Age-related White Matter Changes Score Research Articles

Cerebral small-vessel disease at high altitude: A comparison of patients from plateau and plain.

Cerebral small-vessel disease (CSVD) is prevalent worldwide and one of the major causes of stroke and dementia. For patients with CSVD at high altitude, a special environmental status, limited information is known about their clinical phenotype and specific neuroimaging change. We investigated the clinical and neuroimaging features of patients residing at high altitude by comparing with those in the plain, trying to explore the impact of high altitude environment on CSVD. Two cohorts of CSVD patients from the Tibet Autonomous Region and Beijing were recruited retrospectively. In addition to the collection of clinical diagnoses, demographic information and traditional vascular risk factors, the presence, location, and severity of lacunes and white matter hyperintensities were assessed by manual counting and using age-related white matter changes (ARWMC) rating scale. Differences between the two groups and influence of long-term residing in the plateau were analyzed. A total of 169 patients in Tibet (high altitude) and 310 patients in Beijing (low altitude) were enrolled. Fewer patients in high altitude group were found with acute cerebrovascular events and concomitant traditional vascular risk factors. The median (quartiles) ARWMC score was 10 (4, 15) in high altitude group and 6 (3, 12) in low altitude group. Less lacunes were detected in high altitude group [0 (0, 4)] than in low altitude group [2 (0, 5)]. In both groups, most lesions located in the subcortical (especially frontal) and basal ganglia regions. Logistic regressions showed that age, hypertension, family history of stroke, and plateau resident were independently associated with severe white matter hyperintensities, while plateau resident was negatively correlated with lacunes. Patients of CSVD residing at high altitude showed more severe WMH but less acute cerebrovascular events and lacunes in neuroimaging, comparing to patients residing at low altitude. Our findings suggest potential biphasic effect of high altitude on the occurrence and progression of CSVD.

Diffusion tensor imaging (DTI) studies of cerebral white matter integrity in normal to moderate cardiovascular risk patients

Background & Objectives: The cerebral small vessel disease (CSVD) manifest as white matter lesion (WML) in magnetic resonance imaging (MRI). The diffusion tensor imaging (DTI) study shows a lower white matter integrity in white matter lesion (WML) and its penumbra region, suggesting cerebral white matter damage. The aim of this study is to establish correlation between the DTI values of white matter with the age related white matter changes (ARWMC) visual rating score and identify predictors of ARWMC score. Methods: 63 brain MRI images of subjects were selected. Relevant clinical information of the subjects which satisfied QRISK2 risk factors were retrieved from the patients’ folder. DTI parameters were obtained via postprocessing at OsiriX DTImap workstation. Results: FA frontal (r = -0.36; p = 0.003) and AD frontal (r = -0.26; p = 0.040) had a substantial and negative correlation with the ARWMC score. There was a significant positive correlation shown between the ARWMC score and RD frontal (r = 0.30; p = 0.018). There were positive significant association between the ARWMC score and age (b(95%CI): 0.106 (0.061, 0.151); p<0.001) and QRISK2 score (b(95%CI): 0.235 (0.036, 0.433)). Conclusion: DTI is a good method to study the cerebral white matter integrity. It was found that frontal lobe is the first region affected in relation to ageing, in particular the myelin integrity. Increasing age and higher QRISK2 cardiovascular risk factors were shown to increase the ARWMC score.

White matter hyperintensities are an independent predictor of cognitive decline 3 years following first-ever stroke—results from the PROSCIS-B study

BackgroundWhite matter hyperintensities (WMH) are the result of cerebral small vessel disease and may increase the risk of cognitive impairment (CI), recurrent stroke, and depression. We aimed to explore the association between selected cerebrovascular risk factors (CVRF) and WMH load as well as the effect of increased WMH burden on recurrent vascular events, CI, and depression in first-ever ischemic stroke patients.Methods431 from the PROSpective Cohort with Incident Stroke (PROSCIS) were included; Age-Related White Matter Changes (ARWMC) score was used to assess WMH burden on FLAIR. The presence of CVRF (defined via blood pressure, body-mass-index, and serological markers of kidney dysfunction, diabetes mellitus, and hyperlipoproteinemia) was categorized into normal, borderline, and pathological profiles based on commonly used clinical definitions. The primary outcomes included recurrent vascular events (combined endpoint of recurrent stroke, myocardial infarction and/or death), CI 3 years post-stroke, and depression 1-year post-stroke.ResultsThere was no clear association between CVRF profiles and WMH burden. High WMH lesion load (ARWMC score ≥ 10) was found to be associated with CI (adjusted OR 1.05 [95% CI 1.00–1.11]; p < 0.02) in a mixed-model analysis. Kaplan–Meier survival analysis showed a visible increase in the risk of recurrent vascular events following stroke; however, after adjustment, the risk was non-significant (HR 1.5 [95% CI 0.76–3]; p = 0.18). WMH burden was not associated with depression 1-year post stroke (adjusted OR 0.72 [95% CI 0.31–1.64]; p = 0.44).ConclusionHigher WMH burden was associated with a significant decline in cognition 3 years post-stroke in this cohort of first-ever stroke patients.

