Distrofia miotónica tipo 1: 13 años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo / Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation

Introducción: Se desconoce la incidencia de la distrofia miotónica tipo 1 (DM1), enfermedad con gran variedad fenotípica, en nuestra región. El objetivo de nuestro trabajo es estimar la incidencia de DM1 en nuestro centro (referencia en Aragón) e identificar las características propias de nuestra población (correlación genotipo-fenotipo). Métodos: Estudio descriptivo retrospectivo de 459 pacientes clasificados según número de repeticiones CTG en: normal (5-35), premutado (36-50), protomutado (51-80), pequeñas expansiones (81-150), intermedias (151-1.000) y grandes (> 1.000). Además, según el fenotipo mostrado, se categorizaron como: no afectos (5-50 CTG), forma leve o asintomática (51-150 CTG), clásica (151-1.000 CTG) y severa (> 1.000 CTG). Resultados: La incidencia de DM1 fue de 20,61 (IC 95%: 19,59-21,63) casos por millón de individuos-año. Se evidenció una correlación inversa entre el número de CTG y la edad al diagnóstico genético (ρ = −0,547; IC 95%: −0,610 a −0,375; p < 0,001). El CTG5 fue el alelo polimórfico más frecuente en sanos. Del total de afectos, el 28,3% presentaron la forma leve o asintomática, el 59,1% la forma clásica y el 12,6% la forma severa. El 35,1% presentaron herencia materna, el 59,4% herencia paterna y el 5,5% herencia incierta. En las formas leves la calvicie frontal en varones fue el rasgo fenotípico más prevalente, junto con miotonía y cataratas, mientras que en la clásica predominó la ptosis palpebral, la debilidad facial, las alteraciones en la voz y la pronunciación, la miotonía y la sensación de cansancio/somnolencia. Conclusiones: La incidencia de DM1 es relevante en Aragón. La revisión multidisciplinar del fenotipo de pacientes con DM1 es clave para un diagnóstico precoz y medicina personalizada.(AU)

Introduction: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). Methods: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). Results: The incidence of DM1 was 20.61 cases per million person-years (95% CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = −0.547; 95% CI: −0.610 to −0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. Conclusions: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.(AU)

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation.

INTRODUCTION: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = -0.547; 95% CI, -0.610 to -0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Myotonic dystrophy type1: 13years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation. / Distrofia miotónica tipo1: 13años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo.

INTRODUCTION: The incidence of myotonic dystrophy type1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (>1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (>1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95%CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ=-0.547; 95%CI: -0.610 to -0.375; P<.001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

[Uncommon case of Mycobacterium bovis brain abscess complicated by suppurative fistula]. / Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa.

TITLE: Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa.

[The importance of chronic migraine in a general neurology service]. / Importancia de la migraña crónica en una consulta general de neurología.

INTRODUCTION: Chronic migraine is a primary headache that is difficult to treat and has an important impact on the patient's quality of life. The international headache classification recently modified the criteria for chronic migraine and therefore few studies have been conducted that analyse groups according to these new criteria. AIM. To analyse a group of patients with chronic migraine who were referred to a general neurology service. PATIENTS AND METHODS: The first 100 patients with migraine were selected. Researchers established and analysed a number of subgroups of patients with episodic, chronic or chronic migraine with probable headache due to medication abuse, in accordance with the International Headache Society (IHS) headache classification and its revised version from 2006. RESULTS: Of the total sample of 738 new patients, 100 (13.5%) suffered from migraines and of these 100 new patients with migraine 42 (5.6% of the total series) satisfied criteria for chronic migraine and 15 patients with chronic migraine met the criteria for probable headache due to medication abuse. Before visiting the neurology service, only 41% had been diagnosed as suffering from migraine, 38% had received no information about this condition, only 17% took triptans for symptomatic relief and 23% had followed some kind of preventive treatment. CONCLUSIONS: One notable finding was the importance of episodic and chronic migraine in a general neurology service, on applying the recent IHS criteria. A high percentage of patients with chronic migraine who were referred to the neurology service have not been diagnosed or given any information or proper treatment; an elevated degree of self-medication and medication abuse also exists. Preventive treatment and triptans in cases of intense migraines are still not commonly used in primary care.

