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Background: The harm-benefit balance for early out-of-bed mobilisation of patients with severe acquired brain injury (ABI) in neurointensive care units (neuro-ICUs) is unclear, and there are no clinical guidelines. This study aimed to survey the current clinical practice and perceptions among clinicians involved in first out-of-bed mobilisation in Scandinavian neuro-ICUs., Methods: This was a cross-sectional, anonymous, web-based survey; the reporting follows the recommended CROSS checklist. Clinicians involved in the first out-of-bed mobilisation in all 14 Scandinavian neuro-ICUs were eligible to participate. The questionnaire was distributed to local contact persons. Respondents were asked about their clinical practice regarding the first out-of-bed mobilisation, and perceived harms and benefits of early mobilisation., Results: One hundred eighty clinicians (53% nurses, 31% physicians, and 14% therapists) completed the questionnaire. Eighty-one percent indicated that more than half of patients underwent their first out-of-bed mobilisation in the neuro-ICU. More respondents from Denmark than the remaining countries indicated that both physicians, nurses and physiotherapists contributed to the decision on when to mobilise. Intracranial pressure, cerebral perfusion pressure, sedation, presence of vasospasm and arterial blood pressure were the most used safety clinical indicators for deciding about mobilisation. Clinicians stated several positive effects of mobilisation, for example, improved bowel movements, level of consciousness, motor function, and reduced risk of pneumonia, contractures, delirium, and deep vein thrombosis., Conclusions: Mobilisation out of bed is frequently performed in patients with severe ABI in Scandinavian neuro-ICUs. The perceived clinical safety indicators for mobilisation were ICP, CPP, level of sedation, presence of vasospasms, and ABP., (© 2025 Acta Anaesthesiologica Scandinavica Foundation.)

Background: Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis., Methods: We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision., Results: We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%)., Conclusions: The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity., Study Registration: PROSPERO CRD42021273811., (© 2024. The Author(s).)

The mean flow index-usually referred to as Mx-has been used for assessing dynamic cerebral autoregulation (dCA) for almost 30 years. However, concerns have arisen regarding methodological consistency, construct and criterion validity, and test-retest reliability. Methodological nuances, such as choice of input (cerebral perfusion pressure, invasive or non-invasive arterial pressure), pre-processing approach and artefact handling, significantly influence mean flow index values, and previous studies correlating mean flow index with other established dCA metrics are confounded by inherent methodological flaws like heteroscedasticity, while the mean flow index also fails to discriminate individuals with presumed intact versus impaired dCA (discriminatory validity), and its prognostic performance (predictive validity) across various conditions remains inconsistent. The test-retest reliability, both within and between days, is generally poor. At present, no single approach for data collection or pre-processing has proven superior for obtaining the mean flow index, and caution is advised in the further use of mean flow index-based measures for assessing dCA, as current evidence does not support their clinical application., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Research in animal models on cerebral metabolism after brain injury highlights the potential benefits of ketosis in reducing secondary brain injury, but studies in humans are lacking., Aim: This study aimed to examine if a 6-week ketogenic diet intervention with added medium-chain triglycerides (MCT) was feasible in adult patients with acquired brain injury in the subacute phase, whether ketosis could be achieved and maintained, and to what extent serious adverse reactions, adverse reactions, serious adverse events, and adverse events occured., Methods: Patients ≥18 years of age diagnosed with subacute acquired brain injury and an expectation of hospitalisation ≥6 weeks were included in the intervention group. Patients not included in the intervention group were included in a standard care reference group. The intervention consisted of a ketogenic diet supplemented with MCT to obtain a plasma concentration of β-hydroxybutyrate (BHB) ≥0.5 mmol/L. Patients who were enterally fed were given KetoCal® 2.5:1 LQ MCT Multi Fiber (Nutricia A/S, Allerød, Denmark), supplemented with Liquigen® (Nutricia A/S, Allerød, Denmark). Patients consuming oral nutrition were given KetoCal® 2.5:1 LQ MCT Multi Fiber supplemented with Liquigen®, in addition to ketogenic meals., Results: During a 13-week inclusion period, 12 of 13 eligible patients (92% [95% CI: 67% to 99%]) were included in the intervention group, and 17 of 18 excluded patients (94% [95% CI: 74% to 99%]) were included in the reference group. Eight patients (67%) completed the 6-week intervention. It took a median of 1 day to achieve ketosis from starting a 100% MCT ketogenic diet, and it was maintained for 97% of the intervention period after ketosis was obtained. There were no serious adverse reactions to the MCT ketogenic diet, and patients experienced adverse reactions not considered serious in 9.5% of days with the intervention. The MCT ketogenic diet was accepted by patients on all intervention days, and in the two patients transitioning from enteral feeding to oral intake, there were no complications related to transitioning., Conclusion: Intervention with MCT ketogenic diet is feasible and tolerated for 6 weeks in hospitalised adult patients with subacute acquired brain injury. Randomised controlled trials are needed to assess the benefits and harms of the MCT ketogenic diet and the effect on patients' recovery. Clinical trial registration: ClinicalTrials.gov, identifier [NCT04308577]., Competing Interests: The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Edwards, Andersen, Curtis, Riberholt and Poulsen.)

