A Patterned Architecture of Monoaminergic Afferents in the Cerebellar Cortex: Noradrenergic and Serotonergic Fibre Distributions within Lobules and Parasagittal Zones.

The geometry of the glutamatergic mossy-parallel fibre and climbing fibre inputs to cerebellar cortical Purkinje cells has powerfully influenced thinking about cerebellar functions. The compartmentation of the cerebellum into parasagittal zones, identifiable in olivo-cortico-nuclear projections, and the trajectories of the parallel fibres, transverse to these zones and following the long axes of the cortical folia, are particularly important. Two monoaminergic afferent systems, the serotonergic and noradrenergic, are major inputs to the cerebellar cortex but their architecture and relationship with the cortical geometry are poorly understood. Immunohistochemistry for the serotonin transporter (SERT) and for the noradrenaline transporter (NET) revealed strong anisotropy of these afferent fibres in the molecular layer of rat cerebellar cortex. Individual serotonergic fibres travel predominantly medial-lateral, along the long axes of the cortical folia, similar to parallel fibres and Zebrin II immunohistochemistry revealed that they can influence multiple zones. In contrast, individual noradrenergic fibres run predominantly parasagittally with rostral-caudal extents significantly longer than their medial-lateral deviations. Their local area of influence has similarities in form and size to those of identified microzones. Within the molecular layer, the orthogonal trajectories of these two afferent systems suggest different information processing. An individual serotonergic fibre must influence all zones and microzones within its medial-lateral trajectory. In contrast, noradrenergic fibres can influence smaller cortical territories, potentially as limited as a microzone. Evidence is emerging that these monoaminergic systems may not supply a global signal to all of their targets and their potential for cerebellar cortical functions is discussed.

Distribution of neural plasticity in cerebellum-dependent motor learning.

The cerebellum is essential for some forms of motor learning. Two examples that provide useful experimental models are modification of the vestibulo-ocular reflex and classical conditioning of the nictitating membrane response (NMR) in the rabbit. There has been considerable analysis of these behavioral models and of conditioning of the eyelid blink reflex, which is similar in several respects to NMR conditioning but with some key differences in its control circuitry. The evidence is consistent with the suggestion that storage of these motor memories is to be found within the cerebellum and its associated brainstem circuitry. The cerebellum presents many advantages as a model system to characterize the cellular and molecular mechanisms underpinning behavioral learning. And yet, localizing the essential synaptic changes has proven to be difficult. A major problem has been to establish to what extent these neural changes are distributed through the cerebellar cortex, cerebellar nuclei, and associated brainstem nuclei. Inspired by recent theoretical work, here we review evidence that the distribution of plasticity across cortical and cerebellar nuclear (or brainstem vestibular system) levels for different learning tasks may be different and distinct. Our primary focus is on classical conditioning of the NMR and eyelid blink, and we offer comparisons with mechanisms for modifications of the vestibulo-ocular reflex. We describe a view of cerebellar learning that satisfies theoretical and empirical analysis.

No reductions and some improvements in South African lay HIV/AIDS counsellors' motivational interviewing competence one year after brief training.

In South Africa, lay HIV/AIDS counsellors are trained in both client-centred and more directive, health-advising techniques. Both approaches are limited in facilitating health behaviour when clients are ambivalent. Motivational interviewing (MI) is a counselling approach that develops the client's intrinsic motivation to change. Evangeli et al. evaluated a 12-hour course of MI delivered to 17 lay HIV/AIDS counsellors in Western Cape Province, South Africa. There was a marked change from MI non-adherent practice to more MI adherent practice at the end of the training. Few counsellors, however, reached the level of beginning proficiency in MI. The current study was a one-year follow-up of MI competence in the same cohort of lay HIV counsellors. Ten counsellors participated. Results confirmed that changes in lay HIV counsellors' level of MI competence as a result of a brief MI course were maintained over a one-year period and in some cases were enhanced. MI competence was independent of self-report and demographic factors. As in Evangeli et al., the majority of counsellors did not attain beginning proficiency level. Reasons for the findings are explored, including consideration of baseline level of counselling, characteristics of the training and individual motivation. Ideas for future research are outlined.

Surgical compared with nonoperative treatment for lumbar degenerative spondylolisthesis. four-year results in the Spine Patient Outcomes Research Trial (SPORT) randomized and observational cohorts.

