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The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain from June 26th to 29th 2016. For the first time, the last day of the conference focused solely on new medical devices and neuromodulation. The current article summarises the presentations of that day, focusing first on EEG- and ECG based methods and devices for seizure detection. These methodologies form the basis for novel cardiac-based methods of vagal nerve and responsive deep brain stimulation that rely on the prediction or early detection of seizures and that are also included in this article.

The Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV) took place in Madrid, Spain from May 13th to 16th 2018. Again, presentations on new medical devices and neuromodulation and discussions on device-related regulatory aspects were included in the programme. The virtual special issue on "neuromodulation" summarises the presentations focusing firstly, on the pre-clinical developments and the difficulties of clinical trial designs for neuromodulatory therapies, including vagus nerve stimulation (VNS) and Brain-Responsive Neurostimulation (RNS), and the use of transcutaneous vagus nerve stimulation (tVNS) as a potential screening tool for determining the efficacy of neuromodulatory treatments in individual patients; secondly, on wearable devices for seizure monitoring through indices of peripheral sympathetic nervous activity, the use of such devices in combination with biofeedback for the treatment of epilepsy, and its potential for improving epilepsy specialist services, particularly in remote areas.

Summary The prevailing understanding of generalized epilepsy is shaped by the traditional definition that “the responsible neuronal discharge takes place, if not throughout the entire grey matter, then at least in the greater part of it and simultaneously on both sides”. This view is no longer tenable since concurrent findings using multiple methods have accumulated to reveal the role of bilateral networks of distributed and selective cortical and subcortical structures in so-called generalized ictogenesis. Most of this research has been focused on juvenile myoclonic epilepsy (JME), which today is commonly considered the archetypical syndrome of the idiopathic generalized epilepsies. Based upon recent research in the fields of clinical epileptology, neuropsychology and psychiatry, clinical neurophysiology, neuroimaging and epilepsy genetics this article, for the first time, unites these new findings into a comprehensive nosological view. Genetically determined dysfunctions of important cognitive systems like visuomotor coordination and linguistic communication appear now as key mechanisms of seizure generation in JME. This review suggests a new paradigm to consider JME as a system disorder of the brain analogous to other neurological system disorders.

Summary Purpose To investigate cerebral grey matter (GM) volumetric abnormalities in temporal lobe epilepsy (TLE) patients who develop de novo depression following TLE surgery using voxel-based morphometry (VBM). Methods We retrospectively examined pre-surgical grey matter (GM) volumes in 30 patients with TLE due to unilateral left-sided hippocampal sclerosis using 1.5-T MRI scan, which were segmented with optimised VBM parameters and normalised to a sample template using DARTEL, with SPM8 software. Voxel-wise GM differences between patients that developed de novo post-surgical depression ( n =5) were compared with patients with no pre- or postoperative psychiatric diagnoses ( n =25), using independent samples t -tests with age, gender and secondary generalised tonic–clonic seizures (SGTCS) as covariates ( p Key findings Reduced preoperative bilateral GM in orbitofrontal cortices (OFC) and ipsilateral cingulate gyrus and thalamus were significantly associated with the development of de novo depression within 4 years postoperatively. Further analyses revealed no differences in seizure freedom (ILAE 1 vs 2–6) or postoperative memory decline between the groups. Significance Although the development of postoperative de novo depression following TLE surgery is likely to be multi-factorial, our results suggest that bilateral OFC and ipsilateral cingulate gyrus and thalamic atrophy in left-sided TLE patients may play a modulatory role. Abnormalities in these areas have also been implicated in primary mood disorders. Prospective neuroimaging studies with larger cohorts are warranted to replicate these results, and further elucidate the neural correlates of de novo depression.

Objective Verbal fluency functional MRI (fMRI) is used for predicting language deficits after anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE), but primarily engages frontal lobe areas. In this observational study we investigated fMRI paradigms using visual and auditory stimuli, which predominately involve language areas resected during ATLR. Methods Twenty-three controls and 33 patients (20 left (LTLE), 13 right (RTLE)) were assessed using three fMRI paradigms: verbal fluency, auditory naming with a contrast of auditory reversed speech; picture naming with a contrast of scrambled pictures and blurred faces. Results Group analysis showed bilateral temporal activations for auditory naming and picture naming. Correcting for auditory and visual input (by subtracting activations resulting from auditory reversed speech and blurred pictures/scrambled faces respectively) resulted in left-lateralised activations for patients and controls, which was more pronounced for LTLE compared to RTLE patients. Individual subject activations at a threshold of T>2.5, extent >10 voxels, showed that verbal fluency activated predominantly the left inferior frontal gyrus (IFG ) in 90% of LTLE, 92% of RTLE, and 65% of controls, compared to right IFG activations in only 15% of LTLE and RTLE and 26% of controls. Middle temporal (MTG) or superior temporal gyrus (STG) activations were seen on the left in 30% of LTLE, 23% of RTLE, and 52% of controls, and on the right in 15% of LTLE, 15% of RTLE, and 35% of controls. Auditory naming activated temporal areas more frequently than did verbal fluency (LTLE: 93%/73%; RTLE: 92%/58%; controls: 82%/70% (left/right)). Controlling for auditory input resulted in predominantly left-sided temporal activations. Picture naming resulted in temporal lobe activations less frequently than did auditory naming (LTLE 65%/55%; RTLE 53%/46%; controls 52%/35% (left/right)). Controlling for visual input had left-lateralising effects. Conclusion Auditory and picture naming activated temporal lobe structures, which are resected during ATLR, more frequently than did verbal fluency. Controlling for auditory and visual input resulted in more left-lateralised activations. We hypothesise that these paradigms may be more predictive of postoperative language decline than verbal fluency fMRI.

