Unmasking the Mimic: Radionecrotic Lesion Masquerading as Brain Neoplasia on Magnetic Resonance Imaging.

Corpus callosotomy is a therapeutic approach for drug-resistant epilepsy, with positive outcomes observed in managing atonic seizures. Despite a decline in its usage, radiosurgical callosotomy remains a viable option for drug-resistant epilepsy due to its low risks of post-radiation neoplasia, albeit not with exceptions. Brain radionecrosis is characterized by tissue death and vascular endothelial damage following the procedure. Despite the low risk of intracranial secondary malignancy associated with radiation in some cases, post-radiation lesions might present with distinct characteristics needing a thorough diagnostic approach. Herein, we present a unique case of a patient with focal epilepsy who developed a radionecrotic lesion following radiosurgical callosotomy, affecting the anterior cingulate cortex, and mimicking a central nervous system (CNS) tumor. Molecular imaging techniques, including 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT) and 11C-acetate PET/CT scans, were employed to differentiate the lesion from a tumor. This case underscores the importance of considering radionecrosis as a differential diagnosis in patients who undergo radiosurgical callosotomy presenting with ring-like enhancement lesions on magnetic resonance imaging (MRI).

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.

Protein expression of P-glycoprotein in neocortex from patients with frontal lobe epilepsy.

Frontal lobe epilepsy (FLE) is the second most frequent type of epilepsy and the surgical outcome depends on the etiology. For instance, patients with posttraumatic FLE (PTE) have a worse surgical outcome compared to patients with FLE related to a tumoral lesion (TL). The present study focuses to determine if the FLE etiology is associated with the P-glycoprotein (P-gp) expression, a condition associated with drug resistance. P-gp expression and cellular localization were determined by Western Blot and immunohistochemical experiments in cortical brain samples obtained from patients with PTE (n = 5), TL (n = 5), and autopsies (n = 5). The neuronal count was estimated by Nissl and stereology procedure. Results showed that the autopsies tissue showed a neuronal count of 3514 ± 304.2 neurons per mm3. The P-gp expression ratio was 0.33 ± 0.02. Its expression was found in endothelial cells. Negligible P-gp expression was detected in neurons and astrocytes. Compared to the autopsies group, the TL group showed no changes in the neuronal count but, there was a decreased P-gp expression ratio (46%, p < 0.05). P-gp was located mainly in neurons, slight in astroglial, and endothelial cells. The PTE group showed a similar P-gp expression ratio compared to the autopsies group. P-gp was expressed in neurons, astrocytes, and endothelial cells in these samples. However, experiments revealed a high P-gp expression in a lower neuronal count (38%, p < 0.05 vs autopsy group). The present study reveals that patients with PTE present neuronal P-gp overexpression. This finding could underlie their worst surgical outcome.

Relevance of NR1I2 variants on carbamazepine therapy in Mexican Mestizos with epilepsy at a tertiary-care hospital.

Aim: We evaluated the potential influence of genetic (CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug reactions and CBZ plasma concentrations in 126 Mexican Mestizos (MM) with epilepsy. Subjects & methods: Patients were genotyped for 27 variants using TaqMan® assays. Results: CBZ response was associated with NR1I2 variants and lamotrigine cotreatment. CBZ-induced adverse drug reactions were related to antiepileptic polytherapy and SCN1A rs2298771/rs3812718 haplotype. CBZ plasma concentrations were influenced by NR1I2-rs2276707 and -rs3814058, and by phenytoin cotreatment. CBZ daily dose was also influenced by NR1I2-rs3814055 and EPHX1-rs1051740. Conclusion: Interindividual variability in CBZ treatment was partly explained by NR1I2, EPHX1 and SCN1A variants, as well as antiepileptic cotreatment in MM with epilepsy.

Temporal lobe epilepsy: Evaluation of central and systemic immune-inflammatory features associated with drug resistance.

Neuroinflammation is probably one of the factors involved in drug resistance in people with epilepsy. Finding peripheral markers reflecting the intensity of neuroinflammation could be of great help to decide for which patients anti-inflammatory treatment might be an option. In this context, peripheral cytokines levels and lymphocyte phenotypes were assessed by ELISA and flow cytometry in 3 groups of subjects: drug resistant patients with temporal lobe epilepsy (DR-TLE), non DR-TLE patients and healthy controls. The same parameters were assessed in brain tissue in the DR-TLE group. Differences in the peripheral immune-inflammatory status between the 3 groups of subjects, and correlations between the central and peripheral immune-inflammatory status in DR-TLE patients were evaluated. Forty-one patients with DR-TLE, ten with non-DR-TLE and twenty controls were included. In the periphery, decrease in regulatory cells were observed in DR-TLE patients compared to controls. In addition, significant increase of IL-6 and IL-5 was observed in patients with epilepsy (particularly DR-TLE patients). Two groups of DR-TLE patients with significant differences in several central inflammatory parameters were identified in a cluster analysis. The inflammatory cluster was associated with a peripheral increase of CD4+CD38+ cells and different significant correlations between central and systemic inflammatory parameters were observed. Although their interpretation is not immediate, they demonstrate a clear dialogue between central and peripheral inflammatory reactions. In conclusion, our results add new elements to better understand the interactions between the central and peripheral compartments in patients with DR-TLE, and to help better define treatment options in this group of patients.

