The international spinal cord injury pain basic data set (version 3.0).

STUDY DESIGN: Expert opinion, feedback, revisions, and final consensus. OBJECTIVES: To update the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS version 2.0) and incorporate suggestions from the SCI pain clinical and research community with respect to overall utility. SETTING: International. METHODS: The ISCIPBDS working group evaluated these suggestions and made modifications. The revised ISCIPBDS (Version 3.0) was then reviewed by members of the International SCI Data Sets Committee, the American Spinal Injury Association (ASIA) Board, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, individual reviewers and societies, and posted on the ASIA and ISCoS websites for 1 month to elicit comments before final approval by ASIA and ISCoS. RESULTS: The ISCIPBDS (Version 3.0) was updated to make the dataset more flexible and useful: 1. The assessment can be based on the patient's perception of several of his/her "worst" pain(s) or based on the International SCI Pain (ISCIP) Classification-defined or other pain types, depending on the specific research questions or clinical needs. 2. Pain interference should usually be rated for overall pain but may also be used for specific pain problems if needed. 3. An optional pain drawing was added to complement the check box documentation of pain location. 4. Data categories consistent with the Extended Pain Dataset list of current treatments were added. 5. Several new training cases were added.

Effects of whole-body vibration on neuropathic pain and the relationship between pain and spasticity in persons with spinal cord injury.

OBJECTIVE: Whole-body vibration (WBV) appears to modulate reflex hyperexcitability and spasticity. Due to common underlying neural mechanisms between spasticity and neuropathic pain, WBV may also reduce chronic pain after spinal cord injury (SCI). Our objective was to determine whether there are dose-related changes in pain following WBV and to examine the relationships between neuropathic pain and reflex excitability. STUDY DESIGN: Secondary analysis of a sub-population (participants with neuropathic pain, n = 16) from a larger trial comparing the effects of two different doses of WBV on spasticity in persons with SCI. SETTING: Hospital/Rehabilitation Center in Atlanta, GA, USA. METHODS: Participants were randomized to 8-bout or 16-bout WBV groups. Both groups received ten sessions of sham intervention, followed by ten sessions of WBV. Primary measures included the Neuropathic Pain Symptom Inventory (NPSI) for pain symptom severity and H-reflex paired-pulse depression (PPD) for reflex excitability. RESULTS: Mean change in NPSI scores were not significantly different between the groups (7 ± 6; p = 0.29; ES = 0.57); however, 8-bouts of WBV were consistently beneficial for participants with high neuropathic pain symptom severity (NPSI total score >30), while 16-bouts of WBV appeared to increase pain in some individuals with high NPSI scores. A baseline NPSI cut score of 30 predicted PPD response (sensitivity = 1.0, specificity = 0.83), with higher NPSI scores associated with decreased PPD in response to WBV. CONCLUSIONS: WBV in moderate doses appears to decrease neuropathic pain symptoms and improve reflex modulation. However, at higher doses neuropathic pain symptoms may be aggravated. Lower baseline NPSI scores were associated with improved reflex modulation.

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.

Barriers and Facilitators to Optimal Neuropathic Pain Management: SCI Consumer, Significant Other, and Health Care Provider Perspectives.

OBJECTIVE: Persistent neuropathic pain is a common and often severe consequence of spinal cord injury (SCI). There is a critical need to better understand how to overcome barriers and promote facilitators to optimal pain management. The present study was designed to identify, from the perspectives of persons living with SCI, their significant others, and SCI health care professionals, the barriers and facilitators to optimal pain management for intense neuropathic pain. DESIGN: Qualitative interviews. SETTING: University laboratory. SUBJECTS: People with SCI who had experienced intense neuropathic pain for a minimum of a year (N = 15), their significant others (N = 15), and SCI health care providers (N = 15). METHODS: Qualitative interviews were recorded, transcribed, and analyzed based on grounded theory using ATLAS.ti software. RESULTS: Inadequate access to care, information, or pain management expertise were frequently perceived barriers to optimal pain management across all three groups. Another major barrier was SCI stakeholders' concerns regarding the risks of adverse effects and addiction to pain medication. Facilitators included having a better understanding of pain and available treatment options, effective patient-provider communication, resilience, and access to nonpharmacological treatment options. CONCLUSIONS: Managing intense neuropathic pain poses significant challenges after SCI. SCI stakeholders felt that accessible treatment options were limited and primarily focused on pain medications with minimal benefit but with significant risks for addiction and adverse effects. Actionable facilitators to optimal pain management after SCI include education regarding neuropathic pain and treatment options for all stakeholders, better communication regarding neuropathic pain among stakeholders, and improved patient access to nonpharmacological treatment options.

Utility of the Neuropathic Pain Symptom Inventory in people with spinal cord injury.

STUDY DESIGN: Cohort/psychometric study OBJECTIVES: The primary objective was to determine the psychometric properties and the utility of the Neuropathic Pain Symptom Inventory (NPSI) in subgrouping people with moderate to severe neuropathic pain after spinal cord injury (SCI). SETTING: University-based laboratory in Miami, FL USA. METHODS: Seventy-two people with chronic SCI and neuropathic pain were included in this study. The NPSI, Numeric Rating Scale (NRS), Multidimensional Pain Inventory pain severity and perceived support subscales (MPI-PS and MPI-S, respectively), and the Coping Strategies Questionnaire were administered. The NPSI was administered twice, with a 2-4-week period between measurement sessions. RESULTS: The NPSI total score demonstrated good internal consistency with a Cronbach's alpha of 0.70. The test-retest reliability (intraclass correlations) ranged from 0.65 to 0.73 for the NPSI subscores and 0.79 for the total NPSI score. Further, construct validity was supported by moderate and significant positive correlations with the pain intensity NRS and pain severity subscale of the MPI (MPI-PS) (r > 0.40). Cluster analysis of factor scores derived from NPSI subscales, NRS, and MPI-PS scores revealed three distinct subgroups: (1) low-moderate, (2) moderate, and (3) high pain symptom severity with mean NPSI sum scores of 7.1, 17.5, and 33.8, respectively. CONCLUSION: The NPSI demonstrated good psychometric properties in people with neuropathic pain after SCI. Moreover, it has utility for establishing pain symptom phenotypes.

The Graph-DCK Scale: a measure of dorsal column function after spinal cord injury.

STUDY DESIGN: Cohort/psychometric study. OBJECTIVES: Assessment of dorsal column medial lemniscus (DCML) function is important for the clinical evaluation of people with spinal cord injury (SCI) because it provides useful information to guide rehabilitation and for prognosticating outcomes. For example, research suggests that damage to the DCML pathway may be associated with neuropathic pain after SCI. Tests for graphesthesia and directional cutaneous kinesthesia (DCK) are commonly used clinically to assess DCML function. However, the reliability and validity of these assessments in people with SCI have not been investigated. Moreover, there is a poor consistency between studies in the methodology of graphesthesia and DCK assessment. The purpose of this study was to determine the psychometric properties of the Graph-DCK Scale, which is a simple and potentially useful scale for assessing graphesthesia and DCK. The Graph-DCK Scale does not require expensive equipment and it takes less than 5 min to administer. SETTING: A university-based laboratory in Miami, FL, USA. METHODS: Sixty-seven people with chronic SCI and neuropathic pain were included in this study. The Graph-DCK Scale and vibration detection were measured twice in each participant, with a two- to four-week period between measurement sessions. RESULTS: The scale demonstrated an excellent internal consistency (Cronbach's alpha > 0.90) and test-retest reliability (ICC values > 0.80). Further, convergent validity was supported by moderate and significant positive correlations to vibration detection (r values > 0.40). CONCLUSION: The Graph-DCK Scale is quick and easy to administer, and it provides a reliable and valid assessment of DCML function in people with SCI. SPONSORSHIP: Craig Neilsen Foundation.

Living With Chronic Pain After Spinal Cord Injury: A Mixed-Methods Study.

OBJECTIVE: To identify the relative importance of positive (facilitators) and negative (barriers) contributors to living with chronic pain after spinal cord injury (SCI). DESIGN: Mixed-methods: (1) Qualitative (n=35): individual, semistructured, open-ended interviews identifying facilitator/barrier themes; (2) Quantitative (n=491): converting the most common themes into statements and quantifying agreement with these in an online survey to determine relative importance, underlying dimensions, and their associations with perceived difficulty in dealing with pain. SETTING: University-based research setting and general community. PARTICIPANTS: Volunteers (N=526) with SCI experiencing moderate to severe chronic pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interview guides, facilitator/barrier statements, and pain inventories. RESULTS: Exploratory factor analyses reduced agreement ratings into 4 facilitators (information regarding pain and treatments, resilience, coping, medication use) and 5 barriers (poor health care communication, pain impact and limitations, poor communication about pain, difficult nature of pain, treatment concerns). Greater "pain impact and limitations," "difficult nature of pain," "poor communication from provider," lower "resilience," greater "medication use," and younger age predicted greater difficulty in dealing with pain (r=.75; F=69.02; P<.001). CONCLUSIONS: This study revealed multiple facilitators and barriers to living with chronic pain after SCI. The principal barrier, "poor health care communication," indicated that consumers do not receive adequate information from their health care providers regarding pain. "Information regarding pain and treatments" had greater agreement scores and factor loadings than all other facilitators, indicating that most participants view provider-patient communication and educational efforts regarding pain and pain management as priorities and critical needs. Further initiatives in these areas are important for improving pain management post-SCI.

Understanding therapeutic benefits of overground bionic ambulation: exploratory case series in persons with chronic, complete spinal cord injury.

OBJECTIVE: To explore responses to overground bionic ambulation (OBA) training from an interdisciplinary perspective including key components of neuromuscular activation, exercise conditioning, mobility capacity, and neuropathic pain. DESIGN: Case series. SETTING: Academic research center. PARTICIPANTS: Persons (N=3; 2 men, 1 woman) aged 26 to 38 years with complete spinal cord injury (SCI) (American Spinal Injury Association Impairment Scale grade A) between the levels of T1 and T10 for ≥1 year. INTERVENTION: OBA 3d/wk for 6 weeks. MAIN OUTCOME MEASURES: To obtain a comprehensive understanding of responses to OBA, an array of measures were obtained while walking in the device, including walking speeds and distances, energy expenditure, exercise conditioning effects, and neuromuscular and cortical activity patterns. Changes in spasticity and pain severity related to OBA use were also assessed. RESULTS: With training, participants were able to achieve walking speeds and distances in the OBA device similar to those observed in persons with motor-incomplete SCI (10-m walk speed, .11-.33m/s; 2-min walk distance, 11-33m). The energy expenditure required for OBA was similar to walking in persons without disability (ie, 25%-41% of peak oxygen consumption). Subjects with lower soleus reflex excitability walked longer during training, but there was no change in the level or amount of muscle activity with training. There was no change in cortical activity patterns. Exercise conditioning effects were small or nonexistent. However, all participants reported an average reduction in pain severity over the study period ranging between -1.3 and 1.7 on a 0-to-6 numeric rating scale. CONCLUSIONS: OBA training improved mobility in the OBA device without significant changes in exercise conditioning or in neuromuscular or cortical activity. However, pain severity was reduced and no severe adverse events were encountered during training. OBA therefore opens the possibility to reduce the common consequences of chronic, complete SCI such as reduced functional mobility and neuropathic pain.

Perspectives of people with spinal cord injury on a pain education resource.

Introduction: Spinal cord injury (SCI) often leads to neuropathic pain that negatively affects quality of life. Several qualitative research studies in individuals with SCI who experience neuropathic pain indicate the lack of adequate information about pain. We previously developed an educational resource, the SeePain, based on scientific literature and a series of qualitative interviews of people with SCI, their significant others/family members, and SCI healthcare providers. Methods: However, to quantitatively evaluate the utility of this educational resource in a larger sample, we examined the agreement and usefulness ratings of statements regarding clarity/comprehensibility, content, and format of the SeePain, derived from the thematic analysis of our previous qualitative interviews. Participants completed a survey that provided a digital version of the SeePain and then rated their agreement/usefulness with the statements using numerical rating scales. Results: There were overall high perceived agreement and usefulness ratings regarding the SeePain's clarity, content, and format. A factor analysis reduced the agreement and usefulness ratings into 4 components (content, clarity, format, and delivery medium). Group comparisons showed that individuals with higher education were more likely to endorse electronic and website formats, and the usefulness of a shorter version of the SeePain; females and younger individuals showed greater endorsement for clarity. Finally, higher pain intensity ratings were associated with greater agreement and usefulness of the content of the SeePain. Discussion: Overall, these results support the utility of the SeePain as a source of information regarding pain that may facilitate communication about pain and its management following SCI.

Neuropathic Pain and Spinal Cord Injury: Management, Phenotypes, and Biomarkers.

Chronic neuropathic pain after a spinal cord injury (SCI) continues to be a complex condition that is difficult to manage due to multiple underlying pathophysiological mechanisms and the association with psychosocial factors. Determining the individual contribution of each of these factors is currently not a realistic goal; however, focusing on the primary mechanisms may be more feasible. One approach used to uncover underlying mechanisms includes phenotyping using pain symptoms and somatosensory function. However, this approach does not consider cognitive and psychosocial mechanisms that may also significantly contribute to the pain experience and impact treatment outcomes. Indeed, clinical experience supports that a combination of self-management, non-pharmacological, and pharmacological approaches is needed to optimally manage pain in this population. This article will provide a broad updated summary integrating the clinical aspects of SCI-related neuropathic pain, potential pain mechanisms, evidence-based treatment recommendations, neuropathic pain phenotypes and brain biomarkers, psychosocial factors, and progress regarding how defining neuropathic pain phenotypes and other surrogate measures in the neuropathic pain field may lead to targeted treatments for neuropathic pain after SCI.

Event-related potentials during mental rotation of body-related stimuli in spinal cord injury population.

Mental rotations of body-related stimuli are known to engage the motor system and activate body schema. Sensorimotor deficits following spinal cord injury (SCI) alter the representation of the body with a negative impact on the performance during motor-related tasks, such as mental rotation of body parts. Here we investigated the relationship between event-related potentials in SCI participants and the difficulty in mentally rotating a body-part. Participants with SCI and healthy control subjects performed a laterality judgment task, in which left or right images of hands, feet or animals (as a control stimulus) were presented in two different orientation angles (75° and 150°), and participants reported the laterality of the stimulus. We found that reaction times of participants with SCI were slower for the rotation of body-related stimuli compared to non-body-related stimuli and healthy controls. At the brain level, we found that relative to healthy controls SCI participants show: 1) reduced amplitudes of the posterior P100 and anterior N100 and larger amplitudes of the anterior P200 for overall stimuli; 2) an absence of the modulation of the rotation related negativity by stimulus type and rotation angles. Our results show that body representation changes after SCI affecting both components of early stimulus processing and late components that process high-order cognitive aspects of body-representation and task complexity.

Neuropsychological Function in Traumatic Brain Injury and the Influence of Chronic Pain.

Cognitive dysfunction, pain, and psychological morbidity all present unique challenges to those living with traumatic brain injury (TBI). In this study we examined (a) the impact of pain across domains of attention, memory, and executive function, and (b) the relationships between pain and depression, anxiety, and post-traumatic stress disorder (PTSD) in persons with chronic TBI. Our sample included 86 participants with a TBI and chronic pain (n = 26), patients with TBI and no chronic pain (n = 23), and a pain-free control group without TBI (n = 37). Participants visited the laboratory and completed a comprehensive battery of neuropsychological tests as part of a structured interview. Multivariate analysis of covariance using education as a covariate, failed to detect a significant group difference for neuropsychological composite scores of attention, memory, and executive function (p = .165). A follow-up analysis using multiple one-way analysis of variance (ANOVA) was conducted for individual measures of executive function. Post-hoc testing indicated that those in both TBI groups preformed significantly worse on measures of semantic fluency when compared to controls (p < 0.001, ηρ2 = .16). Additionally, multiple ANOVAs indicated that those with TBI and pain scored significantly worse across all psychological assessments (p < .001). We also found significant associations between measures of pain and most psychological symptoms. A follow-up stepwise linear regression among those in the TBI pain group indicated that post concussive complaints, pain severity, and neuropathic pain symptoms differentially contributed to symptoms of depression, anxiety, and PTSD. These findings suggest deficits in verbal fluency among those living with chronic TBI, with results also reinforcing the multidimensional nature of pain and its psychological significance in this population.

A preliminary study evaluating self-reported effects of cannabis and cannabinoids on neuropathic pain and pain medication use in people with spinal cord injury.

Approximately 60% of individuals with a spinal cord injury (SCI) experience neuropathic pain, which often persists despite the use of various pharmacological treatments. Increasingly, the potential analgesic effects of cannabis and cannabinoid products have been studied; however, little research has been conducted among those with SCI-related neuropathic pain. Therefore, the primary objective of the study was to investigate the perceived effects of cannabis and cannabinoid use on neuropathic pain among those who were currently or had previously used these approaches. Additionally, the study aimed to determine if common pain medications are being substituted by cannabis and cannabinoids. Participants (N = 342) were recruited from existing opt-in listserv sources within the United States. Of those, 227 met the inclusion criteria and were enrolled in the study. The participants took part in an anonymous online survey regarding past and current use of cannabis and their perceived effects on neuropathic pain, including the use of pain medication. Those in the sample reported average neuropathic pain intensity scores over the past week of 6.8 ± 2.1 (0 to 10 scale), reflecting a high moderate to severe level of pain. Additionally, 87.9% noted that cannabis reduced their neuropathic pain intensity by more than 30%, and 92.3% reported that cannabis helped them to better deal with their neuropathic pain symptoms. Most participants (83.3%) also reported substituting their pain medications with cannabis, with the most substituted medication categories being opioids (47.0%), gabapentinoids (42.8%) and over-the-counter pain medications (42.2%). These preliminary results suggest that cannabis and cannabinoids may be effective in reducing neuropathic pain among those with SCI and may help to limit the need for certain pain medications.

Neurometabolite alterations in traumatic brain injury and associations with chronic pain.

Traumatic brain injury (TBI) can lead to a variety of comorbidities, including chronic pain. Although brain tissue metabolite alterations have been extensively examined in several chronic pain populations, it has received less attention in people with TBI. Thus, the primary aim of this study was to compare brain tissue metabolite levels in people with TBI and chronic pain (n = 16), TBI without chronic pain (n = 17), and pain-free healthy controls (n = 31). The metabolite data were obtained from participants using whole-brain proton magnetic resonance spectroscopic imaging (1H-MRSI) at 3 Tesla. The metabolite data included N-acetylaspartate, myo-inositol, total choline, glutamate plus glutamine, and total creatine. Associations between N-acetylaspartate levels and pain severity, neuropathic pain symptom severity, and psychological variables, including anxiety, depression, post-traumatic stress disorder (PTSD), and post-concussive symptoms, were also explored. Our results demonstrate N-acetylaspartate, myo-inositol, total choline, and total creatine alterations in pain-related brain regions such as the frontal region, cingulum, postcentral gyrus, and thalamus in individuals with TBI with and without chronic pain. Additionally, NAA levels in the left and right frontal lobe regions were positively correlated with post-concussive symptoms; and NAA levels within the left frontal region were also positively correlated with neuropathic pain symptom severity, depression, and PTSD symptoms in the TBI with chronic pain group. These results suggest that neuronal integrity or density in the prefrontal cortex, a critical region for nociception and pain modulation, is associated with the severity of neuropathic pain symptoms and psychological comorbidities following TBI. Our data suggest that a combination of neuronal loss or dysfunction and maladaptive neuroplasticity may contribute to the development of persistent pain following TBI, although no causal relationship can be determined based on these data.

Development of a pain education resource for people with spinal cord injury.

Many people with spinal cord injury (SCI) develop chronic pain, including neuropathic pain. Unfortunately, current treatments for this condition are often inadequate because SCI-associated neuropathic pain is complex and depends on various underlying mechanisms and contributing factors. Multimodal treatment strategies including but not limited to pharmacological treatments, physical rehabilitation, cognitive training, and pain education may be best suited to manage pain in this population. In this study, we developed an educational resource named the SeePain based on published pain literature, and direct stakeholder input, including people living with SCI and chronic pain, their significant others, and healthcare providers with expertise in SCI. The SeePain was then 1) systematically evaluated by stakeholders regarding its content, comprehensibility, and format using qualitative interviews and thematic analysis, and 2) modified based on their perspectives. The final resource is a comprehensive guide for people with SCI and their significant others or family members that is intended to increase health literacy and facilitate communication between SCI consumers and their healthcare providers. Future work will quantitatively validate the SeePain in a large SCI sample.

Maladaptive reorganization following SCI: The role of body representation and multisensory integration.

In this review we focus on maladaptive brain reorganization after spinal cord injury (SCI), including the development of neuropathic pain, and its relationship with impairments in body representation and multisensory integration. We will discuss the implications of altered sensorimotor interactions after SCI with and without neuropathic pain and possible deficits in multisensory integration and body representation. Within this framework we will examine published research findings focused on the use of bodily illusions to manipulate multisensory body representation to induce analgesic effects in heterogeneous chronic pain populations and in SCI-related neuropathic pain. We propose that the development and intensification of neuropathic pain after SCI is partly dependent on brain reorganization associated with dysfunctional multisensory integration processes and distorted body representation. We conclude this review by suggesting future research avenues that may lead to a better understanding of the complex mechanisms underlying the sense of the body after SCI, with a focus on cortical changes.

Multisensory integration in humans with spinal cord injury.

Although multisensory integration (MSI) has been extensively studied, the underlying mechanisms remain a topic of ongoing debate. Here we investigate these mechanisms by comparing MSI in healthy controls to a clinical population with spinal cord injury (SCI). Deafferentation following SCI induces sensorimotor impairment, which may alter the ability to synthesize cross-modal information. We applied mathematical and computational modeling to reaction time data recorded in response to temporally congruent cross-modal stimuli. We found that MSI in both SCI and healthy controls is best explained by cross-modal perceptual competition, highlighting a common competition mechanism. Relative to controls, MSI impairments in SCI participants were better explained by reduced stimulus salience leading to increased cross-modal competition. By combining traditional analyses with model-based approaches, we examine how MSI is realized during normal function, and how it is compromised in a clinical population. Our findings support future investigations identifying and rehabilitating MSI deficits in clinical disorders.

Multidimensional pain phenotypes after Traumatic Brain Injury.

More than 50% of individuals develop chronic pain following traumatic brain injury (TBI). Research suggests that a significant portion of post-TBI chronic pain conditions is neuropathic in nature, yet the relationship between neuropathic pain, psychological distress, and somatosensory function following TBI is not fully understood. This study evaluated neuropathic pain symptoms, psychological and somatosensory function, and psychosocial factors in individuals with TBI (TBI, N = 38). A two-step cluster analysis was used to identify phenotypes based on the Neuropathic Pain Symptom Inventory and Beck's Anxiety Inventory scores. Phenotypes were then compared on pain characteristics, psychological and somatosensory function, and psychosocial factors. Our analyses resulted in two different neuropathic pain phenotypes: (1) Moderate neuropathic pain severity and anxiety scores (MNP-AS, N = 11); and (2) mild or no neuropathic pain symptoms and anxiety scores (LNP-AS, N = 27). Furthermore, the MNP-AS group exhibited greater depression, PTSD, pain severity, and affective distress scores than the LNP-AS group. In addition, thermal somatosensory function (difference between thermal pain and perception thresholds) was significantly lower in the MNP-AS compared to the LNP-AS group. Our findings suggest that neuropathic pain symptoms are relatively common after TBI and are not only associated with greater psychosocial distress but also with abnormal function of central pain processing pathways.

Phase 1 Safety Trial of Autologous Human Schwann Cell Transplantation in Chronic Spinal Cord Injury.

A phase 1 open-label, non-randomized clinical trial was conducted to determine feasibility and safety of autologous human Schwann cell (ahSC) transplantation accompanied by rehabilitation in participants with chronic spinal cord injury (SCI). Magnetic resonance imaging (MRI) was used to screen eligible participants to estimate an individualized volume of cell suspension to be implanted. The trial incorporated standardized multi-modal rehabilitation before and after cell delivery. Participants underwent sural nerve harvest, and ahSCs were isolated and propagated in culture. The dose of culture-expanded ahSCs injected into the chronic spinal cord lesion of each individual followed a cavity-filling volume approach. Primary outcome measures for safety and trend-toward efficacy were assessed. Two participants with American Spinal Injury Association Impairment Scale (AIS) A and two participants with incomplete chronic SCI (AIS B, C) were each enrolled in cervical and thoracic SCI cohorts (n = 8 total). All participants completed the study per protocol, and no serious adverse events related to sural nerve harvest or ahSC transplantation were reported. Urinary tract infections and skin abrasions were the most common adverse events reported. One participant experienced a 4-point improvement in motor function, a 6-point improvement in sensory function, and a 1-level improvement in neurological level of injury. Follow-up MRI in the cervical (6 months) and thoracic (24 months) cohorts revealed a reduction in cyst volume after transplantation with reduced effect over time. This phase 1 trial demonstrated the feasibility and safety of ahSC transplantation combined with a multi-modal rehabilitation protocol for participants with chronic SCI.

Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson's disease: study protocol for a prospective, pilot trial.

BACKGROUND: Freezing of gait (FOG) is a particularly debilitating motor deficit seen in a subset of Parkinson's disease (PD) patients that is poorly responsive to standard levodopa therapy or deep brain stimulation (DBS) of established PD targets such as the subthalamic nucleus and the globus pallidus interna. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN) to address FOG, was based on its observed pathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region, a functionally defined area of the midbrain that elicits locomotion in both intact animals and decerebrate animal preparations with electrical stimulation. Initial reports of PPN DBS were met with much enthusiasm; however, subsequent studies produced mixed results, and recent meta-analysis results have been far less convincing than initially expected. A closer review of the extensive mesencephalic locomotor region (MLR) preclinical literature, including recent optogenetics studies, strongly suggests that the closely related cuneiform nucleus (CnF), just dorsal to the PPN, may be a superior target to promote gait initiation. METHODS: We will conduct a prospective, open-label, single-arm pilot study to assess safety and feasibility of CnF DBS in PD patients with levodopa-refractory FOG. Four patients will receive CnF DBS and have gait assessments with and without DBS during a 6-month follow-up. DISCUSSION: This paper presents the study design and rationale for a pilot study investigating a novel DBS target for gait dysfunction, including targeting considerations. This pilot study is intended to support future larger scale clinical trials investigating this target. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04218526 (registered January 6, 2020).