Validating epilepsy diagnoses in routinely collected data.

PURPOSE: Anonymised, routinely-collected healthcare data is increasingly being used for epilepsy research. We validated algorithms using general practitioner (GP) primary healthcare records to identify people with epilepsy from anonymised healthcare data within the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK. METHOD: A reference population of 150 people with definite epilepsy and 150 people without epilepsy was ascertained from hospital records and linked to records contained within SAIL (containing GP records for 2.4 million people). We used three different algorithms, using combinations of GP epilepsy diagnosis and anti-epileptic drug (AED) prescription codes, to identify the reference population. RESULTS: Combining diagnosis and AED prescription codes had a sensitivity of 84% (95% ci 77-90) and specificity of 98% (95-100) in identifying people with epilepsy; diagnosis codes alone had a sensitivity of 86% (80-91) and a specificity of 97% (92-99); and AED prescription codes alone achieved a sensitivity of 92% (70-83) and a specificity of 73% (65-80). Using AED codes only was more accurate in children achieving a sensitivity of 88% (75-95) and specificity of 98% (88-100). CONCLUSION: GP epilepsy diagnosis and AED prescription codes can be confidently used to identify people with epilepsy using anonymised healthcare records in Wales, UK.

Hyperconnectivity in juvenile myoclonic epilepsy: a network analysis.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas. METHODS: Using diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients. RESULTS: Neuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance. CONCLUSIONS: Our findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients.

Tunable mega-ampere electron current propagation in solids by dynamic control of lattice melt.

The influence of lattice-melt-induced resistivity gradients on the transport of mega-ampere currents of fast electrons in solids is investigated numerically and experimentally using laser-accelerated protons to induce isochoric heating. Tailoring the heating profile enables the resistive magnetic fields which strongly influence the current propagation to be manipulated. This tunable laser-driven process enables important fast electron beam properties, including the beam divergence, profile, and symmetry to be actively tailored, and without recourse to complex target manufacture.

Annular fast electron transport in silicon arising from low-temperature resistivity.

Fast electron transport in Si, driven by ultraintense laser pulses, is investigated experimentally and via 3D hybrid particle-in-cell simulations. A transition from a Gaussian-like to an annular fast electron beam profile is demonstrated and explained by resistively generated magnetic fields. The results highlight the potential to completely transform the beam transport pattern by tailoring the resistivity-temperature profile at temperatures as low as a few eV.

Long term monitoring in refractory epilepsy: the Gowers Unit experience.

INTRODUCTION: Guidelines from the National Institute for Health and Clinical Excellence (NICE) and the International League Against Epilepsy recommend long term EEG monitoring (LTM) in patients for whom seizure or syndrome type is unclear, and in patients for whom it is proving difficult to differentiate between epilepsy and non-epileptic attack disorder (NEAD). The purpose of this study was to evaluate this recommended use of LTM in the setting of an epilepsy tertiary referral unit. METHODS: This study reviewed the case notes of all admissions to the Sir William Gowers Unit at the National Society for Epilepsy in the years 2004 and 2005. A record was made of the type, duration and result of all LTM performed both prior to and during the admission. Pre- and post-admission diagnoses were compared, and patients were divided according to whether LTM had resulted in a change in diagnosis, refinement in diagnosis or no change in diagnosis. The distinction between change and a refinement in the diagnosis was made on the basis of whether or not this alteration resulted in a change in management. RESULTS: 612 patients were admitted during 2004 and 2005, 230 of whom were referred for diagnostic clarification. Of these, LTM was primarily responsible for a change in diagnosis in 133 (58%) and a refinement of diagnosis in 29 (13%). In 65 (29%) patients the diagnosis remained the same after LTM. In those patients in whom there was a change in diagnosis, the most common change was in distinguishing epilepsy from NEAD in 73 (55%) and in distinguishing between focal and generalised epilepsy in 47 (35%). LTM was particularly helpful in differentiating frontal lobe seizures from generalised seizures and non-epileptic attacks. Inpatient ambulatory EEG proved as effective as video telemetry in helping to distinguish between NEAD, focal and generalised epilepsy. DISCUSSION: The study revealed that LTM led to an alteration in the diagnosis of 71% of patients referred to a tertiary centre for diagnostic clarification of possible epilepsy. Although LTM is relatively expensive, time consuming and of limited availability, this needs to be balanced against the considerable financial and social cost of misdiagnosed and uncontrolled seizures. This service evaluation supports the use of performing LTM (either video or ambulatory) in a specialist setting in patients who present diagnostic difficulty.

Tractography of the parahippocampal gyrus and material specific memory impairment in unilateral temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. METHODS: We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. RESULTS: There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. CONCLUSION: Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.

Combined EEG-fMRI and tractography to visualise propagation of epileptic activity.

