CSF rhinorrhoea after endonasal intervention to the anterior skull base (CRANIAL): proposal for a prospective multicentre observational cohort study.

BACKGROUND: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. METHODS: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. ETHICS AND DISSEMINATION: Formal institutional ethical board review was not required owing to the nature of the study - this was confirmed with the Health Research Authority, UK. CONCLUSIONS: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.

Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote fusion in spinal surgery, but its safety has been questioned. PURPOSE: To evaluate the effectiveness and safety of rhBMP-2. DATA SOURCES: Individual-participant data obtained from the sponsor or investigators and data extracted from study publications identified by systematic bibliographic searches through June 2012. STUDY SELECTION: Randomized, controlled trials of rhBMP-2 versus iliac crest bone graft (ICBG) in spinal fusion surgery for degenerative disc disease and related conditions and observational studies in similar populations for investigation of adverse events. DATA EXTRACTION: Individual-participant data from 11 eligible of 17 provided trials sponsored by Medtronic (Minneapolis, Minnesota) (n = 1302) and 1 of 2 other eligible trials (n = 106) were included. Additional aggregate adverse event data were extracted from 35 published observational studies. DATA SYNTHESIS: Primary outcomes were pain (assessed with the Oswestry Disability Index [ODI] or Short Form-36), fusion, and adverse events. At 24 months, ODI scores were 3.5% lower (better) with rhBMP-2 than with ICBG (95% CI, 0.5% to 6.5%) and radiographic fusion was 12% higher (CI, 2% to 23%). At or shortly after surgery, pain was more common with rhBMP-2 (odds ratio, 1.78 [CI, 1.06 to 2.95]). Cancer was more common after rhBMP-2 (relative risk, 1.98 [CI, 0.86 to 4.54]), but the small number of events precluded definite conclusions. LIMITATION: The observational studies were diverse and at risk of bias. CONCLUSION: At 24 months, rhBMP-2 increases fusion rates, reduces pain by a clinically insignificant amount, and increases early postsurgical pain compared with ICBG. Evidence of increased cancer incidence is inconclusive. PRIMARY FUNDING SOURCE: Yale University Open Data Access Project.

Real-world experience with 11C-methionine positron emission tomography in the management of acromegaly.

BACKGROUND: L-[methyl-11C]-methionine-positron emission tomography (Met-PET) is a potentially important imaging adjunct in the diagnostic workup of pituitary adenomas, including somatotroph tumors. Met-PET can identify residual or occult disease and make definitive therapies accessible to a subgroup of patients who would otherwise require lifelong medical therapy. However, existing data on its use are still limited to small case series. Here, we report the largest single-center experience (n = 61) in acromegaly. METHODS: A total of 189 cases of acromegaly were referred to our national Met-PET service in the last 12 years. For this analysis, we have reviewed outcomes in those 61 patients managed exclusively by our multidisciplinary team (single center, single surgeon). Referral indications were as follows: indeterminate magnetic resonance imaging (MRI; n = 38, 62.3%), occult residual (n = 14, 23.0%), (radio-)surgical planning (n = 6, 9.8%), and occult de novo tumor (n = 3, 4.9%). RESULTS: A total of 33/61 patients (54.1%) underwent PET-guided surgery. Twenty-four of 33 patients (72.7%) achieved complete biochemical remission following (re-)surgery. Insulin-like growth factor 1 levels were reduced to <2 × upper limit of normal (ULN) in 6 of the remaining 9 cases, 3 of whom achieved levels of <1.1 × ULN compared with mean preoperative levels of 2.4 × ULN (SD 0.8) for n = 9. Only 3 patients developed single new hormonal deficits (gonadotropic/thyrotropic insufficiency). There were no neurovascular complications after surgery. CONCLUSION: In patients with persistent/recurrent acromegaly or occult tumors, Met-PET can facilitate further targeted intervention (surgery/radiosurgery). This led to complete remission in most cases (24/33) or significant improvement with comparatively low risk of complications. L-[methyl-11C]-methionine-positron emission tomography should therefore be considered in all patients who are potential candidates for further surgical intervention but present no clear target on MRI.

