Welcome to the WSC 2022 Interactive Program

Background and Aims

PET biomarkers of Aβ can detect amyloid pathology in hemorrhagic small vessel disease (SVD), but the high cost limits their availability. We aimed to assess whether blood biomarkers could be used as surrogates for cerebral amyloid angiopathy (CAA) diagnosis.

Methods

Plasma levels of total tau (t-tau), phosphorylated tau 181 (p-tau 181), Aβ42 and Aβ 40 were measured in 67 spontaneous intracerebral hemorrhage (ICH) survivors who underwent brain MRI and 11C-PiB PET. A subgroup of patients also received 18F-T807 PET for measuring tau burden. We selected patients with CAA by modified Boston criteria who also had positive amyloid scan, compared to patients with hypertensive SVD (HTN-SVD) who had negative amyloid scan. We assessed the correlation between blood and radiological biomarkers using linear regression models. The diagnostic performance of blood biomarkers was analyzed using operating characteristic (ROC) curve.

Results

Patients with CAA (n=20, age 74.8 ± 6.7) had higher cerebral amyloid and tau burden compared to HTN-SVD (n=47, age 62.4 ± 11.7). Plasma p-tau 181 levels were higher in CAA compared to HTN-SVD (3.27 ± 2.30 vs. 2.00 ± 1.15 pg/mL, p=0.004) but the t-tau, Aβ42 and Aβ40 levels were comparable between groups. In CAA, p-tau 181 was significantly correlated to lobar CMB counts after adjustment for age and sex (standardized β=0.569, p=0.024). ROC curve showed an area-under-curve of 0.79 for p-tau 181 in differentiating CAA from HTN-SVD (cutoff 2.17 ng/mL, sensitivity 80%, specificity 77%).

Conclusions

Plasma p-tau 181 may serve as a non-invasive biomarker for amyloid scan positive CAA.

Background and Aims

Small fraction of lacunar stroke patients have a fluctuating course,described as stuttering lacunar syndrome(SLS). There is scant literature on predictors of SLS.We studied the predictors and short term outcome of stuttering lacunar strokes in comparison with an early stable course.

Methods

Single centre retrospective study where patients with lacunar strokes from 2016 to 2020 were included in the study. Fluctuation was defined as increase in stroke severity(NIHSS)from baseline without imaging evidence of new infarcts or haemorrhagic transformation. Clinical variables, risk factors, imaging and outcome of subjects with SLS were compared with those of stable course.

Results

Of the 216 patients with lacunar strokes, with a mean age 63.17 years,fluctuations were noted in 56 subjects(26%).Majority of the fluctuations occurred within 24 hours of onset of symptoms. Stroke severity at admission was comparable between the 2 groups. Bivariate analysis showed that SLS were more likely to present as ataxic hemiparesis ,with capsuloganglionic and pontine location, have hypertriglyceridemia, and receive thrombolytic therapy, while thalamic infarcts and atypical lacunar syndromes were associated with stable course.Thrombolysis was associated with worse outcome in SLS.Age,gender,risk factors,cardiac parameters and leukoaraiosis in imaging did not differ between the 2 subgroups. Outcome was comparable at ,discharge,3 and 9 month follow-up.Multivariate logistic regression showed independent association of hypertriglyceridemia,thrombolysis,pure motor syndrome and ataxic hemiparesis with SLS.

Conclusions

Stuttering course is seen in a quarter of lacunar strokes,mostly occurring within 24 hours of stroke onset.Thrombolysed patients had increased fluctuations with worse outcome. Discharge disability,short term outcomes of SLS were comparable with rest of the lacunar strokes.

Background and Aims

Preexisting brain frailty may determine clinical outcomes after EVT, irrespective of the chronological age. Markers of cerebral small vessel disease (CSVD), such as white matter hyperintensities (WMH), are important surrogates of brain frailty. We aim to investigate the impact of WMH-burden, detected on stroke CT, on functional outcome after EVT.

Methods

We included patients with interpretable CT from the ESCAPE-NA1-dataset. We visually scored WMH by using the Fazekas scale (WMH-burden score 0-6; the sum of periventricular and deep WMH). The primary outcome was mRS at 90 days (ordinal-shift-analysis). The secondary outcome was repeated mRS measures at different time points (pre-stroke, day 5, 30 and 90). The models were adjusted for age, sex, final infarct volume (FIV), laterality, cortical atrophy, Nerinetide-Alteplase interaction, and study site.

