Interictal cerebral metabolism in partial epilepsies of neocortical origin

We performed interietal [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG PET) in 24 patients with partial epilepsy of neocortical origin. Two-thirds of patients had regions of hypometabolism. The zone of intracranially recorded electrographic ictal onset was always located in a region of hypometabolism, in those with hypometabolism. Hypometabolic regions in partial epilepsies of neocortical origin were usually associated with structural imaging abnormalities. Regional hypometabolism occasionally occurred without localizing ictal scalp EEG and cerebral magnetic resonance imaging findings, however. FDG PET may be useful in directing placement of intracranial electrodes for presurgical evaluation of refractory neocortical seizures.     

Interictal patterns of cerebral glucose metabolism,perfusion, and magnetic field in mesial temporal lobe epilepsy

PURPOSE: To characterize the epileptogenic condition of patients with mesial temporal lobe epilepsy, the interictal patterns of glucose metabolism, perfusion, and magnetic field in the temporal lobe were evaluated by using [18F]fluorodeoxyglucose-positron emission tomography, [99mTc]-ethylcysteinate dimer-single photon emission computed tomography, and magnetoencephalography (MEG). METHODS: Twenty-one patients with mesial temporal lobe epilepsy related to hippocampal sclerosis were studied. The ictal-onset area was located by continuous video-EEG monitoring. Quantitative analysis of glucose metabolism and perfusion in the temporal lobe was performed, and the cerebral magnetic field was evaluated to measure the equivalent current dipole (MEG-ECD). RESULTS: Although hypometabolism and hypoperfusion in the temporal lobe were lateralized with the ictal-onset area in 16 (76.2%) and in 11 (52.4%) respectively, they were localized in diverse ways without any coupling. MEG-ECD was distributed in diverse ways unrelated to the ictal-onset area: ipsilateral medial temporal origin in five (23.8%), ipsilateral lateral temporal origin in two (9.5%), ipsilateral mixed (medial and lateral) temporal origin in six (28.6%), bilateral temporal origin in four (19.0%), and contralateral temporal origin in two (9.5%). CONCLUSIONS: MEG-ECD was distributed in varied ways with the disorder and uncoupling of glucose metabolism and perfusion in the temporal lobe. These results may help resolve the clinical controversy over the possibility that the cortical irritative area generating the interictal epileptic discharge is distinct from the ictal-onset area, and also may have some functional implications in identifying different brain compartments in the generation of metabolic signals.     

Positron emission tomography studies of cerebral glucose metabolism in chronic partial epilepsy

Positron emission tomography (PET) performed with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) was used to measure local cerebral metabolic rate for glucose (lCMRGlc) interictally in 31 patients with chronic partial epilepsy and 16 age-matched normal subjects. Hypometabolic zones were visualized in 25 patients (81%). Cortical lCMRGlc in hypometabolic zones was within 2 standard deviations of the mean for normal temporal cortex in all but 8 patients. However, in 24 patients asymmetry between the hypometabolic cortex and homologous contralateral cortex was more than 2 standard deviations above the mean cortical asymmetry for normals. There was good correlation between hypometabolic zones and electroencephalogram (EEG) foci in patients with unilateral well-defined EEG foci. Diffuse or shifting EEG abnormalities were often associated with normal PET scans. Of 28 patients who underwent magnetic resonance imaging, 10 showed focal temporal lobe abnormalities corresponding to focal hypometabolism. While the [18F]FDG PET scan cannot currently localize an epileptogenic zone independently, the absence of focal hypometabolism or its presence contralateral to a presumed EEG focus suggests the need for additional electrophysiological data.     

Interictal EEG changes in eclampsia

The pathogenesis of seizures and encephalopathy in eclampsia remains obscure even today. There are only a few reports on EEG findings in eclampsia. This is a report of the interictal EEG changes in 8 patients with eclampsia who were evaluated prospectively. The major EEG changes observed were (1) slowing of the background activity (generalized slowing in 4 patients and focal slowing in 3 patients) and (2) intermittent spike and sharp wave transients (5 patients). These abnormalities had disappeared in all except 2 patients when the EEG was repeated on the seventh day. A comparison is drawn between eclampsia and hypertensive encephalopathy for the clinical, EEG and CT/MRI findings. The pathogenesis of seizures and encephalopathy could be similar in these two conditions. It is worth while considering then; EEG changes while planning the treatment of eclampsia.     

Interictal EEG pattern in rabbit penicillin epilepsy

The effects of Na-penicillin G (1,000,000 I.U./kg i.v.) were studied in 28 rabbits implanted with surface and deep electrodes in the medial (mT) and lateral (lT) nuclei of the thalamus and in the cornu Ammonis dorsalis (CAd). Attention was focused on interictal spike activity, cortical spindle activity and spikes-spindles relationship.A multifocal interictal EEG pattern, represented by cortical and thalamic spikes, was observed in 20 animals. A clear association between cortical spikes and spindles occurred almost constantly. Moreover a statistically significant increase in the average duration of spindles without changes in the average frequency was noticed. Seizure discharges had always a focal start and secondary generalization.The EEG features of parenteral penicillin epilepsy in the rabbit appeared to be more similar to those of the rat than to those of the cat.The spindle activity changes and the paroxysmal spike activity can be interpreted as two independent penicillin induced features appearing during raised cortical excitability periods.

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Sommario Sono stati studiati gli effetti della penicillina G-sodica (1.000.000 I.U./Kg.i.v.) in 28 conigli impiantati con elettrodi di superficie e con elettrodi profondi nel corno di Ammone dorsale (CAd) e nei nuclei talamici laterali (lT) e mediali (mT). In particolare sono stati esaminati l'attività di spiking intercritico, l'attività corticale di spindling e le relazioni spikes-spindles.In 20 animali la penicillina ha indotto un pattern EEG intercritico multifocale con spikes presenti a livello corticale e talamico. A livello corticale le spikes erano quasi sempre associate a spindles. Inoltre le spindles, dopo penicillina, presentavano un significativo aumento della durata media, senza modificazioni della frequenza.Il pattern EEG da somministrazione sistemica di penicillina nel coniglio appare più simile al pattern descritto nel ratto che a quello del gatto.Le variazioni della attività di spindles e l'attività parossistica di spikes potrebbero essere due fenomeni indipendenti indotti dalla penicillina e presenti durante periodi di aumentata eccitabilità corticale.

     

EEG power changes are related to regional cerebral glucose metabolism in vascular dementia.

OBJECTIVE: In patients with vascular dementia (VD), the relationship between the EEG power within the 4 frequency bands and the regional metabolic disturbances was investigated. METHODS: Twenty-eight patients (age 69.0+/-6.54 years) with VD according to NINDS-AIREN criteria underwent quantitative EEG recording, according to the 10-20 system, and fluodeoxyglucose F18 positron emission tomography (PET) at resting condition within 24 h. EEG power FFT-analysis was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz) and beta (13.5-20 Hz) frequency bands. Regional EEG power bands were related to regional glucose metabolism in anatomically defined regions corresponding to locations of the 10-20 system. RESULTS: Correlation between slow frequency band power and glucose metabolism was found. A widespread inverse relationship of delta power to metabolism was found between various regions; additionally, delta power was negatively correlated to cerebral glucose metabolism in individual regions. Frontal theta power correlated especially with thalamic CMRglc. Alpha power correlated directly with metabolism in the occipital lobe. No significant relationships were found between beta power and metabolism. CONCLUSION: We conclude that EEG power in VD is linked to glucose metabolism, indicating specific regional dependencies.     

