Sonolysis in Risk Reduction of Symptomatic and Silent Brain Infarctions during Coronary Angioplasty and Stenting

Background: Cerebral complications of coronary catheterizations are transient ischemic attack (TIA) and stroke. Silent stroke (SCI) does not cause acute neurological dysfunction. It might cause many disorders including dementia. Sonolysis is therapeutic method. Sonolysis should be the method for reducing the risk of symptomatic and asymptomatic brain ischemic lesions in patients undergoing elective coronary angioplasty or stenting. Aims: To analyse patients with cardiac disease indicated for elective coronary catheterization: 1) Assess the incidence of acute/subacute SCI on brain magnetic resonance (MR) imaging; 2) Investigate factors influencing the frequency and type of microembolic signals (MES) detected using transcranial Doppler (TCD) in patients undergoing elective coronary intervention, and to correlate the frequency and type of MES with detection of new brain ischemic lesions using MR. Examine changes in cognitive function at 30 days post procedure in relation to pretreatment scores; 3) Test the clinical efficacy and safety of perioperative sonolysis in patients undergoing elective coronary catheterization. Methods: 1) 144 patients were enrolled to the study. Brain MR was performed before cardiac intervention. The presence of acute and subacute SCI was evaluated, SCI volume was measured and risk...Úvod: Mezi cerebrální komplikace koronárních katetrizací patří zejména tranzitorní ischemická ataka (TIA) a cévní mozková příhoda (CMP). Tichý mozkový infarkt (silent cerebral infarction, SCI) nezpůsobuje potíže v době vzniku, ale v průběhu měsíců a let se mohou objevit určité nemoci, včetně demence. Sonolýza je terapeutická metoda, při které se využívá efekt ultrazvuku a mohla by představovat léčebný postup, který by chránil pacienty před vznikem mozkového infarktu v průběhu koronárních zákroků. Cíle práce: Analýza údajů pacientů se srdečním onemocněním, kteří podstupují koronární katetrizaci, a to: 1) Zjistit incidenci akutního/subakutního SCI před koronární katetrizací pomocí magnetické rezonance (MR) mozku; 2) Vyhodnotit faktory, které ovlivňují početnost a druh mikroembolických signálů (MES) v povodí obou arteria cerebri media (ACM) detekovaných transkraniálním dopplerem (TCD) v průběhu plánované koronární intervence; otestovat vztah MES a nových mozkových ischémií na MR a jejich vztah vůči kognitivní dysfunkci 30 dní po intervenci; 3) Zjistit efekt a bezpečnost periprocedurální transkraniální sonolýzy při koronárním výkonu. Metodika: 1) Do studie bylo zařazeno 144 pacientů. Před intervencí absolvovali MR mozku, na kterém se hodnotila přítomnost akutního/subakutního SCI, jeho objem a vztah jednotlivých...Department of NeurologyNeurologická klinikaLékařská fakulta v Hradci KrálovéFaculty of Medicine in Hradec Králov

Sonolysis in Risk Reduction of Symptomatic and Silent Brain Infarctions during Coronary Angioplasty and Stenting

Background: Cerebral complications of coronary catheterizations are transient ischemic attack (TIA) and stroke. Silent stroke (SCI) does not cause acute neurological dysfunction. It might cause many disorders including dementia. Sonolysis is therapeutic method. Sonolysis should be the method for reducing the risk of symptomatic and asymptomatic brain ischemic lesions in patients undergoing elective coronary angioplasty or stenting. Aims: To analyse patients with cardiac disease indicated for elective coronary catheterization: 1) Assess the incidence of acute/subacute SCI on brain magnetic resonance (MR) imaging; 2) Investigate factors influencing the frequency and type of microembolic signals (MES) detected using transcranial Doppler (TCD) in patients undergoing elective coronary intervention, and to correlate the frequency and type of MES with detection of new brain ischemic lesions using MR. Examine changes in cognitive function at 30 days post procedure in relation to pretreatment scores; 3) Test the clinical efficacy and safety of perioperative sonolysis in patients undergoing elective coronary catheterization. Methods: 1) 144 patients were enrolled to the study. Brain MR was performed before cardiac intervention. The presence of acute and subacute SCI was evaluated, SCI volume was measured and risk..

RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.

RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients

Homology of identified RNF213 variants.

<p>Homology of identified RNF213 variants.</p

Migration assay using HUVECs transfected with <i>RNF213</i> D4013N, R4019C and V4146A.

<p>Representative images are shown in upper panel. The re-endothelialized areas were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3 or 4). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT according to Student’s <i>t</i>-test.</p

MAF in database and prediction of functional change of identified RNF213 variants.

<p>MAF in database and prediction of functional change of identified RNF213 variants.</p

Imaging data of II-2 in Family 1.

<p>(A) MRA image. TOF-3D MRA verifies typical steno-occlusive changes of the circle of Willis. Distal T segments of both internal carotid arteries are occluded and basal moyamoya vessels are clearly seen (anteroposterior view, left panel). Typical “puff-of-smoke” look of moyamoya vessels. Internal carotid arteries are relatively hypoplastic compared with the vertebrobasilar system (lateral view, right panel). (B) Digital subtraction angiography. Catheterization angiography of left vertebral artery (left panel), left carotid artery (middle panel), and right carotid artery (right panel). (C) Transcranial color-coded sonography. Severely dampened flow in the M1 segment of the left middle cerebral artery.</p

Schematic diagram of <i>RNF213</i> rare variants identified in MMD patients.

<p>Variants in Asian and white patients are shown above and below the protein, respectively. The five variants identified in MMD patients from this study are shown in bold characters. AA, amino acid; AAA+, ATPase associated with diverse cellular activities domain; RING, RING-finger domain. This figure was modified from the original version described in Reference 6.</p

Tube formation assay of HUVECs transfected with <i>RNF213</i> D4013N and V4146A.

<p>Representative images are shown in upper panel. The tube areas, total tube length, and number of tube branches were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT, †<i>P</i> < 0.05 compared with D4013N according to Student’s <i>t</i>-test.</p

Identification of <i>RNF213</i> rare variants in three families.

<p>(A) Pedigree chart and genotypes of <i>RNF213</i> rare variants and microsatellite markers of the three families. Filled and unfilled symbols indicate affected and unaffected individuals, respectively. Squares and circles represent males and females, respectively. Arrows indicate index case. (B) Sequence chromatography of the identified <i>RNF213</i> rare variants. (C) Haplotype for p.R4019C and p.E4042K determined by cloning in II-1 in Family 2.</p