Introduction: The physical activity level in patients hospitalised for rehabilitation across multiple diagnoses is low. Moderate to severe acquired brain injury further reduces activity levels as impaired physical and cognitive functioning affect mobility independence. Therefore, supervised out-of-bed mobilisation and physical activity training are essential rehabilitation strategies. Few studies have measured the physical activity patterns in the early phases of rehabilitation after moderate to severe brain injury., Objectives: To map and quantify physical activity patterns in patients admitted to brain injury rehabilitation. Further, to investigate which factors are associated with activity and if the early physical activity level is associated with functional outcome at discharge., Methods: This observational study includes patients admitted to rehabilitation after moderate to severe acquired brain injury. Mobility and physical activity patterns are measured continuously during rehabilitation at two separate seven-day periods using a wearable activity tracker. Activity will be categorised into four levels and presented descriptively. Linear and logistic regression models will analyse associations between descriptive variables and activity levels., Discussion: This protocol describes an observational study investigating patients' mobility and physical activity patterns with moderate to severe acquired brain injury during in-hospital rehabilitation. The ability to increase the amount of mobilisation and physical activity in subgroups may have profound consequences on the rehabilitation outcome. Furthermore, data from this study may be used to inform a large variety of trials investigating physical rehabilitation interventions. (NCT05571462)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF - and thereby oxygen delivery - passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred., Methods: The study was carried out within 5 days after ictus. Data were recorded at baseline and after 20 min of noradrenaline infusion to increase mean arterial blood pressure (MAP) by a maximum of 30 mmHg and to an absolute level of no more than 130 mmHg. The primary outcome was the difference in middle cerebral artery blood flow velocity (MCAv) measured by transcranial Doppler (TCD), while differences in intracranial pressure (ICP), brain tissue oxygen tension (PbtO 2 ), and microdialysis markers of cerebral oxidative metabolism and cell injury were assessed as exploratory outcomes. Data were analysed using Wilcoxon signed-rank test with correction for multiplicity for the exploratory outcomes using the Benjamini-Hochberg correction., Results: Thirty-six participants underwent the intervention 4 (median, IQR: 3-4.75) days after ictus. MAP was increased from 82 (IQR: 76-85) to 95 (IQR: 88-98) mmHg (p-value: <.001). MCAv remained stable (baseline, median 57, IQR: 46-70 cm/s; controlled blood pressure increase, median: 55, IQR: 48-71 cm/s; p-value: .054), whereas PbtO 2 increased significantly (baseline, median: 24, 95%CI: 19-31 mmHg; controlled blood pressure increase, median: 27, 95%CI: 24-33 mmHg; p-value <.001). The remaining exploratory outcomes were unchanged., Conclusion: In this study of patients with SAH, MCAv was not significantly affected by a brief course of controlled blood pressure increase; despite this, PbtO 2 increased. This suggests that autoregulation might not be impaired in these patients or other mechanisms could mediate the increase in brain oxygenation. Alternatively, a CBF increase did occur that, in turn, increased cerebral oxygenation, but was not detected by TCD., Trial Registration: clinicaltrials.gov (NCT03987139; 14 June 2019)., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

