["Ictal" Bradyarrhythmias in Patients with Drug-Resistant Epilepsy: Results of Long-Term Heart Rhythm Monitoring].

Aim      To determine the type and incidence of ictal bradyarrhythmias in patients with drug-resistant types of epilepsy by long-term electrocardiogram (ECG) monitoring.Material and methods  Subcutaneous ECG monitors programed for recording pauses >3 sec and episodes of bradycardia ≤45 bpm were implanted in 193 patients with persistent epileptic seizures without organic pathology of the myocardium. Recording was activated by the patient/family at the onset of epileptic seizure. The follow-up period was 36 months with visits to the clinic every three months.Results For 36 months of monitoring, 6494 ECG fragments were recorded. Ictal bradycardia was observed in 6.7 % of patients, including ictal asystole in 2.6 % of patients. Episodes of bradycardia and asystole during epileptic seizures were transient and developed significantly more frequently in men, patients with long duration of the disease, bilateral tonic-clonic or focal seizures with disorder of consciousness, during sleep, on the background of treatment with several antiepileptic agents, mostly from the group of potassium channel blockers.Conclusion      Bradyarrhythmias accompanying epileptic seizures are transient and reproducible from seizure to seizure. They reflect functional changes in the myocardium and do not determine the life prediction for patients with epilepsy without organic pathology of the heart.

[Study of the practice of prescribing phenosanic acid in epilepsy accompanied by asthenic disorders]. / Izuchenie effektivnosti primeneniya fenozanovoi kisloty pri epilepsii, soprovozhdayushcheisya astenicheskimi narusheniyami.

OBJECTIVE: To evaluate the experience of prescribing phenosanic acid in the practice of a neurologist/epileptologist when prescribing the second, third anticonvulsant drug (AED) as part of combination therapy for patients with manifestations of fatigue due to epilepsy. MATERIAL AND METHODS: 501 patients with focal epilepsy accompanied by asthenic disorders were included in the observational program. The observation program protocol included 5 visits, including visit 1, at which screening and inclusion in the OP took place. The observation period was 10 months. At baseline and at the end of the 10-month follow-up, the patients' condition was assessed according to the following indicators: frequency and transformation of attacks with focal onset, severity of fatigue (self-assessment scale MFI-20); quality of life (questionnaire QoLiE-10-P); frequency of attacks with focal onset. The safety of phenosanic acid (Dibufelon) was also assessed. RESULTS: In 10 months after the inclusion of Dibufelon as the 2nd, 3rd AED in the treatment regimen, a statistically significant (p<0.01) decrease in the frequency of seizures was observed: in general - in 88% of patients; by 50% or more - in 76% of patients; transition from the group with a large number of seizures to the group with a smaller number of seizures - 74% of patients. Also when taking phenosanic acid, a positive dynamics of seizure type was noted: a reliable decrease in the proportion of patients with seizures with secondary generalization from 70% to 56%; a decrease in the number of focal seizures with impaired consciousness from 65% to 53%. In addition, there was a 38% decrease in the severity of fatigue on the MFI-20 scale (the greatest decrease on the «Mental fatigue¼ scale), improvement in the quality of life - a 2.7-fold increase in the mean values of the QOLIE-10 questionnaire. CONCLUSION: The addition of phenosanic acid to antiepileptic therapy as a second or third AED allows for better control of seizures, leading to a decrease the frequency and severity of attacks and the severity of fatigue both, and an increase of the quality of life of patients with epilepsy.

[EEG changes in patients with Alzheimer's disease]. / Izmeneniya elektroentsefalogrammy u patsientov s bolezn'yu Al'tsgeimera.

The prevalence of cognitive impairment is steadily increasing compared to previous years. According to the World Health Organization, the number of people living with dementia will increase reaching 82 million in 2030 and 152 million in 2050. The most common cause is Alzheimer's disease (AD). The pathophysiological process in AD begins several years before the onset of clinical symptoms; so identifying it at an early stage would likely improve the clinical prognosis. The article presents EEG changes in patients with AD, and discusses the possibility of using EEG as a screening method for examining patients with cognitive impairment.

