Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs

Methods@#Forty NP tissues were snap-frozen in liquid nitrogen (–196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). @*Results@#Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan–collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. @*Conclusions@#COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

In Vertebral Hemangiomas with Neurological Deficit, Is a Less Extensive Approach Adequate

Methods@#Twenty-one patients who underwent surgery for AVH between 2009 and 2018 were analyzed. Demographic and clinical details of patients were retrieved from hospital information system. Imaging information (i.e., radiography, computed tomography, magnetic resonance imaging) of all patients was accessed and analyzed in picture archiving and communication system. Tumor staging was performed using Enneking and Weinstein–Boriani–Biagini classifications and Spinal Instability Neoplastic Score. At followup, neurological and radiological evaluations were performed. @*Results@#Twenty-one patients (13 [61.9%] females and 8 [38.1%] males) were included with a mean age of 44.29 years (range, 14–72 years). All patients in the study had neurological deficit. Back pain was present in 80.9% of patients. Mean duration of symptoms was 4.6 months (range, 1 day to 10 months). Most common lesion location was thoracic spine (n=12), followed by thoracolumbar (D11– L2; n=7) and lumbar (n=2) regions. Ten patients had multiple level lesions. All patients underwent preoperative embolization. Nine patients underwent intralesional spondylectomy with reconstruction; another nine patients underwent stabilization, decompression, and vertebroplasty; three patients underwent decompression and stabilization. Neurology improved in all patients, and only one case of recurrence was noted in a mean follow-up of 55.78±25 months (range, 24–96 months). @*Conclusions@#In AVH, good clinical and neurological outcomes with low recurrence rates can be achieved using less extensive procedures, such as posterior instrumented decompression with vertebroplasty and intralesional tumor resection.

Analysis of Postoperative Clinical Outcomes in Cervical Myelopathy due to Ossification of Posterior Longitudinal Ligament Involving C2

Methods@#We retrospectively studied 61 patients with C2 (+) OPLL who had posterior instrumented laminectomy and fusion at Ganga Hospital, Coimbatore between July 2011 and January 2021, with a minimum follow-up of 2 years. Data on demographics, clinical outcomes, radiology, and post-surgical outcomes were gathered. @*Results@#Among 61 patients, 56 were males and five were females. The OPLL pattern was mixed in 32 cases (52.5%), continuous in 26 cases (42.6%), segmental in two cases (3.3%), and circumscribed in one patient (1.6%). All of our patients showed signs of neurological improvement after a 24-month follow-up. The mean preoperative modified Japanese Orthopaedic Association (mJOA) score was 10.6 (range, 5–11) and the postoperative mJOA score was 15.8 (range, 12–18). The recovery rate was >75% in 27 patients (44.6%), >50% in 32 patients (52.5%), and >25% in two patients (3.3%). The average recovery rate was 71% (range, 33%–100%). The independent risk factor for predicting recovery rate is the preoperative mJOA score. @*Conclusions@#In C2 (+) OPLL, posterior instrumented decompression and fusion provide a relatively safe approach and satisfactory results.

Subclinical infection can be an initiator of inflammaging leading to degenerative disk disease: evidence from host-defense response mechanisms.

PURPOSE: There is considerable controversy on the role of genetics, mechanical and environmental factors, and, recently, on subclinical infection in triggering inflammaging leading to disk degeneration. The present study investigated sequential molecular events in the host, analyzing proteome level changes that will reveal triggering factors of inflammaging and degeneration. METHODS: Ten MRI normal disks (ND) from braindead organ donors and 17 degenerated disks (DD) from surgery were subjected to in-gel-based label-free ESI-LC-MS/MS analysis. Bacterial-responsive host-defense response proteins/pathways leading to Inflammaging were identified and compared between ND and DD. RESULTS: Out of the 263 well-established host-defense response proteins (HDRPs), 243 proteins were identified, and 64 abundantly expressed HDRPs were analyzed further. Among the 21 HDRPs common to both ND and DD, complement factor 3 (C3) and heparan sulfate proteoglycan 2 (HSPG2) were significantly upregulated, and lysozyme (LYZ), superoxide dismutase 3 (SOD3), phospholipase-A2 (PLA2G2A), and tissue inhibitor of metalloproteinases 3 (TIMP-3) were downregulated in DD. Forty-two specific HDRPs mainly, complement proteins, apolipoproteins, and antimicrobial proteins involved in the complement cascade, neutrophil degranulation, and oxidative-stress regulation pathways representing an ongoing host response to subclinical infection and uncontrolled inflammation were identified in DD. Protein-Protein interaction analysis revealed cross talk between most of the expressed HDRPs, adding evidence to bacterial presence and stimulation of these defense pathways. CONCLUSIONS: The predominance of HDRPs involved in complement cascades, neutrophil degranulation, and oxidative-stress regulation indicated an ongoing infection mediated inflammatory process in DD. Our study has documented increasing evidence for bacteria's role in triggering the innate immune system leading to chronic inflammation and degenerative disk disease.