The EXOPULSE Mollii is designed to reduce spasticity through low-current electrical stimulation of major muscle groups. The effect on severe cerebellar ataxia has not been investigated. This case describes the use of the EXOPULSE Mollii in an adult male with severe cerebellar ataxia 4 months after cardiac arrest and ischaemic stroke. The patient used the suit in 15 of 19 possible sessions (78.9%). He improved in the sit-to-stand test, arm function test and 10 m walking test. He described improved visual focus, ability to speak and swallow. Improvements were maintained for 1 week after the last session. The EXOPULSE Mollii is relevant to consider in the early stages of inpatient rehabilitation for patients with severe ataxia, but further research is warranted., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury., Methods: We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/, http://www., Clinicaltrials: gov/, www.eudraCT.com, http://centerwatch.com/, The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach., Discussion: The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice., (© 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Objective . Invasively measured arterial blood pressure (ABP) is associated with complications, while non-invasively measured ABP is generally considered risk-free. This study aimed to investigate the reliability of non-invasive ABP measured using finger-cuff volume-clamp device compared to invasive ABP measured by an arterial catheter in patients with aneurysmal subarachnoid haemorrhage (SAH). Approach . In 30 patients admitted for neurointensive care with SAH, invasive and non-invasive ABP were recorded simultaneously. Reliability was assessed for mean, diastolic and systolic ABP separately using intraclass correlation coefficient (ICC) agreement for each full period and each 3 s average. Main results. A median of 3 (IQR: 2-3) periods were included for each participant. The full periods ( n  = 81) showed an ICC of 0.34 (95% CI: 0.14-0.52), 0.31 (95% CI: 0.10-0.49), and 0.20 (95% CI: 0.00-0.39) for mean, diastolic, and systolic ABP, respectively. Three-second averages ( n  = 33 786) for mean (ICC: 0.35; 95% CI: 0.33-0.36), diastolic (ICC: 0.25; 95% CI: 0.25-0.28), and systolic ABP (ICC: 0.26; 95% CI: 0.18-0.33) yielded similar findings. Pearson's correlation coefficient showed an R 2 of 0.15 ( p  < 0.001), 0.15 ( p  < 0.001), 0.06 ( p  = 0.027) for mean, diastolic and systolic ABP, respectively. Significance. In patients with SAH, non-invasive measurement of ABP using the widely used Nano system from Finapres Medical Systems-a finger-cuff volume-clamp device (Finapres, Chennai, India) showed poor reliability and therefore cannot be used interchangeably with invasively measured ABP., (© 2022 Institute of Physics and Engineering in Medicine.)

Background: Adequately conducted systematic reviews with meta-analyses are considered the highest level of evidence and thus directly defines many clinical guidelines. However, the risks of type I and II errors in meta-analyses are substantial. Trial Sequential Analysis is a method for controlling these risks. Erroneous use of the method might lead to research waste or misleading conclusions., Methods: The current protocol describes a systematic review aimed to identify common and major mistakes and errors in the use of Trial Sequential Analysis by evaluating published systematic reviews and meta-analyses that include this method. We plan to include all studies using Trial Sequential Analysis published from January 2018 to January 2022, an estimated 400 to 600 publications. We will search Medical Literature Analysis and Retrieval System Online and the Cochrane Database of Systematic Reviews, including studies with all types of participants, interventions, and outcomes. Two independent reviewers will screen titles and abstracts, include relevant full text articles, extract data from the studies into a predefined checklist, and evaluate the methodological quality of the study using the AMSTAR 2, assessing the methodological quality of the systematic reviews., Discussion: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). The identified mistakes and errors will be published in peer reviewed articles and form the basis of a reviewed guideline for the use of Trial Sequential Analysis. Appropriately controlling for type I and II errors might reduce research waste and improve quality and precision of the evidence that clinical guidelines are based upon., (© 2022. The Author(s).)

Introduction: In the early phase after severe brain injury, patients are often bedridden in an attempt to control intracranial homeostasis; however, prolonged immobilisation may trigger complications. There is limited knowledge about the physiological effects of mobilisation in this early phase., Objective: To investigate changes in brain tissue oxygen tension when patients are mobilised using a Sara Combilizer® in the early phase after severe brain injury, in a randomised cross-over design., Methods: Patients with traumatic brain injury, subarachnoid haemorrhage or intracranial haematoma, will be randomised to early mobilisation or rest (no mobilisation = control) on the first day that the patient is deemed to be fit for mobilisation, and the opposite on the next day. On both days, patients will undergo continuous multimodal monitoring measuring brain tissue oxygen tension (primary outcome), invasive blood pressure, heart rate, middle cerebral artery blood flow velocity by transcranial Doppler ultrasound, intracranial pressure, and microdialysis markers of cerebral oxidative metabolism., Discussion: Intensive care unit patients with acute brain injury are frequently immobilised in the early phase after the ictus. The optimal timing and intensity of mobilisation is unknown. The present study attempts to establish if early mobilisation is safe with respect to intracranial homeostasis. Protocol version 1.1. Date: 19.02.2022. Ethical registration: H-21002728; approved on August 11, 2021. GDPR registration: P-2021 - 105; approved on February 10, 2021., Clinicaltrials: govidentifier:NCT05038930; approved on September 8, 2021. Electronic case report file: REDCap-database; created on August 13, 2021., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Dynamic cerebral autoregulation to spontaneous fluctuations in cerebral perfusion pressure (CPP) is often assessed by transcranial Doppler (TCD) in the time domain, yielding primarily the mean flow index (Mx), or in the frequency domain using transfer function analysis (TFA), yielding gain and phase. For both domains, the measurement of blood pressure is critical. This study assessed the inter-method reliability of dynamic cerebral autoregulation using three different methods of pressure measurement. In 39 patients with aneurysmal subarachnoid hemorrhage, non-invasive arterial blood pressure (ABP), invasive ABP (measured in the radial artery) and CPP were recorded simultaneously with TCD. Intraclass correlation coefficient (ICC) was used to quantify reliability. Mx was higher when calculated using invasive ABP (0.39; 95% confidence interval [95% CI]: 0.33; 0.44) compared to non-invasive ABP, and CPP. The overall ICC showed poor to good reliability (0.65; 95% CI: 0.11; 0.84; n = 69). In the low frequency domain, the comparison between invasively measured ABP and CPP showed good to excellent (normalized gain, ICC: 0.87, 95CI: 0.81; 0.91; n = 96; non-normalized gain: 0.89, 95% CI: 0.84; 0.92; n = 96) and moderate to good reliability (phase, ICC: 0.69, 95% CI: 0.55; 0.79; n = 96), respectively. Different methods for pressure measurement in the assessment of dynamic cerebral autoregulation yield different results and cannot be used interchangeably., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Cerebral autoregulation is a complex mechanism that serves to keep cerebral blood flow relatively constant within a wide range of cerebral perfusion pressures. The mean flow index (Mx) is one of several methods to assess dynamic cerebral autoregulation, but its reliability and validity have never been assessed systematically. The purpose of the present systematic review was to evaluate the methodology, reliability and validity of Mx.Based on 128 studies, we found inconsistency in the pre-processing of the recordings and the methods for calculation of Mx. The reliability in terms of repeatability and reproducibility ranged from poor to excellent, with optimal repeatability when comparing overlapping recordings. The discriminatory ability varied depending on the patient populations; in general, those with acute brain injury exhibited a higher Mx than healthy volunteers. The prognostic ability in terms of functional outcome and mortality ranged from chance result to moderate accuracy.Since the methodology was inconsistent between studies, resulting in varying reliability and validity estimates, the results were difficult to compare. The optimal method for deriving Mx is currently unknown.

