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STUDY DESIGN: This is a retrospective analysis of data that was collected prospectively from 2 concurrent FDA IDE lumbar arthroplasty clinical trials performed at a single center. OBJECTIVE: To determine if there is a clinical difference between the 1-level ProDisc patients versus the 2-level ProDisc patients at a minimum of 2 years of follow-up. SUMMARY OF BACKGROUND DATA: Marnay's work with ProDisc I prompted the U.S. Clinical Trials of the ProDisc II under the direction of the FDA. Disc replacement surgery in the United States has shown promising results for all types of prostheses up to 6 months. Marnay and colleagues showed that their results at 10 years were still promising, and they saw no significant difference between 1-level and multilevel disc replacements. The findings of Ipsen and colleagues suggest that multilevel arthroplasty cases may be less successful than disc replacement at a single level. METHODS: Patients were part of the FDA clinical trial for the Prodisc II versus circumferential fusion study at a single institution. We identified 27 patients who received ProDisc at 1 level and 32 who received it at 2 levels with at least a 2-year follow-up, for a total of 59 patients. Unpaired t tests were performed on the mean results of Visual Analog Scale, Oswestry Disability Index, SF-36 Healthy Survey Physical Component Summary, and satisfaction using 10-cm line visual scale scores to determine a clinical difference if any between the 2 populations. RESULTS: While patients receiving ProDisc at 2 levels scored marginally lower in all evaluation indexes, score differences in each category were also found to hold no statistical significance. CONCLUSION: This study was unable to identify a statistically significant difference in outcome between 1- and 2-level ProDisc arthroplasty patients in a cohort from a single center. The equality of clinical effectiveness between 1- and 2-level ProDisc has yet to be determined. [ABSTRACT FROM AUTHOR]

Haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1) is a recently discovered autoinflammatory disorder with significant rheumatologic, immunologic, and hematologic manifestations. Here we report a case of SOCS1 haploinsufficiency in a 5-year-old child with profound arthralgias and immune-mediated thrombocytopenia unmasked by SARS-CoV-2 infection. Her clinical manifestations were accompanied by excessive B cell activity, eosinophilia, and elevated IgE levels. Uniquely, this is the first report of SOCS1 haploinsufficiency in the setting of a chromosomal deletion resulting in complete loss of a single SOCS1 gene with additional clinical findings of bone marrow hypocellularity and radiologic evidence of severe enthesitis. Immunologic profiling showed a prominent interferon signature in the patient's peripheral blood mononuclear cells, which were also hypersensitive to stimulation by type I and type II interferons. The patient showed excellent clinical and functional laboratory response to tofacitinib, a Janus kinase inhibitor that disrupts interferon signaling. Our case highlights the need to utilize a multidisciplinary diagnostic approach and consider a comprehensive genetic evaluation for inborn errors of immunity in patients with an atypical immune-mediated thrombocytopenia phenotype., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Kagami-Ogata syndrome (KOS14) is a rare imprinting disorder characterized by a unique constellation of phenotypes including bell-shaped small thorax with coat-hanger appearance of the ribs. We encountered an African American female infant with KOS14 phenotype and 46,XX,t(2;14)(q11.2;q32.2)mat. After excluding upd(14)pat and an epimutation (hypermethylation) and a deletion affecting the maternally derived 14q32.2 imprinted region, we performed whole-genome sequencing, revealing that the translocation was generated between noncoding region at 2q11.2 and intron 6 of MEG3 at 14q32.2. Subsequent Sanger sequencing for the fusion points showed that the chromosomal fusion on the der(2) chromosome occurred between Chr2:102,193,994 (bp) and Chr14:101,314,628 (bp) in association with an insertion of 5-bp segment of unknown origin and that on the der(14) chromosome took place between Chr14:101,314,627 (bp) and Chr2:102,193,995 (bp) in association with an insertion of 1-bp segment of unknown origin (according to GRCh37/hg19). The results, together with the previous data in patients with KOS14, imply that the MEG3 disruption by 46,XX,t(2;14)(q11.2;q32.2)mat caused silencing of all MEGs including RTL1as and resultant excessive RTL1 expression, leading to the development of KOS14. To our knowledge, while Robertsonian translocations involving chromosome 14 have been reported in KOS14, this is the first case of KOS14 caused by a chromosomal translocation involving the 14q32.2 imprinted region.

