The Berlin Bimanual Test for Tetraplegia (BeBiTT): development, psychometric properties, and sensitivity to change in assistive hand exoskeleton application.

BACKGROUND: Assistive hand exoskeletons are promising tools to restore hand function after cervical spinal cord injury (SCI) but assessing their specific impact on bimanual hand and arm function is limited due to lack of reliable and valid clinical tests. Here, we introduce the Berlin Bimanual Test for Tetraplegia (BeBiTT) and demonstrate its psychometric properties and sensitivity to assistive hand exoskeleton-related improvements in bimanual task performance. METHODS: Fourteen study participants with subacute cervical SCI performed the BeBiTT unassisted (baseline). Thereafter, participants repeated the BeBiTT while wearing a brain/neural hand exoskeleton (B/NHE) (intervention). Online control of the B/NHE was established via a hybrid sensorimotor rhythm-based brain-computer interface (BCI) translating electroencephalographic (EEG) and electrooculographic (EOG) signals into open/close commands. For reliability assessment, BeBiTT scores were obtained by four independent observers. Besides internal consistency analysis, construct validity was assessed by correlating baseline BeBiTT scores with the Spinal Cord Independence Measure III (SCIM III) and Quadriplegia Index of Function (QIF). Sensitivity to differences in bimanual task performance was assessed with a bootstrapped paired t-test. RESULTS: The BeBiTT showed excellent interrater reliability (intraclass correlation coefficients > 0.9) and internal consistency (α = 0.91). Validity of the BeBiTT was evidenced by strong correlations between BeBiTT scores and SCIM III as well as QIF. Wearing a B/NHE (intervention) improved the BeBiTT score significantly (p < 0.05) with high effect size (d = 1.063), documenting high sensitivity to intervention-related differences in bimanual task performance. CONCLUSION: The BeBiTT is a reliable and valid test for evaluating bimanual task performance in persons with tetraplegia, suitable to assess the impact of assistive hand exoskeletons on bimanual function.

Personalized neurorehabilitative precision medicine: from data to therapies (MWKNeuroReha) - a multi-centre prospective observational clinical trial to predict long-term outcome of patients with acute motor stroke.

BACKGROUND: Stroke is one of the most frequent diseases, and half of the stroke survivors are left with permanent impairment. Prediction of individual outcome is still difficult. Many but not all patients with stroke improve by approximately 1.7 times the initial impairment, that has been termed proportional recovery rule. The present study aims at identifying factors predicting motor outcome after stroke more accurately than before, and observe associations of rehabilitation treatment with outcome. METHODS: The study is designed as a multi-centre prospective clinical observational trial. An extensive primary data set of clinical, neuroimaging, electrophysiological, and laboratory data will be collected within 96 h of stroke onset from patients with relevant upper extremity deficit, as indexed by a Fugl-Meyer-Upper Extremity (FM-UE) score ≤ 50. At least 200 patients will be recruited. Clinical scores will include the FM-UE score (range 0-66, unimpaired function is indicated by a score of 66), Action Research Arm Test, modified Rankin Scale, Barthel Index and Stroke-Specific Quality of Life Scale. Follow-up clinical scores and applied types and amount of rehabilitation treatment will be documented in the rehabilitation hospitals. Final follow-up clinical scoring will be performed 90 days after the stroke event. The primary endpoint is the change in FM-UE defined as 90 days FM-UE minus initial FM-UE, divided by initial FM-UE impairment. Changes in the other clinical scores serve as secondary endpoints. Machine learning methods will be employed to analyze the data and predict primary and secondary endpoints based on the primary data set and the different rehabilitation treatments. DISCUSSION: If successful, outcome and relation to rehabilitation treatment in patients with acute motor stroke will be predictable more reliably than currently possible, leading to personalized neurorehabilitation. An important regulatory aspect of this trial is the first-time implementation of systematic patient data transfer between emergency and rehabilitation hospitals, which are divided institutions in Germany. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT04688970 ) on 30 December 2020.

Post-stroke Rehabilitation of Severe Upper Limb Paresis in Germany - Toward Long-Term Treatment With Brain-Computer Interfaces.

