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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]

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]

The article presents abstracts of presentations about research to improve standards of care in patients with amyotrophic lateral sclerosis (ALS). These include: neuroprotective agents for clinical trials in ALS; complications of quantitative muscular assessment for ALS patients; prevalence and management of burning mouth syndrome in motor neuron disease; and gastrostomy in motor neuron disease.

Patient care and minimizing complications post gastrostomy have to date received little attention in ALS patients. We compare the complications associated with pigtail and mushroom type percutaneous radiological gastrostomy tubes in this patient group. Patients requiring PRG received either Wills‐Oglesby TM or the skin level Entristar TM . Retrospective review of the clinical notes was performed capturing demographic data, peristomal infection, tube displacement, tube failure, nutritional status, site of disease onset, and survival. Thirty‐five patients (Group 1) had the Wills‐Oglesby TM tube of which 14 (40%) tubes required replacement. The Entristar TM tube was inserted in 29 patients (Group 2) where 8 (28%) required replacement (NS). The incidence of infection was significantly lower with the Entristar TM tube, ( p [ABSTRACT FROM AUTHOR]

The article presents a discussion on primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and mutations in the alsin gene. The concepts encompassing these conditions depend upon the definition of amyotrophic lateral sclerosis (ALS), which is central to the discussion of all the other three conditions and is therefore the starting point. ALS is a disease of both upper and lower motor neurons, as identified by clinical signs, electrophysiology, and post mortem histopathology. Prospective follow-up is required to determine the variations in the natural history of uncomplicated PLS and whether it is ultimately merely a form of ALS. This determination currently depends on post mortem examination. Now that HSP and alsin have introduced molecular genetics, classification is certain to be affected, animal models will appear, and advances in theories of pathogenesis are expected.

Presents several abstracts on respiratory and nutritional management for Amyotrophic Lateral Sclerosis (ALS) published in the December 2004 issue of the journal "Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders." "Evidence Based Guidelines for the Management of Respiration in MND/ALS Patients," by C. Heffernan and colleagues; "Non-Invasive Home Mechanical Ventilation in ALS: A Systematic Review of the Literature," by S. Piepers and colleagues; "Respiratory Profile of Motor Neurone Disease/ALS Patients: Prospective Study," by M. C. Berto.

OBJECTIVE: To determine if the publication in 1999 of the AAN Practice Parameter on ALS was associated with an improvement in the standard of management of the disease. METHODS: Data on 646 patients enrolled in the ALS CARE database and on 465 patients who died in the period May 2001 to November 2002 were compared with similar data obtained from the database from 1996 to May 1999. RESULTS: The specialty ALS clinics were the most important source of information about ALS. The internet was a source for 39%. The treatment of sialorrhea, pseudobulbar emotional lability, and failure of swallowing and breathing had all improved significantly in the period after the publication of the Practice Parameter. However many patients still did not receive a gastrostomy tube or non-invasive positive pressure ventilation when indicated by the Practice Parameter, mainly because of lack of patient compliance. Cost was the main reason why 41% of patients did not receive riluzole, though they spent a third of the cost of this medication on alternative medicines. CONCLUSIONS: The publication of the AAN Practice Parameter was associated with improvement in the standard of care. Most cases in the database come from specialized ALS centers, and further information on the community care of ALS patients is needed. [ABSTRACT FROM AUTHOR]

Presents the review of the use of rating scale in clinics to provide an assessment of rate of progression and efficacy of therapeutics in amyotrophic lateral sclerosis. Five components of scale; Mensuration of the strength of grip and lateral pinch; Goal of the rating scale.

