BackgroundThe predominant treatment for epilepsy is pharmacotherapy, yet 20–40% do not respond to anti-epileptic drugs. After becoming pharmacoresistant, some patients are worked-up to determine candidacy for epilepsy surgery. Despite the 2009 American Epilepsy Society guidelines, there is no broadly accepted criteria for the investigatory pathway and principles of patient selection for epilepsy surgery candidates. The objective of this systematic review is to elucidate what diagnostic pathways clinicians globally utilize.MethodsUtilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Cochrane Handbook of Systemic Reviews of Interventions, we conducted a systematic review through MEDLINE, Embase, and CENTRAL.ResultsFrom 2092 screened articles, 14 met inclusion criteria for qualitative synthesis. Structural MRI was required in all investigatory pathways. All but two articles required neuropsychological assessment. Six required neuropsychiatric assessment. Two protocols mentioned assessing the patient’s support network. Three other protocols mentioned discussing expectations with patients. One also motioned conducing an occupational evaluation and making all surgery decisions in a multidisciplinary management conference. fMRI and the Wada test were required assessments in seven of the protocols. [18F]FDG-PET and SPECT were ancillary for all but three articles (where they were required). MEG and intracranial EEG were only mentioned as ancillary. Magnetic resonance (MR) spectroscopy was required at two institutes. With regards to the actual indication for selecting patients to begin the investigatory pathway, seven of the articles used a variation of the International League Against Epilepsy definition of refectory epilepsy, while one incorporated patient social history.ConclusionsDespite attempts to standardize patient selection and investigatory pathways, no two protocols were identical. Scalp video/EEG telemetry, structural MRI, and neuropsychological assessment were the only assessments utilized in nearly all protocols. Socioeconomic restrictions appear to play a role in determining which tests are utilized in the investigatory pathway—not just for developing countries. However, cost-effective assessments, such as assessing patient support network and providing realistic expectation of outcomes, were only utilized in few protocols. In addition, no advanced imaging technologies (i.e., qMRI, 3D-MMI) were utilized. Overall, even amongst expert examiners there is significant variation throughout epilepsy centers globally, in selecting candidates and working up patients.