Add-on topiramate in the treatment of refractory partial-onset epilepsy: Clinical experience of outpatient epilepsy clinics from 11 general hospitals

SummaryAn open, prospective, observational study was performed to assess efficacy and adverse-event profile of topiramate as add-on therapy in epilepsy. Outpatient neurology clinics from 11 general hospitals in Greece participated in the study. In total, 211 patients with treatment resistant partial-onset seizures who met the inclusion criteria, were studied. After baseline evaluation, topiramate was given at a target dose of 200mg/day over a 1-month titration period. In the subsequent maintenance period, the topiramate dose could be varied according to the clinical results. Patients were followed for in total 6 months, with monthly visits and regular physical, neurological and laboratory examinations. Seizure frequencies decreased to 35–40% of baseline values following 3 months of treatment and remained relatively constant thereafter. The average monthly seizure frequency over the 6-month study period was 4.61, compared to 9.21 at baseline. The number of responders (patients with at least 50% reduction in seizure frequency) followed a similar pattern, i.e., increase during the first 3 months levelling off at a final 80–85% response rate. Of those completing the study, 30% had been seizure-free for at least 3 months and 12% for 5 months. Topiramate was well tolerated, no deviations in laboratory values were found. Adverse events appeared to occur less frequently, and antiepileptic effects were more pronounced in this prospective open-label study than in earlier reports from randomised controlled trials. The nature of the patient population and the application of individualised dose optimisation are proposed as contributing factors to explain the favourable results of this study

Independent component analysis: a reliable alternative to general linear model for task-based fMRI

BackgroundFunctional magnetic resonance imaging (fMRI) is a valuable tool for the presurgical evaluation of patients undergoing neurosurgeries. Although many pre-processing steps have been modified according to advances in recent years, statistical analysis has remained largely the same since the first days of fMRI. In this study, we examined the ability of Independent Component Analysis (ICA) to separate the activation of a language task in fMRI, and we compared it with the results of the General Lineal Model (GLM).MethodsSixty patients undergoing evaluation for brain surgery due to various brain lesions and/or epilepsy and 20 control subjects completed an fMRI language mapping protocol that included three tasks, resulting in 259 fMRI scans. Depending on brain lesion characteristics, patients were allocated to (1) static/chronic not-expanding lesions (Group 1) and (2) progressive/expanding lesions (Group 2). GLM and ICA statistical maps were evaluated by fMRI experts to assess the performance of each technique.ResultsIn the control group, ICA and GLM maps were similar without any superiority of either technique. In Group 1 and Group 2, ICA performed statistically better than GLM, with a p-value of < 0.01801 and < 0.0237, respectively. This indicated that ICA performs as well as GLM when the subjects are able to cooperate well (less movement, good task performance), but ICA could outperform GLM in the patient groups. When both techniques were combined, 240 out of 259 scans produced reliable results, showing that the sensitivity of task-based fMRI can be increased when both techniques are integrated with the clinical setup.ConclusionICA may be slightly more advantageous, compared to GLM, in patients with brain lesions, across the range of pathologies included in our population and independent of symptoms chronicity. Our findings suggest that GLM analysis may be more susceptible to brain activity perturbations induced by a variety of lesions or scanner-induced artifacts due to motion or other factors. In our research, we demonstrated that ICA is able to provide fMRI results that can be used in surgery, taking into account patient and task-wise aspects that differ from those when fMRI is used in research

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

BACKGROUND: Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. / METHODS: We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). / RESULTS: The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. / CONCLUSIONS: In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.

Thin isotropic FLAIR MR images at 1.5T increase the yield of focal cortical dysplasia transmantle sign detection in frontal lobe epilepsy

Objective The transmantle sign is a distinctive imaging marker of focal cortical dysplasia (FCD) type II in frontal lobe epilepsy (FLE), which is revealed predominantly by fluid-attenuation inversion recovery (FLAIR) sequences. Although the transmantle sign detection yield is high by routine imaging protocols for epilepsy at 3T, most centers around the world have access to 1.5T MR technology and FLE patients often receive negative imaging reports. This study investigates the optimization of transmantle detection yield at 1.5T by introducing a 3D thin-slice isotropic FLAIR sequence in the epilepsy imaging protocol. Methods Twenty FLE patients underwent diagnostic imaging for epilepsy with typical 2D thick-slice (3.0 mm) coronal FLAIR sequences and a 3D thin-slice (1.0 mm) isotropic FLAIR sequences at 1.5T, and transmantle sign detection yields and thickness measurements were derived. Results The 2D thick-slice FLAIR detected a transmantle sign in seven (35.0%) patients. The 3D isotropic thin-slice FLAIR detected a transmantle sign in eleven (55.0%) patients, thereby increasing the transmantle sign detection yield by 57.4%. The mean transmantle sign thickness by thick images was 12.3 mm, by thin images was 8.9 mm, and in the patients undetected by thick FLAIR was 3.5 mm. Significance This study showed that the extratemporal transmantle sign in FLE patients can be thin enough to be missed by thick-slice FLAIR sequences at 1.5T. By introducing 3D thin-slice isotropic FLAIR, false-negative reports can be reduced without reference for higher MR field structural scanning or other modalities, and more FLE patients can benefit from epilepsy surgery candidacy. © 2017 Elsevier B.V

Standardization of presurgical language fMRI in Greek population: Mapping of six critical regions

Abstract Background Mapping the language system has been crucial in presurgical evaluation especially when the area to be resected is near relevant eloquent cortex. Functional magnetic resonance imaging (fMRI) proved to be a noninvasive alternative of Wada test that can account not only for language lateralization but also for localization when appropriate tasks and MRI sequences are being used. The tasks utilized during the fMRI acquisition are playing a crucial role as to which areas will be activated. Recent studies demonstrated that key language regions exist outside the classical model of “Wernicke–Lichtheim–Geschwind,” but sensitive tasks must take place in order to be revealed. On top of that, the tasks should be in mother tongue for appropriate language mapping to be possible. Methods For that reason, in this study, we adopted an English protocol that can reveal six language critical regions even in clinical setups and we translated it into Greek to prove its efficacy in Greek population. Twenty healthy right‐handed volunteers were recruited and performed the fMRI acquisition in a standardized manner. Results Results demonstrated that all six language critical regions were activated in all subjects as well as the group mean map. Furthermore, activations were found in the thalamus, the caudate, and the contralateral cerebellum. Conclusion In this study, we standardized an fMRI protocol in Greek and proved that it can reliably activate six language critical regions. We have validated its efficacy for presurgical language mapping in Greek patients capable to be adopted in clinical setup

A hemodynamic network involving the insula, the cingulate, and the basal forebrain correlates with EEG synchronization phases of sleep instability

The cyclic alternating pattern (CAP) encompasses the pseudoperiodic appearance of synchronized brain waves and rhythms and is considered a regulator of the nonrapid eye movement (NREM) sleep vigilance level, reflecting sleep instability. To determine the brain regions responsible for this phenomenon, we scored and analyzed sleep functional magnetic resonance imaging data acquired with simultaneous electroencephalography (EEG-fMRI). Group analysis revealed a set of brain areas showing statistically significant blood oxygen-level dependent signal correlated positively with the synchronization phase of the CAP, most prominent being the insula, the middle cingulate gyrus, and the basal forebrain. These areas may form a network acting as a synchronization pacemaker, controlling the level of NREM sleep vigilance and the sleeper's arousability