The catastrophization effects of an MRI report on the patient and surgeon and the benefits of 'clinical reporting': results from an RCT and blinded trials.

PURPOSE: Inappropriate use of MRI leads to increasing interventions and surgeries for low back pain (LBP). We probed the potential effects of a routine MRI report on the patient's perception of his spine and functional outcome of treatment. An alternate 'clinical reporting' was developed and tested for benefits on LBP perception. METHODS: In Phase-I, 44 LBP patients were randomized to Group A who had a factual explanation of their MRI report or Group B, who were reassured that the MRI findings showed normal changes. The outcome was compared at 6 weeks by VAS, PSEQ-2, and SF-12. In Phase-II, clinical reporting was developed, avoiding potential catastrophizing terminologies. In Phase-III, 20 MRIs were reported by both routine and clinical methods. The effects of the two methods were tested on four categories of health care professionals (HCP) who read them blinded on their assessment of severity of disease, possible treatment required, and the probability of surgery. RESULTS: Both groups were comparable initial by demographics and pain. After 6 weeks of treatment, Group A had a more negative perception of their spinal condition, increased catastrophization, decreased pain improvement, and poorer functional status(p = significant for all). The alternate method of clinical reporting had significant benefits in assessment of lesser severity of the disease, shift to lesser severity of intervention and surgery in three groups of HCPs. CONCLUSION: Routine MRI reports produce a negative perception and poor functional outcomes in LBP. Focussed clinical reporting had significant benefits, which calls for the need for 'clinical reporting' rather than 'Image reporting'.

Posterior Stabilization of Unstable Sacral Fractures: A Single-Center Experience of Percutaneous Sacroiliac Screw and Lumbopelvic Fixation in 67 Cases

Methods@#Out of the 67 patients, 40 and 27 were in the SI and LPF groups, respectively. The electronic medical record for each patient was reviewed, including patient demographic data, mode of trauma, coexisting injuries, neurological status (Gibbon’s four-grade system), Injury Severity Score, time from admission to operative stabilization, type of surgical stabilization, complications, return to the operating room, and treatment outcome measures using Majeed’s functional grading system and Matta’s radiological criteria. The minimum follow-up period was 2 years. @*Results@#Noncomminuted longitudinal injuries with normal neurology and acceptable closed reduction have undergone SI screw fixation (n=40). Irreducible, comminuted, or high transverse fractures associated with dysmorphic anatomy or neurodeficit were managed by LPF (n=27). Excellent and good Majeed and Matta scores at 86.57% and 92.54% of the patients, respectively, were postoperatively achieved. @*Conclusions@#Unstable sacral fractures can be effectively managed with percutaneous SI screw including vertically unstable injuries by paying strict attention to preoperative patient selection whereas LPF can be reserved for comminuted fractures, unacceptable closed reduction, associated neurodeficit, lumbosacral dysmorphism, and high transverse fractures.

A Randomized Control Trial Comparing Local Autografts and Allografts in Single Level Anterior Cervical Discectomy and Fusion Using a StandAlone Cage

Methods@#We randomly sampled participants requiring a single level ACDF for degenerative conditions (n=27) between allograft (n=13) and local graft (n=14) groups. Follow-up of patients occurred at 6 weeks, 3 months, 6 months, and 1 year using Numerical Pain Rating Scale (NPRS) scores for arm and neck pain, Neck Disability Index (NDI), 2-item Short Form Health Survey (SF-12), and lateral disk height. We then assessed radiological fusion using computed tomography (CT) scan at 12 months, and graded as F- (no fusion), F (fusion seen through the cage), F+ (fusion seen through the cage, with bridging bone at one lateral edge), and F++ (fusion seen through cage with bridging bone bilaterally). @*Results@#There were no significant differences in the age, sex, duration of intervention, blood loss, and hospital stay between the two groups (p>0.05). Both groups showed significant improvements in all functional outcome scores including NPRS for arm and neck pain, NDI, and SF-12 at each visit (p<0.01). We observed a marked improvement in disk height in both groups (p<0.05), but at 1 year of follow-up, there was a significant though slight subsidence (p=0.47). CT at 1 year showed no non-unions. We recorded F, F+, and F++ grades of fusion in 23.2%, 38.4%, and 38.4% in allograft group and 28.6%, 42.8%, and 28.6% in local graft group, respectively, though no significant differences observed (p=0.73). @*Conclusions@#Marginal osteophytes are effective as graft inside cages for ACDF, since they provide similar radiological outcomes, and equivalent improvements in functional outcomes, as compared to allografts.

