Differences in Daily Activity Performance Between Inpatient Rehabilitation Facility and Home Among Stroke Survivors.

BACKGROUND: Stroke survivors are one of the largest consumer groups of rehabilitation services. Despite improvement in daily activities while in inpatient rehabilitation, many have difficulty performing daily activities at home after discharge. The difference in performance between a standard clinical context and at home is poorly understood. OBJECTIVE: To better understand differences in activity performance during transition from inpatient rehabilitation facility (IRF) to home, we examined daily activity performance scores from 2 different environments (IRF and home) at the same time point (discharge). METHODS: This was a cross-sectional analysis using baseline data from a randomized controlled trial. Participants were stroke survivors aged ≥50 who planned to discharge home from the IRF. The Functional Independence Measure and Section GG codes (both converted to International Classification of Functioning, Disability, and Health scores) were conducted per protocol first at home and then in the IRF at discharge (≤3 days apart, order not randomized). RESULTS: Among 57 participants, activity scores at home were significantly worse than scores at IRF discharge. Over 40% of participants had discharge scores indicating no-to-mild impairment for shower/tub transfer, walking, and going up/down stairs, while home visit scores indicated moderate-to-complete impairment for those activities. The greatest differences in scores were for shower/tub transfer (median difference 1.5, 95% CI 1.00-2.00) and going up/down stairs (median difference 1.50, 95% CI 1.00-2.00). CONCLUSION: The environment plays an important role in stroke survivors' functioning at home. Future studies should further examine how the environment impacts activity performance upon returning home following stroke.

IpsiHand Brain-Computer Interface Therapy Induces Broad Upper Extremity Motor Recovery in Chronic Stroke.

Background and Purpose: Chronic hemiparetic stroke patients have very limited benefits from current therapies. Brain-computer interface (BCI) engaging the unaffected hemisphere has emerged as a promising novel therapeutic approach for chronic stroke rehabilitation. This study investigated the effectiveness of the IpsiHand System, a contralesionally-controlled BCI therapy in chronic stroke patients with impaired upper extremity motor function. We further explored neurophysiological features of motor recovery affected by BCI. We hypothesized that BCI therapy would induce a broad motor recovery in the upper extremity (proximal and distal), and there would be corresponding changes in baseline theta and gamma oscillations, which have been shown to be associated with motor recovery. Methods: Thirty chronic hemiparetic stroke patients performed a therapeutic BCI task for 12 weeks. Motor function assessment data and resting state electroencephalogram (EEG) signals were acquired before initiating BCI therapy and across BCI therapy sessions. The Upper Extremity Fugl-Meyer assessment (UEFM) served as a primary motor outcome assessment tool. Theta-gamma cross-frequency coupling (CFC) was computed and correlated with motor recovery. Results: Chronic stroke patients achieved significant motor improvement with BCI therapy. We found significant improvement in both proximal and distal upper extremity motor function. Importantly, motor function improvement was independent of Botox application. Theta-gamma CFC enhanced bilaterally over the C3 and C4 motor electrodes following BCI therapy. We observed significant positive correlations between motor recovery and theta gamma CFC increase across BCI therapy sessions. Conclusions: BCI therapy resulted in significant motor function improvement across the proximal and distal upper extremities of patients. This therapy was significantly correlated with changes in baseline cortical dynamics, specifically theta-gamma CFC increases in both the right and left motor regions. This may represent rhythm-specific cortical oscillatory mechanism for BCI-driven motor rehabilitation in chronic stroke patients.

Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression.

At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. Thus, we sought to identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These "RSNM targets" were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region ("sgACC-derived targets"). The TBI-D cohort was also randomized to receive active (n = 9) or sham (n = 4) rTMS to RSNM targets with 20 daily sessions of sequential high-frequency left-sided stimulation and low-frequency right-sided stimulation. We found that the group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were thus identified based on DAN anti-correlation and DMN correlation. These RSNM targets showed greater test-retest reliability than sgACC-derived targets. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was also stronger and more reliable for RSNM-derived targets than for sgACC-derived targets. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment also led to increased connectivity within and between the stimulation sites, the sgACC, and the DMN. Overall, these results suggest that RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.

The Role of Extra-motor Networks in Upper Limb Motor Performance Post-stroke.

BACKGROUND: Motor improvement post-stroke may happen even if resting state functional connectivity between the ipsilesional and contralesional components of the sensorimotor network is not fully recovered. Therefore, we investigated which extra-motor networks might support upper limb motor gains in response to treatment post-stroke. METHODS: Both resting state functional connectivity and upper limb capacity were measured prior to and after an 8-week intervention of task-specific training in 29 human participants [59.24 ± (SD) 10.40 yrs., 12 females and 17 males] with chronic stroke. The sensorimotor and five extra-motor networks were defined: default mode, frontoparietal, cingulo-opercular, dorsal attention network, and salience networks. The Network Level Analysis toolbox was used to identify network pairs whose connectivities were enriched in connectome-behavior relationships. RESULTS: Mean upper limb capacity score increased 5.45 ± (SD) 5.55 following treatment. Baseline connectivity of some motor but mostly extra-motor network interactions of cingulo-opercular and default-mode networks were predictive of upper limb capacity following treatment. Also, changes in connectivity for extra-motor interactions of salience with default mode, cingulo-opercular, and dorsal attention networks were correlated with gains in upper limb capacity. CONCLUSIONS: These connectome-behavior patterns suggest larger involvement of cingulo-opercular networks in prediction of treatment response and of salience networks in maintenance of improved skilled behavior. These results support our hypothesis that cognitive networks may contribute to recovery of motor performance after stroke and provide additional insights into the neural correlates of intensive training.

A pilot randomized sham controlled trial of bilateral iTBS for depression and executive function in older adults.

INTRODUCTION: Executive function deficits (EFD) in late life depression (LLD) are associated with poor outcomes. Dysfunction of the cognitive control network (CCN) has been posited in the pathophysiology of LLD with EFD. METHODS: Seventeen older adults with depression and EFD were randomized to iTBS or sham for 6 weeks. Intervention was delivered bilaterally using a recognized connectivity target. RESULTS: A total of 89% (17/19) participants completed all study procedures. No serious adverse events occurred. Pre to post-intervention change in mean Montgomery-Asberg-depression scores was not different between iTBS or sham, p = 0.33. No significant group-by-time interaction for Montgomery-Asberg Depression rating scale scores (F 3, 44  = 0.51; p = 0.67) was found. No significant differences were seen in the effects of time between the two groups on executive measures: Flanker scores (F 1, 14  = 0.02, p = 0.88), Dimensional-change-card-sort scores F 1, 14  = 0.25, p = 0.63, and working memory scores (F 1, 14  = 0.98, p = 0.34). The Group-by-time interaction effect for functional connectivity (FC) within the Fronto-parietal-network was not significant (F 1, 14  = 0.36, p = 0.56). No significant difference in the effect-of-time between the two groups was found on FC within the Cingulo-opercular-network (F 1, 14  = 0, p = 0.98). CONCLUSION: Bilateral iTBS is feasible in LLD. Preliminary results are unsupportive of efficacy on depression, executive function or target engagement of the CCN. A future Randomized clinical trial requires a larger sample size with stratification of cognitive and executive variables and refinement in the target engagement.

Theta-gamma coupling as a cortical biomarker of brain-computer interface-mediated motor recovery in chronic stroke.

Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain-computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain-computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain-computer interface. This study investigated whether the motor improvements in chronic stroke patients induced with a brain-computer interface therapy are associated with alterations in phase-amplitude coupling, a type of cross-frequency coupling. Seventeen chronic hemiparetic stroke patients used a robotic hand orthosis controlled with contralesional motor cortical signals measured with EEG. Patients regularly performed a therapeutic brain-computer interface task for 12 weeks. Resting-state EEG recordings and motor function data were acquired before initiating brain-computer interface therapy and once every 4 weeks after the therapy. Changes in phase-amplitude coupling values were assessed and correlated with motor function improvements. To establish whether coupling between two different frequency bands was more functionally important than either of those rhythms alone, we calculated power spectra as well. We found that theta-gamma coupling was enhanced bilaterally at the motor areas and showed significant correlations across brain-computer interface therapy sessions. Importantly, an increase in theta-gamma coupling positively correlated with motor recovery over the course of rehabilitation. The sources of theta-gamma coupling increase following brain-computer interface therapy were mostly located in the hand regions of the primary motor cortex on the left and right cerebral hemispheres. Beta-gamma coupling decreased bilaterally at the frontal areas following the therapy, but these effects did not correlate with motor recovery. Alpha-gamma coupling was not altered by brain-computer interface therapy. Power spectra did not change significantly over the course of the brain-computer interface therapy. The significant functional improvement in chronic stroke patients induced by brain-computer interface therapy was strongly correlated with increased theta-gamma coupling in bihemispheric motor regions. These findings support the notion that specific cross-frequency coupling dynamics in the brain likely play a mechanistic role in mediating motor recovery in the chronic phase of stroke recovery.

Spatial neglect treatment: The brain's spatial-motor Aiming systems.

Animal and human literature supports spatial-motor "Aiming" bias, a frontal-subcortical syndrome, as a core deficit in spatial neglect. However, spatial neglect treatment studies rarely assess Aiming errors. Two knowledge gaps result: spatial neglect rehabilitation studies fail to capture the impact on motor-exploratory aspects of functional disability. Also, across spatial neglect treatment studies, discrepant treatment effects may also result from sampling different proportions of patients with Aiming bias. We review behavioural evidence for Aiming spatial neglect, and demonstrate the importance of measuring and targeting Aiming bias for treatment, by reviewing literature on Aiming spatial neglect and prism adaptation treatment, and presenting new preliminary data on bromocriptine treatment. Finally, we review neuroanatomical and network disruption that may give rise to Aiming spatial neglect. Because Aiming spatial neglect predicts prism adaptation treatment response, assessment may broaden the ability of rehabilitation research to capture functionally-relevant disability. Frontal brain lesions predict both the presence of Aiming spatial neglect, and a robust response to some spatial neglect interventions. Research is needed that co-stratifies spatial neglect patients by lesion location and Aiming spatial neglect, to personalize spatial neglect rehabilitation and perhaps even open a path to spatial retraining as a means of promoting better mobility after stroke.

A case of aphemia following non-dominant sub-insular stroke: unveiling the Foix-Chavany-Marie phenomenon.

Aphemia refers to the clinical syndrome of inability to orally produce speech with intact comprehension and written expression. Aphemia has been primarily reported in dominant frontal lobe strokes resulting in apraxia of speech (AoS), and in Foix-Chavany-Marie (FCM) syndrome where bilateral opercular or sub-opercular lesions result in anarthria due to deafferentation of brainstem nuclei supplying the oro-facio-lingual and pharyngeal musculature. Aphemia is not reported in non-dominant sub-insular strokes. Here, we present a case of aphemia following non-dominant sub-insular stroke in a patient who had previously recovered from a homologous dominant sub-insular stroke without any apparent residual deficits. We discuss the accepted definitions, theories and controversies in the use of the terminology - aphemia, apraxia of speech (AoS), anarthria related to FCM syndrome, a concomitant pathology - unilateral upper motor neuron (UUMN) dysarthria, and their neuro-anatomical bases. We also highlight the importance of attributing localization value to sequential homologous lesions of the brain that can unveil symptoms due to a "loss of compensation phenomenon" that we propose be termed as "FCM phenomenon." These pathological mechanisms may alone or in certain combinations contribute to the clinical syndrome of aphemia included in the diagnostic approach proposed here. The distinction between these mechanisms requires serial careful neurological examination and detailed speech evaluation including in the recovery phase.

White matter integrity of contralesional and transcallosal tracts may predict response to upper limb task-specific training in chronic stroke.

OBJECTIVE: To investigate white matter (WM) plasticity induced by intensive upper limb (UL) task specific training (TST) in chronic stroke. METHODS: Diffusion tensor imaging data and UL function measured by the Action Research Arm Test (ARAT) were collected in 30 individuals with chronic stroke prior to and after intensive TST. ANOVAs tested the effects of training on the entire sample and on the Responders [ΔARAT ≥ 5.8, N = 13] and Non-Responders [ΔARAT < 5.8, N = 17] groups. Baseline fractional anisotropy (FA) values were correlated with ARATpost TST controlling for baseline ARAT and age to identify voxels predictive of response to TST. RESULTS: While ARAT scores increased following training (p < 0.0001), FA changes within major WM tracts were not significant at p < 0.05. In the Responder group, larger baseline FA of both contralesional (CL) and transcallosal tracts predicted larger ARAT scores post-TST. Subcortical lesions and more severe damage to transcallosal tracts were more pronounced in the Non-Responder than in the Responder group. CONCLUSIONS: The motor improvements post-TST in the Responder group may reflect the engagement of interhemispheric processes not available to the Non-Responder group. Future studies should clarify differences in the role of CL and transcallosal pathways as biomarkers of recovery in response to training for individuals with cortical and subcortical stroke. This knowledge may help to identify sources of heterogeneity in stroke recovery, which is necessary for the development of customized rehabilitation interventions.

Cingulo-opercular control network and disused motor circuits joined in standby mode.

Whole-brain resting-state functional MRI (rs-fMRI) during 2 wk of upper-limb casting revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula. Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.

Plasticity and Spontaneous Activity Pulses in Disused Human Brain Circuits.

To induce brain plasticity in humans, we casted the dominant upper extremity for 2 weeks and tracked changes in functional connectivity using daily 30-min scans of resting-state functional MRI (rs-fMRI). Casting caused cortical and cerebellar regions controlling the disused extremity to functionally disconnect from the rest of the somatomotor system, while internal connectivity within the disused sub-circuit was maintained. Functional disconnection was evident within 48 h, progressed throughout the cast period, and reversed after cast removal. During the cast period, large, spontaneous pulses of activity propagated through the disused somatomotor sub-circuit. The adult brain seems to rely on regular use to maintain its functional architecture. Disuse-driven spontaneous activity pulses may help preserve functionally disconnected sub-circuits.

Individualized Connectome-Targeted Transcranial Magnetic Stimulation for Neuropsychiatric Sequelae of Repetitive Traumatic Brain Injury in a Retired NFL Player.

OBJECTIVE: The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial interindividual variability in anatomical localization of brain networks identified by using resting-state functional MRI (rsfMRI). RSNM enables personalized targeting of focal neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS). rTMS is believed to exert antidepressant efficacy by modulating connectivity between the stimulation site, the default mode network (DMN), and the subgenual anterior cingulate cortex (sgACC). Personalized rTMS may be particularly useful after repetitive traumatic brain injury (TBI), which is associated with neurodegenerative tauopathy in medial temporal limbic structures. These degenerative changes are believed to be related to treatment-resistant neurobehavioral disturbances observed in many retired athletes. METHODS: The authors describe a case in which RSNM was successfully used to target rTMS to treat these neuropsychiatric disturbances in a retired NFL defensive lineman whose symptoms were not responsive to conventional treatments. RSNM was used to identify left-right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and DMN correlations. These targets were spatially distinct from those identified by prior methods. Twenty sessions of left-sided excitatory and right-sided inhibitory rTMS were administered at these targets. RESULTS: Treatment led to improvement in Montgomery-Åsberg Depression Rating Scale (72%), cognitive testing, and headache scales scores. Compared with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with the medial temporal lobe (MTL). Serial rsfMRI scans revealed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with sgACC. CONCLUSIONS: These results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

Repetitive Transcranial Magnetic Stimulation with Resting-State Network Targeting for Treatment-Resistant Depression in Traumatic Brain Injury: A Randomized, Controlled, Double-Blinded Pilot Study.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated antidepressant efficacy but has limited evidence in depression associated with traumatic brain injury (TBI). Here, we investigate the use of rTMS targeted with individualized resting-state network mapping (RSNM) of dorsal attention network (DAN) and default mode network (DMN) in subjects with treatment-resistant depression associated with concussive or moderate TBI. The planned sample size was 50 with first interim analysis planned at 20, but only 15 were enrolled before the study was terminated for logistical reasons. Subjects were randomized to 20 sessions of bilateral rTMS (4000 left-sided excitatory pulses, 1000 right-sided inhibitory pulses) or sham. Treatment was targeted to the dorsolateral prefrontal cluster with maximal difference between DAN and DMN correlations based on resting-state functional magnetic resonance imaging with individualized RSNM. Mean improvement in the primary outcome, Montgomery-Asberg Depression Rating Scale (MADRS), was 56% ± 14% (n = 9) with active treatment and 27% ± 25% (n = 5) with sham (Cohen's d = 1.43). One subject randomized to sham withdrew before starting treatment. There were no seizures or other significant adverse events. MADRS improvement was inversely correlated with functional connectivity between the right-sided stimulation site and the subgenual anterior cingulate cortex (sgACC; r = -0.68, 95% confidence interval 0.03-0.925). Active treatment led to increased sgACC-DMN connectivity (d = 1.55) and increased sgACC anti-correlation with the left- and right-sided stimulation sites (d = -1.26 and -0.69, respectively). This pilot study provides evidence that RSNM-targeted rTMS is feasible in TBI patients with depression. Given the dearth of existing evidence-based treatments for depression in this patient population, these preliminarily encouraging results indicate that larger controlled trials are warranted.

Biomarkers of Stroke Recovery: Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable.

The most difficult clinical questions in stroke rehabilitation are "What is this patient's potential for recovery?" and "What is the best rehabilitation strategy for this person, given her/his clinical profile?" Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.

Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable.

The most difficult clinical questions in stroke rehabilitation are "What is this patient's potential for recovery?" and "What is the best rehabilitation strategy for this person, given her/his clinical profile?" Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.

Descriptive data analysis examining how standardized assessments are used to guide post-acute discharge recommendations for rehabilitation services after stroke.

BACKGROUND: Use of standardized assessments in acute rehabilitation is continuing to grow, a key objective being to assist clinicians in determining services needed postdischarge. OBJECTIVE: The purpose of this study was to examine how standardized assessment scores from initial acute care physical therapist and occupational therapist evaluations contribute to discharge recommendations for poststroke rehabilitation services. DESIGN: A descriptive analysis was conducted. METHODS: A total of 2,738 records of patients admitted to an acute care hospital with a diagnosis of stroke or transient ischemic attack were identified. Participants received an initial physical therapist and occupational therapist evaluation with standardized assessments and a discharge recommendation of home with no services, home with services, inpatient rehabilitation facility (IRF), or skilled nursing facility (SNF). A K-means clustering algorithm determined if it was feasible to categorize participants into the 4 groups based on their assessment scores. These results were compared with the physical therapist and occupational therapist discharge recommendations to determine if assessment scores guided postacute care recommendations. RESULTS: Participants could be separated into 4 clusters (A, B, C, and D) based on assessment scores. Cluster A was the least impaired, followed by clusters B, C, and D. In cluster A, 50% of the participants were recommended for discharge to home without services, whereas 1% were recommended for discharge to an SNF. Clusters B, C, and D each had a large proportion of individuals recommended for discharge to an IRF (74%-80%). There was a difference in percentage of recommendations across the clusters that was largely driven by the differences between cluster A and clusters B, C, and D. LIMITATIONS: Additional unknown factors may have influenced the discharge recommendations. CONCLUSIONS: Participants poststroke can be classified into meaningful groups based on assessment scores from their initial physical therapist and occupational therapist evaluations. These assessment scores, in part, guide poststroke acute care discharge recommendations.

Clinician adherence to a standardized assessment battery across settings and disciplines in a poststroke rehabilitation population.

OBJECTIVES: (1) To examine clinician adherence to a standardized assessment battery across settings (acute hospital, inpatient rehabilitation facilities [IRFs], outpatient facility), professional disciplines (physical therapy [PT], occupational therapy, speech-language pathology), and time of assessment (admission, discharge/monthly), and (2) to evaluate how specific implementation events affected adherence. DESIGN: Retrospective cohort study. SETTING: Acute hospital, IRF, and outpatient facility with approximately 118 clinicians (physical therapists, occupational therapists, speech-language pathologists). PARTICIPANTS: Participants (N=2194) with stroke who were admitted to at least 1 of the above settings. All persons with stroke underwent standardized clinical assessments. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Adherence to Brain Recovery Core assessment battery across settings, professional disciplines, and time. Visual inspections of 17 months of time-series data were conducted to see if the events (eg, staff meetings) increased adherence ≥5% and if so, how long the increase lasted. RESULTS: Median adherence ranged from .52 to .88 across all settings and professional disciplines. Both the acute hospital and the IRF had higher adherence than the outpatient setting (P≤.001), with PT having the highest adherence across all 3 disciplines (P<.004). Of the 25 events conducted across the 17-month period to improve adherence, 10 (40%) resulted in a ≥5% increase in adherence the following month, with 6 services (60%) maintaining their increased level of adherence for at least 1 additional month. CONCLUSIONS: Actual adherence to a standardized assessment battery in clinical practice varied across settings, disciplines, and time. Specific events increased adherence 40% of the time with those gains maintained for >1 month 60% of the time.

Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature.

The use of intramuscular injections of Botulinum neurotoxin A (BoNT-A) is common in the treatment of hypertonicity and movement disorders. Although most side effects are mild, systemic effects, manifested by generalized weakness distant from the site of injection, have been reported. Previously reported occurrences are discussed, and 3 new cases of patients, who developed systemic weakness after administration of BoNT-A (Botox), despite having tolerated similar injections on several previous occasions, are presented. A review of the literature and reported cases indicate that risk of developing systemic effects does not seem to be related to dose based on body weight. It may be more likely that risk for systemic effects is related to total injection dose and injection frequency. The results of our 3 patients would indicate that injections of greater than 600 units of Botox with follow-up injections occurring every 3 months may lead to an increased risk. We would recommend careful consideration of reinjection frequency if injections of greater than 600 units of Botox are given. Reduction in systemic side effects may occur if reinjection frequency occurs in intervals of 4 months or greater in these individuals.

Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning.

Neurotrophins were initially identified as critical regulators of neuronal survival. However, these factors have many additional functions. In the developing cerebellum the roles of the neurotrophins BDNF and NT3 include a surprising effect on patterning, as revealed by changes in foliation in neurotrophin-deficient mice. Here we examine the potential role of p75NTR in cerebellar development and patterning. We show that p75NTR is expressed at highest levels in the region of the cerebellum where foliation is altered in BDNF and NT3 mutants. Although the cerebellar phenotype of p75NTR mutant animals is indistinguishable from wild type, mutation of p75NTR in BDNF heterozygotes results in defects in foliation and in Purkinje cell morphologic development. Taken together, these data suggest that p75NTR activity is critical for cerebellar development under pathologic circumstances where neurotrophin levels are reduced.

5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic.

5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5] imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide) (RWJ-51204) binds selectively and with high affinity (K(i) = 0.2-2 nM) to the benzodiazepine site on GABA(A) receptors. Considering the GABA shift, the intrinsic modulatory activity of RWJ-51204 is lower than that of full agonist anxiolytics (lorazepam, diazepam, alprazolam, and clonazepam) but similar to partial agonists (bretazenil, abecarnil, panadiplon, and imidazenil). RWJ-51204 was orally active in anxiolytic efficacy tests; pentylenetetrazole induced seizure inhibition in mice (ED(50) = 0.04 mg/kg), Vogel conflict in rats (ED(50) = 0.36 mg/kg), elevated plus-maze in rats (minimal effective dose = 0.1 mg/kg), and conflict in squirrel monkeys (ED(50) = 0.49 mg/kg). RWJ-51204 attenuated chlordiazepoxide-induced motor impairment in mice. Usually, RWJ-51204 was more potent than reference anxiolytics in rodent efficacy tests but less potent in monkey conflict. Usually, the slope of the dose-response lines for RWJ-51204 was more shallow than the full agonist anxiolytics but steeper than partial agonists in efficacy tests but typically shallow in tests for central nervous system side effects. In monkeys only mild or moderate sedation was observed at doses equivalent to 20 or 40 times the anxiolytic ED(50). RWJ-51204 fits into the partial agonist class of GABA(A) receptor modulators. In conclusion, RWJ-51204 exhibits a profile in in vitro experiments and in animal models, in mice and monkeys (but not in rats), suggesting that it has a profile of anxiolytic activity associated with less sedation, motor impairment, or muscle relaxation than currently available GABA(A) receptor modulators, i.e., the benzodiazepines.