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Despite considerable involvement of the spinal cord in amyotrophic lateral sclerosis (ALS), current biomarker research is primarily centred on brain imaging and CSF proteomics. In clinical practice, spinal cord imaging in ALS is performed primarily to rule out alternative conditions in the diagnostic phase of the disease. Quantitative spinal cord imaging has traditionally been regarded as challenging, as it requires high spatial resolution while minimizing partial volume effects, physiological motion and susceptibility distortions. In recent years however, as acquisition and post-processing methods have been perfected, a number of exciting and promising quantitative spinal imaging and electrophysiology techniques have been developed. We performed a systematic review of the trends, methodologies, limitations and conclusions of recent spinal cord studies in ALS to explore the diagnostic and prognostic potential of spinal markers. Novel corrective techniques for quantitative spinal cord imaging are systematically reviewed. Recent findings demonstrate that imaging techniques previously used in brain imaging, such as diffusion tensor, functional and metabolic imaging can now be successfully applied to the human spinal cord. Optimized electrophysiological approaches make the non-invasive assessment of corticospinal pathways possible, and multimodal spinal techniques are likely to increase the specificity and sensitivity of proposed spinal markers. In conclusion, spinal cord imaging is an emerging area of ALS biomarker research. Novel quantitative spinal modalities have already been successfully used in ALS animal models and have the potential for development into sensitive ALS biomarkers in humans.

In conclusion, given the lack of demonstrated effectiveness, and the above-documented concerns about product safety and supplier identity and reliability, ALSUntangled does not support the use of mototab for amyotrophic lateral sclerosis or any other motor neuron disease. If Oslo Health Solutions ever contacts us with additional useful information on this product we will gladly publish an addendum to this investigation.

There is little in the literature comparing experiences of patients with disabling and uniformly terminal illness (e.g. amyotrophic lateral sclerosis) and illness characterized by episodic disability and prognostic uncertainty (e.g. multiple sclerosis). This study aimed to compare experiences of disability, quality of life (QoL) and psychological well-being in ALS and MS. One hundred patients with ALS and MS were interviewed at baseline and at six months. Variables measured included function, health related QoL, individualized QoL and psychological distress. Despite the divergent illness experiences of ALS and MS patients, groups did not differ on individualized QoL or mental well-being, and distress was in the normal range. Despite marked deterioration in ALS patients' health, there was no change in mental well-being and QoL. Psychological well-being appeared more important in maintaining QoL (individualized QoL and mental aspects of health related QoL) than physical factors. At the individual level, there was evidence of psychological adaptation to deteriorating function, which underlined the role of specific illness related challenges in determining perceived life quality and emotional well-being. In conclusion, the complex interplay between psychosocial and illness specific factors such as certainty with regard to prognosis has considerable implications for well-being and life quality. Recognizing such factors is essential when designing clinical interventions to promote adjustment and self-management among patients with neurological conditions.

The objective was to investigate the familial occurrence of the neurodegenerative condition amyotrophic lateral sclerosis (ALS), Parkinson's disease and dementia in the relatives of Irish ALS patients. A retrospective case control chart review study was conducted to extract the neurological family histories of Irish ALS patients and controls who attended the National Neurological Centre between January 2001 and January 2006. In total, details were extracted from 197 ALS and 235 general neurology pedigrees. Using the recurrence risk, lambda, ALS (lambda (1st degree)=7.77), Parkinson's disease (lambda (1st degree)=2.67) and dementia (lambda (1st degree)=6.21) were reported more frequently in relatives of ALS patients compared to those of non-ALS controls. Within sporadic ALS kindreds, the presence of neurodegenerative disease was not uniformly distributed. This study supports the conjecture that neurodegenerative disease aggregates within ALS kindreds, and indicates a shared genetic susceptibility towards some neurodegenerative phenotypes.

