Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes.

OBJECTIVES: To explore serum cytokine levels over time in patients with chronic low back pain (cLBP) and Modic changes (MCs), difference in change between treatment groups in the Antibiotics in Modic Changes (AIM) study and associations between change in cytokines and low back pain. METHODS: Serum concentrations of 39 cytokines were measured at baseline and 1 year from 73 participants in the AIM study; 30 randomized to placebo, 43 to Amoxicillin. Low back pain intensity was measured by numeric rating scale. Change in cytokine levels over time were assessed by paired t-tests. Difference in change in cytokine levels between treatment groups and associations between changes in LBP and cytokine levels were assessed by linear regression models. Networks of cytokine changes in each treatment groups were explored by Pearson's correlations. RESULTS: Five cytokines changed from baseline to 1 year, (mean change, log transformed values with CI) C-X-C motif chemokine ligand (CXCL) 10 (IP-10) (0.11 (0.01-0.20)), CXCL13 (0.61 (0.00-0.12)), C-C motif chemokine ligand (CCL)26 (0.05 (0.01-0.1)), granulocyte macrophage-colony stimulating factor (GM-CSF) (-0.12 (-0.23 to 0.00)) and CXCL11 (0.12 (0.03-0.22)). Treatment group only influenced change in CCL21 (ß 0.07 (0.01-0.12)), and IL-6 (ß -0.17 (-0.30 to -0.03)). Change in CXCL13 (ß 2.43 (0.49-4.38)), CCL27 (ß 3.07 (0.46-5.69)), IL-8 (ß 1.83 (0.08-3.58)) and CCL19 (ß 3.10 (0.86-5.43)) were associated with change in LBP. The correlation networks of cytokine changes demonstrate small differences between treatment groups. CONCLUSIONS: Cytokine levels are relatively stable over time in our sample, with little difference between treatment groups. Some cytokines may be associated with LBP intensity. The differences between the correlation networks suggest that long-term Amoxicillin-treatment may have longstanding effects to be further explored.

Subjective health complaints predict functional outcome six months after stroke.

OBJECTIVES: Cerebrovascular stroke is a main cause of lasting disability in older age, and initial stroke severity has been established as a main determinant for the degree of functional loss. In this study, we searched for other predictors of functional outcome in a cohort of stroke patients participating in an early supported discharge randomised controlled trial. METHODS: Thirty candidate variables related either to premorbid history or to the acute stroke were examined by ordered logistic regression in 229 stroke patients. Dependent variables were modified Rankin Scale (mRS) at 6 months and mRS change from baseline to 6 months. RESULTS: For mRS at 6 months, Barthel Index at stable baseline post-stroke was the main predictor, with sex, age, previous cerebrovascular disease, previous peripheral artery disease and the necessity for tube feeding in the acute phase also contributing to the final model. For mRS change, only age and previous cerebrovascular disease were significant predictors. Prestroke subjective health complaints added significantly to all final models concurrently with sex losing its predictive power. CONCLUSIONS: Initial stroke severity was the main predictor of functional outcome. Subjective health complaints score was a potent predictor for both outcome and improvement from baseline to 6 months and at the same time ameliorated the predictive impact of sex. The poorer functional prognosis for women after stroke may therefore be related to their higher load of subjective health complaints rather than to their sex itself. Treating these complaints may possibly improve the functional prognosis.

Efficacy of classification-based cognitive functional therapy in patients with non-specific chronic low back pain: a randomized controlled trial.

BACKGROUND: Non-specific chronic low back pain disorders have been proven resistant to change, and there is still a lack of clear evidence for one specific treatment intervention being superior to another. METHODS: This randomized controlled trial aimed to investigate the efficacy of a behavioural approach to management, classification-based cognitive functional therapy, compared with traditional manual therapy and exercise. Linear mixed models were used to estimate the group differences in treatment effects. Primary outcomes at 12-month follow-up were Oswestry Disability Index and pain intensity, measured with numeric rating scale. Inclusion criteria were as follows: age between 18 and 65 years, diagnosed with non-specific chronic low back pain for >3 months, localized pain from T12 to gluteal folds, provoked with postures, movement and activities. Oswestry Disability Index had to be >14% and pain intensity last 14 days >2/10. A total of 121 patients were randomized to either classification-based cognitive functional therapy group n = 62) or manual therapy and exercise group (n > = 59). RESULTS: The classification-based cognitive functional therapy group displayed significantly superior outcomes to the manual therapy and exercise group, both statistically (p < 0.001) and clinically. For Oswestry Disability Index, the classification-based cognitive functional therapy group improved by 13.7 points, and the manual therapy and exercise group by 5.5 points. For pain intensity, the classification-based cognitive functional therapy improved by 3.2 points, and the manual therapy and exercise group by 1.5 points. CONCLUSIONS: The classification-based cognitive functional therapy produced superior outcomes for non-specific chronic low back pain compared with traditional manual therapy and exercise.

