Anil Man Tuladhar

Radboud University Medical Centre (Radboudumc) · Department of Neurology

Approximately one in ten young stroke patients (18-50 years) will develop post-stroke epilepsy, which is associated with cognitive impairment. While previous studies have shown altered brain connectivity in patients with epilepsy, little is however known about the changes in functional brain connectivity in young stroke patients with post-stroke ep...

Background: To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism. Methods: In a prospective cohort (RUN DMC study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident...

Background: Cerebral small vessel disease (SVD) contributes to 45% of dementia cases worldwide, yet we lack a reliable model for predicting dementia in SVD. Past attempts largely relied on traditional statistical approaches. Here, we investigated whether machine learning (ML) methods improved prediction of incident dementia in SVD from baseline SV...

In coronavirus disease 2019 (COVID-19), endothelial cells play a central role and an inadequate response is associated with vascular complications. PET imaging with gallium-68 labelled RGD-peptide (⁶⁸Ga-RGD) targets αvβ3 integrin expression which allows quantification of endothelial activation. In this single-center, prospective observational study...

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of...

The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to dete...

White matter hyperintensities of presumed vascular origin (WMH) are the most common imaging feature of cerebral small vessel disease (cSVD) and are associated with cognitive impairment, especially information processing speed (IPS) deficits. However, it is unclear how WMH can directly impact IPS or whether the cortical thickness and brain connectiv...

It remains unknown which factors influence how brain disconnectivity derived from White Matter Hyperintensity (WMH) lesions leads to psychomotor speed dysfunction, one of the earliest and most common cognitive manifestations in the cerebral Small Vessel Disease (cSVD) population. While the burden of WMH has been strongly linked to psychomotor speed...

Objective: Cerebral small vessel disease (SVD) is considered the most important vascular contributor to cognitive decline and dementia, although a causal relation between its MRI markers and dementia still needs to be established. The authors investigated the relation between baseline SVD severity as well as SVD progression on MRI markers and inci...

Background: Cerebral small vessel disease is a leading cause of cognitive decline and vascular dementia. Small vessel disease pathology changes structural brain networks, but its impact on functional networks remains poorly understood. Structural and functional networks are closely coupled in healthy individuals, and decoupling is associated with...

Background and objectives It has been suggested that white matter hyperintensity lesions (WMHs), which typically progress over time, can also regress, and that this might be associated with favourable cognitive performance. We determined the prevalence of WMH regression in patients with cerebral small vessel disease (SVD) and examined which demogra...

Background: Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of t...

There is evidence that blood pressure variability (BPV) is associated with cerebral small vessel disease (SVD) and may therefore increase the risk of stroke and dementia. It remains unclear if BPV is associated with SVD progression over years. We examined whether visit-to-visit BPV is associated with White Matter Hyperintensity (WMH) progression ov...

Objective: Cerebral small vessel disease (SVD) is associated with motor impairments and parkinsonian signs cross-sectionally, however, there are little longitudinal data on whether SVD increases risk of incident parkinsonism itself. We investigated the relation between baseline SVD severity as well as SVD progression, and incident parkinsonism ove...

Background: Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current classification systems (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] and atherosclerosis, small vessel disease, cardiac pathology,...

Introduction We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular cognitive disorder, and the prevalence of subjective cognitive complaints and their relation with objective cognitive performance. Patients and methods...

In coronavirus disease 2019 (COVID-19), endothelial cells play a central role and inadequate response is associated with vascular complications. PET imaging with gallium-68 labelled RGD-peptide (⁶⁸Ga-RGD) targets αvβ3 integrin expression which allows quantification of endothelial activation. In this single-center, prospective observational study, w...

Background: Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their...

BACKGROUND The underlying mechanisms of incident lacunes regarding their spatial distribution remain largely unknown. We investigated the spatial distribution pattern and MRI predictors of incident lacunes in relation to white matter hyperintensity (WMH) over 14 years follow-up in sporadic small vessel disease. METHODS Five hundred three participa...

Background and Objectives Causes of stroke in young adults differ from those in the elderly, and in a larger percentage no cause can be determined. To gain more insight in the etiology of (cryptogenic) stroke in the young, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role. Methods Patie...

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of earl...

Alzheimer’s disease and cerebral small vessel disease are the two leading causes of cognitive decline and dementia and co-exist in most­ memory clinic patients. White matter damage as assessed by diffusion MRI is a key feature in both Alzheimer’s and cerebral small vessel disease. However, disease-specific biomarkers of white matter alterations are...

Background DTI is sensitive to white matter (WM) microstructural damage and has been suggested as a surrogate marker for phase 2 clinical trials in cerebral small vessel disease (SVD). The study’s objective is to establish the best way to analyse the diffusion-weighted imaging data in SVD for this purpose. The ideal method would be sensitive to cha...

