One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted ‘gold-standard’ subcohort of seizure-free patients with FCD type IIB who had T₁ and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Objective: Drug‐resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.Methods: The MELD (Multi‐centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging‐based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.Results: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%.Significance: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data‐driven atlases and predictive models are essential for evidence‐based, precision medicine and risk counseling in epilepsy.

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990–2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. β_FSIQ = −1.9, SE_FSIQ = 0.3, P_FSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%–43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%–60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. r_rb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. β_FSIQ = 0.9, SE_FSIQ = 0.3, P_FSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

With their ‘all-or-none’ action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal literature to support the mechanistic importance of studying neuronal firing as a way to understand neuronal microcircuits and brain function. Although most studies have emphasized physiology, there is increasing recognition that studying single units provides novel insight into system-level mechanisms of disease. Microelectrode recordings are becoming more common in humans, paralleling the increasing use of intracranial electroencephalography recordings in the context of presurgical evaluation in focal epilepsy. In addition to single-unit data, microelectrode recordings also record local field potentials and high-frequency oscillations, some of which may be different to that recorded by clinical macroelectrodes. However, microelectrodes are being used almost exclusively in research contexts and there are currently no indications for incorporating microelectrode recordings into routine clinical care. In this review, we summarize the lessons learnt from 65 years of microelectrode recordings in human epilepsy patients. We cover the electrode constructs that can be utilized, principles of how to record and process microelectrode data and insights into ictal dynamics, interictal dynamics and cognition. We end with a critique on the possibilities of incorporating single-unit recordings into clinical care, with a focus on potential clinical indications, each with their specific evidence base and challenges.

Object: The incidence of chronic subdural hematoma (CSDH) is expected to increase substantially over the next 25 years. Continuing refinement of techniques for surgical evacuation is essential for optimizing patient outcomes. A novel technique involving a hollow screw, which is threaded through a twist-drill hole in the cranium and then connected to a closed drainage system, has been increasing in popularity. The aim of this systematic review is to collate and analyze the published experience with this novel technique and to evaluate its efficacy in comparison with the other surgical treatment methods. Methods: This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and has been registered with the PROSPERO International Prospective Register of Systematic Reviews (registration number CRD42013003544). MEDLINE, Web of Knowledge, EMBASE, and the Cochrane Database of Systematic Reviews were searched for published series involving more than 10 patients treated with these new techniques. Results: Nine eligible studies were found (6 case series and 3 case-control studies) comprising 796 patients treated with these new techniques. Pooled analysis showed a “success rate” of 77.6% (95% CI 74.6%–80.4%), recurrence rate of 22.4%, and in-hospital mortality of 1.4%. Conclusions: This systematic review adds further evidence to the pool of data assessing the safety and efficacy of the use of this novel, minimally invasive technique for the treatment for CSDH. Overall, twist-drill craniostomy with hollow screws appears to be safe and effective. Class I evidence is necessary to optimize the surgical management of patients with CSDH.