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1.  Endoscopic Foraminal Decompression for Failed Back Surgery Syndrome under local Anesthesia 
Background
The most common causes of failed back surgery are residual or recurrent herniation, foraminal fibrosis and foraminal stenosis that is ignored, untreated, or undertreated. Residual back ache may also be from facetal causes or denervation and scarring of the paraspinal muscles.1–6 The original surgeon may advise his patient that nothing more can be done on the basis of his opinion that the nerve was visually decompressed by the original surgery, supported by improved post-op imaging and follow-up studies such as EMG and conduction velocity studies. Post-op imaging or electrophysiological assessment may be inadequate to explain all the reasons for residual or recurrent symptoms. Treatment of Failed back surgery by repeat traditional open revision surgery usually incorporates more extensive decompression causing increased instability and back pain, therefore necessitating fusion. The authors, having limited their practice to endoscopic MIS surgery over the last 15-20 years, report on their experience gained during that period to relieve pain by endoscopically visualizing and treating unrecognized causative patho-anatomy in FBSS.7
Methods
Thirty consecutive patients with FBSS presenting with back and leg pain that had supporting imaging diagnosis of lateral stenosis and /or residual / recurrent disc herniation, or whose pain complaint was supported by relief from diagnostic and therapeutic injections (Figure 1), were offered percutaneous transforaminal endoscopic discectomy and foraminoplasty over a repeat open procedure. Each patient sought consultation following a transient successful, partially successful or unsuccessful open translaminar surgical treatment for disc herniation or spinal stenosis. Endoscopic foraminoplasty was also performed to either decompress the bony foramen for foraminal stenosis, or foraminoplasty to allow for endoscopic visual examination of the affected traversing and exiting nerve roots in the axilla, also known as the “hidden zone” of Macnab (Figure 2).8, 9 The average follow up time was, average 40 months, minimum 12 months. Outcome data at each visit included Macnab, VAS and ODI.
A diagnostic and therapeutic epidural gram may help identify unrecognized lateral recess stenosis underestimated by MRI. An excellent result from a therapeutic block lends excellent prognosis for a more lasting and “permanent” result from transforaminal endoscopic lateral recess decompression.
Kambin's Triangle provides access to the “hidden zone” of Macnab by foraminoplasty. The foramen and lateral recess is decompressed by removing the ventral aspect and tip of the superior articular process to gain access to the axilla between the traversing and exiting nerve. FBSS contains patho-anatomy in the axilla between the traversing and exiting nerve that hides the pain generators of FBSS.
Results
The average pre-operative VAS improved from 7.2 to 4.0, and ODI 48% to 31%. While temporary dysesthesia occurred in 4 patients in the early post-operative period, all were happy, as all received additional relief of their pre-op symptoms. They were also relieved to be able to avoid “open” decompression or fusion surgery.
Conclusions / Level of Evidence 3
The transforaminal endoscopic approach is effective for FBSS due to residual/recurrent HNP and lateral stenosis. Failed initial index surgery may involve failure to recognize patho-anatomy in the axilla of the foramen housing the traversing and the exiting nerve, including the DRG, which is located cephalad and near the tip of SAP.10 The transforaminal endoscopic approach effectively decompresses the foramen and does not further destabilize the spine needing stabilization.11 It also avoids going through the previous surgical site.
Clinical Relevance
Disc narrowing as a consequence of translaminar discectomy and progressive degenerative narrowing and spondylolisthesis (Figure 3) as a natural history of degenerative disc disease can lead to central and lateral stenosis. The MRI may underestimate the degree of stenosis from a bulging or a foraminal disc protrusion and residual lateral recess stenosis. Pain can be diagnosed and confirmed by evocative discography and by clinical response to transforaminal diagnostic and therapeutic steroid injections.12 Foraminal endoscopic decompression of the lateral recess is a MIS technique that does not “burn bridges” for a more conventional approach and it adds to the surgical armamentarium of FBSS.
Cadaver Illustration of Foraminal Stenosis (courtesy of Wolfgang Rauschning). As the disc narrows, the superior articular process impinges on the exiting nerve and DRG, creating lateral recess stenosis, lumbar spondylosis, and facet arthrosis.
doi:10.14444/1022
PMCID: PMC4325507
Failed Back Surgery Syndrome(FBSS); Hidden zone; Foraminal decompression; Recurrent herniation; Lateral stenosis; Foraminal osteophyte
2.  Electrophysiological diagnosis using sensory nerve action potential for the intraforaminal and extraforaminal L5 nerve root entrapment 
European Spine Journal  2012;22(4):833-839.
Background
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.
Methods
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.
Results
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 %.
Conclusions
Measurement of SNAP could be useful to diagnose a unilateral L5/S foraminal stenosis.
doi:10.1007/s00586-012-2592-5
PMCID: PMC3631025  PMID: 23179988
Electrodiagnosis; Sensory nerve action potential; L5 radiculopathy; Intraforaminal and extraforaminal root entrapment
3.  Clinical applications of diffusion magnetic resonance imaging of the lumbar foraminal nerve root entrapment 
European Spine Journal  2010;19(11):1874-1882.
Diffusion-weighted imaging (DWI) can provide valuable structural information about tissues that may be useful for clinical applications in evaluating lumbar foraminal nerve root entrapment. Our purpose was to visualize the lumbar nerve root and to analyze its morphology, and to measure its apparent diffusion coefficient (ADC) in healthy volunteers and patients with lumbar foraminal stenosis using 1.5-T magnetic resonance imaging. Fourteen patients with lumbar foraminal stenosis and 14 healthy volunteers were studied. Regions of interest were placed at the fourth and fifth lumbar root at dorsal root ganglia and distal spinal nerves (at L4 and L5) and the first sacral root and distal spinal nerve (S1) on DWI to quantify mean ADC values. The anatomic parameters of the spinal nerve roots can also be determined by neurography. In patients, mean ADC values were significantly higher in entrapped roots and distal spinal nerve than in intact ones. Neurography also showed abnormalities such as nerve indentation, swelling and running transversely in their course through the foramen. In all patients, leg pain was ameliorated after selective decompression (n = 9) or nerve block (n = 5). We demonstrated the first use of DWI and neurography of human lumbar nerves to visualize and quantitatively evaluate lumbar nerve entrapment with foraminal stenosis. We believe that DWI is a potential tool for diagnosis of lumbar nerve entrapment.
doi:10.1007/s00586-010-1520-9
PMCID: PMC2989261  PMID: 20632042
Diffusion-weighted imaging; Apparent diffusion coefficient; Lumbar foraminal stenosis; Magnetic resonance (MR) imaging; Neurography
4.  Differentiation between Symptomatic and Asymptomatic Extraforaminal Stenosis in Lumbosacral Transitional Vertebra: Role of Three-Dimensional Magnetic Resonance Lumbosacral Radiculography 
Korean Journal of Radiology  2012;13(4):403-411.