Interictal cognitive changes in epilepsy

There is little evidence for significant intellectual deterioration in well-controlled seizure disorders. With recurrent convulsive seizures, the picture is less clear and depends on severity, type, age of onset, and frequency of toxic levels of antiepileptic drugs (see Table 1). In the interictal state, deficits in verbal language and memory have been observed, especially in patients with complex partial seizure foci in the left (dominant) hemisphere. The memory deficits appear to affect new learning and retention of material; the verbal deficits are more subtle, affecting word-finding, verbal fluency, and comprehension abilities. Both of these changes may either go unnoticed by the patient in day to day activities or be attributed to the effects of antiepileptic medication. Antiepileptic drugs can also affect interictal cognitive functioning. The worst of these appears to be phenobarbital; phenytoin has an intermediate effect; valproic acid and carbamazepine as single agents seem to produce fewer adverse effects. However, individual patients may be particularly sensitive to cognitive side effects of certain drugs. Finally, attention deficits and slowing of cognitive processes, either chronically or intermittently, appear to affect all seizure patients to some extent. The syndrome is more prominent in frontal or generalized seizure patterns. The intermittent nature of these disturbances has been emphasized in recent research on subclinical interictal spike-wave electrical phenomena.     

Interictal EEG in temporal lobe epilepsy in childhood.

The authors clarified the value of interictal discharges and verified which extratemporal regions may also show epileptiform activity in temporal lobe epilepsy (TLE) in childhood. Thirty consecutive patients aged 3 to 18 years (mean age = 12.16 years; 16 male) with TLE associated with hippocampal atrophy were studied. Each patient had 1 to 15 interictal EEG recordings (mean: 5.6; total = 192 EEGs). Video-EEG monitoring was performed in 20 patients. All patients had MRI. The findings were compared with a control group of 53 consecutive TLE adult outpatients with hippocampal atrophy. Each adult patient underwent 3 to 21 routine EEGs (mean: 10.67; total = 566). Interictal EEGs of children with TLE showed extratemporal epileptiform discharges more frequently than EEGs of adults with TLE. Frontal, parietal, and occipital discharges were more frequently seen in children (P < 0.05). These results suggest a close interaction between temporal and other cerebral regions in children with epilepsy and provide further evidence of the existence of neural networks.     

Interictal regional cerebral blood flow during non specific activation test in partial epilepsy.

In order to investigate, during activation testing, the interictal cortical cerebral blood flows (rCBF) of epileptic patients suffering from complex partial seizures, 40 epileptic patients (divided into "lesional", this is, with abnormal CT findings, and "non lesional", that is, with normal CT findings) were submitted to rCBF measurements with the 133 xenon intravenous technique, at rest and during intermittent light stimulation (ILS). The findings compared with normal volunteers seem to demonstrate that, during ILS, (1) in non lesional patients, the suspected epileptic focus shows a significant rCBF increase (2) in lesional patients, the significant rCBF increases were not in the region of the suspected epileptic focus but in adjacent or in contralateral ones. It was concluded that activation interictal rCBF measurements are more useful than resting ones for the determination of epileptic foci when CT findings are normal and that the nature of the epileptic focus influences markedly the interhemispheric activation pattern.     

Interictal changes in behavior and cerebral metabolism in the rat: opioid involvement

Interictal changes in locomotor and shock-response behaviors were examined in rats that were kindled unilaterally or bilaterally in the amygdala. 2-Deoxyglucose and naloxone were used to test whether alterations in cerebral glucose metabolism or opioid functioning, respectively, correlated with changes in these behaviors. Bilaterally kindled rats, at 14 to 28 days after their last seizure, displayed increased locomotion (square crossing) in an open field compared with unilaterally kindled or control rats. Bilaterally kindled rats also showed elevated thresholds for the elicitation of a multiple squeak response to tail shocks. Single squeak or tail withdrawal responses to tail shock were not affected by bilateral kindling. Likewise, unilaterally kindled rats did not differ from controls on any of the behavioral measures. Naloxone (10 mg/kg, i.p.) reversed the increase in locomotion and elevation of multiple squeak thresholds in the bilaterally kindled rats. By itself, naloxone did not influence any of the behaviors. Finally, cerebral glucose metabolism was decreased, globally, in the forebrain of the bilaterally kindled rats, and naloxone normalized this change. Cerebral metabolism was not altered in unilaterally kindled rats compared with controls. Thus, changes in cerebral metabolism and opioid functioning may be involved in the mediation of interictal changes in locomotor and emotional behavior in rats.     

EEG mapping in partial epilepsy

Even if mathematic treatment of EEG signals by Fast Fourier Transformation (FFT) in cases of transient epileptic discharges is still controversial, this method has been applied to 21 cases of epileptic partial seizures. Examples are shown, and compared to CT-Scan data. In 17 cases, EEG mapping identified alterations of basic activities upon a definite area. In addition, a focal peak of maximal alterations displacing itself into the limits of the whole epileptogenic area is demonstrated; it is furthermore suggested that the power spectrum keeps, especially during seizures, a peculiar ("combing") morphology, possibly specific of epileptic diseases.     

Interictal spike EEG source analysis in hypothalamic hamartoma epilepsy.

OBJECTIVE: The epilepsy associated with the hypothalamic hamartomas constitutes a syndrome with peculiar seizures, usually refractory to medical therapy, mild cognitive delay, behavioural problems and multifocal spike activity in the scalp electroencephalogram (EEG). The cortical origin of spikes has been widely assumed but not specifically demonstrated. METHODS: We present results of a source analysis of interictal spikes from 4 patients (age 2-25 years) with epilepsy and hypothalamic hamartoma, using EEG scalp recordings (32 electrodes) and realistic boundary element models constructed from volumetric magnetic resonance imaging (MRIs). Multifocal spike activity was the most common finding, distributed mainly over the frontal and temporal lobes. A spike classification based on scalp topography was done and averaging within each class performed to improve the signal to noise ratio. Single moving dipole models were used, as well as the Rap-MUSIC algorithm. RESULTS: All spikes with good signal to noise ratio were best explained by initial deep sources in the neighbourhood of the hamartoma, with late sources located in the cortex. Not a single patient could have his spike activity explained by a combination of cortical sources. CONCLUSIONS: Overall, the results demonstrate a consistent origin of spike activity in the subcortical region in the neighbourhood of the hamartoma, with late spread to cortical areas.     

Drug-induced changes in cerebral glucose consumption in bifrontal epilepsy

PURPOSE: Positron emission tomography (PET) using 18F-radiolabeled deoxyglucose (18F-FDG) is a sensitive procedure for detection of epileptogenic foci. Although alterations in glucose consumption are not restricted to the area of seizure generation itself, the magnitude and extent of cerebral metabolic disturbances induced by epileptic discharges can be detected. Despite two decades of epilepsy research using 18F-FDG-PET, little is known about the metabolic changes during therapy of focal epilepsy. We report on a child with frontal epilepsy with severe glucose hypometabolism that was nearly completely normalized during drug therapy. METHODS: Interictal 18F-FDG-PET was performed at the onset of epilepsy and after optimized drug therapy in a 5-year-old boy with behavioral abnormalities and repetitive seizures of frontal origin with bifrontal interictal EEG slowing for 8 weeks. Both scans were anatomically matched; initial and intratherapeutic glucose metabolism were compared. RESULTS: In accordance with the epileptogenic focus as identified by EEG and ictal/interictal perfusion single-photon emission tomography (SPECT), bifrontal hypometabolism was depicted by 18F-FDG-PET. Magnetic resonance imaging (MRI) was unremarkable. After dual-drug therapy (valproate, carbamazepine), the boy became seizure free, and his initial behavioral deficits disappeared. A control PET study after 3 months of therapy showed restored glucose consumption; the frontal EEG slowing was normalized. CONCLUSIONS: This case demonstrates that reduction of glucose metabolism in epileptogenic foci may be a result of reversible neuronal dysfunction that correlates with the electroclinical follow-up.     

