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1. Functional MRI of focal and generalised interictal epileptiform discharges

Author

Hamandi, K.

Subjects
616.07
Abstract

Localizing the source of epileptic discharges is important in gaining a greater understanding of the disease, classifying epilepsy, and identifying areas suitable for potentially curable surgical resection. Functional imaging measures haemodynamic, metabolic or neurochemical correlates to localise neural activity. Combining EEG with functional MRI (EEG-fMRI) allows the localisation of haemodynamic correlates of neuronal events recorded on surface EEG. The work in this thesis aims to identify the spatial haemodynamic correlates of interictal epileptiform discharges (IED) in patients with epilepsy using EEG-fMRI. Five studies form the main body of this thesis. In the first study, 46 patients with frequent generalised spike wave activity (GSW) were studied with EEG-fMRI on a 1.5 Tesla scanner. The main finding was of a characteristic pattern of fMRI signal decrease in frontal, parietal and posterior cingulate cortex, areas of association cortex, during GSW. In the second study, 4 patients from this first series were re-studied with a 3 Tesla scanner. A high degree of reproducibility was seen in the spatial distribution of fMRI changes. Perfusion MRI with an arterial spin label sequence was used that showed a decrease in blood flow to these areas during GSW. In the third study, a novel method for the analysis of fMRI data in epilepsy, temporal clustering analysis (TCA) was assessed. The technique was confounded by subject motion, and we were unable to reliably detect correlates of IED. The fourth study moves away from correlating visually identified IEDs on the EEG, and correlates power fluctuations in the delta frequency band with simultaneously acquired fMRI. Finally a combination of EEG-fMRI and MR tractography were used to study a patient with temporal lobe epilepsy. The issues surrounding potential use of EEG-fMRI as a clinical tool are discussed.

Published
2008

2. Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults

Author

Ferreira-Atuesta, C, de Tisi, J, McEvoy, AW, Miserocchi, A, Khoury, J, Yardi, R, Vegh, DT, Butler, J, Lee, HJ, Deli-Peri, V, Yao, Y, Wang, F-P, Zhang, X-B, Shakhatreh, L, Siriratnam, P, Neal, A, Sen, A, Tristram, M, Varghese, E, Biney, W, Gray, WP, Peralta, AR, Rainha-Campos, A, Goncalves-Ferreira, AJC, Pimentel, J, Arias, JF, Terman, S, Terziev, R, Lamberink, HJ, Braun, KPJ, Otte, WM, Rugg-Gunn, FJ, Gonzalez, W, Bentes, C, Hamandi, K, O'Brien, TJ, Perucca, P, Yao, C, Burman, RJ, Jehi, L, Duncan, JS, Sander, JW, Koepp, M, Galovic, M, Ferreira-Atuesta, C, de Tisi, J, McEvoy, AW, Miserocchi, A, Khoury, J, Yardi, R, Vegh, DT, Butler, J, Lee, HJ, Deli-Peri, V, Yao, Y, Wang, F-P, Zhang, X-B, Shakhatreh, L, Siriratnam, P, Neal, A, Sen, A, Tristram, M, Varghese, E, Biney, W, Gray, WP, Peralta, AR, Rainha-Campos, A, Goncalves-Ferreira, AJC, Pimentel, J, Arias, JF, Terman, S, Terziev, R, Lamberink, HJ, Braun, KPJ, Otte, WM, Rugg-Gunn, FJ, Gonzalez, W, Bentes, C, Hamandi, K, O'Brien, TJ, Perucca, P, Yao, C, Burman, RJ, Jehi, L, Duncan, JS, Sander, JW, Koepp, M, and Galovic, M

Abstract

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.g

Published
2023

5. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author

Park, B.-y., Larivière, S., Rodríguez-Cruces, R., Royer, J., Tavakol, S., Wang, Y., Caciagli, L., Caligiuri, M.E., Gambardella, A., Concha, L., Keller, S.S., Cendes, F., Alvim, M.K.M., Yasuda, C., Bonilha, L., Gleichgerrcht, E., Focke, N.K., Kreilkamp, B.A.K., Domin, M., Podewils, F. von, Langner, S., Rummel, C., Rebsamen, M., Wiest, R., Martin, P., Kotikalapudi, R., Bender, B., O’Brien, T.J., Law, M., Sinclair, B., Vivash, L., Kwan, P., Desmond, P.M., Malpas, C.B., Lui, E., Alhusaini, S., Doherty, C.P., Cavalleri, G.L., Delanty, N., Kälviäinen, R., Jackson, G.D., Kowalczyk, M., Mascalchi, M., Semmelroch, M., Thomas, R.H., Soltanian-Zadeh, H., Davoodi-Bojd, E., Zhang, J., Lenge, M., Guerrini, R., Bartolini, E., Hamandi, K., Foley, S., Weber, B., Depondt, C., Absil, J., Carr, S.J.A., Abela, E., Richardson, M.P., Devinsky, O., Severino, M., Striano, P., Parodi, C., Tortora, D., Hatton, S.N., Vos, S.B., Duncan, J.S., Galovic, M., Whelan, C.D., Bargalló, N., Pariente, J., Conde-Blanco, E., Vaudano, A.E., Tondelli, M., Meletti, S., Kong, X.Z., Francks, C., Fisher, S.E., Caldairou, B., Ryten, M., Labate, A., Sisodiya, S.M., Thompson, P.M., McDonald, C.R., Bernasconi, A., Bernasconi, N., Bernhardt, B.C., Park, B.-y., Larivière, S., Rodríguez-Cruces, R., Royer, J., Tavakol, S., Wang, Y., Caciagli, L., Caligiuri, M.E., Gambardella, A., Concha, L., Keller, S.S., Cendes, F., Alvim, M.K.M., Yasuda, C., Bonilha, L., Gleichgerrcht, E., Focke, N.K., Kreilkamp, B.A.K., Domin, M., Podewils, F. von, Langner, S., Rummel, C., Rebsamen, M., Wiest, R., Martin, P., Kotikalapudi, R., Bender, B., O’Brien, T.J., Law, M., Sinclair, B., Vivash, L., Kwan, P., Desmond, P.M., Malpas, C.B., Lui, E., Alhusaini, S., Doherty, C.P., Cavalleri, G.L., Delanty, N., Kälviäinen, R., Jackson, G.D., Kowalczyk, M., Mascalchi, M., Semmelroch, M., Thomas, R.H., Soltanian-Zadeh, H., Davoodi-Bojd, E., Zhang, J., Lenge, M., Guerrini, R., Bartolini, E., Hamandi, K., Foley, S., Weber, B., Depondt, C., Absil, J., Carr, S.J.A., Abela, E., Richardson, M.P., Devinsky, O., Severino, M., Striano, P., Parodi, C., Tortora, D., Hatton, S.N., Vos, S.B., Duncan, J.S., Galovic, M., Whelan, C.D., Bargalló, N., Pariente, J., Conde-Blanco, E., Vaudano, A.E., Tondelli, M., Meletti, S., Kong, X.Z., Francks, C., Fisher, S.E., Caldairou, B., Ryten, M., Labate, A., Sisodiya, S.M., Thompson, P.M., McDonald, C.R., Bernasconi, A., Bernasconi, N., and Bernhardt, B.C.

