✓ Bone grafts are usually an integral part of cervical spine fixation following spinal trauma. Unfortunately, many currently used bone graft donor sites (including the rib, iliac crest, and fibula) cause unacceptable patient morbidity, especially postoperative pain. A readily available source of autologous bone graft for posterior cervical fusion is the occipital bone. This membranous bone offers the advantage of strength and less bone resorption. It has been used at the Sunnybrook Health Science Centre for 4 years as a standard source of bone graft with no morbidity and excellent results for fusion.
Beverly C. Walters
Mark A. Mittler, Beverly C. Walters and Edward G. Stopa
✓ This study provides an objective assessment of the reliability of histological grading of astrocytoma specimens obtained using stereotactic biopsy. Pathological diagnosis of brain tumors provides an index of disease severity and guides clinical practice in their treatment. It also functions as the gold standard in assessing the validity of diagnostic tests such as magnetic resonance imaging. Often diagnoses are made from biopsy material obtained using stereotactic technique. The current study was designed to evaluate this gold standard with regard to interobserver and intraobserver variability.
Four certified neuropathologists from academic centers in the United States and Canada were asked to grade 30 brain biopsy specimens obtained stereotactically in patients with astrocytomas. Intraobserver agreement was analyzed in individual observers by comparing their first and second readings, separated by 5 to 14 weeks. Interobserver data were analyzed by comparing initial readings across all observers for individual diagnoses. Kappa analysis was used to measure agreement beyond chance.
Intraobserver agreement was 74.73% for glioblastomas multiforme, 51.43% for anaplastic astrocytomas, and 65.22% for low-grade astrocytomas. The most common disagreements were between anaplastic astrocytomas and glioblastomas multiforme, followed by disagreements between anaplastic and low-grade astrocytomas. Interobserver agreement on initial readings was 62.41% (κ 0.39) for glioblastomas, 36.04% (κ 0.06) for anaplastic astrocytomas, and 57.14% (κ 0.48) for low-grade astrocytomas.
A significantly greater degree of reliability was seen in histopathological diagnoses of low- or high-grade astrocytomas than in those of intermediate-grade astrocytomas. Therefore, the highest variability occurs at the point of clinical decision making—namely, intermediate-grade tumors that may or may not be selected to receive adjuvant therapy. This considerable variability is an issue that needs to be recognized and further addressed by analysis of current and proposed astrocytoma grading schemes.
Influences on initial management and subsequent outcome
Beverly C. Walters, Harold J. Hoffman, E. Bruce Hendrick and Robin P. Humphreys
✓ A retrospective study of the management of patients with infected cerebrospinal fluid (CSF) shunts was undertaken, covering the 20 years from 1960 to 1979, inclusive, and involving 222 patients with 267 infections. The data were analyzed with emphasis on influences surrounding treatment choice and subsequent outcome. Treatment was classified into three major categories: medical management (antibiotics alone), surgical management (antibiotics plus operative removal of the infected shunt), and no treatment (ranging from admission and observation only to shunt revision), the diagnosis of shunt infection having been missed. Results showed surgical treatment to be more efficacious than medical or no treatment, with a higher rate of initial cure, and lower morbidity and mortality rates.
Also examined were the relationships among clinical presentation, infection rate, and results of specimens sent for culture, and initial treatment. The definitive nature of initial treatment was revealed to be directly proportional to the aggressiveness of microbiological investigation. This latter aspect was related to clinical presentation, with shunt malfunction being the least recognized symptom of shunt infection. Patients presenting with blocked shunts were less likely to receive therapy appropriate for infection than any other group, leading to the conclusion that shunt malfunction may be more specific to infection than heretofore believed.
Amber S. Gordon, Ashly C. Westrick, Michael I. Falola, Chevis N. Shannon, Beverly C. Walters and Winfield S. Fisher
This study was undertaken to assess the reliability of observations of postoperative photographs in assigning House-Brackmann scores as outcome measures for patients following resection of vestibular schwannomas.