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.

Continuous Visual Focal Status Epilepticus as the Primary Presentation of NMDA-R and GAD65-R Autoimmune Epilepsy.

Epilepsia partialis continua (EPC) has changed in its clinical and pathophysiological definition throughout time. Several etiologies have been described in addition to classic causes of EPC. The following case depicts a young woman who had a peculiar onset of epilepsy with a continuous visual aura becoming a form of chronic recurrent and non-progressive EPC. The patient was initially misdiagnosed as a non-neurological entity (assumed psychiatric in origin), but finally, an immune-mediated epilepsy was diagnosed, and EEG showed focal status epilepticus during evolution. Once the diagnosis was achieved and immune treatment was established, the patient is seizure free. Early identification of an immune basis in patients with epilepsy is important because immunotherapy can reverse the epileptogenic process and reduce the risk of chronic epilepsy. To date, this is the only case reported with EPC manifesting as a continuous visual aura associated with antiglutamic acid decarboxylase 65 (anti-GAD65) and anti-N-methyl-d-aspartate (anti-NMDA) antibodies.

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.

Herramientas de salud digital para superar la brecha de atención en epilepsia antes, durante y después de la pandemia de COVID-19 / E-health tools to overcome the gap in epilepsy care before, during and after COVID-19 pandemics

INTRODUCCIÓN: La epilepsia es un trastorno neurológico crónico común que afecta a alrededor de 50 millones de personas en el mundo y abunda la bibliografía sobre la brecha de atención en salud a este sector de la población. Dicha brecha aumentará con la pandemia actual de COVID-19. OBJETIVO: Evaluar la disponibilidad actual de herramientas de salud digital para la atención a personas con epilepsia según la literatura médica mundial y su uso durante dicha pandemia. Desarrollo. Se hizo una revisión de las publicaciones en revistas científicas en la última década que tuvieran como tema principal el uso de herramientas de salud digital o telemedicina enfocada a la atención de los pacientes con epilepsia, incluyendo cuatro meses después de las cuarentenas nacionales por la aparición del virus SARS-CoV2. Se encontraron 17 publicaciones sobre el uso de telemedicina enfocada a la epilepsia. Las herramientas más utilizadas internacionalmente son las plataformas en línea, seguidas de las aplicaciones móviles, videoconferencias, sistemas de captación de crisis epilépticas, listas de verificación, algoritmos de comprensión de datos médicos, llamadas telefónicas, teleelectroencefalografía y mensajes de texto. Ninguna se publicó durante la presente pandemia. CONCLUSIONES: Hay poca bibliografía sobre herramientas de salud digital enfocadas a epilepsia, pero existen varias que pueden emplearse para luchar contra la brecha de atención, especialmente en esta pandemia mundial de COVID-19 que obliga a las personas y comunidades a mantenerse en cuarentena por la emergencia sanitaria. Es necesario eliminar barreras y facilitar el pronto acceso de los pacientes a estas nuevas tecnologías de información

INTRODUCTION: Epilepsy is a common chronic neurological disorder that affects around 50 million worldwide and there is an abundance of literature on the health care gap for this sector of the population. This gap will increase with the current pandemic due to COVID-19. AIM: To evaluate the current availability of digital health tools for the care of people with epilepsy according to the world medical literature and their use during said pandemic. Development. We reviewed the publications in scientific journals in the last decade that had as their main topic the use of digital health tools or telemedicine focused on the care of patients with epilepsy, including 4 months after the national quarantines due to the appearance of the virus SARS-CoV2. Seventeen publications were found on the use of telemedicine focused on epilepsy. The most widely used tools internationally are online platforms, followed by mobile applications, videoconferences, epileptic seizure capture systems, checklists, algorithms for understanding medical data, phone calls, tele-encephalography and text messages. None was published during the COVID-19 current pandemic. CONCLUSIONS: Although there is little literature on the use of digital health tools focused on epilepsy, there are several that can be used to fight the attention gap, especially in this global pandemic by COVID-19 that forces quarantines of people and communities for long periods. It is necessary to remove barriers and facilitate patient access to these new information technologies

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.

Resolution of ictal bradycardia and asystole following temporal lobectomy: A case report, and review of available cases using pacemakers.

Ictal bradycardia (IB) and ictal asystole (IA) are uncommonly recognized phenomena that increase morbidity in patients with epilepsy by causing syncope and seizure-related falls. These arrhythmias are also suspected to be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We report a case of a 57-year-old male with left temporal lobe epilepsy who experienced both IB and IA. This patient was initially managed with pacemaker implantation, prior to undergoing left temporal lobectomy. Following surgery, the patient had no ongoing IB or IA on his pacemaker recordings, and his seizure control was greatly improved. His pacemaker was removed approximately one year post-operatively and he continued treatment with anti-seizure drugs (ASDs). A literature review of cases of IB and IA that were managed with pacemakers was performed. Pacemaker implantation appears to be quite effective for reducing seizure-related syncope and falls in the setting of IB/IA. Epilepsy surgery also seems to be an effective treatment option for IB/IA, as many patients are able to have their pacemakers removed post-operatively. Further investigations into the pathophysiology of IB and IA and long-term outcomes using different treatment modalities are clearly needed to help formulate treatment guidelines and, potentially, to reduce the occurrence of SUDEP in these patients.