Contrast-induced encephalopathy (CIE) is a rare encephalopathic condition after the administration of a contrast agent. The diagnosis of CIE is challenging because of the heterogeneity and non-specificity of the clinical presentation. The clinical course is usually favorable with full recovery within 48–72 h in most patients, although comorbidity i...

Cerebral small vessel disease (SVD) is an important cause of stroke and dementia and is associated with a progressive, but highly unpredictable clinical course and increased mortality.1 Serum neurofilament (sNfL) has shown to be a candidate marker of various neurological diseases, including cerebral SVD.2 sNfL is a component of the neuroaxonal cyto...

Background: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to...

We aimed to provide practical recommendations for the screening of subclinical atrial fibrillation (AF) in patients with ischaemic stroke or transient ischaemic attack (TIA) of undetermined origin. These guidelines are based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Five relevant Population, Inte...

Background The aim of this study is to investigate the temporal dynamics of small vessel disease (SVD) and the effect of vascular risk factors and baseline SVD burden on progression of SVD with 4 neuroimaging assessments over 14 years in patients with SVD. Methods Five hundred three patients with sporadic SVD (50–85 years) from the ongoing prospec...

Background COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods CORONavirus and Ischemic Strok...

Introduction Post-stroke fatigue is frequently present in young adults, but its underlying mechanism is still unclear. The aim of the study was to investigate the association between lesion location, network efficiency and chronic post-stroke fatigue based on voxel-based lesion-symptom mapping and structural network connectivity analysis. Patients...

Background With a growing, younger population of head and neck cancer survivors, attention to long-term side-effects of prior, often radiotherapeutic, treatment is warranted. Therefore, we studied the long-term cognitive effects in young adult patients irradiated for head and neck neoplasms (HNN). Methods Young to middle-aged adults with HNN (aged...

Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to better understand pathogenesis and to predict disease progression and severity. We analysed dat...

Cerebral small vessel disease (SVD) is considered a disconnection syndrome, which can be quantified using structural brain network analysis obtained from diffusion MRI. Network analysis is a demanding analysis approach and the added benefit over simpler diffusion MRI analysis is largely unexplored in SVD. In this pre-registered study, we assessed t...

Background and Objectives There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional healthcare services. To study the global distribution of risk factors, causes and...

Introduction: Cerebral hypoperfusion is thought to play an important role in the etiology of cerebral small vessel disease (SVD). Orthostatic hypotension (OH) is assumed to be a cause of cerebral hypoperfusion by causing recurrent hypoperfusion episodes, and might thus be related to progression of SVD. Here, we investigated whether presence of OH i...

Objectives It has been suggested that diffusion tensor imaging (DTI) measures sensitive to white matter (WM) damage may predict future dementia risk not only in cerebral small vessel disease (SVD), but also in mild cognitive impairment. To determine whether DTI measures were associated with cognition cross-sectionally and predicted future dementia...

Introduction It is unclear why cerebral small vessel disease (SVD) leads to lacunar stroke in some and to non–lobar intracerebral hemorrhage (ICH) in others. We investigated differences in MRI markers of SVD in patients with lacunar stroke or non–lobar ICH. Patients and methods We included patients from two prospective cohort studies with either l...

Background To investigate changes in gait performance over time and how these changes are associated with the decline in structural network efficiency and cognition in older patients with cerebral small vessel disease (SVD). Methods In a prospective, single-center cohort with 217 older participants with SVD, we performed 1.5T MRI scans, cognitive...

Objectives: Given the strong association between systemic inflammation and cognitive decline, we aimed to determine whether nonneurologic infections are associated with accelerated cognitive decline and structural changes in the brain using pre- and post-infection neuropsychologic assessments and repeated brain MR images. Design: Additional anal...

Recent studies suggest that a subset of cortical microinfarcts may be identifiable on T2* but invisible on T1 and T2 follow-up images. We aimed to investigate whether cortical microinfarcts are associated with iron accumulation after the acute stage. The RUN DMC – InTENse study is a serial MRI study including individuals with cerebral small vessel...

Cerebral small vessel disease (SVD) is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors in order to better understand pathogenesis and to predict disease progression and severity....

Background: The etiology of cerebral small vessel disease (SVD) remains elusive, though evidence is accumulating that inflammation contributes to its pathophysiology. We recently showed retrospectively that pro-inflammatory monocytes are associated with the long-term progression of white matter hyperintensities (WMHs). In this prospective high-freq...

Cerebral small vessel disease (SVD), including white matter hyperintensities (WMH), microbleeds, lacunes, was related to gait disturbances, while the underlying mechanism is unclear. Here, we investigated the relation between structural network efficiency, cognition and gait performance in 272 elderly subjects with SVD. All participants underwent 1...

Background Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to...

Objective: To test the hypothesis that multi-shell diffusion models improve the characterization of microstructural alterations in cerebral small vessel disease (SVD), we assessed associations with processing speed performance, longitudinal change and reproducibility of diffusion metrics. Methods: We included 50 sporadic and 59 genetically defined...

Background and aims Given the unexplored potential of physical activity to reduce the progression of cerebral small vessel disease (cSVD, the purpose of this study was to prospectively (across nine-year follow-up) examine the relation between (baseline) physical activity and the (clinical and imaging) consequences of the whole spectrum of cerebral...

Objective We report a case series of patients with prolonged but reversible unconsciousness following COVID-19 related severe respiratory failure. Methods A case series of patients who were admitted to the ICU due to COVID-19 related acute respiratory failure is described. Results After cessation of sedatives the described cases all showed a prol...

The presence of white matter lesions in patients with cerebral small vessel disease (SVD) is among the main causes of cognitive decline. We investigated the relation between white matter hyperintensity (WMH) locations and executive and language abilities in 442 SVD patients without dementia with varying burden of WMH. We used Stroop Word Reading, S...

Background and purpose: Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) cross-sectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally. Methods: From 503 subjects with SVD, b...

Objective To determine whether apathy or depression predicts all-cause dementia in small vessel disease (SVD) patients. Methods Analyses used two prospective cohort studies of SVD: St. George’s Cognition and Neuroimaging in Stroke (SCANS; n=121) and Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC; n=352). Multiv...

Cerebral small vessel disease (SVD) is a common disease in older adults and a major contributor to vascular cognitive impairment and dementia. White matter network damage is a potentially important mechanism by which SVD causes cognitive impairment. Earlier studies showed that a higher degree of white matter network damage, indicated by lower globa...

Dementia poses a growing public health challenge due to the ageing population with tens of millions being affected worldwide; a number that is expected to double the next twenty years.1,2 Unfortunately, there is still no proven effective treatment against dementia. Therefore, identifying modifiable determinants of early cognitive decline may provid...

Objective To determine whether a simple small vessel disease (SVD) score, which uses information available on rapid visual assessment of clinical MRI scans, predicts risk of cognitive decline and dementia, above that provided by simple clinical measures. Methods Three prospective longitudinal cohort studies (SCANS [St George's Cognition and Neuroi...

Apathy is a reduction in motivated goal-directed behavior (GDB) that is prevalent in cerebrovascular disease, providing an important opportunity to study the mechanistic underpinnings of motivation in humans. Focal lesions, such as those seen in stroke, have been crucial in developing models of brain regions underlying motivated behavior, while stu...

While structural network analysis consolidated the hypothesis of cerebral small vessel disease (SVD) being a disconnection syndrome, little is known about functional changes on the level of brain networks. In patients with genetically defined SVD (CADASIL, n = 41) and sporadic SVD (n = 46), we independently tested the hypothesis that functional net...

Ischaemic stroke at young age is an increasing problem in both developing and developed countries due to rising incidence, high morbidity and mortality and long-term psychological, physical and social consequences. Compared with stroke in older adults, stroke in young adults is more heterogeneous due to the wide variety of possible underlying risk...

Objectives To investigate whether longitudinal structural network efficiency is associated with cognitive decline and whether baseline network efficiency predicts mortality in cerebral small vessel disease (SVD). Methods A prospective, single-centre cohort consisting of 277 non-demented individuals with SVD was conducted. In 2011 and 2015, all par...

Introduction Worldwide, 2 million patients aged 18–50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provisi...

Cerebral small vessel disease (SVD) is considered the most important vascular contributor to the development of cognitive impairment and dementia. There is increasing awareness that SVD exerts its clinical effects by disrupting white matter connections, predominantly disrupting connections between rich club nodes, a set of highly connected and inte...

Objective: To investigate the prevalence of asymptomatic diffusion-weighted imaging-positive (DWI+) lesions in individuals with cerebral small vessel disease (SVD) and identify their role in the origin of SVD markers on MRI. Methods: We included 503 individuals with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance...

Objective: To determine the contribution of acute infarcts, evidenced by diffusion-weighted imaging positive (DWI+) lesions to progression of white matter hyperintensities (WMH) and other cerebral small vessel disease (SVD) markers. Methods: We performed 10 monthly 3 T MRIs in 54 elderly individuals with SVD. MRI included high-resolution multi-s...

This scientific commentary refers to ‘Dissociating thalamic alterations in alcohol use disorder defines specificity of Korsakoff’s syndrome’, by Segobin et al. (doi:10.1093/brain/awz056).

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrom...

Objective: To investigate whether white matter network disruption underlies the pathogenesis of apathy, but not depression, in cerebral small vessel disease (SVD). Methods: Three hundred thirty-one patients with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study completed measures of apathy an...

Introduction: Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods: Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessment...