Shang-Yeong Kwan

Antiepileptic Drug Withdrawal in Patients with Temporal Lobe Epilepsy Undergoing Presurgical Video-EEG Monitoring

Summary:  Purpose: To investigate antiepileptic drug (AED) withdrawal during video‐EEG monitoring in adult patients with temporal lobe epilepsy (TLE).

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy: Comparison with scalp EEG recordings

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Quality of Life and Life Satisfaction in Families After a Child Has Undergone Corpus Callosotomy

: Epilepsy is a chronic neurological condition which can have a detrimental effect on patients’quality of life (QOL). We evaluated the overall satisfaction with QOL and changes in QOL in 25 families with children who had undergone corpus callosotomy for severe epilepsy. The mean age of seizure onset was 3.4 years, and the mean period from seizure onset to operation was 5.2 years. Mean follow‐up was 19.3 months. Twenty of 22 patients had various degrees of mental retardation. Mean reduction in severity of seizure activity was 64%. Nineteen of 25 (76%) parents were satisfied with the surgical result. Eighteen of 25 parents (72%) described a good level of satisfaction with their families QOL after callosotomy. Reduction in severity of seizure activity was significantly correlated with how successful families considered the surgery to be and how satisfied they were with their QOL (r= 0.72 and 0.77, respectively). Life domains showing one greatest improvement after callosotomy included level of self‐care, family life, and school performance. Improvements in level of self‐care, family life, and school performance were associated with higher levels of life satisfaction (r= 0.69, 0.60, and 0.59, respectively). Hyperactivity, attention span, and social skills improved significantly in 11 patients after surgery. Callosotomy did not improve mental performance. We conclude that improved seizure control after callosotomy is also associated with improved QOL.

Ictal Speech Manifestations in Temporal Lobe Epilepsy: A Video‐EEG Study

Summary: To evaluate ictal speech manifestations in complex partial seizures (CPS), we reviewed videotapes of 68 consecutive patients who underwent anterior temporal lobectomy (ATL) for treatment of intractable epilepsy in Taiwan. In all, 261 CPS were collected from their video‐EEG (VEEG) recordings. Cerebral speech dominance was determined by intracarotid injection of sodium amobarbital (Wada test) in all cases. Ictal speech manifestations, classified as verbalization or vocalization, occurred in 32 patients (47.1%) with 96 seizures (36.8%). Ictal verbalization occurred in 10 patients (14.7%). Ictal vocalization was observed in 28 patients (41.2%); including 6 patients who also had ictal verbalization. Thirty‐six patients (52.9%) had no seizure with ictal speech manifestations. Ictal verbalization had significant lateralization value: 90% of patients with this manifestation had seizure focus in the nondominant temporal lobe (p = 0.049). Seizures of patients with ictal vocalization were not more likely to arise from either temporal lobe. We also observed bilingual patients who exclusively spoke in their mother tongue (Taiwanese) rather than the acquired language (Mandarin) in 72.2% of seizures with verbalization. This finding is significant and contrary to a commonly held notion that the acquired language is used in seizures associated with speech behaviors.

Seizure outcome after corpus callosotomy: the Taiwan experience.

Abstract From September 1989 to August 1996, we performed anterior corpus callosotomy in 83 patients. Unfortunately, 9 patients were lost to follow-up. Among the remaining 74 patients, 59 had Lennox-Gastaut syndrome (evolved from infantile spasms in 22), 9 had complex partial seizures with or without secondary generalized seizures, 1 had multifocal independent epileptogenic foci (MISF) syndrome, 3 had hemiconvulsion-hemiplegia-epilepsy (HHE), and 2 had infantile spasms. All cases were followed up for at least 2 years after surgery. The highest rate of significant improvement (more than 50% reduction in seizure frequency) was noted in the patients with generalized tonic-clonic seizures, 82.1% of whom experienced significant improvement, followed by those with generalized tonic seizures (76.7%), atonic seizures (72.7%), myoclonic seizures (64.9%), atypical absences (58.6%), and complex partial seizure with or without secondary generalization (61.5%). Complete freedom from seizures was noted in 14 cases (18.9%). One patient had the anterior half of his right palm amputated following radial artery thrombosis complicated by insertion of an arterial line during anesthesia. Otherwise, there were no major postoperative complications except for brief mutism and multifocal jerks in some patients during the 1st postoperative week. Thus, we conclude that corpus callosotomy is a safe alternative treatment for all kinds of medically intractable seizures, especially generalized epilepsy.

Prognostic value of electrocorticography findings during callosotomy in children with Lennox-Gastaut syndrome.

OBJECTIVE To analyze findings and acute changes in electrocorticograms (ECoGs) obtained during corpus callosotomy in order to identify any relationships with the postoperative outcome of seizure activity. METHODS We retrospectively analyzed ECoGs obtained during anterior callosotomy (4-6 cm) in 48 patients with Lennox-Gastaut syndrome (32 boys and 16 girls, age 1-20 years, mean age 7.6 years) who underwent surgery between July 1993 and November 1996 to correlate recording findings with postoperative seizure activity. At the time of analysis, all patients had been followed postoperatively for more than 4 years. RESULTS Of 48 patients, 31 (64.6%) had significant improvement in seizure control after surgery. In pre-excisional ECoGs, 38 (79.2%) of 48 patients had bisynchronous epileptiform discharges. Patients (23 of 33 patients, 69.7%) with significant blockage of bisynchronous discharges recorded during callosotomy achieved the best postoperative seizure outcomes, but the difference did not reach statistical significance (P>0.05). CONCLUSIONS Based on our experience, changes in ECoG during callosotomy do not predict postoperative seizure outcome. Insignificant blockage of bisynchronous epileptiform discharges in ECoGs during callosotomy does not predict a worse prognosis than that associated with significant intraoperative blockage.

Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.

Theory of mind and social functioning in patients with temporal lobe epilepsy.

This study aimed to explore the effects of theory of mind (ToM) and related potential risk factors, including cognitive functions, psychiatric status, and seizure‐related clinical variables, on social functioning in patients with temporal lobe epilepsy (TLE).

PRRT2 mutations lead to neuronal dysfunction and neurodevelopmental defects

Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene cause a wide spectrum of neurological diseases, ranging from paroxysmal kinesigenic dyskinesia (PKD) to mental retardation and epilepsy. Previously, seven PKD-related PRRT2 heterozygous mutations were identified in the Taiwanese population: P91QfsX, E199X, S202HfsX, R217PfsX, R217EfsX, R240X and R308C. This study aimed to investigate the disease-causing mechanisms of these PRRT2 mutations. We first documented that Prrt2 was localized at the pre- and post-synaptic membranes with a close spatial association with SNAP25 by synaptic membrane fractionation and immunostaining of the rat neurons. Our results then revealed that the six truncating Prrt2 mutants were accumulated in the cytoplasm and thus failed to target to the cell membrane; the R308C missense mutant had significantly reduced protein expression, suggesting loss-of function effects generated by these mutations. Using in utero electroporation of shRNA into cortical neurons, we further found that knocking down Prrt2 expression in vivo resulted in a delay in neuronal migration during embryonic development and a marked decrease in synaptic density after birth. These pathologic effects and novel disease-causing mechanisms may contribute to the severe clinical symptoms in PRRT2–related diseases.

Magnetoencephalographic study of rhythmic mid-temporal discharges in non-epileptic and epileptic patients

To evaluate the source location and clinical significance of rhythmic mid-temporal theta discharges (RMTD) by MEG in non-epileptic and epileptic patients, we conducted simultaneous MEG and EEG recordings with a whole-scalp 306-channel neuromagnetometer in three patients: one with right temporal lobe epilepsy (TLE), one with right frontal lobe epilepsy (FLE), and one with tension headache. We visually detected the RMTD activity and interictal spikes, and then localised their generators by MEG source modelling. We repeated MEG measurement 3 months after right anterior temporal lobectomy (ATL) in the TLE patient; 3 months after anticonvulsant medication in the FLE patient. In epileptic patients, RMTD activities were found during drowsiness over the left temporal channels of both MEG and EEG recordings, and their generators were localised to the left posterior inferior temporal region. In the patient with tension headache, RMTD was localised in the right inferior temporal area. When the epileptic patients became seizure free with disappearance of epileptic spikes, RMTD was still found over the left temporal channels. Besides, some bursts of RMTD appeared also in the right temporal channels in our TLE patient after ATL. Our results indicate that the source of RMTD activity is located in the fissural cortex of the posterior inferior temporal region. As a physiologic rhythm related to dampened vigilance, RMTD has no direct relation to epileptogenic activity.