Software tool for visualization of a probabilistic map of the epileptogenic zone from seizure semiologies.

Around one third of epilepsies are drug-resistant. For these patients, seizures may be reduced or cured by surgically removing the epileptogenic zone (EZ), which is the portion of the brain giving rise to seizures. If noninvasive data are not sufficiently lateralizing or localizing, the EZ may need to be localized by precise implantation of intracranial electroencephalography (iEEG) electrodes. The choice of iEEG targets is influenced by clinicians' experience and personal knowledge of the literature, which leads to substantial variations in implantation strategies across different epilepsy centers. The clinical diagnostic pathway for surgical planning could be supported and standardized by an objective tool to suggest EZ locations, based on the outcomes of retrospective clinical cases reported in the literature. We present an open-source software tool that presents clinicians with an intuitive and data-driven visualization to infer the location of the symptomatogenic zone, that may overlap with the EZ. The likely EZ is represented as a probabilistic map overlaid on the patient's images, given a list of seizure semiologies observed in that specific patient. We demonstrate a case study on retrospective data from a patient treated in our unit, who underwent resective epilepsy surgery and achieved 1-year seizure freedom after surgery. The resected brain structures identified as EZ location overlapped with the regions highlighted by our tool, demonstrating its potential utility.

Probabilistic landscape of seizure semiology localizing values.

Semiology describes the evolution of symptoms and signs during epileptic seizures and contributes to the evaluation of individuals with focal drug-resistant epilepsy for curative resection. Semiology varies in complexity from elementary sensorimotor seizures arising from primary cortex to complex behaviours and automatisms emerging from distributed cerebral networks. Detailed semiology interpreted by expert epileptologists may point towards the likely site of seizure onset, but this process is subjective. No study has captured the variances in semiological localizing values in a data-driven manner to allow objective and probabilistic determinations of implicated networks and nodes. We curated an open data set from the epilepsy literature, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, linking semiology to hierarchical brain localizations. A total of 11 230 data points were collected from 4643 patients across 309 articles, labelled using ground truths (postoperative seizure-freedom, concordance of imaging and neurophysiology, and/or invasive EEG) and a designation method that distinguished between semiologies arising from a predefined cortical region and descriptions of neuroanatomical localizations responsible for generating a particular semiology. This allowed us to mitigate temporal lobe publication bias by filtering studies that preselected patients based on prior knowledge of their seizure foci. Using this data set, we describe the probabilistic landscape of semiological localizing values as forest plots at the resolution of seven major brain regions: temporal, frontal, cingulate, parietal, occipital, insula, and hypothalamus, and five temporal subregions. We evaluated the intrinsic value of any one semiology over all other ictal manifestations. For example, epigastric auras implicated the temporal lobe with 83% probability when not accounting for the publication bias that favoured temporal lobe epilepsies. Unbiased results for a prior distribution of cortical localizations revised the prevalence of temporal lobe epilepsies from 66% to 44%. Therefore, knowledge about the presence of epigastric auras updates localization to the temporal lobe with an odds ratio (OR) of 2.4 [CI95% (1.9, 2.9); and specifically, mesial temporal structures OR: 2.8 (2.3, 2.9)], attesting the value of epigastric auras. As a further example, although head version is thought to implicate the frontal lobes, it did not add localizing value compared with the prior distribution of cortical localizations [OR: 0.9 (0.7, 1.2)]. Objectification of the localizing values of the 12 most common semiologies provides a complementary view of brain dysfunction to that of lesion-deficit mappings, as instead of linking brain regions to phenotypic-deficits, semiological phenotypes are linked back to brain sources. This work enables coupling of seizure propagation with ictal manifestations, and clinical support algorithms for localizing seizure phenotypes.

Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson's Disease: Interim Results from a Randomized Double-Blind Clinical Trial.

BACKGROUND: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson's disease (PD). OBJECTIVE: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. METHODS: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platformResults:The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st-3rd quartile] of 3.07 [3.12-4.62] cm with sham-DBS, 1.95 [2.29-3.85] cm with PPN-DBS and 2.78 [1.66-4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. CONCLUSION: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.

Machine Learning for Localizing Epileptogenic-Zone in the Temporal Lobe: Quantifying the Value of Multimodal Clinical-Semiology and Imaging Concordance.

Background: Epilepsy affects 50 million people worldwide and a third are refractory to medication. If a discrete cerebral focus or network can be identified, neurosurgical resection can be curative. Most excisions are in the temporal-lobe, and are more likely to result in seizure-freedom than extra-temporal resections. However, less than half of patients undergoing surgery become entirely seizure-free. Localizing the epileptogenic-zone and individualized outcome predictions are difficult, requiring detailed evaluations at specialist centers. Methods: We used bespoke natural language processing to text-mine 3,800 electronic health records, from 309 epilepsy surgery patients, evaluated over a decade, of whom 126 remained entirely seizure-free. We investigated the diagnostic performances of machine learning models using set-of-semiology (SoS) with and without hippocampal sclerosis (HS) on MRI as features, using STARD criteria. Findings: Support Vector Classifiers (SVC) and Gradient Boosted (GB) decision trees were the best performing algorithms for temporal-lobe epileptogenic zone localization (cross-validated Matthews correlation coefficient (MCC) SVC 0.73 ± 0.25, balanced accuracy 0.81 ± 0.14, AUC 0.95 ± 0.05). Models that only used seizure semiology were not always better than internal benchmarks. The combination of multimodal features, however, enhanced performance metrics including MCC and normalized mutual information (NMI) compared to either alone (p < 0.0001). This combination of semiology and HS on MRI increased both cross-validated MCC and NMI by over 25% (NMI, SVC SoS: 0.35 ± 0.28 vs. SVC SoS+HS: 0.61 ± 0.27). Interpretation: Machine learning models using only the set of seizure semiology (SoS) cannot unequivocally perform better than benchmarks in temporal epileptogenic-zone localization. However, the combination of SoS with an imaging feature (HS) enhance epileptogenic lobe localization. We quantified this added NMI value to be 25% in absolute terms. Despite good performance in localization, no model was able to predict seizure-freedom better than benchmarks. The methods used are widely applicable, and the performance enhancements by combining other clinical, imaging and neurophysiological features could be similarly quantified. Multicenter studies are required to confirm generalizability. Funding: Wellcome/EPSRC Center for Interventional and Surgical Sciences (WEISS) (203145Z/16/Z).

A self-supervised learning strategy for postoperative brain cavity segmentation simulating resections.

PURPOSE: Accurate segmentation of brain resection cavities (RCs) aids in postoperative analysis and determining follow-up treatment. Convolutional neural networks (CNNs) are the state-of-the-art image segmentation technique, but require large annotated datasets for training. Annotation of 3D medical images is time-consuming, requires highly trained raters and may suffer from high inter-rater variability. Self-supervised learning strategies can leverage unlabeled data for training. METHODS: We developed an algorithm to simulate resections from preoperative magnetic resonance images (MRIs). We performed self-supervised training of a 3D CNN for RC segmentation using our simulation method. We curated EPISURG, a dataset comprising 430 postoperative and 268 preoperative MRIs from 430 refractory epilepsy patients who underwent resective neurosurgery. We fine-tuned our model on three small annotated datasets from different institutions and on the annotated images in EPISURG, comprising 20, 33, 19 and 133 subjects. RESULTS: The model trained on data with simulated resections obtained median (interquartile range) Dice score coefficients (DSCs) of 81.7 (16.4), 82.4 (36.4), 74.9 (24.2) and 80.5 (18.7) for each of the four datasets. After fine-tuning, DSCs were 89.2 (13.3), 84.1 (19.8), 80.2 (20.1) and 85.2 (10.8). For comparison, inter-rater agreement between human annotators from our previous study was 84.0 (9.9). CONCLUSION: We present a self-supervised learning strategy for 3D CNNs using simulated RCs to accurately segment real RCs on postoperative MRI. Our method generalizes well to data from different institutions, pathologies and modalities. Source code, segmentation models and the EPISURG dataset are available at https://github.com/fepegar/resseg-ijcars .

A generative model of hyperelastic strain energy density functions for multiple tissue brain deformation.

PURPOSE: Estimation of brain deformation is crucial during neurosurgery. Whilst mechanical characterisation captures stress-strain relationships of tissue, biomechanical models are limited by experimental conditions. This results in variability reported in the literature. The aim of this work was to demonstrate a generative model of strain energy density functions can estimate the elastic properties of tissue using observed brain deformation. METHODS: For the generative model a Gaussian Process regression learns elastic potentials from 73 manuscripts. We evaluate the use of neo-Hookean, Mooney-Rivlin and 1-term Ogden meta-models to guarantee stability. Single and multiple tissue experiments validate the ability of our generative model to estimate tissue properties on a synthetic brain model and in eight temporal lobe resection cases where deformation is observed between pre- and post-operative images. RESULTS: Estimated parameters on a synthetic model are close to the known reference with a root-mean-square error (RMSE) of 0.1 mm and 0.2 mm between surface nodes for single and multiple tissue experiments. In clinical cases, we were able to recover brain deformation from pre- to post-operative images reducing RMSE of differences from 1.37 to 1.08 mm on the ventricle surface and from 5.89 to 4.84 mm on the resection cavity surface. CONCLUSION: Our generative model can capture uncertainties related to mechanical characterisation of tissue. When fitting samples from elastography and linear studies, all meta-models performed similarly. The Ogden meta-model performed the best on hyperelastic studies. We were able to predict elastic parameters in a reference model on a synthetic phantom. However, deformation observed in clinical cases is only partly explained using our generative model.

Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.

OBJECTIVE: Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes. We aim to validate an automated trajectory planning platform against manually planned trajectories to objectively standardize the process. METHODS: Using the EpiNav platform, we compare automated trajectory planning parameters derived from expert opinion and machine learning to undertake a multicenter validation against manually planned and implemented trajectories in 95 patients with MTLE. We estimate ablation volumes of regions of interest and quantify the size of the avascular corridor through the use of a risk score as a marker of safety. We also undertake blinded external expert feasibility and preference ratings. RESULTS: Automated trajectory planning employs complex algorithms to maximize ablation of the mesial hippocampal head and amygdala, while sparing the parahippocampal gyrus. Automated trajectories resulted in significantly lower calculated risk scores and greater amygdala ablation percentage, whereas overall hippocampal ablation percentage did not differ significantly. In addition, estimated damage to collateral structures was reduced. Blinded external expert raters were significantly more likely to prefer automated to manually planned trajectories. SIGNIFICANCE: Retrospective studies of automated trajectory planning show much promise in improving safety parameters and ablation volumes during LITT for MTLE. Multicenter validation provides evidence that the algorithm is robust, and blinded external expert ratings indicate that the trajectories are clinically feasible. Prospective validation studies are now required to determine if automated trajectories translate into improved seizure freedom rates and reduced neuropsychological deficits.