Importancia de la migraña crónica en una consulta general de neurología / The importance of chronic migraine in a general neurology service

La migraña crónica es una cefalea primaria difícil de tratar que produce gran afectación de la calidadde vida del paciente. La clasificación internacional de cefaleas modificó los criterios de migraña crónica recientemente, por lo que existen pocos trabajos que analicen grupos con estos nuevos criterios. Objetivo. Analizar un grupo de pacientes con migrañacrónica remitidos a una consulta de neurología general. Pacientes y métodos. Se seleccionaron los primeros 100 pacientes con migraña. Se establecieron y analizaron subgrupos de pacientes con migraña episódica, crónica o crónica con probable cefalea por abuso de fármacos según la clasificación de cefaleas de la Sociedad Internacional de Cefaleas (IHS) y su revisión delaño 2006. Resultados. Del total de 738 nuevos pacientes, 100 (13,5%) sufrieron migrañas. De estos 100 nuevos pacientes con migraña, 42 (el 5,6% de la serie total) cumplieron los criterios de migraña crónica, y 15 pacientes con migraña crónica, los criteriosde probable cefalea por abuso de fármacos. Antes de acudir a la consulta de neurología, sólo al 41% se le había diagnosticado migraña, un 38% no había recibido información sobre esta entidad, sólo el 17% tomaba triptanes como tratamiento sintomático,y un 23% había seguido tratamiento preventivo. Conclusiones. Destacamos la importancia de la migraña episódica y crónica en una consulta general de neurología, aplicando los criterios recientes de la IHS. Los pacientes con migraña crónica enviados a la consulta de neurología siguen, en un alto porcentaje, sin haber sido diagnosticados, ni informados, ni tratados correctamente, con un alto grado de automedicación y abuso frecuente de fármacos. Los tratamientos preventivos y triptanes en migrañasintensas se siguen utilizando poco en atención primaria (AU)

Chronic migraine is a primary headache that is difficult to treat and has an important impact on the patient’s quality of life. The international headache classification recently modified the criteria for chronic migraine and therefore few studies have been conducted that analyse groups according to these new criteria. Aim. To analyse a group of patients with chronic migraine who were referred to a general neurology service. Patients and methods. The first 100 patients with migraine were selected. Researchers established and analysed a number of subgroups of patients with episodic, chronic or chronic migraine with probable headache due to medication abuse, in accordance with the International Headache Society (IHS) headache classification and its revised version from 2006. Results. Of the total sample of 738 new patients, 100 (13.5%) suffered from migraines and of these 100 new patients with migraine 42 (5.6% of the total series) satisfied criteria for chronic migraine and 15 patients with chronic migraine met the criteria for probable headache due to medication abuse. Before visiting the neurology service, only 41% had been diagnosed as suffering from migraine, 38% had received no information about this condition, only 17% took triptans for symptomatic relief and 23% had followed some kind of preventive treatment.Conclusions. One notable finding was the importance of episodic and chronic migraine in a general neurology service, on applying the recent IHS criteria. A high percentage of patients with chronic migraine who were referred to the neurology service have not been diagnosed or given any information or proper treatment; an elevated degree of self-medication and medication abuse also exists. Preventive treatment and triptans in cases of intense migraines are still not commonly used in primary care (AU)

[Magnetic resonance imaging with spectroscopy, perfusion and cerebral diffusion in the diagnosis of brain tumours]. / Resonancia magnética con espectroscopia, perfusión y difusión cerebral en el diagnóstico de los tumores cerebrales.

AIM: We review three of the most important functional techniques in magnetic resonance imaging, it means spectroscopy, perfusion and diffusion; we do emphasize in its applications, particularly in the diagnostic and treatment of brain tumors. First, we discuss the physical principles and results interpretation of each technique. After that, we discuss its major applications. DEVELOPMENT AND CONCLUSIONS: Choline containing compounds using contralateral creatine and choline for normalization or ipsilateral N-acetyl-aspartate appeared to correlate best with the degree of tumor infiltration, regardless o tumor histological grade. Magnetic resonance spectroscopy imaging (MRSI) seems more accurate than conventional magnetic resonance imaging (MRI) in defining indistinct tumor boundaries and quantifying the degree of tumor infiltration. MRSI is the choice of site within a lesion for biopsy and use in image-guided therapy, including definition of radiation ports. Angiogenesis, and increased vascular permeability, are characteristic of cerebral neoplasms; these processes can be imaged using perfusion MRI. Most commonly, tumor perfusion is measured using rapid gradient T2-weighted imaging during bolus injection of gadolinium dimeglumine gadopentetate. Care has to be taken to avoid blood-brain barrier leakage affecting perfusion results. Pharmacokinetic models are available for estimation of blood-brain permeability. Cerebral blood volume increases with tumor grade, and maybe helpful in identifying tumor recurrence, and peri-tumoral edema, and distinguishing malignant from benign lesions.

