Concept: Degenerative disc disease
Degenerative changes are commonly found in spine imaging but often occur in pain-free individuals as well as those with back pain. We sought to estimate the prevalence, by age, of common degenerative spine conditions by performing a systematic review studying the prevalence of spine degeneration on imaging in asymptomatic individuals.
Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells. We used primary Ercc1 (-/-) murine embryonic fibroblasts with reduced DNA repair capacity, which senesce rapidly if grown at atmospheric oxygen. This platform was used to screen a small library of compounds that regulate autophagy, identifying two inhibitors of the HSP90 chaperone family as having significant senolytic activity in mouse and human cells. Treatment of Ercc1 (-/∆) mice, a mouse model of a human progeroid syndrome, with the HSP90 inhibitor 17-DMAG extended healthspan, delayed the onset of several age-related symptoms and reduced p16(INK4a) expression. These results demonstrate the utility of our screening platform to identify senotherapeutic agents as well as identified HSP90 inhibitors as a promising new class of senolytic drugs.The accumulation of senescent cells is thought to contribute to the age-associated decline in tissue function. Here, the authors identify HSP90 inhibitors as a new class of senolytic compounds in an in vitro screening and show that administration of a HSP90 inhibitor reduces age-related symptoms in progeroid mice.
Cervical Spondylotic Myelopathy: The Clinical Phenomenon and the Current Pathobiology of an Increasingly Prevalent and Devastating Disorder.
- The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
- Published over 7 years ago
Cervical spondylotic myelopathy (CSM) is a common disorder involving chronic progressive compression of the cervical spinal cord due to degenerative disc disease, spondylosis, or other degenerative pathology. CSM is the most common form of spinal cord impairment and causes functional decline leading to reduced independence and quality of life. Despite a sound understanding of the disease process, clinical presentation and management, a universal definition of CSM and a standardized index of severity are not currently used universally. Work is required to develop a definition and establish clinical predictors of progression to improve management of CSM. Despite advances in decompressive and reconstructive surgery, patients are often left with residual disability. Gaps in knowledge of the pathobiology of CSM have limited therapeutic advances to complement surgery. Although the histopathologic and pathophysiologic similarities between CSM and traumatic spinal cord injury have long been acknowledged, the unique pathomechanisms of CSM remain unexplored. Increased efforts to elucidate CSM pathobiology could lead to the discovery of novel therapeutic targets for human CSM and other spinal cord diseases. Here, the natural history of CSM, epidemiology, clinical presentation, and current methods of clinical management are reported, along with the current state of basic scientific research in the field.
Object The purpose of the study was to evaluate the safety and initial efficacy of NuQu allogeneic juvenile chondrocytes delivered percutaneously for the treatment of lumbar spondylosis with mechanical low-back pain (LBP). NuQu is a cell-based biological therapy for disc repair. The authors report the results at 12 months of the NuQu Phase I investigational new drug (IND) single-arm, prospective feasibility study for the treatment of LBP for single-level degenerative disc disease (Pfirrman Grades III-IV) at L3-S1. Methods Fifteen patients (6 women and 9 men) were enrolled at 2 sites. Institutional review board approval was obtained, and all patients signed a study-specific informed consent. All patients have completed a minimum of 1 year of follow-up. Patients were evaluated pretreatment and at 1, 3, 6, and 12 months posttreatment. Evaluations included routine neurological examinations, serum liver and renal function studies, MRI, the Oswestry Disability Index (ODI), the Numerical Rating Scale (NRS), and the 36-Item Short Form Health Survey (SF-36). Results Fifteen patients were treated with a single percutaneous delivery of NuQu juvenile chondrocytes. The mean patient age was 40 years (19-47 years). Each treatment consisted of 1-2 ml (mean injection 1.3 ml) of juvenile chondrocytes (approximately 10(7) chondrocyte cells/ml) with fibrin carrier. The mean peak pressure during treatment was 87.6 psi. The treatment time ranged from 5 to 33 seconds. The mean ODI (baseline 53.3, 12-month 20.3; p < 0.0001), NRS (baseline 5.7, 12-month 3.1; p = 0.0025), and SF-36 physical component summary (baseline 35.3, 12-month 46.9; p = 0.0002) scores all improved significantly from baseline. At the 6-month follow-up, 13 patients underwent MRI (one patient underwent CT imaging and another refused imaging). Ten (77%) of these 13 patients exhibited improvements on MRI. Three of these patients showed improvement in disc contour or height. High-intensity zones (HIZs), consistent with posterior anular tears, were present at baseline in 9 patients. Of these, the HIZ was either absent or improved in 8 patients (89%) by 6 months. The HIZ was improved in the ninth patient at 3 months, with no further MRI follow-up. Of the 10 patients who exhibited radiological improvement at 6 months, findings continued to improve or were sustained in 8 patients at the 12-month follow-up. No patient experienced neurological deterioration. There were no disc infections, and there were no serious or unexpected adverse events. Three patients (20%) underwent total disc replacement by the 12-month follow-up due to persistent, but not worse than baseline, LBP. Conclusions This is a 12-month report of the clinical and radiographic results from a US IND study of cell-based therapy (juvenile chondrocytes) in the treatment of lumbar spondylosis with mechanical LBP. The results of this prospective cohort are promising and warrant further investigation with a prospective, randomized, double-blinded, placebo-controlled study design. Clinical trial registration no.: BB-IND 13985.
