily closed their doors to patients except for emergency treatments. Due to the daily occupational exposure, the risk of SARS-CoV-2 transmission among dentists and their team is presumed to be higher than that in the general population. This study examined this issue among dental teams across Germany. MATERIALS AND METHODS: In total, 2784 participants provided usable questionnaires and dry blood samples. Dry blood samples were used to detect IgG antibodies against SARS-CoV-2. The questionnaires were analyzed to investigate demographic data and working conditions during the pandemic. Multivariable logistic mixed-effects models were applied. RESULTS: We observed 146 participants with positive SARS-CoV-2 IgG antibodies (5.2%) and 30 subjects with a borderline finding (1.1%). Seventy-four out of the 146 participants with SARS-CoV-2 IgG antibodies did not report a positive SARS-CoV-2 PCR test (50.7%), while 27 participants without SARS-CoV-2 IgG antibodies reported a positive SARS-CoV-2 PCR test (1.1%). Combining the laboratory and self-reported information, the number of participants with a SARS-CoV-2 infection was 179 (6.5%). Though after adjustment for region, mixed-effects models indicated associations of use of rubber dams (OR 1.65; 95% CI: 1.01-2.72) and the number of protective measures (OR 1.16; 95% CI: 1.01-1.34) with increased risk for positive SARS-CoV-2 status, none of those variables was significantly associated with a SARS-CoV-2 status in fully adjusted models. CONCLUSIONS: The risk of SARS-CoV-2 transmission was not higher among the dental team compared to the general population. CLINICAL RELEVANCE: Following hygienic regulations and infection control measures ensures the safety of the dental team and their patients.

A flow cytometric assay to detect platelet-activating antibodies in VITT after ChAdOx1 nCov-19 vaccination.

Vaccination is crucial in combatting the severe acute respiratory syndrome coronavirus 2 pandemic. The rare complication of thrombocytopenia and thrombotic complications at unusual sites after ChAdOx1 nCov-19 vaccination is caused by platelet-activating antibodies directed against platelet factor 4 (PF4). We present a widely applicable whole-blood standard flow cytometric assay to identify the pathogenic antibodies associated with vaccine-induced immune-mediated thrombotic thrombocytopenia (VITT) after ChAdOx1 nCov-19 vaccination. This assay will enable rapid diagnosis by many laboratories. This trial was registered at www.clinicaltrials.gov as #NCT04370119.

Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2.

Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.

External Validation of Five Scores to Predict Stroke-Associated Pneumonia and the Role of Selected Blood Biomarkers.

BACKGROUND AND PURPOSE: Several clinical scoring systems as well as biomarkers have been proposed to predict stroke-associated pneumonia (SAP). We aimed to externally and competitively validate SAP scores and hypothesized that 5 selected biomarkers would improve performance of these scores. METHODS: We pooled the clinical data of 2 acute stroke studies with identical data assessment: STRAWINSKI and PREDICT. Biomarkers (ultrasensitive procalcitonin; mid-regional proadrenomedullin; mid-regional proatrionatriuretic peptide; ultrasensitive copeptin; C-terminal proendothelin) were measured from hospital admission serum samples. A literature search was performed to identify SAP prediction scores. We then calculated multivariate regression models with the individual scores and the biomarkers. Areas under receiver operating characteristic curves were used to compare discrimination of these scores and models. RESULTS: The combined cohort consisted of 683 cases, of which 573 had available backup samples to perform the biomarker analysis. Literature search identified 9 SAP prediction scores. Our data set enabled us to calculate 5 of these scores. The scores had area under receiver operating characteristic curve of 0.543 to 0.651 for physician determined SAP, 0.574 to 0.685 for probable and 0.689 to 0.811 for definite SAP according to Pneumonia in Stroke Consensus group criteria. Multivariate models of the scores with biomarkers improved virtually all predictions, but mostly in the range of an area under receiver operating characteristic curve delta of 0.05. CONCLUSIONS: All SAP prediction scores identified patients who would develop SAP with fair to strong capabilities, with better discrimination when stricter criteria for SAP diagnosis were applied. The selected biomarkers provided only limited added predictive value, currently not warranting addition of these markers to prediction models. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01264549 and NCT01079728.

Inflammatory and stress markers predicting pneumonia, outcome, and etiology in patients with stroke: Biomarkers for predicting pneumonia, functional outcome, and death after stroke.

