Posterolateral lumbar spine fusion using a novel demineralized bone matrix: a controlled case pilot study

Introduction: Intertransverse posterolateral fusion along with instrumentation is a common technique used for spinal fusion. Iliac crest bone graft (ICBG) offers good fusion success rates with a low risk for disease transmission but is, however, linked with certain morbidity. In an effort to eliminate or reduce the amount of iliac graft needed, bone substitutes including demineralized bone matrix (DBM) have been developed. This study evaluates a novel DBM (Accell Connexus®) used in one or two-level instrumented posterolateral lumbar fusion. Materials and methods: A total of 59 consecutive patients were studied as two groups. Group 1 consisted of 33 patients having Accell Connexus® used to augment either ICBG or local decompression material. Group 2 consisted of 26 consecutive patients, operated prior to the introduction of this novel DBM, having either ICBG alone or local decompression material. Fusion was assessed by two independent observers, blinded to graft material, using standardized criteria found in the literature. All adverse events were recorded prospectively. Results: The results show no statistically significant differences between the two groups in fusion rates, complications, surgery duration, ODI, or pain on VAS. Logistical regression showed no relation between fusion and age, smoking status or comorbidities. Furthermore, no adverse events related to the use of the novel DBM were observed. Conclusion: The results from this study demonstrate that the novel DBM presented performs equally as well as that of autologous bone, be it either ICBG or a local decompression material, and can therefore be used as a graft extende

Massive Uterine Leiomyoma in a Patient with Friedreich's Ataxia: Is There a Possible Association?

A possible association between Friedreich's ataxia (FA) and neoplastic development has been recognized. FA patients have low frataxin levels and insufficient response to oxidative stress. In these patients fibroblasts are characterized by a high rate of mutations. Herein, a case of a 39-year-old woman with FA tetraplegia, who was admitted in our department with intestinal obstruction due to a huge uterine tumor, is described. An abdominal CT revealed a huge intra-abdominal mass originating from the right cornu of the uterus. Tumor excision and adhesionlysis were performed. The histological examination of the tumor revealed a leiomyoma. FA patients seem to present with a variety of neoplasms uncommon for their young age. This is the first report of a leiomyoma originating from the genital system in a female patient with FA tetraplegia. Therefore it is important to identify neoplasms at an early stage in patients with FA and start immediate therapy

Neuroprotection in the Injured Spinal Cord : Novel Strategies using Immunomodulation, Stem cell Transplantation and Hyaluronic acid Hydrogel carriers

The overall aim of this thesis was to establish strategies to minimize secondary damage to the injured spinal cord. Secondary damage that follows spinal cord injury (SCI) involves inflammatory and excitotoxic pathways. Regulation of these pathways using immunomodulatory and neuroprotective substances potentially protects the injured spinal cord from further damage. We also developed and studied resorbable biomaterials to be used as carriers for potential neuroprotectants to the injured spinal cord. We used transversal spinal cord slice cultures (SCSCs) derived from postnatal mice as a model. SCSCs were maintained on different biomaterials and were studied after treatment with immunomodulatory and/or neurotrophic factors. They were further excitotoxically injured and subsequently treated with interleukin-1 receptor antagonist (IL1RA) or by neural crest stem cell (NCSC)-transplantation. The results show that biocompatible and resorbable hydrogels based on hyaluronic acid (HA) preserved neurons in SCSCs to a much higher extent than a conventional collagen-based biomaterial or standard polyethylene terephthalate (PET) membrane inserts. Glial activation was limited in the cultures maintained on HA-based hydrogel. The anti-inflammatory factor IL1RA protected SCSCs from degenerative mechanisms that occur during in vitro incubation, and IL1RA also protected SCSCs from excitotoxic injury induced by N-Methyl-d-Aspartate (NMDA). IL1RA specifically protected neurons that resided in the ventral horn, while other neuronal populations such as dorsal horn neurons and Renshaw cells did not respond to treatment. Finally, transplantation of NCSCs onto excitotoxically injured SCSCs protected from neuronal loss, apoptosis and glial activation, while NCSCs remained undifferentiated. The results presented in this thesis indicate that carriers based on HA seem to be more suitable than conventional collagen-based biomaterials since they enhance neuronal survival per se. The observed neuroprotection is likely due to biomechanical properties of HA. IL1RA protects SCSCs from spontaneous degeneration and from NMDA-induced injury, suggesting that excitotoxic mechanisms can be modulated through anti-inflammatory pathways. Different neuronal populations are affected by IL1RA to various degrees, suggesting that a combination of different neuroprotectants should be used in treatment strategies after SCI. Finally, NCSCs seem to protect SCSCs from excitotoxic injury through paracrine actions, since they remain undifferentiated and do not migrate into the tissue during in vitro incubation. It seems that combinations of neuroprotectants and carrier substances should be considered rather than one single strategy when designing future treatments for SCI. Incorporation of neuroprotectants such as IL1RA combined with stem cells in injectable biocompatible carriers based on HA is the final goal of our group in the treatment of SCI

Preoperative MRI and Intraoperative Monitoring Differentially Prevent Neurological Sequelae in Idiopathic Scoliosis Surgical Correction, While Curves >70 Degrees Increase the Risk of Neurophysiological Incidences

