Microglial TRPV1 in epilepsy:Is it druggable for new antiepileptic treatment?

Epilepsy is one of the most common neurological diseases worldwide with a high prevalence and unknown pathogenesis.Further,its control is challenging.It is generally accepted that an imbalance between the excitatory and inhibitory properties of the central nervous system(CNS)leads to a large number of abnormally synchronized neuronal discharges in the brain.Transient receptor potential vanilloid protein type 1(TRPV1)is a non-selective cation channel that contributes to the regulation of the nervous system and influences the excitability of the nervous system.This includes the release of neurotransmitters,action potential generation due to alterations in ion channels,synaptic transmission,and the changes in glial cells.There is abundant evidence that TRPV1 is widely expressed in the central nervous system(including microglia)and is involved in the development of epilepsy through neuroinflammation.In conclusion,microglial TRPV1 participates in neuroinflammatory reactions and functions as a potential proinflammatory mediator.This presents a novel treatment approach to regulate seizures brought on by neuroinflammation.

New Progress in the Treatment of Myasthenia Gravis

In recent decades, the treatment of myasthenia gravis has been extensively developed, but a standardized standard still needs to be used. Its treatment strategy is associated with patient prognosis, economic costs, and complications. This article reviews the pathogenesis, treatment methods, and complications of myasthenia gravis, providing new ideas for diagnosing and treating myasthenia gravis and fully embodies the principle of safety and precision.

Analysis of Risk Factors Associated with Cognitive Dysfunction in Patients with Atrial Fibrillation

Objective: To discuss the risk factors of cognitive dysfunction in patients with atrial fibrillation. Methods: The 150 cases of patients with atrial fibrillation were analyzed in the first affiliated hospital of Nanchang University who were treated in the cardiovascular department, general medicine department and gerontology department from August 2018 to June 2019. We used Mini-Mental State Examination (MMSE) score to evaluate cognitive function of patients with atrial fibrillation. According to the level of education and MMSE score, patients with atrial fibrillation were divided into three groups: normal cognitive function group, mild cognitive impairment group (MCI) and dementia group. And then the demographic data, the previous use of taking drugs, the results of ultrasonic cardiogram (UCG) and laboratory test were analyzed. Results: 1) The basic situation of research object: a total of 150 patients with atrial fibrillation were enrolled in the study, and the average age of these patients was 65.05 ± 8.74 years old, which included 78 males (52%) and 72 females (48%). The mean MMSE score was 23.42 ± 4.65. According to MMSE score, 86 cases (57.3%) of cognitive dysfunction occurred in 150 patients with atrial fibrillation, which included 41 cases (27.3%) of mild cognitive impairment and 45 cases (30%) of dementia. 2) The comparison of general clinical data: there were significant differences in age, smoking, level of education, left ventricular ejection fraction, left atrial diameter, D-dimer, fibrinogen, homocysteine, platelet and previous use of taking warfarin, dabigatran, CCB, statins among the three groups (P < 0.05). 3) The linear correlational analysis between risk factors of cognitive function and MMSE score in patients with atrial fibrillation: there was a positive correlation between left ventricular ejection fraction and MMSE score, but age, left atrial diameter, homocysteine, low density lipoprotein, platelet, BMI, NT-proBNP, D-dimer were negatively correlated with MMSE score. 4) The risk factors with statistical significance in ANOVA were analyzed by ordinal and multinomial logistic regression, which showed that age (OR = 1.174, 95% CI: 0.091 - 0.231), the level of education (illiteracy OR = 4.162, 95% CI: -0.032 - 2.955, primary school OR = 2.751, 95% CI: -0.172 - 2.197, junior high school OR = 3.539, 95% CI: -0.048 - 2.577, senior high school and special secondary school OR = 1.332, 95% CI: -1.080 - 1.655), no CCB (OR = 1.174, 95% CI: 0.091 - 0.231), no warfarin (OR = 13.749, 95% CI: 1.480 - 3.762), no dabigatran (OR = 16.395, 95% CI: 1.462 - 4.131), D-dimer (OR = 2.745, 95% CI: -0.611 - 2.631), fibrinogen (OR = 3.228, 95% CI: 0.399 - 1.946) were related to the high occurrence of cognitive dysfunction. Conclusions: 1) Patients with atrial fibrillation had a higher risk of cognitive dysfunction (the incidence of 57.4%). 2) There was a positive correlation between left ventricular ejection fraction and MMSE score, but age, left atrial diameter, homocysteine, low density lipoprotein, platelet, BMI, NT-proBNP, and D-dimer were negatively correlated with MMSE score. 3) High level of education, previous use of taking warfarin and dabigatran etexilate were protective factors for cognitive function in patients with atrial fibrillation;but age, previous use of taking CCB, D-dimer and fibrinogen were the risk factors in patients with atrial fibrillation.

Progress of Autophagy in Epilepsy Research

Epilepsy is a clinical syndrome caused by highly synchronized abnormal discharges of neurons in the brain. It is a common disease of the nervous system. The pathogenesis of epilepsy has not been fully understood yet. The main pathological changes after seizures are programmed neuronal death and glial proliferation. Autophagy is a catabolic process. Moderate autophagy is critical to maintain the homeostasis and cell health, while abnormal autophagy can lead to disease. A number of studies have proved that abnormal autophagy mechanism can lead to epilepsy, and there are also literatures that autophagy induced by endoplasmic reticulum stress can reduce the neuronal damage triggered by epilepsy, thus playing a protective role in neurons. This article reviews the relationship between autophagy and epilepsy in order to provide basis for further study of autophagy pathway and pathophysiology of epilepsy.

Study on MiRNA Epigenetic Intervention for Epilepsy

MiRNAs are a family of small non-coding RNAs that control levels of multiple proteins by post-transcriptionally decreasing messenger RNA stability and translation. MiRNA is a part of the epigenetic machinery. In addition to post-transcriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of epilepsy. However, miRNA not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene. There is a strong connection between epigenetic and MiRNA, and any dysregulation of this complex system can result in various physiological and pathological conditions. Currently, there is an unmet need for antiepileptic drugs that truly prevent the development of epilepsy in high-risk populations. New findings in animal models and human brain tissue suggest that microRNAs play a crucial role in epileptogenesis and the pathophysiology of chronic epilepsy. Objectives: This paper focuses on the epigenetic role of miRNA in the development of epilepsy and potential targets for drug therapy. Methods: In this paper, through the keywords epilepsy, epigenetic, methylation, miRNA, non-coding RNA search in PubMed, SPIS, GeenMedical, Google Scholar and Web of Science, to study the potential application of miRNA epigenetic regulation in the treatment of epilepsy. Results: Future treatments that manipulate miRNA epigenetic processes, such as Anti-oligonucleotides, DNA methylation and Nucleic Acid Aptamers, to treat or prevent epilepsy. Conclusion: Overall, miRNA epigenetic drugs have become a new frontier target to achieve a cure for epilepsy.

The Analysis of the Treatment of Rhabdomyolysis by Snake Bites

Objective: To explore the treatment measure of rhabdomyolysis caused by snake bites, and provide guidance for further prevention and control of snake bites. Methods: To retrospectively analyze the 841 cases of serpentine bites in our hospital from January 2006 to July 2017;127 cases of patients with rhabdomyolysis syndrome were screened out, and their clinical manifestations, laboratory results, related treatment and prognosis were analyzed. Results: 127 cases patients were rhabdomyolysis out of 841 cases, 28 cases patients developed acute renal failure;treatment measures included local wound treatment, application of tetanus antitoxin, anti-snake venom serum, anti-infection, fluid “hydration” and diuretic, alkaline urine and hybrid renal replacement therapy. 112 cases were cured, improved conditions in 9 cases, 3 cases of death, 3 cases uncured. The improvement rate of is 95.26% after treatment. Conclusion: The rhabdomyolysis had a high incidence in snake bite patients, severe cases often developed acute renal failure. Serum myopsin and related biochemical blood tests could be used to diagnose rhabdomyolysis quickly. Combined treatment methods are the main measure to increase the cured rate and decrease the death rate.

The Influence of Gastrodin on Expression of IL-10, STAT3 and JAK2 in Epileptic Rats’ Hippocampus

Objective: To explore the influence of gastrodin on IL-10, JAK2 and STAT3 in hippocampus of epileptic rats induced by pentylenetetrazol and the role of the IL-10 pathway in epilepsy. Methods: 50 adult male Wistar rats were randomly divided into 5 groups: normal control group (NC Group), epilepsy model group (EP Group), low doses of gastrodin + EP Group (GE1 Group), medium doses of gastrodin + EP Group (GE2 Group), high doses of gastrodin + EP Group (GE3 Group). EP group and GE Groups were injected subthreshold doses of pentylenetetrazole (PTZ) by intraperitoneal once a day until reaching the ignited standards. GE groups were respectively injected 4, 6, 8 mg/kg gastrodin by intraperitoneal. All groups were administered for 28 consecutive days. The behavioral changes of the rats were observed and recorded daily 1 hour after the injection. mRNAs of IL-10, STAT3 and JAK2 in hippocampus were measured by RT-qPCR, and proteins by Western blot. Results: Compared GE2 group with EP group, the incubation of seizure was significantly prolonged (P Conclusions: Gastrodin can increase the expression of IL-10, and reduce the expression of STAT3 and JAK2, which may play an antiepileptic effect through regulating JAK2/STAT3 signaling pathways by IL-10.

Analysis of the Q-T Dispersion and T Wave Alternans in Patients with Epilepsy

Objectives: There is a high rate of sudden death in epilepsy patients, part of which is sudden cardiac death. By investigating ECG T wave alternans and Q-T dispersion changes of epilepsy patients, we may predict the possibility of the occurrence of sudden death and provide basis for clinical prevention. Methods: Selecting 587 cases of epilepsy patients as the study group, 672 same period cases of healthy persons as the control group;Analyzing the effect of epilepsy on ECG T wave alternans and Q-T dispersion with the standard 12 lead ECG. Results: The study group had a significantly prolonged Q-T dispersion and an increased incidence of T wave alternans than that of the control group;Compared with other seizure types, tonic clonic seizure and absence seizure had a significantly prolonged Q-T dispersion and an increased occurrence rate of T wave alternans. Conclusions: Epilepsy patients ECG T wave alternans and Q-T dispersion has higher abnormal rate, and are prone to sudden cardiac death;Routine ECG(RECG) T wave alternans and Q-T dispersion changes can provide guidance for clinical prevention of sudden unexpected death in epilepsy (SUDEP).

Tolosa Hunt Syndrome: Current Diagnostic Challenges and Treatment

Tolosa-Hunt syndrome (THS) is an uncommon diagnosis with an incidence of nearly 1 to 2 cases per million hallmarked by the presence of painful ophthalmoplegia (PO) due to a granulomatous inflammation (GI). Diagnostically, the major THS challenges encountered are owing to the exclusion of other GI presenting conditions necessitating multi-specialization consultations. This article presents uniquely advances in diagnosis and challenges encountered attempting to exclude THS mimics, details on physical examination and laboratory investigations have been incorporated. Tolosa Hunt MRI protocol (contrast-enhanced MRI), restricted diffusion and CISS MRI have lately proved to be precise investigations for THS diagnosis and follow up, on the contrary, number of false-negative/positive MRI diagnoses appears to be rising, hence proposed that MRI or biopsy shouldn’t be mandatory criteria for diagnosis as opposed to IHS 2018 guidelines. Despite corticosteroids being the cornerstone therapy for THS, there are controversies concerning the better administration route, optimal dosage, and therapy longevity, through case reports, high dose IV mPSL of 500 mg BID for 3 days, followed with maintenance dose of prednisone 60 mg resulted in the earliest recovery, hereafter standardized guidelines are required. Alternatively, infliximab (300 mg infusion), azathioprine, methotrexate, and acupuncture can be used, farther studies are required to appraise the effectiveness and their safety. On the other side, microsurgery can be utilized for GI evacuation however associated risks of permanent CN VI palsy have been stated, nonetheless, GKRS can be employed when contraindication or corticosteroid intolerability exists though the hazard of late malignancy is a drawback.

Application of T-Wave Alternans in Evaluation of Prognosis in Patients with Intracerebral Hemorrhage

Objective: To explore the application value of electrocardiograph (ECG) T-wave Alternans (TWA) anomaly in acute stage of intracerebral hemorrhage patients. Methods: We choose 1175 intracerebral hemorrhage patients whose conventional 12-lead ECG has TWA in our hospital from January 2011 to December 2015, 751 patients without TWA in the same period as the control group, compared the volume of intracerebral hemorrhage, bleeding site and mortality between the 2 groups. Results: In TWA group, 247 cases died, 361 cases with massive intracerebral hemorrhage, 298 cases with brain stem hemorrhage;in TWA negative group (control group), 41 cases died, 93 cases with massive brain hemorrhage, 64 cases with brain stem hemorrhage. There are statistical differences between two groups (P Conclusion: The occurrence of TWA is significantly related to the volume of bleeding, the bleeding site and mortality, and can be used as an important parameter in the prognosis of intracerebral hemorrhage.

Analysis of Etiology and Clinical Characteristics of 1170 Patients with Symptomatic Epilepsy in Jianghan Plain

Objective: The etiology, clinical manifestations and treatment of 1170 patients with symptomatic epilepsy were retrospectively analyzed and provided guidance for further treatment of symptomatic epilepsy. Method: A retrospective analysis of 1170 cases of symptomatic epilepsy admitted to the First Affiliated Hospital of Yangtze University from January 2013 to June 2018 was conducted to analyze the etiology, clinical manifestations and treatment of different age groups. Results: Symptomatic epilepsy is high in the elderly, and men are more than women. Among the 1170 patients with symptomatic epilepsy, there were 81 (6.9%) cases of brain injury, 721 (61.6%) cases of cerebrovascular disease, 223 (19.0%) cases of tumor, 59 (5.0%) cases of central nervous system infection, 33 (2.8%) cases of immune metabolic disease, 11 (0.9%) cases of drugs, 6 (0.5%) cases of cortical dysplasia, 6 (0.5%) cases of neurodegenerative disease, 4 (0.3%) cases of parasites, 4 (0.3%) cases of poisons, and 22 (1.9%) cases of other diseases. Among them, central nervous system infection and cerebrovascular disease ranked first among the patients aged 0 - 18 years, followed by immune metabolic diseases;cerebrovascular disease ranked first among the patients aged 19 - 39 years, followed by tumors and brain trauma;cerebrovascular disease ranked first among the patients aged 40 - 65 years, followed by tumors and brain trauma;cerebrovascular disease ranked first among the patients aged over 65 years, followed by tumors, among the types of seizures, 74 (6.3%) cases of tonic seizures, 68 (5.8%) cases of clonic seizures, 856 (73.2%) cases of tonic-clonic seizures, 27 (2.3%) cases of myoclonic seizures, 12 (1.0%) cases of absence seizures, 116 (9.9%) cases of complicated partial seizures, and 17 (1.5%) cases of partial seizures, in addition to the etiology, 795 (67.9%) cases of sodium valproate, 152 (13.0%) cases of carbamazepine, 56 (4.8%) cases of topiramate, 117 (10.0%) cases of levetiracetam, 23 (2.0%) cases of lamotrigine, and 27 (2.3%) cases of others were taken. Conclusion: In symptomatic epilepsy, different age groups have different causes. Among them, cerebrovascular disease, central nervous system infection, brain trauma, and brain tumor are the main causes. The most common type of seizures is the occurrence of tonic-clonic seizures. The most common drugs are sodium valproate and carbamazepine.