Forty pictures of differing facial expressions typically elicited from patients for assigning House-Brackmann scores were individually evaluated by neurosurgery residents and faculty members at the University of Alabama at Birmingham; a score was assigned to each picture by the individual raters. The interrater reliability was measured using the Spearman correlation coefficient, Kendall coefficient of concordance, and kappa statistic; internal consistency was calculated using the Cronbach alpha reliability estimate.
The Spearman correlation coefficients showed strong positive association among raters, with a range of values of 0.66 to 0.90. Internal consistency measured by the Cronbach alpha coefficient was excellent (α = 0.97). The Kendall coefficient of concordance for the ordinal grades suggested a substantial degree of agreement among the raters (w = 0.76, p < 0.001).
Static postoperative photographs are a reliable outcome measure for determining facial nerve function after vestibular schwannoma resection and may serve as a surrogate for the dynamic patient interview.
Paul M. Foreman, Michelle Chua, Mark R. Harrigan, Winfield S. Fisher III, Nilesh A. Vyas, Robert H. Lipsky, Beverly C. Walters, R. Shane Tubbs, Mohammadali M. Shoja and Christoph J. Griessenauer
Delayed cerebral ischemia (DCI) is a recognized complication of aneurysmal subarachnoid hemorrhage (aSAH) that contributes to poor outcome. This study seeks to determine the effect of nosocomial infection on the incidence of DCI and patient outcome.
An exploratory analysis was performed on 156 patients with aSAH enrolled in the Cerebral Aneurysm Renin Angiotensin System study. Clinical and radiographic data were analyzed with univariate analysis to detect risk factors for the development of DCI and poor outcome. Multivariate logistic regression was performed to identify independent predictors of DCI.
One hundred fifty-three patients with aSAH were included. DCI was identified in 32 patients (20.9%). Nosocomial infection (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.09–11.2, p = 0.04), ventriculitis (OR 25.3, 95% CI 1.39–458.7, p = 0.03), aneurysm re-rupture (OR 7.55, 95% CI 1.02–55.7, p = 0.05), and clinical vasospasm (OR 43.4, 95% CI 13.1–143.4, p < 0.01) were independently associated with the development of DCI. Diagnosis of nosocomial infection preceded the diagnosis of DCI in 15 (71.4%) of 21 patients. Patients diagnosed with nosocomial infection experienced significantly worse outcomes as measured by the modified Rankin Scale score at discharge and 1 year (p < 0.01 and p = 0.03, respectively).
Nosocomial infection is independently associated with DCI. This association is hypothesized to be partly causative through the exacerbation of systemic inflammation leading to thrombosis and subsequent ischemia.
Christoph J. Griessenauer, Robert M. Starke, Paul M. Foreman, Philipp Hendrix, Mark R. Harrigan, Winfield S. Fisher III, Nilesh A. Vyas, Robert H. Lipsky, Mingkuan Lin, Beverly C. Walters, Jean-Francois Pittet and Mali Mathru
Endothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated.
Blood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation. The CARAS study prospectively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015. Common endothelin SNPs were detected using 5′ exonnuclease (TaqMan) genotyping assays. Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed.
Samples from 149 patients with aSAH and 50 controls were available for analysis. In multivariate logistic regression analysis, the TG (odds ratio [OR] 2.102, 95% confidence interval [CI] 1.048–4.218, p = 0.036) and TT genotypes (OR 7.884, 95% CI 1.003–61.995, p = 0.05) of the endothelin-1 T/G SNP (rs1800541) were significantly associated with aSAH. There was a dominant effect of the G allele (CG/GG genotypes; OR 4.617, 95% CI 1.311–16.262, p = 0.017) of the endothelin receptor A G/C SNP (rs5335) on clinical vasospasm. Endothelin SNPs were not associated with DCI or functional outcome.
Common endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm. Further studies are required to elucidate the relevant pathophysiology and its potential implications in the treatment of patients with aSAH.
Christoph J. Griessenauer, Joseph H. Miller, Bonita S. Agee, Winfield S. Fisher III, Joel K. Curé, Philip R. Chapman, Paul M. Foreman, Wilson A. M. Fisher, Adam C. Witcher and Beverly C. Walters
The aim of this study was to examine observer reliability of frequently used arteriovenous malformation (AVM) grading scales, including the 5-tier Spetzler-Martin scale, the 3-tier Spetzler-Ponce scale, and the Pollock-Flickinger radiosurgery-based scale, using current imaging modalities in a setting closely resembling routine clinical practice.