Objective
To investigate the role of lumbosacral radiculography using 3-dimentional (3D) magnetic resonance (MR) rendering for diagnostic information of symptomatic extraforaminal stenosis in lumbosacral transitional vertebra.
Materials and Methods
The study population consisted of 18 patients with symptomatic (n = 10) and asymptomatic extraforaminal stenosis (n = 8) in lumbosacral transitional vertebra. Each patient underwent 3D coronal fast-field echo sequences with selective water excitation using the principles of the selective excitation technique (Proset imaging). Morphologic changes of the L5 nerve roots at the symptomatic and asymptomatic extraforaminal stenosis were evaluated on 3D MR rendered images of the lumbosacral spine.
Results
Ten cases with symptomatic extraforaminal stenosis showed hyperplasia and degenerative osteophytes of the sacral ala and/or osteophytes at the lateral margin of the L5 body. On 3D MR lumbosacral radiculography, indentation of the L5 nerve roots was found in two cases, while swelling of the nerve roots was seen in eight cases at the exiting nerve root. Eight cases with asymptomatic extraforaminal stenosis showed hyperplasia and degenerative osteophytes of the sacral ala and/or osteophytes at the lateral margin of the L5 body. Based on 3D MR lumbosacral radiculography, indentation or swelling of the L5 nerve roots was not found in any cases with asymptomatic extraforaminal stenosis.
Conclusion
Results from 3D MR lumbosacral radiculography Indicate the indentation or swelling of the L5 nerve root in symptomatic extraforaminal stenosis. Based on these findings, 3D MR radiculography may be helpful in the diagnosis of the symptomatic extraforaminal stenosis with lumbosacral transitional vertebra.
doi:10.3348/kjr.2012.13.4.403
PMCID: PMC3384821  PMID: 22778561
Extraforaminal stenosis; MRI; Spinal nerve root
5.  Transforaminal Endoscopic Lumbar Decompression & Foraminoplasty: A 10 Year prospective survivability outcome study of the treatment of foraminal stenosis and failed back surgery 
Background
Conventional diagnosis between axial and foraminal stenosis is suboptimal and long-term outcomes limited to posterior decompression. Aware state Transforaminal Endoscopic Lumbar Decompression and Foraminoplasty (TELDF) offers a direct aware state means of localizing and treating neuro-claudicant back pain, referred pain and weakness associated with stenosis failing to respond to conventional rehabilitation, pain management or surgery. This prospective survivability study examines the outcomes 10 years after TELDF in patients with foraminal stenosis arising from degeneration or failed back surgery.
Methods
For 10 years prospective data were collected on 114 consecutive patients with multilevel spondylosis and neuro-claudicant back pain, referred pain and weakness with or without failed back surgery whose symptoms had failed to respond to conventional rehabilitation and pain management and who underwent TELDF. The level responsible for the predominant presenting symptoms of foraminal stenosis, determined on clinical grounds, MRI and or CT scans, was confirmed by transforaminal probing and discography. Patients underwent TELDF at the spinal segment at which the predominant presenting symptoms were reproduced. Those that required treatment at an additional segment were excluded. Outcomes were assessed by postal questionnaire with failures being examined by the independent authors using the Visual Analogue Pain Scale (VAPS), the Oswestry Disability Index (ODI) and the Prolo Activity Score.
Results
Cohort integrity was 69%. 79 patients were available for evaluation after removal of the deceased (12), untraceable (17) and decliners (6) from the cohort.
VAP scores improved from a pre-operative mean of 7.3 to 2.4 at year 10. The ODI improved from a mean of 58.5 at baseline to 17.5 at year 10. 72% of reviewed patients fulfilled the definition of an “Excellent” or “Good Clinical Impact” at review using the Spinal Foundation Outcome Score. Based on the Prolo scale, 61 patients (77%) were able to return and continue in full or part-time work or retirement activity post-TELDF. Complications of TELDF were limited to transient nerve irritation, which affected 19% of the cohort for 2 – 4 weeks. TELDF was equally beneficial in those with failed back surgery.
Conclusions
TELDF is a beneficial intervention for the long-term treatment of severely disabled patients with neuro-claudicant symptoms arising from spinal or foraminal stenosis with a dural diameter of more than 3mm, who have failed to respond to conventional rehabilitation or chronic pain management. It results in considerable improvements in symptoms and function sustained 10 years later despite co-morbidity, ageing or the presence of failed back surgery.
Clinical Relevance
The long term outcome of TELDF in severely disabled patients with neuro-claudicant symptoms arising from foraminal stenosis which had failed to respond to conventional rehabilitation, surgery or chronic pain management suggests that foraminal pathology is a major cause of lumbar axial and referred pain and that TELDF should be offered as primary treatment for these conditions even in the elderly and infirm. The application of TELDF at multiple levels may further widen the benefits of this technique.
doi:10.14444/1021
PMCID: PMC4325492
Lateral Recess Stenosis; Axial Stenosis; Foraminal stenosis; Spinal Decompression; Failed Back Surgery; Endoscopic Decompression; Foraminoplasty; Foraminotomy; Failed Fusion Surgery; Failed Chronic Pain Management; Differential Discography; Transforaminal Spinal Probing; disc degeneration; Disc Protrusion; Long-Term Outcome
6.  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.
doi:10.3346/jkms.2004.19.1.101
PMCID: PMC2822244  PMID: 14966350
Cervical Vertebrae; Intervertebral Disk; Magnetic Resonance Imaging; Tomography, X-Ray Computed
7.  Degenerative lumbar spinal stenosis: correlation with Oswestry Disability Index and MR Imaging 
European Spine Journal  2008;17(5):679-685.
Because neither the degree of constriction of the spinal canal considered to be symptomatic for lumbar spinal stenosis nor the relationship between the clinical appearance and the degree of a radiologically verified constriction is clear, a correlation of patient’s disability level and radiographic constriction of the lumbar spinal canal is of interest. The aim of this study was to establish a relationship between the degree of radiologically established anatomical stenosis and the severity of self-assessed Oswestry Disability Index in patients undergoing surgery for degenerative lumbar spinal stenosis. Sixty-three consecutive patients with degenerative lumbar spinal stenosis who were scheduled for elective surgery were enrolled in the study. All patients underwent preoperative magnetic resonance imaging and completed a self-assessment Oswestry Disability Index questionnaire. Quantitative image evaluation for lumbar spinal stenosis included the dural sac cross-sectional area, and qualitative evaluation of the lateral recess and foraminal stenosis were also performed. Every patient subsequently answered the national translation of the Oswestry Disability Index questionnaire and the percentage disability was calculated. Statistical analysis of the data was performed to seek a relationship between radiological stenosis and percentage disability recorded by the Oswestry Disability Index. Upon radiological assessment, 27 of the 63 patients evaluated had severe and 33 patients had moderate central dural sac stenosis; 11 had grade 3 and 27 had grade 2 nerve root compromise in the lateral recess; 22 had grade 3 and 37 had grade 2 foraminal stenosis. On the basis of the percentage disability score, of the 63 patients, 10 patients demonstrated mild disability, 13 patients moderate disability, 25 patients severe disability, 12 patients were crippled and three patients were bedridden. Radiologically, eight patients with severe central stenosis and nine patients with moderate lateral stenosis demonstrated only minimal disability on percentage Oswestry Disability Index scores. Statistical evaluation of central and lateral radiological stenosis versus Oswestry Disability Index percentage scores showed no significant correlation. In conclusion, lumbar spinal stenosis remains a clinico-radiological syndrome, and both the clinical picture and the magnetic resonance imaging findings are important when evaluating and discussing surgery with patients having this diagnosis. MR imaging has to be used to determine the levels to be decompressed.
doi:10.1007/s00586-008-0646-5
PMCID: PMC2367417  PMID: 18324426
Spine, abnormalities; Spine, MR; Lumbar spinal stenosis; Oswestry Disability Index
8.  Morphometric analysis of the lumbar intervertebral foramen in patients with degenerative lumbar scoliosis by multidetector-row computed tomography 
European Spine Journal  2012;21(12):2594-2602.
Purpose
How the lumbar neural foramina are affected by segmental deformities in patients in whom degenerative lumbar scoliosis (DLS) is unknown. Here, we used multidetector-row computed tomography (MDCT) to measure the morphology of the foramina in three dimensions, which allowed us to elucidate the relationships between foraminal morphology and segmental deformities in DLS.
Methods
In 77 DLS patients (mean age, 69.4) and 19 controls (mean age, 69), the foraminal height (FH), foraminal width (FW), posterior disc height (PDH), interval between the pedicle and superior articular process (P-SAP), and cross-sectional foraminal area (FA) were measured on reconstructed MDCT data, using image-editing software, at the entrance, minimum-area point, and exit of each foramen. The parameters of segmental deformity included the intervertebral wedging angle and anteroposterior and lateral translation rate, measured on radiographs, and the vertebral rotation angle, measured using reconstructed MDCT images.
Results
The FH, PDH, P-SAP, and FA were smaller at lower lumbar levels and on the concave side of intervertebral wedging (p < 0.05). In the DLS patients, the FH, P-SAP, and FA were significantly smaller than for the control group at all three foraminal locations and every lumbar level (p < 0.05). Intervertebral wedging strongly decreased the FA of the concave side (p < 0.05). Anteroposterior translation caused the greatest reduction in P-SAP (p < 0.05). Vertebral rotation decreased the P-SAP and FA at the minimum-area point on the same side as the rotation (p < 0.05).
Conclusion
The new analysis method proposed here is useful for understanding the pathomechanisms of foraminal stenosis in DLS patients.
doi:10.1007/s00586-012-2408-7
PMCID: PMC3508233  PMID: 22743646
Degenerative lumbar scoliosis; Segmental deformity; Intervertebral foramina; Multidetector-row computed tomography
9.  A New Electrophysiological Method for the Diagnosis of Extraforaminal Stenosis at L5-S1 
Asian Spine Journal  2014;8(2):145-149.
Study Design
A retrospective study.
Purpose
To examine the effectiveness of using an electrodiagnostic technique as a new approach in the clinical diagnosis of extraforaminal stenosis at L5-S1.
Overview of Literature
We introduced a new effective approach to the diagnosis of extraforaminal stenosis at the lumbosacral junction using the existing electrophysiological evaluation technique.
Methods
A consecutive series of 124 patients with fifth lumbar radiculopathy were enrolled, comprising a group of 74 patients with spinal canal stenosis and a second group of 50 patients with extraforaminal stenosis at L5-S1. The technique involved inserting a pair of needle electrodes into the foraminal exit zone of the fifth lumbar spinal nerves, which were used to provide electrical stimulation. The compound muscle action potentials from each of the tibialis anterior muscles were recorded.
Results
The distal motor latency (DML) of the potentials ranged from 11.2 to 24.6 milliseconds in patients with extraforaminal stenosis. In contrast, the DML in patients with spinal canal stenosis ranged from 10.0 to 17.2 milliseconds. After comparing the DML of each of the 2 groups and at the same time comparing the differences in DML between the affected and unaffected side of each patient, we concluded there were statistically significant differences (p<0.01) between the 2 groups. Using receiver operating characteristic curve analysis, the cutoff values were calculated to be 15.2 milliseconds and 1.1 milliseconds, respectively.
Conclusions
This approach using a means of DML measurement enables us to identify and localize lesions, which offers an advantage in diagnosing extraforaminal stenosis at L5-S1.
doi:10.4184/asj.2014.8.2.145
PMCID: PMC3996337  PMID: 24761195
Diagnosis; Evoked potencials; Spinal stenosis; Diagnostic techniques and procedures; Far-out syndrome
10.  Clinical correlation of magnetic resonance imaging with symptom complex in prolapsed intervertebral disc disease: A cross-sectional double blind analysis 
Introduction:
Low backache (LBA) is one of the most common problems and herniated lumbar disc is one of the most commonly diagnosed abnormalities associated with LBA. Disc herniation of the same size may be asymptomatic in one patient and can lead to severe nerve root compromise in another patient.
Objective:
To evaluate correlation between the clinical features of disc collapse and magnetic resonance imaging (MRI) finding to determine the clinical importance of anatomical abnormalities identified by MRI technique.
Summary:
From January 2010 to January 2012, 75 otherwise healthy patients (43 males 32 females) between the age of 19 and 55 years (average age was 44.5 years) with low back pain and predominant complaint of root pain who presented to our clinic were included in the study.
Materials and Methods:
Proper screening was done to rule out previous spine affection and subjected to MRI.
Results:
The results were analyzed under four headings viz. disc herniation, disc degeneration, thecal sac deformation and neural foramen effacement. All patients had a visual analog score (VAS) score more than 6. The interrater correlation coefficient kappa was calculated to be k=0.51. There were total 44 patients with herniation, 25 patients had mild, one patient had moderate degree of thecal sac deformation, 21 patients had one or more levels of foraminal effacement by the herniated tissue, 100% of the patients had disc degeneration ranging from grade 1 to 3 at different levels; and 48 patients (64%) had radiculopathy, six (8%) patients had bilateral and others had ipsilateral affection.
Conclusion:
In our study, the correlation was made between clinical findings and MRI findings. It can safely be concluded that treating physician should put more emphasis on history, clinical examination, and make the inference by these and then should correlate the clinical findings with that of MRI to reach a final diagnosis.
doi:10.4103/0974-8237.121619
PMCID: PMC3872655  PMID: 24381451
Disc degeneration; disc herniation; neural foramen effacement; thecal sac deformation
11.  Reliability of Readings of Magnetic Resonance Imaging Features of Lumbar Spinal Stenosis 
Spine  2008;33(14):1605-1610.
Study Design
A reliability assessment of standardized magnetic resonance imaging (MRI) interpretations and measurements.
Objective
To determine the intra- and inter-reader reliability of MRI features of lumbar spinal stenosis (SPS), including severity of central, subarticular, and foraminal stenoses, grading of nerve root impingement, and measurements of cross-sectional area of the spinal canal and thecal sac.
Summary of Background Data
MRI is commonly used to assess patients with spinal stenosis. Although a number of studies have evaluated the reliability of certain MRI characteristics, comprehensive evaluation of the reliability of MRI readings in spinal stenosis is lacking.
Methods
Fifty-eight randomly selected MR images from patients with SPS enrolled in the Spine Patient Outcomes Research Trial were evaluated. Qualitative ratings of imaging features were performed according to defined criteria by 4 independent readers (3 radiologists and 1 orthopedic surgeon). A sample of 20 MRIs was reevaluated by each reader at least 1 month later. Weighted κ statistics were used to characterize intra- and inter-reader reliability for qualitative rating data. Separate quantitative measurements were performed by 2 other radiologists. Intraclass correlation coefficients and summaries of measurement error were used to characterize reliability for quantitative measurements.
Results
Intra-reader reliability was higher than interreader reliability for all features. Inter-reader reliability in assessing central stenosis was substantial, with an overall κ of 0.73 (95% CI 0.69-0.77). Foraminal stenosis and nerve root impingement showed moderate to substantial agreement with overall κ of 0.58 (95% CI 0.53-0.63) and 0.51 (95% CI 0.42-0.59), respectively. Subarticular zone stenosis yielded the poorest agreement (overall κ 0.49; 95% CI 0.42-0.55) and showed marked variability in agreement between reader pairs. Quantitative measures showed inter-reader intraclass correlation coefficients ranging from 0.58 to 0.90. The mean absolute difference between readers in measured thecal sac area was 128 mm2 (13%).
Conclusion
The imaging characteristics of spinal stenosis assessed in this study showed moderate to substantial reliability; future studies should assess whether these findings have prognostic significance in SPS patients.
doi:10.1097/BRS.0b013e3181791af3
PMCID: PMC2754786  PMID: 18552677
spinal stenosis; MRI; reliability
12.  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
Objective
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1097/BRS.0b013e31828ce66d
PMCID: PMC3683115  PMID: 23429684
Intervertebral Disc Herniation; Lumbar; surgical outcome; Magnetic Resonance Imaging; Modic Change; Thecal Sac Compression
13.  Interspinous spacers for lumbar foraminal stenosis: formal trials are justified 
European Spine Journal  2013;22(Suppl 1):47-53.
Purpose
To determine whether preliminary evidence supports X-STOP implants as an effective treatment for lumbar radiculopathy secondary to foraminal stenosis, and if larger formal trials are warranted.
Methods
Participants had a clinical diagnosis of lumbar radiculopathy supported by MRI findings of foraminal stenosis and relevant nerve root compression. Self-reported disability and pain were measured pre-operation, early and late post-operation using the widely used Oswestry Disablity Index (ODI) and the bodily pain scale of the Medical Outcomes Study 36-item Short Form Health Survey (SF-36BP). The statistical significance (paired samples t test; Wilcoxon signed ranks test), and clinical significance (Cohen’s effect size; Standardised response means) of change scores was determined.
Results
Fifteen people had X-STOP implants. Data pre- early- and late post-operation were available for ten. Self-reported disability and pain improved substantially by the early post operative measurement. Mean change scores (ODI = 29; SF-36BP = −45), significant at the p < 0.05 but not significant at the p < 0.001, were very large and effect sizes exceeded notably criteria for large clinical improvements (>0.80). Improvements were maintained at 2–3 years. Both scales had floor and ceiling effects implying changes may be underestimated. There were no surgical complications.
Conclusions
In this small study, X-STOP appeared safe and effective. It is less invasive than other established surgical procedures, but does not jeopardise other options in the event of failure. Large scale clinical trials are justified but floor and ceiling effects suggest that the ODI and SF-36 may not be the best choice of outcome measures for those studies.
doi:10.1007/s00586-012-2650-z
PMCID: PMC3578516  PMID: 23354776
Lumbar radiculopathy; Foraminal stenosis; Interspinous implant; X-STOP; Outcome measures; Oswestry disability index; SF-36; Ceiling/floor effects
14.  Influence of preoperative nucleus pulposus status and radiculopathy on outcomes in mono-segmental lumbar total disc replacement: results from a nationwide registry 
Background
Currently, herniated nucleus pulposus (HNP) with radiculopathy and other preconditions are regarded as relative or absolute contraindications for lumbar total disc replacement (TDR). In Switzerland it is left to the surgeon's discretion when to operate. The present study is based on the dataset of SWISSspine, a governmentally mandated health technology assessment registry. We hypothesized that preoperative nucleus pulposus status and presence or absence of radiculopathy has an influence on clinical outcomes in patients treated with mono-segmental lumbar TDR.
Methods
Between March 2005 and April 2009, 416 patients underwent mono-segmental lumbar TDR, which was documented in a prospective observational multicenter mode. The data collection consisted of perioperative and follow-up data (physician based) and clinical outcomes (NASS, EQ-5D).
Patients were divided into four groups according to their preoperative status: 1) group degenerative disc disease ("DDD"): 160 patients without HNP and no radiculopathy, classic precondition for TDR; 2) group "HNP-No radiculopathy": 68 patients with HNP but without radiculopathy; 3) group "Stenosis": 73 patients without HNP but with radiculopathy, and 4) group "HNP-Radiculopathy": 132 patients with HNP and radiculopathy. The groups were compared regarding preoperative patient characteristics and pre- and postoperative VAS and EQ-5D scores using general linear modeling.
Results
Demographics in all four groups were comparable. Regarding the improvement of quality of life (EQ-5D) there were no differences across the four groups. For the two main groups DDD and HNP-Radiculopathy no differences were found in the adjusted postoperative back- and leg pain alleviation levels, in the stenosis group back- and leg pain relief were lower.
Conclusions
Despite higher preoperative leg pain levels, outcomes in lumbar TDR patients with HNP and radiculopathy were similar to outcomes in patients with the classic indication; this because patients with higher preoperative leg pain levels benefit from a relatively greater leg pain alleviation. The group with absence of HNP but presence of radiculopathy showed considerably less benefits from the operation, which is probably related to ongoing degenerative processes of the posterior segmental structures. This observational multicenter study suggests that the diagnoses HNP and radiculopathy, combined or alone, may not have to be considered as absolute or relative contraindications for mono-segmental lumbar TDR anymore, whereas patients without HNP but with radiculopathy seem to be suboptimal candidates for the procedure.
doi:10.1186/1471-2474-12-275
PMCID: PMC3250959  PMID: 22136141
15.  Perioperative complications with rhBMP-2 in transforaminal lumbar interbody fusion 
European Spine Journal  2010;20(4):612-617.
Bone morphogenetic protein (BMP) is commonly used as an ICBG substitute for transforaminal lumbar interbody spine fusion (TLIF). However, multiple recent reports have raised concerns regarding a substantial incidence of perioperative radiculopathy. Also, given the serious complications reported with anterior cervical BMP use, risks related to swelling and edema with TLIF need to be clarified. As TLIF related complications with rhBMP-2 have generally been reported in small series or isolated cases, without a clear denominator, actual complication rates are largely unknown. The purpose this study is to characterize perioperative complications and complication rates in a large consecutive series of TLIF procedures with rhBMP-2. We reviewed inpatient and outpatient medical records for a consecutive series of 204 patients [113 females, 91 males, mean age 49.3 (22–79) years] who underwent TLIF using rhBMP-2 between 2003 and 2007. Complications observed within a 3-month perioperative interval were categorized as to etiology and severity. Wound problems were delineated as wound infection, hematoma/seroma or persistent drainage/superficial dehiscence. Neurologic deficits and radiculopathies were analyzed to determine the presence of a clear etiology (screw misplacement) and identify any potential relationship to rhBMP-2 usage. Complications were observed in 47 of 204 patients (21.6%) during the 3-month perioperative period. Major complications occurred in 13 patients (6.4%) and minor complications in 34 patients (16.7%). New or more severe postoperative neurologic complaints were noted in 13 patients (6.4%), 6 of whom required additional surgery. These cases included one malpositioned pedicle screw and one epidural hematoma. In four patients (2.0%), localized seroma/hematoma in the area of the foramen caused neural compression, and required revision. In one additional patient, vertebral osteolysis caused foraminal narrowing and radiculopathy, but resolved without further surgery. Persistent radiculopathy without clear etiology on imaging studies was seen in six patients. Wound related problems were seen in six patients (2.9%), distributed as wound infection (3), hematoma/seroma (1) and persistent drainage/dehiscence (2). Overall, this study demonstrates a modest complication rate for TLIF using rhBMP-2. While perioperative complications which appeared specific to BMP usage were noted, they occurred infrequently. It will be necessary to weigh this incidence of complications against the complication rate associated with ICBG harvest and any differential benefit in obtaining a solid arthrodesis.
doi:10.1007/s00586-010-1494-7
PMCID: PMC3065615  PMID: 20582554
Bone graft substitute; Bone morphogenetic protein; Transforaminal interbody fusion; Morbidity; Spine fusion
16.  COMPARABLE EFFECTIVENESS OF CAUDAL VS. TRANS-FORAMINAL EPIDURAL STEROID INJECTIONS 
Study Design: Retrospective case-control study.
Objective: To compare the effectiveness between caudal and trans-foraminal epidural steroid injections for the treatment of primary lumbar radiculopathy.
Summary of Background Data: Spinal injections with steroids play an important role in non-operative care of lumbar radiculopathy. The trans-foraminal epidural steroid injection (TESI) theoretically has a higher success rate based on targeted delivery to the symptomatic nerve root. To our knowledge, these results have not been compared with other techniques of epidural steroid injection.
Methods: 93 patients diagnosed with primary lumbar radiculopathy of L4, L5, or SI were recruited for this study: 39 received caudal epidural steroid injections (ESI) and 54 received trans-foraminal epidural steroid injections (TESI). Outcomes scores included the SF-36, Oswestry disability index (ODI) and pain visual analogue scale (VAS), and were recorded at baseline, post-treatment (<6 months), long-term (>1 year). The average follow-up was 2 years, and 16 patients were lost to follow-up. The endpoint “surgical intervention” was a patient-driven decision, and considered failure of treatment. Intent-to-treat analysis, and comparisons included t-test, Chi-square, and Wilcoxon rank-sum test.
Results: Baseline demographics and outcomes scores were comparable for both treatment groups (ESI vs. TESI): (SF-36 PCS (32.3 ± 7.5 vs. 29.5 ± 8.9 respectively; p = 0.173), MCS (41.2 ± 12.7 vs. 41.1 ± 10.9, respectively; p = 0.971), and VAS (7.4 ±2.1 vs. 7.9 ± 1.2, respectively; p = 0.228)). Surgery was indicated for failure of treatment at a similar rate for both groups (41.0% vs. 44.4%, p=0.743). Symptom improvement was comparable between both treatment groups (ESI vs. TESI): SF-36 PCS improved to 42.0±11.8 and 37.7±12.3, respectively; p=0.49; ODI improved from 50.0±21.2 to 15.6±17.9and from 62.1±17.9 to 26.1±20.3, respectively (p=0.407).
Conclusions: The effectiveness of TESI is comparable to that of ESI (approximately 60%) for the treatment of primary lumbar radiculopathy. The increased complexity of TESI is not justified for primary cases, and may have a more specific role in recurrent disease or for diagnostic purposes.
PMCID: PMC2723700  PMID: 19742093
17.  Intraoperative neurophysiological monitoring in spinal root surgical interventions 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 84.
Abstract:
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Keywords:
Spinal surgery, Transpedicular screw, Multimodal intraoperative monitoring
PMCID: PMC3571610
18.  A practical MRI grading system for cervical foraminal stenosis based on oblique sagittal images 
The British Journal of Radiology  2013;86(1025):20120515.
Objective:
To propose a new and practical MRI grading method for cervical neural foraminal stenosis and to evaluate its reproducibility.
Methods:
We evaluated 50 patients (37 males and 13 females, mean age 49 years) who visited our institution and underwent oblique sagittal MRI of the cervical spine. A total of 300 foramina and corresponding nerve roots in 50 patients were qualitatively analysed from C4–5 to C6–7. We assessed the grade of cervical foraminal stenosis at the maximal narrowing point according to the new grading system based on T2 weighted oblique sagittal images. The incidence of each of the neural foraminal stenosis grades according to the cervical level was analysed by χ2 tests. Intra- and interobserver agreements between two radiologists were analysed using kappa statistics. Kappa value interpretations were poor (κ<0.1), slight (0.1≤κ≤0.2), fair (0.2<κ≤0.4), moderate (0.4<κ≤0.6), substantial (0.6<κ≤0.8) and almost perfect (0.8<κ≤1.0).
