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1.  Minimally invasive surgical procedures for the treatment of lumbar disc herniation 
In up to 30% of patients undergoing lumbar disc surgery for herniated or protruded discs outcomes are judged unfavourable. Over the last decades this problem has stimulated the development of a number of minimally-invasive operative procedures. The aim is to relieve pressure from compromised nerve roots by mechanically removing, dissolving or evaporating disc material while leaving bony structures and surrounding tissues as intact as possible. In Germany, there is hardly any utilisation data for these new procedures – data files from the statutory health insurances demonstrate that about 5% of all lumbar disc surgeries are performed using minimally-invasive techniques. Their real proportion is thought to be much higher because many procedures are offered by private hospitals and surgeries and are paid by private health insurers or patients themselves. So far no comprehensive assessment comparing efficacy, safety, effectiveness and cost-effectiveness of minimally-invasive lumbar disc surgery to standard procedures (microdiscectomy, open discectomy) which could serve as a basis for coverage decisions, has been published in Germany.
Against this background the aim of the following assessment is:
Based on published scientific literature assess safety, efficacy and effectiveness of minimally-invasive lumbar disc surgery compared to standard procedures. To identify and critically appraise studies comparing costs and cost-effectiveness of minimally-invasive procedures to that of standard procedures. If necessary identify research and evaluation needs and point out regulative needs within the German health care system. The assessment focusses on procedures that are used in elective lumbar disc surgery as alternative treatment options to microdiscectomy or open discectomy. Chemonucleolysis, percutaneous manual discectomy, automated percutaneous lumbar discectomy, laserdiscectomy and endoscopic procedures accessing the disc by a posterolateral or posterior approach are included.
In order to assess safety, efficacy and effectiveness of minimally-invasive procedures as well as their economic implications systematic reviews of the literature are performed. A comprehensive search strategy is composed to search 23 electronic databases, among them MEDLINE, EMBASE and the Cochrane Library. Methodological quality of systematic reviews, HTA reports and primary research is assessed using checklists of the German Scientific Working Group for Health Technology Assessment. Quality and transparency of cost analyses are documented using the quality and transparency catalogues of the working group. Study results are summarised in a qualitative manner. Due to the limited number and the low methodological quality of the studies it is not possible to conduct metaanalyses. In addition to the results of controlled trials results of recent case series are introduced and discussed.
The evidence-base to assess safety, efficacy and effectiveness of minimally-invasive lumbar disc surgery procedures is rather limited:
Percutaneous manual discectomy: Six case series (four after 1998)Automated percutaneous lumbar discectomy: Two RCT (one discontinued), twelve case series (one after 1998)Chemonucleolysis: Five RCT, five non-randomised controlled trials, eleven case seriesPercutaneous laserdiscectomy: One non-randomised controlled trial, 13 case series (eight after 1998)Endoscopic procedures: Three RCT, 21 case series (17 after 1998)
There are two economic analyses each retrieved for chemonucleolysis and automated percutaneous discectomy as well as one cost-minimisation analysis comparing costs of an endoscopic procedure to costs for open discectomy.
Among all minimally-invasive procedures chemonucleolysis is the only of which efficacy may be judged on the basis of results from high quality randomised controlled trials (RCT). Study results suggest that the procedure maybe (cost)effectively used as an intermediate therapeutical option between conservative and operative management of small lumbar disc herniations or protrusions causing sciatica. Two RCT comparing transforaminal endoscopic procedures with microdiscectomy in patients with sciatica and small non-sequestered disc herniations show comparable short and medium term overall success rates. Concerning speed of recovery and return to work a trend towards more favourable results for the endoscopic procedures is noted. It is doubtful though, whether these results from the eleven and five years old studies are still valid for the more advanced procedures used today. The only RCT comparing the results of automated percutaneous lumbar discectomy to those of microdiscectomy showed clearly superior results of microdiscectomy. Furthermore, success rates of automated percutaneous lumbar discectomy reported in the RCT (29%) differ extremely from success rates reported in case series (between 56% and 92%).
The literature search retrieves no controlled trials to assess efficacy and/or effectiveness of laser-discectomy, percutaneous manual discectomy or endoscopic procedures using a posterior approach in comparison to the standard procedures. Results from recent case series permit no assessment of efficacy, especially not in comparison to standard procedures. Due to highly selected patients, modi-fications of operative procedures, highly specialised surgical units and poorly standardised outcome assessment results of case series are highly variable, their generalisability is low.
The results of the five economical analyses are, due to conceptual and methodological problems, of no value for decision-making in the context of the German health care system.
Aside from low methodological study quality three conceptual problems complicate the interpretation of results.
Continuous further development of technologies leads to a diversity of procedures in use which prohibits generalisation of study results. However, diversity is noted not only for minimally-invasive procedures but also for the standard techniques against which the new developments are to be compared. The second problem refers to the heterogeneity of study populations. For most studies one common inclusion criterion was "persisting sciatica after a course of conservative treatment of variable duration". Differences among study populations are noted concerning results of imaging studies. Even within every group of minimally-invasive procedure, studies define their own in- and exclusion criteria which differ concerning degree of dislocation and sequestration of disc material. There is the non-standardised assessment of outcomes which are performed postoperatively after variable periods of time. Most studies report results in a dichotomous way as success or failure while the classification of a result is performed using a variety of different assessment instruments or procedures. Very often the global subjective judgement of results by patients or surgeons is reported. There are no scientific discussions whether these judgements are generalisable or comparable, especially among studies that are conducted under differing socio-cultural conditions. Taking into account the weak evidence-base for efficacy and effectiveness of minimally-invasive procedures it is not surprising that so far there are no dependable economic analyses.
Conclusions that can be drawn from the results of the present assessment refer in detail to the specified minimally-invasive procedures of lumbar disc surgery but they may also be considered exemplary for other fields where optimisation of results is attempted by technological development and widening of indications (e.g. total hip replacement).
Compared to standard technologies (open discectomy, microdiscectomy) and with the exception of chemonucleolysis, the developmental status of all other minimally-invasive procedures assessed must be termed experimental. To date there is no dependable evidence-base to recommend their use in routine clinical practice. To create such a dependable evidence-base further research in two directions is needed: a) The studies need to include adequate patient populations, use realistic controls (e.g. standard operative procedures or continued conservative care) and use standardised measurements of meaningful outcomes after adequate periods of time. b) Studies that are able to report effectiveness of the procedures under everyday practice conditions and furthermore have the potential to detect rare adverse effects are needed. In Sweden this type of data is yielded by national quality registries. On the one hand their data are used for quality improvement measures and on the other hand they allow comprehensive scientific evaluations. Since the year of 2000 a continuous rise in utilisation of minimally-invasive lumbar disc surgery is observed among statutory health insurers. Examples from other areas of innovative surgical technologies (e.g. robot assisted total hip replacement) indicate that the rise will probably continue - especially because there are no legal barriers to hinder introduction of innovative treatments into routine hospital care. Upon request by payers or providers the "Gemeinsamer Bundesausschuss" may assess a treatments benefit, its necessity and cost-effectiveness as a prerequisite for coverage by the statutory health insurance. In the case of minimally-invasive disc surgery it would be advisable to examine the legal framework for covering procedures only if they are provided under evaluation conditions. While in Germany coverage under evaluation conditions is established practice in ambulatory health care only (“Modellvorhaben") examples from other European countries (Great Britain, Switzerland) demonstrate that it is also feasible for hospital based interventions. In order to assure patient protection and at the same time not hinder the further development of new and promising technologies provision under evaluation conditions could also be realised in the private health care market - although in this sector coverage is not by law linked to benefit, necessity and cost-effectiveness of an intervention.
PMCID: PMC3011322  PMID: 21289928
2.  Endoscopic lumbar discectomy: Experience of first 100 cases 
Indian Journal of Orthopaedics  2010;44(2):184-190.
Various modalities of treatment from standard discectomy, microdiscectomy, percutaneous discectomy, and transforaminal endoscopic discectomy have been in use for lumbar intervertebral disc prolapse. The access to spine is kept to a minimum without stripping paraspinal muscles minimizing muscle damage by posterior interlaminar endoscopic approach. The aim of this study was to evaluate technical problems, complications, and overall initial results of microendoscopic discectomy.
Materials and Methods:
First 100 consecutive cases aged 19-65 years operated by microendoscopic dissectomy between August 2002 – December 2005 are reported. All patients with single nerve root lesions including sequestrated or migrated and selected central disc at L4-5 and L5-S1 were included. The patients with bilateral radiculopathy were excluded. All patients had preoperative MRI and first 11 patients had postoperative MRI to check the adequacy of decompression. Diagnostic selective nerve root blocks were done in selective cases to isolate the single root lesion when MRI was inconclusive (n=7). All patients were operated by a single surgeon with the Metrx system (Medtronics). 97 were operated by 18-mm ports, and only three patients were operated by 16-mm ports. Postoperatively, all patients were mobilized as soon as the pain subsided and discharged within 24–48 h postsurgery. Patients were evaluated for technical problems, complications, and overall results by modified Macnab criteria. Patients were followed up at 2, 6, and 12 weeks.
The mean follow up was 12 months (range 3 months – 4 years). Open conversion was required in one patient with suspected root damage. Peroperatively single facet removal was done in 5 initial cases. Minor dural punctures occurred in seven cases and root damage in one case. The average surgical time was 70 min (range 25-210 min). Average blood loss was 20-30 ml. Technical difficulties encountered in initial 25 cases were insertion of guide pin, image orientation, peroperative dissection and bleeding problems, and reaching wrong levels suggestive of a definitive learning curve. Postoperative MRI (n=11) showed complete decompression. Overall 91% of patients had good-to-excellent results, with four patients having recurrence of whom three were reoperated. Four patients had postoperative discitis. One of the patients required fusion for discitis and rest were managed conservatively. One patient had root damage to L5 root that had paresthesia in L5 region even on 4 years of follow-up.
Microendoscopic discectomy is minimally invasive procedure for discectomy with early encouraging results. Once definite learning curve was over and expertise is acquired, the results of this procedure are acceptable safe and effective.
PMCID: PMC2856394  PMID: 20419006
Lumbar discectomy; microendo system; endoscopic lumbar discectomy
3.  The Use of Magnetic Resonance Imaging to Predict the Clinical Outcome of Non-Surgical Treatment for Lumbar Interverterbal Disc Herniation 
Korean Journal of Radiology  2007;8(2):156-163.
We wanted to investigate the relationship between the magnetic resonance (MR) findings and the clinical outcome after treatment with non-surgical transforaminal epidural steroid injections (ESI) for lumbar herniated intervertebral disc (HIVD) patients.
Materials and Methods
Transforaminal ESI were performed in 91 patients (50 males and 41 females, age range: 13-78 yrs) because of lumbosacral HIVD from March 2001 to August 2002. Sixty eight patients whose MRIs and clinical follow-ups were available were included in this study. The medical charts were retrospectively reviewed and the patients were divided into two groups; the successful (responders, n = 41) and unsatisfactory (non-responders, n = 27) outcome groups. A successful outcome required a patient satisfaction score greater than two and a pain reduction score greater than 50%. The MR findings were retrospectively analyzed and compared between the two groups with regard to the type (protrusion, extrusion or sequestration), hydration (the T2 signal intensity), location (central, right/left central, subarticular, foraminal or extraforaminal), and size (volume) of the HIVD, the grade of nerve root compression (grade 1 abutment, 2 displacement and 3 entrapment), and an association with spinal stenosis.
There was no significant difference between the responders and non-responders in terms of the type, hydration and size of the HIVD, or an association with spinal stenosis (p> 0.05). However, the location of the HIVD and the grade of nerve root compression were different between the two groups (p< 0.05).
MRI could play an important role in predicting the clinical outcome of non-surgical transforaminal ESI treatment for patients with lumbar HIVD.
PMCID: PMC2626775  PMID: 17420633
Spine, intervertebral disks; Spine, MR
4.  Recurrent lumbar disc herniation: A prospective comparative study of three surgical management procedures 
Asian Journal of Neurosurgery  2013;8(3):139-146.
The optimal surgical treatment of recurrent lumbar disc herniation is controversial.
To compare prospectively the clinical outcomes of surgical treatment of recurrent lumbar disc herniation by three different methods; discectomy alone, discectomy with transforaminal lumbar interbody fusion (TLIF), and diecectomy with posterolateral fusion (PLF), regardless of the postoperative radiological findings.
Study Design:
This is a prospective, randomized, comparative study.
Materials and Methods:
This is a prospective, randomized, comparative study on 45 patients with first time recurrent lumbar disc herniation. Patients were evaluated clinically by using the criteria of the Japanese Orthopedic Association's evaluation system for low back pain syndrome (JOA score). The patients were classified into three groups: Group A; patients who had revision discectomy alone, group B; patients who had revision discectomy with TLIF, and group C; patients who had revision discectomy with PLF. The mean follow-up period was 37 (±7.85 STD) months.
The mean overall recovery rate was 87.2% (±19.26 STD) and the satisfactory rate was 88.9%. Comparison between the three groups showed no significant difference with regard to the mean total postoperative JOA score, recovery rate, and satisfactory rate. However, the postoperative low back pain was significantly higher in group A than that of group B and C. Two patients in group A required further revision surgery. The incidences of dural tear and postoperative neurological deficit were higher in group A. The intraoperative blood loss and length of operation were significantly less in group A. The total cost of the procedure was significantly different between the three groups, being least in group A and highest in group B. There was no significant difference between the three groups with regard to the length of postoperative hospital stay.
Revision discectomy is effective in patients with recurrent lumbar disc herniation. Fusion with revision discectomy improves the postoperative low back pain, decreases the intraoperative risk of dural tear or neural damage and decreases the postoperative incidence of mechanical instability or re-recurrence. TLIF and PLF have comparable results when used with revision discectomy, but PLF has significantly less total cost than TLIF.
PMCID: PMC3877500  PMID: 24403956
Anterior lumbar interbody fusion; posterior lumbar interbody fusion; posterolateral fusion; recurrent lumbar disc herniation; transforaminal lumbar interbody fusion
5.  Higher risk of dural tears and recurrent herniation with lumbar micro-endoscopic discectomy 
European Spine Journal  2010;19(3):443-450.
Existing studies on micro-endoscopic lumbar discectomy report similar outcomes to those of open and microdiscectomy and conflicting results on complications. We designed a randomised controlled trial to investigate the hypothesis of different outcomes and complications obtainable with the three techniques. 240 patients aged 18–65 years affected by posterior lumbar disc herniation and symptoms lasting over 6 weeks of conservative management were randomised to micro-endoscopic (group 1), micro (group 2) or open (group 3) discectomy. Exclusion criteria were less than 6 weeks of pain duration, cauda equina compromise, foraminal or extra-foraminal herniations, spinal stenosis, malignancy, previous spinal surgery, spinal deformity, concurrent infection and rheumatic disease. Surgery and follow-up were made at a single Institution. A biomedical researcher independently collected and reviewed the data. ODI, back and leg VAS and SF-36 were the outcome measures used preoperatively, postoperatively and at 6-, 12- and 24-month follow-up. 212/240 (91%) patients completed the 24-month follow-up period. VAS back and leg, ODI and SF36 scores showed clinically and statistically significant improvements within groups without significant difference among groups throughout follow-up. Dural tears, root injuries and recurrent herniations were significantly more common in group 1. Wound infections were similar in group 2 and 3, but did not affect patients in group 1. Overall costs were significantly higher in group 1 and lower in group 3. In conclusion, outcome measures are equivalent 2 years following lumbar discectomy with micro-endoscopy, microscopy or open technique, but severe complications are more likely and costs higher with micro-endoscopy.
