Chronic Cervical Spinal Cord Injury Research Articles

Reaching and Grasping Training Improves Functional Recovery After Chronic Cervical Spinal Cord Injury.

Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life. In this study, we used a clinically relevant chronic cervical contusion to study the therapeutic efficacy of rehabilitation in forelimb functional recovery. Nude rats received a moderate C5 unilateral contusive injury and were then divided into two groups with or without Modified Montoya Staircase (MMS) rehabilitation. For the rehabilitation group, rats were trained 5 days a week starting at 8 weeks post-injury (PI) for 6 weeks. All rats were assessed for skilled forelimb functions with MMS test weekly and for untrained gross forelimb locomotion with grooming and horizontal ladder (HL) tests biweekly. Our results showed that MMS rehabilitation significantly increased the number of pellets taken at 13 and 14 weeks PI and the accuracy rates at 12 to 14 weeks PI. However, there were no significant differences in the grooming scores or the percentage of HL missteps at any time point. Histological analyses revealed that MMS rehabilitation significantly increased the number of serotonergic fibers and the amount of presynaptic terminals around motor neurons in the cervical ventral horns caudal to the injury and reduced glial fibrillary acidic protein (GFAP)-immunoreactive astrogliosis in spinal cords caudal to the lesion. This study shows that MMS rehabilitation can modify the injury environment, promote axonal sprouting and synaptic plasticity, and importantly, improve reaching and grasping functions in the forelimb, supporting the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI.

Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury.

Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined with non-invasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar spinal cord injury were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motor neuronal stimulation (PCMS) or sham-PCMS. In an additional experiment, we tested the effect of PCMS without exercise in 13 individuals with spinal cord injury with similar characteristics. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation over the primary motor cortex arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles (depending on the injury level), 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after all protocols. We found that the time to complete subcomponents of the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and the 10-m walk test decreased on average by 20% after all protocols. However, the amplitude of corticospinal responses elicited by transcranial magnetic stimulation and the magnitude of maximal voluntary contractions in targeted muscles increased on overage by 40-50% after PCMS combined or not with exercise but not after sham-PCMS combined with exercise. Notably, behavioural and physiological effects were preserved 6 months after the intervention in the group receiving exercise with PCMS but not in the group receiving exercise combined with sham-PCMS, suggesting that the stimulation contributed to preserve exercise gains. Our findings indicate that targeted non-invasive stimulation of spinal synapses might represent an effective strategy to facilitate exercise-mediated recovery in humans with different degrees of paralysis and levels of spinal cord injury.

Modulation of the extrinsic tongue muscle activity in response to bronchopulmonary C-fiber activation following midcervical contusion in the rat.

This study was designed to investigate extrinsic tongue muscle activity in response to bronchopulmonary C-fiber activation following midcervical spinal contusion in the rat. Esophageal pressure and electromyogram of the extrinsic tongue muscles (genioglossus and hyoglossus) were monitored before and after inhalation of capsaicin (25 and 100 µg/mL) at the acute (3 days), subchronic (12-16 days), and chronic (52-65 days) injured stages following unilateral midcervical spinal contusion. Three days after injury, the preinspiratory burst amplitude of the extrinsic tongue muscle at baseline was significantly greater in midcervical spinal-contused animals than in sham animals. At this time, capsaicin induced a significant reduction in both preinspiratory and inspiratory activity of the extrinsic tongue muscle in sham but not contused animals at the acute stage. During the chronic injured stage, capsaicin at 100 µg/mL induced stronger suppression of preinspiratory genioglossus muscle activity in the contused animals than in sham animals. These results demonstrated that cervical spinal cord injury alters upper airway motor outputs and their reflex modulation by bronchopulmonary C-fibers. The compensatory increase in respiratory activity of the extrinsic tongue muscle early after cervical spinal cord injury may help to maintain upper airway patency. However, under the condition of chronic cervical spinal cord injury, the increased suppression of genioglossus muscle activity by bronchopulmonary C-fiber activation may increase the risk of airway obstruction following chronic cervical spinal cord injury.NEW & NOTEWORTHY Tongue muscle activity plays an important role in the regulation of upper airway patency. This study aimed to investigate the respiratory activity of the extrinsic tongue muscle in response to capsaicin-induced bronchopulmonary C-fiber activation following cervical spinal cord contusion. Midcervical spinal-contused animals exhibited a greater baseline preinspiratory burst amplitude of the extrinsic tongue muscle and were resistant to inhaled capsaicin-induced reduction of respiratory tongue muscle activity at the acute injured stage. However, inhalation of capsaicin caused a more severe attenuation of preinspiratory activity of the extrinsic tongue muscle at the chronic injured stage. These results suggest that the upper airway may be predisposed to collapse in response to bronchopulmonary C-fiber activation following chronic cervical spinal cord injury.

5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion

Background. Intermittent hypoxia can induce respiratory neuroplasticity to enhance respiratory motor outputs following hypoxic treatment. This type of respiratory neuroplasticity is primarily mediated by the activation of Gq-protein-coupled 5-HT2 receptors and constrained by Gs-protein-coupled 5-HT7 receptors. Objective. The present study hypothesized that the blockade of 5-HT7 receptors can potentiate the effect of intermittent hypercapnic-hypoxia on respiratory function after cervical spinal cord contusion injury. Methods. The ventilatory behaviors of unanesthetized rats with midcervical spinal cord contusions were measured before, during, and after daily acute intermittent hypercapnic-hypoxia (10 episodes of 5 minutes of hypoxia [10% O2, 4% CO2, 86% N2] with 5 minutes of normoxia intervals for 5 days) at 8 weeks postinjury. On a daily basis, 5 minutes before intermittent hypercapnic-hypoxia, rats received either a 5-HT7 receptor antagonist (SB269970, 4 mg/kg, intraperitoneal) or a vehicle (dimethyl sulfoxide). Results. Treatment with intermittent hypercapnic-hypoxia induced a similar increase in tidal volume between rats that received SB269970 and those that received dimethyl sulfoxide within 60 minutes post-hypoxia on the first day. However, after 2 to 3 days of daily acute intermittent hypercapnic-hypoxia, the baseline tidal volumes of rats treated with SB269970 increased significantly. Conclusions. These results suggest that inhibiting the 5-HT7 receptor can transiently improve daily intermittent hypercapnic-hypoxia–induced tidal volume increase in midcervical spinal contused animals. Therefore, combining pharmacological treatment with rehabilitative intermittent hypercapnic-hypoxia training may be an effective strategy for synergistically enhancing respiratory neuroplasticity to improve respiratory function following chronic cervical spinal cord injury.

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia.

An increasing number of studies supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes functional recovery in humans with spinal cord injury (SCI). However, the neural mechanisms contributing to these effects remain poorly understood. Here we examined motor-evoked potentials in arm muscles elicited by cortical and subcortical stimulation of corticospinal axons before and after 20 min of TESS (30 Hz pulses with a 5 kHz carrier frequency) and sham-TESS applied between C5 and C6 spinous processes in males and females with and without chronic incomplete cervical SCI. The amplitude of subcortical, but not cortical, motor-evoked potentials increased in proximal and distal arm muscles for 75 min after TESS, but not sham-TESS, in control subjects and SCI participants, suggesting a subcortical origin for these effects. Intracortical inhibition, elicited by paired stimuli, increased after TESS in both groups. When TESS was applied without the 5 kHz carrier frequency both subcortical and cortical motor-evoked potentials were facilitated without changing intracortical inhibition, suggesting that the 5 kHz carrier frequency contributed to the cortical inhibitory effects. Hand and arm function improved largely when TESS was used with, compared with without, the 5 kHz carrier frequency. These novel observations demonstrate that TESS influences cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. We hypothesized that these parallel effects contribute to further the recovery of limb function following SCI.SIGNIFICANCE STATEMENT Accumulating evidence supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes recovery of function in humans with spinal cord injury (SCI). Here, we show that a single session of TESS over the cervical spinal cord in individuals with incomplete chronic cervical SCI influenced in parallel the excitability cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. Importantly, these parallel physiological effects had an impact on the magnitude of improvements in voluntary motor output.

Hand function recovery using nerve segment insert grafting in patients with chronic incomplete lower cervical spinal cord injury: a preliminary clinical report

Objective:The objective of this study was to show that hand functions could be recovered using nerve segment insert grafting in quadriplegic patients with chronic incomplete lower cervical spinal cord injury (CSCI) (C5/6/7/8).Methods:A retrospective analysis was performed in 18 quadriplegic patients (12 male and 6 female patients; mean age, 27 years; age range, 17–55 years) with chronic incomplete lower CSCI who had undergone nerve segment insert grafting from January 2001 to June 2015. Among the 18 patients, the right upper limb was involved in 7, left upper limb in 4, and bilateral upper limbs in 7 patients.Results:The mean follow-up period was 16 months (range, 3 months–3 years), and all patients exhibited obvious relief of limb spasm. Among all patients, 15 patients experienced no obvious spasm attacks and exhibited recovery of living abilities, i.e., recovery of the hand functions of grasping, holding, and pinching, and recovery of pain and temperature sensation in the fingers and palms; furthermore, they were able to steer an ordinary wheelchair independently postoperatively. The remaining three patients exhibited a significant and continuous improvement in hand functions over time, without any significant donor nerve dysfunction.Conclusions:Nerve segment insert grafting is an effective method that helps recover hand functions in quadriplegic patients with chronic incomplete lower CSCI. Moreover, spasticity can be relieved and partial normal innervation can be obtained in the spastic muscles postoperatively.

Changes in motoneuron excitability during voluntary muscle activity in humans with spinal cord injury.

The excitability of resting motoneurons increases following spinal cord injury (SCI). The extent to which motoneuron excitability changes during voluntary muscle activity in humans with SCI, however, remains poorly understood. To address this question, we measured F waves by using supramaximal electrical stimulation of the ulnar nerve at the wrist and cervicomedullary motor-evoked potentials (CMEPs) by using high-current electrical stimulation over the cervicomedullary junction in the first dorsal interosseous muscle at rest and during 5 and 30% of maximal voluntary contraction into index finger abduction in individuals with chronic cervical incomplete SCI and aged-matched control participants. We found higher persistence (number of F waves present in each set) and amplitude of F waves at rest in SCI compared with control participants. With increasing levels of voluntary contraction, the amplitude, but not the persistence, of F waves increased in both groups but to a lesser extent in SCI compared with control participants. Similarly, the CMEP amplitude increased in both groups but to a lesser extent in SCI compared with controls. These results were also found at matched absolutely levels of electromyographic activity, suggesting that these changes were not related to decreases in voluntary motor output after SCI. F-wave and CMEP amplitudes were positively correlated across conditions in both groups. These results support the hypothesis that the responsiveness of the motoneuron pool during voluntary activity decreases following SCI, which could alter the generation and strength of voluntary muscle contractions.NEW & NOTEWORTHY How the excitability of motoneurons changes during voluntary muscle activity in humans with spinal cord injury (SCI) remains poorly understood. We found that F-wave and cervicomedullary motor-evoked potential amplitude, outcomes reflecting motoneuronal excitability, increased during voluntary activity compared with rest in SCI participants but to a lesser extent that in controls. These results suggest that the responsiveness of motoneurons during voluntary activity decreases following SCI, which might affect functionally relevant plasticity after the injury.

A Fully Implantable Brain Machine Interface for Volitional Hand Grasp Restoration in Cervical Quadriplegia

Abstract INTRODUCTION Neural interface research has been strongly motivated by the need to restore communication and control to the estimated 5.3 million people in the US population which currently suffer from some form of paralysis. We recently enrolled a patient with a chronic traumatic cervical spinal cord injury (C5 ASIA A) to undergo placement of a brain machine interface aimed at restoring unilateral upper distal extremity function (ClinicalTrials.gov NCT02564419). The objective of this study was to evaluate the safety and efficacy of a fully implanted brain machine interface consisting of the Medtronic PC + S and the Bioness H200 hand rehabilitation orthosis for the functional restoration of hand grasp in a patient with cervical quadriplegia. METHODS A computer task was developed to engage the subject in thinking of either hand movement or rest while electrocorticographic (ECoG) activity was recorded. “Open-loop” trials were used to train various classifiers for predicting "move" or "rest" states based on observations of the ECoG activity. In "closed-loop" experiments, the decoded desired hand state was used to drive functional electrical stimulation of the dominant hand utilizing the Bioness H200 orthosis. Functional performance was measured by a modified Jebson Taylor Hand Function (JTHF) test and range of motion. RESULTS Movement intent information was decoded with an online accuracy of 88.2% with a tree bagging classifier over 21 sessions. Functional improvement was observed in reduction of the average time to perform subtasks within the JTHF test. CONCLUSION Our results demonstrate that a fully implanted brain machine interface can be safely implanted and used to reliably decode movement intent from motor cortex allowing for volitional control of hand grasp in a laboratory setting. Further work will aim to allow use of the device in a home setting, a critical step for the widespread use of these approaches to restore motor function in patients living with paralysis.

Risk-benefit value of upper extremity function by an implanted electrical stimulation device targeting chronic cervical spinal cord injury.

Study designA cross-sectional stated-preference survey using direct-assessment questions.ObjectiveTo determine the relative value placed on different outcomes to be used in a pivotal trial for the upper extremity configuration of the Networked Neuroprosthesis (NNP) as well as the tolerance of the expected adverse event profile.SettingAcademic medical center in the United States.MethodsDistribution of an online survey to adults living with tetraplegia; extent of agreement with each question/statement was obtaining using a 1–7 Likert scale.ResultsThere were 8 statements about potential benefits in arm/hand function; for all statements, more than 70% of participants rated the functions as “1-very important” to regain. There were variable degrees of concern related to risks that could occur during the 30-day post-surgical period and increasing degrees of concern related to risks that could occur in the first 5 years, potentially due to the device, based on the increasing degree of invasiveness of the intervention required to address the event. When analysing the results based on all degrees of interest, more than 64% of responders were interested in getting the NNP with a success rate threshold as low as 50% regardless of time post-injury. Chi-squared analyses revealed some associations between responses and sex, injury level, and injury duration; however, none of these were statistically significant upon post-hoc analysis.ConclusionData here indicate that people with tetraplegia are highly interested in a range of arm/hand functions and are tolerant of expected risks that may be associated with implanted neuroprosthetics.SponsorshipThe Institute for Functional Restoration funded this project through a sub-contract to K.D. Anderson from a larger Special Projects Award (grant number FP0020773) from the Craig H. Neilsen Foundation.

Functional passive range of motion of individuals with chronic cervical spinal cord injury

ObjectiveFunctional passive range of motion (PROM) requirements for individuals with cervical spinal cord injury (SCI) are clinically accepted despite limited evidence defining the specific PROM needed to perform functional tasks. The objective of this investigation was to better define the minimum PROM needed for individuals with cervical SCI to achieve optimal functional ability, and as a secondary outcome gather self-reported standardized functional data via the Spinal Cord Independence Measure-III (SCIM-III), and the Spinal Cord Injury Functional Index (SCI-FI).DesignObservational cohort.Setting128-bed rehabilitation hospital with inpatient and outpatient spinal cord injury rehabilitation programs.ParticipantsA convenience sample of 29 community-dwelling individuals with chronic (greater than one year) tetraplegic SCI (C5-8) who use a wheelchair for mobility.InterventionsNone.Outcome measuresTherapist goniometric measurement of upper and lower extremity PROM, and participant completion of a demographic questionnaire and two functional self-report measures (SCIM-III and SCI-FI) were completed.ResultsCompared to the general population, differences observed in our study participants included limitations in forearm pronation and elbow extension and increased shoulder extension and wrist extension (likely related to prop sitting). Elbow hyperextension was noted in one-third of the participants. Limitations in straight leg raise, hip flexion, abduction, and internal rotation, in combination with increased hip external rotation suggested these individuals with cervical SCI potentially completed activities of daily living (ADLs) in frog-sitting, rather than long-sitting. Ankle plantarflexion contractures were found in many participants. Shoulder horizontal adduction, elbow extension, hip flexion, knee flexion, ankle plantarflexion, and forefoot eversion ROM were associated with functional performance.ConclusionBased on our results healthcare providers should work with individuals with cervical SCI to develop long term PROM plans to optimize functional abilities.

Daily acute, but not chronic, intermittent hypoxia enhances phrenic motor plasticity in chronic cervical spinal cord injury

Daily acute intermittent hypoxia (dAIH; 3–15 hypoxic episodes per day) is a promising therapeutic strategy to improve respiratory function after incomplete spinal cord injury by inducing spinal respiratory motor plasticity. Conversely, chronic intermittent hypoxia (CIH; >100 episodes per day) elicits multisystem pathology and is a hallmark of moderate sleep apnea, a condition highly prevalent in individuals with cervical spinal injury. In intact rats, 7 days of dAIH preconditioning enhances phrenic motor facilitation whereas it is abolished by 7 days of CIH, an effect likely due to CIH‐induced neuroinflammation. Since the impact of prolonged CIH (> 1 wk) or dAIH on the capacity for phrenic motor facilitation with chronic spinal cord injury has not been explored, we compared the effect of 28 days of normoxia (21% O2; 8hrs/day), dAIH (10, 5 min episodes of 10.5% O2 with 5 min normoxic intervals/day) or CIH (2 min hypoxic episodes with 2 min intervals; 8 hrs/day) on phrenic output in rats with chronic C2 spinal hemisection (C2Hx). Neurophysiology experiments were conducted one day after the final hypoxic exposure; bilateral phrenic nerve activity and moderate AIH‐induced phrenic long‐term facilitation (pLTF) were assessed. Ipsilateral phrenic nerve activity during baseline conditions and maximal chemoreflex activation was: 1) reduced in all injury groups vs intact rats (p<0.0001 and p<0.009, respectively); and 2) unaffected by dAIH or CIH (p>0.94 and p>0.98, respectively). No group differences in contralateral phrenic nerve activity were observed in either condition (p>0.49 and p>0.18, respectively). dAIH enhanced ipsilateral pLTF vs. all other groups (p=0.01); in contrast, CIH had no effect on pLTF (p=0.43). In conclusion, neither dAIH nor CIH had any detectable impact on phrenic nerve activity in rats with chronic C2Hx, but dAIH enhanced the capacity for additional pLTF. Further work is needed to explore: 1) mechanisms of enhanced respiratory plasticity following dAIH; 2) if detrimental effects of CIH can be resolved by treatments that mitigate inflammation; and 3) how enhanced/restored phrenic motor plasticity can be harnessed to improve breathing ability in individuals with chronic cervical spinal cord injury.Support or Funding InformationNIH: OT2OD023854, K12 HDO55929 (EGR), T32 HD055929 (LLA); Department of Defense: SCI160123 (EGR)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pilot study of feasibility and effect of anodal transcutaneous spinal direct current stimulation on chronic neuropathic pain after spinal cord injury.

A single-blind crossover study. This study aimed to evaluate neuropathic pain in persons with spinal cord injury (SCI) after the application of transcutaneous spinal direct current stimulation (tsDCS). Outpatient Clinic of the Rehabilitation Department, Seoul National University Hospital. The effect of single sessions of both anodal and sham tsDCS (2 mA, 20 min) on chronic neuropathic pain in ten volunteers with complete motor cervical SCI was assessed. The active electrode was placed over the spinal process of the tenth thoracic vertebra and the reference electrode, at the top of the head. Pre- to post-tsDCS intervention changes in pain intensity (numeric rating scale, NRS), patient global assessment, and present pain intensity (PPI) were assessed before and after the tsDCS session (immediately post stimulation, and at 1 and 2 h post stimulation). All participants underwent the stimulation procedure without dropout. Our results showed no significant pre- to post-treatment difference in pain intensity between the active and sham tsDCS groups. Only in the sham tsDCS stimulation, NRS and PPI scores were reduced after the stimulation session. Furthermore, in the mixed effect model analysis, the response in the second period appeared to be more favorable. The results suggest that a single session of anodal tsDCS with the montage used in this study is feasible but does not have a significant analgesic effect in individuals with chronic cervical SCI. The study was funded by Seoul National University Hospital (No. 0420160470) and Korea Workers' Compensation & Welfare Service.

Alterations in Motor Cortical Representation of Muscles Following Incomplete Spinal Cord Injury in Humans.

(1) Background: The primary motor cortex (M1) experiences reorganization following spinal cord injury (SCI). However, there is a paucity of research comparing bilateral M1 organization in SCI and questions remain to be answered. We explored the presence of somatotopy within the M1 representation of arm muscles, and determined whether anatomical shifts in these representations occur, and investigated the symmetry in organization between the two hemispheres.; (2) Methods: Transcranial magnetic stimulation (TMS) was used to map the representation of the biceps, flexor carpi radialis and abductor pollicis brevis (APB) bilaterally in nine individuals with chronic incomplete cervical spinal cord injury and nine aged- and handed-matched uninjured controls. TMS was delivered over a 6 × 5 point grid that encompassed M1 using an intensity specific to the resting motor threshold for each muscle tested.; (3) Results: Results indicate that, compared to controls, muscle representations in SCI are shifted medially but preserve a general somatotopic arrangement, and that territory dedicated to the APB muscle is greater.; (4) Conclusions: These findings demonstrate differences in the organization of M1 between able-bodied controls and those with incomplete cervical SCI. This altered organization may have future implications in understanding the functional deficits observed in SCI and rehabilitation techniques aimed at restoring function.

Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury

Human neural stem cell transplantation (HuCNS-SC®) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. In Cohort I (n = 6) dose escalation from 15,000,000 to 40,000,000 cells was performed to determine the optimum dose. In Cohort II an additional six participants were transplanted at target dose (40,000,000) and compared with four untreated controls. Within the transplant group, there were nine American Spinal Injury Association Impairment Scale (AIS) B and three AIS A participants with a median age at transplant of 28 years with an average time to transplant post-injury of 1 year. Immunosuppression was continued for 6 months post-transplant, and immunosuppressive blood levels of tacrolimus were achieved and well tolerated. At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.

Epidural Spinal Cord Stimulation Training and Sustained Recovery of Cardiovascular Function in Individuals With Chronic Cervical Spinal Cord Injury

Epidural Spinal Cord Stimulation Training and Sustained Recovery of Cardiovascular Function in Individuals With Chronic Cervical Spinal Cord Injury

EEG-controlled functional electrical stimulation for hand opening and closing in chronic complete cervical spinal cord injury

Background. There are over 33 000 people in the US living with complete tetraplegia due to spinal cord injury (SCI). People with complete tetraplegia rank restoration of hand and arm function as their highest priority, as it would offer greater independence and improved quality of life. In this study, we show that subjects with chronic (>1-year post-injury) C5 or C6 level, motor-complete SCI are able to control a brain computer interface-functional electrical stimulation (BCI-FES) system to enable hand opening and closing. Methods: 8 subjects with C5 or C6 motor-level SCI and 6 uninjured, control subjects participated in 6 sessions of BCI-FES sessions. Electroencephalographic (EEG) signals were acquired using a wireless EEG system and subjects were asked to ‘imagine moving their right hand’ for motor imagery. Average power was extracted in 5 Hz bins (6–35 Hz) from C3, C1, Cz, C2, and C4 electrodes and input as features to a support vector machine classification algorithm. When ‘movement intention’ was classified correctly from the motor imagery period, a custom-designed stimulation sequence was delivered to the forearm muscles via surface electrodes to enable opening and closing of the hand. Results: Average online decoding accuracy during the closed-loop BCI-FES sessions was similar for the SCI (74.8% ± 17.76) and the control (75.5% ± 11.94) group. Online decoding accuracies were validated using Monte Carlo simulations that used 30%, 50%, and 70% training data to validate the decoded online accuracy and Wilcoxon rank sum test found no significant differences between the SCI and Control subjects. Conclusions: This study demonstrates that subjects with motor complete, cervical SCI were able to control a BCI-FES system with decoding accuracies similar to healthy controls after minimal BCI-training. Non-invasive BCI-FES systems may have the potential to restore hand function in people with motor-complete SCI to improve their quality of life.

Thoraco-abdominal asynchrony analysis using optoelectronic plethysmography in patients with cervical spinal cord injury

Patients with acute cervical spinal cord injury (CSCI) sometimes present paradoxical respiratory pattern, that is, the chest cage is displaced inward during inspiration. It is known as an example of thoraco-abdominal asynchrony which increases work of breathing. On the other hand, it is known that respiratory movement of such paralytic patients are influenced by position change. The aim of this study was to investigate thoraco-abdominal asynchrony and influence of posture on it in patients with chronic cervical spinal cord injury using optoelectronic plethysmography. Five patients with chronic CSCI (aged 42 ± 14, ASIA impairment scale classified into A in all patients, neurological level C4: 2, C5: 2, C8: 1) were recruited from outpatient clinic of regional rehabilitation center. As control group, 5 age-gender matched healthy subjects were recruited. Volume change of the rib cage and the abdomen were measured with 3 dimention optoelectronic motion analysis system (VICON MX, Motion Capture Systems, Oxford, UK), using 45 reflective markers on the chest wall monitored by 6 infrared cameras. The breath which showed maximum volume change among 3 deep breaths was sampled for analysis in each patient. Measurement was done in the supine position and 30 and 60 degrees head elevation position. With obtained volume change of rib cage and abdomen, Konno Mead Diagram was drawn for each sample. Then we calculated the phase shift angle. The phase shift angle was 47 ± 2 degrees for the patients and 9 ± 6 degrees for healthy controls in supine position, that is, the CSCI patients group showed larger abdominal contribution. The angle tended to increase as head elevation in both groups. Patients with chronic CSCI showed larger asynchrony than healthy controls. Asynchrony tended to increase with head raising in both CSCI patients and controls.

Reliability of the International Spinal Cord Injury Upper Extremity Basic Data Set.

It is a psychometrics study. To assess the inter-rater reliability of the International Spinal Cord Injury Upper Extremity Basic Data Set (ISCI-UE). Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand. Individuals with subacute and chronic cervical spinal cord injury (SCI) were recruited. One examiner rated five parts of the ISCI-UE, including the ability to reach and grasp, the shoulder function classification, utilization of adaptive devices used to enhance upper-extremity function, complications affecting upper-extremity function, and upper extremity/hand reconstructive surgery. A second blinded examiner repeated the procedures within 1 day. Quadratic weighted kappa was calculated to determine the inter-rater reliability. Sixty participants were included in the study. Fifty-two patients were men, and the mean (SD) age of participants was 42.9 (14.3) years. The median (interquartile range) time since injury was 9.5 (1-53) months. A total of 117 upper limbs were assessed. The inter-rater reliability was substantial, with almost perfect agreement in all items (ability to reach and grasp = 0.98; shoulder function classification = 0.97; use of assistive devices = 0.89; complications = 0.74; and surgery = 1). The International Spinal Cord Injury Upper Extremity Basic Data Set (ISCI-UE) has very good inter-rater reliability for evaluating individuals with cervical SCI.

Potentiating paired corticospinal-motoneuronal plasticity after spinal cord injury

BackgroundPaired corticospinal-motoneuronal stimulation (PCMS) increases corticospinal transmission in humans with chronic incomplete spinal cord injury (SCI).Objective/Hypothesis: Here, we examine whether increases in the excitability of spinal motoneurons, by performing voluntary activity, could potentiate PCMS effects on corticospinal transmission. MethodsDuring PCMS, we used 100 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ∼1–2 ms before antidromic potentials were elicited in motoneurons by electrical stimulation of the ulnar nerve. PCMS was applied at rest (PCMSrest) and during a small level of isometric index finger abduction (PCMSactive) on separate days. Motor evoked potentials (MEPs) elicited by TMS and electrical stimulation were measured in the FDI muscle before and after each protocol in humans with and without (controls) chronic cervical SCI. ResultsWe found in control participants that MEPs elicited by TMS and electrical stimulation increased to a similar extent after both PCMS protocols for ∼30 min. Whereas, in humans with SCI, MEPs elicited by TMS and electrical stimulation increased to a larger extent after PCMSactive compared with PCMSrest. Importantly, SCI participants who did not respond to PCMSrest responded after PCMSactive and those who responded to both protocols showed larger increments in corticospinal transmission after PCMSactive. ConclusionsOur findings suggest that muscle contraction during PCMS potentiates corticospinal transmission. PCMS applied during voluntary activity may represent a strategy to boost spinal plasticity after SCI.

Sustained cell body reactivity and loss of NeuN in a subset of axotomized bulbospinal neurons after a chronic high cervical spinal cord injury

Following central nervous system lesion, the ability of injured axons to regrowth may depend on the level and duration of the injured cell body response (CBR). Therefore, to investigate whether axotomized brainstem neurons maintain a durable growth-competent state after spinal cord injury, we studied the effect of a chronic C2 hemisection in rats on the expression of various CBR markers involved in axon regeneration, such as c-Jun, ATF-3, HSP27, NO synthase (NOS), and also of the neural mature phenotype marker NeuN, in the bulbospinal respiratory neurons as compared to the gigantocellularis nucleus. Both at 7 and 30days post-lesion (DPL), c-Jun and HSP27 were present in, respectively, ~60 and ~20% of the axotomized respiratory neurons, whereas the apoptotic factor caspase 3 was not detected in these cells. NOS appeared belatedly, and it was detected in ~20% of the axotomized respiratory neurons at 30DPL. At 30DPL, these different CBR markers were strongly colocalized in a sub-population of axotomized respiratory neurons and also in a sub-population of injured neurons within the gigantocellularis nucleus. Such CBR was also accompanied by a sustained alteration of the neural mature phenotype, as indicated by a loss of NeuN immunoreactivity selectively in HSP27+ bulbospinal neurons at 7DPL and 30DPL. Altogether, this study shows that a subset of axotomized medullary respiratory neurons remains in a growth-competent state after a chronic injury, suggesting that they may play a preferential role in long-lasting respiratory neuroplasticity processes.