Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.

The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.

Association Between the rs1229984 Polymorphism in the Alcohol Dehydrogenase 1B Gene and Risk for Restless Legs Syndrome.

Background/Objectives: Several studies have raised the possibility of an association between alcohol consumption and the risk of developing restless legs syndrome (RLS). Moreover, an important percentage of patients under alcohol detoxification therapy develop RLS symptoms that fulfil the criteria for idiopathic RLS during alcohol withdrawal. We have aimed to establish the possible association between two common single nucleotide polymorphisms (SNPs) in the alcohol-dehydrogenase 1B (ADH1B) gene and the risk for RLS. Methods: We studied, using specific TaqMan assays, the genotype and allelic variant frequencies of ADH1B rs1229984 and ADH1B rs6413413 SNPs in 205 RLS patients and 505 gender-matched healthy controls. Results: The sum of the frequencies of rs1229984CT and rs1229984TT genotypes, as well as the frequency of the rs1229984T allelic variant, was significantly higher in RLS patients than in controls, both in the whole group and in females. The frequencies of genotypes and allelic variants of the rs6413413 SNP were similar between the two groups. RLS patients with the rs1229984CT genotype were younger, and those with the rs122984TT genotype older, at onset of RLS symptoms than those with the rs1229984CC genotype. None of the studied SNPs were related either with positivity of family history for RLS or with RLS severity. Conclusions: These results suggest an association between rs1229984 SNP and the risk for RLS.

Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome.

A recent meta-analysis suggests an association between the rs11558538 single nucleotide polymorphism in the histamine-N-methyl-transferase (HNMT) gene and the risk for Parkinson's disease. Based on the possible relationship between PD and restless legs syndrome (RLS), we tried to establish whether rs11558538 SNP is associated with the risk for RLS. We studied the genotype and allelic variant frequencies of HNMT rs11558538 SNP 205 RLS patients and 410 healthy controls using a TaqMan assay. The frequencies of the HNMT rs11558538 genotypes allelic variants were similar between RLS patients and controls, and were not influenced by gender, family history of RLS, or RLS severity. RLS patients carrying the genotype rs11558538TT had an earlier age at onset, but this finding was based on three subjects only. These results suggest a lack of major association between HNMT rs11558538 SNP and the risk for RLS.

Association Between Vitamin D Receptor rs731236 (Taq1) Polymorphism and Risk for Restless Legs Syndrome in the Spanish Caucasian Population.

Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS.We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay.The frequencies of the rs731236AA genotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P < 0.005 and < 0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS.These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.

Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs Syndrome.

Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS.We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls.The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs.The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.

Actividad asistencial neurológica en un hospital comarcal de reciente creación: modelo de alta eficiencia / Neurological health care activity in a recently created district hospital: model of high efficiency

Objetivo. Analizar la actividad asistencial de un hospital comarcal de reciente creación, con especial énfasis en los indicadores asistenciales en consultas externas y en actos médicos de pacientes ingresados. Pacientes y métodos. Describimos la actividad asistencial realizada por nuestra sección de neurología durante los años 2008-2013. Se comparan nuestros indicadores asistenciales de los años 2012 y 2013 (quinto y sexto año de actividad), tanto en consultas externas como en pacientes ingresados, con los de otros dos hospitales de características similares, otros tres de nivel secundario y otros cuatro de nivel terciario. Resultados. La sección de neurología de nuestro hospital fue la que realizó mayor número de primeras consultas por facultativo, tuvo el mejor índice de consultas sucesivas/primeras y el mayor porcentaje de consultas de alta resolución, tuvola menor estancia media en los dos grupos relacionados por el diagnóstico (GRD) más frecuentes en nuestra especialidad, y fue la segunda en ingresos por facultativo del GRD ‘ictus con infarto’ y la tercera en ingresos por facultativo del GRD ‘otros trastornos del sistema nervioso’. Conclusiones. Los indicadores asistenciales de la sección de neurología de nuestro hospital muestran un modelo de muy alta eficiencia, al cual sólo se aproximan los de otros dos de características y desarrollo similares al nuestro. La implantación gradual de modelos similares al de estos tres hospitales en los niveles secundario y terciario podría ser de utilidad en la mejora de su eficiencia asistencial (AU)

Aim. To analyze the neurological attention of a county hospital of recent creation, with a special emphasis in the health care indicators, both in hospital out-patients consultations and in patients admitted to the hospital. Patients and methods. We have made a descriptive analysis of the neurological attention developed by our Neurology Section between the years 2008 and 2013. We also made a comparative analysis of health care indicators corresponding to the years 2012 and 2013 (5th and 6th years of clinical activity) of our hospital with those of two other hospitals with similar features, other three hospitals of secondary level, and four of tertiary level. Results. The Neurology Section of our hospital was the best in the number of first visits divided by number of physicians, in the follow-up/first visit index, in the percentage of high-resolution visits, and was the best in the mean stay in hospital for the two most frequent diagnostic related groups (DRG) in our speciality, the second in number of hospital admissions divided by number of physicians for the DRG ‘stroke with infarction’ and the third in number of hospital admissions divided by number of physicians for the DRG ‘other nervous system disorders’. Conclusions. The health care indicators of the Neurology Section of our hospital showed a very high efficiency model of medical assistance, which was only followed by other two hospitals with similar features to ours. The gradual implementation of assistance models similar to that used in these hospitals in other of secondary or tertiary levels could be useful in theimprovement of their health care efficiency (AU)

[Neurological health care activity in a recently created district hospital: model of high efficiency]. / Actividad asistencial neurológica en un hospital comarcal de reciente creación: modelo de alta eficiencia.

