Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 âˆ¼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

Family cohesion and quality of life significantly affecting personality changes in adult epilepsy patients: a case-control study.

OBJECTIVE: The goal of epilepsy treatment is not only to control convulsive seizures but also to improve the quality of life of patients. This study aimed to investigate personality changes and the risk factors for their development in adult epilepsy patients. METHODS: A case-control study in a Class III, Class A hospital. The study comprised 206 adult epilepsy patients admitted to the Neurology Department at the First Hospital of Jilin University between October 2019 and December 2021, while the control group consisted of 154 community volunteers matched with the epilepsy group based on age, sex, and education. No additional treatment interventions were determined to be relevant in the context of this study. RESULTS: There is a significantly higher incidence of personality changes in epilepsy than in the general population, and patients with epilepsy were more likely to become psychoticism, neuroticism, and lie. Epilepsy patient's employment rate and average quality of life score were significantly lower than that of the general population and had strong family intimacy but poor adaptability in this study. There are many factors affecting personality change: sleep disorders, economic status, quality of life, use of anti-seizure drugs, family cohesion and adaptability. The independent risk factors were quality of life and family cohesion.

Effect of intranasal and oral administration of levetiracetam on the temporal and spatial distributions of SV2A in the KA-induced rat model of SE.

To investigate the effectiveness of nasal delivery of levetiracetam (LEV) on the distributions of synaptic vesicle protein 2 isoform A (SV2A) in epileptic rats with injection of kainic acid (KA) into amygdala. A total of 138 rats were randomly divided into four groups, including the Sham surgery group, the epilepsy group (EP), and the LEV oral administration (LPO) and nasal delivery (LND) groups. The rat intra-amygdala KA model of epilepsy was constructed. Pathological changes of rat brain tissue after status epilepticus (SE) were detected using haematoxylin and eosin staining. Expression of SV2A in rat hippocampus after SE was evaluated using the western blotting analysis. Expression and distribution of SV2A in rat hippocampus after SE were detected based on immunofluorescence staining. The EP group showed evident cell loss and tissue necrosis in the CA3 area of hippocampus, whereas the tissue damage in both LPO and LND groups was significantly reduced. Western blotting analysis showed that the expressions of SV2A in the hippocampus of both EP and LND groups were significantly decreased 1 week after SE, increased to the similar levels of the Sham group in 2 weeks, and continuously increased 4 weeks after SE to the level significantly higher than that of the Sham group. Results of immunofluorescence revealed largely the same expression patterns of SV2A in the CA3 area of hippocampus as those in the entire hippocampus. Our study revealed the same antiepileptic and neuronal protective effects by the nasal and oral administrations of LEV, without changing the expression level of SV2A.

Seizure characteristics, treatment, and outcome in autoimmune synaptic encephalitis: A long-term study.

OBJECTIVES: The objective of this study was to report seizure characteristics, long-term outcome, and potential factors associated with persistent seizures in patients with autoimmune synaptic encephalitis (ASE). METHOD: Clinical data and courses of 52 patients with ASE who presented with seizures at the Department of Neurology of the First Hospital of Jilin University from January 2015 to August 2017 were reviewed. Seizure outcomes were assessed with a median follow-up duration of 30 months (8-40 months). RESULTS: Most patients (71.2%) presented with seizure at initial consultation; focal to bilateral tonic-clonic seizures (50.0%) were the most common type. The temporal lobe (73.5%) was the prominent region of seizure origin, which was incident with hippocampal lesions on magnetic resonance imaging (MRI) in 62.1% of the patients. Status epilepticus, subclinical seizures, and nonepileptic events were observed in 28.9%, 36.8%, and 28.9% of the patients, respectively. Twenty-seven out of the 43 followed-up patients (62.8%) exhibited seizure remission after initial immunotherapy. Others (37.2%) developed persistent seizures to different extents. Six out of 9 patients experienced additional seizure freedom because of antiepileptic drugs (AEDs); however, the seizures of the other three patients, with serious conditions, showed poor response. Patients with anti-N-methyl-d-aspartate receptor antibodies had a lower risk of developing persistent seizures than those with anti-leucine-rich glioma-inactivated 1 (LGI1) or anti-γ-aminobutyric acid receptor type B receptor (GABABR) antibodies (P = 0.001). CONCLUSIONS: A complex of clinical and subclinical seizures, and nonepileptic events characterize ASE. Patients with anti-LGI1 or anti-GABABR antibodies have a higher risk of developing persistent seizures; AEDs are suitable for achieving additional seizure freedom, but not for patients with serious conditions. A few patients present with super-refractory epilepsy despite multiple treatments.

The c-Jun N-terminal kinase signaling pathway in epilepsy: activation, regulation, and therapeutics.

Epilepsy affects approximately 50-70 million people worldwide and 30-40% of patients do not benefit from medication. Therefore, it is necessary to identify novel targets for epileptic treatments. c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) family that activates diverse substrates, such as transcriptional factors, adaptor proteins, and signaling proteins, and has a wide variety of functions in both physiological and pathological conditions. The excessive activation of JNK is found not only in the acute phase of epilepsy, but also in the chronic phase, which potentiates it as a promising target in epilepsy control. In this review, we discuss the activation of the JNK pathway in epilepsy and its role in neuronal death, astrocyte activation, and mossy fiber sprouting (MFS) based on recent updates. Finally, we briefly introduce the current agents that target JNK signaling to control epilepsy.

Cognitive Impairment and Personality Traits in Epilepsy: Characterization and Risk Factor Analysis.

Cognitive impairment and personality disorders are severe comorbidities commonly observed in patients with epilepsy, and together they decrease the quality of patients' life. This study aimed to evaluate cognitive function and personality traits in patients with epilepsy with the Wechsler Adult Intelligence Scale-Chinese revised and Eysenck Personality Questionnaire and investigate the underlying influencing factors. Compared with the control group, our results showed that patients with epilepsy were presented with significant cognitive impairment and particular personality traits. Epileptic seizure-related factors including earlier age of onset, longer duration of epileptic history, and higher seizure frequency were significantly associated with the observed defects in cognition and personality traits. In addition, the temporal lobe was more likely to affect cognition and personality, and the left hemisphere was closely related to verbal intelligence quotient, which needs to be the focus of future research. These results will be instrumental for guiding the treatment of epilepsy.

A rare case of Primary Central Nervous System Lymphoma initially diagnosed as demyelinating encephalopathy.

We report a case of histopathologically-confirmed primary central nervous system lymphoma who was initially diagnosed as demyelinating encephalopathy. A 58-year-old woman was admitted with confusion and left hemiparesis. Head MR showed abnormal flaky hypointense T1 and hyperintense T2 signals at right thalamus, splenium of corpus callosum, bilateral cerebral peduncle, pons, medulla oblongata, basal ganglia and right corona radiata. Her mental status improved a little and she was discharged from hospital after neuroprotective treatment. 10 days after her discharge, her confusion appeared again with hallucination and unsteady walking. Pathological examination revealed non-Hodgkin's lymphoma (WHO classification: DLBCL). The patient continued to deteriorate after the surgery and died 10 days later.

[Effect of exogenous calcium on seed germination and seedling physiological characteristics of Lycium ruthenium].

OBJECTIVE: In order to get the method for improving the salt resistance of Lycium ruthenium seeds and seedlings under NaCl stress, the seed germination and physiological characteristics of L. ruthenium seedlings was studied. METHOD: Several physiological indexes of L. ruthenium seeds under NaCl stress, such as the germination rate (Gr), germination vigor (Gv), germination index (Gi), vigor index (Vi), and relative salt damage rate were measured. Other indexes of the seedlings like relative water contents (RWC) , chlorophyll contents, soluble protein contents, electrolyte leakage, the contents of malondialdehyde (MDA), and peroxidase (POD) were also measured. RESULT: NaCl at lower concentration could promote the seed germination but inhibit the seed germination at higher concentration. After the treatment by CaCl2 at the different concentrations, all germination indexes were increased. With the increase of salt concentration, the relative water contents and the contents of chlorophyll were decreased, the content of MDA and electrolyte leakage were increased. The change trend of POD activity showed the first increase and then decrease with the increase of salt concentration, which was similar to that of the soluble protein. After the treatment by CaCl2, relative water contents, chlorophyll and POD activities were decreased more slowly, and also electrolyte leakage and MDA contents increased slowly. CONCLUSION: The CaCl2 could significantly alleviate the damages to the seeds and seedlings of L. ruthenium under NaCl stress, and promote the salt resistance to the seeds and seedlings of L. ruthenium.

[Retracted] Effects of Grb2­associated binding protein 2­specific siRNA on the migration and invasion of MG­63 osteosarcoma cells.

[This retracts the article DOI: 10.3892/ol.2017.7375.].