BACKGROUND: The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial. Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years. Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment. METHODS: Surgical candidates from thirteen centers with symptoms of at least twelve weeks' duration as well as confirmatory imaging showing degenerative spondylolisthesis with spinal stenosis were offered enrollment in a randomized cohort or observational cohort. Treatment consisted of standard decompressive laminectomy (with or without fusion) or usual nonoperative care. Primary outcome measures were the Short Form-36 (SF-36) bodily pain and physical function scores and the modified Oswestry Disability Index at six weeks, three months, six months, and yearly up to four years. RESULTS: In the randomized cohort (304 patients enrolled), 66% of those randomized to receive surgery received it by four years whereas 54% of those randomized to receive nonoperative care received surgery by four years. In the observational cohort (303 patients enrolled), 97% of those who chose surgery received it whereas 33% of those who chose nonoperative care eventually received surgery. The intent-to-treat analysis of the randomized cohort, which was limited by nonadherence to the assigned treatment, showed no significant differences in treatment outcomes between the operative and nonoperative groups at three or four years. An as-treated analysis combining the randomized and observational cohorts that adjusted for potential confounders demonstrated that the clinically relevant advantages of surgery that had been previously reported through two years were maintained at four years, with treatment effects of 15.3 (95% confidence interval, 11 to 19.7) for bodily pain, 18.9 (95% confidence interval, 14.8 to 23) for physical function, and -14.3 (95% confidence interval, -17.5 to -11.1) for the Oswestry Disability Index. Early advantages (at two years) of surgical treatment in terms of the secondary measures of bothersomeness of back and leg symptoms, overall satisfaction with current symptoms, and self-rated progress were also maintained at four years. CONCLUSIONS: Compared with patients who are treated nonoperatively, patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years.

Hyper-use of the ED.

OBJECTIVES: This study aims to describe the population that averages one or more emergency department (ED) visits per month and compare them to the general ED population to determine if there are associated characteristics. METHODS: A retrospective cohort study conducted in a teaching hospital between January 1, 2001, and December 31, 2004, identified all patients with more than 35 visits. This hyper-user (HU) cohort (n = 49) was compared to a randomly selected group of non-HU patients (n = 50) on the following measures: age, sex, insurance coverage, primary medical doctor (PMD), dwelling location, chief complaint, comorbidities, and disposition. RESULTS: The HU group was significantly older (mean, 49.45 years) than the non-HU group (37.32 years) with a P < .0001. There was no difference between the groups in sex, insurance coverage, PMD, dwelling location, and disposition. A univariant logistical regression found that previous cardiovascular, genitourinary, or psychiatric disease were predictors of hyper-use. CONCLUSIONS: The HU group is older and more likely to have a history of cardiovascular, genitourinary, and psychiatric disease but is similar to the non-HU group in other measured parameters. The HU group appears to have equal access to a PMD and is not more likely to be admitted to the hospital than the non-HU group.

Surgical treatment of spinal stenosis with and without degenerative spondylolisthesis: cost-effectiveness after 2 years.

BACKGROUND: The SPORT (Spine Patient Outcomes Research Trial) reported favorable surgery outcomes over 2 years among patients with stenosis with and without degenerative spondylolisthesis, but the economic value of these surgeries is uncertain. OBJECTIVE: To assess the short-term cost-effectiveness of spine surgery relative to nonoperative care for stenosis alone and for stenosis with spondylolisthesis. DESIGN: Prospective cohort study. DATA SOURCES: Resource utilization, productivity, and EuroQol EQ-5D score measured at 6 weeks and at 3, 6, 12, and 24 months after treatment among SPORT participants. TARGET POPULATION: Patients with image-confirmed spinal stenosis, with and without degenerative spondylolisthesis. TIME HORIZON: 2 years. PERSPECTIVE: Societal. INTERVENTION: Nonoperative care or surgery (primarily decompressive laminectomy for stenosis and decompressive laminectomy with fusion for stenosis associated with degenerative spondylolisthesis). OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: Among 634 patients with stenosis, 394 (62%) had surgery, most often decompressive laminectomy (320 of 394 [81%]). Stenosis surgeries improved health to a greater extent than nonoperative care (QALY gain, 0.17 [95% CI, 0.12 to 0.22]) at a cost of $77,600 (CI, $49,600 to $120,000) per QALY gained. Among 601 patients with degenerative spondylolisthesis, 368 (61%) had surgery, most including fusion (344 of 368 [93%]) and most with instrumentation (269 of 344 [78%]). Degenerative spondylolisthesis surgeries significantly improved health versus nonoperative care (QALY gain, 0.23 [CI, 0.19 to 0.27]), at a cost of $115,600 (CI, $90,800 to $144,900) per QALY gained. RESULT OF SENSITIVITY ANALYSIS: Surgery cost markedly affected the value of surgery. LIMITATION: The study used self-reported utilization data, 2-year time horizon, and as-treated analysis to address treatment nonadherence among randomly assigned participants. CONCLUSION: The economic value of spinal stenosis surgery at 2 years compares favorably with many health interventions. Degenerative spondylolisthesis surgery is not highly cost-effective over 2 years but could show value over a longer time horizon.

Corrective osteotomies in spine surgery.

Spinal deformities can result in increasing thoracic kyphosis or loss of lumbar lordosis, leading to imbalance in the sagittal plane. Such deformities can be functionally and psychologically debilitating. The Smith-Petersen osteotomy can achieve approximately 10 degrees of correction in the sagittal plane at each spinal level at which it is performed. This osteotomy is beneficial for patients who have a degenerative imbalance in the sagittal plane. The pedicle subtraction osteotomy can achieve approximately 30 degrees to 40 degrees of correction in the sagittal plane at each spinal level at which it is performed. It is the preferred osteotomy for patients with ankylosing spondylitis who have an imbalance of the spine in the sagittal plane. The cervical extension osteotomy is performed in the cervical spine, at the cervicothoracic junction, in patients who have a cervical flexion deformity that impedes their ability to look straight ahead while walking or who have difficulty swallowing. The vertebral column resection is used when the imbalance is severe enough that the other osteotomies cannot correct the deformity, especially in patients who have a combined sagittal and coronal spinal imbalance. Neurologic problems, whether transient or permanent, are the most commonly encountered complications following these procedures. Recent results have shown a high patient satisfaction rate and good functional outcomes after spinal osteotomies done to treat a variety of disorders.

