Jane de Tisi - Academia.edu (original) (raw)

Papers by Jane de Tisi

Epilepsia, Jan 24, 2023

ObjectiveEpilepsy surgery fails to achieve seizure freedom in 30%–40% of cases. It is not fully u... more ObjectiveEpilepsy surgery fails to achieve seizure freedom in 30%–40% of cases. It is not fully understood why some surgeries are unsuccessful. By comparing interictal magnetoencephalography (MEG) band power from patient data to normative maps, which describe healthy spatial and population variability, we identify patient‐specific abnormalities relating to surgical failure. We propose three mechanisms contributing to poor surgical outcome: (1) not resecting the epileptogenic abnormalities (mislocalization), (2) failing to remove all epileptogenic abnormalities (partial resection), and (3) insufficiently impacting the overall cortical abnormality. Herein we develop markers of these mechanisms, validating them against patient outcomes.MethodsResting‐state MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band‐power spatial maps were computed using source‐localized recordings. Patient and region‐specific band‐power abnormalities were estimated as the maximum absolute z‐score across five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative magnetic resonance imaging (MRI). We hypothesized that our mechanistically interpretable markers would discriminate patients with and without postoperative seizure freedom.ResultsOur markers discriminated surgical outcome groups (abnormalities not targeted: area under the curve [AUC] = 0.80, p = .003; partial resection of epileptogenic zone: AUC = 0.68, p = .053; and insufficient cortical abnormality impact: AUC = 0.64, p = .096). Furthermore, 95% of those patients who were not seizure‐free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure‐free.SignificanceThe mapping of abnormalities across the brain is important for a wide range of neurological conditions. Here we have demonstrated that interictal MEG band‐power mapping has merit for the localization of pathology and improving our mechanistic understanding of epilepsy. Our markers for mechanisms of surgical failure could be used in the future to construct predictive models of surgical outcome, aiding clinical teams during patient pre‐surgical evaluations.

Epilepsy Research, Feb 1, 2023

Anteromesial temporal lobe resection is the most common surgical technique used to treat drugresi... more Anteromesial temporal lobe resection is the most common surgical technique used to treat drugresistant mesial temporal lobe epilepsy, particularly when secondary to hippocampal sclerosis. Structural and functional imaging data suggest the importance of sparing the posterior hippocampus for minimising language and memory deficits. Recent work has challenged the view that maximal posterior hippocampal resection improves seizure outcome. This study was designed to assess whether resection of posterior hippocampal atrophy was associated with improved seizure outcome. Methods: Retrospective analysis of a prospective database of all anteromesial temporal lobe resections performed in individuals with hippocampal sclerosis at our epilepsy surgery centre, 2013-2021. Pre-and post-operative MRI were reviewed by 2 neurosurgical fellows to assess whether the atrophic segment, displayed by automated hippocampal morphometry, was resected, and ILAE seizure outcomes were collected at 1 year and last clinical follow-up. Data analysis used univariate and binary logistic regression. Results: Sixty consecutive eligible patients were identified of whom 70% were seizure free (ILAE Class 1 & 2) at one year. There was no statistically significant difference in seizure freedom outcomes in patients who had complete resection of atrophic posterior hippocampus or not (Fisher's Exact test statistic 0.69, not significant at p < .05) both at one year, and at last clinical follow-up. In the multivariate analysis only a history of status epilepticus (OR=0.2, 95%CI:0.042-0.955, p = .04) at one year, and pre-operative psychiatric disorder (OR=0.145, 95%CI:0.036-0.588, p = .007) at last clinical follow-up, were associated with a reduced chance of seizure freedom.

CNS Neuroscience & Therapeutics, Jun 27, 2018

INTRODUCTION Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in... more INTRODUCTION Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30-40% of patients have prominent memory impairment and experience significant post-operative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. AIMS We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. METHODS In the present study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), post-operative cognitive change (n = 126) and fMRI activation patterns during memory-encoding and language paradigms in two groups of patients with mTLE (n = 37 and 34). RESULTS mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. CONCLUSIONS Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE.

arXiv (Cornell University), Mar 23, 2020

Quantification of brain morphology has become an important cornerstone in understanding brain str... more Quantification of brain morphology has become an important cornerstone in understanding brain structure. Measures of cortical morphology such as thickness and surface area are frequently used to compare groups of subjects or characterise longitudinal changes. However, such measures are often treated as independent from each other. A recently described scaling law, derived from a statistical physics model of cortical folding, demonstrates that there is a tight covariance between three commonly used cortical morphology measures: cortical thickness, total surface area, and exposed surface area. We show that assuming the independence of cortical morphology measures can hide features and potentially lead to misinterpretations. Using the scaling law, we account for the covariance between cortical morphology measures and derive novel independent measures of cortical morphology. By applying these new measures, we show that new information can be gained; in our example we show that distinct morphological alterations underlie healthy ageing compared to temporal lobe epilepsy, even on the coarse level of a whole hemisphere. We thus provide a conceptual framework for characterising cortical morphology in a statistically valid and interpretable manner, based on theoretical reasoning about the shape of the cortex.

