diagnosis and imaging

Lin Kooi Ong, PhD
@DrLinOng

Brodtmann A, Khlif MS, Egorova N, Veldsman M, Bird LJ, Werden E. Dynamic Regional Brain Atrophy Rates in the First Year After Ischemic Stroke. Stroke. 2020;51:e183–e192.

Brain atrophy refers to a loss of brain cells or a loss in the networks between brain cells, and is a common feature for many neurodegenerative diseases. Ischemic stroke is usually viewed as an acute cerebrovascular injury, and not as a neurodegenerative condition. Nevertheless, there is now emerging evidence demonstrating that stroke can cause persistent regional brain atrophy for months and even years after the initial event. Further, this regional brain atrophy after stroke has been linked to several late phase functional disturbances, including cognitive impairment. Notably, stroke increases the risk of developing vascular dementia.

The CANVAS study (Cognition and Neocortical Volume After Stroke) is a longitudinal study in people recruited from Melbourne hospitals, Australia, following ischemic stroke, comparing brain volume and cognitive function over 3 years with a group of healthy age- and sex-matched control participants.(1) In this article, Brodtmann and colleagues examined the trajectories of total and regional brain volume changes in the first year following stroke. Specifically, brain magnetic resonance imaging (MRI) was performed on stroke and healthy control participants, with 86 stroke participants completing testing at baseline, 125 at 3 months, and 113 participants at 12 months, as well as 40 healthy control participants. Five brain measures — hippocampal volume, thalamic volume, total brain and hemispheric brain volume, and cortical thickness — were examined to evaluate whether brain atrophy rates differed between time points and groups.

Charlotte Zerna, MD, MSc
@CharlotteZerna

Egorova N, Dhollander T, Khlif SM, Khan W, Werden E, Brodtmann. Pervasive White Matter Fiber Degeneration in Ischemic Stroke. Stroke. 2020;51:1507–1513.

Studies have shown that ischemic stroke does not only lead to focal tissue destruction, but can also result in the remote loss of gray matter and disruption of functional connectivity. However, less is known about the remote and regional white matter degeneration after ischemic stroke. Prior studies have been limited by using diffusion-tensor imaging metrics that are non-specific voxel-averaged measures and can lead to erroneous interpretations in locations where white matter fibers are crossing. The objective of the study by Egorova et al. was, therefore, to examine white matter degeneration in a cohort of participants at 3 months post-infarct using a novel fixel-based analysis (fiber population within an MRI voxel). This method allowed the authors to assess complex microstructural fiber geometry in greater detail.

Participants with ischemic stroke (confirmed both clinically and radiologically) were recruited within 6 weeks of their index event at 3 hospitals in Melbourne, Australia. Both patients with first ever (85.6%) and recurrent ischemic stroke (14.4%) in any vascular territory and of any etiology were considered. Age-matched controls (that were also comparable in sex and education status) were selected from a database of volunteers who had previously undertaken MRI research at one of the recruiting hospitals. Of the 165 recruited participants who completed scanning at 3 months, complete usable MRI diffusion data were available for 104 stroke and 40 control participants and could be used for analysis after successfully undergoing pre-processing.

Lina Palaiodimou, MD

Cheng B, Boutitie F, Nickel A, Wouters A, Cho T-H, Ebinger M, et al. Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial. Stroke. 2019.

Advanced neuroimaging has already changed the scene in acute stroke treatment, allowing patients with unknown or extended time windows to receive recanalization therapies (intravenous thrombolysis, mechanical thrombectomy). The cornerstone of this recent breakthrough is the demonstration of viable brain tissue regardless of time elapsed since stroke onset. That was also the case in the WAKE-UP trial, which proved clinical benefit in alteplase-treated acute stroke patients with unknown time of onset, but clearly presenting salvageable brain tissue, as was demonstrated by diffusion-weighted imaging (DWI) – fluid-attenuated inversion recovery (FLAIR) mismatch.   

The study by Cheng et al. presents a post-hoc analysis of the WAKE-UP trial with the aim to associate quantitatively measured relative signal intensity in FLAIR (rSI-FLAIR) with the clinical outcomes of the treated patients. The objective of this study was rationalized by previous studies, which correlated rSI-FLAIR with time elapsed since stroke onset. That correlation was linear; higher rSI-FLAIR corresponded to longer time since stroke onset and, actually, when the clock was ticking, FLAIR was glowing. Consequently, Cheng et al. moved to the next logical reasoning that, since rSI-FLAIR is associated with time and time is associated with clinical outcomes, rSI-FLAIR may relate to clinical outcomes of alteplase-treated patients. 

Kristina Shkirkova, BSc

Wyss A, Dawson J, Arba F, Wardlaw JM, Dickie DA, on behalf of the VISTA-Prevention Collaborators. “Combining Neurovascular and Neurodegenerative Magnetic Resonance Imaging Measures in Stroke.” Stroke. 2019; 50:1136-1139.

To characterize age and stroke-related tissue damage, the total small vessel disease score and the brain health index have recently been developed for clinical use. The total small vessel disease score combines presence of lacunes, microbleeds, and moderate to severe white matter hyperintensities (WMH) by visual scoring based on clinical imaging. The brain health index uses automatic processing of MRI scans to quantify visible injury from small vessel disease and brain atrophy. However, the total small vessel disease score is prone to granularity and measurement limitations, whereas the brain health index requires high-resolution T1, T2, T2 gradient echo, and fluid attenuated inversion recovery scans, which are not often available in routine clinical imaging.

The study by Wyss et al. argues that individual markers of cerebral small vessel disease and brain atrophy have limited potential to explain high proportion of variance in neurovascular and neurodegenerative disease. The authors propose to combine markers of white matter hyperintensity and cerebral atrophy, represented by cerebrospinal fluid (CSF) volume, into a single measure capable of more accurate predictions of cognitive impairment.

Alejandro Fuerte, MD
@DrFuerte1

Fullerton H, Stence N, Hills N, Jiang B, Amlie-Lefond C, Bernard T, et al. Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History. Stroke. 2018

Focal cerebral arteriopathy (FCA) of childhood is an acute disease causing unilateral stenosis of the cerebral arteries. It appears to be caused by an inflammatory process, and corticosteroids are used in its treatment in the absence of clinical trial data. Because it is one of the most common causes of arterial ischemic stroke (AIS) in healthy children and it increases the risk of recurrent stroke, a Delphi consensus identified this issue as the highest priority for a clinical trial in the field of childhood stroke.

The main goal of Fullerton et al. was to develop a severity score for this disease (Focal Arteriopathy Childhood Severity Score; FCASS). For this they used data from the VIPS study (Vascular Effects of Infection in Pediatric Stroke), a large, international, prospective cohort study that enrolled 355 children (29 days to 18 years of age) with AIS and collected clinical, imaging data and serum samples.