[Epilepsy syndromes associated with hearing loss]. / Epilepticheskie sindromy, assotsiirovannye so snizheniem slukha.

Patients with epilepsy who have also hearing loss represent a distinct group of patients, often with aggravated medical history, comorbidities and high potential for disability. The etiopathogenetic factors of epilepsy and hearing loss may be common to these conditions (neuroinfections, craniocerebral injuries, cerebral circulatory disorders, perinatal pathology, etc.). In addition, these two syndromes may occur as part of hereditary diseases, so their timely recognition and genetic diagnosis are important for determining further medical and genetic prognosis. This article provides an overview of orphan genetic diseases associated with epilepsy and hearing loss - MERRF syndrome, MELAS syndrome, EAST syndrome, Ayme-Grippsyndrome, epilepsy, hearing loss and mental retardation syndromes, associated with mutations in SPATA5 gene, DOOR syndrome, Gustavson syndrome.

[COVID-19-associated damage of the peripheral nervous system]. / COVID-19-assotsiirovannye porazheniya perifericheskoi nervnoi sistemy.

Based on the available literature data, the article discusses the prevalence of various forms of damage of the peripheral nervous system in COVID-19 and in the post-COVID period. Information about the clinical features and the course of individual cranial neuropathies, chronic dysimmune neuropathies, Guillain-Barré syndrome, drug-induced neuropathies, fine fiber neuropathy, myasthenia gravis and polyneuropathy of critical conditions was systemized in the context of coronavirus infection. SARS-CoV-2 can trigger various stages of pathogenesis, including neuroimmune ones, which cause long-term consequences of COVID-19, including those associated with the damage of the peripheral nervous system. Awareness of COVID-19-associated pathological conditions will allow assessment of the possible risks of damage of the peripheral nervous system, recognize them at early stages and develop more effective approaches for treatment.

[Molecular genetic mechanisms of individual sensitivity to synthetic fatty acids in case of valproic acid].

Individual sensitivity to structural analogues of free fatty acids (FFA), some of which are endocrine destructors, resulting in hormonal metabolic disturbances, was studied using valproic acid (VA) as an example. The individual sensitivity was considered by the example of polymorphism in the PPAR@g2 gene. The homozygous genotype Pro12Pro of this gene was proved to be responsible for weight gain and development of insulin resistance during VA administration, which should be kept in mind when developing the safe levels of exposure to FFA-like substances.

[Healthcare of Russia today. Epileptological service]. / Zdravookhranenie Rossii segodnya. Epileptologicheskaya sluzhba.

OBJECTIVE: To examine the state of the epileptological service in Russia by conducting a survey of epileptologists working in different regions of the Russian Federation. MATERIAL AND METHODS: To assess the structure and mechanisms of the antiepileptic service in the Russian Federation, the Russian League Against Epilepsy (RLAE) offered a questionnaire to 63 epileptologists, which has been answered by 37 epileptologists from 28 regions of the country. RESULTS AND CONCLUSION: Among the respondents, 43% are focused on the care of outpatients, 35% work both in outpatient and inpatient appointments, 22% work only in hospitals. 24% of doctors are employees of neurological departments. 84% of epileptologists noted the neurological profile of their medical institution. The most common patient routing options were: «therapist-neurologist-epileptologist¼ (59%), «Neurologist-epileptologist¼ (81%), self-referral to an epileptologist (22%), «Psychiatrist-epileptologist¼ (16%). 59.5% of epileptologists work with adults and with children. 27% of respondents noted that they work with psychiatric patients. Interaction between the departments of neurology and practical health care is carried out in the form of consultations and training events, as noted by 68% of epileptologists. 73% of the epileptologist reported the willingness to actively interact with the RLAE. 54% of the respondents conduct socially oriented schools for patients and their relatives. In the context of the planned reorganization of the health care system, the epileptologists gave the outlook on the work of the epileptological service. CONCLUSION: The main initiatives mentioned by the respondents were the following increasing the availability of medicines and examination methods, increase of continuity in the work of the epileptological service, creation of unified databases, creation of specialized epileptological centers and/or offices of epileptologists.

