Epidemiology and molecular characterization of adult genetic myopathies in a southeastern region of Spain. / Epidemiología y caracterización molecular de las miopatías genéticas en adultos en una región del sureste de España.

INTRODUCTION: Genetic myopathies constitute a collection of rare diseases that significantly impact patient functionality and quality of life. Early diagnosis of genetic myopathies can prevent future complications and provide families with genetic counselling. Despite the substantial impact of genetic myopathies on the adult population, the global epidemiology of these disorders is inadequately addressed in the literature. AIMS: To enhance understanding of both the epidemiology and genetics of these disorders within the province of Alicante, situated in southeastern Spain. MATERIAL AND METHODS: Between 2020 and 2022, a prospective observational study was conducted at the Alicante Health Area-General Hospital, enrolling patients aged 16 years or older with suspected genetic myopathies. Sociodemographic, clinical, and genetic data were collected. The reference date for prevalence calculation was established as December 31, 2022. Official demographic data of the health area were used to set the population at risk. RESULTS: In total, 83 patients were identified with confirmed genetically related myopathy, resulting in an overall prevalence of 29.59 cases per 100,000 inhabitants. The diagnostic yield for molecular genetic testing was found to be 69.16%. The most prevalent genetic myopathies identified included myotonic dystrophy (27.5%), dystrophinopathies (15.7%), and facioscapulohumeral dystrophy (15.7%). CONCLUSION: The prevalence of GMs can vary considerably depending on the geographical region and the studied population. The analysis of diagnostic yield suggests that genetic studies should be considered useful in the diagnosis of genetic myopathies.

TITLE: Epidemiología y caracterización molecular de las miopatías genéticas en adultos en una región del sureste de España.Introducción. Las miopatías genéticas constituyen un conjunto de enfermedades raras que impactan significativamente en la funcionalidad y la calidad de vida del paciente. Un diagnóstico temprano de las miopatías genéticas puede prevenir complicaciones futuras y proporcionar a las familias asesoramiento genético. A pesar del impacto sustancial de las miopatías genéticas en población adulta, la epidemiología global de estos trastornos está inadecuadamente abordada en la bibliografía. Objetivos. Mejorar el entendimiento tanto de la epidemiología como de la genética de estos trastornos en la provincia de Alicante, situada en el sureste de España. Material y métodos. Entre 2020 y 2022, se llevó a cabo un estudio observacional prospectivo en el área de salud Alicante-Hospital General, que incluyó a pacientes de 16 años o más con sospecha de miopatías genéticas. Se recopilaron datos sociodemográficos, clínicos y genéticos. La fecha de referencia para el cálculo de la prevalencia se estableció el 31 de diciembre de 2022. Se utilizaron datos demográficos oficiales del área de salud para establecer la población en riesgo. Resultados. En total, se identificó a 83 pacientes con miopatía genéticamente confirmada, lo que dio lugar a una prevalencia total de 29,59 casos por cada 100.000 habitantes. El rendimiento diagnóstico de las pruebas genéticas moleculares fue del 69,16%. Las miopatías genéticas más frecuentes incluyeron la distrofia miotónica (27,5%), las distrofinopatías (15,7%) y la distrofia facioescapulohumeral (15,7%). Conclusión. La prevalencia de las miopatías genéticas puede variar considerablemente dependiendo de la región geográfica y la población estudiada. El análisis del rendimiento diagnóstico sugiere que los estudios genéticos deberían considerarse útiles en el diagnóstico de las miopatías genéticas.

[Drug exposure associated with exacerbation of symptoms in patients with myasthenia gravis]. / Exposición a fármacos asociados a agravamiento de síntomas en pacientes con miastenia grave.