In a patient with refractory temporal lobe epilepsy, EEG-fMRI showed activation in association with left anterior temporal interictal discharges, in the left temporal, parietal and occipital lobes. Dynamic causal modelling suggested propagation of neural activity from the temporal focus to the area of occipital activation. Tractography showed connections from the site of temporal lobe activation to the site of occipital activation. This demonstrates the principle of combining EEG-fMRI and tractography to delineate the pathways of propagation of epileptic activity.

Imaging language pathways predicts postoperative naming deficits.

Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used MR tractography preoperatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR.

Preoperative fMRI predicts memory decline following anterior temporal lobe resection.

BACKGROUND: Anterior temporal lobe resection (ATLR) benefits many patients with refractory temporal lobe epilepsy (TLE) but may be complicated by material specific memory impairments, typically of verbal memory following left ATLR, and non-verbal memory following right ATLR. Preoperative memory functional MRI (fMRI) may help in the prediction of these deficits. OBJECTIVE: To assess the value of preoperative fMRI in the prediction of material specific memory deficits following both left- and right-sided ATLR. METHODS: We report 15 patients with unilateral TLE undergoing ATLR; eight underwent dominant hemisphere ATLR and seven non-dominant ATLR. Patients performed an fMRI memory paradigm which examined the encoding of words, pictures and faces. RESULTS: Individual patients with relatively greater ipsilateral compared with contralateral medial temporal lobe activation had greater memory decline following ATLR. This was the case for both verbal memory decline following dominant ATLR and for non-verbal memory decline following non-dominant ATLR. For verbal memory decline, activation within the dominant hippocampus was predictive of postoperative memory change whereas activation in the non-dominant hippocampus was not. CONCLUSION: These findings suggest that preoperative memory fMRI may be a useful non-invasive predictor of postoperative memory change following ATLR and provide support for the functional adequacy theory of hippocampal function. They also suggest that fMRI may provide additional information, over that provided by neuropsychology, for use in the prediction of postoperative memory decline.

Abnormalities of language networks in temporal lobe epilepsy.

Functional magnetic resonance imaging (fMRI) in patients with temporal lobe epilepsy (TLE) has demonstrated reorganisation of language functions with greater involvement of the non-dominant hemisphere. The structural brain connections supporting this atypical language dominance have not previously been identified. We performed fMRI of language functions and imaging of white matter connections using MR tractography in 14 patients with unilateral TLE and hippocampal sclerosis and 10 controls. Verb generation and reading comprehension paradigms were used to define functional regions which were used to generate starting regions for tractography. Controls and right TLE patients had a left-lateralised pattern of both language-related activations and the associated structural connections. Left TLE patients showed more symmetrical language activations, along with reduced left hemisphere and increased right hemisphere structural connections. Subjects with more lateralised functional activation had also more highly lateralised connecting pathways. We provide evidence for structural reorganisation of white matter tracts that reflects the altered functional language lateralisation in left TLE patients. The combination of fMRI and tractography offers a promising tool for studying the reorganisation of language functions in many neurological conditions and may prove useful in predicting language deficits following temporal lobe surgery.

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis.

PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material-specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients. METHODS: We report 14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI memory paradigm of word, picture, and face encoding. RESULTS: Compared with controls, patients with left TLE demonstrated less left MTL and greater right MTL activation and patients with right TLE demonstrated less right MTL and greater left MTL activation. Correlations between fMRI activation and memory performance revealed greater activation in the damaged left hippocampus to be correlated with better verbal memory performance in left TLE patients and greater right hippocampal activation to be correlated with better nonverbal memory in right TLE patients. Conversely, greater fMRI activation in the contralateral hippocampus correlated with worse memory performance. CONCLUSIONS: Our findings suggest that memory function in unilateral TLE is better when it is sustained by activation within the damaged hippocampus and that reorganization to the undamaged MTL is an inefficient process, incapable of preserving memory function.

Hemispheric asymmetries in language-related pathways: a combined functional MRI and tractography study.

Functional lateralization is a feature of human brain function, most apparent in the typical left-hemisphere specialization for language. A number of anatomical and imaging studies have examined whether structural asymmetries underlie this functional lateralization. We combined functional MRI (fMRI) and diffusion-weighted imaging (DWI) with tractography to study 10 healthy right-handed subjects. Three language fMRI paradigms were used to define language-related regions in inferior frontal and superior temporal regions. A probabilistic tractography technique was then employed to delineate the connections of these functionally defined regions. We demonstrated consistent connections between Broca's and Wernicke's areas along the superior longitudinal fasciculus bilaterally but more extensive fronto-temporal connectivity on the left than the right. Both tract volumes and mean fractional anisotropy (FA) were significantly greater on the left than the right. We also demonstrated a correlation between measures of structure and function, with subjects with more lateralized fMRI activation having a more highly lateralized mean FA of their connections. These structural asymmetries are in keeping with the lateralization of language function and indicate the major structural connections underlying this function.

MR tractography predicts visual field defects following temporal lobe resection.

A superior homonymous quadrantanopia is a well recognized complication of anterior temporal lobe resection and occurs because of disruption of the Meyer loop, the anterior part of the optic radiation. The authors used diffusion tensor imaging tractography to visualize the optic radiation before and after surgery, demonstrating the disruption of Meyer loop in a patient who developed a quadrantanopia. Preoperative imaging of the optic radiation will be useful in predicting visual field defects following temporal lobe resection.

Material-specific lateralization of memory encoding in the medial temporal lobe: blocked versus event-related design.

Lesion-deficit studies have provided evidence for a functional dissociation between the left medial temporal lobe (MTL) mediating verbal memory encoding and right MTL mediating non-verbal memory encoding. While a small number of functional MRI studies have demonstrated similar findings, none has looked specifically for material-specific lateralization using subsequent memory effects. In addition, in many fMRI studies, encoding activity has been located in posterior MTL structures, at odds with lesion-deficit and positron emission tomography (PET) evidence. In this study, we used an event-related fMRI memory encoding paradigm to demonstrate a material-specific lateralization of encoding in the medial temporal lobes of ten healthy control subjects. Activation was left-lateralized for word encoding, bilateral for picture encoding, and right-lateralized for face encoding. Secondly, we demonstrated the locations of activations revealed using an event-related analysis to be more anterior than those revealed using a blocked analysis of the same data. This suggests that anterior MTL structures underlie memory encoding as judged by subsequent memory effects, and that more posterior activity detected in other fMRI studies is related to deficiencies of blocked designs in the analysis of memory encoding.

Functional magnetic resonance imaging for assessment of language and memory in clinical practice.

PURPOSE OF REVIEW: There has been considerable interest in the role that functional magnetic resonance imaging (fMRI) may play in the assessment of patients with epilepsy. This review considers recent progress in this field and the current role of fMRI in the preoperative assessment of language and memory function. RECENT FINDINGS: Many studies have compared fMRI with the intracarotid amytal test for establishing language dominance, with most showing over 90% concordance between the two tests. Atypical dominance is greater in patients with left temporal lobe epilepsy and has been shown to be associated with increased epileptic activity. Preoperative fMRI has been used to predict language deficits following left anterior temporal lobe resection. A variety of paradigms have been used to assess memory function, and novel paradigms have demonstrated robust medial temporal lobe activation. Different patterns of encoding activity have been observed between patients with unilateral temporal lobe epilepsy and control individuals. SUMMARY: The application of fMRI paradigms used in cognitive neuroscience to patients with epilepsy is complicated by several factors. Although fMRI is increasingly being used clinically to establish language dominance, further work is required to localize accurately those specific language functions that are most at risk following surgery. Memory paradigms are not yet validated for use in surgical planning, although methodological and technical advances should make this possible in the near future. Further studies looking at the reorganization of language and memory function after surgery are also required.

The application of functional MRI of memory in temporal lobe epilepsy: a clinical review.

Functional MRI (fMRI) is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions. Since its introduction, there has been considerable speculation regarding the role it may play in the presurgical assessment of temporal lobe epilepsy (TLE). This review considers the progress made to date in using fMRI to investigate memory processing in the medial temporal lobe in normal subjects and in those with TLE. Results so far suggest that fMRI will be incorporated into the presurgical assessment of TLE in the coming years to improve definition of eloquent cerebral areas, with the objective of minimizing the adverse cognitive sequelae of anterior temporal lobe resection.

Noninvasive in vivo demonstration of the connections of the human parahippocampal gyrus.

MR tractography techniques provide a method for noninvasively studying white matter pathways in vivo. In this study we have used diffusion tensor imaging (DTI) and the fast marching tractography (FMT) algorithm to plot the structural connectivity of the human parahippocampal gyrus (PHG) in 10 healthy subjects, using seed points selected in the anterior parahippocampal gyrus. Our results demonstrate connectivity between the parahippocampal gyrus and the anterior temporal lobe, orbitofrontal areas, posterior temporal lobe and extrastriate occipital lobe via the lingual and fusiform gyri. We also demonstrate for the first time noninvasively direct connectivity between the parahippocampal gyrus and the hippocampus itself. These results agree with previous histological tract-tracing studies in animals. The connections demonstrated between neocortical areas and the hippocampus via the parahippocampal gyrus may provide the structural basis for theoretical models of memory and higher visual processing.

Epilepsy and perisylvian polymicrogyria in a patient with Kabuki syndrome.

Kabuki syndrome is a dysmorphogenic syndrome which has been reported in over 300 patients since it was first described in Japan in 1981. In addition to its cardinal features (typical facies, mild-to-moderate learning disability, short stature, skeletal anomalies, and dermatoglyphic abnormalities with persistent foetal fingerpads), neurological anomalies are frequently reported, including epilepsy in 8% of those with the syndrome. We present here a 22-year-old white female patient with refractory partial epilepsy, Kabuki syndrome, and bilateral perisylvian polymicrogyria on MRI: the first reported case of this association. The aetiology of the syndrome, including the diverse genetic changes recognized, is then discussed.