PMCID: PMC2899770  PMID: 20127495
Lumbar disc herniation; Discectomy; Microdiscectomy; Micro-endoscopic discectomy
6.  Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results  
Study type: Basic science
Introduction: Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3
Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3 b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)—Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time
Objective: The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics.
Methods: Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5).
Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: Bone
Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc space
Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a–c H&E (overall tissue staining for light micrsocopy) d–f Alcian blue (proteoglycans) g–i Picrosirius red (collagen I and II)
Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body bone
MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NP
7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP)
Results: The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months.
Conclusions: This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d–f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants.
PMCID: PMC3623095  PMID: 23637671
7.  Electrophysiological diagnosis using sensory nerve action potential for the intraforaminal and extraforaminal L5 nerve root entrapment 
European Spine Journal  2012;22(4):833-839.
The diagnosis of lumbar intraforaminal and extraforaminal stenosis (lumbar foraminal stenosis) is sometimes difficult. However, sensory nerve action potential (SNAP) decreases in amplitude when the lesion is at or distal to the dorsal root ganglion. Therefore, the amplitude of SNAP with lumbar foraminal stenosis should be decreased. In this cohort study, the usefulness of SNAP for the preoperative diagnosis of L5/S foraminal stenosis was assessed.
In 63 patients undergoing unilateral L5 radiculopathy, bilateral SNAPs were recorded for the superficial peroneal nerve (L5 origin). The patients were divided into two groups according to the results of imaging examinations. Group A (37 patients) included patients whose lesion was located only at the intraspinal canal. In group B (26 patients), the lesion was located only at the intra- or extraforaminal area. All patients received surgery and the symptoms were diminished. The ratios of the amplitudes of SNAPs on the affected side to that on the unaffected side were compared between groups A and B.
SNAPs could not be elicited bilaterally in four patients. The amplitude ratio for group B (median 0.42, max 1.17, min 0) was significantly lower than that in group A (median 0.85, max 1.43, min 0) (p < 0.001 by Mann–Whitney U test). Using a cut-off value of 0.5 for the amplitude ratio, the sensitivity for the diagnosis of lumbar foraminal stenosis was 91.3 % with a specificity of 85.7 %.
Measurement of SNAP could be useful to diagnose a unilateral L5/S foraminal stenosis.
PMCID: PMC3631025  PMID: 23179988
Electrodiagnosis; Sensory nerve action potential; L5 radiculopathy; Intraforaminal and extraforaminal root entrapment
8.  A Prospective, Observational Study of the Relationship Between Body Mass Index and Depth of the Epidural Space During Lumbar Transforaminal Epidural Steroid Injection 
Background and Objectives
Previous studies have concluded that transforaminal epidural steroid injections (ESIs) are more effective than interlaminar injections in the treatment of radiculopathies due to lumbar intervertebral disk herniation. There are no published studies examining the depth of epidural space using a transforaminal approach. We investigated the relationship between body mass index (BMI) and the depth of the epidural space during lumbar transforaminal ESIs.
Eighty-six consecutive patients undergoing lumbar transforaminal ESI at the L3-L4, L4-L5, and L5-S1 levels were studied. Using standard protocol, the foraminal epidural space was attained using fluoroscopic guidance. The measured distance from needle tip to skin was recorded (depth to foraminal epidural space). The differences in the needle depth and BMI were analyzed using regression analysis.
Needle depth was positively associated with BMI (regression coefficient [RC], 1.13; P < 0.001). The median depths (in centimeters) to the epidural space were 6.3, 7.5, 8.4, 10.0, 10.4, and 12.2 for underweight, normal, preobese, obese I, obese II, and obese III classifications, respectively. Sex (RC, 1.3; P = 0.02) and race (RC, 0.8; P = 0.04) were also significantly associated with needle depth; however, neither factor remained significant when BMI was accounted as a covariate in the regression model. Age, intervertebral level treated, and oblique angle had no predictive value on foraminal depth (P > 0.2).
There is a positive association between BMI and transforaminal epidural depth, but not with age, sex, race, oblique angle, or intervertebral level.
PMCID: PMC2715548  PMID: 19282707
9.  Evaluation of unilateral cage-instrumented fixation for lumbar spine 
To investigate how unilateral cage-instrumented posterior lumbar interbody fusion (PLIF) affects the three-dimensional flexibility in degenerative disc disease by comparing the biomechanical characteristics of unilateral and bilateral cage-instrumented PLIF.
Twelve motion segments in sheep lumbar spine specimens were tested for flexion, extension, axial rotation, and lateral bending by nondestructive flexibility test method using a nonconstrained testing apparatus. The specimens were divided into two equal groups. Group 1 received unilateral procedures while group 2 received bilateral procedures. Laminectomy, facectomy, discectomy, cage insertion and transpedicle screw insertion were performed sequentially after testing the intact status. Changes in range of motion (ROM) and neutral zone (NZ) were compared between unilateral and bilateral cage-instrumented PLIF.
Both ROM and NZ, unilateral cage-instrumented PLIF and bilateral cage-instrumented PLIF, transpedicle screw insertion procedure did not revealed a significant difference between flexion-extension, lateral bending and axial rotation direction except the ROM in the axial rotation. The bilateral group's ROM (-1.7 ± 0. 8) of axial rotation was decreased significantly after transpedicle screw insertion procedure in comparison with the unilateral group (-0.2 ± 0.1). In the unilateral cage-instrumented PLIF group, the transpedicle screw insertion procedure did not demonstrate a significant difference between right and left side in the lateral bending and axial rotation direction.
Based on the results of this study, unilateral cage-instrumented PLIF and bilateral cage-instrumented PLIF have similar stability after transpedicle screw fixation in the sheep spine model. The unilateral approach can substantially reduce exposure requirements. It also offers the biomechanics advantage of construction using anterior column support combined with pedicle screws just as the bilateral cage-instrumented group. The unpleasant effect of couple motion resulting from inherent asymmetry was absent in the unilateral group.
PMCID: PMC2993665  PMID: 21070626
10.  The Relationship between Disc Degeneration and Morphologic Changes in the Intervertebral Foramen of the Cervical Spine: A Cadaveric MRI and CT Study 
Journal of Korean Medical Science  2004;19(1):101-106.
A cadaveric study was performed to investigate the relationship between disc degeneration and morphological changes in the intervertebral foramen of cervical spine, including the effect on the nerve root. Seven fresh frozen human cadavers were dissected from C1 to T1, preserving the ligaments, capsules, intervertebral disc and the neural structures. The specimens were scanned with MRI and then scanned through CT scan in the upright position. Direct mid-sagittal and 45 degree oblique images were obtained to measure the dimension of the intervertebral disc height, foraminal height, width, area and segmental angles. Disc degeneration was inversely correlated with disc height. There was a significant correlation between disc degeneration and foraminal width (p<0.005) and foraminal area (p<0.05), but not with foraminal height. Disc height was correlated with foraminal width but not with height. The segmental angles were decreased more in advanced degenerated discs. There was a correlation between nerve root compression and decreased foraminal width and area (p<0.005). This information and critical dimensions of the intervertebral foramen for nerve root compression should help in the diagnosis of foraminal stenosis of the cervical spine in patients presenting with cervical spondylosis and radiculopathy.
PMCID: PMC2822244  PMID: 14966350
Cervical Vertebrae; Intervertebral Disk; Magnetic Resonance Imaging; Tomography, X-Ray Computed
11.  Lumbar Nerve Root Occupancy in the Foramen in Achondroplasia 
Lumbar stenosis is common in patients with achondroplasia because of narrowing of the neural canal. However, it is unclear what causes stenosis, narrowing of the central canal or foramina. We performed a morphometric analysis of the lumbar nerve roots and intervertebral foramen in 17 patients (170 nerve roots and foramina) with achondroplasia (eight symptomatic, nine asymptomatic) and compared the data with that from 20 (200 nerve roots and foramina) asymptomatic patients without achondroplasia presenting with low back pain without neurologic symptoms. The measurements were made on left and right parasagittal MRI scans of the lumbar spine. The foramen area and root area were reduced at all levels from L1 to L5 between the patients with achondroplasia (Groups I and II) and the nonachondroplasia group (Group III). The percentage of nerve root occupancy in the foramen between Group I and Group II as compared with the patients without achondroplasia was similar or lower. This implied the lumbar nerve root size in patients with achondroplasia was smaller than that of the normal population and thus there is no effective nerve root compression. Symptoms of lumbar stenosis in achondroplasia may be arising from the central canal secondary to degenerative disc disease rather than a true foraminal stenosis.