Severe upper limb paresis can represent an immense burden for stroke survivors. Given the rising prevalence of stroke, restoration of severe upper limb motor impairment remains a major challenge for rehabilitation medicine because effective treatment strategies are lacking. Commonly applied interventions in Germany, such as mirror therapy and impairment-oriented training, are limited in efficacy, demanding for new strategies to be found. By translating brain signals into control commands of external devices, brain-computer interfaces (BCIs) and brain-machine interfaces (BMIs) represent promising, neurotechnology-based alternatives for stroke patients with highly restricted arm and hand function. In this mini-review, we outline perspectives on how BCI-based therapy can be integrated into the different stages of neurorehabilitation in Germany to meet a long-term treatment approach: We found that it is most appropriate to start therapy with BCI-based neurofeedback immediately after early rehabilitation. BCI-driven functional electrical stimulation (FES) and BMI robotic therapy are well suited for subsequent post hospital curative treatment in the subacute stage. BCI-based hand exoskeleton training can be continued within outpatient occupational therapy to further improve hand function and address motivational issues in chronic stroke patients. Once the rehabilitation potential is exhausted, BCI technology can be used to drive assistive devices to compensate for impaired function. However, there are several challenges yet to overcome before such long-term treatment strategies can be implemented within broad clinical application: 1. developing reliable BCI systems with better usability; 2. conducting more research to improve BCI training paradigms and 3. establishing reliable methods to identify suitable patients.

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.

Cerebrolysin after moderate to severe traumatic brain injury: prospective meta-analysis of the CAPTAIN trial series.

INTRODUCTION: This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. MATERIALS AND METHODS: The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. RESULTS: A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a "small-to-medium" sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. DISCUSSION: The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.

Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial.

INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.

VaD - An Integrated Framework for Cognitive Rehabilitation.

BACKGROUND & OBJECTIVE: Vascular dementia is the second most common cause of dementia, with clinical features that depend on neural substrates affected by the vascular lesions. Like most neurological disorders, it involves alterations that range from the molecular level to neuronal networks. Such alterations begin as compensatory mechanisms that reshape every subsystem involved in the brain's homeostasis. Although there have been recent huge advances in understanding the pathophysiology of cognitive dysfunction, a suitable therapeutic approach to vascular dementia remains elusive. Pharmacological interventions have failed to sustainably improve cognitive function, and it is a well-known fact that there is a need to change the current view for providing neuroprotection and enhancing neurorecovery after stroke. Studies regarding cognitive training are also faced with the difficulty of drawing up protocols that can embrace a holistic approach in cognitively impaired patients. CONCLUSION: This review will present a brief synthesis of current results from basic research data and clinical studies regarding pharmacological and non-pharmacological interventions in vascular dementia and will offer an integrated view from the perspective of systems biology.

Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials.

This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30-50 ml Cerebrolysin once daily for 10-21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.

European core curriculum in neurorehabilitation.

To date, medical education lacks Europe-wide standards on neurorehabilitation. To address this, the European Federation of NeuroRehabilitation Societies (EFNR) here proposes a postgraduate neurorehabilitation training scheme. In particular, the European medical core curriculum in neurorehabilitation should include a two-year residency in a neurorehabilitation setting where trainees can gain practical experience. Furthermore, it should comprise six modules of classroom training organized as weekend seminars or summer/winter schools. In conclusion, after defining the European medical core curriculum in neurorehabilitation, the next activities of the EFNR will be to try and reach the largest possible consensus on its content among all national societies across Europe in order to further validate it and try to extend it to the other, non-medical, professionals on the neurorehabilitation team in line with their core curricula defined by each professional association.

Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool.

INTRODUCTION: Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. METHODS: From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. RESULTS: Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02). DISCUSSION: The association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation.

Cerebrolysin Asian Pacific trial in acute brain injury and neurorecovery: design and methods.

Traumatic brain injury (TBI) is one of the leading causes of injury-related death. In the United States alone, an estimated 1.7 million people sustain a TBI each year, and approximately 5.3 million people live with a TBI-related disability. The direct medical costs and indirect costs such as lost productivity of TBIs totaled an estimated $76.5 billion in the U.S. in the year 2000. Improving the limited treatment options for this condition remains challenging. However, recent reports from interdisciplinary working groups (consisting primarily of neurologists, neurosurgeons, neuropsychologists, and biostatisticians) have stated that to improve TBI treatment, important methodological lessons from the past must be taken into account in future clinical research. An evaluation of the neuroprotection intervention studies conducted over the last 30 years has indicated that a limited understanding of the underlying biological concepts and methodological design flaws are the major reasons for the failure of pharmacological agents to demonstrate efficacy. Cerebrolysin is a parenterally-administered neuro-peptide preparation that acts in a manner similar to endogenous neurotrophic factors. Cerebrolysin has a favorable adverse effect profile, and several meta-analyses have suggested that Cerebrolysin is beneficial as a dementia treatment. CAPTAIN is a randomized, double-blind, placebo-controlled, multi-center, multinational trial of the effects of Cerebrolysin on neuroprotection and neurorecovery after TBI using a multidimensional ensemble of outcome scales. The CAPTAIN trial will be the first TBI trial with a 'true' multidimensional approach based on full outcome scales, while avoiding prior weaknesses, such as loss of information through "dichotomization," or unrealistic assumptions such as "normal distribution."