Minimally invasive lumbar decompression: long-term outcome, morbidity, and the learning curve from the first 50 cases.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To describe our experience with the first 50 cases of minimally invasive lumbar canal decompression in terms of patient outcome up to 2 years, the learning curve incurred, and complications when compared with our most recent 50 cases. SUMMARY OF BACKGROUND DATA: Lumbar canal stenosis is a common condition in the elderly population, the symptoms of which respond well to surgical decompression. A minimally invasive approach offers potential short and long-term benefits to patients but the technique is associated with a learning curve and equivalence to open surgery regarding efficacy and complications needs to be demonstrated. METHODS: Fifty patients (mean age 70 y) who presented with clinical and radiological features of lumbar canal stenosis and who had failed a period of conservative management underwent lumbar canal decompression through a paramedian oblique, muscle splitting approach using a 16 to 18 mm operating tube and microscope. Outcome was assessed using the Oswestry Disability Index and Short Form-36 at 3 months, 1 year, and 2 years. RESULTS: Significant clinical improvements were seen at 3 months that were sustained at 1 and 2 years. Clinical outcome improved whereas operative time and complications fell as experience increased, helping to define the learning curve with this technique. CONCLUSIONS: Minimally invasive lumbar decompression seems to offer patients a clinical benefit comparable to that observed in published open series, with potential advantages in terms of postoperative pain and recovery. However, there is a learning curve and whether this technique offers long-term benefits with regard to a reduction in back pain or postoperative spondylolisthesis is not yet known.

Using Molecular Imaging to Enhance Decision Making in the Management of Pituitary Adenomas.

In most patients with suspected or confirmed pituitary adenomas (PAs), MRI, performed using T1- (with or without gadolinium enhancement) and T2-weighted sequences, provides sufficient information to guide effective clinical decision making. In other patients, additional MR sequences (e.g., gradient recalled echo, fluid-attenuation inversion recovery, MR elastography, or MR angiography) may be deployed to improve adenoma detection, assess tumoral consistency, or aid distinction from other sellar/parasellar lesions (e.g., aneurysm, meningioma). However, there remains a small but important subgroup of patients in whom primary or secondary intervention (e.g., first or redo transsphenoidal surgery, stereotactic radiosurgery) is limited by the inability of MRI to accurately localize the site(s) of de novo, persistent, or recurrent PA. Emerging evidence indicates that hybrid imaging, which combines molecular (e.g. 11C-methionine PET) and cross-sectional (MRI) modalities, can enable the detection and precise localization of sites of active tumor to guide targeted intervention. This not only increases the likelihood of achieving complete remission with preservation of remaining normal pituitary function but may mitigate the need for long-term (even lifelong) high-cost medical therapies. Here, we review published evidence supporting the use of molecular imaging in the management of PAs, including our own 10-y experience with 11C-methionine PET.

A novel tool for the assessment of pain: validation in low back pain.

BACKGROUND: Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. METHODS AND FINDINGS: Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%-97%) and specificity (97%; 95% CI 89%-100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. CONCLUSIONS: We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.

Results of Transcranial Resection of Olfactory Groove Meningiomas in Relation to Imaging-Based Case Selection Criteria for the Endoscopic Approach.

