MR Spectroscopy of the Cervical Spinal Cord in Chronic Spinal Cord Injury.

Purpose To investigate metabolic changes in chronic spinal cord injury (SCI) by applying MR spectroscopy in the cervical spinal cord. Materials and Methods Single-voxel short-echo spectroscopic data in study participants with chronic SCI and healthy control subjects were prospectively acquired in the cervical spinal cord at C2 above the level of injury between March 2016 and January 2017 and were compared between groups. Concentrations of total N-acetylaspartate (tNAA), myo-inositol (mI), total choline-containing compounds (tCho), creatine, and glutamine and glutamate complex were estimated from the acquired spectra. Participants were assessed with a comprehensive clinical evaluation investigating sensory and motor deficits. Correlation analysis was applied to investigate relationships between observed metabolic differences, lesion severity, and clinical outcome. Results There were 18 male study participants with chronic SCI (median age, 51 years; range, 30-68 years) and 11 male healthy control subjects (median age, 45 years; range, 30-67 years). At cervical level C2, tNAA/mI and tCho/mI ratios were lower in participants with SCI (tNAA/mI: -26%, P = .003; tCho/mI: -18%; P = .04) than in healthy control subjects. The magnitude of difference was greater with the severity of cord atrophy (tNAA/mI: R2 = 0.44, P = .003; tCho/mI: R2 = 0.166, P = .09). Smaller tissue bridges at the lesion site correlated with lower ratios of tNAA/mI (R2 = 0.69, P = .006) and tCho/mI (R2 = 0.51, P = .03) at the C2 level. Lower tNAA/mI and tCho/mI ratios were associated with worse sensory and motor outcomes (P < .05). Conclusion Supralesional metabolic alterations are observed in chronic spinal cord injury, likely reflecting neurodegeneration, demyelination, and astrocytic gliosis in the injured cervical cord. Lesion severity and greater clinical impairment are both linked to the biochemical changes in the atrophied cervical cord after spinal cord injury. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Lin in this issue.

Vitamin D3 improves respiratory adjustment to fatigue and H-reflex responses in paraplegic adult rats.

We previously demonstrated that vitamin D2 (ergocalciferol) triggers axon regeneration in a rat model of peripheral nerve transection. In order to confirm the regenerative potential of this neuroactive steroid, we performed a study in which vitamin D3 (cholecalciferol) was delivered at various doses to paralytic rats. After spinal cord compression at the T10 level, rats were given orally either vehicle or vitamin D3 at the dose of 50 IU/kg/day or 200 IU/kg/day. Three months later, M and H-waves were recorded from rat Tibialis anterior muscle in order to quantify the maximal H-reflex (H(max)) amplitude. We also monitored the ventilatory frequency during an electrically induced muscle fatigue known to elicit the muscle metaboreflex and an increase in respiratory rate. Spinal cords were then collected, fixed and immunostained with an anti-neurofilament antibody. We show here that vitamin D-treated animals display an increased number of axons within the lesion site. In addition, rats supplemented with vitamin D3 at the dose of 200 IU/kg/day exhibit (i) an improved breathing when hindlimb was electrically stimulated; (ii) an H-reflex depression similar to control animals and (iii) an increased number of axons within the lesion and in the distal area. Our data confirm that vitamin D is a potent molecule that can be used for improving neuromuscular adaptive mechanisms and H-reflex responses.

One year of home-based daily FES in complete lower motor neuron paraplegia: recovery of tetanic contractility drives the structural improvements of denervated muscle.

OBJECTIVE: Spinal cord injury (SCI) causes muscle atrophy, which is particularly severe, due to inability to perform tetanic contractions, when lower motor neurons (LMN) are involved. We performed a longitudinal study in 25 Europeans suffering from complete conus cauda syndrome from 0.7 to 8.7 years comparing functional and structural thigh muscle properties before and after 2 years of home-based daily training by functional electrical stimulation (FES). The mid-term results after 1 year and preliminary muscle biopsy observations at project end-point from a subset of subjects are here reported. METHODS: Muscles were electrically stimulated at home by means of large surface electrodes and a custom-designed stimulator. The poor excitability of the LMN denervated muscles was first improved by twitch-contraction training. Then, tetanic contractions against progressively increased loading were elicited. Finally, standing-up exercises were daily performed. The bulk of thigh muscle was estimated by transverse computer tomography (CT) scan and force measurements. Needle biopsies of vastus lateralis were harvested before and after 2 years of FES. RESULTS: The 1 year home-based daily FES training induced: (1) very similar increases in muscle excitability and contractility in right and left legs; (2) feasibility to elicit tetanic contractions by means of train-stimulation with about ten times improvement of muscle force; (3) increase in the 26% of muscle bulk, as shown by CT scan analyses, improving appearance of limbs and muscle cushioning; (4) myofiber size increase (+94%) in a small series of muscle biopsies obtained after 2 years of FES. None of the subjects that performed 1 year home-based daily FES training (20 persons) had worsened their functional class, while 20% (4/20) improved to functional class 4, that is, the ability to stand. DISCUSSION: The European Union (EU) Project Rise shows that 'home-based daily FES training' is a safe and effective therapy that may maintain life-long physical exercise by active muscle contraction (FES is the only option for denervated muscle) as a procedure to recover the early-lost tetanic contractility of denervated muscle, and to counteract muscle atrophy in order to prevent clinical complications.

