Introduction
Epilepsy surgery is the only potentially curative treatment for patients with drug-resistant focal epilepsy1–3 with postoperative seizure freedom rates of up to 80%, depending on the epilepsy syndrome.1 4 Identification of the epileptogenic zone (EZ), defined as the area of the brain responsible for seizure initiation and organisation, and evaluation of its resectability are the major aims of presurgical evaluation.5
If non-invasive presurgical workup does not allow to proceed directly to surgery but does enable to formulate a reasonable hypothesis of the localisation of the EZ, stereoelectroencephalography (SEEG) is the gold standard to further delineate the EZ.6 SEEG is an invasive diagnostic procedure using stereotactically placed intracerebral EEG electrode recordings to localise the seizure-onset zone (SOZ), a surrogate marker for the EZ. It poses adverse event rates of 0.6%–4.0%,7–10 is strenuous for patients and physicians alike and is cost-intensive and resource-intensive. More importantly, up to 30%–40% of patients do not qualify for subsequent surgery, as no focal seizure generator can be identified or the SOZ is located in eloquent cortex.7–9 Therefore, accurate identification of patients who are unlikely to benefit from this invasive procedure is important.
We developed an easily applicable score derived from non-invasive presurgical workup, the ‘5-SENSE Score’, to help predict whether a focal SOZ is likely to be identified by SEEG.11 By retrospective analysis of 128 patients who underwent SEEG at the Montreal Neurological Institute and Hospital, Montreal, Canada, five variables were identified to be predictive for focality. Based on these variables, a five-point score reflecting the main pillars of presurgical evaluation, the ‘5-SENSE Score’, was established. The score comprises the following five predictive variables: focal lesion on structural magnetic resonance imaging (S), absence of bilateral independent spikes in interictal scalp EEG (E), localising neuropsychological deficit (N), strongly localising semiology (S) and regional ictal scalp EEG onset (E) (figure 1). Score performance in the development cohort showed high sensitivity (83.3%; 95% CI 72.3% to 94.1%) and specificity (76.3%; 95% CI 66.7% to 85.8%), using a mean probability cut-off for focality of 37.6 (SD=3.5). An international multicentre validation study confirmed good diagnostic accuracy (specificity 76%; 95% CI 67.5% to 84.6%; sensitivity 52%; 95% CI 43.0% to 61.5%) of the 5-SENSE Score in a retrospective cohort study including 207 patients from 9 epilepsy centres in Europe (Paracelsus Medical University Hospital Salzburg, Austria; Masaryk University, Brno, Czech Republic; Carol Davila University of Medicine and Pharmacy Bucharest, Romania; Grenoble Institute of Neurosciences Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France) and North America (Dalhousie University and Hospital, Halifax, Canada; Massachusetts General Hospital, Boston; Montreal Neurological Institute and Hospital, Montreal, Canada; Northwestern University, Chicago, Illinois; University of Pittsburgh, Pittsburgh, Pennsylvania) (figure 1).
However, scores in medicine often show great performance in the original publication but suffer a significant decrease in diagnostic accuracy when applied to independent patient cohorts in clinical routine settings. Proof of score performance in a large-scale prospective setting is essential to demonstrate generalisability and clinical utility.12 13 Therefore, we now aim to validate the score in a large-scale international multicentre prospective validation study including more than 200 patients to demonstrate the prognostic value of the 5-SENSE Score in the prediction of focality in SEEG (objective #1). Auxiliary diagnostic methods (magnetic and electrical source imaging, fluorodeoxyglucose positron emission tomography (FDG-PET) and ictal hexamethylpropyleneamine oxime single-photon emission computerised tomography (SPECT))—currently not reflected in the score—are all now routinely used for non-invasive presurgical evaluation. We aim to evaluate, whether the incorporation of these auxiliary diagnostic methods might improve score performance and lead to an optimised ‘5-SENSE-Plus Score’ with increased diagnostic accuracy (objective #2). Last, we aim to assess the concordance of the 5-SENSE Score with the expert decisions regarding implantation, which is routinely made in the multidisciplinary team discussion (MTD) (objective #3). This is an essential step to prove generalisability and clinical utility of the 5-SENSE-Score to assist clinicians in identifying the important subset of patients where SEEG will reliably localise a circumscribed EZ. Such accurate prediction would decrease unnecessary invasive EEG procedures and spare patients’ associated risks. If successful, the necessary next step will be to perform a prospective multicentre clinical trial to confirm clinical utility and added value of the 5-SENSE Score in clinical practice.