Independent role of circle of Willis for peri-procedural evaluation of carotid endarterectomy in patients with severe carotid stenosis

ObjectivesIn patients with severe carotid stenosis (CS), collateral circulation via circle of Willis (CoW) is considered a compensatory response to maintain blood flow. The aim of this study was to evaluate the impact of CoW in patients with severe CS throughout carotid endarterectomy (CEA). MethodsA database of patients (n = 124) undergoing CEA was sampled from 2013 to 2020. Severe CS was defined as 90–99% caliber stenosis and collateral circulation was identified by CoW opening. Baseline characteristics, Age-related white matter change (ARWMC) score, immediate neurologic events (INEs) and manifestations were recorded and compared. Correlation and regression analysis for CoW were further investigated. ResultsAll patients enrolled were divided into two groups regarding to the visualized CoW opening and complete CoW was noticed in 57 patients. The prevalence of complete CoW was higher among asymptomatic patients (n = 39, 68.4%), while higher percentage of TIA or previous stroke were noticed in incomplete CoW (n = 45, 67.2%). Patients with incomplete CoW had a significantly higher median ARWMC score and remarkable cerebral perfusion deficit (P < 0.05*). Totally, 4 INEs (6.0%) were noted in patients with incomplete CoW after CEA. Cerebral hyperperfusion syndrome (CHS) was noticed in 10 patients and early-phase of postoperative hypertension (EPOH) in 15 ones with incomplete CoW versus patients with complete CoW (14.9% and 22.4% vs 3.5% and 7.0%, P < 0.05). Correlation analysis showed strong relationship between CoW opening and peri-operative factors like pre-operative symptoms, ARWMC, CHS and EPOH (P < 0.05*). Overall, CoW opening was an independent predictor of both CHS and EPOH (95% CI, 0.021–0.715 and 0.060–0.949, P < 0.05*) with logistic regression. ConclusionsSufficient collateral circulation via CoW may promote ipsilateral cerebral perfusion and mitigate WMC in patients with severe CS. In addition, collaterals may improve the predictive power of the risk scale for post-procedural complications after CEA.

Abstract P329: White Matter Score Does Not Predict Post-tPA Hemorrhage in Elderly Patients Evaluated Acutely via Telestroke

Background: While tPA may be safe in the elderly, increasing age appears to augment risk of post-tPA symptomatic intracranial hemorrhage (sICH). Age-related white matter changes (ARWMC) are associated with increased sICH. Patients evaluated for acute ischemic stroke (AIS) via telestroke (TS) may not have access to MRI to allow incorporation of microbleeds in tPA decisions. We assessed if increased CT-based ARWMC was associated with increased sICH in elderly patients. Methods: Patients 80 years and older who received tPA for AIS at spoke hospitals were selected from our TS network registry from 9/2015 to 12/2018. TS spoke CT scans from patient presentation were reviewed by three of the authors for periventricular white matter (PWMC) and deep white matter (DWMC) changes. Total ARWMC score, based on the Fazekas score, was collected. Total ARWMC score was either mild (0-2), moderate (3-4), or severe (5-6). PWMC and DWMC were either mild (0-1) or moderate-severe (2-3). Logistic regression adjusted for age, sex, race, ethnicity, NIHSS and premorbid mRS was used to analyze relationship of ARWMC scores with sICH and patient-outcomes. Results: Of 241 patients, median age overall was 86 years (IQR 83-90), and 66% were female. The overall median ARWMC score was 3 (IQR 2-5). Regression analysis showed that more severe ARWMC scores did not lead to higher frequency of post-tPA ICH (moderate OR 0.57, CI 0.19-1.71; severe OR 1.32, CI 0.48-3.65) including sICH (moderate OR 0.78, CI 0.21-2.94; severe OR 2.09, CI 0.62-7.02). Similarly, severe PWMC and DWMC were not associated with increased risk of post-tPA ICH (PWMC OR 1.31, CI 0.51-3.38; DWMC OR 1.25, CI 0.52-3.01), including sICH (PWMC OR 1.61, CI 0.51-5.08; DWMC OR 1.81, CI 0.65-5.01). In our cohort, older patients had no difference in hemorrhage (ICH OR 0.93 CI 0.85-1.00: sICH OR 0.95 CI 0.86-1.04), and patients with less severe stroke were more likely to have hemorrhage (ICH OR 1.06 CI 1.02-1.10; sICH OR 1.08 CI 1.03-1.13). IRR among the CT scan readers was moderate (k=0.504). Conclusions: ARWMC scores were not associated with post-tPA ICH in the elderly. Our analysis lends support for the use of tPA despite severity of white matter disease. ARWMC should not be used to assist in tPA decision-making in elderly patients via telestroke.

