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

Background: Functional 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). Methods: Sixty 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. Results: In 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. Conclusion: ICA 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.

Frontal lobe epilepsy and mild malformation with oligodendroglial hyperplasia: Further observations on electroclinical and imaging phenotypes, and surgical perspectives.

OBJECTIVE: Mild malformation with oligodendroglial hyperplasia (MOGHE) is a recently described clinicopathologic entity, associated with drug-resistant epilepsy and extensive epileptogenic networks. Knowledge is accumulating about particular electroclinical phenotypes, correlations with imaging, and potential prognostic significance for surgical outcomes. The study adds relevant information by documenting the presence of a hyperkinetic frontal lobe seizure phenotype in adolescents and an epileptic encephalopathy phenotype in young children. METHODS: Five cases were subjected to a structured presurgical evaluation protocol, including EEG-FMRI, chronic and acute invasive EEG, subjected to frontal lobe surgery with postoperative follow-up between 15 months and 7 years. RESULTS: In the two adult cases, surface EEG demonstrated lateralized widespread frontal lobe epileptogenicity and hyperkinetic semiological features. MRI demonstrated cortical white matter blurring and deeper white matter abnormalities. EEG-FMRI suggested concordant frontal lobe involvement. iEEG demonstrated a widespread frontal lobe epilepsy network. The three young children demonstrated a diffuse epileptic encephalopathy phenotype, with nonlocalizing, nonlateralizing surface EEG, and "spasms" as the main seizure type. MRI demonstrated extensive frontal lobe subcortical gray and white matter abnormalities, consistent with MOGHE literature for this age, while EEG-FMRI, in 2/3, demonstrated concordant frontal lobe involvement. They did not undergo chronic iEEG, and the resection was assisted by acute intraoperative ECoG. All cases were subjected to extensive frontal lobectomies with Engel class IA (2/5), IB (1/5), and IIB (2/5) outcomes. SIGNIFICANCE: The study confirms the presence of frontal lobe epilepsy and epileptic encephalopathy phenotypes, in accordance with epilepsy phenotypes already described in MOGHE literature. Presurgical evaluation studies, including EEG-FMRI, can provide strong lateralizing and localizing evidence of the epileptogenic networks involved. All responded favorably to extensive frontal lobe resections, despite widespread epileptic activity recorded by surface and intracranial EEG pre- and postoperatively; an epileptic encephalopathy phenotype, in the first years of life, should not discourage such a resection.

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

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.

Altered Sleep-Related Consolidation and Neurocognitive Comorbidity in CECTS.

Our aim is to use neurophysiological sleep-related consolidation (SRC) phenomena to identify putative pathophysiological mechanisms in CECTS linked to diffuse neurocognitive deficits. We argue that there are numerous studies on the association between seizure aspects and neurocognitive functioning but not as many on interictal variables and neurocognitive deficits. We suggest two additional foci. First, the interictal presentation in CECTS and second, neuronal oscillations involved in SRC processes. Existing data on mechanisms through which interictal epileptiform spikes (IES) impact upon SRC indicate that they have the potential to: (a) perturb cross-regional coupling of neuronal oscillations, (b) mimic consolidation processes, (c) alter the precision of the spatiotemporal coupling of oscillations, and (d) variably impact upon SRC performance. Sleep spindles merit systematic study in CECTS in order to clarify: (a) the state of the slow oscillations (SOs) with which they coordinate, (b) the precision of slow oscillation-spindle coupling, and (c) whether their developmental trajectories differ from those of healthy children. We subsequently review studies on the associations between IES load during NREM sleep and SRC performance in childhood epilepsy. We then use sleep consolidation neurophysiological processes and their interplay with IES to help clarify the diffuse neurocognitive deficits that have been empirically documented in CECTS. We claim that studying SRC in CECTS will help to clarify pathophysiological mechanisms toward diverse neurocognitive deficits. Future developments could include close links between the fields of epilepsy and sleep, as well as new therapeutic neurostimulation targets. At the clinical level, children diagnosed with CECTS could benefit from close monitoring with respect to epilepsy, sleep and neurocognitive functions.

Temporal lobe "plus" epilepsy associated with oligodendroglial hyperplasia (MOGHE).

BACKGROUND: Mild malformation of cortical dysplasia (mMCD) with oligodendroglial hyperplasia (MOGHE) is an epilepsy-related pathologic entity highlighted in post-surgical specimens of frontal lobe epilepsy (FLE) patients. AIMS OF THE STUDY: We present two temporal lobe epilepsy (TLE) cases with MOGHE and discuss clinical, neurophysiological, and neuroimaging features that may be indicative of surgical outcome. METHODS: We identified two cases with MOGHE out of 30 temporal lobe epilepsy (TLE) surgical patient cohort, whose pathological distribution spared the hippocampal structures. RESULTS: The TLE cases shared common features with the FLE series in terms of patient profiles, MRI findings and post-surgical outcome. TLE plus seizure semiology combined with extratemporal scalp electroencephalographic (EEG) and electrocorticographic (ECoG) epileptiform elements at a distance from the imaging lesion were suggestive of an underlying multifocal pathology. CONCLUSIONS: MOGHE pathology has to be considered in the decision-making process for TLE epilepsy surgery when this constellation of features is met.