INTRODUCTION: Numerous drugs have been related to exacerbation of myasthenia gravis. So far there are no studies examining the extent of use of drugs related to exacerbation of myasthenia gravis. AIMS: We sought to assess the extent of use of drugs related to exacerbations and the annual incidence rate of exacerbations in a cohort of myasthenia gravis patients. We explored possible risk factors of severe exacerbations. PATIENTS AND METHODS: We performed a retrospective cohort study. We included adult patients followed in neurology department. We estimated frequencies, rates and built a recurrent events model. RESULTS: We included 91 patients. 94.51% of patients had at least one prescription of a drug. 51 patients had at least one prescription of a drug contraindicated according to its drug label. 145 exacerbation episodes were reported in 50 patients. The annual incidence rate of exacerbation episodes was 0.35. 48 exacerbations were severe (in 18 patients). The annual incidence rate of severe exacerbation episodes was 0.12. Generalized myasthenia gravis and thymectomy were associated with a higher risk of severe exacerbation episodes. CONCLUSIONS: Our patients were extensive and widespread exposed to drugs during the follow-up period but we did not find and association with severe exacerbation episodes. Just over half of the patients had at least one exacerbation episode during the study period, most of them were mild. Further studies with larger sample sizes are necessary to corroborate these conclusions and to study possible correlations between the use of drugs and the risk of exacerbation episodes.

TITLE: Exposición a fármacos asociados a agravamiento de síntomas en pacientes con miastenia grave.Introducción. Numerosos fármacos se han relacionado con el agravamiento de síntomas en pacientes con miastenia grave, pero hasta la fecha no existen estudios sobre la exposición a fármacos en estos pacientes. Objetivos. Describir el consumo de fármacos y calcular la tasa anual de episodios de exacerbación en una cohorte de pacientes con miastenia grave, y explorar posibles factores de riesgo de exacerbaciones graves. Pacientes y métodos. Estudio observacional longitudinal retrospectivo que incluye a pacientes adultos con miastenia grave seguidos en consulta. Cálculo de frecuencias, tasas y construcción de modelo de eventos repetidos. Resultados. De 91 pacientes incluidos, el 94,51% estuvo expuesto al menos a un fármaco durante el período de estudio (siete años y un mes). De ellos, 51 tuvieron al menos una prescripción de un fármaco contraindicado en la ficha técnica (56,04%). Se contabilizaron 145 exacerbaciones en 50 pacientes. La tasa anual de incidencia fue de 0,35 exacerbaciones por paciente y año. De estas exacerbaciones, 48 fueron graves (en 18 pacientes), con una tasa anual de incidencia de 0,12. Se halló una posible asociación entre diagnóstico de miastenia grave generalizada y timectomía, con un aumento del riesgo de episodios de exacerbación graves. Conclusiones. En esta cohorte se encontró una amplia exposición a fármacos, pero no asociación con el riesgo de episodios de exacerbación graves. Algo más de la mitad de pacientes tuvo al menos un episodio de exacerbación durante el período de estudio, la mayoría leves. Son necesarios estudios que corroboren estas conclusiones y puedan estudiar posibles correlaciones entre fármacos y el riesgo de episodios de exacerbación.

[Multiple mononeuropathy associated to treatment with pravastatin]. / Mononeuropatía múltiple asociada a tratamiento con pravastatina.

INTRODUCTION: The first reports of neuropathy due to treatment with statins appeared in 1994, although it is an infrequent complication. It usually consists of an axonal polyneuropathy, which is predominantly sensory, distal and symmetric, and may be subacute or chronic. We present here the second case reported in the literature of multiple mononeuropathy associated to the use of statins. CASE REPORT: A 51-year-old female patient who, after beginning therapy with pravastatin, presented with progressive, asymmetrically distributed, distal paresthesias in the limbs and an unstable gait. An electromyographic study was compatible with multiple mononeuritis. Results of complementary tests that were carried out to preclude other causes of multiple mononeuropathy were normal. The patient's condition improved on withdrawing treatment with the drug and it became worse again when therapy was restarted. When pravastatin therapy was stopped for good, the patient's condition progressively improved until she was practically free of symptoms. CONCLUSIONS: The relationship between treatment with statins and the appearance of polyneuropathy has been proved in different epidemiological case-control studies. It does not only appear as the classical distal symmetrical polyneuropathy, but has also been reported as taking on atypical clinical forms including a few cases, like ours, of multiple mononeuropathy. The risk of developing this complication is low and is offset by the cardiovascular benefits offered by statins, although it may become more common in the future due to the increasing rate of use of these agents. It is important to bear this cause of neuropathy in mind, given the fact that it is potentially reversible.

