Plasma bioactive adrenomedullin predicts outcome after acute stroke in early rehabilitation.

An early and reliable prediction of outcomes after stroke is important for early effective stroke management and the adequate optimal planning of post-stroke rehabilitation and long-term care. Bioactive adrenomedullin (bio-ADM) is a 52-amino acid peptide that is an important peptide hormone in nervous system diseases. The aim of this study was to investigate the prognostic value of bio-ADM on outcomes after rehabilitation in patients with stroke. A total of 557 consecutive patients with a primary diagnosis of ischemic or hemorrhagic stroke (age 69.6-12.9 years, male 51.3%, ischemic stroke 72.5%), who were admitted to an in-patient early rehabilitation center directly after discharge from acute stroke hospital care, were enrolled in this prospective observational study. Plasma concentrations of bio-ADM were determined by using a chemiluminescence immunoassay (functional assay sensitivity 8 pg/ml). The early rehabilitation barthel index (ERBI) was used for the neurological assessment of the patients. The plasma bio-ADM level was analyzed in association with 6-month all-cause mortality as well as a composite outcome of all-cause mortality, unscheduled re-hospitalization, or transfer to a long-term care facility in a vegetative or minimally conscious state. Bio-ADM levels significantly increased in patients with ischemic stroke who died compared to surviving patients (40.4 pg/ml vs. 23.8 pg/ml, p < 0.001) or in those with composite outcomes compared to those with no events (36.9 pg/ml vs. 23.5 pg/ml, p < 0.001). Six-month all-cause mortality was higher in all patients with bio-ADM levels > 70 pg/ml (HR 4.83 [CI 2.28-10.2]). Patients with bio-ADM levels > 70 pg/ml also had higher rates of 6-month composite outcomes (HR 3.82 [CI 2.08-7.01]). Bio-ADM was an independent predictor of all-cause mortality and 6-month composite outcomes after adjusting for age, gender, and ERBI (adjusted OR 1.5; 95% CI 1.0-2.1; p = 0.047 and adjusted OR 1.48; 95% CI 1.1-2.0; p = 0.01, respectively). Bio-ADM may be a suitable novel biomarker to assess the outcomes of patients in rehabilitation after acute stroke. Elevated bio-ADM concentrations may have prognostic value for fatal and nonfatal events in patients with ischemic stroke during early rehabilitation.

Prominent Fatigue but No Motor Fatigability in Non-Hospitalized Patients With Post-COVID-Syndrome.

Objectives: Fatigue is a frequent and often disabling symptom in patients with post-COVID syndrome. To better understand and evaluate the symptom of motor fatigue in the context of the post-COVID syndrome, we conducted treadmill walking tests to detect the phenomenon of motor fatigability or to evaluate whether evidence of organic lesions of the motor system could be found, similar to patients with multiple sclerosis. Method: Twenty-nine non-hospitalized patients with post-COVID syndrome completed the Fatigue Scale for Motor and Cognitive Function (FSMC) questionnaire to determine the trait component of subjective fatigue before they were tested on a treadmill walking at a moderate speed for up to 60 min or until exhaustion. During the walking test oxygen uptake, ventilation and acceleration data of both feet were collected. To determine motor performance fatigability, the Fatigue Index Kliniken Schmieder (FKS) was calculated using the attractor method. Results: The average walking duration was 42.7 ± 18.6 min with 15 subjects stopping the walking test prematurely. The FSMC score revealed a severe cognitive (37.6 ± 8.2) and motor (37.1 ± 7.8) fatigue averaged over all subjects but only two subjects showed an FKS above the normal range (>4), representing performance fatigability. There was no significant correlation between subjective fatigue (FSMC) and FKS as well as walking time. Absolute values of oxygen uptake and ventilation were in the normal range reported in literature (r = 0.9, p < 0.05), although eight subjects did not produce a steady-state behavior. Conclusion: Almost all patients with post-COVID syndrome and subjectively severe motor fatigue, did not show motor fatigability nor severe metabolic anomalies. This is argued against organic, permanent damage to the motor system, as is often seen in MS. Many of the patients were - to our and their own surprise - motorically more exertable than expected.

Iron deficiency is related to low functional outcome in patients at early rehabilitation after acute stroke.

