Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert / Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease

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Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Propedéutica médica y neurología / No disponible

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[Medical propaedeutics and neurology]. / Propedeutica medica y neurologia.

TITLE: Propedeutica medica y neurologia.

Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort.

We aimed to screen for Pompe disease in patients with unclassified limb-girdle muscular dystrophy (LGMD) or asymptomatic hyperCKemia using dried blood spot (DBS) assays. Subsequently, we aimed to calculate the diagnostic delay between initial symptom presentation and the diagnosis. A prospective, multicenter, observational study was conducted in 348 patients: 146 with unclassified LGMD and 202 with asymptomatic or paucisymptomatic hyperCKemia. We quantified levels of acid alpha-glucosidase (GAA) from dried blood spots analyzed fluorometrically. The test was positive in 20 patients, and Pompe disease was confirmed by genetic testing in 16. Undiagnosed Pompe disease was detected in 7.5% of patients with LGMD and in 2.5% of patients with persistent, idiopathic elevation of serum creatine kinase. The c.-32-13 T > G mutation was found most commonly. The diagnostic delay was 15 years on average. In conclusion, DBS tests are useful and reliable screening tools for Pompe disease. We recommend the dried blood spot test to be included in the diagnostic work-up of patients with unclassified myopathies with proximal weakness and/or hyperCKemia of unknown cause and, when positive, to define the diagnosis, it will have to be confirmed by biochemical and/or molecular genetic analysis.

Clinical guidelines for late-onset Pompe disease.

Before 2006, Pompe disease or glycogenosis storage disease type II was an incurable disease whose treatment was merely palliative. The development of a recombinant human alpha-glucosidase enzymatic replacement therapy has become the first specific treatment for this illness. The aim of this guide is to serve as reference for the management of the late-onset Pompe disease, the type of Pompe disease that develops after one year of age. In the guide a group of Spanish experts make specific recommendations about diagnosis, follow-up and treatment of this illness. With regard to diagnosis, the dried blood spots method is essential as the first step for the diagnosis of Pompe disease. The confirmation of the diagnosis of Pompe disease must be made by means of an study of enzymatic activity in isolated lymphocytes or a mutation analysis of the alpha-glucosidase gene. With regard to treatment with enzymatic replacement therapy, the experts say that is effective improving or stabilizating the motor function and the respiratory function and it must be introduced when the first symptoms attributable to Pompe disease appear.

[Latency values of 248 H reflexes in 124 normal subjects]. / Valores de latencia de 248 reflejos H en 124 sujetos normales.

INTRODUCTION: The Hoffmann reflex or H reflex is an electrical counterpart of the myotatic reflex. In normal adults is elicited with stimulating the tibial and the median nerves. It is useful as an adjunct study of neuroexamination and assesses the corresponding arc reflexes in their integrity. SUBJECTS AND METHODS: 248 H reflexes were studied stimulating the tibial nerve in 124 healthy subjects. RESULTS: The latency values were: minimum 23.6 ms; maximum 29.8 ms; mean value 27.6 ± 1.41 ms. CONCLUSION: This work explains the technique to obtain the H reflex and discusses the need for normalized values for each neurophysiology lab.

Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies

Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies (AU)

Síndrome de fatiga crónica / No disponible

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Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder caused by mutations in the CAPN3 gene. Its definitive diagnosis is laborious, since the clinical phenotype is often similar to other types of muscular dystrophy and since the CAPN3 gene encompasses a large genomic region with more than 300 pathogenic mutations described to date. In fact, it is estimated that nearly 25% of the cases with a phenotype suggestive of LGMD2A do not have mutations in the CAPN3 gene and that, in up to 22% of the cases, only one mutation is identified. In the present work, we have characterised CAPN3 messenger RNA (mRNA) expression in peripheral blood, and we have performed a retrospective diagnostic study with 26 LGMD2A patients, sequencing a transcript of CAPN3 present in white blood cells (WBCs). The 25% of the mutations presented in this paper (7/28) act modifying pre-mRNA splicing of the CAPN3 transcript, including the first deep-intronic mutation described to date in the CAPN3 gene. Our results determine that the sequencing of CAPN3 transcripts present in WBCs could be applied as a new approach for LGMD2A diagnosis. This method improves and simplifies diagnosis, since it combines the advantages of mRNA analysis in a more accessible and rapidly regenerated tissue. However, the lack of exon 15 in the CAPN3 isoforms present in blood, and the presence of mRNA degradation make it necessary to combine mRNA and DNA analyses in some specific cases.

Cuantificación electromiográfica de la denervación / Electromyographic quantification of denervation

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Cuantificación electromiográfica de la denervación / No disponible

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[Ethical controversies on the use of placebo as control treatment in clinical trials in neurology]. / Controversias éticas sobre la utilización de placebo como tratamiento control en los ensayos clínicos en neurología.

Under certain circumstances, the best design to answer a therapeutic question is to conduct a randomized, blinded, placebo-controlled clinical trial. This paper suggests and comments the most controversial aspects of placebo use in clinical research in neurology. It also aims to provide criteria and alternatives, with a multidisciplinary approach (bioethics, research methodology and clinical neurology). ETHICAL ASPECTS OF PLACEBO USE IN CLINICAL PHARMACOTHERAPEUTIC RESEARCH: Use of placebo as control treatment mainly affects four of the seven usually recognized requirements to consider a clinical trial as ethical: social or scientific value of the research, scientific validity, benefit/risk balance and informed consent. These four aspects are considered separately within the context of clinical trials with drugs in Neurology. The main questions at stake, ethical conflicts and possible options are stressed. DISCUSSION AND RECOMMENDATIONS: The use of placebo-controlled clinical trials in Neurology is subject to many ethical controversies. Nevertheless, there are ethical reasons that justify study designs that use placebo, provided that the rights and safety of participants are adequately safeguarded. We need to increase our understanding of the concept of equipoise and recognize the benefit society obtains with research, thus requiring joint assessment of the benefit/risk ratio of a given clinical trial. Likewise, accurate information on the real risks and benefits of patients taking part in placebo-controlled clinical trials should be collected.

[Treatment of neuropathic pain in neurology units. The PREVADOL study]. / Tratamiento del dolor neuropático en las consultas de neurología. Estudio PREVADOL.

INTRODUCTION: Neuropathic pain (NPP) is defined as a pain started or caused by an injury to or dysfunction of the nervous system. Its treatment is different to that of nociceptive pain since it does not respond to conventional analgesics or non-steroidal antiinflammatory drugs. AIM: To describe the treatment being received by patients with NPP in the daily clinical practice of the specialist in neurology. PATIENTS AND METHODS: An observational, epidemiological, cross-sectional study was conducted in 36 neurology units (24 extra-hospital and 12 belonging to hospitals). We collected the clinical data and the treatment administered to the first 20 patients with NPP to visit the neurology units over a period of 20 consecutive working days. RESULTS: Data were collected for a total of 451 patients with NPP. The pharmacological groups most frequently used in patients with NPP attended in neurology units are antiepileptics (71%) and antidepressants (15%). Of these patients, 60% were being treated with a single drug (an antiepileptic agent in 84.5% of cases; antidepressants in 10.3%). Two pharmacological treatments were being received by 23.7%, and 2.3% of patients were given treatment involving three or more pharmacological agents. A total of 30% received non-pharmacological treatments, especially physiotherapy (50.4%). CONCLUSIONS: Most patients with NPP attended in neurology units follow first-order pharmacological treatments (antiepileptics or antidepressants). Over half the patients are controlled with monotherapy, usually with an antiepileptic agent. Non-pharmacological treatments (especially physiotherapy) are used in a third of the patients.

[Epidemiological study of prevalence, incidence and neuropathic pain characterization in neurology units. PREVADOL study]. / Estudio de prevalencia, incidencia y caracterización del dolor neuropático en consultas de neurología. Estudio PREVADOL.

INTRODUCTION: Neuropathic pain is defined as a pain initiated or caused by a lesion or dysfunction in the nervous system. The objectives of the study were to estimate the prevalence and incidence of neuropathic pain in hospital neurology units and primary care centres, to characterize the clinical profile of the patient with neuropathic pain and to know the most frequent treatments in the pharmacological management of this type of pain. METHODS: Observational, cross-sectional epidemiological survey carried out in 36 Neurology Units of the national territory (24 primary care centres and 12 hospitals). During 20 consecutive days neurologists collected the diagnoses of all the attended patients by any reason, up to 30 patients/day. In parallel the 20 first consecutive patients with neuropathic pain were chosen for their characterization in depth by means of a specific questionnaire. RESULTS: A total of 12,688 patients were attended and a total of 13,555 diagnoses were collected through 713 consultation days. The most frequent diagnosis was migraine/cephalea, with a prevalence of 23.40% (95% CI: 22.66%-24.14%). Neuropathic pain represented the eighth more frequent diagnosis, with a prevalence in neurology units of 3.88% (95% CI: 3.54%- 4.22%). The prevalence of neuropathic pain was 2.92% in primary care centres and 6.09% in hospital units (p < 0.01). The daily incidence of new neuropathic pain cases was 1.24% (95% CI: 1.05%-1.53%); 1.14% in primary care neurology centres and 1.45% in hospital units. CONCLUSIONS: The data obtained indicate that neuropathic pain is the eighth more frequent diagnosis in the neurology units. Medical assistance request by neuropathic pain is higher in the hospital units.

Estudio de prevalencia, incidencia y caracterización del dolor neuropático en consultas de neurología. Estudio PREVADOL / Epidemiological study of prevalence, incidence and neuropathic pain characterization in neurology units. PREVADOL study

Introducción. El dolor neuropático (DNP) se define como un dolor iniciado o causado por una lesión o disfunción del sistema nervioso. Los objetivos del estudio fueron estimar la prevalencia e incidencia de DNP en consultas de neurología hospitalarias y extrahospitalarias, caracterizar el perfil del paciente con DNP y conocer los tratamientos más utilizados en el manejo farmacológico de este tipo de dolor. Métodos. Se realizó un estudio observacional, epidemiológico y transversal, en 36 consultas de neurología del territorio nacional (24 extrahospitalarias y 12 hospitalarias). Durante 20 días consecutivos se recogieron los diagnósticos de los pacientes que acudieron a consulta por cualquier motivo, hasta un máximo de 30 pacientes/día. Paralelamente se eligieron los primeros 20 pacientes consecutivos que presentaban DNP, para su caracterización en profundidad mediante un cuestionario específico. Resultados. Se recogieron 13.555 diagnósticos de un total de 12.688 pacientes atendidos en 713 días de consulta. El diagnóstico más frecuente fue migrañas/cefaleas, con una prevalencia del 23,40% (IC 95%: 22,66-24,14%). El DNP representó el octavo diagnóstico más frecuente, con una prevalencia en consultas de neurología del 3,88 % (lC 95 %: 3,544,22%). La prevalencia de DNP fue del 2,92 % en consultas extrahospitalarias y del 6,09 % en consultas hospitalarias (p < 0,01). La incidencia diaria de casos nuevos de DNP se situó en el 1,24% (lC 95%: 1,05-1,53 %); 1,14% en consultas de neurología extrahospitalarias y 1,45% en consultas hospitalarias. Conclusiones. Los datos obtenidos indican que el DNP es el octavo diagnóstico más frecuente en las consultas de neurología. La demanda asistencial por DNP es más elevada en las consultas hospitalarias

Introduction. Neuropathic pain is defined as a pain initiated or caused by a lesion or dysfunction in the nervous system. The objectives of the study were to estimate the prevalence and incidence of neuropathic pain in hospital neurology units and primary care centres, to characterize the clinical profile of the patient with neuropathic pain and to know the most frequent treatments in the pharmacological management of this type of pain. Methods. Observational, cross-sectional epidemiological survey carried out in 36 Neurology Units of the national territory (24 primary care centres and 12 hospitals). During 20 consecutive days neurologists collected the diagnoses of all the attended patients by any reason, up to 30 patients/day. In parallel the 20 first consecutive patients with neuropathic pain were chosen for their characterization in depth by means of a specific questionnaire. Results. A total of 12,688 patients were attended and a total of 13,555 diagnoses were collected through 713 consultation days. The most frequent diagnosis was migraine/cephalea, with a prevalence of 23.40 % (95 % Cl: 22.66 %-24.14 %). Neuropathic pain represented the eighth more frequent diagnosis, with a prevalence in neurology units of 3.88 O/o (95 % CI: 3.540/04.22 %). The prevalence of neuropathic pain was 2.92 % in primary care centres and 6.09 % in hospital units (p < 0.01). The daily incidence of new neuropathic pain cases was 1.24 % (95 % CI: 1.05 %-1.53 %); 1.14 % in primary care neurology centres and 1.45 % in hospital units. Conclusions. The data obtained indicate that neuropathic pain is the eighth more frequent diagnosis in the neurology units. Medical assistance request by neuropathic pain is higher in the hospital units

LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.