BACKGROUND: Endoscopic endonasal surgery (EES) is increasingly used for olfactory groove meningiomas (OGMs). The role of EES for large (≥4 cm) or complex OGMs is debated. Specific imaging features have been reported to affect the degree of gross total resection (GTR) and complications following EES for OGMs. The influence of these factors on transcranial resection (TCR) is unknown. OBJECTIVE: To examine the impact of specific imaging features on outcome following TCR to provide a standard for large and endoscopically less favorable OGMs against which endoscopic outcomes can be compared. METHODS: Retrospective study of patients undergoing TCR for OGMs 2002 to 2016. RESULTS: Fifty patients (mean age 62.1 yr, mean maximum tumor diameter 5.04 cm and average tumor volume of 48.8 cm3) were studied. Simpson grade 1 and 2 resections were achieved in 80% and 12%, respectively. A favorable functional outcome (modified Rankin Scale [mRS] 0-2) was attained in 86%. The degree of resection, mRS, mortality (4%), recurrence (6%), infection (8%), and cerebrospinal fluid leak requiring intervention (12%) were not associated with tumor calcification, absence of cortical cuff, T2 hyperintensity, tumor configuration, tumor extension beyond midpoint of superior orbital roof, or extension to posterior wall of frontal sinus. There was no difference in resection rates but a trend towards greater complications between 3 arbitrarily divided groups of large meningiomas of increasing complexity based on extensive extension or vascular adherence. CONCLUSION: Favorable outcomes can be achieved with TCR for large and complex OGMs Factors that may preclude endoscopic resection do not negatively affect outcome following TCR.

Anterolateral Approach for Central Thoracic Disc Prolapse-Surgical Strategies Used to Tackle Differing Operative Findings: 3-Dimensional Operative Video.

Thoracic disc prolapses causing cord compression can be challenging. For compressive central disc protrusions, a posterior approach is not suitable due to an unacceptable level of cord manipulation. An anterolateral transthoracic approach provides direct access to the disc prolapse allowing for decompression without disturbing the spinal cord. In this video, we describe 2 cases of thoracic myelopathy from a compressive central thoracic disc prolapse. In both cases, informed consent was obtained. Despite similar radiological appearances of heavy calcification, intraoperatively significant differences can be encountered. We demonstrate different surgical strategies depending on the consistency of the disc and the adherence to the thecal sac. With adequate exposure and detachment from adjacent vertebral bodies, soft discs can be, in most instances, separated from the theca with minimal cord manipulation. On the other hand, largely calcified discs often present a significantly greater challenge and require thinning the disc capsule before removal. In cases with significant adherence to dura, in order to prevent cord injury or cerebrospinal fluid leak a thinned shell can be left, providing total detachment from adjacent vertebrae can be achieved. Postoperatively, the first patient, with a significantly calcified disc, developed a transient left leg weakness which recovered by 3-month follow-up. This video outlines the anatomical considerations and operative steps for a transthoracic approach to a central disc prolapse, whilst demonstrating that computed tomography appearances are not always indicative of potential operative difficulties.

Cord compression defined by MRI is the driving factor behind the decision to operate in Degenerative Cervical Myelopathy despite poor correlation with disease severity.

OBJECTIVES: The mainstay treatment for Degenerative Cervical Myelopathy (DCM) is surgical decompression. Not all cases, however, are suitable for surgery. Recent international guidelines advise surgery for moderate to severe disease as well as progressive mild disease. The goal of this study was to examine the factors in current practice that drive the decision to operate in DCM. STUDY DESIGN: Retrospective cohort study. METHODS: 1 year of cervical spine MRI scans (N = 1123) were reviewed to identify patients with DCM with sufficient clinical documentation (N = 39). Variables at surgical assessment were recorded: age, sex, clinical signs and symptoms of DCM, disease severity, and quantitative MRI measures of cord compression. Bivariate correlations were used to compare each variable with the decision to offer the patient an operation. Subsequent multivariable analysis incorporated all significant bivariate correlations. RESULTS: Of the 39 patients identified, 25 (64%) were offered an operation. The decision to operate was significantly associated with narrower non-pathological canal and cord diameters as well as cord compression ratio, explaining 50% of the variance. In a multivariable model, only cord compression ratio was significant (p = 0.017). Examination findings, symptoms, functional disability, disease severity, disease progression, and demographic factors were all non-significant. CONCLUSIONS: Cord compression emerged as the main factor in surgical decision-making prior to the publication of recent guidelines. Newly identified predictors of post-operative outcome were not significantly associated with decision to operate.