Genetic variation in the beta-2 adrenergic receptor is associated with chronic musculoskeletal complaints in adolescents.

BACKGROUND: There is significant evidence to suggest that psychological and stress-related factors are important predictors of the onset of chronic widespread pain (CWP) and fibromyalgia (FM). The hypothalamic-pituitary-adrenal axis, together with the efferent sympathetic/adrenomedullary system, influence all body organs (including muscles) during short- and long-term threatening stimuli. The aim of this study was to investigate the relationship between genetic variants in adrenergic candidate genes and chronic musculoskeletal complaints (MSCs) in adolescents. METHODS: Adolescents from the Western Australian Pregnancy (Raine) Cohort attending the 17-year cohort review completed a questionnaire containing a broad range of psychosocial factors and pain assessment (n = 1004). Blood samples were collected for DNA extraction and genotyping. Genotype data was obtained for 14 single nucleotide polymorphisms (SNPs) in two candidate genes - beta-2 adrenergic receptor (ADRB2) and catecholamine-O-methyltransferase (COMT). Haplotypes were reconstructed for all individuals with genotype data. RESULTS AND CONCLUSION: Both female gender and poor mental health were associated with (1) an increased risk for chronic, disabling comorbid neck and low back pain (CDCP); and (2) an increase in the number of areas of pain. Of the 14 SNPs evaluated, only SNP rs2053044 (ADRB2, recessive model) displayed an association with CDCP [odds ratio (OR) = 2.49; 95% confidence interval (CI) = 1.25, 4.98; p = 0.01] and pain in three to four pain areas in the last month (OR = 1.86; 95% CI = 1.13, 3.06; p = 0.02). These data suggest that genetic variants in ADRB2 may be involved in chronic MSCs.

Integration of subclassification strategies in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for non-specific chronic low back pain: a systematic review.

BACKGROUND: There is lack of evidence for specific treatment interventions for patients with non-specific chronic low back pain (NSCLBP) despite the substantial amount of randomised controlled clinical trials evaluating treatment outcome for this disorder. HYPOTHESIS: It has been hypothesised that this vacuum of evidence is caused by the lack of subclassification of the heterogeneous population of patients with chronic low back pain for outcome research. STUDY DESIGN: A systematic review. METHODS: A systematic review with a meta-analysis was undertaken to determine the integration of subclassification strategies with matched interventions in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for NSCLBP. A structured search for relevant studies in Embase, Cinahl, Medline, PEDro and the Cochrane Trials Register database, followed by hand searching all relevant studies in English up to December 2008. RESULTS: Only 5 of 68 studies (7.4%) subclassified patients beyond applying general inclusion and exclusion criteria. In the few studies where classification and matched interventions have been used, our meta-analysis showed a statistical difference in favour of the classification-based intervention for reductions in pain (p=0.004) and disability (p=0.0005), both for short-term and long-term reduction in pain (p=0.001). Effect sizes ranged from moderate (0.43) for short term to minimal (0.14) for long term. CONCLUSION: A better integration of subclassification strategies in NSCLBP outcome research is needed. We propose the development of explicit recommendations for the use of subclassification strategies and evaluation of targeted interventions in future research evaluating NSCLBP.

Inter-examiner reliability of a classification system for patients with non-specific low back pain.

There is a lack of studies examining whether mechanism-based classification systems (CS) acknowledging biological, psychological and social dimensions of long-lasting low back pain (LBP) disorders can be performed in a reliable manner. The purpose of this paper was to examine the inter-tester reliability of clinicians' ability to independently classify patients with non-specific LBP (NSLBP), utilising a mechanism-based classification method. Twenty-six patients with NSLBP underwent an interview and full physical examination by four different physiotherapists. Percentage agreement and Kappa coefficients were calculated for six different levels of decision making. For levels 1-4, percentage agreement had a mean of 96% (range 75-100%). For the primary direction of provocation Kappa and percentage agreement had a mean between the four testers of 0.82 (range 0.66-0.90) and 86% (range 73-92%) respectively. At the final decision making level, the scores for detecting psychosocial influence gave a mean Kappa coefficient of 0.65 (range 0.57-0.74) and 87% (range 85-92%). The findings suggest that the inter-tester reliability of the system is moderate to substantial for a range of patients within the NSLBP population in line with previous research.

