What is a Case-Control Study?

Case-control (case-control, case-controlled) studies are beginning to appear more frequently in the neurosurgical literature. They can be more robust, if well designed, than the typical case series or even cohort study to determine or refine treatment algorithms. The purpose of this review is to define and explore the differences between case-control studies and other so-called nonexperimental, quasiexperimental, or observational studies in determining preferred treatments for neurosurgical patients.

What Isn't a Case-Control Study?

BACKGROUND: Confusion exists among neurosurgeons when choosing and implementing an appropriate study design and statistical methods when conducting research. We noticed particular difficulty with mislabeled and inappropriate case-control studies in the neurosurgical literature. OBJECTIVE: To quantify and to rigorously review this issue for appropriateness in publication and to establish quality of the manuscripts using a rigorous technique. METHODS: Following a literature search, pairs drawn from 5 independent reviewers evaluated a complete sample of 125 manuscripts claiming to be case-control studies with respect to basic case-control criteria. Seventy-five papers were then subjected to a more rigorous appraisal for quality using the SIGN Methodology Checklist for case-control studies. RESULTS: Fifty publications were rejected based on basic criteria used to identify case-control design. Of the 75 subjected to quality analysis, 46 were felt to be acceptable for publication. Only 11 papers (9%) achieved the designation of high quality. Of the original 125 papers evaluated, 79 (63%) were inappropriately labeled case-control studies. CONCLUSION: Mislabeling and use of inappropriate study design are common in the neurosurgical literature. Manuscripts should be evaluated rigorously by reviewers and readers, and neurosurgical training programs should include instruction on choice of appropriate study design and critical appraisal of the literature.

Voice and swallowing outcomes following reoperative anterior cervical discectomy and fusion with a 2-team surgical approach.

OBJECTIVE Dysphagia and vocal cord palsy (VCP) are common complications after anterior cervical discectomy and fusion (ACDF). The reported incidence rates for dysphagia and VCP are variable. When videolaryngostroboscopy (VLS) is performed to assess vocal cord function after ACDF procedures, the incidence of VCP is reported to be as high as 22%. The incidence of dysphagia ranges widely, with estimates up to 71%. However, to the authors' knowledge, there are no prospective studies that demonstrate the rates of VCP and dysphagia for reoperative ACDF. This study aimed to investigate the incidence of voice and swallowing disturbances before and after reoperative ACDF using a 2-team operative approach with comprehensive pre- and postoperative assessment of swallowing, direct vocal cord visualization, and clinical neurosurgical outcomes. METHODS A convenience sample of sequential patients who were identified as requiring reoperative ACDF by the senior spinal neurosurgeon at the University of Alabama at Birmingham were enrolled in a prospective, nonrandomized study during the period from May 2010 until July 2014. Sixty-seven patients undergoing revision ACDF were enrolled using a 2-team approach with neurosurgery and otolaryngology. Dysphagia was assessed both preoperatively and postoperatively using the MD Anderson Dysphagia Inventory (MDADI) and fiberoptic endoscopic evaluation of swallowing (FEES), whereas VCP was assessed using direct visualization with VLS. RESULTS Five patients (7.5%) developed a new postoperative temporary VCP after reoperative ACDF. All of these cases resolved by 2 months postoperatively. There were no new instances of permanent VCP. Twenty-five patients had a new swallowing disturbance detected on FEES compared with their baseline assessment, with most being mild and requiring no intervention. Nearly 60% of patients showed a decrease in their postoperative MDADI scores, particularly within the physical subset. CONCLUSIONS A 2-team approach to reoperative ACDF was safe and effective, with no new cases of VCP on postoperative VLS. Dysphagia rates as assessed through the MDADI scale and FEES were consistent with other published reports.

Recurrent laryngeal nerve injury following reoperative anterior cervical discectomy and fusion: a meta-analysis.