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.

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 (3.0mm) coronal FLAIR sequences and a 3D thin-slice (1.0mm) 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 12.3mm, by thin images was 8.9mm, and in the patients undetected by thick FLAIR was 3.5mm. 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.

Spike pattern recognition by supervised classification in low dimensional embedding space.

Epileptiform discharges in interictal electroencephalography (EEG) form the mainstay of epilepsy diagnosis and localization of seizure onset. Visual analysis is rater-dependent and time consuming, especially for long-term recordings, while computerized methods can provide efficiency in reviewing long EEG recordings. This paper presents a machine learning approach for automated detection of epileptiform discharges (spikes). The proposed method first detects spike patterns by calculating similarity to a coarse shape model of a spike waveform and then refines the results by identifying subtle differences between actual spikes and false detections. Pattern classification is performed using support vector machines in a low dimensional space on which the original waveforms are embedded by locality preserving projections. The automatic detection results are compared to experts' manual annotations (101 spikes) on a whole-night sleep EEG recording. The high sensitivity (97 %) and the low false positive rate (0.1 min-1), calculated by intra-patient cross-validation, highlight the potential of the method for automated interictal EEG assessment.

EEG-fMRI findings in late seizure recurrence following temporal lobectomy: A possible contribution of area tempestas.

Late seizure relapses following temporal lobectomy for drug-resistant temporal lobe epilepsy occur in 18-30% of operated-on cases, and recent evidence suggests that a significant proportion of them are due to maturation and activation of proepileptic tissue having defied initial resection and located at the vicinity of or at a short distance from its borders, usually over the posterior medial, basal temporal-occipital, and lateral temporal regions. Experimental studies in animals and functional imaging studies in humans suggest that the area tempestas, a particular region of the basal-frontal piriform cortex, is critical for kindling and initiation and propagation of seizure activity arising from different cortical foci, especially limbic ones. This case report of a patient with late seizure relapse, three years following an initially successful right temporal lobectomy for ipsilateral medial temporal sclerosis, is the first one in the literature to demonstrate interictal EEG-fMRI evidence of significant BOLD signal changes over the inferior, basal and lateral temporal and temporooccipital cortices posterior to the resection margin, plus a significant BOLD signal change over the ipsilateral basal frontal region, closely corresponding to the piriform cortex/area tempestas. Our case study provides further functional imaging evidence in support of maturation/activation of proepileptic tissue located at the vicinity of the initial temporal lobe resection in cases of late seizure relapses and suggests, in addition, a possible role for the piriform cortex/area tempestas in the relapsing process.

Surgical outcome in neocortical resections of type IIId focal cortical dysplasia with accompanying medial temporal pathology.

Focal cortical dysplasia (FCD) type IIId is a newly proposed type associated with early-life brain insults. Such patients are often considered unsuitable for resective epilepsy surgery, given the usually wide extent of the lesion and the poor correlation of MRI to the epileptogenic pathology. Two patients with intractable epilepsy, early-life ischemic/traumatic injury and MRI findings of extensive unilateral cystic-gliotic and ipsilateral medial temporal sclerotic-malformative lesions were subjected to presurgical evaluation revealing well-localized neocortical ictal onsets. They underwent tailored neocortical resections sparing medial temporal areas and achieved Engel class I postsurgical outcomes. Histopathology was consistent with type IIId focal cortical dysplasia. Successful outcomes with tailored resections may be achieved in cases with this subtype of focal cortical dysplasia, in the presence of converging and well-localized semiological, EEG and functional imaging data, even on a background of complex and extensive MRI abnormalities. Medial temporal pathology, although often present in this setting, is not necessarily the site of ictal onsets, and its resection may not be always mandatory for a favorable outcome.

Extratemporal surface EEG features do not preclude successful surgical outcomes in drug-resistant epilepsy patients with unitemporal MRI lesions.

Of 47 patients with onset of intractable partial seizures and temporal lobe MRI lesions, subjected to presurgical evaluation and temporal lobe surgery, we identified eight (mean age: 24 years; range: 7-52 years) demonstrating surface interictal and/or ictal EEG features suggestive of an extratemporal localisation. All eight patients underwent surgery aiming to predominantly resect the lesion, without extending to the extratemporal region. The patients were prospectively followed (mean follow-up duration: 38 months; range: 12-66 months) and all achieved excellent postoperative seizure control. Extratemporal surface interictal/ictal EEG features were more often encountered in tumoural and focal cortical dysplasia cases, compared with medial temporal sclerosis cases, and were most frequently localised over frontopolar and suprasylvian-pericentral locations. We postulate that propagation of interictal/ictal activity from the epileptogenic region of the temporal lobe to extratemporal neocortical areas, perhaps utilising the temporal pole and insula as intermediary nodes of a common epileptogenic network, accounts for the presence of our cohort's discordant lesion and EEG features.

Epileptogenic networks in two patients with hypothalamic hamartoma.

Hypothalamic hamartomas (HH) are typically associated with gelastic seizures but also implicated in the genesis of other seizure types. In order to identify networks involved in seizure generation, we performed EEG-fMRI in two adult patients with HH, the first with predominantly gelastic seizures and the second with complex partial and no typical gelastic seizures. The ictal and interictal analysis of the patient with gelastic seizures revealed the involvement of the HH, the cingulate gyrus, the precuneus and the prefrontal cortex. The interictal analysis of the patient with complex partial seizures, showed changes in blood oxygen-level dependent signal over the temporal lobes, the base of the frontal lobe, the cingulate, the precuneus and the prefrontal cortex, but not the HH. The differences in the neural networks implicated may account for differences in clinical manifestation of seizures owing to HH.

Hemispherotomy or lobectomy? The role of presurgical neuroimaging in a young case of a large porencephalic cyst with intractable epilepsy.

A young patient with a large left hemisphere porencephalic cyst underwent neuroimaging investigation (functional magnetic resonance imaging (fMRI), EEG-fMRI, DTI tractography) during presurgical evaluation for intractable epilepsy. The functional workup showed that (a) the healthy hemisphere had undertaken language processing, primary and secondary sensory functions of bilateral upper and lower extremities, and bilateral feet motion, and (b) the porencephalic hemisphere had retained contralateral arm and shoulder motion. EEG-fMRI localized the epileptogenic area occipitally. Tractography anatomically supported the above. Neuroimaging tailored surgery into selective lobectomy, thereby preserving all sensorimotor functionality and strongly supporting its use for presurgical evaluation of patients with large hemispheric lesions.

An open-label, add-on study of pregabalin in patients with partial seizures: a multicenter trial in Greece.

INTRODUCTION: Pregabalin efficacy and safety as an adjunctive treatment for partial seizures was evaluated using an open-label, flexible-dose. STUDY DESIGN: In 98 adults with refractory partial epilepsy taking 1-3 anti-epileptic drugs with ≥2 seizures during an 8-week baseline period. METHODS: Pregabalin was increased to ≤600 mg/day during a 9-week dose optimization period with dosage maintained for 12 additional weeks. Primary endpoint was the percentage change in partial seizure frequency between the 8-week baseline and 12-week observation period. RESULTS: Pregabalin treatment was associated with a significant reduction in partial seizure frequency: median percent change in partial seizure frequency from baseline to 12 weeks was -33% and -22% in patients with a baseline seizure frequency of ≤3 and >3 per 28 days, respectively. The 50% and 75% responder rates were 41.94% (95% CI: 31.91-51.96) and 30.11% (95% CI: 20.78-39.43), respectively. Nineteen percent of subjects were seizure-free throughout the last 12 weeks. Pregabalin administration resulted in a significant reduction in anxiety (mean reduction in Hospital Anxiety and Depression Scale scores of 1.68 units, 95% CI: -2.60 to -0.76). Most patients were much improved or very much improved on Patient Global Impression of Change (53.8%) and Clinical Global Impression of Change (53.8%). The most frequently self-reported adverse events (AEs) were mild or moderate somnolence (20.4%) and dizziness (5.1%) with a low AE discontinuation rate (5.1%). CONCLUSIONS: The efficacy and side-effect profile of pregabalin were similar to previous pregabalin double-blind, controlled studies. Additionally, pregabalin, as an add-on treatment for partial epilepsy, exhibits significant anti-anxiety properties.

Limited resection of focal cortical dysplasia and associated epileptogenic cortex may lead to positive surgical outcome.

A drug-resistant epilepsy patient with premotor type IIb focal cortical dysplasia is described with a positive postoperative outcome following partial resection of the lesion and epileptogenic zone. Presurgical fMRI of the sensorimotor areas showed haemodynamic responses over the posterior border of the lesion and ictal EEG-fMRI revealed activation of both the primary sensorimotor strip and premotor lesion area. Almost continuous 1-2 Hz interictal spiking was recorded during a chronic ECoG study over the primary sensorimotor cortex. Following partial resection of the lesion, an acute ECoG revealed marked reduction of epileptic activity over the sensorimotor area. Post-operatively, seizure control was significantly improved (class IV ILAE outcome). Although partial FCD resections predict a worse postoperative outcome, individual patients may still respond favourably. The type of lesion, resected portion, and histopathology may be included among factors related to successful outcome.