Magnetic resonance (MR) imaging in patients with persistent low back pain and sciatica effectively demonstrates spine anatomy and the relationship of nerve roots and intervertebral disks. Except in cases with nerve root compression, disk extrusion, or central stenosis, conventional anatomic MR images do not help distinguish effectively between painful and nonpainful degenerating disks. Hypoxia, inflammation, innervation, accelerated catabolism, and reduced water and glycosaminoglycan content characterize degenerated disks, the extent of which may distinguish nonpainful from painful ones. Applied to the spine, “functional” imaging techniques such as MR spectroscopy, T1ρ calculation, T2 relaxation time measurement, diffusion quantitative imaging, and radio nucleotide imaging provide measurements of some of these degenerative features. Novel minimally invasive therapies, with injected growth factors or genetic materials, target these processes in the disk and effectively reverse degeneration in controlled laboratory conditions. Functional imaging has applications in clinical trials to evaluate the efficacy of these therapies and eventually to select patients for treatment. This report summarizes the biochemical processes in disk degeneration, the application of advanced disk imaging techniques, and the novel biologic therapies that presently have the most clinical promise.
Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet rich plasma (PRP) can be obtained from peripheral blood. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF and PRP intra-discally into patients with degenerative disc disease.
Study Design. A case report by Kara Krajewski and Jan Regelsberger.Objective. To demonstrate a case of intradural lumbar disc herniation including imaging studies, intraoperative imaging and an intraoperative video.Summary of Background Data. The first case of lumbar intradural disc herniation was reported as early as 1942; since then over 150 cases have been reported, mostly in the lumbar spine. Gadolinium-enhanced MRI is considered the gold standard for diagnosing this entity, though it is rarely peformed routinely in lumbar disc disease and diagnosis is often made intraoperatively.Methods. A 70-year-old man presented to the emergency department as a referral complaining of lower back pain, loss of sensation in the right thigh and difficulty walking. On examination, he showed uneven gait, right-sided foot drop (1/5), hypesthesias in the right inguinal area and ventral thigh and a positive straight leg raise test on the right. Anal sphincter tone was within normal limits. An MRI of the lumbar spine showed a large mediolateral herniated disc at L3/4, with caudal displacement and unclear signal changes intradurally.Results. Intraoperatively, the herniated disc was found upon opening the dural sac.Conclusion. Intradural disc herniations are a rare entity. The opening and inspection of the dural sack should be considered when the correct spinal level can be confirmed and insufficient herniated disc material can be visualized extradurally.
STUDY DESIGN:: Retrospectively study. OBJECTIVES:: To evaluate clinical and radiological outcomes of skip-level anterior cervical discectomy and fusion (ACDF) with self-locking stand-alone polyetheretherketone (PEEK) cages for the treatment of two noncontiguous levels of cervical disc degenerative disease (CDDD). SUMMARY OF BACKGROUND DATA:: The use of stand-alone PEEK cages in ACDF has been proved to be safe and effective to treat CDDD. For two noncontiguous levels of CDDD, skip-level ACDF with self-locking stand-alone PEEK cages, which fuses only the involved levels without anterior plates, may be the optimal treatment choice. METHODS:: Sixteen consecutive patients with two noncontiguous levels of CDDD underwent skip-level ACDF with self-locking stand-alone PEEK cages. Clinical outcomes were evaluated using Japanese Orthopaedic Association (JOA) scores and Odom’s criteria. Fusion rate and time, cages subsidence, spinal curvature, intervertebral height at the operated level, and adjacent disc degeneration were assessed. RESULTS:: Patients were followed up for average 43.6 months (range 24-78 mo). The mean operative time was 113 minutes (range 98-134 min) with an average blood loss of 62 mL (range 47-76 mL). The JOA score, degree of spinal curvature, and intervertebral height were significantly increased at the final follow-up examination compared with preoperatively (P<0.05). Fifteen patients (93.8%) achieved solid fusion in an average time of 5.1 months. Three cages (9.38%) in two patients subsided. Radiological evidence of adjacent segment degeneration was observed in three segments (6.25%; two infra-adjacent segments and one intermediate segment). No case had neurological deterioration postoperatively. No implant failure or migration was observed during follow-up. CONCLUSIONS:: Treatment of two noncontiguous levels of CDDD with skip-level ACDF with self-locking stand-alone cages achieved good clinical and radiological outcomes including a high fusion rate, low complication rate, and excellent maintenance of spinal curvature and intervertebral height.
- Journal of neurological surgery. Part A, Central European neurosurgery
- Published over 7 years ago
Background Minimally invasive techniques in spine surgery have gained significant popularity due to decreased tissue dissection and destruction, postoperative pain, and hospital stay. The laparoscopic anterior lumbar interbody fusion (ALIF), an innovation in minimally invasive spine surgery, is rarely done because it has marginal benefit over the mini-open ALIF technique in rates of retrograde ejaculation and vascular complications. We propose these outcomes can be improved with enhanced robotic-assisted dissection and exposure for ALIF. Patients Two patients with single-level degenerative spine disease at L5-S1, associated with mechanical back pain, underwent anterior spinal exposure using the da Vinci S Surgical Robot during ALIF. Results In this report, we provide the first description of the use of a surgical robot in the dissection and exposure for ALIF in patients with degenerative spine disease. We demonstrate successful use of the da Vinci Surgical Robot in separating the presacral nervous plexus from retroperitoneal structures without postoperative vascular or urological complications over a 1-year follow-up period. Conclusion Use of the robotic assistance in the performance of ALIF is possible without significant operative complications. This technique may provide added benefit over conventional laparoscopic approaches to the spine.
In part, people’s quality of life depends on the “health” of their cartilage because its damage or deterioration causes pain that limits mobility and reduces autonomy. Predisposing genetic factors and modern-life environmental factors, such as diet, excessive physical exercise, or the absence of any physical exercise, in addition to injuries that can occur, all contribute to the onset and development of chronic degenerative diseases such as osteoarthritis. Regenerative medicine focuses on the repair, replacement, or regeneration of cells, tissues, or organs to restore impaired function from any cause, including congenital defects, disease, and trauma.