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INTRODUCTION: Huntington's disease (HD) is a genetic neurodegenerative disorder with dominant inheritance. Our center in Mexico City has offered presymptomatic testing (PT) since 1995. OBJECTIVE: To describe the main clinical and demographic characteristics of at-risk HD individuals who applied to the PT program, the reasons for seeking it, and the molecular results. METHODS: A cross-sectional study was conducted with sociodemographic and clinical data of all PT applicants from 1995-2023. Reasons for seeking PT were assessed using a modified questionnaire. In addition, anxiety, and depressive symptoms before and after PT were evaluated with Beck's instruments; cognitive impairment (CI) was assessed with the Mini-Mental State Examination (MMSE) and molecular results. RESULTS: 214 people applied for PT (2.1% of the at-risk population identified in our center); 63% were women (mean age of 37.11 years). 204 (95.3%) were accepted and 190 received results. 70% indicated that the main reason for applying for PT was to inform their offspring about the risk of inheriting HD. Significant differences were observed in the reasons for seeking PT by age group. Although some subjects received treatment, Beck's instrument scores did not indicate special attention or pharmacological treatment. The MMSE showed probable CI in 20 subjects. Of those who received results, 37% were carriers of a full penetrance allele. CONCLUSION: Our center has the only formal PT program for HD in Mexico. The reasons for seeking PT are varied and age-related. Although PT is offered to all subjects at risk for HD, uptake remains low.

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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.

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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.

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BACKGROUND AND PURPOSE: Juvenile-onset Huntington disease (JHD) is defined when symptoms initiate before 20 years of age. Mechanisms explaining differences between juvenile and adult onset are not fully understood. Our aim was to analyze the distribution of initial symptoms in a cohort of JHD patients and to explore its relationship with CAG expansion and relative telomere length (RTL). METHODS: A total of 84 JHD patients and 54 neurologically healthy age and sex matched individuals were recruited. CAG length was measured by southern blot or triplet repeat primed polymerase chain reaction. RTL was measured using the Cawthon method. RESULTS: Psychiatric symptoms were most frequent when considering the entire cohort. When divided into onset before or after 10 years, cognitive symptoms were more frequent in the youngest, whilst in the older group psychiatric symptoms prevailed. Motor symptoms were rare in the youngest and epilepsy was observed only in this group as well as a larger CAG expansion. RTL analysis revealed shorter telomeres in JHD patients compared to controls. This difference is not influenced by age, initial symptoms, time of disease or CAG expansion. CONCLUSIONS: To the best of our knowledge this is the largest cohort of JHD patients reported. Psychiatric manifestations deserve special attention when JHD is suspected and epilepsy is especially important in the youngest patients. Initial symptoms seem to be influenced by CAG expansion and therefore age of onset. RTL is significantly reduced in JHD patients which can influence the characteristic neurodegeneration of JHD and contribute to the clinical discrepancy between adult and juvenile forms of Huntington disease.

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Huntington disease (HD) is the most common neurogenetic disorder caused by expansion of the CAG repeat in the HTT gene; nevertheless, the molecular bases of the disease are not fully understood. Non-coding RNAs have demonstrated to be involved in the physiopathology of HD. However, the role of circRNAs has not been investigated. The aim of this study was to identify the circRNAs with differential expression in a murine cell line model of HD and to identify the biological pathways regulated by the differentially expressed circRNAs. CircRNA expression was analyzed through a microarray, which specifically detects circular species of RNA. The expression patterns between a murine cell line expressing mutant Huntingtin and cells expressing wild-type Huntingtin were compared. We predicted the miRNAs with binding sites for the differentially expressed circRNAs and the corresponding target genes for those miRNAs. Using the target genes, we performed a function enrichment analysis. We identified 23 circRNAs differentially expressed, 19 downregulated and four upregulated. Most of the downregulated circRNAs derive from the Rere gene. The dopaminergic synapse, MAPK, and long-term depression pathways were significantly enriched. The three identified pathways have been previously associated with the physiopathology of HD. The understanding of the circRNA-miRNA-mRNA network involved in the molecular mechanisms driving HD can lead us to identify novel biomarkers and potential therapeutic targets. To the best of our knowledge, this is the first study analyzing circRNAs in a model of Huntington disease.

