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.

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.

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.

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.

Medium-chain triglyceride ketogenic diet is effective for treatment of an adult with super-refractory status epilepticus: a case report and literature review.

BACKGROUND: The ketogenic diet (KD) has been shown to be effective in controlling super-refractory status epilepticus (SRSE) in adult. To the best of our knowledge, there has been no previous report of the MCT KD in adult with SRSE. CASE REPORT: A 19-year-old female was hospitalized due to SRSE from autoimmune encephalitis despite pulsed methylprednisolone, intravenous immunoglobulin, and eight antiepileptic drug treatments. The MCT KD treatment was initiated and rapid seizure control was observed within 6 days despite negative ketosis. CONCLUSION: We report the first successful treatment with MCT KD in a female adult with SRSE who was refractory to classic KD with severe hypertriglyceridemia, and reviewed all SE adults with KD treatment. Dramatic seizure control without positive ketosis might lead to a new focus on fatty acids instead, paving the way for further prospective study regarding the effects of the MCT KD in this fatal condition.

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.