Observational Studies in Neurosurgery: Structure, Functioning, and Uses.

INTRODUCTION: Although randomized interventional studies are the gold standard of clinical study designs, they are not always feasible or necessary. In such cases, observational studies can bring insights into critical questions while minimizing harm and cost. There are numerous observational study designs, each with strengths and demerits. Unfortunately, it is not uncommon for observational study designs to be poorly designed or reported. In this article, the authors discuss similarities and differences between observational study designs, their application, and tenets of good use and proper reporting focusing on neurosurgery. METHODS: The authors illustrated neurosurgical case scenarios to describe case reports, case series, and cohort, cross-sectional, and case-control studies. The study design definitions and applications are taken from seminal research methodology readings and updated observational study reporting guidelines. RESULTS: The authors have given a succinct account of the structure, functioning, and uses of common observational study designs in Neurosurgery. Specifically, they discussed the concepts of study direction, temporal sequence, advantages, and disadvantages. Also, they highlighted the differences between case reports and case series; case series and descriptive cohort studies; and cohort and case-control studies. Also, they discussed their impacts on internal validity, external validity, and relevance. CONCLUSION: This paper disambiguates widely held misconceptions on the different observational study designs. In addition, it uses case-based scenarios to facilitate comprehension and relevance to the academic neurosurgery audience.

Bilateral sphenoid sinus mucocele observed in Yaoundé-Cameroon: a case report.

A mucocele is a cystic and expansive lesion of the sinus cavities. It is uncommon in the sphenoid sinus and its management is quite challenging especially in low to middle income countries like Cameroon. A 43-years-old female was referred to us by a neurologist for chronic headache and visual disturbances. The pain was unresponsive to analgesics. Physical examination was non-remarkable and a head CT scan realized showed a cyst-like lesion in the sphenoid sinus cavity. Surgical endoscopic treatment was proposed and realized with basic endoscopic instruments, consisting of opening the cavity with drainage of the mucocele. A large opening was made on the anterior wall of the sphenoid sinus, in order to ensure continuous drainage and prevent a recurrence. Sphenoid sinus mucocele is a rare condition, and its diagnosis can be difficult. Confirmation requires specific imaging and treatment is presently well established, but it can be managed with basic tools.

Prevalence of human immunodeficiency virus infection in brain glioma patients: Is the virus protective from gliomas?

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is associated with an increased prevalence of some malignancies. However, some observational studies have revealed an ever-decreasing prevalence of HIV in glioma patients. The relationship between HIV and brain gliomas has not been well established. METHODS: A cross-sectional study was carried out in sub-Sahara Africa, a high HIV prevalence setting, to determine the prevalence of HIV among all glioma patients over a 2-year period. RESULTS: A markedly reduced prevalence of HIV was found in glioma patients (8.3%) in comparison to the general population (14.3%). The presumably "antiglioma effect" of HIV and/or its treatment resulted in a 42% decrease in glioma occurrence in HIV positive patients compared to HIV negative individuals. Age and sex-adjusted prevalence were also lower among glioma patients with the protective effect observed more in younger patients and female sex. CONCLUSION: Our results corroborate the protective effect of HIV positivity vis-à -vis gliomas. This "antiglioma effect" could be attributed to either the HIV, its treatment, or both. Future studies focused on this "effect" may help unveil better preventative and possible therapeutic avenues for gliomas.

Misclassification of Case-Control Studies in Neurosurgery and Proposed Solutions.

OBJECTIVE: Case-control studies (CCS) and cohort studies (CS) are common research designs in neurosurgery. But the term case-control study is frequently misused in the neurosurgical literature, with many articles reported as CCS, even although their methodology does not respect the basic components of a CCS. We sought to estimate the extent of these discrepancies in neurosurgical literature, explore factors contributing to mislabeling, and shed some light on study design reporting. METHODS: We identified 31 top-ranking pure neurosurgical journals and searched them for articles reported as CCS, either in the title or in the abstract. The articles were read to determine if they really were CCS according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Article assessment was conducted in duplicate (agreement [κ statistics] = 99.82%). RESULTS: Two hundred and twenty-four articles met our inclusion criteria, 133 of which (59.38%) correctly labeled the case-control design, whereas 91 (40.62%) misclassified this study design. Cohort studies (CS) were the most common design mislabeled as case-control studies in 76 articles (33.93%), 57 of which (25.45%) were retrospective CS. The mislabeling of CCS impairs the appropriate indexing, classification, and sorting of evidence. Mislabeling CS for CCS leads to a downgrading of evidence as CS represent the highest level of evidence for observational studies. Odds ratios instead of relative risk are reported for these studies, resulting in a distortion of the measurement of the effect size, compounded when these are summarized in systematic reviews and pooled in meta-analyses. CONCLUSIONS: Many studies reported as CCS are not true CCS. Reporting guidelines should include items that ensure that studies are labeled correctly. STROBE guidelines should be implemented in assessment of observational studies. Researchers in neurosurgery need better training in research methods and terminology. We also recommend accrued vigilance from reviewers and editors.

Ethical clinical translation of stem cell interventions for neurologic disease.

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease.

Pure spinal epidural cavernous hemangioma: A case series of seven cases.

