V Meininger

..At the ultrastructural level, the nuclear inclusions were made of straight filaments (10-12 nm in diameter) arranged at random, reminiscent of the polyglutamine intranuclear hyaline inclusions...

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..It made possible large collaborative programs in and among many countries. We do hope that this impulse will continue and be stimulated by additional results both in the field of basic science and clinical research...

..An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS...

..It made possible large collaborative programs in and among many countries. We do hope that this impulse will continue and be stimulated by additional results both in the field of basic science and clinical research...

..In view of the similarities with ALS, we consider that PLS may represent a slowly progressive syndrome closely related to this disease...

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..Our clinical, electrophysiological and pathological investigations provide evidence that the disease has a heterogeneous clinical presentation and that degeneration is not restricted to the central motor system...

..A simplified score, RL401S, was constructed, designed to be easy to use and interpret. The predictive powers of the two scores were similar...

..Isolated cases of BP in patients with other neurological disorders further support a pathogenic association between cutaneous and neurological diseases. Any description of BP in patients with amyotrophic lateral sclerosis is lacking...

..To assess the efficacy and safety of pentoxifylline, a US Food and Drug Administration-approved drug, in patients with ALS treated with riluzole...

..However, of five patients who had significantly high anti-GM1 titres (>3200) at baseline, four responded to IVIg. This trial confirms that IVIg is a promising therapeutic option for multifocal motor neuropathy...

..5+/-1.6 months and above it was equal to 18.5+/-1.5; relative risk was 3.31. These data confirm the importance of nocturnal oxymetry on survival in ALS patients both in clinical practice and in view of therapeutic trials...

..Clinicians in charge of patients with progressive spinal cord signs should bear in mind that the field of degenerative diseases is a moving one and that a degenerative aetiology has to be suspected more widely than in the past...

..In ALS patients, our results show that subcortical lesions extend beyond the corticospinal tract and are clinically relevant...

..These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study...

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..CONCLUSIONS: This open-label extension study reinforces and extends the results of the preceding double-blind trials regarding the safety of riluzole and shows that the drug is well tolerated for long periods of up to almost 7 years...

..However, when reviewing known cases of PLS drawn from the literature, rigorous retrospective application of these new PLS criteria raises an unanswered question: does pure PLS exist?..

..Median survival time was dramatically shorter (217 d) in Group 1 than in Group 2 (619 d, p = 0.015)...

..To appreciate why this remains so, the development of our understanding of ALS as documented by case reports in the literature will be discussed in this paper...

..We suggest that, in addition to dysfunction of basal ganglia-dependent systems, degeneration of the supplementary motor area could also be involved in the patient's bradykinesia...

..In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01)...

..To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study...

..Missense mutations in the glycyl-tRNA synthetase (GARS) gene have been recently reported in families with either dHMN-V, CMT2D, or both...

..8% in the placebo group), comparable to the known profile of 20 mg GA. In conclusion, GA at a dose of 40 mg/day did not show any beneficial effect in ALS patients, and safety and tolerability of GA were good in this population...

..An effort has to be made for a better understanding of the causes of deterioration of ALS patients. A more proactive attitude to treat respiratory infections could have a significant impact on survival...

..All these data have allowed new therapeutic molecules to be tested alone or in combination with riluzole. Despite the negative results obtained until now, we hope to demonstrate very soon a greater improvement in therapy...

..Both were correlated with balance and posture impairment (UPDRS and Berg's scale, P < 0.001). This study suggests that extrapyramidal involvement plays a role in stiffness and balance impairment in a subset of ALS patients...

..The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation...

..This review suggests that in these trials there is a discrepancy between drug effects on survival versus function. These results suggest that a reappraisal of strategies to identify therapeutic targets for ALS is required...

..Mutations in SOD1, ANG, VAPB, TARDBP and FUS genes have been identified in amyotrophic lateral sclerosis (ALS)...

..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...

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..Mutations in the ALS2 gene cause juvenile-onset autosomal recessive amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia...

..Moreover, since skeletal muscle is a key metabolic tissue, our findings suggest that ALS may not solely arise from neuronal events but also from more generalized metabolic defects...

..Thus, the alteration in Nogo expression pattern, common to sporadic and familial ALS, represents a potential diagnosis tool and points strongly to Nogo having a central role in disease...

..It remains to be determined if the group of patients with high CSF glutamate concentrations represents a specific subgroup of patients in terms of mechanism of disease, or only in terms of the spatial extent of motor neuron insult...

..The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus...

..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...

..These results suggest that PRPH mutations may be responsible for a small percentage of ALS, cases and they provide further support of the view that neurofilament disorganization may contribute to pathogenesis...

..This review details the potential role the KP has in ALS and advances a testable hypothetical model...

..Identifying different disease subtypes is an unavoidable step toward the understanding of the physiopathology of ALS and will hopefully help to design specific treatments for each subset of patients...

..A locus was established between the markers D9S2154 and D9S1791 by comparing haplotypes between these families...

..Our study confirms that in ALS the cortical involvement is asymmetrical and predominant in the premotor region and the insula...

..Together, our findings show that energy metabolism in mSOD1 mice shifts toward an increase in the peripheral use of lipids. This metabolic shift probably accounts for the protective effect of dietary lipids in this model...

..Nogo-A immunoreactivity was observed selectively in atrophic slow-twitch type I fibers. These results suggest that Nogo expression in muscle is a marker of amyotrophic lateral sclerosis severity...

..In this workshop, clinical and preclinical researchers established in the field of ALS/MND met in Holland in March 2006 in order to establish guidelines for the community for drug testing in mouse models...

..Second, they identify specific gene regulations to be explored in the search for therapeutic strategies that could alleviate disease before motor neuron death manifests clinically...

..These findings further corroborate that TDP-43 is involved in ALS pathogenesis...

..However, the cellular and molecular mechanisms that link ANG, a multidomain protein, to ALS are still unknown...