Hereditary spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders for which ⩾14 different genetic loci have been identified. In some SCA ...types, expanded tri- or pentanucleotide repeats have been identified, and the length of these expansions correlates with the age at onset and with the severity of the clinical phenotype. In several other SCA types, no genetic defect has yet been identified. We describe a large, three-generation family with early-onset tremor, dyskinesia, and slowly progressive cerebellar ataxia, not associated with any of the known SCA loci, and a mutation in the
fibroblast growth factor 14 (
FGF14) gene on chromosome 13q34. Our observations are in accordance with the occurrence of ataxia and paroxysmal dyskinesia in Fgf14-knockout mice. As indicated by protein modeling, the amino acid change from phenylalanine to serine at position 145 is predicted to reduce the stability of the protein. The present
FGF14 mutation represents a novel gene defect involved in the neurodegeneration of cerebellum and basal ganglia.
To systematically review the literature for studies on cognitive functioning in patients with low-grade glioma to evaluate assessment methods and prevalence of cognitive dysfunction.
A search was ...made in PubMed, Embase, and PsycINFO for articles published between January 2002 and June 2012 using cognition, memory, attention, executive functioning, and low-grade glioma as search terms.
Two reviewers independently performed the study selection and data extraction. Inclusion criteria were: studies including at least 10 adult patients, with suspected or confirmed low-grade glioma and cognitive functioning as outcome measure.
A standard data extraction form was used, with items regarding study quality, patient characteristics, type of measurement instruments, cognitive domain, definition of cognitive dysfunction, and reported prevalence.
Of the 312 articles screened on title/abstract, 69 were screened on full-text and, finally, 17 were included. A total of 46 different measurement instruments were found for the assessment of cognitive functioning; 5 of these were used 5 or more times. There was variability in the definition of cognitive dysfunction. The reported prevalence of cognitive dysfunction ranged from 19% to 83%.
Many patients with low-grade glioma experience cognitive dysfunction. However, there is no consensus on how to assess cognitive functioning in these patients.
Abstract Impaired cognition in later life may result from Alzheimer's disease-related pathology, but also from vascular pathology. We studied to what extent vascular risk explained heritability of ...cognition in 780 individuals, related in one extended pedigree in a genetically isolated population, in the ERF study. Heritability was estimated using variance components modelling (SOLAR). Univariate analyses included models with and without vascular disease; bivariate analyses included both cognitive and vascular traits, such as blood pressure, serum glucose or lipids. Heritability for immediate and delayed recall, recognition, semantic fluency, Trail making B and Stroop tests was significant, with estimates from 0.16 to 0.36. Vascular factors did not affect cognitive functions, except immediate recall and the Stroop test. Heritability estimates did not change significantly when adjusted for vascular disease. We found no genetic correlation between cognition and vascular traits. Therefore, in this population vascular disease is mildly associated with cognitive dysfunction, and in those with vascular disease, the underlying genetic risk factors are not likely to account for the genetic variation in cognition at adult age.
The effects of the timing of insemination relative to ovulation on fertilization rate, accessory sperm count and early embryo development were studied in sows. Oestrus detection was performed at ...intervals of 8 h. Sows were artificially inseminated once with 3 x 10(9) spermatozoa. Transrectal ultrasonography was performed at intervals of 4 h to determine when ovulation occurred and sows were killed at 120 +/- 6 h after ovulation. For each insemination-ovulation interval of 8 h, fertilization rates were as follows: > 48 h, 35% (n = 1); 48-40 h, 51 +/- 36% (n = 6); 40-32 h, 54 +/- 36% (n = 14); 32-24 h, 79 +/- 32% (n = 19); 24-16 h, 94 +/- 11% (n = 24); 16-8 h, 92 +/- 21% (n = 24); 8-0 h, 95 +/- 22% (n = 21) and for the sows that were inseminated after ovulation: 0 to -8 h, 75 +/- 38% (n = 26); -8 to -16 h, 74 +/- 43% (n = 15) and < -16 h, 0% (n = 1). The median accessory sperm count differed among the groups from 1 (insemination 40-48 h before ovulation) to 126 (insemination 0-8 h after ovulation) (P = 0.0001). Within each 8 h time interval, the normal embryos from sows with less than 90% normal embryos were less developed and had a lower sperm count than did the normal embryos from sows with more than 90% normal embryos (P < 0.05).
We studied the diagnostic accuracy of single-photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) in 48 patients with probable ...Alzheimer's disease (AD) according to NINCDS-ADRDA criteria and in 60 controls recruited from a population-based study. With logistic regression, we identified decreased temporal regional cerebral blood flow as the best discriminating variable between patients and controls. Receiver-operator characteristic curves showed that the discriminative ability of SPECT improved with increasing dementia severity. With specificity set at 90%, sensitivity figures were 42% in mild, 56% in moderate, and 79% in severe AD. The diagnostic gain as a function of the prior probability of the disease being present was computed for those with mild AD. When the prior probability varied at around 50%, the diagnostic gain for mild AD patients was substantial (a maximum of 34%) for a positive test result but poor for a negative test result. The results suggest that the practical usefulness of SPECT as a diagnostic adjunct in patients suspected of having mild AD is confined to situations in which, on clinical grounds, there is considerable diagnostic doubt.
Plasma levels of several amino acids were studied in 14 patients with early stage probable Alzheimer's disease (AD) and 17 age-matched controls. In the AD patients a possible relationship between ...amino acid levels and behavioural symptomatology was also investigated. We found significantly reduced levels of tryptophan and methionine in plasma samples from the AD patients compared to the control subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and the ratio of plasma taurine and the product of the plasma levels of methionine and serine (TSM-ratio) were significantly increased in the AD patients in comparison with the controls. However, no difference was found in plasma tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning the behavioural symptomatology no significant correlation was found between the Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported findings suggest that abnormal amino acid metabolism is present in the early stages of AD. We hypothesize that this abnormality could play a role in the pathogenesis of behavioural changes occurring in later stages of AD.
OBJECTIVE To investigate the effect of missing values due to behavioural disturbances on the neuropsychological test profile in frontotemporal dementia (FTD). The neuropsychological examination of ...patients with FTD poses a methodological problem. In many patients it is impossible to administer a complete test battery, due to behavioural disturbances inherent to the disease. This study describes the test behaviour of patients with FTD, the number of missing values due to disturbed test behaviour, and its influence on neuropsychological test results. METHODS Thirty one patients with probable FTD were administered a neuropsychological test battery including measures of memory, intelligence, and executive functioning. Moreover, patients were rated on a global deterioration scale and a test behaviour scale, constructed for this study. RESULTS The more disturbing the test behaviour, the less tests were assessable, leading to many missing values. The most disturbing features were “positive symptoms” of FTD, such as perseveration and stimulus boundedness. The effect of test behaviour was largest for tests measuring executive functions and reasoning capabilities. The replacement of the missing values due to behavioural disturbances by the lowest score also showed the largest effect on tests of executive function and reasoning abilities. CONCLUSION Data imputation of missing values due to test behaviour disturbances provides a more differentiated picture of cognitive deficits in FTD.
Abstract
Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): ZonMW: The Netherlands Organisation for Health Research and Development
Background
Stable ...angina pectoris (SAP) is a highly common condition. Despite optimal medical treatment (OMT) patients often remain symptomatic and at high risk for cardiovascular morbidity and mortality. In daily practice the standard treatment consists of OMT usually followed by an invasive strategy, consisting of coronary angiography and subsequent coronary revascularization. However, recent studies showed that these costly and invasive procedures do not result in superior effects on re-events and prognosis as compared to drug therapy alone in patients with SAP. On the other hand, the effect of lifestyle-related interventions on vascular function and the progression of atherosclerotic coronary artery disease is well-known. Yet, contemporary RCTs comparing lifestyle interventions with coronary revascularization in patients with SAP are lacking.
Purpose
To compare the impact of a 12-month cardiac rehabilitation (CR) programme versus a routinely applied invasive approach (including coronary angiography and subsequent coronary revascularization) on anginal complaints and cost-effectiveness in SAP patients. We hypothesize that CR is at least equally effective as an invasive approach.
Methods
216 SAP patients with residual anginal complaints under OMT will be randomized to usual care or a 12-month CR intervention aiming at angina relief and sustainable behavioural change for long-lasting improvement in cardiovascular health. The CR programme consists of multiple lifestyle interventions including an exercise programme, a dietary intervention and a psychoeducation module with a stepped decline in guidance by health care professionals. Patients in the CR group will receive access to an online platform, a chatbot and a smartwatch enabling patients and professionals to monitor the progress and adherence to lifestyle advices. During the first 3 months patients will receive face to face guidance, the next 3 months will consist of telerehabilitation using the smartwatch with weekly video consulting and the last 6 months will be focussed on relapse prevention and guidance on demand.
The primary outcome will be the quantity of anginal complaints (evaluated by the Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, the ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing.
Future implications
This will be the first study evaluating a comprehensive disease-specific multimodal lifestyle intervention as a primary treatment for patients with SAP. If proven successful this study will have a great impact on the daily care of these patients as coronary revascularizations can partly be replaced by a less invasive, less costly and better sustainable treatment.
PDF
