Seppo Seitsalo

Surgical or nonoperative treatment for lumbar spinal stenosis? A randomized controlled trial.

Study Design. A randomized controlled trial. Objectives. To assess the effectiveness of decompressive surgery as compared with nonoperative measures in the treatment of patients with lumbar spinal stenosis. Summary of Background Data. No previous randomized trial has assessed the effectiveness of surgery in comparison with conservative treatment for spinal stenosis. Methods. Four university hospitals agreed on the classification of the disease, inclusion and exclusion criteria, radiographic routines, surgical principles, nonoperative treatment options, and follow-up protocols. A total of 94 patients were randomized into a surgical or nonoperative treatment group: 50 and 44 patients, respectively. Surgery comprised undercutting laminectomy of the stenotic segments in 10 patients augmented with transpedicular fusion. The primary outcome was based on assessment of functional disability using the Oswestry Disability Index (scale, 0–100). Data on the intensity of leg and back pain (scales, 0–10), as well as self-reported and measured walking ability were compiled at randomization and at follow-up examinations at 6, 12, and 24 months. Results. Both treatment groups showed improvement during follow-up. At 1 year, the mean difference in favor of surgery was 11.3 in disability (95% confidence interval [CI], 4.3–18.4), 1.7 in leg pain (95% CI, 0.4–3.0), and 2.3(95% CI, 1.1–3.6) in back pain. At the 2-year follow-up, the mean differences were slightly less: 7.8 in disability (95% CI, 0.8–14.9) 1.5 in leg pain (95% CI, 0.3–2.8), and 2.1 in back pain (95% CI, 1.0–3.3). Walking ability, either reported or measured, did not differ between the two treatment groups. Conclusions. Although patients improved over the 2-year follow-up regardless of initial treatment, those undergoing decompressive surgery reported greater improvement regarding leg pain, back pain, and overall disability. The relative benefit of initial surgical treatment diminished over time, but outcomes of surgery remained favorable at 2 years. Longer follow-up is needed to determine if these differences persist.

A controlled immunohistochemical study of inflammatory cells in disc herniation tissue

Study Design The presence and abundance of inflammatory cells was studied immunocytochemically in lumbar disc herniations (DH) and macroscopically normal discs for comparison. Objectives The objective of the study was to characterize inflammatory cells that appear in herniated disc tissue and to study the relative abundance of various types of inflammatory cells. Summary of Background Data Only few macrophages were observed in control discs, whereas abundant macrophages were present in half of the DH.Other types of inflammatory cells were less often abundant in the present material. In about a third of the DH interleukin-1 beta-expressing cells were also observed. Methods Twenty-four DH and control tissue from five discs were studied immunocytochemically, using specific monoclonal antibodies to various types of inflammatory cells and interleukin-1 beta. The results were compared with corresponding clinical data. Macrophages were studied with an antibody to CD68 antigen and Ber-MAC3 antibody separately. Results The obtained results suggest a variable inflammatory cell response in DH, which seems to be often dominated by macrophages at the time of operation. Thus previous suggestions of sometimes very active inflammation in DH tissue are supported. Conclusions Inflammation may be important in disc tissue pathophysiology, possibly also in discogenic pain mechanisms.

Progression of spondylolisthesis in children and adolescents: A long-term follow-up of 272 patients

The radiologic progression of spondylolisthesis during a long-term follow-up was studied in 272 children and adolescents. There were 134 girls and 138 boys. The mean age at the first visit was 14.3 years (girls, 13.8 years; boys, 14.9 years). The radiologic follow-up time was 14.8 years on average (range, 5–32). The operation was done in 190 patients younger than 20 years of age. Fusion in situ, using a posterior or posterolateral technique, had no statistically significant effect on progression. Surgically treated patients did not differ from conservatively treated patients. Ninety percent of the slip, on average, had already occurred at the time of the first radiologic examination compared with the final amount of slip. More than 10% progression occurred in 62 patients, mainly within the first year postoperatively or after the first examination. Progression of the lumbosacral kyphosis and sinking of the vertebral body was noted in severe slips. Although female gender and dysplasia (spina bifida) at the lumbosacral junction were more frequent in severe slips, they statistically had no value in predicting progression. A wedge form of L5 or sacral rounding also had no prognostic value. These were secondary to the slip and expressed it but did not predict it. The only radiologic variable with predictive value of progression was the percentage amount of the primary slip. In age groups corresponding to the growth spurt in early puberty (girls, 9–12 years; boys, 11–14 years), there was a tendency to progress.