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.

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.).

Barreras de acceso a la cirugía de la epilepsia: revisión de la bibliografía / Barriers impeding access to epilepsy surgery: a review of the literature

La epilepsia farmacorresistente es una condición crónica con consecuencias a largo plazo que puede ser tratada quirúrgicamente. La eficacia y la seguridad de la cirugía de la epilepsia del lóbulo temporal se han establecido a través de un gran número de estudios de cohorte retrospectivos y prospectivos y dos ensayos clínicos controlados aleatorizados. A pesar de los excelentes resultados comunicados con la cirugía, la bibliografía sugiere que este procedimiento es un tratamiento subutilizado. Aunque no existe evidencia de esto, entre algunos de los motivos descritos se apuntan el fallo de los médicos de atención primaria y los neurólogos en proveer información, identificar y remitir a los pacientes a un centro de cirugía; los diferentes niveles de tecnología en los centros, lo que provoca distintas estrategias de selección de los candidatos; la creencia de que la cirugía de la epilepsia es un procedimiento arriesgado que debería contemplarse sólo como última opción; la preferencia del paciente por evitar la cirugía; el deseo de los padres de esperar hasta que sus hijos sean lo suficientemente mayores para participar en el proceso de toma de decisiones; el hecho de que las aseguradoras no cubran los gastos asociados con las evaluaciones prequirúrgicas o la carencia de un seguro médico, y la desigualdad racial y social, entre otros. En este artículo se revisan los datos epidemiológicos disponibles en relación con la falta de acceso a la cirugía de la epilepsia (AU)

Drug-resistant epilepsy, a chronic condition with long-term consequences can be treated with surgery. The efficacy and safety of surgery for temporal lobe epilepsy have been established through a large number of retrospective and prospective cohort studies and two randomized controlled clinical trials. Despite the excellent outcomes reported after surgery, the literature suggests that this procedure is an underutilized treatment. While evidence is lacking as to why epilepsy surgery is underused, cited reasons include: failure of primary care physicians and neurologists to provide information and identify patients who could be referred for surgery; different levels of technology at various centers, resulting in different candidate selection strategies; the belief that epilepsy surgery is a risky procedure and that it should be only viewed as the last option; patient preference to avoid surgery; parents wanting to wait until their child is old enough to participate in the decision-making process regarding surgery; unwillingness of insurers to cover the expenses associated with presurgical evaluations or lack of insurance; racial and social disparities, among others. In this paper we review the available epidemiological data about lack of utilization of epilepsy surgery (AU)

A comparison of waiting times for assessment and epilepsy surgery between a Canadian and a Mexican referral center.

Objective: To provide a comprehensive transnational overview of wait times for epilepsy surgery in Canada and Mexico. Methods: We reviewed all cases referred for epilepsy surgery between 2007 and 2015 at the Saskatchewan Epilepsy Program Royal University Hospital (SEP) (n = 70; Saskatoon, Canada) and the National Institute of Neurology and Neurosurgery (NINN) (n = 76; Mexico City, Mexico) and compared wait times, calculated as the time from diagnosis of epilepsy on assessment at an epilepsy center to epilepsy surgery. Results: Mean wait times were similar across centers. Mean patient age was 37.4 ± 9 years (NINN) and 36.7 ± 13.2 years (SEP). The mean time from epilepsy diagnosis to referral was 18.9 (NINN) and 16.9 years (SEP), p = 0.30; first consult with the epileptologist, 19.7 (NINN) and 17.4 years (p = 0.23); neuropsychology consult, 21.4 (NINN) and 17.9 years (SEP); video electroencephalogram (video-EEG) telemetry, 21.1 (NINN) and 18.6 months (SEP); initial neurosurgical consult, 21.9 (NINN) and 19.1 years (SEP) (p = 0.35); and epilepsy surgery, 19.7 (NINN) and 19.6 years (SEP) (p = 0.29). Significance: This is the first study to compare wait times between Canada and Mexico. Despite disparity in their health delivery systems and financial resources, surgical wait times appeared to be protracted in both nations, confirming that delayed treatment is a universal problem that requires collaborative scrutiny.

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.

PURPOSE: EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. METHODS: We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1-/- KO mice recapitulate CTC convulsions and "microdysgenesis" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. RESULTS: Nine variants were classified as "pathogenic," 14 as "likely pathogenic," 9 as "benign," and 2 as "likely benign." Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. CONCLUSIONS: NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and "microdysgenesis" neuropathology of JME.Genet Med 19 2, 144-156.