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Purpose: To evaluate the clinical significance of interictal regional polyspikes in focal epilepsies secondary to cortical dysplasia.
Methods: We performed a data search for the term “regional polyspikes” in the database of our epilepsy-monitoring unit. Patients with generalized epilepsies including Lennox-Gastaut syndrome were excluded. Regional interictal epileptiform discharges were recorded in 513 patients with noninvasive EEG.
Results: We identified 29 patients with interictal regional polyspikes and focal epilepsies. Another 484 patients showed regional epileptiform discharges other than polyspikes. The etiology of the epilepsy was significantly more frequently cortical dysplasia in the group of patients with regional polyspikes (35%, 10 of 29 patients) than in the patients with other regional epileptiform discharges (5%, 24 of 484 patients) (p < 0.01). The polyspikes were significantly more frequently localized to the extratemporal (72%; n = 21) than temporal (28%; n = 8) regions (p < 0.01). In contrast, regional epileptiform discharges other than polyspikes were significantly more frequently localized to the temporal lobe (75%; n = 362) than extratemporal regions (25%; n = 122) (p < 0.01). Eight of the 10 patients with focal cortical dysplasia had extratemporal polyspikes.
Discussion: Noninvasively recorded regional polyspikes suggest cortical dysplasias as etiology of predominantly extratemporal epilepsies.
Malformations of cortical development are disorders of cortical formation (proliferation, migration, and differentiation) and are frequently associated with medically refractory epilepsy (Brodtkorb et al., 1998; Hashizume et al., 2000). In selected patients, particularly with focal cortical dysplasia (FCD), resective epilepsy surgery is an option. Results of epilepsy depend on the complete resection of dysplastic cortex (Edwards et al., 2000). Preoperative evaluation includes EEG-video recording, MRI, positron emission tomography (PET) and single photon emission computerized tomography (SPECT) to identify the epileptogenic zone (Rosenow & Luders, 2001). MRI typically underestimates the extent of the pathology, which tends to be larger in histological investigations (Yagishita et al., 1997; Tassi et al., 2001, 2002). Several authors have indicated that dysplastic cortex has intrinsic epileptogenicity and they have reported this especially with intracranial studies (Palmini et al., 1995; Avoli et al., 1999; Kuruvilla & Flink, 2002). Selected patients, in whom electrocorticography (ECoG) showed polyspikes had also polyspikes in noninvasive EEG recordings (Gambardella et al., 1996).
In the present study, we investigated the frequency of regional interictal polyspikes in noninvasive EEG recordings and identified the relation to FCD in an unselected consecutive sample of patients with different focal epilepsy syndromes who underwent EEG-video monitoring for differential diagnosis of epilepsy and planning of epilepsy surgery.
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We identified 29 patients with regional polyspikes and focal epilepsies out of 513 patients who underwent noninvasive EEG video monitoring. This comprises 5.7% of the study population (n = 513). Another 484 patients showed regional IED other than polyspikes (94.3%) such as spikes, sharp waves, spike-wave complexes (Noachtar et al., 1999). Three of the 29 patients with regional polyspikes showed only polyspikes and did not have any other IEDs. The etiologies of epilepsy of all patients are summarized in Table 1. Table 2 provides all data on the 29 patients with regional polyspikes. The duration of interictal regional polyspikes lasted between 0.5 s and 3 s. Sleep and wake periods had no effect on localization and frequency of the regional polyspikes (Table 2).
Table 1. Etiology of epilepsy in patients with regional polyspikes and other regional interictal epileptiform discharges (IEDs)
|Etiology||Regional polyspikes n = 29 (5.7%)||Other IEDs n = 484 (94.3%)||p|
|Mesial temporal sclerosis|| 1a||(3) ||75||(15)||–|
|Focal cortical dysplasia (FCD)||10||(34)||24||(5) ||0.01|
|Perinatal lesion||–||–||23||(5) ||–|
|Congenital malformation||–||–||22||(5) ||–|
|Other|| 4||(14)||36||(7) ||–|
|Total||29|| (100)||484 || (100)|| |
Patients with regional polyspikes had significantly more frequently cortical dysplasia (34%, 10 of 29 patients) than the patients with other regional nonpolyspike IEDs (5%, 24 of 484 patients; p < 0.01) (Fig. 2). Tumors were more commonly the etiology of epilepsy in patients with nonpolyspike IEDs than in the polyspike group (n = 3 of 29 vs. n = 79 of 484) (Table 1) (p < 0.03). Pure mesial temporal sclerosis only occurred in the nonpolyspike IED (Table 1). One patient with frontal polyspikes had a dual pathology with a frontal FCD and an ipsilateral mesial temporal sclerosis (Table 1).
Figure 2. Right frontal polyspikes during sleep EEG (longitudinal bipolar montage) in a 31-year-old patient with a right FCD.
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The polyspikes were significantly more frequently localized to extratemporal (72%; n = 21) than temporal (28%, n = 8) regions (p < 0.01) (Table 3). In contrast, regional IEDs other than polyspikes were significantly more frequently localized to the temporal lobes (75%, n = 362) than extratemporally (25%, n = 122) (p < 0.01) (Table 3). Eight of the 10 patients with FCD had extratemporal polyspikes. The localizations of the regional polyspikes and the FCDs were consistent in 9 of 10 patients. In one patient with right frontal FCD the polyspikes were midcentral.
Table 3. Frequency of patients with regional polyspikes and other regional interictal epileptiform discharges (IEDs) (n = 513) and localization of the IEDs
|Localization||Total subjects n = 513||Significance|
|Regional polyspikes n = 29 (5.7%)||Other regional IEDs n = 484 (94.3%)|
|Temporal|| 8 (28%)||362 (75%)||p < 0.01|
|Extratemporal||21 (72%)||122 (25%)||p < 0.01|
|Significance||p < 0.01||p < 0.01|| |
The regional polyspikes had a repetition rate of 10–22 Hz and occurred during wakefulness and sleep in patients with and without FCD. For the purpose of this study, we did not quantify the occurrence of regional polyspikes during sleep or wakefulness. There was no significant difference in the frequency and duration of the regional polyspikes in patients with and without FCD.
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This study shows that scalp-recorded interictal regional polyspikes are more commonly associated with FCD than other epileptiform discharges in epilepsy surgery candidates with poor antiepileptic drug (AED) control. To avoid the selection bias of former studies who primarily look at children with cortical dysplasia (Quirk et al., 1993) or patients who underwent invasive ECoG (Gambardella et al., 1996), we evaluated a series of unselected consecutive patients who all underwent noninvasive EEG-video monitoring. Our patient population was heterogeneous and reflects all patients referred to an epilepsy-monitoring unit for evaluation of possible epilepsy surgery and differential diagnosis of focal epilepsy. Thus, different etiologies of epilepsy are represented.
In invasive recordings (ECoG), FCD was associated with high-frequency spiking (polyspiking), and the prolonged epileptic activity in dysplastic tissue was considered a consequence of impairment of local inhibitory circuits (Palmini et al., 1995). Most common findings were recruiting/derecruiting spikes (48%), high-frequency rhythmic polyspikes (bursting pattern, 30%), and continuous/quasicontinuous rhythmic spiking pattern on intraoperative ECoG recordings (35%). In a retrospective analysis of the surface EEG of these patients, the occurrence of rhythmic epileptiform discharges on the noninvasive EEG and continuous epileptiform discharges on ECoG recordings were compared in patients who underwent resective epilepsy surgery (Gambardella et al., 1996). It was concluded that repetitive spiking/polyspiking was highly specific and a sensitive indicator for focal cortical dysplastic lesions. Autoradiography of surgical specimen of FCD revealed reduced density of GABA-A receptors as visualized preoperatively by flumazenil PET (Arnold et al., 2000). Although continuous spiking was also described in patients with gliosis after traumatic brain injury or brain tumors, it has been suggested that continuous spiking on preresection ECoG can predict the presence of coexisting cortical dysplasia in a high proportion of patients (91%) with a specificity of 96% (Ferrier et al., 2006). These results and our findings support that continuous spiking and regional polyspikes are seen significantly frequent in FCD. However, the specificity of these invasive EEG findings for cortical dysplasia has been questioned by others who found polyspiking in invasive recordings also in other etiologies such as tumors (Rosenow et al., 1998). In electrocorticographic recordings, continuous spiking has been seen in 55% versus 12% of patients with FCD and glioneural tumors (GNT), respectively, and the FCDs were more frequently localized extratemporally when compared to GNTs (Ferrier et al., 2006). In concordance with this invasive study, we found that regional extratemporal polyspikes in noninvasive EEG are highly associated with cortical dysplasia (80%).
Cortical dysplasias used to be recognized only in the resected tissue during surgical treatment of patients with intractable epilepsy until the development of modern imaging techniques. CT has a low sensitivity for FCD but MRI enabled the recognition and classification of the different types of lesions (Andermann, 2000). High-resolution MRI using special techniques may reveal dysplastic cortex, which was not detected by standard MRI (Hakamada et al., 1979; Quirk et al., 1993; Palmini et al., 1995; Raymond et al., 1995; Raymond & Fish, 1996). However there are medically refractory epilepsy patients with normal MRI (Sisodiya, 2000; Tassi et al., 2002). In some of these patients, postsurgical histological examination helps detecting cortical dysplasia, which was not identified by MRI (Raymond & Fish, 1996; Yagishita et al., 1997; Tassi et al., 2001; Tassi et al., 2002).
Our study shows the diagnostic value of interictal regional polyspikes as a correlate of FCD, which was more significant in extratemporal localizations. We conclude that regional polyspikes, especially in extratemporal location, should lead the clinician to perform advanced MRI studies to detect cortical dysplasia.
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The authors thank E. Sincini, R. Grossmann, E. Scherbaum, R. Tschackert, O. Klein for technical assistance in the EEG-video monitoring unit of the Epilepsy Center, Department of Neurology, University of Munich.
Conflict of interest: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The authors report no conflicts of interest.