Explore the vast range of titles available.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study’s primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI. In the CELLTOP Phase I trial, stem cells were harvested from patients with spinal cord injury and injected into their central nervous system after processing. The procedure was safe, with no reported serious adverse events during the 2-year follow-up period.

Spinal cord injury (SCI) is a devastating condition with limited pharmacological treatment options to restore function. Regenerative approaches have recently attracted interest as an adjuvant to current standard of care. Adipose tissue–derived (AD) mesenchymal stem cells (MSCs) represent a readily accessible cell source with high proliferative capacity. The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI. In this initial report, we describe the outcome of the first treated patient, a 53-year-old survivor of a surfing accident who sustained a high cervical American Spinal Injury Association Impairment Scale grade A SCI with subsequent neurologic improvement that plateaued within 6 months following injury. Although he improved to an American Spinal Injury Association grade C impairement classification, the individual continued to be wheelchair bound and severely debilitated. After study enrollment, an adipose tissue biopsy was performed and MSCs were isolated, expanded, and cryopreserved. Per protocol, the patient received an intrathecal injection of 100 million autologous AD-MSCs infused after a standard lumbar puncture at the L3-4 level 11 months after the injury. The patient tolerated the procedure well and did not experience any severe adverse events. Clinical signs of efficacy were observed at 3, 6, 12, and 18 months following the injection in both motor and sensory scores based on International Standards for Neurological Classification of Spinal Cord Injury. Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.

Intervertebral disc degeneration (IDD) is a common condition associated with aging and degeneration of the disc. Type 2 diabetes mellitus (T2DM) is linked to various musculoskeletal disorders, including IDD, but its molecular effects on IDD remain understudied. To explore the molecular differences in IDD between T2DM and non-T2DM patients, we conducted a quantitative proteomic analysis of nucleus pulposus (NP) tissues from patients with T2DM-IDD or non-T2DM-IDD individuals. We identified 3,720 proteins, with 221 significantly upregulated and 233 downregulated in T2DM-IDD. Multiple mitochondrial proteins were upregulated (NDUFV2, NDUFB5, NDUFA13, MPC2) indicating a potential increase in oxidative stress in the NP tissues from T2DM-IDD. Conversely, downregulated proteins such as versican (VCAN), an extracellular matrix proteoglycan, IL17B, a pro-inflammatory cytokine, and vascular endothelial growth factor A (VEGFA) indicate possible alterations in ECM composition and structure that impact the mechanical properties and integrity of the IVD as well as a reduced inflammatory response in NP tissues from non-T2DM-IDD. Additionally, T2DM-IDD showed enrichment in fatty acid metabolism pathways, while non-T2DM-IDD samples were enriched in epithelial mesenchymal transition and hypoxia pathways. Altogether, these results provide novel insights into the molecular mechanisms of T2DM-IDD and may guide future therapies.

Background Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. Methods Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. Results The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913–0.931). Conclusions Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.

Spinal cord injuries (SCI) are traumatic events with limited treatment options. Following injury, the lesion site experiences a drastic change to both its structure and vasculature which reduces its ability for tissue regeneration. Despite the lack of clinical options, researchers are investigating therapies to induce neuronal regeneration. Cell-based therapies have long been assessed in the context of SCI to promote neuronal protection and repair. Vascular endothelial growth factor (VEGF) not only demonstrates this ability, but also demonstrates angiogenic potential to promote blood vessel formation. While there have been numerous animal studies investigating VEGF, further research is still warranted to pinpoint its role following SCI. This review aims to discuss the literature surrounding the role of VEGF following SCI and its potential in promoting functional recovery.

Purpose Primary glioblastoma of the spinal cord (spinal GBM) is a rare central nervous system tumor, relative to its cranial counterpart (cranial GBM). Our current knowledge of spinal GBM epidemiology, tumor characteristics and treatment are insufficient and mostly based on single-institution case series. Methods All patients diagnosed with grade-4 GBM from 2004 to 2014 were queried from the National Cancer Database. Chi square analysis was used to compare presenting characteristics while Kaplan–Meier and Cox regression analyses were employed for survival analyses. Results Total 103,496 patients with cranial GBM and 190 patients with spinal GBM were analyzed. Median survival for spinal GBM was found to be higher compared to cranial GBM (p = 0.07). Spinal GBM patients had significant better survival in 18 to 65 years age group than < 18 years and > 65 years age group (p = 0.003). Overall survival time for 95 spinal GBM patients with available treatment data was not statistically different among the four treatment modalities (radiation with or without chemotherapy, surgery alone, surgery with adjuvant therapy, and palliative therapy; p = 0.28).On multivariable analysis, < 18 years age group was associated with improved survival (HR 0.50, 95% CI 0.23–1.00, p = 0.046), while tumor extension was associated with poor survival (HR 2.71, 95% CI 1.04–6.22, p = 0.041). Interestingly surgery with adjuvant therapy was unable to show increase survival compared to other treatment modalities. Conclusions Our study adds to the growing literature on spinal GBM with a focus on comparative trends with cranial GBM and outcomes with different treatment modalities.

Background The long-term efficacy of endovascular treatment (EVT) for cavernous sinus dural arteriovenous fistulae (CS-dAVF) was assessed with a special focus on residual shunts after initial EVT. Patients and methods This retrospective survey included 50 patients who had undergone EVT and were followed for 1 month or longer (median follow-up 56 months). Results Common preoperative symptoms were chemosis (78%), extra-ocular motor palsy (72%), exophthalmos (66%), and tinnitus (26%). CS-dAVF were addressed by transvenous embolization (tVE, n  = 48), tVE only was used in 43 instances and tVE plus transarterial embolization (tAE) in five. Two patients underwent tAE only. Procedure-related morbidity (brainstem infarction) was recorded in one patient (2%) and transient symptom exacerbation (paradoxical worsening) in 12 patients (24%). Postoperative digital subtraction angiography showed no major retrograde shunt or cortical venous reflux in any of the 50 patients. Anterograde or minor retrograde residual shunt was observed in 17 patients (34%); three of these underwent additional tVE and four had Gamma Knife surgery. The shunt flow disappeared in all 17 patients 12.6 ± 13.4 (mean ± SD) months after initial EVT. At the latest follow-up, 65.7 ± 52.6 months after the initial operation, no shunt flow was observed in any of the 50 patients. None had remaining or newly developed chemosis or tinnitus on follow-up. The rate of persistent cavernous sinus symptoms at the latest follow-up was higher in patients with than without post-procedural paradoxical worsening (5/12, 41.7% vs. 2/38, 5.3%, p  = 0.0059 by Fisher’s exact test). Conclusions Long-term follow-up showed that EVT, especially tVE, is an efficient and safe treatment for CS-dAVF. It resulted in the eventual disappearance of shunt flow. Residual shunt without major retrograde flow or cortical venous reflux can be monitored without additional treatment.

The study design is literature review. The sex-determining region Y gene (SRY)–related high mobility group box (HMG)-box (SOX) gene family has primarily been associated with neural development and sex determination and is a key component of human embryonic development. Recent studies on zebrafish models have demonstrated that the unique ability of the latter for central nervous tissue (CNS) repair following injury is largely mediated by SOX genes. Given that efforts aimed at the structural regeneration and functional restoration of neural tissue still represent a major therapeutic challenge in patients suffering CNS injury, these findings have initiated a discussion regarding the development of novel therapeutic strategies for SCI focusing on neural tissue regeneration. Spinal cord injury (SCI), in particular, represents a field that could greatly benefit from studies related to the function of the SOX genes. Neuro-informatics Laboratory, Mayo Clinic, Rochester, MN. A literature review was conducted, with a focus on SOX gene that has been described in the experimental studies of SCI. In this review, the existing evidence linking the SOX gene family to the pathophysiology of SCI is summarized, and future research steps regarding the potential implications of the SOX genes in neurological recovery following SCI are discussed, especially focusing on highlighting potential therapeutic targets. The potential implications of the latter could play a crucial role in future efforts to advance the treatment approaches to SCI.

PurposeGlioblastoma multiforme (GBM) is a common and aggressive malignancy associated with poor prognosis. Characteristics and treatment of long-term survivors are of particular interest in efforts to improve outcomes. Therefore, the objective of this study was to examine trends and prognostic factors for 3-year survival from a national database.MethodsThe National Cancer Database (NCDB) was queried for patients diagnosed with cranial GBM from 2004 to 2013 and with 3-year follow-up. Trends in 3-year and overall survival, patient characteristics, tumor properties, and treatment modalities were examined. Multivariable logistic regression was utilized to investigate the association of these factors with 3-year survival. Predictor importance analysis was conducted using a metric defined as Wald χ2 penalized by degrees of freedom.ResultsA total of 88,919 GBM patients with 3-year follow-up were identified. Overall, 8757 (9.8%) patients survived ≥ 3 years. Three-year survival significantly improved from 8.0 to 10.5% (p < 0.001) from 2004 to 2013. Trimodal treatment administration also significantly increased from 38.7 to 55.9% (p < 0.001). During this span, patients increasingly presented as older (p = 0.040), without private insurance (p < 0.001), and with a higher comorbidity index (p < 0.001). On multivariable regression, factors such as trimodal treatment (p < 0.001), younger age (p < 0.001), and MGMT methylation (p < 0.001) were significantly associated with increased odds of 3-year survival. Predictor importance analysis indicated that MGMT methylation, age, and treatment modality were the most significant relative determinants of 3-year survival.ConclusionThese findings illustrate an improved 3-year survival rate for GBM patients from 2004 to 2013 with a concurrent increase in trimodal treatment administration despite more adverse patient presenting characteristics.