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Introduction : The importance of excessive cerebral tumor necrosis factor (TNF) concentrations as one of the central tenets of the pathogenesis of the neurodegenerative diseases is now widely known, but variably accepted. Areas covered : Here we update the field by including material that is freely available on the large databases, particularly PubMed. We include the therapeutic outcomes with etanercept (a widely used specific anti-TNF biological), XPro1595 (a new double negative TNF inhibitor), 3,6 1 -dithiothalidomide, implanted SB623 stem cells, maraviroc (a CCR5 inhibitor used to treat AIDS), MCC950 (an NLRP3 inhibitor), and changes in the hormone irisin. Expert opinion : Remarkably, considering the ample literature that links SB623 cells, maraviroc, MCC950 and irisin to TNF, these publications do not mention this cytokine, and therefore not their implicit involvement with controlling its cerebral levels. With regard to developments demonstrated by MCC950, we note that DAMPs and PAMPs recognize and activate both TLRs and inflammasomes in these disease states. Here, as in other illnesses, data suggests that preventing a pathogenic interaction could be achieved through shutting down either of these arms of innate immunity.

Background and Aim: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are one of the sources of adult stem cells being explored for potential use in repairing neurodegenerative disorders. In this study, it was aimed to investigate the useful effects of BM-MSCs therapy on the streptozotocin-induced neurodegeneration in rats., Materials and Methods: Adult female Wistar rats were bilaterally injected intra-cerebroventricularly with streptozotocin (3 mg/kg) for neurodegeneration. Water maze tests were used to monitor spatial learning and memory. One or two intravenous injections of BM-MSCs were administrated to rat via the tail veins. At the end of the study, all rats were sacrificed for histological evaluation and immunohistochemistry., Results: Streptozotocin group demonstrated a significant increase in escape latency in comparison with both control groups (Sham and Saline), whereas rats treated with BM-MSCs exhibited a decrease in escape latency in comparison with streptozotocin group. The percentage of time spent in the target quadrant and the mean number of platform crossings did not change in all the groups. BM-MSCs administration improved spatial learning but not memory. However, improvement in neuronal cells in hippocampal CA1 region was only observed in the rats treated with BM-MSCs twice as opposed to the rats treated with BM-MSCs once or with saline., Conclusions: In this study, mesenchymal stem cells therapy failed to improve the streptozotocin-induced neurodegeneration like Alzheimer's disease in rats.

Introduction: An accidental durotomy is a recognised and not infrequent complication of lumbar spine surgery, and may lead to postoperative low-pressure headaches, pseudomeningocele and CSF leak. Conventional postoperative management involves a period of flat bed rest. There is no agreement as to the need for and duration of postoperative bed rest. This study aims to determine whether the duration of flat bed rest alters the rate of these complications., Materials and Methods: This is a retrospective study. All patients who underwent surgery for degenerative spinal disease between May 2010 and May 2011 were reviewed. All patients who incurred an accidental durotomy and who were repaired using fibrin glue were included in this study. Their notes were reviewed for evidence of complications for a minimum of 12 months after surgery. The following complications were identified: postural headache, pseudomeningocele, CSF leak wound infection, subdural haematoma., Results: Eight hundred and eighty-nine patients underwent lumbar spine surgery. Sixty-one (6.8%) patients suffered an accidental durotomy and were repaired with fibrin glue. Twenty-six patients were mobilised on the first postoperative day, 9 patients on the second, and a further 26 patients were mobilised on the third postoperative day or later. The overall incidence of complications related to the durotomy was 18%. There was no statistical significance between the day of mobilisation and the rate of complication (p = 0.433)., Conclusion: A longer period of mandatory bed rest does not decrease the rate of complications. Patients should be mobilised as soon as they can. This could potentially reduce the length of hospital stay and the cost of aftercare.

Summary of Background Data: Physical outcomes following surgery for degenerative spine disease have been well studied whereas the importance of psychological factors has only recently been acknowledged. Previous studies suggest that pre-operative psychological distress predicts poor outcome from spinal surgery. In the drive to identify patients who will not benefit, these patients risk being denied surgery., Study Design: This is a prospective series from a spinal surgical register., Aim: The study examines the relationship between the physical symptoms, pre-operative psychological distress and outcome following surgery., Methods: The Short Form 36 (SF36) Health Survey Questionnaire and the Hospital Anxiety and Depression Scale (HADS) were administered to patients undergoing elective surgery for degenerative spine disease pre-operatively and at 3 and 12 months post-operatively. Levels of physical disability (SF-36 physical functioning (SF36PF) and bodily pain (SF36BP) scores) and psychological distress (HADS-anxiety and HADS-depression scores) before and after surgery were compared., Results: A total of 302 patients were included (169 men, 133 women, mean age 55 years). Pre-operatively patients had worse physical scores than age-matched controls (SF36PF normative mean (S.D.) 80.97 (12.69) vs. pre-op 33.31 (24.7) P < 0.05). Of the 302 patients, 117 (39%) had significant anxiety or depression. Increased levels of anxiety or depression pre-operatively correlated with worse physical (SF-36PF and SF-36BP) scores pre-operatively (Spearman's r P < 0.05). Levels of anxiety and depression were reduced post-operatively and physical outcomes improved post-operatively. Physical function remained worse in those groups who had high levels of anxiety and depression pre-operatively but when matched for pre-operative physical function, psychological distress did not have any additional effect on outcome., Conclusions: Poor physical function pre-operatively correlates with psychological distress. Both physical and psychological symptoms improve after surgery. Physical outcome after surgery is strongly influenced by pre-operative physical functioning but not independently by psychological distress. Anxious and depressed patients should continue to be offered surgery if clinically indicated.

Background: This study compared prospectively the quality of life (QoL), function and mood of patients about to undergo surgery for either an intracranial supratentorial tumour or a spinal degenerative condition. The QoL scores were also compared to that of cohorts with a range of extracranial cancers., Material and Methods: The study took place in a Scottish NHS Neurosurgical Unit. Patients were assessed on the day prior to surgery for their QoL (European Organisation for Research and Treatment of Cancer (EORTC)-QLQ C30), mood status (Hospital Anxiety and Depression Score), Performance status (Karnosky Score, timed 10-m walk) and disability (Barthel Disability Index). All tests were performed by a single trained psychologist., Results: Between 2007 and 2009, 101 patients with intracranial tumours, 75 age- and gender-matched patients with degenerative spinal disorders and 80 healthy adults were evaluated. There was no difference in the mood or disability scores between the two patient cohorts, but mood was significantly worse than a matched healthy cohort. The spinal cohort had significantly worse scores on the Karnovsky Scale, timed 10-m walk and for Global Health than those of the brain tumour cohort. They also had worse mean scores on all five functional scales, as well as six of the nine symptom/single-item scales, of the EORTC QLQ C30., Summary: Patients with degenerative spinal disorders awaiting surgery on the NHS have significantly impaired QoL in multiple domains as well as other functional and mood disorders. Not only are their scores worse than a brain tumour cohort but they are also worse than many cancer cohorts described in the literature using the EORTC QLQ C30. These findings suggest that preoperative care, assessment and management of NHS patients with degenerative spinal disorders could be improved and that the EORTC QLQ C30 may be a useful tool for audit purposes in this cohort.

Objectives: Advances in spinal fusion techniques have led to an increase in the need for safe access to the lumbar spine anteriorly. The aim of this study is to examine the procedure-related complications of anterior lumbar inter-body fusion (ALIF) or anterior lumbar disc replacement (ALDR) when performed jointly by a vascular-surgeon and a neurosurgeon in a single centre., Methods: A retrospective cohort analysis was conducted for all patients who underwent ALIF or ALDR between 2004 and 2010. Operative notes were examined to identify any procedure-specific complications. In-hospital postoperative complications were recorded. Outpatients' records were reviewed to record any late-onset postoperative complications., Results: A total of 121 patients (68 female and 53 males) were included. Mean age was 44 years (range of 25-76). Eighty patients (66%) had ALIF while 24 patients (20%) underwent ALDR. The remaining 17 patients (14%) had combined procedure for multilevel disease. In all patients, a transperitoneal approach was performed by vascular surgeon. The main indication (88%) for performing surgery was degenerative lumbar disc disease. No visceral or 'major vascular' complications were reported in any patients. Only three patients had 'minor vascular' injuries. The only significant postoperative complication was self-limiting paralytic ileus affecting 18 patients (14.8%). Hospital stay ranged from 4 to 9 days (median of 5 days)., Conclusions: The anterior lumbar approach is not generally favoured by many neurosurgeons, despite its many advantages, due to the significant risk of vascular injuries as reported in the literature. This risk is especially acknowledged by the emerging generation of neurosurgeons with very little general surgical exposure during the training years. Adopting a combined vascular and neurosurgical approach has been reported to reduce the risk of vascular injury in anterior lumbar surgery acceptably low. This team approach provides an excellent opportunity to preserve some key 'general' surgical skills for neurosurgeons and ensure safe outcome for the patients.

One of the most promising methods to treat neurodegeneration is noninvasive transcranial near-infrared laser therapy (NILT), which appears to promote acute neuroprotection by stimulating mitochondrial function, thereby increasing cellular energy production. NILT may also promote chronic neuronal function restoration via trophic factor-mediated plasticity changes or possibly neurogenesis. Clearly, NILT is a treatment that confers neuroprotection or neurorestoration using pleiotropic mechanisms. The most advanced application of NILT is for acute ischemic stroke based upon extensive preclinical and clinical studies. In laboratory settings, NILT is also being developed to treat traumatic brain injury, Alzheimer's disease and Parkinson's disease. There is some intriguing data in the literature that suggests that NILT may be a method to promote clinical improvement in neurodegenerative diseases where there is a common mechanistic component, mitochondrial dysfunction and energy impairment. This article will analyze and review data supporting the continued development of NILT to treat neurodegenerative diseases.

Introduction: Cell transplants to replace cells lost due to injury or degenerative diseases, for which there are currently no cures, are being pursued in a wide range of experimental models. Thus, the application of stem cell-based therapies to treat neurodegenerative and traumatic injuries is now a clinical reality. However, the monitoring of cellular grafts, non-invasively, is an important aspect of the ongoing efficacy and safety assessment of cell-based therapies. Hence, there is a need for non-invasive imaging techniques to ensure that transplants are not only administered to the relevant site, but also allow the monitoring of inappropriate cellular migration to improve our understanding of stem cell migration in the context of the whole organism., Areas Covered: This review provides an up to date overview of molecular imaging approaches that have been used for visualizing and tracking transplanted stem cells, in vivo., Expert Opinion: It's important to emphasize that the application of molecular imaging to interrogate transplanted cells may require one or even two imaging modalities to provide a reasonable assessment of transplanted cells in specific organs.

Background: Stem-cell-based therapy is a promising new approach to handling neurodegenerative diseases. One of the most promising cellular sources is bone-marrow-derived mesenchymal stem cells (MSCs) also termed multipotent stromal cells. MSCs represent an autologous source and are abundant and non-tumorigenic. Additionally, MSCs possess the useful characteristics of homing and chemokine secretion., Objective/methods: Since neurodegenerative diseases have many pathological processes in common, a specific therapeutic agent could potentially ameliorate the symptoms of several distinct neurodegenerative diseases. In this review we demonstrate the wide variety of mechanisms by which MSCs can influence neurodegenerative processes., Results/conclusions: The mechanisms by which transplanted MSCs influence neurodegenerative diseases can be broadly classified as cellular replacement or paracrine secretion, with the latter subdivided into trophic factor secretion or immunomodulation by cytokines. Emerging research suggests that genetic manipulations before transplantation could enhance the therapeutic potential of MSCs. Such manipulation could turn the cells into a 'Trojan horse', to deliver specific proteins, or promote reprogramming of the MSCs into the neural lineage. Clinical trials testing MSC-based therapies for familial amyotrophic lateral sclerosis and multiple sclerosis are in progress.

Many neurodegenerative diseases are attributed to the degeneration of neurons with subsequent functional loss. Cell transplantation is a strategy with potential for treating such diseases, and many kinds of cells are considered candidates for transplantation therapy. Bone marrow stromal cells (MSCs) have great potential as therapeutic agents, as they are easy to isolate and expand from patients without serious ethical and technical problems. The authors have found a method for the highly efficient, exclusive and specific induction of functional postmitotic neuronal cells from both rat and human MSCs. Gene transfer of Notch intracellular domain (NICD) followed by the administration of certain trophic factors induced mature neurons expressing neuronal markers, some of which showed action potentials. Induced neurons were transplanted to animal models of neurodegenerative disorders, including Parkinson's disease and ischaemic brain injury, resulting in the successful integration of transplanted cells and improvement in function of the transplanted animals. This review summarises the respective potentials, benefits and drawbacks of MSC-derived neurons, and discusses the possibility of their clinical application in neurodegenerative diseases.