Wrist-worn smartwatch and predictive models for seizures.

OBJECTIVE: This study was undertaken to describe extracerebral biosignal characteristics of overall and various seizure types as compared with baseline physical activities using multimodal devices (Empatica E4); develop predictive models for overall and each seizure type; and assess diagnostic performance of each model. METHODS: We prospectively recruited patients with focal epilepsy who were admitted to the epilepsy monitoring unit for presurgical evaluation during January to December 2020. All study participants were simultaneously applied gold standard long-term video-electroencephalographic (EEG) monitoring and an index test, E4. Two certified epileptologists independently determined whether captured events were seizures and then indicated ictal semiology and EEG information. Both were blind to multimodal biosignal findings detected by E4. Biosignals during 5-min epochs of both seizure events and baseline were collected and compared. Predictive models for occurrence overall and of each seizure type were developed using a generalized estimating equation. Diagnostic performance of each model was then assessed. RESULTS: Thirty patients had events recorded and were recruited for analysis. One hundred eight seizure events and 120 baseline epochs were collected. Heart rate (HR), acceleration (ACC), and electrodermal activity (EDA) but not temperature were significantly elevated during seizures. Cluster analysis showed trends of greatest elevation of HR and ACC in bilateral tonic-clonic seizures (BTCs), as compared with non-BTCs and isolated auras. HR and ACC were independent predictors for overall seizure types, BTCs, and non-BTCs, whereas only HR was a predictor for isolated aura. Diagnostic performance including sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve of the predictive model for overall seizures were 77.78%, 60%, and .696 (95% confidence interval = .628-.764), respectively. SIGNIFICANCE: Multimodal extracerebral biosignals (HR, ACC, EDA) detected by a wrist-worn smartwatch can help differentiate between epileptic seizures and normal physical activities. It would be worthwhile to implement our predictive algorithms in commercial seizure detection devices. However, larger studies to externally validate our predictive models are required.

Development and validation of the Thai version of the Adult Epilepsy Self-Management Scale (Thai-ESMS).

OBJECTIVE: Self-management is an important strategy for helping people with epilepsy (PWE) control their seizures and improve their quality of life. To date, there are scarce standard measurement tools for assessing self-management practices. This study aimed to develop and validate a Thai version of the Epilepsy Self-Management Scale (Thai-ESMS) for Thai people with epilepsy. METHODS: The translation of the Thai-ESMS was created using the adaptation of Brislin's translation model. Content validity of the developed Thai-ESMS was independently assessed by 6 neurology experts and reported as item content validity index (I-CVI) and scale-CVI (S-CVI). We consecutively invited epilepsy patients at our outpatient epilepsy clinic to participate in the study from November to December 2021. Participants were asked to complete our 38-item Thai-ESMS. Based on the participant's responses, construct validity was evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Cronbach's alpha coefficient was employed to evaluate internal consistency reliability. RESULTS: Overall, our 38-item Thai ESMS scale showed high content validity (S-CVI = 0.89), assessed by neurology experts. Responses from 216 patients were then used for the assessment of construct validity and internal consistency. The results showed good construct validity of 5 domains (5 factors with Eigenvalue > 1 upon EFA and good fitness index upon CFA) meaning that the developed scale is an adequate measure of the concept it was designed to evaluate and had good internal consistency (Cronbach's alpha 0.819), which both values were comparable to the original English version. However, some items or domains had poorer validity and reliability than the overall scale. CONCLUSIONS: We developed a robust 38-item Thai ESMS with high validity and good reliability to be used to help assess the magnitude of self-management skills in Thai PWE. However, more work on this measure is needed before distribution to a wider population.

Is anti-seizure medication the culprit of SUDEP?