The aim was to investigate the role of preoperative magnetic resonance imaging (MRI) and intraoperative monitoring (IOM) in the prevention of correction-related complications in idiopathic scoliosis (IS). We conducted a retrospective case study of 129 patients with juvenile and adolescent IS. The operations took place between 2005 and 2018 in Uppsala University Hospital. Data from MRI scans and IOM were collected. The patients were divided into groups depending on Lenke's classification, sex, major curve (MC) size, and onset age. Neurophysiological incidences were reported in ten patients (7.8%), while nine of them had no signs of intraspinal pathology. Six patients (4.7%) had transient incidences; however, in four patients (3.1%), an intervention was required for the normalization of action potentials. Three of them had an MC >70 degrees, which was significantly higher than the expected value. Eight patients (6.1%) had intraspinal pathologies, and two of them (1.5%) underwent decompression. We suggest the continuation of MRI screening preoperatively and, most importantly, the use of IOM. In three cases with no signs of pathology in the MRI, IOM prevented possible neurological injuries. MCs >70 degrees should be considered a risk factor for the occurrence of neurophysiological deficiencies that require action to be normalized

Coexistence of up-regulated NMDA receptor 1 and glutamate on nerves, vessels and transformed tenocytes in tendinopathy

Elevated levels of the neurotransmitter glutamate and the presence of its receptor, N-methyl-d-aspartate receptor type 1 (NMDAR1), have been established in patients with tendinopathy, i.e. chronic tendon pain and degeneration. However, whether NMDAR1 is up- or down-regulated in tendinopathy and co-localized with glutamate is still unexplored. We hypothesize that an alteration in tissue expression and in the coexistence of NMDAR1 and glutamate occurs in tendinopathy and might play a role in nociception and possibly also progression of tendon degeneration (tendinosis). We therefore examined the tissue distribution and levels of NMDAR1 and glutamate in biopsies from patients with patellar tendinopathy (n=10) and from controls (n=8). The biopsies were single- and double-stained immunohistochemically for glutamate and NMDAR1 and assessed subjectively and semi-quantitatively. The chronic painful tendons exhibited a significant elevation of NMDAR1 (ninefold), which was independent of the observed increase in glutamate (10-fold). This up-regulation of NMDAR1 and glutamate was found to be co-localized on nerve fibers as well as on morphologically altered tenocytes and blood vessels. None of the controls exhibited neuronal coexistence of glutamate and NMDAR1. The neuronal coexistence of glutamate and NMDAR1, observed in painful tendinosis but not in controls, suggests a regulatory role in intensified pain signalling

Neural crest stem cells protect spinal cord neurons from excitotoxic damage and inhibit glial activation by secretion of brain-derived neurotrophic factor

The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to N-methyl-d-aspartate (NMDA)-induced injury. Immunohistochemistry and TUNEL staining were used to quantitatively study cell populations and apoptosis. Concentrations of neurotrophic factors were measured by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of NeuN-positive neurons that was otherwise observed after NMDA-induced excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced activation of both microglial cells and astrocytes. The concentration of brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects of NCSC application on SCSCs. NCSCs migrated superficially across the surface of SCSCs and showed no signs of neuronal or glial differentiation but preserved their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord tissue, some of these effects mediated by secretion of BDNF. However, the investigated NCSCs seem not to undergo neuronal or glial differentiation in the short term since markers indicative of an undifferentiated state were expressed during the entire observation period

Study protocol for a randomised controlled trial with clinical, neurophysiological, laboratory and radiological outcome for surgical versus non-surgical treatment for lumbar spinal stenosis : the Uppsala Spinal Stenosis Trial (UppSten)

Introduction: Symptomatic lumbar spinal stenosis is the most common indication for spinal surgery. However, more than one-third of the patients undergoing surgery for lumbar stenosis report dissatisfaction with the results. On the other hand, conservative treatment has shown positive results in some cases. This trial will compare the outcomes of surgical versus non-surgical treatment for lumbar stenosis. The study includes a multidimensional follow-up, aiming to study the association between outcome and other studied parameters, mainly electromyography and nerve conduction. Moreover, it may contribute to a better understanding of the pathophysiology of lumbar stenosis and to the development of future pharmacological treatments. Methods and analysis: UppSten is a single-centre randomised controlled trial in which 150 patients with symptomatic lumbar spinal stenosis will be randomised into one of two treatment arms. The patients in the surgical arm will undergo laminectomy; the patients in the non-surgical arm will be given a structured physical training programme. The primary outcome of the study will be the Oswestry Disability Index. Secondary outcomes will include motor amplitude and degree of denervation activity obtained by means of nerve conduction studies and electromyography. Patient-reported outcome measures will be also used as secondary outcomes. Blood sample analysis and the investigation of potential inflammation markers are the additional secondary outcome parameters. Laboratory evaluation will include blood sample collection before the treatment initiation and after 6 months. Flavum ligament biopsies will be performed in the surgical group. Finally, tertiary outcomes will include neurophysiological measures, the objective walking ability and radiological evaluation. Ethics and dissemination: The study is approved by the Local Ethics Committee (Dnr 2017-506), the Hospital's Clinical Trials Committee (2018-0001) and the National Biobank Council and Uppsala Biobank (BbA-827-2018-025).

Lung cancer induced from chemotherapy a 20 years old case

Lung cancer is diagnosed at a late stage although we have novel diagnostic tools. The association of smoking and other environmental factors are well known. However; there are cases where a malignancy is associated with previous radiation treatment. There is an association between radiotherapy treatment and cancer incidence. We present a case where lung cancer and laryngeal cancer was induced 20 years after radiation therapy of a hogkin lymphoma. Keywords: Hodgkin lymphoma, Laryngeal cancer, Lung cancer, Radiation, EBU