Abstract P431: White-Matter Disease Burden and Cerebral Microbleeds After Extracorporeal Membrane Oxygenation Support

Introduction: Cerebral microbleeds (CMBs) have been increasingly reported in patients receiving extracorporeal membrane oxygenation (ECMO) support. Both, CMBs and cerebral white-matter disease (WMD) are thought to be a result of microvascular lipo-hyalinosis; as commonly seen in an aging brain. The pathogenesis of microbleeds after ECMO, has not yet been definitively established. We sought to examine the relationship between cerebral WMD burden and microbleeds after ECMO-support at a single tertiary referral academic hospital with high volumes of ECMO patients. Methods: All patients receiving venovenous (vv) and venoarterial (va) ECMO between January 2013 to January 2018 were retrospectively examined. The distribution of white matter hyperintensities was quantified using the Walhund age-related white matter changes (ARWMC) scale and correlated with the presence of cerebral microbleeds on brain MRI studies with Susceptibility Weighted Imaging (SWI) performed shortly after cessation of ECMO. Results: A total of 307 ECMO patients were reviewed, among whom 44 patients (vv:va= 13:31; male:female= 29:15) received at-least one MRI-brain study with SWI sequences after ECMO decannulation. The median duration of ECMO support was 4 days (range 1-25 days), with median duration from decannulation-to-MRI being 11.5 days (range 3-724 days). Microbleeds were present in 77.3% (n=34) patients, with 38.2% (n=13), 14.7% (n=5), and 47.1% (n=16) having mild (&lt;10), moderate (10-30) and severe (&gt;30) CMBs respectively. The median Walhund ARWMC score was 1 (range 0-22). Age and sex adjusted Walhund scores were not found predictive of CMB presence (p=0.578 [0.90-1.19]). Of 44 patients with at-least one post-ECMO MRI, 10 patients had a follow-up MRI scan at a median duration of 4 months (range 0.22-55 months); all of whom had unchanged CMB burden. At 10-month median clinical follow-up (range 0-76 months), none of the 34 patients with CMBs on initial MRI-study had presented with an intracranial hemorrhage. Conclusion: Development of CMBs after ECMO support is independent of microvascular lipo-hyalinosis, as estimated from cerebral white-matter disease burden. This requires further study in a larger sample-size.

Silent cerebral embolisation during TAVI: evolution, predictors and neurocognitive effects

Abstract Background Most patients undergoing transcatheter aortic valve implantation (TAVI) develop silent cerebral ischemic lesions (SCIL) detectable at magnetic resonance imaging (MRI). The natural history and clinical relevance of SCIL are not well established. We aimed to assess the characteristics, predictors, evolution, and neurocognitive effects of SCIL. Methods Cerebral MRI was performed within 7 days before TAVI to assess baseline status and age-related white matter changes (ARWMC) score. MRI was repeated postoperatively to assess the occurrence, location, number and dimensions of SCIL. Patients developing SCIL underwent a third MRI at 3–5 months follow-up. A neurocognitive evaluation was performed before TAVI, at discharge and at 3-month follow-up. Results Of the 117 patients enrolled, 96 underwent a postprocedural MRI; SCIL were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, median diameter 4.5 mm, and median total volume 140 mm3. Independent predictors of SCIL occurrence were a higher baseline ARWMC score and the use of self-expanding or mechanically-expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of postprocedural SCIL evolved into a gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVI and with a lower recovery at follow-up. Conclusions SCIL occur in the vast majority of patients undergoing TAVR and are predicted by a more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCIL disappear within months, their occurrence has a limited but significant impact on neurocognitive function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): unrestricted grants from Edwards Lifesciences SA, Nyon, Switzerland, and from Medtronic Italia SpA, Milan, Italy

Evolution, Predictors, and Neurocognitive Effects of Silent Cerebral Embolism During Transcatheter Aortic Valve Replacement

ObjectivesThe aim of this study was to assess the characteristics, predictors, evolution, and neurocognitive effects of silent cerebral ischemic lesions (SCILs). BackgroundMost patients undergoing transcatheter aortic valve replacement (TAVR) develop SCILs detectable on magnetic resonance imaging (MRI). The natural history and clinical relevance of SCILs are not well established. MethodsCerebral MRI was performed within 7 days before TAVR to assess baseline status and age-related white matter change score. MRI was repeated post-operatively to assess the occurrence, location, number, and dimensions of SCILs. Patients developing SCILs underwent a third MRI examination at 3- to 5-month follow-up. A neurocognitive evaluation was performed before TAVR, at discharge, and at 3-month follow-up. ResultsOf the 117 patients enrolled, 96 underwent post-procedural MRI; SCILs were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, a median diameter of 4.5 mm, and a median total volume of 140 mm3. Independent predictors of SCIL occurrence were higher baseline age-related white matter change score and the use of self-expanding or mechanically expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of post-procedural SCILs evolved into gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVR and with lower recovery at follow-up. ConclusionsSCILs occur in the vast majority of patients undergoing TAVR and are predicted by more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCILs disappear within months, their occurrence has a limited but significant impact on neurocognitive function.