SPORT lumbar intervertebral disk herniation and back pain: does treatment, location, or morphology matter?

STUDY DESIGN: Diskectomy candidates with at least 6 weeks of sciatica and confirmatory imaging were enrolled in a randomized or observational cohort. OBJECTIVE: This study sought to determine: (1) whether diskectomy resulted in greater improvement in back pain than nonoperative treatment, and (2) whether herniation location and morphology affected back pain outcomes. SUMMARY OF BACKGROUND DATA: Previous studies have reported that lumbar diskectomy is less successful for relief of back pain than leg pain and patients with central disc herniations or protrusions have worse outcomes. METHODS: Patients underwent diskectomy or received "usual" nonoperative care. Data from the randomized cohort and observational cohort were combined in an as-treated analysis. Low back pain was recorded on a 0 to 6 point scale, and changes in low back pain were compared between the surgical and nonoperative treatment groups. The effects of herniation location and morphology on back pain outcomes were determined. RESULTS: The combined analysis included 1191 patients with 775 undergoing surgery within 2 years, whereas 416 remained nonoperative. Overall, leg pain improved more than back pain in both treatment groups. Back pain improved in both surgical and nonoperative patients, but surgical patients improved significantly more (treatment effect favoring surgery -0.9 at 3 months, -0.5 at 2 years, P < 0.001). Patients who underwent surgery were more likely to report no back pain than nonoperative patients at each follow-up period (28.0% vs. 12.0% at 3 months, P < 0.001, 25.5% vs. 17.6% at 2 years, P = 0.009). At baseline, central herniations were associated with more severe back pain than more lateral herniations (4.3 vs. 3.9, P = 0.012). Patients with central herniations and protrusionshad a beneficial treatment effect from surgery similar to the overall surgical group. CONCLUSION: Diskectomy resulted in greater improvement in back pain than nonoperative treatment, and this difference was maintained at 2 years for all herniation locations and morphologies.

Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis.

BACKGROUND: Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials. METHODS: Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, with higher scores indicating less severe symptoms) and the modified Oswestry Disability Index (100-point scale, with lower scores indicating less severe symptoms) at 6 weeks, 3 months, 6 months, 1 year, and 2 years. RESULTS: We enrolled 304 patients in the randomized cohort and 303 in the observational cohort. The baseline characteristics of the two cohorts were similar. The one-year crossover rates were high in the randomized cohort (approximately 40% in each direction) but moderate in the observational cohort (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to-treat analysis for the randomized cohort showed no statistically significant effects for the primary outcomes. The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years. The treatment effects at 2 years were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for physical function (95% CI, 14.6 to 21.9), and -16.7 for the Oswestry Disability Index (95% CI, -19.5 to -13.9). There was little evidence of harm from either treatment. CONCLUSIONS: In nonrandomized as-treated comparisons with careful control for potentially confounding baseline factors, patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically. (ClinicalTrials.gov number, NCT00000409 [ClinicalTrials.gov].).

Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery.

BACKGROUND: Recombinant human bone morphogenetic protein-2 soaked into an absorbable collagen sponge (rhBMP-2/ACS) has been shown in a nonhuman primate study and in a pilot study in humans to promote new bone formation and incorporation of an allograft device when implanted in patients undergoing anterior lumbar interbody arthrodesis. However, a larger series with longer follow-up is needed to demonstrate its superiority to autogenous iliac crest bone graft. METHODS: Between 1998 and 2001, a two-part, prospective, randomized, multicenter study of 131 patients was conducted to determine the safety and efficacy of the use of rhBMP-2/ACS as a replacement for autogenous iliac crest bone graft in anterior lumbar spinal arthrodesis with threaded cortical allograft dowels. Patients were randomly assigned to a study group that received rhBMP-2/ACS or to a control group that received autograft. The clinical and radiographic outcomes were determined with use of well-established instruments and radiographic assessments. RESULTS: The patients in the study group had significantly better outcomes than the control group with regard to the average length of surgery (p < 0.001), blood loss (p < 0.001), and hospital stay (p = 0.020). Fusion rates were significantly better in the study group (p < 0.001). The average Oswestry Disability Index scores, Short-Form-36 physical component summary scores, and low-back and leg-pain scores were significantly better in the study group (p < 0.05). CONCLUSIONS: In patients undergoing anterior lumbar interbody arthrodesis with threaded allograft cortical bone dowels, rhBMP-2/ACS was an effective replacement for autogenous bone graft and eliminated the morbidity associated with graft harvesting.