Visual Stimuli Modulate Local Field Potentials But Drive No High-Frequency Activity in Human Auditory Cortex.

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices (ACs). Whether these influences reflect active visual processing in human ACs, which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants (7 women, 9 men) with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Analyses of intracranial event-related potentials (iERPs) suggested cross-sensory responses to visual stimuli in ACs, which lagged the earliest auditory responses by several tens of milliseconds. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15-30 Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs.

Development and construction of the Multidimensional Self-Efficacy Scale for Epilepsy (MSESE) and its psychometric properties.

PURPOSE: It has become evident that patients with epilepsy require strong self-efficacy support in various domains, including work, social interaction, and academic performance, to ensure their complete social functioning. Nevertheless, previous studies have predominantly assessed the self-efficacy of individuals with epilepsy from a singular perspective of disease management. This study aimed to develop the Multidimensional Self-Efficacy Scale for Epilepsy (MSESE) to assess multiple dimensions and establish its psychometric properties. METHODS: We compiled a total of 25 questions for the initial version of the questionnaire based on a review of the literature and insights from experts, patients, and family members. The study included 180 adult patients with epilepsy who met the research criteria, with 126 of them serving as pre-test samples. All participants completed the MSESE, Brief Symptom Rating Scale-50 (BSRS-50), Rosenberg Self-Esteem Scale-Chinese version (RSES-C), and General Self-Efficacy Scale (GSES). RESULTS: The final scale consisted of 12 items across four dimensions, with item factor loadings ranging from .51 to .90. Most of the fit indices indicated a good fit. Construct validity was established through significant correlations with the BSRS-50, RSES-C, and GSES (r = -0.51 to 0.69, p < 0.01). Internal consistency coefficients for the MSESE were strong at .90, with individual dimensions ranging from 0.71 to 0.89. The MSESE also demonstrated a satisfactory test-retest reliability of 0.72. CONCLUSIONS: The MSESE is a convenient, multidimensional, and easy-to-use scale with good psychometric properties, making it suitable for both clinical assessments and research purposes.

Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

Neuronal intranuclear inclusion disease in patients with adult-onset non-vascular leukoencephalopathy.

Neuronal intranuclear inclusion disease (NIID), caused by an expansion of GGC repeats in the 5'-untranslated region of NOTCH2NLC, is an important but underdiagnosed cause of adult-onset leukoencephalopathies. The present study aimed to investigate the prevalence, clinical spectrum and brain MRI characteristics of NIID in adult-onset nonvascular leukoencephalopathies and assess the diagnostic performance of neuroimaging features. One hundred and sixty-one unrelated Taiwanese patients with genetically undetermined nonvascular leukoencephalopathies were screened for the NOTCH2NLC GGC repeat expansions using fragment analysis, repeat-primed PCR, Southern blot analysis and/or nanopore sequencing with Cas9-mediated enrichment. Among them, 32 (19.9%) patients had an expanded NOTCH2NLC allele and were diagnosed with NIID. We enrolled another two affected family members from one patient for further analysis. The size of the expanded NOTCH2NLC GGC repeats in the 34 patients ranged from 73 to 323 repeats. Skin biopsies from five patients all showed eosinophilic, p62-positive intranuclear inclusions in the sweat gland cells and dermal adipocytes. Among the 34 NIID patients presenting with nonvascular leukoencephalopathies, the median age at symptom onset was 61 years (range, 41-78 years) and the initial presentations included cognitive decline (44.1%; 15/34), acute encephalitis-like episodes (32.4%; 11/34), limb weakness (11.8%; 4/34) and parkinsonism (11.8%; 4/34). Cognitive decline (64.7%; 22/34) and acute encephalitis-like episodes (55.9%; 19/34) were also the most common overall manifestations. Two-thirds of the patients had either bladder dysfunction or visual disturbance. Comparing the brain MRI features between the NIID patients and individuals with other undetermined leukoencephalopathies, corticomedullary junction curvilinear lesions on diffusion weighted images were the best biomarkers for diagnosing NIID with high specificity (98.4%) and sensitivity (88.2%). However, this diffusion weighted imaging abnormality was absent in 11.8% of the NIID patients. When only fluid-attenuated inversion recovery images were available, the presence of white matter hyperintensity lesions either in the paravermis or middle cerebellar peduncles also favoured the diagnosis of NIID with a specificity of 85.3% and sensitivity of 76.5%. Among the MRI scans of 10 patients, performed within 5 days of the onset of acute encephalitis-like episodes, five showed cortical hyperintense lesions on diffusion weighted images and two revealed focal brain oedema. In conclusion, NIID accounts for 19.9% (32/161) of patients with adult-onset genetically undiagnosed nonvascular leukoencephalopathies in Taiwan. Half of the NIID patients developed encephalitis-like episodes with restricted diffusion in the cortical regions on diffusion weighted images at the acute stage. Corticomedullary junction hyperintense lesions, white matter hyperintensities in the paravermis or middle cerebellar peduncles, bladder dysfunction and visual disturbance are useful hints to diagnosing NIID.

Pilot study of focused ultrasound for drug-resistant epilepsy.

OBJECTIVE: The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans. METHODS: Patients with DRE undergoing SEEG for localization of the seizure onset zone (SOZ) were prospectively enrolled. FUS was delivered to the SOZ using a neuronavigation-guided FUS system (ceiling spatial-peak temporal-average intensity level = 2.8 W/cm2 , duty cycle = 30%, modulating duration = 10 min). Simultaneous SEEG recordings were obtained during sonication and for 3 days after treatment. Seizures, interictal epileptiform discharges, and adverse events after FUS were monitored. RESULTS: Six patients met the eligibility criteria and completed FUS treatment. A decrease in seizure frequency was observed in two patients within the 3-day follow-up; however, one patient presented an increase in the frequency of subclinical seizures. Posttreatment magnetic resonance imaging revealed neither lesion nor brain edema. Significant changes in spectral power of SEEG were noted at the targeted electrodes during FUS treatment. One patient reported subjective scalp heating during FUS, and one patient developed transient naming and memory impairment that resolved within 3 weeks after FUS. SIGNIFICANCE: FUS can be safely delivered to the SOZ of patients with DRE, resulting in significant changes in spectral power of SEEG. A larger sample cohort and pursuing optimal sonication parameters will be required to elucidate the neuromodulatory effects of FUS when used for seizure control.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. METHODS: This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61). RESULTS: Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. SIGNIFICANCE: Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Validation of the Taiwanese version of the Epilepsy Surgery Satisfaction Questionnaire (Tw-ESSQ-19).

OBJECTIVE: Satisfaction with epilepsy surgery in Mandarin-speaking countries remains unknown. We aimed to validate in our Taiwanese patients an existing instrument to measure patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). METHODS: Consecutive patients with epilepsy who received epilepsy surgery one year earlier in Taipei Veterans General Hospital were recruited and provided clinical and demographic data. The Mandarin version of the ESSQ-19 for the Taiwanese population and eight other questionnaires were completed to assess construct validity. To evaluate the validity and reliability of the tool, the data were analyzed by confirmatory factor analysis, Spearman's rank correlation, and internal consistency analysis. RESULTS: The study involved 120 patients (70 F/50 M, median age 35 years [IQR = 28-41]). The mean summary score (±SD) of the Tw-ESSQ-19 was 82.5 ±â€¯14.5. The mean scores of the four domains were 90.3 ±â€¯15.4 (surgical complications), 83.2 ±â€¯16.7 (seizure control), 80.1 ±â€¯17.3 (recovery from surgery), and 76.6 ±â€¯18.3 (psychosocial functioning). The questionnaire was shown to have good construct validity with satisfactory goodness-of-fit of the data (standardized root mean square residual = 0.0492; comparative fit index = 0.946). It also demonstrated good discriminant validity (being seizure free [AUC 0.78; 95% CI 0.68-0.89], endorsing depression [AUC 0.84; 95% CI 0.76-0.91], self-rating epilepsy as disabling [AUC 0.71; 95% CI 0.58-0.84], and self-rating epilepsy as severe [AUC 0.78; 95% CI 0.64-0.93]), high internal consistency in four domains (Cronbach's alpha = 0.83-0.96), and no significant floor/ceiling effects of the summary score. SIGNIFICANCE: The Mandarin version of the ESSQ-19 adapted for the Taiwanese population is a reliable and valid self-reported questionnaire for assessing patient satisfaction with epilepsy surgery.

Counseling about sudden unexpected death in epilepsy (SUDEP): A global survey of neurologists' opinions.

OBJECTIVE: To investigate the opinions and attitudes of neurologists on the counseling about sudden unexpected death in epilepsy (SUDEP) worldwide. METHODS: Practicing neurologists from around the world were invited to participate in an online survey. On February 18th, 2021, we emailed an invitation including a questionnaire (using Google-forms) to the lead neurologists from 50 countries. The survey anonymously collected the demographic data of the participants and answers to the questions about their opinions and attitudes toward counseling about SUDEP. RESULTS: In total, 1123 neurologists from 27 countries participated; 41.5% of the respondents reported they discuss the risk of SUDEP with patients and their care-givers only rarely. Specific subgroups of patients who should especially be told about this condition were considered to be those with poor antiseizure medication (ASM) adherence, frequent tonic-clonic seizures, or with drug-resistant epilepsy. The propensity to tell all patients with epilepsy (PWE) about SUDEP was higher among those with epilepsy fellowship. Having an epilepsy fellowship and working in an academic setting were factors associated with a comfortable discussion about SUDEP. There were significant differences between the world regions. CONCLUSION: Neurologists often do not discuss SUDEP with patients and their care-givers. While the results of this study may not be representative of practitioners in each country, it seems that there is a severe dissociation between the clinical significance of SUDEP and the amount of attention that is devoted to this matter in daily practice by many neurologists around the world.

Reliability and validity of the traditional Chinese version of the GAD-7 in Taiwanese patients with epilepsy.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: The traditional Chinese version of the GAD-7 is a reliable and valid self-report questionnaire for detecting GAD in Taiwanese PWE.

Distributed source modeling of intracranial stereoelectro-encephalographic measurements.

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.

Acute withdrawal of new-generation antiepileptic drugs in epilepsy monitoring units: Safety and efficacy.

INTRODUCTION: Acute withdrawal of antiepileptic drugs (AEDs) is a safe and effective approach to provoking seizures in order to complete video-electroencephalogram (V-EEG) studies in a timely manner. Previous studies have focused only on withdrawal from conventional AEDs, and the effects of withdrawal from new-generation AEDs have not been extensively studied. MATERIALS AND METHODS: This study examined adult patients with drug-resistant epilepsy admitted to an epilepsy monitoring unit between 2015 and 2018. Patients were classified according to whether they received conventional AEDs (Con; n = 13) or new-generation AEDs (N-Gen; n = 26). We then compared the effects of withdrawing these two types of AEDs over a period of one week in terms of efficacy (time to complete V-EEG monitoring) and safety, including the incidence of cluster seizures (CS), focal to bilateral tonic-clonic seizures (FBTCS) and status epilepticus (SE). RESULTS: In both groups, approximately one week was required to complete V-EEG analysis: N-Gen group (5.6 days) and Con group (6.3 days). No differences were observed between the two groups in terms of the median number of seizures, the onset of the 1st seizure, the distribution of CS, FBTCS, or SE. Following acute withdrawal of medication, a high percentage of patients with a history of CS or FBTCS, respectively, presented CS or FBTCS. CONCLUSIONS: We did not observe significant differences between patients taking new-generation AEDs and those taking conventional AEDs following withdrawal during V-EEG recording. In the current study, we employed a standard protocol for the rapid withdrawal of AEDs (daily dose reduction of 50%), which was sufficient for 80% of patients to complete V-EEG monitoring within one week.

Social functioning and health-related quality of life trajectories in people with epilepsy after epilepsy surgery.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Cingulate gyrus epilepsy: semiology, invasive EEG, and surgical approaches.

OBJECTIVE: The 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. METHODS: Eighteen 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). RESULTS: Patients 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. CONCLUSIONS: In 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.

Ictal-Interictal Comparison of FDG-PET Findings in Sporadic Hemiplegic Migraine.

PURPOSE: Sporadic hemiplegic migraine (SHM) is characterized by a prolonged motor aura that accompanies a migraine attack, and its underlying pathophysiology remains unclear. Functional image during the event can help to explore the mechanism. CASE REPORT: We report a finding of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in a 15-year-old female with SHM. She presented with recurrent right arm weakness and pain with migrainous headache. A video electroencephalogram showed no evidence of epilepsy during the events. Subtraction of ictal-interictal FDG-PET coregistered to magnetic resonance imaging was performed for the image analysis. In comparison with the interictal state, the FDG-PET image showed decreased glucose metabolism in the bilateral dorsal lateral frontal cortices and bilateral occipital cortices, whereas increased metabolism in the left precentral motor cortex and right premotor cortex. CONCLUSION: These findings reveal an increase in metabolism in the motor cortex during general cortical dysfunction in the frontal and occipital cortices in SHM. Key words: FDG-PET, hemiplegic migraine, migraine, positron emission tomography, SISCOM.

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

OBJECTIVE: 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.

Long-term health-related quality of life in drug-resistant temporal lobe epilepsy after anterior temporal lobectomy.

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.

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Cognitive and epilepsy outcomes after epilepsy surgery caused by focal cortical dysplasia in children: early intervention maybe better.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001) with three patients that received more than one surgery to accomplish complete resection. The patients who had early seizure onset, no significant cognitive function deficit, and early surgical intervention with complete resection in less than 2 years of seizure duration showed best outcomes on seizure control, cognitive function, and quality of life. CONCLUSION: Delay in cognitive development and poor quality of life is common in children treated for FCDs. Early surgical intervention and complete resection of the lesion help for a better seizure control, cognitive function development, and quality of life. FCDs involved eloquent cortex may not prohibit complete resection for better outcomes.

Neuromodulatory Focused Ultrasound for Epilepsy: Are Animal Models Useful?

Ultrasound neuromodulation is a potential alternative therapy for suppressing epileptic discharges. Recently, several human clinical trials have reported promising results from repeated focused ultrasound (FUS) treatments for temporal lobe epilepsy. In this Viewpoint, we highlight the valuable guidance of preclinical validation methods for choosing the optimal FUS parameters, thus ensuring consistency with the outcomes of clinical trials and leading human trials to the safest and most effective approaches.

Glucose Metabolism of Hippocampal Subfields in Medial Temporal Lobe Epilepsy.

PURPOSE: Reduced glucose metabolism in the hippocampus is commonly observed in cases of medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). Glucose metabolism among the various hippocampal subfields has not been thoroughly investigated. PATIENTS AND METHODS: This study examined 29 patients (18 females; 15-58 years) diagnosed with HS who underwent surgery for drug-resistant epilepsy. FreeSurfer 7.1.1 was used in the processing of MRI data and 18 F-FDG PET scans to derive volumetric data and the FDG SUVr in the whole hippocampus and hippocampal subfields, including the CA1, CA2-4, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), and subiculum. Asymmetries in the volume and SUVr between the 2 sides from the subfields of the hippocampus were defined in terms of an asymmetry index. Comparisons of the asymmetry index among these regions were performed. The correlations between asymmetry index values and postoperative outcomes and presurgical neuropsychological test results were also evaluated. RESULT: The CA1, CA2-4, subiculum, GC-ML-DG, and whole hippocampus presented reductions in volume and hypometabolism ipsilateral to MTLE. Asymmetries in volume and SUVr were significantly less pronounced in the CA1 and subiculum than in the CA2-4 or GC-ML-DG. Postoperative seizure outcomes were not correlated with the asymmetry index for volume or SUVr in any hippocampal subfield. In cases of left MTLE, scores of immediate logical memory and delayed logical memory were positively correlated with the asymmetry index for SUVr in the following subfields: CA1 ( R = 0.829, P = 0.021; R = 0.770, P = 0.043), CA2-4 ( R = 0.825, P = 0.022; R = 0.894, P = 0.007), subiculum ( R = 0.882, P = 0.009; R = 0.853, P = 0.015), GC-ML-DG ( R = 0.850, P = 0.015; R = 0.796, P = 0.032), and whole hippocampus ( R = 0.841, P = 0.018; R = 0.822, P = 0.023). In cases of right MTLE, the scores for delayed face memory were positively correlated with the asymmetry index for SUVr in the subiculum ( R = 0.935, P = 0.006). CONCLUSIONS: In cases of HS, changes in glucose metabolism levels varied among the hippocampal subfields. Asymmetries in glucose metabolism among the CA-1, CA2-4, subiculum, and GC-ML-DG subregions were correlated with scores for verbal memory among patients with left MTLE. Asymmetric glucose metabolism in the subiculum was also correlated with visual memory scores among patients with right MTLE.