Congenital Osseous Anomalies of the Cervical Spine: Occurrence, Morphological Characteristics, Embryological Basis and Clinical Significance: A Computed Tomography Based Study

STUDY DESIGN: Observational retrospective computed tomography (CT) based study. PURPOSE: To analyze the congenital anomalies of the cervical spine, their morphological variations and their clinical significance. OVERVIEW OF LITERATURE: Studies published to date have focused mainly on upper cervical anomalies; no study has comprehensively reported on anomalies of both the occipitocervical and subaxial cervical spine. METHODS: Nine hundred and thirty cervical spine CT scans performed in Ganga Hospital, Coimbatore, India between January 2014 and November 2017 were screened by two independent observers to document anomalies of both the upper and lower cervical spine. CT scans conducted for infection, tumor, and/or deformity were excluded. Different morphological variations, embryological basis, and clinical significance of the anomalies were discussed. RESULTS: Of the 930 CT scans screened, 308 (33.1%) had congenital anomaly. Of these, 184 (59.7%) were males and 124 (40.2.7%) were females, with a mean age of 44.2 years (range, 14–78 years). A total of 377 anomalies were identified, with 69 cases (7.4%) having more than one anomaly. Two hundred and fifty (26.8%) anomalies of the upper cervical region (occiput to C2–C3 disk space) were identified, with the most common upper cervical anomalies being high-riding vertebral artery (108 cases, 11.6%) and ponticulus posticus (PP) (75 cases, 8%). One hundred and twenty seven (13.6%) anomalies of the lower cervical spine (C3–C7) were noted, of which double foramen transversarium was the most common anomaly observed in 46 cases (4.8%). CONCLUSIONS: We found that 33.1% of CT scans had at least one congenital anomaly. Some anomalies, such as abnormal facet complex and arch anomalies, have to be differentiated from fractures in a trauma patient. Other anomalies, like PP, have to be looked for during preoperative planning to avoid complications during surgery. Therefore, knowledge of these anomalies is important as different anomalies have different clinical courses and management.

Factors Influencing Postoperative Urinary Retention Following Elective Posterior Lumbar Spine Surgery: A Prospective Study

STUDY DESIGN: Prospective observational study. PURPOSE: To determine the incidence of postoperative urinary retention (POUR) in patients undergoing elective posterior lumbar spine surgery and identify the risk factors associated with the development of POUR. OVERVIEW OF LITERATURE: POUR following surgery can lead to detrusor dysfunction, urinary tract infections, prolonged hospital stay, and a higher treatment cost; however, the risk factors for POUR in spine surgery remain unclear. METHODS: A prospective, consecutive analysis was conducted on patients undergoing elective posterior lumbar surgery in the form of lumbar discectomy, lumbar decompression, and single-level lumbar fusions during a 6-month period. Patients with spine trauma, preoperative neurological deficit, previous urinary disturbance/symptoms, multiple-level fusion, and preoperative catheterization were excluded from the study. Potential patient- and surgery-dependent risk factors for the development of POUR were assessed. Univariate analysis and a multiple logistical regression analysis were performed. RESULTS: A total of 687 patients underwent posterior lumbar spine surgery during the study period; among these, 370 patients were included in the final analysis. Sixty-one patients developed POUR, with an incidence of 16.48%. Significant risk factors for POUR were older age, higher body mass index (BMI), surgery duration, intraoperative fluid administration, lumbar fusion versus discectomy/decompression, and higher postoperative pain scores (p < 0.05 for all). Sex, diabetes, and the type of inhalational agent used during anesthesia were not significantly associated with POUR. Multiple logistical regression analysis, including age, BMI, surgery duration, intraoperative fluid administration, fusion surgery, and postoperative pain scores demonstrated a predictive value of 92% for the study population and 97% for the POUR group. CONCLUSIONS: POUR was associated with older age, higher BMI, longer surgery duration, a larger volume of intraoperative fluid administration, and higher postoperative pain scores. The contribution of postoperative pain scores in the multiple regression analysis was a significant predictor of POUR.

