Pr. Jacques LUAUTE

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Most of motor recovery usually occurs within the first 3 months after stroke. Herein is reported a remarkable late recovery of the right upper-limb motor function after a left middle cerebral artery stroke. This recovery happened progressively, from two to 12 years post-stroke onset, and along a proximo-distal gradient, including dissociated finger movements after 5 years. Standardized clinical assessment and quantified analysis of the reach-to-grasp movement were repeated over time to characterize the recovery. Twelve years after stroke onset, diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation (TMS) analyses of the corticospinal tracts were carried out to investigate the plasticity mechanisms and efferent pathways underlying motor control of the paretic hand. Clinical evaluations and quantified movement analysis argue for a true neurological recovery rather than a compensation mechanism. DTI showed a significant decrease of fractional anisotropy, associated with a severe atrophy, only in the upper part of the left corticospinal tract (CST), suggesting an alteration of the CST at the level of the infarction that is not propagated downstream. The finger opposition movement of the right paretic hand was associated with fMRI activations of a broad network including predominantly the contralateral sensorimotor areas. Motor evoked potentials were normal and the selective stimulation of the right hemisphere did not elicit any response of the ipsilateral upper limb. These findings support the idea that the motor control of the paretic hand is mediated mainly by the contralateral sensorimotor cortex and the corresponding CST, but also by a plasticity of motor-related areas in both hemispheres. To our knowledge, this is the first report of a high quality upper-limb recovery occurring more than 2 years after stroke with a genuine insight of brain plasticity mechanisms.

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Introduction: Patients with right stroke lesion have postural and balance disorders, including weight-bearing asymmetry, more pronounced than patients with left stroke lesion. Spatial cognition disorders post-stroke, such as misperceptions of subjective straight-ahead and subjective longitudinal body axis, are suspected to be involved in these postural and balance disorders. Prismatic adaptation has showed beneficial effects to reduce visuomotor disorders but also an expansion of effects on cognitive functions, including spatial cognition. Preliminary studies with a low level of evidence have suggested positive effects of prismatic adaptation on weight-bearing asymmetry and balance after stroke. The objective is to investigate the effects of this intervention on balance but also on postural disorders, subjective straight-ahead, longitudinal body axis and autonomy in patients with chronic right stroke lesion. Methods and analysis: In this multicentre randomised double-blind sham-controlled trial, we will include 28 patients aged from 18 to 80 years, with a first right supratentorial stroke lesion at chronic stage (≥12 months) and having a bearing ≥60% of body weight on the right lower limb. Participants will be randomly assigned to the experimental group (performing pointing tasks while wearing glasses shifting optical axis of 10 degrees towards the right side) or to the control group (performing the same procedure while wearing neutral glasses without optical deviation). All participants will receive a 20 min daily session for 2 weeks in addition to conventional rehabilitation. The primary outcome will be the balance measured using the Berg Balance Scale. Secondary outcomes will include weight-bearing asymmetry and parameters of body sway during static posturographic assessments, as well as lateropulsion (measured using the Scale for Contraversive Pushing), subjective straight-ahead, longitudinal body axis and autonomy (measured using the Barthel Index). Ethics and dissemination: The study has been approved by the ethical review board in France. Findings will be submitted to peer-reviewed journals relative to rehabilitation or stroke.

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Pas de résumé

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Neuroscientific and clinical studies on auditory perception often use headphones to limit sound interference. In these conditions, sounds are perceived as internalized because they lack the sound-attributes that normally occur with a sound produced from a point in space around the listener. Without the spatial attention mechanisms that occur with localized sounds, auditory functional assessments could thus be underestimated. We hypothesize that adding virtually externalization and localization cues to sounds through headphones enhance sound discrimination in both healthy participants and patients with a disorder of consciousness (DOC). Hd-EEG was analyzed in 14 healthy participants and 18 patients while they listened to self-relevant and irrelevant stimuli in two forms: diotic (classic sound presentation with an “internalized” feeling) and convolved with a binaural room impulse response (to create an “externalized” feeling). Convolution enhanced the brains’ discriminative response as well as the processing of irrelevant sounds itself, in both healthy participants and DOC patients. For the healthy participants, these effects could be associated with enhanced activation of both the dorsal (where/how) and ventral (what) auditory streams, suggesting that spatial attributes support speech discrimination. Thus, virtually spatialized sounds might “call attention to the outside world” and improve the sensitivity of assessment of brain function in DOC patients.

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Background and purpose: Additional therapy may improve poststroke outcomes. Self-rehabilitation is a useful means to increase rehabilitation time. Mechanized systems are usual means to extend time for motor training. The primary aim was to compare the effects of self-rehabilitation using a mechanized device with control self-exercises on upper extremity impairment in patients with stroke. Methods: Phase III, parallel, concealed allocation, randomized controlled, multicenter trial, with 12-month follow-up. Patients aged 18 to 80 years, 3 weeks to 3 months poststroke with a Fugl-Meyer Assessment score of 10 to 40 points, were randomized to the Exo or control groups. All undertook two 30-minute self-rehabilitation sessions/day, 5 days/wk for 4 weeks in addition to usual rehabilitation. The Exo group performed games-based exercises using a gravity-supported mechanical exoskeleton (Armeo Spring). The control group performed stretching plus basic active exercises. Primary outcome was change in upper extremity Fugl-Meyer Assessment score at 4 weeks. Results: Two hundred fifteen participants were randomly allocated to the Exo group (107) or the control group (108). Mean age (SD), 58.3 (13.6) years; mean time poststroke, 54.8 (22.1) days; and mean baseline Fugl-Meyer Assessment score, 26.1 (9.5). There was no between-group difference in mean change in Fugl-Meyer Assessment score following the intervention: 13.3 (9.0) in the Exo group and 11.8 (8.8) in the control group (P=0.22). There were no significant between-group differences in changes for any of the other outcomes at any time point (except for perception of the self-rehabilitation). There was no between-group difference in cost utility at 12 months. Conclusions: In patients with moderate-to-severe impairment in the subacute phase of stroke, the purchase and use of complex devices to provide additional upper limb training may not be necessary: simply educating patients to regularly move and stretch their limbs appears sufficient.

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Background: Cystinosis is a rare autosomal recessive disorder caused by intracellular cystine accumulation. Proximal tubulopathy (Fanconi syndrome) is one of the first signs, leading to end-stage renal disease between the age of 12 and 16. Other symptoms occur later and encompass endocrinopathies, distal myopathy and deterioration of the central nervous system. Treatment with cysteamine if started early can delay the progression of the disease. Little is known about the neurological impairment which occurs later. The goal of the present study was to find a possible neuroanatomical dysmorphic pattern that could help to explain the cognitive profile of cystinosis patients. We also performed a detailed review of the literature on neurocognitive complications associated with cystinosis. Methods: 17 patients (mean age = 17.6 years, [5.4-33.3]) with cystinosis were included in the study. Neuropsychological assessment was performed including intelligence (Intelligence Quotient (IQ) with Wechsler’s scale), memory (Children Memory Scale and Wechsler Memory Scale), visuo-spatial (Rey’s figure test) and visuo-perceptual skills assessments. Structural brain MRI (3 T) was also performed in 16 out of 17 patients, with high resolution 3D T1-weighted, 3D FLAIR and spectroscopy sequences. Results: Intellectual efficiency was normal in patients with cystinosis (mean Total IQ = 93). However the Perceptual Reasoning Index (mean = 87, [63-109]) was significantly lower than the Verbal Comprehension Index (mean = 100, [59-138], p = 0.003). Memory assessment showed no difference between visual and verbal memory. But the working memory was significantly impaired in comparison with the general memory skills (p = 0.003). Visuospatial skills assessment revealed copy and reproduction scores below the 50th percentile rank in more than 70% of the patients. Brain MRI showed cortical and sub-cortical cerebral atrophy, especially in the parieto-occipital region and FLAIR hypersignals in parietal, occipital and brain stem/cerebellum. Patients with atrophic brain had lower Total IQ scores compared to non-atrophic cystinosis patients. Conclusions: Patients with cystinosis have a specific neuropsychological and neuroanatomical profile. We suggest performing a systematic neuropsychological assessment in such children aiming at considering adequate management.

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The extent to which a tool is an extension of its user is a question that has fascinated writers and philosophers for centuries [1]. Despite two decades of research [2-7], it remains unknown how this could be instantiated at the neural level. To this aim, the present study combined behavior, electrophysiology and neuronal modeling to characterize how the human brain could treat a tool like an extended sensory “organ.” As with the body, participants localize touches on a hand-held tool with near-perfect accuracy [7]. This behavior is owed to the ability of the somatosensory system to rapidly and efficiently use the tool as a tactile extension of the body. Using electroencephalography (EEG), we found that where a hand-held tool was touched was immediately coded in the neural dynamics of primary somatosensory and posterior parietal cortices of healthy participants. We found similar neural responses in a proprioceptively deafferented patient with spared touch perception, suggesting that location information is extracted from the rod’s vibrational patterns. Simulations of mechanoreceptor responses [8] suggested that the speed at which these patterns are processed is highly efficient. A second EEG experiment showed that touches on the tool and arm surfaces were localized by similar stages of cortical processing. Multivariate decoding algorithms and cortical source reconstruction provided further evidence that early limb-based processes were repurposed to map touch on a tool. We propose that an elementary strategy the human brain uses to sense with tools is to recruit primary somatosensory dynamics otherwise devoted to the body.

