Safety and potential efficacy of expanded mesenchymal stromal cells of bone marrow and umbilical cord origins in patients with chronic spinal cord injuries: a phase I/II study.

BACKGROUND AIMS: Spinal cord injury (SCI) affects patients' physical, psychological, and social well-being. Presently, treatment modalities for chronic SCI have restricted clinical effectiveness. Mesenchymal stromal cells (MSCs) demonstrate promise in addressing nervous tissue damage. This single-center, open-label, parallel-group randomized clinical trial aimed to assess the safety and efficacy of intraoperative perilesional administration of expanded autologous bone marrow-derived MSCs (BMMSCs), followed by monthly intrathecal injections, in comparison to monthly intrathecal administration of expanded allogeneic umbilical cord-derived MSCs (UCMSCs) for individuals with chronic SCI. METHODS: Twenty participants, who had a minimum of 1 year of SCI duration, were enrolled. Each participant in Group A received perilesional BMMSCs, followed by monthly intrathecal BMMSCs for three injections, while Group B received monthly intrathecal UCMSCs for three injections. Safety and efficacy were evaluated using the American Spinal Cord Injury Association (ASIA) score for at least 1 year post the final injection. Statistical analysis was conducted using the Wilcoxon signed-rank test. RESULTS: Group A comprised 11 participants, while Group B included 9. The mean follow-up duration was 22.65 months. Mild short-term adverse events encompassed headaches and back pain, with no instances of long-term adverse events. Both groups demonstrated significant improvements in total ASIA scores, with Group A displaying more pronounced motor improvements. CONCLUSIONS: Our findings indicate that perilesional administration of expanded autologous BMMSCs, followed by monthly intrathecal BMMSCs for three injections, or monthly intrathecal UCMSCs for three injections appear to be safe and hold promise for individuals with chronic SCI. Nonetheless, larger-scale clinical trials are imperative to validate these observations.

Metastatic epidural spinal cord compression: does timing of surgery influence the chance of neurological recovery? An observational case-control study.

PURPOSE: Metastatic epidural spinal cord compression (MESCC) is radiologically defined as an epidural metastatic lesion causing the displacement of the spinal cord from its normal position in the vertebral canal. The purpose of this paper is the evaluation of the influence of timing of surgery on the chance of neurological recovery. METHODS: This is a retrospective observational case-control study performed on patients with MESCC from solid tumors surgically treated at our institute from January 2010 to December 2016. Patients included were divided in two groups depending on surgery that was performed within or after 24 h the admission to the hospital. Neurological status was assessed with American Spine Injury Association (ASIA) Impairment Scale. RESULTS: No statistically significant difference was observed in the variation of ASIA if surgery is performed within or after 24 h from the admission to the hospital. A statistically significant difference was observed after surgery in each group in the improvement of neurological status. A statistically significant difference was reported in the early post-operative complications in patients surgically treated within 24 h. CONCLUSION: MESCC management is challenge for spine surgeons and may represent an oncologic emergency and if not promptly diagnosed can lead to a permanent neurological damage. According to this study, there is no difference in the chance of neurological recovery if surgery is performed within or after 24 h the admission to hospital, but there is a greater rate of early post-operative complications when surgery is performed within 24 h from the admission to the hospital.

Relationship between magnetic resonance imaging findings and spinal cord injury in extension injury of the cervical spine.

OBJECTIVE: The purpose of this study was to determine the relationship between magnetic resonance imaging (MRI) findings and neurologic symptoms in cervical spine extension injury and to analyze the MRI parameters associated with neurologic outcome. MATERIALS AND METHODS: This study included 102 patients with cervical spine extension injury, whose medical records and MRI scans at the time of injury were available. Quantitative MRI parameters such as maximum spinal canal compression (MSCC), maximum cord compromise (MCC), and lesion length showing intramedullary signal changes were measured. Furthermore, intramedullary hemorrhage, spinal cord edema, and soft tissue damage were evaluated. Fisher's exact test was used for a cross-analysis between the MRI findings and the three American Spinal Injury Association category groups depending on the severity level of neurologic injury: complete (category A), incomplete (categories B-D), and normal (category E). RESULTS: MSCC accounted for 23.05, 19.5, and 9.94 % for the complete, incomplete, and normal AIS categories, respectively, without showing statistically significant differences (P = 0.085). MCC was noted in 22.05, 15.32, and 9.2 %, respectively, with the complete-injury group (AIS category A) showing significantly higher. In particular, cases of complete injury had >15 % compression, accounting for 87.5 % (P < 0.001). The mean intramedullary lesion length was significantly higher in complete-injury patients than in incomplete-injury patients (24.22 vs. 8.24 mm). Intramedullary hemorrhage and spinal cord edema were significantly more frequently observed in complete-injury cases (P < 0.001). The incidence of complete injury was proportional to the severity of soft tissue damage. CONCLUSION: MCC, intramedullary lesion length, intramedullary hemorrhage, and spinal cord edema were MRI parameters associated with poor neurologic outcomes in patients with cervical spine extension injury.