Five experienced raters, including 1 vascular neurosurgeon, 2 neuroradiologists, and 2 senior neurosurgical residents independently reviewed 15 MRI studies, 15 CT angiograms, and 15 digital subtraction angiograms obtained at the time of initial diagnosis. Assessments of 5 scans of each imaging modality were repeated for measurement of intrarater reliability. Three months after the initial assessment, raters reassessed those scans where there was disagreement. In this second assessment, raters were asked to justify their rating with comments and illustrations. Generalized kappa (κ) analysis for multiple raters, Kendall's coefficient of concordance (W), and interclass correlation coefficient (ICC) were applied to determine interrater reliability. For intrarater reliability analysis, Cohen's kappa (κ), Kendall's correlation coefficient (tau-b), and ICC were used to assess repeat measurement agreement for each rater.
Interrater reliability for the overall 5-tier Spetzler-Martin scale was fair to good (ICC = 0.69) to extremely strong (Kendall's W = 0.73) on initial assessment and improved on reassessment. Assessment of CT angiograms resulted in the highest agreement, followed by MRI and digital subtraction angiography. Agreement for the overall 3-tier Spetzler-Ponce grade was fair to good (ICC = 0.68) to strong (Kendall's W = 0.70) on initial assessment, improved on reassessment, and was comparable to agreement for the 5-tier Spetzler-Martin scale. Agreement for the overall Pollock-Flickinger radiosurgery-based grade was excellent (ICC = 0.89) to extremely strong (Kendall's W = 0.81). Intrarater reliability for the overall 5-tier Spetzler-Martin grade was excellent (ICC > 0.75) in 3 of the 5 raters and fair to good (ICC > 0.40) in the other 2 raters.
The 5-tier Spetzler-Martin scale, the 3-tier Spetzler-Ponce scale, and the Pollock-Flickinger radiosurgery-based scale all showed a high level of agreement. The improved reliability on reassessment was explained by a training effect from the initial assessment and the requirement to defend the rating, which outlines a potential downside for grades determined as part of routine clinical practice to be used for scientific purposes.
Christoph J. Griessenauer, R. Shane Tubbs, Paul M. Foreman, Michelle H. Chua, Nilesh A. Vyas, Robert H. Lipsky, Mingkuan Lin, Ramaswamy Iyer, Rishikesh Haridas, Beverly C. Walters, Salman Chaudry, Aisana Malieva, Samantha Wilkins, Mark R. Harrigan, Winfield S. Fisher III and Mohammadali M. Shoja
Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin Angiotensin System (CARAS) study prospectively evaluated associations of common RAS polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage (aSAH).
The CARAS study prospectively enrolled aSAH patients at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensin converting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5′exonuclease genotyping assays and pyrosequencing. Analysis of associations of RAS polymorphisms and clinical course after aSAH were performed.
A total of 166 patients were screened, and 149 aSAH patients were included for analysis. A recessive effect of allele I (insertion) of the ACE I/D (insertion/deletion) polymorphism was identified for Hunt and Hess grade in all patients (OR 2.76, 95% CI 1.17–6.50; p = 0.0206) with subsequent poor functional outcome. There was a similar effect on delayed cerebral ischemia (DCI) in patients 55 years or younger (OR 3.63, 95% CI 1.04–12.7; p = 0.0439). In patients older than 55 years, there was a recessive effect of allele A of the angiotensin II receptor Type 2 (AT2) A/C single nucleotide polymorphism (SNP) on DCI (OR 4.70, 95% CI 1.43–15.4; p = 0.0111).
Both the ACE I/D polymorphism and the AT2 A/C single nucleotide polymorphism were associated with an age-dependent risk of delayed cerebral ischemia, whereas only the ACE I/D polymorphism was associated with poor clinical grade at presentation. Further studies are required to elucidate the relevant pathophysiology and its potential implication in the treatment of patients with aSAH.