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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.

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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.

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INTRODUCTION: Huntington´s disease (HD) is a neurodegenerative disorder characterized by neuropsychiatric, motor and cognitive manifestations. It is caused by expansion of the trinucleotide CAG on HTT. The molecular bases are not completely understood, DNA damage, such as double and single strand breaks and oxidative stress (OS) have been implicated. At telomeres, DNA breaks are less efficiently repaired. Double strand breaks evoke the break induced replication (BIR) mechanism. BIR, plus inefficient repair can produce telomere shortening and cellular senescence. Our aim was to investigate the correlation between leukocyte relative telomeric length (RTL) and HD. METHODS: 206 samples were analyzed, 71 patients with molecular diagnosis and symptomatology (HD), 29 individuals with positive molecular test but asymptomatic (PP) and 106 healthy individuals (NP). RESULTS: We found a significant difference in RTL between HD patients compared with both, PP and NP, independently of subjects' age. DISCUSSION: Here we present evidence supporting an association between telomere shortening and HD. Telomere shortening could be related to DNA damage caused by ROS and defective DNA repair mechanism. Both events have been probed to occur in the presence of a mutant Huntingtin. This study contributes with current evidence suggesting a potential role of telomere shortening as HD biomarker.

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Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy accounting for 3-12% of adult cases of epilepsy. Valproate has proven to be the first-choice drug in JME for controlling the most common seizure types: myoclonic, absence, and generalized tonic-clonic (GTC). In this retrospective study, we analyzed seizure outcome in patients with JME using valproate monotherapy for a minimum period of one year. Low valproate dose was considered to be 1000mg/day or lower, while serum levels were considered to be low if they were at or below 50mcg/dl. One hundred three patients met the inclusion criteria. Fifty-six patients (54.4%) were female. The current average age was 28.4±7.4years, while the age of epilepsy onset was 13.6±2.9years. Most patients corresponded to the subsyndrome of classic JME. Forty-six (44.7%) patients were free from all seizure types, and 76 (73.7%) patients were free from GTC seizures. No significant difference was found in seizure freedom among patients using a low dose of valproate versus a high dose (p=0.535) or among patients with low blood levels versus high blood levels (p=0.69). In patients with JME, it seems appropriate to use low doses of valproate (500mg to 1000mg) for initial treatment and then to determine if freedom from seizures was attained.

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Spontaneous cervico-cerebral artery dissection (CCAD) is a common condition found among young patients with ischemic stroke. We examined the possible association between the polymorphism of methylenetetrahydrofolate reductase (MTHFR)-C677T and the gene mutation in transforming growth factor beta receptor II (TGFBR2) in a cohort of CCAD patients. One-hundred CCAD cases (65 males; mean age: 38.08 ± 10.68 years) and 100 matching controls were included. Ancestry informative markers (AIMs) were used to increase internal validity of the genetic analysis. Genotypes of the C677T polymorphism in the MTHFR gene were determined by polymerase chain reaction and restriction fragment length polymorphism; direct sequencing was used for a mutation analysis of the TGFBR2 gene. Associations were evaluated using a multivariate statistics, and Hardy-Weinberg equilibrium was analyzed. We also incorporated our data into a meta-analysis of the MTHFR-C677T. Sixty-three patients presented with vertebral and 37 with carotid artery dissection. Ancestry markers found a call rate on each over 95 %. All AIMs did not deviate from Hardy-Weinberg equilibrium (p > 0.05). The homozygous TT genotype was more frequent in cases (OR 2.04, CI 95 % 1.53-2.72, p = 0.005), whereas no significant difference was found on heterozygous CT genotype. TGFBR2 mutation was not present in our samples. In the meta-analysis of MTHFR/C677T variant, a total 613 cases and 1547 controls were analyzed; we found a moderate association for the recessive model genotype (OR 2.04, CI 95 % 1.53-2.72; p = 0.342; Z = 4.83; I (2) = 11.3). This study supports a positive association between the MTHFR-C677T polymorphism and genetically confirmed Mexican mestizo CCAD patients.

