Radiofrequency ablation of the centromedian thalamic nucleus in the treatment of drug-resistant epilepsy.

OBJECTIVE: To determine the usefulness and efficacy of radiofrequency ablations (RFA) of the Centromedian thalamic nucleus (CMN) to control primarily generalized or multifocal seizures in refractory epilepsy. METHODS: Six patients with clinical diagnosis of multifocal or primarily generalized drug-resistant epilepsy were included. Bilateral RFA of the CMN was performed through a monopolar 1.8 mm. tip electrode with a temperature of 80 °C during 90 seconds. Patients were followed in every 3 months visit for 20 to 36 months and kept a monthly seizure count calendar. We also compared maximal paroxysmal electroencephalogram (EEG) activity and neuropsychological evaluation pre and 6 months postoperatively. RESULTS: A significant reduction in the number of generalized seizures was observed in all subjects in the range of 79-98%, starting the first post-operative month. Although focal aware seizures remained unchanged throughout follow-up, there was an important reduction on paroxysmal activity between the pre and postoperative EEG. No major changes on cognitive status were detected. There was post-operative dysphagia and odynophagia lasting one week and there was no mortality in this group of patients. CONCLUSION: Preliminary results of CMN RFA suggest safety and a trend toward reduction of some seizure types, it may reduce the seizure frequency like other palliative procedures since the first post-operative month, but a larger, controlled study would be needed to establish the value of this therapy.

Association of white matter diffusion characteristics and cognitive deficits in temporal lobe epilepsy.

OBJECTIVE: The purpose of this study was to evaluate the relation between cognitive performance and white matter (WM) integrity in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS). METHODS: We included 26 patients with TLE (10 right, 16 left onset) as well as 24 healthy controls matched for age, gender, and years of education. In addition to quantitative hippocampal volume and transverse relaxation (T2) evaluation, whole-brain WM was analyzed using fractional anisotropy (FA) maps, derived from the diffusion tensor model. Average FA values were obtained from 38 regions of interest (ROI) of the main WM fascicles using an atlas-based approach. All subjects underwent extensive coFignitive assessments, Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Fractional anisotropy was correlated with neuropsychological scores, and group effects were evaluated. Finally, patients were clustered based on their cognitive performance to evaluate if clinical and structural variables relate to specific cognitive profiles. RESULTS: Patients had differential alterations in the integrity of the WM dependent on seizure laterality and presence of hippocampal sclerosis. Patients with TLE showed, on average, lower scores in most of the cognitive assessments. Correlations between cognition and WM followed specific trajectories per group with TLE, particularly in Left-TLE, in which we found a marked association between cognitive abilities and WM abnormalities. Cluster analysis of cognitive performance revealed three cognitive profiles, which were associated with the degree and spread of WM abnormalities. SIGNIFICANCE: White matter diffusion characteristics differ between patients, particularly in relation to seizure laterality and hippocampal damage. Moreover, WM abnormalities are associated with cognitive performance. The extent of WM alterations leads to disrupted cerebral intercommunication and therefore negatively affects cognition.

Human amygdala activation during rapid eye movements of rapid eye movement sleep: an intracranial study.

The amygdaloid complex plays a crucial role in processing emotional signals and in the formation of emotional memories. Neuroimaging studies have shown human amygdala activation during rapid eye movement sleep (REM). Stereotactically implanted electrodes for presurgical evaluation in epileptic patients provide a unique opportunity to directly record amygdala activity. The present study analysed amygdala activity associated with REM sleep eye movements on the millisecond scale. We propose that phasic activation associated with rapid eye movements may provide the amygdala with endogenous excitation during REM sleep. Standard polysomnography and stereo-electroencephalograph (SEEG) were recorded simultaneously during spontaneous sleep in the left amygdala of four patients. Time-frequency analysis and absolute power of gamma activity were obtained for 250 ms time windows preceding and following eye movement onset in REM sleep, and in spontaneous waking eye movements in the dark. Absolute power of the 44-48 Hz band increased significantly during the 250 ms time window after REM sleep rapid eye movements onset, but not during waking eye movements. Transient activation of the amygdala provides physiological support for the proposed participation of the amygdala in emotional expression, in the emotional content of dreams and for the reactivation and consolidation of emotional memories during REM sleep, as well as for next-day emotional regulation, and its possible role in the bidirectional interaction between REM sleep and such sleep disorders as nightmares, anxiety and post-traumatic sleep disorder. These results provide unique, direct evidence of increased activation of the human amygdala time-locked to REM sleep rapid eye movements.

Optimizing deep brain stimulation for the treatment of drug-resistant temporal lobe epilepsy: a pilot study.

