Mesial Temporal Lobe Seizures Research Articles

Evoked potential study of hippocampal efferent projections in the human brain

Objective To explore in human potential hippocampal projections within and outside the temporal lobe. Methods We performed intra-cerebral electrical stimulations in seven patients investigated by depth electrodes for refractory epilepsy and analyzed the presence of evoked potentials (EPs) in all brain regions explored. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in a total of 36 hippocampal stimulations sites. Results Reproducible EPs were recorded in several brain regions with variable latencies, amplitudes and morphologies. Within the temporal lobe, EPs were present in the amygdala, entorhinal cortex, temporal pole and temporal neocortex. EPs were also observed in the frontal lobe, anterior cingulate gyrus and orbito-frontal cortex, midcingulate and posterior cingulate gyrus, insula and thalamic pulvinar nucleus. Conclusion Our results demonstrate a large distribution of direct or indirect hippocampal projections. Significance This widespread connectivity supports the previous definition of different networks involved mainly in memory and behavioral processes, implicating the temporal lobe, the cingulate gyrus or the prefrontal region. Our data provide some clues to further evaluate potential pathways of propagation of mesial temporal lobe seizure, via the insula or the pulvinar nucleus.

Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis

To describe a distinctive seizure semiology that closely associates with voltage-gated potassium channel (VGKC)-complex/Lgi1 antibodies and commonly precedes the onset of limbic encephalitis (LE). Twenty-nine patients were identified by the authors (n = 15) or referring clinicians (n = 14). The temporal progression of clinical features and serum sodium, brain magnetic resonance imaging (MRI), positron emission tomography/single photon emission computed tomography, and VGKC-complex antibodies was studied. Videos and still images showed a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affected the arm and ipsilateral face. We have termed these faciobrachial dystonic seizures (FBDS). All patients tested during their illness had antibodies to VGKC complexes; the specific antigenic target was Lgi1 in 89%. Whereas 3 patients never developed LE, 20 of the remaining 26 (77%) experienced FBDS prior to the development of the amnesia and confusion that characterize LE. During the prodrome of FBDS alone, patients had normal sodium and brain MRIs, but electroencephalography demonstrated ictal epileptiform activity in 7 patients (24%). Following development of LE, the patients often developed other seizure semiologies, including typical mesial temporal lobe seizures. At this stage, investigations commonly showed hyponatremia and MRI hippocampal high T2 signal; functional brain imaging showed evidence of basal ganglia involvement in 5/8. Antiepileptic drugs (AEDs) were generally ineffective and in 41% were associated with cutaneous reactions that were often severe. By contrast, immunotherapies produced a clear, and often dramatic, reduction in FBDS frequency. Recognition of FBDS should prompt testing for VGKC-complex/Lgi1 antibodies. AEDs often produce adverse effects; treatment with immunotherapies may prevent the development of LE with its potential for cerebral atrophy and cognitive impairment.

Foramen ovale electrodes in the preoperative evaluation of temporal lobe epilepsy in children

Foramen ovale electrodes (FOEs) can localize the epileptogenic zone in adults with mesial temporal lobe epilepsy (TLE). Our aim was to investigate the feasibility and safety of using FOEs to investigate refractory TLE in children. Thirty-eight children with seizure semiology and video-EEG (electroencephalography) consistent with medically refractory TLE, and/or the presence of a lesion in the temporal lobe, had FOEs inserted. Complications occurring during the monitoring and up to 3 months after surgery and the long-term seizure outcome were registered. Forty electrodes were placed in 38 patients. The mean age of the patients was 9.8 years (range 2.3-15.4 years). FOEs confirmed a unilateral mesial temporal lobe seizure onset in 14 patients, onset in both FOEs and lateral electrodes in two patients, and onset in the anterior temporal electrodes in only one patient. Six patients had seizures recorded but were not considered surgical candidates; four patients had no seizures recorded, and 11 patients were further investigated with depth electrodes. One patient (2.6%) developed a hematoma in the cheek, and in two patients the electrodes were extracranial but could still be used for recording. Twenty-eight children had a temporal resection; 25 were Engel class I at follow-up. FOEs are safe to use in children and provide valuable information on the mesial temporal lobe structures in the preoperative investigation of pediatric TLE. Patient selection for FOE investigation is, however, essential for a conclusive result.

