Disease progression and regression in sporadic small vessel disease–insights from neuroimaging

2017 ◽  
Vol 131 (12) ◽  
pp. 1191-1206 ◽  
Author(s):  
Esther M.C. van Leijsen ◽  
Frank-Erik de Leeuw ◽  
Anil M. Tuladhar
Keyword(s):  
Disease Progression ◽  
Time Course ◽  
Temporal Dynamics ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Course Of Disease ◽  
Vessel Disease ◽  
Clinical Consequences ◽  
Dynamic Time

Cerebral small vessel disease (SVD) is considered the most important vascular contributor to the development of dementia. Comprehensive characterization of the time course of disease progression will result in better understanding of aetiology and clinical consequences of SVD. SVD progression has been studied extensively over the years, usually describing change in SVD markers over time using neuroimaging at two time points. As a consequence, SVD is usually seen as a rather linear, continuously progressive process. This assumption of continuous progression of SVD markers was recently challenged by several studies that showed regression of SVD markers. Here, we provide a review on disease progression in sporadic SVD, thereby taking into account both progression and regression of SVD markers with emphasis on white matter hyperintensities (WMH), lacunes and microbleeds. We will elaborate on temporal dynamics of SVD progression and discuss the view of SVD progression as a dynamic process, rather than the traditional view of SVD as a continuous progressive process, that might better fit evidence from longitudinal neuroimaging studies. We will discuss possible mechanisms and clinical implications of a dynamic time course of SVD, with both progression and regression of SVD markers.

Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013077
Author(s):  
Corey W Bown ◽  
Roxana O Carare ◽  
Matthew S Schrag ◽  
Angela L Jefferson
Keyword(s):  
Fluid Transport ◽  
Small Vessel Disease ◽  
Treatment Strategies ◽  
Small Vessel ◽  
Aging Brain ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Clinical Consequences ◽  
The Brain

Perivascular spaces (PVS) are fluid filled compartments that are part of the cerebral blood vessel wall and represent the conduit for fluid transport in and out of the brain. PVS are considered pathologic when sufficiently enlarged to be visible on magnetic resonance imaging. Recent studies have demonstrated that enlarged PVS (ePVS) may have clinical consequences related to cognition. Emerging literature points to arterial stiffening and abnormal protein aggregation in vessel walls as two possible mechanisms that drive ePVS formation. In this review, we describe the clinical consequences, anatomy, fluid dynamics, physiology, risk factors, and in vivo quantification methods of ePVS. Given competing views of PVS physiology, we detail the two most prominent theoretical views and review ePVS associations with other common small vessel disease markers. As ePVS are a marker of small vessel disease and ePVS burden is higher in Alzheimer’s disease, a comprehensive understanding about ePVS is essential in developing prevention and treatment strategies.

Characterization of Cerebral Small Vessel Disease by Proton Spectroscopy and Morphological Magnetic Resonance

2001 ◽  
Vol 12 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Margret Hund-Georgiadis ◽  
David G. Norris ◽  
Thomas Guthke ◽  
D. Yves von Cramon
Keyword(s):  
Magnetic Resonance ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Proton Spectroscopy ◽  
Vessel Disease

scholarly journals Nonlinear temporal dynamics of cerebral small vessel disease

Neurology ◽  
2017 ◽  
Vol 89 (15) ◽  
pp. 1569-1577 ◽  
Author(s):  
Esther M.C. van Leijsen ◽  
Ingeborg W.M. van Uden ◽  
Mohsen Ghafoorian ◽  
Mayra I. Bergkamp ◽  
Valerie Lohner ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Quadratic Term ◽  
Vessel Disease ◽  
Semiautomatic Segmentation ◽  
Over Time

Objective:To investigate the temporal dynamics of cerebral small vessel disease (SVD) by 3 consecutive assessments over a period of 9 years, distinguishing progression from regression.Methods:Changes in SVD markers of 276 participants of the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) cohort were assessed at 3 time points over 9 years. We assessed white matter hyperintensities (WMH) volume by semiautomatic segmentation and rated lacunes and microbleeds manually. We categorized baseline WMH severity as mild, moderate, or severe according to the modified Fazekas scale. We performed mixed-effects regression analysis including a quadratic term for increasing age.Results:Mean WMH progression over 9 years was 4.7 mL (0.54 mL/y; interquartile range 0.95–5.5 mL), 20.3% of patients had incident lacunes (2.3%/y), and 18.9% had incident microbleeds (2.2%/y). WMH volume declined in 9.4% of the participants during the first follow-up interval, but only for 1 participant (0.4%) throughout the whole follow-up. Lacunes disappeared in 3.6% and microbleeds in 5.7% of the participants. WMH progression accelerated over time: including a quadratic term for increasing age during follow-up significantly improved the model (p < 0.001). SVD progression was predominantly seen in participants with moderate to severe WMH at baseline compared to those with mild WMH (odds ratio [OR] 35.5, 95% confidence interval [CI] 15.8–80.0, p < 0.001 for WMH progression; OR 5.7, 95% CI 2.8–11.2, p < 0.001 for incident lacunes; and OR 2.9, 95% CI 1.4–5.9, p = 0.003 for incident microbleeds).Conclusions:SVD progression is nonlinear, accelerating over time, and a highly dynamic process, with progression interrupted by reduction in some, in a population that on average shows progression.

scholarly journals Neuropsychiatric Correlates of Small Vessel Disease Progression in Incident Cognitive Decline: Independent and Interactive Effects

2020 ◽  
Vol 73 (3) ◽  
pp. 1053-1062
Author(s):  
Cheuk Ni Kan ◽  
Bibek Gyanwali ◽  
Saima Hilal ◽  
Kok Pin Ng ◽  
Narayanaswamy Venketasubramanian ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Disease Progression ◽  
Small Vessel Disease ◽  
Interactive Effects ◽  
Small Vessel ◽  
Vessel Disease

Abstract 40: Time Course of Cerebral Small Vessel Disease Lesions and Sensory Motor Changes in Spontaneously Hypertensive Stroke Prone Rats

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Eder Caceres ◽  
Cameron Rink ◽  
Jay L Zweier ◽  
Yousef Hannawi
Keyword(s):  
Time Course ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Male Rats ◽  
Small Vessel ◽  
Therapeutic Drug ◽  
Time Points ◽  
Vessel Disease ◽  
Average Group

Introduction: Animal models of human cerebral small vessel disease (CSVD) are important for the study of the disease underlying mechanisms and testing therapeutic interventions. Spontaneusly Hypertensive Rats - Stroke Prone (SHRSP) are used as an animal model of human CSVD. However, there is a lack of data regarding the time course of cognitive and motor impairment. Methods: Male age-matched SHRSP and Wistar Kyoto rats (WKY) were studied. Sensorimotor testing (open field test) and tail-cuff systolic blood pressure (SBP) measurements (Visitech Systems, Inc.) were performed weekly starting from 6 until 24 weeks of age. Brain MRI at 7 and 24 weeks was acquired using a 9.4T MRI system. Brain histology was completed at the same time points. Statistical analysis was performed using a linear mixed model with repeated measurements. P< 0.05 was considered significant. Results: 20 SHRSP and 20 WKY male rats were studied. 10 per group were euthanized following brain MRI at 7 weeks and the rest were followed until 24 weeks. SHRSP weighed on average 30 grams less than WKY throughout the study (P=0.0003). At 7 weeks SBP was not different (WKY 106.6±5.4 vs SHRSP 120.8±5.4, P=0.06). SHRSP started to develop hypertension at 9-12 weeks and maintained hypertension until 24 weeks (average group difference across time P<0.0001; SBP at 21 weeks WKY 134.8±5.4 vs SHRSP 168.9±5.4, P<0.0001). Sensorimotor testing showed higher total distance travelled (TDT) at 7 weeks in SHRSP that trended down with ageing. Both groups became similar at 21 weeks (TDT: at 7 weeks WKY 3.78±1.3 vs SHRSP 7.8±1.3, P =0.037; at 21 weeks: WKY 4±1.3 vs SHRSP 4.4±1.3, P=0.83; average group difference across time P=0.014). Brain MRI was normal at 7 weeks, but small white matter hyperintensities were seen at 24 weeks. Brain Histology showed normal histology on hematoxylin & eosin staining at 7 weeks in both groups, while at 24 weeks SHRSP showed CSVD histopathological changes including microbleed formation, homeostasis and vascular hyalinosis. Conclusions: SHRSP develops hypertension, sensorimotor deficits and CSVD pathology as they age suggesting their utility as human CSVD model. Intervention time points should be selected carefully in future therapeutic drug interventions.

scholarly journals Large Perivascular Spaces Visible on Magnetic Resonance Imaging, Cerebral Small Vessel Disease Progression, and Risk of Dementia

2017 ◽  
Vol 74 (9) ◽  
pp. 1105 ◽  
Author(s):  
Jie Ding ◽  
Sigurður Sigurðsson ◽  
Pálmi V. Jónsson ◽  
Gudny Eiriksdottir ◽  
Andreas Charidimou ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Disease Progression ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Resonance Imaging ◽  
Vessel Disease

scholarly journals Investigating the origin and evolution of cerebral small vessel disease: The RUN DMC – InTENse study

2018 ◽  
Vol 3 (4) ◽  
pp. 369-378 ◽  
Author(s):  
Annemieke ter Telgte ◽  
Kim Wiegertjes ◽  
Anil M Tuladhar ◽  
Marlies P Noz ◽  
José P Marques ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Small Vessel Disease ◽  
Clinical Importance ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Acute Ischaemia ◽  
Origin And Evolution ◽  
Vessel Disease ◽  
And Function

Background Neuroimaging in older adults commonly reveals signs of cerebral small vessel disease (SVD). SVD is believed to be caused by chronic hypoperfusion based on animal models and longitudinal studies with inter-scan intervals of years. Recent imaging evidence, however, suggests a role for acute ischaemia, as indicated by incidental diffusion-weighted imaging lesions (DWI+ lesions), in the origin of SVD. Furthermore, it becomes increasingly recognised that focal SVD lesions likely affect the structure and function of brain areas remote from the original SVD lesion. However, the temporal dynamics of these events are largely unknown. Aims (1) To investigate the monthly incidence of DWI+ lesions in subjects with SVD; (2) to assess to which extent these lesions explain progression of SVD imaging markers; (3) to investigate their effects on cortical thickness, structural and functional connectivity and cognitive and motor performance; and (4) to investigate the potential role of the innate immune system in the pathophysiology of SVD. Design/methods The RUN DMC – InTENse study is a longitudinal observational study among 54 non-demented RUN DMC survivors with mild to severe SVD and no other presumed cause of ischaemia. We performed MRI assessments monthly during 10 consecutive months (totalling up to 10 scans per subject), complemented with clinical, motor and cognitive examinations. Discussion Our study will provide a better understanding of the role of DWI+ lesions in the pathophysiology of SVD and will further unravel the structural and functional consequences and clinical importance of these lesions, with an unprecedented temporal resolution. Understanding the role of acute, potentially ischaemic, processes in SVD may provide new strategies for therapies.

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