Introduction: Dysphagia is a common and critical consequence of acquired brain injury (ABI) and can cause severe complications. Dysphagia rehabilitation is transforming from mainly compensatory strategies to the retraining of swallowing function using principles from neuroscience. However, there are no studies that map interventions available to retrain swallowing function in patients with moderate-to-severe ABI., Objective: To systematically map the accessible research literature to answer the research question: Which non-surgical, non-pharmacological interventions are used in the treatment of dysphagia in patients with moderate and severe ABI in the acute and subacute phase? DESIGN: Scoping review based on the methodology of Arksey and O'Malley and methodological advancement by Levac et al. DATA SOURCES: MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, Web of Science, OTseeker, speechBITE and PEDro were searched up until 14 March 2021., Eligibility Criteria: All studies reporting rehabilitative interventions within 6 months of injury for patients with moderate-to-severe ABI and dysphagia were included., Data Extraction and Synthesis: Data was extracted by two independent reviewers and studies were categorised based on treatment modality., Results: A total of 21 396 records were retrieved, and a final of 26 studies were included. Interventions were categorised into cortical or non-cortical stimulation of the swallowing network. Cortical stimulation interventions were repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation. Non-cortical were complex swallowing interventions, neuromuscular electrical stimulation, pharyngeal electrical stimulation (PES), sensory stimulation, strengthening exercises and respiratory muscle training., Conclusion: This scoping review provides an overview of rehabilitative dysphagia interventions for patients with moderate and severe ABI, predominantly due to stroke, in the acute and subacute phase. Positive tendencies towards beneficial effects were found for rTMS, complex swallowing interventions, PES and cervical strengthening. Future studies could benefit from clear reporting of patient diagnosis and disease severity, the use of more standardised treatment protocols or algorithms and fewer but standardised outcome measures to enable comparison of effects across studies and interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early mobilization on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomized clinical trials are lacking. This detailed statistical analysis plan describes the analyses of data collected in a randomized clinical feasibility trial for early mobilization by head-up tilt with stepping versus standard care after severe traumatic brain injury., Methods: Primary feasibility outcomes are the proportion of included participants who were randomized out of all screened patients; the proportion of participants allocated to the experimental intervention who received at least 60% of the planned exercise sessions; and safety outcomes such as adverse events and reactions and serious adverse events and reactions. Exploratory clinical outcomes are suspected unexpected serious adverse reactions; and functional outcomes as assessed by the Coma Recovery Scale-Revised at four weeks; Early Functional Ability Scale and Functional Independence Measure at three months. The description includes the statistical analysis plan, including the use of multiple imputations and Trial Sequential Analysis., Competing Interests: The authors declare that they have no known competing interests., (© 2021 The Authors.)

In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthostatic intolerance after four weeks of regular orthostatic exercise by head-up tilt using a tilt table with integrated stepping using the ERIGO® tilt-table and comparing it to standard care. Thirty-four patients with severe traumatic brain injury admitted to a neurocritical care unit were included in this randomized clinical trial. Middle cerebral artery blood flow velocity (MCAv), non-invasive mean arterial pressure, heart rate and PaCO 2 were recorded; dCA was measured by the non-invasive mean flow index (nMxa). Transition from the supine position to head-up tilt triggered a 10-16% decrease in MCAv and increased nMxa in both groups at all time points (P < 0.05), with no differences between groups. There was no difference in the number of episodes with orthostatic intolerance (5 vs 3; 1 vs 2; 1 vs 0) at baseline, two weeks and four weeks, respectively, and no association between changes in PaCO 2 -adjusted nMxa and the occurrence of orthostatic reactions (P = 0.35). Early orthostatic exercise does not affect dynamic cerebral autoregulation and does not protect against orthostatic intolerance in patients with severe traumatic brain injury. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3rd October 2016., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Mean flow index (Mxa) for evaluating dynamic cerebral autoregulation is derived using varying approaches for calculation, which may explain that the reliability ranges from poor to excellent. The comparability, repeatability, stability, and internal consistency of approaches have not previously been assessed., Methods: We included 60 recordings from resting healthy volunteers and calculated Mxa using four different approaches: three without overlapping calculations, using intervals for averaging wave-form data (blocks) of 3, 6, and 10 s, and correlation periods (epochs) of 60, 240, and 300 s (3-60-F, 6-240-F, and 10-300-F); and one using 10-second blocks, 300 s epochs, and overlaps of 60 s (10-300-60). The comparability between the approaches was assessed using Student's t test, intraclass correlation coefficients (ICC), and Bland-Altman plot., Results: Overall, 3-60-F resulted in a higher Mxa than the other indices (p < 0.001, for all). The reliability when comparing all the approaches ranged from moderate to good (ICC: 0.68; 95%CI: 0.59-0.84), which was primarily due to similarities between 10-300-F and 10-300-60 (ICC: 0.94; 95%CI: 0.86-0.98). The reliability when comparing the first and last half was poor for 10-300-F and ranged from poor to moderate for the other approaches. Additional random artifacts resulted in poor reliability for 10-300-F, while the other approaches were more stable., Conclusions: Mxa in general has a low sensitivity to artifacts, but otherwise seems highly dependent on the approach, with a repeatability that is moderate at best. The varying accuracy and precision renders Mxa unreliable for classifying impaired cerebral autoregulation when using healthy adults for comparison., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

