Association between blood-brain barrier permeability and changes in pulse wave velocity following a recent small subcortical infarct.

Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r [95% CI], WB 0.651 [0.363-0.839]; GM 0.657 [0.373-0.845], WM 0.530[0.197-0.777]) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b[95% CI], WB 0.725[0.384-1.127], GM 0.629 [0.316-1.369], WM 0.865 [0.455-0.892]) or Δ24-h DBP (b[95% CI], WM 0.707 [0.370-1.103], GM 0.643 [0.352-1.371], WM 0.772 [0.367-0.834]). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.

Relationship of arterial stiffness and baseline vascular burden with new lacunes and microbleeds: A longitudinal cohort study.

INTRODUCTION: Arterial stiffness may have a significant impact on the development of cerebral small vessel disease (cSVD). PATIENTS AND METHODS: We obtained pulse wave velocity (24-h PWV) by means of ambulatory blood pressure monitoring (ABPM) in patients with a recent small subcortical infarct (RSSI). Patients with known cardiac or arterial embolic sources were excluded. Lacunes, microbleeds, white matter hyperintensities and enlarged perivascular spaces at baseline were assessed in a brain MRI and included in a cSVD score. A follow-up MRI was obtained 2 years later and assessed for the appearance of new lacunes or microbleeds. We constructed both unadjusted and adjusted models, and subsequently selected the optimal models based on the area under the curve (AUC) of the predicted probabilities. RESULTS: Ninety-two patients (mean age 67.04 years, 69.6% men) were evaluated and 25 had new lacunes or microbleeds during follow-up. There was a strong correlation between 24-h PWV and age (r = 0.942, p < 0.001). cSVD was associated with new lacunes or microbleeds when adjusted by age, 24-h PWV, NT-proBNP and hypercholesterolemia (OR 2.453, CI95% 1.381-4.358). The models exhibiting the highest discrimination, as indicated by their area under the curve (AUC) values, were as follows: 1 (AUC 0.854) - Age, cSVD score, 24-h PWV, Hypercholesterolemia; 2 (AUC 0.852) - cSVD score, 24-h PWV, Hypercholesterolemia; and 3 (AUC 0.843) - Age, cSVD score, Hypercholesterolemia. CONCLUSIONS: cSVD score is a stronger predictor for cSVD progression than age or hemodynamic parameters in patients with a RSSI.

NT-proBNP, cerebral small vessel disease and cardiac function in patients with a recent lacunar infarct.

NT-proBNP is produced from both atria and ventricles and it is increased in patients with cardiac disease. NT-proBNP is also associated with cerebral small vessel disease(cSVD) but there are no studies that had carried out a systematic evaluation of cardiac function in this specific setting. We conducted a prospective observational study in 100 patients within 30 days after a recent lacunar infarct by means of brain MRI, 24 h ambulatory blood pressure monitoring, transthoracic echocardiography, and plasmatic NT-proBNP. Global cSVD burden was quantified using a validated visual score (0 to 4) and dichotomized into 2 groups (0-2 or 3-4). Age (73.8 vs 63.5 years) and NT-proBNP (156 vs 76 pg/ml) were increased in patients with SVD 3-4, while daytime augmentation index normalized for the heart rate of 75 bpm (AIx75) (22.5 vs 25.6%) was decreased. The proportion of patients with left atrial enlargement, left ventricular hypertrophy, or septal e' velocity <7 cm/s was not different between both groups. NT-proBNP was increased in patients with left atrial enlargement (126 vs 88 pg/ml). In multivariate analysis, age (OR 1.129 CI 95% 1.054-1.209), daytime AIx75 (OR 0.91 CI 95% 0.84-0.987,) and NT-proBNP (OR 1.007 CI 95% 1.001-1.012,) were independently associated with cSVD score 3-4. In conclusion, as well as in other patients with cSVD we found an association between NT-proBNP and cSVD. This association was independent of cardiac function.

The role of specialist nurses in detecting spasticity and related symptoms in multiple sclerosis.

BACKGROUND: Spasticity is a frequent symptom of multiple sclerosis (MS), which may negatively influence daily living activities (ADL). OBJECTIVES: To (1) explore the feasibility to conduct a structured interview by specialist nurses about limitations in ADL; (2) determine the percentage of people with MS (PwMS) with limitations in ADL related to spasticity; (3) to assess the knowledge about spasticity and describe its clinical features. DESIGN: Observational, cross-sectional, multicentre study in 16 MS units of Catalonia (Spain). Participants were recruited from the outpatient facility and day-care hospital between July 2018 and June 2019 and met the following criteria: (1) age 18 or older, (2) diagnosis of MS according to McDonald criteria 2010 and (3) no clinical relapse in previous 30 days. METHODS: Specialist nurses conducted a structured interview divided in two parts: the assessment of (1) limitations in the ADL and (2) the presence of spasticity and associated symptoms. The usefulness of this intervention was requested. This study met the STROBE reporting guidelines checklist for observational studies. RESULTS: Three hundred sixty eight pwMS (244 women) with a mean age of 46 years and a median Expanded Disability Status Scale score of 2.5 (range, 0-8.5) were included. 262 (71%) pwMS had limitations in the ADL, and spasticity was reported as the most limiting symptom in 59 (23%). As a result of the interview, spasticity was observed in 199 (76%) participants; 47 (24%) of them were unaware that they had spasticity and 102 (51%) would not have reported it spontaneously. The level of the interview satisfaction was high (90%). CONCLUSIONS: Spasticity is a complex and limiting symptom in MS. The structured interview conducted by specialist nurses is feasible and has good acceptance. PATIENT CONTRIBUTION: Specialist nurses can be proactive in MS clinical assessment, which may help to detect symptoms with negative impact on quality of life.

Biomarkers levels and brachial and central blood pressure during the subacute phase of lacunar stroke and other ischemic stroke subtypes.

We aimed to evaluate brachial and central blood pressure (BP) estimates and biomarker levels in lacunar ischemic stroke (IS) and other IS subtypes (nonlacunar stroke). We studied 70 functionally independent subjects consecutively admitted to our institution after a first episode of IS. Subjects with previous heart failure were excluded. BP was measured at admission and during the subacute phase of stroke (5-7 days after stroke onset). Aortic pulse wave velocity (aPWV), augmentation index (AIx), and 24 h brachial and central BP (24h-ABPM) were measured by means of a Mobil-O-Graph device during the subacute phase of stroke. Determination of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), urinary albumin excretion, and echocardiography were performed in all subjects. After adjusting for age and clinical severity, lacunar IS had significantly higher levels of BP at admission (systolic BP 173 ± 37 vs 153 ± 28 mmHg, p = 0.006; diastolic BP: 97 ± 21 vs 86 ± 16 mmHg, p = 0.035) and during the subacute phase of stroke (systolic BP 152 ± 23 vs 134 ± 19 mmHg, p = 0.001; diastolic BP: 84 ± 14 and 77 ± 10 mmHg, respectively; p = 0.038) but lower NT-proBNP levels (median: 36,277 vs 274 pg/mL, p = 0.009) than nonlacunar IS. Central BP, aPWV, and AIx were not different between lacunar and nonlacunar IS, neither the rate of target organ damage. In conclusion, patients with a first episode of lacunar IS have higher BP values at admission and during the subacute phase of stroke and lower levels of NT-proBNP, suggesting a closer relationship with hypertension of this IS subtype.