INTRODUCTION: Pure spinal epidural cavernous hemangiomas (PSECHs) are rare vascular lesions with about 100 cases reported. Herein, we present a case series of 7 PSECHs discussing their clinical presentation, radiological characteristics, surgical technique and intraoperative findings, pathological features, and functional outcome. MATERIALS AND METHODS: We retrieved from the retrolective databases of the senior authors, patients with pathologically confirmed PSECH operated between January 2002 and November 2015. From their medical records, the patients' sociodemographic, clinical, radiological, surgical, and histopathological data were retrieved and analyzed. RESULTS: The mean age of the seven cases was 50.3 years. Four were females. All the five cases (71.4%) in the thoracic spine had myelopathy and the 2 (28.6%) lumbar cases had sciatica. Local pain was present in all the cases. All the lesions were isointense on T1-weighted images, hyperintense on T2-weighted images, and in five cases there was strong homogeneous enhancement. In six cases (85.7%), classical laminectomy was done; lesions resected in one piece in five cases. Total excision was achieved in all the cases. Lesions were thin-walled dilated blood vessels, lined with endothelium, and engorged with blood and with scanty loose fibrous stroma. The median follow-up was 12 months (range: 1-144 months). All patients gradually improved neurologically and achieved a good outcome with no recurrence at the last follow-up. CONCLUSION: PSECH although rare is increasing reported and ought to be included in the differential diagnosis of spinal epidural lesions. Early surgical treatment with total resection is recommended as would result in a good prognosis.

Gamma Knife radiosurgery for low-grade tectal gliomas.

BACKGROUND: Tectal gliomas are present in a critical location that makes their surgical treatment difficult. Stereotactic radiosurgery presents an attractive noninvasive treatment option. However, tectal gliomas are also commonly associated with aqueductal obstruction and consequently hydrocephalus. This necessitates some form of CSF diversion procedure before radiosurgery. The aim of the study was to assess the efficacy and safety of Gamma Knife radiosurgery for tectal gliomas. PATIENTS AND METHODS: Between October 2002 and May 2011, 11 patients with tectal gliomas were treated with Gamma Knife radiosurgery. Five patients had pilocytic astrocytomas and six nonpilocytic astrocytomas. Ten patients presented with hydrocephalus and underwent a CSF diversion procedure [7 V-P shunt and 3 endoscopic third ventriculostomy (ETV)]. The tumor volume ranged between 1.2-14.7 cc (median 4.5 cc). The prescription dose was 11-14 Gy (median 12 Gy). RESULTS: Patients were followed for a median of 40 months (13-114 months). Tumor control after radiosurgery was seen in all cases. In 6/11 cases, the tumors eventually disappeared after treatment. Peritumoral edema developed in 5/11 cases at an onset of 3-6 months after treatment. Transient tumor swelling was observed in four cases. Four patients developed cysts after treatment. One of these cases required aspiration and eventually disappeared, one became smaller spontaneously, and two remained stable. CONCLUSION: Gamma Knife radiosurgery is an effective and safe technique for treatment of tectal gliomas. Tumor shrinkage or disappearance after Gamma Knife radiosurgery may preclude the need for a shunt later on.

Image guided surgery in the management of craniocerebral gunshot injuries.

BACKGROUND: A craniocerebral trauma caused by firearms is a complex injury with high morbidity and mortality. One of the most intriguing and controversial part in their management in salvageable patients is the decision to remove the bullet/pellet. A bullet is foreign to the brain and, in principle, should be removed. Surgical options for bullet extraction span from conventional craniotomy, through C-arm-guided surgery to minimally invasive frame or frameless stereotaxy. But what is the best surgical option? METHODS: We prospectively followed up a cohort of 28 patients with cranio-cerebral gunshot injury (CCHSI) managed from January to December 2012 in our department of neurosurgery. The missiles were extracted via stereotaxy (frame or frameless), C-arm-guided, or free-hand-based surgery. Cases managed conservatively were excluded. The Glasgow Outcome Score was used to assess the functional outcome on discharge. RESULTS: Five of the eight "stereotactic cases" had an excellent outcome after missile extraction while the initially planned stereotaxy missed locating the missile in three cases and were thus subjected to free hand craniotomy. Excellent outcome was obtained in five of the nine "neuronavigation cases, five of the eight cases for free hand surgery based on the bony landmarks, and five of the six C-arm-based surgery. CONCLUSION: Conventional craniotomy isn't indicated in the extraction of isolated, retained, intracranial firearm missiles in civilian injury but could be useful when the missile is incorporated within a surgical lesion. Stereotactic surgery could be useful for bullet extraction, though with limited precision in identifying small pellets because of their small sizes, thus exposing patients to same risk of brain insult when retrieving a missile by conventional surgery. Because of its availability, C-arm-guided surgery continues to be of much benefit, especially in emergency situations. We recommend an extensive long-term study of these treatment modalities for CCGSI.

Diagnostic performance of the medial hamstring reflex in L5 radiculopathy.

BACKGROUND: An avalanche of literature exists on almost every aspect of lumbar disc pathology but very limited studies have quantified the diagnostic performance of elements of clinical examination in predicting disc level, meticulously collated the reflex changes in lumbar disc herniation (LDH) as well as assessed the diagnostic performance of the medial hamstring reflex (MHR). Our study underscores the diagnostic performance of the MHR in L5 radiculopathy comparing its diagnostic power to that of the knee and ankle reflexes. METHODS: One hundred consecutive patients operated for de novo LDH in our department between January and December 2011 were prospectively followed-up. A nested case control study was designed from our cohort to assess the performance of the MHR in L5 sciatica. All patients were examined by two independent examiners pre-operatively for the MHR and the results collated and correlated to MRI and intra-operative findings. RESULTS: The MHR has a diagnostic performance intermediate to that of knee and ankle reflexes. The percentages correctly classified were respectively: 86%, 79% and 67% for the knee, MHR and ankle reflexes. The MHR is highly precise with an intra-rater reliability of 100% and inter-rater repeatability of above 90% and test-retest reproducibility of 100%. CONCLUSION: The MHR hitherto described as elusive has a high diagnostic performance and is a valid neurologic test that should be included in the routine neurologic examination of patients with suspected L5 radiculopathy.