The efficacy of intrathecal methyl-prednisolone for acute spinal cord injury: A pilot study.

Study design: Randomized clinical trial. Objectives: To evaluate the safety and effectiveness of intrathecal methyl-prednisolone compared to intravenous methyl-prednisolone in acute spinal cord injuries. Setting: Imam Reza Hospital, Tabriz University of Medical Sciences. Methods: Patients meeting our inclusion and exclusion criteria were enrolled in the study and divided randomly into two treatment arms: intrathecal and intravenous. Standard spinal cord injury care (including surgery) was given to each patient based on our institutional policy. Patients were then assessed for neurological status (based on ASIA scores, Frankel scores) and complications for six months and compared to baseline status after injury. To better understand the biological bases of methyl-prednisolone on spinal cord injuries, we measured two biomarkers for oxidative stress (serum malondialdehyde and total antioxidant capacity) in these patients at arrival and day three after injury. Results: The present study showed no significant difference between the treatment arms in neurological status (sensory scores or motor scores) or complications. However, the within-group analysis showed improvement in neurological status in each treatment arm within six months. Serum malondialdehyde and total antioxidant capacity were analyzed, and no significant difference between the groups was seen. Conclusion: This is the first known clinical trial investigating the effect of intrathecal MP in acute SCI patients. Our finding did not show any significant differences in complication rates and neurological outcomes between the two study arms. Further studies should be conducted to define the positive and negative effects of this somehow novel technique in different populations as well.

Percutaneous screw fixation versus open fusion for the treatment of traumatic thoracolumbar fractures: A retrospective case series of 185 Patients with a single-level spinal column injury.

STUDY DESIGN: Retrospective Single-Center Review of Data at a Level 1 Trauma Center. OBJECTIVE: Compare deformity correction and surgical outcomes of percutaneous instrumentation and open fusion in traumatic thoracolumbar fractures. METHODS: In our retrospective study, all patients undergoing elective spine surgery for TL fractures at a Level 1 trauma center between 2000 and 2017 were reviewed. Patients who underwent percutaneous fixation were given the option of hardware removal after the fracture had healed. RESULTS: A total of 185 patients were included in the study, with 109 treated with an open fusion, and 76 with percutaneous fixation. Twenty-five patients in the latter group had the instrumentation removed after the fracture had healed. None of them required reoperation. In the open fusion group 54.1% of patients required a decompressive laminectomy. Percutaneous fixation patients had a shorter operative time (98.3 min vs 214 min, p < 0.0001), shorter length of stay (9.8 days vs 13.5 days, p = 0.04), and less blood loss (68.4 cc vs 691 cc, p < 0.001). They also had a better correction of their traumatic kyphosis after surgery (p = 0.005). CONCLUSION: Percutaneous fixation is a valuable option for the treatment of TL fractures in cases without evidence of neural compression. It is still unclear whether hardware removal helps prevent adjacent segment degeneration. Percutaneous fixation could allow for better reduction of the fracture with improvement of postoperative alignment.

Microsurgical repair of severed thoracic spinal cord and clinical outcome: technical case report.