Results

We included 1102 patients with interpretable CT. The total WMH-burden score was 0-1 in 696/1102 (63%), 2 in 211/1102 (19%); and ≥3 in 195/1102 (18%). The WMH-burden was significantly associated with 90-day-mRS (cOR [per point increase in Fazekas score] of 1.09; 95%CI:1.05-1.14). Furthermore, mRS outcomes over the course of follow-up differed by WMH-burden. For example, the mRS of patients with substantial WMH-burden (score ≥3) was on average 0.47 points higher at 30-days (95%CI 0.22-0.72) and 0.6 points higher at 90-days (95%CI 0.36-0.85), compared to patients with no/minimal WMH (score 0-1), figure1.

Figure 1.

Conclusions

In patients with AIS undergoing EVT within 12 hours of onset, an increasing burden of WMH assessed on CT is associated with worse functional outcome over time.

Background and Aims

Cerebral Amyloid Angiopathy (CAA) is a major cause of intracerebral hemorrhages and cognitive decline in the elderly. Vascular reactivity is an early marker of CAA, but its relation to structural brain damage remains unclear. We studied the relationship between reactivity alterations and structural brain damage measured by diffusion MRI in (pre-)symptomatic mutation carriers with Dutch-type hereditary CAA (D-CAA).

Methods

3T diffusion tensor imaging (DTI) and reactivity measurements by visually stimulated fMRI were acquired in 25 D-CAA mutation carriers (mean 45yrs, range 28-71yrs, 64% women; 15 pre-symptomatic). From the fMRI data we calculated normalized time to peak (TTP), time to baseline (TTB), and amplitude based on a trapezoid fit. When the amplitude was too low, TTP and TTB were not calculated. Based on the DTI, robust peak width of skeletonized mean diffusivity (PSMD) was calculated (Figure 1A). Associations between the vascular reactivity measures (TTP, TTB, and amplitude) and PSMD were tested using linear regression analysis.

Results

BOLD amplitude is decreased and PSMD, TTP, and TTB are increased in symptomatic versus pre-symptomatic D-CAA (Figure 1B-E). Amplitude, TTP, and TTB are significantly related to PSMD values (β=-1.154e-02,p=.0005; β =1.080e-05,p=.0092; β=8.635e-06,p=.0039). When looking only at the pre-symptomatic D-CAA patients, these relations are no longer statistically significant.

Conclusions

Reduced vascular reactivity as depicted by reduced BOLD amplitude, and delayed TTP and TTB is related to structural brain damage as measured with PSMD. This indicates that vascular and structural deterioration go hand-in-hand in D-CAA although with this cross-sectional study no causal relation can be proven.

Background and Aims

Silent cerebrovascular disease or small vessels disease are considered major risk factors for developing stroke. It was estimated that 90% of stroke cases are preventable, if detected early enough. However, these conditions are not evaluated in the routine clinical care. In this study we will display clinically accessible physiological biomarkers for silent cerebrovascular disease that enable objective and early detection and promote stroke prevention.

Methods

The study included 168 healthy patients with at least one risk factor for stroke (hypertension, dyslipidemia, diabetes, smoking etc.). Brain network status was evaluated utilizing direct electrophysiological imaging (DELPHI) system which measures magnetically induced brain network electrophysiological biomarkers of network response and MRI scans including T1, T2, FLAIR, Diffusion Weighted Imaging (DWI) and (SWI) which were analyzed according to Fazakes scale for white matter lesions, White Matter Hyperintensities (WMH) and Lacunar infarctions.

Results

DELPHI physiological evaluation displays sensitivity of 82%, and specificity of 60% to detect WM changes of WMH and/or infarctions in subjects with risk factors for stroke (Fig.1a). DELPHI measure of Wave Form Adherence (WFA) correlates with changes in MRI WMH and lacunar infarction and significantly differentiates between severity levels ((fig.1b,c; WMH ,p<0.0001; Lacunar infarctions, p<0.0001) .

Conclusions

Routine evaluation and detection of silent cerebrovascular disease is crucial for the prevention of stroke. Brain network physiology evaluation utilizing DELPHI technology provides means for clinically accessible and objective routine detection of silent cerebrovascular disease related findings and progression.

Background and Aims

Our purpose is to verify the relationship between the inferior frontal sulcal hyperintensity (IFSH) on fluid-attenuated inversion recovery and the cerebrospinal fluid (CSF) clearance function via the putative meningeal lymphatics, and to explore its correlation with cerebral small vessel disease(CSVD).

Methods

We included patients receiving magnetic resonance imaging before and at multiple time points after intrathecal administration of contrast agent. We quantitatively assessed the phenomenon of IFSH by measuring the mean signal intensity of the inferior frontal sulci. The CSF clearance function of the putative meningeal lymphatics and perineural pathways of olfactory nerve was assessed by the signal unit ratio change of parasagittal dura and turbinate from baseline to 39 hours, respectively.

Imaging evaluation of cerebral small vessel disease included: lacunas, microbleeds, white matter hyperintensities, enlarged perivascular space (EPVS). Grading score of these imaging markers was used to assess the severity of CSVD.

Results

A total of 72 patients were included. We found that higher mean signal intensity of the inferior frontal sulci was associated with worse CSF clearance function via the meningeal lymphatics（r=0.311， p=0.014 ）, increasing age（r=0.292， p=0.013 ）, higher scores of both periventricle and deep white matter hyperintensities（r=0.402，p=0.001;r=0.248,p=0.037）and higher grade of enlarged perivascular spaces in centrum semiovale（r=0.285，p=0.016）

Conclusions

Inferior frontal sulcal hyperintensity on FLAIR may be a non-invasive imaging marker for glymphatic circulation CSF outflow dysfunction, and its formation may be related to the pathogenesis and development of cerebral small vessel disease

Background and Aims

Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a rare, but treatable CAA phenotype. Recent studies suggest that mild or subclinical episodes of inflammation can occur, as demonstrated on MRI. We determined the frequency of subclinical MRI lesions suggestive of inflammation with no clinical signs or symptoms in sporadic CAA (sCAA) and Dutch-type hereditary CAA (D-CAA).

Methods

In this cross-sectional study, we included sCAA patients and D-CAA mutation carriers from our ongoing CAA natural history studies (AURORA and FOCAS) at the Leiden University Medical Center between 2018 and 2020. Absence of clinical symptoms was confirmed by an interview and neurological examination. 3-Tesla MRI scans were assessed for presence of asymmetric cortical-subcortical white matter hyperintensity (WMH) lesions on FLAIRimages suggestive of inflammation.

Results

We included 44 sCAA patients (mean age 73 years, 57% with a history of intracerebral hemorrhage (ICH)) and 46 D-CAA mutation carriers (mean age 50 years, 57% with a history of ICH). Two (5%, 95%CI: 1-14) sCAA patients and one (2%, 95%CI: 0-10) D-CAA mutation carrier had a cortical-subcortical WMH lesion that was suspected of inflammation. All lesions were <1cm and were located in the frontal or parietal lobes. One sCAA patient had multiple lesions and presented with lobar ICH in the same hemisphere as these lesions one week after MRI (figure 1).

Conclusions

Subclinical MRI lesions suggestive of inflammation are a rare radiological finding in sCAA and D-CAA. Even though these small lesions are subclinical with an unclear pathophysiological substrate, they might precede CAA-related intracerebral hemorrhage.

Background and Aims

In single subcortical infarction (SSI), an increase in the size of the initial lesion plays an important role in prognosis. Therefore, if it is possible to simply obtain the infarct growth velocity (IGV) at the time of admission, it would be helpful to predict the early prognosis of SSI patients. In this study, we evaluated the association between IGV and early neurological deterioration (END) in patients with SSI.

Methods

We included consecutive SSI stroke patients between 2010 and 2016. END was defined as an increase of ≥ 1 in the motor NIHSS score, or that of ≥ 2 in the total NIHSS score within the first 72 hours of admission. IGV was calculated by dividing the initial diffusion weighted imaging lesion size (mL) by the time from symptom onset to conducting magnetic resonance imaging.

Results

A total of 245 patients with SSI were evaluated. In multivariable analysis, IGV was closely related to END [adjusted odds ratio (aOR) = 1.64, 95% confidence interval (CI) = 1.19-2.27]. Initial NIHSS score and proximal SSI were also positively associated with END. In subgroup analysis according to lesion location, IGV showed statistical significance with END only in distal SSI (aOR = 3.87, 95% CI = 1.78-8.40). On the other hand, in proximal SSI, IGV did not show any statistical relationship with END.

Conclusions

High IGV was closely associated with END in patients with SSI. This relationship was particularly pronounced in distal SSI, suggesting that IGV may be involved in the lacunar mechanism.

Background and Aims

Cerebral venous sinus thrombosis(CVST) is a rare cause of stroke in young. Hyperdense sinus in CVST in Noncontrast Computed tomography(NCCT) scans is known. The aim is to understand the relationship between change of sinus density in serial CT scans with clinical outcomes, with low dose heparin protocol.

Methods

Retrospective case analysis of CVST cases managed at our tertiary care referral center over past six months was performed. Patients with CVST with at least 2 NCCT scans in the hospital stay were included and those where sinus hyperdensity was unascertainable were excluded. All patients received unfractionated heparin 5000IU 6^th hourly for 7-10 days followed by oral acenocoumarol, dose titrated to maintain INR at 1.5 to 2. Serial scans were reviewed and the density of the involved sinuses were measured using Hounsfield units (HU). Functional outcome was assessed by Modified Rankin scale(mRS).

Results

Fifty patients met the criteria. Mean age was 37.2 ±11.1years. Male: female-24:26. Anaemia and hyperhomocysteinemia were common risk factors. Clinical features included headache(100%), encephalopathy in16(32%), seizures in 15(30%), focal deficits in 27(54%), vision loss in 7(14%), aphasia in 5(10%). CT showed parenchymal lesions in 41(82%). Superior Sagittal Sinus was involved in 27(54%), transverse sinus in 31(62%), both in 16(32%), deep sinuses in 5(1%). There was statistically significant reduction in venous sinus density in all patients and all patients improved with our treatment regimen

Conclusions

Lowdose unfractionated heparin protocol used at our centre is safe, effective as evidenced by statiscally significant serial reduction in sinus density and good functional outcome.

Background and Aims

Alzheimer’s disease (AD) and ischemic stroke are risk factors to each other. The comorbidity of these two diseases in the same patients represents an eminent gap in basic and clinical research. AD and stroke share common pathophysiological mechanisms such as NMDA receptor (NMDAR) hyperactivity and Ca2+-associated excitotoxicity. We identified that deficiency of the NMDAR GluN3A subunit is a novel pathogenic mechanism of AD. Memantine (MEM) is a safe NMDAR antagonist. We test the hypothesis that early treatment of MEM is a disease modifying therapy for preventing AD development and simultaneously increasing tolerance against ischemic attack that occurs to 50% of AD patients.

Methods

The anti-AD and anti-stroke effects of preconditioning treatments were tested in AD mouse models before and after a focal ischemic insult. Cellular, molecular and functional assessments were performed in brain sections and aging animals before and after stroke.

Results

In the GluN3A knockout mouse and 5XFAD mouse, oral MEM (10 mg/kg/day in drinking water) for 3 months during preclinical stage of AD attenuated ischemia-induced infarct formation. MEM daily treatments before and after stroke improved sensorimotor and psychological functions, suppressed inflammatory factors such as TNF-alpha and interleukins while increased the Bcl-2 expression in the AD brain. The MEM treatment prevented age-dependent memory loss in AD mice.

Conclusions

This investigation demonstrates the dual benefits of the clinical drug MEM in AD mouse models before and after ischemic stroke. The early MEM preventive therapy is a mechanism-based treatment for people susceptible to AD and stroke.

Background and Aims

Brain diffusion-restriction on magnetic resonance diffusion-weighted imaging (MR-DWI) identifies acute cerebral infarction. Central retinal artery occlusion (CRAO) is a neurovascular emergency that may exhibit diffusion-restriction of the retina and/or optic nerve (ON). We aimed to evaluate the rates and inter-rater reliability of retina and ON diffusion-restriction identification on standard brain MR-DWI performed for non-arteritic CRAO.

Methods

We retrospectively reviewed consecutive CRAO patients with brain MR-DWI performed within 14 days of visual loss in our academic center, between 2013-2021. Two experienced neuroradiologists masked to the CRAO side independently reviewed each MRI to determine the presence of retina and ON diffusion-restriction. Their inter-rater reliability was calculated using kappa statistics. The error rate was defined as diffusion-restriction identified in the eye contralateral to the CRAO after the neuroradiologists reached a consensus agreement.

Results

129 non-arteritic CRAO patients, 55% right eye and 45% left eye, mean age 68.9 years were included. The median time from CRAO to MRI was 2 days (IQR 1-4). 28/129 (21.7%) had a discrepancy among the readers. Diffusion-restriction was present in 56/129 (43.4%) [error rate = 6/56 (10.7%)]. The overall inter-rater reliability was satisfactory (Kappa 0.64), retina (0.75) better than ON (0.63). Overall error rate differed between readers (1/54 (1.9%) versus 5/58 (8.6%) (p<0.001)).

Conclusions

Less than half of non-arteritic CRAO exhibited diffusion-restriction of the ON and/or retina on brain MR-DWI, with satisfactory inter-rater reliability in our case series. Future prospective studies should assess the applicability of retina and/or ON diffusion-weighted imaging in routine CRAO diagnosis in the hyperacute clinical setting.

Background and Aims

Existing evidence suggests that changes in white matter fiber tracts are closely related to neurological deficits after stroke. Basing on fiber tract-based spatial statistical analysis (TBSS), we observe the improvement effect of long-term oral butylphthalide on white matter fiber tracts in stroke patients in this study.

Methods

This is a randomized, double-blind, placebo-controlled observational study of butylphthalide, which includes 110 stroke patients (56 in butylphthalide group and 54 in placebo group). The course of treatment is 24 weeks, and the patient takes 2 capsules at a time, 3 times a day. DTI images were collected at baseline, one month, three months, and six months after taking the drug, and FA values were analyzed.

Results

Results: Comparing with the control group, the FA value of the bilateral corticospinal tracts in the experimental group gradually increased (p < 0.05) after taking the drug of six months, while the FA value in the control group gradually decreased (p < 0.05). It indicates that the integrity of the white matter fiber tracts in the experimental group tends to be good, while the integrity of the white matter fiber tracts in the control group is still being destroyed.

Conclusions

Conclusions: Long-term (6 months) oral administration of butylphthalide sustainably improves the integrity of white matter fiber tracts in stroke patients.

Background and Aims

Acute ischemic stroke (AIS) patients have variable outcomes which may be explained by brain reserve, where the unaffected brain compensates for acquired brain insult. Cortical atrophy is one of the imaging markers of brain reserve. Although it is routinely assessed on MRI, CT is widely used in AIS. We aim to compare CT and MRI in measuring cortical atrophies in AIS.

Methods

Patients with an interpretable baseline CT and available follow-up MRI were included from the ESCAPE-NA1 trial, which studied AIS patients. Cortical atrophies were measured using standard rating scales for global cortical atrophy (GCA); parietal, frontal, occipital atrophies (Koedam score); medial temporal atrophy (MTA); and cerebellar atrophy. Correlation and agreement were calculated, including subgroup analysis of MTA between cases with and without MRI coronal view.

Results

Interpretable baseline CT and follow-up MRI were available in 566 of 1105 patients (51.2%). No global cortical atrophy was observed in 433 (76.5%) CT scans and 319 (56.4%) MRI. The highest GCA severities observed on CT and MRI were moderate and severe, respectively. GCA and other supratentorial cortical atrophies had moderate correlation between CT and MRI. The parietal atrophy had the highest correlation (Spearman rho 0.599, p<0.0001; agreement 64.5%). Subgroup analysis of MTA showed moderate correlation in cases with (Spearman rho 0.484, p<0.0001) and without (Spearman rho 0.482, p<0.0001) MRI coronal view.

Conclusions

Parietal cortical atrophy showed the highest correlation between CT and MRI. MTA measured on MRI with and without coronal view had equal level of correlation with CT.

Background and Aims

There are limited data on HR-MRI in Stroke care in Vietnam. Using high-resolution magnetic resonance imaging (HR-MRI), our aim was to investigate the vessel wall characteristics of intracranial artery stenosis in ischemic stroke patients.

Methods

This is a retrospective observational study including 38 patients with diagnosis of ischemic stroke associated with intracranial stenosis referred to the Neurology Department of Hochiminh City University Medical Center- Vietnam from January 2020 to July 2020.

Results

Eccentric stenosis was observed in 32 (84.2%) patients and concentric stenosis in 6 (15.8%) patients. Eccentric stenosis was more frequently reported in the patients > 45 years old and concentric stenosis was more common in the patients ≤ 45 years old (P=0.008).All concentric stenosis (6/6, 100%) had enhanced images on HR-MRI, as compared with eccentric stenosis(24/32, 75%; P=0.309). Mean degree of stenosis was 48.7± 21.7%. Mean remodeling ratio was 0.88±0.26. Constrictive artery remodeling was observed in 23 patients (62.2%), expansive artery remodeling in 9 (24.3%).In 7 patients with intracranial artery dissection, 3 patients had positive dissection findings such as string sign and double lumen on MRA; theremainderwere diagnosed dissection based on HR-MRI fndings of double lumen and hemorrhage in false lumen.

Conclusions

Eccentric stenosis was observed more frequently in our study suggesting that atherosclerosis is the important cause of intracranial stenosis. Concentric stenosis was more common in young patients suggesting of non-atherosclerosis disease as an important etiology in youth stroke. HR-MRI can help find thevessel wall characteristics of intracranial artery dissection such as double lumen and intimal flap.

Background and Aims

To assess diffusion abnormalities of the optic nerve in giant cell arteritis (GCA) patients with acute onset of vision loss using standard diffusion-weighted magnetic resonance imaging (DWI).

Methods

DWI scans of GCA patients with acute loss of vision were evaluated within the scope of a retrospective case-control study. Two blinded neuroradiologists assessed randomized DWI scans of GCA and control patients (cerebral stroke or transient ischemic attack) for the presence and localization of optic nerve (ON) restricted diffusion. Statistical quality criteria, as well as inter-rater reliability were calculated. DWI findings in GCA patients were compared to corresponding ophthalmologic diagnoses.

Results

Results: 35 GCA patients (76.2 ± 6.4 years; 37 scans) and 35 controls (75.7±7.6 years; 38 scans) were included. ON restricted diffusion was detected in 81.1% (Reader 1) of GCA scans, respectively. Localization of ON restricted diffusion was at the level of the optic nerve head in 80.6%, intraorbital in 11.1% and affecting both segments in 3 eyes 8.3%. DWI discerned affected from unaffected optic nerves with a sensitivity, specificity, positive and negative predictive value of 87%/99%/96%/96%. Interrater reliability for ON restricted diffusion was “substantial” with κ_inter = 0.72 (95% CI 0.59‑0.86). DWI findings challenged ophthalmologic diagnoses in 4 cases (11.4%).

Conclusions

Standard DWI is capable of visualizing anterior and posterior ON ischemia in GCA patients with high sensitivity and specificity, as well as substantial inter-rater reliability. DWI may complement ophthalmologic examination in patients with acute loss of vision.

Background and Aims

Stroke consists of the loss of brain functions resulting from the interruption of cerebral blood flow (CBF) to a region of the brain, and represents the second cause of death and the leading cause of major disability in adults in the world. Mechanical thrombectomy (MT) has gained full acceptance: Class A, Level 1 in 2015 after the publication of numerous trials. It signalled the ushering in of a new era. Along with the treatment development, it became necessary to develop novel diagnostic technique.

Methods

Magnetic Resonance Imaging (MRI) is one of the most powerful tools that scientist and clinicians have for the study of the onset, progression of the disease, as well as for the monitoring of the success of available treatments, or for the development of novel therapeutic strategies. Chemical exchange saturation transfer (CEST) MRI has emerged as a novel means for sensitive detection of dilute labile protons and chemical exchange rates. CEST MRI has shown promising results in monitoring tissue statuses such as pH changes in disorders like acute cerebrovascular syndrome, brain tumor, and seizure by sensitizing to pH-dependent chemical exchange.

Results

We investigated tissue perfusion (CBF), pH (CEST), diffusion (diffusion weighted imaging: DWI), and kurtosis (diffusion kurtosis imaging: DKI) from regions of the contralateral normal area, each sequence’s positive lesion and their mismatch in an animal model of acute stroke.

Conclusions

In this conference briefly reviews the basic principles for CEST imaging, quantitative measures, and possibility of various clinical applications.