Sleep disordered breathing and small vessel disease in mild to moderate stroke: acute and six months follow-up

Background: Association between high homocysteine level and cerebral small-vessel disease has been implicated in cross-sectional studies, but results from longitudinal studies have been less clear. The aim of this study was to investigate whether homocysteine level at 3-months poststroke relates to the occurrence of white matter changes (WMC), the surrogate of cerebral small-vessel disease. We also investigated whether it relates to the prognosis after ischemic stroke regarding the risk of dementia at 3-months and mortality in long-term follow-up. Methods: A total of 321 consecutive acute ischemic stroke patients aged 55 to 85 were included in the study and followed up to 12 years. Plasma homocysteine level and occurrence of WMC in MRI were measured 3 months poststroke and dementia according to DSM-III was evaluated at the same time. Findings: The median homocysteine level was 13.50 μmol/l (interquartile range [IQR] 10.60-18.50 μmol/l). Total of 81 patients (25.2%) had homocysteine level above 18.50 μmol/l. In logistic regression analysis, homocysteine level above 18.50 μmol/l was not associated with severe WMC nor with dementia at 3 months poststroke. In Kaplan-Meier analysis, homocysteine level above 18.50 μmol/l was not associated with survival in 12-year follow-up. For further analysis, the group was divided in quartiles according to homocysteine level. The quartiles did not differ in occurrence of severe WMC at baseline, in the risk of dementia at 3 months, nor in the risk of mortality in 12-year follow-up. Interpretation: In our poststroke cohort homocysteine level is not associated with WMC. Further, it does not relate to impaired prognosis manifested as dementia at 3 months or mortality in 12-year follow-up.

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P2806A novel sirolimus drug eluting stent for Small-Vessel Disease: results from en-ABL e-registry

European Heart Journal ◽

10.1093/eurheartj/ehz748.1118 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Testa ◽

S Dani ◽

D Desai ◽

R Pandya ◽

P Parekh ◽

...

Keyword(s):

Stent Thrombosis ◽

Small Vessel Disease ◽

Large Vessel ◽

Small Vessel ◽

Drug Eluting Stent ◽

Vessel Disease ◽

Significant Difference ◽

Myocardial Infraction ◽

Drug Eluting

Abstract Objective The aim of the study was to assess the clinical outcome of Abluminus DES in patients with small vessels. Background Percutaneous coronary intervention (PCI) of small coronary vessel (≤2.75 mm) associated with more chances of restenosis and repeat revascularization even when drug eluting stent employed. Methods A total of 2,500 patients enrolled in en-ABL e-registry which is a prospective, multicentre observational post market registry. Out of 2,500 patients, 1,253 patients had small vessel (SV, ≤2.75 mm) while 1,247 had large vessel (LV, >3mm) disease. The primary endpoint was major adverse cardiac events (MACE) which is composite of cardiac death, target vessel myocardial infraction (TV-MI) and target lesion/vessel revascularization (TLR) at 1 year follow up. The secondary endpoint were stent thrombosis and MACE up to 2 years. Results Baseline characteristics were well matched in both groups. In the SV group had higher prevalence of diabetes as compared to large vessel 43.0% vs 25.7%. Total 1,400 lesions treated with 1,612 Abluminus DES and 1,569 lesions treated with 1,675 Abluminus DES in SV and LV groups respectively. The mean diameter of stent was 2.61±0.23 and 3.3±0.3 mm in SV and LV groups respectively. There was a significant difference in MACE in treatment groups (3.7% vs. 1.4%, p=0.004 respectively) at 1 year. No significant differences were observed between SV and LV groups in terms of death/myocardial infarction or stent thrombosis. There were increment of only one TLR and no stent thrombosis reported at 2-year follow-up. Conclusion This result suggests the efficacy and safety of novel Abluminus DES in small vessel disease.

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Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease

European Stroke Journal ◽

10.1177/2396987320920110 ◽

2020 ◽

Vol 5 (3) ◽

pp. 297-308

Author(s):

Joanna Wardlaw ◽

Philip M W Bath ◽

Fergus Doubal ◽

Anna Heye ◽

Nikola Sprigg ◽

...

Keyword(s):

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Large Trial ◽

Intervention Trial ◽

Vascular Events ◽

Phase 3 ◽

Full Dose ◽

Vessel Disease

Background Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease. Aim We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial. Methods and design LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35. Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability. Summary LACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.

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Total Cerebral Small Vessel Disease Burden Is Related to Worse Performance on the Mini-Mental State Examination and Incident Dementia: A Prospective 5-Year Follow-Up

Journal of Alzheimer s Disease ◽

10.3233/jad-181135 ◽

2019 ◽

Vol 69 (1) ◽

pp. 253-262 ◽

Cited By ~ 8

Author(s):

Yanfeng Jiang ◽

Yingzhe Wang ◽

Ziyu Yuan ◽

Kelin Xu ◽

Kexun Zhang ◽

...

Keyword(s):

Mental State ◽

Disease Burden ◽

Mini Mental State Examination ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Incident Dementia ◽

State Examination

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Nonlinear temporal dynamics of cerebral small vessel disease

Neurology ◽

10.1212/wnl.0000000000004490 ◽

2017 ◽

Vol 89 (15) ◽

pp. 1569-1577 ◽

Cited By ~ 35

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.

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Total small vessel disease score and cerebro-cardiovascular events in healthy adults: The Kashima scan study

International Journal of Stroke ◽

10.1177/1747493020908144 ◽

2020 ◽

Vol 15 (9) ◽

pp. 973-979 ◽

Cited By ~ 1

Author(s):

Kohei Suzuyama ◽

Yusuke Yakushiji ◽

Atsushi Ogata ◽

Masashi Nishihara ◽

Makoto Eriguchi ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Heart Disease ◽

Magnetic Resonance ◽

Cardiovascular Events ◽

Small Vessel Disease ◽

Small Vessel ◽

Disease Score ◽

Resonance Imaging ◽

Vessel Disease

Background and aims We explored the association between the total small vessel disease score obtained from baseline magnetic resonance imaging and subsequent cerebro-cardiovascular events in neurologically healthy Japanese adults. Methods The presence of small vessel disease features, including lacunae, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on magnetic resonance imaging, was summed to obtain a “total small vessel disease score” (range, 0–4). After excluding participants with previous stroke or ischemic heart disease, intracranial artery stenosis (≥50%), or cerebral aneurysm (≥4 mm), a total of 1349 participants (mean age, 57.7 years; range, 22.8–85.0 years; 46.9% male) were classified into three groups by total small vessel disease score: 0 ( n = 984), 1 ( n = 269), and ≥2 ( n = 96). Cerebro-cardiovascular events (i.e., any stroke, transient ischemic attack, ischemic heart disease, acute heart failure, and aortic dissection) were defined as the primary end point. The hazard ratio (HR) of events during follow-up was calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, diabetes mellitus, and smoking. Cumulative event-free rates were estimated using the Kaplan–Meier method. Results During follow-up (mean, 6.7 years), 35 cerebro-cardiovascular (16 cerebrovascular) events were identified. Higher small vessel disease score was associated with increased risk of cerebro-cardiovascular events (HR per unit increase, 2.17; 95% confidence interval, 1.36–3.46; P = 0.001). Events were more frequent among participants with higher score ( P < 0.001, log-rank test). Conclusions This study offered additional evidence for the clinical relevance of total small vessel disease score, suggesting the score as a promising tool to predict the risk of subsequent vascular events even in healthy populations.

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Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽

10.1212/wnl.0000000000004645 ◽

2017 ◽

Vol 89 (20) ◽

pp. 2108-2114 ◽

Cited By ~ 49

Author(s):

Thomas Gattringer ◽

Daniela Pinter ◽

Christian Enzinger ◽

Thomas Seifert-Held ◽

Markus Kneihsl ◽

...

Keyword(s):

Single Molecule ◽

Small Vessel Disease ◽

Brain Mri ◽

Cerebral Small Vessel Disease ◽

Community Dwelling ◽

Small Vessel ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Vessel Disease

Objective:To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.Methods:In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.Results:Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up.Conclusions:Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

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