Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases最新文献

{"title":"The stem cell problem: expectations and reality.","authors":"Michael Swash","doi":"10.1080/14660820500417541","DOIUrl":"https://doi.org/10.1080/14660820500417541","url":null,"abstract":"Everyone with experience of ALS understands the need for an effective therapy for the disease and, even better, for a strategy that will ensure prevention. Since the introduction of riluzole, a medication with beneficial effects which vary from case to case and are usually rather mild, merely slowing progression of the disease, no additional effective agents have been recognized, despite a number of large, expensive and carefully designed clinical trials testing putative new therapies. The rigour of design and execution of these trials has, in general, been exemplary. This failure in the development of new pharmacological therapies has been disappointing for everyone concerned, not least for people living with ALS. In such a situation, when public awareness and expectations have been raised by a combination of educational efforts by major charities and foundations, especially by ALSA, the Les Turner ALS Association and the MND Association, and by media and internet-sourced information, those affected by the disease are likely to search non-orthodox sources for suggestions regarding possible treatments. Indeed, there is some evidence of a gradual recent loss of public confidence in the ability of conventional medical and scientific research to solve intractable problems such as ALS. There are, of course, many historical examples of unorthodox therapies for ALS, and for most other incurable or ill-understood progressive diseases, but virtually none of these has resulted in the introduction of successful therapeutic agents. Nonetheless, there are examples of the discovery of effective therapies from folk remedies and other sources; e.g. digitalis for congestive heart failure (dropsy), cinchona bark for malaria, curare (hardly a therapy but an invaluable drug in modern anaesthesia), morphine for pain and, more recently, taxanes for ovarian cancer. Such searches through a confused morass of opinion, anecdote, folklore and ‘complementary medicine’ are therefore not inevitably doomed to failure. Indeed, the recent interest in searching through the pharmacological and chemical and biological properties of established and licensed drugs for some chance property that might be effective in ALS attests to scientific recognition of the possible value of such serendipity in the search for effective remedies. Clearly, one must respect the efforts of all those engaged in these searches. Stem cell therapy has been much publicized in the media and there are tens of thousands of internet pages extolling its promise in many different areas of medicine. Indeed, stem cell therapy is already in use in the management of certain haematological malignancies and is under trial in the management of some myocardial diseases. Hopes are high in the public mind for ‘breakthroughs’ in the application of stem cell technology to human neurodegenerative diseases, and ALS is seen as a prime target since it has been regarded, falsely, as a pure motor cell disease. There are a number ","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"195-6"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820500417541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25715264","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":"A rare Cu/Zn superoxide dismutase mutation causing familial amyotrophic lateral sclerosis with variable age of onset and incomplete penetrance in China.","authors":"Huagang Zhang,&nbsp;Hongshan Zhao,&nbsp;Ming Lu,&nbsp;Yingshuang Zhang,&nbsp;Liping Wang,&nbsp;Jun Zhang,&nbsp;Dalon Ma,&nbsp;Dongsheng Fan","doi":"10.1080/14660820510044478","DOIUrl":"https://doi.org/10.1080/14660820510044478","url":null,"abstract":"<p><p>More than 100 mutations in the Cu/Zn superoxide dismutase (SOD) gene have been found, accounting for about 20% of familial ALS (FALS). However, few have been identified in Chinese patients with FALS. We present a five-generation Chinese family with FALS with a rare mutation in exon 4 of the Cu/Zn SOD gene codon position 105, converting serine to leucine. Forty-seven family members including the proband were examined clinically; two affected persons had EMG and nerve conduction studies. Genomic DNA was extracted from peripheral blood leukocytes of the family members after informed consent. All five exons of the Cu/Zn SOD gene were amplified by polymerase chain reaction (PCR) and DNA sequencing was performed on purified products. Exon 4 of the Cu/Zn SOD gene was amplified from genomic DNA isolated from not only the family members but also from 50 unrelated healthy Chinese control subjects. A rare S105L mutation, which is heterozygous with C by T at position 1,125 of the coding sequence in exon 4 of the Cu/Zn SOD gene, was found in the proband and her affected elder brother. The clinical phenotype within the FALS patients in this family is relatively variable. The age at onset ranged from 32 to 65 years, with initial symptoms in either the upper or lower extremities in different family members. Two subjects aged 72 and 60 years remained asymptomatic until their death from other causes, although their offspring carrying the same mutation have already developed clinical evidence of the disease. The S105L mutation was identified in another seven asymptomatic family members, aged 7 to 59 years. It is concluded that the S105L mutation in exon 4 of the Cu/Zn SOD gene is pathogenic. The phenotype is characterized by relatively variable clinical symptoms, with incomplete penetrance.