Pediatric thrombocytopenia has a wide differential diagnosis, and recently, genetic testing to identify its etiology has become more common. We present a case of a 16-year-old boy with a history of chronic moderate thrombocytopenia, who later developed constitutional symptoms and bilateral hand edema with cold exposure. Laboratory evaluation revealed evidence both of inflammation and elevated muscle enzymes. These abnormalities persisted over months. His thrombocytopenia was determined to be immune mediated. Imaging revealed lymphadenopathy and asplenia, and a muscle biopsy was consistent with tubular aggregate myopathy. Ophthalmology evaluation noted photosensitivity, pupillary miosis, and iris hypoplasia. Genetic testing demonstrated a pathogenic variant in STIM1 consistent with autosomal dominant Stormorken syndrome. Our case is novel because of the overlap of phenotypes ascribed to both gain-of-function and loss-of-function pathogenic variants in STIM1, thereby blurring the distinctions between these previously described syndromes. Pediatricians should consider checking muscle enzymes when patients present with thrombocytopenia and arthralgia, myalgia, and/or muscle weakness. Our case highlights the importance of both multidisciplinary care and genetic testing in cases of chronic unexplained thrombocytopenia. By understanding the underlying genetic mechanism to a patient's thrombocytopenia, providers are better equipped to make more precise medical management recommendations., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Mr Jacher is a current employee of Blueprint Genetics, and his affiliation during the drafting and submission of this article was as a full-time employee of the University of Michigan; the remaining authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Purpose: EPHB4 variants were recently reported to cause capillary malformation-arteriovenous malformation 2 (CM-AVM2). CM-AVM2 mimics RASA1-related CM-AVM1 and hereditary hemorrhagic telangiectasia (HHT), as clinical features include capillary malformations (CMs), telangiectasia, and arteriovenous malformations (AVMs). Epistaxis, another clinical feature that overlaps with HHT, was reported in several cases. Based on the clinical overlap of CM-AVM2 and HHT, we hypothesized that patients considered clinically suspicious for HHT with no variant detected in an HHT gene (ENG, ACVRL1, or SMAD4) may have an EPHB4 variant., Methods: Exome sequencing or a next-generation sequencing panel including EPHB4 was performed on individuals with previously negative molecular genetic testing for the HHT genes and/or RASA1., Results: An EPHB4 variant was identified in ten unrelated cases. Seven cases had a pathogenic EPHB4 variant, including one with mosaicism. Three cases had an EPHB4 variant of uncertain significance. The majority had epistaxis (6/10 cases) and telangiectasia (8/10 cases), as well as CMs. Two of ten cases had a central nervous system AVM., Conclusions: Our results emphasize the importance of considering CM-AVM2 as part of the clinical differential for HHT and other vascular malformation syndromes. Yet, these cases highlight significant differences in the cutaneous presentations of CM-AVM2 versus HHT.

Purpose: To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI)., Methods: A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test., Results: A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg)., Conclusions: Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Loss-of-function mutations in the X-linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo-obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering. Survival in male hemizygotes for such mutations is dependent on retention of residual FLNA function but it is unclear why a subgroup of males with mutations in the 5' end of the gene can present with CIPO alone. Here, we demonstrate evidence for the presence of two FLNA isoforms differing by 28 residues at the N-terminus initiated at ATG +1 and ATG +82 . A male with CIPO (c.18&#95;19del) exclusively expressed FLNA ATG +82 , implicating the longer protein isoform (ATG +1 ) in smooth muscle development. In contrast, mutations leading to reduction of both isoforms are associated with compound phenotypes affecting the brain, heart, and intestine. RNA-seq data revealed three distinct transcription start sites, two of which produce a protein isoform utilizing ATG +1 while the third utilizes ATG +82 . Transcripts sponsoring translational initiation at ATG +1 predominate in intestinal smooth muscle, and are more abundant compared with the level measured in fibroblasts. Together these observations describe a new mechanism of tissue-specific regulation of FLNA that could reflect the differing mechanical requirements of these cell types during development., (© 2017 Wiley Periodicals, Inc.)

Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelopmental disorders highlighted mutations in PPM1D as a possible cause of ID. PPM1D is a type 2C phosphatase that functions as a negative regulator of cellular stress-response pathways by mediating a feedback loop of p38-p53 signaling, thereby contributing to growth inhibition and suppression of stress-induced apoptosis. We identified 14 individuals with mild to severe ID and/or developmental delay and de novo truncating PPM1D mutations. Additionally, deep phenotyping revealed overlapping behavioral problems (ASD, ADHD, and anxiety disorders), hypotonia, broad-based gait, facial dysmorphisms, and periods of fever and vomiting. PPM1D is expressed during fetal brain development and in the adult brain. All mutations were located in the last or penultimate exon, suggesting escape from nonsense-mediated mRNA decay. Both PPM1D expression analysis and cDNA sequencing in EBV LCLs of individuals support the presence of a stable truncated transcript, consistent with this hypothesis. Exposure of cells derived from individuals with PPM1D truncating mutations to ionizing radiation resulted in normal p53 activation, suggesting that p53 signaling is unaffected. However, a cell-growth disadvantage was observed, suggesting a possible effect on the stress-response pathway. Thus, we show that de novo truncating PPM1D mutations in the last and penultimate exons cause syndromic ID, which provides additional insight into the role of cell-cycle checkpoint genes in neurodevelopmental disorders., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Exome sequencing is an effective way to identify genetic causes of etiologically heterogeneous conditions such as developmental delay and intellectual disabilities. Using exome sequencing, we have identified four patients with similar phenotypes of developmental delay, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects who all have the same de novo R331W missense variant in C-terminal binding protein 1 (CTBP1). CTBP1 is a transcriptional regulator critical for development by coordinating different regulatory pathways. The R331W variant found in these patients is within the C-terminal portion of the PLDLS (Pro-Leu-Asp-Leu-Ser) binding cleft, which is the domain through which CTBP1, interacts with chromatin-modifying enzymes and mediates chromatin-dependent gene repression pathways. This is the first report of mutations within CTBP1 in association with any human disease.

Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis-trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.

Treatment of the complex injury to the spine produced by a gunshot wound remains controversial. Treatment depends on the physician's ability to understand mechanism of injury, principles of medical management, diagnostic imaging, and surgical options. Antibiotics are an important component of treatment and should be continued for a minimum of 7 days in cases of wounds that both perforate the colon and injure the spine. Corticosteroids do not affect neurologic outcome and therefore should not be used. Decompression and removal of intracanal bullets at T12 and below may improve motor function. In select cases of cervical injuries, removal of intracanal bullet fragments may be justified, particularly with incomplete lesions. Regardless of injury level, new-onset or progressive neurologic deterioration is an indication for urgent decompression. Optimal surgical timing remains a controversial issue, and more study is needed to develop treatment guidelines. Intrathecal migratory missiles represent a very rare subset of the gunshot wounds to the spine, and their treatment should be individualized. In this article, we review the literature and then describe the case of a migratory intrathecal bullet in the lumbar spine of a patient who presented with cauda equina-type symptoms.

Study Design: Biomechanical., Objective: To determine if cement injection into the spinous process will improve compression strength., Summary of Background Data: The X STOP (St. Francis Medical Technologies) has been shown to be a safe and effective means for decompressing 1- or 2-level lumbar spinal stenosis (LSS). The X STOP is indicated for LSS patients with osteoporosis, but contraindicated for patients with severe osteoporosis. In an attempt to address these LSS patients with demonstrably weaker bone, a technique to strengthen the spinous process with polymethylmethacrylate (PMMA) injection is presented., Methods: Nine pairs of adjacent fresh frozen cadaveric lumbar vertebrae were DEXA scanned before testing. They were randomly assigned to the PMMA group and a control group. Nine of the specimens were injected with PMMA. Each spinous process was then compressed between 2 X STOPs. The testing model was designed to simulate the loading of a 2-level X STOP placement. The mean load to failure and stiffness values of the treated and untreated groups were calculated. The specimens were inspected carefully for PMMA infiltration and extrusion., Results: The mean bone mineral density (BMD) values of the control and PMMA treatment groups were 0.99 +/- 0.13 g/cm and 0.98 +/- 0.10 g/cm, respectively; P > 0.616. The mean volume of cement injected was 2.2 +/- 0.3 cc. The mean failure load values of the control and PMMA treatment groups were 1250 +/- 627 N and 2386 +/- 1034 N, respectively; P < 0.001. The mean stiffness values of the control and PMMA treatment groups were 296 +/- 139 N/mm and 381 +/- 131 N/mm, respectively; P > 0.059. Most specimens had flow of the cement into the laminae and some into the facet and pedicle. No PMMA was found within the spinal canal., Conclusion: This first reported technique of posterior element vertebroplasty may increase the indications and success for patients with decreased BMD who seek an interspinous implant such as the X STOP. A possible role may exist in increasing the effectiveness of such devices. However, clinical trials have yet been performed. These results demonstrate that PMMA injection in the spinous processes is effective in increasing resistance to compressive forces in an X STOP model.