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Patients lying in a vegetative state present severe impairments of consciousness [1] caused by lesions in the cortex, the brainstem, the thalamus and the white matter [2]. There is agreement that this condition may involve disconnections in long-range cortico-cortical and thalamo-cortical pathways [3]. Hence, in the vegetative state cortical activity is ‘deafferented’ from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity [3]. The likelihood of consciousness recovery depends on the extent of brain damage and patients’ etiology, but after one year of unresponsive behavior, chances become low [1]. There is thus a need to explore novel ways of repairing lost consciousness. Here we report beneficial effects of vagus nerve stimulation on consciousness level of a single patient in a vegetative state, including improved behavioral responsiveness and enhanced brain connectivity patterns.

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Prism adaptation induces rapid recalibration of visuomotor coordination. The neural mechanisms of prism adaptation have come under scrutiny since the observations that the technique can alleviate hemispatial neglect following stroke, and can alter spatial cognition in healthy controls. Relative to non-imaging behavioral studies, fMRI investigations of prism adaptation face several challenges arising from the confined physical environment of the scanner and the supine position of the participants. Any researcher who wishes to administer prism adaptation in an fMRI environment must adjust their procedures enough to enable the experiment to be performed, but not so much that the behavioral task departs too much from true prism adaptation. Furthermore, the specific temporal dynamics of behavioral components of prism adaptation present additional challenges for measuring their neural correlates. We developed a system for measuring the key features of prism adaptation behavior within an fMRI environment. To validate our configuration, we present behavioral (pointing) and head movement data from 11 right-hemisphere lesioned patients and 17 older controls who underwent sham and real prism adaptation in an MRI scanner. Most participants could adapt to prismatic displacement with minimal head movements, and the procedure was well tolerated. We propose recommendations for fMRI studies of prism adaptation based on the design-specific constraints and our results.

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The reestablishment of communication is one of the main goals for patients with disorders of consciousness (DOC). It is now established that many DOC patients retain the ability to process stimuli of varying complexity even in the absence of behavioural response. Motor impairment, fatigue, attention disorders might contribute to the difficulty of communication in this population. Brain-computer interfaces (BCI) might be helpful in restoring some communication ability in these patients. After a definition of the different disorders of consciousness that might benefit from BCI, brain markers able to detect cognitive processes and awareness in the absence of behavioural manifestation are described. Can these markers be willfully modulated and used to restore communication in DOC patients? In order to answer this question, three paradigmatic articles using either functional imaging or electrophysiology are critically analysed with regard to clinical applications. It appears that the use of fMRI is limited from a clinical point of view, whereas the EEG seems more feasible with possible BCI applications at the patient’s bedside. However, at this stage, several limitations are pointed out: the lack of awareness in itself, the lack of sensitivity of the technique, atypical pattern of brain activity in brain damaged patients. The challenge is now to select the best candidates, to improve the efficiency, portability and cost of these techniques. Although this innovative technology may concern a minority of DOC patients, it might offer the possibility to restore or improve communication to heavily disabled patients and meanwhile detect a signature of awareness.

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Unilateral neglect is a neurological condition responsible for many debilitating effects on everyday life, poor functional recovery, and decreased ability to benefit from treatment. Prism adaptation (PA) to a right lateral displacement of the visual field is classically known to directionally bias visuo-motor and sensory-motor correspondences. One longstanding issue about this visuo-motor plasticity is about its specificity to the exposure condition. In contrast to very poor transfer to unexposed effectors classically described in healthy subjects, therapeutic results obtained in neglect patients suggested that PA can generate unexpected “expansion”. Prism adaptation affects numerous levels of neglect symptomatology, suggesting that its effects somehow expand to unexposed sensory, motor and cognitive systems. The available body of evidence in support for this expansion raises important questions about the mechanisms involved in producing unexpected cognitive effects following a simple and moderate visuo-motor adaptation. We further develop here the idea that prism adaptation expansion to spatial cognition involves a cerebello-cortical network and review support for this model. Building on the basic, therapeutical and pathophysiological knowledge accumulated over the last 15 years, we also provide guidelines for the optimal use of prism adaptation in the clinic. Although further research and clinical trials are required to precisely define the ideal regime for routine applications, the current state of the art allows us to outline practical recommendations for therapeutical use of prisms.