Right and left mesial temporal lobe seizures in one patient: Bona fide semiological, interictal, ictal, and MRI evidence

We present the case of a 36-year-old patient with bilateral independent manual automatisms associated with seizures coming independently from the left and right temporal lobes, as documented by surface EEG ictal recordings. An MRI showed evidence of bilateral mesial temporal sclerosis, more prominent on the right side. We speculate whether clinical semiology (along with the ictal EEG and imaging findings) discourages the pursuit of invasive monitoring, leading to more aggressive medical management in this particular case.

Small-world networks and epilepsy: Graph theoretical analysis of intracerebrally recorded mesial temporal lobe seizures

Objective Neuronal networks with a so-called ‘small-world’ topography (characterized by strong clustering in combination with short path lengths) are known to facilitate synchronization, and possibly seizure generation. We tested the hypothesis that real functional brain networks during seizures display small-world features, using intracerebral recordings of mesial temporal lobe seizures. Methods We used synchronization likelihood (SL) to characterize synchronization patterns in intracerebral EEG recordings of 7 patients for 5 periods of interest: interictal, before-, during- and after rapid discharges (in which the last two periods are ictal) and postictal. For each period, graphs (abstract network representations) were reconstructed from the synchronization matrix and characterized by a clustering coefficient C (measure of local connectedness) and a shortest path length L (measure of overall network integration). Results were also compared with those obtained from random networks. Results The neuronal network changed during seizure activity, with an increase of C and L most prominent in the alpha, theta and delta frequency bands during and after the seizure. Conclusions During seizures, the neuronal network moves in the direction of a more ordered configuration (higher C combined with a slightly, but significantly, higher L) compared to the more randomly organized interictal network, even after correcting for changes in synchronization strength. Significance Analysis of neuronal networks during seizures may provide insight into seizure genesis and development.

Are Ictal Fast Ripples an “Electronic Signature” for the Seizure-onset Zone?

High-Frequency Oscillations during Human Focal Seizures. Jirsch JD, Urrestarazu E, LeVan P, Olivier A, Dubeau F, Gotman J. Brain 2006;129(Pt 6):1593–1608. Discrete high-frequency oscillations (HFOs) in the range of 100–500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe, for the first time, similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing presurgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF 250–500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF 100–200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral perihippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic etiologies.

Comparison of neuropsychological outcomes after selective amygdalohippocampectomy versus anterior temporal lobectomy

Transsylvian selective amygdalohippocampectomy (TSA) is an operative technique designed to spare unaffected brain tissue during surgical treatment for mesial temporal lobe epilepsy. In contrast to standard anterior temporal lobectomy (ATL), the advantages of TSA with respect to postoperative cognitive outcome are equivocal. We compared cognitive function before and after surgery in 49 patients with unilateral mesial temporal lobe seizures who underwent either ATL ( n = 17) or TSA ( n = 32). All patients received neuropsychological testing before and 1 year after surgery. The intelligence quotient (IQ) increased postoperatively in both surgical groups. Memory evaluation in the ATL group revealed a postoperative decline in nonverbal memory after right-sided resection and a postoperative decline in verbal memory after left-sided resection. In the TSA group, there was a slight postoperative decline only in verbal memory after left-sided resection, but other memory function was well preserved. In particular, there was significant postoperative improvement in verbal memory after right-sided resection. Overall, memory function was better preserved in the TSA group than in the ATL group.

High-frequency oscillations during human focal seizures

Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.

Differentiability of simulated MEG hippocampal, medial temporal and neocortical temporal epileptic spike activity.

Previous studies have shown that magnetoencephalography (MEG) can measure hippocampal activity, despite the cylindrical shape and deep location in the brain. The current study extended this work by examining the ability to differentiate the hippocampal subfields, parahippocampal cortex, and neocortical temporal sources using simulated interictal epileptic activity. A model of the hippocampus was generated on the MRIs of five subjects. CA1, CA3, and dentate gyrus of the hippocampus were activated as well as entorhinal cortex, presubiculum, and neocortical temporal cortex. In addition, pairs of sources were activated sequentially to emulate various hypotheses of mesial temporal lobe seizure generation. The simulated MEG activity was added to real background brain activity from the five subjects and modeled using a multidipole spatiotemporal modeling technique. The waveforms and source locations/orientations for hippocampal and parahippocampal sources were differentiable from neocortical temporal sources. In addition, hippocampal and parahippocampal sources were differentiated to varying degrees depending on source. The sequential activation of hippocampal and parahippocampal sources was adequately modeled by a single source; however, these sources were not resolvable when they overlapped in time. These results suggest that MEG has the sensitivity to distinguish parahippocampal and hippocampal spike generators in mesial temporal lobe epilepsy.

Hippocampal-orbitofrontal connectivity in human: An electrical stimulation study

Objective The identification of the pathways involved in seizure propagation remains poorly understood in humans. For instance, the respective role of the orbitofrontal cortex (OFC) and of the commissural pathways in the interhemispheric propagation of mesial temporal lobe seizures (mTLS) is a matter of debate. In order to address this issue, we have directly tested the functional connectivity between the hippocampus and the OFC in 3 epileptic patients undergoing an intra-cranial stereotactic EEG investigation. Methods Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in the hippocampus. Evoked potentials (EPs) were analysed for each series, separately. Grand average of reproducible EPs was then used to calculate latency of the first peak of each individual potential. Results Hippocampal stimulations evoked reproducible responses in the OFC in all 3 patients, with a mean latency of the first peak of 222 ms (range: 185–258 ms). Conclusions Our data confirm a functionnal connectivity between the hippocampus and the OFC in human. Significance This connectivity supports the potential role of the OFC in the propagation of mTLS.

Preictal state identification by synchronization changes in long-term intracranial EEG recordings

Objective There is accumulated evidence that mesial temporal lobe seizures are preceded by a preictal transition that evolves over minutes to hours. In the present study, we investigated these possible preictal changes in long-term intracranial recordings of five patients by a measure of phase synchronization. In order to clearly distinguish preictal changes from all the other interictal states, we developed an automatic extraction of representative patterns of interictal synchronization activity. This reference library was used to classify the successive synchronization patterns of long-term recordings into groups of similar patterns. Altered states of brain synchronization were identified as deviating from patterns in the reference library and were evaluated relative to the times of seizure onset in terms of sensitivity and specificity. Methods A phase-locking measure was estimated using a sliding window analysis on 15 frequency bands (2 Hz steps between 0 and 30 Hz), for all pairs of EEG channels in the epileptogenic temporal lobe (14–20 channels), over the entire data sets (total analyzed duration 305 h). The preictal identification encompasses three basic stages: (1) a preprocessing stage involving the determination of a reference library of characteristic interictal synchronization patterns using a K-means algorithm, and the identification of discriminant variables differentiating interictal from preictal states, (2) a classification stage of the synchronization pattern via a minimum Mahalanobis distance to the reference patterns, as well as detection of outliers, (3) an evaluation stage of the sensitivity and specificity of the detection by receiver-operating characteristic curves. Results In most of the cases (36 of 52 seizures, i.e. 70%), a specific state of brain synchronization can be observed several hours before the actual seizure. The changes involved both increases and decreases of the synchronization levels, occurring mostly within the 4–15 Hz frequency band, and were often localized near the primary epileptogenic zone. Conclusions The analysis of phase synchronization offers a way to distinguish between a preictal state and normal interictal activity. These findings suggest that brain synchronizations are preictally altered in the epileptogenic temporal lobe, inducing a pathological state of higher susceptibility for seizure activity. Significance Phase synchronization is capable of extracting information from the EEG that allow the definition of a preictal state. Although the proposed analysis does not constitute genuine seizure anticipation, these changes in neuronal synchronization may provide helpful information for prospective seizure warning.

Intracranial EEG study of seizure-associated nose wiping.

The authors studied the relation between seizure-associated nose wiping (NW) and intracerebral EEG data in 32 patients. NW was more frequent in mesial temporal lobe seizures (TLSs; 65%) than in other TLSs (36%; p < 0.05) and in frontal lobe seizures (3%; p < 0.0001). It was associated with the presence of an amygdala discharge at seizure onset (p < 0.05) and with the recording of an ictal low-voltage fast activity within that structure (p < 0.05), supporting the role of an amygdala dysfunction in the pathophysiology of NW.

Mesial temporal lobe seizures may activate thermoregulatory mechanisms in humans: an infrared study of facial temperature

Facial temperature T f , an important link in cerebral thermoregulation and an ignored index of autonomic activity, was studied in three patients with mesial temporal epilepsy. Sets of infrared images were obtained automatically during seizures and also hourly, round-the-clock. For each patient, scan sets were sorted into: (1) ictal; (2) interictal with negligible motion; and (3) interictal with motion. Comparisons of mean, variance, and trend in each scan set among these groups showed considerable variability. However, significant trends in T f occurred ( P<0.05) in two-thirds of seizures in one patient, three-fourths in another, and two-ninths in the third, consisting of steady decreases in T f beginning at peak seizure intensity R max and continuing into the postictus. Maximal ictal T f was greater than interictal T f ( P<0.05), but it negatively correlated with R max in two subjects. The ictal changes in T f , which may have a homeostatic role, suggest activation of thermoregulatory mechanisms during mesial temporal seizures.

The role of the insular cortex in temporal lobe epilepsy

The role of the insular cortex in the genesis of temporal lobe epileptic (TLE) seizures has been investigated in 21 patients with drug-refractory TLE using chronic depth stereotactic recordings of the insular cortex activity and video recordings of ictal symptoms during 81 spontaneous electroclinical seizures. All of the recorded seizures were found to invade the insula, most often after a relay in the ipsilateral hippocampus (19/21 patients). However, 2 patients had seizures that originated in the insular cortex itself. Ictal symptoms associated with the insular discharges were similar to those usually attributed to mesial temporal lobe seizures, so that scalp video-electroencephalographic monitoring does not permit making any difference between ictal symptoms of temporo-mesial and insular discharges. A favorable outcome was obtained after a temporal cortectomy sparing the insular cortex in 15 of 17 operated patients. Seizures propagating to the insular cortex were found to be fully controlled by surgery, whereas those originating in the insular cortex persisted after temporal cortectomy. The fact that seizures originating in the insular cortex are not influenced by temporal lobectomy is likely to explain some of the failures of this surgical procedure in TLE.

Relationship of Temporal Lobe Seizures to Sleep and Arousal: A Combined Scalp-Intracranial Electrode Study

The role of arousal from sleep in promoting epileptic seizures is controversial. To examine the question of whether seizures precede or follow arousals from sleep, we defined the timing of temporal lobe seizures in relation to sleep and arousal using combined scalp-intracranial electrodes. Retrospective review of 67 sleep-related mesial temporal lobe seizures in 14 subjects. Inpatient epilepsy monitoring laboratory. Subjects with medically refractory mesial temporal lobe seizures undergoing epilepsy surgery evaluations. None Electroencephalographic (EEG) and/or polygraphic recordings and videotapes were independently reviewed to determine intracranial electrode seizure onset times and time of initial arousal from sleep. In 60 seizures in 13 subjects, intracranial ictal onsets always preceded clinical arousals from sleep. Electrographic signs of arousal in the scalp EEG, defined by the presence of sustained alpha or theta activity, either coincided with or followed, but never preceded, intracranial ictal onsets. In seven seizures in one subject with known seizures upon awakening, intracranial ictal onsets always followed clinical arousals and electrographic signs of arousal from sleep. Seven of the 14 subjects had electrooculogram and chin electromyogram monitoring; in these subjects, no seizures occurred during REM sleep with the majority occurring during NREM stage 2 sleep. Most sleep-related temporal lobe seizures occurred during NREM sleep and preceded arousals, supporting the premise that processes involved in the initiation and maintenance of NREM sleep play a greater role in facilitating temporal seizures than those involved in promoting REM sleep and arousal. However, arousal from sleep may provoke seizures in exceptional cases.

When is imaging enough?

ABSTRACT Despite tremendous recent advances in both structural and functional neuroimaging, these tests alone are not enough to recommend surgery for medically refractory epilepsy. A detailed history, careful description of the ictal events, and the neurological examination will always be necessary. Interictal EEG and neuropsychological testing also add important information. In many situations, however, video‐EEG monitoring of habitual seizures now plays a confirmatory, rather than a primary, role in the presurgical evaluation, and can occasionally contribute confounding data that delay or prevent surgical intervention. In the present climate of cost‐containment, it is reasonable to ask if this expensive diagnostic tool is always needed when it is clear by other means that seizures are not psychogenic, particularly in certain pediatric surgically remediably syndromes such as those catastrophic epilepsys of infants and young children amenable to hemispherectomy, and drop attack that can be treated with corpus callosotomy, as well as mesial temporal lobe epilepsy and seizures due to discrete resectable lesions that often become medically intractable in adolescence. Retrospective studies should be carried out to determine when long‐term, in‐patient, video‐EEG monitoring in these conditions add information that appropriately changes the therapeutic approach.

Application of the directed transfer function method to mesial and lateral onset temporal lobe seizures.

The directed transfer function (DTF) method is a multichannel analysis based on an autoregressive model that detects flow of seizure activity. This report extends the application of the DTF method to compare patterns of flow of seizures with different sites of origin. Analysis of a seizure originating from mesial temporal structures is compared with a seizure originating from lateral temporal neocortex; both complex partial seizures were recorded with intracranial electrodes that combine subdural grid arrays and depth electrodes. The DTF method has the potential to determine patterns of flow of activity, including periods when visual analysis of the intracranial ictal EEG may not allow for definitive source localization. The extension of the DTF analyses into integrated DTF (IDTF) formats is also illustrated. When activity of a relatively discrete frequency can be identified, the IDTF analysis facilitates display of patterns of flow of this selected activity.

Olfactory bedside test. A simple approach to identify temporo-orbitofrontal dysfunction.

Olfactory memory and discrimination are processed by the anteromesial temporal cortex and the orbitofrontal cortex. Both functions may therefore be impaired in limbic epilepsy. Twenty-seven patients with mesial temporal lobe seizures (MTLS), 10 patients with neocortical seizures (NS), and 10 matched healthy control subjects underwent evaluation for olfactory quality discrimination (OD) and delayed recognition memory (OM). All patients were referred for presurgical evaluation. The olfactory tests were performed in a same-different paradigm with 10 seconds (OD) and 60 minutes (OM) between presentations of the odors, using the standardized University of Pennsylvania Smell Identification Test. The presentations were monorhinal in the OD and birhinal in the OM tests. The results were related to regional glucose metabolism measured with fludeoxyglucose F 18 positron emission tomography. Patients with MTLS had an impaired OD ipsilateral to the epileptogenic region (P < .001) and a higher total number of errors (including both tests) (P = .002). They also had lower OM scores, but not significantly lower than those of patients with NS (P = .05). The combined OM and OD tests correctly identified patients with MTLS with a sensitivity of 85% and a specificity of 90%, offering a correct lateralization in 74% of patients. Patients with MTLS whose OD was more impaired than OM differed from those with more impaired OM by having a significant hypometabolism not only over the neocortex of the epileptogenic temporal lobe (P = .02) but also in the ipsilateral anterior (P = .008) and orbitofrontal cortex (P = .007) (2-way analysis of variance). Tests of olfactory function are useful in distinguishing between NS and MTLS. The impairments of OM and OD can be dissociated in pathological states and therefore mediated by different structures.

Pattern of Interictal Hypometabolism in PET Scans With Fludeoxyglucose F 18 Reflects Prior Seizure Types in Patients With Mesial Temporal Lobe Seizures

Interictal hypometabolism is routinely used as an indicator of the epileptogenic zone in patients with complex partial seizures (CPSs). However, the regional pattern of hypometabolism varies without obvious reasons, even among patients with identical epileptogenic zones and causes. To investigate whether this pattern may be related to the electroencephalographic and clinical features of the seizure that precedes the positron emission tomographic (PET) scan with fludeoxyglucose F 18. Fifty-three patients with CPSs were first classified into 4 groups, depending on the features of the seizure that preceded the PET scan (determined from findings from electroencephalography and videotelemetry). In 14 patients, this seizure was focal limbic (characterized by aurae or staring spells); in 18, the CPS was widespread limbic (including automatisms). Ten patients had a CPS with posturing, and 11 had a secondarily generalized CPS. Regions with a hemisphere-normalized concentration of fludeoxyglucose F 18 below the 95% confidence interval of values from 8 control subjects were defined as hypometabolic. The location of these regions was then compared among the 4 groups, and the degree of hypometabolism was related to the time from the seizure to the PET scan with fludeoxyglucose F 18. The hypometabolic area was limited to the epileptogenic zone if the preceding seizure was focal limbic, whereas in patients with widespread limbic seizures, it included one or several additional areas of the limbic cortex (P = .03). Patients with posturing differed from both previous groups by having hypometabolism in the extralimbic frontal lobe (P < .001), and subjects with secondarily generalized seizures differed from all others because of cerebellar (P < .001) and parietal lobe (P < .05) reductions. The time between the seizure and the performance of the PET scan did not correlate with the degree or extent of hypometabolism. Mechanisms involved in the generation of a seizure that precedes a PET scan with fludeoxyglucose F 18 seem to influence the "interictal" hypometabolic pattern. Therefore, caution should be used when interpreting scans that are preceded by a nonhabitual seizure.

Localized cerebellar reductions in benzodiazepine receptor density in human partial epilepsy.

Previous studies suggest that the morphological substrate for cerebellar dysfunction is destruction of Purkinje cells, but disagree on whether this is caused by seizure- or drug-related toxicity. The benzodiazepine (BZ) receptor antagonist flumazenil tagged with carbon 11 is a sensitive marker of Purkinje cells. To investigate whether cerebellar dysfunction in partial epilepsy is related to seizures through cerebrocerebellar connections. Positron emission tomography with [11C] flumazenil was conducted in 5 patients with frontal lobe seizures, 12 patients with mesial temporal lobe seizures, and 7 healthy men. Eight patients also had [18F]-fluorodeoxyglucose positron emission tomography. Cerebellar regions of interest were delineated using magnetic resonance imaging and a computerized anatomical brain atlas, and the epileptogenic regions were determined with a multimethod assessment. Patients with frontal lobe seizures had a significantly reduced BZ receptor density in the anterior cerebellum contralateral to the seizure onset region (P < or = .001), 2-way repeated-measure analysis of variance). Patients with mesial temporal lobe seizures had reductions in the ipsilateral (posterior and anterior) cerebellum (P < or = .001 for both). No significant asymmetries were found in regional glucose metabolism. The observed distribution of BZ receptor reductions is congruent with animal experiments showing tht frontal lobe projections to the cerebellum are crossed, whereas projections from mesial temporal loe are predominantly ipsilateral. The results thus indicate a functional relation with seizures and may reflect excitotoxic lesions or specific changes in the gamma-aminobutyric BZ system.