A comparison of radiological descriptions of spinal cord compression with quantitative measures, and their role in non-specialist clinical management.

INTRODUCTION: Magnetic resonance imaging (MRI) is gold-standard for investigating Degenerative Cervical Myelopathy (DCM), a disabling disease triggered by compression of the spinal cord following degenerative changes of adjacent structures. Quantifiable compression correlates poorly with disease and language describing compression in radiological reports is un-standardised. STUDY DESIGN: Retrospective chart review. OBJECTIVES: 1) Identify terminology in radiological reporting of cord compression and elucidate relationships between language and quantitative measures 2) Evaluate language's ability to distinguish myelopathic from asymptomatic compression 3) Explore correlations between quantitative or qualitative features and symptom severity 4) Investigate the influence of quantitative and qualitative measures on surgical referrals. METHODS: From all cervical spine MRIs conducted during one year at a tertiary centre (N = 1123), 166 patients had reported cord compression. For each spinal level deemed compressed by radiologists (N = 218), four quantitative measurements were calculated: 'Maximum Canal Compromise (MCC); 'Maximum Spinal Cord Compression' (MSCC); 'Spinal Canal Occupation Ratio' (SCOR) and 'Compression Ratio' (CR). These were compared to associated radiological reporting terminology. RESULTS: 1) Terminology in radiological reports was varied. Objective measures of compromise correlated poorly with language. "Compressed" was used for more severe cord compromise as measured by MCC (p<0.001), MSCC (p<0.001), and CR (p = 0.002). 2) Greater compromise was seen in cords with a myelopathy diagnosis across MCC (p<0.001); MSCC (p = 0.002) and CR (p<0.001). "Compress" (p<0.001) and "Flatten" (p<0.001) were used more commonly for myelopathy-diagnosis levels. 3) Measurements of cord compromise (MCC: p = 0.304; MSCC: p = 0.217; SCOR: p = 0.503; CR: p = 0.256) and descriptive terms (p = 0.591) did not correlate with i-mJOA score. 4) The only variables affecting spinal surgery referral were increased MSCC (p = 0.001) and use of 'Compressed' (p = 0.045). CONCLUSIONS: Radiological reporting in DCM is variable and language is not fully predictive of the degree of quantitative cord compression. Additionally, terminology may influence surgical referrals.

Hsp27 upregulation and phosphorylation is required for injured sensory and motor neuron survival.

Peripheral nerve transection results in the rapid death by apoptosis of neonatal but not adult sensory and motor neurons. We show that this is due to induction and phosphorylation in all adult axotomized neurons of the small heat shock protein Hsp27 and the failure of such induction in most neonatal neurons. In vivo delivery of human Hsp27 but not a nonphosphorylatable mutant prevents neonatal rat motor neurons from nerve injury-induced death, while knockdown in vitro and in vivo of Hsp27 in adult injured sensory neurons results in apoptosis. Hsp27's neuroprotective action is downstream of cytochrome c release from mitochondria and upstream of caspase-3 activation. Transcriptional and posttranslational regulation of Hsp27 is necessary for sensory and motor neuron survival following peripheral nerve injury.

Mechanism-based MRI classification of traumatic brainstem injury and its relationship to outcome.

