Epilepsy duration, febrile seizures, and cerebral glucose metabolism

PURPOSE: Studies using magnetic resonance imaging have shown that reduced hippocampal volume is associated with a history of febrile seizures, the duration of epilepsy, and the number of generalized tonic-clonic seizures. It is uncertain whether these factors have the same influence on functional as on structural measures of the integrity of the epileptogenic zone. METHODS: We used positron emission tomography (PET) with fluorine 18 2-deoxyglucose to study 91 patients with temporal lobe seizure foci localized by ictal video-EEG. PET was performed in the awake interictal resting state with ears plugged and eyes patched. We recorded surface EEG during injection (5 mCi) and the 30-min uptake period. We used a standard template to analyze PET scans. RESULTS: A significant negative relation was found between the duration of epilepsy and hippocampal glucose metabolism ipsilateral to the epileptic focus. Patients with a history of either any febrile seizures, or complex, or prolonged febrile seizures, did not have greater hypometabolism ipsilateral to the epileptic focus than did patients without a febrile seizure history. We found no effect of generalized tonic-clonic seizure history. CONCLUSIONS: Longer epilepsy duration is associated with greater hypometabolism, suggesting that epilepsy is a progressive disease.     

Relationship of seizure frequency to hippocampus volume and metabolism in temporal lobe epilepsy

PURPOSE: To examine the relationship between frequency of complex partial (CPS) and secondarily generalized tonic-clonic seizures (sGTCS) on hippocampal volume (HV) and temporal lobe metabolism. METHODS: We performed volumetric magnetic resonance imaging (MRI) and positron emission tomography with 18fluorodeoxyglucose (18FDG-PET) in 32 patients with epilepsy. Temporal lobe foci were localized by ictal video-EEG. RESULTS: We did not find any association between CPS frequency or lifetime number of sGTCS and HV or metabolism ipsilateral to electroencephalographic focus. CONCLUSION: The progress of metabolic or pathologic abnormalities of temporal lobe epilepsy may not be altered by adequate seizure control. The presence of an epileptic focus might be associated with progressive neuronal injury even in clinically well-controlled patients.     

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.     

Hippocampal Atrophy Is Not a Major Determinant of Regional Hypometabolism in Temporal Lobe Epilepsy

Summary: Purpose : The pathophysiologic basis for the [¹⁸F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS.
Methods : Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippocampal magnetic resonance imaging (MRI) volume ratios.
Results : There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r =−0.09, r =−0.04). When the right/left asymmetry index was compared with the right/left hippocampal volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippocampal atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%).
Conclusions : The lack of correlation between the magnitudes of the ratios argues against hippocampal atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.     

Regional brain glucose metabolism in patients with complex partial seizures investigated by intracranial EEG.

We performed interictal 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) studies in 57 patients with complex partial epilepsy (CPE), not controlled by medical treatment and considered for surgical resection of their epileptic focus. A precise localization of the epileptic focus was obtained in 37 of these patients with a combination of subdural and depth electrodes. We visually inspected the metabolic images; we also measured glucose consumption in a number of brain regions and compared the values with those obtained in 17 normal controls. Eighty-two percent of the 57 patients had an area of glucose hypometabolism on the 18FDG-PET images. Six patients had a frontal epileptic focus, 3 of them had a frontal lobe hypometabolism. Twenty-six patients had a unilateral temporal lobe focus and all of them displayed a temporal lobe hypometabolism. The asymmetry was more pronounced in the lateral temporal cortex (-20%) than in the mesial part of the temporal lobe (-9.6%). In each cortical brain region on the side of the epileptic focus (except the sensorimotor cortex), glucose consumption rate was lower than in the contralateral region or than in controls. No differences could be found between patients with a seizure onset restricted to the hippocampus and patients with a seizure onset involving the hippocampus and the adjacent neocortex. Divergent metabolic patterns were obtained in 5 patients with bilateral temporal seizure foci. Combined with other non invasive techniques (EEG, neuroradiology), PET contributes increasingly to the selection of patients with CPE who could benefit from surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic changes of subcortical structures in intractable focal epilepsy

PURPOSE: Intractable focal epilepsy is commonly associated with cortical glucose hypometabolism on interictal 2-deoxy-2[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET). However, subcortical brain structures also may show hypometabolism on PET and volume changes on magnetic resonance imaging (MRI) studies, and these are less well understood in terms of their pathophysiology and clinical significance. In the present study, we analyzed alterations of glucose metabolism in subcortical nuclei and hippocampus by using FDG-PET in young patients with intractable epilepsy. METHODS: Thirty-seven patients (mean age, 7.5 years; age range, 1-27 years) with intractable frontal (n = 23) and temporal (n = 14) lobe epilepsy underwent FDG-PET scanning as part of their presurgical evaluation. Normalized glucose metabolism was measured in the thalamus and caudate and lentiform nuclei, as well as in hippocampus, both ipsi- and contralateral to the epileptic focus, and correlated with duration and age at onset of epilepsy, presence or absence of secondary generalization, location of the epileptic focus, and extent of cortical glucose hypometabolism. RESULTS: Long duration of epilepsy was associated with lower glucose metabolism in the ipsilateral thalamus and hippocampus. Duration of epilepsy was a significant predictor of ipsilateral thalamic glucose metabolism in both temporal and frontal lobe epilepsy. Presence of secondarily generalized seizures also was associated with lower normalized metabolism in the ipsilateral thalamus and hippocampus. Extent of cortical hypometabolism did not correlate with subcortical metabolism, and glucose metabolism in the caudate and lentiform nuclei did not show any correlation with the clinical variables. CONCLUSIONS: The findings suggest that metabolic dysfunction of the thalamus ipsilateral to the seizure focus may become more severe with long-standing temporal and frontal lobe epilepsy, and also with secondary generalization of seizures.     

Differences between lateral and mesial temporal metabolism interictally in epilepsy of mesial temporal origin

We performed interictal [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in 17 patients with well-defined unilateral anterior mesial temporal epileptogenic foci as determined by EEG procedures. Sixteen of these patients subsequently underwent surgical resection of the epileptogenic focus. We measured local cerebral metabolic rates for glucose in mesial and lateral temporal structures and compared them with metabolic rates for analogous regions in 16 healthy normal volunteers and the contralateral hemisphere of the epileptic patients. We found relative hypometabolism ipsilateral to the seizure focus more frequently and to a greater degree in the lateral than in the mesial temporal cortex. Since the physiologic abnormalities involved mesial temporal structures, this observation suggests that functional pathways exist between mesial and lateral temporal cortex normally and that these pathways are altered in epilepsy of mesial temporal origin. Hypometabolism did not correlate well with histologic abnormalities in the surgical specimens.     

Cerebral metabolism and depression in patients with complex partial seizures.

Twenty-three patients with complex partial seizures were evaluated with 18F-2-deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions.     

Contralateral medial temporal lobe damage in right but not left temporal lobe epilepsy: a (1)H magnetic resonance spectroscopy study

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) of the hippocampus is useful in lateralising the epileptic focus in temporal lobe epilepsy for subsequent surgical resection. Previous studies have reported abnormal contralateral MRS values in up to 50% of the patients. OBJECTIVE: To identify the contributing factors to contralateral damage, as determined by MRS, and its extension in patients with temporal lobe epilepsy. METHODS: Single voxel MRS was carried out in the hippocampus and lateral temporal neocortex of both hemispheres in 13 patients with left temporal lobe epilepsy (LTLE) and 16 patients with right temporal lobe epilepsy (RTLE). All patients had mesial temporal lobe epilepsy with hippocampal sclerosis. Controls were 21 healthy volunteers of comparable age. RESULTS: Consistent with previous studies, the NAA/(Cho+Cr) ratio was abnormally low in the hippocampus ipsilateral to the focus (p < 0.0001), and there were lower values in both patient groups in the ipsilateral temporal neocortex (p < 0.0001). Patients with RTLE had left hippocampal MRS anomalies (p = 0.0018), whereas the right hippocampus seemed to be undamaged in LTLE patients. CONCLUSIONS: Unilateral mesial temporal lobe epilepsy is associated with widespread metabolic abnormalities which involve contralateral mesial and neocortical temporal lobe structures. These abnormalities appear to be more pronounced in patients with RTLE.     

Bilateral Hippocampal Atrophy in Medial Temporal Lobe Epilepsy

Summary: Quantitative evidence of hippocampal atrophy has been correlated with site of seizure onset, hippocampal neuronal loss, and seizure relief after resection. Most studies have quantified hippocampal atrophy using ratios or differences between right and left hippocampal values. However, bilateral hippocampal atrophy may remain undetected by these techniques. To assess the frequency and implications of bilateral hippocampal atrophy, we studied absolute hippocampal volumes in 53 temporal lobectomy patients who had undergone intracranial electroencephalogram recordings preoperatively. Coronal images were constructed perpendicular to the longitudinal axis of the hippocampus. Atrophy was defined as >2 SD below control values in the volume of the posterior. 5 cm of the hippocampus. Five of 53 patients (9%)had bilateral hippocampal atrophy; four of these cases were undetected by ratios. Surgery was performed on the side of ictal onset in all five patients; four have been seizure-free for >2 years. These results suggest that (a) mesial temporal sclerosis can be present bilaterally and may go undetected by hippocampal ratio or difference measures; (b) ab-solute hippocampal volume values as well as ratios are needed to detect all patients with bilateral hippocampal atrophy; and (c) temporal lobectomy is not contraindicated in patients with bilateral hippocampal atrophy, but success depends on electroencephalographic documentation of the side of predominant ictal onset.