Adding methylphenidate to prism-adaptation improves outcome in neglect patients. A randomized clinical trial.

Spatial neglect is one of the main predictors of poor functional recovery after stroke. Many therapeutic interventions have been developed to alleviate this condition, but to date the evidence of their effectiveness is still scarce. OBJECTIVE: The purpose of this study was to test whether combining prism adaptation (PA) and methylphenidate (MP) could enhance the recovery of neglect patients at a functional level. METHODS: RITAPRISM is a multicentre, randomized, double-blind, placebo-controlled study comparing PA plus placebo (control) versus PA plus MP. 24 patients were prospectively enrolled (10 in the placebo group and 14 in the MP group). RESULTS: The main result is a long-term functional improvement (on the functional independence measure (FIM) and on Bergego's scale) induced by MP combined with PA. No serious adverse event occurred. CONCLUSIONS: The long-term benefit on activities of daily living (ADL) obtained in this randomized controlled trial set this intervention apart from previous attempts and supports with a high level of evidence the value of combining PA and MP in order to improve the autonomy of neglect patients. Further studies will be needed to clarify the mechanism of this improvement. Although not specifically assessed at this stage, a part of the improvement in ADL might be related to the collateral effect of MP on mood, executive functions or fatigue, and/or the combined effect of PA and MP on motor intentional bias of neglect patients. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that adding MP to PA improves the functional outcome of neglect patients. WHO TRIAL REGISTRATION ID: EUCTR2008-000325-20-FR.

Tonal cues modulate line bisection performance: preliminary evidence for a new rehabilitation prospect?

The effect of the presentation of two different auditory pitches (high and low) on manual line-bisection performance was studied to investigate the relationship between space and magnitude representations underlying motor acts. Participants were asked to mark the midpoint of a given line with a pen while they were listening a pitch via headphones. In healthy participants, the effect of the presentation order (blocked or alternative way) of auditory stimuli was tested (Experiment 1). The results showed no biasing effect of pitch in blocked-order presentation, whereas the alternative presentation modulated the line-bisection. Lower pitch produced leftward or downward bisection biases whereas higher pitch produced rightward or upward biases, suggesting that visuomotor processing can be spatially modulated by irrelevant auditory cues. In Experiment 2, the effect of such alternative stimulations in line bisection in right brain damaged patients with a unilateral neglect and without a neglect was tested. Similar biasing effects caused by auditory cues were observed although the white noise presentation also affected the patient's performance. Additionally, the effect of pitch difference was larger for the neglect patient than for the no-neglect patient as well as for healthy participants. The neglect patient's bisection performance gradually improved during the experiment and was maintained even after 1 week. It is therefore, concluded that auditory cues, characterized by both the pitch difference and the dynamic alternation, influence spatial representations. The larger biasing effect seen in the neglect patient compared to the no-neglect patient and healthy participants suggests that auditory cues could modulate the direction of the attentional bias that is characteristic of neglect patients. Thus, the alternative presentation of auditory cues could be used as rehabilitation for neglect patients. The space-pitch associations are discussed in terms of a generalized magnitude system.

Quality of life one year after a road accident: results from the adult ESPARR cohort.

BACKGROUND: There are a few studies assessing repercussions in road accident victims, which reported their results in quality of life (QoL), on an epidemiologic point of view. METHODS: ESPARR (follow-up of victims of road accident in the Rhône) is a prospective cohort study of 1,168 individuals (age ≥ 16 years) involved in road traffic accidents, having been admitted to one of the hospitals in the Rhône département (France). The World Health Organization Quality of Life Questionnaire-Brief Version (WHOQOL-Bref) was used to assess QoL at the 1-year follow-up. χ(2) analysis was performed to test differences between groups, logistic regression was performed to examine predictors of global QoL and health, and linear regression was performed to examine predictors of the four functioning domains of the WHOQOL-Bref. RESULTS: Lesion severity (New Injury Severity Index ≥ 16; odds ratio, 2.6; 95% confidence interval, 1.7-3.9) and presence of head lesions (odds ratio, 1.5; 95% confidence interval, 1.1-2.2) were predictive of unsatisfactory QoL. Female sex, educational level lower than school graduation, severe injury, intention to lodge a complaint, early postaccident medical complications were predictive of health dissatisfaction. Several factors seemed to be associated to a poor QoL; notably, posttraumatic stress disorder was associated with low scores in all four WHOQOL-Bref domains. Socioeconomic factors were also significant, notably financial problems. CONCLUSION: The strong points of the present study lie in the fact that it is based on a representative cohort of road accident victims in an area in which all those treated within the hospital system after a road accident have been registered. The present study shows the strong correlation between QoL and posttraumatic stress disorder. LEVEL OF EVIDENCE: Prognostic study, level II.

