Chronic Cervical Spinal Cord Injury Research Articles

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.

Reticulospinal Contributions to Gross Hand Function after Human Spinal Cord Injury.

Multiple descending motor pathways likely contribute to the recovery of hand motor function following spinal cord injury (SCI). Reticulospinal neurons project to spinal motor neurons controlling hand muscles and extensively sprout into gray matter structures after SCI; therefore, it has been proposed that the reticulospinal tract is one of the descending motor pathways involved in recovery of hand function after injury. To test this hypothesis, we examined the StartReact response, an involuntary release of a planned movement via a startling stimulus that engages the reticulospinal tract, by measuring reaction times from electromyographic activity in an intrinsic finger muscle during three motor tasks requiring different degrees of hand dexterity: index finger abduction, a precision grip, and a power grip. Males and females with and without incomplete chronic cervical SCI were tested. We found that although SCI participants voluntarily responded to all tasks, reaction times were shorter during a startle cue while performing a power grip but not index finger abduction or precision grip. Control subjects had similarly shorter reaction times during a startle cue in all motor tasks. These results provide the first evidence for a contribution of the reticulospinal tract to hand control in humans with SCI during gross finger manipulations and suggest that this contribution is less pronounced during fine dexterous finger movements.SIGNIFICANCE STATEMENT It has been long proposed that brainstem pathways contribute to the recovery of hand function in humans with spinal cord injury (SCI). Here, we show that individuals with anatomically incomplete chronic cervical SCI responded to a startle stimulus, a test that engages the reticulospinal tract, while performing a power grip but not during index finger abduction or precision grip. Control subjects responded to a startle stimulus similarly across tasks. These observations suggest that reticulospinal outputs after SCI contribute to hand motor tasks involving gross finger movements. Interestingly, this contribution is less pronounced during fine dexterous finger movements.

Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury: Functional Outcomes at 12 Months in a Phase II Clinical Trial.

Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury: Functional Outcomes at 12 Months in a Phase II Clinical Trial.

Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury.

Traumatic spinal cord injuries (SCIs) affect millions of people worldwide; the majority of whom are in the chronic phase of their injury. Unfortunately, most current treatments target the acute/subacute injury phase as the microenvironment of chronically injured cord consists of a well-established glial scar with inhibitory chondroitin sulfate proteoglycans (CSPGs) which acts as a potent barrier to regeneration. It has been shown that CSPGs can be degraded in vivo by intrathecal Chondroitinase ABC (ChABC) to produce a more permissive environment for regeneration by endogenous cells or transplanted neural stem cells (NSCs) in the subacute phase of injury. Using a translationally-relevant clip-contusion model of cervical spinal cord injury in mice we sought to determine if ChABC pretreatment could modify the harsh chronic microenvironment to enhance subsequent regeneration by induced pluripotent stem cell-derived NSCs (iPS-NSC). Seven weeks after injury—during the chronic phase—we delivered ChABC by intrathecal osmotic pump for one week followed by intraparenchymal iPS-NSC transplant rostral and caudal to the injury epicenter. ChABC administration reduced chronic-injury scar and resulted in significantly improved iPSC-NSC survival with clear differentiation into all three neuroglial lineages. Neurons derived from transplanted cells also formed functional synapses with host circuits on patch clamp analysis. Furthermore, the combined treatment led to recovery in key functional muscle groups including forelimb grip strength and measures of forelimb/hindlimb locomotion assessed by Catwalk. This represents important proof-of-concept data that the chronically injured spinal cord can be ‘unlocked’ by ChABC pretreatment to produce a microenvironment conducive to regenerative iPS-NSC therapy.

Contribution of 5-HT2A receptors on diaphragmatic recovery after chronic cervical spinal cord injury

Unilateral C2 spinal cord hemisection (C2Hx) interrupts bulbospinal respiratory pathways innervating ipsilateral phrenic motoneurons, resulting in cessation of ipsilateral diaphragm motor output. Plasticity within the spinal neural circuitry controlling the diaphragm can induce partial recovery of phrenic bursting which correlates with the time-dependent return of spinal serotonin (5-HT) immunoreactivity in the vicinity of phrenic motoneurons. The 5-HT2A receptor subtype is present on phrenic motoneurons and its expression is up-regulated after cervical spinal cord injury; however the functional role of these receptors following injury has not been clearly defined. The present study evaluated the functional role of 5-HT2A receptors by testing the hypothesis that pharmacologic blockade would attenuate diaphragm activity in rats with chronic cervical spinal cord injury. Bilateral diaphragm electromyography (EMG) was performed in vagal-intact and spontaneously breathing rats before and after intravenous administration of the 5-HT2A receptor antagonist Ketanserin (1mg/kg). Intravenous ketanserin significantly attenuated ipsilateral diaphragm EMG activity in C2Hx animals but had no impact on diaphragm output in uninjured animals. We conclude that 5-HT2A receptor activation contributes to the recovery of ipsilateral phrenic motor output after chronic cervical spinal cord injury.

Abstracts from The 35th Annual National Neurotrauma Symposium July 7-12, 2017 Snowbird, Utah.

Abstracts from The 35th Annual National Neurotrauma Symposium July 7-12, 2017 Snowbird, Utah.

White matter changes in corticospinal tract associated with improvement in arm and hand functions in incomplete cervical spinal cord injury: pilot case series.

This is a prospective clinical pilot case series. Improvement of arm and hand functions after spinal cord injury (SCI) is one of the major rehabilitation goals. Electrical stimulation of the primary motor cortex via transcranial direct current stimulation (tDCS) coupled with high-intensity repetitive motor training may have potential to facilitate improvement in motor function in chronic, incomplete cervical SCI. We investigated the relationship between motor recovery and changes in white matter integrity in response to treatment intervention. This study was conducted in The Institute for Rehabilitation and Research Memorial Hermann, Houston, USA. Four right-handed adults with chronic, incomplete cervical SCI (age, 36-63 years, American Spinal Injury Association Impairment Scale grade C-D) were enrolled in 10 sessions of anodal tDCS at 2 mA versus sham tDCS followed by 1 h of robotic-assisted arm training. Changes in arm and hand function were measured with Jebsen-Taylor Hand Function Test and Motor Activity Log-Amount of Use. Diffusion tension imaging was used to measure changes in fractional anisotropy (FA) of corticospinal tracts (CSTs). After 10 sessions of treatment, we found greater improvement in hand function and hand usage in patients who received active tDCS treatment versus sham treatment. There was an overall positive change in FA values across all patients. We show changes in arm and hand function associated with changes in CST tractographic mapping to quantify the motor system components in chronic incomplete cervical SCI.

High-frequency epidural stimulation across the respiratory cycle evokes phrenic short-term potentiation after incomplete cervical spinal cord injury.

C2 spinal hemilesion (C2Hx) paralyzes the ipsilateral diaphragm, but recovery is possible through activation of "crossed spinal" synaptic inputs to ipsilateral phrenic motoneurons. We tested the hypothesis that high-frequency epidural stimulation (HF-ES) would potentiate ipsilateral phrenic output after subacute and chronic C2Hx. HF-ES (300 Hz) was applied to the ventrolateral C4 or T2 spinal cord ipsilateral to C2Hx in anesthetized and mechanically ventilated adult rats. Stimulus duration was 60 s, and currents ranged from 100 to 1,000 µA. Bilateral phrenic nerve activity and ipsilateral hypoglossal (XII) nerve activity were recorded before and after HF-ES. Higher T2 stimulus currents potentiated ipsilateral phasic inspiratory activity at both 2 and 12 wk post-C2Hx, whereas higher stimulus currents delivered at C4 potentiated ipsilateral phasic phrenic activity only at 12 wk (P = 0.028). Meanwhile, tonic output in the ipsilateral phrenic nerve reached 500% of baseline values at the high currents with no difference between 2 and 12 wk. HF-ES did not trigger inspiratory burst-frequency changes. Similar responses occurred following T2 HF-ES. Increases in contralateral phrenic and XII nerve output were induced by C4 and T2 HF-ES at higher currents, but the relative magnitude of these changes was small compared with the ipsilateral phrenic response. We conclude that following incomplete cervical spinal cord injury, HF-ES of the ventrolateral midcervical or thoracic spinal cord can potentiate efferent phrenic motor output with little impact on inspiratory burst frequency. However, the substantial increases in tonic output indicate that the uninterrupted 60-s stimulation paradigm used is unlikely to be useful for respiratory muscle activation after spinal injury.NEW & NOTEWORTHY Previous studies reported that high-frequency epidural stimulation (HF-ES) activates the diaphragm following acute spinal transection. This study examined HF-ES and phrenic motor output following subacute and chronic incomplete cervical spinal cord injury. Short-term potentiation of phrenic bursting following HF-ES illustrates the potential for spinal stimulation to induce respiratory neuroplasticity. Increased tonic phrenic output indicates that alternatives to the continuous stimulation paradigm used in this study will be required for respiratory muscle activation after spinal cord injury.

A novel cortical target to enhance hand motor output in humans with spinal cord injury.

A main goal of rehabilitation strategies in humans with spinal cord injury is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following spinal cord injury, the role of cortical targets remain poorly understood. Here, we use 180 pairs of transcranial magnetic stimulation for ∼30 min over the hand representation of the motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order. Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following spinal cord injury. Motor evoked potentials elicited by transcranial magnetic stimulation, paired-pulse intracortical inhibition, spinal motor neuron excitability (F-waves), index finger abduction force and electromyographic activity as well as a hand dexterity task were measured before and after both protocols in 15 individuals with chronic incomplete cervical spinal cord injury and 17 uninjured participants. We found that motor evoked potentials size increased in spinal cord injury and uninjured participants after the I-wave but not the control protocol for ∼30 to 60 min after the stimulation. Intracortical inhibition decreased and F-wave amplitude and persistence increased after the I-wave but not the control protocol, suggesting that cortical and subcortical networks contributed to changes in corticospinal excitability. Importantly, hand motor output and hand dexterity increased in individuals with spinal cord injury after the I-wave protocol. These results provide the first evidence that late synaptic input to corticospinal neurons may represent a novel therapeutic target for improving motor function in humans with paralysis due to spinal cord injury.

Effects of Overground Locomotor Training on Walking Performance in Chronic Cervical Motor Incomplete Spinal Cord Injury: A Pilot Study

ObjectiveTo determine the effects of a novel overground locomotor training program on walking performance in people with chronic cervical motor incomplete spinal cord injury (iSCI). DesignBefore-after pilot study. SettingHuman performance research laboratory. ParticipantsAdults (N=6, age >18y) with chronic cervical iSCI with American Spinal Injury Association Impairment Scale grades C and D. InterventionsOverground locomotor training included two 90-minute sessions per week for 12 to 15 weeks. Training sessions alternated between uniplanar and multiplanar stepping patterns. Each session was comprised of 5 segments: joint mobility, volitional muscle activation, task isolation, task integration, and activity rehearsal. Main Outcome MeasuresOverground walking speed, oxygen consumption (V˙o2), and carbon dioxide production (V˙co2). ResultsOverground locomotor training increased overground walking speed (.36±.20 vs .51±.24 m/s, P<.001, d=.68). Significant decreases in V˙o2 (6.6±1.3 vs 5.7±1.4mL·kg·min, P=.038, d=.67) and V˙co2 (753.1±125.5 vs 670.7±120.3mL/min, P=.036, d=.67) during self-selected constant work rate treadmill walking were also noted after training. ConclusionsThe overground locomotor training program used in this pilot study is feasible and improved both overground walking speed and walking economy in a small sample of people with chronic cervical iSCI. Future studies are necessary to establish the efficacy of this overground locomotor training program and to differentiate among potential mechanisms contributing to enhanced walking performance in people with iSCI after overground locomotor training.

Altered corticospinal function during movement preparation in humans with spinal cord injury.

In uninjured humans, transmission in the corticospinal pathway changes in a task-dependent manner during movement preparation. We investigated whether this ability is preserved in humans with incomplete chronic cervical spinal cord injury (SCI). Our results show that corticospinal excitability is altered in the preparatory phase of an upcoming movement when there is a need to suppress but not to execute rapid index finger voluntary contractions in individuals with SCI compared with controls. This is probably related to impaired transmission at a cortical and spinal level after SCI. Overall our findings indicate that deficits in corticospinal transmission in humans with chronic incomplete SCI are also present in the preparatory phase of upcoming movements. Corticospinal output is modulated in a task-dependent manner during the preparatory phase of upcoming movements in humans. Whether this ability is preserved after spinal cord injury (SCI) is unknown. In this study, we examined motor evoked potentials elicited by cortical (MEPs) and subcortical (CMEPs) stimulation of corticospinal axons and short-interval intracortical inhibition in the first dorsal interosseous muscle in the preparatory phase of a reaction time task where individuals with chronic incomplete cervical SCI and age-matched controls needed to suppress (NOGO) or initiate (GO) ballistic index finger isometric voluntary contractions. Reaction times were prolonged in SCI participants compared with control subjects and stimulation was provided ∼90ms prior to movement onset in each group. During NOGO trials, both MEPs and CMEPs remained unchanged compared to baseline in SCI participants but were suppressed in control subjects. Notably, during GO trials, MEPs increased to a similar extent in both groups but CMEPs increased only in controls. The magnitude of short-interval intracortical inhibition increased in controls but not in SCI subjects during NOGO trials and decreased in both groups in GO trials. These novel observations reveal that humans with incomplete cervical SCI have an altered ability to modulate corticospinal excitability during movement preparation when there is a need to suppress but not to execute upcoming rapid finger movements, which is probably related to impaired transmission at a cortical and spinal level. Thus, deficits in corticospinal transmission after human SCI extend to the preparatory phase of upcoming movements.

Nerve Transfer Surgery in Tetraplegia

Objective: Spinal cord injury leads to upper motor neuron paralysis below the level of the injury. However, emerging evidence suggests lower motor neuron denervation is evident in these paralyzed muscle groups. We aimed to study patients with chronic cervical spinal cord injuries who underwent nerve transfer surgery for evidence of lower motor neuron dysfunction in the upper limb preoperatively. Methods: Patients with cervical spine injuries who were being considered for nerve transfer surgery were examined using electromyography for evidence of spontaneous activity in the form of fibrillations. The neuromuscular units were divided into clinically functional “donors”—teres minor, brachialis, and supinator—and into clinically low-functional or nonfunctional “recipients”—flexor digitorum profundus (FDP), flexor pollicis longus (FPL), extensor digitorum communis (EDC), extensor pollicis longus (EPL), and triceps. The aim of the nerve transfer surgery was to restore pivotal upper limb functions such as elbow extension, key pinch, grasp, and release. Results: A retrospective review of the preoperative electromyography results for 25 upper limbs from 17 male patients was performed. A significant proportion of the recipient muscles showed evidence of fibrillations: FDP 96%, triceps 92%, and FPL 91%. Incidence of fibrillations for EDC and EPL was significantly lower despite also being in the recipient group. Interestingly, donor muscle groups with volitional control also showed evidence of fibrillations. Although at a much lower rate than most of the recipient groups, the incidence of fibrillations in the donor muscles were as follows: supinator 8%, brachialis 14%, and teres minor 34%. Conclusion: Patients with cervical spinal cord injury show evidence of lower motor neuron injury on electromyography. This finding has implications for the timing of nerve transfer surgery. The authors propose that, to maximize outcomes, prospective recipient muscles demonstrating denervation should be reinnervated using nerve transfers early (6-12 months post injury) before the neuromuscular endplate degeneration that follows denervation occurs. The presence of fibrillation potentials in prospective donor nerves, which are clinically normal on examination, may have implications for the outcome of nerve transfer surgery using these nerves.

Transcranial direct current stimulation (tDCS) of the primary motor cortex and robot-assisted arm training in chronic incomplete cervical spinal cord injury: A proof of concept sham-randomized clinical study

After cervical spinal cord injury, current options for treatment of upper extremity motor functions have been limited to traditional approaches. However, there is a substantial need to explore more rigorous alternative treatments to facilitate motor recovery. To demonstrate whether anodal-primary motor cortex (M1) excitability enhancement (with cathodal-supra orbital area) (atDCS) combined with robot-assisted arm training (R-AAT) will provide greater improvement in contralateral arm and hand motor functions compared to sham stimulation (stDCS) and R-AAT in patients with chronic, incomplete cervical spinal cord injury (iCSCI). In this parallel-group, double-blinded, randomized and sham-controlled trial, nine participants with chronic iCSCI (AIS C and D level) were randomized to receive 10 sessions of atDCS or stDSC combined with R-AAT. Feasibility and tolerability was assessed with attrition rate and occurrence of adverse events, Changes in arm and hand function were assessed with Jebson Taylor Hand Function Test (JTHFT). Amount of Use Scale of Motor Activity Log (AOU-MAL), American Spinal Injury Association Upper Extremity Motor Score and Modified Ashworth Scale (MAS) at baseline, after treatment, and at two-month follow-up. None of the participants missed a treatment session or dropped-out due to adverse events related to the treatment protocol. Participants tended to perform better in JTHFT and AOU-MAL after treatment. Active group at post-treatment and two-month follow-up demonstrated better arm and hand performance compared to sham group. These preliminary findings support that modulating excitatory input of the corticospinal tracts on spinal circuits may be a promising strategy in improving arm and hand functions in persons with incomplete tetraplegia. Further study is needed to explore the underlying mechanisms of recovery.

Using surface electromyography to detect changes in innervation zones pattern after human cervical spinal cord injury.

Human spinal cord injuries (SCI) disrupt the pathways between brain and spinal cord, resulting in substantial impairment and loss of function. Currently, we do not have the ability to precisely quantify the "functional" level of motor injury. The aim of this study is to determine if high-density surface electromyography imaging (SEI) can be used to characterize the location and extent of the spinal lesion. SEI is a safe and non-invasive technique, which uses several electrodes to provide a map of muscle activity. We applied the SEI technique to characterize muscle activity in individuals with chronic incomplete cervical SCI. Surface electromyogram signals (sEMG) from Biceps Brachii (BB) were recorded at submaximal levels (20%, 40%, and 60%) of maximum voluntary contractions (MVC) during isometric elbow flexion, shoulder flexion, and elbow abduction in two individuals with SCI. Through time-domain analysis of the collected data, we detected signs of de-innervation and re-innervations by analyzing the innervation zones (IZ) on the left and right BB muscles. We found that the distribution of IZs was different between the two sides. In addition, analysis of sEMG data collected at rest (no voluntary contraction) showed evidence of superficial active motor units that were active during rest (in the absence of spasms). These findings highlight the potential of SEI technique as a potential clinical tool to quantitatively describe the extent of the damage to motor spinal circuitry, and provide added precision to the clinical examinations and radiological findings.

Time-Dependent Discrepancies between Assessments of Sensory Function after Incomplete Cervical Spinal Cord Injury.

We recently demonstrated that the electrical perceptual threshold (EPT) examination reveals spared sensory function at lower spinal segments compared with the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we investigated whether discrepancies in sensory function detected by both sensory examinations change over time after SCI. Forty-five participants with acute (<1 year), chronic (≥1-10 years), and extended-chronic (>10 years) incomplete cervical SCI and 30 control subjects were tested on dermatomes C2-T4 bilaterally. EPT values were higher in subjects with acute (2.5 ± 0.8 mA), chronic (2.2 ± 0.7 mA), or extended-chronic (2.8 ± 1.1 mA) SCI compared with controls (1.0 ± 0.1 mA). The EPT examination detected sensory impairments in spinal segments above (2.3 ± 0.9) and below (4.2 ± 2.6) the level detected by the ISNCSCI sensory examination in participants with acute and chronic SCI, respectively. Notably, both examinations detected similar levels of spared sensory function in the extended-chronic phase of SCI (0.8 ± 0.5). A negative correlation was found between differences in EPT and ISNCSCI sensory levels and time post-injury. These observations indicate that discrepancies between EPT and ISNCSCI sensory scores are time-dependent, with the EPT revealing impaired sensory function above, below, or at the same spinal segment as the ISNCSCI examination. We propose that the EPT is a sensitive tool to assess changes in sensory function over time after incomplete cervical SCI.

Phrenic motor outputs in response to bronchopulmonary C-fibre activation following chronic cervical spinal cord injury.

Activation of bronchopulmonary C-fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity. Following chronic cervical spinal cord injury, bronchopulmonary C-fibre activation-induced inhibition of phrenic activity was exaggerated. Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C-fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord-injured animals. These data suggest that activation of bronchopulmonary C-fibres may retard phrenic output recovery following cervical spinal cord injury. The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin-induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8-9weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra-jugular capsaicin (1.5μgkg-1 ) injection was performed to activate the bronchopulmonary C-fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin-induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic activity was robustly reduced after capsaicin treatment compared to uninjured animals. Single phrenic fibre recording experiments demonstrated that C2Hx animals had a higher proportion of late-inspiratory phrenic motoneurons that were relatively sensitive to capsaicin treatment compared to early-inspiratory phrenic motoneurons. Moreover, late-inspiratory phrenic motoneurons in C2Hx animals had a weaker discharge frequency and slower recovery time than uninjured animals. These results suggest bilateral phrenic nerves differentially respond to bronchopulmonary C-fibre activation following unilateral cervical hemisection, and the severe inhibition of phrenic bursting is due to a shift in the discharge pattern of phrenic motoneurons.

RTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

Repetitive transcranial magnetic stimulation study. The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. Merano (Italy) and Salzburg (Austria). In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

Evaluation of a Task-Based Intervention After Tendon Transfer to Restore Lateral Pinch

ObjectiveTo quantify changes in pinch force and brachioradialis (BR) activation after a task-based training program designed to improve pinch force after BR to flexor pollicis longus (FPL) transfer. DesignOne-group repeated-measures design compared pinch force and BR activation pre- and posttraining. Significant differences were tested with Wilcoxon signed-rank tests for pairwise comparisons at the P≤.05 level. SettingTesting occurred in a Veterans Affairs Medical Center research laboratory and training was in a home setting. ParticipantsParticipants with cervical spinal cord injury (SCI) and previous BR to FPL transfer were enrolled in the study (N=8). Six patients completed the training program and posttraining measures. InterventionsThe 10-week training was a home program that included novel activities to increase BR activation and practice producing pinch force in a variety of upper limb postures. Participants were provided with the task-based training equipment and instructed to practice 3 times per week. Main Outcome MeasuresFine-wire electromyography of the transferred BR was recorded in maximum effort pinch force (N). Secondary measures included the strength and activation of the antagonist elbow extensor. ResultsPinch force increased 3.7N (.38kg) and BR muscle activation increased 10% (P≤.05) after the training. There was no increase in elbow extension strength, but participants with previous posterior deltoid to triceps transfer achieved greater activation of the antagonist elbow extensor. ConclusionsThe findings from this pilot study suggest that outcomes of tendon transfer and conventional therapy can be improved for patients with chronic cervical SCI.