OBJECTIVE: The authors sought to determine the antiseizure effects of deep brain stimulation (DBS) of the parahippocampal cortex (PHC) for treatment of drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: After a 3-month baseline period, 6 adult patients with drug-resistant MTLE and hippocampal sclerosis (HS) had stereoelectroencephalography (SEEG)-DBS electrodes implanted at the PHC for identification of the seizure onset zone (SOZ). Patients entered an 8-month, randomized, double-blind protocol for DBS, followed by a 12-month open-phase study. Monthly reports of seizure frequency were collected, with separate counting of focal seizures with or without awareness impairment (focal impaired awareness seizures [FIAS] or focal aware seizures [FAS], respectively) and focal evolving to bilateral generalized tonic clonic seizures (GTCS). Stimulation parameters were 130 Hz, 450 µsec, 2.5-3 V, and cyclic stimulation 1 minute on/4 minutes off. RESULTS: The total seizure rate decrement during follow-up was 41% (CI 25%-56%), with better seizure control for GTCS (IQR 19%-20%) and FIAS (IQR 0%-16%), with FAS being less responsive (IQR 67%-236%). No neuropsychological deterioration was observed. CONCLUSIONS: PHC DBS induced important antiseizure effects in patients with incapacitating FIAS and GTCS, most likely through blocking the propagation of hippocampal-onset seizures. The PHC target can be easily and safely approached due to positioning away from vascular structures, and there was no evidence of DBS-induced cognitive deterioration.

[Brain activity associated with a nouns-reading task]. / Activación cerebral asociada a una tarea de lectura de sustantivos.

BACKGROUND: Word reading involves several steps, from the visual perception of each of its constitutent elements to its recognition as an entity with a specific meaning. Various brain structures participate in these processes, depending of the linguistic and cognitive characteristics of the stimulus. Our objective was to characterize brain activity through the use of functional magnetic resonance imaging (FMRI) associated with the process of noun reading. METHODS: Eleven healthy right-handed volunteers participated in a lexical decision task involving 58 written nouns. An equal number of letter sequences were used as control stimuli. Reaction times were also recorded. RESULTS: There was a difference (p < 0.05) in reaction time between nouns and letter sequences in the lexical decision task. FMRI contrasted between conditions revealed significant activations in several areas involved in reading. CONCLUSIONS: The brain activation may reflect the different perceptual demands associated with the initial processing of nouns, as compared to meaningless letter sequences. We attribute the difference between our results and those previously reported to the particular characteristics of the pronunciation rules of written Spanish.

Enhanced emotional reactivity after selective REM sleep deprivation in humans: an fMRI study.

Converging evidence from animal and human studies suggest that rapid eye movement (REM) sleep modulates emotional processing. The aim of the present study was to explore the effects of selective REM sleep deprivation (REM-D) on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging (fMRI). Twenty healthy subjects were randomly assigned to two groups: selective REM-D, by awakening them at each REM sleep onset, or non-rapid eye movement sleep interruptions (NREM-I) as control for potential non-specific effects of awakenings and lack of sleep. In a within-subject design, a visual emotional reactivity task was performed in the scanner before and 24 h after sleep manipulation. Behaviorally, emotional reactivity was enhanced relative to baseline (BL) in the REM deprived group only. In terms of fMRI signal, there was, as expected, an overall decrease in activity in the NREM-I group when subjects performed the task the second time, particularly in regions involved in emotional processing, such as occipital and temporal areas, as well as in the ventrolateral prefrontal cortex, involved in top-down emotion regulation. In contrast, activity in these areas remained the same level or even increased in the REM-D group, compared to their BL level. Taken together, these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity, both at behavioral and neural levels, and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness.

Evaluation of opioid peptide and muscarinic receptors in human epileptogenic neocortex: an autoradiography study.

PURPOSE: The main goal of the present study was to evaluate possible alterations in opioid peptide and muscarinic receptors in human neocortical epileptic focus and the surrounding area removed from patients with pharmacologically resistant epilepsy and epilepsy secondary to cerebral lesion by tumor or other causes. METHODS: In vitro quantitative autoradiography experiments were carried out to label mu, delta, and muscarinic receptors of neocortical epileptic focus and surrounding area obtained from patients with pharmacologically resistant primary epilepsy and epilepsy caused by tumors and angioma cavernosa, and compared with neocortex obtained from patients with dementia and tumors without epilepsy. RESULTS: The mu receptor levels were lower in surrounding areas (-46%). The delta receptor binding was reduced in epileptic focus obtained from patients with epilepsy secondary to cerebral lesion (-25%) and surrounding areas (-31%). In contrast, muscarinic receptor levels were higher in the focus from patients with primary epilepsy (layers I-II, 52%; layers III-IV, 44%; layers V-VI, 36%). CONCLUSIONS: It is suggested that the increased muscarinic receptors in the epileptic focus and the decreased mu and delta receptors in the surrounding area are associated with the initiation and propagation of seizure activity in human epileptogenic neocortex.