[Is this iatrogenic pathology or rare disease?] / Yatrogennaya patologiya ili redkaya bolezn'?

The article is devoted to the problem of diagnosis and treatment strategy of Buerger's disease rarely found in the expert and clinical practice, that is inflammatory disease of unknown etiology, affecting mainly small and medium arteries and veins of limbs. Vascular surgeons around the world have been solving this problem for many years, both in terms of timely diagnosis of this disease and its proper pathogenic treatment. The authors of the article described an expert case of Buerger's disease larvated course in 15-years-old girl, which primarily was mistakenly assessed by specialists as iatrogenic pathology of right forearm vessels in injecting aminazin solution that, according to the clinicians' opinion, led to dry gangrene formation of right wrist and its subsequent amputation. The results of the forensic histological study and retrospective analysis of all child's medical documents allowed to correctly diagnose this rare pathology but only on the stage of commission forensic medical examination in the framework of the initiated criminal proceeding against several leading medical organizations in Saint-Petersburg with a pediatric profile. The authors noted the role of routine medical manipulation in manifestation of larvated pathologic process in a teenage girl in addition to full health and well-being. The objective of present article is devoted to understanding this problem.

[Lung pathology in children with a long-term novel coronavirus infection COVID-19]. / Patologiya legkikh u detei pri dlitel'no tekushchei novoi koronavirusnoi infektsii COVID-19.

New coronavirus infection is registered less frequently in children than in adults. Among all patients with COVID-19, the share of children is 8.6%. Clinical practice shows that in children, COVID-19 can be severe and even fatal. Articles have been published reflecting the clinical manifestations of Long Covid in children, while data on pathomorphological examination of the lungs during long-term COVID-19 in children are not available in the literature. On the basis of the Department of Pathological Anatomy with a course of Forensic Medicine and the Pathological-Anatomical Department of the Clinic of St. Petersburg State Pediatric Medical University, an analysis of medical documentation was carried out, autopsy materials were selected from 3 observations of the death of children from COVID-19. The selection criterion was the duration of the disease. A histological examination using standard methods and IHC analysis using antibodies to the nucleocapsid of SARS-Cov-2, CD95, CD31 were carried out on the lung tissue of 3 children aged 2 months to 2 years who died from a new coronavirus infection. Microscopically, all three patients showed microvessels damage, their thrombosis, angiogenesis, as well as signs of diffuse alveolar damage The combination of expression of the SARS-CoV-2 nucleocapsid and the apoptosis marker on the vascular endothelium of the MCR is of interest. CONCLUSION: The data obtained indicate infection with coronavirus and death of endothelial cells due to apoptosis. Endothelial damage in the microvessels of the lungs is the initiating factor in the development of capillary-alveolar block, tissue hypoxia, and disseminated intravascular coagulation syndrome, leading in some cases to respiratory/multiple organ failure and death.

[To the 90th anniversary of the department of pathological anatomy with a course of forensic medicine named after professor D.D.Lokhov of Saint Petersburg State Pediatric Medical University]. / K 90-letiyu kafedry patologicheskoi anatomii s kursom sudebnoi meditsiny im. professora D.D. Lokhova Sankt-Peterburgskogo gosudarstvennogo pediatricheskogo meditsinskogo universiteta.

The article is devoted to the history of Professor D.D. Lokhov Department of Pathological Anatomy with a course of forensic medicine of the St. Petersburg State Pediatric Medical University of the Ministry of Health of Russia, founded by one of founders of the national pathological anatomy of childhood and adolescence, Professor D.D. Lokhov, whose name has been awarded to the Department since 2022. The updated advances of the Department in research, teaching and diagnostic activity are presented.

A rare case of diagnosed absent aortic valve and severely hypoplastic pulmonary valve with double outlet right ventricle: A case report.

Agenesis of the aortic and pulmonary valves is a very rare congenital malformation of the semilunar valves. The literature describes no more than thirty cases of such anomaly in combination with congenital heart disease. Most descriptions include aplasia of either the aortic or pulmonic valve. The combination of such defect in both valves has been described in a much smaller number of scientific papers. In this article, we present a clinical case of the treatment of a patient with agenesis of aortic valve and severely hypoplastic pulmonary valve. As a result circulatory arrest occurred immediately after birth, which required the implementation of cardiopulmonary resuscitation. The child was resuscitated and transferred to the intensive care unit for further examination and treatment.

[Cerebellar degeneration associated with HIV infection]. / Mozzhechkovye degeneratsii, assotsiirovannye s VICh-infektsiei.

OBJECTIVE: To describe the features of the clinical presentation and evaluate the incidence of HIV-associated cerebellar degeneration in patients with progressive cerebellar ataxia. MATERIAL AND METHODS: Three hundred and seventy-seven patients with progressive cerebellar ataxia were studied. Brain MRI study, assessment by the Scale for the Assessment and Rating of Ataxia (SARA), screening for cognitive impairment by the Montreal Cognitive Assessment Scale (MoCA) were performed. In patients with HIV infection, autoimmune, deficient and other causes of ataxia, as well as opportunistic infections, multiple system atrophy and frequent forms of hereditary spinocerebellar ataxias were excluded. RESULTS: Five patients (1.3%) were identified with a combination of cerebellar ataxia and HIV infection (2 men, 3 women, aged 31 to 52 years). The median duration of HIV infection was 5 years, the duration of ataxia was 1 year. In the clinical findings, in addition to progressive ataxia, pyramidal signs, dysphagia, less often ophthalmoparesis, dystonia, postural hand tremor, affective and mild cognitive impairment were observed. In three patients, brain MRI revealed signs of olivopontocerebellar atrophy, two patients had isolated cerebellar degeneration (mainly of the vermis). All patients received combination of antiretroviral therapy in various regimens, but despite this, ataxia was progressive. CONCLUSION: HIV infection is a rare cause of cerebellar degeneration. This diagnosis remains a diagnosis of exclusion to this day. Cerebellar degeneration can occur and progress even after achieving a stable remission of HIV infection while taking highly active antiretroviral therapy.

MicroRNA Expression Profile Changes in the Leukocytes of Parkinson's Disease Patients.

Parkinson's disease (PD) is one of the most common movement disorders. It is primarily diagnosed clinically. A correct diagnosis of PD in its early stages is important for the development of a pathogenic treatment, which necessitates a search for potential biomarkers of the disease. We evaluated the diagnostic value of several microRNAs and their relationship with the clinical characteristics of PD. The study included 70 PD patients and 40 healthy volunteers. We analyzed the expression of 15 microRNAs in blood leukocytes, which were selected based on literature data and modern concepts of molecular PD pathogenesis. All patients were evaluated using the Hoehn and Yahr scale, UPDRS, NMSQ, and PDQ-39. The data analysis revealed a statistically significant increase in the expression of miR-7-5p, miR-29c-3p, and miR-185-5p and a statistically significant decrease in the expression of miR-29a-3p and miR-30c-1-5p in leukocytes in PD. However, the altered microRNA profile was shown to have a moderate diagnostic value for PD diagnosis. MicroRNA expression changes were associated with the motor and non-motor phenotypic features of PD and administration of anti-Parkinson's drugs. Also, a relationship between some of the microRNAs studied and the duration and severity of PD was found, which may potentially be used to monitor disease progression.

[Spinocerebellar ataxia type 8 in Russian patients]. / Spinotserebellyarnaya ataksiya 8-go tipa u rossiiskikh bol'nykh.

OBJECTIVE: To assess the incidence of spinocerebellar ataxia type 8 (SCA8) in patients with progressive cerebellar ataxia and describe the clinical features of the SCA8 phenotype in Russian patients. MATERIAL AND METHODS: Genotyping of CTA/CTG repeats in ATXN8OS gene was carried out in 411 patients with degenerative ataxias using fragment analysis. SCA types 1, 2, 3 and 6 as well as Friedreich's ataxia were preliminarily excluded. All patients underwent brain MRI study. Scale for the Assessment and Rating of Ataxia (SARA), and the Montreal Cognitive Assessment Scale (MoCA) to screen for cognitive impairment were used. RESULTS: Six patients with SCA8 (1.5%) were identified as carriers of the expansion in the ATXN8OS gene (91-152 CTA/CTG repeats). All cases were sporadic. Age of onset ranged from 14 to 42 years. All patients had slowly progressive cerebellar ataxia, oculomotor disturbances, dysarthria, pyramidal signs, and two patients had cognitive impairment. In one patient the clinical presentation corresponded to multiple system atrophy cerebellar type (ataxia, orthostatic hypotension, cerebellum and brainstem atrophy). Brain MRI study in all patients revealed cerebellar atrophy. CONCLUSION: SCA8 is a rare form of autosomal dominant ataxia with a predominance of the classical phenotype. All identified cases of SCA8 were sporadic, which should be taken into account when planning genetic testing in patients with spinocerebellar ataxia.

[Arterial fibromuscular dysplasia as a factor in sudden cardiac death in young adults]. / Fibromuskulyarnaya displaziya arterii ­ odin iz faktorov vnezapnoi serdechnoi smerti lits molodogo vozrasta.

The objective of the study is to consider the problem of diagnostics of a rare vasculopathy, fibromuscular dysplasia of coronary arteries, by the case study of a 19-year-old serviceman, an athlete with sudden death occurred during slight physical exertion. After repeated histological examination as part of the forensic medical examination, the diagnosis was made: «multifocal fibromuscular dysplasia of the coronary arteries and ascending aortic arch, complicated by acute left ventricular failure.¼ This disease often manifests with the acute coronary syndrome in people of young age. Therefore, special attention was given to the macroscopic and histological features of fibromuscular dysplasia of arteries.

[Roadmap for ecosystem-based approach for patients with Alzheimer disease in Russia: current needs, barriers, and possible solutions (resolution of the scientific and practical experts meeting)]. / Dorozhnaya karta po okazaniyu pomoshchi patsientu s bolezn'yu Al'tsgeimera v Rossii v formate ekosistemy: tekushchie potrebnosti, bar'ery i vozmozhnye resheniya (rezolyutsiya nauchno-prakticheskoi vstrechi ekspertov).

The care of a patient with Alzheimer's disease (AD) is considered from the perspective of an ecosystem, that is, a systemic approach describing effective partnership, collaboration and research aimed at creating value, involving all participants in the AD patient journey. The effectiveness of this ecosystem is only possible with the involvement of all stakeholders in its development, including patients, healthcare professionals at all levels, government agencies, private companies, and patient organizations. The unmet health care and information needs of patients with AD are a consequence of barriers in the AD ecosystem. Key barriers for the patient include low awareness and stigmatization of the disease in society, lack of quality epidemiological data, difficulties in timely diagnosis, lack of prevention programs, unpreparedness of most physicians to conduct AD patient rehabilitation, and other factors. Based on the analysis of the ecosystem of AD and the patient pathway, 10 main directions (strategies) necessary for the formation of the ecosystem were identified: conducting research in the diagnosis and epidemiology of AD, creating and implementing a cognitive health program, forming a legal framework, raising public awareness, optimizing patient routing for timely diagnosis, organizing a network of memory clinics/laboratories, creating a register of patients with dementia, developing digital solutions and supporting social projects.

[C9orf72-associated frontotemporal dementia in the Russian population]. / C9orf72-assotsiirovannaya forma lobno-visochnoi dementsii v rossiiskoi populyatsii.