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Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy with classic adolescent onset of stimuli sensitive seizures. Patients typically deteriorate rapidly with dementia, ataxia, vegetative failure and death by 25 years of age. LD is caused by homozygous mutations in EPM2A or EPM2B genes. We found four novel mutations in EPM2A - three in exon 4 (Q247X, H265R G279C) and one in exon 1 (Y86D) - and a previously described mutation in exon 4 (R241X). These five EPM2A mutations were found in four index cases and affected relatives. Patient 1 with classic LD was doubly heterozygous for H265R and R241X in exon 4; while Patient 2, who also had classic LD, was homozygous for Q247X in exon 4. Patient 3 with classic LD was homozygous for Y86D in exon 1, but the same mutation in his affected brother manifested an atypical earlier childhood onset. For the first time, we describe a later onset and slower progression of EPM2A-deficient LD seen in Patient 4 and her three sisters who were doubly heterozygous for R241X and G279C in exon 4. In these sisters, seizures started later at 21 to 28 years of age and progressed slowly with patients living beyond 30 years of age. Our observations suggest that variations in phenotypes of EPM2A-deficient LD, like an earlier childhood or adolescent or later adult onset with a rapid or slower course, depend on a second modifying factor separate from pathogenicity or exon location of EPM2A mutations. A modifying gene amongst the patient's genetic background or environmental factors may condition age of onset and rapid or slow progression of LD.

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PURPOSE: The purpose of this study was to identify the prevalence of mutations in the Myoclonin1/EFHC1 gene in Mexican patients with juvenile myoclonic epilepsy (JME). METHOD: We studied forty-one patients at the National Institute of Neurology and Neurosurgery in Mexico City and 100 healthy controls. DNA was extracted from the peripheral venous blood of all participants. The exons of EFHC1 were then amplified and sequenced. RESULTS: We found three new putative mutations, all of which were heterozygous missense mutations located in exon 3. The first identified mutation, 352C>T, produces a R118C change in the protein and cosegregated in the patient's affected father and brother. The second identified mutation, 544C>T, produces a R182L change in the protein and was found in the patient's asymptomatic father. The third identified mutation, 458>A, produces a R153Q change in the protein and was also found in the patient's father. These mutations were not found in controls. CONCLUSIONS: The frequency of Myoclonin1/EFHC1 mutations in our sample is 7.3%. Thus, we conclude that mutations in the Myoclonin1/EFHC1 gene are an important cause of JME in Mexican patients.

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The presence of different ethnic groups in Mexico may give rise to genetic diversity between the native Indian population and the Mestizos. It is therefore of medical and anthropological interest to analyze the genotypes of disease-associated loci, such as polymorphism in the apolipoprotein E gene, whose 4/4 allele increases the risk of Alzheimer's disease and coronary heart disease in other populations. We studied a Nahua Indian-population in the State of Morelos (Santo Domingo Ocotitlan). The ABO blood type of all individuals was determined and compared with the findings of other Nahua group from the State of Puebla. Without statistical significant differences in O, A and AB groups between both populations (p > 0.05). The allelic and genotypic frequency of apolipoprotein E was similar to that observed in other Mexican indian (Mazatecans, Mayans) and Mestizo populations, however there was a statistically significant difference when the results were compared to the allelic frequencies of other Amerinds: The Cayapa (Ecuador) for the epsilon 3 and epsilon 4 alleles (p < 0.002); the Nuuk (Greenland) for epsilon 3 and epsilon 4 alleles (p < 0.0001 and p < 0.002 respectively); and the Ammssalik (Greenland) for both alleles with p < 0.0001 and p = 0.04 respectively. In the case of the genotypes, there was statistically significant difference for the 4/3 genotypes, but a non significant difference for the 4/4 genotype. This is a descriptive study which contributes to the knowledge of the genetic structure of Mexican population.

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Algunos autores han informado que las alteraciones en el número de cromosomas sexuales son más frecuentes en pacientes epilépticos. En este trabajo se estudió la cromatina X y Y en una población de pacientes epilépticos con objeto de detectar alteraciones en el número de cromosomas sexuales en ellos. Se estudiaron 608 hombres y 537 mujeres mediante la cromatina X, no encontrándose ninguna alteración en esta prueba. En 279 hombres se determinó la cromatina Y en la cual tampoco se encontraron anormalidades

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