International audience; We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for clinical trials design. The median survival time from onset to death ranges from 20 to 48 months, but 10-20% of ALS patients have a survival longer than 10 years. Older age and bulbar onset are consistently reported to have a worse outcome. There are conflicting data on gender, diagnostic delay and El Escorial criteria. The rate of symptom progression was revealed to be an independent prognostic factor. Psychosocial factors, FTD, nutritional status, and respiratory function are also related to ALS outcome. The effect of enteral nutrition on survival is still unclear, while NIPPV has been found to improve survival. There are no well established biological markers of progression, although some are likely to emerge in the near future. These findings have relevant implications for the design of future trials. Randomization, besides the type of onset, should take into account age, respiratory status at entry, and a measure of disease progression pre-entry. Alternative trial designs can include the use of natural history controls, the so-called minimization method for treatment allocation, and the futility approach.

The objective was to test the hypothesis that a described association between homozygosity for a 50bp deletion in the SOD1 promoter 1684bp upstream of the SOD1 ATG and an increased age of onset in SALS can be replicated in additional SALS and control sample sets from other populations. Our second objective was to examine whether this deletion attenuates expression of the SOD1 gene. Genomic DNA from more than 1200 SALS cases from Ireland, Scotland, Quebec and the USA was genotyped for the 50bp SOD1 promoter deletion. Reporter gene expression analysis, electrophoretic mobility shift assays and chromatin immunoprecipitation studies were utilized to examine the functional effects of the deletion. The genetic association for homozygosity for the promoter deletion with an increased age of symptom onset was confirmed overall in this further study (p=0.032), although it was only statistically significant in the Irish subset, and remained highly significant in the combined set of all cohorts (p=0.001). Functional studies demonstrated that this polymorphism reduces the activity of the SOD1 promoter by approximately 50%. In addition we revealed that the transcription factor SP1 binds within the 50bp deletion region in vitro and in vivo. Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations.

Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.

Motor fatigue is a common complaint of polio survivors and has a negative impact on activities of daily living. The aim of this study was to establish a normative database for hand grip strength and fatigue and to investigate differences between prior-polio subjects and normal controls. Static and dynamic hand grip fatigue and maximum voluntary isometric contraction (MVIC) of hand grip were measured in subjects with a prior history of polio (n = 44) and healthy controls (n = 494). A normative database of fatigue was developed using four indices of analysis. Compared with healthy controls, subjects with prior polio had significantly reduced hand grip strength but developed greater hand grip fatigue in only one fatigue index. Quantitative measurement of fatigue in the prior-polio population may be useful in order to detect change over time and to evaluate treatment strategies.

Maximum voluntary isometric contraction (MVIC) is a standardized method for measurement of muscle strength in patients with neuromuscular disease. Values obtained from MVIC testing are difficult to interpret at present as normative data are limited. The objective of this study was to generate reference values for MVIC. A convenience sample of 494 healthy men and women aged 20-76 years was recruited. MVIC testing was performed on nine muscle groups bilaterally: neck flexors, shoulder abductors, shoulder adductors, elbow and knee flexors and extensors, and hip and ankle flexors. MVIC was performed using the Quantitative Muscle Assessment system. Age and sex related reference values were calculated for each muscle group using quantile regression. A clinical reporting system was developed to facilitate interpretation of patient values with reference to normal percentiles. Reference values generated from this study can be used to determine the presence and extent of muscle weakness in a given population and to evaluate the effectiveness of treatment interventions.

The mechanism of Aimspro remains unproven; if it is an immunomodulator and/or a modulator of sodium channels, it theoretically could be useful in ALS. A single, detailed but significantly flawed case report documents slowing in decline of certain respiratory functions in a patient claiming to have ALS, who started Aimspro shortly after bipap. Based upon this limited information, ALSUntangled supports further study of Aimspro, either in ALS animal models or in a small phase 2 trial with clear and objective endpoints carried out by skilled trialists familiar with the problems inherent with ALS clinical studies. Until a trial is undertaken, however, we do not support further use of this product by PALS.

The ALS journal celebrated its tenth birthday this year. The pace of experimental and clinical ALS research has been impressive in the past decade. There has been an explosion of new genes, new ani...