Comparison of ictal SPECT and interictal PET in the presurgical evaluation of temporal lobe epilepsy

We retrospectively compared ictal technetium 99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) and interictal ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) in 35 patients with well-lateralized temporal lobe epilepsy (TLE). Based on SPECT scans the two observers correctly lateralized seizure foci with certainty in 89% of patients; interobserver agreement was excellent. Both observers incorrectly lateralized the seizure focus on two SPECT scans; one error was explained by rapid electroencephalographic spread to the contralateral side and for the other patient, isotope was injected during a brief aura. Based on PET scans, observers correctly lateralized the foci with certainty in 63% and with lesser confidence in 83%; four incorrect lateralizations were made by one observer and none by the other. PET interobserver disagreement was explained by differences between observers in weighting the relative hypometabolism in medial and lateral temporal regions. The detection rate for PET was lower in the absence of structural imaging abnormalities (60 vs 87%). PET yielded correct lateralizations in the 2 patients for whom SPECT interpretation was difficult. We conclude that both ictal SPECT and interictal PET are sensitive methods for the lateralization of TLE, but SPECT can be interpreted with greater certainty and is more sensitive when magnetic resonance imaging findings are negative. False lateralization is rare with ictal SPECT and can be explained when interpreted in conjunction with electroclinical data. Both investigations have complementary roles when localization is difficult.     

Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy

OBJECTIVE: To assess the clinical implications and the pathophysiologic determinants of interictal bitemporal hypometabolism (BTH) in temporal lobe epilepsy (TLE) not associated with bilateral MRI abnormalities or intracranial space-occupying lesions. METHODS: The authors compared the clinical, interictal, and ictal EEG, Wada test, and neuropsychology data of 15 patients with intractable complex partial seizures of temporal lobe origin and BTH with those of 13 consecutive patients with unilateral TLE associated with unilateral temporal hypometabolism (UTH) who remained seizure free for more than 3 years after anterior temporal lobectomy. 18F-fluorodeoxyglucose PET scans were analyzed visually and semiquantitatively, and ratios of counts in individual temporal areas to the rest of the cerebrum were compared with the corresponding values from 11 normal control subjects and with the nonepileptogenic hemisphere of the 13 patients with UTH. BTH was defined as more than 2.5 SDs below control values for two or more temporal areas on each side irrespective of any asymmetry. RESULTS: BTH reflected bilateral independent seizure onset in eight patients (53%). The topography of the metabolic depression was not a reliable predictor of epileptogenicity, but involvement of the inferior temporal gyrus was related specifically to ipsilateral seizure onset (70% sensitivity, 100% specificity). In patients with unilateral TLE, contralateral hypometabolism was associated with longer disease duration and worst memory performance during the Wada test, which amounted to global amnesia after ipsilateral injection in three patients, precluding surgical treatment. Contralateral seizure spread in the ictal EEG was significantly faster in patients with BTH. CONCLUSIONS: In TLE, symmetric or asymmetric BTH may signal bilateral independent seizure onset in approximately half the patients, especially when involving the inferior temporal gyrus. Alternatively, it may reflect an advanced stage of the disease process, characterized by a breakdown of the inhibitory mechanisms in the contralateral hemisphere, and secondary memory deficit associated with higher risk of postoperative memory decline. Patients with TLE and BTH but without bilateral MRI changes may still be operated on successfully, but surgical suitability should be proved by comprehensive intracranial EEG studies and Wada test.     

Display of consistent ictal networks in refractory mesial temporal lobe epilepsy

ObjectiveExploration of emergent ictal networks was performed in homogeneous subjects with refractory medial temporal lobe epilepsy.MethodsMaximal Synchrony Index (SI) values were calculated for all electrode pairs for each second during 25 seizures and displayed as connectivity animations. Consistent temporal patterns of SI value and spatial connectivity were observed across seizures and subjects, and used to define a sequence of network stages.ResultsHighest SI values were found in electrodes within the area of surgical resection. Analysis of these electrodes by network stage demonstrated lateral temporal cortex dominance at seizure initiation, giving way to hippocampal synchrony during the major portion of the seizure, with lateral temporal regions re-emerging as the seizure terminated. SI values also corresponded to behavioral severity of seizures, and lower SI values were associated with post-surgical seizure freedom.ConclusionSI based methods of network characterization consistently display the intrinsic MTLE ictal network and may be sensitive to clinical features.SignificanceConsistency of EEG-derived network patterns is an important step as network features are applied towards improvement of clinical management. These data confirm consistency of network patterns within and across subjects and support the potential for these methods to distinguish relevant clinical variables.     

Neuroaminidase reduces interictal spikes in a rat temporal lobe epilepsy model

Interictal spikes have been implicated in epileptogenesis and cognitive dysfunction in epilepsy. Unfortunately, antiepileptic drugs have shown poor efficacy in suppressing interictal discharges; novel therapies are needed. Surface charge on neuronal membranes provides a novel target for abolishing interictal spikes. This property can be modulated through the use of neuraminidase, an enzyme that decreases the amount of negatively charged sialic acid. In the present report we determined whether applying neuraminidase to brains of rats with a history of status epilepticus would reduce number of interictal discharges. Following pilocarpine-induced status epilepticus, rats received intrahippocampal injections of neuraminidase, which significantly decreased the number of interictal spikes recorded in the CA1 region. This study provides evidence that sialic acid degradation can reduce the number of interictal spikes. Furthermore, the results suggest that modifying surface charge created by negatively charged sialic acid may provide new opportunities for reducing aberrant epileptiform events in epilepsy.     

A case of right mesial temporal lobe epilepsy accompanied with ictal polyopsia]

A 59-year-old, right-handed woman had a paroxysmal polyoptic visual illusion, in which multiple copies of the object she saw spread horizontally in the left hemi-visual field. Polyopsia appeared for a few seconds. Neurological examination was normal. Magnetic resonance imaging (MRI) showed a tumor-like lesion involving the cortical and subcortical matters in the right mesial temporal regions. An interictal EEG showed frequent spikes in the right mesial temporal area and intermittent theta waves in the right fronto-temporal area. Video-EEG monitoring using the sphenoidal electrodes showed the seizure discharges originating in the right sphenoidal lead accompanying the polyoptic visual illusion. The seizure discharges were restricted within the right mesial temporal lobe. Paroxysmal visual illusion disappeared after administration of anti-epileptic drugs. EEG showed rare spikes in the right mesial temporal area. Polyopsia in this patient presumed to be associated with right mesial temporal lobe epilepsy because polyopsia and seizure activities on the ictal EEG were coupled and polyopsia ceased after administration of anti-epileptic drugs. Polyopsia is recognized as visual perseveration in space and a rare visual illusion. The lesion causing polyopsia has been reported to be mostly within posterior cerebral areas including occipital, parietal and temporal regions. This patient whose ictal polyopsia associated with mesial temporal lobe epilepsy is a very rare case because most reported cases presenting ictal polyopsia are neocortical temporal lobe epilepsy. The precise mechanism of polyopsia remains unknown. The mesial temporal lobe includes the hippocampus and parahippocampal formation that have been reported to receive information from the diverse association cortex and work as memory controllers. Ictal polyopsia may result from dysfunction of the visual association cortex or visual memory systems induced by the epileptic activities in the mesial temporal lobe. Polyopsia is a rare ictal semeiology of mesial temporal lobe epilepsy and may be one of the important ictal symptoms.     

Topographical reliability of mesio-temporal sources of interictal spikes in temporal lobe epilepsy

Purpose: Localization of hippocampal paroxysmal activities in temporal lobe epilepsy (TLE) by means of dipole modeling has often been criticized because of the supposed inaccuracy of this technique in localizing deep sources of EEG signals. This study aimed at assessing the relevance of mesio-temporal dipoles, as identified by modeling of scalp recorded spikes in TLE.Methods: Surface and depth EEG activities were simultaneously recorded using scalp and intracranial electrodes implanted through the foramen ovale (FO) in 3 patients with refractory TLE seizures. Intracranial FO spikes were used as triggers for scalp EEG averaging. The averaged signals were modeled by current dipoles, the localization of which were fused with patients' 3D-MRI.Results: Individual FO spikes were undetectable on visual analysis of raw scalp EEG but were reflected by low-amplitude scalp EEG transients on averaged signal. Dipole modeling of this EEG deflection consistently identified a mesio-limbic source in a position close to that of the FO pole recording the intracranial spike with its maximal amplitude.Conclusion: This result suggests that mesio-temporal sources can be accurately localized by modeling the signals recorded on the scalp, thus validating the anatomical and clinical relevance of hippocampal sources identified by modeling scalp interictal averaged spikes in TLE.     

Volumetric evidence of bilateral damage in unilateral mesial temporal lobe epilepsy

PURPOSE: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for >or=4 years of postsurgical follow-up. METHODS: Forty-six (23 male) TLE patients, operated on between 1996 and 2001, with histopathologic diagnosis of MTLS, and a postsurgical follow-up of >or=4 years, had their temporal lobe structures manually segmented, measured, and compared with those of 23 normal volunteers, paired as groups for sex, age, and handedness. RESULTS: The mean volumes of the contralateral temporal pole, hippocampus, and parahippocampal gyrus in TLE patients were significantly lower than those in controls. CONCLUSIONS: MRI volumetric data show that the damage in TLE due to MTS may be more widespread and bilateral, even in patients with unilateral TLE by clinical and neurophysiological criteria. Our results are relevant to the discussion of epileptogenic mechanisms in TLE.     

Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy

PURPOSE: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non-rapid eye movement (NREM) sleep than in wakefulness, overnight sleep-EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs. METHODS: Twenty-four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep-EEG recordings. Subjects were seizure free > or =24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long-term monitoring, brain magnetic resonance images (MRIs), and surgical outcome. RESULTS: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (>95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal-onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal-onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal-onset regions had good to excellent surgical outcomes. CONCLUSIONS: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.     

Hypometabolism and interictal spikes during positron emission tomography scanning in temporal lobe epilepsy

To study the influence of interictal spikes on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), EEG monitoring was performed during PET scanning in 21 patients with temporal lobe epilepsy. Asymmetry indices were calculated in the polar, mesial, anterior-lateral, mid-lateral and posterior-lateral temporal region of interests of FDG-PET (PET-AI). 70.7% of spikes were recorded with their maximum at the anterior temporal region (F(7), F(8), FT(9), FT(10)), 29.3% at mid-temporal (T(7), T(8)), and none at posterior temporal region (P(7), P(8)). Regardless of the side of epileptic focus, right-left difference of the total spikes had a significant negative correlation with right/left PET-AIs of the anterior-lateral temporal region (Spearman's rho = -0.565, p = 0.009), polar (rho = -0.500, p = 0.021) and whole temporal region (rho = -0.480, p = 0.028). FDG-PET hypometabolism may reflect not only a permanent functional deficit but also a transient regional cerebral dysfunction related to the occurrence of interictal spikes.     

Benign mesial temporal lobe epilepsy

Benign mesial temporal lobe epilepsy (bMTLE), which is defined as at least 24 months of seizure freedom with or without antiepileptic medication, has probably been under-recognized because of a literature bias toward refractory epilepsy cases. Seizure onset in bMTLE tends to be in adolescence or adulthood, and patients frequently have a family history of febrile seizures and epilepsy. Long-term seizure freedom is observed with or without antiepileptic medication. On brain MRI, nearly 40% of patients with long-standing bMTLE show evidence of hippocampal sclerosis, a feature usually associated with refractory temporal lobe epilepsy. Prospective studies are needed to determine the features that allow prediction of a benign course, and to clarify the significance of hippocampal MRI changes.     

Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy.

PURPOSE: To analyze the spatio-temporal relationship between seizure propagation and interictal epileptiform discharges (IEDs) in patients with bitemporal epilepsy. METHODS: We investigated 18 adult patients with intractable temporal lobe epilepsy (TLE) who had undergone continuous video-EEG monitoring during presurgical evaluation. Only those patients were selected who had independent IEDs over both temporal lobes. Two authors evaluated the ictal and interictal EEG data independently. RESULTS: We analyzed 52 lateralized seizures of 18 patients. Thirty-one seizures showed ipsilateral seizure spread exclusively, whereas in 21 seizures the contralateral hemisphere was also involved. In lateralized seizures without contralateral propagation, we found that spikes ipsilateral to the seizure onset occurred postictally in a greater ratio than preictally (P<0.001). In lateralized seizures with contralateral propagation, we found no significant changes in the postictal spike distribution. CONCLUSIONS: Our findings showed that the lateralization of IEDs may depend on the brain areas involved by the preceding seizures, suggesting that spikes can be influenced by the seizure activity, and are not independent signs of epileptogenicity.     

发作期直流电漂移与难治性伴海马硬化内侧颞叶癫痫的相关性研究

目的探讨发作期直流电漂移(ictal DC shift)在难治性伴海马硬化的内侧颞叶癫痫(MTLE-HS)中的定位价值。方法回顾性分析18例MTLE-HS患者的临床资料,进行非侵袭性和侵袭性术前评估,对发作起始区分别使用传统频段颅内电极脑电(iEEG)技术和基于宽频脑电技术的ictal DC shift进行定位,比较两组之间的时空分布差异及其与术后病理和预后之间的关系。结果 Ictal DC shift组空间分布明显较iEEG组更为局限,时间分布晚于iEEG组。结论 Ictal DC shift可能为致痫灶的电生理标志物。     

Outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis without preoperative ictal recording

Purpose:   We report on the surgical outcome obtained in patients with refractory temporal lobe epilepsy with mesial temporal sclerosis (MTS) who were evaluated preoperatively without ictal recording and were submitted to corticoamygdalohippocampectomy.
Methods:   Two hundred twelve patients with refractory temporal lobe epilepsy were evaluated by means of clinical history, neurological examination, interictal electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological testing. MRI disclosed unilateral MTS in all patients. All patients were submitted to corticoamygdalohippocampectomy at the side determined by MRI.
Results:   Interictal EEG showed unilateral temporal lobe spiking in 176 patients; in 36 patients, bilateral discharges were found. Mean follow-up time was 2.7  years. One hundred ninety-four patients (92%) were classified as Engel's class I. Eighteen patients (8%) were rated as Engel's class II. Thirty-two out of 36  patients, in whom bilateral discharges were found, were in Engel's class I. Sixty percent of the patients had an improvement in memory function related to the nonoperated temporal lobe. Fifty-nine percent of the patients had a 10-point increase in general IQ postoperatively. Verbal memory decline was noted in three patients. Pathological examination showed MTS in all patients.
Conclusions:   It is possible to adequately select good surgical candidates for temporal lobe resection using MRI and interictal EEG alone. In patients with MRI-defined MTS, we should expect a 90% postoperative remission rate. Cognitive decline was very rarely seen in this patient population. The finding of MTS on MRI is the single most important prognostic factor for good outcome after temporal lobe surgery.