Search

Background: We aimed to explore the prevalence of autoimmune antibodies (Abs) in a large consecutive series with "chronic" epilepsy and without symptoms of autoimmune encephalitis; and to compare the immunopathology of brain tissue from drug-resistant epilepsy (DRE) with and without Abs positivity., Methods: Neuronal and glial antibodies were detected in the serum of patients who were admitted to the wards of West China Hospital from October 2016 to September 2019 and had epilepsy by cell-based assays and tissue-based assays., Results: Twenty-one (6.8 %) of 328 patients had positive Ab findings for the following: dipeptidyl-peptidase-like protein-6 (n = 7), contactin-associated protein-like 2 (n = 5), glutamic acid decarboxylase 65 (n = 4), gamma aminobutyric acid beta receptor (n = 2), N-methyl-d-aspartate receptor (n = 2), and dopamine D2 receptor (n = 1). Antibodies were detected in 6.9 % (13/187) of epilepsy people with unknown etiology and 5.6 % (8/141) of patients with known etiology, respectively. Among 190 patients with DRE, 14 (7.3 %) patients were Abs-positive. There was no significant difference between individuals with seropositive and seronegative results in clinical manifestations, except that the history of febrile seizure was significantly more frequent in the seropositive group. Moreover, brain samples from 3 patients with Abs-positive DRE (with DPPX in 2 patients, and CASPR2 in 1 patient) and 18 patients with Abs-negative DRE were analyzed for immunopathology. We found higher expression of CD8-positive T-cells in the hippocampus of Abs-positive DRE group., Conclusions: Neuronal antibodies are potentially involved in the process of "chronic" epilepsy, and CD8-positive T-cells may play an important role in this process., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: The aim of this qualitative study was to explore the challenges that patients with epilepsy (PWEs) face and the opportunities or areas where changes in nursing care may improve epilepsy care in western China., Methods: Semi-structured interviews with open-ended questions based on a review of the literature were conducted at the epilepsy center of a tertiary hospital in western China. A total of 18 PWEs, 18 caregivers and 11 neurology nurses were interviewed by using purposive sampling. The data were transcribed verbatim, and a content analysis was used to conduct the framework analysis., Results: Three key themes were identified, namely, the impact of epilepsy, barriers to epilepsy management, and measures in nursing care for improving epilepsy care. Psychological stress, the side effects of drugs and accidental injury related to seizures were reported to be the main negative impacts on patients. Limited knowledge about epilepsy, poor adherence to therapy, and a lack of effective communication between patients and medical staff were the major barriers to epilepsy management. Strengthening health education, assessing the frequency and type of seizures, screening for psychological disorders and mental intervention, and maintaining continuity of care were identified as crucial measures for nurses to improve epilepsy care., Conclusions: This study highlights the challenges among PWEs and opportunities for improving the quality of epilepsy care in western China. Limited knowledge and poor drug adherence are the main barriers to epilepsy management, which might be improved by more health education and continuing care provided by nurses. Assessing seizures, screening for psychological disorders and providing appropriate psychological care would help improve epilepsy care., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gliomas, especially low-grade gliomas, are highly epileptogenic brain tumors. Histopathological information is valuable in evaluating the diagnosis and/or biologic behavior of various gliomas. Here we explored the clinical data and histopathological predictors of the occurrence of epilepsy in patients with gliomas. A retrospective study examined 310 consecutive patients who had undergone surgical treatment for gliomas in our institution from January 2013 to January 2015. Clinical data and pathological examination results were analyzed. Literatures regarding the predictors and etiology of glioma associated epileptic seizures in the period of 1995-2015 were also reviewed. A total of 234 (75.5%) astrocytic tumors and 76 (24.5%) oligodendrial tumors were included. At diagnosis, 33.6% of patients had epileptic seizures. Multivariate analysis revealed cortex involvement (OR=7.991, 95%CI=1.599-39.926), lower World Health Organization grade (OR=3.584, 95%CI=1.032-12.346) and topoisomerase II (TopoII) positivity (OR=0.943, 95%CI=0.903-0.982) were strong predictors for preoperative epileptic seizures. Gender, disease course, tumor classification, location or volume did not significantly affect epileptic seizure occurrence. Forty-three publications involved glioma-associated epilepsy were found in PubMed online database and key data were extracted and summarized. The present studies on glioma-related epilepsy are relatively limited and inconsistent. Low-grade gliomas, cortex involvement and TopoII positivity were independent predictors of a history of epileptic seizures at diagnosis. Further studies to examine the underlying mechanism of topoisomerase II as well as other molecules in epilepsy occurrence in brain gliomas are needed in the future., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: This study aimed to evaluate the effectiveness of levetiracetam (LEV) use for seizure control in patients who had undergone resective surgery for intractable epilepsy in routine clinical practice., Methods: This was a prospective, observational study. Refractory epilepsy patients who underwent epilepsy surgery from January 2008 to December 2011 in the Department of Neurosurgery, West China Hospital were prospectively analyzed. Patients were divided into two groups according to antiepileptic drug (AED) treatment used immediately after epilepsy surgery (group A: therapy with LEV; group B: therapy without LEV). AED regimens were compared with regard to seizure-outcome for a period of more than 2 years. The International League Against Epilepsy (ILAE) classification was used to categorize seizure outcome., Results: A total of 319 patients (184 male and 135 female patients; mean age 28.2±13.4 years) were studied. The mean postoperative follow-up period was 3.9±1.2 years. The two groups showed was no significant difference in preoperative baseline data. At the 6-month follow-up, the proportion of patients with seizure freedom was significantly higher in group A than in group B (78.8% vs. 67.5%, p=0.03). Seizure outcomes after 2 years were assessed using the ILAE classification. The proportion of patients under ILAE seizure-outcome classification I (seizure freedom) was significantly higher in group A than in group B (74.3% vs. 60.7%, p=0.01). Seizure recurrence rates at the final assessment, after planned reduction or withdrawal, were 26.3% for group A and 40.6% for group B (p=0.04)., Conclusions: AED strategy after resective surgery may be a potentially modifiable prognostic indicator influencing seizure outcome in patients with intractable epilepsy. Compared to other AEDs, LEV appears to be more effective in controlling postoperative seizures in our long-term follow-up, and the advantage can be seen in early stage after surgery., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Human herpesvirus-7 (HHV-7) is a β-herpesvirus associated with febrile seizures. No association between HHV-7 and epilepsy has been confirmed., Objectives: The aim of this study was to investigate the presence of HHV-7 protein (KR4) in brain tissue from patients with drug-resistant epilepsy and to determine whether inflammatory molecules are activated in the presence of HHV-7 infection., Study Design: We used immunohistochemistry (IHC) to detect HHV-7 protein KR4 in samples from 305 patients with drug-resistant epilepsy. Liquid nitrogen-preserved hippocampal sclerosis (HS) samples from 63 of these patients were available, and we used nested polymerase chain reaction (PCR) to detect HHV-7 DNA. Inflammatory molecules including tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin-1 (IL-1) and interleukin-6 (IL-6) were identified by real-time PCR (rt-PCR) and IHC., Results and Conclusions: The study sample included 201 male subjects. The mean age was 23.9, SD 6.2 years (range 15-45). HS was the pathology in 69 samples (23%). The HHV-7 protein was detected in 27 (9%) of the 305 samples and in none of the 42 controls. The factors associated with HHV-7 infection were HS (11/69), glial scar (8/58), arachnoid cyst (2/21), focal cortical dysplasia (2/31) and vascular malformation (4/52). HHV-7 antigen was distributed mainly in the cytoplasm of astrocyte and oligodendrocyte in HS samples. HHV-7 DNA was detected in 20 of the 63 nitrogen preserved HS samples. The expression of TGF-β was up-regulated in samples that were positive for the HHV-7 protein and was mainly detected in neurons. This finding suggests a possible association between HHV-7 positivity, activation of TGF-β and drug-resistant epilepsy, especially HS, but these data need to be replicated., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to explore the most appropriate antiepileptic drug strategies after successful epilepsy surgery., Methods: A total of 131 refractory epilepsy patients who underwent epilepsy surgery from January 2005 to December 2008 in the Department of Neurosurgery, West China Hospital, were retrospectively reviewed. Patients were divided into three groups (monotherapy, duotherapy, and polytherapy) according to drug combinations used immediately after epilepsy surgery. Seizure outcomes were followed up for more than 2 years. Engel classification was used to evaluate seizure outcomes., Results: The mean postoperative follow-up period was 3.7±1.0 years. Preoperative baseline data among the three groups were comparable. Seizure recurrence rate in monotherapy was obviously higher than in other groups (34.1% vs. 15.1%, 7.1%) at 6-month follow-up, which showed a statistically significant difference (p=0.02). Seizure outcomes for 2 years were assessed using Engel classification. In the duotherapy group, the rate of Engel class I was definitely higher than in the other two groups (69.9% vs. 47.7%, 57.1%, p=0.02). Seizure relapse rates at the 2-year follow-up, after planned reduction or withdrawal, were 46.4% for monotherapy, 16.9% for duotherapy, and 25.0% for polytherapy (p=0.01)., Conclusions: Monotherapy may be not sufficient enough to control seizures completely. It appears to have a higher risk for seizure relapse when considering drug reduction. It suggests that duotherapy may be more effective and safer than monotherapy. Even after successful epilepsy surgery, duotherapy seems preferable to monotherapy or polytherapy for control of residual seizures., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To investigate the different expression of GluR5 and GluR6 in rat astrocyte induced with Coriaria Lactone (CL) and ATPA and to discuss the possible mechanism of the inducing epileptic model., Methods: Astrocyte of neonate rats was treated with CL and ATPA respectively and the astrocyte treated with normal saline as control. The mRNA and protein levels of GluR5 and GluR6 were detected by RT-PCR and western blotting., Results: Compared with the control, the expression of GluR5 was increased significantly in the astrocyte induced by ATPA (P < 0.05), however, there was no alteration of GluR6 expression. The expression of GluR5 and GluR6 were decreased significantly in CL-treated group (P < 0.05)., Conclusion: The present study showed ATPA up-regulated mRNA and protein levels of GluR5, but coriaria lactone down-regulated the GluR5 and GluR6 of astrocyte. The results indicate that there are different pathologic mechanisms of GluR5 and GluR6 in different neurotoxicants inducing model of epilepsy. The molecular mechanism need to be studied further in the future.

We investigated laminin beta1 expression in the hippocampi of patients with intractable epilepsy and explored the role of laminin beta1 in the pathogenesis of this condition. Fluorescence quantitative PCR, immunofluorescence, immunohistochemistry and Western blotting were used to measure laminin beta1 expression in surgically removed hippocampi of patients with intractable epilepsy, and the results were compared with control hippocampi. Fluorescence quantitative PCR showed increased expression of laminin beta1 mRNA in patient hippocampi compared with control tissues. Immunohistochemical staining demonstrated that laminin beta1 protein expression was significantly increased in patient hippocampi, and immunofluorescence microscopy showed accumulation of laminin beta1 in the cell membrane and cytoplasm of patient hippocampi. These findings were confirmed by Western blotting of protein preparations from patient hippocampi. Elevated expression of laminin beta1 mRNA and protein in the hippocampus suggests that laminin beta1 may play a role in the development of epileptic seizures in patients with intractable epilepsy.

Neuronal circuit remodeling is the most critical pathological characteristic closely associated with the initiation and maintenance of epilepsy; however, the exact mechanisms of neuronal remodeling need further elucidation. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton that causes actin polymerization and thus neurite extension. Our previous research demonstrated that the upstream regulator of N-WASP, cell division cycle 42 GTP-binding protein (Cdc42), is significantly upregulated in the brains of patients with intractable epilepsy (IE). In addition, cDNA microarray analysis has shown that gene expression of N-WASP is notably enhanced in the epileptic brain, suggesting a possible role for N-WASP in epileptogenesis. Here, we investigated the expression of N-WASP and its downstream effector, actin-related protein 2/3 (Arp2/3), at the protein level in the temporal lobe of IE patient brains to explore its possible role in the genesis of IE. Forty surgical samples from brains of patients with IE and 20 control brain tissues were obtained for this study. The expression of N-WASP in the anterior temporal neocortex was detected using immunohistochemistry, immunofluorescence and western blotting; Arp2/3 expression was detected by western blotting. Compared with controls, N-WASP expression in brains of IE patients was significantly higher; similarly, Arp2/3 level was markedly increased in the IE patient group. These results suggest that increased expression of N-WASP in the human brain may be associated with human IE.

TDAG51 (T cell death-associated gene 51) is an apoptosis-associated protein. Our aim was to investigate TDAG51 expression in the anterior temporal neocortex of patients with intractable epilepsy (IE), and then to discuss the possible role of TDAG51 in IE. Tissue samples from the anterior temporal neocortex of 33 patients who had surgery for IE were used to detect TDAG51 expression by immunohistochemistry, immunofluorescence, and Western blotting. We compared these tissues with nine histologically normal anterior temporal lobes from intracranial hypertension patients who had decompression procedures. TDAG51 was mainly expressed in the cytoplasm of neurons and glial cells. TDAG51 in IE was significantly higher than that in the controls. These findings were consistently observed using Western blotting, immunofluorescence, and immunohistochemistry techniques. TDAG51 in patients with IE was significantly higher when compared with levels in the controls. This finding suggests TDAG51 is consistent with a possible role of this gene in the evolution of the pathology in IE.

Heat Shock Protein BAP1 (heat shock 27-kDa-associated protein 1, HSPBAP1) inhibits the function of heat shock protein 27, which has a neuroprotective effect during experimentally induced epileptic neuropathology. In our study, fluorescence quantitative polymerase chain reaction, immunohistochemistry, immunofluorescence, western blot were used to test the levels of HSPBAP1 mRNA and protein in surgical samples of the anterior temporal neocortex of patients with intractable epilepsy (IE) and normal controls samples. HSPBAP1 mRNA was abnormally expressed in the anterior temporal neocortex of patients with IE. Moreover, HSPBAP1 was found extensively in the cytoplasm of neurons and glial cells in all epilepsy specimens. Western blot showed a clear immunoreactive band of HSPBAP1 in IE specimens whereas it was absent in control specimens. The expression of HSPBAP1 mRNA and protein in the anterior temporal neocortex from patients with IE may play a role in the development of epileptic seizures in patients with cell loss in this brain region. Additional studies will be required to elucidate the mechanism by which HSPBAP1 affects brain function in IE.

Objective: To investigate the expression of cell division cycle 42 GTP-binding protein (Cdc42) in the brain tissue of patients with intractable temporal epilepsy and discuss its effect on epileptogenesis., Methods: Twenty samples brain tissues were collected from the brain tissue bank of intractable temporal epilepsy established by Epilepsy Preventive and Therapeutic Center of Chongqing. The expression of Cdc42 was determined by immunohistochemistry and fluoroimmunoassay. Twenty brain tissue samples were collected from autopsy on 20 sex and age-matched persons who died from accident were used as controls., Results: The absorption values of Cdc42 in the temporal lobe of the patients was 0.038 +/- 0.016, significantly higher than that of the controls (0.020 +/- 0.005, t = 14.59, P < 0.01). The absorption values of Cdc42 in the hippocampus of the patients was 0.049 +/- 0.009, t = 12.01, P < 0.01). Fluoroimmunoassay showed that the fluorescence intensity of Cdc42 in the temporal lobe of the patients was 18.3 +/- 2.5, significantly higher than that of the controls (11.8 +/- 2.9, t = 33.77, P < 0.01), and the Fluorescence intensity of Cdc42 in the hippocampus of the patients was and control hippocampus were 23.8 +/- 3.3, significantly higher than that of the controls (10.1 +/- 2.6, t = 12.01, P < 0.01)., Conclusion: The overexpression of Cdc42 in the cortex of temporal lobe and hippocampus may play an important role in the epileptogenic mechanisms of intractable epilepsy.

Objective: To investigate the expression of PSD-93 mRNA and NR2B mRNA in the brain tissue from the patients with epilepsy so as to explore the possible mechanisms of the pathogenesis of the epilepsy., Methods: Fifty-six patients with epilepsy were divided into intractable epilepsy (IE) and non-intractable epilepsy (NIE) groups. cDNA microarrays prepared from the brain tissues obtained from these two groups were scanned and comparison to those from the non-epileptogenic control (C) was made. Expression level of PSD-93mRNA and NR2BmRNA were examined by reverse transcription polymerase chain reaction (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate each gene relative expression level., Results: The cDNA microarray analysis showed that the expression of PSD-93 mRNA related to the function of NMDAR-NO signal transduction pathway was significantly higher in epilepsy patients than those in the controlled group. The results of RT-PCR were consistent with those of the cDNA microarrays. The relative expression ratio of PSD-93 in patients with non-epileptogenic control, NIE, and IE was 0.159, 0.368, and 0.341, respectively. Correspondingly, that of NR2B was 0.198, 0.738, and 0.903, respectively. The expressions of PSD-93 and NR2B in the NIE and IE were significantly higher than those of control, respectively (P<0.05). However, there was no significantly difference the expression of PSD-93 between NIE and IE. (P>0.05), neither do that of NR2B (P>0.05)., Conclusions: The upregulated expressions of PSD-93 mRNA and NR2BmRNA may be involved in the pathogenesis of epilepsy.

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control., Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery., Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy., Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.

Purpose: To re-examine drug-resistant epilepsy cases using the revised 2011 ILAE classification of focal cortical dysplasia (FCD).Methods: Patients with drug-resistant epilepsy who have undergone epilepsy surgery in West China Hospital between July 2012 and Jun 2014 were included. Clinical histories, pathological diagnoses, and surgical outcomes were reviewed. A questionnaire was developed to investigate the clinical practice of the new classification. A short-term training program on FCD was carried out to improve pathological diagnosis accuracy.Results: 260 consecutive cases (177 male and 83 female) were included. Pathological diagnosis was changed in 70 cases (26.9%) after re-examination. The five most common pathological types were hippocampal sclerosis (19.2%, 50/260), brain tumors (17.7%, 46/260), vascular malformations (16.2%, 42/260), glial scars (11.2%, 29/260) and FCD (10.0%, 26/260). The most common subtype of isolated FCD was FCD IIb (53.8%, 14/26), followed by FCD IIa (42.3%, 11/26) and FCD Ib (3.8%, 1/26). In addition, forty-five cases were diagnosed as associated FCD type III (17.3%, 45/260). Half of patients with FCD achieved Engel class I at two-year follow-up. Questionnaire investigation suggested most participant pathologists lack sufficient knowledge on the new classification. The diagnostic sensitivity for different FCD subtypes was significantly improved by two to six folds after short-term training.Conclusions: FCD is an important etiology of drug-resistant epilepsy in western China. It is essential to provide continuing trainings to improve diagnostic precision of FCD in developing countries. [ABSTRACT FROM AUTHOR]