Neurorehabilitation approaches to facilitate motor recovery.

Over the last decade a dramatic change has occurred in the field of neurorehabilitation in motor recovery that is marked by three transitions: first, by movement away from intuitive and ideology-based approaches to evidence-based therapy practices; second, by a change from hands-on treatment of patients to hands-off coaching approaches by motor therapists, who incorporate knowledge about motor reorganization and motor learning; and, finally, by a transition from one-on-one treatments to group-oriented treatments. General rules (such as the need for repetition, feedback of results, shaping task difficulty) have been derived from the animal experimental and human behavioral literature and incorporated into the design of innovative treatment strategies that can be adapted to individual patients' needs. This chapter reviews the state of the art for most of the evidence-based motor therapy concepts in the rehabilitation of patients with motor deficits after stroke, traumatic brain injury, etc., and other conditions. Treatment approaches derived from neuromodulation techniques such as stimulation or blockage of peripheral nerves, noninvasive brain stimulation, and pharmacological means are addressed. Finally, a modular concept is proposed to define optimal therapeutic approaches according to the individual level and type of impairment.

Distinct cortico-cerebellar activations in rhythmic auditory motor synchronization.

We investigated the role of the cerebellum in differential aspects of temporal control of rhythmic auditory motor synchronization using positron emission tomography (PET). Subjects tapped with their right index finger to metronome tones at a mean frequency of .8 Hz during 5 conditions: (1) an isochronous rhythm condition, (2) random changes in interval durations, and while the duration of rhythmic intervals was continuously time-modulated following a cosine-wave function at (3) 3%, (4) 7%, and (5) 20% of base interval. Anterior lobe cerebellar neuronal populations showed similar motor-associated activity across all conditions regardless of rhythmic time structure in vermal and hemispheric parts ipsilateral to the movements. Neuronal populations in bilateral anterior posterior lobe, especially in the simple lobule, increased their activity stepwise with each increase in tempo modulation from a steady beat. Neuronal populations in other parts of the posterior lobe showed an increase of activity only during the 20% condition, which involved conscious monitoring of rhythmic pattern synchronization, especially on the left side contralateral to the movements. Differential cerebellar activation patterns correspond to those in contralateral primary (primary sensorimotor), ipsilateral secondary (inferior parietal close to the intraparietal sulcus) and bilateral tertiary (dorsolateral prefrontal cortex) sensorimotor areas of the cerebral cortex, suggesting that distinct functional cortico-cerebellar circuits subserve differential aspects of rhythmic synchronization in regard to rhythmic motor control, conscious and subconscious response to temporal structure, and conscious monitoring of rhythmic pattern tracking.

Relationship between interhemispheric inhibition and motor cortex excitability in subacute stroke patients.

BACKGROUND: Studies of stroke patients using functional imaging and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) demonstrated increased recruitment and abnormally decreased short interval cortical inhibition (SICI) of the M1 contralateral to the lesioned hemisphere (contralesional M1) within the first month after infarction of the M1 or its corticospinal projections. OBJECTIVE: The authors sought to identify mechanisms underlying decreased SICI of the contralesional M1. METHODS: In patients within 6 weeks of their first ever infarction of the M1 or its corticospinal projections, SICI in the M1 of the lesioned and nonlesioned hemisphere was studied using paired-pulse TMS. Interhemispheric inhibition (IHI) was measured by applying TMS to the M1 of the lesioned hemisphere and a second pulse to the homotopic M1 of the nonlesioned hemisphere and vice versa with the patient at rest. The results were compared to M1 stimulation of age-matched healthy controls. RESULTS: SICI was decreased in the M1 of lesioned and nonlesioned hemispheres regardless of cortical or subcortical infarct location. IHI was abnormally decreased from the M1 of the lesioned on nonlesioned hemisphere. In contrast, IHI was normal from the M1 of the nonlesioned on the lesioned hemisphere. Abnormal IHI and SICI were correlated in patients with cortical but not with subcortical lesions. CONCLUSIONS: In subacute stroke patients, abnormally decreased SICI of a contralesional M1 can only partially be explained by loss of IHI from the lesioned on nonlesioned hemisphere. As decreased SICI of the contralesional M1 did not result in excessive IHI from the nonlesioned on lesioned hemisphere with subsequent suppression of ipsilesional M1 excitability and all patients showed excellent recovery of motor function, decreased SICI of the contralesional M1 may represent an adaptive process supporting recovery.

Activation differences in observation of hand movements for imitation or velocity judgement.

