[Assessment of the significance of dilated perivascular spaces and nocture arterial hypertension in the development of Alzheimer's disease]. / Otsenka znacheniya rasshirennykh perivaskulyarnykh prostranstv i nochnoi arterial'noi gipertenzii v razvitii bolezni Al'tsgeimera.

OBJECTIVE: To study the severity and localization of dilated perivascular spaces (DPVS), the levels of protein markers of amyloidosis and neurodegeneration in the cerebrospinal fluid (CSF) at different daily blood pressure (BP) profiles in patients with Alzheimer's disease (AD) and other types of cognitive impairment. MATERIAL AND METHODS: A total of 119 people, aged 53 to 92 years, including 55 patients with AD, 27 patients with vascular cognitive disorders (VCD), 19 patients with frontotemporal degeneration (FTD). All patients underwent BP monitoring for 24 hours using a standard oscillometric measurement method, lumbar puncture to assess Aß-42 and Aß-40 amyloid protein, total and phosphorylated tau protein in the CSF, magnetic resonance imaging tomography of the brain with subsequent assessment of the severity of expansion and localization of DPVS according to the G.M. Potter scale. RESULTS: In 58.3% of patients with AD, there is no adequate reduction in BP at night in comparison with patients with VCD (p<0.05). A significant degree of expansion of the DPVS turned out to be most typical for patients with AD: grade 3 was detected in 45.7% of patients, and the maximum, grade 4, was detected in 13.4%. At the same time, DPVSs were significantly more often detected in the group of subjects with insufficient reduction in diastolic BP (DBP) at night. A strong inverse correlation was established between the level of Aß-42 in the CSF and the variability of DBP at night (r= -0.92; p<0.05). The decrease in the level of Aß-42 in AD, especially at the prodromal stage, is directly related to the low variability of DBP at night, which is more characteristic of an insufficient decrease or increase in BP during night sleep. CONCLUSION: Patients with AD were characterized by an insufficient decrease in BP at night, which is associated with the severity and degree of maximum expansion of the DPVS. A decrease in the level of Aß-42 amyloid protein in the CSF strongly correlates with the variability of DBP at night.

[Multi-center open comparative randomized study of efficacy and safety of Akatinol Memantine 20 mg (single-doses) vs Akatinol Memantine 10 mg (double-doses) in patients with vascular dementia]. / Mnogotsentrovoe otkrytoe sravnitel'noe randomizirovannoe issledovanie effektivnosti i bezopasnosti primeneniya preparata Akatinol Memantin, 20 mg (odnokratnyi priem) v sravnenii s preparatom Akatinol Memantin, 10 mg (dvukratnyi priem) u patsientov s sosudistoi dementsiei.

OBJECTIVE: Evaluation of the efficacy and safety of the drug Acatinol Memantine, 20 mg (once daily) in comparison with the drug Acatinol Memantine, 10 mg (twice daily) in patients with moderate to moderate severe vascular dementia. MATERIAL AND METHODS: The study included 130 patients aged 50-85 years of both sexes with instrumentally and clinically confirmed vascular dementia. The patients were randomized into 2 groups. Group I consisted of 65 patients receiving Akatinol Memantine, 20 mg once daily, group II - 65 patients receiving Akatinol Memantine, 10 mg twice daily for 24 weeks. Clinical, parametric and statistical research methods were used. The Alzheimer's disease assessment scale, the cognitive subscale (ADAS-cog), the short mental Status Assessment Scale (MMSE) and the general clinical impression scale for patients condition and illness severity (CGI-C and CGI-S) and the Hamilton Depression Rating scale (HAM-D) were used. Adverse events were collected and analyzed. RESULTS: At week 24, both groups showed statistically significant positive change in ADAS-cog total score: in group I the total score was 27.2±8.76 points (absolute difference from baseline 3.5 points; p<0.01), and in group II - 26.1±7.86 points (absolute difference from baseline 2.5 points; p<0.01) with no statistically significant differences between groups. Evaluation of secondary efficacy criteria (change in ADAS-cog total score at week 12 and MMSE at weeks 4, 12, and 24) also revealed statistically significant benefit in both groups compared to baseline with no significant differences between groups. Statistically significant improvement was noticed on CGI-S and CGI-C scales in both groups. Akatinol Memantine was safe and well tolerated in both groups. CONCLUSION: The study showed no lesser efficacy and safety of Akatinol Memantine, 20 mg (once daily) compared to Akatinol Memantine, 10 mg (twice daily) in patients with moderate and moderately severe vascular dementia.

[Traumatic brain injury as risk factor of Alzheimer's disease and possibilities of pathogenetic therapy]. / Cherepno-mozgovaya travma kak faktor riska bolezni Al'tsgeimera i vozmozhnosti patogeneticheskoi terapii.

The article examines the potential role of brain mechanical damage as a trigger for the development of neurodegenerative changes. Attention is paid to dysfunction of the neurovascular unit, and disruption of the functional and compensatory capabilities of blood flow. The importance of microhemorrhages that occur in the acute period of injury and the formation of first focal and then diffuse neuroinflammation is emphasized. The importance of mitochondrial dysfunction was separately determined as a significant factor in increasing the risk of developing Alzheimer's disease (AD) in patients after traumatic brain injury (TBI). In TBI, there is a decrease in the expression of tight junction (TC) proteins of endothelial cells, such as occludin, claudin, JP, which leads to increased permeability of the blood-brain barrier. TBI, provoking endothelial dysfunction, contributes to the development of metabolic disorders of ß-amyloid and tau protein, which in turn leads to worsening vascular damage, resulting in a vicious circle that can ultimately lead to the development of AD and dementia. Age-related changes in cerebral arteries, which impair perivascular transport of interstitial fluid, are currently considered as an important part of the «amyloid cascade¼, especially against the background of genetically mediated disorders of glial membranes associated with defective aquaporin-4 (encoded by the APOE4). Studies in animal models of TBI have revealed an increase in tau protein immunoreactivity and its phosphorylation, which correlates with the severity of injury. A comprehensive analysis of research results shows that the cascade of reactions triggered by TBI includes all the main elements of the pathogenesis of AD: disorders of energy metabolism, microcirculation and clearance of cerebral metabolic products. This leads to a disruption in the metabolism of amyloid protein and its accumulation in brain tissue with the subsequent development of tauopathy. Cerebrolysin, by modulating the permeability of the blood-brain barrier, blocks the development of neuroinflammation, reduces the accumulation of pathological forms of proteins and may be slow down the progression of neurodegeneration.

[Diagnosis and treatment of early forms of cognitive impairment: possibilities of influencing neuronal energy metabolism. Resolution of the Council of Experts]. / Diagnostika i lechenie rannikh form kognitivnykh narushenii. Vozmozhnosti vozdeistviya na energeticheskii metabolizm neironov. Rezolyutsiya Soveta ekspertov.

Diagnosis and treatment of early forms of cognitive impairment: possibilities of influencing neuronal energy metabolism. Resolution of the Council of Experts.

[Psychological, psychiatric and neurological aspects of COVID-19]. / Psikhologicheskie, psikhiatricheskie i nevrologicheskie aspekty COVID-19.

OBJECTIVE: To analyze neurological, psychological and psychiatric aspects of COVID-19, as well as to study the current state of the problem. MATERIAL AND METHODS: The study included 103 patients with COVID-19. The main research method was clinical/psychopathological. To study the impact of activities related to the care of patients with COVID-19 in a hospital setting, the medical and psychological state of 197 hospital workers involved in the treatment of patients with COVID-19 was assessed. The level of anxiety distress was assessed with the Psychological Stress Scale (PSM-25), distress indicators corresponded to values of more than 100 points. The severity of anxiety and depressive symptoms was assessed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: When considering psychopathological disorders in the context of COVID-19, it is necessary to distinguish between two main groups of disorders: mental disorders during the pandemic, and mental disorders directly caused by the causative agent SARS-CoV-2. The analysis of psychological and psychiatric aspects in various periods of the initial stage of COVID-19 showed that each of them was characterized by specific features depending on the nature of the influence of different pathogenic factors. In the structure of nosogenic mental disorders in patients with COVID-19 (103 patients), the following clinical forms were identified: acute reaction to stress (9.7%), anxiety-phobic disorders (41.7%), depressive symptoms (28.1%), hyponosognosic nosogenic reactions (20.5%). At the same time, the majority of the patients had manifestations of somatogenic asthenia (93.2%). A comparative analysis of neurological and psychological/psychiatric aspects of COVID-19 showed that the main mechanisms of the impact of highly contagious coronaviruses, including the SARS-CoV-2, on the central nervous system are: cerebral thrombosis and cerebral thromboembolism, damage to the neurovascular unit, neurodegeneration, including that induced by cytokines, and immune-mediated demyelinating nerve damage. CONCLUSION: Neurological and psychological/psychiatric aspects of COVID-19 should be taken into account both at the stage of disease treatment and in the post-infection period due to the pronounced neurotropism of SARS-CoV-2 and its effect on the neurovascular unit. Along with helping patients, an important aspect is the preservation of the mental health of medical personnel working in hospitals for infectious diseases, due to special working conditions and a high level of professional stress.

EPHA4 Genetic Variant in a Patient with Epilepsy, Ophthalmological Anomalies, and Neurodevelopmental Delay.

We present the findings of a Whole Exome Sequencing in a 2-year-old boy, conceived via In Vitro Fertilization with donor sperm, who suffers from an undiagnosed neurological syndrome. The following heterozygous variant in the EPHA4 gene was identified and classified as likely pathogenic: c.1655_1656, p.(Ser552CysfsTer23). Subsequent segregation analysis showed that the variant was not inherited from the mother and the sperm donor is not accessible for genetic testing. The presented results can further expand upon the genetic variants considered when diagnosing complex neurological syndromes and shows the importance of access to biological samples from donor banks in genetically ambiguous cases.

[Prospects of use of research results for drugs with anitihypoxic and antioxidative properties in neuroprotective treatment strategies (Opinion of the Council of Experts dated 26 March 2022)]. / Perspektiva ispol'zovaniya rezul'tatov issledovaniya preparatov s anitigipoksantnymi i antioksidantnymi svoistvami v neiroprotektivnoi strategii lecheniya (Zaklyuchenie soveta ekspertov ot 26 marta 2022 g.).

Cerebrovascular diseases are one of the main causes of death and permanent disability. Effective and timely neuroprotective therapy can reduce the burden of cerebrovascular disease. The possibilities of neuroprotection as a method of prevention and medical rehabilitation of acute and chronic cerebrovascular diseases are addressed.

[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.

[A new paradigm for the development of neurodegenerative diseases on the example of Alzheimer's disease and Parkinson's disease.]

The role of neuronal inflammation developing during the formation of amyloid plaques and Lewy bodies has been investigated. The influence of various exogenous and endogenous factors on the development of neuroinflammation has been established, but the role of various infectious agents in the development of this process has been much less studied. Today, the existence of a universal trigger mechanism of the neurodegenerative process is obvious: a specific pathogen of a bacterial or viral nature (including a long-term persistent in the nervous tissue in a latent state), reactivating, penetrates into certain cerebral structures, where it is influenced by either Aß or resident macrophages of the central nervous system, which, in turn, are activated and induce the release of pro-inflammatory cytokines, leading to the development of neuronal inflammation, autophagy and neurodegeneration. Reactivation of latent, such as herpes, infection in individuals who are carriers of APOE4 significantly increases the risk of developing Alzheimer's disease. Class II genes of the HLA locus (HLA II) may be related to the progression of neurodegenerative diseases. The increase in iron levels in the glia is induced by inflammation, which leads to neurodegeneration. Disruption of the homeostasis of redox-active metals, iron and copper, is an integral part of the pathogenesis of Alzheimer's disease and Parkinson's disease. The developing neuroinflammation leads to the intensification of the processes of peroxidation, oxidation of metals and the development of ferroptosis.

[Some psychiatric and neurological aspects of the asymptomatic and mild course of COVID-19]. / Nekotorye psikhiatricheskie i nevrologicheskie aspekty bessimptomnogo i legkogo techeniya COVID-19.

OBJECTIVE: To study neurological and mental disorders associated with the inapparent and mild course of COVID-19. MATERIAL AND METHODS: The study included 50 patients (mean age 35.2±11.4 years) admitted to a psychiatric hospital due to depressive spectrum disorders. Patients were divided into two groups: patients (n=16) who had IgG antibodies to SARS-CoV-2 (main group) and patients (n=34) without a history of COVID-19 (comparison group). RESULTS AND CONCLUSION: Patients of the main group showed a difference in the structure of asthenic disorders compared with the comparison group. Also, there was a significant predominance of the severity of asthenic symptoms and anxiety in the structure of psychopathological disorders in depressive spectrum disorders. The viral intoxication contributes to the formation of a kind of asthenic «soil¼ (with characteristic manifestations). In the future, in the case of the development of any stress-associated disorder, more pronounced psychopathological disorders are noted compared with patients of the comparison group. The authors describe a variant of the course of COVID-19, in which the development of ischemic stroke was the first clinical manifestation of the disease. These disorders are based on the pronounced neurotropic effect of SARS-CoV-2 and its effect on the neurovascular unit.

[Clinical and morphological risk factors for epilepsy in patients with glial and metastatic brain tumors]. / Kliniko-morfologicheskie faktory riska razvitiya epilepsii u bol'nykh s glial'nymi i metastaticheskimi opukholyami golovnogo mozga.

OBJECTIVES: To estimate the incidence of epileptic seizures in patients with glial and metastatic brain tumors and to identify clinical and morphological risk factors for epileptic seizures in patients with glial and metastatic brain tumors. MATERIAL AND METHODS: The study included 225 (88.6%) patients with glial brain tumors and 29 patients (11.4%) with metastatic tumors. RESULTS: Statistically significant differences in the incidence of epileptic seizures depending on age, histological characteristics of the tumor, degree of malignancy, tumor localization, involvement of the cerebral cortex, the presence of the midline shift were obtained. CONCLUSIONS: Epilepsy and epileptic seizures was found to develop in 51.11% and 24.14% of cases in glial and metastatic brain tumors, respectively. Risk factors for developing epileptic seizures include younger age (up to 57 years), histological characteristics corresponding to diffuse astrocytomas, anaplastic astrocytomas, oligodendrogliomas, oligoastrocytomas, grade I-III malignancy, lesion of the temporal lobe, involvement of the cerebral cortex. Factors that reduce the risk for attacks include age over 57, histological characteristics corresponding to glioblastomas and metastatic tumors, grade IV malignancy, subcortical localization of the tumor, damage to the occipital lobe, involvement of the commissural pathways, subtentorial localization of the tumor, the absence of lesions of the temporal and frontal lobes of the brain, the involvement of both brain hemispheres, damage to two or more brain lobes, the presence of a midline shift.

[Cholinergic profile as a target of rational therapy of central nervous system diseases and injuries]. / Kholinergicheskii profil' kak mishen' ratsional'noi terapii zabolevanii i travm tsentral'noi nervnoi sistemy.

AIM: A comparative analysis of the clinical efficacy of cholinergic drugs and acetylcholinesterase inhibitors (IHE), as well as their combination, in the treatment of cerebrovascular disease and consequences of intracranial injury according to clinical, instrumental and laboratory dynamic observations. MATERIAL AND METHODS: Ninety patients with cerebrovascular pathology, including 45 with chronic brain ischemia stage 2 (ICD-10 I67) and 45 with sequelae of intracranial injury (ICD-10 T90.5), were enrolled in the study. Complex treatment of patients included basic and specific therapy. The groups were divided into 3 subgroups of 15 people: the neuromidin group, the gliatilin group and the neuromidin + gliatilin group. The duration of treatment was 2 months. All patients underwent a comprehensive clinical, neurophysiological and laboratory examination prior to therapy, after 1 month and 2 month from the beginning of therapy: a study of cholinesterase activity in the blood, testing on MMSE and Hamilton scales, transcranial magnetic stimulation with determination of Central motor conduction time and somatosensory evoked potentials with calculation of Central afferent conduction time. RESULTS: Prior to treatment, a significant positive strong correlation was found between the age of patients and the level of CE activity in serum (Rs=0.77; p=0.0001). The treatment resulted in a significant (p<0.05) improvement of all parameters (except for MMSE that showed a trend towards improvement) in the neuromidin and the neuromidin + gliatilin subgroups of each group compared to those in the gliatilin subgroups. In addition, after 2 months from the beginning of treatment, there was a significant decrease in the activity of CE in serum in the neuromidin and the neuromidin + gliatilin subgroups. CONCLUSION: The study of deviations of the 'cholinergic profile' (the level of CE activity in the blood) in patients with cerebral pathology and the strategy using cholinergic drugs, IHE and their combination for the treatment of neuropsychiatric disorders, is one of the important directions in the optimization of combined therapy of patients of this profile.

[Manual differential diagnosis of migraine and cervicogenic headache]. / Manual'naia differentsial'naia diagnostika migreni i tservikogennoi golovnoi boli.

AIM: To study the informative nature of manual therapy for differential diagnosis of migraine and cervicogenic headache (CH). MATERIAL AND METHODS: The authors analyze two clinical cases of patients with a previously established diagnosis of migraine, with the duration of the disease of over ten years and neuroimaging signs of degenerative-dystrophic changes in the upper cervical spine. In both cases, there was no hereditary history and low efficacy of the previous drug therapy was noted. The informative value of the tests performed by methods of manual medicine followed by manipulation procedures of neck structures for the differential diagnosis of migraine and CH was assessed. RESULTS: Despite the absence of complaints, both patients demonstrated the limitation of the volume of neck movements during the tests performed by methods of manual medicine. After a course of manipulation procedures, headaches in both patients were completely stopped for a period of six to ten months. The analysis of literature suggests that manipulative effects on neck structures in cases of migraine can reduce the intensity and the duration of pain, and the frequency of attacks by no more than 20%. The therapeutic effectiveness of manual therapy for CH is much higher; this method provides an opportunity to reduce the severity of these pain characteristics by 30-80%. These results are the basis for changing the previously established diagnosis to CH. CONCLUSION: The complex of diagnostic and therapeutic techniques of manual therapy is an important tool for the differential diagnosis of migraine and CH.

[Characteristics of postoperative cerebral dysfunction depending on the type and position of the implanted prosthetic heart valve]. / Osobennosti posleoperatsionnoi mozgovoi disfunktsii v zavisimosti ot tipa i pozitsii implantiruemogo proteza klapana serdtsa.

AIM: To study the prevalence and structure of postoperative cerebral dysfunction depending on the type and position of the implanted prosthetic heart valve in patients who underwent surgery for the acquired heart valve disease. MATERIAL AND METHODS: The study included 115 patients (70 men and 45 women; 64 [56; 72] years old), who underwent elective replacement or repair surgery for the acquired heart valve disease. RESULTS AND CONCLUSION: The postoperative cerebral dysfunction was diagnosed in 40.9% patients, including replacement in the aortic position (45.5%), in the mitral position (55%), in several positions (20%). Replacement surgery was accompanied by three clinical types of postoperative cerebral dysfunction and repair surgery - by deferred cognitive impairment only. Postoperative cerebral dysfunction after the replacement in the mitral position was more common (odds ratio 4.47, 95% confidence interval 1.21-18.35, p=0.041), including its acute clinical types - perioperative stroke and symptomatic delirium of the early postoperative period (p=0.029), compared to that after the repair heart valve surgery. After the replacement in the aortic position, acute clinical types of postoperative cerebral dysfunction were more common (p=0.036). After the replacement with biological prosthesis, symptomatic delirium of the early postoperative period was more common (p=0.047). The occurrence of the deferred cognitive impairment didn't depend on the type and position of the implanted prosthetic heart valve.

[Eye as an object of investigation of cognitive impairment in Parkinson's disease]. / Organ zreniia kak ob''ekt izucheniia narushenii kognitivnykh funktsii pri bolezni Parkinsona.

AIM: To study visual and spatial disorders in Parkinson's disease (PD). MATERIAL AND METHODS: One hundred and eighteen patients with PD and 30 healthy people (the control group) were studied. All participants underwent neurological and ophthalmological examinations. PD progression was assessed using The Hoehn and Yahr scale. MMSE, FAB and other psychological tests were administered. Optical coherence tomography (OCT) and MRI of the brain were performed. RESULTS AND CONCLUSION: The relationship of the variation in the thickness of various parts of the retina and brain cortex with cognitive deficit that manifests itself as visual-spatial disturbances is shown. The complex diagnostic technique, including neuropsychological and instrumental method (OCT of the retina, MRI of the brain with MRI-morphometry), should be used.

Molecular genetic diagnostics of tuberous sclerosis complex in Bulgaria: six novel mutations in the TSC1 and TSC2 genes.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of hamartomas localized in various tissues which can occur in the skin, brain, kidney and other organs. TSC is caused by mutations in the TSC1 and TSC2 genes. Here we report the results from the first molecular testing of 16 Bulgarian patients and one Romanian patient in whom we found six novel mutations: four in the TSC22 gene, of which one is nonsense, two frame shift and one large deletion of 16 exons; and two in the TSC1 gene, one nonsense and other frame shift. In addition, we detected 10 previously reported mutations; some of which are described only once in the literature. Our data is similar to the previous studies with exception of the larger number of TSC1 mutations than that reported in the literature data. In total, 40% (4/10) of the mutation in the TSC2 gene are located in the GTPase-activating protein domain, while 50% (3/6) are in the TSC1 gene and clustered in exon 15. All the cases represent the typical clinical symptoms and meet the clinical criteria for TSC diagnosis. In 35% of our cases the family history was positive. Our results add novel findings in the genetic heterogeneity and pathogenesis of TSC. The genetic heterogeneity might correlate to the clinical variability among the TSC-affected families, which makes the genetic counselling a real challenge.

[Perioperative stroke in heart valve surgery: pathogenesis, clinical findings, diagnosis, prevention, treatment]. / Perioperatsionnyi mozgovoi insul't v khirurgii klapanov serdtsa: patogenez, klinika, diagnostika, lechenie i profilaktika.

AIM: To study risk factors, characteristics of clinical symptoms and diagnosis, and possibilities of prevention of perioperative stroke and other clinical types of cerebral dysfunction in main types of heart valve surgery. MATERIAL AND METHODS: The study included 83 patients, aged 63 (54; 70) years, undergoing heart valve surgery with cardiopulmonary bypass. RESULTS: Postoperative cerebral dysfunction was diagnosed in 37.3% of cases, including perioperative stroke in 3.6% of cases. In cases of aortic stenosis, the frequency of perioperative stroke was 9.5%. The cardioembolic subtype of perioperative ischemic stroke in cardiac valve surgery was most likely. The risk factors of the symptomatic delirium of the early postoperative period are: age over 75 years, preoperative frontal dysfunction, duration of artificial respiratory care more than 20 hours after the surgery. CONCLUSION: The results suggest the efficacy of preventive use of cytoflavin for reducing the frequency and severity of perioperative stroke and symptomatic delirium of the early postoperative period in heart valve surgery with cardiopulmonary bypass.

Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases. Homozygous p.G31A/EXOSC3 mutation was identified in 14 Roma patients, representing three fourths of all our SMN1-negative Roma SMA cases. The phenotype of the p.G31A/EXOSC3 homozygotes was compared to the clinical presentation of all reported to date genetically verified PCH1 cases. Signs of antenatal onset of disease present at birth were common in all PCH1 sub-types except in the homozygous p.D132A/EXOSC3 patients. The PCH1sub-types with early death (between ages 1 day and 17 months), seen in patients with p.G31A/EXOSC3 or SLC25A46 mutations have a SMA type 1-like clinical presentation but with global developmental delay, visual and hearing impairment, with or without microcephaly, nystagmus and optic atrophy. Mutations with milder presentation (homozygous p.D132A/EXOSC3 or VRK1) may display additionally signs of upper motor neuron impairment, dystonia or ataxia and die at age between 5 and 18 years. Other EXOSC3 mutations and EXOSC8 cases are intermediate - SMA type 1-like presentation, spasticity (mostly in EXOSC8) and death between 3 months and 5 years. There is no correlation between neurological onset and duration of life. We add marble-like skin and congenital laryngeal stridor as features of PCH1. We show that imaging signs of cerebellar and pontine hypoplasia may be missing early in infancy. EMG signs of anterior horn neuronopathy may be missing in PCH1 patients with SLC25A46 mutations. Thus, there is considerable phenotypic variability in PCH1, with some cases being more SMA-like, than PCH-like. Detailed clinical evaluation and ethnicity background may guide genetic testing and subsequent genetic counseling.

[Modern conception of the pathogenesis of neurodegenerative diseases and therapeutic strategy]. / Sovremennaia kontseptsiia patogeneza neirodegenerativnykh zabolevanii i strategiia terapii.

Here we discuss the pathogenesis of the inflammatory and degenerative nervous system disorders on the example of Parkinson's disease, Alzheimer's disease, multiple sclerosis. Common mechanisms of neurodegeneration in these diseases are reviewed. The role of neurodegeneration as the main process leading to the resistant disability of patients with multiple sclerosis is discussed. The authors consider a contribution of inflammatory process and chronic infection to the manifestation and progressing of a neurodegenerative disease and discuss the use of treatment not usually indicated including interferon, anti-inflammatory drugs, statin, vitamin D, monoclonal antibodies, correction of the intestinal microbiota in Parkinson's disease and Alzheimer's disease.

[Postoperative cerebral dysfunction]. / Posleoperatsionnaia mozgovaia disfunktsiia.

AIM: To study the structure, risk factors and methods of prevention of postoperative brain dysfunction on the example of coronary artery bypass surgery with cardiopulmonary bypass. MATERIAL AND METHODS: The study included 77 patients who undergone elective coronary artery bypass surgery at the beating heart (22 patients) or with cardiopulmonary bypass (55 patients, including 24 patients, who received cerebroprotective treatment with cytoflavin in the preoperative period). All patients underwent dynamic (pre- and postoperative) neurological, neuropsychological, instrumental examinations. RESULTS: The postoperative cerebral dysfunction was diagnosed in 34 (44,2%) patients. The frequency of the clinical types of postoperative cerebral dysfunction significantly differed: perioperative stroke - 3 (3,9%) cases, symptomatic delirium of the early postoperative period - 11 (14,3%) cases, delayed cognitive impairment - 28 (36,4%) cases. The risk factors of postoperative cerebral dysfunction after the coronary artery bypass surgery with cardiopulmonary bypass were identified. Preventive preoperative use of the neuroprotective drug cytoflavin reduces the severity of delayed cognitive impairment after the coronary artery bypass surgery with cardiopulmonary bypass and has a good safety profile. CONCLUSION: An analysis of the literature data and the results of our own studies show that postoperative cerebral dysfunction is the nosological entity with various etiological factors, pathogenetic mechanisms and the characteristic clinical types, which has an effect on the outcome of surgical treatment.