Complete Spinal Cord Lesion Research Articles

Clinical characteristics of ultra-longitudinally extensive transverse myelitis in a Peruvian cohort

IntroductionUltra-longitudinally extensive transverse myelitis (uLETM) is defined as an inflammatory lesion involving 10 or more spinal cord segments. The aim of our study is to describe the clinical and radiological features of this atypical form of myelitis. MethodsWe conducted a descriptive cross-sectional study of clinical data from 57 patients older than 18 years diagnosed with longitudinally extensive transverse myelitis. Nineteen cases were classified as uLETM. ResultsTwelve of the 19 patients were women, age ranged between 18 and 76 years, and the main aetiology was neuromyelitis optica spectrum disorder (8 patients), followed by anti-MOG antibody myelitis (3 patients). The main region involved was at cervical-thoracic spinal cord. Two patients presented complete spinal cord lesion. ConclusionsOur results are consistent with previous reports suggesting that neuromyelitis optica spectrum disorder remains the main aetiology in uLETM; however, anti-MOG antibodies should be considered within the differential diagnosis.

Sensations Reported During Urodynamic Bladder Filling in Spinal Cord Injury Patients Give Additional Important Information.

PurposeThis study investigated the sensations reported during filling cystometry in patients with spinal cord lesions (SCLs) of different levels and completeness.MethodsIn this retrospective cohort study, information was gathered on patients’ age and sex, cause of SCL, American Spinal Injury Association Impairment Scale (AIS), and lower urinary tract-related sensations in daily life. Filling cystometry (videourodynamics) was performed following the International Continence Society Good Urodynamic Practice Guidelines. In addition to bladder filling sensations (first sensation of bladder filling, first desire to void, strong desire to void), other sensations, such as detrusor overactivity related sensation and pain, were noted.ResultsIn total, 170 patients were included (age, 45±17 years; 114 males and 56 females, 92 with complete and 78 with incomplete SCL). The test was done 6±4 years post-SCL. Sensation was reported by 57% of all patients. Half of the patients with complete SCL (46 of 92) had sensation, while 36% of those with incomplete SCL (28 of 78) reported no sensation. Bladder awareness was not predictable by the AIS. The filling sensations reported were equivalent to those given in the terminology of ICS. Pain was seldom present (6%, 10 of 170), and detrusor overactivity contraction was felt by 45 of 78 (58%). Very few patients used sensory information for bladder management at home.ConclusionsAfter SCL, most patients retained the ability to be aware of the lower urinary tract, and were assessable and gradable during urodynamic testing. The filling sensations were not different from those described in healthy individuals, but the number and sequence of the sensations were altered in a minority of patients. Pain and a sensation of unstable contractions gave additional important information. As different sensations relate to different spinal afferent pathways, the sensory evaluation during cystometry provided additional important information on the spinal cord’s condition.

Intraspinal Administration of Netrin-1 Promotes Locomotor Recovery after Complete Spinal Cord Transection.

Complete spinal cord lesions interrupt the connection of all axonal projections with their neuronal targets below and above the lesion site. In particular, the interruption of connections with the neurons at lumbar segments after thoracic injuries impairs voluntary body control below the injury. The failure of spontaneous regrowth of transected axons across the lesion prevents the reconnection and reinnervation of the neuronal targets. At present, the only treatment in humans that has proven to promote some degree of locomotor recovery is physical therapy. The success of these strategies, however, depends greatly on the type of lesion and the level of preservation of neural tissue in the spinal cord after injury. That is the reason it is key to design strategies to promote axonal regrowth and neuronal reconnection. Here, we test the use of a developmental axon guidance molecule as a biological agent to promote axonal regrowth, axonal reconnection, and recovery of locomotor activity after spinal cord injury (SCI). This molecule, netrin-1, guides the growth of the corticospinal tract (CST) during the development of the central nervous system. To assess the potential of this molecule, we used a model of complete spinal cord transection in rats, at thoracic level 10-11. We show that in situ delivery of netrin-1 at the epicenter of the lesion: (1) promotes regrowth of CST through the lesion and prevents CST dieback, (2) promotes synaptic reconnection of regenerated motor and sensory axons, and (3) preserves the polymerization of the neurofilaments in the sciatic nerve axons. These anatomical findings correlate with a significant recovery of locomotor function. Our work identifies netrin-1 as a biological agent with the capacity to promote the functional repair and recovery of locomotor function after SCI. These findings support the use of netrin-1 as a therapeutic intervention to be tested in humans.