BACKGROUND: Iron deficiency (ID) is a common co-morbidity in patients with cardiovascular disease and contributes to impaired functional capacity. The relevance of ID in patients in recovery after acute stroke is not known. We assessed the prevalence of ID and anaemia in relation to functional capacity and to recovery during early rehabilitation after stroke. METHODS: This observational study enrolled consecutively 746 patients with ischaemic or haemorrhagic stroke at in-patient early rehabilitation (age 68 ± 13 years, female 47%, ischaemic stroke 87%). Functional capacity was assessed before and after rehabilitation using Barthel index (reha-BI), motricity index (MI), trunk control test (TCT), and functional ambulatory category (FAC). ID was defined as ferritin <100 µg/L or as transferrin saturation (TSAT) < 20% if ferritin was 100- < 300 µg/L or if CrP > 5 mg/L. Anaemia was defined as Hb < 12 g/dL (women) and <13 g/dL (men). RESULTS: The prevalence of ID and anaemia before rehabilitation were 45% and 46%, respectively, and remained high at discharge (after 27 ± 17 days) at 40% and 48%, respectively. Patients with ID had lower functional capacity compared with patients without ID (reha-BI 20 [±86] vs. 40 [±80], MI 64 [±66] vs. 77 [±41], TCT 61 [±76] vs. 100 [±39], FAC 1 [±4] vs. 4 [±4]; median [IQR], all P < 0.001). ID was related to inflammation (OR 2.68 [95% CI 1.98-3.63], P < 0.001), female sex (OR 2.13 [95% CI 1.59-2.85], P < 0.001), haemorrhagic stroke (OR 1.70 [95% CI 1.11-2.61], P = 0.015), initial treatment on stroke unit (OR 3.59 [95% CI 1.08-11.89], P < 0.001), and anaemia (OR 2.94 [95% CI 2.18-3.96], P < 0.001), while age, BMI, and renal function were not related to ID. In adjusted analysis, ID was associated with low functional capacity in all functional scores: reha-BI (OR 1.66 [95% CI 1.08-2.54], P = 0.02), motricity index (OR 1.94 [95% CI 1.36-2.76], P < 0.001), trunk control test (OR 2.34 [95% CI] 1.64-3.32, P < 0.001) and functional ambulatory category (OR 1.77 [95% CI 1.2-2.63], P < 0.02). Functional capacity improved during rehabilitation regardless of presence of ID, but functional outcome remained significantly lower in patients with ID at the end of rehabilitation (rehab BI and MI, both P < 0.001). CONCLUSIONS: Iron deficiency and anaemia are common and persistent findings in patients after acute stroke. ID and anaemia are independently related to lower functional capacity after acute stroke and to poor functional outcome after rehabilitation. Regular assessment of iron status may identify patients at risk of low functional recovery.

Reaching higher: External scapula assistance can improve upper limb function in humans with irreversible scapula alata.

BACKGROUND: Scapular dyskinesis, i.e., the deviant mobility or function of the scapula, hampers upper limb function in daily life. A typical sign of scapular dyskinesis is a scapula alata-a protrusion of the shoulder blade during arm elevation. While some reversible causes of scapula alata can be treated with therapy, other, irreversible causes require invasive surgical interventions. When surgery is not an option, however, severe limitations arise as standard approaches for assisting the scapula in daily life do not exist. The aim of this study was to quantify functional improvements when external, i.e., non-invasive, scapula assistance is provided. METHODS: The study was designed as a randomized controlled crossover trial. Eight participants with a scapula alata due to muscular dystrophy performed arm elevations in shoulder flexion and abduction while unassisted (baseline), externally assisted by a trained therapist, and externally assisted by a novel, textile-based scapula orthosis. RESULTS: With therapist assistance, average arm elevation increased by 17.3° in flexion (p < 0.001, 95% confidence interval of the mean [Formula: see text]), and by 11.2° in abduction (p < 0.01, [Formula: see text]), constituting the potential of external scapula assistance. With orthosis assistance, average arm elevation increased by 6.2° in flexion ([Formula: see text]) and by 5.8° in abduction ([Formula: see text]). Remarkably, in three participants, the orthosis was at least as effective as the therapist. Moreover, orthosis assistance reduced average perceived exertion by 1.25 points (Borg Scale) when elevating a filled bottle during a simulated daily living task. CONCLUSION: These findings indicate a large potential for future advancements in orthotics. Already now, the textile-based scapula orthosis presented here is a feasible tool for leveraging the benefits of external scapula assistance when a therapist is unavailable, as encountered in daily life scenarios. Trial Registration ClincalTrials.gov (ID NCT04154098). Registered: November 6th 2019, https://clinicaltrials.gov/ct2/show/NCT04154098?term=scapula+orthosis&draw=2&rank=1.

Cognitive Fatigability, not Fatigue predicts employment status in patients with MS three months after rehabilitation.

BACKGROUND: Fatigue is potentially the most important factor causing unemployment in people with Multiple Sclerosis (PwMS). Widely accepted is a discrimination between fatigue as subjective sensation and fatigability as objective measure of change in performance. The aim of this study was to identify, whether cognitive fatigue or cognitive fatigability is a better predictor for employment status three months after discharge from a neurological rehabilitation center. METHODS: 64 PwMS (mean age 48.9, 43 females, mean time since diagnosis 14.7 years, median Expanded Disability Status Scale (EDSS) 3.8), complaining of fatigue and reporting difficulties with their working capacity, participated in a cognitive loading task during inpatient rehabilitation. Reaction time performance was measured using a standardized alertness test (TAP-M). Tonic alertness was measured at 8 a.m., 11 a.m. and 2 p.m. Patients worked on a standardized test battery during the morning and after lunch to induce fatigability. All of them completed the Fatigue Scale for Motor and Cognition (FSMC), a standardized questionnaire to rate the trait component of cognitive and motor fatigue. Their employment status was rated within a standardized interview by phone three months after discharge from the clinic. RESULTS: Mean cognitive fatigue according to the FSMC was 38.9 ± 7.4 and mean motor fatigue 41.0 ± 5.6, indicating severe cognitive and motor fatigue. 15 (88%) of 17 patients working fulltime had severe fatigue according to the FSMC. The cognitive subscale of the FSMC ("FSMC cognition") did not correlate (rs = -.084, p = .512) and the motor subscale of the FSMC ("FSMC motor") correlated rather weakly but not significantly (rs= -.220, p = .080) with the employment status. In contrast, there was a significant and medium correlation between alertness at 8 a.m. (alertness1) and employment status (rs = -.304, p = .014). Ordered logistic regression revealed that only alertness1 and the alertness difference between afternoon and noon (alertness difference32) predicted significantly the employment status. The FSMC motor and cognition subscales had no predictive value for employment. CONCLUSION: Cognitive fatigability (tonic alertness at 8 a.m. or increase of reaction time during the afternoon) is more adequate to predict employment status in PwMS three months after discharge from the clinic than the subjective sensation of fatigue as determined by the FSMC.

Early rehabilitation after stroke: relationship between the heart rate variability and functional outcome.

AIMS: Impaired autonomic nervous system regulation is frequently observed in patients with stroke. The aim of this prospective study was to evaluate the impact of cardiac autonomic tone on functional outcome after the early post-stroke rehabilitation. METHODS AND RESULTS: One hundred and three consecutive patients (67 ± 11 years, body mass index (BMI) 27.1 ± 5.4 kg/m2 , 64% men) with ischaemic (84% of patients) and haemorrhagic stroke were studied. Depressed heart rate variability (HRV), as a surrogate marker of increased sympathetic tone, was defined by the standard deviation of NN intervals < 100 ms and HRV triangular index ≤ 20 assessed from a 24 h Holter electrocardiogram at admission to rehabilitation (23 ± 16 days after stroke). Twenty-two per cent of patients had depressed HRV at baseline and were comparable with patients with normal HRV with regard to their functional [Barthel Index (BI), modified Rankin Scale (mRS), and Rivermead Motor Assessment (RMA)] and biochemical status. After a 4-week follow-up, 70% of patients with depressed HRV showed a cumulative functional disability, defined by mRS ≥ 4, BI ≤ 70, and RMA ≤ 5, in contrast to patients with normal HRV (35%, P = 0.003). Patients with depressed HRV showed a worse functional status by BI (-16%, P < 0.001), RMA (-12%, P < 0.05), and mRS (+16%, P < 0.01), compared with patients with normal HRV. Cumulative functional disability was associated with depressed HRV (odds ratio 4.25, 95% confidence interval 1.56-11.54, P < 0.005) after adjustment for age, sex, and body mass index (odds ratio 4.6, 95% confidence interval 1.42-14.97, P < 0.05). CONCLUSIONS: The presence of autonomic cardiovascular dysregulation in patients with subacute stroke was associated with adverse functional outcome after the early post-stroke rehabilitation.