Abstract

Contains fulltext : 252489.pdf (Publisher’s version ) (Open Access)

Published
2022

6. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author

Park, B-Y, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Tavakol, S, Wang, Y, Caciagli, L, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Alvim, MKM, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Kreilkamp, BAK, Domin, M, von Podewils, F, Langner, S, Rummel, C, Rebsamen, M, Wiest, R, Martin, P, Kotikalapudi, R, Bender, B, O'Brien, TJ, Law, M, Sinclair, B, Vivash, L, Kwan, P, Desmond, PM, Malpas, CB, Lui, E, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Parodi, C, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Galovic, M, Whelan, CD, Bargallo, N, Pariente, J, Conde-Blanco, E, Vaudano, AE, Tondelli, M, Meletti, S, Kong, X-Z, Francks, C, Fisher, SE, Caldairou, B, Ryten, M, Labate, A, Sisodiya, SM, Thompson, PM, McDonald, CR, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Park, B-Y, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Tavakol, S, Wang, Y, Caciagli, L, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Alvim, MKM, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Kreilkamp, BAK, Domin, M, von Podewils, F, Langner, S, Rummel, C, Rebsamen, M, Wiest, R, Martin, P, Kotikalapudi, R, Bender, B, O'Brien, TJ, Law, M, Sinclair, B, Vivash, L, Kwan, P, Desmond, PM, Malpas, CB, Lui, E, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Parodi, C, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Galovic, M, Whelan, CD, Bargallo, N, Pariente, J, Conde-Blanco, E, Vaudano, AE, Tondelli, M, Meletti, S, Kong, X-Z, Francks, C, Fisher, SE, Caldairou, B, Ryten, M, Labate, A, Sisodiya, SM, Thompson, PM, McDonald, CR, Bernasconi, A, Bernasconi, N, and Bernhardt, BC

Abstract

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine ou

Published
2022

7. A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies

Author

Altmann, A, Ryten, M, Di Nunzio, M, Ravizza, T, Tolomeo, D, Reynolds, RH, Somani, A, Bacigaluppi, M, Iori, V, Micotti, E, Di Sapia, R, Cerovic, M, Palma, E, Ruffolo, G, Botia, JA, Absil, J, Alhusaini, S, Alvim, MKM, Auvinen, P, Bargallo, N, Bartolini, E, Bender, B, Bergo, FPG, Bernardes, T, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Blackmon, K, Braga, B, Caligiuri, ME, Calvo, A, Carlson, C, Carr, SJA, Cavalleri, GL, Cendes, F, Chen, J, Chen, S, Cherubini, A, Concha, L, David, P, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP, Domin, M, Focke, NK, Foley, S, Franca, W, Gambardella, A, Guerrini, R, Hamandi, K, Hibar, DP, Isaev, D, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kowalczyk, MA, Kuzniecky, R, Kwan, P, Labate, A, Langner, S, Lenge, M, Liu, M, Martin, P, Mascalchi, M, Meletti, S, Morita-Sherman, ME, O'Brien, TJ, Pariente, JC, Richardson, MP, Rodriguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Striano, P, Thesen, T, Thomas, RH, Tondelli, M, Tortora, D, Vaudano, AE, Vivash, L, Podewils, F, Wagner, J, Weber, B, Wiest, R, Yasuda, CL, Zhang, G, Zhang, J, Leu, C, Avbersek, A, Thom, M, Whelan, CD, Thompson, P, McDonald, CR, Vezzani, A, Sisodiya, SM, Altmann, A, Ryten, M, Di Nunzio, M, Ravizza, T, Tolomeo, D, Reynolds, RH, Somani, A, Bacigaluppi, M, Iori, V, Micotti, E, Di Sapia, R, Cerovic, M, Palma, E, Ruffolo, G, Botia, JA, Absil, J, Alhusaini, S, Alvim, MKM, Auvinen, P, Bargallo, N, Bartolini, E, Bender, B, Bergo, FPG, Bernardes, T, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Blackmon, K, Braga, B, Caligiuri, ME, Calvo, A, Carlson, C, Carr, SJA, Cavalleri, GL, Cendes, F, Chen, J, Chen, S, Cherubini, A, Concha, L, David, P, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP, Domin, M, Focke, NK, Foley, S, Franca, W, Gambardella, A, Guerrini, R, Hamandi, K, Hibar, DP, Isaev, D, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kowalczyk, MA, Kuzniecky, R, Kwan, P, Labate, A, Langner, S, Lenge, M, Liu, M, Martin, P, Mascalchi, M, Meletti, S, Morita-Sherman, ME, O'Brien, TJ, Pariente, JC, Richardson, MP, Rodriguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Striano, P, Thesen, T, Thomas, RH, Tondelli, M, Tortora, D, Vaudano, AE, Vivash, L, Podewils, F, Wagner, J, Weber, B, Wiest, R, Yasuda, CL, Zhang, G, Zhang, J, Leu, C, Avbersek, A, Thom, M, Whelan, CD, Thompson, P, McDonald, CR, Vezzani, A, and Sisodiya, SM

Abstract

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Published
2022

8. Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study

Author

Wagstyl, K, Whitaker, K, Raznahan, A, Seidlitz, J, Vertes, PE, Foldes, S, Humphreys, Z, Hu, W, Mo, J, Likeman, M, Davies, S, Lenge, M, Cohen, NT, Tang, Y, Wang, S, Ripart, M, Chari, A, Tisdall, M, Bargallo, N, Conde-Blanco, E, Carlos Pariente, J, Pascual-Diaz, S, Delgado-Martinez, I, Perez-Enriquez, C, Lagorio, I, Abela, E, Mullatti, N, O'Muircheartaigh, J, Vecchiato, K, Liu, Y, Caligiuri, M, Sinclair, B, Vivash, L, Willard, A, Kandasamy, J, McLellan, A, Sokol, D, Semmelroch, M, Kloster, A, Opheim, G, Yasuda, C, Zhang, K, Hamandi, K, Barba, C, Guerrini, R, Gaillard, WD, You, X, Wang, I, Gonzalez-Ortiz, S, Severino, M, Striano, P, Tortora, D, Kalviainen, R, Gambardella, A, Labate, A, Desmond, P, Lui, E, O'Brien, T, Shetty, J, Jackson, G, Duncan, JS, Winston, GP, Pinborg, L, Cendes, F, Cross, JH, Baldeweg, T, Adler, S, Wagstyl, K, Whitaker, K, Raznahan, A, Seidlitz, J, Vertes, PE, Foldes, S, Humphreys, Z, Hu, W, Mo, J, Likeman, M, Davies, S, Lenge, M, Cohen, NT, Tang, Y, Wang, S, Ripart, M, Chari, A, Tisdall, M, Bargallo, N, Conde-Blanco, E, Carlos Pariente, J, Pascual-Diaz, S, Delgado-Martinez, I, Perez-Enriquez, C, Lagorio, I, Abela, E, Mullatti, N, O'Muircheartaigh, J, Vecchiato, K, Liu, Y, Caligiuri, M, Sinclair, B, Vivash, L, Willard, A, Kandasamy, J, McLellan, A, Sokol, D, Semmelroch, M, Kloster, A, Opheim, G, Yasuda, C, Zhang, K, Hamandi, K, Barba, C, Guerrini, R, Gaillard, WD, You, X, Wang, I, Gonzalez-Ortiz, S, Severino, M, Striano, P, Tortora, D, Kalviainen, R, Gambardella, A, Labate, A, Desmond, P, Lui, E, O'Brien, T, Shetty, J, Jackson, G, Duncan, JS, Winston, GP, Pinborg, L, Cendes, F, Cross, JH, Baldeweg, T, and Adler, S

Abstract

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 l

Published
2022

9. The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Author

Sisodiya, SM, Whelan, CD, Hatton, SN, Huynh, K, Altmann, A, Ryten, M, Vezzani, A, Caligiuri, ME, Labate, A, Gambardella, A, Ives-Deliperi, V, Meletti, S, Munsell, BC, Bonilha, L, Tondelli, M, Rebsamen, M, Rummel, C, Vaudano, AE, Wiest, R, Balachandra, AR, Bargallo, N, Bartolini, E, Bernasconi, A, Bernasconi, N, Bernhardt, B, Caldairou, B, Carr, SJA, Cavalleri, GL, Cendes, F, Concha, L, Desmond, PM, Domin, M, Duncan, JS, Focke, NK, Guerrini, R, Hamandi, K, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kowalczyk, MA, Kreilkamp, BAK, Kwan, P, Lariviere, S, Lenge, M, Lopez, SM, Martin, P, Mascalchi, M, Moreira, JCV, Morita-Sherman, ME, Pardoe, HR, Pariente, JC, Raviteja, K, Rocha, CS, Rodriguez-Cruces, R, Seeck, M, Semmelroch, MKHG, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Thomopoulos, SI, Velakoulis, D, Vivash, L, Weber, B, Yasuda, CL, Zhang, J, Thompson, PM, McDonald, CR, Sisodiya, SM, Whelan, CD, Hatton, SN, Huynh, K, Altmann, A, Ryten, M, Vezzani, A, Caligiuri, ME, Labate, A, Gambardella, A, Ives-Deliperi, V, Meletti, S, Munsell, BC, Bonilha, L, Tondelli, M, Rebsamen, M, Rummel, C, Vaudano, AE, Wiest, R, Balachandra, AR, Bargallo, N, Bartolini, E, Bernasconi, A, Bernasconi, N, Bernhardt, B, Caldairou, B, Carr, SJA, Cavalleri, GL, Cendes, F, Concha, L, Desmond, PM, Domin, M, Duncan, JS, Focke, NK, Guerrini, R, Hamandi, K, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kowalczyk, MA, Kreilkamp, BAK, Kwan, P, Lariviere, S, Lenge, M, Lopez, SM, Martin, P, Mascalchi, M, Moreira, JCV, Morita-Sherman, ME, Pardoe, HR, Pariente, JC, Raviteja, K, Rocha, CS, Rodriguez-Cruces, R, Seeck, M, Semmelroch, MKHG, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Thomopoulos, SI, Velakoulis, D, Vivash, L, Weber, B, Yasuda, CL, Zhang, J, Thompson, PM, and McDonald, CR

Abstract

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

Published
2022

10. Surface-based tracking for short association fibre tractography

Author

Shastin, D., Genc, S., Parker, G.D., Koller, K., Tax, C.M.W., Evans, J., Hamandi, K., Gray, W.P., Jones, D.K., Chamberland, M., Shastin, D., Genc, S., Parker, G.D., Koller, K., Tax, C.M.W., Evans, J., Hamandi, K., Gray, W.P., Jones, D.K., and Chamberland, M.

Abstract

Contains fulltext : 286295.pdf (Publisher’s version ) (Open Access)

Published
2022

11. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Author

Lariviere, S, Royer, J, Rodriguez-Cruces, R, Paquola, C, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, CL, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Lui, E, Vaudano, AE, Meletti, S, Tondelli, M, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Winston, GP, Griffin, A, Singh, A, Tiwari, VK, Kreilkamp, BAK, Lenge, M, Guerrini, R, Hamandi, K, Foley, S, Ruber, T, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Kaestner, E, Hatton, SN, Vos, SB, Caciagli, L, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, Bernhardt, BC, Lariviere, S, Royer, J, Rodriguez-Cruces, R, Paquola, C, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, CL, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Lui, E, Vaudano, AE, Meletti, S, Tondelli, M, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Winston, GP, Griffin, A, Singh, A, Tiwari, VK, Kreilkamp, BAK, Lenge, M, Guerrini, R, Hamandi, K, Foley, S, Ruber, T, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Kaestner, E, Hatton, SN, Vos, SB, Caciagli, L, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, and Bernhardt, BC

Abstract

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Published
2022

12. Surface-based tracking for short association fibre tractography.

Author

Shastin, D, Genc, S, Parker, GD, Koller, K, Tax, CMW, Evans, J, Hamandi, K, Gray, WP, Jones, DK, Chamberland, M, Shastin, D, Genc, S, Parker, GD, Koller, K, Tax, CMW, Evans, J, Hamandi, K, Gray, WP, Jones, DK, and Chamberland, M

Abstract

It is estimated that in the human brain, short association fibres (SAF) represent more than half of the total white matter volume and their involvement has been implicated in a range of neurological and psychiatric conditions. This population of fibres, however, remains relatively understudied in the neuroimaging literature. Some of the challenges pertinent to the mapping of SAF include their variable anatomical course and proximity to the cortical mantle, leading to partial volume effects and potentially affecting streamline trajectory estimation. This work considers the impact of seeding and filtering strategies and choice of scanner, acquisition, data resampling to propose a whole-brain, surface-based short (≤30-40 mm) SAF tractography approach. The framework is shown to produce longer streamlines with a predilection for connecting gyri as well as high cortical coverage. We further demonstrate that certain areas of subcortical white matter become disproportionally underrepresented in diffusion-weighted MRI data with lower angular and spatial resolution and weaker diffusion weighting; however, collecting data with stronger gradients than are usually available clinically has minimal impact, making our framework translatable to data collected on commonly available hardware. Finally, the tractograms are examined using voxel- and surface-based measures of consistency, demonstrating moderate reliability, low repeatability and high between-subject variability, urging caution when streamline count-based analyses of SAF are performed.

Published
2022

13. Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study

Author

Spitzer, H, Ripart, M, Whitaker, K, D'Arco, F, Mankad, K, Chen, AA, Napolitano, A, De Palma, L, De Benedictis, A, Foldes, S, Humphreys, Z, Zhang, K, Hu, W, Mo, J, Likeman, M, Davies, S, Guttler, C, Lenge, M, Cohen, NT, Tang, Y, Wang, S, Chari, A, Tisdall, M, Bargallo, N, Conde-Blanco, E, Pariente, JC, Pascual-Diaz, S, Delgado-Martinez, I, Perez-Enriquez, C, Lagorio, I, Abela, E, Mullatti, N, O'Muircheartaigh, J, Vecchiato, K, Liu, Y, Caligiuri, ME, Sinclair, B, Vivash, L, Willard, A, Kandasamy, J, McLellan, A, Sokol, D, Semmelroch, M, Kloster, AG, Opheim, G, Ribeiro, L, Yasuda, C, Rossi-Espagnet, C, Hamandi, K, Tietze, A, Barba, C, Guerrini, R, Gaillard, WD, You, X, Wang, I, Gonzalez-Ortiz, S, Severino, M, Striano, P, Tortora, D, Kalviainen, R, Gambardella, A, Labate, A, Desmond, P, Lui, E, O'Brien, T, Shetty, J, Jackson, G, Duncan, JS, Winston, GP, Pinborg, LH, Cendes, F, Theis, FJ, Shinohara, RT, Cross, JH, Baldeweg, T, Adler, S, Wagstyl, K, Spitzer, H, Ripart, M, Whitaker, K, D'Arco, F, Mankad, K, Chen, AA, Napolitano, A, De Palma, L, De Benedictis, A, Foldes, S, Humphreys, Z, Zhang, K, Hu, W, Mo, J, Likeman, M, Davies, S, Guttler, C, Lenge, M, Cohen, NT, Tang, Y, Wang, S, Chari, A, Tisdall, M, Bargallo, N, Conde-Blanco, E, Pariente, JC, Pascual-Diaz, S, Delgado-Martinez, I, Perez-Enriquez, C, Lagorio, I, Abela, E, Mullatti, N, O'Muircheartaigh, J, Vecchiato, K, Liu, Y, Caligiuri, ME, Sinclair, B, Vivash, L, Willard, A, Kandasamy, J, McLellan, A, Sokol, D, Semmelroch, M, Kloster, AG, Opheim, G, Ribeiro, L, Yasuda, C, Rossi-Espagnet, C, Hamandi, K, Tietze, A, Barba, C, Guerrini, R, Gaillard, WD, You, X, Wang, I, Gonzalez-Ortiz, S, Severino, M, Striano, P, Tortora, D, Kalviainen, R, Gambardella, A, Labate, A, Desmond, P, Lui, E, O'Brien, T, Shetty, J, Jackson, G, Duncan, JS, Winston, GP, Pinborg, LH, Cendes, F, Theis, FJ, Shinohara, RT, Cross, JH, Baldeweg, T, Adler, S, and Wagstyl, K