BACKGROUND: This report describes a case of successful repair of severed thoracic spine in a young man who presented with a penetrating stab injury to spine resulting in Brown-Séquard syndrome. Surgical technique and post-operative management is discussed. CASE PRESENTATION: A 34-year-old fit and well healthy man was admitted with a history of stab injury to the thoracic spine at thoracic T2/3 level with ASIA impairment score (AIS) score D with an incomplete spinal cord affecting his left lower limb with complete paralysis and right lower limb paresis with impaired sensation below T6 level to L5. Neuroimaging confirmed a penetrating knife injury traversing the T2/3 level causing hemi-section of the spinal cord confirmed intraoperatively. He underwent an urgent exploratory surgery of his spine and a T2/3 laminectomy was performed to aid removal of the knife. The dura was noted to be contused and severed spinal cord was noted to be severed with associated cord oedema. A microsurgical repair of the severed cord was performed with duroplasty followed by intense neuro-rehabilitation. On a 3 month follow up his AIS score is E with lower limb power is 5/5 bilaterally and he is able to mobilise independently up to 8-10 steps without any supportive aid and with crutches he is independently functional and mobile. CONCLUSION: This is the first documented case of microsurgical repair of severed thoracic spinal cord secondary to traumatic knife injury. In the management of such scenario, apart from the removal of foreign body, repair of the cord with duroplasty should be carefully considered. The role of spinal neuroplasticity in healing following timely repair of the spinal cord along with intense rehabilitation remains the key. This had resulted in a good clinical and functional outcome with in a 18-month follow up.

The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis.

Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.

Electrophysiological Study in Acute Spinal Cord Injury Patients: Its Correlation to Neurological Deficit and Subsequent Recovery Assessment by ASIA Score.

BACKGROUND: To investigate the relationship between neurological deficit and subsequent recovery as assessed by ASIA score and findings of electrodiagnostic study in acute spinal cord injury (SCI) patients. METHODS: Thirty-five patients with acute SCI presenting within 48 h of injury were clinically evaluated for the level, extent, and severity of SCI according to the ASIA standards in a tertiary-level care center. Electrodiagnostic studies of bilateral two motor (tibial and peroneal), one sensory (sural) nerves, and five muscles [iliopsoas, vastus medialis, tibialis anterior, gastrocnemius, and extensor hallucis longus (EHL)] were conducted and repeated at 3 months and 6 months. RESULTS: The neurological recovery was highly significant (p < 0.001) at 6 months. The difference in mean amplitude was statistically significant (p < 0.05) for all the nerves; mean conduction velocity significant for peroneal and sural nerves, and with no significant difference in mean latency. The differences in mean recruitment of motor unit potential (MUP) and mean peak-to-peak amplitude were highly significant (p < 0.001). Statistically significant kappa agreement between neurological recovery according to ASIA score and nerve conduction velocity was found for right tibial nerve (K = 0.324); electromyography finding of recruitment of MUP with right and left tibialis anterior (k = 0.400) and left EHL (k = 0.407); peak-to-peak amplitude with right tibialis anterior (k = 0.211), right gastrocnemius (k = 0.390), and right EHL (k = 0.211). CONCLUSIONS: There is a strong relationship between electrodiagnostic findings and ASIA scoring to predict neurological deficit and subsequent recovery after acute traumatic SCI. Serial neurologic evaluation by ASIA score and electrodiagnostic studies may help in designing customized rehabilitation programs for the patients according to the expected neurological recovery; and evaluating future research in the field of SCI with more scientific authenticity.

Correlation of qualitative and quantitative MRI parameters with neurological status: a prospective study on patients with spinal trauma.

INTRODUCTION: Spinal trauma is relatively more common in young active individuals. Although its mortality is low, it is an important cause of long term disability. Magnetic resonance imaging (MRI) can accurately depict presence and extent of spinal cord injury (SCI) in these patients. This study was aimed to look for various qualitative and quantitative MRI findings which are predictive of initial neurological deficit in patients with spinal trauma and final outcome on follow-up. MATERIALS AND METHODS: The present study was conducted on 50 patients with suspected acute cervical or dorsal spinal trauma presenting for MRI study. American Spinal Injury Association (ASIA) motor score was used for assessing neurological status at the time of presentation, at the time of discharge/2weeks and at 3-6 months follow up. Various MRI qualitative and quantitative parameters were evaluated for correlation with severity of spinal injury. RESULTS: Normal baseline MRI (pattern 0) was seen in 12 subjects and was associated with incomplete SCI in 4 subjects (ASIA grade D) followed by complete recovery in all patients on follow-up examination. Pattern I (haemorrhage) was associated with complete spinal cord injury. Pattern II (oedema) was associated with incomplete SCI and good functional recovery on follow up.Pattern III (contusion) was associated with intermediate severity of injury. Compression and transection patterns were associated with complete neurological deficit at presentation and increased mortality at subsequent follow-up. All the three quantitative parameters i.e. lesion length,maximum (bony) canal compromise (MCC), maximum spinal cord compression (MSCC) were significantly increased in patients with complete SCI as compared to those with incomplete SCI. The best predictors for baseline ASIA score were MCC, cord oedema and cord haemorrhage. For the final ASIA score, the best predictors were baseline ASIA score and cord haemorrhage. CONCLUSION: MRI is excellent imaging modality for detecting and assessing severity of spinal trauma. In our study, presence of cord haemorrhage, MCC and cord oedema were best predictors of baseline neurological status at presentation, whereas baseline ASIA score and cord haemorrhage were best predictors of final neurological outcome.

Hypothermia as a clinical neuroprotectant.

Applying therapeutic hypothermia (TH) for the purposes of neuroprotection, originally termed "hibernation," started nearly 100 years ago. Because TH cooling systems have improved to the point where it is practical and safe for general application, interest in providing such treatment in conditions such as spinal cord injury, traumatic brain injury, stroke, and cardiac arrest has increased. This article reviews the mechanisms by which TH mitigates secondary neurologic injury, the clinical scenarios where TH is being applied, and reviews selected published studies using TH for central nervous system neuroprotection.

Neurologic injury because of trauma after type II odontoid nonunion.

BACKGROUND CONTEXT: Treatment of Type II odontoid fractures remains controversial, whereas nonoperative treatment is well accepted for isolated Type III odontoid fractures. Little is known about long-term sequelae of nonoperative management or risk of recurrent injury after nonsurgical treatment. We hypothesize that a substantial proportion of odontoid fractures assumed to be acute are actually chronic injuries and have a high rate of late displacement resulting in neurologic injury. PURPOSE: To identify patients presenting with previously unrecognized odontoid fracture nonunions and to document the incidence of new neurologic injury after secondary trauma in this population. STUDY DESIGN: Retrospective case series. PATIENT SAMPLE: One hundred thirty-three patients with Type II odontoid fractures presenting to a Level I trauma center. OUTCOME MEASURES: Computed tomography (CT) and magnetic resonance imaging (MRI) scans, American Spinal Injury Association Motor Score (AMS), and neurologic examination. METHODS: All patients presenting after traumatic injury to a Level I trauma center from May 2005 to May 2010 with a Type II odontoid fracture on CT scan were included. Patients aged less than 18 years and those with pathologic fractures were excluded. Fractures were classified as chronic or acute based on CT evidence of chronic injury/nonunion including fracture resorption, sclerosis, and cyst formation. Magnetic resonance imaging was then examined for evidence of fracture acuity (increased signal in C2 on T2 images). Patients without evidence of acute fracture on MRI were considered to have chronic injuries. Computed tomography and MRI scans were interpreted independently by two reviewers. Chart review was performed to document demographics, AMS, and new-onset neurologic deficit associated with secondary injury. RESULTS: One hundred thirty-three patients presented with Type II odontoid fractures and no known history of cervical fracture with an average age of 79 years. Based on CT criteria, 31/133 (23%) fractures were chronic injuries. Nine additional fractures appeared acute on CT but were determined to be chronic by MRI findings. The overall number of chronic fractures was therefore 40 (30%). Interobserver reliability analysis for classification of fractures as chronic demonstrated κ=0.65 representing substantial agreement. Of the 40 chronic fractures, 7 patients (17.5%) had new-onset neurologic deficits after secondary injury including 4 motor deficits, 2 sensory deficits, and 1 combined deficit. Although the chronic injury group as a whole had similar AMS to the acute injury group (89 vs. 84, p=.27), the seven patients with new-onset neurologic deficit had an average AMS of 52.4. CONCLUSIONS: A substantial proportion of patients presenting after cervical trauma with Type II odontoid fractures have evidence of nonacute injury. Of these patients, 17% presented with a new neurologic deficit caused by an "acute-on-chronic" injury.