Level of Evidence: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2504658  PMID: 18259829
12.  Comparison of the aorta impingement risks between thoracolumbar/lumbar curves with different convexities in adolescent idiopathic scoliosis: a computed tomography study 
European Spine Journal  2012;21(10):2043-2049.
To compare the positions of the aorta relative to vertebral bodies and the potential risk of the aorta impingement for pedicle screw (PS) placement between right-sided and left-sided thoracolumbar/lumbar curves of adolescent idiopathic scoliosis (AIS).
Thirty-nine AIS patients with a main thoracolumbar or lumbar curve were recruited. The Lenke’s classification was type 5C in all patients. According to the convexity of the thoracolumbar or lumbar curves, the patients were divided into either group R or Group L. The patients in Group R had a main right-sided thoracolumbar/lumbar curve, and the patients in Group L had a main left-sided thoracolumbar/lumbar curve. Axial CT images from T12 to L4 at the midvertebral body level were obtained to evaluate Aorta-vertebra angle (α), Vertebral rotation angle (β), Lefty safety distance (LSD), and Right safety distance (RSD). The risks of the aorta impingement from T12 to L4 were calculated and then compared between the two groups.
The α increased from T12 through L4 in Group R, increased from T12 through L1, and then decreased from L1 through L4 in Group L. The β decreased from T12 through L4 in both groups. The LSD constantly increased from T12 through L4 in Group R, increased from T12 through L3, and then decreased from L3 through L4 in Group L. The RSD increased from T12 through L3 and then decreased from L3 through L4 in both groups. With the increment of the lengths of the simulated screws, the aorta impingement risks were constantly elevated at all levels in both groups. The aorta was at a high risk of impingement from left PS regardless of the diameters of the simulated screws in Group R (80–100 % at T12 and 53.3–100 % at L1). In Group L, the aorta was completely safe when using 35 mm (0 at all levels) PS and at high risks of the aorta impingement on the right side from 45 mm PSs (31.8–72.7 %). In all, the risks of the aorta impingement were mainly from left PS in Group R and from right PS in Group L, and the risk of the aorta impingement from PS placement was generally higher in right thoracolumbar or lumbar curves when compared with that of the left.
The present study illustrated different changed positions of the aorta relative to vertebrae between thoracolumbar/lumbar curves with different convexities. In right-sided curve, the risks of the aorta impingement were mainly from left PS while in left-sided curves, from right PS. The aorta was more proximal to entry points in right-sided lumbar curve when compared with left-sided curve; thus placing PS carries more risks in right-sided thoracolumbar/lumbar curve. Surgeons should be more cautious when placing PSs on the concave sides of T12 and L1 vertebrae of right-sided thoracolumbar/lumbar curves.
PMCID: PMC3463682  PMID: 22526705
Aorta impingement; Thoracolumbar/lumbar curve; Convexity; Adolescent idiopathic scoliosis
13.  Morphologic Changes of L5 Root at Coronal Source Images of MR Myelography in Cases of Foraminal or Extraforaminal Compression 
Two findings easily found at coronal source images of MR myelography (MRM) were evaluated : dorsal root ganglion (DRG) swelling and running course abnormality (RCA) of L5 exiting root at foramen or extraforamen. We tried to find the sensitivity of each finding when root was compressed.
From 2004 July to 2006, one hundred and ten patients underwent one side paraspinal decompression for their L5 root foraminal or extraforaminal compression at L5-S1 level. All kinds of conservative treatments failed to improve leg symptom for several months. Before surgery, MRI, CT and MRM were done. Retrospective radiologic analysis for their preoperative MRM coronal source images was done to specify root compression sites and L5 root morphologic changes.
DRG swelling was found in 66 (60%) of 110 patients. DRG swelling has statistically valuable meaning in foraminal root compression (chi-square test, p < 0.0001). Seventy-two (66%) in 110 patients showed abnormal alteration of running course. Abnormal running course has statistically valuable meaning in foraminal or extraforaminal root compression (chi-square test, p < 0.0001).
Three-dimensional MRM provides precise thin sliced coronal images which are most close to real operative views. DRG swelling and running course abnormality of L5 exiting root are two useful findings in diagnosing L5 root compression at L5-S1 foramen or extraforamen. MRM is thought to provide additional diagnostic accuracy expecially in L5-S1 foraminal and extraforaminal area.
PMCID: PMC2729818  PMID: 19707488
MR myelography; Foraminal or extraforaminal; Lumbar disc herniation
14.  Treatment outcomes of 130 patients underwent an endoscopic discectomy 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 34.
Endoscopic discectomy method is a novel technique that is increasingly used in spine surgery. Previous studies have reported that some common complications like dural adhesions are lower in this technique compared with the other techniques. Furthermore, treatment outcomes are reportedly higher because of minimal invasion. Thepresent study aims to determine the outcome of percutaneous endoscopic discectomy.
A total of 130 patients underwent the lumbar disc prolapse operations during 2008 to 2012 in all of them the entire procedure was performed endoscopically. All procedures were carried out from a posterior approach using a 4-mm Hopkins 0 degrees-telescope placed in the working insert equipped with channels for suction tube, operative instruments and nerve root retractor (ENDOSPINE instrumentation (Karl STORZ GmbH and Co. KG). The pre- and post-operation pain was assessed using a Visual Analog Scale (VAS). Furthermore, the treatment outcome was assessed using modified MacNab criteria before operation, 24 hours, one month, 2 months, 6 months, one year, and two years after operation .
Good to excellent outcome was achieved in 89% of patients, which is comparable with the results of classic microdiscectomy. The mean age of patients was 35.6 years old and the mean length of follow-up was 3.4 years. There was significant reduction in the severity of back pain and lower limb symptoms at 6 months and 2 years post-operation. There was significant improvement in all aspects of the Quality of Life scores at 6 months and 2 years post-operation. In 3 patients the dural sac was lacerated but none of the tears was exceed a few mm in length with not association with neural injury.
Findings of this study showed that percutaneous endoscopic lumbar discectomy is associated with improvement in back pain and lower limb symptoms. It has the advantage that it can be performed on a day case basis with short length of hospitalization and early return to work thus improving quality of life earlier.
Endoscopic discectomy, Spine surgery, Lumbar disc prolapse operation, Outcome
PMCID: PMC3571560
15.  Intraoperative neurophysiological monitoring in spinal root surgical interventions 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 84.
Surgical interventions around spinal roots may result in rootlets injury and neurological deficits. Multimodal introperative neurophysiological monitoring (MIOM) can allow for early detection and then reversal of nerve roots potential injuries. These utilities have been currently used to evaluate spinal sensorimotor pathways and nerve root function during posterior spinal approches for transpedicular screw fixations in a rotine base in our setting (Vali-e ASR Hospital, Arak, Iran) since 1998.