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"234-8"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510044478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25714092","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":"Motor protein diseases of the nervous system.","authors":"C Oliver Hanemann,&nbsp;Albert C Ludolph","doi":"10.1080/14660820510035360","DOIUrl":"https://doi.org/10.1080/14660820510035360","url":null,"abstract":"<p><p>Motor proteins link concepts of impaired axonal transport with concepts of impaired energy metabolism in motor neuron disease. Thus it is not surprising that in recent years several reports on the relevance of motor protein function in mice models for motor neuron disease as well as motor neuron patients have appeared. This article summarizes the broad spectrum of neurological phenotypes, which are caused by alterations of motor protein function. This is likely to add to the understanding of motor neuron disease and may be relevant in terms of future therapeutic approaches.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"197-201"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510035360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25715265","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":"Dementia of frontal lobe type in Kennedy's disease.","authors":"H Kessler,&nbsp;J Prudlo,&nbsp;S Kraft,&nbsp;T Supprian","doi":"10.1080/14660820510036558","DOIUrl":"https://doi.org/10.1080/14660820510036558","url":null,"abstract":"<p><p>The pathomorphological correlate of Kennedy's disease (KD) is a degeneration of spinal and bulbar alpha-motor neurons. The disease is caused by a CAG repeat expansion in the first exon of the X-chromosomal androgene receptor gene. Contrary to the common belief that cognitive disorders in motor neuron diseases (MND) are either rare or only mild, there is now an increasing number of case reports on dementia in amyotrophic lateral sclerosis (ALS). In ALS, dementia of the frontal lobe type (frontotemporal dementia, FTD) seems to be the characteristic pattern. However, in KD cognitive dysfunction has not been studied systematically. Here we present a case with clinical characteristics of FTD in a patient with genetically confirmed KD. It remains speculative whether there is an association between KD and FTD comparable to a genetic linkage between ALS and FTD, which has been proposed in recent years. However, we suggest that cognitive dysfunction may be more common in KD than reported until today.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"250-3"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510036558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25714095","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":"Psychopathology in amyotrophic lateral sclerosis: a preliminary study with 27 ALS patients.","authors":"Catherine Bungener,&nbsp;Ambre Piquard,&nbsp;Pierre-François Pradat,&nbsp;François Salachas,&nbsp;Vincent Meininger,&nbsp;Lucette Lacomblez","doi":"10.1080/14660820510037863","DOIUrl":"https://doi.org/10.1080/14660820510037863","url":null,"abstract":"<p><p>Considering the few studies published on the psychopathology of ALS patients, we carried out a preliminary study evaluating depression, anxiety, emotional reactions and coping strategies in such patients. Twenty-seven ALS patients were included and evaluated using a semi-structured interview, after which they were asked to complete a questionnaire. The rater asessed the DSM-IV criteria for a major depressive episode, dysthymia and generalized anxiety, using the MADRS scale for depression, the Covi anxiety scale and the Depressive Mood scale. Subsequently, patients completed the Ways of Coping checklist. Patients were neither anxious nor depressed. Patients whose diagnosis was recent (less than six months) presented greater emotional deficit. Patients younger than 50 years of age used problem focused strategies more frequently. Those having received the diagnosis in the preceeding six months used emotion focused strategies significantly more often.The absence of characterized depression and anxiety confirmed results of the literature. The significance of this study is found in the observation of specific emotional reactions present in the first six months following diagnosis disclosure. The results show that it is useful to continue the affective evaluation of these patients and to undertake longitudinal studies starting at the time of diagnosis disclosure.