Study Design: Ex vivo biomechanical study using osteoporotic cadaveric fractured vertebral bodies., Objective: To investigate the behavior of fractured osteoporotic vertebral bodies treated with either vertebroplasty or kyphoplasty under repetitive loading conditions., Summary of Background Data: Vertebroplasty and kyphoplasty are newer alternatives for the treatment of osteoporotic vertebral fractures. Loading conditions that can lead to fractures treated with these methods will likely be encountered subsequently; as such, it is important to understand differences in the biomechanical behavior of the resultant constructs., Methods: There were 7 pairs of osteoporotic T8 and T10 vertebral bodies cyclically loaded to produce a vertebral compression fracture. Of each pair, one was assigned to the kyphoplasty group and the other to the vertebroplasty group. After treatment, specimens were cyclically loaded to 100,000 cycles, between 20% and 70% of the predicted failure load., Results: Height was restored with kyphoplasty, but the vertebral bodies showed significant height loss during cyclic loading. Vertebroplasty specimens had higher compression stiffness and smaller height reduction., Conclusions: Under repetitive loading conditions, fractured vertebral bodies treated with kyphoplasty were initially taller, but because of a progressive loss of height during loading, the resulting constructs were shorter after 100,000 cycles than those treated with vertebroplasty.

X-STOP is the first interspinous process decompression device that was shown to be superior to nonoperative therapy in patients with neurogenic intermittent claudication secondary to spinal stenosis in the multicenter randomized study at 1 and 2 years. We present 4-year follow-up data on the X-STOP patients. Patient records were screened to identify potentially eligible subjects who underwent X-STOP implantation as part of the FDA clinical trial. The inclusion criteria for the trial were age of at least 50 years, leg, buttock, or groin pain with or without back pain relieved during flexion, being able to walk at least 50 feet and sit for at least 50 minutes. The exclusion criteria were fixed motor deficit, cauda equina syndrome, previous lumbar surgery or spondylolisthesis greater than grade I at the affected level. Eighteen X-STOP subjects participated in the study. The average follow-up was 51 months and the average age was 67 years. Twelve patients had the X-STOP implanted at either L3-4 or L4-5 levels. Six patients had the X-STOP implanted at both L3-4 and L4-5 levels. Six patients had a grade I spondylolisthesis. The mean preoperative Oswestry score was 45. The mean postoperative Oswestry score was 15. The mean improvement score was 29. Using a 15-point improvement from baseline Oswestry Disability Index score as a success criterion, 14 out of 18 patients (78%) had successful outcomes. Our results have demonstrated that the success rate in the X-STOP interspinous process decompression group was 78% at an average of 4.2 years postoperatively and are consistent with 2-year results reported by Zucherman et al previously and those reported by Lee et al. Our results suggest that intermediate-term outcomes of X-STOP surgery are stable over time as measured by the Oswestry Disability Index.

Objective: To determine whether an immunologic abnormality exists in patients with lymphatic malformation (LM)., Design: Retrospective case series., Setting: Tertiary care pediatric hospital., Patients: Twenty-one consecutive patients (11 male and 10 female) undergoing LM treatment., Interventions: Clinical data (ie, age, clinical LM stage, radiographic appearance, and histologic findings) were correlated with complete blood cell count and detailed lymphocyte differential. Complete blood cell counts and lymphocyte subsets were measured in 21 and 18 patients, respectively., Results: The average age at the time of testing was 67 months (range, 1-231 months). The patients were categorized according to LM stage, including 4 (19%) with stage 1, 4 (19%) with stage 2, 4 (19%) with stage 3, 7 (33%) with stage 4, and 2 (10%) with stage 5 disease. Radiographic LM appearance was macrocystic in 6 patients (29%), mixed macrocystic and microcystic in 8 (38%), and microcystic in 7 (33%). Complete blood cell count data demonstrated lymphocytopenia in 6 patients (29%). The results of the lymphocyte subset tests showed concomitant T-, B-, and natural killer (NK)-cell deficiency in 6 (33%) of 18 patients. All 6 patients with T-cell lymphocytopenia had normal neutrophil and platelet counts. Spearman rank and chi(2) analyses showed that LM stage 4 or 5 and microcystic LM were significantly associated with lymphocytopenia (P = .002 and P = .008, respectively). Histologic analysis did not demonstrate increased lymphocytes in any LM specimens., Conclusion: We found T, B, and NK lymphocytopenia in patients with large bilateral or microcystic LM. Although the relationship between lymphocytopenia and infection was not addressed in this study, the recognition of lymphocytopenia in patients with LM may have important clinical and prognostic implications.

Study Design: Measurement of the monotonic and fatigue properties of osteoporotic thoracic vertebral bodies., Objectives: To determine the loading values at which osteoporotic vertebral bodies are susceptible to failure., Summary of Background Data: Vertebral compression fractures are the most common osteoporotic fracture. Eighty-three percent of vertebral compression fractures are caused by moderate or less trauma, and there is not a specific traumatic event in 59% of these cases. Fatigue loading can lead to premature failure, although the relationship between loading and cycles to failure is not well established., Methods: Eighteen osteoporotic thoracic vertebral bodies were tested in monotonic compression to determine the correlation between the bone mineral content and the ultimate compressive load. Seventeen osteoporotic thoracic vertebral bodies were cyclically loaded at varying percentages of the ultimate compressive load until failure to determine the relationship between loading and fatigue life., Results: The bone mineral content was linearly correlated with ultimate compressive load. Based on our regression analysis, a 10% decrease in bone mineral content will lead to an approximate 10% decrease in ultimate compressive load. The percentage of ultimate compressive load was inversely correlated to the logarithm of cycles to failure, with specimens loaded at 60%, 70%, and 80% of ultimate compressive load lasting on average 5.6 x 10, 4.0 x 10, and 31 cycles to failure, respectively., Conclusions: The bone mineral content is a strong predictor of the ultimate compressive load, while the percentage of the ultimate compressive load is a strong predictor of the cycles to failure for osteoporotic thoracic vertebral bodies.

The diagnostic evaluation of chronic LBP is at best a complex and involved undertaking. The most important part of the process lies in the knowledge of the patient and a solid history and physical examination. From there, most of the serious and life-threatening causes of LBP can be elucidated and studies may be used for confirmation. Imaging studies are used most practically as confirmation studies once a working diagnosis is determined. MRI, although excellent at defining tumor, infection, and nerve compression, can be too sensitive with regard to degenerative disease findings and commonly displays pathology that is not responsible for the patient's symptoms. As an example, the high-intensity zones (HIZ) seen on MRI are reliable in determining annular defects in the disc but are not reliable in establishing internal disc disruption as the cause of LBP. Discography is the primary tool used by many physicians to determine the true pain generator when discogenic LBP is suspected. Because the reliability of the patient response is fundamental to discography, interpreting the test in different settings must be considered. In individuals with disc degeneration and annular defects, discography may elicit LBP with injection whether the patient is symptomatic with serious LBP or not. The pain response may be amplified in those subjects with issues of chronic pain, social stressors, such as secondary gain or litigation claims, or psychologic distress disorder. These factors have been shown experimentally to be associated with an increased risk for a false positive injection. The ability of an individual to differentiate the true site of LBP by the quality of sensation with disc injection (concordancy) of pain produced by the injected disc also may not be reliable. In fact, individuals may not have the neural discrimination to differentiate sclerotomal pain originating from different sites in the low back and pelvis. One may realize that chronic LBP illness may not stem from a mechanical spinal disorder alone. In fact, the mechanical pathology may be just a portion of the problem with amplification by neurophysiologic, social, and psychologic issues. Chronic disabling LBP commonly is confounded by chronic pain, emotional troubles, poor job satisfaction, alcohol and narcotic abuse, and compensation issues, just to identify a few. It would follow that expecting to identify a single cause for this symptom complex is impractical and any single test may not be a reasonable approach. Furthermore, surgical correction of the mechanical portion of chronic LBP. even if correctly identified, then can be expected only to relieve a portion of a patient's symptoms as long as the confounding issues continue to be significant or have become life long adaptive mechanisms. In the end, the discogram and other diagnostic tests are tools that have clear limitations. In this field, clinical judgment begins and ends with an understanding of a patient's life and circumstances as much as with their specific spinal pathology.