AIM: To analyze the neurological attention of a county hospital of recent creation, with a special emphasis in the health care indicators, both in hospital out-patients consultations and in patients admitted to the hospital. PATIENTS AND METHODS: We have made a descriptive analysis of the neurological attention developed by our Neurology Section between the years 2008 and 2013. We also made a comparative analysis of health care indicators corresponding to the years 2012 and 2013 (5th and 6th years of clinical activity) of our hospital with those of two other hospitals with similar features, other three hospitals of secondary level, and four of tertiary level. RESULTS: The Neurology Section of our hospital was the best in the number of first visits divided by number of physicians, in the follow-up/first visit index, in the percentage of high-resolution visits, and was the best in the mean stay in hospital for the two most frequent diagnostic related groups (DRG) in our speciality, the second in number of hospital admissions divided by number of physicians for the DRG 'stroke with infarction' and the third in number of hospital admissions divided by number of physicians for the DRG 'other nervous system disorders'. CONCLUSIONS: The health care indicators of the Neurology Section of our hospital showed a very high efficiency model of medical assistance, which was only followed by other two hospitals with similar features to ours. The gradual implementation of assistance models similar to that used in these hospitals in other of secondary or tertiary levels could be useful in the improvement of their health care efficiency.

TITLE: Actividad asistencial neurologica en un hospital comarcal de reciente creacion: modelo de alta eficiencia.Objetivo. Analizar la actividad asistencial de un hospital comarcal de reciente creacion, con especial enfasis en los indicadores asistenciales en consultas externas y en actos medicos de pacientes ingresados. Pacientes y metodos. Describimos la actividad asistencial realizada por nuestra seccion de neurologia durante los años 2008-2013. Se comparan nuestros indicadores asistenciales de los años 2012 y 2013 (quinto y sexto año de actividad), tanto en consultas externas como en pacientes ingresados, con los de otros dos hospitales de caracteristicas similares, otros tres de nivel secundario y otros cuatro de nivel terciario. Resultados. La seccion de neurologia de nuestro hospital fue la que realizo mayor numero de primeras consultas por facultativo, tuvo el mejor indice de consultas sucesivas/primeras y el mayor porcentaje de consultas de alta resolucion, tuvo la menor estancia media en los dos grupos relacionados por el diagnostico (GRD) mas frecuentes en nuestra especialidad, y fue la segunda en ingresos por facultativo del GRD 'ictus con infarto' y la tercera en ingresos por facultativo del GRD 'otros trastornos del sistema nervioso'. Conclusiones. Los indicadores asistenciales de la seccion de neurologia de nuestro hospital muestran un modelo de muy alta eficiencia, al cual solo se aproximan los de otros dos de caracteristicas y desarrollo similares al nuestro. La implantacion gradual de modelos similares al de estos tres hospitales en los niveles secundario y terciario podria ser de utilidad en la mejora de su eficiencia asistencial.

Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome.

Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.

The solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, rs3794087 variant and assessment risk for restless legs syndrome.

OBJECTIVE: A glutamatergic dysfunction has been postulated to play a role in restless legs syndrome (RLS) pathophysiology, as glutamate concentrations have been found to increase in the thalamus of RLS patients. The aim of our study was to investigate the possible association between the single nucleotide polymorphism (SNP) rs3794087 in the solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, related with glutamate transport and the risk for RLS. METHODS: We studied the allelic and genotype frequencies of the SNP rs3794087 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. RESULTS: The rs3794087 genotype and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, and family history of RLS. CONCLUSIONS: The results of our study suggest that the rs3794087 polymorphism is not related to the risk for RLS.

MAPT1 gene rs1052553 variant is unrelated with the risk for restless legs syndrome.

Mutations in the microtubule-associated protein tau gene (MAPT) can cause frontotemporal dementia with Parkinsonism linked to the chromosome 17, and are associated with the risk for progressive supranuclear palsy, Parkinson's disease, corticobasal degeneration, and multiple system atrophy. We tried to establish, whether MAPT H1 discriminating haplotype single nucleotide polymorphisms (SNP) (rs1052553) is associated with the risk for restless legs syndrome (RLS). We studied the allelic and genotype frequencies of the SNP rs1052553 in 205 patients with RLS and 324 healthy controls using TaqMan genotyping. rs1052553 genotype and allelic frequencies did not differ significantly between patients with RLS and controls, and were unrelated with the age at onset of RLS, gender, family history of RLS, and severity of RLS. The results of the present study suggest that the SNP rs1052553 is not related with the risk for RLS.

Puntualizaciones acerca de las unidades de toxina botulínica tipo A. Réplica / No disponible

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[Treatment of severe bruxism with botulinum toxin type A]. / Tratamiento del bruxismo grave con toxina botulínica tipo A.

INTRODUCTION: The possible usefulness of botulinum toxin type A in the treatment of bruxism has not been studied exhaustively, being limited to some isolated case reports, two short case-series and a double-blind study involving a small number or patients. This article report our long-term experience in the treatment of bruxism with botulinum toxin type A. PATIENTS AND METHODS: The outcome of 19 patients with severe bruxism who underwent periodical treatment with botulinum toxin A infiltrations in both temporal and masseter muscles, using initial doses of 25 IU per muscle, during a follow-up period ranging from 0.5 to 11 years, is described. Doses were adjusted in follow-up visits according the response degree. RESULTS: None of the patients reported side-effects. Final doses ranged from 25 to 40 IU per muscle (mean: 29.7 ± 4.9 UI), and duration of the effect from 13 to 26 weeks (mean: 16.7 ± 5.1 weeks). CONCLUSION: Botulinum toxin A infiltrations are a safe and useful treatment for patients with severe bruxism.

Tratamiento del bruxismo grave con toxina botulínica tipo A / Treatment of severe bruxism with botulinum toxin type A

Introducción. La posible utilidad de la toxina botulínica tipo A en el tratamiento del bruxismo no se ha estudiado exhaustivamente, estando limitado su estudio a algunos casos aislados y a dos series cortas de casos y un estudio doble ciego con placebo en un número limitado de pacientes. Presentamos nuestra experiencia a largo plazo en el tratamiento del bruxismo con toxina botulínica tipo A. Pacientes y métodos. Se describe la evolución de 19 pacientes con bruxismo grave que fueron tratados periódicamente con infiltraciones de toxina botulínica tipo A en ambos músculos temporales y maseteros, usando dosis iniciales de 25 UI por músculo, durante períodos de seguimiento de 0,5 a 11 años. Las dosis se fueron ajustando a lo largo del seguimiento de acuerdo con el grado de respuesta observada. Resultados. Ninguno de los pacientes presentó efectos secundarios. Los rangos de dosis finales alcanzados oscilaron entre 25 a 40 UI por músculo (media: 29,7 ± 4,9 UI), y la duración de los efectos osciló entre 13 y 26 semanas (media: 16,7 ± 5,1 semanas). Conclusión. Las infiltraciones con toxina botulínica tipo A son un tratamiento seguro y eficaz para pacientes con bruxismo grave (AU)

Introduction. The possible usefulness of botulinum toxin type A in the treatment of bruxism has not been studied exhaustively, being limited to some isolated case reports, two short case-series and a double-blind study involving a small number or patients. This article report our long-term experience in the treatment of bruxism with botulinum toxin type A. Patients and methods. The outcome of 19 patients with severe bruxism who underwent periodical treatment with botulinum toxin A infiltrations in both temporal and masseter muscles, using initial doses of 25 IU per muscle, during a follow-up period ranging from 0.5 to 11 years, is described. Doses were adjusted in follow-up visits according the response degree. Results. None of the patients reported side-effects. Final doses ranged from 25 to 40 IU per muscle (mean: 29.7 ± 4.9 UI), and duration of the effect from 13 to 26 weeks (mean: 16.7 ± 5.1 weeks). Conclusion. Botulinum toxin A infiltrations are a safe and useful treatment for patients with severe bruxism (AU)

Influence of age and gender in motor performance in healthy subjects.

BACKGROUND/OBJECTIVES: Slowing of motor performance in human aging is a well demonstrated clinical observation. Information on the influence of gender in motor performance is less well-established. With the aim of analyzing the possible influence of age and gender in motor performance, we studied basic motor function in a large series of healthy sex-matched individuals aged >40 years. METHODS: We studied 246 subjects (123 males and 123 females; mean age 63.67 ± 10.79 and 63.61 ± 11.04 years, respectively), stratified by age in 7 groups for each gender. Evaluation included four timed tests (pronation-supination, finger tapping and movement between two points, all with both hands, and walking test), and the three tests performed on a personal computer (speed for pressing repetitively a key - frequency, visual reaction time and movement time, all with both hands). Statistical analysis included two-way analysis of variance (ANOVA) for two factors (age and gender) and Pearson's or Spearman's correlation tests where appropriate. RESULTS: The analysis of motor performance between subgroups showed a clear influence of age on motor performance of all the tests, with the exception of the left visual reaction time. The results of all the motor tests performed were inversely correlated with age. Gender influenced the performance (the speed of motor performance was significantly better in males) of all the tasks with the exception of left pronation-supination, and left and right visual reaction time. CONCLUSION: Our results confirm in a large series of healthy subjects that basic motor performance deteriorates with age and is influenced by gender.