Analysis of Spinopelvic Parameters with L5 as the New Sacrum after Fusion in High-Grade Spondylolisthesis: A Possible Explanation for Satisfactory Results with In-Situ Fusion

Shanmuganathan Rajasekaran,Gurudip Das,Siddharth Narasimhan Aiyer,Rishi Mugesh Kanna,Ajoy Prasad Shetty 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.1

Study Design: Retrospective case series. Purpose: To correlate functional outcomes with spinopelvic parameters in patients with high-grade spondylolisthesis (HGS) treated with instrumented in-situ surgery or reduction and fusion Overview of Literature: Satisfactory functional outcomes are reported with reduction and in-situ fusion strategies in HGS. However, reasons for this are unclear. We hypothesize that following lumbosacral fusion, the L5 becomes part of the sacrum, which improves spinopelvic parameters, resulting in equivalent functional outcomes in both surgical methods. Methods: Twenty-six patients undergoing HGS (reduction group A, 13; in-situ group B, 13) were clinically evaluated using the Os- westry Disability Index (ODI), short form-12 (SF-12), and Visual Analogue Scale (VAS) scores. Spinopelvic parameters, including pelvic incidence, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), lumbosacral kyphosis (LSK) angle, and sacrofemoral distance (SFD) were measured preoperatively from S1 and postoperatively from L5 as the new sacrum at 1 year follow-up. Sagittal alignment was assessed using the sagittal vertical axis. Results: Both groups were comparable in terms of age, sex, severity of slip, and preoperative spinopelvic parameters (p >0.05). Postoperative VAS, SF-12, and ODI scores significantly improved in both groups (p <0.05). Compared with preoperative values, the mean postoperative PT, SFD, and LSK significantly changed in both groups. In reduction group, PT changed from 26.98° to 10.78°, SFD from 61.24 to 33.56 mm, and LSK from 74.76° to 109.61° (p <0.05). In in-situ fusion group PT changed from 26.78° to 11.08°, SFD from 62.9 to 36.99 mm, and LSK from 67.23° to 113.38° (p <0.05 for all). In both groups, SS and LL did not change significantly (p >0.05). Conclusions: After fusion, the L5 becomes the new sacrum and influences spinopelvic parameters to change favorably. This possibly explains why reduction and in-situ fusion achieve equivalent functional outcomes in HGS.

Proteomic Signatures of Healthy Intervertebral Discs From Organ Donors: A Comparison With Previous Studies on Discs From Scoliosis, Animals, and Trauma

Shanmuganathan Rajasekaran,Chitraa Tangavel,Dilip Chand Raja Soundararajan,Sharon Miracle Nayagam,Monica Steffi Matchado,Raveendran Muthurajan,K.S. Sri Vijay Anand,Sunmathi Rajendran,Ajoy Prasad Shett 대한척추신경외과학회 2020 Neurospine Vol.17 No.2

Objective: To catalog and characterize the proteome of normal human intervertebral disc (IVD). Methods: Nine magnetic resonance imaging (MRI) normal IVDs were harvested from 9 different brain dead yet alive voluntary organ donors and were subjected to electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LC-MS/MS) acquisition. Results: A total of 1,116 proteins were identified. Functional enrichment analysis tool DAVID ver. 6.8 categorized: extracellular proteins (38%), intracellular (31%), protein-containing complex (13%), organelle (9%), membrane proteins (6%), supramolecular complex (2%), and 1% in the cell junction. Molecular function revealed: binding activity (42%), catalytic activity (31%), regulatory activity (14%), and structural activity (7%). Molecular transducer, transporter, and transcription regulator activity together contributed to 6%. A comparison of the proteins obtained from this study to others in the literature showed a wide variation in content with only 3% of bovine, 5% of murine, 54% of human scoliotic discs, and 10.2% of discs adjacent to lumbar burst fractures common to our study of organ donors. Between proteins reported in scoliosis and lumbar fracture patients, only 13.51% were common, further signifying the contrast amongst the various MRI normal IVD samples. Conclusion: The proteome of “healthy” human IVDs has been defined, and our results show that proteomic data on IVDs obtained from scoliosis, fracture patients, and cadavers lack normal physiological conditions and should not be used as biological controls despite normal MRI findings. This questions the validity of previous studies that have used such discs as controls for analyzing the pathomechanisms of disc degeneration.