Time course of functional changes in locomotor and sensory systems after spinal cord lesions in lamprey.

Changes in motor and sensory properties occur either side of spinal cord lesion sites from lower vertebrates to humans. We have previously examined these changes in the lamprey, a model system for studying recovery after spinal cord injury. These analyses were performed 8-12 wk after complete spinal cord lesions, a time when most animals have recovered good locomotor function. However, anatomical analyses have been performed at earlier and later times than this. Because there have been no functional studies at these times, in this study we have examined changes between 2 and 24+ wk after lesioning. Functional changes developed at different times in different regions of the spinal cord. Spinal cord excitability was significantly reduced above and below the lesion site less than 6 wk after lesioning but showed variable region-specific changes at later times. Excitatory synaptic inputs to motor neurons were increased above the lesion site during the recovery phase (2-8 wk after lesioning) but only increased below the lesion site once recovery had occurred (8 wk and later). These synaptic effects were associated with lesion-induced changes in connectivity between premotor excitatory interneurons. Sensory inputs were potentiated at 8 wk and later after lesioning but were markedly reduced at earlier times. There are thus time- and region-specific changes in motor and sensory properties above and below the lesion site. Although animals typically recover good locomotor function by 8 wk, there were further changes at 24+ wk. With the assumption that these changes can help to compensate for the reduced descending input to the spinal cord, effects at later times may reflect ongoing modifications as regeneration continues. NEW & NOTEWORTHY The lamprey is a model system for studying functional recovery and regeneration after spinal cord injury. We show that changes in spinal cord excitability and sensory inputs develop at different times above and below the lesion site during recovery. These changes may occur in response to the lesion-induced removal of descending inputs and may subsequently help to compensate for the reduction of the descending drive to allow locomotor recovery. Changes also continue once animals have recovered locomotor function, potentially reflecting adaptations to further regeneration at later recovery times.

Nerve sprouting and neurogenic inflammation characterize the neurogenic detrusor overactive bladder of patients no longer responsive to drug therapies.

Urothelium and Lamina Propria (LP) are considered an integrate sensory system which is able to control the detrusor activity. Complete supra‐sacral spinal cord lesions cause Neurogenic Detrusor Overactivity (NDO) whose main symptoms are urgency and incontinence. NDO therapy at first consists in anti‐muscarinic drugs; secondly, in intra‐vesical injection of botulinum toxin. However, with time, all the patients become insensitive to the drugs and decide for cystoplastic surgery. With the aim to get deeper in both NDO and drug's efficacy lack pathogenesis, we investigated the innervation, muscular and connective changes in NDO bladders after surgery by using morphological and quantitative methodologies. Bladder innervation showed a significant global loss associated with an increase in the nerve endings located in the upper LP where a neurogenic inflammation was also present. Smooth muscle cells (SMC) anomalies and fibrosis were found in the detrusor. The increased innervation in the ULP is suggestive for a sprouting and could condition NDO evolution and drug efficacy length. Denervation might cause the SMC anomalies responsible for the detrusor altered contractile activity and intra‐cellular traffic and favour the appearance of fibrosis. Inflammation might accelerate these damages. From the clinical point of view, an early anti‐inflammatory treatment could positively influence the disease fate.

Dorsal Longitudinal T-Myelotomy (Bischof II Technique): A Useful, Antiquated Procedure for the Treatment of Intractable Spastic Paraplegia

Dorsal longitudinal T-myelotomy is a long-established operation to treat severe spastic paraplegia. The present study aimed to report this surgical technique and investigate the efficacy of T-myelotomy for spasticity relief. All cases undergoing T-myelotomy for treatment of intractable spastic paraplegia during 2009-2017 were included. The severity of spasticity was evaluated with the Modified Ashworth Scale, Penn Spasm Frequency Scale, Adductor Tone Rating Scale, degree of passive range of motion, and occurrence of abdominal muscle spasms. Other clinical assessments included deep tendon reflex assessed by the National Institute of Neurological Disorders and Stroke scale, Babinski sign, healing of decubitus ulcers, and ambulatory status. Fourteen patients with a mean age of 39.3±13.4 years were included. The 7 patients with abdominal muscle spasms before surgery had no spasms after surgery. The Babinski sign was absent in all cases after surgery. Unhealed pressure ulcers in all 9 cases were healed after surgery. All 4 patients with a preoperative bed-bound condition were able to ambulate with a wheelchair. Astatistically significant improvement in mean Modified Ashworth Scale score, degree of passive range of motion, and National Institute of Neurological Disorders and Stroke scale score was found in the subgroup and overall analyses. There was also a statistically significant improvement in the Penn Spasm Frequency Scale and Adductor Tone Rating Scale scores. Dorsal longitudinal T-myelotomy remains an effective option for the treatment of intractable spastic paraplegia. It is suitable for, and may be an alternative to, intrathecal baclofen therapy for patients with complete spinal cord lesion or patients without hope of regaining motor function.