[Multifocal encephalitis as a neurological manifestation of COVID-19 infection]. / Encefalitis multifocal como manifestación neurológica de la infección por COVID-19.

TITLE: Encefalitis multifocal como manifestación neurológica de la infección por COVID-19.

[Stroke in young people]. / Enfermedad cerebrovascular en jóvenes.

We retrospectively studied 75 consecutive patients with acute stroke. They made up 3.7% of all acute cerebrovascular pathologies. Average age of patients was 37.45 (SD 7.37) and the number of men exceeded women at a ratio of 1.8:1 73% had ischaemic pathology. Those risk factors most often found were tobacco and alcohol consumption and migraine. The most frequent causes were arteriosclerosis and cardioembolism. Etiological diagnosis was not reached in a third of cases. Most patients were treated with antiagregants with aspirin being the most used at a dose of about 200 mg per day. Initial death rate was 4% and more than 60% of patients were asymptomatic or with minimal deficiencies upon discharge.

[Ambulatory neurological care in the Marina Baixa area, Alicante]. / Asistencia neurológica ambulatoria en el área de la Marina Baixa, Alicante.

INTRODUCTION: The demand for neurological care depends on the type of population to be attended, among other variables. The Marina Baixa area, which includes towns such as Altea and Benidorm, has its own peculiar characteristics due to its being one of the places that is often chosen by pensioners from northern and central Spain and Europe to set up residence. AIM: The aim of this study was to determine the characteristics of the ambulatory neurological care in our health area. PATIENTS AND METHODS: Data on 1,000 patients attended in the Neurological Clinic at the Specialty Centre in Benidorm (age, sex, reason for visit, tests requested and destination on discharge) were recorded prospectively and consecutively. RESULTS: The mean age was 58.04 years (range 14-94) and 56.4% were females. 25% of the patients attended were over 75 years old. The main reasons for visiting were headache (28.2%) and cognitive impairment (21%). 26.5% were first-time visits, with a mean age of 55.02 years, which is significantly lower than that of the review patients (59.12 years; p = 0.003). 15.6% of the patients were discharged from hospital. A prolonged follow-up was foreseen for over 50% of them. The demand for care in 2003 was 27.5 per 1,000 inhabitants/year in the population above the age of 14 years. CONCLUSIONS: The higher the mean age of the population is, the greater the prevalence of neurodegenerative diseases will become and the more demand there will be for ambulatory care. Resources must be adjusted to this new situation and there is also a need to adopt the most suitable model of health care for chronic neurological patients.

[Analytical epidemiological study of multiple sclerosis in Alcoi]. / Estudio epidemiológico analítico sobre la esclerosis múltiple en Alcoi.

INTRODUCTION: Multiple sclerosis (MS) is a disease of controversial epidemiology, which has frequently been studied. The results of an epidemiological descriptive study in the Alcoi area led to a first case-control study to give information about the factors associated with the illness in this area. It was seen from this that migration, contact with dogs and with cloth might be related to it. OBJECTIVE: To carry out a second analytical study, maintaining the migration factor stable to avoid the possible confounding effect with other associated factors. MATERIAL AND METHODS: For this case-control study we grouped one case with four controls from the population according to age, sex and place of birth. All cases fulfilled criteria defined for MS and the controls were randomly selected from the census. We also classified the cases and controls into three groups, according to whether or not migration was involved (group A: Autochthonous; group B: Immigrants who arrived before the age of 13, and group C: Immigrants who arrived after the age of 13). RESULTS: We analyzed 40 patients and 160 controls. We obtained significant values for 'social group'. The cases belonged to the less favored social group both on overall analysis and in the autochthonous group. Pneumonia was the only infection with significant figures in patients over 15. Contact with dogs gave new statistically significant figures, together with cloth and cloth products. CONCLUSIONS: Persistence of positive correlation of MS with contact with dogs and cloth suggest the possible influence of these two factors in the increase in incidence of MS in this area.

[Validity and reliability of the migraine self-questionnaire Alcoi-1995]. / Validez y fiabilidad del autocuestionario para migraña 'Alcoi-1995'.

INTRODUCTION: In epidemiological investigation valid, reliable means of diagnosing the illnesses studies are essential. OBJECTIVE: To validate the self-questionnaire 'Alcoi 1995' for the diagnosis of migraine. METHODS: We used the questionnaire Alcoi-1992 (which had been validated previously) to find the prevalence of migraine in homogeneous populations. After this, we selected the significant items to obtain a shorter, more specific questionnaire for diagnosis of migraine, which we called 'Alcoi 1995'. We selected a population of patients and healthy volunteers. The diagnosis of migraine (neurologist and self-questionnaire) was made on criteria of the International Headache Society (IHS, 1988). RESULTS: There were 71 persons included in the study, 40 patients (5 men and 35 women those average age was 39.7 +/- 14.4 years) and 31 healthy volunteers (15 men and 16 women with an average age of 36 +/- 14.4). The sensitivity, specificity, positive and negative predictive value, and the Kappa concordance index for migraine (100%, 100%, 100%, 100% and 1); migraine with no aura (75%, 100%, 100%, 86% and 0.79) and migraine with a typical aura (100%, 88%, 63%, 100% and 0.71) were calculated. CONCLUSIONS: Our results show a high degree of validity and reliability when the self-questionnaire is used for the diagnosis of migraine. It is a tool for use in epidemiological studies which is quick and easy to use, and is cheap.

[Atherosclerosis and brain circulation]. / Aterosclerosis y circulación cerebral.

INTRODUCTION: Atherosclerosis affects the vascular system in a diffuse way and its is clearly implicated in some of the most prevalent diseases in western countries such as cerebrovascular and cardiovascular diseases. Knowing more about the underlying pathogenic mechanisms may contribute to a better understanding of this entities and the development of therapies for both its treatment and prevention. DEVELOPMENT: We review herein the concepts included in the term atherosclerosis, the growth of the atheromatous plaque and its complications and the cellular mechanisms which intervene in its development. We analyze how it influences brain hemodynamics and its implication in cerebrovascular ischemic disease paying attention to the dissimilarities with other vascular territories and the clinical syndromes which derive from its development on different vascular structures. CONCLUSIONS: Under the concept of ischemic cerebrovascular disease we can find a group of heterogeneous clinical syndromes, usually associated to different etiopathogenic mechanisms: cardioembolic, atherothrombotic or hemodynamic. Although their risk factors may be common, these processes are clearly different form each other. Therefore including ischemic brain infarctions all together without attending to their etiology may produce important methodological biases when interpreting the results in clinical trials or other studies, and may also be a suitable explanation for differences between authors.

[A control and case study of multiple sclerosis in the Alicante and Villajoyosa areas]. / Estudio de casos y controles sobre la esclerosis múltiple en las áreas de Alicante y Villajoyosa.

INTRODUCTION: Three studies have been carried out in the area of Alcoy (Spain) which show an association between contact with dogs and multiple sclerosis. We present a control and case study conducted in a different geographical area, the area of Alicante. AIMS. To examine environmental factors linked with multiple sclerosis in the health care district of Alicante, and to compare findings with those from the health care district of Alcoy. PATIENTS AND METHODS: A study of cases and controls was conducted with 47 patients, each of which was paired with four controls according to gender, age and place of residence. All the cases fulfilled criteria of defined multiple sclerosis. The controls were obtained from the Emergency and Casualty Services at different hospitals in the area. Each of the environmental factors studied was stratified by genders. RESULTS: A total of 47 patients and 188 controls were analysed. A statistically significant association was found between the disease and smoking, a low educational level, a social level 2 on the classification developed by Koch Henriksen, having had measles before the age of 15 and contact with dogs. The fact of being the third, or later, child in a family and a family history of cephalea were more frequent among controls than among cases. CONCLUSIONS: Multiple sclerosis in the Alicante area is related with contact with dogs, smoking, a low educational level, a high social level and measles before the age of 15. Since an association between contact with dogs and multiple sclerosis has been shown repeatedly in other previous studies conducted in the town of Alcoy, we are now in a position to state that this factor is indeed linked with the appearance of multiple sclerosis.

[The epidemiology of multiples sclerosis in Alcoi. Analytical data]. / Epidemiología de la esclerosis múltiple en Alcoi. Datos analíticos.

INTRODUCTION: The epidemiology of multiple sclerosis (ME) in the Alcoi area has been studied by our groups for many years. When studying the factors linked to ME in this area initially we observed that migration, contact with dogs and the textile industry were associated with the disorder. A later study, in which the migration factor was controlled, still showed a significant association with contact with dogs and the textile industry. OBJECTIVE: To make an analytical study avoiding the possible confusing effect of contact with the textile industry, since this may be associated with other factors. We also compared the results of previous studies. PATIENTS AND METHODS: We made a case control study in which each case was paired with four controls for age, sex and having worked or not worked in the textile industry. The cases fulfilled the criteria for diagnosis of ME. The control patients came from the Emergency and Trauma Departments of Alcoi hospital. RESULTS. We analyzed 37 patients and 148 controls. Significant values were obtained for smoking, low social class, chickenpox and measles infections when aged under 15 years, pneumonia when aged over 15 years and contact with dogs, sheep and dissolvents. CONCLUSIONS: Contact with dogs was associated with multiple sclerosis in all the studies carried out in the Alcoi area to date. This is therefore a risk factor for the disorder in the Alcoi population.

[Prevalence of migraine in a homogeneous population using the self-questionnaire 'Alcoi-1995']. / Prevalencia de migraña en una población homogénea utilizando el autocuestionario 'Alcoi-1995'.

INTRODUCTION: There are numerous studies of the prevalence of migraine and very varied findings. Amongst the many reasons for this would seem to be the use of questionnaires for screening populations, absent or incorrect validation of these questionnaires and the use of impracticable diagnostic criteria. OBJECTIVE: To determine the prevalence of migraine in a homogeneous population using the self-questionnaire 'Alcoi 1995' which had previously been validated for the diagnosis of migraine. A self-questionnaire was given to all workers in the same company. Diagnostic criteria of the International Headache Society (IHS, 1988) were used for diagnosis of migraine. RESULTS: The study included 140 persons (43.6% men and 56.4% women with an average age of 26.7 +/- 4.8 years). There was a prevalence of headache and migraine (IC 95%): 90.8% (75.01-100) and 24.3% (16.3-32.3) respectively. The sex prevalence of headache and migraine was 88.5% (88.3-88.8) and 11.5% (3.4-19.4) for men and 34.2% (21.5-47) for women respectively. CONCLUSIONS: There are a large number of studies of the prevalence of migraine with wide variability in the figures obtained (1-2 at 35%). These variations depend on the population studied, age and sex sampled, diagnostic criteria used and the method employed in the survey. After validation of the questionnaire for diagnosis of migraine, this should be used in homogeneous populations before use in broad population studies. Our findings support the use of a suitably validated questionnaire as a useful method for the diagnosis of migraine in epidemiological studies.

[A case-control study of multiple sclerosis in Alcoi]. / Estudio caso-control sobre la esclerosis múltiple en Alcoi.

INTRODUCTION: Multiple sclerosis (EM) is a neurological disorder of great epidemiological interest. Considerable variations have been described regarding the initial description of geographical distribution. In the Alcoi health district an epidemiological study showed more cases than would be expected from the latitude. Objective. To care out an analytical study to determine which factors influence this situation. MATERIAL AND METHODS: We carried out a case-control study, pairing one case with four controls from the population, as regards age, sex and place of residence. Only current cases were included, under the control of the only Neurology Unit in the area, and which fulfilled criteria defined by EM. The control group was randomly selected from the census. RESULTS: We analyzed 37 patients and 148 controls. There were no significant differences between the cases and the controls regarding socio-educational level, order of birth within the family, blood group, toxic habits and family history. We found a significantly greater frequency of urinary infections before the age of 15, and of cystitis and pneumonia after reaching the age of 15. Contact with textiles, their finished products and dogs reached significant values. In the patient group there was a significantly higher number of immigrants than in the control group. CONCLUSIONS: The correlation found between certain factors such as contact with textiles, their finished products and dogs should be evaluated in further studies in which the immigration factor is controlled.

[Evaluation of hemodynamic parameters by transcranial Doppler in patients with leukoaraiosis]. / Estudio de los parámetros hemodinámicos en pacientes con leucoaraiosis mediante Doppler transcraneal.

INTRODUCTION: Leukoaraiosis is commonly found in neuroimaging in ancient people. The pathogenic theory that most suitably explains its origin is the vascular one, mainly linked to cerebral hemodynamic abnormalities. The techniques most frequently used in cerebral hemodynamic evaluation (PET and SPECT) are expensive and not widespread. Transcranial Doppler instead is cheaper and much more widespread. OBJECTIVE: Our aim has been to show whether transcranial Doppler is a useful tool for cerebral hemodynamic evaluation in leukoaraiosis. PATIENTS AND METHODS: We have prospectively included 116 patients aged 60-90 who came to the Neurology department with unspecific complaints such as dizziness or mild headache. Patients with recent history of stroke or moderate to severe cognitive impairment were excluded. RESULTS: Mean age was 74.4 +/- 6.3 years old. The prevalence of leukoaraiosis was 68.7%. Leukoaraiosis was significantly correlated with older age, lacunar infarctions, past history of stroke, cognitive impairment and to lower systolic and diastolic velocities in middle cerebral artery (MCA) and higher pulsatility index. Multivariate analysis only retained the lower diastolic velocity in MCA in the model. CONCLUSIONS: Transcranial Doppler can detect hemodynamic abnormalities in patients with leukoaraiosis and is therefore a very useful technique for the evaluation of this entity.

[The phenomenon of immigration within the European Community and its impact on neurological care in the Marina Baixa area, Alicante]. / El fenómeno de la inmigración en la Europa comunitaria y su impacto en la asistencia neurológica en el área de la Marina Baixa, Alicante.

INTRODUCTION: Immigration is shaping a new model of society, with new needs and demands, whose characteristics must guide health-care policies. AIM. To determine the repercussions of the phenomenon of immigration on the extra-hospital neurological care carried out in Department 16 of the Agencia Valenciana de Salud (Valencian Health Service) and how language problems affect visits. PATIENTS AND METHODS: We conducted a prospective study during 26 consecutive outpatient visits in the first three months of 2006. RESULTS: Of all the patients who were attended, 9.5% were foreigners. Of these, 77.7% came from EU countries. And of those from outside the Community, 13% were from Latin American countries, 5% came from European countries that do not belong to the EU and 5% were from Africa. Mean ages were 61.5 years for the EU group and 42.6 years for the other nationalities. The main reasons for visiting were headache and cognitive impairment. The poorer the quality of communication was, the longer the visit lasted. CONCLUSIONS: The high prevalence of immigrants from the EU, mostly elderly persons and with chronic neurological pathologies, together with the ageing of the autochthonous population, have led to a progressive growth in the demand for health care in our area. The language barrier makes clinical practice more complicated and results in an increase in the time needed for each patient. These facts must be taken into account when planning both the health care resources in our area and visiting times per patient.

Iontophoresis of dexamethasone phosphate: competition with chloride ions.

The objective was to study the competition of chloride released from a Ag/AgCl cathode on the iontophoretic delivery of dexamethasone phosphate (Dex-Phos). Iontophoresis of Dex-Phos was performed in side-by-side diffusion cells (0.78 cm(2)) using pig skin. A 0.3 mA constant current was applied via Ag/AgCl electrodes. The amounts of Dex-Phos and dexamethasone (Dex) were also quantified in the stratum corneum (SC), using tape-stripping, after passive and iontophoretic delivery. The profiles of Dex-Phos and Dex, as a function of position in the SC, were deduced. The iontophoretic delivery of Dex-Phos from pure water was unaffected by the accumulation of Cl- released by the donor cathode when the drug's concentration was 4.25 mM to 17 mM. At 0.85 mM, however, Cl- competition was significant and the drug flux was significantly reduced. Formulation of the drug in the presence of Cl- resulted in a non-linear dependence of flux on the molar fraction of the drug. Tape-stripping experiments confirmed the enhanced delivery of Dex-Phos by iontophoresis relative to passive diffusion, with Dex-Phos concentration greater inside the barrier post-iontophoresis than that in the donor. The latter observation could explain the robustness of Dex-Phos delivery to the presence of Cl- in the donor solution.