The transcranial Doppler ultrasound-derived mean flow index (Mxa) is widely used for assessing dynamic cerebral autoregulation (dCA) in different clinical populations. This study aimed at estimating the relative and absolute reliability of Mxa in healthy participants in the supine position and during head-up tilt (HUT). Fourteen healthy participants were examined on two separate occasions during which, mean middle cerebral artery blood flow velocity (MCAv), non-invasive blood pressure, and heart rate were continuously recorded in the supine position and during HUT. Mxa was calculated as the correlation coefficient between mean arterial blood pressure and MCAv using either 3-, 5-, or 10-second averages collected over a 300 second period. Intraclass correlation coefficient (ICC 1.1 ) was calculated to assess relative reliability, while the standard error of measurement (SEM), and limits of agreement (LOA) were used to assess absolute reliability. Mxa-based 3-second averages yielded a similar relative and absolute reliability in both positions. When Mxa was calculated from 5-second averages, the most reliable values were obtained during HUT. The poorest reliability was achieved using 10-second averages, regardless of posture. The Mxa shows fair reliability with acceptable LOA in healthy volunteers when based on 3-second averages, both in the supine position and during HUT., Competing Interests: Declaration of Competing Interest All authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2021. Published by Elsevier Ltd.)

Background: There is increasing focus on earlier rehabilitation in patients with traumatic or hypoxic brain injury or stroke. This systematic review evaluates the benefits and harms of early head-up mobilisation versus standard care in patients with severe acquired brain injury., Methods: We searched Medline, CENTRAL, EMBASE, four other databases and 13 selected clinical trial registries until April 2020. Eligible randomised clinical trials compared early head-up mobilisation versus standard care in patients with severe acquired brain injury and were analysed conducting random- and fixed-effects meta-analyses and Trial Sequential Analysis (TSA). Certainty of evidence was assessed by GRADE., Main Results: We identified four randomised clinical trials (total n = 385 patients) with severe acquired brain injury (stroke 86% and traumatic brain injury 13%). Two trials were at low risk and two at high risk of bias. We found no evidence of a difference between early mobilisation vs. standard care on mortality or poor functional outcome at end of the intervention (relative risk (RR) 1.19, 95% CI 0.93 to 1.53; I2 0%; very low certainty) or at maximal follow-up (RR 1.03, 95% CI 0.89 to 1.21; I2 0%; very low certainty). We found evidence against an effect on quality of life at maximal follow-up. The proportion of patients with at least one serious adverse event did not differ at end of intervention or at maximal follow-up. For most comparisons, TSA suggested that further trials are needed., Conclusions: We found no evidence of a difference between early mobilisation versus standard care for patients with severe acquired brain injury. Early mobilisation appeared not to exert a major impact on quality of life. This systematic review highlights the insufficient evidence in patients with severe brain injury, and no firm conclusions can be drawn from these data., Trial Registration: Protocol uploaded to PROSPERO: April 2018 (revised October 2018, CRD42018088790)., Competing Interests: The authors have declared that no competing interests exist.

