Although morbility and mortality in acromegaly are higher than in the general population, there have been very few previous epidemiological studies. This study tries to answer "why". Seventy-four patients affected by acromegaly in Vizcaya (Spain) between 1970 and 1989 were considered for an epidemiological study. The prevalence of known cases at the end of 1989 was 60 per million inhabitants. The average incidence of newly diagnosed cases was 3.1 per million people per year. Unexpectedly, acromegaly was more frequent in women (n = 48) than in men (n = 26), with a ratio of 1.8:1. Mean age at diagnosis was significantly higher in women (46.1 +/- 2.2 yr) than in men (39.5 +/- 2.2 yr) (p < 0.05) There was a positive correlation between age at diagnosis and the estimated duration of the disease (r = 0.56, p < 0.05) and a negative one between age and basal GH serum levels (r = -0.52 p < 0.002). The age at diagnosis was significantly higher in patients with invasive tumors (grade III and IV) than in those with enclosed tumors (grade I and II) (47.7 +/- 1.8 vs 40.1 +/- 3.3 p < 0.05). In general, mortality was higher than the expected for the control population (standardized mortality ratio, SMR = 3.2, 95% confidence interval. Cl = 1.55-5.93). However, mortality was higher in men (SMR = 7, 95% Cl = 2.81-14.4) but not in women (SMR = 1.4 95% Cl = 0.29-4.17).(ABSTRACT TRUNCATED AT 250 WORDS)
We aimed to perform a comprehensive systematic review of the existing ataxia scales. We described the disorders for which the instruments have been validated and used, the time spent in its application, its validated psychometric properties, and their use in studies of natural history and clinical trials. A search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane databases. The web sites ClinicalTrials.gov and Orpha.net were also used to identify the endpoints used in ongoing randomized clinical trials. We identified and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS); semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS 2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale (FAIS). SARA and ICARS were the best studied and validated so far, and their reliability sustain their use. Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history. Up to now, no clear advantage has been disclosed for any of them; however, we recommend the use of specific measurements of gait since gait ataxia is the first significant manifestation in the majority of ataxia disorders and comment on the best scales to be used in specific ataxia forms. Quantitative ataxia scales will be needed to speed up evidence from phase II clinical trials, from trials focused on the early phase of diseases, and for secondary endpoints in phase III trials. Finally, it is worth remembering that estimation of the actual minimal clinically relevant difference is still lacking; this, together with changes in quality of life, will probably be the main endpoints to measure in future therapeutic studies.
The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. To date, more than 30 genes have been identified triggering the well-described clinical and pathological phenotype, but the underlying cellular and molecular events are still poorly understood. Studies of the functions of the proteins implicated in SCAs and the corresponding altered cellular pathways point to major aetiological roles for defects in transcriptional regulation, protein aggregation and clearance, alterations of calcium homeostasis, and activation of pro-apoptotic routes among others, all leading to synaptic neurotransmission deficits, spinocerebellar dysfunction, and, ultimately, neuronal demise. However, more mechanistic and detailed insights are emerging on these molecular routes. The growing understanding of how dysregulation of these pathways trigger the onset of symptoms and mediate disease progression is leading to the identification of conserved molecular targets influencing the critical pathways in pathogenesis that will serve as effective therapeutic strategies in vivo, which may prove beneficial in the treatment of SCAs. Herein, we review the latest evidence for the proposed cellular and molecular processes to the pathogenesis of dominantly inherited spinocerebellar ataxias and the ongoing therapeutic strategies.
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