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  • 1
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    Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: the DIAGRAM prediction score
    BMJ ; 2018
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 89, No. 7 ( 2018-07), p. 674-679
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 89, No. 7 ( 2018-07), p. 674-679
    Abstract: A substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH. Methods The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%). Results Independent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51–70 years with deep ICH and SVD, to more than 50% in patients aged 18–50 years with lobar or posterior fossa ICH without SVD. Conclusion The DIAGRAM scores help to predict the probability of a macrovascular cause in patients with non-traumatic ICH based on age, ICH location, SVD and CTA.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    URL: Article
    DOI: 10.1136/jnnp-2017-317262
    DOI: 10.1136/jnnp-2017-317262.supp1
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 1480429-3
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  • 2
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    Diffusion-weighted imaging lesions and risk of recurrent stroke after intracerebral haemorrhage
    BMJ ; 2021
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 92, No. 9 ( 2021-09), p. 950-955
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 92, No. 9 ( 2021-09), p. 950-955
    Abstract: To determine whether the presence of diffusion-weighted imaging-positive (DWI+) lesions is associated with recurrent stroke after intracerebral haemorrhage (ICH). Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) assessed the effect of restarting versus avoiding antiplatelet therapy after ICH on major vascular events for up to 5 years. We rated DWI sequences of MRI done before randomisation for DWI+ lesion presence, masked to outcome and antiplatelet use. Cox proportional hazards regression models were used to quantify associations. Results Of 537 participants in RESTART, 247 (median (IQR) age 75.7 (69.6–81.1) years; 170 men (68.8%); 120 started vs 127 avoided antiplatelet therapy) had DWI sequences on brain MRI at a median of 57 days (IQR 19–103) after ICH, of whom 73 (30%) had one or more DWI+ lesion. During a median follow-up of 2 years (1–3), 18 participants had recurrent ICH and 21 had ischaemic stroke. DWI+ lesion presence was associated with all stroke, (adjusted HR 2.2 (95% CI 1.1 to 4.2)) and recurrent ICH (4.8 (95% CI 1.8 to 13.2)), but not ischaemic stroke (0.9 (95% CI 0.3 to 2.5)). DWI+ lesion presence (0.5 (95% CI 0.2 to 1.3)) vs absence (0.6 (95% CI 0.3 to 1.5), p interaction =0.66) did not modify the effect of antiplatelet therapy on a composite outcome of recurrent stroke. Conclusions DWI+ lesion presence in ICH survivors is associated with recurrent ICH, but not with ischaemic stroke. We found no evidence of modification of effects of antiplatelet therapy on recurrent stroke after ICH by DWI+ lesion presence. These findings provide a new perspective on the significance of DWI+ lesions, which may be markers of microvascular mechanisms associated with recurrent ICH. Trial registration number ISRCTN71907627 .
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2021-326116
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 3
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    Prediction of dementia using diffusion tensor MRI measures: the OPTIMAL collaboration
    BMJ ; 2022
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 93, No. 1 ( 2022-01), p. 14-23
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 93, No. 1 ( 2022-01), p. 14-23
    Abstract: 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 risk across the full range of SVD severity, we established the International OPtimising mulTImodal MRI markers for use as surrogate markers in trials of Vascular Cognitive Impairment due to cerebrAl small vesseL disease collaboration which included six cohorts. Methods Among the six cohorts, prospective data with dementia incidences were available for three cohorts. The associations between six different DTI measures and cognition or dementia conversion were tested. The additional contribution to prediction of other MRI markers of SVD was also determined. Results The DTI measure mean diffusivity (MD) median correlated with cognition in all cohorts, demonstrating the contribution of WM damage to cognition. Adding MD median significantly improved the model fit compared to the clinical risk model alone and further increased in all single-centre SVD cohorts when adding conventional MRI measures. Baseline MD median predicted dementia conversion. In a study with severe SVD (SCANS) change in MD median also predicted dementia conversion. The area under the curve was best when employing a multimodal MRI model using both DTI measures and other MRI measures. Conclusions Our results support a central role for WM alterations in dementia pathogenesis in all cohorts. DTI measures such as MD median may be a useful clinical risk predictor. The contribution of other MRI markers varied according to disease severity.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2021-326571
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 4
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    Structural network changes in cerebral small vessel disease
    BMJ ; 2020
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 91, No. 2 ( 2020-02), p. 196-203
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 91, No. 2 ( 2020-02), p. 196-203
    Abstract: 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 participants were scanned with MRI and underwent neuropsychological assessment. We computed network properties using graph theory from probabilistic tractography and calculated changes in psychomotor speed and overall cognitive index. Multiple linear regressions were performed, while adjusting for potential confounders. We divided the group into mild-to-moderate white matter hyperintensities (WMH) and severe WMH group based on median split on WMH volume. Results The decline in global efficiency was significantly associated with a decline in psychomotor speed in the group with severe WMH (β=0.18, p=0.03) and a trend with change in cognitive index (β=0.14, p=0.068), which diminished after adjusting for imaging markers for SVD. Baseline global efficiency was associated with all-cause mortality (HR per decrease of 1 SD 0.43, 95% CI 0.23 to 0.80, p=0.008, C-statistic 0.76). Conclusion Disruption of the network efficiency, a metric assessing the efficiency of network information transfer, plays an important role in explaining cognitive decline in SVD, which was however not independent of imaging markers of SVD. Furthermore, baseline network efficiency predicts risk of mortality in SVD that may reflect the global health status of the brain in SVD. This emphasises the importance of structural network analysis in the context of SVD research and the use of network measures as surrogate markers in research setting.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2019-321767
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1480429-3
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  • 5
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    Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease
    BMJ ; 2020
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 91, No. 9 ( 2020-09), p. 953-959
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 91, No. 9 ( 2020-09), p. 953-959
    Abstract: 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). Multivariate Cox regressions were used to predict dementia using baseline apathy and depression scores in both datasets. Change in apathy and depression was used to predict dementia in a subset of 104 participants with longitudinal data from SCANS. All models were controlled for age, education and cognitive function. Results Baseline apathy scores predicted dementia in SCANS (HR 1.49, 95% CI 1.05 to 2.11, p=0.024) and RUN DMC (HR 1.05, 95% CI 1.01 to 1.09, p=0.007). Increasing apathy was associated with dementia in SCANS (HR 1.53, 95% CI 1.08 to 2.17, p=0.017). In contrast, baseline depression and change in depression did not predict dementia in either dataset. Including apathy in predictive models of dementia improved model fit. Conclusions Apathy, but not depression, may be a prodromal symptom of dementia in SVD, and may be useful in identifying at-risk individuals.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2020-323092
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 6
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    Immune regulation and blood–brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study – a multicentre prospective cohort study
    BMJ ; 2024
    In:  BMJ Open Vol. 14, No. 2 ( 2024-02), p. e084303-
    Details
    In: BMJ Open, BMJ, Vol. 14, No. 2 ( 2024-02), p. e084303-
    Abstract: The INflammation and Small Vessel Disease (INSVD) study aims to investigate whether peripheral inflammation, immune (dys)regulation and blood–brain barrier (BBB) permeability relate to disease progression in cerebral small vessel disease (SVD). This research aims to pinpoint specific components of the immune response in SVD relating to disease progression. This could identify biomarkers of SVD progression, as well as potential therapeutic targets to inform the development and repurposing of drugs to reduce or prevent SVD, cognitive decline and vascular dementia. Methods and analysis INSVD is a prospective observational multicentre cohort study in individuals with symptomatic SVD. This longitudinal study combines comprehensive immunophenotyping of the peripheral blood immune compartment with advanced neuroimaging markers of SVD and BBB permeability. The main SVD marker of interest is white matter microstructure as determined by diffusion tensor imaging, a valuable marker of disease progression owing to its sensitivity to early alterations to white matter integrity. The research is being conducted in two sites—in the UK (Cambridge) and the Netherlands (Nijmegen)—with each site recruiting 100 participants (total n=200). Participants undergo clinical and cognitive assessments, blood draws, and brain MRI at baseline and 2-year follow-up. Ethics and dissemination This study received ethical approval from the local ethics boards (UK: East of England—Cambridge Central Research Ethics Committee (REC) ref: 22/EE/00141, Integrated Research Application System (IRAS) ID: 312 747. Netherlands: Medical Research Ethics Committee (MREC) Oost-Nederland, ref: 2022-13623, NL-number: NL80258.091.22). Written informed consent was obtained from all subjects before the study. Any participant-derived benefits resulting from this research, such as new insights into disease mechanisms or possible novel therapies, will be disseminated to study participants, patient groups and members of the public. Trial registration number NCT05746221 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2024-084303
    DOI: 10.1136/bmjopen-2024-084303.supp1
    Language: English
    Publisher: BMJ
    Publication Date: 2024
    detail.hit.zdb_id: 2599832-8
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  • 7
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    Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study
    BMJ ; 2023
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 94, No. 2 ( 2023-02), p. 144-144
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 94, No. 2 ( 2023-02), p. 144-144
    Abstract: 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 relationship with clinical outcomes. Methods Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI−). Results DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (β=0.36, 95% CI=0.05 to 0.68, p = 0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p 〈 0.001) and greater cognitive decline (β=−0.03, 95% CI=−0.05 to −0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8–13.8) years compared with DWI− participants. No differences were found in risk of all-cause mortality, stroke or dementia. Conclusion Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2022-330091
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2023
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  • 8
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    Global Outcome Assessment Life-long after stroke in young adults initiative—the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis
    BMJ ; 2019
    In:  BMJ Open Vol. 9, No. 11 ( 2019-11), p. e031144-
    Details
    In: BMJ Open, BMJ, Vol. 9, No. 11 ( 2019-11), p. e031144-
    Abstract: 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 provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18–50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. Ethics and dissemination Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2019-031144
    Language: English
    Publisher: BMJ
    Publication Date: 2019
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  • 9
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    Post-stroke fatigue and its association with poor functional outcome after stroke in young adults
    BMJ ; 2015
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 86, No. 10 ( 2015-10), p. 1120-1126
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 86, No. 10 ( 2015-10), p. 1120-1126
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2014-308784
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2015
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  • 10
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    Ischaemic stroke in young adults: a global perspective
    BMJ ; 2020
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 91, No. 4 ( 2020-04), p. 411-417
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 91, No. 4 ( 2020-04), p. 411-417
    Abstract: 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 factors and aetiologies. In this review, we will provide an overview of the global variation in the epidemiology of stroke in young adults, with special attention to differences in geography, ethnicity/race and sex, as well as traditional and novel risk factors for early-onset ischaemic stroke, such as air pollution. Understanding global differences is an important prerequisite for better region-specific prevention and treatment of this devastating condition.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2019-322424
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1480429-3
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