While computed tomography (CT) is the appropriate technique for the urgent detection of hematomas and contusions in the cerebral hemispheres, it is much less effective at documenting diffuse injury and posterior fossa lesions, and is therefore only partially predictive of outcome. More recently, magnetic resonance imaging (MRI) has been used, particularly to examine posterior fossa structures, but the relationship between brainstem injury and outcome is unclear and the types of brainstem injury are poorly understood. The aim of this study was to use acute MRI to examine the types of brainstem injury following severe traumatic brain injury (TBI) and their relationship to supratentorial injury. We also aimed to correlate these findings with outcome at 6 months (Glasgow Outcome Scale [GOS] score). Forty-six patients (mean age, 34 years, range, 16-70 years; 76% male) admitted to a regional neurocritical care unit with TBI requiring ventilation underwent CT and MRI (T2, FLAIR, gradient echo) scanning within 3 days (median, 1 day) of injury. GOS was ascertained by outpatient interview. Brainstem lesions were detected in 13 patients by MRI, only two of which were detected by CT. Eleven out of 13 patients with brainstem injury had an unfavorable outcome (death, vegetative state, or severe disability), of whom five died. Of the 33 patients without brainstem lesions, 18 had an unfavorable outcome, of whom four died. The direct relationship between brainstem lesions and unfavorable outcome was statistically significant (p < 0.05, chi-squared test). With regard to supratentorial injury, all but two brainstem lesions were seen either in the context of severe diffuse axonal injury or a significant mass lesion, and all of these patients had a poor outcome. However, the two patients with brainstem injury and good outcome had relatively few supratentorial abnormalities. From these observations, we have devised a simple classification system that is useful clinically and has potential associations with outcome. Poor prognosis is common following major TBI but is more common in those with brainstem injury. However, brainstem injury is not an absolute indicator of poor outcome. Understanding the anatomy and extent of brainstem injury, as well as its relationship to supratentorial abnormalities, will facilitate a more accurate use of early MRI as a prognostic tool and assist in the counseling of families.

Toward a Mechanism-Based Approach to Pain Diagnosis.

UNLABELLED: The past few decades have witnessed a huge leap forward in our understanding of the mechanistic underpinnings of pain, in normal states where it helps protect from injury, and also in pathological states where pain evolves from a symptom reflecting tissue injury to become the disease itself. However, despite these scientific advances, chronic pain remains extremely challenging to manage clinically. Although the number of potential treatment targets has grown substantially and a strong case has been made for a mechanism-based and individualized approach to pain therapy, arguably clinicians are not much more advanced now than 20 years ago, in their capacity to either diagnose or effectively treat their patients. The gulf between pain research and pain management is as wide as ever. We are still currently unable to apply an evidence-based approach to chronic pain management that reflects mechanistic understanding, and instead, clinical practice remains an empirical and often unsatisfactory journey for patients, whose individual response to treatment cannot be predicted. In this article we take a common and difficult to treat pain condition, chronic low back pain, and use its presentation in clinical practice as a framework to highlight what is known about pathophysiological pain mechanisms and how we could potentially detect these to drive rational treatment choice. We discuss how present methods of assessment and management still fall well short, however, of any mechanism-based or precision medicine approach. Nevertheless, substantial improvements in chronic pain management could be possible if a more strategic and coordinated approach were to evolve, one designed to identify the specific mechanisms driving the presenting pain phenotype. We present an analysis of such an approach, highlighting the major problems in identifying mechanisms in patients, and develop a framework for a pain diagnostic ladder that may prove useful in the future, consisting of successive identification of 3 steps: pain state, pain mechanism, and molecular target. Such an approach could serve as the foundation for a new era of individualized/precision pain medicine. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION)-American Pain Society (APS) Pain Taxonomy (AAPT) includes pain mechanisms as 1 of the 5 dimensions that need to be considered when making a diagnostic classification. The diagnostic ladder proposed in this article is consistent with and an extension of the AAPT. PERSPECTIVE: We discuss how identifying the specific mechanisms that operate in the nervous system to produce chronic pain in individual patients could provide the basis for a targeted and rational precision medicine approach to controlling pain, using chronic low back pain as our example.

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

OBJECTIVE: We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. DESIGN: Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. METHODS: All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. RESULTS: In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. CONCLUSIONS: (11)C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.

Complications from minimally invasive lumbar interbody fusion: experience from 100 patients.

