Results of a long-term uniform system of neurorehabilitation in patients with incomplete thoracic spinal cord injury.

INTRODUCTION AND OBJECTIVE: The results of kinesiotherapy treatment in patients after incomplete spinal cord injury (iSCI) are inconclusive, mostly due to different, subjective evaluation methods. The study aims to evaluate the range of functional regeneration in long-term 13 months follow-up using comparative neurophysiological tests after uniform kinesiotherapy in patients with thoracic iSCI. MATERIAL AND METHODS: Comparative tests were performed of sensory perception in dermatomes Th1-S1, electromyography (at rest-rEMG and during maximal contraction-mcEMG) in the muscles of the trunk and lower extremities, electroneurography (ENG) of the motor fibres of the lower extremities, and motor-evoked potential induced transcranially (MEP) before and after treatment in 25 iSCI patients. All subjects were treated with the same kinesiotherapeutic procedures. RESULTS: A moderate increase was found in amplitudes in rEMG and mcEMG recordings fromthe rectus abdominis and rectus femoris muscles, MEPs amplitudes, and amplitudes after peroneal nerve stimulations in ENG studies. There was no improvement in sensory perception. CONCLUSIONS: Following the proposed kinesiotherapy algorithm, patients after thoracic iSCI presented a moderate more motor than sensory functions improvement. Applied neurorehabilitation evoked normalization of muscle tension, moderate improvement of rectus abdominis and rectus femoris muscles motor units activity, and motor central and peripheral neural impulses transmission. The comparative neurophysiological assessment provide a more precise and objective insight into the functional status of afferent and efferent systems than the classical clinical approach in iSCI patients.

The Long-Term Effect of Treatment Using the Transcranial Magnetic Stimulation rTMS in Patients after Incomplete Cervical or Thoracic Spinal Cord Injury.

Repetitive transcranial magnetic stimulation (rTMS) may support motor function recovery in patients with incomplete spinal cord injury (iSCI). Its effectiveness mainly depends on the applied algorithm. This clinical and neurophysiological study aimed to assess the effectiveness of high-frequency rTMS in iSCI patients at the C2-Th12 levels. rTMS sessions (lasting 3-5 per month, from 2 to 11 months, 5 months on average) were applied to 26 iSCI subjects. The motor cortex was bilaterally stimulated with a frequency at 20-25 Hz and a stimulus strength that was 70-80% of the resting motor threshold (15.4-45.5% maximal output) during one therapeutic session. Surface electromyography (sEMG) recordings at rest and during maximal contractions and motor evoked potential (MEP) recordings were performed from the abductor pollicis brevis (APB) and the tibialis anterior (TA) muscles. The same neurophysiological studies were also performed in patients treated with kinesiotherapy only (K group, n = 25) and compared with patients treated with both kinesiotherapy and rTMS (K + rTMS). A decrease in sEMG amplitudes recorded at rest from the APB muscles (p = 0.001) and an increase in sEMG amplitudes during the maximal contraction of the APB (p = 0.001) and TA (p = 0.009) muscles were found in the K + rTMS group. A comparison of data from MEP studies recorded from both APB and TA muscles showed significant changes in the mean amplitudes but not in latencies, suggesting a slight improvement in the transmission of spinal efferent pathways from the motor cortex to the lower spinal centers. The application of rTMS at 20-25 Hz reduced spasticity in the upper extremity muscles, improved the recruitment of motor units in the upper and lower extremity muscles, and slightly improved the transmission of efferent neural impulses within the spinal pathways in patients with C2-Th12 iSCI. Neurophysiological recordings produced significantly better parameters in the K + rTMS group of patients after therapy. These results may support the hypothesis about the importance of rTMS therapy and possible involvement of the residual efferent pathways including propriospinal neurons in the recovery of the motor control of iSCI patients.

Treatment of patients with cervical and upper thoracic incomplete spinal cord injury using repetitive transcranial magnetic stimulation.

PURPOSE: To evaluate the short- and long-term effectiveness of repetitive transcranial magnetic stimulation with parameters based on results of comparative neurophysiological studies in patients with incomplete spinal cord injury. Results may help to understand mechanisms responsible for regeneration of the incomplete spinal cord after injury. METHODS: Repetitive transcranial magnetic stimulation sessions (three to five sessions per month for not less than 5 months) to 15 patients with C4-Th2 incomplete spinal cord injury were applied with individually designed parameters. One session consisted of bilateral stimulation of the primary motor cortex (for 10 min each with 800 stimuli in 2-s lasting trains and the inter-train intervals of 28 s) with frequency at 20-22 Hz and stimulus strength that was 70%-80% of the resting motor threshold (0.84-0.96 T). Recordings of surface electromyography at rest and during the attempt of maximal muscle contractions and motor evoked potentials were performed from abductor pollicis brevis and tibialis anterior muscles bilaterally. Amplitude parameters of surface electromyography and motor evoked potentials were used as outcomes. All neurophysiological tests were comparatively applied before and after treatment. RESULTS: Decrease in surface electromyography amplitudes recorded at rest from abductor pollicis brevis (p = 0.009), increase in surface electromyography amplitudes during maximal contraction of abductor pollicis brevis (p = 0.03) and increase in motor evoked potential parameters recorded from abductor pollicis brevis (p = 0.04) were found. CONCLUSION: Proposed repetitive transcranial magnetic stimulation algorithm reduced the increased muscle tension in upper extremity muscles, improved the function of upper extremity muscle motor units and slightly improved the transmission of efferent neural impulses within spinal pathways. Besides functional recovery in descending spinal pathways, repetitive transcranial magnetic stimulation may also inhibit inevitable pathological changes in nerves.

Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging.

Treatment of patients sustaining a complete spinal cord injury remains an unsolved clinical problem because of the lack of spontaneous regeneration of injured central axons. A 38-year-old man sustained traumatic transection of the thoracic spinal cord at upper vertebral level Th9. At 21 months after injury, the patient presented symptoms of a clinically complete spinal cord injury (American Spinal Injury Association class A-ASIA A). One of the patient's olfactory bulbs was removed and used to derive a culture containing olfactory ensheathing cells and olfactory nerve fibroblasts. Following resection of the glial scar, the cultured cells were transplanted into the spinal cord stumps above and below the injury and the 8-mm gap bridged by four strips of autologous sural nerve. The patient underwent an intense pre- and postoperative neurorehabilitation program. No adverse effects were seen at 19 months postoperatively, and unexpectedly, the removal of the olfactory bulb did not lead to persistent unilateral anosmia. The patient improved from ASIA A to ASIA C. There was improved trunk stability, partial recovery of the voluntary movements of the lower extremities, and an increase of the muscle mass in the left thigh, as well as partial recovery of superficial and deep sensation. There was also some indication of improved visceral sensation and improved vascular autoregulation in the left lower limb. The pattern of recovery suggests functional regeneration of both efferent and afferent long-distance fibers. Imaging confirmed that the grafts had bridged the left side of the spinal cord, where the majority of the nerve grafts were implanted, and neurophysiological examinations confirmed the restitution of the integrity of the corticospinal tracts and the voluntary character of recorded muscle contractions. To our knowledge, this is the first clinical indication of the beneficial effects of transplanted autologous bulbar cells.

Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury.

Numerous studies in animals have shown the unique property of olfactory ensheathing cells to stimulate regeneration of lesioned axons in the spinal cord. In a Phase I clinical trial, we assessed the safety and feasibility of transplantation of autologous mucosal olfactory ensheathing cells and olfactory nerve fibroblasts in patients with complete spinal cord injury. Six patients with chronic thoracic paraplegia (American Spinal Injury Association class A-ASIA A) were enrolled for the study. Three patients were operated, and three served as a control group. The trial protocol consisted of pre- and postoperative neurorehabilitation, olfactory mucosal biopsy, culture of olfactory ensheathing cells, and intraspinal cell grafting. Patient's clinical state was evaluated by clinical, neurophysiological, and radiological tests. There were no adverse findings related to olfactory mucosa biopsy or transplantation of olfactory ensheathing cells at 1 year after surgery. There was no evidence of neurological deterioration, neuropathic pain, neuroinfection, or tumorigenesis. In one cell-grafted patient, an asymptomatic syringomyelia was observed. Neurological improvement was observed only in transplant recipients. The first two operated patients improved from ASIA A to ASIA C and ASIA B. Diffusion tensor imaging showed restitution of continuity of some white matter tracts throughout the focus of spinal cord injury in these patients. The third operated patient, although remaining ASIA A, showed improved motor and sensory function of the first spinal cords segments below the level of injury. Neurophysiological examinations showed improvement in spinal cord transmission and activity of lower extremity muscles in surgically treated patients but not in patients receiving only neurorehabilitation. Observations at 1 year indicate that the obtaining, culture, and intraspinal transplantation of autologous olfactory ensheathing cells were safe and feasible. The significance of the neurological improvement in the transplant recipients and the extent to which the cell transplants contributed to it will require larger numbers of patients.