Background: There is little high-level evidence for the effect of the nonverbal facilitation of swallowing on swallowing ability in the subacute stage of rehabilitation following severe acquired brain injury (ABI)., Objective: To pilot test a randomised controlled trial to determine the effect of an intensification of the nonverbal facilitation of swallowing on dysphagia., Methods: Ten patients with severe ABI and dysphagia were randomised into two groups at a highly specialised neurorehabilitation clinic.The intervention group received an intensification of the nonverbal facilitation of swallowing and the control group received basic care of the face and mouth in addition to treatment as usual for two sessions of 20 minutes per day for three weeks.Outcomes were Functional Oral Intake Scale (FOIS), Penetration Aspiration Scale (PAS), and electrophysiological swallowing specific parameters (EMBI)., Results: The intensified intervention was feasible. PAS and FOIS scores improved in both groups, with no differences between groups. The swallowing specific parameters reflected clinically observed changes in swallowing., Conclusions: PAS and FOIS are feasible instruments to measure dysphagia. It is possible and valid to measure swallowing frequency and kinematics using electromyography and bioimpedance. The definitive study should have widened inclusion criteria and optimise intervention timing to maintain patient arousal.

Introduction: Dysphagia is highly prevalent in patients with acquired brain injury (ABI) and is associated with high morbidity and mortality. However, dysphagia management varies greatly between units and internationally, and there is currently no consensus, standard intervention or treatment. A review mapping the existing literature on dysphagia treatment is needed. In this paper, the protocol for a scoping review to identify and map dysphagia treatment following ABI is outlined., Objective: The objective of the scoping review is to systematically map the existing research literature to answer the research question: Which non-surgical, non-pharmacological interventions are used in the treatment of dysphagia in patients with moderate and severe acquired brain injury in the acute and subacute phase? METHODS AND ANALYSIS: The methodological framework for the study is based on methodology by Arksey and O'Malley and methodological advancement by Levac et al . We will search electronic databases in June 2019: MEDLINE (Ovid); Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO; Science Citation Index Expanded on Web of Science; OTseeker; Speechbite and PEDro. The search terms will be limited to patients with moderate to severe ABI and dysphagia. Four review authors will independently conduct an initial screening of title and abstract and subsequent full-text review of included studies. Data will be extracted and summarised in diagrammatic or tabular form (numerical summary), and a descriptive format (narrative summary). The strategy for data synthesis entails qualitative methods to categorise the interventions based on the treatment modality and subgroup diagnosis., Ethics and Dissemination: Scoping the existing literature will provide a foundation for further evaluating and developing our dysphagia treatment and inform future studies assessing the effectiveness of treatments. The review is part of an ongoing expansive research into dysphagia. The results will be disseminated through a peer-reviewed publication and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective : This study investigated the development of contractures, passive stiffness, and spasticity in the ankle joint in patients with severe acquired brain injury (ABI) from admission to rehabilitation unit until 1-year post-injury compared to healthy controls. Design : An observational longitudinal cohort study Methods and procedures : Nineteen patients (26 affected ankle joints) with severe ABI >17 years old and with paresis of a lower limb admitted to sub-acute neurorehabilitation were compared to 14 healthy controls (28 ankle joints). Passive and reflex-mediated ankle joint stiffness was obtained measuring torque, range of motion, velocity and acceleration of the ankle movements. Data was collected at inclusion, after 4-5 weeks, after 8-9 weeks and at 1-year follow-up. Outcomes and results : At admittance to rehabilitation range of motion and stiffness was significantly lower compared to controls. Range of motion decreased by one degree in three weeks and passive ankle joint stiffness increased significantly by 1% per week. More patients than controls had no stretch reflex. Conclusion : Patients with severe ABI show reduced mobility and increased passive stiffness despite less spasticity in the ankle joint compared to healthy controls. Research and clinical practice should therefore focus intensively on the prevention of contractures in the ankle joint. ISRCTN17910097.