Walking performance, medical outcomes and patient training in FES of innervated muscles for ambulation by thoracic-level complete paraplegics.

OBJECTIVE: To discuss functional electric stimulation (FES) gait training of upper motoneuron spinal cord injured complete paraplegics considering ambulation performance, physiologic and metabolic responses as well as psychologic outcome, while providing myologic insight into ambulation via FES when training starts many years post-injury. METHODS: Transcutaneous FES using the Parastep stimulation system, gait training methods with and without major emphasis on muscle reinforcement, cardiovascular and respiratory conditioning. Examination of myofiber tissues and correlation of normal muscles histology versus innervated muscles of upper motor neuron and of denervated muscles of lower motor neuron paraplegics. RESULTS: Published works in literature reviewed in this paper report average walking distance of 440 m/walk when major muscle reinforcement and preconditioning cardiovascular and respiratory systems precedes gait training, versus average 115 m/walk when undergoing direct gait training. Medical, metabolic and psychologic outcomes, as reported in several works, point to benefits of FES walking, including 60% increase in blood flow to lower extremities. Myofiber tissues of patients with upper motor neuron paralysis compare well with those of normal tissue even many years post-injury, while adipose tissue substitute muscle fibers in patients with lower motor neuron lesions. DISCUSSION: Transcutaneous FES allows considerably longer walking distances and speed at the end of training when training involves an extensive pre-conditioning program than with direct gait training. Medical and psychologic benefits are observed, especially concerning blood flow to the lower extremities. Myofiber examinations provide myologic understanding of effectiveness of FES many years post-injury.

Huge epidural hematoma after surgery for spinal cord stimulation.

OBJECTIVE AND IMPORTANCE: Spinal epidural haematoma (SEH) following implantation of an epidural spinal cord electrode is a very rare complication but one that must not be overlooked. This case is unusual because of the almost "holocord" extension of the haematoma and the excellent recovery obtained by prompt surgical treatment. CLINICAL PRESENTATION: A 69 years old man with normal serum coagulation parameters was submitted to spinal cord stimulation (SCS) for chronic pain syndrome. After a minimal L1 laminotomy the patient developed paraplegia due to a large haematoma at D4-L2. INTERVENTION: Surgical removal of the entire clot by a D4-L2 laminectomy was performed immediately. CONCLUSION: Large epidural haematoma can result from SCS and this complication may be cured by appropriate and prompt surgery.

Transplantation of embryonal spinal cord nerve cells cultured on biodegradable microcarriers followed by low power laser irradiation for the treatment of traumatic paraplegia in rats.

This pilot study examined the effects of composite implants of cultured embryonal nerve cells and laser irradiation on the regeneration and repair of the completely transected spinal cord. Embryonal spinal cord nerve cells dissociated from rat fetuses and cultured on biodegradable microcarriers and embedded in hyaluronic acid were implanted in the completely transected spinal cords of 24 adult rats. For 14 consecutive post-operative days, 15 rats underwent low power laser irradiation (780 nm, 250 mW), 30 min daily. Eleven of the 15 (73%) showed different degrees of active leg movements and gait performance, compared to 4 (44%) of the 9 rats with implantation alone. In a controlgroup of seven rats with spinal cord transection and no transplantation or laser, six (86%) remained completely paralyzed. Three months after transection, implantation and laser irradiation, SSEPs were elicited in 69% of rats (p = 0.0237) compared to 37.5% in the nonirradiated group. The control group had no SSEPs response. Intensive axonal sprouting occurred in the group with implantation and laser. In the control group, the transected area contained proliferating fibroblasts and blood capillaries only. This suggests: 1. These in vitro composite implants are a regenerative and reparative source for reconstructing the transected spinal cord. 2. Post-operative low power laser irradiation enhances axonal sprouting and spinal cord repair.