Abstract

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

Published
2022

14. Detecting microstructural deviations in individuals with deep diffusion MRI tractometry.

Author

Chamberland, M, Genc, S, Tax, CMW, Shastin, D, Koller, K, Raven, EP, Cunningham, A, Doherty, J, van den Bree, MBM, Parker, GD, Hamandi, K, Gray, WP, Jones, DK, Chamberland, M, Genc, S, Tax, CMW, Shastin, D, Koller, K, Raven, EP, Cunningham, A, Doherty, J, van den Bree, MBM, Parker, GD, Hamandi, K, Gray, WP, and Jones, DK

Abstract

Most diffusion magnetic resonance imaging studies of disease rely on statistical comparisons between large groups of patients and healthy participants to infer altered tissue states in the brain; however, clinical heterogeneity can greatly challenge their discriminative power. There is currently an unmet need to move away from the current approach of group-wise comparisons to methods with the sensitivity to detect altered tissue states at the individual level. This would ultimately enable the early detection and interpretation of microstructural abnormalities in individual patients, an important step towards personalized medicine in translational imaging. To this end, Detect was developed to advance diffusion magnetic resonance imaging tractometry towards single-patient analysis. By operating on the manifold of white-matter pathways and learning normative microstructural features, our framework captures idiosyncrasies in patterns along white-matter pathways. Our approach paves the way from traditional group-based comparisons to true personalized radiology, taking microstructural imaging from the bench to the bedside.

Published
2021

18. Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study

Author

Lariviere, S, Rodriguez-Cruces, R, Royer, J, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, Bernhardt, BC, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, and Bernhardt, BC

Abstract

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

Published
2020

19. Uncovering a Role for the Dorsal Hippocampal Commissure in Recognition Memory

Author

Postans, M., Parker, G. D., Lundell, H., Ptito, M., Hamandi, K., Gray, W. P., Aggleton, J. P., Dyrby, T. B., Jones, D. K., Winter, M., Postans, M., Parker, G. D., Lundell, H., Ptito, M., Hamandi, K., Gray, W. P., Aggleton, J. P., Dyrby, T. B., Jones, D. K., and Winter, M.

Abstract

The dorsal hippocampal commissure (DHC) is a white matter tract that provides interhemispheric connections between temporal lobe brain regions. Despite the importance of these regions for learning and memory, there is scant evidence of a role for the DHC in successful memory performance. We used diffusion-weighted magnetic resonance imaging (DW-MRI) and white matter tractography to reconstruct the DHC in both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings demonstrate a close consistency between the known anatomy and tract reconstructions of the DHC. Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in nonhuman primates. Finally, we derived diffusion tensor MRI metrics from the DHC in a large sample of human subjects to investigate whether interindividual variation in DHC microstructure is predictive of memory performance. The mean diffusivity of the DHC correlated with performance in a standardized recognition memory task, an effect that was not reproduced in a comparison commissure tract-the anterior commissure. These findings highlight a potential role for the DHC in recognition memory, and our tract reconstruction approach has the potential to generate further novel insights into the role of this previously understudied white matter tract in both health and disease.

