One-year outcomes of early-crossover patients in a cohort receiving nonoperative care for lumbar disc herniation.

OBJECTIVE The authors comprehensively studied the recovery course and 1-year outcomes of early-crossover patients who were randomized to the nonoperative care arm of the Leiden-The Hague Spine Intervention Prognostic Study. The primary goal was to gain insight into the differences in the recovery patterns of early-crossover patients and those treated nonoperatively; secondary goals were to identify predictors of good 1-year outcomes, and to understand when and why patients were likely to cross over. METHODS Individual EuroQol-5D scores were obtained at baseline and at 2, 4, 8, 12, 26, 38, and 52 weeks for 142 patients. Early-crossover patients were defined as those electing to undergo surgery during the first 12 weeks of treatment. Crossover and noncrossover groups were compared using Kruskal-Wallis, Wilcoxon-Mann-Whitney, and chi-square tests. Linear mixed-effects models were used to examine the growth trajectories of crossover and noncrossover groups. Recursive partitioning trees were used to model crossover events and the timing of crossover decisions. Multivariable logistic regression models were used to identify predictors of good 1-year outcomes. RESULTS Of the 142 patients randomized to receive prolonged nonoperative care, 136 were selected for the study. In this cohort, 43/136 (32%) opted for surgery, and 31/43 (72%) of crossover events occurred before the 12-week time point. Early-crossover patients had significantly greater functional impairment at Week 2 than noncrossover patients (p = 0.031), but experienced greater recovery by 26 weeks and better 1-year outcomes (p = 0.045). Patients who did not experience an improvement in their symptoms between 2 and 8 weeks were more likely to cross over (OR 3.5, 95% CI 1.2-10.1; p = 0.01). Recursive partitioning trees were able to identify crossover patients with 76% accuracy. Regression models suggested that better recovery at 26 weeks (p < 0.01) was predictive of good 1-year outcome; declining health status between Weeks 4 and 8 was negatively predictive of good outcome (p < 0.01). CONCLUSIONS This study is the first to comprehensively analyze the recovery and outcomes of crossover patients, and compare them to nonoperatively treated patients. The results suggest that patients who have a low EuroQol-5D score during the early weeks of treatment and who do not respond to nonoperative care during the first few weeks of treatment are most likely to cross over. Early-crossover patients experience a greater rate of recovery and more frequently have a good 1-year outcome when compared with nonoperatively treated patients. The current results motivate a broader investigation into the timing of surgery and the identification of patient populations that will be most benefited by early surgical treatment for lumbar disc herniation.

The impact of early recovery on long-term outcomes in a cohort of patients undergoing prolonged nonoperative treatment for lumbar disc herniation: clinical article.

OBJECT: The authors comprehensively studied the recovery of individual patients undergoing treatment for lumbar disc herniation. The primary goal was to gain insight into the variability of individual patient utility scores within a treatment cohort. The secondary goal was to determine how the rates and variability of patient recovery over time, represented by improvement in utility scores, affected long-term patient outcomes. METHODS: EuroQol Group-5 Dimension (EQ-5D) scores were obtained at baseline and at 2, 4, 8, 12, 26, 38, and 52 weeks for 93 patients treated under a prolonged conservative care protocol for lumbar disc herniation. Gaussian kernel densities were used to estimate the distribution of utility scores at each time point. Logistic regression and multistate Markov models were used to characterize individual patient improvement over time. Fisher exact tests were used to compare the distribution of EQ-5D domain scores. RESULTS: The distribution of utility scores was bimodal at 1 year and effectively sorted patients into a "higher" utility group (EQ-5D = 1; 43% of cohort) and a "lower" utility group (EQ-5D ≤ 0.86; 57% of cohort). Fisher exact tests revealed that pain/discomfort, mobility, and usual activities significantly differed between the 2 utility groups (p ≪ 0.001). The utility groups emerged at 8 weeks and were stable for the remainder of the treatment period. Using utility scores from 8 weeks, regression models predicted 1-year outcomes with 62% accuracy. CONCLUSIONS: This study is the first to comprehensively consider the utility recovery of individual patients within a treatment cohort for lumbar disc herniation. The results suggest that most utility is recovered during the early treatment period. Moreover, the findings suggest that initial improvement is critical to a patient's long-term outcome: patients who do not experience significant initial recovery appear unlikely to do so at a later time under the same treatment protocol.

The use of bone morphogenetic protein-6 gene therapy for percutaneous spinal fusion in rabbits.

OBJECT: Fusion procedures in the lumbar spine have been performed in the US since 1911. Since that time, the indications and techniques for spinal fusion have evolved. Despite technical advancements, spinal fusion remains a major operation, and fusion nonunion rates of up to 35% are still reported. In this study, the authors were able to induce intertransverse process fusions in immune-competent New Zealand White rabbits by percutaneous administration of an adenoviral vector containing the bone morphogenetic protein (BMP-6) gene (Ad-BMP-6). The results represent an important step forward in finding new methods to increase the success and decrease the morbidity associated with spinal fusion. METHODS: Five New Zealand White rabbits were used. Injection of the adenoviral construct was performed at multiple levels (bilaterally) in each animal while using fluoroscopic guidance. Injection consisted of either Ad-BMP-6 or Ad-beta-galactosidase (beta-gal) (control). Because multiple levels were injected, each animal served as an internal control. The animals underwent postinjection computerized tomography (CT) scanning at 7 and 14 weeks. After undergoing final CT scanning, the animals were killed and the spines were harvested. The fusion sites were analyzed by gross inspection, histopathological methods, and micro-CT studies. CONCLUSIONS: The results of this study show that an anatomically precise fusion can be accomplished by percutaneous administration of gene therapy. The next step in these studies will be extension of the technique to nonhuman primates and eventually to human clinical studies.

Clinical characteristics of silent corticotrophic adenomas and creation of an internet-accessible database to facilitate their multi-institutional study.

OBJECTIVE: Silent corticotrophic adenomas (SCAs) of the pituitary gland present as clinically nonfunctioning sellar lesions, with normal serum and urine hormone testing results, but stain positively for adrenocorticotropic hormone in immunohistochemical analyses. These tumors are now more readily recognized, but determination of their natural history and responses to treatment is difficult because of their rarity. We report the diagnoses and outcomes for a series of patients with SCAs, and we describe the creation of an Internet-accessible database (www.hsc.virginia.edu/neuro/neurosurgery/pituitary.html) for collection of multi-institutional data on these lesions. METHODS: The medical records of patients with documented SCAs who were treated at the University of Virginia between 1991 and 2002 were reviewed. A comprehensive data collection form was then created and posted online. RESULTS: Twenty-seven patients with SCAs were identified, with a female predominance (70%, P = 0.04). Headache was the most common presenting symptom (70%), followed by visual field deficits (52%), acute or subacute pituitary apoplexy (33%), cavernous sinus syndrome (18.5%), and hypopituitarism (11.1%). Extrasellar extension was noted for 92.6% of patients on preoperative magnetic resonance imaging scans. Transsphenoidal surgery was performed for all patients. Follow-up information was available for all patients (median, 60 mo; range, 3-254 mo). Postoperatively, 33% of patients received radiotherapy. Recurrence was noted for 37% of all patients and 41.7% of patients who did not receive postoperative radiotherapy. CONCLUSION: SCAs, although clinically nonfunctioning, may behave like aggressive adrenocorticotropic hormone-secreting adenomas and therefore should receive vigorous follow-up monitoring, with consideration being given to the recommendation of radiotherapy in cases with residual tumor.

Pediculotomy as an adjunct to posterior cervical hemilaminectomy, foraminotomy, and discectomy.

Currently the posterior approach undertaken to perform cervical hemilaminectomy and foraminotomy provides sufficient exposure to treat the majority of lateral soft-disc herniations or osteophytes causing radiculopathy. Limitations imposed by the surgical field, however, often necessitate excessive retraction of the nerve root and epidural venous plexus, which may potentially exacerbate a preexisting radiculopathy or increase intraoperative blood loss. Partial resection of the inferior pedicle augments exposure and enlarges the neural foramen, thus facilitating decompression while minimizing manipulation of the nerve root and epidural venous plexus. With the patient in the prone position, partial hemilaminectomy and foraminotomy are performed using a highspeed 3-mm diamond burr with continuous irrigation. The thecal sac and nerve root are exposed, and the overlying fibroareolar layer is coagulated and incised. With the nerve root protected and under direct vision, the superomedial portion of the inferior pedicle is removed. Nerve root decompression is then performed through this augmented exposure. Partial excision of the pedicle allows for more expeditious removal of the pathological elements causing cervical radiculopathy and requires minimal manipulation of the nerve root and epidural venous plexus. This procedure results in a potential decrease in transient postoperative radiculopathy and minimization of intraoperative blood loss. In addition, the resulting foraminal enlargement enhances the decompression provided by traditional foraminotomy, even if discectomy is not performed.