Stephen E. Nadeau

Robot-Assisted Therapy for Long-Term Upper-Limb Impairment after Stroke

BACKGROUND Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. METHODS In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. RESULTS At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. CONCLUSIONS In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.)

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Creative Innovation: Possible Brain Mechanisms

This article reviews and develops some theories about the neurobiological basis of creative innovation (CI). CI is defined as the ability to understand and express novel orderly relationships. A high level of general intelligence, domain-specific knowledge and special skills are necessary components of creativity. Specialized knowledge is stored in specific portions of the temporal and parietal lobes. Some anatomic studies suggest that talented people might have alterations of specific regions of the posterior neocortical architecture, but further systematic studies are needed. Intelligence, knowledge and special skills, however, are not sufficient for CI. Developing alternative solutions or divergent thinking has been posited to be a critical element of CI, and clinical as well as functional imaging studies suggest that the frontal lobes are important for these activities. The frontal lobes have strong connections with the polymodal and supramodal regions of the temporal and parietal lobes where concepts and knowledge are stored. These connections might selectively inhibit and activate portions of posterior neocortex and thus be important for developing alternative solutions. Although extensive knowledge and divergent thinking together are critical for creativity they alone are insufficient for allowing a person to find the thread that unites. Finding this thread might require the binding of different forms of knowledge, stored in separate cortical modules that have not been previously associated. Thus, CI might require the co-activation and communication between regions of the brain that ordinarily are not strongly connected. The observations that CI often occurs during levels of low arousal and that many people with depression are creative suggests that alterations of neurotransmitters such as norepinephrine might be important in CI. High levels of norepinephrine, produced by high rates of locus coeruleus firing, restrict the breadth of concept representations and increase the signal to noise ratio, but low levels of norepinephrine shift the brain toward intrinsic neuronal activation with an increase in the size of distributed concept representations and co-activation across modular networks. In addition to being important in divergent thinking, the frontal lobes are also the primary cortical region that controls the locus coeruleus-norepinephrine system. Thus creative people may be endowed with brains that are capable of storing extensive specialized knowledge in their temporoparietal cortex, be capable of frontal mediated divergent thinking and have a special ability to modulate the frontal lobe-locus coeruleus (norepinephrine) system, such that during creative innovation cerebral levels of norepinephrine diminish, leading to the discovery of novel orderly relationships.

Conduction Aphasia and the Arcuate Fasciculus: A Reexamination of the Wernicke–Geschwind Model ☆

Wernicke, and later Geschwind, posited that the critical lesion in conduction aphasia is in the dominant hemispheres arcuate fasciculus. This white matter pathway was thought to connect the anterior language production areas with the posterior language areas that contain auditory memories of words (a phonological lexicon). Alternatively, conduction aphasia might be induced by cortical dysfunction, which impairs the phonological output lexicon. We observed an epileptic patient who, during cortical stimulation of her posterior superior temporal gyrus, demonstrated frequent phonemic paraphasias, decreased repetition of words, and yet had intact semantic knowledge, a pattern consistent with conduction aphasia. These findings suggest that cortical dysfunction alone may induce conduction aphasia.

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

BackgroundLocomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention.The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions.Methods/DesignWe will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks.Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment.LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean difference in gait speed change between the two LTP groups.DiscussionThe goal of this single-blinded, phase III randomized clinical trial is to provide evidence to guide post-stroke walking recovery programs.Trial registrationNCT00243919.

Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial.

Malcolm MP, Triggs WJ, Light KE, Gonzalez Rothi LJ, Wu S, Reid K, Nadeau SE: Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial. Am J Phys Med Rehabil 2007;86:707–715. Objective:To test the potential adjuvant effect of repetitive transcranial magnetic stimulation (rTMS) on motor learning in a group of stroke survivors undergoing constraint-induced therapy (CIT) for upper-limb hemiparesis. Design:This was a prospective randomized, double-blind, sham-controlled, parallel group study. Nineteen individuals, one or more years poststroke, were randomized to either a rTMS + CIT (n = 9) or a sham rTMS + CIT (n = 10) group and participated in the 2-wk intervention. Results:Regardless of group assignment, participants demonstrated significant gains on the primary outcome measures: the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL)–Amount of Use, and on secondary outcome measures including the Box and Block Test (BBT) and the MAL–How Well. Participants receiving rTMS failed to show differential improvement on either primary outcome measure. Conclusions:Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect, it provided no support for adjuvant use of rTMS.

Category-specific naming deficits for objects and actions: semantic attribute and grammatical role hypotheses

Research on category-specific naming deficits and on noun and verb naming has raised questions about how organization of knowledge in the brain impacts word retrieval. The semantic attribute hypothesis posits that lexical access is mediated by brain systems that process the most definitive attributes of specific concepts. For example, it has been suggested that the most definitive attribute of living things is their visual form, whereas the most definitive attribute of non-living things is their function. The competing grammatical role hypothesis posits that access to a word depends on the grammatical role it plays in a sentence. Since nouns and verbs have different roles, it is assumed that the brain uses different systems to process them. These two hypotheses were tested in experimental subjects who had undergone left anterior temporal lobectomy (LATL) or right anterior temporal lobectomy (RATL) by assessing confrontation naming of living things, tools/implements, non-human actions, and human actions. The names of living things and implements are nouns and the names of actions are verbs. Within each grammatical class, items were characterized either predominantly by visual attributes (living things and non-human actions) or by attributes related to human activity (implements and human actions). Our results support the semantic attribute hypothesis. Patients with LATL were worse at naming tools/implements and human actions than RATL patients. Dysfunction in or removal of the left anterior temporal lobe disrupts fronto-temporal connections from the uncinate fasciculus. These connections may mediate activation of action-related information (i.e. movement plan and/or motor use) that facilitates the retrieval of names for tools/implements and human actions.

Effect of Verb Network Strengthening Treatment (VNeST) on lexical retrieval of content words in sentences in persons with aphasia

Background: Verb Network Strengthening Treatment (VNeST) is a semantic treatment that aims to improve lexical retrieval of content words in sentence context by promoting systematic retrieval of verbs (e.g., measure) and their thematic roles—i.e., agent (doer of the action, e.g., carpenter, chef) and patient (receiver of the action, e.g., lumber, sugar). VNeST is influenced by Loverso and colleagues (e.g., Loverso, Selinger, & Prescott, 1979) who used “verb as core” treatment to improve sentence production with encouraging results, and McRae and colleagues who showed that verbs prime typical agents (e.g., pray–nun) and patients (arrest–criminal) (Ferretti, McRae, & Hatherell, 2001) and vice‐versa (McRae, Hare, Elman, & Ferretti, 2005). Aims: There are four specific questions in this study. Does training a set of verbs using VNeST generalise to the ability to produce (1) an agent (carpenter), trained verb (measure), and patient (stairs) in response to novel picture stimuli and (2) an agent (nurse), untrained semantically related verb (weigh), and patient (baby) in response to novel picture stimuli? (3) Are generalisation effects maintained? (4) Does VNeST generalise to the ability to retrieve nouns and verbs not directly related to treatment items in single word naming, picture description, and connected speech tasks? Methods & Procedures: Four participants with aphasia participated. Participants received VNeST, which involves retrieval of agent–patient pairs (e.g., chef/sugar, surveyor/land) related to trained verbs (e.g., measure), twice per week. A single‐participant, repeated probe, multiple baseline experimental design was used. Generalisation to sentence production for sentences containing trained verbs and untrained semantically related verbs was tested weekly. Outcomes & Results: Results demonstrated generalisation to lexical retrieval of content words in sentences with trained and untrained verbs across participants. Additionally, pre‐ to post‐treatment generalisation was observed on single verb and noun naming and lexical retrieval in sentences across a variety of tasks across participants. Generalisation to connected speech was observed for three of four participants. Conclusions: Although preliminary, these results indicate that VNeST may be effective in promoting generalisation from single word naming to connected speech in persons with moderate aphasia. A number of clinical implications related to treatment efficiency are discussed. The authors would first like to thank the four individuals who participated in this study. Additional thanks go Laura K. Allred for creating the artwork for developed stimuli, and Michela Palmieri and Adam Jacks for assistance with reliability.

Effect of mitoxantrone on MRI in progressive MS: Results of the MIMS trial

Krapf et al. and the Mitoxantrone in Multiple Sclerosis study group (MIMS)1,2 describe a disappointing impact of mitoxantrone treatment on MRI gadolinium enhancing lesions. Coming from this highly respected group, this article is likely to be influential. The MIMS investigators have also distinguished themselves for their statistical sophistication yet the disparity between the data and the conclusions born of statistical analysis is dramatic. The authors should further clarify the statistical approach, which was not adequately detailed. The authors concluded that at months 12 and 24, neither mitoxantrone 5 mg/m2 (M5) nor mitoxantrone 12 mg/m2 (M12) produced a statistically significant difference in the total number of scans exhibiting gadolinium enhancement (GE), relative to the placebo group. However, in the M12 group, 10 of 34 subjects had GE at baseline and 1/34 had GE …

Phoneme-Based Rehabilitation of Anomia in Aphasia.

This study investigated the effects of phonologic treatment for anomia in aphasia. We proposed that if treatment were directed at the level of the phonologic processor, opportunities for naming via a phonological route, as opposed to a strictly whole word route, would be enhanced, thereby improving naming. The participants, ten people with anomia and aphasia due to left hemisphere stroke, received 96 h of phoneme based treatment in 12 weeks. To learn if treatment improved naming, a single-subject, repeated probe design with replication was employed. The primary outcome measure was confrontation naming. Secondary outcome measures included phonologic production, nonword repetition and discourse production. Results suggest a positive treatment effect (confrontation naming), improvements in phonologic production and nonword repetition, and generalization to discourse production. When tested 3 months after the completion of treatment the effects appeared to be maintained.