Cross-Correlation of Motor Activity Signals from dc-Magnetoencephalography, Near-Infrared Spectroscopy, and Electromyography

Neuronal and vascular responses due to finger movements were synchronously measured using dc-magnetoencephalography (dcMEG) and time-resolved near-infrared spectroscopy (trNIRS). The finger movements were monitored with electromyography (EMG). Cortical responses related to the finger movement sequence were extracted by independent component analysis from both the dcMEG and the trNIRS data. The temporal relations between EMG rate, dcMEG, and trNIRS responses were assessed pairwise using the cross-correlation function (CCF), which does not require epoch averaging. A positive lag on a scale of seconds was found for the maximum of the CCF between dcMEG and trNIRS. A zero lag is observed for the CCF between dcMEG and EMG. Additionally this CCF exhibits oscillations at the frequency of individual finger movements. These findings show that the dcMEG with a bandwidth up to 8 Hz records both slow and faster neuronal responses, whereas the vascular response is confirmed to change on a scale of seconds

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

Clinical Characterization of Symptomatic Microangiopathic Brain Lesions

Background: Microangiopathic brain lesions can be separated in diffuse lesions – leukoaraiosis – and focal lesions – lacunes. Leukoaraiosis and lacunes are caused by common cerebrovascular risk factors, but whether they represent a common entity is not sufficiently investigated. The present study aimed to determine the clinical profiles associated with the extent of leukoaraiosis and lacunes. Methods: Sixty-four consecutive patients with acute microangiopathic stroke were studied. Leukoaraiosis and lacunes were stratified according to their MRI-based extent. Standardized clinical assessment included clinical syndromes, cerebrovascular risk factors, cognitive performance, retinal imaging, ultrasonography, blood, and urine parameters. Results: Different clinical profiles for leukoaraiosis and lacunes were found. Regarding leukoaraiosis, the cognitive scores (SISCO, mini mental score examination, mental examination) and the presence of hyperlipidemia decreased as the severity of leukoaraiosis increased. Univariate and multivariate analysis revealed that these cognitive score values as well as the presence of hyperlipidemia correlated significantly with no or only mild leukoaraiosis. Regarding lacunes, the percentage of migraine, previous stroke events, hydrocephalus, left ventricular hypertrophy, and a higher National Institutes of Health Stroke Scale increased as the number of lacunar lesions increased. Statistical analysis revealed that these parameters correlated not significantly with the number of lacunes. Conclusions: The findings suggests that leukoaraiosis and lacunes are different microangiopathic entities potentially requiering different treatment concepts

GLM analysis of time resolved NIRS data of motor activation during different motor tasks

The hemodynamic response to motor activation was investigated by time-resolved NIRS in healthy subjects and patients with unilateral impairment in motor ability. Healthy subjects performed a simple and a complex finger movement task, patients a handgrip task. A General Linear Model approach (GLM) was applied during NIRS data processing. In general, compared to the integral (continuous wave signal), higher significance of activation was found for the variance signal that selectively represents changes in the deep compartment. A discussion of GLM results with respect to task complexity and difficulty is provided

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.peerReviewe

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry

Aims We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. Methods The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. Results At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. Conclusion At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge