Pathological Spinal Cord Research Articles

C1-2 hypermobility and its impact on the spinal cord: a finite element analysis.

The authors present a finite element analysis (FEA) evaluating the mechanical impact of C1-2 hypermobility on the spinal cord. The Code_Aster program was used to perform an FEA to determine the mechanical impact of C1-2 hypermobility on the spinal cord. Normative values of Young's modulus were applied to the various components of the model, including bone, ligaments, and gray and white matter. Two models were created: 25° and 50° of C1-on-C2 rotation, and 2.5 and 5 mm of C1-on-C2 lateral translation. Maximum von Mises stress (VMS) throughout the cervicomedullary junction was calculated and analyzed. The FEA model of 2.5 mm lateral translation of C1 on C2 revealed maximum VMS for gray and white matter of 0.041 and 0.097 MPa, respectively. In the 5-mm translation model, the maximum VMS for gray and white matter was 0.069 and 0.162 MPa. The FEA model of 25° of C1-on-C2 rotation revealed maximum VMS for gray and white matter of 0.052 and 0.123 MPa. In the 50° rotation model, the maximum VMS for gray and white matter was 0.113 and 0.264 MPa. This FEA revealed significant spinal cord stress during pathological rotation (50°) and lateral translation (5 mm) consistent with values found during severe spinal cord compression and in patients with myelopathy. While this finite element model requires oversimplification of the atlantoaxial joint, the study provides biomechanical evidence that hypermobility within the C1-2 joint leads to pathological spinal cord stress.

Diffusion tensor imaging in differentiation of spinal cord lesions

Background Spinal lesions sometimes remain insufficiently visualized by ‘conventional’ magnetic resonance imaging techniques; indeed very often the lesions seen on T2 weighted images do not completely display the effects of pathology on the long tracts. Diffusion imaging, which enables the imaging of molecular water motion, has been applied recently to spinal cord diseases Aim The purpose of this study was to assess the role of Diffusion tensor imaging in in differentiation between different spinal cord lesions Patients & methods This prospective study included 30 patients with myelopathy symptoms. All patients were subjected to full history taking, clinical examination, magnetic resonance imaging and diffusion tensor imaging MRI. Results The mean FA values at the site of the lesion was significantly lower than the normal appearing spinal cord in inflammation/demyelination, compressive myelopathy and traumatic spinal cord injury groups while the mean apparent diffusion coefficient values at the site of the lesions was significantly higher than the normal appearing spinal cord in inflammation/demyelination group. FA was sensitive than apparent diffusion coefficient in the detection of the spinal cord abnormalities with a sensitivity of 90% versus 60% respectively. Conclusion Diffusion tensor imaging with its quantitative indices is a non-invasive tool that is used in functional assessment of normal and pathologic spinal cord white matter, giving detailed information about different pathology and helping early management.

Natural history of craniovertebral abnormalities in a single-center study in 54 patients with Hurler syndrome.

Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention. Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements. A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age. Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1β signaling pathway

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.

A transgenic mouse embryonic stem cell line for puromycin selection of V0V interneurons from heterogenous induced cultures

BackgroundSpinal interneurons (INs) relay sensory and motor control information between the brain and body. When this relay circuitry is disrupted from injury or disease, it is devastating to patients due to the lack of native recovery in central nervous system (CNS) tissues. Obtaining a purified population of INs is necessary to better understand their role in normal function and as potential therapies in CNS. The ventral V0 (V0V) INs are excitatory neurons involved in locomotor circuits and are thus of interest for understanding normal and pathological spinal cord function. To achieve scalable amounts of V0V INs, they can be derived from pluripotent sources, such as mouse embryonic stem cells (mESCs), but the resultant culture is heterogenous, obscuring the specific role of V0V INs. This study generated a transgenic mESC line to enrich V0V INs from induced cultures to allow for a scalable, enriched population for future in vitro and in vivo studies.MethodsThe transgenic Evx1-PAC mESC line was created by CRISPR-Cas9-mediated insertion of puromycin-N-acetyltransferase (PAC) into the locus of V0V IN marker Evx1. Evx1 and PAC mRNA expression were measured by qPCR. Viability staining helped establish the selection protocol for V0V INs derived from Evx1-PAC mESCs inductions. Immunostaining was used to examine composition of selected inductions. Cultures were maintained up to 30 days to examine maturation by expression of mature/synaptic markers, determined by immunostaining, and functional activity in co-cultures with selected motor neurons (MNs) and V2a INs on microelectrode arrays (MEAs).ResultsV0V IN inductions were best selected with 4 µg/mL puromycin on day 10 to 11 and showed reduction of other IN populations and elimination of proliferative cells. Long-term selected cultures were highly neuronal, expressing neuronal nuclear marker NeuN, dendritic marker MAP2, pre-synaptic marker Bassoon, and glutamatergic marker VGLUT2, with some cholinergic VAChT-expressing cells. Functional studies on MEAs showed that co-cultures with MNs or MNs plus V2a INs created neuronal networks with synchronized bursting.ConclusionsEvx1-PAC mESCs can be used to purify V0V IN cultures for largely glutamatergic neurons that can be used in network formation studies or for rodent models requiring transplanted V0V INs.

Editorial Comment on the Article by Mushkin M.A. et al. “Effect of Prehospital Pause on the Outcomes of Emergency Decompression and Stabilization Procedures in Patients with Tumor and Infectious Spine Diseases”

The editorial comment evaluates the current state of issue of medical care at urgent states caused by pathological vertebral fractures and spinal cord compression in patients with spine destructive diseases. The rare occurrence of pathology and the deficiency of objective data determine the lack of consensus on the medical care for this category of patients. The article by M.A. Mushkin et al helps to understand how the prehospital pause affects the outcomes of emergency decompression and stabilization procedures in patients with tumor and infectious diseases of the spine, as well as to determine how much time the surgeon has at his disposal. The author of the comment believes that close cooperation of orthopedic surgeons, neurosurgeons, oncologists is necessary to solve this problem. Even despite the absence of oncologists in the staff of emergency hospitals, telemedicine allows to receive methodological support in a timely manner for making a correct decision for each patient. Interaction between clinicians, radiologists and pathologists is equally important. An important aspect is continuity in patient care. An urgently performed spinal cord decompression is only a stage of the complex treatment. Such patients should be provided with accurate routing depending on the diagnosis and the treatment early outcome.

Lithium promotes recovery after spinal cord injury.

Lithium is associated with oxidative stress and apoptosis, but the mechanism by which lithium protects against spinal cord injury remains poorly understood. In this study, we found that intraperitoneal administration of lithium chloride (LiCl) in a rat model of spinal cord injury alleviated pathological spinal cord injury and inhibited expression of tumor necrosis factor α, interleukin-6, and interleukin 1 β. Lithium inhibited pyroptosis and reduced inflammation by inhibiting Caspase-1 expression, reducing the oxidative stress response, and inhibiting activation of the Nod-like receptor protein 3 inflammasome. We also investigated the neuroprotective effects of lithium intervention on oxygen/glucose-deprived PC12 cells. We found that lithium reduced inflammation, oxidative damage, apoptosis, and necrosis and up-regulated nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 in PC12 cells. All-trans retinoic acid, an Nrf2 inhibitor, reversed the effects of lithium. These results suggest that lithium exerts anti-inflammatory, anti-oxidant, and anti-pyroptotic effects through the Nrf2/heme oxygenase-1 pathway to promote recovery after spinal cord injury. This study was approved by the Animal Ethics Committee of Xi'an Jiaotong University (approval No. 2018-2053) on October 23, 2018.

Developing a mechanically matched decellularized spinal cord scaffold for the in situ matrix-based neural repair of spinal cord injury

Tissue engineering is a promising strategy to repair spinal cord injury (SCI). However, a bioscaffold with mechanical properties that match those of the pathological spinal cord tissue and a pro-regenerative matrix that allows robust neurogenesis for overcoming post-SCI scar formation has yet to be developed. Here, we report that a mechanically enhanced decellularized spinal cord (DSC) scaffold with a thin poly (lactic-co-glycolic acid) (PLGA) outer shell may fulfill the requirements for effective in situ neuroengineering after SCI. Using chemical extraction and electrospinning methods, we successfully constructed PLGA thin shell-ensheathed DSC scaffolds (PLGA-DSC scaffolds) in a way that removed major inhibitory components while preserving the permissive matrix. The DSCs exhibited good cytocompatibility with neural stem cells (NSCs) and significantly enhanced their differentiation toward neurons in vitro. Due to the mechanical reinforcement, the implanted PLGA-DSC scaffolds showed markedly increased resilience to infiltration by myofibroblasts and the deposition of dense collagen matrix, thereby creating a neurogenic niche favorable for the targeted migration, residence and neuronal differentiation of endogenous NSCs after SCI. Furthermore, PLGA-DSC presented a mild immunogenic property but prominent ability to polarize macrophages from the M1 phenotype to the M2 phenotype, leading to significant tissue regeneration and functional restoration after SCI. Taken together, the results demonstrate that the mechanically matched PLGA-DSC scaffolds show promise for effective tissue repair after SCI.

Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury.

Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 µM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi'an Jiaotong University on March 6, 2014.

Abnormal spinal cord motion at the craniocervical junction in hypermobile Ehlers-Danlos patients.

The craniocervical junction (CCJ) is anatomically complex and comprises multiple joints that allow for wide head and neck movements. The thecal sac must adjust to such movements. Accordingly, the thecal sac is not rigidly attached to the bony spinal canal but instead tethered by fibrous suspension ligaments, including myodural bridges (MDBs). The authors hypothesized that pathological spinal cord motion is due to the laxity of such suspension bands in patients with connective tissue disorders, e.g., hypermobile Ehlers-Danlos syndrome (EDS). The ultrastructure of MDBs that were intraoperatively harvested from patients with Chiari malformation was investigated with transmission electron microscopy, and 8 patients with EDS were compared with 8 patients without EDS. MRI was used to exclude patients with EDS and craniocervical instability (CCI). Real-time ultrasound was used to compare the spinal cord at C1-2 of 20 patients with EDS with those of 18 healthy control participants. The ultrastructural damage of the collagen fibrils of the MDBs was distinct in patients with EDS, indicating a pathological mechanical laxity. In patients with EDS, ultrasound revealed increased cardiac pulsatory motion and irregular displacement of the spinal cord during head movements. Laxity of spinal cord suspension ligaments and the associated spinal cord motion disorder are possible pathogenic factors for chronic neck pain and headache in patients with EDS but without radiologically proven CCI.

Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

Extensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.

Traumatic subaxial cervical spine injury - Improving initial evaluation through correlation of diffusion tensor imaging and subaxial cervical spine injury classification SLIC score.

Background: Traumatic injury to spine and spinal cord represents a devastating condition, with a huge risk for permanent severe disabilities. Predicting the long-term outcome in this type of trauma is a very difficult task being under the influence of a wide spectrum of biomechanical and pathophysiological factors. The advent of magnetic resonance imaging (MRI) structural evaluation of the spinal cord brought critical supplementary data in the initial evaluation of these cases. Although edema and hemorrhage proved to be valuable in predicting the outcome, there is a well-documented discrepancy between MRI findings and clinical status.Methods: We performed diffusion tensor imaging (DTI) MR in 22 symptomatic patients with traumatic cervical spine injuries (mean age 49.6 ± 16, range from 17 to 74 years, 20 males and 2 females). DTI parameters were computed in 15 patients. Regional apparent diffusion coefficient, fractional anisotropy (FA), and fiber length (FL) were calculated in the region of interest defined as the region of maximum structural MR alterations and in the normal cord (above or below the level of the injury). The values for normal and pathological cord were compared. The clinical deficit was assessed with ASIA and subaxial cervical spine injury classification (SLIC) scores. We looked at the correlation between the DTI measures and clinical scores.Results: There is a highly significant difference between normal and pathological spinal cord for all DTI properties measured. There is also a strong correlation between DTI measures and SLIC clinical score, especially for FA. Significant results were obtained for CDA and FL as well although with lesser statistical power.Conclusion: Our results suggest that DTI measures, especially FA, represent a strong indicator of the severity of the traumatic cervical cord injury. It correlates very well with SLCI score and can be used as an additional confirmation of the real degree of level lesioning and as a prognostic factor for the neurological outcome regardless of the choice of treatment.

Vertebral fracture due to Actinobacillus pleuropneumoniae osteomyelitis in a weaner

BackgroundOsteomyelitis is relatively frequent in young pigs and a few bacterial species have been postulated to be potential causative agents. Although Actinobacillus (A.) pleuropneumoniae has been sporadically described to cause osteomyelitis, typically, actinobacillosis is characterized by respiratory symptoms. Nevertheless, subclinical infections are a challenging problem in pig herds. To the authors’ knowledge, this is the first case description that reports clinical, diagnostic imaging, pathological and histopathological findings of vertebral osteomyelitis in a pig and first describes A. pleuropneumoniae as the causative agent identified by advanced molecular methods.Case presentationAn eight-week-old female weaner was presented with a non-ambulatory tetraparesis. The neurological signs were consistent with a lesion in the C6-T2 spinal cord segments. Imaging studies revealed a collapse of the seventh cervical vertebral body (C7) with a well demarcated extradural space-occupying mass ventrally within the vertebral canal severely compressing the spinal cord. Post-mortem examination identified an abscess and osteomyelitis of C7 and associated meningitis and neuritis with subsequent pathological fracture of C7 and compression of the spinal cord. In the microbiological analysis, A. pleuropneumoniae was identified using PCR and DNA sequence analysis.ConclusionsA. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.

Spatio-temporal and Cellular Expression Patterns of PTK7 in the Healthy and Traumatically Injured Rat and Human Spinal Cord.

Despite the emerging role of protein tyrosine kinase 7 (PTK7) as a Wnt co-receptor and the relevant functions of the Wnt family of proteins in spinal cord injury (SCI), the potential involvement of PTK7 in SCI is currently unknown. As a first essential step to shed light on this issue, we evaluated the spatio-temporal and cellular expression patterns of PTK7 in healthy and traumatically injured rat and human spinal cords. In the uninjured rats, PTK7 expression was observed in the ependymal epithelium, endothelial cells, meningeal fibronectin-expressing cells, and specific axonal tracts, but not in microglia, astrocytes, neurons, oligodendrocytes, or NG2+ cells. After rat SCI, the mRNA expression of PTK7 was significantly increased, while its spatio-temporal and cellular protein expression patterns also suffered evident changes in the injured region. Briefly, the expression of PTK7 in the affected areas was observed in axons, reactive astrocytes, NG2+ and fibronectin-expressing cells, and in a subpopulation of reactive microglia/macrophages and blood vessels. Finally, in both healthy and traumatically injured human spinal cords, PTK7 expression pattern was similar to that observed in the rat, although some specific differences were found. In conclusion, we demonstrate for the first time that PTK7 is constitutively expressed in the healthy adult rat and human spinal cord and that its expression pattern clearly varied after rat and human SCI which, to our knowledge, constitutes the first experimental evidence pointing to the potential involvement of this co-receptor in physiological and pathological spinal cord functioning.

Magnetic resonance imaging for assessing treatment response in bone marrow metastases.

Cancer metastasis to bone is a frequent observation in malignancy that may result in complications such as pathological fractures and spinal cord compression. Monitoring treatment effects is the main concern in oncology; however, the evaluation of treatment response in bone is particularly challenging as it lacks well-established criteria. In addition, bone metastases have traditionally been considered non-measurable manifestations of cancer. Magnetic resonance imaging (MRI) is one of the most specific and sensitive methods for imaging skeletal metastases. The aim of this article is to highlight the diagnostic performance of MRI in the treatment monitoring of bone metastases, to review the current literature, and to provide an overview of recommendations for the evaluation of treatment response in bone.

Restless Legs Syndrome/Willis-Ekbom Disease in Multiple Sclerosis Patients with Spinal Cord Lesions.

Spinal cord lesions in Multiple Sclerosis (MS) patients are associated with a higher risk of restless legs syndrome (RLS). In this study, we investigated the prevalence of RLS, sleep quality, presence and severity of depression, and the relationship of these parameters with cervical cord lesions in patients with RRMS. This study was conducted in the outpatient multiple sclerosis clinic of Marmara University Hospital between October 2013 - February 2014, including 93 patients with the diagnosis of MS. After signing informed consent, demographic data, comorbidities and actual medication of the patients were collected. All patients completed the surveys including Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Beck Depression Inventory (BDI). Prevalence of HBS, sleep quality and depression severity were compared between those with and without cervical cord lesions. Furthermore, the relationship between RLS and sleep quality, depression and expanded disability status scale (EDSS) was assessed. From overall patients, 72% were women (n=67) and 28% (n=26) were men. From all subjects, 32% (n=30) fulfilled IRLSSG diagnostic criteria. Fifty-seven percent of the patients (n=53) had pathological spinal cord lesions. Patients with RLS had significantly higher prevalence of pathological spinal cord lesions compared to patients without RLS (p=0.04). Sleep quality was found to be poor in both patients with cervical cord lesions and patients with RLS and this was statistically significant (p=0.031, p=0.0001). In summary, the possibility of RLS development in RRMS patients increases with the presence of lesions in spinal cord. Sleep quality was found to be poor in both patients with cervical cord lesions and patients with RLS. As RLS is a potentially treatable condition, increased awareness of diagnosis of RLS in MS patients may be important for early treatment and improve the comfort of the patient.

Frequency of skeletal-related events and associated healthcare resource use and costs in US patients with multiple myeloma

Objective:A potential complication for all new multiple myeloma (MM) patients is the clinical presentation of osteolytic lesions which increase the risk for skeletal-related events (SREs). However, the contribution of SREs to the overall economic impact of MM is unclear. The impact of SREs on healthcare resource utilization (HCRU) and costs for US patients with MM was analyzed in Truven Health Marketscan Commercial Claims and Medicare Supplemental Databases.Methods:Adults diagnosed with MM between January 1, 2005 and December 31, 2010 with ≥2 claims ≥30 days apart (first claim = index date) were included. SREs included: hypercalcemia, pathologic fracture, surgery for the prevention and treatment of pathologic fractures or spinal cord compression, and radiation for bone pain. Rates of HCRU (outpatient [OP], inpatient [IP], emergency room [ER], orthopedic consultation [OC], and ancillary) and healthcare costs were compared between MM patients with and without SREs. Inverse propensity weighting was applied to adjust for potential bias.Results:Of 1028 MM patients (mean age = 67, standard deviation = 13.2), 596 patients with ≥1 SRE and 432 without SREs were assessed. HCRU rates in IP, ER, and ancillary (p < 0.01) and mean total costs of OP, IP, and ER were significantly higher (p < 0.05) for patients with vs without SREs during follow-up. HCRU rates also increased with SRE frequency (p < 0.05 in OP, IP, ER, OC, and ancillary), as did mean total healthcare costs, except for OC (p < 0.001).Limitations:A broad assessment of pharmacotherapy for the treatment of MM was not an objective of the current study. Bisphosphonate use was evaluated; however, results were descriptively focused on frequency of utilization only and were not included in the broader cost and HCRU analysis.Conclusions:Among US patients with MM, higher SRE frequency was associated with a significant trend of higher HCRU and total healthcare costs in several settings.

Segmentation of the human spinal cord.

Segmenting the spinal cord contour is a necessary step for quantifying spinal cord atrophy in various diseases. Delineating gray matter (GM) and white matter (WM) is also useful for quantifying GM atrophy or for extracting multiparametric MRI metrics into specific WM tracts. Spinal cord segmentation in clinical research is not as developed as brain segmentation, however with the substantial improvement of MR sequences adapted to spinal cord MR investigations, the field of spinal cord MR segmentation has advanced greatly within the last decade. Segmentation techniques with variable accuracy and degree of complexity have been developed and reported in the literature. In this paper, we review some of the existing methods for cord and WM/GM segmentation, including intensity-based, surface-based, and image-based methods. We also provide recommendations for validating spinal cord segmentation techniques, as it is important to understand the intrinsic characteristics of the methods and to evaluate their performance and limitations. Lastly, we illustrate some applications in the healthy and pathological spinal cord. One conclusion of this review is that robust and automatic segmentation is clinically relevant, as it would allow for longitudinal and group studies free from user bias as well as reproducible multicentric studies in large populations, thereby helping to further our understanding of the spinal cord pathophysiology and to develop new criteria for early detection of subclinical evolution for prognosis prediction and for patient management. Another conclusion is that at the present time, no single method adequately segments the cord and its substructure in all the cases encountered (abnormal intensities, loss of contrast, deformation of the cord, etc.). A combination of different approaches is thus advised for future developments, along with the introduction of probabilistic shape models. Maturation of standardized frameworks, multiplatform availability, inclusion in large suite and data sharing would also ultimately benefit to the community.

Endogenous Two-Photon Excited Fluorescence Provides Label-Free Visualization of the Inflammatory Response in the Rodent Spinal Cord.

Activation of CNS resident microglia and invasion of external macrophages plays a central role in spinal cord injuries and diseases. Multiphoton microscopy based on intrinsic tissue properties offers the possibility of label-free imaging and has the potential to be applied in vivo. In this work, we analyzed cellular structures displaying endogenous two-photon excited fluorescence (TPEF) in the pathologic spinal cord. It was compared qualitatively and quantitatively to Iba1 and CD68 immunohistochemical staining in two models: rat spinal cord injury and mouse encephalomyelitis. The extent of tissue damage was retrieved by coherent anti-Stokes Raman scattering (CARS) and second harmonic generation imaging. The pattern of CD68-positive cells representing postinjury activated microglia/macrophages was colocalized to the TPEF signal. Iba1-positive microglia were found in areas lacking any TPEF signal. In peripheral areas of inflammation, we found similar numbers of CD68-positive microglia/macrophages and TPEF-positive structures while the number of Iba1-positive cells was significantly higher. Therefore, we conclude that multiphoton imaging of unstained spinal cord tissue enables retrieving the extent of microglia activation by acquisition of endogenous TPEF. Future application of this technique in vivo will enable monitoring inflammatory responses of the nervous system allowing new insights into degenerative and regenerative processes.

Potential Use of Diffusion Tensor Imaging in Level Diagnosis of Multilevel Cervical Spondylotic Myelopathy

A prospective study on a series of consecutive patients. To investigate the use of diffusion tensor imaging (DTI) and orientation entropy in level localization in patients diagnosed with multilevel cervical spondylotic myelopathy (CSM). Multilevel CSM presents complex neurological signs that make level localization difficult. DTI is recently found to be able to assess the microstructural changes of the white matter caused by cord compression. Sixteen patients with CSM with multilevel compression were recruited. The level(s) responsible for the clinical symptoms were determined by detailed neurological examination, T2-weighted (T2W) magnetic resonance imaging (MRI), and DTI. On T2W MRI, anterior-posterior compression ratio and increased signal intensities were used to determine the affected level(s). The level diagnosis results from T2W MRI, increased signal intensities, DTI, and combination method were correlated to that of neurological examination on a level-to-level basis, respectively. The accuracy, sensitivity, and specificity were calculated. When correlated with the clinical level determination, the weighted orientation entropy-based DTI analysis was found to have higher accuracy (82.76% vs. 75.86%) and sensitivity (84.62% vs. 76.92%) than those of the anterior-posterior compression ratio. The increased signal intensities have the highest specificity (100.00%) but the lowest accuracy (58.62%) and sensitivity (53.85%). When combined with the level diagnosis result of wOE with that of anterior-posterior compression ratio, it demonstrated the highest accuracy and sensitivity that were 93.10% and 96.15%, respectively, and equal specificity (66.67%) with using them individually. DTI can be a useful tool to determine the pathological spinal cord levels in multilevel CSM. This information from orientation entropy-based DTI analysis, in addition to conventional MRI and clinical neurological assessment, should help spine surgeons in deciding the optimal surgical strategy.