Presymptomatic Testing for Huntington's Disease in Mexico: 28 Years of Experience.

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.

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.

Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease.

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.

Frontostriatal Circuits Alterations Associated with Cognitive Flexibility Deterioration in Huntington's Disease.

BACKGROUND: Recent resting-state functional magnetic resonance imaging studies have reported abnormal functional connectivity (FC) in the prefrontal cortex (PFC)-striatum circuit in patients with premanifest Huntington's disease (HD). However, there is a lack of evidence showing persistence of abnormal frontostriatal FC and its relation to cognitive flexibility performance in patients with clinically manifest HD. OBJECTIVE: The aim of this study was to evaluate the resting-state FC integrity of the frontostriatal circuit and its relation to cognitive flexibility in HD patients and healthy controls (HCs). METHOD: Eighteen patients with early clinical HD manifestation and 18 HCs matched for age, sex, and education participated in this study. Both groups performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional (IED) set-shift task, which measures cognitive flexibility. Resting-state functional magnetic resonance images were also acquired to examine the FC in specific frontostriatal circuits. Eight regions of interest were preselected based on regions previously associated with extradimensional (ED) shifting in patients with premanifest HD. RESULTS: Significant negative correlations between the number of attentional set-shifting errors and the ventral striatum-ventrolateral PFC FC were found in the HD group. This group also showed negative FC correlations between the total errors and the FC between right ventral striatum-right ventrolateral PFC, left ventral striatum-left ventrolateral PFC, and right ventral striatum-left ventrolateral PFC. Negative correlations between the ED errors and left ventral striatum-left ventrolateral PFC and right ventral striatum-right ventrolateral PFC FC were also found. Finally, a positive correlation between the number of stages completed and left ventral striatum-left ventrolateral PFC FC was found. CONCLUSIONS: Manifest HD patients show significant cognitive flexibility deficits in attentional set-shifting that are associated with FC alterations in the frontostriatal circuit. These results show that FC abnormalities found in the prodromal stage of the disease can also be associated with cognitive flexibility deficits at a later clinical stage, making them good candidates to be explored in longitudinal studies.

Clinical and Molecular Findings of Intermediate Allele Carriers in the HTT Gene from the Mexican Mestizo Population.

INTRODUCTION: There are reports of different clinical statuses in carriers of intermediate alleles (IAs) of CAG trinucleotide repeats in the HTT gene, from individuals affected by a clinical picture indistinguishable from Huntington's disease (HD) to those without manifestations. Therefore, the possible clinical significance of these alleles has been widely debated. OBJECTIVES: The aim of this study was to describe general and clinical features and discard HD phenocopies by molecular assessment in a case series of IA carriers on the HTT gene of a laboratory sample from a neurological center in Mexico. METHODS: We selected individuals who had previously been tested for the HTT gene expansion, which resulted in IAs. Clinical information was obtained from medical records, and molecular analysis of the JPH3, PRNP, and TBP genes was performed only in IA carriers with clinical manifestations. In addition, two patients with IA and acanthocytes were evaluated by whole-exome sequencing. The scientific and ethical committees of the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez (NINNMVS) approved this study. RESULTS: From 1994 to 2019, the Genetics Department of the NINNMVS confirmed 34 individuals with IAs, 15 of whom belonged to 11 families with HD (IA-HD) and 19 of whom had no family history of HD (IA-non-HD). We found a high proportion of manifestations of the HD phenotypic spectrum in the IA-non-HD subgroup. In addition, among the 20 samples of IA carriers with manifestations molecularly evaluated, we identified two unrelated subjects with CAG/CTG repeat expansions on the JPH3 gene, confirming HD-like 2 (HDL2), and one patient with the homozygous pathogenic c.3232G>T variant (p.Glu1078Ter) in the VPS13A gene, demonstrating choreoacanthocytosis. DISCUSSION/CONCLUSION: Our results show the most extensive series of subjects with IAs and clinical manifestations. In addition, we identify three HD phenocopies, two HDL2 cases, and one choreoacanthocytosis case. Therefore, we emphasize evaluating other HD phenocopies in IA carriers with clinical manifestations whose family background is not associated with HD.

circRNA Regulates Dopaminergic Synapse, MAPK, and Long-term Depression Pathways in Huntington Disease.

