Objective: We sought to define the significance of brachial amyotrophic diplegia (flail arm syndrome [FA]) and the pseudopolyneuritic variant (flail leg syndrome [FL]) of amyotrophic lateral sclerosis (ALS; motor neuron disease). Methods:We analyzed survival in clinic cohorts in London, UK (1,188 cases), and Melbourne, Australia (432 cases). Survival from disease onset was analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results:In the London cohort, the FA syndrome represented 11% and the FL syndrome 6% of the sample. Median survival was 35 months for limb onset and 27 months for bulbar onset ALS, whereas this was 61 months for FA syndrome (p Ͻ 0.001) and 69 months for FL syndrome (p Ͻ 0.001). Five-year survival in this cohort was 8.8% for bulbar onset, 20% for limb onset, 52% for FA syndrome, and 64% for FL syndrome. The ratio of men to women was 4:1 in the FA group compared to 2:1 in other limb onset cases. Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. In the Melbourne cohort, median survival for limb onset ALS was 31 months, bulbar onset 27 months, FA syndrome 66 months (p Ͻ 0.001), and FL syndrome 71 months (p ϭ 0.001). Amyotrophic lateral sclerosis (ALS) comprises several clinical phenotypes united by a common cellular and molecular pathology. Conclusions:1 The three main clinical categories defined by Aran, Charcot, Duchenne, and others in the 19th century and which were subsequently shown to have both diagnostic and prognostic significance were progressive bulbar palsy (bulbar onset ALS), classic limb onset (Charcot) ALS, and a lower motor neuron form termed progressive muscular atrophy (PMA).2-5 Prognostic factors in these forms of ALS have been delineated through clinic and population-based studies. 6,7 Bulbar onset tends to have a worse prognosis than limb onset, and both forms have a worse prognosis than PMA.2,4-7 However, these three phenotypic categories do not fully capture the spectrum of clinical heterogeneity in ALS. This heterogeneity may contribute to diagnostic error and delay, and with the advent of large-scale whole genome studies that have the potential to identify genetic variants influencing both risk and phenotype,

Replicable risk factors for ALS include increasing age, family history and being male. The male: female ratio has been reported as being between 1 and 3. We tested the hypothesis that the sex ratio changes with age in a population register covering the south-east of England. The sex ratio before and after the age of 51 years was compared using a Z-test for proportions. Kendall's tau was used to assess the relationship between age group and sex ratio using incidence and prevalence data. Publicly available data from Italian and Irish population registers were compared with results. There was a significant difference in the proportion of females with ALS between those in the younger group (30.11%) and those in the older group (43.66%) (p = 0.013). The adjusted male: female ratio dropped from 2.5 in the younger group to 1.4 in the older group using prevalence data (Kendall's tau = -0.73, p = 0.039). Similar ratios were found in the Italian but not the Irish registry. We concluded that sex ratios in ALS may change with age. Over-representation of younger patients in clinic registers may explain the variation in sex ratios between studies. Menopause may also play a role.

Background/Aims: We aimed to estimate the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the South East of England. The reported incidence of ALS varies between 0.44 and 3.2 per 100,000 person years. This can partly be explained by differences in design and diagnostic criteria used. There is little population data concerning England, particularly the South East. Methods: A population study of South-East England (total population: 2,890,482) was carried out and multiple sources including our tertiary centre and district general hospitals were used for complete case ascertainment. Results: Between 1 January 2002 and 30 June 2006 we identified 138 people (76 males; 62 females) with a new diagnosis of ALS, giving a crude incidence of 1.06 per 100,000 person years. The projected age- and gender-adjusted annual incidence rate for England and Wales was 1.10 (95% CI 0.80–1.40). 142 people were alive on 30 June 2006, giving a point prevalence of 4.91 per 100,000 population. Conclusion: Our incidence and prevalence rates are similar to those reported in comparable studies from other countries. This argues against the role of a specific exogenous factor in the aetiology of ALS in South-East England.

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This systematic review comprises an objective appraisal of the evidence in regard to the management of respiration in patients with motor neuron disease (MND/ALS). Studies were identified through computerised searches of 32 databases. Internet searches of websites of drug companies and MND/ALS research web sites, 'snow balling' and hand searches were also employed to locate any unpublished study or other 'grey literature' on respiration and MND/ALS. Since management of MND/ALS involves a number of health professionals and care workers, searches were made across multiple disciplines. No time frame was imposed on the search in order to increase the probability of identifying all relevant studies, although there was a final limit of March 2005. Recommendations for patient and carer-based guidelines for the clinical management of respiration for MND/ALS patients are suggested on the basis of qualitative analyses of the available evidence. However, these recommendations are based on current evidence of best practice, which largely comprises observational research and clinical opinion. There is a clear need for further evidence, in particular randomised and non-randomised controlled trials on the effects of non-invasive ventilation and additional larger scale cohort studies on the issues of initial assessment of respiratory symptoms, and management and timing of interventions.