Ephraim Church

Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis

Importance Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. Objective To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. Data Sources Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. Study Selection Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. Data Extraction and Synthesis Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each others results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. Main Outcome and Measures Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. Results The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. Conclusion and Relevance This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Development of and psychometric testing for the Brief Pain Inventory-Facial in patients with facial pain syndromes

OBJECT Outcomes in clinical trials on trigeminal pain therapies require instruments with demonstrated reliability and validity. The authors evaluated the Brief Pain Inventory (BPI) in its existing form plus an additional 7 facial-specific items in patients referred to a single neurosurgeon for a diagnosis of facial pain. The complete 18-item instrument is referred to as the BPI-Facial. METHODS This study was a cross-sectional analysis of patients who completed the BPI-Facial. The diagnosis of classic versus atypical trigeminal neuralgia (TN) was made before analyzing the questionnaire results. A hypothesis-driven factor analysis was used to determine the principal components of the questionnaire. Item reliability and questionnaire validity were tested for these specific constructs. RESULTS Data from 156 patients were analyzed, including 114 patients (73%) with classic and 42 (27%) with atypical TN. Using orthomax rotation factor analysis, 3 factors with an eigenvalue > 1.0 were identified-pain intensity, interference with general activities, and facial-specific pain interference-accounting for 97.6% of the observed item variance. Retention of the 3 factors was confirmed via a Cattell scree plot. Internal reliability was demonstrated by calculating Cronbachs alpha: 0.86 for pain intensity, 0.89 for interference with general activities, 0.95 for facial-specific pain interference, and 0.94 for the entire instrument. Initial validity of the BPI-Facial instrument was supported by the detection of statistically significant differences between patients with classic versus atypical pain. Patients with atypical TN rated their facial pain as more intense (atypical 6.24 vs classic 5.03, p = 0.013) and as having greater interference in general activities (atypical 6.94 vs classic 5.43, p = 0.0033). Both groups expressed high levels of facial-specific pain interference (atypical 6.34 vs classic 5.95, p = 0.527). CONCLUSIONS The BPI-Facial is a rigorous measure of facial pain in patients with TN and appears to have sound psychometric properties and is responsive to differences between classic and atypical TN. Future studies must assess the instruments test-retest reliability, validity in additional populations, and responsiveness with respect to changes in patient outcomes following neurosurgical interventions and medical therapies.

Intracerebral microdialysis during deep brain stimulation surgery.

BACKGROUND This report describes the use of microdialysis in conjunction with deep brain stimulation (DBS) surgery to assess extracellular levels of neurotransmitters within the human basal ganglia (BG). Electrical stimulation of the subthalamic nucleus (STN) is an efficacious treatment for advanced Parkinsons disease, yet the mechanisms of STN DBS remain poorly understood. Measurement of neurotransmitter levels within the BG may provide insight into mechanisms of DBS, but such an approach presents technical challenges. METHODS After microelectrode recordings confirmed location of STN, a custom microdialysis guide cannula was inserted. A CMA (Stockholm, Sweden) microdialysis probe was then positioned to the same depth as the microrecording electrode in STN or 2mm inferiorly to record in the substantia nigra. The catheter was perfused at a rate of 2.0 microL/min with a sterile mock CSF solution and samples of extracellular fluid were collected at regular intervals. Dialysate samples were analyzed using high-pressure liquid chromatography (HPLC) detection procedures for quantitation of glutamate, gamma-aminobutyric acid (GABA), and dopamine. RESULTS Levels of neurotransmitters were reliably identified in dialysate samples using HPLC. By monitoring concentrations of glutamate, GABA and dopamine, we were able to demonstrate what seemed to be a steady state baseline within approximately 30 min. CONCLUSION Microdialysis during DBS surgery is a feasible method for assessing levels of glutamate, GABA and dopamine within the human BG. Obtaining a steady state baseline of neurotransmitter levels appears feasible, thus making future studies of intraoperative microdialysis during DBS meaningful.

Systematic Review and Meta-analysis of Chiropractic Care and Cervical Artery Dissection: No Evidence for Causation.

