Outcome of spine surgery in patients with depressed mental states: a Canadian spine outcome research network study.

BACKGROUND CONTEXT: Depression is higher among spine patients than among the general population. Some small studies, but not others, have suggested that depression may be a predictor of worse outcome after surgery. PURPOSE: Determination whether there is an association between depression and worse response to surgery among spine patients. STUDY DESIGN/SETTING: The national, prospective, Canadian Spine Outcome Research Network (CSORN) surgical outcome registry. PATIENT SAMPLE: All patients in the CSORN registry who received surgery for thoracic or lumbar degenerative deformity, stenosis, spondylolisthesis, disc disease, or disc herniation with a minimum of 12 months follow-up postoperation (n = 2310). OUTCOME MEASURES: Oswestry Disability Index (ODI), SF12 Physical Component Score (PCS), European Quality of Life (EuroQoL), and pain scales. METHODS: Change in preoperative to 12-month postoperative ODI, and secondary measures, were compared to assess if there was an association between preoperative depression, as measured by PHQ9, and smaller response to surgery. Multivariate regression analysis was used to search for preoperative factors which might interact with PHQ9 to predict ODI outcome. RESULTS: Patients with PHQ9<5, associated with minimal to no depression, had the smallest ODI improvement (-16.8 [95%CI -18.1 to -15.3]) and patients with severe preoperative depression (PHQ9 ≥ 10) had the largest ODI improvement (-22.8 [95%CI -24.1 to -21.5]; p<.00001). Similar findings were found in the EQ5D and PCS. Pain improvement was not different between depression levels. Multivariate modeling found worse baseline PHQ9 and ODI, greater age, nicotine use, more operative levels, and worse American Society of Anesthesiology score was predictive of worse ODI outcomes. CONCLUSIONS: Depressed patients have similar or better relative improvements in disability, quality of life, and pain, when compared to nondepressed patients, although their preoperative and postoperative levels of disability are higher. Surgeons should not be concerned that depression will reduce the patient-reported beneficial response to surgical intervention.

Midterm outcomes of total hip arthroplasty with a modular Birmingham head.

INTRODUCTION: Birmingham Hip Resurfacing (BHR) implants may be combined with a conventional femoral stem to create a modular metal-on-metal total hip arthroplasty (BHR MoM THA). There is little outcome data regarding this construct. This study examines midterm outcomes of BHR MoM THA compared to oxidised zirconium total hip arthroplasty (THA). METHODS: A retrospective institutional review identified all patients receiving BHR MoM THA between April 2005 and February 2011 and a matched control cohort of zirconium THA patients. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and SF-12 Health status scores were obtained. Revisions and complications were collected from clinical records. Radiographs were assessed for evidence of component malposition, loosening, osteolysis, or heterotopic ossification. RESULTS: 63 modular BHR MoM THA were identified in 61 patients (36 with BHR cups, 27 with R3 cups) and 63 zirconium THA in 58 matched controls. Mean follow-up was 58 months. 14 BHR MoM THA hips (22.2%) were revised (4 infections, 1 dislocation, 9 soft tissue reactions) compared to 3 (4.8%) zirconium THA (all infections). At latest follow-up, 18.4% of surviving BHR MoM THA hips were painful compared to 0.5% of zirconium THA controls (p < 0.001). WOMAC, HHS, and SF-12 did not differ significantly between surviving members of the 2 groups. DISCUSSION: BHR MoM THA demonstrated a high revision rate, largely for adverse local soft tissue reaction and pain. Among those not revised, many reported some residual pain despite similar quality of life measures to those who received zirconium THA.

Effect of preoperative symptom duration on outcome in lumbar spinal stenosis: a Canadian Spine Outcomes and Research Network registry study.