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"221-5"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510037863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25715268","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":"16th International Symposium on ALS/MND, Dublin, Republic of Ireland, 8-10 December 2005. Abstracts.","authors":"","doi":"10.1080/17434470510045087","DOIUrl":"https://doi.org/10.1080/17434470510045087","url":null,"abstract":"‘Alternative medicine’ has become the politically correct term for questionable practices formerly labeled quack and fraudulent. During the past 15 years, many reports, even in medical journals, have contained no critical evaluation and have featured the views of proponents and their satisfied clients. To avoid confusion, ‘alternative’ methods should be classified as genuine, experimental, or questionable. Genuine alternatives are comparable methods that have met science-based criteria for safety and effectiveness. Experimental alternatives are unproven but have a plausible rationale and are undergoing responsible investigation. The most noteworthy is use of a 10%-fat diet for treating coronary heart disease. Questionable alternatives are groundless and lack a scientifically plausible rationale. The archetype is homeopathy, which claims that ‘remedies’ so dilute that they contain no active ingredient can exert powerful therapeutic effects. Blurring these distinctions enables promoters of quackery to argue that because some practices labeled ‘alternative’ have merit, the rest deserve equal consideration and respect. Enough is known, however, to conclude that most questionable ‘alternatives’ are worthless. The ‘alternative movement’ is part of a general societal trend toward rejection of science as a method of determining truths. In line with this philosophy, ‘alternative’ proponents assert that scientific medicine (which they mislabel as allopathic, conventional, or traditional medicine) is but one of a vast array of health care options. Instead of subjecting their work to scientific standards, they would like to change the rules by which they are judged and regulated. ‘Alternative’ promoters often gain public sympathy by portraying themselves as a beleaguered minority fighting a self-serving, monolithic ‘Establishment’. Under the rules of science, people who make the claims bear the burden of proof. It is their responsibility to conduct suitable studies and report them in sufficient detail to permit evaluation and confirmation by others. Instead of subjecting their work to scientific standards, promoters of questionable ‘alternatives’ would like to change the rules by which they are judged. ‘Alternative’ promoters may pay lip service to these standards. However, they regard personal experience, subjective judgement, and emotional satisfaction as preferable to objectivity and hard evidence. Instead of conducting scientific studies, they use anecdotes and testimonials to promote their practices and political maneuvering to keep regulatory agencies at bay. C2 PHENOTYPIC VARIATION IN MND/ALS","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 Suppl 1 ","pages":"7-165"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/17434470510045087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25704112","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":"Clinical trials in ALS: a review of the role of clinical and neurophysiological measurements.","authors":"Mamede de Carvalho,&nbsp;João Costa,&nbsp;Michael Swash","doi":"10.1080/14660820510011997","DOIUrl":"https://doi.org/10.1080/14660820510011997","url":null,"abstract":"<p><p>We have reviewed all the published clinical trials of ALS and, from those considered sufficiently large, and containing a control group, we have evaluated their methodology with regard to statistical power. This implies a critical analysis of the endpoint measurements. We have concluded that clinical endpoints used in clinical trials of ALS have frequently been insufficiently sensitive, non-linear, or even not intuitively highly relevant to the disease. We suggest that the ALS-FRS, perhaps also MUNE and the Neurophysiological Index, may be the best measures currently available. These techniques have complementary characteristics that allow them to be used to address different aspects of the disease and its treatment in various trials designs. In the past some trials may have failed to demonstrate a treatment effect because the chosen endpoint measures and the trial design were inappropriate.