Resonancia magnética con espectroscopia, perfusión y difusión cerebral en el diagnóstico de los tumores cerebrales / Magnetic resonance imaging with spectroscopy, perfusion and cerebral diffusion in the diagnosis of brain tumours

Objetivo. Se revisan las técnicas de espectroscopia, perfusión y difusión por resonancia magnética (RM), haciendo particular énfasis en sus aplicaciones para el diagnóstico y tratamiento de los tumores cerebrales. Se discuten los principios físicos de cada técnica y el significado e interpretación de sus resultados, dejando en última instancia sus principales aplicaciones. Desarrollo y conclusiones. Las lesiones que contienen colina relacionadas con la creatina y con la colina del hemisferio contralateral, así como el N-acetil-aspartato ipsilateral, tienen buena correlación con el grado de infiltración o grado histológico tumoral. La espectroscopia por RM es más precisa que la RM convencional para definir los márgenes tumorales y cuantificar el grado de infiltración tumoral. La espectroscopia por RM está indicada para seleccionar el lugar donde se debe realizar la biopsia o biopsia estereotáxica, así como para definir la zona a irradiar. La angiogénesis y el incremento dela permeabilidad vascular son característicos de las neoplasias cerebrales; esto se puede reproducir con la utilización de la perfusión por RM. Habitualmente, la perfusión tumoral se mide usando imágenes rápidas en gradiente T2 durante el paso de un bolo de contraste paramagnético intravenoso. Los resultados pueden verse afectados si existe una ruptura de la barrera hematoencefálica. Pueden utilizarse modelos farmacocinéticos para estimar la permeabilidad de la barrera. El volumen sanguíneo cerebral se incrementa con el grado tumoral, pudiendo servir de ayuda para identifica recidivas tumorales o el edema perilesional y diferenciar lesiones malignas de benignas (AU)

Aim. We review three of the most important functional techniques in magnetic resonance imaging, it means spectroscopy, perfusion and diffusion; we do emphasize in its applications, particularly in the diagnostic and treatment of brain tumors. First, we discuss the physical principles and results interpretation of each technique. After that, we discuss its major applications. Development and conclusions. Choline containing compounds using contralateral creatine and choline for normalization or ipsilateral N-acetyl-aspartate appeared to correlate best with the degree of tumor infiltration, regardless o tumor histological grade. Magnetic resonance spectroscopy imaging (MRSI) seems more accurate than conventional magnetic resonance imaging (MRI) in defining indistinct tumor boundaries and quantifying the degree of tumor infiltration. MRSI is the choice of site within a lesion for biopsy and use in image-guided therapy, including definition of radiation ports. Angiogenesis,and increased vascular permeability, are characteristic of cerebral neoplasms; these processes can be imaged using perfusion MRI. Most commonly, tumor perfusion is measured using rapid gradient T2-weighted imaging during bolus injection ofgadolinium dimeglumine gadopentetate. Care has to be taken to avoid blood-brain barrier leakage affecting perfusion results. Pharmacokinetic models are available for estimation of blood-brain permeability. Cerebral blood volume increases with tumor grade, and maybe helpful in identifying tumor recurrence, and peri-tumoral edema, and distinguishing malignant from benign lesions (AU)

Silent brain infarctions in patients with coronary heart disease. A Spanish population survey.

Coronary artery disease is a recognized risk factor for symptomatic ischaemic stroke but the influence on asymptomatic stroke has not been clearly determined. The purpose of this work was to determine the relationship between coronary heart disease and silent brain infarcts and the influence of vascular risk factors and carotid atherosclerosis in a representative sample of Spanish patients with symptomatic coronary artery disease. A consecutive sample of 100 subjects with myocardial infarction, angina or both were included in the survey. Patients with a potential source of emboli from the heart were excluded. As main baseline variables, we considered vascular risk factors; complete cardiological study, including coronary angiography; brain computed tomography (CT) to detect infarcts; echo-Doppler of supra-aortic vessels to detect stenosis; and carotid angiography, when appropriate. As the outcome variable, we observed the incidence of symptomatic stroke after an 18 month mean follow-up. We found silent brain infarction in 30 patients (93% were of lacunar type). None of the vascular risk factors was related to brain infarcts either in univariate or multivariate analysis. Carotid atherosclerosis was the only significant predictor in a model of logistic regression (P < 0.0005), although the lesions were bilateral in the majority of cases. We observed a very low incidence of symptomatic stroke after a mean follow-up of 18 months. Silent brain infarcts are a frequent finding on brain CT in patients with coronary heart disease and are associated with carotid atherosclerosis; however, it does not seem to have important prognostic significance.

Prevalence of multiple sclerosis in the province of Teruel, Spain.

There have been few reports about the frequency of multiple sclerosis (MS) in Spain. We undertook a prevalence study in the province of Teruel, which is served by two hospitals as referral centres for a population of 143,680. We found a total of 46 patients who fulfilled Poser's criteria for clinically definite or probable MS with a prevalence rate of 32/100,000 [95% confidence interval (CI): 22.8-41.3]. The prevalence rates for males and females were 23.5 (95% CI: 12.3-34.7) and 40.6 (95% CI: 25.8-55.4) respectively. We found an incidence rate of 2.2/year per 100,000 in the last 5 years. The sex ratio (females/males) was 1.7. The mean age on prevalence day was 40.6 years (range: 15-76). The clinical course was relapsing-remitting in 82% of patients, progressive in 9% and secondary progressive in the other 9%. The mean EDSS score was 3.73 (range: 1-8.5). Our results confirm the hypothesis that Spain is an area at high risk for MS.

Comparative study of aprosody in Alzheimer's disease and in multi-infarct dementia.

Prosody is defined as the melodic line of language. In this study we included 25 patients with probable Alzheimer's disease and 14 with multi-infarct dementia for a comparative cross-sectional study of prosody. Neuropsychological analysis was based on Mini-Mental test, Blessed Scale and Clinical Dementia Rating. We used the criteria of Monrad-Krohn to evaluate prosodic categories. We found intrinsic aprosody in 8 patients with Alzheimer's disease and in none of the patients with multi-infarct dementia (prevalence ratio: 1.82, 95% CI: 1.32-2.51), and emotional aprosody in 17 patients with Alzheimer's disease in comparison to 4 with multi-infarct dementia (prevalence ratio: 1.8, 95% CI: 1.04-3.18). The differences in intellectual and inarticulate aprosody were not significant. We conclude that aprosody is more frequent and severe in Alzheimer's disease than in multi-infarct dementia.

[Binswanger's disease and its relationship with vascular risk factors]. / Leucoaraiosis y su relación con los factores de riesgo vascular.

INTRODUCTION: Lesions in the periventricular white matter are a quite common neuroradiological finding in older patients. They are called leukoaraiosis and can be associated to several syndromes. OBJECTIVE: To study the relation between leukoaraiosis and the different vascular risk factors that can be involved in its development. METHOD: Fifty consecutive patients with leukoaraiosis in CT scan were included as well as fifty age and sex-matched controls; all of them belonged to the same population. Previously vascular risk factors were defined according to strict criteria. RESULTS: The commonest vascular risk factor was arterial hypertension, in second place previous cerebrovascular accidents and in third place heart diseases. There was a very significant difference for hypertension in the univariant analysis, which was subsequently confirmed in the multivariant analysis. CONCLUSIONS: The vascular risk factor most strongly associated to leukoaraiosis was arterial hypertension followed by cerebrovascular disease and heart diseases. The remaining of the analysed factors had a insignificant prediction power.

[Emotional components of language in multi-infarct dementia]. / Estudio de los componentes emocionales del lenguaje en la demencia multiinfarto.

BACKGROUND: Prosody is the faculty of language by which different meanings may be referred through variations in the tone, rhythm and accent with independence of the words and grammatical structures. Alteration of this sphere may modify the emotional components and proposals of the language. The aim of this study was to evaluate the existence of aprosody in a series of patients with multiinfartion dementia, quantify the disorder and ascertain the factors to which it is related. METHODS: Fourteen patients with criteria of multiinfarction dementia were included in the study. Aprosody was evaluated according to the Monrad-Krohn criteria. Neuropsychological examination included the MiniMental State Examination, the Blessed scale and the Hachinshi ischemic scale. RESULTS: Changes were seen in the prosody of 13 patients. Upon univariant statistical analysis a significant correlation was observed between the grade of alteration in prosody and the deterioration observed in the MiniMental and Blessed scale. This finding was confirmed following correction of the influence of depressive symptoms, age and time of evolution by multivariant analysis. CONCLUSIONS: The disturbances in prosody are a sensitive indicator of right hemisphere lesion in vascular dementia and are fundamentally related with the degree of neuropsychological deterioration.

[Cognitive functions in agenesis of the corpus callosum]. / Estudio de las funciones superiores en la agenesia del cuerpo calloso.

Four patients with agenesis of the corpus callosum diagnosed through neuroradiologic tests has been studied, from the upper cerebral functions point of view. Three had consulted because of seizure, and the other because of cerebellar hemorrhage. Multiple fields of the cognitive functions were examined and the presence of an interhemispheric disconnection syndrome was investigated. All tests were absolutely normal in the four patients. We discuss clinical and radiologic aspects as well as other associated malformations.