Small Infarcts Research Articles

Effects of Acute Triiodothyronine Treatment in Patients with Anterior Myocardial Infarction Undergoing Primary Angioplasty: Evidence from a Pilot Randomized Clinical Trial (ThyRepair Study).

Background: Thyroid hormone has a differential action on healthy and ischemic heart. Triiodothyronine (T3) administration improved postischemic cardiac function while it limited apoptosis in experimentally induced ischemia. Thus, the present study investigated the potential effects of acute liothyronine (LT3) treatment in patients with anterior myocardial infarction. Methods: This study is a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair study). We randomized 52 patients and analyzed data from 37 patients (n = 16 placebo and n = 21 LT3), per prespecified per protocol analysis. We excluded three patients who had died of cardiovascular causes (one in placebo and two in LT3 arm), four with small infarct size below a pre-specified threshold (in the placebo arm), and the rest, who lacked follow-up data. LT3 treatment started after stenting as an intravenous (i.v.) bolus injection of 0.8 μg/kg of LT3 followed by a constant infusion of 0.113 μg/kg/h i.v. for 48 hours. All patients had cardiac magnetic resonance (CMR) at hospital discharge and 6 months follow-up. The primary end point was CMR left ventricular (LV) ejection fraction (LVEF) and secondary endpoints were LV volumes, infarct volume (IV), and safety. Results: The CMR LVEF% at 6 months was 53.6 ± 9.5 for the LT3-treated group and 48.6 ± 11 for placebo, p = 0.15. Acute LT3 treatment resulted in a significantly lower LV end-diastolic volume index (92.2 ± 16.8 mL/m2 vs. 107.5 ± 22.2, p = 0.022) and LV systolic volume index (47.5 ± 13.9 mL/m2 vs. 61.3 ± 21.7, p = 0.024) at hospital discharge, but not at 6 months. There was no statistically significant difference in CMR IV at hospital discharge between the groups (p = 0.24). CMR IV tended to be lower in the LT3-treated group at 6 months (18.7 ± 9.5 vs. 25.9 ± 11.7, in placebo, p = 0.05). Serious, life-threatening events related to LT3 treatment were not observed. A tendency for an increased incidence of atrial fibrillation (AF) was found in the LT3 group during the first 48 hours (19% for T3 group vs. 5% for placebo, p = 0.13). Conclusion: This pilot randomized, placebo-controlled trial study suggests potential favorable effects (acute cardiac dilatation and 6-month IV) as well as potential concerns regarding a higher risk of AF after LT3 administration early after myocardial infarction, which should be tested in a larger scale study.

A Case of Recurrent Ischemic Stroke Associated with Immunoglobulin G4-Related Disease

Immunoglobulin G4-related disease (IgG4 RD) is a systemic immune-mediated inflammatory disease that presents as multiple organ dysfunction or mass lesions with lympho-plasmacytic infiltration. However, there are few case reports presenting central nervous system involvements. Herein, we report a case of a 70-year-old man with recurrent ischemic stroke which induced by IgG4 RD. IgG4 RD should be considered and treated as one of etiologies manifesting small vessel disease infarctions, especially when it occurs multiply and recurrently.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism rather than homocysteine increase the risk of ischemic stroke-associated executive dysfunction

Background: An executive dysfunction is a form of cognitive impairment commonly found in ischemic stroke patients with a significant impact on the patients' quality of life. The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and homocysteine ​​are considered important risk factors for stroke and various forms of cognitive dysfunction. This study aimed to investigate the association between the MTHFR C677T polymorphism and serum homocysteine levels and the risk of ischemic stroke-associated executive dysfunction. Method: 87 ischemic stroke patients within the first three months of stroke onset in West Nusa Tenggara General Hospital, Siti Hajar Hospital, and Mataram General Hospital were recruited. Serum homocysteine levels were assessed using ELISA. The MTHFR C677T polymorphism was analyzed using the PCR-RFLP procedure. The executive function of the patients was evaluated using Trail Making Test Part-B, verbal fluency, and backward digit span tests. Results: The mean age of the subjects was 54.1 years. CT scan data revealed that 78.2% of subjects had a small infarct size. The MTHFR C677T polymorphism frequency was 25.3%, consisting of 2.3% homozygous and 23.0% heterozygous mutants. Multivariate logistic regression analysis showed that patients with MTHFR C677T polymorphism were more likely to have executive dysfunction than those with the wild-type genotype of the MTHFR gene (OR 4.53, 95% CI 1.06–19.27, p = 0.041). However, patients with hyperhomocysteinemia (≥13 μmol/l) were not associated with an increased risk of executive dysfunction. Conclusion: The MTHFR C677T polymorphism was the risk factor for ischemic stroke executive dysfunction.

The Role of Intra-Operative Duplex Ultrasonography Following Translabyrinthine Approach for Vestibular Schwannoma.

ObjectiveSigmoid sinus (SS) stenosis is a complication of translabyrinthine approach. Velocity changes in the SS measured by intra-operative doppler ultrasound may help in identifying patients at risk for sinus occlusion.PatientsSS velocity was measured using doppler ultrasound prior to opening dura and again prior to placement of the abdominal fat graft.InterventionData collected included: patient age, surgical side, sinus dominance, tumor volume, intra-operative doppler ultrasound measurements, post-operative venous sinus imaging, anticoagulation, and morbidities and mortalities.Main Outcome MeasureSS patency and velocity.ResultsEight patients were included in the analysis (22 to 69 years). Four had left-sided and four had right-sided craniotomies. Sigmoid sinuses were either right-side dominant or co-dominant. The mean velocity ± standard deviation (SD) prior to dura opening and abdominal fat packing was 23.2 ± 11.3 and 25.5 ± 13.9 cm/s, respectively, p = 0.575. Post-operative Magnetic Resonance Venography (MRV) imaging showed four sigmoid sinus occlusions; seven patients showed sigmoid sinus stenosis, and one internal jugular vein occlusion. One patient had post-operative Computed Tomography Venography (CTV) only. Of the four patients with MRV occlusions, CTVs were performed with three showing occlusion and all four-showing stenosis. One patient with internal jugular vein occlusion on MRV received warfarin anticoagulation. There was one cerebrospinal fluid leak requiring ear closure, one small cerebellar infarct, and one with facial nerve palsy (House-Brackman Grade 3).ConclusionSS velocity changes before and after tumor resection were not predictive of sinus occlusion. We hypothesize that sinus occlusion may be caused by related factors other than thrombosis, such as external compression of the sinus secondary to abdominal fat grafting.

Advances in the Role of Endothelial Cells in Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) poses a serious socio-economic burden due to its high prevalence and severe impact on the quality of life of elderly patients. Pathological changes in CSVD mainly influence small cerebral arteries, microarteries, capillaries, and small veins, which are usually caused by multiple vascular risk factors. CSVD is often identified on brain magnetic resonance imaging (MRI) by recent small subcortical infarcts, white matter hyperintensities, lacune, cerebral microbleeds (CMBs), enlarged perivascular spaces (ePVSs), and brain atrophy. Endothelial cell (EC) dysfunction is earlier than clinical symptoms. Immune activation, inflammation, and oxidative stress may be potential mechanisms of EC injury. ECs of the blood–brain–barrier (BBB) are the most important part of the neurovascular unit (NVU) that ensures constant blood flow to the brain. Impaired cerebral vascular autoregulation and disrupted BBB cause cumulative brain damage. This review will focus on the role of EC injury in CSVD. Furthermore, several specific biomarkers will be discussed, which may be useful for us to assess the endothelial dysfunction and explore new therapeutic directions.

Prediction of Symptoms on Admission with Early Neurological Deterioration in Single Small Subcortical Infarct.

Early neurological deterioration (END) often occurs during hospitalization in single small subcortical infarct (SSSI). While, symptoms on admission were rarely reported about its performance on predicting the risk of END. The objective of this study is to explore the relationship between symptoms on admission and END in SSSI. Patients with SSSI in the lenticulostriate artery (LSA) territory presenting within 72 hours of stroke onset were screened prospectively. Clinical characteristics, including symptoms on admission, laboratory tests and imaging findings, were collected. Based on the body regions involved including spherical face (SF), upper limb (UL) or lower limb (LL), symptoms on admission were classified into single spherical face (sSF) and any involvement of limbs (AL). END was defined as ≥2 points increase in total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 point increase in motor score within 72 hours after admission. Multivariate logistic regression was used to analyze factors associated with END. Out of 5,832 ischemic stroke patients in the database, 394 patients were finally enrolled in analysis. 65 patients (16.5%) developed END. Multivariable logistic regression revealed that symptoms with LL (OR 2.337, 95% CI 1.041-5.246), UL (OR 2.936, 95% CI 1.349-6.390) were both associated with END, while the involvement of SF (OR 0.447, 95% CI 0.249-0.804) showed the opposite result. Further analysis found that symptoms with AL (OR 3.958, 95% CI 1.355-11.565) showed a higher risk of END compared to sSF after adjustment. Our results discovered that symptoms with AL carried a higher risk of END than those involving sSF in SSSI.

Prognosis and antiplatelet therapy of small single subcortical infarcts in penetrating artery territory: a post hoc analysis of the Third China National Stroke Registry

BackgroundSmall single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and...

Coexistent cerebral small vessel disease and multiple infarctions predict recurrent stroke

Background and purposeTo investigate the association of different status of cerebral small vessel disease (CSVD) and infarction number with recurrence after acute minor stroke and transient ischaemic attack (TIA).MethodsThis study was a post hoc analysis of the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial, and includes 886 patients with acute minor stroke and TIA. The status of CSVD and infarction number was recorded for each individual. Infarction number were classified as multiple acute infarctions (MAIs≥2), single acute infarction (SAI =1), and non-acute infarction (NAI =0). The CSVD burden were grouped into non-CSVD (0 score) and CSVD (1–4 score). The primary outcome was a recurrent stroke at the 1-year follow-up. The secondary outcomes were recurrent ischaemic stroke, composite vascular event (CVE), and TIA. We analyzed the relationships between different status of CSVD burden and infarction pattern with the risk of outcomes using multivariable Cox regression models.ResultsAmong all 886 patients included in present analysis, recurrent stroke was occurred in 93 (10.5%) patients during 1-year follow-up. After adjusted for all potential covariates, compared with patients with non-CSVD and NAI, patients with CSVD and MAIs were associated with approximately 9.5-fold increased risk of recurrent stroke at 1 year (HR 9.560, 95% CI 1.273–71.787, p=0.028). Similar results observed in ischaemic stroke and CVE.ConclusionThe status of CSVD and infarction number predicted recurrent stroke in patients with acute minor stroke and TIA, especially for those with coexistent CSVD and MAIs.

IgG4-Related Disease Masquerading as Culture-Negative Endocarditis

We detail an extremely rare case of noninfective endocarditis secondary to IgG4-related disease on the mitral valve. A 75-year-old-woman with mitral valve ring annuloplasty presented with subacute, intermittent, self-limiting neurologic deficits. Magnetic resonance imaging of her brain revealed multiple small infarcts consistent with a cardioembolic phenomenon. Transesophageal echocardiogram revealed mobile, strand-like vegetations. She was taken for surgical repair of her mitral valve and tissue biopsy confirmed the diagnosis of IgG4-related disease. Our knowledge of this rare disease is continuously evolving, and this case highlights an exceptionally rare manifestation of this poorly understood disease.

Evaluation of clinical relevance and underlying pathology for hemodynamic compromise in acute small subcortical infarction using MRI-based neuroimaging markers

BackgroundHemodynamic compromise has been observed in patients with acute small subcortical infarction (SSI), and it may play a critical role in the development of early neurological deterioration (END). This study aimed to evaluate the clinical relevance and underlying pathology of hemodynamic compromise in SSI using MRI-based neuroimaging markers. MethodsWe retrospectively analyzed data and imaging of previous prospective studies. Patients with acute SSI in penetrating artery territories were recruited, all of whom underwent perfusion MRI within 24 h of stroke onset. We examined the relationships among perfusion defects and neuroimaging markers of small vessel disease, including white matter hyperintensities, cerebral microbleeds, enlarged perivascular spaces (EPVSs) and lacunes. ResultsOne hundred and seven patients were recruited, of whom 21 (19.6%) had END and 55 (51.4%) had visible perfusion defects. Patients with perfusion defects were associated with a higher rate of END (34.5% vs. 3.8%; p < 0.001), higher initial National Institutes of Health Stroke Scale scores (5.4 vs. 3.4, p < 0.001), higher rate of branch atheromatous disease (61.8% vs. 34.6%, p = 0.005) and higher rate of poor outcome at 3 months (40.0% vs. 5.4%; p = 0.005). In multiple logistic regression, perfusion defects were significantly associated with basal ganglia EPVS scores (adjusted odds ratio [aOR]: 3.93; 95% confidence interval [CI]: 1.76–8.77; p = 0.001) and branch atheromatous disease (aOR: 2.64; 95% CI: 1.06–6.60; p = 0.037). ConclusionHemodynamic compromise in acute SSI was highly related to the development of END, basal ganglia EPVS and branch atheromatous disease, suggesting the correlation with underlying pathologies of hypertensive arteriopathy and atherosclerosis.

Thrombotic Thrombocytopenic Purpura (ADAMTS13 [a Disintegrin and Metalloproteinase With a Thrombospondin Type 1 Motif, Member 13] Deficiency) as Cause of Recurrent Multiterritory Ischemic Strokes.

Thrombotic Thrombocytopenic Purpura (ADAMTS13 [a Disintegrin and Metalloproteinase With a Thrombospondin Type 1 Motif, Member 13] Deficiency) as Cause of Recurrent Multiterritory Ischemic Strokes.

Anterior Spinal Cord Ischemia due to an Acute Aortic Intramural Type B Hematoma

Anterior Spinal Cord Ischemia due to an Acute Aortic Intramural Type B Hematoma

Increased level of FAM19A5 is associated with cerebral small vessel disease and leads to a better outcome.

ObjectiveFAM19A5 plays an essential role in the development and acute or chronic inflammation of the central nervous system. The present study aimed to explore the association between FAM19A5 and cerebral small vessel disease (cSVD).MethodsA total of 344 recent small subcortical infarct (RSSI) patients and 265 healthy controls were included in this study. The difference in the FAM19A5 level between the two groups was compared and the correlation between FAM19A5 and cerebral infarction volume was analyzed. Also, the association between FAM19A5 and the total magnetic resonance imaging (MRI) burden with its imaging characteristics was explored. Moreover, the correspondence of FAM19A5 with the outcome was assessed via Δ National Institutes of Health Stroke Scale score (NIHSS) and the percentage of NIHSS improvement.ResultsFAM19A5 was highly expressed in the RSSI group (P = 0.023), showing a positive correlation with cerebral infarction volume (P < 0.01). It was positively correlated with total MRI cSVD burden (P < 0.001) and reflected the severity of white matter hyperintensity (WMH) (P < 0.01) and enlarged perivascular space (EPVS) (P < 0.01), but did not show any association with cerebral microbleed (CMB) and lacune. Moreover, FAM19A5 suggested a larger Δ NIHSS (P = 0.021) and NIHSS improvement percentage (P = 0.007).ConclusionSerum FAM19A5 was increased in RSSI and positively correlated with the infarct volume. It also reflects the total MRI burden of cSVD, of which the imaging characteristics are positively correlated with WMH and EPVS. In addition, higher FAM19A5 levels reflect better outcomes in RSSI patients.

Hemorrhagic Focus Within the Recent Small Subcortical Infarcts on Long-Term Follow-Up Magnetic Resonance Imaging.

Hemorrhagic Focus Within the Recent Small Subcortical Infarcts on Long-Term Follow-Up Magnetic Resonance Imaging.

Should Primary Stroke Centers Perform Advanced Imaging?

Should Primary Stroke Centers Perform Advanced Imaging?

Research progress in atrial fibrillation with cerebral small vessel disease.

Non-valvular atrial fibrillation is a common arrhythmia and a major risk factor for cardioembolic stroke. Small cerebral vascular disease is a syndrome of clinical, cognitive, imaging, and pathological manifestations caused by intracranial small vascular lesions. The imaging findings on cranial magnetic resonance usually shows recent subcortical small infarction, vascularised lacunae, white matter hypersignal, perivascular space enlargement, cerebral microhemorrhage, and brain atrophy. It is a major cause of neurological loss and cognitive function decline in the elderly. Current studies suggest that atrial fibrillation may increase the imaging load of cerebral small vessel disease through a series of mechanisms such as microembolization, hypoperfusion, inflammation, endothelial dysfunction, and lymphoid system dysfunction. The imaging of cerebral small vessel disease with atrial fibrillation has a potential relationship with cognitive function decline and is related to the occurrence and prognosis of stroke, even more has a potential role in suggesting the etiology and secondary prevention strategies of ischemic stroke.

Silent brain infarcts impact on cognitive function in atrial fibrillation.

AimsWe aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients.Methods and resultsWe enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [−0.12 (−0.22; −0.07)] than patients without new brain infarcts [0.07 (−0.09; 0.25)]. New WML or Mb were not associated with cognitive decline.ConclusionIn a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline.Clinical Trial Registration ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844

Safety and Effectiveness Outcomes of a Novel Automated Titanium Suture Fastener Device Applied for Heart Valve Surgery in an Ovine Model.

ObjectiveThis study was designed to evaluate the operability, effectiveness, and safety of the automated titanium suture fastener in a preclinical ovine model in comparison with manual tying in a mitral valve annuloplasty ring implantation surgery.MethodsEighteen adult Small-tailed Han sheep were prepared for the surgery of mitral valve annuloplasty ring implantation through lateral thoracotomy under cardiopulmonary bypass (CBP). A total of 12 stitches were performed to secure an annuloplasty ring, with 6 stitches done with the automated fastener and the other 6 by manual tying. The knotting time for the automated fastener or manual tying was recorded, respectively. The firmness of knots, mitral valve integrity, biocompatibility, thrombosis, local reactions, and other aspects were also compared at follow-up time (Days 30, 60, 90, and 180).ResultsOf the 18 sheep, 16 survived to the designated endpoints and were enrolled for further analysis. Compared with the control group, the knotting time was significantly reduced with the automated fastener (p < 0.01). All the annuloplasty rings were tightly secured by 6 fastener clips and 6 hand-made knots without any disengagement or displacement. All the mitral valves were intact without any defect, stenosis, prolapse, valve insufficiency, or perforation. Endothelialization was comparable between the two groups by Day 60. Small red thrombi formed at the thread end of the suture in both groups. No thrombus was found on the surface of the titanium clip. All the thrombi were within the acceptable range for the antithrombotic property. Thrombosis showed no significant difference by Day 60. No significant differences in the inflammatory response and pathological lesions were observed by Day 60. One case of diffuse renal infarction (area ratio = 20%) and 1 case of small focal renal infarction (area ratio < 5%) were caused by thromboembolism.ConclusionsThe automated fastener significantly shortened the procedure time of tying knots for the implantation of the annuloplasty ring in the ovine model, with comparable safety and effectiveness as manual tying.

Sequential transplantation of exosomes and mesenchymal stem cells pretreated with a combination of hypoxia and Tongxinluo efficiently facilitates cardiac repair

BackgroundBone marrow-derived mesenchymal stem cells (MSCs), which possess immunomodulatory characteristic, are promising candidates for the treatment of acute myocardial infarction (AMI). However, the low retention and survival rate of MSCs in the ischemic heart limit their therapeutic efficacy. Strategies either modifying MSCs or alleviating the inflammatory environment, which facilitates the recruitment and survival of the engrafted MSCs, may solve the problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and combinatorial pretreated MSCs in the treatment of AMI.MethodsExosomes derived from MSCs were delivered to infarcted hearts through intramyocardial injection followed by the intravenous infusion of differentially pretreated MSCs on Day 3 post-AMI. Enzyme linked immunosorbent assay (ELISA) was performed to evaluate the inflammation level as well as the SDF-1 levels in the infarcted border zone of the heart. Echocardiography and histological analysis were performed to assess cardiac function, infarct size, collagen area and angiogenesis.ResultsSequential transplantation of exosomes and the combinatorial pretreated MSCs significantly facilitated cardiac repair compared to AMI rats treated with exosomes alone. Notably, compared to the other three methods of cotransplantation, combinatorial pretreatment with hypoxia and Tongxinluo (TXL) markedly enhanced the CXCR4 level of MSCs and promoted recruitment, which resulted in better cardiac function, smaller infarct size and enhanced angiogenesis. We further demonstrated that exosomes effectively reduced apoptosis in MSCs in vitro.ConclusionSequential delivery of exosomes and pretreated MSCs facilitated cardiac repair post-AMI, and combined pretreatment with hypoxia and TXL better enhanced the cardioprotective effects. This method provides new insight into the clinical translation of stem cell-based therapy for AMI.

Compartmentalized Actions of the Plasminogen Activator Inhibitors, PAI-1 and Nsp, in Ischemic Stroke.

Tissue plasminogen activator (tPA) is a multifunctional protease. In blood tPA is best understood for its role in fibrinolysis, whereas in the brain tPA is reported to regulate blood-brain barrier (BBB) function and to promote neurodegeneration. Thrombolytic tPA is used for the treatment of ischemic stroke. However, its use is associated with an increased risk of hemorrhagic transformation. In blood the primary regulator of tPA activity is plasminogen activator inhibitor 1 (PAI-1), whereas in the brain, its primary inhibitor is thought to be neuroserpin (Nsp). In this study, we compare the effects of PAI-1 and Nsp deficiency in a mouse model of ischemic stroke and show that tPA has both beneficial and harmful effects that are differentially regulated by PAI-1 and Nsp. Following ischemic stroke Nsp deficiency in mice leads to larger strokes, increased BBB permeability, and increased spontaneous intracerebral hemorrhage. In contrast, PAI-1 deficiency results in smaller infarcts and increased cerebral blood flow recovery. Mechanistically, our data suggests that these differences are largely due to the compartmentalized action of PAI-1 and Nsp, with Nsp deficiency enhancing tPA activity in the CNS which increases BBB permeability and worsens stroke outcomes, while PAI-1 deficiency enhances fibrinolysis and improves recovery. Finally, we show that treatment with a combination therapy that enhances endogenous fibrinolysis by inhibiting PAI-1 with MDI-2268 and reduces BBB permeability by inhibiting tPA-mediated PDGFRα signaling with imatinib significantly reduces infarct size compared to vehicle-treated mice and to mice with either treatment alone.