In three consecutive patients (1 male, 16 years old. and 2 female, 17 and 16 years old) kyphoscoliosis corrections, patient’s history, preoperative physical examination and MIOM were performed using a multimodal 40-channel electrophysiologic monitoring system (Nicolet Endeavor, VIASYS Healthcare, 2005, USA). In all cases somatosensory evoked potentials (SSEPs) and F-wave responses corresponding tothe related myotome, were recorded 2 days prior surgery. The SSEPs, bilateral EMGs of paravertebrals and related muscle, stimulus-evoked evoked EMGs by mid-dural spinal stimulation, stimulus-evoked EMGs through root stimulation (pre/post foraminal) were performed when required during different stages of operation procedure. The compound muscle action potentials (CMAPs) were recorded using a pair of 1 Cm2 golden cup surface electrode. A paired-pulse stimulation consisting of two pulses with 2 ms interstimulus interval (ISI), 100-300 µs duration and 10-40 mA intensity was applied through a surgical probe pair electrode touched to the intact dura, over the midline of dorsal column, 2 segments above the involved root, to evoke constant reproducible EMGs in paravertebrals and/or approperiate myotomes of the segment in both lower limbs. Latency of CMAPs were measured for dorsal culumn, foramen entrance and root exit site stimulations. Following the measurements of the F-wave latencies, the central root conduction time and foramenal segments were calculated and used for further monitoring.
The SSEPs of ascending valleis from medial tibial nerve stimulation were recorded at C7 spine and C3´ or C4´of the operation side. A unilateral, sustained loss of 50% of the SSEP amplitude and/or increase by 10% of latency from average values after anesthesia, and SSEP/CMAP waveform change to an asynchronous polyphasic wave, were considered to be pathologic. Drilling and screw positionings were evaluated intraoperatively with standard posteroanterior and lateral radiographs.
None of the 3 patients showed significant change in the SSEPsor post-operative radiculopathies distinct from their preoperative presentations. One hour after the start of surgery, when the spinal column was exposed to the operating theatre temperature, a minimal prolongation of latencies as well as amplitude reduction of SSEPs was observed. The SSEP waveforms were not affected subsequently. A reverse change appeared again after paravertebral muscles stitching at the final hour of surgery.
In our cases, latencies of different root segments were kept intact during the operation and also during the transfer to the recovery room. Propofol or Propofol/Ketamine mixture plus narcotic is suitable to obtain stable reproducible SSEPs and EMGs. Atracurium or other nondepolarizing skeletal muscle relaxants should be avoided. Muscle relaxants application or mean arterial pressure (MAP) below 70 mmHg may cause bilateral reduction or loss of SSEPs and EMGs. There was no postoperative clinically detectable complication.
Findings of our study demonstrated that MIOM should be used in all patients undergoing surgery around spinal roots. Monitoring can practically reduce possibilities of neurological deficit. Futhermore, it can be concluded that the use of SSEPs to evaluate the pedicle screw placement or similar interventions is not an appropriate tool itself, since, , it could be practically limited to sensory fibers of root. In these settings and similar procedures, if IOM is required, alternative multimodal methods with greater sensitivity and efficacy should be explored. To aquire MIOM modalities, close collaboration of an anesthesioloist is nessesary.
Spinal surgery, Transpedicular screw, Multimodal intraoperative monitoring
PMCID: PMC3571610
16.  A comparison of angled sagittal MRI and conventional MRI in the diagnosis of herniated disc and stenosis in the cervical foramen 
European Spine Journal  2009;18(8):1109-1116.
The object of this study is to demonstrate that angled sagittal magnetic resonance imaging (MRI) enables the precise diagnosis of herniated disc and stenosis in the cervical foramen, which is not available with conventional MRI. Due to both the anatomic features of the cervical foramen and the limitations of conventional MR techniques, it has been difficult to identify disease in the lateral aspects of the spinal canal and foramen using only conventional MRI. Angled sagittal MRI oriented perpendicular to the true course of the foramina facilitates the identification of the lateral disease. A review of 43 patients, who underwent anterior cervical discectomy and interbody fusion, is presented with a herniated disc and/or stenosis in the cervical foramen. They all had undergone conventional MRI and angled sagittal MRI. Fifty levels were surgically explored for evidence of foraminal herniated disc and stenosis. The results of each test were correlated with what was found at each explored surgical level. The sensitivity, specificity, and accuracy of both examinations for making the diagnosis of foraminal herniated disc and stenosis were compared. During the diagnosis of foraminal herniated disc, the sensitivity, specificity, and accuracy of angled sagittal MRI were 96.7, 95.0, and 96.0%, respectively, compared with 56.7, 85.0, and 68.0% for conventional MRI. In making the diagnosis of foraminal stenosis, the sensitivity, specificity, and accuracy of angled sagittal MRI were 96.3, 95.7, and 96.0%, respectively, compared with 40.7, 91.3, and 66.0% for conventional MRI. In the above groups, the difference between the tests for making the diagnosis of both foraminal herniated disc and stenosis was found to be statistically significant in sensitivity and accuracy. Angled sagittal MRI was a more accurate test compared to conventional MRI for making the diagnosis of herniated disc and stenosis in the cervical foramen. It can be utilized for the precise diagnosis of foraminal herniated disc and stenosis difficult or ambiguous in conventional MRI.
PMCID: PMC2899504  PMID: 19294432
Angled sagittal MRI; Foraminal herniated disc; Foraminal stenosis; Cervical spine
17.  Comparison of postural control in unilateral stance between healthy controls and lumbar discectomy patients with and without pain 
European Spine Journal  2005;15(4):423-432.
Main problem: Previous studies have demonstrated that sciatica patients have poorer postural control than healthy controls and that postural control remains unchanged 3 months after lumbar discectomy in sciatica patients. The aims of the current study were to investigate whether static balance control recovers in pain-free discectomy patients long-term after lumbar discectomy. Next is to determine whether static balance responses of asymptomatic and symptomatic lumbar discectomy patients differed from each other and from healthy controls. In addition, the influence of the extent of disc resection (unilateral/bilateral removal) and the side of operation on static balance control were investigated. Methods: Fifteen pain-free lumbar discectomy patients, 23 lumbar discectomy patients with residual pain and 72 controls performed unilateral stance tasks with eyes open and eyes closed on a force plate were taken up for the investigation. Three repetitions of a 10 s unilateral stance test were performed on each leg. Postural sway was determined. Patients were divided into three age groups. Results: In the eyes open condition, there was no significant difference between postural sway of pain-free lumbar discectomy patients and controls (P=0.68), whereas balance of patients with pain was significantly worse than in controls (P=0.003). In the eyes closed condition, the sway in both groups of lumbar discectomy patients was significantly worse than in controls (pain-free P=0.009/painful P<0.001). No significant differences were found in postural sway between patients with unilateral and bilateral disc resection. In unilateral stance on the leg of the operated side, centre of gravity sway was not significantly different in the eyes open condition compared to the eyes closed condition, whereas in stance on the leg of the non-operated side, postural sway was significantly lower in the eyes open condition compared to the eyes closed condition. In both conditions, postural sway in the age group of 50–65 years was significantly higher than in the age groups of 30–39 years (eyes open P=0.005; eyes closed P<0.001) and 40–49 years (eyes open P=0.002; eyes closed P=0.006). There was no significant difference between the age group of 30–39 years and the age group of 40–49 years (P=0.51). Conclusion: As for long-term following lumbar discectomy, there is no complete recovery of postural control. Patients seem to develop visual compensation mechanisms for underlying sensory–motor deficits, which are, however, sufficient in case of pain relief only. Further study is needed to determine the cause of the balance disturbances in lumbar discectomy patients.
PMCID: PMC3489320  PMID: 16133081
Postural control; Unilateral stance; Lumbar discectomy; Visual compensation
18.  Is a single anterolateral screw-plate fixation sufficient for the treatment of spinal fractures in the thoracolumbar junction? A Biomechanical in vitro Investigation 
European Spine Journal  2004;14(2):197-204.
Controversy exists about the indications, advantages and disadvantages of various surgical techniques used for anterior interbody fusion of spinal fractures in the thoracolumbar junction. The purpose of this study was to evaluate the stabilizing effect of an anterolateral and thoracoscopically implantable screw-plate system. Six human bisegmental spinal units (T12–L2) were used for the biomechanical in vitro testing procedure. Each specimen was tested in three different scenarios: (1) intact spinal segments vs (2) monosegmental (T12/L1) anterolateral fixation (macsTL, Aesculap, Germany) with an interbody bone strut graft from the iliac crest after both partial corpectomy (L1) and discectomy (T12/L1) vs (3) bisegmental anterolateral instrumentation after extended partial corpectomy (L1), and bisegmental discectomy (T12/L1 and L1/L2). Specimens were loaded with an alternating, nondestructive maximum bending moment of ±7.5 Nm in six directions: flexion/extension, right and left lateral bending, and right and left axial rotation. Motion analysis was performed by a contact-less three-dimensional optical measuring system. Segmental stiffness of the three different scenarios was evaluated by the relative alteration of the intervertebral angles in the three main anatomical planes. With each stabilization technique, the specimens were more rigid, compared with the intact spine, for flexion/extension (sagittal plane) as well as in left and right lateral bending (frontal plane). In these planes the bisegmental instrumentation compared to the monosegmental case had an even larger stiffening effect on the specimens. In contrast to these findings, axial rotation showed a modest increase of motion after bisegmental instrumentation. To conclude, the immobilization of monosegmental fractures in the thoracolumbar junction can be secured by means of bone grafting and the implant used in this study for all three anatomical planes. After bisegmental anterolateral stabilization a sufficient reduction of the movements was registered for flexion/extension and lateral bending. However, the observed slight increase of the range of motion in the transversal plane may lead to loosening of the implant before union. Therefore, the use of an additional dorsal fixation device should be considered.
PMCID: PMC3476694  PMID: 15243790
Spine; Biomechanics; In vitro testing
19.  Clinical Features and Treatments of Upper Lumbar Disc Herniations 
Disc herniations at the L1-L2 and L2-L3 levels are different from those at lower levels of the lumbar spine with regard to clinical characteristics and surgical outcome. Spinal canals are narrower than those of lower levels, which may compromise multiple spinal nerve roots or conus medullaris. The aim of this study was to evaluate the clinical features and surgical outcomes of upper lumbar disc herniations.
We retrospectively reviewed the clinical features of 41 patients who had undergone surgery for single disc herniations at the L1-L2 and L2-3 levels from 1998 to 2007. The affected levels were L1-L2 in 14 patients and L2-L3 in 27 patients. Presenting symptoms and signs, patient characteristics, radiologic findings, operative methods, and surgical outcomes were investigated.
The mean age of patients with upper lumbar disc was 55.5 years (ranged 31 to 78). The mean follow-up period was 16.6 months. Most patients complained of back and buttock pain (38 patients, 92%), and radiating pain in areas such as the anterior or anterolateral aspect of the thigh (32 patients, 78%). Weakness of lower extremities was observed in 16 patients (39%) and sensory disturbance was presented in 19 patients (46%). Only 6 patients (14%) had undergone previous lumbar disc surgery. Discectomy was performed using three methods : unilateral laminectomy in 27 cases, bilateral laminectomy in 3 cases, and the transdural approach in 11 cases, which were performed through total laminectomy in 10 cases and unilateral laminectomy in 1 case. With regard to surgical outcomes, preoperative symptoms improved significantly in 33 patients (80.5%), partially in 7 patients (17%), and were aggravated in 1 patient (2.5%).
Clinical features of disc herniations at the L1-L2 and L2-L3 levels were variable, and localized sensory change or pain was rarely demonstrated. In most cases, the discectomy was performed successfully by conventional posterior laminectomy. On the other hand, in large central broad based disc herniation, when the neural elements are severely compromised, the posterior transdural approach could be an alternative.
PMCID: PMC2941853  PMID: 20856659
Clinical feature; Disc herniation; Transdural; Upper lumbar
20.  Monoarticular antigen-induced arthritis leads to pronounced bilateral upregulation of the expression of neurokinin 1 and bradykinin 2 receptors in dorsal root ganglion neurons of rats 
Arthritis Research  2000;2(5):424-427.
This study describes the upregulation of neurokinin 1 and bradykinin 2 receptors in dorsal root ganglion (DRG) neurons in the course of antigen-induced arthritis (AIA) in the rat knee. In the acute phase of AIA, which was characterized by pronounced hyperalgesia, there was a substantial bilateral increase in the proportion of lumbar DRG neurons that express neurokinin 1 receptors (activated by substance P) and bradykinin 2 receptors. In the chronic phase the upregulation of bradykinin 2 receptors persisted on the side of inflammation. The increase in the receptor expression is relevant for the generation of acute and chronic inflammatory pain.
Ongoing pain and hyperalgesia (enhanced pain response to stimulation of the tissue) are major symptoms of arthritis. Arthritic pain results from the activation and sensitization of primary afferent nociceptive nerve fibres ('pain fibres') supplying the tissue (peripheral sensitization) and from the activation and sensitization of nociceptive neurons in the central nervous system (central sensitization). After sensitization, nociceptive neurons respond more strongly to mechanical and thermal stimulation of the tissue, and their activation threshold is lowered. The activation and sensitization of primary afferent fibres results from the action of inflammatory mediators such as bradykinin (BK), prostaglandins and others on membrane receptors located on these neurons. BK is a potent pain-producing substance that is contained in inflammatory exudates. Up to 50% of the primary afferent nerve fibres have receptors for BK. When primary afferent nerve fibres are activated they can release neuropeptides such as substance P (SP) and calcitonin gene-related peptide from their sensory endings in the tissue. SP contributes to the inflammatory changes in the innervated tissue (neurogenic inflammation), and it might also support the sensitization of nociceptive nerve fibres by binding to neurokinin 1 (NK1) receptors. NK1 receptors are normally expressed on a small proportion of the primary afferent nerve fibres.
Because the expression of receptors on the primary afferent neurons is essential for the pain-producing action of inflammatory mediators and neuropeptides, we investigated in the present study whether the expression of BK and NK1 receptors on primary afferent neurons is altered during the acute and chronic phases of an antigen-induced arthritis (AIA). AIA resembles in many aspects the inflammatory process of human rheumatoid arthritis. Because peptide receptors are expressed not only in the terminals of the primary afferent units but also in the cell bodies, we removed dorsal root ganglia (DRGs) of both sides from control rats and from rats with the acute or chronic phase of AIA and determined, after short-term culture of the neurons, the proportion of DRG neurons that expressed the receptors in the different phases of AIA. We also characterized the inflammatory process and the nociceptive behaviour of the rats in the course of AIA.
Materials and methods:
In 33 female Lewis rats 10 weeks old, AIA was induced in the right knee joint. First the rats were immunized in two steps with methylated bovine serum albumin (m-BSA) emulsified with Freund's complete adjuvant, and heat-inactivated Bordetella pertussis. After immunization, m-BSA was injected into the right knee joint cavity to induce arthritis. The joint swelling was measured at regular intervals. Nociceptive (pain) responses to mechanical stimulation of the injected and the contralateral knee were monitored in the course of AIA. Groups of rats were killed at different time points after the induction of AIA, and inflammation and destruction in the knee joint were graded by histological examination. The DRGs of both sides were dissected from segments L1–L5 and C1–C7 from arthritic rats, from eight immunized rats without arthritis and from ten normal control rats. Excised DRGs were dissociated into single cells which were cultured for 18 h.
The expression of the receptors was determined by assessment of the binding of SP-gold or BK-gold to the cultured neurons. For this purpose the cells were slightly fixed. Binding of SP-gold or BK-gold was detected by using enhancement with silver and subsequent densitometric analysis of the relative grey values of the neurons. Displacement controls were performed with SP, the specific NK1 receptor agonist [Sar9, Met(O2)11]-SP, BK, the specific BK 1 (B1) receptor agonist D-Arg (Hyp3-Thi5,8-D-Phe7)-BK and the specific BK 2 (B2) receptor agonist (Des-Arg10)-Lys-BK.
The inflammatory process in the injected right knee joint started on the first day after induction of AIA and persisted throughout the observation period of 84 days (Fig. 1). The initial phase of AIA was characterized by strong joint swelling and a predominantly granulocytic infiltration of the synovial membrane and the joint cavity (acute inflammatory changes). In the later phases of AIA (10–84 days after induction of AIA) the joint showed persistent swelling, and signs of chronic arthritic alterations such as infiltration of mononuclear leucocytes, hyperplasia of synovial lining layer (pannus formation) and erosions of cartilage and bone were predominant. The contralateral knee joints appeared normal at all time points. Destruction was observed only in the injected knee but some proteoglycan loss was also noted in the non-injected, contralateral knee. In the acute and initial chronic phases of AIA (1–29 days) the rats showed mechanical hyperalgesia in the inflamed knee (limping, withdrawal response to gentle pressure onto the knee). In the acute phase (up to 9 days) a pain response was also seen when gentle pressure was applied to the contralateral knee.
Figure 2 displays the changes in the receptor expression in the DRG neurons during AIA. The expression of SP–gold-binding sites in lumbar DRG neurons (Fig. 2a) was substantially increased in the acute phase of arthritis. In untreated control rats (n = 5), 7.7 ± 3.8% of the DRG neurons from the right side and 10.0 ± 1.7% of the DRG neurons from the left side showed labelling with SP–gold. The proportion of SP–gold-labelled neurons in immunized animals without knee injection (n = 3) was similar. By contrast, at days 1 (n = 2 rats) and 3 (n = 5 rats) of AIA in the right knee, approximately 50% of the DRG neurons exhibited labelling with SP–gold, and this was seen both on the side of the injected knee and on the opposite side. At day 10 of AIA (n = 3 rats), 26.3 ± 6.1% of the ipsilateral DRG neurons but only 15.7 ± 0.6% of the contralateral neurons exhibited binding of SP–gold. At days 21 (n = 5 rats), 42 (n = 3 rats) and 84 (n = 5 rats) of AIA, the proportion of SP–gold-positive neurons had returned to the control values, although the arthritis, now with signs of chronic inflammation, was still present. Compared with the DRG neurons of the untreated control rats, the increase in the proportion of labelled neurons was significant on both sides in the acute phase (days 1 and 3) and the intermediate phase (day 10) of AIA (Mann–Whitney U-test). The size distribution of the neurons was similar in the DRG neurons of all experimental groups. Under all conditions and at all time points, SP–gold binding was found mainly in small and medium-sized (less than 700 μm2) neurons. In the cervical DRGs the expression of NK1 receptors did not change in the course of AIA. The binding of SP–gold to the neurons was suppressed by the coadministration of the specific NK1 receptor agonist [Sar9, Met(O2)11]–SP in three experiments, showing that SP–gold was bound to NK1 receptors.
The expression of BK–gold-binding sites in the lumbar DRG neurons showed also changes in the course of AIA, but the pattern was different (Fig. 2b). In untreated control rats (n = 5), 42.3 ± 3.1% of the DRG neurons of the right side and 39.6 ± 2.6% of the DRG neurons of the left side showed binding of BK–gold. At days 1 (n = 2 rats) and 3 (n = 5 rats) of AIA, approximately 80% of the DRG neurons on the side of the knee injection (ipsilateral) and approximately 70% on the opposite side were labelled. In comparison with the untreated control group, the increase in the proportion of labelled neurons was significant on both sides. The proportion of labelled neurons in the ipsilateral DRGs remained significantly increased in both the intermediate phase (day 10, n = 3 rats) and chronic phase (days 21, n = 5 rats, and 42, n = 3 rats) of inflammation. At 84 days after the induction of AIA (n = 5 rats), 51.0 ± 12.7% of the neurons showed an expression of BK–gold-binding sites and this was close to the prearthritic values. However, in the contralateral DRG of the same animals the proportion of BK–gold-labelled neurons declined in the intermediate phase (day 10) and chronic phase (days 21–84) of AIA and was not significantly different from the control value. Thus the increase in BK–gold-labelled neurons was persistent on the side where the inflammation had been induced, and transient on the opposite side. The size distribution of the DRG neurons of the different experimental groups was similar. In the cervical DRGs the expression of BK receptors did not change in the course of AIA. In another series of experiments, we determined the subtype(s) of BK receptor(s) that were expressed in DRGs L1–L5 in different experimental groups. In neither untreated control animals (n = 5) nor immunized rats without knee injection (n = 5) nor in rats at 3 days (n = 5) and 42 days (n = 5) of AIA was the binding of BK–gold decreased by the coadministration of BK–gold and the B1 agonist. By contrast, in these experimental groups the binding of BK–gold was suppressed by the coadministration of the B2 agonist. These results show that B2 receptors, but not B1 receptors, were expressed in both normal animals and in animals with AIA.
These results show that in AIA in the rat the expression of SP-binding and BK-binding sites in the perikarya of DRGs L1–L5 is markedly upregulated in the course of knee inflammation. Although the inflammation was induced on one side only, the initial changes in the binding sites were found in the lumbar DRGs of both sides. No upregulation of SP-binding or BK-binding sites was observed in the cervical DRGs. The expression of SP-binding sites was upregulated only in the first days of AIA, that is, in the acute phase, in which the pain responses to mechanical stimulation were most pronounced. By contrast, the upregulation of BK-binding sites on the side of AIA persisted for up to 42 days, that is, in the acute and chronic phase of AIA. Only the B2 receptor, not the B1 receptor, was upregulated. The coincidence of the enhanced expression of NK1 and BK receptors on sensory neurons and the pain behaviour suggests that the upregulation of these receptors is relevant for the generation and maintenance of arthritic pain.
In the acute phase of AIA, approximately 50% of the lumbar DRG neurons showed an expression of SP-binding sites. Because peptide receptors are transported to the periphery, the marked upregulation of SP-binding receptors probably leads to an enhanced density of receptors in the sensory endings of the primary afferent units. This will permit SP to sensitize more neurons under inflammatory conditions than under normal conditions. However, the expression of NK1 receptors was upregulated only in the acute phase of inflammation, suggesting that SP and NK1 receptors are less important for the generation of hyperalgesia in the chronic phase of AIA.
Because BK is one of the most potent algesic compounds, the functional consequence of the upregulation of BK receptors is likely to be of immediate importance for the generation and maintenance of inflammatory pain. The persistence of the upregulation of BK receptors on the side of inflammation suggests that BK receptors should be an interesting target for pain treatment in the acute and chronic phases. Only B2 receptors were identified in normal animals and in rats with AIA. This is surprising because previous pharmacological studies have provided evidence that, during inflammation, B1 receptors can be newly expressed.
Receptor upregulation in the acute phase of AIA was bilateral and almost symmetrical. However, hyperalgesia was much more pronounced on the inflamed side. It is most likely that receptors on the contralateral side were not readily activated because in the absence of gross inflammation the local concentration of the ligands BK and SP was probably quite low. We hypothesize that the bilateral changes in receptor expression are generated at least in part by mechanisms involving the nervous system. Symmetrical segmental changes can be produced only by the symmetrical innervation, involving either the sympathetic nervous system or the primary afferent fibres. Under inflammatory conditions, primary afferent fibres can be antidromically activated bilaterally in the entry zone of afferent fibres in the spinal cord, and it was proposed that this antidromic activation might release neuropeptides and thus contribute to neurogenic inflammation. Because both sympathetic efferent fibres and primary afferent nerve fibres can aggravate inflammatory symptoms, it is also conceivable that they are involved in the regulation of receptor expression in primary afferent neurons. A neurogenic mechanism might also have been responsible for the bilateral degradation of articular cartilage in the present study.
PMCID: PMC17819  PMID: 11056677
antigen-induced arthritis; bradykinin receptor; dorsal root ganglion neurons; neurokinin 1 receptor; pain
21.  Magnetic Resonance Imaging Predictors of Surgical Outcome in Patients with Lumbar Intervertebral Disc Herniation 
Spine  2013;38(14):1216-1225.
Study Design
A retrospective cohort design
To determine if baseline MRI findings including central/foraminal stenosis, Modic change, disc morphology, facet arthropathy, disc degeneration, nerve root impingement, and thecal sac compression are associated with differential surgical treatment effect.
Summary of Background Data
Intervertebral Disc Herniation (IDH)remains the most common source of lumbar radiculopathy treated either with discectomy or non-operative intervention. Although MRI remains the reliable gold standard for diagnosis, uncertainty surrounds the relationship between MRI findings and treatment outcomes.
Three-hundred-and-seven “complete” images from patients enrolled in a previous trial were de-identified and evaluated by one of 4 independent readers. Findings were compared to outcome measures including the Oswestry Disability Index. Differences in surgery and non-operative treatment outcomes were evaluated between image characteristic subgroups and TE determined by the difference in ODI scores.
The cohort was comprised of 40% females with an average age of 41.5 (±11.6), 61% of which underwent discectomy for IDH. Patients undergoing surgery with Modic type I endplate changes had worse outcomes (−26.4 versus −39.7 for none and −39.2 for type 2, p=0.002) and smaller treatment effect (−3.5 versus −19.3 for none and −15.7 for type 2, p=0.003). Those with compression >=1/3 showed the greatest improvement within the surgical group (−41.9 for >=1/3 versus −31.6 for none and −38.1 for <1/3,p=0.007), and the highest TE (−23 compared to −11.7 for none and −15.2 for <1/3, p=0.015). Furthermore, patients with minimal nerve root impingement demonstrated worse surgical outcomes(−26.5 versus −41.1 for “displaced” and −38.9 for “compressed”, p=0.016).
Among patients with IDH, those with thecal sac compression >=1/3 had greater surgical treatment effect than those with small disc herniations and Modic type I changes. Additionally, patients with nerve root “compression” and “displacement” benefit more from surgery than those with minimal nerve-root impingement.
PMCID: PMC3683115  PMID: 23429684
Intervertebral Disc Herniation; Lumbar; surgical outcome; Magnetic Resonance Imaging; Modic Change; Thecal Sac Compression
22.  Cervical disc herniation presenting with neck pain and contralateral symptoms: a case report 
Cervical disc herniation often results in neck and arm pain in patients as a result of direct impingement of nerve roots and associated inflammatory processes. The clinical presentation usually corresponds with the side of herniation and ipsilateral symptoms predominate the clinical picture.
Case presentation
A 35-year-old Caucasian man presented to our facility with neck pain and left-sided upper and lower extremity pain. A magnetic resonance imaging scan revealed a right paramedian herniated disc at the C5 to C6 level. All other cervical levels were normal without central canal stenosis or neural foraminal stenosis. Results from magnetic reasonance imaging scans of the brain and lumbar spine were negative. An anterior cervical discectomy was performed at the C5 to C6 level, and an inter-body graft and plate were placed. Our patient had complete resolution of his neck and left arm pain.
Anterior discectomy and fusion of the cervical spine resulted in complete resolution of our patient’s neck and left arm symptoms and improvement of his contralateral left leg pain. Cervical disc herniation may present with contralateral symptoms that are different from the current perception of this disease.
PMCID: PMC3411405  PMID: 22741922
Cervical; Contralateral symptoms; Disc herniation; Radiculopathy
23.  Symptomatic Post-Discectomy Pseudocyst after Endoscopic Lumbar Discectomy 
The objectives of this study were to determine the frequency of symptomatic postdiscectomy pseudocyst (PP) after endoscopic discectomy and to compare the results of surgical and conservative management of them.
Initial study participants were 1,503 cases (1,406 patients) receiving endoscopic lumbar discectomy by 23-member board of neurosurgeons from March 2003 to October 2008. All patients' postoperative magnetic resonance imaging (MRI) scans were evaluated. On the postoperative MRI, cystic lesion of T2W high and T1W low at discectomy site was regarded as PP. Reviews of medical records and radiological findings were done. The PP patients were divided into two groups, surgical and conservative management by treatment modality after PP detection. We compared the results of the two groups using the visual analogue scale (VAS) for low back pain (LBP), VAS for leg pain (LP) and the Oswestry disability index (ODI).
Among 1,503 cases of all male soldiers, the MRIs showed that pseudocysts formed in 15 patients, about 1.0% of the initial cases. The mean postoperative interval from surgery to PP detection was 53.7 days. Interlaminar approach was correlated with PP formation compared with transforaminal approach (p=0.001). The mean VAS for LBP and LP in the surgical group improved from 6.5 and 4.8 to 2.0 and 2.3, respectively. The mean VAS for LBP and LP in the conservative group improved from 4.4 and 4.4 to 3.9 and 2.3, respectively. There was no difference in treatment outcome between surgical and conservative management of symptomatic PP.
Although this study was done in limited environment, symptomatic PP was detected at two months' postoperative period in about 1% of cases. Interlaminar approach seems to be more related with PP compared with transforaminal approach.
PMCID: PMC3070892  PMID: 21494360
Endoscopic discectomy; Herniated disc; Lumbar; Postoperative complication; Pseudocyst
24.  The Role of Computed Tomography in the Presurgical Diagnosis of Foraminal Entrapment of Lumbosacral Junction 
On the basis of preoperative computed tomography (CT) scans, we studied the change of the size of anterior primary division (APD) of the L5 spinal root in the presence of foraminal/extraforaminal entrapment of the L5 spinal root.
Two independent radiologists retrospectively reviewed the preoperative CT scans of 27 patients treated surgically and compared the sizes of the APDs on bilateral L5 spinal roots. If one side APD size was larger than the other side APD size, it was described as left or right "dominancy" and regarded this as "consensus (C)" in case that there was a consensus between the larger APD and the location of sciatica, and regarded as "non-consensus (NC)" in case that there was not a consensus. Oswestry Disability Index (ODI) scores were used for preoperative and postoperative evaluation.
On CT scans, twenty-one (77%) of 27 patients were the consensus group (APD swelling) and 6 (22%) were a non-consensus group (APD no swelling). In 9 patients with acute foraminal disc herniations, asymmetric enlargement of the APD on L5 spinal root was detected in all cases (100%) and detected in 11 (64%) of 17 patients with stenosis. Preoperative ODI score was 75-93 (mean 83) and postoperative ODI scores were improved to 13-36 (mean 21). The mean follow-up period was 6 months (range, 3-11 months).
An asymmetric enlargement of the APD on L5 spinal root on CT scans is meaningfully associated with a foraminal or extraforaminal entrapment of the L5 spinal root on the lumbosacral junction.
PMCID: PMC2817508  PMID: 20157370
Computed tomography; Foraminal-extraforaminal entrapment; Lumbosacral junction; Radiculopathy; Surgery
25.  Posterior endoscopic discectomy: Results in 300 patients 
Indian Journal of Orthopaedics  2012;46(1):81-85.
Posterior endoscopic discectomy is an established method for treatment of lumbar disc herniation. Many studies have not been reported in literature for lumbar discectomy by Destandau Endospine System. We report a series of 300 patients operated for lumbar dissectomy by Destandau Endospine system.
Materials and Methods:
A total of 300 patients suffering from lumbar disc herniations were operated between January 2002 and December 2008. All patients were operated as day care procedure. Technique comprised localization of symptomatic level followed by insertion of an endospine system devise through a 15 mm skin and fascial incision. Endoscopic discectomy is then carried out by conventional micro disc surgery instruments by minimal invasive route. The results were evaluated by Macnab's criteria after a minimum followup of 12 months and maximum up to 24 months.
Based on modified Macnab's criteria, 90% patients had excellent to good, 8% had fair, and 2% had poor results. The complications observed were discitis and dural tear in five patients each and nerve root injury in two patients. 90% patients were able to return to light and sedentary work with an average delay of 3 weeks and normal physical activities after 2 months.
Edoscopic discectomy provides a safe and minimal access corridor for lumbar discectomy. The technique also allows early postoperative mobilization and faster return to work.
PMCID: PMC3270611  PMID: 22345812
Endoscope; endoscopic discectomy; endospine; facetectomy; laminotomy; radiculopathy

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