Low incidence of abnormal (18)FDG-PET in children with new-onset partial epilepsy: a prospective study

OBJECTIVE: Patients with refractory partial epilepsy often exhibit regional hypometabolism. It is unknown whether the metabolic abnormalities are present at seizure onset or develop over time. METHODS: The authors studied 40 children within 1 year of their third unprovoked partial seizure with EEG, MRI, and [(18)F]-fluorodeoxyglucose ((18)FDG)-PET (mean age at seizure onset = 5.8 years, range 0.9 to 11.9 years; mean epilepsy duration = 1.1 years, range 0.3 to 2.3 years; mean number of seizures = 30, range 3 to 200). The authors excluded children with abnormal structural MRI, except four with mesial temporal sclerosis and two with subtle hippocampal dysgenesis. (18)FDG-PET was analyzed with a region of interest template. An absolute asymmetry index, [AI], greater than 0.15 was considered abnormal. RESULTS: Thirty-three children had a presumptive temporal lobe focus, five frontotemporal, and two frontal. Mean AI for all regions was not different from 10 normal young adults, even when children less likely to have a temporal focus were excluded. Eight of 40 children (20%) had focal hypometabolism, all restricted to the temporal lobe, especially inferior mesial and inferior lateral regions. Abnormalities were ipsilateral to the presumed temporal lobe ictal focus. CONCLUSIONS: Abnormalities of glucose utilization may be less common and profound in children with new-onset partial seizures than in adults with chronic partial epilepsy. Although these patients' prognosis is uncertain, resolution of epilepsy after three documented seizures is uncommon. If the subjects develop a higher incidence of hypometabolism in the future with planned follow-up studies, metabolic dysfunction may be related to persistent epilepsy rather than present at seizure onset.     

Temporal Lobe Epilepsy Subtypes: Differential Patterns of Cerebral Perfusion on Ictal SPECT

Summary: Purpose : We studied cerebral perfusion patterns in the various subtypes of TLE, as determined by pathology and good outcome after temporal lobectomy (as confirmation of temporal origin).
Methods : We studied clinical features and ictal technetium ^99m hexamethyl-propyleneamineoxime (99mTc-HM-PAO) single-photon emission-computed tomography (SPECT) in four subgroups of patients with intractable temporal lobe epilepsy (TLE) treated with surgery: hippocampal sclerosis (group 1, n = 10), foreign-tissue lesion in mesial temporal lobe (group 2, n = 8), foreign-tissue lesion in lateral temporal lobe (group 3, n = 7), and normal temporal lobe tissue with good surgical outcome (group 4, n = 5).
Results : No major clinical differences in auras, complex partial seizures or postictal states were identified among the groups. Ictal SPECT showed distinct patterns of cerebral perfusion in these subtypes of TLE. In groups 1 and 2, hyperperfusion was seen in the ipsilateral mesial and lateral temporal regions. In group 3, hyperperfusion was seen bilaterally in the temporal lobes with predominant changes in the region of the lesion. Hyperperfusion was restricted to the ipsilateral anteromesial temporal region in group 4. Ipsilateral temporal hyperperfusion in mesial onset seizures can be explained by known anatomic projections between mesial structures and ipsilateral temporal neocortex. Bilateral temporal hyperperfusion in lateral onset seizures can be explained by the presence of anterior commissural connections between lateral temporal neocortex and the contralateral amygdala.
Conclusions : We conclude that the perfusion patterns seen on ictal SPECT are helpful for subclassification of temporal lobe seizures, whereas clinical features are relatively unhelpful. These perfusion patterns provide an insight into preferential pathways of seizure propagation in the subtypes of TLE.     

Bilateral Temporal Hypometabolism in Epilepsy

Summary: Purpose: Positron emission tomography (PET) has proven useful in epilepsy surgery for its ability to identify unilateral temporal hypometabolism (UTH), which is predictive of good surgical outcome. The significance of bilateral temporal hypometabolism (BTH) is not known.
Methods: We identified all patients who had marked bilateral reduction in temporal lobe metabolism relative to the cerebellar hemispheres and compared their clinical features and treatment outcomes with those of control patients with UTH.
Results: BTH was evident in 10% of PET scans for epilepsy at our institution. We compared these patients with age-matched controls with UTH. The BTH patients had a higher percentage of generalized seizures; were more likely to have bilateral, diffuse or extratemporal seizure onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings. UTH patients were more likely to have unilateral mesial temporal atrophy on MFU. Even when electrical seizure onsets were well localized, surgical outcomes were markedly worse in these patients than in controls. Medical treatment was also less successful. Social and cognitive functioning was worse in the BTH group. The only death occurred in the group with BTH.
Conclusions: Patients with BTH have features distinct from those with UTH and have a worse prognosis for seizure remission after surgery.     

Sex differences in patients with mesial temporal lobe epilepsy

Possible sex differences in the pattern of interictalhypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobehypometabolism ipsilateral to the seizure onset (p<0.0001) and aspread of epileptiform activity to this region (p=0.001). By contrast,female patients more often exhibited hypometabolism (p=0.0052) and anictal spread to the contralateral temporal lobe (p=0.0097). Thesefindings suggest sex differences in spatial distribution of braindysfunction in MTLE, perhaps reflecting sexual dimorphism in regionalcerebral connectivity.

     

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.     

Comparison of the intracarotid amobarbital procedure and interictal cerebral 18-fluorodeoxyglucose positron emission tomography scans in refractory temporal lobe epilepsy.

The relationship between interictal focal hypometabolism determined by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans and memory function with the intracarotid amobarbital procedure (IAP) was evaluated in 23 patients with temporal lobe epilepsy. All patients underwent prolonged EEG/video monitoring. The epileptogenic focus was defined by interictal epileptiform discharges and ictal onsets. All 23 patients had recorded seizures arising exclusively from one temporal lobe. PET showed temporal lobe hypometabolism ipsilateral to the epileptogenic focus in 86% (20 of 23) of patients; IAP showed impaired memory of the hemisphere of seizure onset in 65% (15 of 23). Sixty-five percent (13 of 20) of patients with focal hypometabolism had ipsilateral memory impairment. Memory impairment contralateral to the hypometabolic zone was not observed. Ninety-five percent (22 of 23) of patients demonstrated functional impairment by either PET or IAP (or both) on the epileptogenic side.     

Role of the frontal lobes in the propagation of mesial temporal lobe seizures.

The depth ictal electroencephalographic (EEG) propagation sequence accompanying 78 complex partial seizures of mesial temporal origin was reviewed in 24 patients (15 from the University of Pittsburgh Epilepsy Center and 9 from UCLA). All patients were monitored with bilateral mesial frontal and mesial temporal depth electrodes and later received anterior temporal lobectomy. Ictal EEG records were categorized according to sequence of spread from the temporal focus to the other regions. Although propagation patterns varied both within and between patients, certain features were notable: (a) It was very common for seizure activity to spread initially to the ipsilateral frontal lobe (observed in 22 of 24 patients). (b) The most common mode of spread (15 of 24 patients) was initiating temporal lobe----ipsilateral frontal lobe----contralateral frontal lobe----contralateral temporal lobe. (c) Occasionally, seizure discharges invaded the frontal lobes but failed to invade the contralateral temporal lobe (2 of 24 patients). (d) Seizure activity occasionally invaded the contralateral temporal lobe prior to invading the frontal lobes (2 of 24 patients). Other notable features included (i) a clear tendency for mesial temporal seizure discharges initially to invade orbitofrontal (as opposed to anterior cingulate) cortex and (ii) the emergence of a period of clear asymmetry in the frontal lobes during which high-amplitude, rapid discharges were present on the side ipsilateral to the initiating temporal lobe. These results suggest that the prefrontal region, especially the orbitofrontal cortex, is strongly influenced by mesial temporal ictal activity. This region appears to be frequently involved in the propagation of seizures initiated in the mesial temporal lobe and may play a role in the interhemispheric propagation of mesial temporal seizures.     

The localizing value of ictal EEG in focal epilepsy.

OBJECTIVE: To investigate the lateralization and localization of ictal EEG in focal epilepsy. METHODS: A total of 486 ictal EEG of 72 patients with focal epilepsy arising from the mesial temporal, neocortical temporal, mesial frontal, dorsolateral frontal, parietal, and occipital regions were analyzed. RESULTS: Surface ictal EEG was adequately localized in 72% of cases, more often in temporal than extratemporal epilepsy. Localized ictal onsets were seen in 57% of seizures and were most common in mesial temporal lobe epilepsy (MTLE), lateral frontal lobe epilepsy (LFLE), and parietal lobe epilepsy, whereas lateralized onsets predominated in neocortical temporal lobe epilepsy and generalized onsets in mesial frontal lobe epilepsy (MFLE) and occipital lobe epilepsy. Approximately two-thirds of seizures were localized, 22% generalized, 4% lateralized, and 6% mislocalized/lateralized. False localization/lateralization occurred in 28% of occipital and 16% of parietal seizures. Rhythmic temporal theta at ictal onset was seen exclusively in temporal lobe seizures, whereas localized repetitive epileptiform activity was highly predictive of LFLE. Seizures arising from the lateral convexity and mesial regions were differentiated by a high incidence of repetitive epileptiform activity at ictal onset in the former and rhythmic theta activity in the latter. CONCLUSIONS: With the exception of mesial frontal lobe epilepsy, ictal recordings are very useful in the localization/lateralization of focal seizures. Some patterns are highly accurate in localizing the epileptogenic lobe. One limitation of ictal EEG is the potential for false localization/lateralization in occipital and parietal lobe epilepsies.     

Comparison of Combined Versus Subdural or Intracerebral Electrodes Alone in Presurgical Focus Localization

Summary: purpose: The yield of subdural versus intracerebra1 electrodes for ictal localization remains a point of controversy. We assessed the relative sensitivity of these two types of electrodes per case. Methods: Eighty-three intracranial recordings obtained from 82 patients were retrospectively reviewed to establish which type of electrode performed best in which patients and which seizure types. Results: Sixty (73%) of 82 patients had temporal lobe seizure onsets, eight frontal, nine widespread or multifoca/multilobar or both, whereas in five, seizure onset was not localized. Exclusive use of intracerebral electrodes would have been sufficient for accurate localization of the seizure—-onset zone in all 35 patients with strictly mesial temporal seizure onsets. In only 20 (57%) of these 35 patients, the same decision would have been reached with exclusive use of subdural electrodes. In wide-spread neocortical and mesial temporal seizures (n = 25). yield of both electrode types was at about the same level, but neither was sufficient to identify the zone of ictal onset on its own. In frontal or multilobar seizures (n = 22), yield of subdural electrodes was slightly better then that of the intracerebral electrodes, but was not sufficient in all cases. Conclusions: This study indicates that, depending on the characteristics of the seizure disorder, exclusive use of either intracerebral or subdural electrodes may easily result in erroneous diagnosis because of insufficient sampling of the brain. These findings are in contrast with other studies emphasizing the high yield of reliable EEG findings in evaluations with a single type of electrode and corroborate the results of one of our previous studies.     

Localization of extratemporal epileptic foci during ictal single photon emission computed tomography.

We obtained single photon emission computed tomography (SPECT) scans with technetium-99M-hexamethyl-propylene-amine-oxime in 11 patients during 12 extratemporal partial seizures (9 simple partial, 3 complex partial). Ten ictal SPECT studies in 9 patients showed a focal region of hyperperfusion, which agreed with electrical seizure onset in 5 and with clinical seizure localization in 4 in whom ictal electroencephalography was not localized. Contralateral cerebellar and ipsilateral basal ganglia hyperperfusion was seen in 3 patients with a frontal lobe seizure focus. Ictal hyperperfusion was well circumscribed, unlike the diffuse hyperperfusion changes reported during temporal lobe seizures. This observation may indicate a different degree of seizure spread in temporal as opposed to extratemporal epilepsy. Because electroencephalographic localization is often elusive in extratemporal seizures, ictal SPECT may be very helpful for the localization of extratemporal foci.