Motion-Preserving Navigated Primary Internal Fixation of Unstable C1 Fractures

Rajasekaran Shanmuganathan,Soundararajan Dilip Chand Raja,Shetty Ajoy Prasad,Kanna Rishi Mugesh 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.4

Study Design: Prospective observational study.Purpose: To assess the safety, efficacy, and benefits of computed tomography (CT)-guided C1 fracture fixation.Overview of Literature: The surgical management of unstable C1 injuries by occipitocervical and atlantoaxial (AA) fusion compromises motion and function. Monosegmental C1 osteosynthesis negates these drawbacks and provides excellent functional outcomes.Methods: The patients were positioned in a prone position, and cranial traction was applied using Mayfield tongs to restore the C0–C2 height and obtain a reduction in the displaced fracture fragments. An intraoperative, CT-based navigation system was used to enable the optimal placement of C1 screws. A transverse rod was then placed connecting the two screws, and controlled compression was applied across the fixation. The patients were prospectively evaluated in terms of their clinical, functional, and radiological outcomes, with a minimal follow-up of 2 years.Results: A total of 10 screws were placed in five patients, with a mean follow-up of 40.8 months. The mean duration of surgery was 77±13.96 minutes, and the average blood loss was 84.4±8.04 mL. The mean combined lateral mass dislocation at presentation was 14.6±1.34 mm and following surgery, it was 5.2±1.64 mm, with a correction of 9.4±2.3 mm (<i>p</i> <0.001). The follow-up CT showed excellent placement of screws and sound healing. There were no complications and instances of AA instability. The clinical range of movement at 2 years in degrees was as follows: rotation to the right (73.6°±9.09°), rotation to the left (71.6°±5.59°), flexion (35.4°±4.5°), extension (43.8°±8.19°), and lateral bending on the right (28.4°±10.45°) and left (24.8°±11.77°). Significant improvement was observed in the functional Neck Disability Index from 78±4.4 to 1.6±1.6. All patients returned to their occupation within 3 months.Conclusions: Successful C1 reduction and fixation allows a motion-preserving option in unstable atlas fractures. CT navigation permits accurate and adequate monosegmental fixation with excellent clinical and radiological outcomes, and all patients in this study returned to their preoperative functional status.

Proteomic Signature of Nucleus Pulposus in Fetal Intervertebral Disc

Rajasekaran Shanmuganathan,Soundararajan Dilip Chand Raja,Tangavel Chitraa,K.S. Sri Vijay Anand,Nayagam Sharon Miracle,Matchado Monica Steffi,Muthurajan Raveendran,Shetty Ajoy Prasad,Kanna Rishi Muges 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.4

Study Design: Profiling proteins expressed in the nucleus pulposus of fetal intervertebral disc (IVD).Purpose: To evaluate the molecular complexity of fetal IVDs not exposed to mechanical, traumatic, inflammatory, or infective insults to generate improved knowledge on disc homeostasis.Overview of Literature: Low back pain is the most common musculoskeletal disorder, causing a significant reduction in the quality of life, and degenerative disc disorders mainly contribute to the increasing socioeconomic burden. Despite extensive research, the causative pathomechanisms behind degenerative disc disorders are poorly understood. Precise molecular studies on the intricate biological processes involved in maintaining normal disc homeostasis are needed.Methods: IVDs of nine fetal specimens obtained from medical abortions were used to dissect out the annulus fibrosus and nucleus pulposus under sterile operating conditions. Dissected tissues were transferred to sterile Cryovials and snap frozen in liquid nitrogen before transporting to the research laboratory for protein extraction and further liquid chromatography tandem mass spectrometry (LC-MS/ MS) analysis. Collected data were further analyzed using Gene Functional Classification Tool in DAVID and STRING databases.Results: A total of 1,316 proteins were identified through LC-MS/MS analysis of nine fetal IVD tissues. Approximately 247 proteins present in at least four fetal discs were subjected to further bioinformatic analysis. The following 10 clusters of proteins were identified: collagens, ribosomal proteins, small leucine-rich proteins, matrilin and thrombospondin, annexins, protein disulfide isomerase family proteins and peroxiredoxins, tubulins, histones, hemoglobin, and prolyl 4-hydroxylase family proteins.Conclusions: This study provides fundamental information on the proteome networks involved in the growth and development of healthy fetal discs in humans. Systematic cataloging of proteins involved in various structural and regulatory processes has been performed. Proteins expressed most abundantly (collagen type XIV alpha 1 chain, biglycan, matrilin 1, and thrombospondin 1) in their respective clusters also elucidate the possibility of utilizing these proteins for potential regenerative therapies.

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

Rajasekaran Shanmuganathan,Soundararajan Dilip Chand Raja,Nayagam Sharon Miracle,Tangavel Chitraa,Raveendran Muthuraja,K. S. Srivijayanand,Shetty Ajoy Prasad,Kanna Rishi Mugesh 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.1

Study Design: Profiling proteins expressed in the nucleus pulposus (NP) of intervertebral discs (IVDs) in five different biological states. Purpose: To evaluate the molecular complexity of the collagen (COL) framework and its role in the health and disease of human IVDs. Overview of Literature: Changes in COL composition have been linked to degenerative disk disease (DDD). Despite the fact that humans have 28 different types of COLs, most of the literature focuses solely on COL-1 and COL-2. This study used high-end proteomic technology to examine the entire COL composition of the human IVD across fetal (developmental-FD), normal (healthy-ND), scoliotic (early degeneration-SD), herniated (degenerate-DH), and degenerated (DD) disk phenotypes. 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.

Vertebral and Intraspinal Anomalies in Indian Population with Congenital Scoliosis: A Study of 119 Consecutive Patients

Neeraj Gupta,Rajasekaran Shanmuganathan,Balamurali G,Ajoy Shetty 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.2

Study Design: Retrospective case study by clinical and radiological data analysis. Purpose: To analyze different types of vertebral anomalies and the incidence of associated intraspinal anomalies in the Indian population. Overview of Literature: This is the largest study of congenital scoliosis and associated intraspinal anomalies in Indian population. Incidence of intraspinal anomaly in this series is 47% which is higher than previous literature. Hemivertebra was the most common anomaly as seen in previous studies. Methods: A total of 119 patients with congenital scoliosis who underwent surgery between December 2006 and December 2012 were studied. Data was reviewed with medical records, plain radiographs, and magnetic resonance imaging (MRI) scans. Results: Thoracolumbar curve was most common, seen in 43.6% of patients. In addition to scoliotic deformity, kyphosis was seen in 26% of patients. Failure of formation, the most common vertebral anomaly, was seen in 51.2% of patients, failure of segmentation was seen in 19.3% of patients, and there were 29.4% patients having both formation and segmentation anomalies. Hemivertebra was the most common vertebral anomaly seen in 66.3% of patients and for whom 63.2% were in thoracic spine. Intraspinal anomalies were associated with 47% of patients with congenital scoliosis. Tethered cord was the most common intraspinal abnormality and was found in 48.2% patients with intraspinal anomalies. The patients with failure of segmentation and mixed deformities were found to have a significantly higher incidence of intraspinal anomalies (65% and 57%, respectively) than those with failure of formation (34%). Out of 31 patients with kyphotic deformity 29% had intraspinal anomalies, and amongst them tethered cord was the most common anomaly seen in 66% patients. Out of 12 patients with neurocutaneous markers, 83% patients had intraspinal anomaly. Conclusions: Intraspinal anomalies were seen in 47% of patients with congenital scoliosis in the Indian population. Tethered cord was the most common intraspinal anomaly, seen in 48% cases of congenital scoliosis. Hemivertebra was seen in 66% cases and was the most common vertebral defect. Hence MRI imaging of whole spine should be done in all cases of congenital scoliosis before any surgical intervention. Special attention should be given to physical examination and visualization of any neurocutaneous markers, which are associated with a higher incidence of intraspinal anomalies; absence of a neurocutaneous marker, however, does not rule out intraspinal anomaly.

Factors Affecting Early and 1-Year Motor Recovery Following Lumbar Microdiscectomy in Patients with Lumbar Disc Herniation: A Prospective Cohort Review

Vibhu Krishnan Viswanathan,Rajasekaran Shanmuganathan,Siddharth Narasimhan Aiyer,Rishi Kanna,Ajoy Prasad Shetty 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.1

Study Design: Prospective cohort study. Purpose: The study was aimed at evaluating clinicoradiological factors affecting recovery of neurological deficits in cases of lumbar disc herniation (LDH) treated by lumbar microdiscectomy. Overview of Literature: The majority of the available literature on neurological recovery following neurodeficit is limited to retrospective series. The literature is currently limited regarding variables that can help predict the recovery of neurodeficits following LDH. Methods: A prospective analysis was performed on 70 consecutive patients who underwent lumbar microdiscectomy (L1–2 to L5–S1) owing to neurological deficits due to LDH. Patients with motor power ≤3/5 in L2–S1 myotomes were considered for analysis. Followup was performed at 2, 6, and 12 months to note recovery of motor deficits. Clinicoradiological parameters were compared between the recovered and nonrecovered groups. Results: A total of 65 patients were available at the final follow-up: 41 (63%) had completely recovered by 2 months; four showed delayed recovery at the 6-month follow-up; and 20 (30.7%) showed no recovery at 1 year. Clinicoradiological factors, including diabetes, complete initial deficit, areflexia, multilevel disc prolapse, longer duration since initial symptoms, and ≥2 previous symptomatic episodes were associated with a significant risk of poorer recovery (p <0.05 for all). Age, sex, occupation, smoking, level/type or location of disc herniation, primary canal stenosis, disc fragment dimensions, precipitating factors, bladder involvement, bilaterality of symptoms, and the presence or absence of anal reflex did not affect neurological recovery (p >0.05 for all). Diabetes mellitus (p =0.033) and complete initial motor deficit (p =0.028) were significantly associated with delayed recovery in the multivariate analysis. Conclusions: The overall neurological recovery rate in our study was 69%. Diabetes mellitus (p =0.033) and complete initial motor deficit were associated with delayed motor recovery.

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

Rishi Mugesh Kanna,Rajasekaran Shanmuganathan,Veera Ranjani Rajagopalan,Senthil Natesan,Raveendran Muthuraja,Kenneth Man Chee Cheung,Danny Chan,Patrick Yu Ping Kao,Anita Yee,Ajoy Prasad Shetty 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.4

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.

Morphometric Evaluation of Occipital Condyles: Defining Optimal Trajectories and Safe Screw Lengths for Occipital Condyle-Based Occipitocervical Fixation in Indian Population

Aju Bosco,Prakash Venugopal,Prakash Venugopal,Rajasekaran Shanmuganathan,Rishi Mugesh Kanna 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.2

Study Design: Computed tomographic (CT) morphometric analysis. Purpose: To assess the feasibility and safety of occipital condyle (OC)-based occipitocervical fixation (OCF) in Indians and to define anatomical zones and screw lengths for safe screw placement. Overview of Literature: Limitations of occipital squama-based OCF has led to development of two novel OC-based OCF techniques. Methods: Morphometric analysis was performed on the OCs of 70 Indian adults. The feasibility of placing a 3.5-mm-diameter screw into OCs was investigated. Safe trajectories and screw lengths for OC screws and C0–C1 transarticular screws without hypoglossal canal or atlantooccipital joint compromise were estimated. Results: The average screw length and safe sagittal and medial angulations for OC screws were 19.9±2.3 mm, ≤6.4°±2.4° cranially, and 31.1°±3° medially, respectively. An OC screw could not be accommodated by 27% of the population. The safe sagittal angles and screw lengths for C0–C1 transarticular screw insertion (48.9°±5.7° cranial, 26.7±2.9 mm for junctional entry technique; 36.7°±4.6° cranial, 31.6±2.7 mm for caudal C1 arch entry technique, respectively) were significantly different than those in other populations. The risk of vertebral artery injury was high for the caudal C1 arch entry technique. Screw placement was uncertain in 48% of Indians due to the presence of aberrant anatomy. Conclusions: There were significant differences in the metrics of OC-based OCF between Indian and other populations. Because of the smaller occipital squama dimensions in Indians, OC-based OCF techniques may have a higher application rate and could be a viable alternative/salvage option in selected cases. Preoperative CT, including three-dimensional-CT-angiography (to delineate vertebral artery course), is imperative to avoid complications resulting from aberrant bony and vascular anatomy. Our data can serve as a valuable reference guide in placing these screws safely under fluoroscopic guidance.

Intraoperative Life Threatening Acute Lung Injury Due to Multiple Septic Pulmonary Emboli during Transpedicular Biopsy and Kyphoplasty

Karuppaiah Karthik,Ajoy Prasad Shetty,Shanmuganathan Rajasekaran 대한척추외과학회 2014 Asian Spine Journal Vol.8 No.2

A 55-year-old gentleman was presented to our clinic two months after a trivial fall with persistent pain, gibbus at the thoraco-lumbar junction and intact neurology. Radiological and laboratory investigations suggested osteoporotic fracture or metastasis. Due to unremitting pain, a plan was made to do transpedicular biopsy and kyphoplasty. Biopsy needles were inserted into both pedicles and an attempt at aspiration was made. Since the aspirate was dry, 5 to 6 mL of saline was injected through one needle and an attempt at aspiration was made through the other. Three-millilitres of sero-sanguineous material mixed with pus came out and kyphoplasty was deferred. After extubation, the patient developed severe bronchospasm and was transferred to the intensive care unit. Investigations confirmed multiple septic pulmonary emboli and the patient recovered completely after treatment. This report highlights that confirmation of the diagnosis is essential before performing any procedure that increases the intravertebral pressure and the place should have appropriate facilities to manage complications.