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The article provides information on the European ALS Consortium's second annual research workshop, held in Nice, France, on May 14-16, 2005. The programme comprised 66 papers and posters. Twenty concerned the pathogenesis of human ALS and 16 dealt with the SOD1 transgenic mouse. Twenty papers were clinical and 10 dealt with animal models, cultured cells or slices, or drug discovery. Jaine Kirby and Christine Teitsma described the use of microarrays for mRNA in fibroblasts to study gene expression in SOD1 mice as an introduction to their use in humans. As described by Christopher Miller, protein transport is slowed in the motor nerves of SOD1 mutant mice and also in neurofilament mutants. Abnormalities of mitochondrial structure and function are found in animal models of ALS, including SOD1 mutants as well as VEGF deficiency and the wobbler mouse.

Among the motor neuron diseases, three share the clinical features of prominent upper motor neuron signs – amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) and the hereditary spastic paraplegias (HSP). While genetic testing can assist in the identification of several variants of the latter, in the remaining cases, including those in which spasticity may be associated with amyotrophy, clinical differentiation of the three disorders may prove difficult. In this paper we review the evidence that these are distinct disorders and conclude that, for ALS and PLS particularly, there may be justification in considering them as single points along a continuum of multisystem disorders with conspicuous motor neuron involvement. Only through the development and application of exacting clinical diagnostic criteria to epidemiological studies, along with greater numbers of post-mortem examinations, however, will these questions be answered fully. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this paper is to discuss the sequential trial design and its advantages in clinical trials for ALS. The sequential trial design is an alternative to the classical trial design, which permits stopping a study as soon as a treatment effect can be significantly demonstrated or denied. METHODS: As an example of a sequential survival analysis, a recently completed clinical trial is described. A secondary outcome measure used in the same trial, the decline of the vital lung capacity, was re-analyzed sequentially, in order to illustrate the use of the sequential method for a non-survival variable. To compare the classical with the sequential trial design, the number of patients needed in trials aiming at survival effects ranging from 10% to 20% with a power of 80% or 90% was calculated for both designs. RESULTS: In the given examples the time needed to prove the null hypothesis in the survival analysis, and the number of patients needed to prove the null hypothesis in the analysis of the vital capacity is lower than would have been the case in a classical analysis. In 18 of 24 different situations, the chance is at least 90% that with a sequential trial design fewer patients are needed. CONCLUSIONS: We argue that, particularly for ALS trials, a sequential design may be superior to a classical trial design, as it most often requires fewer patients than classically designed trials of equal power, and more importantly may avoid unnecessary continuation. [ABSTRACT FROM AUTHOR]

There are wider issues relating to the communication difficulties experienced by people with amyotrophic lateral sclerosis (ALS) than simply the physical problems caused by diminished oral control. In addition, existing literature on ALS rarely considers communication to be a joint interaction which depends on the strategies adopted by both communication partners, nor does it present communication in real life settings. This paper presents some of the findings from a 3-year research project which investigated the communication of people with ALS and their partners in their own homes. It discusses the purpose of human communication, and through examination of conversations in people's own homes has identified a range of strategies and techniques that families with ALS employ. For some people with ALS, although speech may deteriorate, they are still able to communicate closely and in a way that is more focused on topics that are particularly important to them. The findings from this study will be of interest to those who work with people with ALS. [ABSTRACT FROM AUTHOR]

Until fairly recently, interest in stem cells was restricted to neurobiology studies on the principles of embryonic development. This situation has changed rapidly in the last few years when neuronal stems and precursors were isolated in vitro, thus allowing expansion and controlled differentiation of selective populations of neuronal cells. This theoretically unlimited reserve would then supply specific cells for transplantation in diseases characterized by widespread degeneration of selective cell populations as motor neurons in Amyotrophic Lateral Sclerosis (ALS). The recent evidence of cell transdifferentiation has further amplified the potential therapeutic use of stem cells. Stem cell technology is at an early stage but the desperate need for a therapy in ALS patients may legitimize clinical trials in absence of conclusive scientific evidence. This paper discusses the premises for stem cell therapy in ALS. [ABSTRACT FROM AUTHOR]

The current status of evaluation and management provided by individual health-care professionals (HCP) at amyotrophic lateral sclerosis (ALS) centers and clinics needs to be analyzed. This paper describes one ALS center's experiences with the development, analysis, refinement, and utility of an interdisciplinary, HCP-driven ALS database. The purpose and conceptual framework of the database, the general data that needed to be collected, and the types of reports that needed to be generated were determined, and, in collaboration with a computer programmer, database management systems were developed. Data were collected on 234 patients between September 1996 and August 1998, and were analyzed by a data entry and biostatistician. Based on review of the biostatistician's report and discussion of problems encountered with the systems, the database was then refined. Benefits of the database system included: systematization of data collection and reporting, reduction of redundant data collection by individuals, decreased variability of evaluation methods and management decisions from patient to patient, and increased availability of a variety of uniform patient information to assist team members in making care decisions. Ongoing refinement will ensure that this HCP-driven ALS database continues to be informative, practical and effective for decision-making and enhancing delivery of care. (ALS 2001; 2: 39–46). [ABSTRACT FROM AUTHOR]

In tandem with recent progress in basic and clinical research in amyotrophic lateral sclerosis (ALS), clinical care and management has improved substantially. Key processes and practices have been established and are specified in current ALS Practice Parameters; the international ALS databases identify the current status of care and management given by physicians. A number of prospective clinical management research studies are now well underway to establish the effective utility of enteral feeding, assistive ventilatory device, and exercise in patients with ALS. One of the main research objectives in the clinical management of ALS is to improve patients' quality of life. For patients with ALS, only comprehensive multidisciplinary care can effectively improve their overall quality of life from diagnosis to death. This paper will briefly review a number of factors that must be considered if we are to improve the quality of life for these patients, including comprehensive medical management, patient education, the importance of hope, the role of the health care professional, and the patients themselves. (ALS 2000; 1: 329–336). [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of unknown etiology. Although there was a widely held belief that ALS does not cause cognitive impairment, cognitive function in patients with ALS has received more attention recently. In this paper, we discuss the clinical, neuroanatomical and neuropathological basis for cognitive dysfunction in ALS. (ALS 2000; 1: 343–347). [ABSTRACT FROM AUTHOR]

Numerous attempts have been made to visualize the motor cortex and pyramidal tract lesions in patients with ALS using magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET). This paper briefly reviews the applicability of these imaging modalities in ALS. (ALS 2000; 1(suppl 2): S3-S6). [ABSTRACT FROM AUTHOR]

Electromyography (EMG) plays a key role in the diagnostic evaluation of ALS. This paper deals with the contribution of conventional needle EMG and electroneurography to the neurophysiological assessment of ALS. In addition, special EMG techniques such as single fibre EMG and macro EMG are discussed as they mirror the decline of the number of motor units during the disease process and the remodelling capacity of the surviving motor units. (ALS 2000; 1(suppl2):S33-S40). [ABSTRACT FROM AUTHOR]

The 1990s decade has seen the testing of treatments to slow disease progression in patients with ALS. Two such treatments (riluzole and myotrophin) have shown minimal or modest efficacy. Of these, riluzole has been approved for marketing in the United States, in Europe and in other countries. Patients and physicians who are trying to decide whether to use these treatments require background information: (a) to place these treatments in the context of other treatments; (b) to under stand the outcome measures used; and (c) to understand the significance of the efficacy these treatments have shown. For example, in some cases treatment efficacy has been shown by some measures, but not others. This paper attempts to assist in this process. In addition, we attempt to show how to integrate objective data with relative or subjective factors, such as patient values, economic considerations, and the role of hope. (Amyot Lat Scler 1999; 1;3–14). [ABSTRACT FROM AUTHOR]

In their recent paper, Sugai et al. (1) reported a beneficial effect of valproate (VPA) in a G93A mouse model of ALS, showing a significant prolongation of disease duration, without any effect on disease onset. Although this result certainly needs to be further investigated, it is interesting to hypothesize that VPA might exert this beneficial action through a novel mechanism based on the epigenetic rearrangement of the structure of the chromatin, eventually resulting in the modulation of the disease phenotypic traits. [ABSTRACT FROM AUTHOR]

Editorial. Introduces a collection of papers on amyotrophic lateral sclerosis (ALS) released in December 2000. Reviews and current problems in ALS; Background on the revised guidelines of ALS diagnosis; Possible pathogenic mechanisms in ALS.

Editorial. Discusses articles concerned with current issues in the study of amyotrophic lateral sclerosis (ALS) contained in an issue of the periodical 'Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases.' Management strategies in various stages of the disease; Disagreement about the value of management in large centers; Paper addressing quality of life in ALS.