Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Prediction of perinatal mortality at an early stage of pregnancy

AIM: To define the probability of foetal and neonatal death (PFND) in Lithuania by means of the Medical Birth registry. METHODS: The Medical Birth registry for the year 2002 (29,619 pregnancies resulting in delivery) was used, covering social, environmental, health behaviour factors, obstetric history, health status of pregnant women, and delivery. RESULTS: A statistically significant model has been obtained in which 12 out of 45 analysed factors were significant for the risk of perinatal mortality (PM). In the case of previous neonatal pathology, e.g. damage to CNS, the risk of PM (OR 5.2; 95% CI = 2.1-13.3) was similar to the reported manual work or harmful working conditions during pregnancy (OR 4.8; 95% CI = 1.9-12.1 and OR 4.5; 95% CI = 1.3-15.2, respectively). The influence of father's alcohol abuse (OR 2.6; 95% CI = 1.4-4.7) was comparable to that of the stillborns or premature deliveries. The combination of several factors increased PFND significantly: maternal smoking during pregnancy and paternal smoking and alcohol abuse raised PFND to 0.03 (OR 6.8), mother's hard manual work in combination with harmful conditions during pregnancy increased OR more than 10 times (PFND 0.32) as compared with the situation when only one of those factors was present. CONCLUSIONS: The influence of social, environmental, and behavioural factors on the risk of PM was comparable to that of some of the complications during a previous pregnancy. The combination of risk factors significantly increased PFND. Using modelling, the individual prognosis may be presented to every pregnant woman at an early stage of pregnancy to potentially decrease the impact of unfavourable risk factors on PM.     

Social dimensions of mortality from external causes in Lithuania: do education and place of residence matter?

Summary. Objectives To assess inequalities in mortality from external causes by the level of education and the place of residence during the period of socio-economic transition in Lithuania. Methods Information on deaths, place of residence, and the level of education of persons aged 25 and older was derived from the National Database of Lithuania and censuses for 1989 (n = 3537) and 2001 (n = 4790). Results Mortality from external causes of Lithuanian urban and rural populations was strongly associated with the level of education. Educational inequalities increased throughout the period of socio-economic transition. In urban areas, mortality among the least educated population was 3.20 times higher in 1989 and 3.37 times higher in 2001, compared to those with university-level education. In rural areas the educational mortality rate ratios reached 3.47 and 4.33, respectively. The greatest educational inequalities were observed in suicide mortality, especially among males. Conclusions The results of this study disclosed increasing inequalities in mortality from external causes. Less educated populations, especially in rural areas, should receive particular attention in the development of strategies for the prevention of mortality from external causes. Submitted: 29 June 2004; Accepted: 8 March 2006     

Mortality from external causes in Lithuania: looking for critical points in time and place

AIM: A study was undertaken to analyse trends in mortality from major external causes of death, and to detect urban/rural differences by cut points over the period of socioeconomic transition. METHODS: Information on deaths from major external causes (traffic accidents, suicides, and homicides) for the 1990-2000 period was obtained from Lithuanian Department of Statistics. Mortality rates were age standardized, using the European standard, and analysed, according to (urban/rural) residence and sex. The Jointpoint analysis was used to identify the best-fitting points, wherever a statistically significant change in mortality occurred. RESULTS: The most critical point for external causes of mortality during the period of transition was the year 1994, when an increasing mortality trend reversed to a decreasing one. Mortality from suicides primarily caused these positive changes. Changes in mortality from traffic accidents were not significantly associated with the period under analysis. Numerous less favourable trends in rural areas, including suicide rates, traffic accidents, and homicides, are likely to stratify urban/rural health outcomes in the future. CONCLUSION: Despite a recent decline, mortality from external causes remains at an extremely high level in Lithuania. Future progress requires sustained improvements in prevention, and serious attention to external causes of death in health policy development.     

Parkinson patients have a presynaptic serotonergic deficit: A dynamic deep brain stimulation PET study

Patients with Parkinson’s disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Apart from alleviating the motor symptoms, Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how turning DBS off affects the serotonergic system. We here exploit a novel functional PET neuroimaging methodology to evaluate the preservation of serotonergic neurons and capacity to release serotonin. We measured cerebral 5-HT_1BR binding in 13 DBS-STN treated PD patients, at baseline and after turning DBS off. Ten age-matched volunteers served as controls. Clinical measures of motor symptoms were assessed under the two conditions and correlated to the PET measures of the static and dynamic integrity of the serotonergic system. PD patients exhibited a significant loss of frontal and parietal 5-HT_1BR, and the loss was significantly correlated to motor symptom severity. We saw a corresponding release of serotonin, but only in brain regions with preserved 5-HT_1BR, suggesting the presence of a presynaptic serotonergic deficit. Our study demonstrates that DBS-STN dynamically regulates the serotonin system in PD, and that preservation of serotonergic functions may be predictive of DBS-STN effects.