Exploring causal correlations between systemic inflammatory cytokines and epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Inflammation plays a role in the development and advancement of epilepsy, but the relationship between inflammatory cytokines and epilepsy is still not well understood. Herein, we use two-sample Mendelian randomization (MR) to examine the causal association between systemic inflammatory cytokines and epilepsy. METHODS: We conducted a bidirectional two-sample MR analysis based on genome-wide association study data of 41 serum cytokines from 8293 Finnish individuals with various epilepsy subtypes from the International League against Epilepsy Consortium. RESULTS: Our study showed that three inflammatory cytokines were associated with epilepsy, five were associated with generalized epilepsy, four were associated with focal epilepsy, one was associated with focal epilepsy-documented lesion negative, three were associated with juvenile absence epilepsy, one was associated with childhood absence epilepsy, two were associated with focal epilepsy-documented lesion other than hippocampal sclerosis, and two were associated with juvenile myoclonic epilepsy. Furthermore, the expression of systemic inflammatory cytokines was unaffected by genetically predicted epilepsy. CONCLUSION: This study suggested that several inflammatory cytokines are probably the factors correlated with epilepsy. Additional research is required to ascertain if these biomarkers have therapeutic potential to prevent or manage epilepsy.

Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis.

Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.

Cognitive correlates of interictal epileptiform discharges in adult patients with epilepsy in China.

OBJECTIVE: Learning difficulties or cognitive impairment has been observed in many patients with epilepsy. Evidence from neurophysiologic and functional neuroimaging suggests that epileptic seizures and/or epileptiform activity can be the dominant factors inhibiting specific brain areas. However, most previous studies were focused on cognitive performance in children. In this study, we analyzed a new cohort of adult patients with frequent interictal epileptiform discharges (IEDs). METHODS: Data from 67 adult patients with epilepsy were reviewed. Electroencephalography (EEG)-video recording and cognitive testing were performed, and the IED index was estimated as a percentage assigned to one of four categories (<1%, 1-10%, 10-50%, and >50%) during either wakefulness or sleep. Correlations of cognitive test results and clinical characteristics of IED categories were analyzed. The effects of the frequency, duration, location, and sleep-wake cycles of IEDs on cognition (intelligence and memory capacity) were analyzed. RESULTS: Patients with an IED index >10% showed impaired performance on the Chinese Wechsler Adult Intelligence Scale (WAIS-RC) and the Chinese Wechsler Memory Scale (WMS). This effect was detected independently from other IED frequencies and other IED-related variables, such as duration, distribution, and location. The impact of waking or sleeping IEDs was of equal importance in contributing to impaired WAIS-RC and WMS performance. CONCLUSION: An IED frequency of more than 10% in both waking and sleeping EEGs is associated with impaired cognitive performance in adult patients. However, whether patients with a high IED frequency but low seizure frequency will benefit from antiepileptic treatment should be examined in future studies.

A case report of overlapping Bickerstaff brainstem encephalitis and Guillain-Barre syndrome.

We report a case of a 23-year-old man diagnosed with overlapping Bickerstaff brainstem encephalitis (BBE) and Guillain-Barre syndrome (GBS). The patient initially presented with fever and headache and gradually developed ataxia, disturbance of consciousness, respiratory muscle paralysis, bilateral facial paralysis and quadriplegia accompanied by significant atrophy of limb, temporalis and masseter muscles. Brain MRI revealed abnormality in the left basal ganglia, thalamus, and rightside posterior limb of the internal capsule. Electromyogram indicated neurogenic damage (mainly axonal damage) in the upper and lower limbs and bilateral facial nerve damage. Cerebrospinal fluid (CSF) collected via lumbar puncture was colorless and transparent with a pressure of 330 mm H2O. The white blood cell count in CSF was 200×106/L, the protein concentration was 1.25 g/L, and Pandy's reaction was positive. Both the blood and CSF were negative for GQ1b antibody. The patient was clinically diagnosed with overlapping BBE and GBS. After treatment with ventilator assisted breathing, hormone therapy, neurotrophic and anti-infection therapies, and symptomatic and supportive care for more than three months, spontaneous breathing was restored. By the 5-month follow-up examination, the patient had completely recovered and returned to work. Like GBS and Fisher syndrome, BBE might be an anti-GQlb IgG antibody syndrome. Although the serum GQlb IgG antibody-positive rate for BBE is only 66%, a normal brainstem MRI or GQlb lgG antibody-negative finding cannot completely rule out BBE. Therefore, identifying critical illness polyneuropathy for patients with respiratory muscle paralysis and tracheal extubation difficulties at early stages is clinically important.

Association between epileptiform discharges and the sleep cycle in 200 epileptic patients.

OBJECTIVE: The poor sleep quality of epileptic patients may be partly due to the occurrence epileptiform discharges (EDs). We observed the number of interictal discharges in each sleep stage and explored the associations between EDs and sleep phases in epileptic patients. METHODS: Two hundred epileptic patients and 182 healthy volunteers were enrolled in the current study. For all subjects, video electroencephalography (EEG) monitoring and 24-hr night polysomnography were conducted to detect EDs and analyze the sleep structures. RESULTS: EDs were detected in 91% of epileptic patients with the most frequent cases from the temporal lobe. The EDs detected during waking, sleeping, or both waking and nonrapid eye movement (NREM) sleep stages 1-2 accounted for 7.1%, 19.2%, and 25.3% of the total patients, respectively. EDs were rare during NREM stages 3-4 with 1.1% of total patients mainly in the central-temporal lobe. The total sleep time and time spent in REM were similar between the epileptic patients and healthy volunteers. However, epileptic patients spent a significantly longer mean sleep time in NREM stages 1-2 (293.91 ± 27.57 min vs. 223.17 ±15.28; p = .000) and less in NREM stages 3-4 (50.11 ± 12.12 min vs. 133.96 ± 10.77; p = .000) than healthy volunteers. Furthermore, asymmetric sleep spindles and fragmentary sleep structure as well as high inversion frequency were found in 26.7% and 43.3% of epileptic patients, respectively. CONCLUSION: Combination of long-term video EEG with polysomnography is a useful method to analyze associations between EDs and the sleep-wake cycle. This strategy can also help identify the nature of sleep disorders in epileptic patients, which may improve the treatment efficacy.

Adult-onset leukoencephalopathy with brain stem and spinal cord involvement in Chinese Han population: a case report and literature review.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with an autosomal recessive mode of inheritance. We report a case of rare adult-onset LBSL with typical magnetic resonance imaging (MRI) features. The DARS2 gene mutation analysis has identified a c. 228-20_21delTTinsC (p.R76SfsX5) mutation and a c. 850G > A (p. 284E > K) mutation. With glucocorticosteroid treatment the patient has had improvement in bladder symptoms. This is the first reported adult-onset LBSL case in the Chinese Han population. A review of the literature suggests that brain lactate elevation in adult-onset LBSL is lower than early-onset cases (P < 0.01), and early-onset cases show mild intelligence and cognition decline. These observations suggest that age of onset and brain lactate levels probably influence the prognosis of LBSL.

A Chinese patient with POLR3A-related leukodystrophy: a case report and literature review.

Background: Leukodystrophies are hereditary white matter diseases characterized by genetic polymorphisms and considerable phenotypic variability. They can be classified into myelin and non-myelin malformations. These diseases are rare, affecting 1 out of 250,000-500,000 individuals and can manifest at any age. A subtype of leukodystrophy, associated with missense mutations in the RNA polymerase subunit III (POLR3A) gene, is inherited in an autosomal recessive manner. Case report: We report and analyse a case of a 34-year-old female who presented with ataxia. Magnetic Resonance Imaging (MRI) of the brain revealed demyelinating lesions in the white matter. Genetic testing identified the c.4044C > G and c.1186-2A > G variants in the POLR3A gene. The patient was diagnosed with hypomyelinating leukodystrophy type 7 and received neurotrophic and symptomatic supportive therapy. However, after 1 month of follow-up, there was no improvement in her symptoms. Conclusion: POLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Currently, no cure is available for this condition, and treatment is limited to managing symptoms. Further research into new treatment methods for POLR3A-induced leukodystrophy is imperative to improve the quality of life and potentially extend the life expectancy of patients.

The pathogenesis of blepharospasm.

Blepharospasm is a focal dystonia characterized by involuntary tetanic contractions of the orbicularis oculi muscle, which can lead to functional blindness and loss of independent living ability in severe cases. It usually occurs in adults, with a higher incidence rate in women than in men. The etiology and pathogenesis of this disease have not been elucidated to date, but it is traditionally believed to be related to the basal ganglia. Studies have also shown that this is related to the decreased activity of inhibitory neurons in the cerebral cortex caused by environmental factors and genetic predisposition. Increasingly, studies have focused on the imbalance in the regulation of neurotransmitters, including dopamine, serotonin, and acetylcholine, in blepharospasm. The onset of the disease is insidious, and the misdiagnosis rate is high based on history and clinical manifestations. This article reviews the etiology, epidemiological features, and pathogenesis of blepharospasm, to improve understanding of the disease by neurologists and ophthalmologists.

Inflammatory cytokines and stroke and its subtypes: a genetic correlation and two-sample Mendelian randomization study.

Introduction: The causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR). Methods: We performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses. Results: The study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99, p = 0.014), higher interleukin (IL)-1ß, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01-1.18, p = 0.027; OR = 1.08, 95% CI: 1.02-1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87-0.98, p = 0.006; OR = 0.95, 95% CI: 0.91-1.00, p = 0.031), higher levels of IL-1ß, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00-1.19, p = 0.042; OR = 1.07, 95% CI: 1.01-1.15, p = 0.035; OR = 1.06, 95% CI: 1.00-1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28-0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors. Conclusion: In summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition.