A new case of autosomal dominant small vessel disease carrying a novel heterozygous mutation in HTRA1 gene: 2-year follow-up

2018 ◽  
Vol 39 (8) ◽  
pp. 1479-1481 ◽  
Author(s):  
A. R. Pati ◽  
C. Battisti ◽  
I. Taglia ◽  
P. Galluzzi ◽  
M. Bianchi ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Heterozygous Mutation ◽  
Vessel Disease

Cerebral small vessel disease caused by a novel heterozygous mutation in HTRA1

2018 ◽  
Vol 388 ◽  
pp. 19-21 ◽  
Author(s):  
Franziska S. Thaler ◽  
Cihan Catak ◽  
Maximilian Einhäupl ◽  
Susanna Müller ◽  
Klaus Seelos ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Heterozygous Mutation ◽  
Vessel Disease

Abstract TMP119: High Homocysteine Level is not Associated With White Matter Changes, Dementia nor Mortality After Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Susanna Melkas ◽  
Sami Curtze ◽  
Gerli Sibolt ◽  
Niku K Oksala ◽  
Jukka Putaala ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Homocysteine Level ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cross Sectional ◽  
White Matter Changes ◽  
Vessel Disease

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.

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

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.

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

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.

scholarly journals Cysteine-Altering NOTCH3 Variants Are a Risk Factor for Stroke in the Elderly Population

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3562-3569 ◽  
Author(s):  
Remco J. Hack ◽  
Julie W. Rutten ◽  
Thomas N. Person ◽  
Jiang Li ◽  
Ayesha Khan ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Elderly Population ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
The Elderly ◽  
Small Vessel ◽  
Resonance Imaging ◽  
Vessel Disease

Background and Purpose: Cysteine altering NOTCH3 variants, which have previously been exclusively associated with the rare hereditary small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, have a population frequency of 1:300 worldwide. Using a large population database, and taking genotype as a starting point, we aimed to determine whether individuals harboring a NOTCH3 cysteine altering variant have a higher load of small vessel disease markers on brain magnetic resonance imaging than controls, as well as a higher risk of stroke and cognitive impairment. Methods: A cross-sectional study using integrated clinical, neuroimaging, and whole-exome sequencing data of 92 456 participants from the Geisinger DiscovEHR initiative cohort. The case group consisted of individuals harboring a NOTCH3 cysteine altering variant (n=118). The control group consisted of randomly selected age- and sex-matched individuals who did not have any nonsynonymous variants in NOTCH3 (n=184). Medical records including brain magnetic resonance imagings were evaluated for clinical and neuroimaging findings associated with small vessel disease. Group comparisons were done using Fisher exact test and ordinal logistic regression models. Risk of stroke was assessed using Cox regression. Results: Of the 118 cases, 39.0% were men, mean age 58.1±16.9 years; 12.6% had a history of stroke, compared with 4.9% of controls. The risk of stroke was significantly increased after age 65 years (hazard ratio, 6.0 [95% CI, 1.4–26.3]). Dementia, mild cognitive impairment, migraine with aura and depression were equally prevalent in cases and controls. Twenty-nine cases (25%) and 45 controls (24%) had an available brain magnetic resonance imaging. After age 65 years, cases had a higher white matter lesion burden and more lacunes. A severe small vessel disease phenotype compatible with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy was rarely seen. Conclusions: Cysteine altering NOTCH3 variants are an important contributor to the risk of stroke, lacunes, and white matter hyperintensities in the elderly population.

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

2019 ◽  
Vol 64 ◽  
pp. S175
Author(s):  
S.A. Simonsen ◽  
A.V. Andersen ◽  
A.S. West ◽  
F. Wolfram ◽  
P. Jennum ◽  
...  
Keyword(s):  
Sleep Disordered Breathing ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Disordered Breathing

Association of autosomal dominant polycystic kidney disease with cerebral small vessel disease

2021 ◽  
pp. 0271678X2110378
Author(s):  
Woo-Jin Lee ◽  
Keun-Hwa Jung ◽  
Hyunjin Ryu ◽  
Kook-Hwan Oh ◽  
Jeong-Min Kim ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Polycystic Kidney ◽  
Glymphatic System ◽  
Vessel Disease ◽  
Autosomal Dominant Polycystic Kidney

Cilia dysfunction in autosomal-dominant polycystic kidney disease (ADPKD) may impair the integrity of glymphatic system and be implicated in the progression of cerebral small vessel disease (SVD), although the link between the two diseases has not been investigated. We evaluated the association of ADPKD pathology with SVD pattern and severity. Overall, 304 individuals in an ADPKD (chronic kidney disease stage ≤4 and age ≥50 years) cohort and their age, sex, and estimated glomerular filtration rate (eGFR)-matched controls were retrospectively included. ADPKD severity was classified into 1 A-B, 1 C, and 1 D-E, according to age and height-adjusted total kidney volume. SVD parameters included white-matter hyperintensity (WMH) severity scale, enlarged perivascular space (ePVS) score, and degree of lacunes or cerebral microbleeds (CMBs). After adjustments for age, sex, eGFR, and cerebrovascular risk factor parameters, ADPKD was associated with higher ePVS scores ( P < 0.001), but not with the WMH severity or degree of lacunes or CMBs. In the ADPKD subgroup, higher ADPKD severity class was associated with higher ePVS scores ( P < 0.001), WMH severity ( P = 0.003), and degree of lacunes ( P = 0.002). ADPKD associated cilia dysfunction may induce chronic cerebral glymphatic system dysfunction, which may contribute to the specific progression of ePVS compared with other SVD markers.

Abstract 38: New Mutations Linked to Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy in Africa and North America

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adeola Olowu ◽  
Spence Septien ◽  
Alka Khera ◽  
Worthy Warnack ◽  
Ty Shang
Keyword(s):  
Autosomal Recessive ◽  
Clinical Presentation ◽  
Small Vessel Disease ◽  
Hereditary Disease ◽  
Small Vessel ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Stroke Work ◽  
Vessel Disease ◽  
Asian Populations

Introduction: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary disease. It is linked to mutations in the high-temperature requirement A serine peptidase 1 gene ( HTRA1 ). The clinical presentation is characterized by cerebral small vessel disease, alopecia, and spondylosis. CARASIL was initially thought to be a recessive disorder and exclusively exist in Asian populations. The paradigm of CARASIL has recently expanded. Genetically confirmed heterozygous mutations and manifestation in other ethnicities were reported. A few cases were reported in Hispanic and Caucasian populations but none in the African population. Here we report a new homozygous mutation in a Hispanic male and a known heterozygous mutation in an African female. Methods: Patients underwent routine ischemic stroke work up and risk factor management. MRI brain results were consistent with severe small vessel disease out of proportion to age. Genetic testing for vascular dementia for NOTCH-3 and HTRA1 in Patient 1 and only HTRA1 in Patient 2 were performed through Mayo Clinic. Results: Table 1. Patient Characteristics and HTRA1 Mutations Discussion: The prevalence of CARASIL is unknown but probably underestimated. Since the recognition of heterozygous HTRA1 mutation in CARASIL, more cases of heterozygous HTRA1 mutations have been reported. One of the clinical CARASIL triad -alopecia was not reported or observed in our cases. Cases of CARASIL without alopecia have been reported. Thus, CARASIL should still be suspected in the appropriate clinical presentation even if there is no classic triad or in non-Asian populations. Our cases expanded CARASIL mutations and affected populations. Being more aware of the broad clinical presentation of CARASIL can lead to early diagnosis.

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