OBJECTIVE Recurrent laryngeal nerve (RLN) injury is one of the most frequent complications of anterior cervical discectomy and fusion (ACDF) procedures. The frequency of RLN is reported as 1%-11% in the literature. (4 , 15) The rate of palsy after reoperative ACDF surgery is not well defined. This meta-analysis was performed to review the current medical evidence on RLN injury after ACDF surgery and to determine a relative rate of RLN injury after reoperative ACDF. METHODS MEDLINE, PubMed, and Google Scholar searches were performed using several key words and phrases related to ACDF surgery. Included studies were written in English, addressed revisionary ACDF surgery, and studied outcomes of RLN injury. Statistical analysis was then performed using a random-effects model to calculate a pooled rate of RLN injury. The heterogeneity of the studies was assessed using Cochran's Q statistic and I(2) statistic, and a funnel plot was constructed to evaluate publication bias. RESULTS The search initially identified 345 articles on this topic. Eight clinical articles that met all inclusion criteria were included in the meta-analysis. A total of 238 patients were found to have undergone reoperative ACDF. Thirty-three of those patients experienced an RLN injury. This analysis identified a rate of RLN injury in the literature after reoperative ACDF of 14.1% (95% confidence interval [CI] 9.8%-19.1%). CONCLUSIONS The rate of RLN palsy of 14.1% was greater than any published rate of RLN injury after primary ACDF operations, suggesting that there is a greater risk of hoarseness and dysphagia with reoperative ACDF surgeries than with primary procedures as reported in these studies.

Bihemispheric gunshot wounds: survival and long-term neuropsychological follow-up of three siblings.

PURPOSE: Penetrating gunshot wounds to the head (GSWH) have notoriously poor outcomes with extremely high mortality. Long-term follow-up data of affected children is scant in the medical literature. This report summarizes clinical presentation, management, and long-term outcomes from three children who survived "execution style" frontal, bihemispheric gunshot wounds with no or minimal surgical intervention. METHODS: A retrospective chart review of available medical records and outcomes from standardized, validated psychological instruments was undertaken, summarized, and evaluated. RESULTS: Despite bihemispheric injuries in each patient, no patient required operative intervention. Each child survived without readily evident neurologic impairment; however, the extent of impaired executive function varied widely, and severe disinhibition remains profoundly disabling in one survivor. CONCLUSIONS: Bihemispheric penetrating gunshot injuries are not uniformly fatal and can occasionally be associated with long-term favorable survival; however, impaired executive function has significant potential to be profoundly disabling in these injuries.

Prognostic relevance of cytochrome C oxidase in primary glioblastoma multiforme.

Patients with primary glioblastoma multiforme (GBM) have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO) promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%), and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P<0.001 by the log-rank test, hazard ratio = 10.75 for overall survival]. The median survival time for patients with low tumor CcO activity was 14.3 months, compared with 6.3 months for patients with high tumor CcO activity. High CcO activity occurs in a significant subset of high-grade glioma patients and is an independent predictor of poor outcome. Thus, CcO activity may serve as a useful molecular marker for the categorization and targeted therapy of GBMs.

Multidisciplinary staged surgical management of bifrontal meningoencephalocele with long-term follow-up.

The authors report on an infant with a bifrontal encephalocele that was associated with multisuture craniosynostosis, spasticity, and a progressively severe epilepsy. They describe the initial presentation, genetic screening results, staged multidisciplinary operative plans, clinical course, complications, and long-term surgical and developmental follow-up. To their knowledge, the comprehensive surgical management of this type of complicated congenital cranial anomaly has not been previously described. Surgical management was staged and multidisciplinary and required careful attention to all 3 components of the condition: 1) hydrocephalus, 2) frontal meningoencephalocele, and 3) epilepsy.

Reliability of postoperative photographs in assessment of facial nerve function after vestibular schwannoma resection.

OBJECT: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Management of pediatric patients with pseudotumor cerebri.

INTRODUCTION: The care of patients with pseudotumor cerebri (idiopathic intracranial hypertension) involves ophthalmologists, neurologists and neurosurgeons. Its clinical characteristics in the pediatric population are distinct from those in adult patients. PATIENTS AND METHODS: Fifty-nine patients diagnosed with pseudotumor cerebri were identified from the neurosurgery and neurology databases at Children's Hospital, Birmingham, AL, USA. Clinical data were collected from the ophthalmology, neurology and neurosurgery departments. RESULTS: The average age of patients at diagnosis was 11.4 years (range 3-17). The average opening pressure of lumbar puncture (LP) was 37 cm of water. Most of the patients responded well to therapeutic LPs and medical management. Neurosurgical interventions included intracranial pressure monitoring and shunt insertion in nine patients. In three patients who presented with acute visual decline, two recovered and one remains legally blind. CONCLUSIONS: The care of patients with pseudotumor cerebri requires a multiple-disciplinary approach. Neurosurgical interventions are sometimes needed for diagnostic and treatment purpose. Prompt and accurate communication among specialists is necessary to ensure timely treatment and optimal outcomes.

Preventing cerebrospinal fluid leak following transection of a tight filum terminale.

OBJECT: Tethered cord release for a tight filum terminale is a common pediatric operation associated with low morbidity and mortality rates. While almost all would agree that keeping patients lying flat after the operation will prevent a CSF leak, the optimal period of doing so has not been determined. In this study, the authors examined whether a longer length of stay in the hospital for the sole purpose of maintaining patients flat correlates with a decreased rate of CSF leakage. METHODS: Intraoperative and postoperative data were retrospectively collected in 222 cases of simple tethered cord release at 3 large children's hospitals. Risk factors for postoperative CSF leakage were identified. RESULTS: Thirty-eight patients were maintained lying flat for 24 hours, 86 for 48 hours, and 98 for 72 hours at the individual surgeon's discretion. A CSF leak occurred in 13 patients (5.9%) and pseudomeningocele developed in 9 patients (4.1%). In the univariate analysis, operating time, use of the microscope, use of dural sealant, and duration of remaining flat after surgery failed to correlate with the occurrence of complications. CONCLUSIONS: A longer hospital stay for maintaining patients flat after a simple tethered cord release appears not to prevent CSF leakage. However, a larger patient cohort will be needed to detect small differences in complication rates.

Intradural spinal endoscopy in children.

Intracranial endoscopy in the treatment of hydrocephalus, arachnoid cysts, or brain tumors has gained wide acceptance, but the use of endoscopy for intradural navigation in the pediatric spine has received much less attention. The aim of the authors' present study was to analyze their experience in using spinal endoscopy to treat various pathologies of the spinal canal. The authors performed a retrospective review of intradural spinal endoscopic cases at their institution. They describe 4 representative cases, including an arachnoid cyst, intrinsic spinal cord tumor, holocord syrinx, and split cord malformation. Intradural spinal endoscopy was useful in treating the aforementioned lesions. It resulted in a more limited laminectomy and myelotomy, and it assisted in identifying a residual spinal cord tumor. It was also useful in the fenestration of a multilevel arachnoid cyst and in confirming communication of fluid spaces in the setting of a complex holocord syrinx. Endoscopy aided in the visualization of the spinal cord to ensure the absence of tethering in the case of a long-length Type II split spinal cord malformation. Conclusions Based on their experience, the authors found intradural endoscopy to be a useful surgical adjunct and one that helped to decrease morbidity through reduced laminectomy and myelotomy. With advances in technology, the authors believe that intradural endoscopy will begin to be used by more neurosurgeons for treating diseases of this anatomical region.

Meningioma interdigitated with primary central nervous system B-cell lymphoma: A case report and literature review.

BACKGROUND: Simultaneous presentation of multiple primary central nervous system (CNS) malignancies is extremely rare. There have been only eight cases of meningiomas co-existing with primary cerebral lymphoma, reported in the literature. CASE DESCRIPTION: We present a case of a patient who underwent surgical resection of an olfactory grove meningioma that was interdigitated with a primary CNS B-cell lymphoma. Following surgery, the patient was treated with high-dose methotrexate, and has no evidence of recurrence after 18 months. CONCLUSION: Because of the early recognition of these two distinct pathologies, the patient received directed adjuvant therapies, and has exceeded the survival of all other cases reported in the literature.