Frontiers of Neurology and Neuroscience最新文献

{"title":"Assessing Functional Decline in Neurological Diseases Clinical Trials: Duration of Follow-Up - The Case of Multiple Sclerosis.","authors":"Filippo Martinelli Boneschi,&nbsp;Giancarlo Comi","doi":"10.1159/000445418","DOIUrl":"https://doi.org/10.1159/000445418","url":null,"abstract":"<p><strong>Background: </strong>The main objective in the treatment of multiple sclerosis is to prevent or postpone the long-term disability caused by the disease, which in most cases occurs over years. However, most randomized clinical trials (RCTs) assessing the efficacy and safety of disease-modifying drugs have been designed to measure the short-term efficacy of disease-modifying drugs (up to 2-4 years) in reducing relapse rate and disease activity at magnetic resonance imaging (MRI).</p><p><strong>Summary: </strong>In this chapter we will discuss how drug efficacy in reducing short-term relapse rate and MRI activity impact on delaying the accumulation of long-term disability, and we will summarize the available literature on the long-term efficacy of the drugs as assessed by the few long-term observational and long-term extension RCTs on available drugs, focusing on interferon-β treatment as the one with a more extensive literature.</p><p><strong>Key messages: </strong>Additional long-term observational studies and long-term extension of follow-up periods for patients included in RCTs are needed to explore the long-term efficacy of available drugs which are known to be effective at the short-term level.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"39 ","pages":"93-100"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34709094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling and Prediction in Neurological Disorders: The Biostatistical Perspective.","authors":"Massimiliano Copetti,&nbsp;Andrea Fontana,&nbsp;Fabio Pellegrini","doi":"10.1159/000445412","DOIUrl":"https://doi.org/10.1159/000445412","url":null,"abstract":"<p><strong>Background: </strong>Statistical methods are often considered as mere tools to address research questions. The lack of critical understanding can make their use sometimes highly questionable if not inappropriate. Biostatistics should be seen more as a paradigm than a set of tools. Knowledge of methods means a flexible utilization of them, in which modeling and prediction correspond more to an art than to a routine use dictated by circumstances and habits.</p><p><strong>Summary: </strong>Tree-based methods (or tree-growing techniques) are discussed here as a flexible statistical framework for modeling and prediction to address key questions such as prognostic stratification and treatment effects heterogeneity in both randomized clinical trials and observational studies.</p><p><strong>Key messages: </strong>We provide some examples in neurology and possible future extensions in which tree-based methods are shown to be crucial for the assessment of the best available therapy for a patient. We show how trees can represent a clinically interpretable and easy-to-implement approach for stratified medicine and treatment tailoring based on responsiveness, as well as for selecting populations for new studies.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"39 ","pages":"50-9"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34318364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized Trials in Developing Countries: Different Priorities and Study Design?","authors":"Benoît Marin,&nbsp;Gino Cédric Agbota,&nbsp;Pierre-Marie Preux,&nbsp;Farid Boumédiene","doi":"10.1159/000445454","DOIUrl":"https://doi.org/10.1159/000445454","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials are increasingly conducted in the field of neurology in developing countries. To our knowledge, no review has been performed to date about the temporal evolution, geographical distribution, pathological fields, and types of trials conducted. Besides, the validity of those clinical trials needs to be evaluated.</p><p><strong>Summary: </strong>Our main aim was to describe, using a systematic literature review, the clinical trials performed in the field of neurology in developing countries. The specific objectives were (1) to describe the pathologic fields, (2) to evaluate the methodology, and (3) to assess the validity of neurological clinical trials performed in developing countries. A systematic review of the literature was conducted accessing PubMed, Pascal, ScienceDirect, African Journal Online, and the Virtual Library of African Neurology. The 145 studies included allowed us to identify (1) an exponential evolution of the number of clinical trials, (2) the strong contributions from Asia, followed by Africa and Latin America, (3) a fairly good coverage of pathologic fields including noncommunicable diseases, (4) an increasing diversity of intervention type, (5) the lack of early-phase trials (phases I and IIa), and (5) the need of improvement for some critical methodological issues.</p><p><strong>Key message: </strong>There is a need (1) to develop structures dedicated to the early investigation of interventions in humans, and (2) for sustaining the development of structures specialized in the methodology of clinical research and of dedicated courses for researchers in tropical areas about good practice in clinical trials. This would help in improving methodological quality, appropriateness of data management, and statistical analysis.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"39 ","pages":"136-46"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34318538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silas Weir Mitchell: Neurologists and Neurology during the American Civil War.","authors":"F. Boller, D. Birnbaum","doi":"10.1159/000442596","DOIUrl":"https://doi.org/10.1159/000442596","url":null,"abstract":"With few exceptions, neurology was nonexistent in the United States until the Civil War years. From 1861 to 1865, the United States saw a bitter armed conflict between the North (the Union) and the South (the Confederate States or Confederacy), and during those years, neurology was born in the United States. In 1861, Silas Weir Mitchell, together with George Morehouse and William Keen, opened and operated the first neurological hospital in Philadelphia, with the backing of the Surgeon General William Hammond. They treated and studied many peripheral nerve diseases, which led to their making the medical world aware of several conditions, including causalgia (now known as complex regional pain syndrome) and the phantom limb phenomenon. Progress in neurology, both at that time and in subsequent years, owed a great deal to cross-fertilization from Europe. Charles Edouard Brown-Séquard exemplified this. He held multiple medical positions on both sides of the Atlantic, including a position at Harvard in 1864. His teachings, to some extent, contributed to the development of neurology in the United States. In the Confederate states, medical care was less well organized, and neurology only developed later. After the war, in 1874, Mitchell, Hammond, and a few others founded the American Neurological Association. While war influenced the development of medicine, and neurology in particular, medicine also helped to shape the outcome of the war.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"61 1","pages":"93-106"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88515515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Central Role of Neuroscientists under National Socialism.","authors":"L. Zeidman","doi":"10.1159/000442682","DOIUrl":"https://doi.org/10.1159/000442682","url":null,"abstract":"Neuroscientists played central roles in the victimization of colleagues and their patients during the era of National Socialism from 1933 to 1945. After helping dismiss Jewish and nonideologically aligned colleagues, German neuroscientists were among the physicians and researchers who joined the Nazi Party and affiliated groups in record numbers. Forced sterilization and then so-called 'euthanasia' of neurological and psychiatric patients were planned and executed by prominent German and Austrian neuroscientists. Other neuroscientists collaborated indirectly by using patients for unethical experimentation to discover the cause of multiple sclerosis or to try to induce epileptic convulsions in a hypoxic state. Some merely used neuropathological material from murdered patients for publications in scientific journals. In the totalitarian state, research funding and academic advancement were awarded to physicians engaged in eugenics research. Opportunism and ideologically tainted science without regard to medical ethics were the motivating factors for collaborating neuroscientists. Some German and Austrian neuroscientists tried to resist Nazi policies, although much more passively than their colleagues in German-occupied countries. French, Dutch, Norwegian, and Danish neuroscientists actively resisted the Nazification of their profession from the beginning and helped to save some patients and colleagues, at great personal risk. Many German, Austrian, Czech, and Polish neurologists were murdered in the Holocaust, and hundreds of thousands of neurological and psychiatric patients were sterilized or murdered in just 12 years. The Nazis used the 'successful' techniques developed in the 'euthanasia' programs to carry out the mass murder of millions in the Holocaust. Today's neuroscientists are obligated to learn of the ethical violations of their predecessors 70-80 years ago. No law will prevent abandonment of the basic principles of ethical patient care and professionalism that can occur in any totalitarian state, but neuroscientists can possibly prevent it.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"10 1","pages":"168-83"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85539678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age, Comorbidity, Frailty in Observational and Analytic Studies of Neurological Diseases.","authors":"Jan Novy,&nbsp;Josemir W Sander","doi":"10.1159/000445414","DOIUrl":"https://doi.org/10.1159/000445414","url":null,"abstract":"<p><strong>Background: </strong>Comorbidities are rarely taken into account in studies of neurological conditions although they may be a confounder of the outcome and treatment. The relationship between comorbidities and neurological conditions is also problematic as comorbidities may be symptoms of the underlying cause of the neurologic condition or long-term adverse effects of the treatment.</p><p><strong>Summary: </strong>There is evidence that several common neurological conditions have an increased burden of somatic and psychiatric comorbidities compared with matched samples from the general population. Depression is probably the most common comorbidity. Both psychiatric and somatic comorbidities have been shown to account for some of the premature mortality encountered in these neurological conditions. Comorbidities and age can also be important factors in the response and tolerance to treatment, and can alter the general outcome of a disease.</p><p><strong>Key messages: </strong>Age and comorbidities should not be overlooked in the observation and assessment of neurological conditions and their treatment.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"39 ","pages":"71-80"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34709058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological Impact of World War I on the Artistic Avant-Garde: The Examples of André Breton, Guillaume Apollinaire and Blaise Cendrars.","authors":"J. Bogousslavsky, L. Tatu","doi":"10.1159/000442654","DOIUrl":"https://doi.org/10.1159/000442654","url":null,"abstract":"World War I erupted at a time when artistic avant-gardes were particularly thriving across Europe. Young poets, writers, painters and sculptors were called to arms or voluntary enrolled to fight, and several of them died during the conflict. Among others, it dramatically changed their creative output, either through specific wounds or through personal encounters and experiences. These individual events then significantly modified the course of the literary and artistic avant-garde movements. Three particularly illustrative examples of avant-garde French poets are presented here: André Breton (1896-1966), Guillaume Apollinaire (1880-1918) and Blaise Cendrars (1887-1961). The deep source of the surrealist movement can indeed be found in André Breton's involvement as an auxiliary physician with critical interest in neuropsychiatry, which caused him to discover automatic writing. Guillaume Apollinaire's right temporal subdural hematoma strongly modified his emotional state and subsequent artistic activities. Alternatively, after losing his right, writing hand, Blaise Cendrars not only substituted it with a phantom but also rapidly switched from poetry to novels after he learnt to write with his left hand.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"23 1","pages":"155-67"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88083212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychiatric Disturbances, Self-Mutilation and Malingering in the French Armies during World War I: War Strain or Cowardice?","authors":"L. Tatu, J. Bogousslavsky","doi":"10.1159/000442653","DOIUrl":"https://doi.org/10.1159/000442653","url":null,"abstract":"Between 1914 and 1918, war strain appeared under a number of guises and affected, to varying extents, the majority of French soldiers. The most frequent form of war strain was war psychoneurosis, but war strain also induced more paroxystic disorders, such as acute episodes of terror, self-mutilation, induced illnesses and even suicide. Fear was the constant companion of soldiers of the Great War: soldiers were either able to tame it or overwhelmed by an uncontrollable fear. Nonetheless, over the course of the war, some aspects of fear were recognised as syndromes. The French health service poorly anticipated the major consequences of war strain, as with many other types of injuries. After the establishment of wartime neuropsychiatric centres, two main medical stances emerged: listening to soldiers empathetically on the one hand and applying more repressive management on the other. For many physicians, the psychological consequences of this first modern war were synonymous with malingering or cowardice in the face of duty. The stance of French military physicians in relation to their command was not unequivocal and remained ambivalent, swaying between medico-military collusion and empathy towards soldiers experiencing psychological distress. The ubiquity of suspected malingering modified the already porous borders between neuropsychiatric disorders and disobedience. Several war psychoneurotic soldiers were sentenced by councils of war for deserting their posts in the face of the enemy and were shot. Many soldiers suspected of self-mutilation or suffering from induced illnesses were also sentenced and executed without an expert assessment of their wound or their psychological state.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"1 1","pages":"143-54"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88568240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traumatic Brain Injury Studies in Britain during World War II.","authors":"D. Lanska","doi":"10.1159/000442570","DOIUrl":"https://doi.org/10.1159/000442570","url":null,"abstract":"As a result of the wartime urgency to understand, prevent, and treat patients with traumatic brain injury (TBI) during World War II (WWII), clinicians and basic scientists in Great Britain collaborated on research projects that included accident investigations, epidemiologic studies, and development of animal and physical models. Very quickly, investigators from different disciplines shared information and ideas that not only led to new insights into the mechanisms of TBI but also provided very practical approaches for preventing or ameliorating at least some forms of TBI. Neurosurgeon Hugh Cairns (1896-1952) conducted a series of influential studies on the prevention and treatment of head injuries that led to recognition of a high rate of fatal TBI among motorcycle riders and subsequently to demonstrations of the utility of helmets in lowering head injury incidence and case fatality. Neurologists Derek Denny-Brown (1901-1981) and (William) Ritchie Russell (1903-1980) developed an animal model of TBI that demonstrated the fundamental importance of sudden acceleration (i.e., jerking) of the head in causing concussion and forced a distinction between head injury associated with sudden acceleration/deceleration and that associated with crush or compression. Physicist A.H.S. Holbourn (1907-1962) used theoretical arguments and simple physical models to illustrate the importance of shear stress in TBI. The work of these British neurological clinicians and scientists during WWII had a strong influence on subsequent clinical and experimental studies of TBI and also eventually resulted in effective (albeit controversial) public health campaigns and legislation in several countries to prevent head injuries among motorcycle riders and others through the use of protective helmets. Collectively, these studies accelerated our understanding of TBI and had subsequent important implications for both military and civilian populations. As a result of the wartime urgency to understand, prevent, and treat patients with TBI during WWII, clinicians and basic scientists collaborated on research projects that none of them would likely have pursued without these unique circumstances. Very quickly, there was a sharing of information and ideas that not only led to new insights into the mechanisms of TBI but also provided very practical approaches for preventing or ameliorating at least some forms of TBI. Investigators in Great Britain, in particular, pioneered accident investigations, performed epidemiologic studies, and developed animal and physical models that accelerated our understanding of TBI and had subsequent important implications for both military and civilian populations.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"32 1","pages":"68-76"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82144406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcranial Doppler.","authors":"V. Sharma, K. Wong, A. Alexandrov","doi":"10.1159/000448309","DOIUrl":"https://doi.org/10.1159/000448309","url":null,"abstract":"Transcranial Doppler ultrasonography (TCD) is the only diagnostic modality that provides a reliable evaluation of intracranial blood flow patterns in real-time. The physiological information obtained from TCD is complementary to the anatomical details obtained from other neuroimaging modalities. TCD is relatively cheap, can be performed bedside, and allows monitoring in acute emergency settings. TCD criteria for intracranial stenosis have been validated against various forms of angiographic studies and serve as reliable tools for screening, diagnostic as well as follow up purposes. TCD findings of intracranial stenosis have acceptable accuracy parameters for anterior as well as posterior circulation. Extended applications of TCD, especially emboli monitoring and assessment of vasomotor reactivity, provide important information about the pathophysiology of cerebrovascular ischemia and risk stratification. Therefore, TCD has become an integral component of the armamentarium of stroke neurologists for understanding stroke etiopathogenesis, planning and monitoring definitive treatment and determining the prognosis. We present the basic principles of TCD, techniques of test performance, diagnostic methods as well as some of the advanced applications of TCD in patients with intracranial stenosis.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"4 1","pages":"124-140"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81975543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}