[Status epilepticus in a pregnant patient with a previously unrecognized POLG-associated disease]. / Epilepticheskii status u beremennoi patsientki s vpervye vyyavlennym POLG-assotsiirovannym zabolevaniem.

POLG-associated diseases are rare causes of pharmacoresistant epilepsy and status epilepticus, especially in adult patients. Phenotypic and genotypic variability in these conditions causes the complexity of their diagnosis. In the study, we report a case of a 33-year-old female patient who developed recurrent convulsive status epilepticus with focal clonic onset at the week 22/23 of pregnancy. Intensive anti-seizure therapy was administered, including the use of valproic acid, as well as the treatment of somatic complications. Given the acute onset, the semiology of seizures, the presence of psychopathological symptoms, autoimmune etiology of the disease was initially suspected. A month after the withdrawal of valproic acid, the patient began to show signs of toxic hepatitis, which eventually led to death. According to the results of whole-exome sequencing obtained later, the patient was a carrier of a pathogenic homozygous variant c.2243G>C (p.W748S) in the POLG gene. The presented case highlights the importance of molecular genetic testing and the risk associated with valproic acid hepatotoxicity in patients with cryptogenic epileptic status.

[Serum brain damage biomarkers as a diagnostic and prognostic tool in ischemic stroke]. / Syvorotochnye biomarkery porazheniya mozga kak diagnosticheskii i prognosticheskii instrument pri ishemicheskom insul'te.

OBJECTIVE: To study serum quantities of neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) and NR2-antibodies (NR2-ab) in various cerebrovascular pathology and assess their value as a panel used as a diagnostic and predictive tool for stroke. MATERIAL AND METHODS: NSE, GFAP and NR2-ab serum levels were measured twice for 84 patients with ischemic stroke (IS) and 8 patients with hemorrhagic stroke (HI), once for 8 patients with transient ischemic attack (TIA), 26 patients with chronic brain ischemia (CBI), 27 healthy volunteers (HV). RESULTS: NSE and GFAP levels were significantly higher in IS than in CBI and HV patients, and NR2-ab levels in IS were higher than in TIA and lower than in HV. In patients with more pronounced neurological deficiency and less favorable functional outcome by day 10-14 of IS, the levels of NSE, GFAP and NR2-ab were higher. Sensitivity and specificity of biomarker panel was higher than with their separate application. CONCLUSION: The NSE, GFAP and NR2-ab biomarkers have a diagnostic and predictive value for IS.

[Multiple system atrophy]. / Mul'tisistemnaya atrofiya.

The article presents a progressive neurodegenerative disease - multisystem atrophy, characterized by a combination of autonomic failure and various motor disorders, including parkinsonism and/or cerebellar ataxia; etiopathogenetic factors and variants of the clinical picture are described. We describe own clinical observation of a 59-old patient with cerebellar and bulbar syndromes, parkinsonism, pyramidal insufficiency, cognitive deficits, and autonomic dysfunction. The differential diagnosis included a whole range of neurodegenerative and hereditary diseases: Parkinson's disease, vascular parkinsonism, progressive supranuclear palsy, spinocerebellar ataxia, FXTAS, mitochondrial encephalopathies. The moderate severity of parkinsonism and the significant predominance of cerebellar symptoms and autonomic dysfunction make this clinical case difficult to diagnose. However, based on the life and disease history, clinical picture and research methods, a diagnosis of multiple system atrophy, cerebellar type (cerebellar, autonomic, bulbar syndrome, parkinsonism, pyramidal insufficiency and moderate cognitive impairment) was established. Differential search in such patients is a difficult task and includes a whole range of neurodegenerative and hereditary diseases due to the similarity of individual clinical and neuroimaging features and, unfortunately, the limited availability of molecular genetic diagnostic methods. However, earlier diagnosis is necessary to focus in time on the development of a personalized approach to the management of each such patient, taking into account the rate of symptoms development and steady progression, in order to ensure the longest possible survival time with an acceptable level of quality of life.

[Modern strategies of antithrombotic therapy in patients with multifocal atherosclerosis]. / Sovremennye strategii antitromboticheskoi terapii pri mul'tifokal'nom ateroskleroze.

The manuscript is devoted to the problem of selection of antithrombotic therapy in the management of patients with multifocal atherosclerosis. The leading role of cerebrovascular pathology in the structure of mortality and causes of disability is noted. The questions of etiology and pathogenesis of acute cerebrovascular accident are considered. The pathogenetic subtypes of ischemic stroke and the criteria for their diagnosis were analyzed. The important role of antithrombotic therapy in the prevention of noncardioembolic stroke is presented. Considering the evidence-based medicine data based on the analysis of randomized trials results, modern strategies of antithrombotic therapy were demonstrated. A comparative analysis of the clinical trials results was carried out. New ideas about the benefits of combination therapy with acetylsalicylic acid at a dose of 100 mg/day and with rivaroxaban 2.5 mg twice daily, established in the COMPASS study, are presented.

[Clinical features of temporal lobe epilepsy with involvement of the insular lobe]. / Klinicheskie osobennosti visochnoi epilepsii pri vovlechenii v protsess ostrovkovoi doli.

OBJECTIVE: To determine the clinical features of the course of the disease when the insular lobe is involved in the epileptic process. MATERIAL AND METHODS: A comparative analysis of the results of diagnosis and treatment of 55 patients with temporal lobe epilepsy and 46 patients with temporal plus epilepsy was carried out. The results of neuroimaging, clinical and EEG studies were compared. RESULTS: Autonomic paroxysms of nausea and hypersalivation, skin changes, simple motor seizures, emotional seizure and sensory paroxysms are the most reliable signs of the involvement of the insular lobe in the epileptic process in temporal plus epilepsy. For 'pure' temporal lobe epilepsy, cognitive paroxysms of the déjà vu and aura are common. When the insular lobe is involved in the epileptic process, the seizures have a reliably high frequency, polymorphism and are more complex by structure. CONCLUSION: Paroxysmal syndrome in temporal plus epilepsy with involvement of the insular lobe undergoes significant changes in the form of increased seizures and the appearance of specific seizures and characteristic polymorphism.

[Difficulties of cerebral toxoplasmosis diagnosis in a patient with multiple sclerosis and HIV]. / Trudnosti diagnostiki tserebral'nogo toksoplazmoza u patsientki s rasseyannym sklerozom i VICh-infektsiei.

Toxoplasmosis is a widespread parasitic disease. It is caused by an intracellular parasite Toxoplasma gondii. It can affect various tissues and organs, forming cysts and continuing to replicate within them. In people with intact immune system, tissue cysts remain in latent state throughout their whole life. However, in cases of cellular immunodeficiency the infection can be reactivated, which leads to secondary generalization of the process. People with HIV most commonly present with cerebral toxoplasmosis. Non-specific neuroimaging signs, as well as absence of pathognomonic symptoms and specific laboratory data lead to difficulties of cerebral toxoplasmosis diagnosis, particularly in the cases with a history of multiple sclerosis that has similar clinical symptoms and brain MRI data suggesting of tumefactive multiple sclerosis image. A clinical case of cerebral toxoplasmosis in a female patient with multiple sclerosis and HIV infection is described.

[Selective screening of patients with associated somatic diseases as a method of early detection of acromegaly].

Backgraund: Acromegaly is a multi-organ disabling disease, the effectiveness of treatment of which directly depends on timely diagnosis. Latent course and delayed diagnosis increase the exposure of pathological hypersecretion of growth hormone and insulin-like growth factor-1, contributing to the development of irreversible systemic and metabolic changes in the body that negatively affect survival. AIMS: The aim of the study was to clinically test a comprehensive diagnostic approach using selective screening to detect cases of acromegaly in patients with combined somatic diseases. MATERIALS AND METHODS: The diagnostic search algorithm included a 2-stage questionnaire, expert assessment of the clinical status, laboratory and instrumental examination. The inpatient examination included the use of additional laboratory and instrumental methods and expert evaluation of the results obtained by filling out a doctor's questionnaire. When the score was higher than 18 points, a more specific examination was performed: double determination of the insulin-like growth factor-1 level, oral glucose tolerance test with determination of the nadir of growth hormone value, and MRI of the brain with contrast enhancement. The diagnosis of acromegaly was made on the basis of personal data, expert assessment of the clinical status, results of laboratory and instrumental examinations. RESULTS: A survey of 1249 patients with combined systemic and metabolic disorders conducted using the point system allowed us to suspect acromegaly in 367 patients (29.4%), who were offered further examination. The majority of patients were previously seen by specialists for diabetes mellitus (79.3%) or thyroid pathology (10%). In the result of inpatient -examination of 329 patients, 35 (10.6%) patients showed an increase in the blood level of IGF-I. In 19 patients, a persistent increase in the level of IGF-I was combined with the absence of GH suppression of less than 0.4 ng/ml against the background of glucose load. During MRI in 9 patients, pituitary adenoma was detected (in 2 - microadenoma and 7 - -macroadenoma). CONCLUSIONS: As a result of the study, among the group of 1249 patients (mean age 58±13 years) with the presence of concomitant diseases, 9 newly identified patients with acromegaly were found who were prescribed adequate treatment. The introduction of selective screening technology into the practice of an endocrinologist will improve the effectiveness of diagnostic search for patients with acromegaly, more accurately assess the prevalence of the disease in Russia and the need for specialized medical care.

