Expression Analysis of lncRNAs in Refractory and Non-Refractory Epileptic Patients

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the pathogenesis of neuropsychiatric disorders such as epilepsy. In the current study, we evaluated expression of eight lncRNAs in 80 epileptic patients (40 refractory and 40 non-refractory ones) and 40 normal individual using quantitative real-time PCR. Bayesian regression model showed significant higher expression of UCA1 in both refractory and non-refractory groups compared with controls (posterior beta of relative expression (RE) =?2.03, P value?=?0.003, and posterior beta of RE?=?4.05, P value?<?0.0001, respectively). Besides, expression of UCA1 was higher in non-refractory patients compared with refractory ones (posterior beta of RE?=?2.008, P value?=?0.019). When repeating statistical analyses in a gender-based manner, differences in expression of UCA1 were significant in all subgroup analyses except for male non-refractory vs. refractory subgroups analysis. Expression levels of NKILA and ANRIL were higher in both refractory and non-refractory groups compared with controls (posterior beta of RE?=?1.565, P value?=?0.018, and posterior beta of RE?=?1.902, P value?=?0.006 for NKILA; posterior beta of RE?=?1.304, P value?<?0.0001, and posterior beta of RE?=?1.603, P value?=?0.019 for ANRIL, respectively). However, expression levels of these two lncRNAs were not different between refractory and non-refractory groups. Gender-based analysis for these two lncRNAs revealed similar results except for lack of difference in ANRIL expression between male refractory group and controls. Expression of THRIL was significantly lower in both refractory and non-refractory groups compared with controls (posterior beta of RE?=???0.842, P value?=?0.044 and posterior beta of RE?=???1.969, P value?<?0.0001, respectively). Furthermore, expression of this lncRNA was lower in non-refractory patients compared with refractory ones (posterior beta of RE?=???1.129, P value?=?0.002). However, no significant difference was detected between non-refractory and refractory patients either in males or females. The interactions between gender and relative expressions of PACER, DILC, and MALAT1 were significant, so the results were assessed in gender-based manner. In females, expression of DILC was higher in non-refractory patients compared with refractory ones (posterior beta of RE?=?0.959, P value?=?0.044). Expression of MALAT1 was lower in female non-refractory patients compared with controls and in female non-refractory patients compared with refractory ones (posterior beta of RE?=???1.35, P value?=?0.002, and posterior beta of RE?=???0.942, P value?=?0.045, respectively). Finally, expression of PACER was higher in refractory patients vs. controls and non-refractory patients vs. controls in both male and female subgroups. However, comparison between non-refractory and refractory patients revealed significant results only among females. Expression of none of the assessed lncRNAs was correlated with age of study participants. There were robust correlations between expression levels of lncRNAs. The most robust correlations were detected between UCA1 and PACER (r?=?0.84, P?<?0.0001) and between UCA1 and ANRIL (r?=?0.75, P?<?0.0001). Taken together, our study demonstrated dysregulation of lncRNAs in peripheral blood of epileptic patients and potentiated them as biomarkers for this neurologic condition.

     

Computerized Analysis of EEG Background Activity in Epileptic Patients

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.     

Epileptic Seizures in AD Patients

Epileptic seizures have long been recognised as a complication of the clinical syndrome of Alzheimer’s disease, particularly in advanced disease, but have hitherto been viewed essentially as epiphenomena of the neurodegenerative process. Progress with animal models of Alzheimer’s disease has suggested that this view may be incorrect, and that seizures may be a reflection of pathophysiological processes similar to or overlapping with those responsible for cognitive decline. This overlap between neuropsychological and neurophysiological changes suggests that seizures in Alzheimer’s disease may be a valid therapeutic target, over and above symptomatic treatment. This article reviews data on the prevalence of seizures in Alzheimer’s disease, seizure types, pathophysiology and treatment. Seizure prevalence increases with disease duration, but early-onset disease is associated with a greater risk of seizures, in part related to the frequency of presenilin-1 gene mutations in early-onset disease. Seizures are mostly of partial origin, with both complex partial and secondary generalised seizures. Seizure pathophysiology may relate to increased amyloid beta-peptide production, structural alterations in neurones related to cytoskeletal dysfunction, cerebrovascular changes, neurotransmitter dysfunction or combinations thereof. Through modification of these pathophysiological pathways, there may be possible roles for anti-epileptic drugs such as sodium valproate and lacosamide in the treatment of Alzheimer’s disease. In summary, epileptic seizures are part of the AD phenotype, and merit further investigation.     

幕上胶质瘤致癫因素分析

目的分析探讨幕上胶质瘤致癫因素。方法回顾性分析143例幕上胶质瘤患者的病理和影像学资料。所有病人都经神经影像学和病理学检查确诊。结果74.6%的额叶胶质瘤患者以癫痫为首发症状。具有钙化、肿瘤累及皮层和没有明显占位效应的胶质瘤容易产生癫痫,低级别星形细胞瘤、少枝突胶质瘤癫痫发病率较高。结论胶质瘤致癫不仅与其病理类型有关,肿瘤生长特征及部位也是重要因素。     

Inter-relations of Folic Acid and Vitamin B12 in Drug-treated Epileptic Patients

During treatment with folic acid, 15 mg daily for 2 years, serum vitamin B₁₂ levels fell in 24 out of 30 epileptic patients treated with anticonvulsant drugs. The most rapid fall occurred in the first 3 months of folate therapy, from a mean of 360 pg/ml to 221 pg/ml, but it continued more slowly for up to 15 months, or longer in some. In 10 of 11 patients in whom folic acid therapy was stopped but anticonvulsant therapy continued; serum folate levels subsequently fell to subnormal values within 18 months.     

癫痫患者出生与出生后的危险因素分析

目的　调查癫痫患者在出生时与出生后的危险因素。方法　采用华盛顿癫痫心理社会问卷对 2 0 0例成年癫痫患者进行了调查 ,并与 2 0 0例正常人做了对照分析。结果　癫痫分类以全身性发作 134例 (6 7% ) ,16～ 30岁 12 0例 (6 0 % )。危险因素 :难产和产伤 (P <0 .0 5 ) ,新生儿黄疸 ,脑炎 /脑膜炎和高血压 (P <0 .0 5 ) ,发热惊厥和脑外伤 (P <0 .0 1)。家族高危因素有癫痫和偏头痛 (P <0 .0 1) ,精神病、脑中风和高血压 (P <0 .0 5 )。结论　癫痫患者出生时与出生后的危险因素与癫痫的发病密切相关。     

Hemisphere-dependent Cognitive Performances in Epileptic Patients

Short-term memory (STM), long-term memory (LTM), and recency judgment were investigated in 75 right-handed nonaphasic patients without visual deficits who had epileptic foci localized in one of four different regions of the brain: right temporal lobe, left temporal lobe, right frontal lobe, and left frontal lobe. The results led to the following conclusions: (1) left temporal lesions yielded comparatively greater impairment for the verbal LTM task, whereas right temporal lesions were more disruptive for the spatial LTM task; (2) no significant differences between left- and right-brain-damaged patients in STM tasks were obtained; (3) left frontal lesions yielded deficits in a recency task in accordance with hemispheric specialization; (4) only prolonged epileptic syndromes impaired neuropsychological performance in those tests; (5) comparisons between male and female patients and between those with and without clear evidence of a structural lesion did not reach statistical significance.     

Timing of Seizure Recurrence in Adult Epileptic Patients: A Statistical Analysis

Seizure diaries were maintained prospectively in 24 epileptic patients (19 with partial complex, three with partial simple, and three with primary generalized seizures) who were selected consecutively, had stable seizure patterns, were reliable historians, and were known to be compliant with medications. Diaries were maintained for an average of 237 days (range, 61-365), and an average of 18 seizures were recorded per patient (range, 5-76). Seizure patterns were analyzed by using the methods appropriate for a time series of events (point process). Two patients had a decreasing trend in seizure frequency. For 12 patients, seizure occurrence was indistinguishable from that of a Poisson process. The remaining 10 patients had an exponential distribution of seizure intervals, but did not fit other criteria for a Poisson process; 3 of these showed evidence for seizure clustering; none showed evidence for a seizure cycle. It is concluded that the pattern of seizure occurrence in most epileptic people is random, but in approximately 50%, it is not occurring according to a Poisson process. These observations indicate that seizure cycling and/or clustering are not common in epileptic patients, but do not exclude the possibility that seizures have been precipitated by some randomly occurring event, such as sleep deprivation or increased stress.     

Epileptic Seizures in Elderly Patients with Dementia

All inpatients aged greater than 55 years with dementia in the Dundee Psychiatric Service were surveyed for seizure occurrence by interviewing staff and reviewing records. Of 208 patients, 19 (9.1%) were recorded as having seizures. The seizures were major in 92% and occurred at a rate of approximately 2.3 seizures per patient per year. Patients with epilepsy were significantly younger than a control group of dementia inpatients and were significantly more cognitively impaired on the survey Clifton Assessment Procedure for the Elderly (CAPE), but not on the Mini Mental State Examination. Of 111 reported accidents, only 5 appeared to be associated with epilepsy. Although epileptic seizures are relatively common in patients with severe dementia, they rarely caused severe problems.     

托吡酯对戊四氮诱导的癫痫大鼠海马神经元bc1-2、bax基因表达的调控

目的探讨托吡酯对戊四氮癫癎模型大鼠大脑的神经保护作用及可能的机制.方法成年雄性Wistar大鼠54只,随机分为正常对照组(6只);戊四氮组(24只);托吡酯预处理组(24只).癫癎发作后分别于6、12、48 h后处死取脑,进行HE染色和bcl-2、bax免疫组化染色.结果癎性发作后海马HE染色显示;戊四氮组CA1、CA3和DC区神经元变性及坏死较托吡酯预处理组显著.免疫组化染色显示托吡酯预处理组bcl-2 12和48 h在CA1、CA3和DC的表达强于戊四氮组,而bax在上述时段的表达则较戊四氮组弱.结论托吡酯具有一定的神经保护作用,推测可能与其增强大鼠海马神经元bcl-2基因表达,降低bax基因表达有关.     

Clinical Studies of Schizophrenia-Like State in Epileptic Patients

Abstract: Six subjects who suffered from epileptic seizures followed by a schizophrenia-like state were examined. The mean duration between the onset of seizures and the psychotic state was 13.5 ± 6.6 years (mean ± S.D.). Five female subjects had episodic psychotic states and one man had a persistent one. Four subjects had localized temporal EEG abnormalities and the EEGs during psychotic states were different in each subject. During the psychotic state, no seizure was seen in the four subjects, a dierent seiznre frequency in the episodic case and an unchanged frequency in the persistent case. The psychotic features were characterized by K. Schneider's first-rank symptoms. In order to understand the mechanisms of psychotic states, it will be useful to take into consideration the excitatory and inhibitory effects of neurotransmitters on limbic discharges.