Background: Intensive rehabilitation of patients with severe traumatic brain injury is generally applied in the subacute stages of the hospital stay. Few studies have assessed the association between early and intensive physical rehabilitation and functional outcomes. The aim of this trial is to assess the feasibility of an intensive physical rehabilitation intervention focusing on mobilisation to the upright position, starting as early as clinically possible versus standard care in the intensive care unit. The feasibility study is intended to inform a subsequent randomised clinical trial that will investigate benefits and harms of the intervention., Methods: This randomised clinical feasibility trial with a follow-up period of 1 year will use blinded outcome assessors for the Coma Recovery Scale-Revised. A maximum of 60 patients admitted to the neurointensive care unit at Rigshospitalet, Denmark, with traumatic brain injury (age of at least 18 years), a low level of consciousness, and stable intracranial pressure will be included in the trial. Patients will be randomly assigned to experimental intervention versus standard care (1:1) stratified according to their Glasgow Coma Score. The intervention group will receive daily mobilisation in a tilt table with an integrated stepping device (ERIGO ® ). Feasibility is declared if more than 60% (the lower 95% confidence interval of the proportion) of eligible patients are included in the trial and more than 52% (the lower 95% confidence interval of the proportion) of patients in the intervention group receive more than 60% of the planned interventions. Safety is assessed by the occurrence of adverse events and adverse reactions. Exploratory clinical outcomes consist of cerebral haemodynamics (blood flow velocity and pressure autoregulation) and baroreceptor sensitivity in the early phase as well as functional outcomes (Coma Recovery Scale-Revised, Early Functional Ability scale, and Functional Independence Measure)., Discussion: Our findings will inform a future, larger-scale randomised clinical trial on early mobilisation using a tilt table early after severe traumatic brain injury., Trial Registration: ClinicalTrials.gov identifier: NCT02924649 . Registered on 3 October 2016.

Early mobilization is of importance for improving long-term outcome for patients after severe acquired brain injury. A limiting factor for early mobilization by head-up tilt is orthostatic intolerance. The purpose of the present study was to examine cerebral autoregulation in patients with severe acquired brain injury and a low level of consciousness. Fourteen patients with severe acquired brain injury and orthostatic intolerance and fifteen healthy volunteers were enrolled. Blood pressure was evaluated by pulse contour analysis, heart rate and RR-intervals were determined by electrocardiography, middle cerebral artery velocity was evaluated by transcranial Doppler, and near-infrared spectroscopy determined frontal lobe oxygenation in the supine position and during head-up tilt. Cerebral autoregulation was evaluated as the mean flow index calculated as the ratio between middle cerebral artery mean velocity and estimated cerebral perfusion pressure. Patients with acquired brain injury presented an increase in mean flow index during head-up tilt indicating impaired autoregulation (P < 0.001). Spectral analysis of heart rate variability in the frequency domain revealed lower magnitudes of ~0.1 Hz spectral power in patients compared to healthy controls suggesting baroreflex dysfunction. In conclusion, patients with severe acquired brain injury and orthostatic intolerance during head-up tilt have impaired cerebral autoregulation more than one month after brain injury.

Introduction: Patients with severe acquired brain injury (ABI) are often mobilised using a tilt-table. Complications such as orthostatic intolerance have been reported. The primary objective of this study was to investigate if using a tilt-table was feasible for mobilising patients with severe ABI admitted for sub-acute rehabilitation. We also investigated change in arousal, treatment duration before termination due to orthostatic reactions and change in muscle tone., Material and Methods: A total of 16 patients with severe ABI were included. The patients were tilted head-up, and blood pressure, heart rate, breathing frequency and eye opening were recorded before and during the intervention. Furthermore, muscle tone was recorded before and after the intervention., Results: Fifteen of the 16 patients did not complete the 20-min. session of tilt training due to orthostatic intolerance. There was a significant increase in the proportion of time that the patients had open eyes during treatment as compared with before treatment (p < 0.01). The mean time to occurrence of symptoms at the first, second and third tilt was 244 (standard deviation (SD) = ± 234) sec., 277 (SD = ± 257) sec. and 155 (SD = ± 67) sec., respectively., Conclusion: Patients with severe sub-acute ABI show orthostatic intolerance when mobilised on a tilt-table which results in a low mobilisation intensity. However, the patients showed a significant increase in arousal during mobilisation., Funding: No external funding was received for this study. All resources were provided by the Department of Neurorehabilitation, Traumatic Brain Injury Unit, Glostrup University Hospital., Trial Registration: not relevant.