Bo Yan

Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population

Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte antigen (HLA)-B*1502 has been strongly associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this relationship, we performed high-resolution HLA genotyping on LTG-tolerant controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls, and 71 healthy volunteers were enrolled. The differences in the starting dosage of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not statistically significant. HLA-B*1502 frequency was 33.3% (1/3; LTG-induced SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant group), and 8.5% (6/71; healthy volunteers). There was no significant difference in the frequency of subjects with the HLA-B*1502 allele between the SJS/TEN group and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI 0.17-23.9). None of the HLA alleles detected were associated with LTG-induced cADRs. In conclusion, HLA-B*1502 and other HLA alleles are not directly associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated with an increased risk of LTG-induced SJS/TEN could not be excluded.

Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502 allele in Chinese Han population

BACKGROUNDnRecent study demonstrated that HLA-B*1502 was a common risk allele in aromatic antiepileptic drugs (AEDs) induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. However, the association of AEDs-induced mild maculopapular eruption (MPE) with HLA-B*1502 remains unclear until recently. In the present study, we conducted a pilot study to detect a possible association of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han population.nnnMETHODSnWe enrolled 90 subjects involving 9 patients with OXC-induced MPE and two groups of controls, 9 OXC-tolerant and 72 normal controls. High-resolution HLA genotyping was performed by specific kit. The results of HLA genotyping are expressed as positive or negative for HLA-B*1502 allele. Differences in genotype frequencies between groups were assessed by the Fishers exact test.nnnRESULTSnFour cases were detected as positive for HLA-B*1502 amongst 9 patients. However, only 1 subject was positive amongst 9 tolerant controls, and 6 subjects were positive amongst 72 normal controls. The difference in HLA-B*1502 allele frequencies between the MPE group and normal controls was statistically significant (OR: 8.8; 95% CI: 1.853-41.790; P=0.011). In addition, we also observed an increased frequency of HLA-B*1502 allele in patients (44.44%) compared with tolerant controls (11.11%), although it failed to reach statistical significance (P=0.294).nnnCONCLUSIONSnOur findings indicate that HLA-B*1502 allele may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han population. In order to safer AEDs use, we recommend that HLA-B*1502 allele should be tested for patients with OXC-induced MPE before changing to other AEDs, and AEDs with similar chemical structure should be avoided in individuals who test positive for HLA-B*1502 allele. It should be pointed out that, however, our results may well be just by chance owing to the small sample size and should be further confirmed in future studies.

Clinical features of psychogenic nonepileptic seizures: A study of 64 cases in southwest China

This article describes the clinical features of psychogenic nonepileptic seizures (PNES) in people in southwest China. Patients with a confirmed diagnosis of pure PNES by video/EEG monitoring were retrospectively reviewed. A total of 64 patients with PNES were included, 32 (50%) of whom were male. Twenty (31.3%) patients had previously been misdiagnosed and treated for epilepsy. Psychological trauma and head injuries were considered antecedent traumatic factors. A history of abuse was rare. The PNES cases were divided into three subtypes: psychogenic minor motor seizures, psychogenic major motor seizures, and unresponsive seizures. Age at onset was identified as a predictor of prognosis. The results of this study demonstrated a higher prevalence of PNES in males compared with previous studies. The semiology of PNES in China is similar to that in Western countries. Classification of semiology may be helpful in the differential diagnosis of PNES.

Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese

The aims of this study were to clarify the possible associations of carbamazepine (CBZ)- and lamotrigine (LTG)-induced maculopapular exanthema (MPE) with the human leukocyte antigen (HLA) alleles in Chinese patients. A total of 249 subjects, including 40 patients with CBZ-induced MPE (CBZ-MPE), 43 patients with LTG-induced MPE (LTG-MPE), 52 CBZ-tolerant controls, 42 LTG-tolerant controls and 72 healthy controls, were included in this study. High-resolution HLA genotyping was performed by a specific kit. Differences in the allele frequencies among the groups were assessed. The allele frequencies of HLA-A*0201 and HLA-DRB1*1405 were significantly higher (P=0.033 and P=0.003, respectively), but those of HLA-B*5801 and HLA-DRB1*0301 (P=0.037 and P=0.024, respectively) were lower in the CBZ-MPE patients when compared with the CBZ-tolerant group. We also observed two significantly increased alleles of HLA-A*3001 and HLA-B*1302 (P=0.013 and P=0.013, respectively) and a decreased allele of HLA-A*3303 (P=0.048) in the LTG-MPE patients when compared with those in the LTG-tolerant group. Our results support the hypothesis that these HLA alleles contribute to the genetic susceptibility to CBZ/LTG-MPE and may be valuable as potential biomarkers for CBZ/LTG-MPE in Han Chinese.

Quantitative and trajectory analysis of movement trajectories in supplementary motor area seizures of frontal lobe epilepsy

The objectives of this study were to quantitatively analyze the movement trajectories of four types of supplementary motor area (SMA) seizures (hyperkinetic, tonic posturing, fencing posture, tonic head turning), and to compare the movement trajectories of SMA seizures with those of temporal lobe seizures and psychogenic nonepileptic seizures. Ten video/EEG recordings of each type of seizure were obtained. Imaging data collected by video/EEG monitoring were transformed into a digital matrix with image processing software and then transformed into a movement trajectory curve with MATLAB 6.5 software. From these movement trajectories, amplitude, frequency, proximal/distal limb amplitude ratios, and shoulder/abdominal amplitude ratios measurements were calculated. One-way ANOVA revealed statistically significant differences in average amplitude, as well as proximal/distal limb amplitude ratios, in SMA seizures when compared with those of temporal lobe seizures and psychogenic nonepileptic seizures. This study proved the feasibility of quantitative analysis of SMA seizures and suggests it should be further evaluated for its capability to distinguish different seizure semiologies for the diagnosis of epilepsy.

Phenytoin-induced Stevens–Johnson syndrome with negative HLA-B*1502 allele in mainland China: Two cases

Antiepileptic drugs-induced Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction. Recent studies in Thailand and Taiwan showed a significant association between phenytoin (PHT)-induced SJS and human leucocyte antigen HLA-B*1502 allele. Although the US FDA had issued an alert to clinicians, insufficient information is available to recommend testing for HLA-B*1502 in Asian patients in line for PHT treatment. Therefore, extended studies are necessary to further evaluate the potential association between PHT-induced SJS and HLA-B*1502 allele in various populations. To date, no similar data exist in mainland China. Here, we describe two Chinese Han cases of PHT-induced SJS with negative HLA-B*1502 allele, in which HLA high-resolution genotyping showed two heterozygous HLA-B*4601/B*5102 and HLA-B*3701/B*4601 allele, respectively. Our findings provide evidence to support that other genetic markers or nongenetic factors could contribute to the susceptibility of PHT-induced SJS, except for HLA-B*1502 allele. Further studies are encouraged to investigate the genetic link with PHT-induced serious skin reactions in future.

Motor trajectories in automatisms and their quantitative analysis

OBJECTIVEnTo quantitatively analyze trajectory of movement in automatisms with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE).nnnMETHODSnTwenty markers were attached to chosen body parts of patients, and 10 videos of seizures were recorded. The obtained videos were converted into digital matrices. Motor trajectories were established, the amplitude, frequency, limb distal-proximal amplitude ratio, and shoulder-abdominal amplitude ratio were calculated, analyzed and compared between two types of epilepsy.nnnRESULTSnThe average of transient limb distal-proximal ratios in automatism patients with TLE was >3, which suggested that distal limb movements during TLE were predominant. However, the transient limb distal-proximal ratio in patients with FLE was <3, which indicated the predominance of proximal movements. The differences of motor trajectories between these two types of epilepsy were statistically significant.nnnCONCLUSIONnThe quantification system may pave a new way for semiology study of epilepsy and is important in differential diagnosis of different types of epilepsy.

Status epilepticus in pregnant women with epilepsy after valproate adjustment: A case series

PURPOSEnValproate is an effective wide-spectrum anti-epileptic drug that is also known to be teratogenic. Its administration in epileptic women remains controversial. This report aims to draw more attention to valproate adjustment before and during pregnancy.nnnMETHODSnWe collected medical records of pregnant women with epilepsy at West China Hospital in Chengdu, China who developed status epilepticus during pregnancy after valproate withdrawal or reduction in dose from January 2013 to July 2015.nnnRESULTSnA total of 281 pregnancies in patients with epilepsy were examined; 6 episodes of status epilepticus occurred during these pregnancies. Four patients with status epilepticus took long-term valproate before pregnancy. Among them, 2 patients stopped taking valproate 3 months prior to pregnancy, and 2 patients discontinued valproate or reduced their valproate dose when pregnancy was confirmed. All 4 suffered from a convulsive status epilepticus; 3 experienced an increased frequency of seizures. One child was diagnosed with neonatal asphyxia, hypoxic-ischemic encephalopathy, and neonatal pneumonia.nnnCONCLUSIONnValproate adjustment prior to or during pregnancy may result in deterioration of seizure control, which may include resultant status epilepticus. Valproate during pregnancy increases the risk of major congenital malformations, but the significance of maintaining seizure control in pregnant women should be also taken into consideration. Open and careful discussion with every pregnant woman with epilepsy should discuss the risk-benefit ratio of epilepsy medications.

How to effectively constraint the cost of presurgical evaluation for resective surgery in low-income population: Clinically oriented opinions

Epilepsy surgery plays a pivotal role in the successful treatments of intractable epilepsy. In China, economic burden for epileptic patients is heavy. Because of limited economic resources, appropriate utilization of presurgical evaluation technologies is especially important for low-income patients, who could benefit from surgery. This study proposed the strategies for restricting the cost of presurgical evaluation for resective surgery in low-income population with refractory epilepsy. A retrospective study was performed on the database of patients with resective surgery from January 2007 to June 2009 in West China Hospital of Sichuan University. Presurgical evaluation technologies and outcome were analyzed. As a result, 143 patients underwent resective operation were included in this study. Seizure free can be reached at 63.8% patients with (ATL) and 61.1% with focal lesionectomy (FLE). Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), routine electroencephalography (REEG), video-EEG (VEEG) and invasive-EEG (IEEG) were used for investigation. The cost of those technologies was listed for consultation. Based on these findings, how to make the proper choice for surgery candidates was suggested according to different types of epilepsy.