Background Case reports and case control studies have suggested an association between chiropractic neck manipulation and cervical artery dissection (CAD), but a causal relationship has not been established. We evaluated the evidence related to this topic by performing a systematic review and meta-analysis of published data on chiropractic manipulation and CAD. Methods Search terms were entered into standard search engines in a systematic fashion. The articles were reviewed by study authors, graded independently for class of evidence, and combined in a meta-analysis. The total body of evidence was evaluated according to GRADE criteria. Results Our search yielded 253 articles. We identified two class II and four class III studies. There were no discrepancies among article ratings (i.e., kappa=1). The meta-analysis revealed a small association between chiropractic care and dissection (OR 1.74, 95% CI 1.26-2.41). The quality of the body of evidence according to GRADE criteria was “very low.” Conclusions The quality of the published literature on the relationship between chiropractic manipulation and CAD is very low. Our analysis shows a small association between chiropractic neck manipulation and cervical artery dissection. This relationship may be explained by the high risk of bias and confounding in the available studies, and in particular by the known association of neck pain with CAD and with chiropractic manipulation. There is no convincing evidence to support a causal link between chiropractic manipulation and CAD. Belief in a causal link may have significant negative consequences such as numerous episodes of litigation.

Feasibility of an Operational Standardized Checklist for Movement Disorder Surgery

Despite the clinical success of deep brain stimulation (DBS), it remains to be elucidated where within the work process the surgical result could diverge from the surgical plan. We sought to determine this. We implemented a standardized checklist to detect and remediate procedural errors. A consecutive series of 13 patients was studied. Revisions, explantations and thermal lesions were excluded. We tabulated the number and type of errors that could occur when implementing a surgical plan. Errors were categorized as minor or major. The elapsed time was also assessed. A mean of two errors per case were identified: 1.15 major errors/case and 0.85 minor errors per case. The total number of errors identified per case did not change significantly over the course of the series. Time to complete the checklist decreased monotonically from 4 min 5 s to 1 min 10 s. The checklist applied in this scenario is a useful tool to identify and remediate errors during DBS, adding minimal additional operative time and consistently identifying errors.

Subcutaneous heparin for prophylaxis of venous thromboembolism in deep brain stimulation surgery: evidence from a decision analysis.

OBJECTIVEThe addition of subcutaneous heparin (SQH) to mechanical prophylaxis for venous thromboembolism (VTE) involves a balance between the benefit of greater protection from VTE and the added risk of intracranial hemorrhage. There is evidence that the hemorrhage risk outweighs the benefits for patients undergoing craniotomy. We investigated the safety of SQH in patients undergoing deep brain stimulation (DBS) surgery. METHODSA retrospective analysis was performed of all patients with movement disorders (n = 254) undergoing DBS surgery at our institution from 2003 to 2007. Before September 2005, none of the patients undergoing DBS received SQH (non-SQH group) (n = 121). Thereafter, all patients were administered SQH perioperatively (SQH group) (n = 133). All patients wore graduated compression stockings and pneumatic compression boots postoperatively in bed. A postoperative brain magnetic resonance imaging scan was obtained on the day of surgery. RESULTSFive (3.8%) of 133 SQH patients and 1 (0.8%) of 121 non-SQH patients developed asymptomatic intracranial hemorrhage. None of the SQH patients developed clinically significant VTE, whereas 3 (2.5%) non-SQH patients developed VTE (1 deep venous thrombosis, 2 pulmonary embolisms). Using a decision-analysis model, we have shown that the use of SQH plus mechanical prophylaxis together yielded outcomes at least as good as mechanical prophylaxis alone. CONCLUSIONOur findings suggest that SQH for VTE prophylaxis in patients with movement disorders undergoing DBS surgery is safe. SQH protects against VTE in this patient population and merits further investigation.

Cervical laminoforaminotomy for radiculopathy: Symptomatic and functional outcomes in a large cohort with long-term follow-up.