Published
2020

23. Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial

Author

Goldstein, Laura H, primary, Robinson, Emily J, additional, Mellers, John D C, additional, Stone, Jon, additional, Carson, Alan, additional, Reuber, Markus, additional, Medford, Nick, additional, McCrone, Paul, additional, Murray, Joanna, additional, Richardson, Mark P, additional, Pilecka, Izabela, additional, Eastwood, Carole, additional, Moore, Michele, additional, Mosweu, Iris, additional, Perdue, Iain, additional, Landau, Sabine, additional, Chalder, Trudie, additional, Abe, A-M, additional, Adab, N, additional, Agrawal, N, additional, Allroggen, H, additional, Alvares, D, additional, Andrews, T, additional, Angus-Leppan, H, additional, Aram, J, additional, Armstrong, R, additional, Atalaia, A, additional, Bagary, M, additional, Baldellou Lopez, M, additional, Bennett, M, additional, Black, T, additional, Blackburn, D, additional, Bodani, M, additional, Broadhurst, M, additional, Brockington, A, additional, Bruno, E, additional, Buckley, M, additional, Burness, C, additional, Callaghan, H, additional, Chalmers, R, additional, Chong, S, additional, Chowdhury, M, additional, Chowdury, F, additional, Cikurel, K, additional, Cocco, G, additional, Cock, H, additional, Cooper, S, additional, Cope, S, additional, Copping, A, additional, Day, E, additional, Delamont, R, additional, Dennis, G, additional, Derry, C, additional, Devlin, R, additional, Dickson, J.M., additional, Diehl, B, additional, Donnelly, C, additional, Duncan, S, additional, Edwards, M, additional, Ellawella, S, additional, Ellis, C, additional, Elvish, J, additional, Elwes, R, additional, Eriemo, S, additional, Eriksson, S, additional, Evans, K, additional, Faruqui, R, additional, Feehan, S, additional, Finnerty, G, additional, Flores, L, additional, Firth, N, additional, Fung, R, additional, Gardiner, P, additional, Graham, C, additional, Green-Thompson, Z, additional, Grunewald, R, additional, Hadden, R, additional, Hamandi, K, additional, Harding, R, additional, Harikrishnan, S, additional, Harrison, S, additional, Healy, H, additional, Hewamadduma, C, additional, Higgins, S, additional, Howell, S, additional, Hunt, H, additional, Hussain, A, additional, Innocente, M, additional, Jensch, G, additional, Johnson, M, additional, Jordan, H, additional, Karlsson, J, additional, Kelso, A, additional, Kemp, S, additional, Knibb, J, additional, Kock, N, additional, Koutroumanidis, M, additional, Kovac, S, additional, Kumar, G, additional, Laker, A, additional, Leschziner, G, additional, Liu, R, additional, Lozsadi, D, additional, Ludwig, L, additional, MacDonald, B, additional, MacGregor, L, additional, Maguire, M, additional, Manford, M, additional, Martino, D, additional, McCorry, D, additional, McGorlick, A, additional, McKeown, K, additional, McKevitt, F, additional, Meadow, A, additional, Memon, S, additional, Miorelli, A, additional, Mitchell, C, additional, Mitchell, T.N., additional, Moffitt, V, additional, Moran, N, additional, Morgan-Boon, A, additional, Moriarty, J, additional, Mula, M, additional, Mullatti, N, additional, Nashef, L, additional, O'Hara, D, additional, Oakley, L, additional, O'Sullivan, S, additional, Page, L, additional, Patel, D, additional, Petrochilos, P, additional, Phoenix, D, additional, Pickerell, W, additional, Pieters, T, additional, Poole, N, additional, Price, G, additional, Protheroe, D, additional, Pullicino, P, additional, Purnell, J, additional, Quirk, J, additional, Rajakulendran, S, additional, Read, J, additional, Ridha, B, additional, Rockliffe-Fidler, C, additional, Rowbottom, C, additional, Rugg-Gunn, F, additional, Sachar, A, additional, Saha, R, additional, Saldanha, G, additional, Samarasekera, S, additional, Sanchez Sanchez, V, additional, Santhouse, A, additional, Scholes, K, additional, Shetty, A, additional, Shotbolt, P, additional, Simkiss, R, additional, Singh, J, additional, Sivagnanasundaram, J, additional, Slaght, S, additional, Smith, P, additional, Sokhi, D, additional, Stanton, B, additional, Suvorova, L, additional, Tahir, T, additional, Taylor, R, additional, Teare, L, additional, Tedesco, L, additional, Teo, J, additional, Thorpe, J, additional, Toplis, L, additional, Tsakopoulou, M, additional, Tylova, I, additional, Vick, T, additional, Vinnicombe, J, additional, Walker, M, additional, Walsh, C, additional, Watson, G, additional, Webb, T, additional, Wehner, T, additional, Welch, K, additional, Weyrich, K, additional, Whittaker, M, additional, Wickremaratchi, M, additional, Wicks, L, additional, and Yogarajah, M, additional

Published
2020
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24. EpiNet as a way of involving more physicians and patients in epilepsy research: Validation study and accreditation process

Author

Bergin, P. S., Beghi, E., Sadleir, L. G., Brockington, A., Tripathi, M., Richardson, M. P., Bianchi, E., Srivastava, K., Jayabal, J., Legros, B., Ossemann, M., Mcgrath, N., Verrotti, A., Tan, H. J., Beretta, S., Frith, R., Iniesta, I., Whitham, E., Wanigasinghe, J., Ezeala-Adikaibe, B., Striano, P., Rosemergy, I., Walker, E. B., Alkhidze, M., Rodriguez-Leyva, I., Ramirez Gonzalez, J. A., D'Souza, W. J., Calle, A., Palacios, C., Cairns, A., Carney, P., Craig, D., Gill, D., Gupta, S., Lander, C., Laue-Gizzi, H., Hitchens, N., Kiley, M., Lawn, N., Reyneke, E., Riney, K., Tan, M., Thieban, M., Wong, C., van Rijckevorsel, G., Ferrari Strang, A. G., Gifoni, A., Helio, L., Monnerat, B., Brna, P., Donner, E., Jacques, S., Jette, N., Mclachlan, R., Mohamed, I., Tran, T. P. Y., Bo, X., Fan, S., Guang, Y., Li, M., Wang, K., Zhang, S., Ladino, L., Christensen, J., Kӧlmel, M. S., Nikanorova, M., Uusitalo, A., Vieira, P., Auvin, S., Ediberidze, T., Gogatishvili, N., Jishkariani, T., Dennig, D., Grimmer, A., Michaelis, R., Schubert-Bast, S., Stephani, C., Stodieck, S., Vollbrandt, M., Zellner, A., Zafeiriou, D., Fogarasi, A., Halasz, P., Chaurasia, R. N., Jain, S., Nair, R., Passi, P., Rajadhyaksha, S., Sattaluri, S. J., Shah, H., Udani, V., Costello, D., Aguglia, U., Bartocci, A., Benna, P., Ferlazzo, E., Laino, D., Spalice, A., Zanchi, C., Ali, A., Lim, K. S., Ramirez, A., Anderson, N., Barber, A., Cariga, P., Cleland, J., Child, N., Davis, S., Dayal, V., Dickson, C., Doran, J., Duncan, R., Giri, P., Herd, M., Hutchinson, D., Jones, B., Kao, J., Kilfoyle, D., Mottershead, J., Muir, C., Nolan, M., Pereira, J., Ranta, A., Sadani, S., Simpson, M., Spooner, C., Timmings, P., Walker, E., Wei, D., Willoughby, E., Wong, E., Wu, T., Olusola, T., Mahmud, H., Mogul, Z., Espinoza, J., Vizarreta, J. H., Baeta, E. M., Teotonio, R., Jocic-Jakubi, B., Lukic, S., Korosec, M., Zgur, T., Eguilaz, M. G., Asztely, F., Sithinamsuwan, P., Anderson, J., Auce, P., Desurkar, A., Hamandi, K., Kelso, A., Sanchez, V., Sidra, A., Smith, P., Wehner, T., Winston, G., Andrade, E., Bensalem-Owen, M., Boudreau, M., Caller, T., Chapman, K., Chari, G., Davis, K., Droker, B., El-Hagrassy, M., Eliashiv, D., Eze, C., Heck, C., Kabir, A., Kolesnik, D., Lam, A., Lopez, J., Maamoon, T., Cohen, J. M., Maganti, R., Nwankwo, C., Park, K., Proteasa, S., Sandok, E., Seinfield, S., Toub, J., Wirrell, E., Arbildi, M., Thien, T. T., UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (MGD) Service de neurologie

Subjects
0301 basic medicine, medicine.medical_specialty, Validation study, education, Alternative medicine, Multicenter collaboration, Diagnostic accuracy, Accreditation, 03 medical and health sciences, Epilepsy, Clinical trials, 0302 clinical medicine, Clinical Trials, Multicentre Collaboration, medicine, health care economics and organizations, Kappa value, business.industry, medicine.disease, Invited Original Research, Clinical trial, 030104 developmental biology, Neurology, Family medicine, Etiology, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study, Biomedical engineering
Abstract

Objective\ud \ud EpiNet was established to encourage epilepsy research. EpiNet is used for multicenter cohort studies and investigator‐led trials. Physicians must be accredited to recruit patients into trials. Here, we describe the accreditation process for the EpiNet‐First trials.\ud Methods\ud \ud Physicians with an interest in epilepsy were invited to assess 30 case scenarios to determine the following: whether patients have epilepsy; the nature of the seizures (generalized, focal); and the etiology. Information was presented in two steps for 23 cases. The EpiNet steering committee determined that 21 cases had epilepsy. The steering committee determined by consensus which responses were acceptable for each case. We chose a subset of 18 cases to accredit investigators for the EpiNet‐First trials. We initially focused on 12 cases; to be accredited, investigators could not diagnose epilepsy in any case that the steering committee determined did not have epilepsy. If investigators were not accredited after assessing 12 cases, 6 further cases were considered. When assessing the 18 cases, investigators could be accredited if they diagnosed one of six nonepilepsy patients as having possible epilepsy but could make no other false‐positive errors and could make only one error regarding seizure classification.\ud Results\ud \ud Between December 2013 and December 2014, 189 physicians assessed the 30 cases. Agreement with the steering committee regarding the diagnosis at step 1 ranged from 47% to 100%, and improved when information regarding tests was provided at step 2. One hundred five of the 189 physicians (55%) were accredited for the EpiNet‐First trials. The kappa value for diagnosis of epilepsy across all 30 cases for accredited physicians was 0.70.\ud Significance\ud \ud We have established criteria for accrediting physicians using EpiNet. New investigators can be accredited by assessing 18 case scenarios. We encourage physicians with an interest in epilepsy to become EpiNet‐accredited and to participate in these investigator‐led clinical trials.

Published
2017
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25. Characteristics of 698 patients with dissociative seizures: A UK multicenter study

Author

Goldstein, LH, Robinson, EJ, Reuber, M, Chalder, T, Callaghan, H, Eastwood, C, Landau, S, McCrone, P, Medford, N, Mellers, JDC, Moore, M, Mosweu, I, Murray, J, Perdue, I, Pilecka, I, Richardson, MP, Carson, A, Stone, J, Abe, A-M, Adab, N, Agrawal, N, Allroggen, H, Alvares, D, Andrews, T, Angus-Leppan, H, Aram, J, Armstrong, R, Atalaia, A, Bagary, M, Bennett, M, Black, T, Blackburn, D, Bodani, M, Broadhurst, M, Brockington, A, Bruno, E, Buckley, M, Burness, C, Chalmers, R, Chong, S, Chowdhury, M, Chowdury, F, Cikurel, K, Cocco, G, Cock, H, Cooper, S, Cope, S, Copping, A, Day, E, Delamont, R, Dennis, G, Derry, C, Devlin, R, Dickson, JM, Diehl, B, Donnelly, C, Duncan, S, Edwards, M, Ellawella, S, Ellis, C, Elvish, J, Elwes, R, Eriemo, S, Eriksson, S, Evans, K, Faruqui, R, Feehan, S, Finnerty, G, Flores, L, Firth, N, Fung, R, Gardiner, P, Graham, C, Green-Thompson, Z, Grunewald, R, Hadden, R, Hamandi, K, Harding, R, Harikrishnan, S, Harrison, S, Healy, H, Hewamadduma, C, Higgins, S, Howell, S, Hunt, H, Hussain, A, Innocente, M, Jensch, G, Johnson, M, Jordan, H, Karlsson, J, Kelso, A, Kemp, S, Knibb, J, Kock, N, Koutroumanidis, M, Kovac, S, Kumar, G, Laker, A, Leschziner, G, Liu, R, Lozsadi, D, Ludwig, L, MacDonald, B, MacGregor, L, Maguire, M, Manford, M, Martino, D, McCorry, D, McGorlick, A, McKeown, K, McKevitt, F, Meadow, A, Memon, S, Miorelli, A, Mitchell, C, Mitchell, TN, Moffitt, V, Moran, N, Morgan-Boon, A, Moriarty, J, Mula, M, Mullatti, N, Nashef, L, O'Hara, D, Oakley, L, O'Sullivan, S, Page, L, Patel, D, Petrochilos, P, Phoenix, D, Pickerell, W, Pieters, T, Poole, N, Price, G, Protheroe, D, Pullicino, P, Purnell, J, Quirk, J, Rajakulendran, S, Read, J, Ridha, B, Rockliffe-Fidler, C, Rowbottom, C, Rugg-Gunn, F, Sachar, A, Saha, R, Saldanha, G, Samarasekera, S, Sanchez, VS, Santhouse, A, Scholes, K, Shetty, A, Shotbolt, P, Simkiss, R, Singh, J, Sivagnanasundaram, J, Slaght, S, Smith, P, Sokhi, D, Stanton, B, Suvorova, L, Tahir, T, Taylor, R, Teare, L, Tedesco, L, Teo, J, Thorpe, J, Toplis, L, Tsakopoulou, M, Tylova, I, Vick, T, Vinnicombe, J, Walker, M, Walsh, C, Watson, G, Webb, T, Wehner, T, Welch, K, Weyrich, K, Whittaker, M, Wickremaratchi, M, Wicks, L, Yogarajah, M, and Grp, CODESS

Abstract

Objective\ud We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology.\ud \ud Methods\ud We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations.\ud \ud Results\ud In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed.\ud \ud Significance\ud Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

Published
2019

28. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Author

Whelan, Cd, Altmann, A, Botía, Ja, Jahanshad, N, Hibar, Dp, Absil, J, Alhusaini, S, Alvim, Mkm, Auvinen, P, Bartolini, E, Bergo, Fpg, Bernardes, T, Blackmon, K, Braga, B, Caligiuri, Me, Calvo, A, Carr, Sj, Chen, J, Chen, S, Cherubini, A, David, P, Domin, M, Foley, S, França, W, Haaker, G, Isaev, D, Keller, Ss, Kotikalapudi, R, Kowalczyk, Ma, Kuzniecky, R, Langner, S, Lenge, M, Leyden, Km, Liu, M, Loi, Rq, Martin, P, Mascalchi, M, Morita, Me, Pariente, Jc, Rodríguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, Mk, Severino, M, Thomas, Rh, Tondelli, M, Tortora, D, Vaudano, AE39, Vivash, L40, von Podewils F42, Wagner, J43, Weber, B43, Yao, Y46, Yasuda, CL7, Zhang, G47, Bargalló, N15, Bender, B26, Bernasconi, N, Bernasconi, A, Bernhardt, Bc, Blümcke, I, Carlson, C, Cavalleri, Gl, Cendes, F, Concha, L, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP51, Focke, Nk, Gambardella, A, Guerrini, R, Hamandi, K, Jackson, Gd, Kälviäinen, R, Kochunov, P, Kwan, P, Labate, A, McDonald, Cr, Meletti, S, O'Brien, Tj, Ourselin, S, Richardson MP Striano, P, Thesen, T, Wiest, R, Zhang, J, Vezzani, A, Ryten, M, Thompson, Pm, and Sisodiya, Sm.

Subjects
MRI, epilepsy, precentral gyrus, thalamus
Published
2018

34. Hyperconnectivity in juvenile myoclonic epilepsy: A network analysis

Author

Caeyenberghs, Karen, Powell, H.W.R., Thomas, R.H., Brindley, L., Church, C., Evans, J., Muthukumaraswamy, S.D., Jones, D.K., Hamandi, K., Caeyenberghs, Karen, Powell, H.W.R., Thomas, R.H., Brindley, L., Church, C., Evans, J., Muthukumaraswamy, S.D., Jones, D.K., and Hamandi, K.

Published
2015

38. An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity

Author

Carmichael, D. W., Hamandi, K., Laufs, H., Duncan, J. S., Thomas, D. L., and Lemieux, L.

Subjects
EEG-fMRI, generalized spike wave, BOLD, perfusion, correlation, neurovascular coupling, nervous system, behavioral disciplines and activities, psychological phenomena and processes
Abstract

In pathological conditions interpretation of functional magnetic resonance imaging (fMRI) results can be difficult. This is due to a reliance on the assumed coupling between neuronal activity and changes in cerebral blood flow (CBF) and oxygenation. We wanted to investigate the coupling between blood oxygen level dependant contrast (BOLD) and CBF time courses in epilepsy patients with generalised spike wave activity (GSW) to better understand the underlying mechanisms behind the EEG-fMRI signal changes observed, especially in regions of negative BOLD response (NBR). Four patients with frequent GSW were scanned with simultaneous electroencephalographic (EEG)-fMRI with BOLD and arterial spin labeling (ASL) sequences. We examined the relationship between simultaneous CBF and BOLD measurements by looking at the correlation of the two signals in terms of percentage signal change on a voxel-by-voxel basis. This method is not reliant on coincident activation. BOLD and CBF were positively correlated in patients with epilepsy during background EEG activity and GSW. The subject average value of the ΔCBF/ΔBOLD slope lay between +19 and +36 and also showed spatial variation which could indicate areas with altered vascular response. There was not a significant difference between ΔCBF/ΔBOLD during GSW, suggesting that neurovascular coupling to BOLD signal is generally maintained between states and, in particular, within areas of NBR.

Published
2008

39. BOLD and perfusion changes during epileptic generalised spike wave activity

Author

Hamandi, K., Laufs, H., Nöth, U., Carmichael, D. W., Duncan, J. S., and Lemieux, L.

Subjects
genetic structures, nervous system, EEG–fMRI, generalized spike wave activity, ASL–fMRI, behavioral disciplines and activities
Abstract

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity.

Published
2008

48. Irreversible damage to the spinal cord after spinal Anaesthesia. (Proceedings)

Author

Hamandi, K., Mottershead, J., Lewis, T., Ormerod, I.E.C., and Ferguson, I.T.

Subjects
Peridural anesthesia -- Complications and side effects, Spinal cord injuries -- Causes of -- Complications and side effects, Health, Psychology and mental health, Complications and side effects, Causes of
Abstract

Neurological features are a recognised rare complication of spinal and epidural anaesthesia. A number of mechanisms of injury to the spinal cord have been suggested. We report five cases of [...]

Published
2002

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