Deng Chen

The value of 24-hour video-EEG in evaluating recurrence risk following a first unprovoked seizure: A prospective study

PURPOSE To evaluate the value of 24-hour video-EEG (VEEG) in assessing recurrence risk after a first unprovoked seizure. METHOD Consecutively 134 patients with a first unprovoked epileptic seizure were recuited from West China Hospital, Sichuan University, between January 2010 and January 2013. All patients underwent VEEG and magnetic resonance imaging (MRI) of the brain, Each patient had at least 24-month follow up. RESULTS Seventy-six (56.7%) patients had abnormal VEEG, and VEEG abnormalities was associated with an increased risk of seizure recurrence (RR 2.84, 95% CI 1.67-4.82, p<0.001). The overall accumulated seizure recurrence risks were 51.5% in all patients, and 45.6% in generalized seizures subgroup, and with no significant difference. The subgroup of VEEG with epileptiform discharges had an increased seizure recurrence risk compared with normal VEEG (RR 2.76, 95% CI 1.83-5.34, P<0.001) and the nonsignificant abnormality VEEG group (RR 2.05, 95% CI 1.14-3.82, P<0.001). Within the group of whom showed epileptiform discharges, the recurrence rate of those with generalized epileptiform discharge abnormality and focal epileptiform discharge abnormality were not significantly different (RR 1.09, 95% CI 0.44-2.69, P=0.85). CONCLUSIONS An abnormal VEEG is a risk factor for seizure recurrence in patients with a first unprovoked seizure, especially if epileptiform discharges past. The recurrence risks were 73.2% in the epileptiform discharges abnormality VEEG group, which may help the diagnosis of epilepsy according to the practical clinical definition of epilepsy.

A preliminary observation of the adverse effects of phenobarbital among patients with convulsive epilepsy in rural West China

BACKGROUND This study explored the adverse effect (AE) profile of phenobarbital (PB) among patients with active convulsive epilepsy (ACE) from resource-poor areas. METHODS Patients with ACE were enrolled into an epilepsy management project in rural West China. Information was obtained from monthly follow-up questionnaires. The demographic and clinical features of the patients with AE were firstly described. After that, the occurrence rate was estimated for each subtype of AE at three different severity levels (mild, moderate, and serious). Survival analysis was used to determine the potential risk factors of AEs. RESULTS A total of 7231 patients (3780 men) were included in the present cohort. During the follow-up time period (average 33.4months), the most common AEs were drowsiness (moderate: 4.4%, serious: 0.68%), dizziness (moderate: 3.7%, serious: 0.5%), and headache (moderate: 2.9%, serious: 0.41%). In the confirmed AE groups (moderate and serious severity levels), the symptoms tended to be transient, with durations of less than 3months. Polytherapy was an independent risk factor for AEs and had an increasing risk when the severity of the AE increased (Hazard Ratio 1.12, 1.55, and 2.52 for mild AE, moderate AE, and serious AE, respectively). Receiving a high dosage of PB (>180mg/day) indicated a slightly elevated risk (Hazard Ratio 1.22 and 1.27 for mild AE and moderate AE, respectively). CONCLUSION Phenobarbital demonstrates overall tolerability, and serious AEs were not common. Patients receiving a high dose of PB or polytherapy are at increased risk of developing AEs.

The adverse event profile of brivaracetam: A meta-analysis of randomized controlled trials

PURPOSE To comprehensively evaluate the adverse events (AEs) significantly associated with brivaracetam (BRV) treatment in a large selection of randomized control trials. METHODS We conducted an online database search using Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for all available randomized control trials (RCTs) that investigated the therapeutic effects of brivaracetam. Serious AEs (SAEs), withdrawal, and treatment-emergent adverse effects were then assessed for their association with brivaracetam. Finally, a meta-analysis was performed using Review Manager 5.3 software. RESULTS Eight RCTs with a total of 2505 patients were included in our study, 1178 of which were randomized with respect to brivaracetam (BRV). Serious AEs, overall withdrawal, AE-related withdrawal and psychiatric adverse events (PAEs) were not significantly associated with BRV treatment. BRV was also not significantly associated with a heightened risk of AE-related withdrawal and PAEs with increasing doses. Of the 17 AEs included in our meta-analysis, three AEs (dizziness, fatigue, and back pain) were found to be significantly associated with BRV treatment. But we did not find that the risk of them was obviously increasing with the increasing doses. CONCLUSION This meta-analysis showed that BRV treatment was reasonably tolerated by patients and rarely caused serious AEs. Further clinical studies will be needed to more concretely determine the safety and tolerability profile of BRV.

Newer antiepileptic drugs compared to levetiracetam as adjunctive treatments for uncontrolled focal epilepsy: An indirect comparison

PURPOSE Newer antiepileptic drugs (AEDs), such as Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV), have been marketed as adjunctive treatments for partial-onset seizures. Our aim was to compare the efficacy and tolerability of newer AEDs with Levetiracetam (LEV), when used as add-on treatments for uncontrolled focal epilepsy. METHOD We conducted an online database search on PubMed, Embase, Cochrane Online Library and Clinicaltrials.gov for all available randomized controlled trials (RCTs) investigating the therapeutic effects of newer AEDs or LEV vs placebo. Indirect comparisons for clinical efficacy and tolerability at different doses between the newer AEDs and LEV were then performed using Indirect Treatment Comparison (ITC) software. RESULTS Twenty-four RCTs with a total of 8540 patients were included. Compared to LEV, ESL, LAC and BRV did not showed significant difference in efficacy at all dose level. PER showed lower 50% response rates and seizure-free rates at the highest effective recommended dosages. Treatment-emergent adverse events (TEAEs) and withdrawal rates due to adverse events (AEs) of LAC and PER were higher than LEV at the highest effective recommended dosages, and overall AE rates from ESL were higher than LEV. CONCLUSIONS Indirect comparisons suggested that ESL, LAC and BRV were not inferior to LEV in efficacy. ESL, LAC and PER may have a possible worse tolerability profile compared to LEV at high dose. But BRV may exhibit a similar tolerability to LEV. Newer AEDs cannot exceed the LEV on efficacy and tolerability.

Update on causes of premature death in people with convulsive epilepsy in rural West China

This longitudinal prospective study updated a previous report on premature mortality and focused on the risk factors among patients with convulsive epilepsy in resource‐poor settings. The present cohort size (7,231) and follow‐up (mean 33.4 months) were expanded. The basic epidemiologic aspects of this cohort were similar to the original report (case fatality: 3.26% vs. 2.97%, respectively; injury contributed more than half of the deaths). Cox regression analysis suggested that male patients, late ages of onset (>45 years old), short duration of epilepsy (<10 years), and high convulsive seizure frequency (>2 per month) were independent risk factors for overall premature death. Male patients with late ages of onset and high seizure frequency had a higher risk of injury‐specific death. This study emphasizes the preventable nature of injuries that are leading putative causes of death among people with convulsive epilepsy in rural West China. Education on specific populations and efficient seizure control are of paramount importance in reducing the risk of premature mortality.

The focal alteration and causal connectivity in children with new-onset benign epilepsy with centrotemporal spikes

The aim of the current study was to find the epileptic focus and examine its causal relationship to other brain regions in children with new-onset benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 66 children with BECTS and 37 matched control children. We compared the amplitude of low frequency fluctuation (ALFF) signals between the two groups to find the potential epileptogenic zone (EZ), then used Granger causality analysis (GCA) to explore the causal effects of EZ on the whole brain. Children with BECTS had significantly increased ALFF in the right Broca’s area, and decreased ALFF in bilateral fusiform gyrus. The patients also showed increased driving effect from the EZ in Broca’s area to the right prefrontal lobe, and decreased effects to the frontal lobe and posterior parts of the language network. The causal effect on left Wernicke’s area negatively correlated with verbal IQ (VIQ) score. Our research on new-onset BECTS patients illustrates a possible compensatory mechanism in the language network at early stages of BECTS, and the negative correlation of GCA and VIQ suggest the disturbance of epileptiform activity on language. These findings shed light on the mechanisms of and language dysfunction in BECTS.

Terminal seizure frequency and its relation to SUDEP

BACKGROUND Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with epilepsy. Several risk factors have been implicated, including early age of onset, tonic-clonic seizures and antiepileptic drugs. However, whether patients who die from SUDEP have a greater frequency of seizures in the few months before death is unclear. We investigated the terminal seizure frequency and its relation to SUDEP among a large group of patients with tonic-clonic seizures in rural West China. METHODS We used the database from the Convulsive Epilepsy Control and Management Program in West China, which routinely provides phenobarbital (PB) as a treatment for convulsive epilepsy. Patients with probable SUDEP were included according to pre-set criteria. A verbal autopsy was undertaken for each case. By matching each patients age, sex, date of joining the program, time in follow-up, and baseline seizure frequency, we set up a 1:5 ratio control group. SPSS 21.0 statistics were applied to compare the differences in seizure frequency 3months prior to SUDEP between patients with probable SUDEP and controls. Furthermore, the dynamic changes of terminal seizure frequency 6-9months, 3-6months, and 3months prior to SUDEP was also analyzed. RESULTS A total of 41 patients who died from probable SUDEP were identified out of 7844 patients during 10years of follow-up. The SUDEP group had a significantly higher tonic-clonic seizure frequency 3months before their deaths than the control group (p=0.023). At the same time, their seizure-free rate was lower than the control group (p=0.025). Patients with probable SUDEP who were followed up over 12months were further studied as a subgroup. They had more tonic-clonic seizures 3months prior to death compared to the control group (p=0.010). They also had an increase in seizure frequency in their terminal phase (3months prior) compared to an earlier stage (3-6months prior) (p=0.029). Furthermore, the terminal PB dose in the SUDEP group was higher than the control group (p=0.002). CONCLUSION Patients who died from SUDEP had more frequent tonic-clonic seizures 3months before their deaths. Higher seizure frequency increases the exposure to peri-ictal pathophysiological events, which possibly relate to SUDEP. This phenomenon may be due to the drug resistance potential of these patients or the high dose of PB. Further research is required to ascertain the underlying mechanisms of SUDEP.

Risks of probable SUDEP among people with convulsive epilepsy in rural West China

PURPOSE This study aimed to examine the risk factors of probable sudden unexpected death in epilepsy (SUDEP) among patients with convulsive epilepsy in rural communities. METHOD A total of 35 cases with identified probable SUDEP were recruited in the study and compared with three survival controls that were sex and age matched from the same cohort for each case. Three healthy controls per case were chosen as a control group. Risk factors were analyzed using the logistic regression model. The odds ratio (OR) was calculated to determine the risk or protective effect. RESULTS The following three factors significantly increased the risk of probable SUDEP: early-onset age of seizures (≤10 years vs. >10 years) with an OR of 6.8 (95% CI: 1.5-32.6), high seizure frequency at baseline (>10 years vs. ≤10 years) before regular phenobarbital treatment with an OR of 5.9 (95% CI: 2.2-16.6), and experiencing one or more seizures (vs. seizure-free) in the month prior to probable SUDEP with an OR of 9.5 (95% CI: 3.0-30.1). CONCLUSION Lack of seizure freedom before and during regular antiepileptic drug treatment increase the risk of probable SUDEP. Special attention should be given to patients with early convulsive epilepsy-onset, and the proper control of convulsive seizures is critical for the prevention of probable SUDEP.

Clinical utility of EMSE and STESS in predicting hospital mortality for status epilepticus

PURPOSE To explore the applicability of the epidemiology-based mortality score in status epilepticus (EMSE) and the status epilepticus severity score (STESS) in predicting hospital mortality in patients with status epilepticus (SE) in western China. Furthermore, we sought to compare the abilities of the two scales to predict mortality from convulsive status epilepticus (CSE) and non-convulsive status epilepticus (NCSE). METHOD Patients with epilepsy (n = 253) were recruited from the West China Hospital of Sichuan University from January 2012 to January 2016. The EMSE and STESS for all patients were calculated immediately after admission. The main outcome was in-hospital death. The predicted values were analysed using SPSS 22.0 receiver operating characteristic (ROC) curves. RESULT Of the 253 patients with SE who were included in the study, 39 (15.4%) died in the hospital. Using STESS ≥4 points to predict SE mortality, the area under the ROC curve (AUC) was 0.724 (P < 0.05). Using EMSE ≥79 points, the AUC was 0.776 (P < 0.05). To predict mortality in NCSE, STESS ≥2 points was used and resulted in an AUC of 0.632 (P > 0.05), while EMSE ≥90 points gave an AUC of 0.666 (P > 0.05). CONCLUSIONS The hospital mortality rate from SE in this study was 15.4%. Those with STESS ≥4 points or EMSE ≥79 points had higher rates of SE mortality. Both STESS and EMSE are less useful predicting in-hospital mortality in NCSE compared to CSE. Furthermore, the EMSE has some advantages over the STESS.

The efficacy of repetitive transcranial magnetic stimulation for Parkinson disease patients with depression

Objective To evaluate the efficacy of repetitive transcranial magnetic stimulation for Parkinson disease (PD) patients with depression. Methods A meta-analysis was performed using relevant randomized controlled trials (RCTs) from online databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to pre-defined inclusion and exclusion criteria, and the quality of the studies was evaluated using the Jadad Scale. All data were pooled by RevMan 5.2 software for meta-analysis. Results The review covered 528 articles, and 7 articles with Jadad score ≥ 4 were included in the analysis. The meta-analysis showed that, compared to sham repetitive transcranial magnetic stimulation (sham-rTMS), repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) improved depression, but that there was no significant difference in depression improvement between rTMS and selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, rTMS over DLPFC did not improve motor function compared to sham-rTMS or SSRI, and the studies that included neurocognitive measures showed no significant difference between rTMS and sham-rTMS. Conclusion This meta-analysis provides evidence that rTMS over DLPFC can improve depression similar to SSRI treatment, has no effect on the motor function and cognition of PD patients with depression.Abstract Objective: To evaluate the efficacy of repetitive transcranial magnetic stimulation for Parkinson disease (PD) patients with depression. Methods: A meta-analysis was performed using relevant randomized controlled trials (RCTs) from online databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to pre-defined inclusion and exclusion criteria, and the quality of the studies was evaluated using the Jadad Scale. All data were pooled by RevMan 5.2 software for meta-analysis. Results: The review covered 528 articles, and 7 articles with Jadad score ≥4 were included in the analysis. The meta-analysis showed that, compared to sham repetitive transcranial magnetic stimulation (sham-rTMS), repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) improved depression, but that there was no significant difference in depression improvement between rTMS and selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, rTMS over DLPFC did not improve motor function compared to sham-rTMS or SSRI, and the studies that included neurocognitive measures showed no significant difference between rTMS and sham-rTMS. Conclusion: This meta-analysis provides evidence that rTMS over DLPFC can improve depression similar to SSRI treatment, has no effect on the motor function and cognition of PD patients with depression.