The inter-examiner reliability of a classification method for non-specific chronic low back pain patients with motor control impairment.

The importance of classifying chronic low back pain (LBP) patients into homogeneous sub-groups has recently been emphasized. This paper reports on two studies examining clinicians ability to agree independently on patients' chronic LBP classification, using a novel classification system (CS) proposed by O'Sullivan. In the first study, a sub-group of 35 patients with non-specific chronic LBP were independently classified by two 'expert' clinicians. Almost perfect agreement (kappa-coefficient 0.96; %-of-agreement 97%) was demonstrated. In the second study, 13 clinicians from Australia and Norway were given 25 cases (patients' subjective information and videotaped functional tests) to classify. Kappa-coefficients (mean 0.61, range 0.47-0.80) and %-of-agreement (mean 70%, range 60-84%) indicated substantial reliability. Increased familiarity with the CS improved reliability. These studies demonstrate the reliability of this multi-dimensional mechanism-based CS and provide essential evidence in a multi-step validation process. A fully validated CS will have significant research and clinical application.

Relationships between physical findings (GPE-78) and psychological profiles (MMPI-2) in patients with long-lasting musculoskeletal pain.

The purpose of the study was to evaluate possible relationships between physical findings, as measured with the Global Physiotherapeutic Examination (GPE-78), and psychological characteristics, as measured with the revised Minnesota Multiphasic Personality Inventory (MMPI-2), in three groups of patients with long-lasting musculoskeletal pain. A total of 177 patients (114 women, 63 men), sick-listed owing to long-lasting musculoskeletal pain, were studied. The sample was subcategorized on the basis of pain localization, as marked on a pain drawing: group 1 = pain above a horizontal line in the thoracic-lumbar region (n = 24); group 2 = pain below the line (n = 48); group 3 = pain both above and below the line (n = 105). The GPE-78 consists of 78 standardized tests yielding quantitative information within five bodily domains: Posture, Movement, Muscle, Skin, and Respiration. Significant correlations were obtained between the GPE-78 and the MMPI-2 with regard to somatization, somatic concern, and depression. Patients with localized pain (groups 1 and 2) had few correlations between bodily findings and psychological problems compared with many inpatients with generalized pain (group 3). Women showed correlations between the domains Posture, Movement, and Muscle and psychological problems, whereas men showed correlations with Movement, Skin and Respiration. A psychosomatic MMPI-2 "V-profile" was present in groups 1 and 3. Women showed significantly higher scores than men. The relationships found between GPE-78 and MMPI-2 measures were significant, but findings differed depending on pain localization and sex. Patients with generalized pain had significantly more physical and psychological aberrations than patients with more localized pain.

Protein markers in cerebrospinal fluid in experimental nerve root injury. A study of slow-onset chronic compression effects or the biochemical effects of nucleus pulposus on sacral nerve roots.

STUDY DESIGN: Measurement of changes in cerebrospinal fluid concentrations of nerve tissue markers, total proteins, and immunoglobulin after compression of nerve root or application of nucleus pulposus in a pig model. OBJECTIVES: To assess whether compression or application of nucleus pulposus to spinal nerve roots may cause increased levels of cerebrospinal fluid markers of nerve tissue damage and total proteins, and whether synthesis of immunoglobulins may be induced in cerebrospinal fluid. SUMMARY OF BACKGROUND DATA: Previous studies have reported that there seems to be a relationship between elevated cerebrospinal fluid total protein concentrations, nerve tissue markers, clinical findings, and compression of the nerve root evaluated by radiologic changes in patients with sciatica. METHODS: Subjects included 41 pigs, including 5 control animals. In two groups of experimental animals (n = 7; n = 5), an ameroid constrictor was slid onto the S1 nerve root. In two other groups (n = 7; n = 5), nucleus pulposus harvested from the L2-L3 disc was applied to the S1 nerve root. Two sham animal groups (n = 7; n = 5) underwent the same laminectomy. Twenty-one pigs underwent reoperation after 1 week, and 15 pigs after 4 weeks. A syringe was used to remove 3 mL of cerebrospinal fluid at L4-L5. Concentrations of total proteins, the light subunit of the neurofilament protein, S-100 protein, neuron-specific enolase, and glial fibrillary acidic protein were measured, and the presence of oligoclonal bands (immunoglobulins) were assayed in cerebrospinal fluid. RESULTS: The pigs with compressed S1 nerve root had considerably higher neurofilament protein and total protein concentrations in their cerebrospinal fluid than the-control animals (P < 0.001 and P < 0.01, respectively) or the sham animals (P < 0.001 and P < 0.05) in the 1-week experiment. Nucleus pulposus did not induce a significant increase in concentrations of the different protein markers. The presence of oligoclonal bands in cerebrospinal fluid in the experimental groups did not differ between the control and sham animals. CONCLUSIONS: The neurofilament protein and total protein concentrations in cerebrospinal fluid may have diagnostic importance in cases wherein clinical findings are not clearly related to the radiologic changes and vice versa. These protein markers also may be useful tools in different experimental models.

Multimodal cognitive behavioral treatment of patients sicklisted for musculoskeletal pain: a randomized controlled study.

In a randomized controlled study multimodal cognitive behavioral treatment (MMCBT), including physical treatment, cognitive behavioral modification, education, and examination of the work situation for each patient, was given to patients sick-listed for musculoskeletal pain (n = 469). Patients were recruited through the National Insurance System. After a pre-test by an independent physiotherapist the patients were allocated at random to the intervention group (n = 312) or the control group (n = 157). The MMBCT program lasted for 4 weeks. The control group returned to their general practitioners, without any feedback or advice on therapy from the project. At the one year follow-up the MMCBT group had not returned to work at a higher rate than the control group receiving ordinary treatment available through their general practitioners. However, the MMCBT group had improved their ergonomic behavior, work potential, life quality, physical, and psychological health.

Cerebrospinal fluid protein concentrations in patients with sciatica caused by lumbar disc herniation: an investigation of biochemical, neurologic, and radiologic predictors of long-term outcome.

We studied 180 adult patients admitted to the Neurological Department, Haukeland Hospital in Bergen, Norway, for a period of 5 years from 1984 to 1988. One hundred fifty-seven patients were followed up 3.9-9.0 years after admittance to the Neurological Department. The purpose of this study was to find out if the total cerebrospinal fluid (CSF) protein concentration could predict the outcome of lumbar disc surgery or conservative treatment in patients with sciatica. Neurologic and radiologic parameters were also included in the investigation. The increase of the CSF total protein concentration in sciatica without spinal block is assumed to be due to leak of plasma proteins into the CSF from the nerve root. A relationship between CSF protein concentrations and certain clinical parameters has been found. At myelography, 10 ml of CSF was collected for analysis. The patients were evaluated for involvement of the nerve root and/or the dural sac, respectively. The neurologic parameters investigated were: straight leg raising tests, paresis, disturbances of sensibility, and altered reflexes. At follow-up, the patients were asked to fill in questionnaires concerning job function, sick leave or disability pension, subjective physical disability and pain perception, and a clinical examination with the same neurologic parameters was performed. Elevated CSF total protein concentration was related to chronic leg pain, leg pain, and subjective physical disability at follow-up. Nonoperated women reported higher subjective physical disability scores and were more often on sick-leave or disability pension than were men at follow-up. Lateral prolapses were associated with good job function outcome and less risk for sick-leave or disability pension. Reduced lower extremity reflexes, laterally located disc herniation and elevated CSF total protein concentration were associated with a favorable long-term outcome in patients with sciatica. CSF proteins as objective measures on nerve root injury are discussed. CSF total protein concentration can be regarded as an indicator of the functional status of the nerve root and a prognostic factor in patients with sciatica.

Contrast media leakage to the cerebrospinal fluid after intravenous injection. Comparison of stroke patients and controls.

We have tested a method to evaluate leakage of i.v. injected contrast media (CM) through the 3 partitions between blood and cerebrospinal fluid (CSF) in controls and in patients with acute cerebrovascular disease (ACBVD) to detect differences between normal brains and brains with ischemic lesions. High-osmolar (HOCM) and low-osmolar (LOCM) CM were used. In 55 patients and in 41 controls who underwent CT after i.v. contrast administration, lumbar CSF was collected 1 hour after injection and the iodine content in the CSF was measured. The concentration of iodine in CSF was very low, between 0.57 and 11.20 ng/l, and no significant difference could be found between patients and controls or between HOCM and LOCM. We conclude that under the conditions mentioned above, iodine detected in the human lumbar CSF does not reflect the true leakage of contrast agent through the blood-brain barrier.

Cerebrospinal fluid protein concentrations related to clinical findings in patients with sciatica caused by disk herniation.

The protein concentration in the cerebrospinal fluid (CSF) is often increased in patients with sciatica, probably due to leaking of plasma proteins through the blood-nerve root barrier into CSF. Positive straight leg raising test, paresis, altered sensibility, reduced reflexes, and type of treatment were related to the CSF protein concentrations in 180 patients with sciatica caused by verified lumbar disk herniation. Significantly higher values of the CSF/serum albumin ratio and the CSF/serum immunoglobulin G ratio were found both in patients with positive straight leg raising test results and paresis compared with patients with no clinical findings. In the patients who had undergone emergency surgery, the same ratio parameters were significantly higher when compared with those who had undergone routine surgery and those had not undergone surgery. Elevated CSF proteins seem to be important indicators of the functional status of the nerve root and a measure of the degree of seriousness of sciatica. The interaction of smoking on CSF proteins was also studied.

Elevated cerebrospinal fluid proteins in sciatica caused by disc herniation.

We carried out a study of cerebrospinal fluid (CSF) proteins in 180 patients with sciatica caused by lumbar disc herniation to elucidate further the degree and mechanisms of protein elevations. The 63 controls were patients with tension headache or migraine without aura. The CSF/serum albumin ratios were higher in the patients (mean 8.84, SD 5.16) than in the controls (mean 5.60, SD 2.33). Similar differences were found for the CSF/serum IgG ratios and the CSF-total proteins. The CSF/serum albumin ratios, CSF/serum IgG ratios and the CSF-total protein concentrations were higher in men than in women among the patients. We suggest that the significant difference in ratio parameters between patients and controls indicates a leak of plasma albumin, most likely IgG, into the CSF in patients with sciatica. The leak was more pronounced in men. Also in the control group the CSF/serum albumin and CSF/serum IgG ratios were higher in men.

Cerebrospinal fluid proteins as indicators of nerve root compression in patients with sciatica caused by disc herniation.

Patients with sciatica caused by lumbar disc herniation were studied to identify biochemical changes in the cerebrospinal fluid related to myelographic findings and clinical observations. One hundred forty-three patients were evaluated by myelography with regard to involvement of the dural sac and the nerve root. A medial group (20 patients) with evidence of dural sac impingement was compared to a lateral group (63 patients) and an extreme lateral group (9 patients) whose condition primarily affected the nerve root. The remaining 51 patients comprised a mixed group with involvement of both the dural sac and the nerve root. The mean cerebrospinal fluid/serum albumin ratio, cerebrospinal fluid/serum immunoglobulin G ratio, and cerebrospinal fluid total proteins showed a significantly increasing trend from the medial through the lateral to the extreme lateral groups. Patients with lateral lumbar disc herniations more often showed neurologic deficits. These results indicate that the elevated cerebrospinal fluid total protein found in the patients with sciatica is due to leaking of plasma proteins primarily from the nerve root into the cerebrospinal fluid. The cerebrospinal fluid proteins may be used as diagnostic parameters of nerve root compression, especially when surgery is a consideration or in patients in whom sciatica is unlikely.

[What do the waiting lists cost? A study of patients with backache]. / Hva koster ventelistene? En studie av ryggpasienter.

Waiting for treatment usually contributes to patients' psychological and financial problems. In this study we calculate and discuss the economic implications of these patients being on a waiting list for treatment. Our calculations show that the income lost in economic production is higher than the cost of treating patients with degenerative low back pain. This is mainly because these afflictions strike people of working age and render them invalids, whereas early adequate treatment usually allows the patients to take up their previous work.

Paraplegia following epidural anesthesia. A case report and a literature review.

This article reports the case of a man who developed a pure motor paraplegia following epidural anesthesia with a pattern of slow recovery over subsequent months. Reviewing the available literature on post-epidural paraplegia we noted a number of potential etiologies and analyzed their role in its causation. On the basis of this analysis we have identified five distinct clinical groups and a constellation of factors which can lead to an increased risk of post-epidural paraplegia in susceptible surgical patients.