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Philippe Corcia,1 Paul H Gordon21Centre SLA, CHRU de Tours, Tours, France; UMR INSERM U930, Université François Rabelais de Tours (PC), Tours, France; 2AP-HP, Hôpital de la Pitié-Salpêtrière, Département des Maladies du Système Nerveux (PHG), Paris, FranceAbstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to progressive weakness from loss of motor neurons and death on average in less than 3 years after symptom onset. No clear causes have been found and just one medication, riluzole, extends survival. Researchers have identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation, and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration or occur secondary to other cellular processes, and may itself contribute to oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of these pathways. While every agent tested in the 18 years after the approval of riluzole has been ineffective, basic and clinical research methods in ALS have become dramatically more sophisticated. Dexpramipexole (RPPX), the R(+) enantiomer of pramiprexole, which is approved for symptomatic treatment of Parkinson disease, carries perhaps the currently largest body of pre- and early clinical data that support testing in ALS. The neuroprotective properties of RPPX in various models of neurodegeneration, including the ALS murine model, may be produced through protective actions on mitochondria. Early phase trials in human ALS suggest that the drug can be taken safely by patients in doses that provide neuroprotection in preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is underway.Keywords: dexpramipexole, amyotrophic lateral sclerosis, survival, clinical trials, neurodegeneration

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease associated with a life expectancy of approximately 3 years after symptom onset, but the range of survival extends from a few months for some to decades for approximately 5% of patients. There is no clear cause in the majority of cases and just one medication, riluzole, has been shown to modestly prolong survival. Research has identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, generation of free radicals, excitotoxicity, inflammation and apoptosis, but for most patients the underlying cause is unknown. While ALS is considered to be a complex genetic disorder in which multiple genes in combination with environmental exposures combine to render a person susceptible, few genetic or environmental risks have been discovered to date. The diagnosis is based on the history and examination showing progressive upper and lower motor neuron findings. The electromyogram can help confirm the diagnosis, and additional tests are used to exclude other conditions. Published practice parameters guide the care of patients with ALS. Until the elucidation of aetiologies leads to the development of more robust neuroprotective agents, both pharmacological and nonpharmacological treatments are directed at maintaining quality of life and prolonging life to the greatest extent possible. Riluzole, ventilatory support for those with respiratory insufficiency, gastrostomy for those with dysphagia and multidisciplinary care may help extend life. The off-label use of many symptomatic agents can have a meaningful impact for those with the illness. Palliative care ensures dignity toward the end stages of the disease. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of the processes that are initiated after disease onset. Novel therapies currently in trials include potential neuroprotective agents with differing mechanisms of action, vaccine therapies, stem cell injections and diaphragmatic pacing. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate the change in the prevalence of dental erosion, over time, by a review of the data from the published national dental surveys of young people in the UK. A subsidiary objective was to investigate the relationship between erosion and possible associated risk factors. DESIGN: The review was based on cross-sectional prevalence studies incorporating a clinical dental examination and structured interviews. SAMPLE: The data were collated from the 1993 UK childrens' dental health survey and the dental report of the two National Diet and Nutrition Surveys (NDNS) of children aged 1(1/2)-4(1/2) in 1992/3 and 4-18 years in 1996/7. The criteria used for data collection were comparable between the three different studies. RESULTS: Comparing the data from the different studies, the prevalence of erosion was seen to increase from the time of the childrens' dental health survey in 1993 and the NDNS study of 4-18-year-olds in 1996/7. There was a trend towards a higher prevalence of erosion in children aged between 3(1/2) and 4(1/2) and in those who consumed carbonated drinks on most days compared with toddlers consuming these drinks less often. Drinks overnight were associated with an increased prevalence of erosion. More 4-6-year-olds with reported symptoms of gastro-oesophageal reflux had erosion compared with symptom-free children. On multivariate analysis, the strongest independent association with erosion was geography, with children living in the North having twice the odds of having erosion compared with those in London and the South-east. CONCLUSIONS: Comparing prevalence data from cross-sectional national studies indicates that dental erosion increases between different age cohorts of young people over time. Dietary associations with erosion are present but weak. Similarly, there is an association apparent between erosion, symptoms of gastro-oesophageal reflux and socio-demographic variables such as region of domicile, social class, and receipt of social benefits. [ABSTRACT FROM AUTHOR]