The Treatment of Disc Herniation-induced Sciatica With Infliximab: One-year Follow-up Results of First Ii, a Randomized Controlled Trial

Study Design. A randomized controlled trial. Objectives. To evaluate the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α), in patients with acute/subacute sciatica secondary to herniated disc. Summary of Background Data. The results of experimental studies and our open-label trial support the use of infliximab in sciatica. Here we report the 1-year results of a randomized controlled trial (FIRST II, Finnish Infliximab Related STudy) evaluating the efficacy and safety of a single infusion of infliximab for sciatic pain. Methods. Inclusion criteria were unilateral sciatic pain with a disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy. Criteria for discectomy included (in addition to a symptomatic disc herniation on MRI) neural entrapment (straight leg raising [SLR] ≤60°) with either a short-term (2–4 weeks) severe or long-term (4–12 weeks) moderate leg pain. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Differences in the clinical examination parameters (straight leg raise [SLR], muscle strength, sensory defects, tendon reflexes), patient-reported symptoms (leg and back pain using a visual analog scale [VAS], Oswestry disability, quality-of-life [RAND-36]), sick leaves, number of discectomies, and adverse effects between the two treatment groups over the 1-year follow-up were compared using Mann-Whitney U test or Students t test, repeated-measures analysis, or Cox proportional hazards model. Logistic regression was used to assess the predictors of good response. Results. Sixty-seven percent of patients in the infliximab group reported no pain at 52 weeks compared with 63% in the control group (P = 0.72). Similar efficacy was observed between treatment groups for other outcomes. Eight patients in each group required surgery. Three nonserious adverse reactions were encountered in the infliximab group. The response (irrespective of the treatment) was significantly better with shorter symptom duration and less SLR restriction at baseline. Patients in the infliximab group appeared to especially benefit in cases of a L4–L5 (or L3–L4) herniation and if a Modic change was colocalized at the symptomatic level. Conclusions. Although the long-term results of this randomized trial do not support the use of infliximab compared with placebo for lumbar radicular pain in patients with disc herniation-induced sciatica, further study in a subgroup of patients with L4–L5 or L3–L4 herniations, especially in the presence of Modic changes, appears to be warranted.

Retrograde ejaculation after anterior interbody lumbar fusion

SummaryRetrograde ejaculation as a complication of anterior interbody lumbar fusion was investigated. The diagnosis of retrograde ejaculation was made on the basis of interviews. Patients were informed of the risk of retrograde ejaculation preoperatively. At the follow-up study the patients were asked if they had noticed retrograde ejaculation after their operation. In one case (anejaculation) testis biopsy and vasography was performed. On average, the incidence of retrograde ejaculation as a complication of anterior interbody lumbar fusion has been very low, ranging from only a few cases up to 5.9% of cases involving male patients. We studied 40 male patients with severe low back pain retrospectively after they had undergone anterior interbody lumbar fusion. The mean age at operation was 31.9 years and the mean follow-up time 5.0 years. Retrograde ejaculation occurred after anterior interbody fusion in nine patients. Permanent retrograde ejaculation developed in seven of these patients (17.5%). These patients were all operated on using a transabdominal approach. Major bleeding during the operation (over 2500 ml) was observed in two patients. Seven patients with retrograde ejaculation had undergone a two-level operation (L4-SI), and eight patients had undergone between one and three previous spine operations. Retrograde ejaculation has been underestimated as a complication of anterior interbody fusion in multioperated low back patients. The possibility of this complication should be kept in mind when planning a transabdominal approach for interbody lumbar fusion in male patients. We do not recommend the transabdominal approach in male patients because of the risk of retrograde ejaculation.

Surgical treatment of severe isthmic spondylolisthesis in adolescents : reduction or fusion in situ

Twenty-two adolescent patients with severe (more than 50%) slip were surgically treated. Eleven were reduced with Magerl/Dick transpedicular screw devices and fused posteriorly from L4 to S1, and 2 weeks later anteriorly L5-S1; the other 11 were fused in situ L4-S1 (6 patients) or L5-S1 (5 patients) using a circumferential (6 patients), anterior (4 patients) or posterolateral (1 patient) technique without instrumentation. The two groups were comparable as to age at operation, age at follow-up, follow-up time, and preoperative radiologic measurement of the slip, lumbosacral kyphosis, and clinical findings. The mean follow-up times were 56.5 and 59.8 months, respectively. In the reduction group an improvement in the slip of 36.1 percentage points was achieved as compared with 7.7 percentage points in the in situ-fusion group. The sagittal rotation angle improved by 11 in the reduction group and worsened by 2.8 in the in situ-fusion group. There were no differences between the groups in the functional tests or clinical findings concerning pain. Subjective assessment was good in both groups at follow-up; that is, the pain had disappeared. Mean operation time and intraoperative blood loss were significantly higher in the reduction group. Reduction procedures were also associated with a higher number of complications and reoperations. No neurologic complications, however, occurred in the reduction group. Based on this study, in situ fusions are to be preferred in adolescents with severe spondylolisthesis.

Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.

Study Design. An open-label trial. Objectives. To test the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor-alpha (TNF-α), in disc herniation-induced sciatica. Summary of Background Data. Our recent trial indicated that a single infusion of 3 mg/weight-kg of infliximab produced a rapid curative effect in disc herniation-induced sciatica. Here, we describe the 1-year effect of a 3 mg/kg of infliximab in these 10 patients and our experience with a lower dose of 1 mg/kg of infliximab for the same indication in 2 additional patients. Methods. Patients with severe sciatica were treated with a single infusion of infliximab, 3 mg/weight-kg in 10 patients and 1 mg/kg in 2 patients, intravenously over 2 hours. The outcomes (leg and back pain on a 100-mm visual scale, Oswestry disability, clinical signs) were assessed at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year after the infusion. The outcomes with 3 mg/kg of infliximab were compared to 62 patients who received periradicular saline for sciatica in a previous trial. The resorption rate of disc herniations from baseline to 1 year was compared between infliximab and control groups. Results. The response to 1 mg/kg of infliximab for leg pain was good only in 1 of the 2 patients treated, whereas the response to 3 mg/kg of infliximab for leg pain was sustained in most patients over the 1-year follow-up. The 1-year response significantly favored 3 mg/kg of infliximab over periradicular saline in leg pain (P = 0.005) and disability (P = 0.003). Neurologic abnormalities normalized more comprehensively in the infliximab group (P = 0.001). Reduction in disc herniation volume did not differ between the infliximab-treated patients and controls. Conclusions. The results showed that the beneficial effect of a single infusion of 3 mg/kg of infliximab for herniation-induced sciatica is sustained in most patients over a 1-year follow-up period. Furthermore, infliximab does not seem to interfere with the spontaneous resorption of disc herniations.

Neuroimmunohistochemical Analysis of Peridiscal Nociceptive Neural Elements

Twenty-three perioperative tissue samples from lumbar disc operations on 11 patients were studied Immunohistochemically using the sensitive avidin-biotin-peroxidase complex (ABC) method and specific heterologous antisera for the presence of neurofilament-positive neural elements containing nociceptive neuropeptides substance P (SP) and/or calcitonin gene-related peptide (CGRP). Histologically, neural elements were especially abundant in the posterior longitudinal ligament, there being also a few demonstrable nerves in the peripheral anulus fibrosus. These nerves often showed a co-localization of cytoskeletal neurofilaments together with SP and/or CGRP immunoreactivity. It is suggested that pressure and chemical irritation of nociceptive nerves dependent on degenerated discs excite sensory neural elements, especially in the posterior longitudinal ligament and possibly also in the peripheral parts of the anulus fibrosus, while the disc itself, at least if not penetrated by vascular granular tissue, is painless and neuroanatomically lacks a structural basis for pain perception.

The treatment of disc herniation-induced sciatica with infliximab - Results of a randomized, controlled, 3-month follow-up study

Study Design. A randomized controlled trial. Objectives. To evaluate the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF)-&agr; in a randomized controlled setting. Summary of Background Data. Recently, we obtained encouraging results in an open-label study of infliximab in patients with disc herniation-induced sciatica. Furthermore, the results of experimental studies support the use of infliximab in sciatica. Therefore, we initiated a randomized, controlled trial (FIRST II, Finnish Infliximab Related STudy) to confirm the efficacy of a single infusion of infliximab for sciatic pain. Methods. Inclusion criteria were unilateral moderate to severe sciatic pain with an MRI-confirmed disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy, as evaluated by an independent orthopedic surgeon. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Assessments at baseline and various time points included clinical examination with measurement of straight leg raising restriction; questionnaires related to subjective symptoms (leg and back pain by 100-mm visual analog scale, Oswestry disability); sick leaves; number of discectomies; and adverse effects possibly related to treatment. The primary endpoint was a reduction in leg pain from baseline to 12 weeks, which was analyzed using a Mann-Whitney U test and repeated-measures analysis. Results. A significant reduction in leg pain was observed in both groups, with no significant difference between treatment regimens. Similar efficacy was observed between treatment groups for secondary endpoints. Seven patients in each group required surgery. No adverse effects related to treatment were encountered. Conclusions. The results of this randomized trial do not support the use of infliximab for lumbar radicular pain in patients with disc herniation-induced sciatica.

Reoperations After Lumbar Disc Surgery : A Population-Based Study of Regional and Interspecialty Variations

Study Design. A follow-up study using nationwide administrative databases. Objectives. To explore rates of reoperation after lumbar disc surgery and their regional and interspecialty variations. Summary of Background Data. In many Western countries, rates of lumbar disc surgery display significant geographic variations suggesting varying treatment criteria among operating surgeons. Few population-based studies have explored the risk of reoperation after disc surgery, and regional or interspecialty variations in the reoperations are unknown. Methods. Patients who underwent lumbar spine surgery from January 1, 1987 through December 31, 1995, were identified in the Finnish Hospital Discharge Register. Data on the patients’ initial disc operations, subsequent operations, and cause-of-death records were linked using personal identification codes. The Kaplan–Meier method and proportional hazard model were used to analyze risks of reoperation after initial surgery, according to hospital catchment area rates of disc surgery and for neurosurgical and orthopedic patients of university hospitals. Results. 12.3% of 25,359 surgical patients with herniated lumbar discs underwent subsequent lumbar operations corresponding to the cumulative risk of 18.9% in the 9-year follow-up. Reoperation rates increased during the study period with the recent patient cohorts exhibiting risks. The reoperation risk showed a systematic geographic variation: the higher the regional disc surgery rate, the higher the reoperation risk. Overall, neurosurgical patients had a higher reoperation risk than orthopedic patients (relative risk [RR]: 1.57, 95% confidence interval [CI]: 1.17–2.10), but this was not a uniform finding. Conclusions. The reoperation risk after disc surgery increased during the study period and was higher in hospital catchment areas with higher overall discectomy rates. The reoperation risks varied among the university hospitals but tended to be higher for neurosurgical rather than for orthopedic patients.