Minimally invasive lumbar fusion is well described and is reported to offer significant advantages to patients in terms of blood loss, a reduction in post-operative pain and a quicker recovery. However, this technique may expose patients to a greater risk of complications when compared to open lumbar instrumented fusion that may negate these advantages. Between January 2007 and March 2001, we conducted a prospective observational study of 100 consecutive patients (48 males and 52 females, mean age of 54 years) to investigate complications occurring from minimally invasive lumbar interbody fusion surgery using an image-guided technique. All patients underwent post-operative CT scans to assess implant placement. Scanning was repeated at 6 months to assess bony fusion. We observed the following complications: 2.5% (11/435) pedicle screw misplacement, 1.7% (2/120) interbody cage misplacement; 0.8% (1/120) interbody cage migration; 0.8% (1/120) patients requiring a post-operative blood transfusion; 2% (2/100) venous thrombo-embolism and 3% (3/100) patients with complications thought to be related to the use of bone morphogenic protein. There were no occurrences of infection and no cerebrospinal fluid leaks. We concluded that the rate of complications from minimally invasive lumbar interbody fusion is low, and compares favourably with the rates of complication from open procedures. Moreover, computerised navigation systems can be used in place of real-time fluoroscopy to guide implant placement, without an increase in the rate of complications.

Reporting of industry funded study outcome data: comparison of confidential and published data on the safety and effectiveness of rhBMP-2 for spinal fusion.

OBJECTIVE: To investigate whether published results of industry funded trials of recombinant human bone morphogenetic protein 2 (rhBMP-2) in spinal fusion match underlying trial data by comparing three different data sources: individual participant data, internal industry reports, and publicly available journal publications and conference abstracts. DATA COLLECTION AND SYNTHESIS: The manufacturer of rhBMP-2 products (Medtronic; Minneapolis, MN) provided complete individual participant data and internal reports for all its studies of rhMBP-2 in spinal fusion. We identified publications and conference abstracts through comprehensive literature searches. We compared outcomes provided in the individual participant data against outcomes reported in publications. For effectiveness outcomes, we compared meta-analyses of randomised controlled trials based on each of the three data sources. For adverse events, meta-analysis of the published aggregate data was not possible and we compared the number and type of adverse events reported between data sources. RESULTS: 32 publications reported outcomes from 11 of the 17 existing manufacturer sponsored studies. For individual randomised controlled trials, 56% (9/16) to 88% (15/17) of effectiveness outcomes known to have been collected were reported in the published literature. Meta-analyses of effectiveness data were almost identical for pain outcomes and similar for fusion across the three data sources. A minority of adverse event data known to have been collected were reported in the published literature. Several journal articles reported only "serious," "related," or "unanticipated" adverse events, without defining these terms. Others reported a small proportion of the collected adverse event categories. Around 23% (533/2302) of the total adverse events collected in published randomised controlled trials have been reported in the literature, with randomised controlled trials evaluating the licensed preparation (Infuse) reporting around 11% (122/1108) of collected adverse events. CONCLUSIONS: The published literature only partially represents the total data known to have been collected on the effects of rhBMP-2. This did not lead to substantially different results for meta-analysis of effectiveness outcomes. In contrast, reporting of adverse event data in trial publications was inadequate and inconsistent to the extent that any systematic review based solely on the publicly available data would not be able to properly evaluate the safety of rhBMP-2. Analysis of individual participant data enabled the most complete, detailed, and in-depth analysis and was not more resource intensive than extracting, collating, and analysing aggregate data from multiple trial publications and conference abstracts. Confidential internal reports presented considerably more adverse event data than publications, and in the absence of individual participant data access to these reports would support more accurate and reliable investigation, with less time and effort than relying on incomplete published data.

Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial.

BACKGROUND CONTEXT: Postoperative back pain is common after decompression surgery for lumbar stenosis and often delays discharge from hospital. Achieving regional analgesia by intraoperative delivery of epidural opiates after lumbar canal decompression is a promising approach to reduce postoperative pain and enhance early mobilization. However, there have been concerns about opiate-related complications, such as respiratory depression and urinary retention in what is generally an elderly population of patients. PURPOSE: To assess the analgesic efficacy of bolus epidural fentanyl administered intraoperatively after lumbar decompression for degenerative canal stenosis. STUDY DESIGN/SETTING: Patient-blinded randomized controlled trial conducted at two university neurosurgical centers. PATIENT SAMPLE: Adults (older than 18 years) with neurogenic claudication and/or lower limb radiculopathy and concordant lumbar spinal canal stenosis demonstrated on magnetic resonance imaging. Patients with previous lumbar spinal surgery, a contraindication to fentanyl, or requiring instrumentation were excluded. OUTCOME MEASURES: The primary outcome measure was patient-reported Visual Analogue Score (VAS) for pain recorded preoperatively, in recovery, and on the first and second postoperative days if the patient remained in the hospital. Secondary outcomes were duration of surgery, length of stay, and any side effects or complications. METHODS: Patients underwent a one to three level lumbar canal decompression as required, via a midline incision, under general anesthesia. Before wound closure either no drug (control) or a 100-µg bolus of fentanyl was administered via an epidural catheter inserted 10 cm rostral to the operated level. Patients were blinded to group allocation, and analysis was by intention to treat. The trial was approved by the National Health Service Research Ethics Service and the Medicines and Healthcare products Regulatory Agency. No commercial or other source of funding was received. RESULTS: Sixty patients were randomized, 29 to fentanyl and 31 to control. Demographics, duration of surgery, and preoperative VAS were not significantly different between the groups. VAS in recovery was significantly lower in patients treated with fentanyl (mean [standard deviation]: 2.6 [2.7] vs. 4.7 [2.4]; p=.003). Later VAS and postoperative length of stay were similar between groups. More patients in the fentanyl group required temporary urinary catheterization, but there was no significant difference in the incidence of side effects. CONCLUSIONS: Bolus epidural fentanyl provides effective short-term postoperative analgesia after lumbar canal decompression and may be a useful adjunct to pain management in patients undergoing lumbar spine surgery.

Promoting fusion in minimally invasive lumbar interbody stabilization with low-dose bone morphogenic protein-2--but what is the cost?

BACKGROUND: Using bone morphogenic protein (BMP) to augment fusion in spine surgery is widespread and lends itself in particular to minimally invasive lumbar fusion, where the surface area for fusion is significantly less than the equivalent open procedure. PURPOSE: Here we described the use of very low-dose BMP in promoting fusion in minimally invasive lumbar interbody fixation but also highlight some of the potential complications of BMP-2 use and techniques available to reduce or avoid them. STUDY DESIGN: Prospective observational study of consecutive patients undergoing minimally invasive lumbar interbody fusion with percutaneous pedicle screws. PATIENT SAMPLE: Thirty patients aged between 22 and 78 years (mean 53 years). OUTCOME MEASURES: Thin-slice lumbar computed tomography scanning with multiplanar reconstruction at 6 and 12 months postoperative. METHODS: Thirty-six spinal levels were instrumented in total, of which four underwent posterior lumbar interbody fusion and 32 underwent transforaminal lumbar interbody fusion. Bone graft harvested locally was placed in the disc space with low-dose BMP-2 (1.4 mg per level). RESULTS: Thirty-three of 36 spinal levels showed complete fusion at a mean postoperative scan time of 7.1 months. Two levels demonstrated partial fusion at 6 months, which was complete at 12 months. There was one case of nonunion at 12 months, which also demonstrated vertebral body osteolysis. Despite very low-dose BMP-2, two cases of asymptomatic heterotopic ossification were observed, and there were two cases of perineural cyst formation, one of whom required revision of the interbody cage. CONCLUSIONS: The use of BMP with autograft in the disc space during minimally invasive lumbar interbody fusion is associated with a high rate of early fusion. Even with very low-dose BMP used in this study, complications related to BMP usage were not avoided completely.