This prospective uncontrolled open study explored the efficacy and long-term tolerability of sulthiame (STM) in 52 patients with refractory epilepsy and learning disability. Thirty-six patients completed a 14-weeks trial period with STM and 22 patients achieved a seizure reduction>50% of which three became seizure-free. Twenty-six patients continued taking STM for now up to 120 weeks, one continued to be seizure-free, whilst five patients stopped STM during this period. These promising observations require further evaluation in a controlled trial.

In contrast to the well studied long-term memory dysfunction of temporal lobe epilepsy (TLE) syndromes, data on memory performance of frontal lobe epilepsy (FLE) patients are limited and controversial. Behavioural and functional neuroimaging findings suggest that different regions within the frontal lobes contribute to long-term memory functioning, offering an explanation for the variability on memory function observed on patients with frontal lobe damage. Available evidence suggests memory dysfunction is a common finding on neuropsychological evaluation of FLE patients but prevalence and underlying mechanisms remain poorly understood. Variability on memory performance reported in FLE studies suggest this deficit may be dependant on the areas involved in seizure generation and spread. Recent research findings and the application of cognitive fMRI paradigms to FLE patients holds the promise of increasing understanding further.

Purpose: To characterize the pattern of cognitive deficits in patients with temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to examine the relationship between neuropsychological deficits and Magnetization transfer imaging. Methods: Twenty patients with TLE and interictal psychosis were compared to 20 non-psychotic TLE patients. Patients were matched with respect to premorbid IQ, age and conventional MRI findings. A battery of neuropsychological tests was administered. The neuropsychological tests which showed significant group differences were used for correlational analysis with magnetization transfer ratio (MTR) which provides a quantitative measure of macromolecular structural integrity. Results: Patients with interictal psychosis were significantly more impaired on executive and semantic memory tasks than the non-psychotic TLE group. Vocabulary test scores correlated significantly with MTR reduction in the left fusiform gyrus in the psychotic but not the non-psychotic group. Discussion: In this study, patients with TLE and interictal psychosis were more cognitively impaired than non-psychotic TLE patients. Our findings suggest that the cognitive deterioration in these patients may occur as the illness progresses and the causes for this are probably multifactorial. Our study also provides further evidence that MTR may be useful in investigating structural correlates of cognitive impairment.

The pathophysiological and neuroanatomical bases of reading epilepsy (RE) are unclear. We performed video-EEG, high quality MRI and [11C]diprenorphine PET in a patient with RE to detect structural and functional abnormalities. EEG showed multifocal seizure onset bilaterally in temporal and fronto-central regions. MRI was normal, whereas [11C]diprenorphine PET revealed peri-ictal opioid binding decrease in both temporal lobes and the left frontal lobe. These findings confirm that RE is due to abnormal activity in the network subserving reading.

Summary Purpose Topiramate (TPM) is known to cause language impairment in healthy volunteers and patients with epilepsy. We assessed the effects of TPM on functional language networks in both patients with focal epilepsies and healthy controls using functional magnetic resonance imaging (fMRI). Methods We obtained fMRI data in 24 controls and 35 patients with frontal lobe epilepsy using a simple verbal fluency (VF) paradigm. Eight of the 35 patients were treated with TPM in polytherapy. We compared cognitive task related activations and de-activations in patients taking TPM with patients taking other AEDs and healthy controls. In a longitudinal pilot study with VF-fMRI paradigm, we studied two patients with focal epilepsies twice, prior to starting and on stable doses of TPM, two patients twice, before and after tapering TPM completely and two healthy controls twice, before and after single doses of 200 mg TPM. Key findings Cross sectional analyses of VF-fMRI showed a reduction in the task-related deactivation of the default mode network (DMN) in patients taking TPM. The longitudinal study corroborated these findings as both chronic administration and a single dose of TPM were associated with impaired categorical verbal fluency and disruption of task-related deactivations. Significance Similar neuropsychological and fMRI findings in patients and healthy controls indicate a specific effect of TPM in default mode network areas that may be essential components of the language network. Our preliminary data suggest a mechanism by which TPM impairs cognitive processing during language function and highlights the sensitivity of fMRI to detect the effects of AEDs on cognitive brain networks.