[Transverse myelitis syndrom as a result of neuromyelitis optica spectrum disorders, systemic lupus erythematosus and myasthenia gravis combination]. / Sindrom perechnogo mielita v rezul'tate sochetaniya zabolevaniya spektra neirooptikomielita, sistemnoi krasnoi volchanki i miastenii gravis.

Neuromyelitis optica spectrum disorders (NMOSD) - autoimmune condition characterized by an inflammatory lesions mainly of the spinal cord with the development of longitudinally extensive transverse myelitis (LETM) and/or involvement of the optic nerve with the development of usually bilateral optical neuritis (ON). In recent years, there has been increased awareness that NMOSD can be combined with other autoimmune diseases, including myasthenia gravis (MG), systemic lupus erythematosus (SLE) et al. The simultaneous presence of several autoimmune diseases in one patient can adversely affect the course of each of the diseases, causing the so-called mutual burden or «overlap syndrome¼. In this article, we describe our own clinical observation of a 51-year-old woman of European origin who developed acute relapsing TM seropositive for AQP4-IgG, by 23 years after the diagnosis of generalized MG seropositive for antibodies to acetylcholine receptors (AChR-Ab) and the occurrence of SLE, criterially confirmed, several months after the initial TM attack. During the fourth TM attack, partial positive dynamics was achieved only against the background of the combined use of intravenous methylprednisolone (pulse therapy), high-volume plasma exchange, rituximab and cyclophosphamide. The NMOSD is a rare disease leading to severe disability. In patients with MG, when symptoms of damage to the central nervous system appear, an analysis should be performed for AQP4-IgG and possibly for antibodies to myelin glycoprotein of oligodendrocytes (MOG-Ab), as well as markers characteristic of systemic connective tissue diseases (SCTD). In patients with STDD, when symptoms of involvement nervous systemappear, testing for AQP4-IgG (and, if necessary, for MOG-Ab) should be performed to exclude NMOSD, as well as AChR-Ab (and, if necessary, antibodies against muscle specific kinase (MuSK-Ab)) to exclude MG.

[Clinical, structural and functional features of paroxismal syndrome in insular and temporal lobe tumors]. / Klinicheskie i strukturno-funktsional'nye osobennosti paroksizmal'nykh rasstroistv, obuslovlennykh opukholyami ostrovkovoi i visochnoi dolei.

OBJECTIVE: To analyze the characteristics of paroxysmal syndrome in insular and temporal lobe tumors, to determine their relationship with the histological structure of tumor, to assess the effect of tumor growth nature on severity of disease. MATERIAL AND METHODS: A retrospective analysis enrolled 80 patients aged 11 - 80 years with insular and temporal lobe tumors and symptomatic epilepsy. All patients underwent surgery at the Polenov National Research Neurosurgery Center in Almazov National Medical Research Center for the period from 2012 to 2018. RESULTS: The main group consisted of 29 patients with tumors of temporal and insular lobes. Control group of 51 patients with temporal gliomas was formed for comparative analysis. It was found that involvement of insular lobe into paroxysmal syndrome is characterized by attacks with a motor component, somatosensory paroxysms, vegetative manifestations (respiratory attacks, salivation, nausea), speech disorders and taste hallucinations. Derealization, motor arrest and déjà vu/jamis vu paroxysms were more common in patients with temporal lobe lesion. Neoplastic lesion of the insular lobe shortens the period between manifestation of paroxysms and surgical treatment. Moreover, this type of disease is characterized by higher incidence of seizures compared to isolated temporal lobe tumors.

[Virus-induced opsoclonus-myoclonus syndrome during pregnancy]. / Virus-indutsirovannyi sindrom opsoklonusa-mioklonusa pri beremennosti.

Opsoclonus-myoclonus syndrome (OMS) is a very rare condition with various etiologies (paraneoplastic, parainfectious, toxic, idiopathic, etc.) with an autoimmune pathogenetic mechanism of development. The authors describe the case of OMS in a 41-year-old woman at 37 weeks of gestation, who developed opsoclonus, myoclonus, severe trunk ataxia, tremor and bilateral pyramidal symptoms, inability to sit, stand and walk without support. Differential diagnosis was conducted between virus-induced OMS, rotavirus encephalitis, paraneoplastic syndrome, and demyelinating diseases of the central nervous system. Routine laboratory tests of blood and urine, serological tests of blood and cerebrospinal fluid (CSF) revealed no pathology. Only small lymphocytic pleocytosis and a slight increase in protein were observed in CSF. No pathology was detected during magnetic resonance imaging. On the 40th week of pregnancy (20th day of illness), the patient gave birth to a healthy full-term baby through the birth canal. In view of the most likely autoimmune process triggered by rotavirus infection, intravenous immunosuppressive therapy with methylprednisolone (1000 mg/day №3) was performed, followed by switching to prednisolone per os (60 mg/kg/day), as well as neuroprotective and neurometabolic therapy with cytoflavin. On day 42 of the illness (and on day 20 of the immunosuppressive therapy), a significant positive trend was noted. The patient was discharged on day 56 with light residual elements of opsoclonus and ataxia, and could walk independently without support. Thus, in case of suspected OMS, it is necessary to conduct a mandatory full diagnostic search, especially aimed at exclusion of the paraneoplastic process. And also, given the possibility of recurrence, further outpatient monitoring of these patients should be carried out.

[The possibility of using neuron-specific enolase as a biomarker in the acute period of stroke]. / Vozmozhnost' ispol'zovaniia neiron-spetsificheskoi enolazy kak biomarkera v ostrom periode insul'ta.

The article presents a review of the literature on neuron-specific enolase (NSE) as a biomarker of stroke. It is shown that NSE does not allow differentiation of the ischemic and hemorrhagic process in stroke, but is suitable for determining the extent of brain tissue destruction both in the first hours of stroke and in the dynamics. The HSE analysis can be useful for monitoring the course of the disease, control of the dynamics of the pathological process, including when the size of the lesion increases, for evaluating the effectiveness of therapy and as a prognostic biomarker.

Impact of autoimmune comorbidity on fatigue, sleepiness and mood in myasthenia gravis.

BACKGROUND: Disease burden in myasthenia gravis (MG) and in other autoimmune disorders is often determined by common accompanying symptoms such as fatigue, sleepiness and mood disturbances. Many MG patients have a second autoimmune disease, but it is unclear whether autoimmune comorbidities add to the severity of fatigue, sleepiness and mood disturbances. METHODS: We ascertained the presence of autoimmune comorbidities in 69 well-characterized MG patients. To assess fatigue, sleepiness and mood disturbances, we applied the Fatigue Severity Scale (FSS), the Fatigue Impact Scale (FIS), the Epworth Sleepiness Scale (ESS), as well as the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) to all patients. RESULTS: Thirteen MG patients had concomitant autoimmune thyroid disease (AITD), including 1 patient with rheumatoid arthritis as third autoimmune disease. Fatigue (68.1%), excessive daytime sleepiness (14.5%), moderate-severe depression (20.3%) and anxiety (26.1%) were common, but MG patients with and without autoimmune comorbidities had similar FSS, FIS, ESS, BDI and STAI scores. The presence of autoimmune comorbidities was not associated with altered clinical and immunological MG characteristics, but MG patients with autoimmune comorbidities have more often been treated with corticosteroids than patients without autoimmune comorbidities (92.3% vs. 60.7%; p = 0.03). CONCLUSIONS: While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the present study does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity.

Fatigue in patients with myasthenia gravis.

BACKGROUND: The subjective feeling of fatigue in myasthenia gravis (MG) is poorly elucidated, in part because it is often confounded with the objective sign of muscle fatigability. Another reason is the paucity of validated fatigue questionnaires in MG. METHODS: We applied the 9-item Fatigue Severity Scale (FSS) and the 40-item Fatigue Impact Scale (FIS) to 73 MG patients and 230 age- and sex-matched control subjects. We ascertained levels of education, marital status, and comorbidities such as depression, sleepiness, sleep times and sleep debt. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. RESULTS: All fatigue scores, with the exception of the cognitive FIS subscale, were higher in MG patients than controls. In MG, the prevalence of fatigue (defined by FSS scores ≥ 4.0) was 70%. Multiple regression analyses revealed several independent associates of fatigue, including depression (all fatigue scales), MGFA stage (FSS, physical FIS), female sex (cognitive and psychosocial FIS), and sleep debt (physical FIS). CONCLUSION: Fatigue in MG is highly prevalent, mainly physical, and influenced by depressive symptoms, disease severity, female sex and sleep debt. Cognitive fatigue in MG may not be a direct disease manifestation, but secondary to depression. The FSS and FIS represent reliable and validated tools, appropriate to discern meaningful clinical aspects of fatigue in MG. Clinical recognition of the complexity of fatigue may foster individualized treatment approaches for affected MG patients.

[Ultrasound-guided percutaneous cryoablation of renal tumors].

INTRODUCTION: Surgery remains the gold-standard curative treatment for localized (T1) renal carcinoma. However, recent medical-technological advances have led to the development of new minimally invasive treatment options, one of which is percutaneous cryoablation. AIM: To assess the effectiveness and safety of ultrasound-guided percutaneous cryoablation of renal tumors. MATERIALS AND METHODS: The study comprised 12 patients aged 52 to 76 years who underwent ultrasound-guided percutaneous cryoablation of renal tumors from 2015 to 2017. In 11 patients, the size of the renal mass was 3.0 cm (T1a), in 1 patient 4.5 cm (T1b). A Doppler ultrasound, contrast-enhanced MSCT and computer 3D modeling were performed in all patients pre-operatively and 6 months after surgery to assess the tumors size and extent and the spatial location of the tumor internal surface to the pelvicalyceal system. In all patients, the tumors were located along the posterior or lateral surface of the kidney, in the lower or middle segment and without sinus invasion. We used a 3rd generation Galil Medicals SeedNet Gold Cryotherapy System and IceSeed and IceRod cryoprobes. Intraoperatively, immediately before cryoablation, the tumor was biopsied. In all patients the diagnosis of renal cell carcinoma was confirmed morphologically. RESULTS: Mean duration of cryoablation was 60 minutes. Endotracheal, spinal, local and intravenous anesthesia was used in 1, 6, 5 and 1 patients, respectively. Doppler ultrasound at 6 months after surgery showed that in 11 patients (T1a) the tumor size decreased on average by 8 mm, with no blood flow in the tumors. MSCT with 3D modeling also revealed a decrease in tumor size and total absence of contrast agent accumulation, or accumulation gradient not exceeding 10 HU (initially it was about 200 HU). In the patient with T1b stage renal carcinoma, MSCT showed a decrease in tumor size from 4.5 to 3.7 cm, however, there was a mass up to 1.5 cm with a high gradient of contrast agent accumulation. The patient underwent kidney resection. No intra- and postoperative complications were observed. CONCLUSION: The accumulated experience allows to confirm the effectiveness and safety of ultrasound-guided percutaneous cryoablation and to consider it a method of choice for patients with stage T1a renal carcinoma located along the posterior or lateral surface of the kidney in the lower or middle segment, without sinus invasion.

[Clinical and neurologic characteristic and principles of therapy of late-onset Myasthenia gravis].

In the present work the results of the clinic-epidemiological analysis of 223 patients with the onset of the myasthenia at 60 y. o. and later, admitted and treated in the clinic of neurology for the passed 25years are represented. A dynamic growth of incidence of the late-onset myasthenia through the passed 10 years was administered. We administered a prevalence of the generalized form of the myasthenia gravis (61,5 %). The whole clinical table of the myasthenia was developed during an year in 76,7 % of the cases. A wide range of the concomitant somatic pathology in this group of the patients (especially, with a cardio-vascular pathology - 93,3 %) was found to worsen the course of the myasthenia itself. We found that the set of the therapeutic measures in myasthenia in the elderly is determined by the course of the myasthenia and the multiple organ failure due to the concomitant diseases. The scheme of complex corrective therapy of myasthenia gravis in elderly was developed.