Amyotrophic lateral sclerosis (ALS) is a fatal paralytic neurodegenerative disorder. Experimental models of ALS such as the transgenic rodents expressing mutant superoxide dimutase-1 are playing a pivotal role in our understanding of ALS pathogenesis, and in our testing of new therapeutic interventions aimed at protecting against neurodegeneration. Apoptosis has emerged as a significant pathogenic factor in several neurodegenerative diseases, including ALS. Constructed of multiple interacting molecules, the apoptosis machinery offers a host of attractive targets for pharmacological and genetic interventions to be tested in experimental models of ALS. Information generated by these pre-clinical studies holds the promise to provide sound scientific basis for the development of effective neuroprotective therapies for ALS. [ABSTRACT FROM AUTHOR]

Presents the efficacy of using survival as an endpoint in amyotrophic lateral sclerosis (ALS) clinical trials. Advantages of using survivals; Reason for the difficulty in ascertaining the endpoint in ALS; Alternatives used to survival as an endpoint in ALS clinical trials.

Discusses the paradigms for the identification of genes in motor neuron degeneration. Percentage of amyotrophic lateral sclerosis (ALS) are is familial; Gene mutations that are directly causal for motor neuron degeneration in humans; Characteristics of human genetics.

Maximum Voluntary Isometric Contraction (MVIC) is a standardised, objective and sensitive tool for the measurement of muscle strength. The purpose of this study was to investigate different aspects of reliability of MVIC and to determine if a learning effect existed in a relatively new user of the system. Two clinical investigators participated in the study. The inter- and intra-rater reliability of MVIC of 11 muscle groups was tested on healthy subjects (n=35). Intra-class correlation co-efficients (ICCs) were calculated and the statistical methods described by Bland and Altman were applied to the data. ICCs were higher for the more experienced investigator and a learning effect was demonstrated in a relatively new user of the system. Inter-rater reliability was acceptable but lower than intra-rater reliability. Upper limb tests generally yielded higher ICCs and lower ranges of error. The ICC was similar regardless of whether the maximum or average of the two values was taken in a single session. Utilising the statistical methods proposed by Bland and Altman allows estimation of the magnitude of error of MVIC and gives additional information to the ICC. These methods may be useful in the training of investigators and in clinical interpretation of MVIC values. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The involvement of glycation in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) was recently indicated. We previously reported the existence of an Amadori product, 1-hexitol-lysine (1-HL), which is formed in the early glycation reaction, in axonal spheroids of the anterior horn of the ALS spinal cord. OBJECTIVE: The purpose of the present study was to confirm the occurrence of the later-stage glycation reaction that follows the early glycation reaction and leads to the formation of advanced glycation end products (AGEs). METHOD: We examined whether N[sup ε]-(carboxymethyl)lysine (CML) and non-CML AGE are present in ALS spinal cords. RESULTS: Immunohistochemical staining with anti-CML antibody revealed intense positivity in the cell bodies of the remaining atrophic motor neurons and in microglia. Microglia were also positive on staining with anti-non-CML antibody. Axonal spheroids were also positive on anti-non-CML-antibody staining. Vascular endothelial cells were slightly stained by both antibodies. CONCLUSIONS: The presence of non-CML AGE in the anterior horn of the ALS spinal cord indicates that the later stage of the glycation reaction is involved in the pathology of ALS. The presence of CML in the anterior horn was also confirmed, and this may reflect augmented oxidative stress. [ABSTRACT FROM AUTHOR]

Features the International Alliance of Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disorders (MND) Associations. Alliance functions and objectives; Membership of the alliance; Board of directors; Annual members meeting.

The article presents abstracts of presentations about quality of life and palliative care in patients with motor neuron diseases (MND) . These include: new approaches to palliative care; determination of quality of life in amyotrophic lateral sclerosis and other MND; and challenges in addressing quality of life in people with MND.

In the March 2004 issue of the periodical "ALS and Other Motor Neuron Disorders," David Oliver, a British specialist in terminal care well known to those interested in amyotrophic lateral sclerosis, describes a series of decisions made in one patient during the course of the illness. These decisions arose at time points defined not only by the illness itself, but by the exigencies of earlier decisions, themselves made by physicians, nurses, other staff, the patient herself and her relatives. The process described in the article was an advance directive, expressing a considered decision on the part of the patient as to how she should be managed.