Fabio Sebastiano

Ictal heart rate increase precedes EEG discharge in drug-resistant mesial temporal lobe seizures

OBJECTIVE Heart rate (HR) changes, mainly tachycardia, are often observed during seizures originating from the temporal lobe. The aim of this study was to analyze the role of ictal HR changes in localizing both mesial and lateral temporal lobe epilepsy (TLE) in a group of 68 patients. The influence of the gender and the side of epilepsy on HR modulation was also evaluated. METHODS Ictal HR was recorded during prolonged Video-EEG monitoring performed in 68 patients affected by drug-resistant TLE during a non-invasive pre-surgical protocol. According to the electro-clinical correlation, obtained by video-EEG monitoring, one hundred-thirteen seizures (n=113) and one hundred-forty-four auras (n=144) were identified and included in the study. Furthermore, the electro-clinical correlation allowed the classification of all the epileptic events (seizures and auras) as having mesial or lateral origin, based on the temporal lobe seizure onset zone. Ictal HR was calculated with respect to the R-R waves, and assessed from 15 sec (s) before (T(- 15)) to 15 s after (T(+15)) the time of EEG seizure onset (T(0)). RESULTS We observed a high incidence (92%) of ictal HR increase in TLE seizures. When the ictal EEG indicated a seizure onset from the mesial temporal structures, the onset of ictal HR increase preceded by about 5 s the EEG ictal onset (SD+/-18.4), whereas the onset of HR increase coincided with the onset of EEG discharges (SD+/-14.8) when the ictal EEG indicated the onset of seizures from the lateral temporal structures. No significant differences were found between male and female patients; and between right and left TLE. CONCLUSIONS Our findings show that ictal HR increase, preceding the onset of the EEG discharge, is associated with ictal EEG seizure pattern defining temporal lobe seizures originating from the mesial temporal lobe structures; this association suggests that the HR changes may be coupled to the functional impairment of neural circuits involved in sympathetic cardiovascular regulation, in the mesial temporal lobe structures. Further studies investigating the relationship between intracranial EEG monitoring and ECG recording are worthwhile, to confirm our results and to give further indications on the pathogenesis of ictal HR abnormalities.

Cortical sources of resting-state alpha rhythms are abnormal in persistent vegetative state patients.

OBJECTIVE High power of pre-stimulus cortical alpha rhythms (about 8-12 Hz) underlies conscious perception in normal subjects. Here we tested the hypothesis that these rhythms are abnormal in persistent vegetative state (PVS) patients, who are awake but not aware of self and environment. METHODS Clinical and resting-state, eyes-closed electroencephalographic (EEG) data were taken from a clinical archive. These data were recorded in 50 PVS subjects (level of cognitive functioning--LCF score: I-II) and in 30 cognitively normal subjects. Rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical sources were estimated by low-resolution electromagnetic tomography (LORETA). Based on LCF score at 3-months follow-up, PVS patients were retrospectively divided into three groups: 30 subjects who did not recover (NON-REC patients; follow-up LCF: I-II), 8 subjects classified as minimally conscious state patients (MCS patients; follow-up LCF: III-IV), and 12 subjects who recovered (REC patients; follow-up LCF: V-VIII). RESULTS Occipital source power of alpha 1 and alpha 2 was high in normal subjects, low in REC patients, and practically null in NON-REC patients. A Cox regression analysis showed that the power of alpha source predicted the rate of the follow up recovery, namely the higher its power, the higher the chance to recover consciousness. Furthermore, the MCS patients showed intermediate values of occipital alpha source power between REC and NON-REC patients. CONCLUSIONS These results suggest that cortical sources of alpha rhythms are related to the chance of recovery at a 3-months follow-up in patients in persistent vegetative state. SIGNIFICANCE Cortical sources of resting alpha rhythms might predict recovery in PVS patients.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during Rey auditory verbal learning test

It is well known that theta rhythms (3–8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten [“subsequent memory effect” (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug‐resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3–8 Hz) rhythms among hippocampus, amygdala, and temporal‐occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital‐temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40–45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug‐resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal–occipital neocortex. Hum Brain Mapp, 2009.

Localizing significance of temporal intermittent rhythmic delta activity (TIRDA) in drug-resistant focal epilepsy

OBJECTIVE Temporal intermittent rhythmic delta activity (TIRDA) is an EEG pattern characterized by sinusoidal trains of activity, ranging from 1 to 3.5 Hz, and well localized over the temporal regions. It is considered to be an indicator of temporal lobe epilepsy (TLE), but full agreement between different authors has still not been reached. The aim of this study was therefore to assess the role of TIRDA in localizing the epileptogenic zone, which was estimated using anatomo-electro-clinical correlations obtained from non-invasive pre-surgical investigations, in a large group of patients affected by drug-resistant partial epilepsy. METHODS The occurrence of TIRDA was investigated using a prolonged Video-EEG recording of 129 patients affected by drug-resistant partial epilepsy that underwent a non-invasive pre-surgical protocol. Patients were divided into 3 groups: TLE only, extratemporal epilepsy, and multilobar epilepsy including temporal lobe. According to the epileptogenic zone identified using anatomo-clinical-radiological correlations, 3 different subgroups of TLE were identified: mesial, lateral, and mesio-lateral. Statistical analysis was performed in order to evaluate the relationship between TIRDA and the epileptogenic zone, and neuroradiological, neuropathological, EEG interictal and ictal findings. RESULTS The pattern of TIRDA was observed in 52 out of the 129 (40.3%) patients studied. Significant correlations were found between TIRDA and: (i) mesial and mesio-lateral TLE; (ii) mesial temporal sclerosis; (iii) interictal epileptiform discharge localized over the anterior temporal regions; and (iv) 5-9 Hz temporal ictal discharge. CONCLUSIONS Our research shows that TIRDA plays a role in localizing the epileptogenic zone, suggesting that this pattern might be considered as an EEG marker of an epileptogenesis that involves the mesial structures of the temporal lobe. However, further studies investigating the relationship between intracranial EEG monitoring and simultaneous scalp EEG recording are needed in order to confirm our findings and improve our understanding of the significance of TIRDA.

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol

Aim: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on “anatomo–electro–clinical correlations”. Methods: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. “Tailored” surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. Results: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a “hippocampal sclerosis/cryptogenic” group (n = 57) and a “tumours/cortical organisation disorders” group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. Conclusions: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo–electro–clinical data and can be treated effectively and safely with tailored surgery.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmanns area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

Functional isolation within the cerebral cortex in the vegetative state: A nonlinear method to predict clinical outcomes

Background. Establishing prognosis in patients in a persistent vegetative state (VS) is still challenging. Neural networks underlying consciousness may be regarded as complex systems whose outputs show a degree of unpredictability experimentally quantifiable by means of nonlinear parameters such as approximate entropy (ApEn). Objective. The authors propose that the VS might be the result of derangement of the above neural networks, with an ensuing decrease in complexity and mutual interconnectivity: this might lead to a functional isolation within the cerebral cortex and to a reduction in the chaotic behavior of its outputs, with monotony taking the place of unpredictability. To test this hypothesis, the authors investigated whether nonlinear dynamics methods applied to electroencephalography (EEG) recordings may be able to predict outcomes. Methods. A total of 38 vegetative patients and 40 matched healthy controls were investigated. At admission, all patients were assessed by means of the Extended Glasgow Outcomes Coma Scale (E-GOS) and the Coma Recovery Scale–Revised (CRS-R). At the same time an EEG recording was performed and used for time series analysis and ApEn computation. Patients were clinically reassessed at 6 months from the first evaluation. Results. Mean ApEn values (0.73, standard deviation [SD] = 0.12 vs 0.97, SD = 0.02; P < .001) were lower in patients than in controls. Patients with the lowest ApEn values either died (n = 14) or remained in a VS (n = 12), whereas patients with the highest ApEn values became minimally conscious (n = 5) or showed partial (n = 4) or full recovery (n = 3). Conclusions. These findings suggest that dynamic correlates of neural residual complexity might help in predicting outcomes in vegetative patients.

Postoperative EEG and seizure outcome in temporal lobe epilepsy surgery.

OBJECTIVE To assess the prognostic value of scalp electroencephalogram (EEG) after epilepsy surgery, we investigated whether postoperative EEG abnormalities (interictal epileptiform discharges, IED; interictal slow activity, ISA) were associated with seizure outcome and other patient characteristics after resective surgery in patients with temporal lobe epilepsy (TLE). METHODS Sixty-two patients with medically refractory TLE who underwent surgery were studied. Patients were categorized according to etiology (mesiotemporal sclerosis vs. tumors/cortical dysplasias); extent of surgical resection (extensive vs. limited); and amount of preoperative IED on wake EEG (oligospikers, <1 IED/h, vs. spikers). Patients were also classified as seizure-free (SF) or having persistent seizures/auras (not-SF) during follow up visits 1 month and 1 year after surgery. Preoperative 60-min interictal EEGs were evaluated for IED and ISA, and compared to postoperative wake EEGs. RESULTS Seizures/auras persisted in 16/62 (25.8%) patients at 1 month and in 8/62 (12.9%) at 1 year follow up. ISA was not significantly related to outcome. Of 42 patients with EEG negative for IED at 1 month, 4 were not-SF; at 1 year, one of 44 such patients was not-SF. IED was significantly associated with seizure/aura persistence in patients categorized as mesiotemporal sclerosis and with extensive surgery. Oligospikers and spikers on preoperative EEG showed no differences in the postoperative seizure outcome, excellent in both cases; moreover, the presence of postoperative IEDs indicated auras/seizures persistence apart from the preoperative EEG spike frequency. CONCLUSIONS Our study showed that the presence of IED of postoperatve EEG strongly indicates seizure/aura persistence. Therefore, serial EEGs should be included in postoperative follow up schedules as a crucial tool in evaluating seizure outcome.

Alpha, beta and gamma electrocorticographic rhythms in somatosensory, motor, premotor and prefrontal cortical areas differ in movement execution and observation in humans

OBJECTIVE In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. METHODS ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. RESULTS Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. CONCLUSION Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. SIGNIFICANCE Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients.

Heart rate non linear dynamics in patients with persistent vegetative state: a preliminary report

Primary objective: This study evaluated the hypothesis that neural networks derangement in patients with a vegetative state (VS) may cause an alteration of heart rate (HR) non-linear pattern. Methods and procedures: Fifteen consecutive patients with a persistent VS and 15 matched healthy control subjects were included in the study. A 6-hour continuous electrocardiographic recording was used for the time series analysis measuring the occurrence time of the intervals between consecutive normal sinus heart beats (RR’ intervals). Parameters evaluating linear and non-linear HR variability were studied. Approximate Entropy (ApEn), a non-linear parameter that quantifies the unpredictability of fluctuations in an instantaneous HR time series, was calculated from the average values of time series with fixed input variables. Main outcomes and results: All linear parameters, with the only exception being the percentage of RR’ intervals that were by at least 50 ms different from the previous interval (0.56, SD = 1.31 vs 10.35, SD = 12.58; p = 0.005) were similar in patients and in healthy control subjects. Mean ApEn values (0.68, SD = 0.24 vs 1.10, SD = 0.16; p = 0.0001) were lower in patients than in healthy control subjects. Conclusions: The findings support the hypothesis that derangement of neural networks may cause a reduction of non-linear behaviour in HR such as ApEn.