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.

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.

Diversity of HLA Class I and Class II blocks and conserved extended haplotypes in Lacandon Mayans.

Here we studied HLA blocks and haplotypes in a group of 218 Lacandon Maya Native American using a high-resolution next generation sequencing (NGS) method. We assessed the genetic diversity of HLA class I and class II in this population, and determined the most probable ancestry of Lacandon Maya HLA class I and class II haplotypes. Importantly, this Native American group showed a high degree of both HLA homozygosity and linkage disequilibrium across the HLA region and also lower class II HLA allelic diversity than most previously reported populations (including other Native American groups). Distinctive alleles present in the Lacandon population include HLA-A*24:14 and HLA-B*40:08. Furthermore, in Lacandons we observed a high frequency of haplotypes containing the allele HLA-DRB1*04:11, a relatively frequent allele in comparison with other neighboring indigenous groups. The specific demographic history of the Lacandon population including inbreeding, as well as pathogen selection, may have elevated the frequencies of a small number of HLA class II alleles and DNA blocks. To assess the possible role of different selective pressures in determining Native American HLA diversity, we evaluated the relationship between genetic diversity at HLA-A, HLA-B and HLA-DRB1 and pathogen richness for a global dataset and for Native American populations alone. In keeping with previous studies of such relationships we included distance from Africa as a covariate. After correction for multiple comparisons we did not find any significant relationship between pathogen diversity and HLA genetic diversity (as measured by polymorphism information content) in either our global dataset or the Native American subset of the dataset. We found the expected negative relationship between genetic diversity and distance from Africa in the global dataset, but no relationship between HLA genetic diversity and distance from Africa when Native American populations were considered alone.

Telomere length analysis on leukocytes derived from patients with Huntington Disease.

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.

Theory of mind impairment in Huntington's disease patients and their relatives.

Huntington disease (HD) is an autosomal dominant genetic disorder characterized by movement disorders, cognitive impairment, and psychiatric symptoms. Relatives of HD patients experience a great burden as the latter suffer from altered social conduct and deterioration of interpersonal relationships. Theory of mind (ToM) is the ability to attribute mental states (to oneself and others). Deficits in ToM are thought to have a role in the changes in empathy and interpersonal difficulties that HD patients face. METHODS We conducted a cross sectional study to compare ToM task scores of patients with mild to moderate HD, their relatives (spouse or at-risk first-degree relative with a negative gene test) and controls.Individuals with dementia or depression were excluded. The ToM test battery included Spanish versions of the Reading Mind in the Eyes Test (RMET), Happé's Strange Stories (Social and Physical Stories subtests) and the Hinting Task. RESULTS The series comprised 12 HD patients, 12 relatives and 12 controls. The HD patients showed lower affective ToM scores than controls (RMET 19 [3.5] vs 23.9 [2.7], p = 0.016). Cognitive ToM tasks scores were lower in HD patients than controls as well (Happé's Social Stories 9 [2.6] vs 13 [1.9], p = 0.001; the Hinting Task 13.6 [3.4] vs 17.5 [4.0], p = 0.009). In the Hinting Task, HD relatives had lower scores in than controls (13 [3.2] vs 17.5 [4.0], p = 0.009) and similar scores to controls in the rest of the battery. CONCLUSION The HD patients with mild to moderate disease severity and their relatives show ToM deficits.

Implicit learning impairment identified via predictive saccades in Huntington's disease correlates with extended cortico-striatal atrophy.

The ability to anticipate events and execute motor commands prior to a sensory event is an essential capability for human's everyday life. This implicitly learned anticipatory behavior depends on the past performance of repeated sensorimotor interactions timed with external cues. This kind of predictive behavior has been shown to be compromised in neurological disorders such as Huntington disease (HD), in which neural atrophy includes key cortical and basal ganglia regions. To investigate the neural basis of the anticipatory behavioral deficits in HD we used a predictive-saccade paradigm that requires predictive control to generate saccades in a metronomic temporal pattern. This is ideal because the integrity of the oculomotor network that includes the striatum and prefrontal, parietal, occipital and temporal cortices can be analyzed using structural MRI. Our results showed that the HD patients had severe predictive saccade deficits (i.e., an inability to reduce saccade reaction time in predictive condition), which are accentuated in patients with more severe motor deterioration. Structural imaging analyses revealed that these anticipatory deficits correlated with grey-matter atrophy in frontal, parietal-occipital and striatal regions. These findings indicate that the predictive saccade control deficits in HD are related to an extended cortico-striatal atrophy. This suggests that eye movement measurement could be a reliable marker of the progression of cognitive deficits in HD.

Theory of mind impairment in Huntington's disease patients and their relatives / Déficits en teoría de la mente en pacientes con enfermedad de Huntington y sus familiares

ABSTRACT Huntington disease (HD) is an autosomal dominant genetic disorder characterized by movement disorders, cognitive impairment, and psychiatric symptoms. Relatives of HD patients experience a great burden as the latter suffer from altered social conduct and deterioration of interpersonal relationships. Theory of mind (ToM) is the ability to attribute mental states (to oneself and others). Deficits in ToM are thought to have a role in the changes in empathy and interpersonal difficulties that HD patients face. Methods: We conducted a cross sectional study to compare ToM task scores of patients with mild to moderate HD, their relatives (spouse or at-risk first-degree relative with a negative gene test) and controls.Individuals with dementia or depression were excluded. The ToM test battery included Spanish versions of the Reading Mind in the Eyes Test (RMET), Happé's Strange Stories (Social and Physical Stories subtests) and the Hinting Task. Results: The series comprised 12 HD patients, 12 relatives and 12 controls. The HD patients showed lower affective ToM scores than controls (RMET 19 [3.5] vs 23.9 [2.7], p = 0.016). Cognitive ToM tasks scores were lower in HD patients than controls as well (Happé's Social Stories 9 [2.6] vs 13 [1.9], p = 0.001; the Hinting Task 13.6 [3.4] vs 17.5 [4.0], p = 0.009). In the Hinting Task, HD relatives had lower scores in than controls (13 [3.2] vs 17.5 [4.0], p = 0.009) and similar scores to controls in the rest of the battery. Conclusion: The HD patients with mild to moderate disease severity and their relatives show ToM deficits.

RESUMEN La enfermedad de Huntington (EH) es una enfermedad genética autosómica dominante caracterizada por trastornos del movimiento, deterioro cognitivo y síntomas psiquiátricos. Los familiares de las personas con EH experimentan gran carga dado que los pacientes sufren de conducta social alterada y deterioro de relaciones interpersonales. La Teoría de la mente (ToM) consiste en la habilidad para atribuir estados mentales (a uno mismo o a otros). Se piensa que déficits en ToM tienen un rol en los cambios en empatia y en las dificultades interpersonales que los pacientes con EH enfrentan. Métodos: Condujimos un estudio transversal para comparar el desempeño en puntajes de tareas de ToM en pacientes con EH leve a moderada, sus familiares (pareja o familiar en riesgo con prueba genética negativa) y controles sanos. Se excluyó a sujetos con demencia o depresión. La batería de pruebas de ToM incluyó versiones en español de la prueba de lectura de la mente en los ojos (RMET), Historias Extrañas de Happé (subpruebas Social y Física) y Hinting Task. Resultados: La serie consistió de 12 pacientes con EH, 12 familiares y 12 controles. Los pacientes con EH mostraron puntajes menores de tareas de ToM afectiva que los controles (RMET 19 [3.5] vs 23.9 [2.7], p = 0.016). Los puntajes de tareas de ToM cognitiva fueron inferiores a los controles en los pacientes con EH (Historias Sociales de Happé 9 [2.6] vs 13 [1.9], p = 0.001; Hinting task 13.6 [3.4] vs 175 [4.0], p = 0.009). En la Hinting task los familiares de pacientes con EH mostraron puntajes inferiores que los de los controles (13 [3.2] vs 175 [4.0], p = 0.009) y puntajes similares a aquellos de los controles en el resto de la batería. Conclusión: Los pacientes con EH con enfermedad leve a moderada y sus familiares muestran déficits en tareas de ToM.

Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6.

BACKGROUND: Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an adult-onset, autosomal dominant disease involving microvessels of the brain and eye resulting in central nervous system degeneration with visual disturbances, stroke, motor impairment, and cognitive decline. Frameshift mutations at the C-terminus of TREX1 gene are the molecular cause of this disorder. OBJECTIVES: The objective of this study is to present the different clinical manifestations of RVCL in three-related patients and to investigate the presence of TREX1 mutation in the extended genealogy. METHODS: Multidisciplinary testing was performed in three related patients. Based on their family history, the study was extended to 34 relatives from the same small community. Neurological evaluation, sequencing of TREX1, and presymptomatic diagnosis were offered to all participants. RESULTS: The patients exhibited the heterozygous TREX1 mutation p.V235Gfs*6, but with phenotypic variability. In addition, 15 relatives were identified as pre-manifest mutation carriers. The remaining participants did not carry the mutation. CONCLUSIONS: This is the figrst report of a large Mexican genealogy with RVCL, where the same TREX1 mutation causes a variation in organ involvement and clinical progression. The early identification and follow-up of individuals at risk may help provide insights into the basis for this variability in presentation.

Early Huntington's Disease: Impulse Control Deficits but Correct Judgment Regarding Risky Situations.

BACKGROUND: Huntington's disease (HD) patients show alterations in decision making tasks. However, it is still uncertain if these deficits are due to poor judgment regarding risky situations, or to impulse control deficits. OBJECTIVE: To elucidate whether decision-making in patients is related to genuine risk behavior or to impulse control deficits. METHODS: To test between these two alternative possibilities, we evaluated the performance of 19 prodromal HD patients and 19 matched healthy controls in the Cambridge Gambling Task (CGT). This task assesses decision-making while dissociating between genuine risk-taking behaviors (ascending condition) from impulsive behavior (descending condition). RESULTS: The results showed that patients and controls had the same performance during all trials in the ascending condition, reflecting a correct judgment regarding risky situations; however, during the descending condition, patients responded before the controls in all trials, making a significantly larger number of higher bets. Unlike the control group, they did not wait for more optimal subsequent options. CONCLUSION: These results suggest impulse control deficits in HD gene carriers, but unimpaired risk-taking judgment.

Estudio piloto en cuidadores de pacientes con enfermedades neurológicas, sobre el significado y conocimiento de cuidados paliativos / Estudo piloto em cuidadores de pacientes com enfermidades neurológicas, sobre o significado e conhecimento de cuidados paliativos / Pilot study with caregivers attending patients with neurologic diseases, about the meaning and knowledge of palliative care

Objetivo. Describir el significado que atribuyen cuidadores a los cuidados paliativos (CPS), así como su preferencia respecto a informar al paciente y su satisfacción con el papel de cuidador. Metodología. Estudio descriptivo transversal, muestra intencional de 40 cuidadores de enfermos neurológicos con necesidad de CPS. Se aplicó un cuestionario de conocimientos sobre el tema y sobrecarga. Se realizó análisis descriptivo-comparativo con un intervalo de confianza de 95 por ciento (p mayor 0.05). Resultados. Pacientes: 52,6 por ciento hombres, edad promedio de 57,9 por ciento años, tiempo de enfermedad: 5 años, 2 hijos en promedio. Cuidadores: 77,5 mujeres, 25,0 por ciento cónyuges. Edad promedio: 49.3 años, proporcionan 18,5 horas de cuidado diario, 62,5 por ciento tenía estudios de secundaria o superiores, 40 por ciento son cuidadores únicos, 16,7 por ciento no cuenta con redes de apoyo y 42,5 por ciento presenta sobrecarga alta. Un 70 por ciento no tenía información previa sobre CPS. Significado: 50 por ciento mencionó "dar ayuda" (física o emocional), 20 por ciento"mejorar la calidad de vida". El 87,5 por ciento desearía ser informado con detalle si ellos fueran los pacientes, 86,1 por ciento quisiera ser informado por el médico y 62,5 por ciento se mostró a favor de que se le informara con detalle a su familiar. Conclusiones. Es importante difundir los CPS en cuidadores y estimular el derecho de los pacientes a recibir información sobre el pronóstico de su enfermedad.

Aim. To describe the meaning attributed to palliative care (PC) by caregivers, as well as their preference with respect to informing the patient and their satisfaction in their caring role. Methodology: Study descriptive transversal, sample intended of 40 caregivers of neurologic patients needing PC. A questionnaire about knowledge of the topic and their burnout status was applied. A descriptive-comparative analysis was carried out with 95 percent (p higher 0.05) confidence interval. Results: Patients: 52.6 percent men, average age 57.9 years, duration of disease: 5 years, average of 2 children. Caregivers: 77.5 percent women, 25.0 percent married, average age: 49.3 years, daily caring 18.5 hours, 62.5 percent with high School or university studies, 40 percent alone as caregivers, 16.7 percent do not count with support nets and 42.5 percent present high burn out status. Of them 70 percent did not have previous information about PC. Meaning: 50 percent mentioned "to give help" (physical or emotional), 20 percent "to enhance quality of life". 87.5 percent would like to be informed with detail if they were the patients, 86.1 percent would like to be informed by the physician and 62.5 percent were in favor to inform with detail to their family member. Conclusions: It is important to disseminate PC to caregivers and to stimulate the right of patients to receive information about the prognosis of their disease.

Objetivo. Descrever o significado que atribuem cuidadores aos cuidados paliativos (CPS), assim como sua preferência com respeito a informar ao paciente e sua satisfação com o papel de cuidador. Metodologia. Estudo descritivo transversal, amostra intencional de 40 cuidadores de enfermos neurológicos com necessidade de CPS. Aplicou-se um questionário de conhecimentos sobre o tema e sobrecarga. Realizou-se análise descritivo-comparativa com um intervalo de confiança de 95 por cento (p superior 0.05). Resultados. Pacientes: 52,6 por cento homens, idade média de 57,9 anos, tempo de enfermidade: 5 anos, 2 filhos em média. Cuidadores: 77,5 por cento mulheres, 25,0 por cento cônjuges. Idade média: 49.3 anos, proporcionam 18,5 horas de cuidado diário, 62,5 por cento tinham estudos secundários ou superiores, 40 por cento são cuidadores únicos, 16,7 por cento não contam com redes de apoio e 42,5 por cento apresentam sobrecarga alta. 70 por cento não tinham informação prévia sobre CPS. Significado: 50 por cento mencionaram "dar ajuda" (física ou emocional), 20 por cento "melhorar a qualidade de vida". 87,5 por cento desejariam ser informados com detalhe se eles fossem pacientes, 86,1 por cento quiseram ser informados pelo médico e 62,5 por cento se mostraram a favor de que fossem informados com detalhes um seu familiar. Conclusões. É importante difundir os CPS em cuidadores e estimular o direito dos pacientes em receber informação sobre o prognóstico de sua enfermidade.

Founder effect and ancestral origin of the spinocerebellar ataxia type 7 (SCA7) mutation in Mexican families.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disease characterized by progressive cerebellar ataxia and macular degeneration causing progressive blindness. It accounts for 1 to 11.6 % of spinocerebellar ataxias (SCAs) cases worldwide and for 7.4 % of SCA7 cases in Mexico. We identified a cluster of SCA7 families who resided in a circumscribed area of Veracruz and investigated whether the high incidence of the disease in this region was due to a founder effect. A total of 181 individuals from 20 families were studied. Four microsatellite markers and one SNP flanking the ATNX7 gene were genotyped and the ancestral origin and local ancestry analysis of the SCA7 mutation were evaluated. Ninety individuals from 19 families had the SCA7 mutation; all were found to share a common haplotype, suggesting that the mutation in these families originated from a common ancestor. Ancestral origin and local ancestry analysis of SCA7 showed that the chromosomal segment containing the mutation was of European origin. We here present evidence strongly suggesting that the high frequency of SCA7 in Veracruz is due to a founder effect and that the mutation is most likely of European origin with greatest resemblance to the Finnish population.