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Generalized anxiety disorder (GAD) is the second most common psychiatric comorbidity of epilepsy. GAD has a negative impact on seizure control, and it is underrecognized. The Generalized Anxiety Disorder 7-item (GAD-7) questionnaire is useful for screening GAD in patients with epilepsy (PWE). This study aimed to validate the traditional Chinese version of the GAD-7 for Taiwanese patients by obtaining data on adult PWE from our hospital.PWE were recruited from the Taipei Veterans General Hospital from April 2017 to January 2020. The mood disorder module of the Mini International Neuropsychiatric Interview (MINI) was used for the psychiatric assessment. The traditional Chinese version of the GAD-7 and the Beck Anxiety Inventory were included as self-rated psychiatric evaluation. To investigate the psychometric properties, internal consistency, external validation, and receiver operator characteristic (ROC) curve analysis were conducted to assess the utility of the Taiwanese version of the GAD-7.We recruited 109 patients in the present study. Seventeen patients (15.9%) had GAD according to the MINI. The mean GAD-7 score was 10.28 ± 10.68. All the GAD-7 items were significantly and positively associated with the corrected overall GAD-7 score (Cronbach's alpha = 0.928, p 0.0001). The cut-off point for the GAD-7 in ROC curve analysis was 7. The patients with GAD were more likely to be female and single.The traditional Chinese version of the GAD-7 is a reliable and valid self-report questionnaire for detecting GAD in Taiwanese PWE.

Objectives We investigated hippocampal-sparing lesionectomy (HSL) outcomes in temporal lobe epilepsy (TLE) and the significance of high-frequency oscillations (HFOs) detected by hippocampography in HSL. Methods We retrospectively reviewed data from patients who underwent HSL for lesional TLE. Patients were included when MRI confirmed (i) a lesion limited to the temporal lobe with normal hippocampi preoperatively and (ii) hippocampal integrity postoperatively. Factors possibly related to outcomes were collected. Intraoperative hippocampography was reviewed, and spikes, ripples, and fast ripples were marked. Seizure outcomes were tracked ≥ 2 years. Postoperative neuropsychological tests were performed and analyzed. Results We included 67 patients (35 males/32 females, median age at surgery 28 years, 57 seizure-free). Complete resection was significantly associated with being seizure-free without aura, an outcome achieved by 32 (69.6%) patients with complete resection vs 1 (12.5%) with incomplete resection (p = 0.004). Spikes/ripples/fast ripples appeared frequently in the hippocampus, occurring in 86.4%/82.4%/75.0% of cases before resection and 76.7%/78.1%/63.0% after resection. The presence and rate were unconnected to seizure outcome. Postoperative neuropsychological outcomes in intelligence and visual memory improved overall. Conclusions HSL in lesional TLE can produce satisfactory seizure and cognitive outcomes. Intraoperative hippocampography-guided resection of apparently normal hippocampi should be performed cautiously and might not be necessary. Significance This study provided evidence in decision making for patients with lesional TLE with a radiologically normal hippocampus.

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, functional mapping of brain functions has been limited because the implantations have sparse coverage and differ greatly across individuals. Here, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. Our novel approach accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope≈−3.6). The signa-to-noise ratio and sensitivity in the thalamus and brain stem were comparable to those locations at the vicinity of electrode contact implantation. The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized functional mapping of human brain using both iERP and HBBG data.

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p

Purpose We conducted this study to compare the occurrence and prognostic significance of early postoperative interictal epileptiform discharges (IEDs) on seizure outcomes between corticoamygdalohippocampectomy (CAH) and selective amygdalohippocampectomy (SAH). Methods We reviewed our database of patients who had epilepsy surgery with hippocampus atrophy or signal changes on brain MRIs and pathology of mesial temporal sclerosis. One hundred and seventy-seven CAH and 39 SAH patients were enrolled. Postoperative EEG within 30days, other preoperative variables and seizure outcome 2years after surgery were obtained for analysis. Engel's IA and IB were defined as seizure-free. Results There was no significant difference in the seizure-free rate between the two procedures (127 (71.8%) of CAH vs 30 (76.9%) of SAH, p =0.51). Postoperative IEDs were more frequently seen in the SAH group (64.1%) than in the CAH group (29.9%), p 0.001. The IEDs in the SAH group did not show correlation with the seizure outcome 2 years after surgery. In the CAH group, patients who had no postoperative IEDs showed a higher seizure-free rate compared to those with IEDs (78.2% vs 56.6%, p =0.003; OR 2.267, 95% CI 1.09-4.73, p =0.029 in multivariate logistic regression). Conclusions Early postoperative IEDs are more frequently seen in SAH than in CAH. Unlike in patients with CAH, the presence of IEDs after SAH was not a predictor of seizure recurrence. The type of surgery should be considered while utilizing postoperative IEDs for evaluating the prognosis.

Background Epilepsy is a neurological disorder characterized by abnormal neuron discharge, and one-third of epilepsy patients suffer from drug-resistant epilepsy (DRE). The current management for DRE includes epileptogenic lesion resection, disconnection, and neuromodulation. Neuromodulation is achieved through invasive electrical stimulus including deep brain stimulation, vagus nerve stimulation, or responsive neurostimulation (RNS). As an alternative therapy, transcranial focused ultrasound (FUS) can transcranially and non-invasively modulate neuron activity. Objective This study seeks to verify the use of FUS pulsations to suppress spikes in an acute epileptic small-animal model, and to investigate possible biological mechanisms by which FUS pulsations interfere with epileptic neuronal activity. Methods The study used a total of 76 Sprague-Dawley rats. For the epilepsy model, rats were administered pentylenetetrazol (PTZ) to induce acute epileptic-like abnormal neuron discharges, followed by FUS exposure. Various ultrasound parameters were set to test the epilepsy-suppressing effect, while concurrently monitoring and analyzing electroencephalogram (EEG) signals. Animal behavior was monitored and histological examinations were conducted to evaluate the hazard posed by ultrasound exposure and the expression of neuronal activity markers. Western blotting was used to evaluate the correlation between FUS-induced epileptic suppression and the PI3K-mTOR signaling pathway. Results We observed that FUS pulsations effectively suppressed epileptic activity and observed EEG spectrum oscillations; the spike-suppressing effect depended on the selection of ultrasound parameters and highly correlated with FUS exposure level. Expression level changes of c-Fos and GAD65 were confirmed in the cortex and hippocampus, indicating that FUS pulsations deactivated excitatory cells and activated GABAergic terminals. No tissue damage, inflammatory response, or behavioral abnormalities were observed in rats treated with FUS under these exposure parameters. We also found that the FUS pulsations down-regulated the S6 phosphorylation and decreased pAKT expression. Conclusion Our results suggest that pulsed FUS exposure effectively suppresses epileptic spikes in an acute epilepsy animal model, and finds that ultrasound pulsation interferes with neuronal activity and affects the PTZ-induced PI3K-Akt-mTOR pathway, which might help explain the mechanism underlying ultrasound-related epileptic spike control.

OBJECTIVEThe semiology of cingulate gyrus epilepsy is varied and may involve the paracentral area, the adjacent limbic system, and/or the orbitofrontal gyrus. Invasive electroencephalography (iEEG) recording is usually required for patients with deeply located epileptogenic foci. This paper reports on the authors’ experiences in the diagnosis and surgical treatment of patients with focal epilepsy originating in the cingulate gyrus.METHODSEighteen patients (median age 24 years, range 5–53 years) with a mean seizure history of 23 years (range 2–32 years) were analyzed retrospectively. The results of presurgical evaluation, surgical strategy, and postoperative pathology are reported, as well as follow-up concerning functional morbidity and seizures (median follow-up 7 years, range 2–12 years).RESULTSPatients with cingulate gyrus epilepsy presented with a variety of semiologies and scalp EEG patterns. Prior to ictal onset, 11 (61%) of the patients presented with aura. Initial ictal symptoms included limb posturing in 12 (67%), vocalization in 5, and hypermotor movement in 4. In most patients (n = 16, 89%), ictal EEG presented as widespread patterns with bilateral hemispheric origin, as well as muscle artifacts obscuring the onset of EEG during the ictal period in 11 patients. Among the 18 patients who underwent resection, the pathology revealed mild malformation of cortical development in 2, focal cortical dysplasia (FCD) Ib in 4, FCD IIa in 4, FCD IIb in 4, astrocytoma in 1, ganglioglioma in 1, and gliosis in 2. The seizure outcome after surgery was satisfactory: Engel class IA in 12 patients, IIB in 3, IIIA in 1, IIIB in 1, and IVB in 1 at the 2-year follow-up.CONCLUSIONSIn this study, the authors exploited the improved access to the cingulate epileptogenic network made possible by the use of 3D electrodes implanted using stereoelectroencephalography methodology. Under iEEG recording and intraoperative neuromonitoring, epilepsy surgery on lesions in the cingulate gyrus can result in good outcomes in terms of seizure recurrence and the incidence of postoperative permanent deficits.

An improvement in quality of life (QoL) over time after epilepsy surgery has been demonstrated in people with epilepsy; however, social functioning has been less investigated. We conducted this study to examine whether postsurgical improvement is parallel between QoL and social functioning in patients with epilepsy.We retrospectively reviewed patients who underwent epilepsy surgery. All participants completed a comprehensive neuropsychological assessment, the Quality of Life in Epilepsy Inventory (QOLIE-89) questionnaire, and the Social and Occupational Functioning Scale for Epilepsy (SOFSE) before surgery and at 3 months, 6 months, and 1 year after surgery. Demographic and epilepsy-related information was also collected. Generalized estimating equations with identity links were used to model the QOLIE-89 and SOFSE over time and possible associated factors. A p 0.05 was considered statistically significant.A total of 76 patients, including 36 males and 43 females aged 18 to 62 years were collected. Both total QOLIE-89 and overall SOFSE improved over time after epilepsy surgery (adjusted p value 0.001 and 0.002, respectively, with Bonferroni's correction). Total QOLIE-89 improved 3 months after surgery, while overall SOFSE showed no significant improvement until 6 months after surgery. The presurgical Full-Scale Intelligence Quotient (FSIQ) of the Wechsler Adult Intelligence Scale-III and years of education were significantly associated with time-dependent improvement for both total QOLIE-89 and overall SOFSE (p value 0.001). At one year after surgery, overall SOFSE and total QOLIE-89 scores were significantly higher in the seizure-free group than in the nonseizure-free group (p value = 0.040 and 0.032, respectively).Social functioning significantly improved in people with epilepsy after surgery as QoL, but it took more time to exhibit improvement. People with better FSIQ and more years of education had better improvement in social functioning over time. The early intervention of rehabilitation programs after epilepsy surgery might be necessary to facilitate the improvement in social functioning.

Epilepsy surgery is beneficial to patients suffering from drug-resistant temporal lobe epilepsy in the short term, but fewer reports of long-term outcomes have been published. To clarify the long-term outcomes of seizure control and health-related quality of life after epilepsy surgery, we enrolled 48 patients suffering from drug-resistant temporal lobe epilepsy. All of the patients received comprehensive presurgical evaluations, including the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) questionnaire to measure their health-related quality of life. Among the patients, 28 patients received surgery (surgical group) and 20 patients remained under medication (medical group). Eight years later, the seizure frequency and QOLIE-89 were evaluated. The seizure-free rate was much higher in the surgical group (53.6%) than in the medical group (5%), eight years after the initial evaluation. The follow-up QOLIE-89 score was significantly higher in the surgical group than in the medical group. Moreover, the seizure frequency inversely correlated to the QOLIE-89 score, regardless of the treatment group. Our results provide evidence that epilepsy surgery confers benefits with respect to seizure control and health-related quality of life for drug-resistant temporal lobe epilepsy patients based on long-term follow-up.

SummaryObjective 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). Methods Sixty-seven patients with intractable TLE who were potential candidates for epilepsy surgery and 30 matched controls were included. All participants completed four tasks measuring different levels of ToM (False Belief, Faux Pas Recognition, Implication Stories, and Visual Cartoon), the Symptom Checklist-90-Revised (SCL-90-R), the Social and Occupational Functioning Scale for Epilepsy (SOFSE), and neuropsychological tests. Results The patients exhibited impairments in both basic and advanced ToM. Multiple regression analyses revealed the following: (1) the SOFSE total score was significantly predicted by the Faux Pas Recognition (FPR), Global Severity Index (GSI) score of the SCL-90-R, and Full-Scale intelligence quotient (IQ) of the Wechsler Adult Intelligence Scale (WAIS), which accounted for 38%, 11%, and 8% of the variance, respectively; and (2) the FPR was a significant predictor of all SOFSE subscales, whereas the GSI score contributed substantially to the Interpersonal Relationships, Communication, and Occupation subscales of the SOFSE. Significance Advanced ToM, measured by impaired faux pas recognition, is a relatively strong predictor of poor social functioning in surgical candidates for intractable TLE. Identifying ToM impairment may help plan nonpharmacologic treatment for improving social functions in patients with intractable TLE.

Summary Purpose To develop and validate a scale of social functioning for people with epilepsy (PWE)—the Social and Occupational Functioning Scale for Epilepsy (SOFSE). Methods According to the literature review and opinions from a panel of experts, PWE, and caregivers, a total of 31 questions were compiled. Questionnaires were analyzed from 172 adults with epilepsy. Key Findings The final scale had 30 items in six dimensions. The results showed that internal consistency coefficients and test–retest reliabilities for each dimension ranged from 0.70 to 0.84 and 0.72 to 0.89, respectively. Retest reliability for the total SOFSE score was 0.92. Seven factors were extracted through principal factor analysis. Moreover, criterion-related validity was demonstrated by the significant correlations between the SOFSE and the following measures: the Mini Mental Status Examination (r = 0.60, p

Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001, eLife digest The brain adapts to control our behavior in different ways depending on the specific situation, which is particularly useful when deciding how to interpret conflicting sets of information. The 'Stroop task' is a classic demonstration of this process. In this task, individuals are shown words where the color and the meaning of the text conflict – for example, the word 'green' is written in blue. When asked what the color of the text is, individuals must suppress the instinct to read the word. This causes them to make more mistakes and take longer to decide on an answer than when they perform the same task using words that have no conflict (for example, when “red” is written in red). Previous work has suggested that several regions within part of the brain called the frontal cortex play a role in this cognitive control process. However, the relative contributions of each of these regions, and the order in which they are activated, remain unclear. This is in part due to the fact that accurately measuring the electrical activity of the frontal cortex requires implanting electrodes into the brain. Tang et al. took advantage of a rare opportunity to record this activity from a group of patients who had electrodes implanted in their frontal cortex to treat epilepsy. The electrical signals recorded by these electrodes as the subjects performed the Stroop task revealed that four regions in the frontal cortex altered their activity during trials where the color and the meaning of a word conflicted. These responses corresponded with the subject’s reaction time, changed depending on the exact nature of the task, and even reflected the subjects’ errors. These responses arose at different times in different regions, allowing Tang et al. to suggest how signals flow through the frontal cortex during cognitive control. In the future it will be important to further understand how the regions of the frontal cortex identified by Tang et al. interact with each other and to establish their roles in cognitive control. These observations could then be used to produce a theoretical framework that describes how the brain adapts behavior to different circumstances. DOI: http://dx.doi.org/10.7554/eLife.12352.002

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.

Summary Purpose To evaluate whether the selective posterior cerebral artery amobarbital test (PCAAT) can predict postoperative memory function in patients with temporal lobe epilepsy (TLE) for surgical treatment and its clinical safety. Methods The database included adult patients with intractable TLE undergoing presurgical evaluation at Taipei Veterans General Hospital between 1995 and 2002. The PCAAT was carried out on patients who had failed conventional intracarotid amobarbital test (IAT) or had IAT results that evoked a concern of postoperative memory function decline. A battery of learning and memory testing was performed immediately before and after injection of amobarbital into the peduncular segment of the posterior cerebral artery (PCA) on the presumed hemisphere of epileptogenicity. Neuropsychological assessments were followed in surgically treated patients. Results A total of 16 patients completed PCAAT successfully and underwent anterior temporal lobectomy (ATL). Four patients failed PCAAT angiographic procedures due to technical difficulty in one patient, transient signs of vasospasm in two patients, and subarachnoid hemorrhage in one patient. Of the 12 patients who performed well in PCAAT learning and memory testing items by free recall or recognition, only 1 patient demonstrated postoperative memory decline in follow-up neuropsychological assessments. In contrast, two of the four patients with a deficit in PCAAT memory testing showed postoperative memory decline. Regarding subjective memory function (not necessarily associated with objective memory decline), patients not seizure-free after ATL were more likely to have memory complaints (in 3 out of 6 patients) than patients with seizure-free outcomes (in 1 out of 10 patients). Conclusions The PCAAT memory test reliably predicts postoperative memory function in patients with TLE for surgical treatment. However, the inherent risks of PCAAT must be considered and it should be used judiciously.

To demonstrate the high spatiotemporal resolution of magnetoencephalography (MEG), we report three cases with focal epilepsy that exhibited bilateral synchronized spikes on simultaneous scalp EEG and MEG recording. Constant time lags (19.4 ± 3.0 ms and 20.0 ± 5.5) between the leading and the following contralateral spikes were noted on MEG and the current dipole sources were localized in the bilateral homotopic regions symmetrically in Cases 1 and 3. In Case 2, MEG indicated leading spikes in the left frontal region, with a time lag of 42.3 ± 8.4 ms to reach the contralateral frontal and bilateral temporal regions as well. Chronic subdural EEG recording in Cases 1 and 2 confirmed that the leading spike focus in MEG was close to the seizure onset zone in cortical EEG. Spatio-temporal analysis of MEG spikes may be useful to identify the primary epileptic region in patients with synchronized bilateral epileptiform discharges.

Purpose: To determine the lateralising value of leg behaviors in complex partial seizures (CPS) of temporal lobe onset. Methods: Videotapes of 123 seizures from 38 patients who were seizure-free after temporal lobectomy were reviewed. Ictal behaviors including head turning, limb automatisms, tonic/dystonic postures and the latent time for ictal behavior were analysed for their lateralising value. Results: Contralateral versive head turning, ipsilateral arm automatisms, contralateral arm tonic/dystonic posturing, and contralateral arm clonic posturing were found to have high predictive value of lateralisation. As for the lower limbs, meaningful leg behaviors were recorded in 38 (31%) of 123 seizures, far less than behaviors of the upper limbs (79%). The predictive value from leg behaviors were similar to that from upper limbs. Among the leg behaviors, dystonic behaviors were always contralateral to the ictal side. Tonic behaviors were 94% contralateral to the ictal side. Dystonia and clonic movement were always contralateral to the ictal side. Automatisms were 86% ipsilateral to the ictal side. Conclusions: Although incidences were low, leg behaviors could provide useful lateralising value of the seizure foci. Clinicians as well as investigators should recognize the value of lower limbs behavior in studies of ictal semiology.

The purpose of this study was to examine the spatial and temporal relationship between bilateral foci of bilaterally synchronous discharges in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We simultaneously recorded interictal magnetoencephalographic (MEG) and electroencephalographic (EEG) signals in six children with BREC. Interictal spikes were classified into three groups: bilaterally synchronous discharges (BSDs), unilateral discharges on right side (UD-R), and unilateral discharges on left side (UD-L). We used equivalent current dipole (ECD) modelling to analyse the cortical sources of interictal spikes. Both BSDs and UDs were found in Patients 1–4, whereas only UDs were identified in Patients 5 and 6. The ECDs of interictal spikes were located in rolandic regions, 10–20mm anterior and lateral to hand somatosensory cortices. Multi-dipole analysis of BSDs showed two ECDs in homotopic motor areas of the hemispheres. During BSDs, the right-sided activation preceded the left-sided activation by 15–21milliseconds in Patients 1 and 2. In Patients 3 and 4, the activation occurred 17–20milliseconds earlier in the left than the right hemisphere. Within the same hemisphere, the sources of BSDs and UDs were located in similar areas. In conclusion, our results imply the cortical epileptogenicity in bilateral perirolandic areas in BREC. The sequential activation during BSDs in both hemispheres suggest the existence of synaptic connections, possibly via the corpus callosum, between bilateral irritative foci.

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.

Summary Purpose Transcranial magnetic stimulation (TMS) has been used to elucidate the altered balance between excitatory and inhibitory circuits in the motor cortex in epilepsy; however, TMS could not well assess excitability changes beyond the motor cortex. This study aimed to address the spatial profile of cortical excitability changes in patients with temporal lobe epilepsy (TLE) by using TMS and magnetoencephalography (MEG). Methods Eighteen patients with TLE and 18 healthy control subjects were recruited. Resting motor threshold (RMT) and intracortical inhibition (ICI) were measured to reflect motor cortical excitability by using TMS. A whole-head MEG was applied to record auditory and somatosensory evoked responses to paired-pulse stimuli. A paired-pulse inhibition (PPI) ratio, defined as the amplitude ratio between responses to the second and the first stimuli, was used to assess the auditory and somatosensory cortical excitability. A high PPI ratio suggests an increase in cortical excitability, while a low ratio indicates a decrease in excitability. Results Compared to control subjects, TLE patients exhibited increased RMT in motor cortex and higher PPI ratios for auditory P50m and somatosensory P35m responses. Notably, patients with a lower seizure frequency tended to exhibit a higher RMT or a lower P35m PPI ratio. Conclusions Present data suggest that the cortical excitability alteration in focal epilepsy is widely distributed beyond the epileptic focus and the profiles of excitability change correlate with clinical severity in terms of seizure frequency. Combined MEG and TMS studies provide new insight into the inter-ictal cortical excitability profiles in patients with epilepsy.

Focal cortical dysplasia (FCD) is a specific malformation of cortical development harboring intrinsic epileptogenicity, and most of the patients develop drug-resistant epilepsy in early childhood. The detrimental effects of early and frequent seizures on cognitive function in children are significant clinical issues. In this study, we evaluate the effects of early surgical intervention of FCD on epilepsy outcome and cognitive development. From 2006 to 2013, 30 children younger than 18 years old underwent resective surgery for FCDs at Taipei Veterans General Hospital. The mean age at surgery was 10.0 years (range 1.7 to 17.6 years). There were 21 boys and 9 girls. In this retrospective clinical study, seizure outcome, cognitive function, and quality of life were evaluated. To evaluate the effects to outcomes on early interventions, the patients were categorized into four groups according to age of seizure onset, duration of seizure before surgery, and severity of cognitive deficits. Eleven of 22 (50 %) patients demonstrated developmental delay preoperatively. The Engel seizure outcome achievements were class I in 21 (70 %), class II in 2 (7 %), class III in 6 (20 %), and class IV in 1 (3 %) patients. The locations of FCDs resected were in the frontal lobe in 18 cases, temporal lobe in 7, parietal lobe in 2, and in bilobes including frontoparietal lobe in 2 and parieto-occipital lobes in 1. Eight cases that had FCDs involved in the rolandic cortex presented hemiparesis before surgical resection. Motor function in four of them improved after operation. The histopathological types of FCDs were type Ia in 1, type Ib in 7, type IIa in 7, type IIb in 12, and type III in 3 patients. FCDs were completely resected in 20 patients. Eighteen (90 %) of them were seizure free (p

Objectives : Magnetic stimulation of the motor cortex can be used to determine the involvement of the cortex in rhythmic movement disorders. Symptomatic palatal tremor (SPT) is thought to come from a pacemaker that is relatively resistant to internal and external stimulation. In this study, we investigated the effect of magnetic stimulation of motor cortex on SPT. Methods : Five male patients, aged 67–79 years, with SPT after brain stem infarction or hemorrhage, all had a synchronous mouth angle twitch with the palatal movement. Electromyographic activity was recorded with a monopolar needle electrode from orbicularis oris. In experiment 1, transcranial magnetic stimulation (TMS) was delivered at 200% motor threshold (MT) to reset SPT. In experiment 2, the effect of TMS intensities was studied at 80–240% MT in two SPT patients. To determine the influence of the TMS, we used the resetting index (RI). Results : TMS reset the tremor in all 5 SPT patients at 200% MT with RIs of 0.86–0.96. The latency of the tremor reappearance after TMS was longer than the pre-stimulus tremor interval, and the intervals between the subsequent tremor bursts were also prolonged. The degree of tremor resetting was closely correlated with the magnetic stimulus intensity and the latency of the tremor reappearance after TMS. Conclusions : Stimulation of the motor cortex may modulate the generator of SPT.

To understand the treatment-seeking behavior of people with epilepsy (PWE), 403 PWE were surveyed using structured face-to-face interviews. Nearly half (49.1%) of them had previously tried complementary and alternative medicine (CAM); traditional Chinese medicine (51.5%) and temple worship (48.0%) were the most frequently used forms of CAM. In the 155 patients with adult-onset epilepsy, seeking CAM was substantially more common among females (OR=2.11, 95% CI=1.05-4.24, P=0.036), patients with frequent seizures (OR=2.68, 95% CI=1.30-5.53, P=0.008), patients with less educated parents (OR=2.16, 95% CI=1.06-4.41, P=0.034), and patients with religious beliefs (OR=2.84, 95% CI=1.23-6.56, P=0.015). In the 248 patients with childhood-onset epilepsy, frequent seizures (OR=2.23, 95% CI=1.32-3.77, P=0.003) and lower level of parental education (OR=2.71, 95% CI=1.45-5.06, P=0.002) were significantly associated with CAM use. The patients who seek CAM before receiving conventional medical treatment decreased after implementation of the National Health Insurance (NHI) (34/188 before NHI vs 22/215 after NHI, P=0.023). This study showed that the prevalence of CAM use by PWE in Taiwan is high and that a convenient NHI program can affect treatment-seeking behavior.

To investigate the relationship of interictal epileptiform discharges (IEDs) within 1 month of anterior temporal lobectomy (ATL) to seizure outcome, we reviewed data for 202 (107 left ATL, 95 right ATL) patients who had undergone ATL for mesial temporal epilepsy. Postoperative EEGs within 30 days and other preoperative variables were analyzed to examine the significant factors that determine freedom from disabling seizures. IEDs were noted in 29 (22.3%) of the 130 patients without seizures for 2 years after ATL compared with 31 (43.1%) of the 72 patients with recurrent seizures (P = 0.002). Postoperative IEDs remained an independent predictive factor for seizure outcome by logistic regression (adjusted OR = 2.38, 95% CI = 1.18–4.81, P = 0.016, 2 years postoperatively; adjusted OR = 2.22, 95% CI = 1.03–4.82, P = 0.043, 5 years postoperatively) and Cox hazard regression analysis (adjusted HR = 1.76, 95% CI = 1.18–2.62, P = 0.006) after controlling for other predicting factors (unilateral hippocampal atrophy, history of febrile seizures, and IQ scores). In this study, IEDs on the EEG obtained soon after surgery were associated with postoperative seizure recurrence. These results can be used in the assessment of risk of seizure recurrence after ATL.

We reviewed the records of 77 Chinese-speaking adult patients to investigate the relationship between the Wada memory test and outcomes after anterior temporal lobectomy (ATL). The ipsilateral memory scores, contralateral memory scores and Wada asymmetry index (WAI) were calculated to evaluate their relationships with seizure and cognitive outcomes. The seizure outcomes did not correlate with the unilateral memory scores or the WAI. Patients who had a smaller WAI tended to have a post-operative decline in verbal intelligence quotient (VIQ) (odds ratio: 13.54, 95% confidence interval: 1.17-156.11, p=0.037). The seven patients who failed the Wada memory test after ipsilateral injection had a higher percentage of VIQ deterioration than the 70 who passed (p=0.039). However, no patient displayed global amnesia after surgery. The Wada memory test was a predictor for post-operative VIQ changes in our study. Patients who failed the Wada memory test still benefitted from the ATL and showed good seizure outcomes.

To evaluate whether the side of stimulated ear affects the hemispheric asymmetry of auditory evoked cortical activations.Using a whole-head neuromagnetometer, we recorded neuromagnetic approximately 100 ms responses (N100m) in 21 healthy right-handers to 100 ms 1 kHz tones delivered alternatively to left and right ear.Although the peak latencies of N100m were shorter in contralateral than in ipsilateral hemisphere, the difference was significant only for the left ear stimulation. Based on the relative N100m amplitudes across hemispheres, the laterality evaluation showed a rightward predominance of N100m activation to tone stimuli, but the lateralization toward the right hemisphere was more apparent by the left than by the right ear stimulation (laterality index: -0.27 versus -0.10, p=0.008). Within the right hemisphere, the N100m was 2-4 mm more posterior for left ear than for right ear stimulation.The hemispheric asymmetry in auditory processing depends on the side of the stimulated ear. The more anterior localization of right N100m responses to ipsilateral than to contralateral ear stimulation suggests that there might be differential neuronal populations in the right hemisphere for processing spatially different auditory inputs.

We report pilomotor seizures in two patients who had piloerection or gooseflesh spreading in a pattern like the ‘Jacksonian march’, confined ipsilaterally to the lesion side. The first patient presented this in conjunction with complex partial seizures. Left anterior temporal lobectomy abolished pilomotor and other seizures. Pathological study demonstrated hippocampal sclerosis. A meningioma near the left sphenoid region, incompletely removed, is the likely cause of pilomotor seizures in the second patient. Carbamazepine reduced these attacks. To our knowledge, hippocampal sclerosis and meningioma have never been linked to pilomotor seizures.

Leptomeningeal carcinomatosis is characterized by diffuse infiltration of the meninges by metastatic cancer. We report a rare case of leptomeningeal carcinomatosis with an initial presentation of isolated acute hearing loss. Progressive unsteady gait and multiple cranial nerve palsies ensued. Computed tomography of the chest with contrast revealed a 2 cm nodule over the right upper lung. Cytology of cerebrospinal fluid confirmed the diagnosis of adenocarcinoma. The patient was discharged after diagnosis. Isolated acute hearing loss is a rare initial presentation in leptomeningeal carci-nomatosis, not necessarily with a known history of malignancy. A high index of suspicion is mandatory for accurate diagnosis.

There is only 1 report about multiple sclerosis (MS) prevalence in Taiwan, and this was published in 1976 and involved only 25 patients. The clinical features and prevalence of MS in Taiwan still remain to be clarified. The aim of this study was to determine the prevalence and delineate the clinical features of MS in Taiwanese patients.We retrospectively identified 43 ethnic Chinese multiple sclerosis (MS) patients over a 14-year period. The MS prevalence in Taiwan was estimated based on Bureau of National Health Insurance (BNHI) data. The clinical data (gender, family history, age at onset, initial symptoms, clinical course, disability and laboratory findings, evoked response and neuroimaging) were recorded, collected and analyzed.The MS prevalence in Taiwan was as low as 1.9 per 100,000. The distribution of most of the clinical features of our patients, like those in other Asian series, was different from Western series except for the percentage of the conventional form and sensory disturbances. Cerebrospinal fluid analysis for IgG index and OCB seemed to be less sensitive in the diagnosis of MS in our series.The prevalence of MS in Taiwan, as in other Asian countries, was low; the optic-spinal form occurred very often, but predominant spinal cord involvement was not unusual, as well as there being less functional disability. A larger, prospective study is needed to provide more conclusive information.

The purpose of this study was to study the relationship between interictal spike sources and somatosensory cortices in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We recorded spontaneous magnetoencephalography (MEG) and EEG signals and cortical somatosensory-evoked magnetic fields (SEFs) to electric stimulation of the median nerve in 9 children with BREC. Interictal rolandic discharges (RDs) and SEFs were analyzed by equivalent current dipole (ECD) modeling. Based on the orientation and locations of corresponding ECDs, we compared generators of RDs with primary (SI) and second somatosensory cortices (SII). Our results showed that RDs and SII responses had similar ECD orientation on the magnetic field maps. The ECDs of RDs were localized 15.3 +/- 1.9 and 12.2 +/- 2.8 mm anterior to SI and SII, respectively. The spatial distance on average from the location of RDs to SII (21.9 +/- 1.6 mm) cortex was significantly shorter than to SI cortex (29.7 +/- 1.7 mm) (P

Summary: Purpose: To investigate olfactory auras in patients with temporal lobe epilepsy (TLE). Methods: We reviewed medical records of 217 Chinese patients who underwent temporal lobectomy for medically intractable TLE between 1987 and 1998 in Taiwan. Patients with olfactory auras asked for detailed characteristics of their auras. Results: In all, 12 (5.5%) patients had olfactory auras, seven men and five women. All patients except one described and characterized the unpleasant olfactory auras. Olfactory auras were usually combined with other auras, most frequently sensations of epigastric rising, nausea, and fear. Association with gustatory hallucination was uncommon, in only one patient. On neuroimaging study, 11 patients had structural lesions involving the mesial temporal structures, two exclusively involving the amygdala. Histologic diagnosis included gliosis of the mesial temporal regions in seven (58.3%) patients, neoplasm in four (33.3%) patients, and arteriovenous malformation in one patient. Postoperatively, eight patients were seizure free. Three patients had rare seizures; however, none reported residual olfactory auras. Conclusions: Olfactory auras are infrequent in TLE. In this study, mesial temporal sclerosis is the most common etiology rather than tumors. Mesial temporal structures, especially the amygdala, may play important roles in the genesis of olfactory auras. Key Words: Aura—Olfactory aura— Olfactory hallucination—Temporal lobe epilepsy—Temporal lobectomy.

Summary: Purpose: To investigate antiepileptic drug (AED) withdrawal during video-EEG monitoring in adult patients with temporal lobe epilepsy (TLE). Methods: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4–6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS). Results: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16–451 h) was required for completing the monitoring in each patient. Forty-three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal. Conclusions: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video-EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.

Summary: Purpose: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study. Methods: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placcbo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial. Results: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a 50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group. Conclusions: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.

We report 3 cases presenting ictal vomiting during partial seizures of temporal lobe origin. Two patients had complex partial seizures accompanying vomiting characteristics. Ictal vomiting occurred early in the course of the seizure when rhythmic discharges involved predominantly the left hemispere, the language dominance hemispere. The other patient had ictal vomiting in simple partial seizures which originated from the right temporal lobe or the language nondominant side. All 3 patients underwent anterior temporal lobectomy with promising outcomes. Pathologic diagnosis included hippocampal sclerosis in 2 patients and astrocytoma in 1 patient. In our patients, ictal vomiting does not lateralize temporal lobe epilepsy and is not specific to pathology.

BackgroundMutations in the PRRT2 gene have recently been identified in patients with familial paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and patients with sporadic PKD/IC from several ethnic groups. To extend these recent genetic reports, we investigated the frequency and identities of PRRT2 mutations in a cohort of Taiwanese patients with PKD/IC.Methodology and principal findingsWe screened all 3 coding exons of PRRT2 for mutations in 28 Taiwanese patients with PKD/IC. Among them, 13 had familial PKD/IC and 15 were apparently sporadic cases. In total, 7 disparate mutations were identified in 13 patients, including 8 familial cases and 5 apparently sporadic cases. The mutations were not present in 500 healthy controls. Four mutations were novel. One patient had a missense mutation and all other patients carried PRRT2 mutations putatively resulting in a protein truncation. Haplotype analysis revealed that 5 of the 7 patients with the PRRT2 p.R217Pfs*8 mutation shared the same haplotype linked to the mutation.Conclusions and significancePRRT2 mutations account for 61.5% (8 out of 13) of familial PKD/IC and 33.3% (5 out of 15) of apparently sporadic PKD/IC in the Taiwanese cohort. Most patients with the PRRT2 p.R217Pfs*8 mutation in Taiwan likely descend from a single common ancestor. This study expands the spectrum of PKD/IC-associated PRRT2 mutations, highlights the pathogenic role of PRRT2 mutations in PKD/IC, and suggests genetic heterogeneity within idiopathic PKD.

Background/Purpose The objectives of this study were to: (1) survey migraine diagnoses among neurological outpatients in Taiwan; (2) compare neurologists’ migraine diagnoses with the International Classification of Headache Disorders 2nd Edition (ICHD-2) criteria; and (3) evaluate the diagnostic ability of screening items on a patient migraine questionnaire. Methods This prospective study surveyed patients who consulted neurologists for the first time with a chief complaint of headache, excluding those experiencing headaches for ≥ 15 days/month. Each neurologist interviewed a maximum of 10 patients. Patients were asked to complete a self-administered questionnaire and their physicians completed another questionnaire. The physicians were asked if patients could be diagnosed with migraine. In addition, a diagnosis of ICHD-2 migraine was made by the physician's questionnaire through a computer-generated algorithm. In this study, migraine without aura (code 1.1) or migraine with aura (code 1.2) were designated as “strict migraine”, and the combination of strict migraine and ICHD-2 probable migraine (code 1.6) as “any migraine”. Results Among 755 patients who were eligible for analysis, 537 (71%) were diagnosed as having “any migraine”, 363 (48%) with “strict migraine”, and 451 (60%) with physician-diagnosed migraine. Among the 537 patients diagnosed as having “any migraine”, 308 patients (57%) had not been diagnosed by any physician before. A moderate agreement (kappa statistic around 0.5) was found between the physicians’ diagnoses and ICHD-2 “strict migraine” or “any migraine”. In patients with ICHD-2 probable migraine (n = 174), only 52% were diagnosed with migraine by our physicians. Nausea was the best single item for predicting migraine diagnosis, while any combination of two items among nausea/vomiting, moderate or severe pain and photophobia, provided the optimum screening tool. Conclusion Migraine was the most common headache diagnosis in the neurologists’ clinics. Probable migraine was not completely adopted as a migraine spectrum among neurologists. In contrast to ID™, moderate or severe headache intensity replaced headache-related disability as one screening item for migraine in Taiwan.

Purpose IQ tests are frequently used in the preoperative neuropsychological assessment of candidates for anterior temporal lobectomy (ATL). We reviewed IQ test results and surgery outcomes to evaluate the roles of IQ tests in the preoperative work-up. Methods A total of 205 adult patients who had undergone ATL and whose seizure outcomes were followed for 2 years after surgery were included. The short form WAIS-R was used to estimate intelligence. Multiple linear regression and logistic regression analyses were used to examine the variables for IQ and seizure outcomes. Results Education, duration of epilepsy and gender were factors that accounted for 24.6% of the variance in the full-scale IQ (FSIQ) scores. The verbal IQ and performance IQ discrepancies at various magnitudes could not lateralize the seizure foci. Freedom of seizure was noted in 128 (62.4%) of the patients. Seizure outcomes, however, correlated with the preoperative FSIQ. After adjustment for variables that affect seizure outcomes, the FSIQ was an independent predictor of postoperative seizure outcomes (OR 1.04, 95% CI 1.01–1.06, p =0.003). Of patients who had FSIQ lower than 70, 50% became free from seizures by 2 years after surgery. Conclusions In our study, IQ tests were unable to lateralize seizure foci but may serve as an independent predictor of postoperative seizure outcomes. Since a longer duration of epilepsy had deleterious effects on intelligence, earlier surgical intervention might better preserve neuropsychological function and, consequently, allow better seizure control after ATL. Nonetheless, patients with lower IQ scores could still benefit from ATL.

To investigate early head turning, we retrospectively studied videotapes of 262 seizures from 82 patients who were seizure free after temporal lobectomy. Early head movements were arbitrarily classified into non-tonic turning, tonic turning, and absence of turning. Among the 222 seizures which showed early head turning, 168 (75.7%) had non-tonic turning and 54 (24.3%) had tonic turning. The direction of the first head turning was ipsilateral to the epileptogenic foci in 132 (78.6%) seizures with non-tonic turning and in 35 (64.8%) seizures showing tonic head turning. The proportion of seizures with turning towards the ipsilateral side in the presence of tonic and non-tonic head turning were significantly different (P= 0.04). Seventy-four seizures (28.2%) evolved to secondary generalization, more frequently found in seizures with early head turning (P= 0.0015) and especially those showing tonic turning (P< 0.0001). The direction of head turning immediately preceding secondary generalization was contralateral to the lesion side in 53 seizures (82.8%). Dystonic upper limb posturing occurred in 86 seizures (32.8%), exclusively contralateral to the seizure focus, whereas 65 (75.6%) were associated with initial head turning ipsilateral to the focus. In summary, temporal lobe seizures with tonic head turning tends to secondarily generalize and the direction of head turning before secondarily generalized was contralateral to the seizure foci. Earlier in the seizures the direction of non-tonic head turning tends to be towards the epileptogenic hemisphere. In addition, dystonic posturing of the extremities is a significant lateralizing sign to the contralateral hemisphere in temporal lobe seizures.