Outcomes one year after a road accident: Results from the ESPARR cohort.

OBJECTIVE: Reducing the rates of death, trauma and sequelae associated with road accidents is the prime goal of road safety authorities, and success requires having data on victims' outcomes in the long term. The present study examined the outcome of adult road accident victims one year after their accident. DESIGN: A follow-up study. METHODS: The cohort comprised 886 injured road-accident victims, aged ≥16 years, and living in the Rhône administrative Département, France (taken from the ESPARR Cohort). Data were collected on victim characteristics at the time of crash, and self-reported outcomes one year later. The population of respondents at the one-year questionnaire follow-up was divided into two categories according to injury severity, as mild-to-moderate (M.AIS<3) or severe (M.AIS 3+). Qualitative variables were compared between these 2 groups using Chi(2) or Fisher exact tests. RESULTS: At one year post-accident, 45% of the mild-to-moderate injury group versus only 20% of severely injured subjects reported full recovery of health (p<0.001). 20% of the cohort, as a whole, reported permanent pain. More than half of the severely injured subjects reported that the accident had had an impact on the everyday life of their family; this was twice as many as in the mild-to-moderate injury group (55% vs. 22%). Most of the severely injured reported impact on leisure, projects and emotional life: 20% reported relational difficulties in the couple, 16% reported impaired sexual life, and the rate of separation was significantly higher than in the mild-to-moderate injury group (5% vs. 1%; p<0.001). Mean time off work was significantly longer in the severe injury group: 245±158 days vs. 75±104 days (p<0.001); and 32% of the severe injury group (p<0.001) who had stopped work had not returned at 1 year, compared to 5% of the mild-to-moderate injury group. CONCLUSIONS: One year after a road accident, the consequences for victims remain significant. In terms of physical impact, pain frequently persists, impairing daily life for many. There is an elevated rate of chronic PTSD (post-traumatic stress disorder) and a non-negligible impact on affective and occupational life.

Left-deviating prism adaptation in left neglect patient: reflexions on a negative result.

Adaptation to right-deviating prisms is a promising intervention for the rehabilitation of patients with left spatial neglect. In order to test the lateral specificity of prism adaptation on left neglect, the present study evaluated the effect of left-deviating prism on straight-ahead pointing movements and on several classical neuropsychological tests in a group of five right brain-damaged patients with left spatial neglect. A group of healthy subjects was also included for comparison purposes. After a single session of exposing simple manual pointing to left-deviating prisms, contrary to healthy controls, none of the patients showed a reliable change of the straight-ahead pointing movement in the dark. No significant modification of attentional paper-and-pencil tasks was either observed immediately or 2 hours after prism adaptation. These results suggest that the therapeutic effect of prism adaptation on left spatial neglect relies on a specific lateralized mechanism. Evidence for a directional effect for prism adaptation both in terms of the side of the visuomanual adaptation and therefore possibly in terms of the side of brain affected by the stimulation is discussed.

Evaluation of the injury impairment scale, a tool to predict road crash sequelae, in a French cohort of road crash survivors.

OBJECTIVE: The objective of the present study was to validate sequelae prediction by the Maximal Injury Impairment Score (M-IIS) in comparison with the Functional Independence Measure (FIM) assessed at 1-year follow-up of severe road crash victims. METHODS: The study population came from "the Etude et Suivi d'une Population d'Accidentés de la Route dans le Rhône" (ESPARR; Rhône Area Road Crash Victim Follow-up Study) cohort: 178 victims (with Maximal Abbreviated Injury Scale ≥ 3) of road crashes in the Rhône administrative department of France, aged ≥ 16 years and with medical examination including FIM scoring 1 year postaccident. Two thresholds were tested for both scores. Firstly, the relation between FIM and M-IIS was assessed on logistic regression models adjusted on age and presence of complications at 1 year postaccident. The predictive capacity of M-IIS was expressed as its negative and positive predictive values and was considered good when 80 percent or better. RESULTS: Sixty-three of the 178 adult subjects (mean age = 37.7 years; range = 16.1-82.9 years) showed postaccident complications. One-year sequelae prediction on M-IIS was greater in head, spine, and limb lesions but limited to slight impairments (M-IIS = 1). There was a significant correlation between FIM and M-IIS, although age and medical complications were confounding factors on certain multivariate models. The predictive capacity of M-IIS was low for all types of sequelae. CONCLUSIONS: M-IIS, in this severely injured population, failed to predict sequelae at 1 year as measured by the FIM, despite a good correlation between the two. Complications are to be taken into account in assessing the M-IIS's capacity to predict sequelae. Further evaluation will be needed on larger series or assessment of other indicators and measures of sequelae at 1 year to obtain a robust tool to predict road crash sequelae.

Predicting self-reported recovery one year after major road traffic accident trauma.

OBJECTIVE: The aim of this study was to examine the self-reported health status of road traffic accident victims and the predictors of self-assessed recovery 1 year after major trauma in a French population. DESIGN: A follow-up study. METHODS: The cohort comprised 276 seriously injured victims of road traffic accidents, aged > 16 years from the Rhône administrative department, France. Victim characteristics at the time of the crash and self-reported health status 1 year after trauma were collected. Predictive factors for self--assessed recovery were examined using a Poisson regression approach. RESULTS: The majority of victims were male (76%); most had severe injuries (76%), involving mainly the lower limbs and the head (68% and 55%, respectively). At 1-year follow-up, 80% reported being not fully recovered. Self-reported health status was not significantly associated with age, gender, being in employment, type of road user, or health status during the year preceding the accident, but rather with low socio-economic status, high injury severity, and presence of lower limb injury. CONCLUSION: Care for subjects who are at high risk of not fully recovering (manual workers, the very seriously injured, and those with lower limb injury) needs to be extended and improved. Longer follow-up studies on the risk factors for not fully recovering are needed in order to reduce harmful consequences for victims.

Return to work following road accidents: factors associated with late work resumption.

OBJECTIVE: To analyse factors associated with late return to work in road accident victims. MATERIALS AND METHODS: The ESPARR cohort comprises road accident victims monitored over time from initiation of hospital care. A total of 608 ESPARR cohort subjects were working at the time of their accident and answered questionnaires at 6 months and/or 1 year. For each level of overall severity of injury (Maximum - Abbreviated Injury Scale (M-AIS) 1, 2, 3 and 4-5), a time-off-work threshold was defined, beyond which the subject was deemed to be a late returner; 179 subjects were considered to be late in returning to work, while 402 showed a normal pattern of return. Logistic regression identified factors associated with late return. RESULTS: Type of journey, overall injury severity and intention to press charges emerged as factors predictive of late return to work on the basis of the data collected at inclusion alone. After adjustment, pain (odds ratio (OR): 2.6; 95% confidence interval (95% CI) 1.0-6.7) and physical sequelae (OR: 3.8; 95% CI 1.7-8.3) at 6 months and the fact of pressing charges (OR: 2.6; 95% CI 1.2-5.5) remained significantly linked with late return to work. CONCLUSION: Impaired health status at 6 months after the initial accident (in the form of persistent pain and physical sequelae) is a determining factor delaying return to work following a road traffic accident.

Predictive factors of chronic post-traumatic stress disorder 6 months after a road traffic accident.

