FDG-PET and MRI in temporal lobe epilepsy: relationship to febrile seizures, hippocampal sclerosis and outcome

Objective – To correlate the volumetric head magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan findings with the history, intracarotid amobarbital procedure, pathology, and outcome in patients with medically refractory temporal lobe epilepsy. Material and methods – Thirty-eight patients with temporal lobe epilepsy treated surgically following a comprehensive presurgical evaluation. Follow-up ranged from 12 to 44 months. Results – Volumetric MRI showed ipsilateral hippocampal atrophy in 29 (76%), and PET scan showed ipsilateral temporal hypometabolism (PET-TH) in 31 (81.5%) of patients. Eighty-three percent of those patients with hippocampal sclerosis on MRI (MRI-HS) had ipsilateral PET-TH. Sixty-six percent of patients with MRI-HS had a history of prolonged febrile convulsions or a childhood febrile illness accompanied by convulsions, and 77% of patients with MRI-HS had pathologically proven hippocampal sclerosis (HS). Ninety percent became seizure free or had rare seizures. Conclusion – FDG-PET scans and head MRIs were complementary; 95% of patients had either MRI-HS or temporal hypometabolism. MRI-HS correlated with a history of febrile seizures and pathologically demonstrated hippocampal sclerosis. Ninety-three percent of patients had focal functional deficits on the epileptogenic side. Concordance between PET temporal hypometabolism and MRI-HS correlated with better outcome.     

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.     

Coexistence of focal and idiopathic generalized epilepsy in the same patient population.

PURPOSE: To review the clinical, electrographic, radiological, and pathological findings of patients with coexistent idiopathic generalized and partial epilepsy syndromes. METHODS: We performed a medical record review and a phone interview with all patients hospitalized to the Cleveland Clinic epilepsy monitoring unit (EMU) between 1992 and 2002 who fulfilled clinical and EEG criteria of coexistent partial and generalized epilepsy syndromes. RESULTS: Seven patients were identified. Two (29%) were men with a mean age of 26 years. Four had a history of febrile seizures. Family history was positive in five. Mean duration of the generalized epilepsy syndrome was 11 years, and of the focal epilepsy 18 years. An equal number of patients developed focal versus generalized epilepsy first. Interictal EEG activity was predominantly generalized. Four had video-EEG documentation of both types of seizures. In the rest, only focal seizures were recorded but interictal activity strongly suggested a coexistent generalized epilepsy. MRI showed hippocampal atrophy in all, and hippocampal dysplasia in three. Five patients had PET imaging, all with hypometabolism in areas corresponding to the ictal onset on EEG. Four patients underwent epilepsy surgery with good surgical outcome and pathological confirmation of hippocampal sclerosis in all. CONCLUSION: We found a 0.2% incidence of coexistent focal and primary generalized epilepsy. Febrile seizures and a positive family history were common. Good seizure control was achieved after temporal lobectomy, even when interictal generalized activity predominated.     

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.     

Seizure Frequency and Duration of Epilepsy are Not Risk Factors for Postoperative Seizure Outcome in Patients with Hippocampal Sclerosis

PURPOSE: Despite accurate localization of the seizure focus, not all patients are seizure free after temporal lobectomy. This study determined risk factors for seizure recurrence in patients with proven hippocampal sclerosis. METHODS: The outcome from surgery was assessed in 56 consecutive patients with proven hippocampal sclerosis. The age at surgery, duration of epilepsy, history and age of febrile seizures, age of onset of epilepsy, sex ratio, laterality of seizure focus, and seizure frequency were compared between patients seizure free and those not seizure free, and those seizure and aura free and those with seizure recurrence including auras. RESULTS: During a mean follow-up of 38 months, 48 (86%) of 56 are seizure free. The mean age at surgery (37 vs. 36 years), duration of epilepsy (26 vs. 22 years), age (1.6 vs. 1.1 years), and occurrence (58 vs. 75%) of febrile seizures, age of onset of epilepsy (11 vs. 14 years), sex ratio (50 vs. 75% female), laterality of seizure focus (42 vs. 50% left), greater than weekly seizures (40 vs. 38%), and a history of (69 vs. 75%) and frequency of (2.10 vs. 2.38 per year) secondarily generalized seizures did not differ significantly between the two groups. Similarly there was no significant difference between patients seizure and aura free and those with seizure recurrence including auras. CONCLUSIONS: Clinical factors such as seizure frequency and duration of epilepsy are not risk factors for postoperative seizure recurrence.     

Rapidly progressive hippocampal atrophy: evidence for a seizure-induced mechanism

Hippocampal formation atrophy (HFA) developed in an adult, who did not have epilepsy previously, after the occurrence of new-onset partial seizures from acute thrombosis of an ipsilateral parietal venous angioma. There was no evidence of hippocampal injury, and the patient had only one brief, generalized tonic-clonic seizure. Although HFA progressed rapidly over 5.5 months, the partial seizures did not become prolonged or secondarily generalized. Evidence from the patient indicates that partial seizure activity can cause rapid and progressive hippocampal atrophy.     

The genetics of localization-related symptomatic epilepsy: risk of a family history with seizures in patients who have undergone surgery

A family history of epileptic seizures including febrile convulsions was found in 15 of 103 patients (15%) with localization related epilepsy with partial seizures with and without secondary generalization, who were operated on because of drug resistance. This rate was significantly higher than that of the cumulative incidence in the general population (4%). The localization of the brain damage did not play a role (temporal lobe resection left: 15%, right: 17%, extra-temporal lesion excision: 20%, hemispherectomy: 11%). Various family members were involved. Some patients had more than one relative with seizures. Thus, 21 relatives suffered from seizures. Eleven of them had generalized tonic-clonic seizures (one grand mal on awakening), 7 had febrile convulsions (4 complicated), and in 1 patient the grand mal seizures on awakening were preceded by absences; 1 had generalized tonic-clonic and complex partial seizures; 1 after complicated febrile seizures likewise had complex partial seizures; another mentally retarded patient suffered from generalized tonic-clonic, axial tonic and myoclonic-astatic seizures. The seizure type of 3 remote relatives was not known. The first seizure occurred in 16 family members during childhood, in 3 in adolescence and in only 1 in adulthood (1 unknown). Eight showed mental retardation of slight degree in most. It is interesting that only one-third of the patients with a family history with seizures were seizure-free after the operation; 5 still had seizures, mostly reduced in frequency, 3 had seizures and isolated auras and 2 had only isolated auras. On comparing the findings in patients with and without a family history with seizures, those with family members with epileptic seizures showed a lower rate of an intellectual deficit (7 vs 47%) and brain tumours (13 vs 44%). Our earlier findings with a different group of patients are thus confirmed: that genetics play a role in symptomatic epilepsies. Received: 9 July 1996 Received in revised form: 1 April 1997 Accepted: 23 April 1997     

Neuroimaging evidence of progressive neuronal loss and dysfunction in temporal lobe epilepsy.

Whether temporal lobe epilepsy is the result of an isolated, early injury or whether there is ongoing neuronal dysfunction or loss due to seizures is often debated. We attempt to address this issue by using magnetic resonance techniques. Proton magnetic resonance spectroscopic imaging can detect and quantify focal neuronal dysfunction or loss based on reduced signals from the neuronal marker N-acetylaspartate (NAA), and magnetic resonance imaging (MRI)-based measurements of hippocampal volumes (MRIvol) can quantify the amount of atrophy in this structure. We performed magnetic resonance spectroscopic imaging and MRIvol in 82 consecutive patients with medically intractable temporal lobe epilepsy to determine whether there was a correlation between seizure frequency, or type or duration of epilepsy, with NAA to creatine (Cr) values or hippocampal volumes. Volumes and spectroscopic resonance intensities were categorized as to whether they were measured from the temporal lobe ipsilateral or contralateral to the predominant electroencephalographic focus. Ipsilateral and contralateral NAA/Cr was negatively correlated with duration of epilepsy. Hippocampal volumes were negatively correlated with duration ipsilaterally but not contralaterally. Frequency of complex partial seizures was not correlated with any of the magnetic resonance measures. However, patients with frequent generalized tonic-clonic seizures had lower NAA/Cr bilaterally and smaller hippocampal volumes ipsilaterally than patients with none or rare generalized tonic-clonic seizures. The results suggest that although an early, fixed injury may cause asymmetric temporal lobe damage, generalized seizures may also cause progressive neuronal dysfunction or loss.     

Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis

OBJECTIVES: To examine the degree of hippocampal atrophy in patients with temporal lobe epilepsy and proved hippocampal sclerosis to determine whether or not patients with febrile seizures have more severe hippocampal atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippocampal atrophy. METHODS: Hippocampal volumes were measured from volumetrically acquired MR images in 77 consecutive surgical patients with temporal lobe epilepsy (37 febrile seizures (FS)+, 40 FS-) with proved hippocampal sclerosis, and compared with 98 controls. RESULTS: Ipsilateral and contralateral hippocampal volumes were not significantly different between the FS+ and FS- groups. There was no difference in the age of onset of habitual seizures, duration of epilepsy, or age at the time of surgery, between these groups. No clinically significant correlations were found between hippocampal volumes and age of onset of first non-febrile seizure, duration of temporal lobe epilepsy, or complex partial and secondarily generalised seizure frequency, in patients with and without febrile seizures. CONCLUSIONS: Although febrile seizures was associated with hippocampal sclerosis in 48% of patients in this surgical series, the degree of MRI determined hippocampal atrophy was not related to a history of such seizures. The results do not support the view that febrile seizures cause more severe hippocampal sclerosis and are consistent with the hypothesis that hippocampal sclerosis is a pre-existing abnormality.     

Volumetric measurements of subcortical nuclei in patients with temporal lobe epilepsy.

OBJECTIVE: To determine the volumes of subcortical nuclei in patients with chronic epilepsy. BACKGROUND: Animal and human data suggest a crucial role for subcortical structures in the modulation of seizure activity, mostly as seizure-suppressing relays. Although cortical epileptogenic foci can vary in localization and extent, it nevertheless appears that these structures subsequently influence seizure propagation in a universal fashion. There is, however, little knowledge about the size of implicated subcortical structures in patients with epilepsy. METHOD: Using high-resolution MRI, the volumes of selected subcortical nuclei, such as the thalamus, caudate nucleus, putamen, and pallidum, were measured in both hemispheres of 27 patients with temporal lobe epilepsy. Fourteen healthy volunteers served as controls. Statistical analysis was done for both normalized volumes (by total brain volume) and unnormalized volumes. RESULTS: Overall, the patient group had smaller thalamic and striatal volumes in both hemispheres, mostly ipsilateral to the epileptic focus. No significant correlations were noted between volume measurements and age, age at onset, duration of epilepsy, or total seizure frequency, including frequency of generalized seizures. The putamen and thalamus seemed to be affected predominantly in patients with a history of febrile convulsions, whereas patients without febrile convulsions had smaller caudate nuclei bilaterally. CONCLUSIONS: Volumetric measurements of subcortical nuclei reveal atrophy of distinct subcortical nuclei in the patient group, predominantly ipsilateral to the focus. This finding probably reflects persistent abnormalities and not secondary change. In addition, the structural differences between patients with and patients without previous febrile convulsions suggest that these conditions may have different causes.