Effects of electrical stimulation leg training during the acute phase of spinal cord injury: a pilot study.

Four individuals with a spinal cord injury underwent 16 weeks of isometric electrical stimulation training to both legs for 60 min, five times per week during the first 5 months after injury, while two SCI individuals remained untrained. A baseline biopsy sample of the vastus lateralis muscle was obtained within 1 month of injury, and another biopsy sample was taken after a further 16 weeks. The untrained, paralyzed skeletal muscle displayed a reduction in (1) type I fibers (from 50% to 9%), (2) myosin heavy chain (MHC) I (from 27% to 6%), and (3) fiber cross-sectional area of type I, type IIA and type IIX fibers (-62%, -68%, and -55%, respectively) when compared to the baseline sample of muscle taken within 1 month of injury. In contrast, the trained group showed smaller alterations in type I fibers (from 49% to 40%) and MHC I composition (from 39% to 25%), while fiber cross-sectional area was similar to baseline levels for type I, type IIA and type IIX fibers (-3%, -8%, and -4%, respectively). In conclusion, electrical stimulation training can largely prevent the adverse effects of a spinal cord injury upon paralyzed human skeletal muscle if applied soon after the injury.

Functional MR imaging and traumatic paraplegia: preliminary report.

PURPOSE: To evaluate residual activity in the sensorimotor cortex of the lower limbs in paraplegia. METHODS: 5 patients suffering from a complete paralysis after traumatic medullar lesion (ASIA=A). Clinical evaluation of motility and sensitivity. 1. Control functional MR study of the sensorimotor cortex during simultaneous movements of hands, imaginary motor task and passive hands stimulation. 2. Concerning the lower limbs, 3 fMRI conditions: 1-patient attempts to move his toes with flexion-extension, 2-mental imagery task of the same movement, 3-peripheral passive proprio-somesthesic stimulation (squeezing) of the big toes. RESULTS: Activations were observed in the primary sensorimotor cortex (M1), premotor regions and in the supplementary motor area (SMA) during movement and mental imaginary tasks in the control study and during attempt to move and mental imaginary tasks in the study concerning the lower limbs. Passive somesthesic stimulation generated activation posterior to the central sulcus for 2 patients. CONCLUSION: Activations in the sensorimotor cortex of the lower limbs can be generated either by attempting to move or mental evocation. In spite of a clinical evaluation of complete paraplegia, fMRI can show a persistence of sensitive anatomic conduction, confirmed by Somesthesic Evoked Potentials.

Muscle and bone in paraplegic patients, and the effect of functional electrical stimulation.

1. Four paraplegic men volunteered for an exercise programme in which their paralysed quadriceps muscles were stimulated by means of computer-regulated electrical impulses applied through external electrodes. The first exercise regimen consisted of leg raising against a graded load, and during the second regimen exercise took the form of cycling on a modified bicycle ergometer. Each subject exercised five times weekly for 10 weeks during the first regimen and 32 weeks during the second regimen. 2. Whole-body protein turnover determined by L-[1-13C]leucine during feeding remained constant during both exercise regimens, when expressed either in terms of body weight or fat-free mass derived from measurements of total body potassium. 3. Quadriceps muscle protein synthetic rate increased during the study, from 0.0712 to 0.0985%/h (P less than 0.05), as did quadriceps muscle area assessed by computed tomography. 4. Bone mineral content for lumbar vertebrae was normal in all four patients, but for the femoral mid-shaft bone mineral content averaged only 66% of normal for three of the patients. Trabecular bone density in the distal tibia ranged from normal to 2% of normal for the men with the shortest and longest periods of disability, respectively. No changes in bone mineral content or bone density occurred during the exercise period.

Functional electrical stimulation as an orthotic means for the rehabilitation of paraplegic patients.

In rehabilitating paraplegic patients the restoration of locomotion is often planned to enable the disabled person to use the wheelchair as little as possible or eventually even to abandon it. This objective is more easily obtained in those with incomplete spinal lesions. Applied with the view of restoring locomotion are various types of orthoses, but in the present paper the authors deal with functional electrical stimulation (hereinafter FES) as a means of restoring locomotion, demonstrating the advantages of FES over the use of classical orthoses. The paper offers an outline of the methodology of FES in spinal neural lesions, discusses the criteria of patient selection, giving indications and contraindications. The authors conclude by stating their belief that this treatment represents a new way of rehabilitating spinal paralysed patients which will sooner or later become part of the routine rehabilitation of paraplegic patients.