Circumferential Fusion through All-Posterior Approach in Andersson Lesion

STUDY DESIGN: Retrospective case series. PURPOSE: To assess safety and efficacy of single stage, posterior stabilisation and anterior cage reconstruction through the transforaminal or lateral extra-cavitary route for Andersson lesions. OVERVIEW OF LITERATURE: Pseudoarthrosis in ankylosing spondylitis (Andersson lesion, AL) can cause progressive kyphosis and neurological deficit. Management involves early recognition and surgical stabilisation in patients with instability. However, the need and safety of anterior reconstruction of the vertebral body defect remains unclear. METHODS: Twenty consecutive patients with AL whom presented with instability back pain and or neurological deficit were managed by single stage posterior approach with long segment pedicle screw fixation and anterior vertebral reconstruction. Radiological evaluation included- the regional kyphotic angle, measurement of anterior defect in computed tomography (CT) scan and the spinal cord status in magnetic resonance imaging. Radiological outcomes were assessed for fusion and kyphosis correction. Functional outcomes were assessed with visual analogue scale (VAS), ankylosing spondylitis quality of life (ASQoL) and Oswestry disability index (ODI). RESULTS: The mean age of the patients was 50.1 years (male, 18; female, 2). The levels affected include thoracolumbar (n=12), lower thoracic (n=5) and lumbar (n=3) regions. The mean level of fixation was 6.2±2.4 vertebrae. The mean anterior column defect was 1.6±0.6 cm. The mean surgical duration, blood loss and hospital stay were 112 minutes, 452 mL and 6.2 days, respectively. The mean followup was 2.1 years. At final follow up, VAS for back pain improved from 8.2 to 2.4 while ODI improved from 62.7 to 18.5 (p <0.05) and ASQoL improved from 14.3±2.08 to 7.90±1.48 (p <0.05). All patients had achieved radiological union at a mean 7.2±4.6 months. The mean regional kyphotic angle was 27° preoperatively, 16.7° postoperatively and 18.1° at the final follow-up. CONCLUSIONS: Posterior stabilisation and anterior reconstruction with cage through an all-posterior approach is safe and can achieve good results in Andersson lesions.

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes

STUDY DESIGN: A prospective genetic association study. PURPOSE: The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort. OVERVIEW OF LITERATURE: MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors. METHODS: We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software. RESULTS: The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4–5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR (p=0.02) and rs17099008 SNP of MMP20 (p=0.03) were significantly associated with MCs. CONCLUSIONS: Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies.

Closing-opening wedge osteotomy for severe, rigid, thoracolumbar post-tubercular kyphosis.

Childhood spinal tuberculosis, especially when associated with severe vertebral destruction of more than two vertebral bodies can end up in severe deformity. These children show progressive deformity throughout the period of growth and can develop severe kyphosis of >100°. Such kyphosis is severely disabling with significant risk of neurological deficit and respiratory compromise. Surgical correction of these deformities by both anterior and posterior approaches has been described but each have serious limitations of approach, correctability and safety. We describe here a technique of posterior closing-anterior opening osteotomy, which allowed us to correct a rigid post-tubercular deformity of 118° in a 13-year-old boy with neglected spinal tuberculosis. The patient was a 13-year-old boy, who had contracted spinal tuberculosis at the age of 6 years. Although the disease was cured by anti-tubercular chemotherapy, he continued to deteriorate in deformity and presented to us with severe thoracolumbar kyphosis (118°). He was neurologically intact but was beginning to show shortness of breath on exertion. Patient also had fore shortening of the trunk with impingement of the rib cage on the iliac crest. Radiographs revealed complete destruction of T12, L1 and L2 vertebral bodies with the T11 vertebra fusing with L3 anteriorly. CT scans and MRI revealed severe collapse of the vertebral column and the spinal cord being stretched over the 'internal gibbus', which was formed by the remnants of the destroyed vertebrae. A single stage closing-opening osteotomy was done by a midline posterior approach with continuous intraoperative spinal cord monitoring. The procedure involved extensive laminectomy of T11-L2, pedicle screw fixation of three levels above and three levels below the apex, a wedge osteotomy at the apex of the deformity from both sides, anterior column reconstruction by appropriate-sized titanium cage and gradual correction of deformity by closing the posterior column using the cage as a fulcrum. This allowed us to achieve a correction to 38° (68% correction). There was no intraoperative or perioperative adverse event and patient had good functional and radiological outcome at 1-year follow-up. In this Grand Rounds case presentation, we have also discussed the aetiology and evolution of severe post-tubercular kyphosis, which is the most common cause of spinal deformity in the developing world. Early identification of children at risk for severe deformity, the time and ideal methods of prevention of such deformities are discussed. The pros and cons of the available options of surgical correction of established deformity and the merits of our surgical technique are discussed.