John S Duncan

Publications of John S Duncan

• Correlating 3T MRI and histopathology in patients undergoing epilepsy surgery.

  Authors: Georgia Lockwood-Estrin, Maria Thom, Niels K Focke, Mark R Symms, Lillian Martinian, Sanjay M Sisodiya, John S Duncan, Sofia H Eriksson

  Journal of neuroscience methods. 03/2012; 205(1):182-9.

  To investigate whether specific semi-quantitative 3T MRI parameters are associated with particular histological features in temporal lobe specimens in epilepsy surgery patients whose conventional MRITo investigate whether specific semi-quantitative 3T MRI parameters are associated with particular histological features in temporal lobe specimens in epilepsy surgery patients whose conventional MRI scan appeared normal. These MRI techniques have the potential to visualise subtle structural abnormalities currently undetected on conventional MRI; but correlation between pre-operative in vivo MRI and histopathology is needed to understand the basis of these MRI abnormalities. Predicting subtle histopathology with semi-quantitative MRI techniques could contribute to pre-surgical evaluation of epilepsy patients. MRI techniques: normalised FLAIR signal intensity (nFSI), grey matter probability and diffusion tensor imaging (DTI) were correlated with quantitative histopathological measures: NeuN (neuronal nuclear antigen); GFAP (glial fibrillary acidic protein) and MBP (myelin basic protein) field fractions and stereological neuronal densities obtained in grey and white matter regions in twenty-four patients who underwent anterior temporal lobe resections. There were no significant correlations between the histopathological measurements and MRI values in grey or white matter in macroscopically normal appearing tissue. Findings suggest that in macroscopically normal appearing tissue, the studied semiquantitative MRI measurements are not significantly related to the measures of gliosis, neuronal loss/gain and myelin used in the current study. Studies of macroscopically abnormal tissue as well as improvements to the MRI techniques may increase the sensitivity of future correlative studies to improve our understanding of the histopathological basis of MRI signal characteristics.

• Imaging language networks before and after anterior temporal lobe resection: Results of a longitudinal fMRI study.

  Authors: Silvia B Bonelli, Pamela J Thompson, Mahinda Yogarajah, Christian Vollmar, Robert H W Powell, Mark R Symms, Andrew W McEvoy, Caroline Micallef, Matthias J Koepp, John S Duncan

  Epilepsia. 03/2012; 53(4):639-650.

  Purpose:  Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impairPurpose:  Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left-hemisphere-dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods:  We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE-MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings:  Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance:  In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.

• Optic radiation tractography and vision in anterior temporal lobe resection.

  Authors: Gavin P Winston, Pankaj Daga, Jason Stretton, Marc Modat, Mark R Symms, Andrew W McEvoy, Sebastien Ourselin, John S Duncan

  Annals of neurology. 03/2012; 71(3):334-41.

  Anterior temporal lobe resection (ATLR) is an effective treatment for refractory temporal lobe epilepsy but may result in a contralateral superior visual field deficit (VFD) that precludes driving inAnterior temporal lobe resection (ATLR) is an effective treatment for refractory temporal lobe epilepsy but may result in a contralateral superior visual field deficit (VFD) that precludes driving in the seizure-free patient. Diffusion tensor imaging (DTI) tractography can delineate the optic radiation preoperatively and stratify risk. It would be advantageous to incorporate display of tracts into interventional magnetic resonance imaging (MRI) to guide surgery. We studied 20 patients undergoing ATLR. Structural MRI scans, DTI, and visual fields were acquired before and 3 to 12 months following surgery. Tractography of the optic radiation was performed on preoperative images and propagated onto postoperative images. The anteroposterior extent of the damage to Meyer's loop was determined, and visual loss was quantified using Goldmann perimetry. Twelve patients (60%) suffered a VFD (10-92% of upper quadrant; median, 39%). Image registration took <3 minutes and predicted that Meyer's loop was 4.4 to 18.7mm anterior to the resection margin in these patients, but 0.0 to 17.6mm behind the resection margin in the 8 patients without VFD. The extent of damage to Meyer's loop significantly correlated with the degree of VFD and explained 65% of the variance in this measure. The optic radiation can be accurately delineated by tractography and propagated onto postoperative images. The technique is fast enough to propagate accurate preoperative tractography onto intraoperative scans acquired during neurosurgery, with the potential to reduce the risk of VFD. ANN NEUROL 2012;

• Classification and Lateralization of Temporal Lobe Epilepsies with and without Hippocampal Atrophy Based on Whole-Brain Automatic MRI Segmentation.

  Authors: Shiva Keihaninejad, Rolf A Heckemann, Ioannis S Gousias, Joseph V Hajnal, John S Duncan, Paul Aljabar, Daniel Rueckert, Alexander Hammers

  PloS one. 01/2012; 7(4):e33096.

  Brain images contain information suitable for automatically sorting subjects into categories such as healthy controls and patients. We sought to identify morphometric criteria for distinguishingBrain images contain information suitable for automatically sorting subjects into categories such as healthy controls and patients. We sought to identify morphometric criteria for distinguishing controls (n = 28) from patients with unilateral temporal lobe epilepsy (TLE), 60 with and 20 without hippocampal atrophy (TLE-HA and TLE-N, respectively), and for determining the presumed side of seizure onset. The framework employs multi-atlas segmentation to estimate the volumes of 83 brain structures. A kernel-based separability criterion was then used to identify structures whose volumes discriminate between the groups. Next, we applied support vector machines (SVM) to the selected set for classification on the basis of volumes. We also computed pairwise similarities between all subjects and used spectral analysis to convert these into per-subject features. SVM was again applied to these feature data. After training on a subgroup, all TLE-HA patients were correctly distinguished from controls, achieving an accuracy of 96 ± 2% in both classification schemes. For TLE-N patients, the accuracy was 86 ± 2% based on structural volumes and 91 ± 3% using spectral analysis. Structures discriminating between patients and controls were mainly localized ipsilaterally to the presumed seizure focus. For the TLE-HA group, they were mainly in the temporal lobe; for the TLE-N group they included orbitofrontal regions, as well as the ipsilateral substantia nigra. Correct lateralization of the presumed seizure onset zone was achieved using hippocampi and parahippocampal gyri in all TLE-HA patients using either classification scheme; in the TLE-N patients, lateralization was accurate based on structural volumes in 86 ± 4%, and in 94 ± 4% with the spectral analysis approach. Unilateral TLE has imaging features that can be identified automatically, even when they are invisible to human experts. Such morphometric image features may serve as classification and lateralization criteria. The technique also detects unsuspected distinguishing features like the substantia nigra, warranting further study.

• Neuropsychological function in patients who have had epilepsy surgery: a long-term follow-up.

  Authors: Sallie Baxendale, Pamela J Thompson, John S Duncan

  Epilepsy & behavior : E&B. 11/2011; 23(1):24-9.

  We examined the relationship between seizure outcomes and long-term changes in memory and intellectual function in 70 patients who had undergone temporal lobe resection for medically intractableWe examined the relationship between seizure outcomes and long-term changes in memory and intellectual function in 70 patients who had undergone temporal lobe resection for medically intractable epilepsy. Patients were assessed on four occasions: preoperatively (T1), 3 months postoperatively (T2), 1 year postoperatively (T3), and more than 5 years postoperatively (T4). The majority of patients had stable memory function across the assessments. However, many were functioning below the 15th percentile on the test norms preoperatively, with little capacity for further decline. All patients who demonstrated a progressive decline in verbal or visual learning were female and continued to experience seizures postoperatively. Progressive postoperative declines in memory function are associated with poor postoperative seizure control. These patterns can be obscured in group analyses that do not take into account baseline levels of function. Neuropsychological scores must be set in the context of the norms of the test and the associated capacity for further significant change over time to maximize the clinical relevance of long-term surgical follow-up studies.

• Mapping hemodynamic correlates of seizures using fMRI: A review.

  Authors: Umair J Chaudhary, John S Duncan, Louis Lemieux

  Human brain mapping. 11/2011;

  Functional magnetic resonance imaging (fMRI) is able to detect changes in blood oxygenation level associated with neuronal activity throughout the brain. For more than a decade, fMRI alone or inFunctional magnetic resonance imaging (fMRI) is able to detect changes in blood oxygenation level associated with neuronal activity throughout the brain. For more than a decade, fMRI alone or in combination with simultaneous EEG recording (EEG-fMRI) has been used to investigate the hemodynamic changes associated with interictal and ictal epileptic discharges. This is the first literature review to focus on the various fMRI acquisition and data analysis methods applied to map epileptic seizure-related hemodynamic changes from the first report of an fMRI scan of a seizure to the present day. Two types of data analysis approaches, based on temporal correlation and data driven, are explained and contrasted. The spatial and temporal relationship between the observed hemodynamic changes using fMRI and other non-invasive and invasive electrophysiological and imaging data is considered. We then describe the role of fMRI in localizing and exploring the networks involved in spontaneous and triggered seizure onset and propagation. We also discuss that fMRI alone and combined with EEG hold great promise in the investigation of seizure-related hemodynamic changes non-invasively in humans. We think that this will lead to significant improvements in our understanding of seizures with important consequences for the treatment of epilepsy. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.

• Epileptic networks in focal cortical dysplasia revealed using electroencephalography-functional magnetic resonance imaging.

  Authors: Rachel Thornton, Serge Vulliemoz, Roman Rodionov, David W Carmichael, Umair J Chaudhary, Beate Diehl, Helmut Laufs, Christian Vollmar, Andrew W McEvoy, Matthew C Walker, Fabrice Bartolomei, Maxime Guye, Patrick Chauvel, John S Duncan, Louis Lemieux

  Annals of neurology. 11/2011; 70(5):822-37.

  Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magneticSurgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome. Twenty-three patients with FCD-associated focal epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were overlaid on coregistered T1-weighted MRI scans fused with computed tomography scans showing the intracranial electrodes. IED-related hemodynamic changes were compared with the SOZ on icEEG and postoperative outcome at 1 year. Twelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED-related hemodynamic changes. The fMRI results were concordant with the SOZ in 5 of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50% reduction in seizure frequency following resective surgery. The remaining 6 of 11 patients had widespread or discordant regions of IED-related fMRI signal change. Five of 6 had either a poor surgical outcome (<50% reduction in seizure frequency) or widespread SOZ precluding surgery. Comparison of EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional information about the SOZ in FCD. Widely distributed discordant regions of IED-related hemodynamic change appear to be associated with a widespread SOZ and poor postsurgical outcome.

• The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study.

  Authors: Jane de Tisi, Gail S Bell, Janet L Peacock, Andrew W McEvoy, William F J Harkness, Josemir W Sander, John S Duncan

  Lancet. 10/2011; 378(9800):1388-95.

  Surgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome of epilepsy surgerySurgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome of epilepsy surgery in adults by establishing patterns of seizure remission and relapse after surgery. We report long-term outcome of surgery for epilepsy in 615 adults (497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and seven palliative procedures [corpus callosotomy, subpial transection]), with prospective annual follow-up for a median of 8 years (range 1-19). We used Kaplan-Meier survival analysis to estimate time to first seizure, and investigated patterns of seizure outcome. We used survival methods to estimate that 52% (95% CI 48-56) of patients remained seizure free (apart from simple partial seizures [SPS]) at 5 years after surgery, and 47% (42-51) at 10 years. Patients who had extratemporal resections were more likely to have seizure recurrence than were those who had anterior temporal resections (hazard ratio [HR] 2·0, 1·1-3·6; p=0·02); whereas for those having lesionectomies, no difference from anterior lobe resection was recorded. Those with SPS in the first 2 years after temporal lobe surgery had a greater chance of subsequent seizures with impaired awareness than did those with no SPS (2·4, 1·5-3·9). Relapse was less likely the longer a person was seizure free and, conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. 104 of 365 (28%) seizure-free individuals had discontinued drugs at latest follow-up. Neurosurgical treatment is appealing for selected people with refractory focal epilepsy. Our data provide realistic expectations and indicate the scope for further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy. UK Department of Health National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme, Epilepsy Society, Dr Marvin Weil Epilepsy Research Fund.

• Diffusion tensor imaging tractography of the optic radiation for epilepsy surgical planning: a comparison of two methods.

  Authors: Gavin P Winston, Laura Mancini, Jason Stretton, Jonathan Ashmore, Mark R Symms, John S Duncan, Tarek A Yousry

  Epilepsy research. 08/2011; 97(1-2):124-32.

  The optic radiation is a key white matter structure at risk during epilepsy surgery involving the temporal, parietal or occipital lobes. It shows considerable anatomical variability, cannot beThe optic radiation is a key white matter structure at risk during epilepsy surgery involving the temporal, parietal or occipital lobes. It shows considerable anatomical variability, cannot be delineated on clinical MRI sequences and damage may cause a disabling visual field deficit. Diffusion tensor imaging tractography allows non-invasive mapping of this pathway. Numerous methods have been published but direct comparison is difficult as patient, acquisition and analysis parameters differ. Two methods for delineating the optic radiation were applied to 6 healthy controls and 4 patients with epileptogenic lesions near the optic radiation. By comparing methods with the same datasets, many of the parameters could be controlled. The first method was previously developed to accurately identify Meyer's loop for planning anterior temporal lobe resection. The second aimed to address limitations of this method by using a more automated technique to reduce operator time and to depict the entire optic radiation. Whilst the core of the tract was common to both methods, there was significant variability between the methods. Method 1 gave a more consistent depiction of Meyer's loop with fewer spurious tracts. Method 2 gave a better depiction of the entire optic radiation, particularly in more posterior portions, but did not identify Meyer's loop in one patient. These results show that whilst tractography is a promising technique, there is significant variability depending on the method chosen even when the majority of parameters are fixed. Different methods may need to be chosen for surgical planning depending on the individual clinical situation.

• Automated MR image classification in temporal lobe epilepsy.

  Authors: Niels K Focke, Mahinda Yogarajah, Mark R Symms, Oliver Gruber, Walter Paulus, John S Duncan

  NeuroImage. 07/2011; 59(1):356-62.

  In those with drug refractory focal epilepsy, MR imaging is important for identifying structural causes of seizures that may be amenable to surgical treatment. In up to 25% of potential surgicalIn those with drug refractory focal epilepsy, MR imaging is important for identifying structural causes of seizures that may be amenable to surgical treatment. In up to 25% of potential surgical candidates, however, MRI is reported as unremarkable even when employing epilepsy specific sequences. Automated MRI classification is a desirable tool to augment the interpretation of images, especially when changes are subtle or distributed and may be missed on visual inspection. Support vector machines (SVM) have recently been described to be useful for voxel-based MR image classification. In the present study we sought to evaluate whether this method is feasible in temporal lobe epilepsy, with adequate accuracy. We studied 38 patients with hippocampal sclerosis and unilateral (mesial) temporal lobe epilepsy (mTLE) (20 left) undergoing presurgical evaluation and 22 neurologically normal control subjects. 3D T1-weighted images were acquired at 3T (GE Excite), segmented into tissue classes, normalized and smoothed with SPM8. Diffusion tensor imaging (DTI) and double echo images for T2 relaxometry were also acquired and processed. The SVM analysis was done with the libsvm software package in a leave-one-out cross-validation design and predictive accuracy was measured. Local weighting was applied by SPM F-contrast maps. Best accuracies were achieved using the gray matter based segmentation (90-100%) and mean diffusivity (95-97%). For the three-way classification, accuracies were 88 and 93% respectively. Local weighting generally improved the accuracies except in the FA-based processing for which no effect was noted. Removing the hippocampus from the analysis, on the other hand, reduced the obtainable diagnostic indices but these were still >90% for DTI-based methods and lateralization based on gray matter maps. These findings show that automated SVM image classification can achieve high diagnostic accuracy in mTLE and that voxel-based MRI can be used at the individual subject level. This could be helpful for screening assessments of MRI scans in patients with epilepsy and when no lesion is detected on visual evaluation.

• With or without spikes: localization of focal epileptic activity by simultaneous electroencephalography and functional magnetic resonance imaging.

  Authors: Frédéric Grouiller, Rachel C Thornton, Kristina Groening, Laurent Spinelli, John S Duncan, Karl Schaller, Michael Siniatchkin, Louis Lemieux, Margitta Seeck, Christoph M Michel, Serge Vulliemoz

  Brain : a journal of neurology. 07/2011; 134(Pt 10):2867-86.

  In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordingsIn patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40-70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode arrays.

• Seizure freedom following 49 years of refractory epilepsy due to focal cortical dysplasia.

  Authors: Joseph Anderson, Paul Harder, John S Duncan

  Journal of neurology, neurosurgery, and psychiatry. 06/2011; 82(6):706-7.

• Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study.

  Authors: Christian Vollmar, Jonathan O'Muircheartaigh, Gareth J Barker, Mark R Symms, Pamela Thompson, Veena Kumari, John S Duncan, Dieter Janz, Mark P Richardson, Matthias J Koepp

  Brain : a journal of neurology. 06/2011; 134(Pt 6):1710-9.

  Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities,Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

• The evolving classification of seizures and epilepsies.

  Authors: John S Duncan

  Epilepsia. 06/2011; 52(6):1204-5; discussion 1205-9.

• A dialogue with historical concepts of epilepsy from the Babylonians to Hughlings Jackson: persistent beliefs.

  Authors: Umair J Chaudhary, John S Duncan, Louis Lemieux

  Epilepsy & behavior : E&B. 06/2011; 21(2):109-14.

  Epilepsy is one of the few neurological disorders to be recognized in Antiquity. The etiology of epilepsy has evolved from affliction of evil spirits and bad omens to an organic disease of the brain.Epilepsy is one of the few neurological disorders to be recognized in Antiquity. The etiology of epilepsy has evolved from affliction of evil spirits and bad omens to an organic disease of the brain. Geographically separate cultures have recognized the diverse symptomatology of epilepsy from vigorous convulsions to spontaneous localized jerking since times immemorial. Similarly, the diagnostic procedures and treatment options have varied in different milieus. In this review we have followed the course of history chronologically from Babylonians to Hughlings Jackson, mapping the conceptual development of epilepsy and the origin of some of the positive and negative attitudes inherited into today's epileptology. Original writings, such as Hughlings Jackson's letters, and English translations of early Latin work, where available, were used as primary sources of information. Where primary sources were not accessible, we consulted research articles, books, and commentaries by eminent historians and epileptologists.

• The long-term retention of zonisamide in a large cohort of people with epilepsy at a tertiary referral centre.

  Authors: Claudia B Catarino, Emanuele Bartolini, Gail S Bell, Alan W C Yuen, John S Duncan, Josemir W Sander

  Epilepsy research. 05/2011; 96(1-2):39-44.

  Zonisamide (ZNS) is an antiepileptic drug (AED) with multiple putative mechanisms of action. It is chemically unrelated to other AEDs. It has been available in Japan since 1989 but was only licensedZonisamide (ZNS) is an antiepileptic drug (AED) with multiple putative mechanisms of action. It is chemically unrelated to other AEDs. It has been available in Japan since 1989 but was only licensed in Europe in 2005. Its efficacy and tolerability have been shown in several randomised controlled trials, but large studies on long-term performance in Western clinical practice are scarce. We assessed a large cohort of consecutive people who started ZNS at a tertiary epilepsy referral centre, from June 2005 to July 2009. Forty-six percent of the 417 people included were still taking ZNS at last follow-up, with an estimated retention rate at three years of 30%. Almost one third of the population reported a period of improvement in terms of seizure reduction of at least six months duration whilst on ZNS. Sixteen people became seizure free for at least six months and seven of these were seizure free for one year or more. Adverse events occurred in 58%, frequently CNS-related. People on three or more AEDs and people starting zonisamide at 25mg daily rather than 50mg or more, were more likely to discontinue ZNS. Retention rates for ZNS were similar to those previously reported, and comparable to lamotrigine, topiramate, pregabalin, higher than gabapentin, and lower than levetiracetam.

• Hippocampal activation correlates with visual confrontation naming: fMRI findings in controls and patients with temporal lobe epilepsy.

  Authors: Silvia B Bonelli, Rob Powell, Pamela J Thompson, Mahinda Yogarajah, Niels K Focke, Jason Stretton, Christian Vollmar, Mark R Symms, Cathy J Price, John S Duncan, Matthias J Koepp

  Epilepsy research. 05/2011; 95(3):246-54.

  In patients with left temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) decreased naming ability is common, suggesting a critical role for the medial left temporal lobe in this task. WeIn patients with left temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) decreased naming ability is common, suggesting a critical role for the medial left temporal lobe in this task. We investigated the integrity of language networks with functional MRI (fMRI) in controls and TLE patients. We performed an fMRI verbal fluency paradigm in 22 controls and 66 patients with unilateral mesial TLE (37 left HS, 29 right HS). Verbal fluency and naming ability were investigated as part of the standard presurgical neuropsychological assessment. Naming ability was assessed using a visual confrontation naming test. Left TLE patients had significantly lower naming scores than controls and those with right TLE. Right TLE patients performed less well than controls, but better than those with left TLE. Left TLE had significantly lower scores for verbal fluency than controls. In controls and right TLE, left hippocampal activation during the verbal fluency task was significantly correlated with naming, characterised by higher scores in subjects with greater hippocampal fMRI activation. In left TLE no correlation with naming scores was seen in the left hippocampus, but there was a significant correlation in the left middle and inferior frontal gyri, not observed in controls and right TLE. In left and right TLE, out of scanner verbal fluency scores significantly correlated with fMRI activation for verbal fluency in the left middle and inferior frontal gyri. Good confrontation naming ability depends on the integrity of the hippocampus and the connecting fronto-temporal networks. Functional MRI activation in the left hippocampus during verbal fluency is associated with naming function in healthy controls and patients with right TLE. In left TLE, there was evidence of involvement of the left frontal lobe when naming was more proficient, most likely reflecting a compensatory response due to the ongoing epileptic activity and/or underlying pathology.

• Diffusion tensor imaging tractography to visualize the relationship of the optic radiation to epileptogenic lesions prior to neurosurgery.

  Authors: Gavin P Winston, Mahinda Yogarajah, Mark R Symms, Andrew W McEvoy, Caroline Micallef, John S Duncan

  Epilepsia. 05/2011; 52(8):1430-8.

  About one-third of patients with epilepsy are refractory to medical treatment and may be amenable to surgery. However, in patients with lesions on or near the presumed course of the optic radiation,About one-third of patients with epilepsy are refractory to medical treatment and may be amenable to surgery. However, in patients with lesions on or near the presumed course of the optic radiation, the potential benefits of resection must be balanced against the risk of a visual field deficit. This study demonstrates the utility of diffusion tensor imaging (DTI) tractography in delineating the course of the optic radiation and its relationship to the epileptogenic lesion prior to epilepsy surgery. Anatomic and DTI scans were acquired on 10 patients with medically refractory epilepsy undergoing presurgical evaluation at the National Hospital for Neurology and Neurosurgery. Five patients underwent surgery and repeat scans postoperatively. The optic radiation was delineated and visualized in relation to the lesions on anatomic images and in three-dimensional (3D) reconstructions. Preoperative and postoperative visual fields were acquired by Goldmann perimetry. The entire optic radiation was reliably delineated bilaterally in all patients. The results provide helpful additional information in informing the patient of the risks of surgery and in planning the surgical procedure and approach. Postoperative imaging findings correlated with the visual field data. The optic radiation shows significant anatomic variability, but can be reliably delineated by tractography. Because surgical disruption of the optic radiation has serious consequences for the patient, DTI tractography is a useful technique in this population. Future integration with real-time neuronavigation will minimize the risks of neurosurgery.

• Epilepsy in 2010: Refinement of optimal medical and surgical treatments.

  Authors: John S Duncan

  Nature reviews. Neurology. 02/2011; 7(2):72-4.

• Integrating structural and diffusion MR information for optic radiation localisation in focal epilepsy patients.

  Authors: Pankaj Daga, Gavin Winston, Marc Modat, Manuel Jorge Cardoso, Jason Stretton, Mark R. Symms, Andrew W. McEvoy, David J. Hawkes, John S. Duncan, Sébastien Ourselin

  Proceedings of the 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2011, March 30 - April 2, 2011, Chicago, Illinois, USA; 01/2011