Facilitation of Locomotor Spinal Networks Activity by Buspirone after a Complete Spinal Cord Lesion in Mice.

Despite efforts to potentiate spinal cord lesioned (SCL) patients' functional recovery with multi-targeted therapy combining pharmacological treatment and training, consistent improvements in locomotor control by descending transmission or spinal network facilitation are still eluding clinicians and researchers. Lately, United States Food and Drug Administration-approved buspirone has shown promise and promoted locomotor-like movement occurrence in SCL patients, but evidence on how and where it exerts its effects is lacking. The objective of the present study was, first, to verify buspirone effect on locomotor spinal network and to evaluate if it promoted functional recovery when combined with training. Also, we evaluated buspirone impact on locomotion in mice that had recovered from a previous hemisection before sustaining the spinal transection. This dual lesion paradigm has allowed confirmation of spinal network involvement in recovery after an incomplete SCL. Buspirone acutely increased the number of steps taken, the coupling strength between hindlimbs, angular excursion of the hip joint during locomotion, and improved paw positioning at contact and paw drag (ps < 0.05). Moreover, it induced long-lasting improvements of paw positioning at contact and paw drag when combined with training in mice after a dual lesion paradigm. Altogether, the results indicate that buspirone exerts considerable acute facilitation of spinally mediated locomotion, and could be used in combination with training to promote functional recovery after SCL.

The Lesioned Spinal Cord Is a "New" Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey.

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury.

Acquisition of Involuntary Spinal Locomotion (Spinal Walking) in Dogs with Irreversible Thoracolumbar Spinal Cord Lesion: 81 Dogs.

BackgroundSpinal walking (SW) is described as the acquisition of an involuntary motor function in paraplegic dogs and cats without pain perception affected by a thoracolumbar lesion. Whereas spinal locomotion is well described in cats that underwent training trials after experimental spinal cord resection, less consistent information is available for dogs.HypothesisParaplegic dogs affected by a thoracolumbar complete spinal cord lesion undergoing intensive physical rehabilitation could acquire an autonomous SW gait under field conditions.AnimalsEighty‐one acute paraplegic thoracolumbar dogs without pelvic limb pain perception.MethodsRetrospective study of medical records of dogs selected for intensive rehabilitation treatment in paraplegic dogs with absence of pain perception on admission and during the whole treatment. Binary regression and multivariate logistic regression were used to analyze potential associations with the development of SW.ResultsAutonomous SW was achieved in 48 dogs (59%). Median time to achieve SW was of 75.5 days (range: 16–350 days). On univariate analysis, SW gait was associated with younger age (P = .002) and early start of physiotherapy (P = .024). Multivariate logistic regression showed that younger age (≤60 months) and lightweight (≤7.8 kg) were positively associated with development of SW (P = .012 and P < .001, respectively). BCS, full‐time hospitalization, and type and site of the lesion were not significantly associated with development of SW.ConclusionsDogs with irreversible thoracolumbar lesion undergoing intensive physiotherapic treatment can acquire SW. Younger age and lightweight are positively associated with the development of SW gait.

Spinal cord lesions shrink peripersonal space around the feet, passive mobilization of paraplegic limbs restores it.

Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed.

A cost-utility analysis of sacral anterior root stimulation (SARS) compared with medical treatment in patients with complete spinal cord injury with a neurogenic bladder

Background ContextSacral anterior root stimulation (SARS) and posterior sacral rhizotomy restores the ability to urinate on demand with low residual volumes, which is a key for preventing urinary complications that account for 10% of the causes of death in patients with spinal cord injury with a neurogenic bladder. Nevertheless, comparative cost-effectiveness results on a long time horizon are lacking to adequately inform decisions of reimbursement. PurposeThis study aimed to estimate the long-term cost-utility of SARS using the Finetech-Brindley device compared with medical treatment (anticholinergics+catheterization). Study Design/SettingsThe following study design is used for the paper: Markov model elaborated with a 10-year time horizon; with four irreversible states: (1) initial treatment, (2) year 1 of surgery for urinary complication, (3) year >1 of surgery for urinary complication, and (4) death; and reversible states: urinary calculi; Finetech-Brindley device failures. Patient SampleThe sample consisted of theoretical cohorts of patients with a complete spinal cord lesion since ≥1 year, and a neurogenic bladder. Outcome MeasuresEffectiveness was expressed as quality adjusted life years (QALYs). Costs were valued in EUR 2013 in the perspective of the French health system. MethodsA systematic review and meta-analyses were performed to estimate transition probabilities and QALYs. Costs were estimated from the literature, and through simulations using the 2013 French prospective payment system classification. Probabilistic analyses were conducted to handle parameter uncertainty. ResultsIn the base case analysis (2.5% discount rate), the cost-utility ratio was 12,710 EUR per QALY gained. At a threshold of 30,000 EUR per QALY the probability of SARS being cost-effective compared with medical treatment was 60%. If the French Healthcare System reimbursed SARS for 80 patients per year during 10 years (anticipated target population), the expected incremental net health benefit would be 174 QALYs, and the expected value of perfect information (EVPI) would be 4.735 million EUR. The highest partial EVPI is reached for utility values and costs (1.3–1.6 million EUR). ConclusionsOur model shows that SARS using Finetech-Brindley device offers the most important benefit and should be considered cost-effective at a cost-effectiveness threshold of 30,000 EUR per QALY. Despite a high uncertainty, EVPI and partial EVPI may indicate that further research would not be profitable to inform decision-making.

Predictive factors of stress incontinence after posterior sacral rhizotomy.

The Brindley procedure, used since the 1980s, consists of implantation of a stimulator for sacral anterior root stimulation combined with a posterior sacral rhizotomy to enable micturition. Patients suitable for the procedure are patients with detrusor overactivity and a complete spinal cord lesion with intact sacral reflexes. S2 to S4 posterior sacral rhizotomy abolishes sacral hyperreflexia and may lead to decreased urethral closure pressure and loss of reflex adaptation of continence, leading to stress incontinence. In this retrospective study of 96 patients from Nantes or Le Mans, implanted with a Finetech-Brindley stimulator, we analyzed the incidence of stress incontinence one year after surgery and looked for predictive factors of stress incontinence one year after posterior sacral rhizotomy: age, gender, level of injury between T10 and L2 , previous urethral surgery, incompetent bladder neck, Maximum Urethral Closure Pressure before surgery less than 30 cmH2 O, compliance before surgery less than 30 ml/cmH2 0. Patients with persistent involuntary detrusor contractions with or without incontinence after surgery were excluded. One year after surgery, 10.4% of the patients experienced stress incontinence. Urethral closure pressure was significantly decreased by 18% after posterior sacral rhizotomy (P = 0.002). This study highlights the only significant predictive factor of stress incontinence after rhizotomy: incompetent bladder neck (P = 0.002). As screening of patients undergoing the Brindley procedure is essential to achieve optimal postoperative results, on the basis of this study, we propose preoperative assessment to select the population of patients most likely to benefit from the Brindley procedure.

Evaluation of bone mineral loss in patients with chronic traumatic spinal cord injury in Iran

ObjectivesWe described the associations between demographic and injury-related factors on bone mineral density (BMD) of the spine and the hip among adult patients with chronic spinal cord injury (SCI).DesignBMD in spinal and femoral bone sites were assessed. Multivariate analysis was performed to evaluate the relationship between anthropometric and injury-related factors with BMD. Serum level and amount of dietary intake of calcium, phosphor, and 25-hydroxy vitamin D were measured.SettingA referral tertiary rehabilitation center in Iran.ParticipantsPatients with SCI who had no previous history of endocrine disorders and were not on specific medications entered the investigation. Those with non-traumatic SCI, pregnant, or with substance dependency were excluded as well.InterventionsNo interventions were applied.Main study outcome measuresDual X-ray absorptiometry was performed to estimate BMD. Body mass index was positively associated with higher femoral (P < 0.01, r = 0.56) and hip (P < 0.0001, r = 0.82) BMD only in female participants. The high prevalence of vitamin D deficiency (60%) was noticeable.ResultsOlder male patients revealed lower BMD only in spinal vertebrae (P < 0.02, r = −0.21). A significant higher BMD loss in lumbar vertebras in male patients with complete spinal cord lesion (P < 0.009) was detected. Spinal reduction of BMD was more severe when the level of injury was above T6 (P < 0.02).ConclusionAlong with the clarification of age, gender, post injury duration, and the other factors' effect on the BMD in the SCI patients, here we have also shown the noticeable prevalence of the 25-hydoxy vitamin D deficiency in these patients which needs attention.

Risk Factors for Heterotopic Ossification in Patients With Spinal Cord Injury

Case-control study. We designed a case-control study to analyze the risk factors associated with the development of heterotopic ossification (HO) in patients with traumatic spinal cord injury. Patients with spinal cord injury have a high risk of developing HO, although the exact etiopathogenesis is still unknown. Several factors are known to be potential risk factors. However, we are not aware of any large clinical studies evaluating the risk factors for HO. Patients who were treated for a traumatic spinal cord injury in our hospital, and who subsequently developed HO, were identified by querying the electronic database at our hospital from 2002 to 2010. One hundred thirty-two patients and 132 controls were included. Our primary outcome measures were the risk of developing HO according to whether the patient had experienced a complete spinal cord lesion according to American Spinal Injury Association Impairment Scale; tetraplegia or paraplegia; cervical, thoracic, or lumbar injury; severe chest trauma; and the time interval between injury and surgery. Secondary risk factors explored were patient age; sex; presence and number of comorbidities; length of hospital and intensive care unit stay; associated traumatic injuries; presence of spasticity, pressure ulcers, deep venous thrombosis, and urinary tract infection; and pulmonary complications, such as pneumonia and necessity of tracheostomy. Patients with associated spasticity and thoracic trauma, complete lesion, pneumonia, presence of tracheostomy, and urinary tract infection had a higher risk of developing HO. Adequate management of potential risk factors could help reduce the overall incidence of HO and outcome in patients with traumatic spinal cord injury.

Afferent Pathways Arising from the Lower Urinary Tract after Complete Spinal Cord Injury or Cauda Equina Lesion: Clinical Observations with Neurophysiological Implications

Background: Afferents from the urinary tract transmit bladder sensations to the central nervous system. Spinal cord injury (SCI) may affect both efferent motor and afferent sensory pathways. Presence/absence of bladder sensations in patients with complete spinal cord, conus or cauda equina lesions was compared with neurologically unimpaired patients. Methods: During urodynamics, bladder sensations were studied and compared in 59 patients: 21 patients with complete SCI below T6 and above Th12, 7 patients with a complete lesion of the conus medullaris, 11 patients with a complete lesion of the cauda equina, and 20 patients without neurological deficit. Results: Two of 7 patients with complete conus lesion had a preserved filling sensation. Ten of 11 patients with complete lesion of the cauda equina reported a bladder filling sensation. Sensations are perceived at a similar pressure threshold but at a higher volume threshold. Conclusions: In patients with a complete cauda or a lower conus lesion, a sensory input from the bladder is preserved. These findings imply that the preserved bladder filling sensation in complete cauda or lower conus lesions is possibly transferred through the intact hypogastric plexus to the thoracolumbar segments of the spinal cord.

Spinal Cord Injury Induces Serotonin Supersensitivity without Increasing Intrinsic Excitability of Mouse V2a Interneurons

Denervation-induced plastic changes impair locomotor recovery after spinal cord injury (SCI). Spinal motoneurons become hyperexcitable after SCI, but the plastic responses of locomotor network interneurons (INs) after SCI have not been studied. Using an adult mouse SCI model, we analyzed the effects of complete spinal cord lesions on the intrinsic electrophysiological properties, excitability, and neuromodulatory responses to serotonin (5-HT) in mouse lumbar V2a spinal INs, which help regulate left-right alternation during locomotion. Four weeks after SCI, V2a INs showed almost no changes in baseline excitability or action potential properties; the only parameter that changed was a reduced input resistance. However, V2a INs became 100- to 1000-fold more sensitive to 5-HT. Immunocytochemical analysis showed that SCI caused a coordinated loss of serotonergic fibers and the 5-HT transporter (SERT). Blocking the SERT with citalopram in intact mice did not increase 5-HT sensitivity to the level seen after SCI. SCI also evoked an increase in 5-HT(2C) receptor cluster number and intensity, suggesting that several plastic changes cooperate in increasing 5-HT sensitivity. Our results suggest that different components of the spinal neuronal network responsible for coordinating locomotion are differentially affected by SCI, and highlight the importance of understanding these changes when considering therapies targeted at functional recovery.

Les lésions médullaires traumatiques : épidémiologie et perspectives

ObjectiveSpecify the epidemiological data on the acute spinal cord injuries and define a group of patients that could benefit from cellular transplantation therapy designed with the aim of repair and regeneration of damaged spinal cord tissues. Material and methodsFive years monocentric (Gui-de-Chauliac Hospital, Montpellier, France) retrospective analysis of patients suffering from spinal cord injury (SCI). Spinal cord injured-patients, defined as sensory-motor complete, underwent a clinical evaluation following American Spinal Injury Association (ASIA) and functional type 2 Spinal Cord Independence Measure (SCIM2) scorings as well as radiological evaluation through spinal cord magnetic resonance imaging (MRI). ResultsOne hundred and fifty-seven medical records were reviewed and we selected and re-examined 20 patients with complete thoracic spinal cord lesion. Clinical and radiological evaluations of these patients demonstrated, in 75 % of the cases, an absence of clinical progression after a mean of 49months. Radiological abnormalities were constantly present in the initial (at the admission to hospital) and control (re-evaluation) MRI and no reliable predictive criteria of prognosis had been found. Discussion/ConclusionWe compare our results to the literature and discuss advantages and limits of cellular transplantation strategies for these patients.

Forelimb EMG-based trigger to control an electronic spinal bridge to enable hindlimb stepping after a complete spinal cord lesion in rats

BackgroundA complete spinal cord transection results in loss of all supraspinal motor control below the level of the injury. The neural circuitry in the lumbosacral spinal cord, however, can generate locomotor patterns in the hindlimbs of rats and cats with the aid of motor training, epidural stimulation and/or administration of monoaminergic agonists. We hypothesized that there are patterns of EMG signals from the forelimbs during quadrupedal locomotion that uniquely represent a signal for the “intent” to step with the hindlimbs. These observations led us to determine whether this type of “indirect” volitional control of stepping can be achieved after a complete spinal cord injury. The objective of this study was to develop an electronic bridge across the lesion of the spinal cord to facilitate hindlimb stepping after a complete mid-thoracic spinal cord injury in adult rats.MethodsWe developed an electronic spinal bridge that can detect specific patterns of EMG activity from the forelimb muscles to initiate electrical-enabling motor control (eEmc) of the lumbosacral spinal cord to enable quadrupedal stepping after a complete spinal cord transection in rats. A moving window detection algorithm was implemented in a small microprocessor to detect biceps brachii EMG activity bilaterally that then was used to initiate and terminate epidural stimulation in the lumbosacral spinal cord. We found dominant frequencies of 180–220 Hz in the EMG of the forelimb muscles during active periods, whereas these frequencies were between 0–10 Hz when the muscles were inactive.Results and conclusionsOnce the algorithm was validated to represent kinematically appropriate quadrupedal stepping, we observed that the algorithm could reliably detect, initiate, and facilitate stepping under different pharmacological conditions and at various treadmill speeds.

Time course of arterial remodelling in diameter and wall thickness above and below the lesion after a spinal cord injury

Physical inactivity in response to a spinal cord injury (SCI) represents a potent stimulus for conduit artery remodelling. Changes in conduit artery characteristics may be induced by the local effects of denervation (and consequent extreme inactivity below the level of the lesion), and also by systemic adaptations due to whole body inactivity. Therefore, we assessed the time course of carotid (i.e. above lesion) and common femoral artery (i.e. below lesion) lumen diameter and wall thickness across the first 24 weeks after an SCI. Eight male subjects (mean age 35 ± 14 years) with a traumatic motor complete spinal cord lesion between T5 and L1 (i.e. paraplegia) were included. Four subjects were measured across the first 6 weeks after SCI, whilst another four subjects were measured from 8 until 24 weeks after SCI. Ultrasound was used to examine the diameter and wall thickness from the carotid and common femoral arteries. Carotid artery diameter did not change across 24 weeks, whilst femoral artery diameter stabilised after the rapid initial decrease during the first 3 weeks after the SCI. Carotid and femoral artery wall thickness showed no change during the first few weeks, but increased both between 6 and 24 weeks (P < 0.05). In conclusion, SCI leads to a rapid and localised decrease in conduit artery diameter which is isolated to the denervated and paralyzed region, whilst wall thickness gradually increases both above and below the lesion. This distinct time course of change in conduit arterial diameter and wall thickness suggests that distinct mechanisms may contribute to these adaptations.

Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity

Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overactivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity. To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with Parkinson's disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls. Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A significantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition. These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity.