Cognitive functions and patterns of brain activity in patients after simultaneous coronary and carotid artery revascularization

BackgroundOn-pump coronary artery bypass grafting (CABG) is associated with a high risk of neurological complications in patients with severe carotid stenosis. Moreover, early postoperative cognitive dysfunction (POCD) incidence remains high in patients undergoing simultaneous coronary and carotid surgery. Recent studies have shown that even moderate carotid stenosis (≥50%) is associated with postoperative cognitive decline after CABG. Data on brain health in the postoperative period of simultaneous coronary and carotid surgery are limited.ObjectivesThis study aimed to analyze early postoperative changes in the cognitive function and patterns of brain electrical activity in patients after simultaneous coronary and carotid artery revascularization.Materials and methodsBetween January 2017 and December 2020, consecutive patients were assigned to on-pump CABG with or without carotid endarterectomy (CEA) according to clinical indications. An extended neuropsychological and electroencephalographic (EEG) assessment was performed before surgery and at 7–10 days after CABG or CABG + CEA.ResultsA total of 100 patients were included [median age 59 (55; 65), 95% men, MMSE 27 (26; 28)], and among these, 46 underwent CEA. POCD was diagnosed in 29 (63.0%) patients with CABG + CEA and in 32 (59.0%) patients with isolated CABG. All patients presented with a postoperative theta power increase. However, patients with CABG + right-sided CEA demonstrated the most pronounced theta power increase compared to patients with isolated CABG.ConclusionThe findings of our study show that patients with CABG + CEA and isolated CABG have comparable POCD incidence; however, patients with CABG + right-sided CEA presented with lower brain activity

Влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях

HighlightsThe presence of preoperative mild cognitive impairment (MCI) in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting is associated with an increased theta activity at the frontal and parieto-occipital regions of both hemispheres after surgery. AbstractAim. To study the impact of preoperative cognitive impairment on changes in electrical activity of the brain in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting.Methods. Sixty-three patients undergoing combined carotid endarterectomy (CAE) and coronary artery bypass grafting (CABG) were included in the study. The patients were divided into three groups, depending on the preoperative cognitive functions: without cognitive impairment (n = 17), with MCI (n = 29), and with severe cognitive impairment (n = 17). High-resolution electroencephalography (EEG) (62 channels, bandpass filtered between 0.1–50.0 Hz, sampling rate of 1000 Hz) was performed 3–5 days before and 7–10 days after surgery.Results. Patients with severe cognitive impairment at baseline presented with higher theta activity at the frontal region of the left hemisphere compared to patients without cognitive impairment and patients with MCI (p = 0.048). At the same time, patients with MCI showed the most pronounced theta activity increase after surgery compared to preoperative levels at the frontal and parieto-occipital cortical regions of both the left and right hemispheres (p≤0.05). Postoperative changes of theta activity in patients with severe cognitive impairment were minimal and statistically insignificant.Conclusion. Patients without severe preoperative cognitive impairment presented with higher grade brain dysfunction in the form of increased theta activity at the frontal and parieto-occipital regions after combined CAE and CABG. A smaller decrease in theta power after surgery in patients with severe preoperative cognitive impairment, on the one hand, can indicate compensation after cerebral ischemia and resistance to hypoperfusion during on-pump cardiac surgery, and on the other, can be a manifestation of the ceiling effect and insufficiency of brain functional reserves.Основные положенияНаличие предоперационного умеренного когнитивного расстройства у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях, ассоциировано с выраженным послеоперационным увеличением тета-активности во фронтальных и парието-окципитальных отделах обоих полушарий. РезюмеЦель. Изучено влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у больных, перенесших одномоментное вмешательство на каротидных и коронарных артериях.Материалы и методы. В исследовании участвовали 63 пациента, перенесших одномоментно каротидную эндартерэктомию и коронарное шунтирование с применением искусственного кровообращения. В зависимости от предоперационного состояния когнитивных функций участники разделены на три группы: без когнитивного расстройства (n = 17), с умеренным (n = 29) и тяжелым (n = 17) когнитивным расстройством. Электроэнцефалография высокого разрешения (62 канала, полоса пропускания 0,1–50,0 Гц, частота дискретизации 1 000 Гц) проведена за 3–5 дней и на 7–10-е сутки после вмешательства.Результаты. Установлено, что до операции у пациентов с тяжелым когнитивным расстройством показатели тета-активности во фронтальных отделах левого полушария были выше, чем у лиц без когнитивного расстройства и с умеренным когнитивным нарушением (p = 0,048). При этом после вмешательства у пациентов с умеренным когнитивным расстройством наблюдалось максимально выраженное увеличение тета-активности по сравнению с предоперационным уровнем во фронтальных и парието-окципитальных отделах коры левого и правого полушарий (p≤0,05). Тогда как у лиц с тяжелым когнитивным расстройством послеоперационные изменения тета-ритма были минимальны и не достигали статистической значимости.Заключение. Пациенты без тяжелых форм предоперационного когнитивного дефицита после одномоментного вмешательства на каротидных и коронарных артериях демонстрируют большую выраженность мозговой дисфункции по показателям тета-активности фронтальных и парието-окципитальных областей коры мозга. При этом меньшая выраженность изменений тета-ритма после операции у больных с тяжелым предоперационным когнитивным расстройством, с одной стороны, может быть индикатором компенсации хронической ишемии головного мозга и устойчивости к гипоперфузии при искусственном кровообращении, с другой – проявлением потолочного эффекта и недостаточности функциональных резервов

Effect of Carotid Stenosis Severity on Patterns of Brain Activity in Patients after Cardiac Surgery

Background: The negative effects of high-grade carotid stenosis on the brain are widely known. However, there are still insufficient data on the brain state in patients with small carotid stenosis and after isolated or combined coronary and carotid surgery. This EEG-based study aimed to analyze the effect of carotid stenosis severity on associated brain activity changes and the neurophysiological test results in patients undergoing coronary artery bypass grafting (CABG) with or without carotid endarterectomy (CEA). Methods: One hundred and forty cardiac surgery patients underwent a clinical and neuropsychological examination and a multichannel EEG before surgery and 7–10 days after surgery. Results: The patients with CA stenoses of less than 50% demonstrated higher values of theta2- and alpha-rhythm power compared to the patients without CA stenoses both before and after CABG. In addition, the patients who underwent right-sided CABG+CEA had generalized EEG “slowdown” compared with isolated CABG and left-sided CABG+CEA patients. Conclusions: The on-pump cardiac surgery accompanied by specific re-arrangements of frequency–spatial patterns of electrical brain activity are dependent on the degree of carotid stenoses. The information obtained can be used to optimize the process of preoperative and postoperative management, as well as the search for neuroprotection and safe surgical strategies for this category of patients

Establishment of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in Saint Petersburg

Spinal muscular atrophy 5q (SMA) is one of the most common neuromuscular inherited diseases and is the most common genetic cause of infant mortality. SMA is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently developed drugs can improve the motor functions of infants with SMA when they are treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using a real-time PCR assay with dried blood spots (DBS) was performed from January 2022 through November 2022 in Saint Petersburg, which is a representative Russian megapolis. Here, 36,140 newborns were screened by the GenomeX real-time PCR-based screening test, and three genotypes were identified: homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns), and wild-type individuals (35,364 newborns). The disease status of all four newborns that screened positive for the homozygous SMN1 deletion was confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined the incidence of spinal muscular atrophy in Saint Petersburg to be 1 in 9035 and the SMA carrier frequency to be 1 in 47. In conclusion, providing timely information regarding SMN1, confirmation of disease status, and SMN2 copy number as part of the SMA newborn-screening algorithm can significantly improve clinical follow-up, testing of family members, and treatment of patients with SMA

Clinical and Genetic Characteristics of Pediatric Patients with Hypophosphatasia in the Russian Population

(1) Hypophosphatasia (HPP) is a rare inherited disease caused by mutations (pathogenic variants) in the ALPL gene which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by impaired bone mineral metabolism due to the low enzymatic activity of TNSALP. Knowledge about the structure of the gene and the features and functions of various ALPL gene variants, taking into account population specificity, gives an understanding of the hereditary nature of the disease, and contributes to the diagnosis, prevention, and treatment of the disease. The purpose of the study was to describe the spectrum and analyze the functional features of the ALPL gene variants, considering various HPP subtypes and clinical symptoms in Russian children. (2) From 2014–2021, the study included the blood samples obtained from 1612 patients with reduced alkaline phosphatase activity. The patients underwent an examination with an assessment of their clinical symptoms and biochemical levels of TNSALP. DNA was isolated from dried blood spots (DBSs) or blood from the patients to search for mutations in the exons of the ALPL gene using Sanger sequencing. The PCR products were sequenced using a reagent BigDye Terminator 3.1 kit (Applied Biosystems). Statistical analysis was performed using the GraphPad Prism 8.01 software. (3) The most common clinical symptoms in Russian patients with HPP and two of its variants (n = 22) were bone disorders (75%), hypomyotonia (50%), and respiratory failure (50%). The heterozygous carriage of the causal variants of the ALPL gene was detected in 225 patients. A total of 2 variants were found in 27 patients. In this group (n = 27), we identified 28 unique variants of the ALPL gene, of which 75.0% were missense, 17.9% were frameshift, 3.6% were splicing variants, and 3.6% were duplications. A total of 39.3% (11/28) of the variants were pathogenic, with two variants being probably pathogenic, and 15 variants had unknown clinical significance (VUS). Among the VUS group, 28.6% of the variants (7/28) were discovered by us for the first time. The most common variants were c.571G > A (p.Glu191Lys) and c.1171del (Arg391Valfs*12), with frequencies of 48.2% (13/28) and 11% (3/28), respectively. It was found that the frequency of nonsense variants of the ALPL gene was higher (p < 0.0001) in patients with the perinatal form compared to the infantile and childhood forms of HPP. Additionally, the number of homozygotes in patients with the perinatal form exceeded (p < 0.01) the frequencies of these genotypes in children with infantile and childhood forms of HPP. On the contrary, the frequencies of the compound-heterozygous and heterozygous genotypes were higher (p < 0.01) in patients with infantile childhood HPP than in perinatal HPP. In the perinatal form, residual TNSALP activity was lower (p < 0.0005) in comparison to the infantile and childhood (p < 0.05) forms of HPP. At the same time, patients with the heterozygous and compound-heterozygous genotypes (mainly missense variants) of the ALPL gene had greater residual activity (of the TNSALP protein) regarding those homozygous patients who were carriers of the nonsense variants (deletions and duplications) of the ALPL gene. Residual TNSALP activity was lower (p < 0.0001) in patients with pathogenic variants encoding the amino acids from the active site and the calcium and crown domains in comparison with the nonspecific region of the protein