OBJECTIVE: Prognosis of stroke is negatively affected by complications, in particular stroke-associated pneumonia (SAP). We hypothesized that inflammatory and stress biomarkers predict SAP during hospitalization and outcome 3 months after stroke. METHODS: We pooled the clinical data of 2 acute stroke studies with identical assessment: the STRoke Adverse outcome is associated WIth NoSoKomial Infections (STRAWINSKI) and PREDICT studies. Measurement of biomarkers (ultrasensitive procalcitonin [PCTus]; midregional pro-adrenomedullin; midregional pro-atrial natriuretic peptide [MRproANP]; ultrasensitive copeptin [CPus]; C-terminal pro-endothelin) was performed from serum samples drawn on the first 4 days of hospital admission. RESULTS: The combined cohort consists of 573 cases with available backup samples to perform the analysis. SAP was associated with increased admission and maximum levels of all biomarkers. Furthermore, all biomarkers were associated with death and correlated with functional outcome 3 months after stroke. The multivariate logistic regression model retained ultrasensitive CPus and PCTus beyond clinical risk factors for predicting SAP, improving the receiver operating characteristic area under the curve (AUC) from 0.837 to 0.876. In contrast, the biomarkers did not improve the prediction of death and functional outcome in the multivariate model. Cardioembolic strokes were significantly associated with higher values of all biomarkers, whereas discrimination was best for MRproANP (AUC = 0.811 for maximum value). CONCLUSIONS: The tested biomarkers are associated with SAP and poor functional outcome. However, these biomarkers only slightly improve prediction of SAP and do not improve long-term outcome prediction over clinical parameters. MRproANP showed the best discrimination for identifying cardioembolic stroke, warranting further studies to confirm our finding. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01264549 and NCT01079728.

IL-6 Plasma Levels Correlate With Cerebral Perfusion Deficits and Infarct Sizes in Stroke Patients Without Associated Infections.

Introduction: We aimed to investigate several blood-based biomarkers related to inflammation, immunity, and stress response in a cohort of patients without stroke-associated infections regarding their predictive abilities for functional outcome and explore whether they correlate with MRI markers, such as infarct size or location. Methods: We combined the clinical and radiological data of patients participating in two observational acute stroke cohorts: the PREDICT and 1000Plus studies. The following blood-based biomarkers were measured in these patients: monocytic HLA-DR, IL-6, IL-8, IL-10, LBP, MRproANP, MRproADM, CTproET, Copeptin, and PCT. Multiparametric stroke MRI was performed including T2*, DWI, FLAIR, TOF-MRA, and perfusion imaging. Standard descriptive sum statistics were used to describe the sample. Associations were analyzed using Fischer's exact test, independent samples t-test and Spearmans correlation, where appropriate. Results: Demographics and stroke characteristics were as follows: 94 patients without infections, mean age 68 years (SD 10.5), 32.2% of subjects were female, median NIHSS score at admission 3 (IQR 2-5), median mRS 3 months after stroke 1 (IQR 0-2), mean volume of DWI lesion at admission 5.7 ml (SD 12.8), mean FLAIR final infarct volume 10 ml (SD 14.9), cortical affection in 61% of infarctions. Acute DWI lesion volume on admission MRI was moderately correlated to admission/maximum IL-6 as well as maximum LBP. Extent of perfusion deficit and mismatch were moderately correlated to admission/maximum IL-6 levels. Final lesion volume on FLAIR was moderately correlated to admission IL-6 levels. Conclusion: We found IL-6 to be associated with several parameters from acute stroke MRI (acute DWI lesion, perfusion deficit, final infarct size, and affection of cortex) in a cohort of patients not influenced by infections. Clinical Trial Registration: www.ClinicalTrials.gov, identifiers NCT01079728 and NCT00715533.

Selection bias in clinical stroke trials depending on ability to consent.

BACKGROUND: Clinical trials are the hallmark of evidence-based medicine, but recruitment is often challenging, especially in stroke trials investigating patients not being able to give informed consent. In some nations, ethics committees will not approve of inclusion in a clinical study via consent of a legal representative. The ethical dilemma of including or excluding those patients has not been properly addressed, as there is little data on the effect of stroke characteristics on the ability to give informed consent. METHODS: To examine differences between patients able and unable to consent at inclusion to an acute stroke trial, we conducted a post-hoc analysis of monitoring records from a multicentric interventional trial. These records listed patients who gave informed consent by themselves and those who needed a legal representative to do so. This exemplary STRAWINSKI trial aimed at improving stroke outcome by biomarker-guided antibiotic treatment of stroke associated pneumonia and included patients within 40 h after stroke onset, suffering from MCA infarctions with an NIHSS score > 9 at admission. Standard descriptive and associative statistics were calculated to compare baseline characteristics and outcome measures between patients who were able to consent and those who were not. RESULTS: We identified the person giving consent in 228 out of 229 subjects. Patients with inability to consent were older (p < 0.01), suffered from more left-hemispheric (p < 0.01) and more severe strokes (NIHSS, p < 0.01), were more likely to die during hospitalisation (p < 0.01) or have unfavourable outcome at discharge (mRS, p < 0.01), to develop fever (p < 0.01) and tended to be more susceptible to infections (p = 0.06) during the acute course of the disorder. CONCLUSIONS: Demographics, stroke characteristics and outcomes significantly affect stroke patients in their ability to consent. Where selection criteria and primary outcome measures of a trial are significantly affected by ability to consent, excluding patients unable to consent might be unethical. TRIAL REGISTRATION: URL http://www.clinicaltrials.gov . Unique identifier: NCT01264549 .

The Randomized Controlled STRAWINSKI Trial: Procalcitonin-Guided Antibiotic Therapy after Stroke.

BACKGROUND: Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment. AIMS: This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke. METHODS: In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549). RESULTS: In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45-1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001). CONCLUSION: PCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.

Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

Neural Mechanisms Underlying Perilesional Transcranial Direct Current Stimulation in Aphasia: A Feasibility Study.

Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS) impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI). We employed a single subject, cross-over, sham-tDCS controlled design, and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI, which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioral stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS effects on brain functions in aphasia.

Circulating lymphocyte and T memory subsets in glucocorticosteroid versus IVIG treated patients with CIDP.

The present study compared lymphocyte and T memory subsets in currently untreated patients with chronic inflammatory demyelinating polyneuropathy (CIDP) to glucocorticosteroid (GS) and intravenous immunoglobulin (IVIG) treated patients. Peripheral blood from 48 CIDP patients (21 untreated who were either treatment naïve or without treatment during the last 3 months, 17 IVIG and 10 GS treatment) and from 12 age-matched controls was evaluated using flow cytometric analysis. Our data demonstrate that long-term GS treatment is associated with reduced frequencies of total CD4+ T cells, CD4+ memory subsets and NK cells while long-term IVIG treatment is associated with alterations of the CD8+ memory compartment. Reduction of CD4+ naïve T cell counts may explain the observation that GS treatment induces prolonged clinical remission compared to IVIG treatment.

Effective treatment with intravenous immunoglobulins reduces autoreactive T-cell response in patients with CIDP.

OBJECTIVE: To investigate changes in autoreactive T-cell responses against PMP-22 and P2 antigen as well as a T-cell memory repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) induced by repeated intravenous immunoglobulin (IVIg) treatment. METHODS: In an observational trial, we prepared cryopreserved human peripheral blood monocytes from blood from 34 patients with CIDP (18 treatment naïve and 16 maintenance IVIg treatment) and from 14 healthy controls (non-immune neuropathy and healthy control). Treatment response was defined by clinical evaluation. The autoantigen-specific T-cell response was analysed by enzyme linked immunosorbent spot (ELISPOT) assay before IVIg start (baseline) and at follow-up. The T-cell memory subsets were analysed by using flow cytometric analysis. RESULTS: Myelin-derived P2-specific and PMP-22-specific IFN-γ producers were increased in IVIg responders compared with non-responders before treatment, which decreased by repeated IVIg infusion cycles. Treatment responders but not non-responders showed higher frequencies of CD4 T effector memory (TEM) and T central memory frequencies at baseline compared with maintenance IVIg treatment patients and controls. In addition, IVIg treatment was associated with a significant reduction in CD8 TEM at follow-up. CONCLUSIONS: Our data demonstrate that immunomodulatory treatment with IVIgs on a long-term basis reduces the autoreactive T-cell response against PMP-22 and P2-antigens, which may be influenced by the altered maintenance of CD8 and CD4 effector/memory T-cell subsets towards a more anti-inflammatory immune status. Elevated PMP-22 and P2-specific T-cell responses may serve as predictors for treatment responsiveness to IVIgs warranting validation in larger studies.

Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms.

INTRODUCTION: The long preclinical phase of Alzheimer's disease provides opportunities for potential disease-modifying interventions in prodromal stages such as mild cognitive impairment (MCI). Anodal transcranial direct current stimulation (anodal-tDCS), with its potential to enhance neuroplasticity, may allow improving cognition in MCI. METHODS: In a double-blind, cross-over, sham-controlled study, anodal-tDCS was administered to the left inferior frontal cortex during task-related and resting-state functional magnetic resonance imaging (fMRI) to assess its impact on cognition and brain functions in MCI. RESULTS: During sham stimulation, MCI patients produced fewer correct semantic-word-retrieval responses than matched healthy controls, which was associated with hyperactivity in bilateral prefrontal regions. Anodal-tDCS significantly improved performance to the level of controls, reduced task-related prefrontal hyperactivity and resulted in "normalization" of abnormal network configuration during resting-state fMRI. DISCUSSION: Anodal-tDCS exerts beneficial effects on cognition and brain functions in MCI, thereby providing a framework to test whether repeated stimulation sessions may yield sustained reversal of cognitive deficits.

Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in improved performance.

Transcranial direct current stimulation and simultaneous functional magnetic resonance imaging.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity. Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

Changes in chronotype after stroke: a pilot study.

This study aimed to elucidate associations between stroke onset and severity as well as chronotype (phase of entrainment) and internal time of stroke. Fifty-six first-ever ischemic stroke patients participated in a cross-sectional study assessing chronotype (mid-sleep on work-free days corrected for sleep deficit on workdays; MSFsc) by applying the Munich ChronoType Questionnaire (MCTQ). The MCTQ was completed twice, on average 68 ± 24 (SD) days post stroke and retrospectively for the time before stroke. To assess the impact of stroke in relation to internal time, InTstroke was calculated as MSFsc minus local time of stroke. Stroke severity was assessed via the standard clinical National Institute Health Stroke Scale (NIHSS) and modified Ranking Scale (mRS), both at hospital admission and discharge. Overall, most strokes occurred between noon and midnight. There was no significant association between MSFsc and stroke onset. MSFsc changed significantly after stroke, especially in patients with more severe strokes. Changes in MSFsc varied with InTstroke - the earlier the internal time of a stroke relative to MSFsc-before-stroke, the more MSFsc advanced after stroke. In addition, we provide first evidence that MSFsc changes varied between stroke locations. Larger trials are needed to confirm these findings.

A circle-monitor for computerised assessment of visual neglect in peripersonal space.

UNLABELLED: Current assessment of visual neglect involves paper-and-pencil tests or computer-based tasks. Both have been criticised because of their lack of ecological validity as target stimuli can only be presented in a restricted visual range. This study examined the user-friendliness and diagnostic strength of a new "Circle-Monitor" (CM), which enlarges the range of the peripersonal space, in comparison to a standard paper-and-pencil test (Neglect-Test, NET). METHODS: Ten stroke patients with neglect and ten age-matched healthy controls were examined by the NET and the CM test comprising of four subtests (Star Cancellation, Line Bisection, Dice Task, and Puzzle Test). RESULTS: The acceptance of the CM in elderly controls and neglect patients was high. Participants rated the examination by CM as clear, safe and more enjoyable than NET. Healthy controls performed at ceiling on all subtests, without any systematic differences between the visual fields. Both NET and CM revealed significant differences between controls and patients in Line Bisection, Star Cancellation and visuo-constructive tasks (NET: Figure Copying, CM: Puzzle Test). Discriminant analyses revealed cross-validated assignment of patients and controls to groups was more precise when based on the CM (hit rate 90%) as compared to the NET (hit rate 70%). CONCLUSION: The CM proved to be a sensitive novel tool to diagnose visual neglect symptoms quickly and accurately with superior diagnostic validity compared to a standard neglect test while being well accepted by patients. Due to its upgradable functions the system may also be a valuable tool not only to test for non-visual neglect symptoms, but also to provide treatment and assess its outcome.