We aimed to investigate the brain areas engaged in observation of hand movements with the intention of imitation or judging movement velocity. Both processes reflect different analytic approaches in movement observation. We were interested if these two processes can be distinguished or share common activation foci. Twelve healthy, right-handed volunteers were required to observe video clips of hand gestures and of object related grasping movements while the regional cerebral blood flow was measured using positron emission tomography. The subjects were instructed either to imitate the actions or to judge the velocity of the observed movements after scanning. Action observation with the instruction to judge movement velocity engaged bilaterally the temporo-occipital junction and adjacent visual cortical areas. In contrast, observation with the instruction to imitate them afterwards, yielded large activation clusters covering the left parietal and premotor cortex. Both contrasts demonstrated activation in the inferior frontal cortex, however, on opposite sides. Results suggest that movement observation with the goal of imitation activated specific areas of the parietal cortex in the dominant hemisphere probably related to programming of the movement kinematics. In contrast, observation with the goal to characterize the velocity of the finger movements activated the ventral visual pathways. Thus, movement observation recruits non-overlapping cortical networks, depending on the information attended to which are characterised by a dorsal ventral dissociation.

Mental practice improves hand function after hemiparetic stroke.

PURPOSE: In a multiple baseline design, we tested the hypothesis that imagery of finger movements is a specific strategy to improve hand function. METHODS: The effect of mental training of sequential finger movements (n=6) on hand function was compared to the repetitive execution of the same movements (n=6) and conventional physical therapy (n=5) in 17 patients after their first hemiparetic stroke. The behavioral outcome measures consisted of peak force of the pinch grip using a force transducer and manipulation functions of the upper extremity (Jebsen-test). In addition, activities of daily living (Barthel Index) were acquired to describe the population. RESULTS: Mental training resulted in an increase in the peak force of the pinch grip and generalized in a better functionality of the upper extremity (Jebsen-test). This effect was similar to the repetitive execution of the movements and superior to conventional physiotherapy. CONCLUSIONS: Our results suggest that the control of finger movements benefits from mental training of sequential finger movements and, thus, may be employed as a strategy in post-stroke rehabilitation.

Motor recovery as assessed with isometric finger movements and perfusion magnetic resonance imaging after acute ischemic stroke.

OBJECTIVE: Recovery from hemiparetic stroke is variable. An important goal for clinicians and clinical researchers is to identify predictors of recovery. The initial phase after acute ischemic stroke is considered to be of major importance for neurological outcome. The authors sought to determine in patients with acute ischemic stroke whether early motor recovery, as measured by repetitive isometric index-thumb oppositions, is correlated with ischemic lesion volume. METHODS: Thirty-six acute hemiparetic stroke patients with residual hand function were investigated. The European Stroke Scale (ESS) score was determined on admission and at discharge. Performance of repetitive index finger-thumb pinch movements was measured daily during the 1st 8 days after stroke onset. Brain ischemia volume was determined digitally in time-to-peak magnetic resonance images of per-fusion. RESULTS: The recovery of patients with (P = 0.002) and without (P < 0.001) thrombolysis as assessed with the ESS was paralleled by an increase in isometric grip force and movement rate (P < 0.05). Recovery was predicted by the area of moderately impaired perfusion indicated by the per-fusion mismatch volume (r = 0.578, P < 0.001). CONCLUSIONS: In acute stroke, recovery of hand function is predicted by the volume of salvageable ischemic tissue, as determined by the perfusion mismatch.

Reorganisation of cerebral circuits in human ischemic brain disease.

Animal experiments suggest that reorganisation of cerebral representations is the neurobiological basis of post-lesional recovery. In human ischemic brain disease recovery is a dynamic and sustained process beginning after stroke manifestation. The mechanisms underlying recovery can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). In the acute stage, the mismatch area of the perfusion deficit and the impaired water diffusion as assessed by magnetic resonance imaging (MRI) shows the brain tissue that potentially can be rescued by thrombolysis or emergency carotid endarterectomy. Since spontaneous motor recovery is a function of the corticospinal tract integrity, early reperfusion of ischemic tissue is critical. In the subacute and chronic stage after stroke, recovery of motor function was shown to take place irrespective of a concomitant affection of the somatosensory system. Functional MRI with simultaneous recordings of the electromyogram provides evidence that the abnormal activation of motor and premotor cortical areas in both hemispheres related to finger movements has a large interindividual variability. As evident from TMS, recovery results from regression of perilesional inhibition and from remote intracortical disinhibition. Repetitive training, constraint induced training and motor imagery can augment recovery promoting a re-emerging activation in the affected hemisphere. Evolution of altered local perilesional and large-scale bihemispheric circuits appears to allow for post-lesional deficit compensation.