OBJECTIVE: To evaluate the frequency of C9orf72-associated frontotemporal dementia (FTD) in the Russian population and to study clinical features of GGGGCC-repeat expansion carriers. MATERIAL AND METHODS: Twenty-eight patients with FTD are included in the study: 15 with a behavioral variant of FTD (bvFTD) and 13 with a agrammatic/non-fluent variant of primary progressive aphasia (avPPA). The mean age was 62 years (34-80), the mean disease duration was 4 years (1-10). The positive family history was noted in 46% of cases. DNA diagnosis was performed using repeat-primed polymerase chain reaction. RESULTS: The frequency of the C9orf72 repeat expansion in patients with FTD was 14%, in patients with bvFTD 20%, in patients with avPPA 8%. The mean age of disease onset in the expansion carriers was 63 (55-75) years. The frequency of the C9orf72 repeats expansion in familial FTD cases was 31%, in sporadic cases 7%. bvFTD with parkinsonian syndrome was noted in two out of four cases, bvFTD with amyotrophic lateral sclerosis (ALS) was shown in one case, avPPA with ALS was shown in one case. One female patient with bvFTD with parkinsonian syndrome presented with cognitive fluctuations that required a differential diagnosis with Lewy body disease. CONCLUSION: This is the first study of the genetic structure of FTD in the Russian population. The prevalence and clinical characteristics of C9orf72-associated FTD were defined, in particular, the spectrum of motor symptoms was shown along with behavioral and aphasic disturbances. DNA diagnosis plays an important role in confirming the diagnosis and selection of patients for potential disease-modifying treatment.

C9orf72 Gene Expression in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We studied the expression of C9orf72 gene in pathologies associated with hexanucleotide repeats expansion in this gene: frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The study included 7 patients with hexanucleotide repeats expansion in the C9orf72 gene and 9 patients of the control group. The expression of C9orf72 mRNA was evaluated in blood leukocytes by real-time PCR. Methylation of CpG-sites in C9orf72 promotor region was evaluated by DNA sequencing after bisulfite conversion. A 2-fold decrease in the C9orf72 gene expression was found in patients with hexanucleotide repeats expansion in comparison with controls, though the difference did not reach statistical significance due to small sample size. The highest expression was shown for ALS in comparison with FTD and FTD-ALS phenotype. A trend to inverse correlation between C9orf72 mRNA level and promoter methylation of this gene as well as between mRNA level and age of disease onset was demonstrated.

The SNCA-Rep1 Polymorphic Locus: Association with the Risk of Parkinson's Disease and SNCA Gene Methylation.

Neurodegeneration in Parkinson's disease is characterized by the accumulation of alpha-synuclein, a protein encoded by the SNCA gene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of these is a dinucleotide microsatellite: SNCA-Rep1. The mechanisms by which specific configurations of SNCA-Rep1 may contribute to the development of this disease have yet to be clarified. In our study, a relationship between long SNCA-Rep1 alleles and Parkinson's was confirmed in the Russian population. Long allelic variants of SNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of the SNCA gene. Long variants of SNCA-Rep1 are supposed to exert their effect through the hypomethylation of a transcriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinson's disease. Further studies are needed to establish a relationship between our finding and SNCA gene expression.

[Clinical and morphological analysis of a caseof Parkinson's disease]. / Kliniko-morfologicheskii analiz sluchaia bolezni Parkinsona.

Parkinson's disease (PD) is a neurodegenerative disease that belongs to a group of cerebral proteinopathies. The main pathomorphological signs of PD are neuronal degeneration in the midbrain substantia nigra and detection of pathological forms of the synaptic protein α-synuclein in the nigral neurons. At the same time, the pathological forms of α-synuclein in this disease have been recently shown to accumulate in the cells of not only the central, but also peripheral autonomic nervous system. The paper provides a clinical and morphological description of a PD case in a 70-year-old patient, which demonstrates that there are typical α-synuclein-positive inclusions in the brain regions (substantia nigra, caudate nucleus, and frontal cortex), salivary glands and colon. The systemic nature of α-synucleinopathy in PD is important in both clarifying the pathogenesis of the disease and elaborating new approaches to its diagnosis and, in the future, to targeted therapy.

[Genetic Diversity in Frontotemporal Dementia].

Frontotemporal dementia is a progressive neurodegenerative disorder with high clinical, genetic, and pathomorphological diversity It is the third most common cause of dementia in all ages and the most common cause of early onset dementia (below 65). Despite its multifactorial nature, up to 40% of patients have a family history where the autosomal dominant inheritance type is seen in a quarter of cases. In this review, we describe key genes whose mutations can result in the development of frontotemporal dementia, the possible pathogenic mechanisms of the degenerative process, and provide information on the clinical features of the disease for different genetic variants. Special emphasis is placed on the frontotemporal dementia phenotype that is associated with amyotrophic lateral sclerosis.

Generation of induced pluripotent stem cell line RCPCMi004-A derived from patient with Parkinson's disease with deletion of the exon 2 in PARK2 gene.

IPSC line RCPCMi004-A was generated from skin fibroblasts collected from a male patient with early onset Parkinson's disease. The patient carries a heterozygous deletion of the exon 2 of PARK2 gene. The reprogramming of fibroblasts was performed with Sendai viruses containing Oct-4, Sox-2, Klf-4 and c-Myc. Pluripotency was confirmed by immunofluorescence, RT-PCR, and formation of embryoid bodies. The RCPCMi004-A cell line carries the same deletion in PARK2 gene. The RCPCMi004-A cell line can be used to model Parkinson's disease in vitro.

[Epigenetic regulation of clinical manifestations of Friedreich's disease]. / Épigeneticheskaia reguliatsiia klinicheskikh proiavlenii bolezni Fridreikha.

AIM: To study a methylation profile of FXN gene and its influence on the clinical phenotype of Friedreich's desease (FD). MATERIAL AND METHODS: The methylation pattern was analyzed in 17 patients with FD. Forty-five CpG-sites in the promoter region and the region of intron 1 of FXN: before the GAA-expansion (UP-GAA) and after the GAA-expansion (DOWN-GAA), were studied. RESULTS: Correlations between the methylation level of CpG-sites in UP-GAA and DOWN-GAA and the number of GAA repeats in both expanded FXN alleles in patients with FD were found. An analysis revealed an earlier onset and a more severe course of FD in cases with hypermethylation of several CpG-sites in the UP-GAA region. The correlation between the methylation pattern and the presence of extraneural manifestations of FD was also revealed. In FD patients with cardiomyopathy, a hypomethylated CpG-site in the promoter region was found. In FD patients with carbohydrate metabolism disorders, two hypomethylated CpG-sites in the DOWN-GAA region were observed. CONCLUSION: The results indicate a significant contribution of epigenetic modifications of FXN to the clinical presentation of FA.

[Diagnostic algorithm for autosomal recessive ataxia]. / Algoritm diagnostiki autosomno-retsessivnykh ataksii.

AIM: To develop a complex algorithm for autosomal recessive ataxia (ARA) diagnosis applicable for Russian patients with degenerative ataxias. MATERIAL AND METHODS: 48 patients with of presumably degenerative ataxias were examined. Clinical evaluation was performed with the use of the SARA and ICARS scales (for ataxia) and MoCA (cognitive functions), and a set of laboratory tests was carried out, including electromyography, brain MRI, and DNA analysis of mutations responsible for Friedreich's disease and spinocerebellar ataxias (SCAs) types 1, 2, 3, 6 and 17. 28 patients underwent mutation screening using a multigenic MPS panel. RESULTS: 8 patients (16.7%) with non-hereditary causes of ataxia were identified: cerebellar alcoholic degeneration (n = 6) and multiple system atrophy of cerebellar type (n = 2); 3 patients (6.3%) with genetic ataxias were identified using routine DNA tests, such as with SCA type 1, 2 and 17, and 9 (18.8%) patients with Friedreich's disease. The MPS panel enabled molecular diagnosis of ARA in 8 patients (28.6%): ataxia-telangiectasia (n = 2), SANDO syndrome (n = 2), ataxia with oculomotor apraxia type 2 (n = 1), SCAR10 (n = 1), SCAR16 (n = 1), and atypical form of neuroaxonal dystrophy (n = 1). The diagnosis was not established in 20 patients. CONCLUSION: We have proposed an appropriate algorithm for degenerative ataxia diagnosis which is recommended to be used when examining patients with sporadic and autosomal recessive cases of the disorders with dyscoordination of movements.

[Unilateral posteroventral pallidotomy in the treatment of drug-induced dyskinesia in Parkinson's disease]. / Odnostoronniaia posteroventral'naia pallidotomiia v lechenii lekarstvennykh diskinezii pri bolezni Parkinsona.

OBJECTIVE: to determine the efficacy of unilateral posteroventral pallidotomy (PVP) in the treatment of drug-induced dyskinesia (DID) in Parkinson's disease (PD). MATERIAL AND METHODS: We analyzed surgical treatment of 14 patients with PD complicated by DID who underwent unilateral PVP at the Research Center of Neurology in the period between 2012 and 2015. The clinical type of DID was mainly represented by peak-dose choreoathetoid dyskinesia, more pronounced in the distal limbs, and predominantly unilateral. The severity of drug-induced dyskinesia was assessed on the UPDRS scale (part IV-A) before surgery and at 1 week and 6 months after surgery. RESULTS: One week after pallidotomy, all of the 14 patients had a regression of contralateral dyskinesia by 68.3±9.7%; 50% of patients had a regression of ipsilateral dyskinesias by 43%, on average. In 50% of cases, the dose of levodopa was reduced by 15%, on average. On examination at 6 months after surgery, regression of contralateral dyskinesia was 55.7±8.8%, and the severity of ipsilateral DID returned to the preoperative level. The use of pallidotomy significantly improved the indicators of daily activity and quality of life of patients. There were no significant postoperative complications. Three patients had mild speech disorders in the form of dysarthria, which regressed 2-3 weeks after surgery.

A 30-year history of MPAN case from Russia.

We present a patient with progressive spastic ataxia, with dystonia and anarthria undiagnosed until detailed genetic analysis revealed an MPAN mutation. Highlighting the worldwide MPAN distribution, a 30year history of absent diagnosis and the impact and cost saving of an early but detailed genetic analysis in complex progressive movement disorders, particularly the anarthric NBIA group.

[Study cytoflavin dose-dependent effect in the treatment of acute ischemic stroke]. / Izuchenie dozozavisimogo effekta tsitoflavina v terapii ostrogo perioda ishemicheskogo insul'ta.

AIM: To compare the efficacy of cytoflavin in doses of 10 and 20 ml/day in the complex pharmacological therapy of patients with acute ischemic stroke. MATERIAL AND METHODS: Eighty-six patients, aged from 43 to 85 years, were examined. Patient's status was assessed using the NIHSS, the Rankin scale, the Barthel index and the Rivermead mobility index. Patients were stratified into 3 groups: patients of group 1 received standard treatment, patients of group 2 received cytoflavin in dose of 10 ml/day in addition to standard treatment and patients of group 3 were treated with cytoflavin in dose of 20 ml/day in addition to standard treatment. RESULTS AND CONCLUSION: Cytoflavin in doses of 10 and 20 ml/day significantly promotes the regression of neurological deficit, improves day-to-day activity, and therefore, improves functional independence in daily life. The dose-dependent effect of the drug was shown. The use of cytoflavin in dose of 20 ml/day resulted in the more rapid regress of neurological symptoms during inpatient treatment and higher indices of daily activities and functional independence of patients that was important for the further rehabilitation.