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Objective : To perform a comprehensive lipid profiling to evaluate potential lipid metabolic differences between patients with amyotrophic lateral sclerosis (ALS) and controls, and to provide a more profound understanding of the metabolic abnormalities in ALS. Methods : Twenty patients with ALS and 20 healthy controls were enrolled in a cross-sectional study. Untargeted lipidomics profiling in fasting serum samples were performed by optimized UPLC-MS platforms for broad lipidome coverage. Datasets were analyzed by univariate and a variety of multivariate procedures. Results : We provide the most comprehensive blood lipid profiling of ALS to date, with a total of 416 lipids measured. Univariate analysis showed that 28 individual lipid features and two lipid classes, triacylglycerides and oxidized fatty acids (FAs), were altered in patients with ALS, although none of these changes remained significant after multiple comparison adjustment. Most of these changes remained constant after removing from the analysis individuals treated with lipid-lowering drugs. The non-supervised principal component analysis did not identify any lipid clustering of patients with ALS and controls. Despite this, we performed a variety of linear and non-linear supervised multivariate models to select the most reliable features that discriminate the lipid profile of patients with ALS from controls. These were the monounsaturated FAs C24:1n-9 and C14:1, the triglyceride TG(51:4) and the sphingomyelin SM(36:2). Conclusions : Peripheral alterations of lipid metabolism are poorly defined in ALS, triacylglycerides and certain types of FAs could contribute to the different lipid profile of patients with ALS. These findings should be validated in an independent cohort.

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., (Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

«Apuntes en Neurologia» is an initiative in which prominent national and international leaders, with broad academic recognition, came together to synthesise the most outstanding clinical aspects within their area of interest and to discuss the latest developments in a more accessible language. Understanding the factors that affect the onset and progression of any neurological disease through a review is important to be able to develop strategies to reduce the burden of these diseases. Moreover, knowledge of the clinical aspects is essential to solve the problems of daily clinical practice. The data collected here reflect the weight of evidence and some of them anticipate a promising future in the treatment of these diseases. This first edition focuses on common paroxysmal neurological disorders such as migraine, epilepsy and sleep disorders, as well as neurodegenerative disorders such as Parkinson's disease and cognitive impairment. These are clearly different pathologies, although some of them such as migraine and epilepsy, may share clinical symptoms. Sleep disorders, however, are important manifestations of neurodegenerative diseases that are sometimes clinically apparent long before the onset of other neurological symptoms. After recalling pathophysiology and diagnosis, the current review focuses on bringing together the main advances in five of the major neurological diseases.

Introduction: For many years carbamazepine (CBZ) has been the reference drug for the treatment of partial epileptic seizures. However, the problems related with its pharmacokinetics and safety have led to the development of other derivatives, such as oxcarbazepine (OXC) and, more recently, eslicarbazepine acetate (ESL), which do not display these drawbacks., Development: In clinical practice, the possibility of replacing CBZ or OCX by ESL is a relatively frequent occurrence, the aim being to maintain the efficacy of its predecessors and benefit from the advantages in terms of the pharmacokinetics and safety of this latter derivative. To achieve this, it is essential to have an approximate dose equivalence and exchange protocol. This review offers a practical reasoned model for carrying out the change., Conclusions: The shift from OXC to ESL can be completed from one day to the next with a dose equivalence of 1-1.5 to 1. Replacement of CBZ by ESL must be more progressive, and the dose equivalence is established as 1-1.3 to 1.

Introduction: The characteristics of some population groups (patients with comorbidities, women of childbearing age, the elderly) may limit epilepsy management. Antiepileptic treatment in these patients may require adjustments., Development: We searched articles in Pubmed, clinical practice guidelines for epilepsy, and recommendations by the most relevant medical societies regarding epilepsy in special situations (patients with comorbidities, women of childbearing age, the elderly). Evidence and recommendations are classified according to the prognostic criteria of Oxford Centre of Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic interventions., Conclusions: Epilepsy treatment in special cases of comorbidities must be selected properly to improve efficacy with the fewest side effects. Adjusting antiepileptic medication and/or hormone therapy is necessary for proper seizure management in catamenial epilepsy. Exposure to antiepileptic drugs (AED) during pregnancy increases the risk of birth defects and may affect fetal growth and/or cognitive development. Postpartum breastfeeding is recommended, with monitoring for adverse effects if sedative AEDs are used. Finally, the elderly are prone to epilepsy, and diagnostic and treatment characteristics in this group differ from those of other age groups. Although therapeutic limitations may be more frequent in older patients due to comorbidities, they usually respond better to lower doses of AEDs than do other age groups., (Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT., (© 2012 Wiley Periodicals, Inc.)

Introduction: Treatment of narcolepsy-cataplexy is based on the use of different drugs that either stimulate or modify REM sleep, which makes it possible to improve the symptoms that characterise the disease., Aim: To present the characteristics of sodium oxybate, a new drug that has been approved in the United States and in the European Union for use in treating narcolepsy-cataplexy; the main contribution made by this new agent is the possibility of acting on all the symptoms of the disease at the same time., Development: In four randomised, double-blind, placebo-controlled studies and with a class A level of evidence, sodium oxybate has proved to be effective in improving the cardinal symptoms of narcolepsy-cataplexy, that is to say, hypersomnia, cataplexy and fragmentation of nocturnal sleep. Treatment was well tolerated and the side effects, consisting mainly of nausea or symptoms related with the nervous system, such as anxiety, depression, confusion or drowsiness, were mild or moderate in most cases and rarely led to the patient's giving up the treatment. The drug has a favourable pharmacokinetic profile, with little potential to interact with other pharmaceuticals. It seems to have a synergic effect with modafinil, boosting its effects in the treatment of excessive sleepiness. Although it is a substance that has been used as a recreational drug, no cases of addiction or drug abuse have been observed in narcoleptic patients treated in a controlled manner., Conclusions: Sodium oxybate can be considered to be a first-choice drug in the treatment of narcolepsy-cataplexy.

Introduction: Valproic acid is available in two different presentations, Depakine and Depakine Crono. Equivalences in plasmatic levels, efficacy and adverse effects between these two formulations are not fully established., Aim: To compare plasmatic levels, efficacy and plasmatic levels between Depakine and Depakine Crono., Patients and Methods: We studied a retrospective series of 238 patients in treatment with Depakine or Depakine Crono and compared plasmatic levels, efficacy and adverse effects between both formulations., Results: A total of 173 patients had taken one formulation and 54 both. Plasmatic levels were similar in both groups. There were more significantly more patients free of seizures among the Depakine Crono group. Significantly better outcomes were seen with Depakine Crono with respect to secondary effects. Adverse effects are significantly less frequent in men than in women. The higher the dose, the higher the incidence of adverse events., Conclusions: Depakine Crono seems to obtain similar plasmatic levels, is at least as efficacious and is associated with less adverse events that Depakine.

Introduction: Epilepsy is a frequent pathology in the elderly, but its aetiology, clinical presentation and prognosis are different to those seen in younger patients., Development: Beyond a certain age physiological modifications take place in the metabolism that alter the pharmacokinetics of the antiepileptic drugs (AED) and increase the risk of pharmacological interactions, which is already higher in these patients owing to the frequency of polypharmacy. Moreover, elderly patients are especially sensitive to certain side effects of AED, such as cognitive disorders, osteoporosis or weight increase. Since the efficacy of the more important AED is a priori quite similar and the epilepsies we have to deal with at this age usually have a good prognosis, the choice of AED will depend more on their pharmacokinetics and their potential to trigger certain side effects than on their effectiveness., Conclusions: The ones with the most favourable pharmacokinetic profile are levetiracetam and pregabalin, followed oxcarbazepine and lamotrigine. Additionally, these drugs generally have few cognitive effects, do not give rise to osteoporosis and, with the exception of pregabalin, do not alter the patient's weight, all of which makes them first choice drugs for the treatment of epilepsy in the elderly.

Sleep-disordered breathing are frequent processes in Spain. Among them, the obstructive sleep apneas are the best known although not all studies are performed with the same diagnostic criteria with regard to the percentage of apneas and hypopneas per hour of sleep and the need to consider the presence or absence of clinic symptoms. After a reference to the biggest epidemiologic studies performed in different populations, the data of the major populational studies in our environs are analyzed.

Introduction: The objective is to analyze gait and upper extremity movement in a sample of healthy individuals and patients with different muscular dystrophies and to determine the relationship of the obtained variables with the pattern of muscular involvement., Subjects and Methods: Gait and upper limb movement was analyzed with a three-dimensional photogrammetry system. Convenience sample of 28 healthy volunteers, 40 patients with myotonic dystrophy (MD), 9 patients with facioscapulohumeral dystrophy (FSHD) and 14 patients with limb-girdle muscular dystrophy type 2A (LGMD2A). Spatio-temporal and kinematic variables were analyzed., Results: Patients had lower velocity, cadence and shorter stride duration than healthy subjects. Gait and upper extremity kinematic variables suggested proximal muscular involvement in LGMD2A patients and distal muscular abnormalities in MD patients. The most characteristic finding in FSHD patients was related with dorsiflexor muscles' weakness. Some of the variables were also correlated to the patients' functional stage., Conclusions: This analysis allows the distinction of kinematic and spatio-temporal patterns of gait and upper extremity movement that correlate with muscular dystrophy's phenotype. The use of this analysis in the clinical setting to assess disease progression or the potential effects of treatments requires further studies.

Background and Objective: The objective of this study was to analyze the gait abnormalities in patients with idiopathic Parkinson's disease (PD), and their response to dopaminergic treatment., Patients and Method: 15 patients and 15 healthy age-matched subjects were included for comparison between pathologic and "normal" gait, and 24 PD patients were included to assess the effects of treatment. Gait analysis was achieved with a new 3D-photogrammetry system., Results: Patients had significative lower velocity, stride length, step length and hip and knee ranges when compared with control subjects. There were no differences in cadence, step width and relative times of gait-cycle. There were no differences in the patients' gait variables after administration of a dopaminergic medication., Conclusions: Gait analysis allows quantification of gait disturbances in patients with PD and the potential effects of treatment. The results of this study suggest a certain degree of "levodopa-resistance" in gait in these patients.

Introduction and Development: In recent years the progress made in genetics has revolutionised our knowledge of the physiopathological mechanisms governing epilepsy. Just 20 years ago, none of the genes involved in epilepsy were known. Since then 11 genes have been identified and this has enabled us to better understand the mechanisms that generate the seizures. This is not only of interest to academics but can also have a practical application by helping when it comes to making a rational choice of a drug in a particular epileptic syndrome, or by allowing new drugs to be developed as new therapeutic targets are identified., Conclusions: Genetics can help us to understand the mechanisms that cause resistance to drugs and to determine the risk of a patient's suffering from idiosyncratic side effects or not. It is therefore to be expected that over the next few years it will become a fundamental body of doctrine for the daily management of epileptic patients.