Risk factors of white matter hyperintensities in South Asian patients with transient ischemic attack and minor stroke.

Aging and increased burden of cardiovascular risk factors are associated with severity of white matter hyperintensity (WMH). We assessed the burden and risk factor profile of WMHs in South Asian patients with transient ischemic attack (TIA) and minor stroke. Patients with acute ischemic stroke with the National Institute of Health stroke scale (NIHSS) score ≤ 5 who underwent MRI were included. The severity of WMHs was assessed based on age-related white matter change (ARWMC) scale (0-30). A score of > 8 or more was considered moderate-severe involvement. Logistic regression analysis was performed to assess the association with risk factors. A total of 424 patients with a mean ± SD age of 57.4 ± 14.5years [females, 108 (25.5%)] were analyzed. Fifty-four (12.7%) patients had moderate or severe WMHs (ARWMC score > 8). Age (OR 1.03, 95% CI 1.01-1.06; p = 0.004), hypertension (OR 2.3, 95% CI 1.1-5.1; p = 0.03) and smoking tobacco (OR 2.8, 95% CI 1.4-5.6; p = 0.003) were independently associated with ARWMC score > 8. The median (IQR) regional score in patients with ARWMC score > 8 was maximum in frontal areas 4 (4-6, p < 0.0001) and parietooccipital areas 4.5(4-6, p < 0.0001). The presence of microbleeds (OR 6.3, 95% CI 3.1-12.7; p < 0.0001) was independently associated with ARWMC score > 8. South Asian patients with TIA and minor stroke are relatively young, and few patients have moderate and severe WMHs. Hypertension and tobacco smoking increases the risk of WMH. Targeting modifiable risk factors may reduce the burden of WMHs and vascular dementia.

Abstract TP217: Association Between Thrombophilia and Chronic Cerebrovascular Disease in Young Adults With Acute Ischemic Stroke

Introduction: Thrombophilias are a known cause of acute ischemic stroke (AIS) in the young. We hypothesized that thrombophilias would be associated with an increased burden of chronic cerebrovascular disease in these patients. Methods: We included patients enrolled in the prospective Cornell AcutE Stroke Academic Registry (CAESAR) who were 18-65 years of age, diagnosed with AIS by brain MRI between 2011-2015, and had thrombophilia testing within 6 months of their stroke. The exposure variable was thrombophilia, defined as at least one positive thrombophilia test according to standard criteria. The primary outcome was the total Age-Related White Matter Changes (ARWMC) score (0-15). Secondary outcomes were the Fazekas score (0-3) and the number of chronic small vessel (subcortical) cerebral infarcts. Outcomes were determined by a single radiologist blinded to thrombophilia status using clinically-performed brain MRIs at the time of index stroke. Doubly robust estimator analyses were used to test the association between an underlying thrombophilia and outcomes. Models were adjusted for age, gender, race, and vascular risk factors. Results: Among 177 patients meeting eligibility criteria, mean age was 47 (SD, 10) years and 50% were women. Thrombophilia was detected in 77 patients (44%). The mean total ARWMC score, Fazekas score, and number of chronic small vessel infarcts were 1.90 (SD, 1.74), 0.91 (SD, 0.69), and 0.16 (SD, 0.63) in patients with thrombophilia and 2.16 (SD, 1.64), 1.07 (SD, 0.69) and 0.35 (SD, 0.81) in patients without thrombophilia. In multivariable analyses, there was no difference in the total ARWMC score (mean difference -0.05, 95% CI -0.43 to 0.33, p=0.80) or Fazekas score (mean difference -0.05, 95% CI -0.21 to 0.11, p=0.52) between patients with thrombophilia and those without. However, in multivariable analyses, the number of chronic infarcts (mean difference -0.22, 95% CI -0.42 to -0.01, p=0.01) was lower in patients with thrombophilia than in those without. Conclusions: In a single-center study of young adults with AIS, underlying thrombophilia was not associated with white matter disease burden. However, contrary to our hypothesis, it was inversely associated with the number of chronic small vessel infarcts.

White Matter Hyperintensity Predicts the Risk of Incident Cognitive Decline in Community Dwelling Elderly.