Postoperative changes in cerebral metabolism in temporal lobe epilepsy

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452     

Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy

We evaluated reproductive endocrine function in women with unilateral temporolimbic epilepsy and normal control subjects to assess the effects of epilepsy, epilepsy laterality, and antiepileptic drug use on the cerebral regulation of hormonal secretion. The findings indicate that reproductive endocrine function differs between women with epilepsy and normal control subjects. Significant differences exist at all levels of the reproductive neuroendocrine axis, that is, hypothalamus, pituitary, and peripheral gland. Differences show significant relationships to the epilepsy itself as well as to medication use. Reproductive neuroendocrine changes occur in a stochastic manner such that the laterality of unilateral temporolimbic discharges is associated with predictable directional changes in hormonal secretion at all levels of the reproductive neuroendocrine axis. These directional changes are consistent with the finding that different reproductive disorders may develop in relation to left- and right-sided temporolimbic epilepsy. Hormonal changes can show close temporal relationship to the occurrence of interictal epileptiform discharges and may vary in relation to the laterality of the discharges. Antiepileptic drugs differ in their effects on reproductive hormone levels. There are notable differences between enzyme-inducing and noninducing drugs. Menstrual disorders are more common among women with interictal discharges as well as women with abnormal hormonal findings.     

Interictal and ictal dipole modelling in patients with refractory partial epilepsy

Fifteen patients (7 men, 8 women) with mean age of 34 years and mean duration of refractory partial seizures of 17 years were included in a presurgical evaluation protocol. Neuroimaging (CAT, 1.5 T MR) demonstrated intracranial structural lesions (space-occupying: n = 9; atrophic: n = 6) and video-EEG monitoring showed complex partial seizures in all patients. Four patients underwent additional intracranial EEG monitoring that demonstrated hippocampal seizure onset in all. Voltage topography and spatiotemporal dipole mapping of interictal epileptic discharges revealed two distinct dipole types. Patients with lesions in the medial (and lateral) temporal lobe uniformly presented with a negative voltage field with a steep gradient over the inferior temporal area and a stable, combined dipole that consisted of a radial and a tangential component with a high degree of elevation relative to the axial plane. Patients with extratemporal lesions had a more diffuse, less dipolar voltage field and a corresponding dipole which was less stable and had a predominant radial component. Dipole modelling of epochs of early ictal discharges revealed a striking correspondence with the interictal findings in individual patients. Interictal spike voltage topography and corresponding dipole mapping provided additional and reliable information that was relevant in surgical candidates for refractory partial epilepsy, e.g. by suggesting in some patients that the medial temporal structures were not primarily involved. Ictal dipole modelling revealed concordant results with interictal data. It shows promising but needs further confirmation and validation in a larger patient population with intracranial EEG recordings. Despite intrinsic limitations, spike voltage topography and dipole mapping contributes to a better localisation of the underlying brain source of epileptic discharges.     

Patterns of cerebral glucose metabolism in patients with partial seizures

We analyzed local cerebral metabolic rates of glucose (LCMRglu) in 20 regions from 22 patients with complex partial seizures, who were taking neither phenytoin nor phenobarbital and who had normal CTs. Results were compared with data from 19 normal controls. Ten patients had left temporal, eight right temporal, and four bitemporal or generalized EEG discharges. There were no significant differences between patient and control values in any of 20 regions of interest. LCMRglu was depressed at the site of the epileptic focus: L/R ratio was 0.85 +/- 0.12 (p less than 0.003 compared with control), 0.92 +/- 0.08 (p less than 0.05), and 0.84 +/- 0.1 (p less than 0.001), respectively, in mesial, superior, and inferior temporal regions for patients with left temporal foci; 1.7 +/- 0.96 (p less than 0.04), 1.1 +/- 0.1 (NS), and 1.15 +/- 0.04 (p less than 0.001) for patients with right temporal foci. Patients with left temporal EEG foci had significantly lower values than patients with right temporal foci in left superior frontal and thalamic as well as left temporal regions, while patients with right-sided EEG foci had depressed LCMRglu (compared with patients with left temporal EEG foci) restricted to right mesial temporal lobe. The patients with left temporal foci tended to have longer seizure histories (22.7 +/- 5.4 versus 11 +/- 5.6 years; p less than 0.001). There was an inverse correlation between length of seizure history and mean LCMRglu (r = 0.38; 0.1 greater than p greater than 0.05). Our study suggests that LCMRglu is not depressed in regions beyond the epileptic focus when patients are not taking drugs known to decrease cerebral glucose metabolism.