Results:
Significant stenoses (Grades 2 and 3) were rarely found at the C4–5 level. The incidence of Grade 3 at the C5–6 level was higher than that at other levels, a difference that was statistically significant. The overall intra-observer agreement according to the cervical level was almost perfect. The agreement at each level was almost perfect, except for only substantial agreement at the right C6–7 by Reader 2. No statistically significant differences were seen according to the cervical level. Overall kappa values of interobserver agreement according to the cervical level were almost perfect. In addition, the agreement of each level was almost perfect. Overall intra- and interobserver agreement for the presence of foraminal stenosis (Grade 0 vs Grades 1, 2 and 3) and for significant stenosis (Grades 0 and 1 vs Grades 2 and 3) showed similar results and were almost perfect. However, only substantial agreement was seen in the right C6–7.
Conclusion:
A new grading system for cervical foraminal stenosis based on oblique sagittal MRI provides reliable assessment and good reproducibility. This new grading system is a useful and easy method for the objective evaluation of cervical neural foraminal stenosis by radiologists and clinicians.
Advances in knowledge:
The use of the new grading system for cervical foraminal stenosis based on oblique sagittal MRI can be a useful method for evaluating cervical neural foraminal stenosis.
doi:10.1259/bjr.20120515
PMCID: PMC3635796  PMID: 23410800
19.  Cervical foraminal selective nerve root block: a ‘two-needle technique’ with results 
European Spine Journal  2008;17(4):576-584.
Several techniques have been described for selective nerve root blocks. We describe a novel ‘two-needle technique’, performed through the postero-lateral route with the patient in lateral position under C-arm guidance. The aim of the current study is to highlight the effectiveness and safety of cervical selective nerve root block for radiculopathy using this technique. We present results of a retrospective 2-year follow-up study of 33 injections carried out on 33 patients with radiculopathy due to cervical disc disease and or foraminal stenosis using this procedure. Patients with myelopathy, gross motor weakness and any other pathology were excluded. The outcome was measured comparing ‘Visual Analogue Score’ (VAS) and ‘Neck Disability Index’ (NDI) before the procedure with those at 6 weeks and 12 months after the procedure. Thirty patients were included in the final analysis. Average pre-operative VAS score was 7.4 (range 5–10), which improved to 2.2 (range 0–7) at 6 weeks and 2.0 (range 0–4) at 1 year and the mean NDI score prior to intervention was 66.9 (range 44–84), which improved to 31.7 (range 18–66) at 6 weeks and 31.1 (range 16–48) at 1 year. The improvements were statistically significant. Patients with involvement of C6 or C7 nerve roots responded slightly better at 6 weeks with regards to VAS improvement. Mean duration of radiation exposure during the procedure was 27.8 s (range 10–90 s). Only minor complications were noted—transient dizziness in two and transient nystagmus in one patient. Our ‘two-needle technique’ is a new, safe and effective non-surgical treatment for cervical radiculopathy.
doi:10.1007/s00586-008-0600-6
PMCID: PMC2295277  PMID: 18204941
Cervical radiculopathy; Selective nerve root block; Two-needle technique; Steroid; Cervical spondylosis
20.  Ectopic Lymphoid Structures Support Ongoing Production of Class-Switched Autoantibodies in Rheumatoid Synovium 
PLoS Medicine  2009;6(1):e1.
Background
Follicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium.
Methods and Findings
Using immunohistochemistry (IHC) and quantitative Taqman real-time PCR (QT-PCR) in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Iγ-Cμ circular transcripts (identifying ongoing IgM-IgG class-switching) was observed in synovial grafts expressing FDCs/CD21L. Furthermore, synovial mRNA levels of AID were closely associated with circulating human IgG ACPA in mouse sera. Finally, the survival and proliferation of functional B cell niches was associated with persistent overexpression of genes regulating ectopic lymphoneogenesis.
Conclusions
Our demonstration that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells provides strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production. This concept is further confirmed by evidence of sustained AID expression, B cell proliferation, ongoing CSR, and production of human IgG ACPA from GC+ synovial tissue transplanted into SCID mice, independently of new B cell influx from the systemic circulation. These data identify AID as a potential therapeutic target in RA and suggest that survival of functional synovial B cell niches may profoundly influence chronic inflammation, autoimmunity, and response to B cell–depleting therapies.
Costantino Pitzalis and colleagues show that lymphoid structures in synovial tissue of patients with rheumatoid arthritis support production of anti-citrullinated peptide antibodies, which continues following transplantation into SCID mice.
Editors' Summary
Background.
More than 1 million people in the United States have rheumatoid arthritis, an “autoimmune” condition that affects the joints. Normally, the immune system provides protection against infection by responding to foreign antigens (molecules that are unique to invading organisms) while ignoring self-antigens present in the body's own tissues. In autoimmune diseases, this ability to discriminate between self and non-self fails for unknown reasons and the immune system begins to attack human tissues. In rheumatoid arthritis, the lining of the joints (the synovium) is attacked, it becomes inflamed and thickened, and chemicals are released that damage all the tissues in the joint. Eventually, the joint may become so scarred that movement is no longer possible. Rheumatoid arthritis usually starts in the small joints in the hands and feet, but larger joints and other tissues (including the heart and blood vessels) can be affected. Its symptoms, which tend to fluctuate, include early morning joint pain, swelling, and stiffness, and feeling generally unwell. Although the disease is not always easy to diagnose, the immune systems of many people with rheumatoid arthritis make “anti-citrullinated protein/peptide antibodies” (ACPA). These “autoantibodies” (which some experts believe can contribute to the joint damage in rheumatoid arthritis) recognize self-proteins that contain the unusual amino acid citrulline, and their detection on blood tests can help make the diagnosis. Although there is no cure for rheumatoid arthritis, the recently developed biologic drugs, often used together with the more traditional disease-modifying therapies, are able to halt its progression by specifically blocking the chemicals that cause joint damage. Painkillers and nonsteroidal anti-inflammatory drugs can reduce its symptoms, and badly damaged joints can sometimes be surgically replaced.
Why Was This Study Done?
Before scientists can develop a cure for rheumatoid arthritis, they need to know how and why autoantibodies are made that attack the joints in this common and disabling disease. B cells, the immune system cells that make antibodies, mature in structures known as “germinal centers” in the spleen and lymph nodes. In the germinal centers, immature B cells are exposed to antigens and undergo two genetic processes called “somatic hypermutation” and “class-switch recombination” that ensure that each B cell makes an antibody that sticks as tightly as possible to just one antigen. The B cells then multiply and enter the bloodstream where they help to deal with infections. Interestingly, the inflamed synovium of many patients with rheumatoid arthritis contains structures that resemble germinal centers. Could these ectopic (misplaced) lymphoid structures, which are characterized by networks of immune system cells called follicular dendritic cells (FDCs), promote autoimmunity and long-term inflammation by driving the production of autoantibodies within the joint itself? In this study, the researchers investigate this possibility.
What Did the Researchers Do and Find?
The researchers collected synovial tissue from 55 patients with rheumatoid arthritis and used two approaches, called immunohistochemistry and real-time PCR, to investigate whether FDC-containing structures in synovium expressed an enzyme called activation-induced cytidine deaminase (AID), which is needed for both somatic hypermutation and class-switch recombination. All the FDC-containing structures that the researchers found in their samples expressed AID. Furthermore, these AID-containing structures were surrounded by mature B cells making ACPAs. To test whether these B cells were derived from AID-expressing cells resident in the synovium rather than ACPA-expressing immune system cells coming into the synovium from elsewhere in the body, the researchers transplanted synovium from patients with rheumatoid arthritis under the skin of a special sort of mouse that largely lacks its own immune system. Four weeks later, the researchers found that the transplanted human lymphoid tissue was still making AID, that the level of AID expression correlated with the amount of human ACPA in the blood of the mice, and that the B cells in the transplant were proliferating.
What Do These Findings Mean?
These findings show that the ectopic lymphoid structures present in the synovium of some patients with rheumatoid arthritis are functional and are able to make ACPA. Because ACPA may be responsible for joint damage, the survival of these structures could, therefore, be involved in the development and progression of rheumatoid arthritis. More experiments are needed to confirm this idea, but these findings may explain why drugs that effectively clear B cells from the bloodstream do not always produce a marked clinical improvement in rheumatoid arthritis. Finally, they suggest that AID might provide a new target for the development of drugs to treat rheumatoid arthritis.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0060001.
This study is further discussed in a PLoS Medicine Perspective by Rene Toes and Tom Huizinga
The MedlinePlus Encyclopedia has a page on rheumatoid arthritis (in English and Spanish). MedlinePlus provides links to other information on rheumatoid arthritis (in English and Spanish)
The UK National Health Service Choices information service has detailed information on rheumatoid arthritis
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides Fast Facts, an easy to read publication for the public, and a more detailed Handbook on rheumatoid arthritis
The US Centers for Disease Control and Prevention has an overview on rheumatoid arthritis that includes statistics about this disease and its impact on daily life
doi:10.1371/journal.pmed.0060001
PMCID: PMC2621263  PMID: 19143467
21.  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.
doi:10.1007/s11999-008-0142-6
PMCID: PMC2504658  PMID: 18259829
22.  Accuracy of physical examination for chronic lumbar radiculopathy 
Background
Clinical examination of patients with chronic lumbar radiculopathy aims to clarify whether there is nerve root impingement. The aims of this study were to investigate the association between findings at clinical examination and nerve root impingement, to evaluate the accuracy of clinical index tests in a specialised care setting, and to see whether imaging clarifies the cause of chronic radicular pain.
Methods
A total of 116 patients referred with symptoms of lumbar radiculopathy lasting more than 12 weeks and at least one positive index test were included. The tests were the straight leg raising test, and tests for motor muscle strength, dermatome sensory loss, and reflex impairment. Magnetic resonance imaging (n = 109) or computer tomography (n = 7) were imaging reference standards. Images were analysed at the level of single nerve root(s), and nerve root impingement was classified as present or absent. Sensitivities, specificities, and positive and negative likelihood ratios (LR) for detection of nerve root impingement were calculated for each individual index test. An overall clinical evaluation, concluding on the level and side of the radiculopathy, was performed.
Results
The prevalence of disc herniation was 77.8%. The diagnostic accuracy of individual index tests was low with no tests reaching positive LR >4.0 or negative LR <0.4. The overall clinical evaluation was slightly more accurate, with a positive LR of 6.28 (95% CI 1.06–37.21) for L4, 1.74 (95% CI 1.04–2.93) for L5, and 1.29 (95% CI 0.97–1.72) for S1 nerve root impingement. An overall clinical evaluation, concluding on the level and side of the radiculopathy was also performed, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) calculation for diagnostic accuracy of this evaluation was performed.
Conclusions
The accuracy of individual clinical index tests used to predict imaging findings of nerve root impingement in patients with chronic lumbar radiculopathy is low when applied in specialised care, but clinicians’ overall evaluation improves diagnostic accuracy slightly. The tests are not very helpful in clarifying the cause of radicular pain, and are therefore inaccurate for guidance in the diagnostic workup of the patients. The study population was highly selected and therefore the results from this study should not be generalised to unselected patient populations in primary care nor to even more selected surgical populations.
doi:10.1186/1471-2474-14-206
PMCID: PMC3716914  PMID: 23837886
Sensitivity; Accuracy; Likelihood ratio; Lumbar radiculopathy; Physical examination
23.  Endoscopically Guided Foraminal and Dorsal Rhizotomy for Chronic Axial Back Pain Based on Cadaver and Endoscopically Visualized Anatomic Study 
Background
Conventional fluoroscopically guided continuous radiofrequency (CRF) and pulsed Radiofrequency (PRF) lesioning of the medial branch, dorsal ramus, a standard technique to treat facet pain, is compared to an endoscopic visually guided technique. The endoscopic technique (Figure 1) is designed to ablate a larger area of the transverse process where the medial branch crosses to innervate the facet. Endoscopically guided visualization provides confirmation of nerve ablation or transection in the most common location of the branches of the dorsal ramus innervating the facet joint.
Surgical setup for ablation of the medial, intermediate and lateral branches of the dorsal ramus.
Materials and Method
A retrospective non randomized study of 50 initial patients assessed the efficacy of endoscopic rhizotomy. Patients with lumbar spondylosis and facet arthrosis who had at least 50% pain relief by medial branch blocks met the inclusion criteria for the visualized, surgically directed endoscopic technique. A specially designed cannula and endoscope (Richard Wolf, GmBh) (Figure 2) was developed specifically for this purpose. After completion of the initial 50 patient pilot study in 2005, utilizing a low-temperature, ultra-high frequency (1.7-4.0 MHz) bipolar energy radiofrequency source (Elliquence Int, Hewlett, NY) that demonstrated efficacy, 400 subsequent patients were added to this retrospective study by May 2013. The surgical technique refinement was guided by cadaveric variations observed from additional cadaver dissections (Figure 3) and endoscopic visualization of foraminal nerves that revealed variable locations of the dorsal ramus, including the medial branch. The anatomic variations supported a need for visualized rhizotomy. The inclusion criteria also involved increasing the percentage of back pain relief from medial branch blocks to a base of 75% estimated improvement in order to overcome the variable subjectiveness of a 50% improvement threshold that served to disappoint a small percentage of patients who overestimated the reported 50% improvement in hopes that they would qualify for the endoscopic guided procedure.
Richard Wolf YESS Rhizotomy Set. The cannulas, endoscope, bitip and surgical bipolar RF probes by Elliquence are configured ergonomically to provide excellent focal length imaging to keep image in focus with the endoscope scope resting on cannula. The bitip probe cuts tissue, and the RF probe thermally ablates tissue efficiently.
Cadaver dissection of the dorsal ramus and its branches out- lining the areas where branches of the dorsal ramus may be visualized and ablated before it reaches the facet joint.
Results
At one year follow-up in the initial study design, VAS improved 6.2-2.5, and ODI 48-28. All patients had VAS improvement equal or greater than injection. The results remained constant with additional surgical cases that continued to improve when technique and visualized rhizotomy allowed for greater surgical exploration and ablation of the targeted zone where more than just the medial branch could be ablated. Approximately 10 percent of the patients returned at one and two year follow-up with mild recurrence of their axial back pain, but none to the original level of pain. Additional rhizotomy of the upper lumbar facets provided additional relief in selected patients.
Conclusions / level of evidence 3
The cadaver studies demonstrated considerable variability in the location of the medial and lateral branches of the dorsal ramus. Variability was most common cephalad to L3-4. The dorsal ramus and its nerve branches can also be visualized in the foramen ventral to the intertransverse ligament. Neuromas and entrapment of the dorsal ramus has been identified endoscopically, and confirmed by H and E slides (Figure 4). In the upper lumbar spine, we were not able to find the medial branch to the facets consistently at same location. The nerve to the facet joint did not always cross the transverse process. Some branches enter the facet joint before crossing the transverse process adjacent to the tip of the SAP (Figure 5). The nerve can be mistaken for a furcal nerve or foraminal ligament. Nerve Ablation at above L3-4 levels may require lesioning of the dorsal ramus or targeting the nerve innervation on the facet wall, pedicle or capsule.
This H and E slide of the biopsied specimen is consistent with a peripheral nerve fiber.
This foraminal view of a branch of the dorsal ramus is in the foramen at the level of the SAP. The nerve runs along the ventral lateral aspect of the superior facet to the tip, and can also run in the vicinity of the foraminal ligament. Endoscopic rasps, trephines, kerrisons, and burrs can be used for foraminoplasty. The nerve should be preserved, if possible, but transection of a branch of the dorsal ramus contributes to axial back pain relief. Branches of the dorsal ramus originates in the foramen before exiting to traverse the transverse process. These nerves are difficult to differentiate from furcal nerves arising from the spinal nerves. Palpating the nerve using local anesthesia can sometimes demonstrate a pain response, but not always, depending on the level of sedation and anesthetic use.
Clinical Relevance
Endoscopically guided facet rhizotomy provides more consistent ablation of the medial and lateral branches of the lumbar dorsal ramus compared to radiographically guided pulsed radiofrequency. The variations in the location of facet innervation can explain the variability of clinical results in fluoroscopically guided RF lesioning. This observation dictates a need for visually guided MIS procedure for best results.
doi:10.14444/1023
PMCID: PMC4325504
Endoscopic; rhizotomy; visualization
24.  Successful operative management of an upper lumbar spinal canal stenosis resulting in multilevel lower nerve root radiculopathy 
Lumbar stenosis is a common disorder, usually characterized clinically by neurogenic claudication with or without lumbar/sacral radiculopathy corresponding to the level of stenosis. We present a case of lumbar stenosis manifesting as a multilevel radiculopathy inferior to the nerve roots at the level of the stenosis. A 55-year-old gentleman presented with bilateral lower extremity pain with neurogenic claudication in an L5/S1 distribution (posterior thigh, calf, into the foot) concomitant with dorsiflexion and plantarflexion weakness. Imaging revealed grade I spondylolisthesis of L3 on L4 with severe spinal canal stenosis at L3-L4, mild left L4-L5 disc herniation, no stenosis at L5-S1, and no instability. EMG revealed active and chronic L5 and S1 radiculopathy. The patient underwent bilateral L3-L4 hemilaminotomy with left L4-L5 microdiscectomy for treatment of his L3-L4 stenosis. Postoperatively, he exhibited significant improvement in dorsiflexion and plantarflexion. The L5-S1 level was not involved in the operative decompression. Patients with radiculopathy and normal imaging at the level corresponding to the radiculopathy should not be ruled out for operative intervention should they have imaging evidence of lumbar stenosis superior to the expected affected level.
doi:10.4103/0976-3147.143216
PMCID: PMC4244769  PMID: 25552866
Neurogenic claudication; radiculopathy; surgical decompression; upper lumbar stenosis
25.  Translaminar Microendoscopic Herniotomy for Cranially Migrated Lumbar Disc Herniations Encroaching on the Exiting Nerve Root in the Preforaminal and Foraminal Zones 
Asian Spine Journal  2013;7(3):190-195.
Study Design
Case series.
Purpose
The aim of this study was to describe translaminar microendoscopic herniotomy (TL-MEH) for cranially migrated lumbar disc herniations encroaching on the exiting nerve root in the preforaminal and foraminal zones and to report preliminary results of the procedure.
Overview of Literature
Conventional interlaminar approaches for preforaminal and foraminal lumbar disc herniations result in extensive removal of the lamina and facet joint to remove disc fragments safely. More destructive approaches increase the risk of postoperative segmental instability.
Methods
TL-MEH is a minimally invasive procedure for herniotomy via the translaminar approach using a microendoscopic technique. TL-MEH was performed in seven patients with a cranially migrated lumbar disc herniation encroaching on the exiting nerve root. The disc fragments were located in the preforaminal zone in four patients, and in the preforaminal and foraminal zones in three.
Results
All patients experienced immediate relief from symptoms after surgery and satisfactory results at the final follow-up. Surgical complications, such as a dural tear, nerve injury, and surgical site infection, were not investigated.
Conclusions
TL-MEH seemed to be an effective and safe alternative minimally invasive surgical option for patients with a cranially migrated lumbar disc herniation encroaching the exiting nerve root in the preforaminal and foraminal zones.
doi:10.4184/asj.2013.7.3.190
PMCID: PMC3779770  PMID: 24066214
Lumbar disc herniation; Endoscopic surgery; Translaminar approach; Tubular surgery

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