Let's do this together: Bi-Manu-Interact, a novel device for studying human haptic interactive behavior.

Our area of interest is robotic-based rehabilitation after stroke, and our goal is to help patients achieve optimal motor learning during high-intensity repetitive movement training through the assistance of robots. It is important, that the robotic assistance is adapted to the patients' abilities, thereby ensuring that the device is only supporting the patient as necessary ("assist-as-needed"). We hypothesize that natural and learning-effective human-machine interaction can be achieved by programming the robot's control, so that it emulates how a physiotherapist adaptively supports the patients' limb movement during stroke rehabilitation. This paper introduces the design of a novel interactive device Bi-Manu-Interact. This device is suited to be used as an experimental setup for the investigation of haptic human-human interaction and for collecting data to model therapists' haptic behavior. In this paper, we present mechanical and sensory specifications as well as tasks visualizations for future investigations. Results of a pilot clinical evaluation of the Bi-Manu-Interact with nine stroke patients are also presented in this work.

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation.

BACKGROUND: C-terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub-fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke. METHODS: Patients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m(2)) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA. RESULTS: CAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p < 0.001). Simple regression analyses revealed an association between CAF22 levels and parameters of physical performance, hand grip strength, and phase angle, a BIA derived measure of the muscle cellular integrity. Improvement of the handgrip strength of the paretic arm during rehabilitation was independently related to the recovery of CAF22 serum levels only in those patients who showed increased lean mass during the rehabilitation. CONCLUSIONS: CAF22 serum profiles showed a dynamic elevation and recovery in the subacute phase after acute stroke. Further studies are needed to explore the potential of CAF22 as a serum marker to monitor the muscle status in patients after stroke.

Influence of essential amino acids on muscle mass and muscle strength in patients with cerebral stroke during early rehabilitation: protocol and rationale of a randomized clinical trial (AMINO-Stroke Study).

BACKGROUND: Patients with stroke are at a high risk for long-term handicap and disability. In the first weeks after stroke muscle wasting is observed frequently. Early post-stroke rehabilitation programs are directed to improve functional independence and physical performance. Supplementation with essential amino acids (EAAs) might prevent muscle wasting and improve rehabilitation outcome by augmenting muscle mass and muscle strength. We aim to examine this in a double blinded, randomized placebo-controlled clinical trial. METHODS: Patients with ischemic or haemorrhagic stroke will be enrolled at begin of the early post-stroke rehabilitation in a parallel group interventional trial. Oral supplementation of EAAs or placebo will be given for 12 weeks in a double blinded manner. Physical and functional performance will be assessed by exercise testing before supplementation of EAAs as well as at discharge from the in-patient rehabilitation, at 12 weeks and 1 year afterwards. DISCUSSION: This is the first randomized double-blinded placebo-controlled clinical study aiming to assess the effect of the EAAs supplementation on muscle strength, muscle function and physical performance in stroke patients during early post-stroke rehabilitation. Supplementation of EAAs could prevent muscle mass wasting and improve functional independence after stroke. TRIAL REGISTRATION: The study is registered at the German registry for clinical trials as well as at World Health Organization (WHO; number DRKS00005577).

Procedural learning eliminates specific slowing down of response selection in patients with idiopathic Parkinson syndrome.

Patients with idiopathic Parkinson syndrome and normally aged controls participated in a psychological refractory period experiment. Two tasks were presented on each trial: auditory discrimination of high versus low tones, followed by visual classification of letters versus their mirror images. Speeded responses to both tasks were required. Stimulus onset asynchrony between the tasks was varied (short vs. long). Both groups showed equal response times overall, but patients were slower on the second task in the short stimulus onset asynchrony condition. This effect was eliminated with practice. The results were interpreted in terms of reduced capacity for cognitive processes involving decision making as a secondary symptom of the Parkinson syndrome.