Epilepsy Research, Oct 1, 2022

arXiv (Cornell University), Jul 15, 2020

Objective: Previous studies investigating associations between white matter alterations and durat... more Objective: Previous studies investigating associations between white matter alterations and duration of temporal lobe epilepsy (TLE) have shown differing results, and were typically limited to univariate analyses of tracts in isolation. In this study we apply a multivariate measure (the Mahalanobis distance), which captures the distinct ways white matter may differ in individual patients, and relate this to epilepsy duration. Methods: Diffusion MRI, from a cohort of 94 subjects (28 healthy controls, 33 left-TLE and 33 right-TLE), was used to assess the association between tract fractional anisotropy (FA) and epilepsy duration. Using ten white matter tracts, we analysed associations using the traditional univariate analysis (z-scores) and a complementary multivariate approach (Mahalanobis distance), incorporating multiple white matter tracts into a single unified analysis. Results: For patients with right-TLE, FA was not significantly associated with epilepsy duration for any tract studied in isolation. For patients with left-TLE, the FA of two limbic tracts (ipsilateral fornix, contralateral cingulum gyrus) were significantly negatively associated with epilepsy duration (Bonferonni corrected p<0.05). Using a multivariate approach we found significant ipsilateral positive associations with duration in both left, and right-TLE cohorts (left-TLE: Spearman's rho=0.487, right-TLE: Spearman's rho=0.422). Extrapolating our multivariate results to duration equals zero (i.e. at onset) we found no significant difference between patients and controls. Associations using the multivariate approach were more robust than univariate methods. Conclusion: The multivariate Mahalanobis distance measure provides non-overlapping and more robust results than traditional univariate analyses. Future studies should consider adopting both frameworks into their analysis in order to ascertain a more complete understanding of epilepsy progression, regardless of laterality. Mahalanobis distances pertain to ILAE2+ patients relative to ILAE1 patients. Conversely, negative t-statistics indicate the inverse relationship, that larger Mahalanobis distances belong to ILAE1 patients relative to ILAE2+ patients. Ipsilateral: Mahalanobis distance calculated using all ipsilateral ROI's. Contralateral: Mahalanobis distance calculated using all contralateral ROI's. Significance levels; * indicates p<0.05, ** indicates p<0.01, *** indicates p<0.001. Bold indicates significance after multiple comparisons correction.

arXiv (Cornell University), Sep 28, 2020

Objective: To identify if whole-brain structural network alterations in patients with temporal lo... more Objective: To identify if whole-brain structural network alterations in patients with temporal lobe epilepsy (TLE) and focal to bilateral tonic-clonic seizures (FBTCS) differ from alterations in patients without FBTCS. Methods: We dichotomized a cohort of 83 drug-resistant patients with TLE into those with and without FBTCS and compared each group to 29 healthy controls. For each subject, we used diffusion-weighted MRI to construct whole-brain structural networks. First, we measured the extent of alterations by performing FBTCS-negative (FBTCS-) versus control and FBTCS-positive (FBTCS+) versus control comparisons, thereby delineating altered sub-networks of the wholebrain structural network. Second, by standardising each patient's networks using control networks, we measured the subject-specific abnormality at every brain region in the network, thereby quantifying the spatial localisation and the amount of abnormality in every patient. Results: Both FBTCS+ and FBTCS-patient groups had altered sub-networks with reduced fractional anisotropy (FA) and increased mean diffusivity (MD) compared to controls. The altered subnetwork in FBTCS+ patients was more widespread than in FBTCS-patients (441 connections altered at t>3, p<0.001 in FBTCS+ compared to 21 connections altered at t>3, p=0.01 in FBTCS-). Significantly greater abnormalities-aggregated over the entire brain network as well as assessed at the resolution of individual brain areas-were present in FBTCS+ patients (p<0.001, d=0.82 [95%CI 0.32, 1.3]). In contrast, the fewer abnormalities present in FBTCS-patients were mainly localised to the temporal and frontal areas. 3 Significance: The whole-brain structural network is altered to a greater and more widespread extent in patients with TLE and focal to bilateral tonic-clonic seizures. We suggest that these abnormal networks may serve as an underlying structural basis or consequence of the greater seizure spread observed in FBTCS. Key points • Patients with drug resistant TLE and FBTCS have widespread abnormalities in whole-brain structural networks spanning many interconnected regions. • Patient susceptibility to FBTCS can be measured from node abnormality metric which quantifies abnormality load patient-specifically. • Regions in subcortical and parietal lobe-known to be implicated in FBTCS-have marked increase in node abnormality in TLE patients with FBTCS.

Network neuroscience, Aug 9, 2023

Extra temporal lobe epilepsy (eTLE) may involve heterogenous widespread cerebral networks. We inv... more Extra temporal lobe epilepsy (eTLE) may involve heterogenous widespread cerebral networks. We investigated the structural network of an eTLE cohort, at the postulated epileptogenic zone later surgically removed, as a network node: the resection zone (RZ). We hypothesized patients with an abnormal connection to/from the RZ to have proportionally increased abnormalities based on topological proximity to the RZ, in addition to poorer post-operative seizure outcome. Structural and diffusion MRI were collected for 22 eTLE patients pre-and post-surgery, and for 29 healthy controls. The structural connectivity of the RZ prior to surgery, measured via generalized fractional anisotropy (gFA), was compared with healthy controls. Abnormal connections were identified as those with substantially reduced gFA (z < −1.96). For patients with one or more abnormal connections to/from the RZ, connections with closer topological distance to the RZ had higher proportion of abnormalities. The minority of the seizure-free patients (3/11) had one or more abnormal connections, while most non-seizurefree patients (8/11) had abnormal connections to the RZ. Our data suggest that eTLE patients with one or more abnormal structural connections to/from the RZ had more proportional abnormal connections based on topological distance to the RZ and associated with reduced chance of seizure freedom post-surgery.

NeuroImage: Clinical, 2023

Epilepsia

ObjectiveIdentifying abnormalities on interictal intracranial electroencephalogram (iEEG), by com... more ObjectiveIdentifying abnormalities on interictal intracranial electroencephalogram (iEEG), by comparing patient data to a normative map, has shown promise for the localization of epileptogenic tissue and prediction of outcome. The approach typically uses short interictal segments of approximately 1 min. However, the temporal stability of findings has not been established.MethodsHere, we generated a normative map of iEEG in nonpathological brain tissue from 249 patients. We computed regional band power abnormalities in a separate cohort of 39 patients for the duration of their monitoring period (.92–8.62 days of iEEG data, mean = 4.58 days per patient, >4800 hours recording). To assess the localizing value of band power abnormality, we computed —a measure of how different the surgically resected and spared tissue was in terms of band power abnormalities—over time.ResultsIn each patient, the value was relatively consistent over time. The median of the entire recording period separa...

arXiv (Cornell University), Apr 11, 2023

Successful epilepsy surgery depends on localising and resecting cerebral abnormalities and networ... more Successful epilepsy surgery depends on localising and resecting cerebral abnormalities and networks that generate seizures. Abnormalities, however, may be widely distributed across multiple discontiguous areas. We propose spatially constrained clusters as candidate areas for further investigation, and potential resection. We quantified the spatial overlap between the abnormality cluster and subsequent resection, hypothesising a greater overlap in seizure-free patients. Thirty-four individuals with refractory focal epilepsy underwent pre-surgical resting-state interictal MEG recording. Fourteen individuals were totally seizure free (ILAE 1) after surgery and 20 continued to have some seizures post-operatively (ILAE 2+). Band power abnormality maps were derived using controls as a baseline. Patient abnormalities were spatially clustered using the kmeans algorithm. The tissue within the cluster containing the most abnormal region was compared with the resection volume using the dice score. The proposed abnormality cluster overlapped with the resection in 71% of ILAE 1 patients. Conversely, an overlap only occurred in 15% of ILAE 2+ patients. This effect discriminated outcome groups well (AUC=0.82). Our novel approach identifies clusters of spatially similar tissue with high abnormality. This is clinically valuable, providing (i) a data-driven framework to validate current hypotheses of the epileptogenic zone localisation or (ii) to guide further investigation.