ABSTRACT
BACKGROUND: Neurosurgical randomized controlled trials (RCTs) are difficult to carry out due to the low incidence of certain diseases, heterogeneous disease phenotypes, and ethical issues. This results in a weak evidence base in terms of both the number of trials and their robustness. The fragility index (FI) measures the robustness of an RCT and is the minimum number of patients in a trial whose status would have to change from a nonevent to an event to change a statistically significant result to a nonsignificant result. The smaller the FI, the more fragile the trial's outcome. METHODS: RCTs that have influenced neurosurgical practice were included in this analysis. Simulations were run to calculate the FI. To determine associations with a high or low FI, multivariable logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals adjusting for baseline confounders. RESULTS: Of 2975 papers screened, 74 were included. The median FI was 4.5 (interquartile range: 1.5-10). RCTs included a median of 165 patients (interquartile range: 75-330), with a maximum of 10,008. A total of 38 trials had lost to follow-up patients that might have impacted the robustness of the results (51%). CONCLUSION: Results of neurosurgical RCTs on which we base our clinical decision-making and treatment guidelines are often fragile. Improved methodologies, international collaboration, and cooperation between specialties might improve the evidence base in the future.
Subject(s)
Neurosurgical Procedures , Randomized Controlled Trials as Topic , Humans , Sample SizeABSTRACT
The anatomic distribution of the deep cerebral perforators is considered either a given or subject to enormous variability. Most published overviews on this topic only report findings from a limited number of anatomic dissections, and no attempt has been made to date to provide a comprehensive overview of all published data. A comprehensive literature search was performed on MEDLINE, Embase, and Google Scholar with the help of an information specialist. Three types of studies were included: (1) articles that described the anatomy and distribution territories of perforator groups arising from the arteries of the circle of Willis; (2) studies that evaluated the anatomy of the deep cerebral perforators using imaging techniques; and (3) studies that evaluated either microsurgically or radiologically confirmed perforator occlusion and reported the (magnetic resonance imaging-confirmed) distribution territory of the infarction together with a description of the clinical symptoms associated as a result of the infarction. A total of 2715 articles were screened and 53 were included. Of these, 40 dealt with the anatomic and imaging anatomy of perforator groups (37 reported results of dissections and 3 results of imaging studies), with a total of 2421 hemispheres investigated. Another 13 articles with 680 patients were included that evaluated perforator infarction territories. The deep cerebral perforator distribution shows large variability with poor concordance rates among reported studies, with the exception of the posterior communicating and anterior choroidal artery perforators. Despite the assumption that cerebral perforator anatomy is a given, studies show large variability in the anatomic distribution of various perforator groups. Perforator anatomy and relationships between perforator groups, as well as potential collateral circulation in these territories should be prioritized as a research topic in cerebrovascular disease in the near future.