BACKGROUND: Heart rate variability (HRV) reduction is a potential biomarker for sudden cardiac death. This study aimed to study the effects of anti-seizure medications (ASMs), adjusted with reported factors associated with sudden unexpected death in epilepsy (SUDEP) on HRV parameters. METHODS: We recruited patients who were admitted in our epilepsy monitoring unit between January 2013 and December 2021. Two 5-min electrocardiogram epochs during wakefulness and sleep were selected in each patient. HRV analysis with Python® software was performed. The imputed datasets were used for linear regression analysis to assess association between each ASM item and all HRV parameters. The effects of ASM on HRV parameters were subsequently adjusted with the significant clinical characteristics and the concomitant use of other ASMs, respectively. RESULTS: Carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), and clonazepam (CZP) were statistically significantly associated with changes of sleep HRV parameters. Only CBZ showed negative effects with reduction in HRV, evidenced as lower standard deviation of RR interval (SDNN), even when adjusted with concomitant use of other ASMs (p = 0.045) and had a trend of significance when adjusted with significant clinical characteristics of concurrent taking of beta-blocker drug (p = 0.052). LEV and CZP showed opposite effects with increased HRV even when adjusted with significant clinical characteristics and the concomitant use of other ASMs. CONCLUSIONS: CBZ showed negative effects on HRV. We proposed that CBZ should be cautiously used in patients with known risks for SUDEP. In addition, HRV assessment should be performed prior to commencing CBZ and re-performed in follow-up in cases of prolonged use.

Perampanel treatment in highly drug-resistant epilepsies including nonsurgical candidates and failed surgery.

OBJECTIVE: To evaluate the effectiveness and tolerability of perampanel (PER) treatment for patients with highly drug-resistant epilepsies (HDRE) including nonsurgical candidates and failed surgery in real-world setting. METHODS: All patients who were treated with PER during June 2015 to August 2019 were selected. Primary outcomes were percentage of seizure reduction, responder rate, and seizure freedom rate. Seizure frequency after taking PER at 3 and 12 months were compared with baseline seizure frequency within the same time period prior to starting PER. Secondary outcomes were retention rate, side effects, and predictors for a response to PER. Descriptive statistics and the Kernel regression model were employed. RESULTS: Forty-one patients received PER treatment during the study period. Six patients who had no baseline seizure frequency recordings were excluded, for a total of 35 patients included for analysis. Mean age was 40.06 years (SD 12.34). All were highly resistant to several antiseizure drugs (ASDs) with a median number of previously failed ASDs of 8 items. Eleven, 16, 5, and 3 patients were lesional, nonlesional focal epilepsy, nonsurgical candidate, and failed surgery, respectively. At 3 months after PER treatment, the median percentage of seizure reduction was 20 % (-35.71, 100), the responder rate was 22.86 % (8/35), and the seizure freedom rate was 17.14% (6/35). At 12 months after PER treatment, the corresponding outcomes were 25% (-20.57, 91.60), 22.58% (7/31), and 9.68% (3/31), respectively. Retention rates at 3 and 12 months were 100% and 91.43% (32/35), respectively. Nineteen patients (54.29%) experienced side effects from PER. Side effects were somnolence (6/35), dizziness (3/35), irritability (2/35), and ataxia (2/35), and one each for weight loss, nausea, headache, insomnia, verbal aggressivity, and depression. Median duration for 2-mg dose increment was 2.2 months. CONCLUSIONS: In real-world practice, slow-titration PER regimen is well-tolerable and shows benefit in helping control seizures in patients with very difficult-to-treat HDRE.

Seizure focus in the frontal interhemispheric fissure leads to ipsilateral isolated eye deviation.

OBJECTIVE: Few studies have examined the localization of seizures presenting with ictal eye deviation (ED) in the absence of other motor symptoms. We aimed to investigate differences in the localization of the ictal onset zone (IOZ) between patients with isolated ED and those with ED plus head turning (HT) during focal seizures. METHODS: We reviewed intracranial video-EEG data for 931 seizures in 80 patients with focal onset epilepsy in whom the IOZ could be confirmed. The 233 seizures in 49 patients with ED were classified into two semiological groups based on initial ED and the presence/absence of HT: (1) isolated ED (i.e., ED without HT), and (2) ED + HT (i.e., ED with HT). We analyzed the localization and lateralization of IOZs in each semiological group. We performed multivariate logistic regression analysis using a mixed-effects to determine the associations between IOZs and isolated ED/ED + HT. RESULTS: A total of 183 IOZs in 24 patients were included in the isolated ED group, while a total of 143 IOZs in 31 patients were included in the ED + HT group. Sixty-eight IOZs of eight patients in the isolated ED group were located in the ipsilateral frontal interhemispheric fissure (F-IHF). Only ipsilateral F-IHF was significantly associated with isolated ED (odds ratio [OR], 2.43; 95% confidence interval [CI], 0.37-4.49; P = 0.021). The contralateral lateral frontal cortex (latF) (P = 0.007) and ipsilateral mesial temporal region (mT) (P = 0.029) were significantly associated with ED + HT. CONCLUSION: The present study is the first to demonstrate that seizures with an F-IHF focus tend to present with initial ipsilateral isolated ED. This finding may aid in identifying the seizure focus in patients with isolated ED prior to resection.

Effects of antiepileptic drugs on electroencephalography (EEG): Insights and applicability.

OBJECTIVE: The objective of the study was to assess the effects of antiepileptic drugs (AEDs) on posterior alpha rhythm and determine whether they produce pathological slow waves in patients with epilepsy. METHODS: Outpatient electroencephalographs (EEGs) in alert patients were selected. The three compared groups include 1) patients with an interested AED (monotherapy or combined with other AEDs); 2) patients with AEDs other than the interested AED; and 3) patients who did not take AEDs. Outcomes were frequency of posterior alpha rhythm and presence of generalized continuous (CSWs) and generalized intermittent slow waves (ISWs). Analysis of variance was used to assess which AED was associated with slower posterior alpha rhythm. Chi-square and logistic regression were employed to assess association and odds ratio (OR) with 95% confidence interval (CI) between pathological generalized slow waves and each AED. RESULTS: Among 1050 EEG tracings, 638 EEGs met our criteria. Electroencephalographs requested because of cognitive decline and psychiatric symptoms were excluded, leaving 616 EEGs for analysis. Four hundred thirty-seven patients received at least one AED, whereas the remaining 179 patients did not take AED. Conventional AEDs [carbamazepine (CBZ), p = 0.024; phenobarbital (PB), p = 0.013; phenytoin (PHT), p = 0.001] except valproic acid (VPA) were associated with slower alpha frequency. Carbamazepine [adjusted OR: 5.74 (95% CI: 2.07, 15.94)] and PB [adjusted OR: 2.58 (95% CI: 1.15, 5.78)] were significantly associated with generalized ISWs. None were associated with generalized CSWs. CONCLUSIONS: Phenytoin, CBZ, and PB are associated with slower posterior alpha frequency. The latter 2 AEDs also produced pathological generalized ISWs. Valproic acid, benzodiazepines, and new-generation AEDs are not associated with either outcome. The presence of generalized ISWs in patients taking CBZ or PB should be cautiously interpreted since there can be drug effects. Association with cognitive side effects of these slow waves should be further studied.

How and Whom to Monitor for Seizures in an ICU: A Systematic Review and Meta-Analysis.

OBJECTIVES: To pool prevalence of nonconvulsive seizure, nonconvulsive status epilepticus, and epileptiform activity detected by different electroencephalography types in critically ills and to compare detection rates among them. DATA SOURCES: MEDLINE (via PubMed) and SCOPUS (via Scopus) STUDY SELECTION:: Any type of study was eligible if studies were done in adult critically ill, applied any type of electroencephalography, and reported seizure rates. Case reports and case series were excluded. DATA EXTRACTION: Data were extracted independently by two investigators. Separated pooling of prevalence of nonconvulsive seizure/nonconvulsive status epilepticus/epileptiform activity and odds ratio of detecting outcomes among different types of electroencephalography was performed using random-effect models. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and also adhered to the Meta-analyses Of Observational Studies in Epidemiology guidelines. Quality of evidence was assessed with the Newcastle-Ottawa Quality Assessment Scale for observational studies and Cochrane methods for randomized controlled trial studies. DATA SYNTHESIS: A total of 78 (16,707 patients) and eight studies (4,894 patients) were eligible for pooling prevalence and odds ratios. For patients with mixed cause of admission, the pooled prevalence of nonconvulsive seizure, nonconvulsive status epilepticus, either nonconvulsive seizure or nonconvulsive status epilepticus detected by routine electroencephalography was 3.1%, 6.2%, and 6.3%, respectively. The corresponding prevalence detected by continuous electroencephalography monitoring was 17.9%, 9.1%, and 15.6%, respectively. In addition, the corresponding prevalence was high in post convulsive status epilepticus (33.5%, 20.2%, and 32.9%), CNS infection (23.9%, 18.1%, and 23.9%), and post cardiac arrest (20.0%, 17.3%, and 22.6%). The pooled conditional log odds ratios of nonconvulsive seizure/nonconvulsive status epilepticus detected by continuous electroencephalography versus routine electroencephalography from studies with paired data 2.57 (95% CI, 1.11-5.96) and pooled odds ratios from studies with independent data was 1.57 (95% CI, 1.00-2.47). CONCLUSIONS: Prevalence of seizures detected by continuous electroencephalography was significantly higher than with routine electroencephalography. Prevalence was particularly high in post convulsive status epilepticus, CNS infection, and post cardiac arrest.

Predictive values and specificity of electroencephalographic findings in autoimmune encephalitis diagnosis.

OBJECTIVE: Early diagnosis of autoimmune encephalitis (AE) to not delay treatment is challenging but needed in practice. Most previous evidences of electroencephalographic (EEG) findings in AE were derived from descriptive studies. Given paucity of evidence of specific EEG findings to help with early diagnosis of AE, this study aimed to ascertain specific EEG findings and assess their predictive values in diagnosis of AE. METHODS: We included all cases with AE in our institution from January 2013 to June 2017. Cases were matched with controls by age and level of consciousness (1:2 ratio). Potential confounders for EEG findings collected as baseline characteristics were compared. Two epileptologists independently reviewed EEGs. Standardized terminology, definitions, and scoring system of EEG findings were employed. Logistic regression analysis was performed, and diagnostic performance of significant EEG features was assessed. RESULTS: Twenty cases and 40 controls were included in this study. Poorly sustained posterior dominant rhythm (PDR) was significantly associated with AE (p = 0.007) and even more predictive in anti-N-methyl-d-aspartate (NMDA) encephalitis. Inter-rater agreement (kappa) was 0.714. None of the cases had normal EEG nor Grand Total EEG (GTE) score < 4 (negative predictive value (NPV) of 100%). Specificity of well sustained PDR to exclude the diagnosis of anti-NMDA encephalitis was high (91.67%). CONCLUSIONS: Simple EEG assessment can be used to help exclude AE. When AE is suspected, careful assessment of the sustainment of the PDR is warranted. The NPV of GTE score < 4 and specificity of well sustained PDR can be simply used to differentiate many conditions from AE.

High-density electric source imaging patterns and outcomes following temporal lobectomy in patients with hippocampal sclerosis.

OBJECTIVE: The objective of this study was to ascertain specific patterns of electrical source imaging (ESI) that are associated with a good surgical outcome (no seizure recurrence) using 256-channel high-density (HD) electroencephalography (EEG) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) who underwent temporal lobectomy. METHODS: Adult patients (age ≥ 18 years) were prospectively recruited from September 2016 to May 2020 at the authors' center. All patients underwent phase I presurgical evaluation and were subsequently advised to proceed with surgery based on consensus from a multidisciplinary epilepsy conference, without knowing HD-ESI results. All recruited patients were followed for at least 12 months after surgery. The outcome of interest was a status of no seizure recurrence, which was assessed at the end of the study. The association between ESI patterns and outcome was assessed using the chi-square or Fisher exact test. Associated p values as well as odds ratios and 95% CIs were reported. The diagnostic performance of the significant pattern associated with the outcome was also evaluated. RESULTS: Fifty-eight patients with known predictors for either good or worse surgical outcomes were recruited. The mean postoperative follow-up period was 33.34 (SD 13.88) months. Forty-seven patients had sufficient interictal epileptiform discharges for HD-ESI analysis. Thirteen of these 47 patients experienced seizure recurrence. The most common source localizations were at Brodmann area (BA) 20 (inferior temporal area) and BA 21 (middle temporal area). A specific ESI pattern of BA 21 without extratemporal sources was significantly associated with no seizure recurrence (p = 0.047). This pattern had a high positive predictive value of 100% and false-positive rate of 0% associated with no seizure recurrence following the surgery. CONCLUSIONS: A specific ESI pattern that was highly associated with no seizure recurrence following surgery was demonstrated by a 256-channel HD-EEG. If this pattern can be reproducibly proven in further studies, some TLE-HS patients may be able to proceed with surgery without further investigations.

Post-traumatic epilepsy with isolated memory flashbacks.

Some traumatic events can cause both post-traumatic stress disorder and epileptic seizures. We report the case of a woman who experienced a severe head injury which subsequently led to the development of paroxysmal episodes of isolated memory flashbacks related to the injury. Detailed analysis of her symptoms along with video-EEG telemetry recordings was helpful to distinguish between these two conditions. [Published with video sequences].

A Novel method of seizure onset zone localization by serial Tc-99 m ECD brain perfusion SPECT clearance patterns.

In this prospective study, we postulate that there is a difference between clearance of [99mTc]Tc- ethyl cysteinate dimer (ECD) in the seizure onset zone (SOZ) and other brain areas and thus SOZ localization by clearance patterns might become a potential novel method for SOZ localization in epilepsy. The parametric images of brain ECD clearance were generated by linear regression model analysis from serial brain SPECT scans from 30 to 240 min after ECD injection (7-times point) in 7 patients with drug-resistant epilepsy and 3 normal volunteers. Clearance patterns of the SOZ confirmed by good surgical outcome or consensus with other investigations were analyzed quantitatively and semi-quantitatively by visual grading (slower or faster washout than contralateral brain regions). The average [99mTc]Tc-ECD clearance rates of SOZs were + 1.08% ± 2.57%/hr (wash in), -7.02% ± 2.56%/hr (washout), and -5.37% ± 1.71%/hr (washout) in ictal, aura and interictal states, respectively. Paired t-tests between the SOZ and contralateral regions showed statistically significant difference (p = 0.039 in interictal state). Clearance patterns that can define the SOZs were 1) wash in and slow washout on ictal slope, 2) fast washout on aura slope and interictal slope with 100% (6/6), 100% (2/2) and 75% (6/8) localization using ictal, aura, and interictal slope maps, respectively. Our study provided the evidence that clearance pattern methods are potential additive diagnostic tools for SOZ localization when routine one-time point SPECT are unable to define the SOZ.

Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression, anxiety and psychosis.

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase 1 (PON1) status may occur in TLE and these psychiatric conditions. AIM: To examine PON1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in TLE. METHODS: We recruited 40 normal controls and 104 TLE patients, 27 without comorbidities and 77 with comorbidities including mood disorders (n = 25), anxiety disorders (n = 27) and psychosis (n = 25). RESULTS: Four-(chloromethyl)phenyl acetate hydrolysis (CMPAase) and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than those in normal controls. The areas under the receiver operating characteristic curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (± 0.037) for MTS. Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (P < 0.0001) and psychopathology (P < 0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination score. CONCLUSION: The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype, which are mediated by reduced CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Efficacy and economic evaluation of delivery of care with tele-continuous EEG in critically ill patients: a multicentre, randomised controlled trial (Tele-cRCT) study protocol.

INTRODUCTION: Some critically ill patients are confirmed by continuous electroencephalography (cEEG) monitoring that non-convulsive seizure (NCS) and/or non-convulsive status epilepticus (NCSE) are causes of their depressed level of consciousness. Shortage of epilepsy specialists, especially in developing countries, is a major limiting factor in implementing cEEG in general practice. Delivery of care with tele-continous EEG (tele-cEEG) may be a potential solution as this allows specialists from a central facility to remotely assist local neurologists from distant areas in interpreting EEG findings and suggest proper treatment. No tele-cEEG programme has been implemented to help improve quality of care. Therefore, this study is conducted to assess the efficacy and cost utility of implementing tele-cEEG in critical care. METHODS AND ANALYSIS: The Tele-cRCT study is a 3-year prospective, randomised, controlled, parallel, multicentre, superiority trial comparing delivery of care through 'Tele-cEEG' intervention with 'Tele-routine EEG (Tele-rEEG)' in patients with clinical suspicion of NCS/NCSE. A group of EEG specialists and a tele-EEG system were set up to remotely interpret EEG findings in six regional government hospitals across Thailand. The primary outcomes are functional neurological outcome (modified Rankin Scale, mRS), mortality rate and incidence of seizures. The secondary outcomes are cost utility, length of stay, emergency visit/readmission, impact on changing medical decisions and health professionals' perceptions about tele-cEEG implementation. Functional outcome (mRS) will be assessed at 3 and 7 days after recruitment, and again at time of hospital discharge, and at 90 days, 6 months, 9 months and 1 year. Costs and health-related quality of life will be assessed using the Thai version of the EuroQol-five dimensions-five levels (EQ-5D-5L) at hospital discharge, and at 90 days, 6 months, 9 months and 1 year. ETHICS AND DISSEMINATION: This study has been approved by the ethics committees of the Faculty of Medicine, Chulalongkorn University, and of Ramathibodi Hospital, Mahidol University, and registered on Thai Clinical Trials Registry. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: TCTR20181022002; preresults.

Increased Oxidative Stress Toxicity and Lowered Antioxidant Defenses in Temporal Lobe Epilepsy and Mesial Temporal Sclerosis: Associations with Psychiatric Comorbidities.

Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), plays a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown. Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl (-SH) groups in depression due to TLE (n = 25); anxiety disorders due to TLE (n = 27); psychotic disorder due to TLE (n = 25); "pure TLE" (n = 27); and healthy controls (n = 40). TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899), and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, while increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels. These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups plays a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology and psychosis, as well as negative and depressive symptoms.

From international guidelines to real-world practice consensus on investigations and management of status epilepticus in adults: A modified Delphi approach.

OBJECTIVE: To establish a consensus which is practical and ready-to-use on investigations (ISE) and for management of status epilepticus (MSE) in adults using a modified Delphi approach. PATIENTS AND METHODS: A 4-round modified Delphi approach was used. First and second rounds were conducted using Google® survey with structured statements and 6-point Likert scale response. Threshold agreement was set to ≥80%. Third round was a face-to-face meeting aimed to facilitate the development of approach algorithms for ISE and MSE. Fourth round was a final review asking participants to rate the algorithms post completion. RESULTS: The panel consisted of 8 board-certified epileptologists along with 6 neurologists from main regional hospitals across Thailand. Thirty-seven statements for ISE and 68 statements for MSE were used for the Round I survey, 17/37 (45.9%) and 49/68 (72.1%) reached threshold agreement (≥80%). The average absolute-agreement intraclass correlation coefficients for ISE and MSE were 0.82 (95% CI 0.71, 0.89) and 0.81 (95% CI 0.73, 0.87), respectively; indicating good extent of consensus among participants. Upon Round II, further 10/18 (55.6%) for ISE and 10/19 (52.6%) for MSE reached agreement. In Round III, face-to-face point-by-point discussion was performed to generate approach algorithms. All (100%) provided positive responses with the algorithms post completion in Round IV. CONCLUSION: A practical and ready-to-use consensus using modified Delphi approach on ISE and MSE was developed in a Thai regional hospital context. In real practice, this approach is more suitable and feasible for a localized setting when compared with totally adopting international guidelines.

Diagnostic Performance of the Electroencephalogram in the Elderly Manifesting With Episodes of Unresponsiveness.

This study aimed to determine diagnostic performance of the EEG in diagnosing seizures and to ascertain risk factors associated with seizures in the elderly presenting with episodes of unresponsiveness compared with younger patients. This is a cross-sectional study. Only EEGs requested with indication of transient unresponsiveness (TUR) were included. Patients were divided into 2 groups, younger (aged 18-49 years) and elderly (aged >60 years). The EEG was an index test. Reference standard, independently verified by 2 board-certified neurologists, was a clinical diagnosis of presence or absence of epilepsy/probable seizures. Univariate and multivariate analyses were performed to ascertain associated risk factors for epilepsy/probable seizures. Among 2187 total EEG recordings, 244 (11.16%) recordings were requested with indication of TUR. A total of 156 patients (50 younger and 106 elderly) were recruited for analysis. Prevalence of epilepsy/probable seizures in patients with TUR was 26.9%. Prevalence of interictal epileptiform discharges was 16% in the younger and 12.3% in the elderly. Overall diagnostic performance was poorer in the elderly. Associated risk factors for having seizures were presence of intermittent slow waves in the younger and presence of positive motor signs as well as presence of nonepileptiform abnormalities in the elderly. Prevalence of seizures and interictal epileptiform discharges was low in the elderly who manifests with TUR. Overall diagnostic performance of the EEG in diagnosing seizures was poorer in the elderly mainly due to low sensitivity. When we encounter patients with TUR, thorough and detailed history is still a mainstay of a diagnosis of seizures, not the EEG results.

Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population.

PURPOSE: Previous studies found a strong association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations. Even in Han Chinese, the HLA-B*1502 was not associated with CBZ-induced maculopapular eruptions (MPE). This study seeks to identify whether HLA-B*1502 is associated with CBZ- or phenytoin (PHT)-induced SJS or MPE in a Thai population. METHODS: Eighty-one Thai epileptic patients between 1994 and 2007 from the Chulalongkorn Comprehensive Epilepsy Program were recruited. Thirty-one subjects had antiepileptic drug (AED)-induced SJS or MPE (6 CBZ-SJS, 4 PHT-SJS, 9 CBZ-MPE, 12 PHT-MPE), and 50 were AED-tolerant controls. RESULTS: For the first time, a strong association between HLA-B*1502 and PHT-induced SJS was found (p = 0.005). A strong association was also found between the HLA-B*1502 and CBZ-induced SJS (p = 0.0005), making Thai the first non-Chinese population demonstrating such an association. Some patients, who were HLA-B*1502 and suffered from CBZ-induced SJS, could be tolerant to PHT and vice versa. This suggests that HLA-B*1502 may be a common attribute required for a Thai patient to develop SJS from these two AEDs; other different elements, however, are also needed for each AED. In addition, no association between HLA-B alleles and CBZ- or PHT-induced MPE was found. CONCLUSIONS: CBZ- and PHT-induced SJS, but not MPE, is associated with HLA-B*1502 allele in Thai population.

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI.

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively.

Impact of injection time on migration of SPECT seizure onset in temporal lobe epilepsy.

In this work, we investigated an impact of injection time on migration of seizure-onset in ictal/interictal single photon emission computed tomography (SPECT) study for patients with temporal lobe epilepsy. We selected 33 patients with refractory temporal lobe epilepsy who underwent ictal/interictal SPECT studies and had preoperative intracranial EEG result or surgical resection which was used as reference for seizure location. We divided all patients into two groups, which are the fast and the delayed groups; the delayed group comprised patients with injection time more than a cutoff time and vice versa. Using the subtraction ictal-interictal SPECT co-registered with SPECT (SISCOS) with varied Z-threshold (1.0, 1.5, 2.0 and 2.5), a method similar to subtraction ictal SPECT co-registered to magnetic resonance imaging (MRI) (SISCOM), a seizure-onset region in the SISCOS image was localized at the region with maximum sum of Z-scores. For each pair of cutoff time and Z-threshold, we determined the migratory proportion which was defined as the proportion of patients whose seizure-onset location based on SISCOS image was discordant with the reference. At cutoff time of 32-35 seconds and the Z-threshold of 2.0, the migratory proportion values were 7/26 (26.9%) and 5/7 (71.4%) in the fast and the delayed groups, respectively. At the same range of cutoff time with the Z-threshold of 2.5, the migratory proportion was 8/26 (30.8%) in the fast group while the proportion was 5/7 (71.4%) in the delayed group. Using Fisher's exact test, the migratory proportion values at the Z-threshold of 2.0 and 2.5 were significantly different between the fast and the delayed groups (p = 0.0709 and 0.0838, respectively), suggesting that patients with temporal lobe epilepsy who undergo an ictal/interictal SPECT study with injection time longer than 35 seconds tend to have seizure-onset zone migration in the SISCOS analysis with the traditionally-used Z-threshold of 2.0.

Steal phenomenon in Sturge-Weber syndrome imitating an ictal electroencephalography change in the contralateral hemisphere: report of 2 cases.

Infants with Sturge-Weber syndrome (SWS) are considered for surgery if they develop seizures and the seizures prove medically refractory. The authors report on 2 infants (15 and 19 months old) with SWS who underwent scalp video electroencephalography (EEG) and subsequent functional hemispherotomy for intractable partial motor seizures due to extensive left hemispheric angiomatosis. They presented with similar interictal and ictal EEG findings. Ictal EEG showed abrupt high-amplitude delta slow waves, without evolution on the contralateral hemisphere before the build-up of ictal EEG changes on the lesional hemisphere. The patients became seizure free after hemispherotomy. The ictal contralateral slow waves were not a sign of an ictal hemisphere and may indicate prominent ischemic changes resulting from a steal phenomenon of hemispheric angiomatosis during seizure.