BACKGROUND: This study sets out to identify risk factors for post-traumatic stress disorder (PTSD) after a road traffic accident with a view to improving prevention. METHODS: The study used a prospective cohort of road traffic accident casualties. All subjects over 15 years of age were recruited in the course of an interview conducted while they were receiving care in a hospital of the Rhône area administrative département. Six months after their accident, they answered a self-administered postal questionnaire that included the Post-traumatic Check-List Scale (PCLS) in order to evaluate PTSD. Multivariate logistic regression analysis was conducted to compare those subjects with a PCLS score of 44 or over with those with a lower score, in order to identify factors that might be associated with PTSD. RESULTS: 592 subjects (out of 1168) returned the 6-month questionnaire and 541 completed the PCLS test. One hundred subjects had a PCLS score ≥ 44, suggesting PTSD, and 441 subjects did not. The factors associated with PTSD were initial injury severity, post-traumatic amnesia, the feeling of not being responsible for their accident and persistent pain 6 months after it. A lower odds-ratio was associated with users of two-wheel than four-wheel motor vehicles (OR=0.4; 0.2-0.9). CONCLUSION: Besides predictive factors for PTSD (injury severity, post-traumatic amnesia and the feeling of not being responsible for their accident), our study suggested a reduced risk of PTSD among two-wheel motor vehicle users.

Constraint therapy versus intensive training: implications for motor control and brain plasticity after stroke.

Many studies have demonstrated that constraint induced movement therapy (CIMT) improves upper limb motor impairment following stroke. This rehabilitation method combines constraint of the less-affected upperlimb with intensive training of the paretic limb. The aim of the present study was to evaluate, in a single case study, the respective effects of each of these two therapeutic interventions. The patient selected was a 32-year-old right-handed woman. Three and a half years prior to inclusion, she suffered a left capsular infarct responsible for a right hemiparesis. Several assessments were carried out before and after constraint therapy and then after intensive training. Each assessment included measures of hand function as well as a three-dimensional (3D) analysis of prehension. Results showed a significant improvement of motor performance after the constraint period and an additional amelioration after the intensive training period. Kinematic analysis showed that the transport phase of movement (movement time and velocity peaks) was improved after the constraint period, whereas the grasping phase (maximum grip aperture) was modified after intensive training. These data could reflect a specific effect of treatment on each phase of the prehension task, or a more general proximal-to-distal gradient of recovery. Although firm conclusions are not warranted on the basis of this single case study, we confirm the utility of 3D motion analysis to evaluate objectively the effectiveness of a therapeutic intervention. We also discuss the implications of our findings for understanding processes of motor control reorganisation.

Functional outcome after road-crash injury: description of the ESPARR victims cohort and 6-month follow-up results.

OBJECTIVE: It is essential to know about the long-term consequences of road crashes involving corporal injury in order to adopt relevant public health measures. METHODS: The ESPARR cohort comprises 1168 road-crash victims, aged 16 or over, managed in hospitals in the Rhône administrative départment (France). It is based on the Registry of Road Traffic Casualties, which has been collecting exhaustive data since 1995. Two groups are monitored: mild to moderate (M-AIS 1 or 2) and severe (M-AIS > or =3). Patients were interviewed at the point of primary care, between 1 October 2004 and 31 July 2006. 6 months later, their state of health and presence of pain were compared. Multivariate analysis (logistic regression) was performed to identify factors related to residual pain. RESULTS: Adults of the cohort were compared to the road crash population as a whole recorded over the same period in the same area. At 6 months post-accident, only 31.9% of victims deemed their health status to have entirely returned to normal; 63.8% of mild to moderate and 89.2% of severe cases reported residual pain, but neither pain frequency nor intensity correlated with M-AIS. Residual pain was related to lower limb injuries (OR=1.6; 95% CI=1.1-2.4). After adjustment, pain was essentially related to age, seriousness of the lesions and a stay in a rehabilitation unit. CONCLUSION: The ESPARR cohort provides a unique opportunity in France to describe the trajectory of a road crash victim, in terms both of care and rehabilitation and of resumption of work and personal activity.

Dynamic changes in brain activity during prism adaptation.

Prism adaptation does not only induce short-term sensorimotor plasticity, but also longer-term reorganization in the neural representation of space. We used event-related fMRI to study dynamic changes in brain activity during both early and prolonged exposure to visual prisms. Participants performed a pointing task before, during, and after prism exposure. Measures of trial-by-trial pointing errors and corrections allowed parametric analyses of brain activity as a function of performance. We show that during the earliest phase of prism exposure, anterior intraparietal sulcus was primarily implicated in error detection, whereas parieto-occipital sulcus was implicated in error correction. Cerebellum activity showed progressive increases during prism exposure, in accordance with a key role for spatial realignment. This time course further suggests that the cerebellum might promote neural changes in superior temporal cortex, which was selectively activated during the later phase of prism exposure and could mediate the effects of prism adaptation on cognitive spatial representations.

Diseases, consumption of medicines and responsibility for a road crash: a case-control study.

UNLABELLED: The role of medical conditions in crashes is a topic of public debate. Some studies suggest that there has been a reduction in road traffic crashes subsequent to the medical restrictions introduced on drivers with medical deficiencies. As in today's society the car is an important factor for independence and socialization, it seems important to consider whether diseases or consumption of drugs increase the risk of causing a road crash in comparison to well-known major crash risk factors. A case-control study was conducted (733 injured drivers). The cases were subjects who were partly or totally responsible for their crash. The 304 controls were the non-responsible drivers. Diseases and medicine consumption were analyzed using logistic regression models. Cases were characterized by a higher percentage of young men. They were more frequently affected by fatigue, as were subjects who had consumed alcohol. A higher risk in subjects suffering from hypertension is observed (adjusted odds ratio [adjOR]=3.82; 95%CI=[1.42-10.24]). An association between antidepressant consumption and responsibility appeared (adjOR=3.61; 95%CI=[1.30-10.03]). CONCLUSION: Medical factors associated with responsibility were arterial hypertension and antidepressant consumption. Other medical conditions do not seem to play a preponderant role comparing to individual behaviours.

Wheel-chair driving improvement following visuo-manual prism adaptation.

Prism adaptation has been used for several years to improve several aspects of unilateral neglect. Parameters ranging from the classical neuropsychological tests to mental imagery or to tactile extinction have been successfully ameliorated following a brief period of adaptation to wedge prisms shifting the visual field to the right. However the potential therapeutic implications of this technique depend on the investigation of more functional and ecological parameters. Here we describe a patient with left hemiplegia and unilateral neglect who was impaired during wheel-chair navigation in the clinical unit. Following a brief adaptation period, this patient showed a sudden improvement of wheel-chair driving as well as of classical tests. The potential implications of prism adaptation for the rehabilitation of unilateral neglect are highlighted by the long duration of improvement obtained after a single adaptation session.

A hand and a field effect in on-line motor control in unilateral optic ataxia.

Patients with bilateral optic ataxia fail to show rapid perturbation-induced corrections during manual aiming movements. Based on this, it has been proposed that this pathology results from a disruption of processes of on-line motor control in the posterior parietal cortex (PPC). Here, we show that on-line motor control performance in a patient with unilateral optic ataxia is similar to that of pointing towards stationary targets in peripheral vision, showing the same combination of hand and field effects. We also show that in the patient, manual correction towards his ataxic field was possible only when a preceding saccade (100msec earlier) rapidly provides foveal information about the new target location. In control subjects, manual correction was often, but not necessarily preceded by a saccade. These results allow us to put forward a model of visuo-manual transformation, which involves updating of the reach plan based on the target-eye error, and rely upon two dissociated spatial representations (of the hand and of the target, respectively) within the PPC.

Bilateral parietal lesions disrupt the beneficial effects of prism adaptation: evidence from a patient with optic ataxia.

Prism adaptation (PA) alleviates some neglect symptoms, however, the mechanisms underlying these effects are unclear. One brain area that may be important in generating these beneficial effects is the superior parietal lobe (SPL), a region not typically damaged in neglect, and known to be important for attention, visuomotor control, and eye movements. We examined the effects of rightward PA on covert attention in CF, a patient with bilateral SPL lesions, compared to a group of controls (N = 26) who underwent sham adaptation. In contrast to previous work in neglect, there was no reduction in CF's leftward disengage deficit, or rightward attentional bias following PA. These results suggest that the SPL plays an important role in generating the beneficial after-effects of prisms on attention.

Deficits in peripheral visual attention in patients with optic ataxia.

Earlier research has suggested that optic ataxia, a deficit in reaching in peripheral vision, can be isolated from Balint's syndrome as it is primarily a visuomotor disorder, independent of perceptual or attentional deficits. Yet almost no research has examined the attentional abilities of these patients. We examined peripheral visual attention in two patients with unilateral optic ataxia. Results indicated that both patients were slower to respond to targets in their ataxic visual field, irrespective of cuing condition (i.e. validly, invalidly, and no cue conditions), consistent with an overall decrease in the salience of stimuli in the ataxic field. Attentional deficits in peripheral vision are therefore an important factor to consider when examining visuomotor control deficits in optic ataxia.

Prism adaptation first among equals in alleviating left neglect: a review.

PURPOSE: The current paper was designed to provide a critical overview on the different methods proposed for the rehabilitation of left spatial neglect. METHODS: On the basis of a previous systematic review of the literature, we analyzed all articles available aiming at reducing left spatial neglect which included a long term functional assessment. RESULTS: The aim of most early rehabilitation approaches, such as visuo-scanning training, was to re-orient visual scanning toward the neglected side. This review confirmed the utility of this method for rehabilitation purposes. More recent - theory driven - procedures, also based on a training approach, include limb activation, mental imagery training and video-feedback training. Although there is ground for optimism, the functional effectiveness of these methods still relies on few single-case studies. Newer methods have tried to stimulate automatic orientation of gaze or attention towards neglected space in a bottom-up fashion. Sensory stimulations can remove most of the classical signs of left neglect but their effects are short-lived. Such stimulations are not functionally relevant for rehabilitation except for trunk rotation or repeated neck muscle vibrations if they are associated with an extensive training program. A more promising intervention is prism adaptation given the growing evidence of relatively long-term functional gains from comparatively short term usage. CONCLUSION: Overall, there is now evidence for several clinically relevant long-term benefits in the case of visual scanning training, mental imagery training, video feedback training, neck muscle vibration and trunk rotation if associated with visual scanning training and prism adaptation. However, the amount of evidence is still limited to a small number of relevant published articles and it is mandatory to continue the research in this field. In this review, the possible routes for new rehabilitation procedures are discussed on the basis of the actual knowledge regarding the neuro-cognitive mechanisms underlying the therapeutic effect of prism adaptation.

Visuo-spatial neglect: a systematic review of current interventions and their effectiveness.

Left visuo-spatial neglect is a well-recognized predictor of poor functional outcome following right hemisphere stroke. Over the past 60 years, 18 different methods have been described and evaluated aimed at reducing the effects of this impairment. Although there are some grounds for optimism particularly in terms of short-term impairment-based effects, the range and degree of disability borne by many patients remain high and the clinical effectiveness of the different methods viewed in terms of long-lasting functional improvement (i.e. improvement of disabilities or handicap) is not clear. A systematic review of the available clinically relevant literature, using comparative and stringent levels of evidence, indicates that visual scanning training (VST), trunk rotation (TR) or repeated neck muscle vibrations (NMV) when associated with an extensive training program, mental imagery training, video feedback training and prism adaptation (PA) can be recommended for the rehabilitation of patients with left neglect. More studies however are needed to determine the optimal paradigm of limb activation (LA) eliciting a sustained functional improvement. Sensory stimulations alone and Fresnel prisms do not appear to be functionally relevant. For the other methods, the actual literature is not sufficient to conclude whether or not a long-term functional improvement can be achieved.

Late auditory and event-related potentials can be useful to predict good functional outcome after coma.

OBJECTIVE: To investigate whether late auditory and event-related potentials, and in particular N100 and mismatch negativity, together with clinical parameters, can help to predict good functional outcome in comatose patients. DESIGN: Prospective cohort study. SETTING: Hospital. PARTICIPANTS: Consecutively sampled comatose patients (N=346) whose etiologies of coma were stroke (125 patients), brain injury (96 patients), anoxia (64 patients), complication of neurosurgery (54 patients), and encephalitis (7 patients). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Glasgow Outcome Scale score at 1 year postonset. Patients in a minimally conscious state and those who awoke and died during the follow-up period were classified separately. RESULTS: Univariate analysis showed that all variables studied, except brainstem auditory evoked potentials, correlated significantly with functional outcome. Mismatch negativity showed the highest positive predictive value for good outcome. A validated model was obtained with multivariate logistic analysis, including pupillary light reflex, N100, mismatch negativity, etiology, and age. CONCLUSIONS: Late auditory and event-related potentials, and particularly N100 and mismatch negativity, provide strong prognostic factors for good functional outcome. Furthermore, these components may enhance the accuracy of prognosis when associated with other clinical parameters available at the early stage of coma.