Unlike western countries, data on white matter hyperintensity (WMH) in community dwelling elderly in Asian population is very limited. To examine the relation between baseline WMH burden and the risk of incident cognitive decline in a community-based cohort with Chinese-dwelling elderly. We prospectively evaluated the incident cognitive decline for 226 participants in the Shanghai Aging Study. Baseline WMH severity was visually rated by the age-related white matter changes (ARWMC) scale based on MRI. Cox proportional hazards regression model was used to estimate the relative risk (RR) of total ARWMC scale, global ARWMC score, presence of lacune and microbleed, for incident cognitive decline by adjusting potential confounders. Forty subjects were identified with incident cognitive decline (new onset 34 mild cognitive impairment and 6 dementia) during a median duration of 6 years follow-up. The incidence of cognitive decline was 3.0 (95% confidence interval [CI] 2.2-4.1) per 100 person-years. Increasing total ARWMC scale [RR1.21 (95% CI 1.06-1.39), p = 0.004)], confluent WMH [RR3.16 (95% CI 1.50-6.64), p = 0.002), and presence of lacunes [RR 2.73 (95% CI 1.21-6.15)] at baseline were independent predictors of incident cognitive decline. Our study demonstrated that confluent WMH may increase the risk of incident cognitive decline by 3 folds in community dwelling subjects. Small vessel disease may cause heavy burden of cognitive impairment in the elderly in China.

Effect of white matter changes on risk score for peri-procedural complications after carotid artery stenting

ObjectivesThe presence of more severe white matter changes (WMC) may be associated with a higher risk of peri-procedural strokes in patients undergoing carotid artery stenting (CAS). However, to what extent WMC affects peri-procedural risk of CAS is unclear. We aimed to evaluate the effect of WMC on peri-procedural complications by modifying a CAS peri-procedural risk scale through adding the assessment of WMC. Patients and methodsA database of patients undergoing CAS was sampled from 2007 to 2014 in a single Chinese medical center. Risk factors were evaluated for peri-interventional cerebral and cardiac events and mortality. A risk score including contralateral stenosis ≥ 50%, diabetes with HbA1c > 7%, age ≥ 80 years old, symptomatic stenosis or with an ulcer lesion was applied to predict peri-interventional risk. Age-related white matter change (ARWMC) score was calculated and added to this risk scale. The predictive power of the new scale was evaluated. Results151 patients were enrolled in the study. 14 peri-interventional events were recorded. Patients with peri-procedural complications had higher rates of diabetes (57.1% vs 18.2%, P = 0.001), contralateral stenosis (64.29% vs 32.85%, P = 0.019), coronary heart disease (42.9% vs 14.6%, P = 0.008) and ARWMC ≥ 7 (64.3% vs 25.5%, P = 0.002) compared with patients without peri-procedural complications. ARWMC ≥ 7 was an independent risk factor for peri-procedural complications from factors of the CAS scale after adjusting other confounders including contralateral stenosis ≥ 50%, HbA1c > 7%, age ≥ 80 years old and symptomatic stenosis or with an ulcer lesion. After the ARWMC score was added to the original scale, the AUC value of the new scale to predict the risk of peri-procedural complications after CAS was elevated (0.808 vs 0.730, p = 0.068). ConclusionMore severe WMC was a risk factor for peri-procedural complications after CAS in patients with carotid artery stenosis. ARWMC score may help to improve the predictive power of the risk scale for peri-procedural complications after CAS.

Periodic Limb Movements and White Matter Hyperintensities in First-Ever Minor Stroke or High-Risk Transient Ischemic Attack.

Emerging evidence suggests that periodic limb movements (PLMs) may contribute to the development of cerebrovascular disease. White matter hyperintensities (WMHs), a widely accepted biomarker for cerebral small vessel disease, are associated with incident stroke and death. We evaluated the association between increased PLM indices and WMH burden in patients presenting with stroke or transient ischemic attack (TIA), while controlling for vascular risk factors and stroke severity. Thirty patients presenting within 2 weeks of a first-ever minor stroke or high-risk TIA were prospectively recruited. PLM severity was measured with polysomnography. WMH burden was quantified using the Age Related White Matter Changes (ARWMC) scale based on neuroimaging. Partial Spearman's rank-order correlations and multiple linear regression models tested the association between WMH burden and PLM severity. Greater WMH burden was correlated with elevated PLM index and stroke volume. Partial Spearman's rank-order correlations demonstrated that the relationship between WMH burden and PLM index persisted despite controlling for vascular risk factors. Multivariate linear regression models revealed that PLM index was a significant predictor of an elevated ARWMC score while controlling for age, stroke volume, stroke severity, hypertension, and apnea-hypopnea index. The quantity of PLMs was associated with WMH burden in patients with first-ever minor stroke or TIA. PLMs may be a risk factor for or marker of WMH burden, even after considering vascular risk factors and stroke severity. These results invite further investigation of PLMs as a potentially useful target to reduce WMH and stroke burden.

