Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons, with a median survival of 2–3 years. Although various phenotypic and research diagnostic classification systems exist and several prognostic models have been generated, there is no staging system. Staging criteria for amyotrophic lateral sclerosis would help to provide a universal and objective measure of disease progression with benefits for patient care, resource allocation, research classifications and clinical trial design. We therefore sought to define easily identified clinical milestones that could be shown to occur at specific points in the disease course, reflect disease progression and impact prognosis and treatment. A tertiary referral centre clinical database was analysed, consisting of 1471 patients with amyotrophic lateral sclerosis seen between 1993 and 2007. Milestones were defined as symptom onset (functional involvement by weakness, wasting, spasticity, dysarthria or dysphagia of one central nervous system region defined as bulbar, upper limb, lower limb or diaphragmatic), diagnosis, functional involvement of a second region, functional involvement of a third region, needing gastrostomy and non-invasive ventilation. Milestone timings were standardized as proportions of time elapsed through the disease course using information from patients who had died by dividing time to a milestone by disease duration. Milestones occurred at predictable proportions of the disease course. Diagnosis occurred at 35% through the disease course, involvement of a second region at 38%, a third region at 61%, need for gastrostomy at 77% and need for non-invasive ventilation at 80%. We therefore propose a simple staging system for amyotrophic lateral sclerosis. Stage 1: symptom onset (involvement of first region); Stage 2A: diagnosis; Stage 2B: involvement of second region; Stage 3: involvement of third region; Stage 4A: need for gastrostomy; and Stage 4B: need for non-invasive ventilation. Validation of this staging system will require further studies in other populations, in population registers and in other clinic databases. The standardized times to milestones may well vary between different studies and populations, although the stages themselves and their meanings are likely to remain unchanged.

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It has been suggested that interleukin-17 (IL-17) plays a crucial role in the development of several autoimmune diseases. However, there are no data about the relationship between myasthenia gravis and IL-17. The aim of this study was to measure the concentration of IL-17 and determine whether levels depend on the severity of MG. Serum IL-17 concentrations were measured in 25 patients. IL-17 concentrations were higher in generalized MG compared with controls and correlated with anti-acetylcholinesterase receptor antibody titers.

BackgroundAccumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.-10C > T, c.369 + 990C > A, c.370-81_370-77delCAGCC, c.640-16A > G, c.1000-22C > T) within the GLA gene associated with Fabry-like symptoms and galactosphingolipid accumulation.We analysed α-Gal A activity in plasma, leukocytes and skin fibroblasts in patients, and measured accumulation of galactosphingolipids by enzymatic methods and immunofluorescence techniques. Additionally, we evaluated GLA expression using quantitative PCR, EMSA, and cDNA cloning.ResultsCIH carriers had an altered GLA expression pattern, although most of the carriers had high residual enzyme activity in plasma, leukocytes and in skin fibroblasts. Nonetheless, CIH carriers had significant galactosphingolipid accumulation in fibroblasts in comparison with controls, and also glycolipid deposits in renal tubules and glomeruli. EMSA assays indicated that the c.-10C > T variant in the promoter affected a nuclear protein binding site.ConclusionsThus, inheritance of the CIH caused an mRNA deregulation altering the GLA expression pattern, producing a tissue glycolipid storage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0267-z) contains supplementary material, which is available to authorized users.

Previous studies have suggested a lower incidence of ALS in people of African origin. We used a population based register in an urban setting from inner city London postcodes where there is a large population of people of African ancestry to compare the frequency of ALS in people of European and African origin. Population statistics stratified by age, gender and ethnicity were obtained from the 2001 census. Incidence and prevalence were calculated in each ethnic group. Results showed that in a population of 683,194, of which 22% were of African ancestry, 88 individuals with ALS were identified over a seven-year period, including 14 people with African ancestry. The adjusted incidence in people of African ancestry was 1.35 per 100,000 person-years (95% CI 0.72-2.3) and in those of European ancestry 1.97 per 100,000 person-years (95% CI 1.55-2.48). In conclusion, in this small population based study we could not detect a difference in rates of ALS between people of African ancestry and those of European ancestry.