Background: The efficacy and safety of cervical laminoforaminotomy (FOR) in the treatment of cervical radiculopathy has been demonstrated in several series with follow-up less than a decade. However, there is little data analyzing the relative effectiveness of FOR for radiculopathy due to soft disc versus osteophyte disease. In the present study, we review our experience with FOR in a single-center cohort, with long-term follow-up. Methods: We examined the charts of patients who underwent 1085 FORs between 1990 and 2009. A cohort of these patients participated in a telephone interview designed to assess improvement in symptoms and function. Results: A total of 338 interviews were completed with a mean follow-up of 10 years. Approximately 90% of interviewees reported improved pain, weakness, or function following FOR. Ninety-three percent of patients were able to return to work after FOR. The overall complication rate was 3.3%, and the rate of recurrent radiculopathy requiring surgery was 6.2%. Soft disc subtypes compared to osteophyte disease by operative report were associated with improved symptoms (P < 0.05). The operative report of these pathologic subtypes was associated with the preoperative magnetic resonance imaging (MRI) interpretation (P < 0.001). Conclusions: These results suggest that FOR is a highly effective surgical treatment for cervical radiculopathy with a low incidence of complications. Radiculopathy due to soft disc subtypes may be associated with a better prognosis compared to osteophyte disease, although osteophyte disease remains an excellent indication for FOR.

Long-term quality of life after posterior cervical foraminotomy for radiculopathy.

OBJECTIVES Cervical radiculopathy may cause symptoms and loss of function that can lead to a significant reduction in health related quality of life (HRQOL). As part of a comprehensive review of long-term outcomes, we examined HRQOL in a large cohort of patients undergoing posterior cervical foraminotomy (FOR) for radiculopathy. PATIENTS AND METHODS 338 patients who underwent FOR between 1990 and 2009 participated in a telephone interview designed to measure symptomatic and functional improvements following surgery. We also administered the EQ-5D, a standardized tool for assessing HRQOL. We analyzed this data for associations between patient and treatment characteristics, improvements in symptoms and function, and HRQOL as measured by the EQ-5D. RESULTS Mean follow-up was 10.0 years. The average EQ-5D at follow-up was 0.81±0.18, and improvements in pain, weakness and function as well as ability to return to work correlated with improved EQ-5D score (p<0.0001). There was no correlation between length of follow-up and EQ-5D score (p=0.980). Additionally, there was no difference between mean EQ-5D score for soft disc versus osteophyte pathology (0.84 versus 0.81, p=0.21). CONCLUSION These data provide evidence that FOR for cervical radiculopathy is associated with improved HRQOL at long-term follow-up. The lack of correlation between length of follow-up and HRQOL suggests that FOR is a durable treatment option. Moreover, FOR is associated with improved HRQOL whether radiculopathy is due to soft disc or osteophyte pathology.

Training and Standards

It hardly needs to be stated that vascular neurosurgery has changed dramatically over the past 50 years. As neuroendovascular surgery has evolved, more cerebrovascular disease has come to be treated with these techniques. At the same time, fewer but possibly more complex aneurysms must be treated with open cerebrovascular techniques. Together, these changes present unique challenges for training programs and practice standards within vascular neurosurgery. In this chapter, we outline the historical context of training guidelines and certification in neuroendovascular and open cerebrovascular neurosurgery. We then review the current status of these efforts including the Committee on Advanced Subspecialty Training (CAST) certification and other training research and initiatives. We briefly review guidelines for specific operations, as well as hospital privileges. An additional aspect of training and standards, the maintenance of certification process, is discussed in the context of neuroendovascular surgery. We then turn our attention to open cerebrovascular neurosurgery, where fewer but perhaps more complex aneurysms present unique challenges for training the next generation of open cerebrovascular surgeons as well as maintaining standards in this area. Possible solutions to these challenges including simulation training and fellowship training in high-volume centers are discussed. We also review guidelines for competence including CAST certification in cerebrovascular neurosurgery. In conclusion, we offer a checklist of recommendations regarding training and standards in neuroendovascular and open cerebrovascular neurosurgery.