Brain MRI Findings and Neuro-Psychiatric Involvement in Paroxysmal Nocturnal Hemoglobinuria (PNH)

▪PNH is a rare disorder characterized by hemolytic anemia, marrow failure and thrombosis, due to a deficiency in GPI-anchored proteins. Thrombotic events in PNH are commonly described in hepatic, portal, mesenteric, splenic, and renal veins, along with anecdotic case reports of cerebral venous sinus thrombosis and arterial ischemic strokes.This study was aimed at investigate brain involvement in 19 asymptomatic PNH patients by non-enhanced cerebral magnetic resonance imaging (MRI), and by intracranial arterial and venous angio-MRI. Neuroradiological findings were completed with a neuro-psychiatric evaluation, and correlated with clinical/hematologic features and therapy.Seventeen out of 19 patients were classical hemolytic (63% transfusion dependent before treatment with eculizumab and 1 patient also after), and 2 PNH in the context of aplastic anemia (all transfusion-dependent until treatment with ATG-CyA). Median age at diagnosis was 44 years (range 17-80); asthenia and dyspnea on exertion were present in all patients, abdominal pain in 8, and a thrombotic event in 4. Median Hb was 9.6 g/dL (range 6.7-12.9), LDH 3.7-fold (range 1.2-16.3) over upper limit of normal (ULN), and 73% of patients displayed a clone size greater than 50% GPI negative cells; 10/19 of patients were on eculizumab at the moment of the study.On MRI, 11 subjects showed pathological findings: 9 cases displayed white matter (WM) abnormalities related to chronic ischemic small vessel disease, of whom 6 periventricular WM vascular degeneration, and 8 deep WM focal chronic ischemic lesions (5 cases have both sites involved). Moreover, 1 subject showed a focal abnormality >5 mm and 5 subjects a score > 4 as evaluated in WM and basal ganglia by the age related white matter changes (ARWMC) scale. No subject displayed active or previous bleeding, nor were focal alterations of the basal nuclei by the ARWMC scale found. Two patients (80 and 81 yrs) showed atrophy of the cerebral hemispheres. Regarding vascular abnormalities, one subject had hypoplastic left transverse sinus with irregularities in the sinus wall, suspected for prior partial venous thrombosis. Three further cases displayed hypoplastic transverse sinus associated with collateral draining cortical veins, indistinguishable from anatomical variants. Intracranial artery stenosis or aneurysm, and Moya-Moya like alterations were not observed. Finally, cerebral MRI was unremarkable in 8/19 subjects.By comparing patients with or without any MRI abnormality (WM and vascular alterations), mean age was significantly higher in the former (60+17 vs 43+8 yrs, mean+SD, p<0.05), whereas blood counts, hemolytic markers and clone size showed no remarkable differences. Hemoglobin at diagnosis was slightly lower (9.5+1.5 vs 9.9+1.6 g/dL, mean+SD), and LDH greater (5.8+4.4 vs 4.1+2.9 over ULN, mean+SD) in subjects who displayed MRI abnormalities. Moreover, individual hemoglobin levels negatively correlated with the ARWMC score (r=-0.45, p<0.05). No relationship was found between history of abdominal pain/thrombosis and MRI pathological findings. Likewise, MRI abnormalities were not correlated with disease duration. As regards therapy with eculizumab, a pathological MRI was found in 6/10 subjects under treatment and in 5/9 without; the sole significant vascular alteration was detected in a patient under treatment.Neurological examination was unremarkable in all patients but one, who complained of progressive rest tremor in his left arm and leg (twelve years after PNH diagnosis), and was diagnosed with possible Parkinson disease. Previous history of neurological disorders was observed in 3 patients: one typical transient global amnesia (at the age of 60), one seizures (at 5 years), and one headache before the diagnosis of PNH. Regarding psychiatric evaluation, 3/18 patients had a psychiatric disorder according to structured clinical interview for axis I DSM-IV-TR disorders (1 generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder as a consequence of PNH diagnosis). No relationship was observed between MRI findings and neuro-psychiatric assessment.In conclusion, brain MRI revealed chronic ischemic and vascular lesions in 58% of asymptomatic PNH patients. Brain MRI is advisable at diagnosis and during the course of the disease, and WM lesion burden may be useful in the decision to start therapy. DisclosuresBarcellini:Agios: Consultancy.

Striatal silent lacunar infarction is associated with changes to the substantia nigra in patients with early-stage Parkinson’s disease: A diffusion kurtosis imaging study

A recent study has shown that striatal silent infarction may occur secondary to the degeneration of dopaminergic neurons in the substantia nigra (SN) of mice. However, it is uncertain whether this phenomenon occurs in patients with early-stage Parkinson’s disease (PD) and can be detected by diffusion kurtosis imaging (DKI). A total of 72 untreated patients with early-stage PD underwent conventional MRI and DKI. Participants were divided into control and striatal silent lacunar infarction (SSLI) groups. The differences in mean kurtosis (MK) values of the SN, Hoehn–Yahr (H–Y) staging, and Unified Parkinson’s Disease Rating Scale (UPDRS) III score between groups, were analyzed. Linear regression analysis was used to correlate age, SSLI count, silent lacunar infarction count in other brain areas and age-related white matter change score with MK values of the SN. Spearman correlation coefficient analysis was used to correlate MK values of the SN and SSLI count with H–Y staging and UPDRS III score. There was no significant difference in the severity of disease between two groups; however, MK values of the SN with SSLI present were significantly higher than in SN without SSLI. In addition, SSLI count had linear correlation with MK values of the SN, which had positive correlation with H–Y-staging and UPDRS III score. SSLI is associated with structural changes to the SN in patients with early-stage PD, detectable by DKI, and may aggravate their motor impairments.

White Matter Hyperintensities on Brain Magnetic Resonance Imaging in People with Epilepsy: A Hospital-Based Study.

We aim to explore whether people with epilepsy have increased white matter hyperintensities (WMHs). Eligible patients were categorized into newly diagnosed epilepsy (NE) and chronic epilepsy (CE); the latter were subdivided to those treated with enzyme-inducing antiepileptic drugs (EIAEDs) with or without non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those with NEIAEDs only. WMHs were measured using age-related white matter changes (ARWMC) scale and compared between patients and healthy control group. Higher scores indicate greater WMH changes. The strengths of associations were estimated as incidence rate ratios (IRRs) with 95% confidence interval (CI). A total of 217 patients were included in the analysis, of whom 67 had NE, 45 had CE treated with NEIAEDs, and 105 had CE treated with EIAEDs. Age was positively associated with ARWMC score (IRR per year, 1.03; 95%CI, 1.03-1.04, P < 0.001). Compared with the healthy control group (n = 23), all patient groups had higher ARWMC score (P < 0.05). The difference was greatest in patients receiving EIAEDs (IRR, 2.13; 95%CI, 1.22-3.70, P = 0.007). WMHs tended to be observed in people with epilepsy, especially in those treated with EIAEDs. People with epilepsy with white matter changes should be evaluated for stroke risk, particularly if they are receiving EIAEDs.

The effect of hyperbaric oxygen therapy on delayed encephalopathy after carbon monoxide poisoning

Objective To investigate effect of hyperbaric oxygen therapy (HBOT) on delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods This was a prospective random study of 60 patients with DEACMP admitted to Beijing Tiantan Hospital. Among them, 32 constituted the HBOT group and 28 were controls. All of the patients in both groups were given drugs to improve microcirculation and rehabilitation treatment. Additionally, the patients in the HBOT group were given hyperbaric oxygen therapy. The Mini-Mental State Examination (MMSE), the Barthel index and an index of age-related white matter changes (ARWMC) were used assess the patients' cognition, motor function and cerebral white matter lesions on the day of enrollment and on the 35th and 70th day after treatment. Results Before treatment there was no significant difference in average MMSE, Barthel index or ARWMC scores between the groups. In the HBOT group the average MMSE and Barthel index scores on the 35th and 70th day after enrollment were significantly higher than on the day of enrollment and the average ARWMC score on the 70th day was significantly lower than at enrollment. On the 35th day the average MMSE and Barthel index scores of the HBOT group were significantly higher than those of the control group, but there was no significant difference in the groups' average ARWMC scores. On the 70th day after enrollment the HBOT group's average MMSE and Barthel index scores were still significantly higher than those of the control group, but its average ARWMC score was significantly lower. Conclusion HBOT can help improve cognitive and motor function and also alleviate cerebral white matter lesions of DEACMP patients. Key words: Hyperbaric oxygen therapy; Encephalopathy; Carbon monoxide poisoning

Clinico-radiological predictors of vascular cognitive impairment (VCI) in patients with stroke: A prospective observational study

Background and purposeCognitive dysfunction occurs commonly following stroke and varies in severity. This study was aimed to determine the clinical, neuro-imaging, laboratory predictors of post stroke cognitive impairment and factors related to poor functional outcome in patients with post-stroke vascular cognitive impairment (VCI). Material and methodsWe prospectively evaluated 102 of 240 consecutive stroke patients for 6months after incident stroke for development of VCI. Patients with VCI comprised of those with VCI-no dementia (VCIND) and vascular dementia (VaD). Functional outcome was assessed by modified Barthel index (MBI). ResultsFrequency of post-stroke VCI was 45.1% (46/102): 26.5% (27/102) having VCI-ND and 18.6% (19/102) having VaD. Patients with VCI were more likely to have lower educational and socioeconomic status, diabetes, hypertension, prior stroke, multiple risk factors, urinary incontinence, gait abnormality, peripheral signs of atherosclerosis, higher blood sugar level on admission and LDL levels, strategic site lesion, higher ARWMC (age related white matter changes) score, worse stroke severity (NIHSS) and functional outcome scores. On logistic regression analysis, lower educational status, strategic site lesion, higher ARWMC score and baseline stroke severity score were found to independently predict the risk of developing VCI. Worse stroke severity (NIHSS) scores and functional status scores at baseline predicted poor outcome in patients with VCI. ConclusionPost-stroke cognitive impairment is frequent and is associated with poor functional outcome. Predictors like lower educational status, strategic site lesion, greater severity of age related white matter changes and baseline stroke severity independently contributed to the risk of developing VCI in stroke patients.

Abstract W P100: Alterations of γδT Cell Subsets in Stroke Patients with White Matter Disease

Background: γδT cells have been shown in experimental models to play a role in the evolution of ischemic brain injury by increasing cerebral infarct volumes and neurological deficits. We have previously reported decreased levels of γδT cells in the subacute phase of human stroke. In this study we aimed to determine the functional significance of alterations in levels of γδT cells and other T cell subsets on the extent of ischemic brain injury. Methods: Blood was drawn from ischemic stroke patients within 24 hours of recruitment and stained with CD3 (PE-TR), γδTCR (PE), CD4 (FITC) and CD8 (PE-Cy5) monoclonal antibodies. γδT cells were also divided into functional subsets - CD4+ γδT, CD8+ γδT and null γδT cells. Percentages of circulating lymphocytes were measured by a fluorescent activated cell counter. The extent of acute ischemic injury was measured using lesion volume on diffusion weighted images by Image Processing Analysis and Visualization (MIPAV), while the extent of chronic ischemic injury which is manifested as white matter changes(WMC) was assessed using the Age Related White Matter Changes (ARWMC) rating score. Independent T-tests and non-parametric tests were used for between group comparisons. Results: Of the 41 patients recruited, the mean age was 66.8±13 years and 18 (43.9%) were men. Blood was drawn at a mean time of 47 ±30 hours after symptom onset. Compared to patients with absent-mild WMC (ARWMC score of 0-1), patients with moderate-severe WMC (ARWMC of 2-3) had higher percentages of CD8+ γδT cells (6.6% vs. 12.0%, p=0.005) and CD8+ T cells (22.2% vs. 28.5% p=0.036), and lower percentages of CD4+ T cells (71.0% vs. 63.5%, p=0.048) and null γδT cells (72.7% vs. 59.6%, p=0.03). However γδT percentages did not differ significantly. The volumes of acute ischemic stroke lesions did not correlate with γδT levels or with other T cell subsets. Conclusions: Alterations of T cell subsets, most notably, CD8+ γδT and CD8+ T cells were present in stroke patients with cerebral white matter disease. Their role in the formation of cerebral small vessel disease needs to be further studied.

Gait instability measured by dual task gait test and leukoaraiosis

Objective.– Gait unsteadiness is considered as the first step of major health concerns such as fall and dementia. Gait dysfunction has to be measured under dual task gait test (DTGT). The aim of this study was to investigate the relationships between DTGT and brain magnetic resonance imaging (MRI).Material and methods.– Data were collected through a Gait Instability Network including DTGT. Twenty-five patients aged less than 76 years old were tested (age: 71 ± 5 years, F: 8, M: 17, MMSE: 28 ± 2).Methods.– The assessment includes five successive steps: auto questionnaires, nurse evaluation, clinical balance tests, cognitive tests, medical examination, and DTGT. Gait analysis was provided by a three-axis accelerometer (Locometrix), three variables were selected: walking speed (WS), stride frequency (SF) and stride regularity index (SR). The Dual Task (DT) consists in walking and backward counting one by one from fifty. MRI including cortex trophycity, hippocampal Scheltens score, and age-related white matter changes (ARWMC) was performed under blind condition.Results.– Under DT condition, each gait variable decreases significantly. WS: from1.13 ± 0.24 to 0.98 ± 0.23 m/s (P = 0.02), SF: from 0.91 ± 0.09 to 0.79 ± 0.13 Hz (P < 0.001), SR: from 211 ± 51 to 160 ± 60 dimensionless (P < 0.002). Out of 25 patients, three had a vestibular disorder, one had post-stroke effects. No clinical explanation can be found for 21 patients other than hippocampal atrophy (Scheltens score 1.4 ± 0.6), and/or leukoaraiosis (ARWMC score: 4.3 ± 4.3).Discussion.– These results illustrate the interest of measuring not only walking speed and stride regularity, but also stride frequency under DTGT, and raise the question of the role of leukoaraiosis in gait instability