Frequency and Focus of in Vitro Studies of Microglia-Expressed Cytokines in Response to Viral Infection: A Systematic Review.

It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1ß. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted.

Association of variants in the ABCB1, CYP2C19 and CYP2C9 genes for Juvenile Myoclonic Epilepsy.

Juvenile myoclonic epilepsy (JME) is the most common of the generalized genetic epilepsies, with multiple causal and susceptibility genes; however, its etiopathogenesis is mainly unknown. The toxic effects caused by xenobiotics in cells occur during their metabolic transformation, mainly by enzymes belonging to cytochrome P450. The elimination of these compounds by transporters of the ABC type protects the central nervous system, but their accumulation causes neuronal damage, resulting in neurological diseases. The present study has sought the association between single nucleotide genetic variants of the CYP2C9, CYP2C19, and ABCB1 genes and the development of JME in patients compared to healthy controls. The CC1236 and GG2677 genotypes of ABCB1 in women; allele G 2677, genotypes GG 2677 and CC 3435 in men; the CYP2C19*2A allele, and the CYP2C19*3G/A genotype in both sexes were found to be risk factors for JME. Furthermore, carriers of the TTGGCC genotype combination of the ABCB1 gene (1236/2677/3435) have a 10.5 times higher risk of developing JME than non-carriers. Using the STRING database, we found an interaction between the proteins encoded by these genes and other possible proteins. These findings indicate that the CYP450 system and ABC transporters could interact with other genes in the JME.

Low quality of life, increased number of anti-seizure drugs, and the lack of caregiver support are associated with internalized stigma in adult Mexican patients with epilepsy.

BACKGROUND: People with epilepsy (PWE) have been subject to stigma throughout history, a factor that could compromise their performance in daily life. In Mexico, little is known about the factors that may be affecting internalized stigma. OBJECTIVE: To evaluate the internalized stigma in adult PWE, its relationship with the quality of life, cognitive and depressive symptomatology, and clinical-demographic characteristics. MATERIAL AND METHODS: We conducted a cross-sectional study with a consecutive sampling approach in patients with epilepsy treated at the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez (NINNMVS). Sociodemographic and clinical data, depressive symptomatology (Beck's depression inventory, DBI), cognition (MoCA test), quality of life (QOLIE-31 scale), and internalized stigma (King's internalized stigma scale, ISS) were evaluated. Correlations were made between the continuous variables and the ISS to select those with statistical significance and include them in a multiple linear regression model, along with the dummy variables, to explain internalized stigma. RESULTS: Of 128 patients, 74 (58%) were women; 38% of the patients had more than 20 years of epilepsy evolution. In addition, 39% presented depressive symptoms, and around 60% manifested a possible cognitive impairment. The variables that showed statistical significance concerning the ISS were selected along with dummy variables for multiple linear regression analysis. The resultant model considers the QOLIE-31 total score (ß = -0.489), the number of anti-seizure drugs (ASD, ß = 0.253), and those patients without caregiver support (ß = -0.166) with an adjusted R2 value of 0.316. CONCLUSIONS: A diminishing quality of life, an increased number of ASD, and patients without caregiver support influence a slight to moderate variation of internalized stigma in Mexican PWE. Therefore, it is necessary to continue studying other possible factors that influence internalized stigma to generate effective strategies to reduce its negative effects on PWE.

An international consortium in epilepsy surgery education: Clinical case-based discussions between Latin-American and Canadian Epilepsy Centers.

An international consortium with a focus on Epilepsy Surgery Education was established with members from different centers in Latin America and Canada. All members of the consortium and attendees from different centers in Latin America and Canada have been meeting to discuss epilepsy surgery cases in a virtual manner. We surveyed all to assess the value of the meetings. The results and description of these meetings are being presented.

Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy.

BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case-control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick. RESULTS: A variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic-clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia. CONCLUSIONS: Our data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.).

Increased non-attendance at epilepsy clinic in patients with neuropsychiatric comorbidities: A prospective study.

