[Factors of the hemostasis system as biomarkers of severe course of acute viral infections]. / Faktory sistemy gemostaza kak biomarkery tyazhelogo techeniya ostrykh virusnykh infektsii.

The authors give literature review of hemostasis and immune system factors intraction as main biomarkers of a severe cause of viral infectious diseases. Pro-inflamatory cytokines as the main markers of inflammation, can serve both as biomarkers of the clinical severity of the infectious process and reflect the state of the hemostatic and fibrinolytic systems, since components of these systems are present in various structures of the central nervous system and affect the development of neurons and synaptic plasticity. An inverse correlation has been proven between the concentration of D-dimer and the oxygenation index, and the development of DIC is not associated with the presence of respiratory failure in patients with influenza type A, while the ferritin concentration directly reflects the severity of the disease. One of the markers of endothelial damage may be soluble thrombomodulin, which, however, is rarely used in routine clinical practice. Cytoflavin is a highly effective pathogenetic drug that affects various parts of the hemostasis system, has anti-ischemic, antioxidant, antihypoxic, immunocorrective effect, which is indicated for any generalized infectious disease since its debut.

[Difficulties in diagnosing the chronic course of tick-borne encephalitis in children]. / Trudnosti diagnostiki khronicheskogo techeniya kleshchevogo entsefalita u detei.

Infections transmitted by ixodic ticks in childhood account for about 20%, and tick-borne encephalitis accounts for up to 25% of cases. A feature of the course of tick-borne encephalitis is unpredictability and the possibility of chronization in 1-3% of cases with late diagnosis and inadequate therapy. The article presents a clinical observation of the disease in a child whose chronically progressive course of amyotrophic form was diagnosed 1 year and 8 months after the onset of the disease. The presence of anamnestic data, features of clinical manifestations in the dynamics and typical neurovirualization picture of the disease, even with negative results of serological and molecular genetic studies of blood and cerebrospinal fluid, allowed to make a diagnosis, prescribe etio-pathogenetic therapy and thereby stabilize the patient's condition. The use of complex drugs in the treatment, such as Cytoflavin, allows to optimize the course of the disease.

[Immunopatological and genetic aspects of pathogenesis of CNS lesions in VZV infection]. / Immunopatologicheskie i geneticheskie aspekty patogeneza porazhenii TsNS pri VZV-infektsii.

The review article provides information about the features of the Varicella-zoster virus (VZV), about the clinical manifestations of CNS damage in acute and chronic VZV infection in children and adults, about the mechanisms of interaction of the pathogen with the immune system during the development of the disease. The question of whether to consider neurological disorders in VZV infection as a complication or manifestation of the disease caused by a defective virus or the presence of subclinical immunodeficiency is discussed, which is confirmed by modern scientific studies. The critical mechanisms of immune defense against VZV, which are the main reason for the penetration of the virus into the CNS and the development of neurological disorders, as well as the relationship between VZV genotypes, the presence of mutations in the gE gene and the nature of the course, the identification of rare variants of the POLR3A, POLR3C, POLR3E and POLR3F genes associated with violation of IFNs induction, and the development of severe VZV infection, in which vasculopathy also occurs, which is the basis for the use of vascular drugs of complex action, such as Cytoflavin, the effectiveness of which has been proven by the authors. A special place is given to the analysis of intrathecal immunopathogenesis, which is likely to be associated with the presence and severity of neurological manifestations, their relapses. The issue of the causes of the development of a severe course of the disease in patients vaccinated against chickenpox, as well as the issue of resistance to specific antiviral drugs, probably associated with the presence of mutations responsible for the resistance of the virus to therapy, is discussed.

[Modern concepts on the pathogenesis of neuroborreliosis]. / Sovremennye predstavleniya o patogeneze neiroborrelioza.

The analysis of publications on the websites PubMed, ClinicalKey, devoted to the pathogenesis of neuroborreliosis (NB), using keywords for search: «pathogenesis of neuroborreliosis¼, «neuroborreliosis in children¼, «pathogenesis of Lyme disease¼, as well as an analysis of the results of the published research results of the staff of the Research Institute of Pediatric Infections, St-Petersburg, Russia is presented. Syndromes of early and late NB are more often observed among the forms without migrating erythema, and their development can be caused by all representatives of the species B. burgdorferi s.l. (B.b.), but more often - B. garinii, since it most effectively suppresses the factors of innate and adaptive immune response, reducing interferon production, phagocytosis and complement synthesis. The cause of immunosuppression with the development of NB may be simultaneous infection with several genovids and borrelia species or pathogens of other infections transmitted by Ixodes ticks, for example, infection with B.b. and tick-borne encephalitis virus. The ability to move along peripheral nerves, the change of surface antigens of the VlsE protein, as well as the formation of atypical cysts and granular forms allows B.b. to affect different structures of the peripheral and central nervous system, avoid an immune response and persist for a long time, causing chronic neuroinfection. Both the B.b. themselves, capable of being outside and inside glial cells and neurons, and inflammatory reactions developing in response to their introduction and associated with the synthesis of cytokines and chemokines and mimicry, cause damage to the vascular endothelium, vasculitis and impaired blood supply to the brain, demyelination, autoimmune inflammation and degeneration, leading to the development of NB syndromes, the spectrum of which varies depending on the duration of neuroinfection. In the development of NB and its outcomes, the following are also important: early initiation of treatment, the effectiveness of antibacterial drugs, the use of immunotropic agents that optimize the patient's immune response to the fight against neuroinfection, as well as the timely use of pathogenetic drugs, such as Cytoflavin, which have a complex effect on the vascular endothelium.

[Structural epilepsy or herpes simplex encephalitis relapse: diagnostic problems]. / Strukturnaya epilepsiya ili retsidiv gerpeticheskogo entsefalita: diagnosticheskie trudnosti.

The article gives the clinical case of herpes simplex encephalitis relapse with the resistant seizures in a child. What we describe is a clinical approach towards the differential diagnostic of the seizures in structural epilepsy, which are resistant to anticonvulsants, or late herpes simplex encephalitis relapse. Good clinical perspective may be the indication of the intratecal synthesis of the IgG-specific antibodies to the herpes simplex type 1 and 2. Conducting etiotropic treatment with the appointment of acyclovir and pathogenetic therapy with the use of Cytoflavin contributed to the rapid and stable remission of epileptic seizures and regression of neurological deficit.

[Herpesviruses and biomarkers in disseminated encephalomyelitis and multiple sclerosis in children (part II)]. / Gerpesvirusy i biomarkery pri disseminirovannom entsefalomielite i rasseyannom skleroze u detei (chast' II).

Recently, the problem of demyelinating diseases in children is still very acute. This occurs, on the one hand, by high access and specificity of diagnostic methods and, on the other hand - by high morbidity of children different neuroinfectious diseases which can lead to demyelinating diseases. This literature review presents the currently available information on the autoantibodies and neurospecific protein role in the development of multiple sclerosis and acute disseminative encephalitis in children. The authors also describe their experience of complex etiopatogenic therapy and cytoflavin use that helps to reduce frequency and expression of demyelinating process and endothelium dysfunction in case of active herpesvirus infection.

[Herpesviruses and biomarkers in disseminated encephalomyelitis and multiple sclerosis in children]. / Gerpesvirusy i biomarkery pri disseminirovannom entsefalomielite i rasseyannom skleroze u detei.

The relevance of the study of demyelinating diseases is due to their increasing frequency in children, clarification of the role of infectious agents in their genesis, as well as the possibility of transformation of disseminated encephalomyelitis into multiple sclerosis. The literature review presents the currently available information on the causes of the development of demyelinating diseases, biomarkers of disseminated encephalomyelitis and multiple sclerosis, the causes of an unfavorable course and possible laboratory parameters indicating the transition from one disease to another, which can be used as prognostic factors. The authors also noted the experience of the authors on the importance of adequate etiopathogenetic therapy in changing the nature of the course of the disease, in particular, when confirming the relationship between the frequency of exacerbations of ADEM and MS with the activation of herpesvirus infections, courses of specific antiviral therapy are effective, as well as pathogenetic therapy aimed at correcting endothelial dysfunction using the drug cytoflavin.

[The efficacy of anti-viral therapy and serotherapy of tick-borne encephalitis in children]. / Effektivnost' protivovirusnoi terapii i seroterapii kleshchevogo entsefalita u detei.

OBJECTIVE: To evaluate the efficacy of different methods of antivirus therapy of tick-borne encephalitis (TBE) in children in the acute period and during chronic infections. MATERIAL AND METHODS: During 1 year, 130 children, aged 7-17 years, with TBEV received therapy in the acute period (an average in 3.5±1.3 days) in groups 1 (n=84) and 2 (n=20), and in the chronic infection in groups 3 (n=15) and 4 (n=11). Ribavirin orally, recombinant interferon-α2 (IFN-α2) i/m or in suppositories and anaferon orally were prescribed to children of groups 1 and 3. Children of groups 2 and 4 received tick-borne immunoglobulin (IgG)i/m and ribonuclease i/m. At admission, all patients received infusions of cytoflavin in the drip at the rate of 0.6 ml/kg per day. Etiological diagnosis included ELISA (IgM, G, viral antigen), and virus RNA by PCR in the blood and CSF. MRI of the brain and cervical spinal cord using standard programs was performed. All studies were performed prior to and in the course of treatment. RESULTS AND CONCLUSION: In patients of group 1, the period of increase in symptoms was reduced by ~ 4 days, and the duration of impairment of consciousness and pleocytosis in CSF ~ by 5 days, which was accompanied by a faster clearance of the virus in CSF, compared with group 2. In group 1, recovery without neurological deficit was observed in 83.3% (n=70), all patients had no progression of infection. In group 2, 30% of children (n=6) acquired TBEV chronic infection, and in 55% (n=11) there was a neurological deficit without progression. In patients of group 3 with chronic TBEV, the improvement was observed in 86.7% of cases, and complete regression of symptoms occurred in 1 patient, and replication of the virus was arrested in all of them. In group 4, symptoms increased in 72.7%, while virus replication was preserved and atrophic changes in the CNS increased on MRI. Antiviral therapy (ribavirin, IFN-α2 and release of active antibodies to gamma interferon -anaferon children) has the highest efficacy when prescribed for the first 5 days, while IgG and ribonuclease have insufficient efficacy in TBEV.

[Panencephalitis in children in modern conditions: clinical, etiological and mri-aspects]. / Panéntsefality u detei v sovremennykh usloviiakh: kliniko-étiologicheskie i MRT-aspekty.

AIM: To characterize the clinical picture, infectious etiology and MRI results of panencephalitis (PANE) in children, depending on the duration of the disease. MATERIAL AND METHODS: Children (n=32) with PANE at the age from 3 months up to 17 years were examined for a group of actual viral and bacterial infections. The inclusion criterion was a diffuse lesion of white matter hemispheres on MRI. MRI of the brain and spinal cord, CSF study (pleocytosis, oligoclonal IgG, the main myelin protein (MBP) were performed. The follow-up was 5-10 years. The complex therapy included etiotropic (antiviral) and pathogenetic agents, with priority given to cytoflavin as a drug with a multimodal effect. RESULTS: In 84.4% of cases, PANE in children are recorded under the age of 3 years and in 71.9% of cases, are associated with congenital infections with the prevalence of herpes viruses, especially cytomegalovirus (37,8%) and herpes type 6 (21.9%). In 78.3% of cases, PANE have chronic gradual development more often with a delay in the formation of motor and speech/prespeech skills, and manifested with pyramidal, cerebellar and other symptoms in the future. PANE is accompanied by a lesion of the white matter of the hemispheres in 1/2 cases with periventricular localization, less often in infratentorial structures (46.9%) and spinal cord (21.9%). With the duration of symptoms up to 3 months (n=22) PANE are characterized by inflammatory-demyelinating changes, signs of mass effect, contrast+, pleocytosis in CSF and the increase in MBP (average 4.2±0.8 ng/ml), and, with the duration of more than 3 months, by degenerative-sclerosing changes (n=10) and CSF oligoclonal IgG in 90% of cases. CONCLUSION: In almost 2/3 of cases, PANE are associated with congenital infections, accompanied by extensive symmetrical foci of demyelination in the CNS, and their clinical and laboratory parameters and outcomes depend on the start of treatment, with the positive dynamics in 75% of cases.

[Difficulties of differential diagnosis of organic injury of the nervous system in children]. / Trudnosti differentsial'noi diagnostiki organicheskogo porazheniia nervnoi sistemy u detei.

The growth of organic lesions of the central nervous system (CNS) in children, clinical polymorphism, the similarity of clinical and laboratory parameters in inflammatory, demyelinating and oncological diseases necessitate careful differential diagnosis. The clinical case presented in the article confirms the difficulties of differential diagnosis of organic CNS lesion in children, and therefore it is urgent to expand the indications for a brain biopsy, which will allow to timely diagnose correctly, avoid an erroneous diagnostic search and develop adequate tactics.

[Cytoflavin efficacy in the treatment of disseminated encephalomyelitis in children]. / Éffektivnost' tsitoflavina pri disseminirovannykh éntsefalomielitakh u detei.

AIM: To evaluate the efficacy of cytoflavin in the complex therapy of disseminated encephalomyelitis in children. MATERIAL AND METHODS: A blind, placebo - controlled, randomized study was carried out. Thirty-two patients, aged form 1 to 17 years, received cytoflavin from the first day after admission in intravenous drips in 5% glucose solution during 10 days. The control group consisted of 30 children who received a standard infusion therapy. Clinical and laboratory evaluation was carried out on the 11th and 30th days, MRT was performed before hospitalization and on the 30th day. RESULTS AND CONCLUSION: Cytoflavin had a positive effect on the rate of recovery of the majority of neurological symptoms. The average EDSS score decreased by 1.5 times to the 30th day compared with the control group. The complete regression of clinical symptoms and focal changes on MRI on the 30th day was observed in 25% of children of the main group and in 3.3% in the control group (р=0.001). The drug exerted the endothelium protective and antioxidant effects, improved blood rheology and restored the content of circulating endothelial cells, the level of D-dimer and indicators of free radical oxidation to the 30th day of treatment.