White matter changes and gait decline in cerebral small vessel disease.

The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50-85 years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006-2007) and follow-up (2011 - 2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9 years (SD8.2), mean follow-up duration was 5.4 years (SD0.2) and mean gait speed decline was 0.2 m/s (SD0.2). Stride length decline was associated with white matter atrophy (ß = 0.16, p = 0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, ß = - 0.14, p = 0.009; ß = - 0.12, p = 0.018; ß = 0.10, p = 0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5 years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline.

[Ischemic stroke in young women]. / Herseninfarct bij jonge vrouwen.

- In virtually all age groups, the incidence of ischemic stroke is higher in men. However, in women aged between 25-49 years the prevalence is higher than in men. Female-specific risk factors and disorders may explain this peak.- Pregnancy and the post-partum period are associated with physiological changes which can increase blood coagulation. Complications during pregnancy may also increase the risk of ischaemic stroke.- Migraine with aura and antiphospholipid syndrome are disorders which are also associated with an increased risk of ischaemic stroke. These disorders are more common in women compared to men. Furthermore, hormonal contraceptives containing oestrogen are also identified to increase the incidence of ischaemic stroke.- The acute treatment and secondary prevention of ischaemic stroke in young women is identical to that in elderly stroke patients, be it men or women, although thrombolysis and platelet aggregation inhibition in pregnant women should be approached with care.- Clinical outcomes after stroke for women under the age of 50 are worse compared to age-matched men.

[Hypertension due to fibromuscular dysplasia: look for additional disease sites]. / Hypertensie door fibromusculaire dysplasie.

Fibromuscular dysplasia (FMD) is a non-inflammatory, non-atherosclerotic vasculopathy that can lead to arterial stenosis, occlusion, aneurysms, and dissection. FMD of the renal arteries can lead to renovascular hypertension. Percutaneous angioplasty of the renal arteries (PTRA) can lead to normalization of blood pressure in 45% of patients with renal artery stenosis caused by FMD, particularly in younger patients and patients with a short history of hypertension. A considerable number of the patients with renovascular FMD also have cervical FMD, which can lead to ischaemic or haemorrhagic stroke. In this article we discuss diagnostic and therapeutic options, illustrated by two cases of patients with renovascular and carotid FMD. Most of the recommendations are based on data from retrospective studies and expert opinion; prospective studies on the optimal diagnostic strategy and treatment are therefore, urgently required.

Long-term depressive symptoms and anxiety after transient ischaemic attack or ischaemic stroke in young adults.

BACKGROUND AND PURPOSE: Few studies exist on long-term post-stroke depressive symptoms and anxiety in young adults, although these young patients have a particular interest in their long-term prognosis, given their usually long life expectancy and being in the midst of an active social, working and family life. The aims of this study were to investigate the prevalence of depressive symptoms and anxiety and their association with clinical and demographic variables and with functional outcome after stroke in young adults. METHODS AND RESULTS: Long-term prevalence of depressive symptoms and anxiety was calculated in 511 patients with a transient ischaemic attack or ischaemic stroke, aged 18-50 years, using the Hospital Anxiety and Depression scale, compared with 147 controls. Functional outcome was assessed with the modified Rankin Score (mRS) and the Instrumental Activities of Daily Living scale (IADL). 16.8% of patients had depressive symptoms and 23.0% had anxiety, versus 6.1% (P = 0.001) and 12.2% (P < 0.001) in controls. In ischaemic stroke patients, depressive symptoms and anxiety were associated with poor functional outcome (mRS > 2 or IADL < 8). CONCLUSION: Even a decade after stroke at young age, depressive symptoms and anxiety were prevalent and associated with poor functional outcome. Therefore, even in the long term, treating physicians should be aware of the long-term presence of these symptoms as their recognition may be the first step in improving long-term functional independence.

Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study.

INTRODUCTION: Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume. METHODS: The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level. RESULTS: 43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia. CONCLUSION: This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume.

A nurse-led multidisciplinary intervention to improve cardiovascular disease profile of patients.

The aim of this study was to evaluate the impact of a structured screening and nurse-based intervention on cardiovascular risk factors. In patients with established cardiovascular disease, a cardiovascular risk profile was assessed, and lifestyle was evaluated by using an automated questionnaire. A multidisciplinary team proposed an integral individualized plan of care on the basis of these assessments. During follow-up, a nurse-led lifestyle intervention program and the best medical treatment were offered. A total of 328 outpatients were included. After screening, a follow-up term of at least 1 year was reached in 176 patients (59.9%). Low-density lipoprotein cholesterol and systolic blood pressure were significantly reduced. A reduction in the amount of smoking, alcohol consumption, and unhealthy eating habits was observed. However, the amount of physical activity was unaffected, and body mass was increased. A structural evaluation of cardiovascular risk factors and an integrated nurse-led approach can successfully reduce risk in cardiovascular patients.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: the RUN DMC study.

BACKGROUND: Cerebral small vessel disease (SVD) is related to verbal memory failures. It is suggested that early white matter damage, is located, among others, in the (posterior) cingulum at an early stage in neurodegeneration. Changes in the microstructural integrity of the cingulum assessed with diffusion tensor imaging (DTI), beyond detection with conventional MRI, may precede macrostructural changes and be related to verbal memory failures. OBJECTIVE: To investigate the relation between cingular microstructural integrity and verbal memory performance in 503 non-demented elderly with cerebral SVD. METHODS: The RUN DMC study is a prospective cohort study in elderly (50-85 years) with cerebral SVD. All participants underwent T1 MPRAGE, FLAIR and DTI scanning and the Rey Auditory Verbal Learning Test. Mean diffusivity (MD) and fractional anisotropy (FA) were assessed in six different cingular regions of interests (ROIs). Linear regression analysis was used to assess the relation between verbal memory performance and cingular DTI parameters, with appropriate adjustments. Furthermore a TBSS analysis of the whole brain was performed to investigate the specificity of our findings. RESULTS: Both our ROI-based and TBSS analysis showed that FA was positively related to immediate memory, delayed recall, delayed recognition and overall verbal memory performance of the cingulum, independent of confounders. A similar distribution was seen for the inverse association with MD and verbal memory performance with TBSS analysis. No significant relations were found with psychomotor speed, visuospatial memory and MMSE. When stratified on hippocampal integrity, the MD and FA values of the cingular ROIs differed significantly between participants with a good and poor hippocampal integrity. CONCLUSION: Microstructural integrity of the cingulum, assessed by DTI, is specifically related to verbal memory performance, in elderly with SVD. Furthermore we found that when the integrity of the hippocampus is disrupted, the cingulum integrity is impaired as well.

Damage in the dorsal striatum alleviates addictive behavior.

The ventral striatum has been assigned a major role in addictive behavior. In addition, clinical lesion studies have described involvement of the insula and globus pallidus. To the best of our knowledge, this is the first report of alleviation of alcohol and nicotine addiction after a cerebrovascular incident in the dorsal striatum. The patient was still abstinent from alcohol and nicotine at follow-up. This observation suggests that the dorsal striatum may play a critical role in addiction to alcohol and nicotine.

Dementia: Alzheimer pathology and vascular factors: from mutually exclusive to interaction.

Alzheimer's disease (AD) is the most common type of dementia. Both its incidence and prevalence are expected to increase exponentially as populations' age worldwide. Despite impressive efforts of research worldwide, neither cure nor effective preventive strategy is available for this devastating disease. Currently there are several hypotheses on what causes AD, with the amyloid hypothesis being the most investigated and accepted hypothesis over the past 20 years. However the exact role of amyloid-ß in the onset and progression of AD is not yet fully understood, and even the validity of the amyloid hypothesis itself is still being discussed. This debate is fuelled by the vascular hypothesis, as increasing epidemiological, neuroimaging, pathological, pharmacotherapeutic and clinical studies suggest that vascular pathology plays a key role in the onset and progression of AD. We here will discuss arguments in favor and limitations of both hypotheses within the framework of available literature, but also provide arguments for convergence of both hypotheses. Finally we propose approaches that may aid in unraveling the etiology and treatment of AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Depressive Symptoms and Amygdala Volume in Elderly with Cerebral Small Vessel Disease: The RUN DMC Study.

Introduction. Late onset depressive symptoms (LODSs) frequently occur in elderly with cerebral small vessel disease (SVD). SVD cannot fully explain LODS; a contributing factor could be amygdala volume. We investigated the relation between amygdala volume and LODS, independent of SVD in 503 participants with symptomatic cerebral SVD. Methods. Patients underwent FLAIR and T1 scanning. Depressive symptoms were assessed with structured questionnaires; amygdala and WML were manually segmented. The relation between amygdala volume and LODS/EODS was investigated and adjusted for age, sex, intracranial volume, and SVD. Results. Patients with LODS had a significantly lower left amygdala volume than those without (P = 0.02), independent of SVD. Each decrease of total amygdala volume (by mL) was related to an increased risk of LODS (OR = 1.77; 95% CI 1.02-3.08; P = 0.04). Conclusion. Lower left amygdala volume is associated with LODS, independent of SVD. This may suggest differential mechanisms, in which individuals with a small amygdala might be vulnerable to develop LODS.

Risk factors for ischemic stroke and transient ischemic attack in patients under age 50.

To analyze risk factors for ischemic stroke and transient ischemic attack (TIA) in young adults under the age of 50. To make recommendations for additional research and practical consequences. From 97 patients with ischemic stroke or TIA under the age of 50, classical cardiovascular risk factors, coagulation disorders, history of migraine, use of oral contraceptives, cardiac abnormalities on ECG and echocardiography, and the results of duplex ultrasound were retrospectively analyzed. Literature was reviewed and compared to the results. 56.4% of the patients had hypertension, 12.1% increased total cholesterol, 20% hypertriglyceridemia, 31.5% an increased LDL-level, 32.6% a decreased HDL-level and 7.2% a disturbed glucose tolerance. Thrombophilia investigation was abnormal in 21 patients and auto-immune serology was abnormal in 15 patients. Ten of these patients were already known with a systemic disease associated with an increased risk for ischemic stroke (i.e. systemic lupus erythematosus). The ECG was abnormal in 16.7% of the cases, the echocardiography in 12.1% and duplex ultrasound of the carotid arteries was in 31.8% of the cases abnormal. Conventional cardiovascular risk factors are not only important in patients over the age of 50 with ischemic stroke or TIA, but also in this younger population under the age of 50. Thrombophilia investigation and/ or autoimmune serology should be restricted to patients without conventional cardiovascular risk factors and a history or other clinical symptoms associated with hypercoagulability and/ or autoimmune diseases.

Time course and risk factors of post-stroke fatigue: a prospective cohort study.

BACKGROUND: Post-stroke fatigue (PSF) often occurs after stroke and has a negative impact on the rehabilitation process. Several studies focused either on short- or on long-term PSF and their relations with stroke characteristics. However, possible pre-stroke risk factors such as history of depression, pre-existent white matter lesions or brain atrophy were usually not taken into account. Therefore, the precise mechanisms underlying PSF remain still unclear. This study was aimed at assessing the possible contributions of (pre-)stroke factors to both short-term PSF and its course over time. METHODS: This study pertains to 108 patients with an acute cerebral infarction. PSF was rated by the Checklist Individual Strength at 2 months and 1.5 year post-stroke. The relation between (pre-)stroke factors and PSF was assessed with multivariate regression analysis. RESULTS: The prevalence of baseline PSF was 35% and at follow-up 33%. Older age had a protective effect on PSF at baseline (OR 0.95; 95% CI 0.91-0.98), whereas post-stroke depressive symptoms and infratentorial infarctions were related to an increased risk for PSF (OR 1.40; 95% CI 1.21-1.63 and OR 4.69; 95% CI 1.03-21.47, respectively). Baseline fatigue was related to an increased risk of PSF at follow-up (OR 1.15; 95% CI 1.09-1.22). CONCLUSIONS: Predictors for baseline fatigue were younger age, post-stroke depressive symptoms, and infratentorial infarctions. Baseline fatigue did predict fatigue outcome over time, suggesting that early interventions might be useful to prevent deteriorated PSF.