A clinical tool for predicting survival in ALS

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. Methods: 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. Findings: Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. Interpretation: A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors

EAACI Biologicals Guidelines-Recommendations for severe asthma

Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.Peer reviewe

Frontotemporal dementia

Purpose of review: the syndromes of frontotemporal lobar degeneration are increasingly recognized as an important cause of early-onset dementia. Diagnostic consensus criteria have now been established for almost a decade, and form the framework for its clinical classification. While these criteria remain useful, a growing body of evidence suggests that revisions may be necessary to improve their validity and applicability.Recent findings: in each individual syndrome, the core features are not uniformly present, and criteria that are currently used to exclude a condition, such as impaired episodic memory, are often present. Imaging, however, may warrant increased diagnostic prominence, particularly for diagnosis in semantic dementia and prognosis in behavioural syndromes. There is clinical and pathological overlap between the syndromes, but the clinical distinction between progressive nonfluent aphasia and semantic dementia is strengthening. Several series have refined our understanding of the correspondence between clinical syndromes and histopathological subtype: strong for tau-negative, ubiquitin-positive forms and more variable for tau-positive forms, yet prospective studies are still rare. The influence of genetic factors varies substantially across the syndromes.Summary : further research should aim to integrate detailed clinical, radiological, pathological and genetic information.<br/

Making sense of progressive non-fluent aphasia: an analysis of conversational speech

The speech of patients with progressive non-fluent aphasia (PNFA) has often been described clinically, but these descriptions lack support from quantitative data. The clinical classification of the progressive aphasic syndromes is also debated. This study selected 15 patients with progressive aphasia on broad criteria, excluding only those with clear semantic dementia. It aimed to provide a detailed quantitative description of their conversational speech, along with cognitive testing and visual rating of structural brain imaging, and to examine which, if any features were consistently present throughout the group; as well as looking for sub-syndromic associations between these features. A consistent increase in grammatical and speech sound errors and a simplification of spoken syntax relative to age-matched controls were observed, though telegraphic speech was rare; slow speech was common but not universal. Almost all patients showed impairments in picture naming, syntactic comprehension and executive function. The degree to which speech was affected was independent of the severity of the other cognitive deficits. A partial dissociation was also observed between slow speech with simplified grammar on the one hand, and grammatical and speech sound errors on the other. Overlap between these sets of impairments was however, the rule rather than the exception, producing continuous variation within a single consistent syndrome. The distribution of atrophy was remarkably variable, with frontal, temporal and medial temporal areas affected, either symmetrically or asymmetrically. The study suggests that PNFA is a coherent, well-defined syndrome and that varieties such as logopaenic progressive aphasia and progressive apraxia of speech may be seen as points in a space of continuous variation within progressive non-fluent aphasia

Semantic Dementia Versus Nonfluent Progressive Aphasia Neuropsychological Characterization and Differentiation

Background: Early progressive nonfluent aphasia (PNFA) may be difficult to differentiate from semantic dementia (SD) in a nonspecialist setting. There are descriptions of the clinical and neuropsychological profiles of patients with PNFA and SD but few systematic comparisons. Method: We compared the performance of groups with SD (n = 27) and PNFA (n = 16) with comparable ages, education, disease duration, and severity of dementia as measured by the Clinical Dementia Rating Scale on a comprehensive neuropsychological battery. Principal components analysis and intergroup comparisons were used. Results: A 5-factor solution accounted for 78.4% of the total variance with good separation of neuropsychological variables. As expected, both groups were anomic with preserved visuospatial function and mental speed. Patients with SD had lower scores on comprehension-based semantic tests and better performance on verbal working memory and phonological processing tasks. The opposite pattern was found in the PNFA group. Conclusions: Neuropsychological tests that examine verbal and nonverbal semantic associations, verbal working memory, and phonological processing are the most helpful for distinguishing between PNFA and SD.MRCMRCARC (Australian Research Council) [FF0776229]Australian Research Council (ARC)CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior), Brazil [BEX 4335/074]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazi

Evidence of an environmental effect on survival in ALS

Amyotrophic lateral sclerosis (ALS, motor neuron disease) is a neurodegenerative disorder of motor neurons leading to paralysis and eventual death by respiratory failure. Median survival is 2-3 years. Susceptibility genes, environmental triggers and disease related prognostic factors have been established, but environmental effects on survival are yet to be investigated. We analysed survival in the South-East England ALS register (SEALS register). Kaplan-Meier and Cox regression analyses were used to investigate survival in London, coastal and rural areas according to postcode at diagnosis. Results showed that there were 933 cases of ALS identified in the catchment area during the study period (1994-January 2012). Cox regression demonstrated a highly significant model for survival with significant protective variables: coastal residency, riluzole use and younger age at onset. Significantly worse survival was associated with London residency, older age as well as definite and probable El Escorial classifications. In conclusion, these findings suggest the possibility of an environmental effect on survival in ALS