The effect of neuropathic pain treatments on pain interference following spinal cord injury: A systematic review.

CONTEXT: Neuropathic pain is a common and debilitating condition following SCI. While treatments for neuropathic pain intensity have been reviewed, the impact on pain interference has not been summarized. OBJECTIVE: To systematically review the effect of neuropathic pain interventions on pain interference in individuals with spinal cord injury. METHODS: This systematic review included randomized controlled trials and quasi-experimental (non-randomized) studies which assessed the impact of an intervention on pain interference in individuals with spinal cord injury and neuropathic pain. Articles were identified by searching MEDLINE (1996 to April 11, 2022), EMBASE (1996 to April 11, 2022), PsycInfo (1987 to April, week 2, 2022). Studies were assessed for methodologic quality using a modified GRADE approach and were given quality of evidence (QOE) scores on a 4-point scale ranging from very low to high. RESULTS: Twenty studies met the inclusion criteria. These studies fell into the following categories: anticonvulsants (n = 2), antidepressants (n = 1), analgesics (n = 1), antispasmodics (n = 1), acupuncture (n = 2), transcranial direct current stimulation (n = 1), active cranial electrotherapy stimulation (n = 2), transcutaneous electrical nerve stimulation (n = 2), repetitive transcranial magnetic stimulation (n = 1), functional electrical stimulation (n = 1), meditation and imagery (n = 1), self-hypnosis and biofeedback (n = 1), and interdisciplinary pain programs (n = 4). CONCLUSION: When considering studies of moderate to high quality, pregabalin, gabapentin, intrathecal baclofen, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (in 1 of 2 studies) were shown to have beneficial effects on pain interference. However, due to the low number of high-quality studies further research is required to confirm the efficacy of these interventions prior to recommending their use to reduce pain interference.

The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to update the 2016 version of the Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient, outpatient and community SCI rehabilitation settings in Canada. METHODS: The guidelines were updated in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The working group identified and reviewed 46 additional relevant articles published since the last version of the guidelines. The panel agreed on 3 new screening and diagnosis recommendations and 8 new treatment recommendations. Two key changes to these treatment recommendations included the introduction of general treatment principles and a new treatment recommendation classification system. No new recommendations to model of care were made. CONCLUSIONS: The CanPainSCI recommendations for the management of neuropathic pain after SCI should be used to inform practice.

Referral patterns of stroke rehabilitation inpatients to a model system of outpatient services in Ontario, Canada: a 7-year retrospective analysis.

BACKGROUND: While several studies have tracked the care paths of patients in the early phases of stroke recovery, studies examining the transition from inpatient to outpatient rehabilitation are lacking. Examining this transition allows for improved understanding and refinement of the process whereby patients are referred and admitted to programs. The objective of this study was to examine the referral patterns of stroke rehabilitation inpatients to outpatient stroke therapy services, their demographics, and clinical profile. METHODS: This study examined patients who: (1) were admitted to an inpatient stroke rehabilitation unit between January 1, 2009 and March 1, 2016, (2) had a stroke diagnosis, (3) had an inpatient length of stay of > 1 day, and (4) lived within the geographical boundaries of the South West Local Health Integration Network which allowed them access to both hospital-based and home-based stroke rehabilitation outpatient programs. Patient data was collected from the National Rehabilitation Reporting System, as well as three hospital outpatient administrative databases. These databases were cross-referenced to determine each patient's pathway. Those referred to an outpatient therapy program, and those who attended the outpatient programs, were compared to those who were not, and did not, respectively. RESULTS: 1497 inpatients were included in the analysis. Upon discharge, 1037 (69.3%) of patients had an outpatient clinic, follow-up appointment scheduled; of those, 902 (87.0%) patients attended at least one outpatient clinic visit. 891 (59.5%) were referred to one of the interdisciplinary outpatient stroke rehabilitation programs; of those, an outpatient therapy program was attended by 80.9% of patients (n = 721). Of those receiving outpatient therapy services, the number of patients attending the in-hospital versus home-based program were equal, 360 and 361 individuals, respectively. CONCLUSION: This study allows for a better understanding of the transition between inpatient and outpatient stroke care. There is a paucity of this type of information in stroke rehabilitation literature to date. This study acts as a starting point in improving rehabilitation planning across the continuum of care.

Nonpharmacological rehabilitation interventions for motor and cognitive outcomes following pediatric stroke: a systematic review.

The aim of this review was to evaluate the evidence for nonpharmacological rehabilitation interventions for motor and cognitive impairment following pediatric stroke. A literature search was conducted using multiple scientific databases. Studies were included if (1) the study population was > 50% pediatric (< 18 years) stroke, (2) a diagnosis of stroke was explicitly stated, (3) there were ≥ 3 pediatric stroke participants included in the study sample, and (4) motor or cognitive outcome measures were used to assess effect of treatment. Levels of evidence were assigned to each study to determine the strength of the evidence for each intervention. A total of 18 articles met inclusion criteria. Most studies (N = 14) examined rehabilitation of the upper limb, with constraint-induced movement therapy (CIMT) as the most common intervention. Overall, the evidence supports the use of CIMT, forced use therapy, repetitive transcranial magnetic stimulation, functional electrical stimulation, and robotics, but suggests no beneficial effect of transcranial direct current stimulation. Very few studies assessed interventions for the lower limb (N = 1) or cognitive impairment (N = 3).Conclusion: Effective rehabilitation approaches are important for optimizing outcomes in children who have had a stroke. Although the number of published clinical trials has increased in recent years, little evidence-based guidance exists for this clinical population. What is Known: • Pediatric stroke is a significant cause of disability in children that is often associated with long-term motor and cognitive sequelae. • There is a need to establish a knowledge base regarding available evidence-based rehabilitation therapies for this clinical population. What is New: • Most studies examining interventions for motor function focus on upper limb rehabilitation, whereas few studies have investigated interventions for improving lower limb or cognitive impairment. • An important gap exists regarding evidence-based rehabilitative treatment approaches for pediatric stroke.

Opioids and cerebral physiology in the acute management of traumatic brain injury: a systematic review.

BACKGROUND: Following traumatic brain injury (TBI), optimization of cerebral physiology is recommended to promote more favourable patient outcomes. Accompanying pain and agitation are commonly treated with sedative and analgesic agents, such as opioids. However, the impact of opioids on certain aspects of cerebral physiology is not well established. OBJECTIVE: To conduct a systematic review of the evidence on the effect of opioids on cerebral physiology in TBI during acute care. METHODS: A comprehensive literature search was conducted in five electronic databases for articles published in English up to November 2017. Studies were included if: (1) the study sample was human subjects with TBI; (2) the sample size was ≥3; (3) subjects were given an opioid during acute care; and (4) any measure of cerebral physiology was evaluated. Cerebral physiology measures were intracranial pressure (ICP), cerebral perfusion pressure (CPP), and mean arterial pressure (MAP). Subject and study characteristics, treatment protocol, and results were extracted from included studies. Randomized controlled trials were evaluated for methodological quality using the Physiotherapy Evidence Database tool. Levels of evidence were assigned using a modified Sackett scale. RESULTS: In total, 22 studies met inclusion criteria, from which six different opioids were identified: morphine, fentanyl, sufentanil, remifentanil, alfentanil, and phenoperidine. The evidence for individual opioids demonstrated equally either: (1) no effect on ICP, CPP, or MAP; or (2) an increase in ICP with associated decreases in CPP and MAP. In general, opioids administered by infusion resulted in the former outcome, whereas those given in bolus form resulted in the latter. There were no significant differences when comparing different opioids, with the exception of one study that found fentanyl was associated with lower ICP and CPP than morphine and sufentanil. There were no consistent results when comparing opioids to other non-opioid medications. CONCLUSION: Several studies have assessed the effect of opioids on cerebral physiology during the acute management of TBI, but there is considerable heterogeneity in terms of study methodology and findings. Opioids are beneficial in terms of analgesia and sedation, but bolus administration should be avoided to prevent additional or prolonged unfavourable alterations in cerebral physiology. Future studies should better elucidate the effects of different opioids as well as varying dosages in order to develop improved understanding as well as allow for tighter control of cerebral physiology. ABBREVIATIONS: CPP: Cerebral Perfusion Pressure, GCS: Glasgow Coma Scale, ICP: Intracranial Pressure, MAP: Mean Arterial Pressure, PEDro: Physiotherapy Evidence Database, RCT: Randomized Controlled Trial, TBI: Traumatic Brain Injury.

The effect of theta-burst stimulation on unilateral spatial neglect following stroke: a systematic review.

OBJECTIVE:: To evaluate the effectiveness of theta-burst stimulation for the treatment of stroke-induced unilateral spatial neglect. DATA SOURCES:: A systematic literature search was conducted from the inception of each database to 30 June 2018 using CINAHL, EMBASE, PubMed, PsycINFO, and Scopus. REVIEW METHODS:: Articles were included if theta-burst stimulation was used to treat neglect following a stroke. The additional a priori inclusion criteria were as follows: (1) ⩾3 adult (⩾18 years) participants, (2) ⩾50% stroke population, and (3) peer-reviewed journal articles published in English. Extracted data included study and treatment characteristics, results, and adverse events. RESULTS:: Nine studies met the inclusion criteria, generating a total of 148 participants. Eight studies evaluated a continuous stimulation protocol and one study investigated an intermittent stimulation protocol. Overall, both protocols significantly improved neglect severity when compared against placebo or active controls ( P < 0.05). Adding smooth pursuit training to theta-burst stimulation did not improve neglect relative to when the stimulation was delivered alone ( P > 0.05). There was inconsistent reporting of neglect terminology, outcome measures, and adverse events. The treatment characteristics were heterogeneous among the trials. CONCLUSION:: This systematic review found that theta-burst stimulation seems to improve post-stroke unilateral spatial neglect, but because the evidence is limited to a few small studies with varied and inconsistent protocols and use of terminology, no firm conclusion on effectiveness can be drawn.

Caregiver availability for severe stroke results in improved functional ability at discharge from inpatient rehabilitation.

PURPOSE: To evaluate the predictive capacity of caregiver availability on functional ability at time of discharge from inpatient rehabilitation in individuals with severe first-time stroke. METHODS: A retrospective chart review was conducted of severe stroke inpatients admitted to a stroke rehabilitation unit between April 2005 and December 2009. Follow-up telephone interviews were conducted with patients to determine caregiver availability at time of discharge. Hierarchical linear regression analysis was performed to assess the predictive capacity of caregiver availability on functional ability at discharge from an inpatient rehabilitation unit after controlling for covariates. RESULTS: Data from 180 individuals were included in the analysis. Individuals with a caregiver had significantly higher levels of functional ability at discharge compared to those without (85.8 ± 23.6 versus 72.9 ± 20.3; p < 0.01), although both groups achieved a minimal clinically important difference. After controlling for age, gender, admission Functional Independence Measure, and length of hospital stay, caregiver availability explained 1.3% of additional variance, with the final model explaining 41.3% of total variance for functional ability at discharge (F (5,174) = 26.21, p < 0.001). CONCLUSIONS: The presence of a caregiver at time of discharge from inpatient rehabilitation is predictive of significantly higher functional ability at discharge in individuals with severe stroke. Implications for rehabilitation The availability of a caregiver at time of discharge from inpatient rehabilitation is predictive of improved functional ability at discharge in individuals with severe stroke. The presence of an available caregiver positively influences the functional recovery of individuals with severe stroke and may be an important element to successful rehabilitation.

A Systematic Review and Meta-Analysis on the Use of Repetitive Transcranial Magnetic Stimulation for Spasticity Poststroke.

BACKGROUND: Spasticity is a common and potentially debilitating complication that develops after stroke, arising in approximately 30% of patients. OBJECTIVE: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in improving spasticity after stroke. DESIGN: Meta-analysis and systematic review. SETTING: Not applicable. PATIENTS: A total of 273 poststroke (hemorrhagic = 123, ischemic = 150) participants were included with sample sizes ranging from 5 to 80. The majority of participants were male (66.0%) with a mean age ranging from 55.0 to 64.6 years. Mean stroke duration ranged from 6 months to 10 years. METHODS: A literature search of multiple databases was conducted for articles published in English from January 1980 to April 2015 using select keywords. Studies were included if (1) the population included was >50% stroke patients; (2) the sample size included ≥4 subjects; (3) the intervention applied was rTMS; and (4) upper extremity spasticity was assessed pre- and postintervention. Randomized controlled trials (RCTs) were assessed for methodologic quality with the Physiotherapy Evidence Database tool. All research designs were given a level of evidence according to a modified Sackett Scale. MAIN OUTCOME MEASUREMENTS: Modified Ashworth Scale (MAS). RESULTS: Ten studies met the inclusion criteria: 2 RCTs (Physiotherapy Evidence Database scores 8-9) and 8 pre-post studies. Meta-analyses of primarily uncontrolled pre-post studies found significant improvements in MAS for elbow (P < .001), wrist (P < .001), and finger flexors (P < .001). However, a meta-analysis of the 2 available RCTs failed to find a significant rTMS treatment effect on MAS for the wrist (standardized difference = .34, P = .30). CONCLUSIONS: There is limited available evidence to support the use of rTMS in improving spasticity poststroke. Despite the positive findings reported, better powered and appropriately controlled trials are necessary. LEVEL OF EVIDENCE: II.

Patient-Centered Goal Setting in a Hospital-Based Outpatient Stroke Rehabilitation Center.

BACKGROUND: Goal-setting can have a positive impact on stroke recovery during rehabilitation. Patient participation in goal formulation can ensure that personally relevant goals are set, and can result in greater satisfaction with the rehabilitation experience, along with improved recovery of stroke deficits. This, however, not yet been studied in a stroke outpatient rehabilitation setting. OBJECTIVE: To assess patient satisfaction of meeting self-selected goals during outpatient rehabilitation following a stroke. DESIGN: Retrospective chart review. SETTING: Stroke patients enrolled in a multidisciplinary outpatient rehabilitation program, who set at least 1 goal during rehabilitation. PARTICIPANTS: Patients recovering from a stroke received therapy through the outpatient rehabilitation program between January 2010 and December 2013. METHODS: Upon admission and discharge from rehabilitation, patients rated their satisfaction with their ability to perform goals that they wanted to achieve. Researchers independently sorted and labeled recurrent themes of goals. Goals were further sorted into International Classification of Functioning, Disability and Health (ICF) categories. To compare the perception of patients' goal satisfaction, repeated-measures analysis of variance was conducted across the 3 ICF goal categorizations. MAIN OUTCOME MEASURE: Goal satisfaction scores. RESULTS: A total of 286 patients were included in the analysis. Patient goals concentrated on themes of improving hand function, mobility, and cognition. Goals were also sorted into ICF categories in which impairment-based and activity limitation-based goals were predominant. Compared to activity-based and participation-based goals, patients with impairment-based goals perceived greater satisfaction with meeting their goals at admission and discharge (P < .001). Patient satisfaction in meeting their first-, second-, and third-listed goals each significantly improved by discharge from the rehabilitation program (P < .001). CONCLUSION: Within an outpatient stroke rehabilitation setting, patients set heterogeneous goals that were predominantly impairment based. Satisfaction in achieving goals significantly improved after receiving therapy. The type of goals that patients set were related to their goal satisfaction scores, with impairment-based goals being rated significantly higher than activity-based and participation-based goals. LEVEL OF EVIDENCE: III.

Habituation of reflexive and motivated behavior in mice with deficient BK channel function.

Habituation is considered the most basic form of learning. It describes the decrease of a behavioral response to a repeated non-threatening sensory stimulus and therefore provides an important sensory filtering mechanism. While some neuronal pathways mediating habituation are well described, underlying cellular/molecular mechanisms are not yet fully understood. In general, there is an agreement that short-term and long-term habituation are based on different mechanisms. Historically, a distinction has also been made between habituation of motivated versus reflexive behavior. In recent studies in invertebrates the large conductance voltage- and calcium-activated potassium (BK) channel has been implicated to be a key player in habituation by regulating synaptic transmission. Here, we tested mice deficient for the pore forming α-subunit of the BK channel for short-term and long-term habituation of the acoustic startle reflex (reflexive behavior) and of the exploratory locomotor behavior in the open field box (motivated behavior). Short-term habituation of startle was completely abolished in the BK knock-out mice, whereas neither long-term habituation of startle nor habituation of motivated behavior was affected by the BK deficiency. Our results support a highly preserved mechanism for short-term habituation of startle across species that is distinct from long-term habituation mechanisms. It also supports the notion that there are different mechanisms underlying habituation of motivated behavior versus reflexive behavior.

Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory.

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.