BACKGROUND: In patients with epilepsy, regular follow-up is vital for adequate seizure control, antiseizure drugs' (ASDs) side effects, psychiatric comorbidities, and planning for epilepsy surgery. Non-attendance creates barriers to adequate patient care, inefficient allocation of resources, loss of income, and unnecessary emergency department visits due to lack of seizure control. This study aimed to determine the causes and sociodemographic characteristics of the non-attendant population at the Epilepsy Clinic. METHODS: A prospective and observational study was carried out on patients treated at the Epilepsy Clinic of the National Institute of Neurology and Neurosurgery (NINN) in Mexico from August 2015 to June 2016. A phone interview was made with all those patients who did not attend the epilepsy consultation. This call incorporated ad hoc questions to meet the objectives of this study. RESULTS: During the study period, 1299 patients had an appointment at the epilepsy clinic, where 233 (17.9%) patients missed their consultation, 123 (52.8%) were male, mean age was 35.9 ±â€¯14.42 years. The most frequent cause of non-attendance was forgetfulness of the appointment in 62 patients (26.6%). Two patients died; no patient was reported to have experienced SUDEP. Non-attendant patients showed statistically significant overall prevalence of psychiatric comorbidities (41.6%), particularly depression, anxiety, and interictal psychosis. CONCLUSION: Information on non-attendance at various specialist consultations is scarce, and to our knowledge, this is the first study to address non-attendance in patients with epilepsy in Latin America. Improving hospital protocols to reduce non-attendance can increase patient adherence to follow-up, ultimately improving the quality of care in the epilepsy clinic.

Electroencephalographic findings in asymptomatic relatives of patients with juvenile myoclonic epilepsy: relationship with the degree of kinship.

INTRODUCTION: A prevalence of 1 to 71% of electroencephalogram (EEG) abnormalities has been reported in asymptomatic relatives of patients with juvenile myoclonic epilepsy (JME). OBJECTIVE: To determine the frequency of EEG abnormalities in asymptomatic relatives of patients with JME according to the degree of kinship. METHODS: Prospective, analytical study. First-, second, and third-degree relatives of patients with JME who agreed to participate and signed informed consent were included. The analysis was descriptive, bivariate. RESULTS: 209 asymptomatic relatives were included, out of which 115 (55%) were females and 94 (45%) were males, with a mean age of 35.9 ± 16.9 (range between 6 and 73 years). Forty-four (21.1%) relatives had abnormal EEGs. First-degree relatives (12%) had abnormalities more frequently in comparison with second- and third-degree relatives (p = 0.007). CONCLUSIONS: EEG abnormalities were observed in one third of asymptomatic relatives. It is important to highlight that there were more alterations among first-degree relatives. In the future, these findings might enable for the risk of clinically developing the disease to be estimated and for genetic counseling to be provided.

INTRODUCCIÓN: Se ha reportado de 1 a 71 % de prevalencia de anormalidades en el electroencefalograma (EEG) de familiares asintomáticos de pacientes con epilepsia mioclónica juvenil (EMJ). OBJETIVO: Determinar la frecuencia de anormalidades en el EEG en familiares asintomáticos de pacientes con EMJ de acuerdo con el grado de parentesco. MÉTODOS: Estudio prospectivo y analítico. Se incluyeron familiares de primer, segundo y tercer grado de pacientes con EMJ, quienes aceptaron participar y firmaron el consentimiento informado. El análisis fue descriptivo bivariado. RESULTADOS: Se incluyeron 209 familiares asintomáticos, 115 (55 %) mujeres y 94 (45 %) hombres, con edad media de 35.9 ± 16.9 (rango entre seis y 73 años); 44 familiares (21.1 %) tuvieron EEG anormal. Los familiares de primer grado (12 %) cursaron con mayor frecuencia con anormalidades en comparación con los de segundo y tercer grado (p = 0.007). CONCLUSIONES: Se observaron anormalidades en el EEG de una tercera parte de los familiares asintomáticos. Es importante resaltar que existieron más alteraciones entre los familiares de primer grado. En un futuro, estos hallazgos permitirán estimar el riesgo de desarrollar la enfermedad clínicamente y brindar consejo genético.

Influence of genetic variants and antiepileptic drug co-treatment on lamotrigine plasma concentration in Mexican Mestizo patients with epilepsy.

Genetic and nongenetic factors may contribute to lamotrigine (LTG) plasma concentration variability among patients. We simultaneously investigated the association of UGT1A1, UGT1A4, UGT2B7, ABCB1, ABCG2, and SLC22A1 variants, as well as antiepileptic drug co-treatment, on LTG plasma concentration in 97 Mexican Mestizo (MM) patients with epilepsy. UGT1A4*1b was associated with lower LTG dose-corrected concentrations. Patients with the UGT2B7-161T allele were treated with 21.22% higher LTG daily dose than those with CC genotype. Two novel UGT1A4 variants (c.526A>T; p.Thr185= and c.496T>C; p.Ser166Leu) were identified in one patient. Patients treated with LTG + valproic acid (VPA) showed higher LTG plasma concentration than patients did on LTG monotherapy or LTG + inducer. Despite the numerous drug-metabolizing enzymes and transporter genetic variants analyzed, our results revealed that co-treatment with VPA was the most significant factor influencing LTG plasma concentration, followed by UGT1A4*1b, and that patients carrying UGT2B7 c.-161T required higher LTG daily doses. These data provide valuable information for the clinical use of LTG in MM patients with epilepsy.

Source localization of high-frequency activity in tripolar electroencephalography of patients with epilepsy.

OBJECTIVE: The objective of the study was to localize sources of interictal high-frequency activity (HFA), from tripolar electroencephalography (tEEG), in patient-specific, realistic head models. METHODS: Concurrent electroencephalogram (EEG) and tEEG were recorded from nine patients undergoing video-EEG, of which eight had seizures during the recordings and the other had epileptic activity. Patient-specific, realistic boundary element head models were generated from the patient's magnetic resonance images (MRIs). Forward and inverse modeling was performed to localize the HFA to cortical surfaces. RESULTS: In the present study, performed on nine patients with epilepsy, HFA observed in the tEEG was localized to the surface of subject-specific, realistic, cortical models, and found to occur almost exclusively in the seizure onset zone (SOZ)/irritative zone (IZ). SIGNIFICANCE: High-frequency oscillations (HFOs) have been studied as precise biomarkers of the SOZ in epilepsy and have resulted in good therapeutic effect in surgical candidates. Knowing where the sources of these highly focal events are located in the brain can help with diagnosis. High-frequency oscillations are not commonly observed in noninvasive EEG recordings, and invasive electrocorticography (ECoG) is usually required to detect them. However, tEEG, i.e., EEG recorded on the scalp with tripolar concentric ring electrodes (TCREs), has been found to detect narrowband HFA from high gamma (approximately 80 Hz) to almost 400 Hz that correlates with SOZ diagnosis. Thus, source localization of HFA in tEEG may help clinicians identify brain regions of the epileptic zone. At the least, the tEEG HFA localization may help determine where to perform intracranial recordings used for precise diagnosis.

Catatonia in patients with anti-NMDA receptor encephalitis.

AIM: There is a lack of studies related to the frequency, phenomenology, and associated features of catatonic syndrome in patients with anti-NMDA receptor encephalitis (ANMDARE). This study aimed to measure the frequency of catatonia in this condition and to delineate its particular symptoms. METHODS: A prospective study was done with all inpatients who fulfilled the criteria of definite ANMDARE admitted to the National Institute of Neurology and Neurosurgery of Mexico from January 2014 to September 2018. The Bush-Francis Catatonia Rating Scale and Braünig Catatonia Rating Scale were administered at admission. RESULTS: Fifty-eight patients were included and catatonia was diagnosed in 41 of these patients (70.6%). Immobility, staring, mutism, and posturing were the most frequent catatonic signs. Catatonia was associated with delirium, hallucinations, psychomotor agitation, generalized electroencephalography dysfunction, and previous use of antipsychotics. Mortality was present in 10% of the total sample; it was associated with status epilepticus, and was less frequent in the catatonia group. After immunotherapy, all cases showed a complete recovery from catatonic signs. CONCLUSION: This systematic assessment of catatonic syndrome shows that it is a frequent feature in patients with ANMDARE as part of a clinical pattern that includes delirium, psychomotor agitation, and hallucinations. The lack of recognition of this pattern may be a source of diagnostic and therapeutic errors, as most physicians associate catatonia with schizophrenia and affective disorders.