BACKGROUND CONTEXT: Lumbar degenerative stenosis is one of the most common spine pathologies for which surgical intervention is indicated. There is some evidence that a prolonged duration of neurological compression could lead to a failure of surgery to alleviate symptoms. PURPOSE: Determination of whether longer symptom duration was associated with worse postoperative disability outcomes after decompressive surgery for lumbar degenerative stenosis. STUDY DESIGN/SETTING: The Canadian Spine Outcomes and Research Network (CSORN) prospective database includes pre- and postoperative data from 18 tertiary care hospitals. PATIENT SAMPLE: The CSORN database was queried for all cases of degenerative lumbar stenosis receiving surgical decompression for neurogenic claudication or radiculopathy. Patients with tumor, infection, fracture, or previous surgery were excluded. Patients were divided into groups based on symptom duration (<6 weeks, 6-12 weeks, 3-6 months, 6-12 months, 1-2 years, and >2 years). OUTCOME MEASURES: Change between preoperative and 12-month postoperative Oswestry Disability Index (ODI) was compared between symptom duration groups. Secondary outcomes included SF12 physical component score (PCS), and numeric rating scales for leg and back pain. Outcomes were also assessed at 3 months and 24 months postoperatively. METHODS: Change in ODI, and secondary outcome measures, were compared between different symptom duration groups. Multiple regression analysis was used to identify factors interacting with symptom duration to predict change in ODI. RESULTS: Four hundred and seventy-eight cases of lumbar stenosis with 12-month postoperative data were identified. Longer symptom duration correlated with less improvement in ODI (p<.001). Patients with >1 year of symptoms were less likely to achieve a Minimal Clinically Significant Difference in ODI (54.4% vs. 66.1%; p=.03) and were more likely to experience no improvement or worse disability, postoperatively (22.1% vs. 11.3%; p=.008). Similar results were found at 3- and 24-month timepoints. Smaller postoperative improvements in SF12 PCS and leg pain scales were also correlated with longer symptom duration (p<.05). CONCLUSIONS: Multicenter registry data provides important real-world evidence to guide consent, surgical planning, and health resource management. Longer symptom duration was found to correlate with less improvement in pain and disability after lumbar stenosis surgery suggesting that these patients may benefit from earlier treatment.

Quality of Life and Slip Progression in Degenerative Spondylolisthesis Treated Nonoperatively.

STUDY DESIGN: A prospective cohort study of consecutive patients. OBJECTIVE: Determination of the quality of life (QoL) and prevalence of slip progression in patients with degenerative lumbar spondylolisthesis managed nonoperatively. SUMMARY OF BACKGROUND DATA: Lumbar spinal stenosis secondary to degenerative lumbar spondylolisthesis is a common radiographic diagnosis associated with chronic back pain and radicular symptoms. There is limited evidence as to the clinical course in terms of validated QoL measures, and the extent of slip progression in patients with this condition treated nonoperatively. METHODS: Validated disease-specific and generic QoL metrics including SF12 physical and mental scores [SF12-physical component summary (PCS) and SF12-mental component summary (MCS)], Oswestry Disability Index (ODI), and numeric scales for back and leg pain as well as radiographic assessment of slip extent were evaluated at initial consultation (baseline) and at a minimum of 5 years after the baseline assessment. Slip progression was defined by a >5% increase in slip percentage. RESULTS: Thirty-nine of 160 (24.4%) patients elected to switch to operative management, despite no slip progression on preoperative radiographs. Seventy spondylolisthetic levels in 66 participants were assessed after a minimum of 5 years of nonoperative management. Twenty-one participants (31.8%) had slip progression. SF12-PCS, ODI, and leg pain improved similarly in both groups (P < 0.05). SF12-MCS did not change significantly in either group. Back pain improved only in the nonprogressing group. CONCLUSION: The majority of cases of low-grade spondylolisthesis do not progress over 5 years with nonoperative management. Regardless of whether there was progression or not, the mean PCS, ODI, and leg pain improved from baseline, although symptoms remained and a significant number elected to switch to surgical management before 5 years. Back pain improved with nonoperative treatment only in those without progression. LEVEL OF EVIDENCE: 2.

Obesity and spinal epidural lipomatosis in cauda equina syndrome.

BACKGROUND CONTEXT: Although lumbar disc herniations are common, only a small portion of these herniations lead to cauda equina syndrome (CES), which is an uncommon but debilitating disorder. Why some patients with herniation develop CES, when most do not, remains unknown. Preexisting subclinical epidural lipomatosis may limit canal space such that an otherwise benign herniation causes CES. PURPOSE: This study determines whether patients with an acute disc herniation and CES have a greater body mass index (BMI) and greater quantity of epidural fat compared with control subjects with non-CES symptomatic lumbar herniated discs. STUDY DESIGN/SETTING: A retrospective case-control series at a university-based level-1 trauma center was carried out. PATIENT SAMPLE: There were 33 CES and 66 control subjects identified from a prospectively maintained database of patients who underwent surgical management for a lumbar disc herniation between 2007 and 2012. Each CES case had two non-CES control patients matched by gender and age within 5 years except 5 CES cases that matched only one non-CES control. OUTCOME MEASURES: The outcome measures included weight, height, age, gender, and BMI. Radiographic outcome measures included the proportion of lumbar spinal canal occupied by fat and herniated disc on preoperative magnetic resonance imaging. METHODS: Patient charts and preoperative radiographs were retrospectively reviewed. For each patient, a blinded reviewer determined the proportion of lumbar spinal canal occupied by fat, and the maximal proportion of the canal occupied by herniated material at the involved level. Patient demographics and radiographic measures were compared between CES and control groups using chi-square or Student t tests. A second blinded reviewer re-assessed a series of radiographs, and the intraobserver variability was determined by Spearman correlation. Logistic regression was used to model the preoperative factors associated with having an acute disc herniation and CES. RESULTS: The CES cases had higher BMI (31.8 kg/m2, 95% confidence interval [CI] 29.5-34.0 vs. 28.1 kg/m2, 95% CI 26.7-29.5 in controls; p=.007), focally narrower canals (14.6 mm, 95% CI 13.8-15.3 mm vs. 16.4 mm, 95% CI 15.4-17.3 mm in controls; p=.003), and a greater percentage of spinal canal occupied by epidural fat (31.3%, 95% CI 26.1%-36.6% vs. 21.9%, 95% CI 18.7%-25.1% in controls; p=.003) and herniated disc material (54.5%, 95% CI 46.9%-62.0% vs. 34.4%, 95% CI 30.3%-38.5% in controls; p<.0001). Logistic regression confirmed canal width at the involved level, BMI, amount of canal occupied disc, and proportion of canal occupied by fat as independent predictors of having an acute disc herniation and CES. CONCLUSIONS: Obesity is a risk factor for CES from disc herniation. The CES cases also had a greater amount of herniated material, focally narrower canal, and larger epidural fat deposits. The latter may be the mechanism linking obesity with CES.

Stability of DNA methylation patterns in mouse spermatogonia under conditions of MTHFR deficiency and methionine supplementation.

Little is known about the conditions contributing to the stability of DNA methylation patterns in male germ cells. Altered folate pathway enzyme activity and methyl donor supply are two clinically significant factors that can affect the methylation of DNA. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key folate pathway enzyme involved in providing methyl groups from dietary folate for DNA methylation. Mice heterozygous for a targeted mutation in the Mthfr gene (Mthfr(+/-)) are a good model for humans homozygous for the MTHFR 677C>T polymorphism, which is found in 10% of the population and is associated with decreased MTHFR activity and infertility. High-dose folic acid is administered as an empirical treatment for male infertility. Here, we examined MTHFR expression in developing male germ cells and evaluated DNA methylation patterns and effects of a range of methionine concentrations in spermatogonia from Mthfr(+/-) as compared to wild-type, Mthfr(+/+) mice. MTHFR was expressed in prospermatogonia and spermatogonia at times of DNA methylation acquisition in the male germline; its expression was also found in early spermatocytes and Sertoli cells. DNA methylation patterns were similar at imprinted genes and intergenic sites across chromosome 9 in neonatal Mthfr(+/+) and Mthfr(+/-) spermatogonia. Using spermatogonia from Mthfr(+/+) and Mthfr(+/-) mice in the spermatogonial stem cell (SSC) culture system, we examined the stability of DNA methylation patterns and determined effects of low or high methionine concentrations. No differences were detected between early and late passages, suggesting that DNA methylation patterns are generally stable in culture. Twenty-fold normal concentrations of methionine resulted in an overall increase in the levels of DNA methylation across chromosome 9, suggesting that DNA methylation can be perturbed in culture. Mthfr(+/-) cells showed a significantly increased variance of DNA methylation at multiple loci across chromosome 9 compared to Mthfr(+/+) cells when cultured with 0.25- to 2-fold normal methionine concentrations. Taken together, our results indicate that DNA methylation patterns in undifferentiated spermatogonia, including SSCs, are relatively stable in culture over time under conditions of altered methionine and MTHFR levels.

Strain-specific defects in testicular development and sperm epigenetic patterns in 5,10-methylenetetrahydrofolate reductase-deficient mice.

Methylenetetrahydrofolate reductase (MTHFR) is a crucial folate pathway enzyme that contributes to the maintenance of cellular pools of S-adenosylmethionine, the universal methyl donor for several reactions including DNA methylation. Whereas Mthfr(-/-) BALB/c mice show growth retardation, developmental delay, and spermatogenic defects and infertility, C57BL/6 mice appear to have a less severe phenotype. In the present study, we investigated the effects of MTHFR deficiency on early germ cell development in both strains and assessed whether MTHFR deficiency results in DNA methylation abnormalities in sperm. The reproductive phenotype associated with MTHFR deficiency differed strikingly between the two strains, with BALB/c mice showing an early postnatal loss of germ cell number and proliferation that was not evident in the C57BL/6 mice. As a result, the BALB/c MTHFR-deficient mice were infertile, whereas the C57BL/6 mice had decreased sperm numbers and altered testicular histology but showed normal fertility. Imprinted genes and sequences that normally become methylated during spermatogenesis were unaffected by MTHFR deficiency in C57BL/6 mice. In contrast, a genome-wide restriction landmark genomic scanning approach revealed a number of sites of hypo- and hypermethylation in the sperm of this mouse strain. These results showing strain-specific defects in MTHFR-deficient mice may help to explain population differences in infertility among men with common MTHFR polymorphisms.