Lau, L. de

Rotterdam Aphasia Therapy Study (RATS) - 3: " The efficacy of intensive cognitive-linguistic therapy in the acute stage of aphasia"; design of a randomised controlled trial (Article)

2013-01-23T00:00:00Z

Background: Aphasia is a severely disabling condition occurring in 20 to 25% of stroke patients. Most patients with aphasia due to stroke receive speech and language therapy. Methodologically sound randomised controlled trials investigating the effect of specific interventions for patients with aphasia following stroke are scarce. The currently available evidence suggests that intensive speech and language therapy is beneficial for restoration of communication, but the optimal timing of treatment is as yet unclear.In the Rotterdam Aphasia Therapy Study-3 we aim to test the hypothesis that patients with aphasia due to stroke benefit more from early intensive cognitive-linguistic therapy than from deferred regular language therapy.Methods/design: In a single blinded, multicentre, randomised controlled trial, 150 patients with first ever aphasia due to stroke will be randomised within two weeks after stroke to either early intensive cognitive-linguistic therapy (Group A) or deferred regular therapy (Group B). Group A will start as soon as possible, at the latest two weeks after stroke, with a four week period of one hour a day treatment with cognitive-linguistic therapy. In Group B professional speech and language therapy is deferred for four weeks. After this period, patients will follow the conventional procedure of speech and language therapy. Participants will be tested with an extensive linguistic test battery at four weeks, three months and six months after inclusion. Primary outcome measure is the difference in score between the two treatment groups on the Amsterdam-Nijmegen Everyday Language Test, a measure of everyday verbal communication, four weeks after randomisation.Trial registration: This trial is registered in the Dutch Trial Register (http://www.trialregister.nl), NTR3271.

Catechol-O-methyltransferase Val158Met and the risk of dyskinesias in Parkinson's disease (Article)

2012-01-01T00:00:00Z

Background:: The A-allele of the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with decreased enzymatic activity and higher dopamine availability. Methods:: We studied 219 patients with PD who were free of dyskinesias at baseline and underwent thorough annual examinations. Results:: The A-allele of the COMT Val158Met polymorphism was related to an increased risk of developing dyskinesias during follow-up, in a dose-dependent manner (adjusted hazard ratios for the AG and AA genotypes [compared to GG]: 2.09 [95% confidence interval (CI), 1.07-4.06] and 2.81 [CI, 1.43-5.54], respectively). Conclusions:: This finding suggests that genetic factors may affect susceptibility to dyskinesias in PD.

Fibrinogen γ' levels in patients with intracerebral hemorrhage (Article)

2011-09-13T00:00:00Z

Background: The fibrinogen γ' variant (γ') has both antithrombotic and prothrombotic properties when compared to normal fibrinogen. It may therefore be of relevance in intracerebral hemorrhage and intraventricular extension of the bleeding. Objective: To study the role of γ' in intracerebral hemorrhage, and in intraventricular extension of the hemorrhage. Patients/Methods: We performed a case-control study in 156 controls and 55 patients with intracerebral hemorrhage, with and without intraventricular extension. Levels of fibrinogen γ' and the γ'/total fibrinogen ratio were measured in all participants. Results: Levels of γ' were increased in patients with intracerebral hemorrhage when compared with controls (0.40 vs 0.32 g/l, p < 0.001). The γ'/total fibrinogen ratio was similar in patients and controls (0.092 vs 0.096 p = 0.42). There was evidence for an unfavorable outcome in patients with fibrinogen levels in the highest tertile compared with the lowest tertile (OR 4.0, 95%CI 1.1-15.2), and a nonsignificant trend toward unfavorable outcome with higher levels of γ' (p-value for trend = 0.06). Conclusions: Our study shows that absolute levels of fibrinogen γ' are increased in patients with intracerebral hemorrhage, but relative levels are similar in patients and controls, suggesting that the absolute rise in γ' is an acute phase response.

Statins - increasing or reducing the risk of Parkinson's disease? (Article)

2011-03-01T00:00:00Z

Statins - increasing or reducing the risk of Parkinson's disease? (Article)

2011-01-01T00:00:00Z

Genetic variation in homocysteine metabolism, cognition, and white matter lesions (Article)

2010-11-01T00:00:00Z

Several studies have shown an association between homocysteine concentration and cognitive performance or cerebral white matter lesions. However, variations in genes encoding for enzymes and other proteins that play a role in homocysteine metabolism have hardly been evaluated in relation to these outcome measures. In the population-based Rotterdam Scan Study, we examined the association of seven polymorphisms of genes involved in homocysteine metabolism (MTHFR 677C>T, MTHFR 1298A>C, RFC 80G>A, TC 776C > G, MTR 2756A > G, MTRR 66A > G, and CBS 844ins68) with plasma total homocysteine, cognitive performance, and cerebral white matter lesions among 1011 non-demented elderly participants. Of all the studied polymorphisms, only MTHFR 677C > T was associated with homocysteine concentration. No significant relationship was observed for any of the polymorphisms with cognitive performance or severity of cerebral white matter lesions.

