Thornton 2 AbstractBackground: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset.

Summary:Purpose: The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs.Methods: We evaluated the data of the first consecutive and prospectively collected patients in therapy with TPM.Results: Follow-up information was available for 431 patients. PAEs occurred in 103 (23.9%) patients; M/F ratio, 55:48; mean age (±SD), 36.5 ± 11.2. In 46 (10.7%) patients, an affective disorder developed; in 16 (3.7%), a psychotic disorder; in 24 (5.6%), aggressive behavior with or without irritability; in 17 (3.9%), other behavior abnormalities such as agitated behavior, anger/hostility behavior, or anxiety. High starting dose and rapid titration schedule were relevant for the development of PAEs. Family psychiatric history and family history of epilepsy, personal history of febrile convulsions, psychiatric history, and presence of tonic-atonic seizures were found to be significant risk factors. Low seizure frequency before starting TPM and TPM/lamotrigine coadministration had a protective effect for PAEs.Conclusions: We found that PAEs associated with TPM were related to the titration schedule of the drug and that a unique patient profile is suggested by the clinical history. Key Words: Topiramate-Epilepsy-Psychosis-DepressionAdverse effect.Topiramate (TPM) is a sulphamated monosaccharide, structurally distinct from other antiepileptic drugs (AEDs) (1). It has reliably been shown to improve seizure control in children and adults with refractory partial epilepsy and is effective in the treatment of generalized tonic-clonic seizures (2-5). Generally, TPM has demonstrated a favorable side-effect profile, the main identified problems being related to its cognitive adverse effects (6). During recent years, prescribing habits for the drug were changed in our institution. Between 1995 and 1998, for most of the patients, the starting dose was 50 mg/day, with an escalation regimen of 50 mg every 2 weeks to maximum doses; from the second half of 1998, practice changed, and the starting dose and increments were of 25 mg.Psychopathology in epilepsy can be related to three major variables: patient-related risk factors, AED toxicity (7), and epilepsy-related risk factors.The aim of our study was to evaluate the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with TPM. We sought to classify PAEs, assess their severity relative to TPM use, and define a clinical patient profile at risk. METHODSThe case records of the first consecutive and prospectively collected patients treated with TPM in the tertiary referral epilepsy clinics at the National Hospital for Neurology and Neurosurgery (Chalfont and Queen Square sites) were reviewed. The methods of data collection were reported previously (8).Demographic and clinical details were extracted from the case records, and the classification of the epilepsy...

Simultaneous EEG–fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings.Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG–fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA).ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG–fMRI cluster was less than 33 mm, in agreement with previous studies.We conclude that simultaneous ESI and EEG–fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks.

word count: 250 Manuscript Click here to view linked References 2 ABSTRACT Background

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BackgroundSudden unexpected death in epilepsy (SUDEP) is common among young people with epilepsy. Individuals who are at high risk of SUDEP exhibit regional brain structural and functional connectivity (FC) alterations compared with low-risk patients. However, less is known about network-based FC differences among critical cortical and subcortical autonomic regulatory brain structures in temporal lobe epilepsy (TLE) patients at high risk of SUDEP.Methods32 TLE patients were risk-stratified according to the following clinical criteria: age of epilepsy onset, duration of epilepsy, frequency of generalized tonic–clonic seizures, and presence of nocturnal seizures, resulting in 14 high-risk and 18 low-risk cases. Resting-state functional magnetic resonance imaging (rs-fMRI) signal time courses were extracted from 11 bilateral cortical and subcortical brain regions involved in autonomic and other regulatory processes. After computing all pairwise correlations, FC matrices were analyzed using the network-based statistic. FC strength among the 11 brain regions was compared between the high- and low-risk patients. Increases and decreases in FC were sought, using high-risk > low-risk and low-risk > high-risk contrasts (with covariates age, gender, lateralization of epilepsy, and presence of hippocampal sclerosis).ResultsHigh-risk TLE patients showed a subnetwork with significantly reduced FC (t = 2.5, p = 0.029) involving the thalamus, brain stem, anterior cingulate, putamen and amygdala, and a second subnetwork with significantly elevated FC (t = 2.1, p = 0.031), which extended to medial/orbital frontal cortex, insula, hippocampus, amygdala, subcallosal cortex, brain stem, thalamus, caudate, and putamen.ConclusionTLE patients at high risk of SUDEP showed widespread FC differences between key autonomic regulatory brain regions compared to those at low risk. The altered FC revealed here may help to shed light on the functional correlates of autonomic disturbances in epilepsy and mechanisms involved in SUDEP. Furthermore, these findings represent possible objective biomarkers which could help to identify high-risk patients and enhance SUDEP risk stratification via the use of non-invasive neuroimaging, which would require validation in larger cohorts, with extension to patients with other epilepsies and subjects who succumb to SUDEP.

EEG source imaging (ESI) is a model-based imaging technique that integrates temporal and spatial components of EEG to identify the generating source of electrical potentials recorded on the scalp. Recent advances in computer technologies have made the analysis of ESI data less time-consuming, and have rekindled interest in this technique as a clinical diagnostic tool. On the basis of the available body of evidence, ESI seems to be a promising tool for epilepsy evaluation; however, the precise clinical value of ESI in presurgical evaluation of epilepsy and in localization of eloquent cortex remains to be investigated. In this Review, we describe two fundamental issues in ESI; namely, the forward and inverse problems, and their solutions. The clinical application of ESI in surgical planning for patients with medically refractory focal epilepsy, and its use in source reconstruction together with invasive recordings, is also discussed. As ESI can be used to map evoked responses, we discuss the clinical utility of this technique in cortical mapping-an essential process when planning resective surgery for brain regions that are in close proximity to eloquent cortex.

Summary Objective The processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusive, but centrally mediated cardiovascular or respiratory collapse is suspected. Volume changes in brain areas mediating recovery from extreme cardiorespiratory challenges may indicate failure mechanisms and allow prospective identification of SUDEP risk. Methods We retrospectively imaged SUDEP cases (n = 25), patients comparable for age, sex, epilepsy syndrome, localization, and disease duration who were high‐risk (n = 25) or low‐risk (n = 23), and age‐ and sex‐matched healthy controls (n = 25) with identical high‐resolution T1‐weighted scans. Regional gray matter volume, determined by voxel‐based morphometry, and segmentation‐derived structure sizes were compared across groups, controlling for total intracranial volume, age, and sex. Results Substantial bilateral gray matter loss appeared in SUDEP cases in the medial and lateral cerebellum. This was less prominent in high‐risk subjects and absent in low‐risk subjects. The periaqueductal gray, left posterior and medial thalamus, left hippocampus, and bilateral posterior cingulate also showed volume loss in SUDEP. High‐risk subjects showed left thalamic volume reductions to a lesser extent. Bilateral amygdala, entorhinal, and parahippocampal volumes increased in SUDEP and high‐risk patients, with the subcallosal cortex enlarged in SUDEP only. Disease duration correlated negatively with parahippocampal volume. Volumes of the bilateral anterior insula and midbrain in SUDEP cases were larger the closer to SUDEP from magnetic resonance imaging. Significance SUDEP victims show significant tissue loss in areas essential for cardiorespiratory recovery and enhanced volumes in areas that trigger hypotension or impede respiratory patterning. Those changes may shed light on SUDEP pathogenesis and prospectively detect patterns identifying those at risk.