Feasibility and efficacy of an early sensory-motor rehabilitation program on hand function in patients with stroke: a pilot, single-subject experimental design.

OBJECTIVE: Hand and upper limb functional impairments following stroke lead to limitations in performing activities of daily living. We aimed to investigate feasibility and efficacy of an early sensory-motor rehabilitation program on hand and upper limb function in patients with acute stroke. DESIGN: A pilot, single-subject experimental, A-B-A study. SETTING: Stroke unit of an educational hospital and an outpatient occupational therapy clinic. PARTICIPANTS: A convenience sample including five people with acute stroke. PROCEDURES: Participants received 3 h of an intensive hand and upper limb sensory and motor rehabilitation program, 5 days per week for 3 months (15-min mental imagery, 15-min action observation, 30-min mirror therapy, 1.5-h constraint-induced movement therapy, and 30-min bilateral arm training). Activities were chosen based on the task-oriented occupational therapy approach. OUTCOME MEASURES: An assessor blinded to intervention program measured sensory and motor functions using action research arm test, box and block test, Semmes-Weinstein monofilaments, and upper extremity section of Fugl-Meyer assessment. RESULTS: Assessment data points in intervention and follow-up phases compared to baseline were in higher levels, sloped upwardly, and increased significantly for all participants in all outcome measures. CONCLUSIONS: The present pilot study showed that a package of nowadays evidence-based rehabilitation methods including mental imagery, action observation, mirror therapy, modified constraint-induced movement therapy, bilateral arm training, and task-oriented occupational therapy approach is able to improve sensory and motor functions of the hand and upper limb in patients with acute stroke.

Effects of Hand Motor Interventions on Cognitive Outcomes Post-stroke: A Systematic Review and Bayesian Network Meta-analysis.

OBJECTIVE: To synthetize the evidence on the effects of hand rehabilitation (RHB) interventions on cognition post-stroke and compare their efficacy. DATA SOURCES: PubMed, Embase, Cochrane, Scopus, Web of Science, and CINAHL were searched from inception to November 2022. DATA SELECTION: Randomized controlled trials conducted in adults with stroke where the effects of hand motor interventions on any cognitive domains were assessed. DATA EXTRACTION: Data were extracted by 2 independent reviewers. A Bayesian Network Meta-analysis (NMA) was applied for measures with enough studies and comparisons. Risk of bias was assessed with the Cochrane Risk of Bias tool. DATA SYNTHESIS: Fifteen studies were included in qualitative synthesis, and 11 in NMA. Virtual reality (VR) (n=7), robot-assisted (n=5), or handgrip strength (n=3) training were the experimental interventions and conventional RHB (n=14) control intervention. Two separate NMA were performed with MoCA (n=480 participants) and MMSE (n=350 participants) as outcome measures. Both coincided that the most probable best interventions were robot-assisted and strength training, according to SUCRA and rankogram, followed by conventional RHB and VR training. No significant differences between any of the treatments were found in the MoCA network, but in the MMSE, robot-assisted and strength training were significantly better than conventional RHB and VR. No significant differences between robot-assisted and strength training were found nor between conventional RHB and VR. CONCLUSIONS: Motor interventions can improve MoCA/MMSE scores post-stroke. Most probable best interventions were robot-assisted and strength training. Limited literature assessing domain-specific cognitive effects was found.

Observation of others' actions during limb immobilization prevents the subsequent decay of motor performance.

There is rich clinical evidence that observing normally executed actions promotes the recovery of the corresponding action execution in patients with motor deficits. In this study, we assessed the ability of action observation to prevent the decay of healthy individuals' motor abilities following upper-limb immobilization. To this end, upper-limb kinematics was recorded in healthy participants while they performed three reach-to-grasp movements before immobilization and the same movements after 16 h of immobilization. The participants were subdivided into two groups; the experimental group observed, during the immobilization, the same reach-to-grasp movements they had performed before immobilization, whereas the control group observed natural scenarios. After bandage removal, motor impairment in performing reach-to-grasp movements was milder in the experimental group. These findings support the hypothesis that action observation, via the mirror mechanism, plays a protective role against the decline of motor performance induced by limb nonuse. From this perspective, action observation therapy is a promising tool for anticipating rehabilitation onset in clinical conditions involving limb nonuse, thus reducing the burden of further rehabilitation.

Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial.

BACKGROUND: The increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant. OBJECTIVE: To assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI. METHODS: Thirty-four older adults (men, women) with MCI were randomized to the experimental group (n = 17; 75.41 ± 5.76) or control (n = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions). RESULTS: Between groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups (p < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p = 0.28; experimental, p = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level. CONCLUSIONS: The application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

Motor, cognitive, and combined rehabilitation approaches on MS patients' cognitive impairment.

BACKGROUND: At the moment, the possible options for the management of cognitive dysfunctions in patients with MS (pMS) are pharmacological interventions, cognitive rehabilitation (CR), and physical exercise. However, worldwide, multimodal programs are infrequently applied in pMS and CR is not easily accessible through the National Health System as MR. OBJECTIVE: The aim of the study is to explore if the combination of motor and cognitive rehabilitation may favor better outcomes on cognitive efficiency compared to separate trainings. METHODS: Forty-eight pMS were submitted to detailed neuropsychological and motor assessments, before (T0) and after (T1) having performed one of three rehabilitation conditions (two cognitive trainings/week-Reha1; one cognitive and one motor training/week-Reha2; two motor trainings/week-Reha3, for 12 weeks); they were randomly assigned to one condition or another. The CR was focused on memory functioning and performed with the Rehacom program. RESULTS: No significant differences in age, sex, education, and disease course were found between the three groups (sig. > .05). Reha1 patients increased only their cognitive performance, and Reha3 only increased their motor performance, while Reha2 increased both cognitive and motor performances. This benefit was also confirmed by the cognitive efficiency expressed by the Cognitive Impairment Index. CONCLUSIONS: These data confirm that to include cognitive training within rehabilitation programs may induce important benefits in pMS. Furthermore, pMS seem to benefit from a combined approach (cognitive and motor) more than from CR and motor rehabilitation separately (ClinicalTrial.gov ID: NCT05462678; 14 July 2022, retrospectively registered).

Development of a Biomechanical Device for Parameter Quantification Associated with the Sit-to-Stand Movement.

The "sit-to-stand" (STS) movement is essential during activities of daily living (ADL). In individuals with physical-motor diseases, its execution and repetition increases activity levels, which is crucial for a good motor rehabilitation process and daily training. Interestingly, there are no sit-to-stand devices that allow a quantitative assessment of the key variables that happen during STS, and there is a need to come up with a new device. This work presents a developed biomechanical support device that measures the force of the upper limbs during the STS movement, aiming to motivate and encourage people undergoing physical therapy in the lower limbs. The device uses two instrumented beams and allows real-time visualization of both arms' applied force and it records the data for post-processing. The device was tested with a well-defined protocol on a group of 34 healthy young volunteers and an elderly group of 16 volunteers from a continuing care unit. The system showed robust strength and stiffness, good usability, and a user interface that acquired and recorded data effectively, allowing one to observe force-time during the execution of the movement through the application interface developed and in recording data for post-processing. Asymmetries in the applied forces in the STS movement between the upper limbs were identified, particularly in volunteers of the continuing care unit. From the application and the registered data, it can be observed that volunteers with motor problems in the lower limbs performed more strength in their arms to compensate. As expected, the maximum average strength of the healthy volunteers (both arms: force = 105 Newton) was higher than that of the volunteers from the continuing care unit (right arm: force = 54 Newton; left arm: force = 56 Newton). Among others, moderate correlations were observed between weight-applied and height-applied forces and there was a moderately high correlation between the Sequential Clinical Assessment of Respiratory Function (SCAR-F score) and time to perform the movement. Based on the obtained results, the developed device can be a helpful tool for monitoring the evaluation of a patient with limitations in the upper and lower limbs. In addition, the developed system allows for easy evolution, such as including a barometric platform and implementing serious games that can stimulate the execution of the STS movement.

Immersive virtual reality for upper limb rehabilitation: comparing hand and controller interaction.

Virtual reality shows great potential as an alternative to traditional therapies for motor rehabilitation given its ability to immerse the user in engaging scenarios that abstract them from medical facilities and tedious rehabilitation exercises. This paper presents a virtual reality application that includes three serious games and that was developed for motor rehabilitation. It uses a standalone headset and the user's hands without the need for any controller for interaction. Interacting with an immersive virtual reality environment using only natural hand gestures involves an interaction that is similar to that of real life, which would be especially desirable for patients with motor problems. A study involving 28 participants (4 with motor problems) was carried out to compare two types of interaction (hands vs. controllers). All of the participants completed the exercises. No significant differences were found in the number of attempts necessary to complete the games using the two types of interaction. The group that used controllers required less time to complete the exercise. The performance outcomes were independent of the gender and age of the participants. The subjective assessment of the participants with motor problems was not significantly different from the rest of the participants. With regard to the interaction type, the participants mostly preferred the interaction using their hands (78.5%). All four participants with motor problems preferred the hand interaction. These results suggest that the interaction with the user's hands together with standalone headsets could improve motivation, be well accepted by motor rehabilitation patients, and help to complete exercise therapy at home.

Technical innovations in stroke rehabilitation - a survey for development of a non-invasive, brainwave-guided, functional muscle stimulation.

BACKGROUND: Stroke is one of the most frequent causes of death in Germany and the developed countries. After a stroke, those affected often suffer particularly from functional motor restrictions of the upper extremities. Newer techniques such as the BCI-FES systems aim to establish a communication channel between the brain and external devices with a neuromuscular intervention. The electrical activity of the brain is measured, processed, translated into control signals and can then be used to control an application. METHODS: As a mixed-methods design (exploratory design), eight guideline-based expert interviews were conducted first. For the quantitative expert survey, 95 chief physicians from the field of neuromedicine in rehabilitation facilities nationwide were subsequently invited to participate in an online survey. RESULTS: In our data analysis, we found that doctors are largely open-minded towards new technical rehabilitation systems. In addition to the proper functioning of the system, they consider the understanding of the functionality and the meaningfulness of the system to be particularly important. In addition, the system should be motivating for individuals, generate meaningful movements, be easy to use, evidence-based and quick to set up. Concerns were expressed regarding the understanding of the system's processes, especially in the acute phase after a stroke, as well as the excessive expectation of results from the system on the part of the persons. The experts named stroke patients in rehabilitation phase C, which is about mobilization and recovery, as well as all persons who can understand the language requirements as benefiting groups of people. CONCLUSION: The present study shows that more research should and must be done in the field of BCI-FES interfaces, and various development trends have been identified. The system has the potential to play a leading role in the rehabilitation of stroke patients in the future. Nevertheless, more work should be done on the improvement and implementation as well as the system's susceptibility to interference in everyday patient life.

Automatic Selection of Control Features for Electroencephalography-Based Brain-Computer Interface Assisted Motor Rehabilitation: The GUIDER Algorithm.

Sensorimotor rhythms-based Brain-Computer Interfaces (BCIs) have successfully been employed to address upper limb motor rehabilitation after stroke. In this context, becomes crucial the choice of features that would enable an appropriate electroencephalographic (EEG) sensorimotor activation/engagement underlying the favourable motor recovery. Here, we present a novel feature selection algorithm (GUIDER) designed and implemented to integrate specific requirements related to neurophysiological knowledge and rehabilitative principles. The GUIDER algorithm was tested on an EEG dataset collected from 13 subacute stroke participants. The comparison between the automatic feature selection procedure by means of GUIDER algorithm and the manual feature selection executed by an expert neurophysiologist returned similar performance in terms of both feature selection and classification. Our preliminary findings suggest that the choices of experienced neurophysiologists could be reproducible by an automatic approach. The proposed automatic algorithm could be apt to support the professional end-users not expert in BCI such as therapist/clinicians and, to ultimately foster a wider employment of the BCI-based rehabilitation after stroke.

Automatic Evaluation of Motor Rehabilitation Exercises Based on Deep Mixture Density Neural Networks.

An automatic assessment system for physical telerehabilitation could reduce the time and cost of treatments. But such assessment involves stochastic uncertainties, nonlinearities, and complexities of human movement. Probabilistic models and deep structures are two categories that could, respectively, address the stochastic uncertainty and complexity of motion data. In the proposed Deep Mixture Density Network (DMDN), probabilistic models were concurrently processed along with deep neural networks. More specifically, a multi-branch convolutional layer extracted the deep features of motion data, a Long Short Term Memory (LSTM) learned its temporal dependencies, and a Gaussian Mixture Model (GMM) handled the stochastic interaction of its preceding layers in reaching a more valid assessment and improved generalization to new movements. Finally, the weighted mean of the GMM components was used as the performance score for exercises. Input data were the time series related to the joints' position and orientation extracted from the Kinect v2 sensor video. A clinical reference score for each movement was also included for training the DMDN. In addition to comparisons with the state-of-the-art algorithms, an ablation study of the various elements comprising the DMDN was performed. Three configurations of convolutional filter window transitions across input data were also investigated. Results indicate that the proposed DMDN with one-dimensional parallel window transitions outperforms the other competing strategies in the ablation study. It also achieves higher reliability in terms of a lower RMSE standard deviation against a DMDN without GMM strategy while ranking competitively according to the Spearman correlation coefficient and Root Mean Square Error.

Myoelectric interface training enables targeted reduction in abnormal muscle co-activation.

BACKGROUND: Abnormal patterns of muscle co-activation contribute to impaired movement after stroke. Previously, we developed a myoelectric computer interface (MyoCI) training paradigm to improve stroke-induced arm motor impairment by reducing the abnormal co-activation of arm muscle pairs. However, it is unclear to what extent the paradigm induced changes in the overall intermuscular coordination in the arm, as opposed to changing just the muscles trained with the MyoCI. This study examined the intermuscular coordination patterns of thirty-two stroke survivors who participated in 6 weeks of MyoCI training. METHODS: We used non-negative matrix factorization to identify the arm muscle synergies (coordinated patterns of muscle activity) during a reaching task before and after the training. We examined the extent to which synergies changed as the training reduced motor impairment. In addition, we introduced a new synergy analysis metric, disparity index (DI), to capture the changes in the individual muscle weights within a synergy. RESULTS: There was no consistent pattern of change in the number of synergies across the subjects after the training. The composition of muscle synergies, calculated using a traditional synergy similarity metric, also did not change after the training. However, the disparity of muscle weights within synergies increased after the training in the participants who responded to MyoCI training-that is, the specific muscles that the MyoCI was targeting became less correlated within a synergy. This trend was not observed in participants who did not respond to the training. CONCLUSIONS: These findings suggest that MyoCI training reduced arm impairment by decoupling only the muscles trained while leaving other muscles relatively unaffected. This suggests that, even after injury, the nervous system is capable of motor learning on a highly fractionated level. It also suggests that MyoCI training can do what it was designed to do-enable stroke survivors to reduce abnormal co-activation in targeted muscles. Trial registration This study was registered at ClinicalTrials.gov (NCT03579992, Registered 09 July 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03579992?term=NCT03579992&draw=2&rank=1 ).

Enhancing Post-Stroke Rehabilitation and Preventing Exo-Focal Dopaminergic Degeneration in Rats-A Role for Substance P.

Dopaminergic signaling is a prerequisite for motor learning. Delayed degeneration of dopaminergic neurons after stroke is linked to motor learning deficits impairing motor rehabilitation. This study investigates safety and efficacy of substance P (SP) treatment on post-stroke rehabilitation, as this neuropeptide combines neuroprotective and plasticity-promoting properties. Male Sprague Dawley rats received a photothrombotic stroke within the primary motor cortex (M1) after which a previously acquired skilled reaching task was rehabilitated. Rats were treated with intraperitoneal saline (control group, n = 7) or SP-injections (250 µg/kg) 30 min before (SP-pre; n = 7) or 16 h (SP-post; n = 6) after rehabilitation training. Dopaminergic neurodegeneration, microglial activation and substance P-immunoreactivity (IR) were analyzed immunohistochemically. Systemic SP significantly facilitated motor rehabilitation. This effect was more pronounced in SP-pre compared to SP-post animals. SP prevented dopaminergic cell loss after stroke, particularly in the SP-pre condition. Despite its proinflammatory propensity, SP administration did not increase stroke volumes, post-stroke deficits or activation of microglia in the midbrain. Finally, SP administration prevented ipsilesional hypertrophy of striatal SPergic innervation, particularly in the SP-post condition. Mechanistically, SP-pre likely involved plasticity-promoting effects in the early phase of rehabilitation, whereas preservation of dopaminergic signaling may have ameliorated rehabilitative success in both SP groups during later stages of training. Our results demonstrate the facilitating effect of SP treatment on motor rehabilitation after stroke, especially if administered prior to training. SP furthermore prevented delayed dopaminergic degeneration and preserved physiological endogenous SPergic innervation.

Role of virtual reality and active video games in motor and executive functions in cerebral palsy: A systematic review.

OBJECTIVE: To explore current evidence on the role of virtual reality and active video games in motor and executive functions compared to conventional physical therapies in cerebral palsy patients. METHODS: The systematic review was conducted at the University Institute of Physical Therapy, Lahore, Pakistan, and comprised search on MEDLINE via PubMed, Pedro and Cochrane Central related to randomised and clinical controlled trials published from 2005 to 2020. For critical appraisal of the studies, the Pedro tool was used, while methodological quality assessment was done using the Cochrane risk of bias tool. RESULTS: Of the 15 articles reviewed, 14(93.3%) reported significant effect of virtual reality and active video games on motor functions. Critical appraisal found the quality of the studies from fair to high. Low risk was found in 4(26.7%) articles in terms of selection, 3(20%) allocation, 6(40%) detection, and 8(53.3%) had attrition bias. Unclear risk was reported in the performance and reporting bias domain in all the 15(100%) articles. CONCLUSIONS: Virtual reality games cannot be used as a substitute for therapy, but along with the conventional physical therapy, they are very effective and produce significant changes in motor functions in cerebral palsy patients. As for executive functions, more research needs to be done to determine the impact of these games at a higher level of brain.

The Outcomes of Robotic Rehabilitation Assisted Devices Following Spinal Cord Injury and the Prevention of Secondary Associated Complications.

Spinal cord injuries (SCIs) have major consequences on the patient's health and life. Voluntary muscle paralysis caused by spinal cord damage affects the patient's independence. Following SCI, an irreversible motor and sensory deficit occurs (spasticity, muscle paralysis, atrophy, pain, gait disorders, pain). This pathology has implications on the whole organism: on the osteoarticular, muscular, cardiovascular, respiratory, gastrointestinal, genito-urinary, skin, metabolic disorders, and neuro-psychic systems. The rehabilitation process for a subject having SCIs can be considered complex, since the pathophysiological mechanism and biochemical modifications occurring at the level of spinal cord are not yet fully elucidated. This review aims at evaluating the impact of robotic-assisted rehabilitation in subjects who have suffered SCI, both in terms of regaining mobility as a major dysfunction in patients with SCI, but also in terms of improving overall fitness and cardiovascular function, respiratory function, as well as the gastrointestinal system, bone density and finally the psychosocial issues, based on multiple clinical trials, and pilot studies. The researched literature in the topic revealed that in order to increase the chances of neuro-motor recovery and to obtain satisfactory results, the combination of robotic therapy, a complex recovery treatment and specific medication is one of the best decisions. Furthermore, the use of these exoskeletons facilitates better/greater autonomy for patients, as well as optimal social integration.

A New Technology for Recovery of Locomotion in Patients after a Stroke.

Neural networks in the spinal cord can generate the walking pattern and control posture in the absence of supraspinal influences. A technology using transcutaneous electrical spinal cord stimulation (tSCS) was created. During walking, tSCS activated spinal locomotor networks, as well as leg flexor/extensor motor pools in the swing/stance phases, respectively. It was assumed that the use of this technology in subjects with locomotion disorders would improve walking. Patients with hemiparesis were studied 3-11 months after stroke, the duration of the course was 2 weeks. Patients of the main and control groups received standard therapy and rehabilitation using the technology; in the control group, sham tSCS was used. After the course, minimal clinically important differences in walking parameters were achieved in the main group, in contrast to the control group. The developed technology is an effective means of restoring walking in patients with hemiparesis.

[Research progress on mechanical perturbation in stroke rehabilitation].

Sensorimotor disorder can be easily caused by stroke, and there are many targeted movement rehabilitation therapies. With the development of rehabilitation robot technology, robot-assisted therapy combined with mechanical perturbations has become a more effective motor rehabilitation therapy. In this paper, the definition of mechanical perturbation and its physiological mechanism in stroke rehabilitation are introduced, the research progress on mechanical perturbation in the field of stroke rehabilitation therapy is mainly discussed, the application of mechanical perturbation in motor control, postural response and sensory evaluation of stroke rehabilitation is summarized, and the future development direction of mechanical perturbation rehabilitation therapy is also prospected.

[Physical activity in the elderly with a major neurocognitive disorder]. / Activité physique chez le sujet âgé atteint d'un trouble neurocognitif majeur (2/2).

A better knowledge of major neurocognitive disorders and motor learning allows us to propose motor rehabilitation (MR) adapted to subjects with Alzheimer's disease. Recent neuroscientific data on motor functions and cognition allow the construction of physical activity and MR programs, for which the dose-response relationship, content and instructions are determining factors. Further studies are needed to confirm the effectiveness of the methods used.

[Physical activity in the elderly with other major neurocognitive disorders]. / Activité physique chez le sujet âgé atteint d'un trouble neurocognitif majeur.

For decades, the literature was skeptical about the feasibility of motor rehabilitation and its impact, as well as that of physical activity (PA), in subjects with major neurocognitive disorders (MNCD), including Alzheimer's disease. Now, authors report several benefits of PA, both physical and cognitive, by promoting brain perfusion, neurogenesis and synaptic plasticity, as well as decreasing oxidative stress and inflammation. PA should be recommended in cases of TNCM.

[Portable Monitoring Device for Motor Rehabilitation Equipment with Rotor Shaft].

A novel and portable device is proposed to monitor motor rehabilitation equipment, which can be mounted on most equipment with rotor shaft. The software of the device, whose main functions include equipment configuration, monitoring and statistical computation, is developed based on available sensor. The data collected by the device serve both department managers to learn the efficiency of the equipment, and physicians and therapists to understand the physical conditions of the patients who perform training exercises with the monitored rehabilitation equipment. About 2000 hours' monitoring has been carried out, and the experimental result indicates that the monitoring device is applicable to many types of motor rehabilitation equipment and achieves good monitoring accuracy. The data aggregated by the device can be used to evaluate the motor functions of the patients and make rehabilitation training plan. Besides, it is agreed by physicians and therapists that the device is easy-to-use, robust and has good real-time performance. The monitoring device thus holds the promise of boosting the development of digitalized rehabilitation medicine.

European Academy of Neurology and European Federation of Neurorehabilitation Societies guideline on pharmacological support in early motor rehabilitation after acute ischaemic stroke.

BACKGROUND AND PURPOSE: Early pharmacological support for post-stroke neurorehabilitation has seen an abundance of mixed results from clinical trials, leaving practitioners at a loss regarding the best options to improve patient outcomes. The objective of this evidence-based guideline is to support clinical decision-making of healthcare professionals involved in the recovery of stroke survivors. METHODS: This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. PubMed, Cochrane Library and Embase were searched (from database inception to June 2018, inclusive) to identify studies on pharmacological interventions for stroke rehabilitation initiated in the first 7 days (inclusive) after stroke, which were delivered together with neurorehabilitation. A sensitivity analysis was conducted on identified interventions to address results from breaking studies (from end of search to February 2020). RESULTS: Upon manually screening 17,969 unique database entries (of 57,001 original query results), interventions underwent meta-analysis. Cerebrolysin (30 ml/day, intravenous, minimum 10 days) and citalopram (20 mg/day, oral) are recommended for clinical use for early neurorehabilitation after acute ischaemic stroke. The remaining interventions identified by our systematic search are not recommended for clinical use: amphetamine (5, 10 mg/day, oral), citalopram (10 mg/day, oral), dextroamphetamine (10 mg/day, oral), Di-Huang-Yi-Zhi (2 × 18 g/day, oral), fluoxetine (20 mg/day, oral), lithium (2 × 300 mg/day, oral), MLC601(3 × 400 mg/day, oral), phosphodiesterase-5 inhibitor PF-03049423 (6 mg/day, oral). No recommendation 'for' or 'against' is provided for selegiline (5 mg/day, oral). Issues with safety and tolerability were identified for amphetamine, dextroamphetamine, fluoxetine and lithium. CONCLUSIONS: This guideline provides information for clinicians regarding existing pharmacological support in interventions for neurorecovery after acute ischaemic stroke. Updates to this material will potentially elucidate existing conundrums, improve current recommendations, and hopefully expand therapeutic options for stroke survivors.