A review of hereditary and acquired coagulation disorders in the aetiology of ischaemic stroke (Article)

2010-10-01T00:00:00Z

The diagnostic workup in patients with ischaemic stroke often includes testing for prothrombotic conditions. However, the clinical relevance of coagulation abnormalities in ischaemic stroke is uncertain. Therefore, we reviewed what is presently known about the association between inherited and acquired coagulation disorders and ischaemic stroke, with a special emphasis on the methodological aspects. Good-quality data in this field are scarce, and most studies fall short on epidemiological criteria for causal inference. While inherited coagulation disorders are recognised risk factors for venous thrombosis, there is no substantial evidence for an association with arterial ischaemic stroke. Possible exceptions are the prothrombin G20210A mutation in adults and protein C deficiency in children. There is proof of an association between the antiphospholipid syndrome and ischaemic stroke, but the clinical significance of isolated mildly elevated antiphospholipid antibody titres is unclear. Evidence also suggests significant associations of increased homocysteine and fibrinogen concentrations with ischaemic stroke, but whether these associations are causal is still debated. Data on other acquired coagulation abnormalities are insufficient to allow conclusions regarding causality. For most coagulation disorders, a causal relation with ischaemic stroke has not been definitely established. Hence, at present, there is no valid indication for testing all patients with ischaemic stroke for these conditions. Large prospective population-based studies allowing the evaluation of interactive and subgroup effects are required to appreciate the role of coagulation disorders in the pathophysiology of arterial ischaemic stroke and to guide the management of individual patients. © 2010 The Authors. Journal compilation

Screening for coagulation disorders in patients with ischemic stroke (Article)

2010-08-01T00:00:00Z

The role of coagulation disorders in the pathogenesis of (recurrent) ischemic stroke is uncertain. Therefore, the clinical utility of screening patients with ischemic stroke for these conditions and the therapeutic implications of a detected coagulation disorder in a patient who experienced ischemic stroke are uncertain. We reviewed the currently available data on the relationship between various inherited and acquired coagulation abnormalities (factor V Leiden and prothrombin G20210A mutations, deficiencies of protein C, protein S and anti-thrombin, hyperhomocysteinemia, the antiphospholipid syndrome and increased levels of fibrinogen) and ischemic stroke. Based on the existing evidence we discuss the usefulness of screening stroke patients for prothrombotic conditions and current recommendations regarding the optimal management of ischemic stroke patients in whom a coagulation disorder is found.

Acute disseminating encephalomyelitis following legionnaires disease (Article)

2010-05-01T00:00:00Z

Objective: To describe 2 patients presenting with severe neurological deficits and extensive lesions on brain magnetic resonance imaging after having experienced Legionella pneumonia. Design: Case reports. Setting: University hospital. Patients: Two patients who developed severe neurological symptoms, including encephalopathic signs, following Legionella infection, with widespread lesions on magnetic resonance imaging compatible with demyelination. Results: After extensive ancillary investigations, a diagnosis of acute disseminating encephalomyelitis was considered most likely. Steroid therapy was initiated in 1 of the patients, followed by plasmapheresis. In both patients, clinical and radiological signs gradually recovered, with only slight residual deficits. Conclusion: In patients presenting with neurological symptoms after an episode of pneumonia, Legionella infection and a subsequent immune-mediated process such as acute disseminating encephalomyelitis should be considered.

Predicting and preventing stroke after transient ischemic attack (Article)

2009-10-01T00:00:00Z

The prognosis of transient ischemic attacks (TIAs) is not as favorable as previously thought. Given a risk of stroke of approximately 10% in the first week following a TIA, urgent evaluation and initiation of treatment are required. Recently developed scores to predict the early risk of subsequent stroke in individual patients may guide treatment decisions in the acute phase. Lately it has become clear that transient attacks with nonfocal symptoms are not benign either, as these were found to be associated with an increased risk of vascular disease. The significance of this finding and its implications for treatment are not yet clear. There is substantial evidence from a number of clinical trials that adequate secondary prevention therapies can reduce the risk of stroke after TIA. In addition to the conventional vascular risk factors, interest has grown in less strong but more prevalent lifestyle factors, but trials evaluating the effect of modifying these factors are as yet lacking.

Acute CNS white matter lesions in patients with inflammatory bowel disease (Article)

2009-07-17T00:00:00Z

Background: Neurological manifestations in patients with inflammatory bowel disease supposedly are rare, although the exact frequency is not known. Most previous reports involve cerebral venous thrombosis, central nervous system vasculitis, or peripheral nerve inflammation. Methods: Two cases of patients diagnosed with inflammatory bowel disease developing neurological symptoms with corresponding lesions in the white matter of the central nervous system led us to search a neurological database with clinical and radiological data for similar cases. Results: We identified five patients who presented with acute neurological deficits preceding or following a diagnosis of inflammatory bowel disease with evidence of lesions in the central nervous system white matter on magnetic resonance imaging. Ancillary investigations did not provide evidence of systemic infetcion, coagulation disorders, or vasculitis. Conclusions: These cases, together with previous reports, suggest that white matter lesions may be another extraintestinal manifestation of inflammatory bowel disease. Copyright

Plasma vitamin B12 status and cerebral white-matter lesions (Article)

2009-02-01T00:00:00Z

Background and objective: Elevated homocysteine has been associated with a higher prevalence of cerebral white-matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B12, are also related to these outcomes. This study examined the association of several markers of vitamin B12status with cerebral white-matter lesions, infarcts and cognition. Methods: The study evaluated the association of plasma concentrations of vitamin B12, methylmalonic acid, holotranscobalamin and transcobalamin saturation with cerebral white-matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration. Results: Poorer vitamin B12status was significantly associated with greater severity of white-matter lesions, in particular periventricular white-matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B12status with presence of brain infarcts and baseline cognition or cognitive decline during follow-up. Conclusions: These results indicate that vitamin B12status in the normal range is associated with severity of white-matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, it is hypothesised that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms.

Strongly increased levels of fibrinogen elastase degradation products in patients with ischemic stroke (Article)

2008-12-01T00:00:00Z

Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case-control study of 111 ischemic stroke patients and 119 controls, significantly higher FgEDP levels were observed in cases than in controls, both in the acute phase and in the convalescent phase. Results were only slightly affected by adjustment for cardiovascular risk factors, C-reactive protein and fibrinogen. Our findings suggest that FgEDP might be involved in the pathogenesis of stroke.

Serum cholesterol, use of lipid-lowering drugs, and risk of Parkinson disease [4] (Article)

2007-10-15T00:00:00Z

Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease (Article)

2007-10-01T00:00:00Z

Background: Several lines of evidence suggest a role of inflammatory processes in Parkinson disease, although it is still unclear whether inflammation is a cause or rather a consequence of neurodegeneration. Methods: In a prospective population-based cohort study among 6,512 participants aged ≥55 years, with repeated in-person examination, we evaluated the association between cumulative use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease. Complete information on filled prescriptions was available from automated pharmacy records. Data were analyzed by means of Cox proportional hazards regression analysis, adjusted for age, sex, smoking habits and coffee consumption. Results: After an average 9.4 years of follow-up, 88 new cases of Parkinson disease were detected. No association was found between use of NSAIDs and the risk of Parkinson disease (adjusted hazard ratio for any NSAID use, 1.50; 95% confidence interval, 0.95-2.37). Conclusion: Our findings do not support the hypothesis that NSAIDs might decrease the risk of Parkinson disease. Copyright

Relationship of the Ubiquilin 1 gene with Alzheimer's and Parkinson's disease and cognitive function (Article)

2007-08-31T00:00:00Z

Ubiquilin 1 (UBQLN1) is involved in the ubiquitination machinery, which has been implicated in Alzheimer's disease (AD) as well as Parkinson's disease (PD). A polymorphism in the gene encoding for UBQLN1 has been previously associated with a higher risk of AD. We studied the role of the SNP rs12344615 on the UBQLN 1 gene in AD, PD and cognitive function in a population-based study, the Rotterdam Study, and a family-based study embedded in the genetic research in isolated population (GRIP) program. The Rotterdam Study includes 549 patients with AD and 157 patients with PD. The GRIP program includes a series of 123 patients with AD and a study of 1049 persons who are characterized for cognitive function. Data were analysed using logistic and multiple regression analysis. We found no significant difference in risk of AD or PD by the UBQLN1 SNP rs12344615 in our overall and stratified analyses in the Rotterdam Study. In our family-based study, we did not find evidence for linkage of AD to the region including the UBQLN1 gene. In the family-based study we also failed to detect an effect of this polymorphism on cognitive function. Our results suggest that it is unlikely that the SNP rs12344615 of the UBQLN1 gene is related to the onset of AD, PD or cognitive function.

Number of children and risk of Parkinson's disease (Article)

2007-04-15T00:00:00Z

We investigated the association between number of children and Parkinson's disease (PD) in two independent studies. In a case-control study, we identified all subjects who developed PD in Olmsted County, MN, from 1976 through 1995, and matched them individually by age (± 1 year) and sex to population controls (193 cases and 193 controls). The replication study was a population-based cohort study of 6,341 subjects from Rotterdam, the Netherlands (2,610 men). In the Olmsted County study, men who fathered at least one child had an increased risk of PD (unadjusted OR, 2.7; 95% CI, 1.2-6.1; P = 0.02), and the risk increased with increasing number of children. The findings in women were not significant. In the Rotterdam Study, the risk of PD increased significantly with increasing number of children in men (test for linear trend, unadjusted; P = 0.04), but not in women. The findings from both studies remained consistent in direction but reduced in magnitude of the association, and lost significance after simultaneous adjustment for education, cigarette smoking, alcohol consumption, and coffee consumption. The independent replication in two distinct populations and using different epidemiologic study designs may suggest a link between the number of children and PD restricted to men.