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"202-12"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510011997","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25715266","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":"Circulating antibodies to cysteinyl catecholamines in amyotrophic lateral sclerosis and Parkinson's disease patients.","authors":"L Salauze,&nbsp;C van der Velden,&nbsp;I Lagroye,&nbsp;B Veyret,&nbsp;M Geffard","doi":"10.1080/14660820510044469","DOIUrl":"https://doi.org/10.1080/14660820510044469","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a degenerative disease of unknown aetiology, affecting motor neurons. Many radical species, such as O(2)(-) NO, and ONOO(-), and lipoperoxidative products are involved, but not all processes have yet been identified. It is known that the oxidation of catecholamines leads to quinone formation. These orthoquinones react with the sulphhydril group of cysteine to produce neurotoxic cysteinyl catecholamine (Cyst-CA) neo-compounds. We synthesised Cyst-CA in order to mimic their endogenous formation. Using the ELISA method, circulating antibodies to Cyst-CA were found in sporadic ALS sera. First, the antibody titres were compared to those of controls and patients with other neurodegenerative diseases. Significant antibody levels were found for Cyst-CA. The G and A isotypes were found but not the M isotype. A second series of experiments showed that A and G titres were elevated, depending on the type of Cyst-CA and the onset of the disease. IgG to Cyst-3,4-dihydroxyphenylalanine (L-DOPA) were present in cases of bulbar and upper limb onsets. IgA to Cyst-homovanillic acid (HVA), Cyst-adrenaline (A), and Cyst-dopamine (DA) were found in lower limb onset. These results indirectly show that: 1) the oxidation of CA and the formation of Cyst-CA may be involved in ALS; 2) these radical processes have different targets depending on the onset of the disease.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"226-33"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510044469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25714091","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":"Venous thrombosis in an ALS population over four years.","authors":"L B Elman,&nbsp;A Siderowf,&nbsp;G Houseman,&nbsp;M Kelley,&nbsp;L F McCluskey","doi":"10.1080/14660820510043226","DOIUrl":"https://doi.org/10.1080/14660820510043226","url":null,"abstract":"<p><p>We conducted a retrospective chart review of all ALS patients seen at our institution over four years to determine the incidence of venous thromboembolism and to identify risk factors in this population. Events occurred in 13 of 438 patients (2.97%), yielding an annual incidence rate of 33.1 events per 1,000 patients (95% CI 17.5-55.3). ALS patients have a risk of venous thromboembolism that is higher than the general population but lower than the population of patients with acute stroke or spinal cord injury. Immobility was significantly associated with increased risk of venous thrombosis (RR = 4.96; 95% CI 1.39-17.78).</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"246-9"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510043226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25714094","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":"Spirometer-dependence of vital capacity in ALS: validation of a portable device in 52 patients.","authors":"Philippe Couratier,&nbsp;François Vincent,&nbsp;Frederic Torny,&nbsp;Mathieu Lacoste,&nbsp;Boris Melloni,&nbsp;François Lemaire,&nbsp;Marie-Therese Antonini","doi":"10.1080/14660820510043244","DOIUrl":"https://doi.org/10.1080/14660820510043244","url":null,"abstract":"<p><p>Since the evaluation of vital capacity (VC) needs to be carried out every three months in patients with amyotrophic lateral sclerosis (ALS), a portable spirometer would be of value in clinical practice. Over the follow-up of 52 ALS patients, we compared the values of slow vital capacity measured by two spirometers: a reference flow-metered spirometer based on a Hans-Rudolph pneumotachograph and a portable Venturi spirometer. The objectives were to analyse the overall concordance of the measurements from the two devices and determine a discordance cut-off. The correlation between measurements was high (r = 0.936) and significant (p<10(-20)). Bland and Altman analysis showed that the measurements were concordant at a statistical risk of 5%; nevertheless, on examination of the raw differences between the measurements, two sub-populations could be identified on either side of the 56% cut-off where the means of the differences were significantly different (p<0.0001). The 56% cut-off was also statistically significant in plotting differences against the coefficient of variations of the data pairs expressed as (100 x s/mean). The differences observed between the two spirometers could be explained by technical differences between the devices as well as by an increase in variability with progression of the disease. In conclusion, this study demonstrates that a portable spirometer can be used reliably at the bedside. For values of vital capacity below the discordance cut-off of 56%, vital capacity should be determined by operators trained in pulmonary function examinations.</p>","PeriodicalId":80440,"journal":{"name":"Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases","volume":"6 4","pages":"239-45"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14660820510043244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25714093","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}