[Clinical results and prospects for the use of phenosanic acid in patients with focal epilepsy]. / Klinicheskie rezul'taty i perspektivy primeneniya fenozanovoi kisloty u vzroslykh patsientov s fokal'noi epilepsiei.

OBJECTIVE: To study the efficacy and safety of using a new original synthetic antioxidant - phenosanic acid as an adjunct therapy in patients with focal epilepsy. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy and safety of phenosanic acid as an adjunct therapy to basic antiepileptic drugs in 120 patients with focal epilepsy. Primary purpose: to study the dynamic of seizure frequency. Secondary purposes: to study the dynamic of seizure-free days, the dynamics of bilateral tonic-clonic seizures, the results of questionnaires and scales (General Dynamics Assessment, Visual Analogue Scale (VAS), Quality of Life in Epilepsy (QOLIE-31-P), European Quality of Life Questionnaire (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Frontal Asstssment Battery (FAB), Mini-Mental State Examination (MMSE)). RESULTS: Phenosanic acid (Dibufelon) showed statistically significant benefit over placebo in the primary indicator of efficacy (reduction in the frequency of epileptic seizures by at least 50%) and in the secondary indicators. The drug was safe and well tolerated by the patients. CONCLUSION: The addition of phenosanic acid (Dibufelon) to base antiepileptic drugs seems to be perspective because of its positive effect on reducing the number of epileptic seizures, as well as on comorbid disorders in the emotional and cognitive spheres.

[The effectiveness of antiepileptic therapy in patients with epileptic syndromes associated with myoclonic seizures]. / Effektivnost' protivoepilepticheskoi terapii u patsientov s epilepticheskimi sindromami, assotsiirovannymi s mioklonicheskimi pristupami.

OBJECTIVE: To evaluate the effectiveness of antiepileptic therapy of epileptic syndromes associated with myoclonic seizures. MATERIAL AND METHODS: One hundred and three patients with epilepsy, in whom myoclonic seizures were identified during the observation, were examined. The observed myoclonic seizures entered the structure of 11 different epileptic syndromes. RESULTS AND CONCLUSION: Drug remission is achieved in 67% of patients, a decrease in the frequency of seizures by 50% or more was noted in 23,3%, the lack of effect in 9,7%. The effectiveness of antiepileptic therapy was significantly different in different groups of epileptic syndromes. The high effectiveness of antiepileptic therapy in the general group of patients in this study is mainly due to the prevalence of patients with juvenile myoclonic epilepsy, in which the highest percentage of remission was observed.

[Assessment of quality of life and treatment adherence in patients with dizziness treated with vasobral]. / Otsenka kachestva zhizni i priverzhennosti lecheniiu preparatom vazobral patsientov s golovokruzheniem.

AIM: To study indicators of quality of life and adherence to treatment with vazobral in patients with dizziness of vascular genesis. MATERIAL AND METHODS: Vazobral was administered to 330 patients with vertigo due to cerebrovascular disease for 3 months during a non-inferiority, open-label study. Quality of life (measured using VAS and the second part of the EQ-5D questionnaire), severity and frequency of dizziness attacks (using VAS), the overall effectiveness of treatment on the basis of objective (according to the doctor) and subjective (using CGI) assessments, treatment adherence were evaluated. RESULTS AND CONCLUSION: The positive effect of vazobral was reported by 320 patients (97.0%), 223 of them (67.6%) indicated a decrease in the frequency of episodes of dizziness by at least 50%, and 95 patients (28.8%) had complete relief of dizziness. Two hundred and sixty-two (79.4%) patients took the drug in full accordance with recommendations. Patients living alone missed drug intake more often. Improvement of quality of life was noted in 326 (98.8%) patients, scores for all domains of the questionnaire EQ-5D at baseline and in the end of the study were 50.8±18.1 and 78.8±14.7%, respectively (p<0.001). The tolerability of treatment was characterized by good tolerability.

[The possibility of using combination therapy in patients with chronic cerebral ischemia]. / Vozmozhnosti ispol'zovaniia kombinirovannoi terapii u bol'nykh s khronicheskoi ishemiei mozga.

AIM: To evaluate the efficacy and tolerability of mexiB 6 and vinpotropil 10/800 in patients with chronic cerebral ischemia. MATERIAL AND METHODS: The study included 30 outpatients with chronic cerebral ischemia, 1-2 stages. The average age was 55,2±10,04 years. All patients underwent clinical/neurological examination. To assess the efficacy of therapy, the Visual-Analog Scale, the Test of feeling, activity and mood, the Montreal Cognitive Evaluation Scale, the Asthenia Scale, the Hospital Anxiety and Depression Scale were used. All patients were treated with mexicB 6 (1 tablet 3 times a day for 1 month), then vinpotropil 10/800 (1 tablet 3 times a day) was used in addition to mexiB 6. The total duration of follow-up was 2 months. RESULTS AND CONCLUSION: Treatment with mexiB 6 led to a significant regression of patients' complaints starting from the second week of therapy, the improvement in well-being was noted in all patients. Inclusion of vinpotropil in the therapy resulted in the additional symptom regression in 19 (63,3%) patients. At the end of combined therapy, there was a significant improvement on all the scales that indicated improvements in cognitive functions, asthenic and anxiety-depressive disorders. An increase in Mg in the blood (0,91±0,05 mmol/l), which did not change after 2 months of therapy (0,94±0,05 mmol/l) was observed. Undesirable phenomena during treatment were not recorded. MexiB 6 and vinpotropil were well-tolerated in both monotherapy and combined use. The proposed therapy scheme is effective and safe.

[Indication of antiepileptic drugs to patients with epilepsy: results of the survey of neurologists]. / Prioritety v naznachenii protivoépilepticheskikh preparatov patsientam s épilepsiei po rezul'tatam oprosa vrachei-nevrologov.

AIM: To study knowledge and opinions of neurologists about priorities in using antiepileptic drugs (AEP). MATERIAL AND METHODS: Eighty-one neurologists from Moscow and surrounding regions were surveyed to identify the factors that influenced the choice of AEP. RESULTS AND CONCLUSION: Valproic acid was the most frequently used drug followed by levetiracetam and carbamazepine, which reflected the overall picture of PEP indication in patients with epilepsy in the Russian population. Levetiracetam occupies a leading position as the starting drug for treatment of epilepsy; most often prescribed to women, patients with generalized seizures and idiopathic epilepsy. It is the drug of choice as adjuvant remedies for Duo therapy.

[Differential diagnosis of paroxysms of tonic muscle tension in children of early age with delay of psychomotor development and abnormal neurologic status]. / Differentsial'naia diagnostika paroksizmov tonicheskogo napriazheniia myshts épilepticheskoi i neépilepticheskoi prirody u detei rannego vozrasta s zaderzhkoi psikhomotornogo razvitiia i ochagovymi nevrologicheskimi simptomami.

AIM: To study neurologic status, results of video-EEG monitoring and magnetic resonance imaging in children under 3 years old with paroxysms of tonic muscle tension. MATERIAL AND METHODS: One hundred and forty-six infants and young children with motor disturbances and different variants of clinically similar epileptic seizures, hyperkinesis and stereotypes were examined. RESULTS AND CONCLUSION: Cerebral palsy (91%), genetic and chromosomal abnormalities (6%), brain malformations (2%) were identified. Neurological status was characterized by pseudobulbar syndrome (100% of cases), hemiparesis (1%), tetraparesis (81%), diffuse muscular hypotonia (18%), intellectual and speech development delay (76%), autistic behavior (16%). During the prolong video-EEG monitoring, paroxysmal tonic muscle tensions were recorded in all patients: epileptic seizures were observed in 113 patients (77.40%), non-epileptic paroxysms in 51 (34.93%). The combination of epileptic and non-epileptic paroxysms was observed in 18 patients (12.33%). In 4 patients (2.75%), it was not possible to determine the genesis of paroxysms even during the prolong video-EEG-monitoring because of myographic artefacts. Five clinical and electroencephalographic combinations of dystonic attacks, epileptic seizures and epileptiform activity were identified. These data allow improving the diagnosis of epilepsy and avoiding unnecessary treatment with antiepileptic drugs. Our study has shown a high diagnostic value of video-EEG monitoring with the inclusion of sleep in patients with paroxysmal conditions in infancy and early childhood.

[Epileptic syndromes in childhood associated with secondary generalized tonic-clonic seizures]. / Épilepticheskie sindromy v detskom vozraste, assotsiirovannye s vtorichno-generalizovannymi sudorozhnymi pristupami.

AIM: To study a group of patients with secondary generalized tonic-clonic seizures (SGTCS) in view of nosology, medical history, clinical, electroencephalographic and neuroimaging features. MATERIAL AND METHODS: The study included 471 patients, 244 (51.8%) men and 227 (48.2%) women. RESULTS: SGTCS were observed in many epileptic syndromes. The most frequent were symptomatic focal epilepsy (33.8%), cryptogenic focal epilepsy (23.8%), rolandic epilepsy (12.6%), FEBL-BEDC syndrome (12.3%). Other forms of epilepsy were less frequent. The onset of epilepsy ranged over a wide age range from the first month of life to 18 years. The average age of onset was 5.7±4.96 years. SGTCS as the only type of paroxysms were observed in 28.3% of cases. Two or more types of seizures were observed in 71.7% of patients, three or more types in 39.3%. Epileptiform activity on EEG during long VEM was detected in 91.3% of patients with SGTCS. In 37.2% of patients, benign epileptiform discharges of childhood were recorded. Treatment with antiepileptic drugs (AEP) led to complete remission in 57.1% of cases of epilepsy associated with SGTCS. A reduction of the frequency of seizures by 50% or more was found in 33.6% of patients treated with AEP. No effect was observed in 9.3% of patients. CONCLUSION: Significant differences in the prognosis and therapeutic approaches to specific epileptic syndromes associated with SGTCS necessitate the use of the entire spectrum of diagnostic measures, which should include careful history taking, clinical examination, video-EEG monitoring with the inclusion of sleep dynamics, MRI / CT brain, genetic testing.

[Russian experience of lacosamide (vimpat) usage in treatment of uncontrolled focal epilepsy]. / Rossiiskii opyt primeneniya lakosamida (vimpat) pri lechenii patsientov s nekontroliruemoi fokal'noi epilepsiei.

Many patients with epilepsy receive treatment in polytherapy. Selection of antiepileptic drugs (AEDs) for the combination should be carried out in accordance with the principles of rational polytherapy, taking into account the mechanism of action, pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs. Along with levetiracetam, gabapentin, vigabatrin and pregabalin, lacosamide (LCM) shows superior PK profile in rating of all AED and can be combined with any of them. The goal of this study was to evaluate efficacy and tolerability of LCM in patients with uncontrolled partial onset seizures (POS) in routine clinical practice. METHODS: 181 patient's charts from 14 sites in Russia have been analyzed in retrospective manner. Patients 16 years old and older with POS with or without secondary generalization were included. Documented observation period of up to 12 months after initiation or until discontinuation of LCM therapy. Primary effectiveness variables was retention at Observational Point 3 (approximately 12 months). Other variables were: percentage change from historical baseline in seizure frequency, 50% and 75% treatment response and seizure-free status at the Observational Points 1, 2 and 3 (approximately 3, 6 and 12 months) and incidence and reason of treatment discontinuation. RESULTS: retention rate was high with 89.5% after 12-month observation. The development of seizure frequency showed a continuous decrease in terms of 50%, 75% treatment respond rates and seizure free status. A total of 5 adverse drug reactions leading to discontinuation of LCM therapy were recorded in 5 of 181 patients (2.8%) during the observation period. The high retention rate observed in this retrospective chart review is assumed to indicate a good tolerability and effectiveness of an adjunctive LCM treatment in patients with uncontrolled partial epilepsy in Russia.

[Current possibilities of treatment of generalized convulsive seizures].

Current possibilities of treatment of generalized convulsive seizures are presented. Progress in the field of pharmacotherapy of epilepsy allowed to introduce new antiepileptic drugs (AED). Some of them are modified AED with higher efficacy or better tolerability and others represent a generation of new drugs with different mechanisms of action. Perampanel, an agonist of AMPA-receptors, is a new drug approved in more than 40 countries, including Russia. At present, the use of some AED is limited by the high risk of sudden death (sudden unexpected death in epilepsy (SUDEP)). SUDEP is a common cause of death directly associated with epilepsy, with the highest frequency in patients with active epilepsy. Subtherapeutic concentrations of SED in the serum of SUDEP patients may be the consequence of inadequate treatment and low compliance to treatment that causes the development of pseudoresistant seizures and, hence, the higher risk of SUDEP. At the same time, AED per se play an important role in the modification of functions of the autonomic nervous system and may induce disturbances of heart rate and conductivity.

[Dopamine receptor agonists: new forms and new possibilities in the treatment of Parkinson's disease].

Main mechanisms of action of dopamine receptor agonists, efficacy of their use according to the results of earlier clinical trials and possible side-effects are discussed. The authors present their experience of prescription of rotigotine transdermal system in an open study of 30 patients with Parkinson's disease. The duration of the study was 8 weeks. There was a significant improvement of both motor and nonmotor (pain sensations, sleep, mood). The effective dose for treatment of initial stages was 4-6 mg daily and for the full-blown stage - 6-8 mg daily. The tolerability was good.

[Effect of carbamazepine on the structure-function relations in the development of the epileptic structure]. / Vliianie karbamazepina na strukturno-funktsional'nye sviazi v razvitii épilepticheskoi sistemy.

The experiments on white outbred male rats with cobalt-induced epileptogenic focus in the left sensomotor cortical region showed that the anticonvulsant effect of carbamazepine (20 mg/kg) depends on the functional state of the epileptic system (ES). In various stages of the ES development, the drug effect is related to the influence upon the determinant focus generating the epileptic activity. In the initial stage, carbamazepine primarily affects epileptic activity of the cortical foci (ipsi- and contralateral hemisphere). In the second (generalization) stage, the drug decreases the epileptic activity in all structures, but to a greater extent, in the dorsal hippocampus and lateral hypothalamus.

[Clinical and genetic markers of chronic cerebral ischemia].

OBJECTIVE: To study the effectiveness of common neuropsychological tests for the verification of the diagnosis of cerebral ischemia (CE) and a role of polymorphisms in SERT, ApoE and BDNF genes in its development. MATERIAL AND METHODS: We studied 272 inpatients, aged from 37 to 70 years, with CE of the first stage (58 patients), CE of the second stage (121 patients) and CE of the third stage (93 patients). A set of neuropsychological tests, as well as biochemical and molecular-genetic studies were performed. RESULTS AND CONCLUSION: Reitan test was the most effective test for the diagnosis of cognitive impairment. The results of the Clock Drawing Test and MMSE were correlated with the disease severity but did not distinguish between the first and second stages of CE. Arterial hypertension and stenosing atherosclerosis of brain vessels were significant predictors of CE. SERT gene was a marker of the CE risk in men. The genotype SS was associated with the risk of CE with early age-at-onset. No association of ApoE and BDNF genes with CE was found.

[Efficacy and safety of the mono- and combined therapy with oxcarbazepine in adult patients].

The trial included 302 patients with focal and generalized forms of epilepsy, aged from 18 to 73 years (mean age 33.23+/-12.73 years). Oxcarbazepine (trileptal) was prescribed in accordance to recommendations and titration schemes (continuous and single-stage) conventional in Russia. Trileptal was prescribed as the start antiepileptic therapy to 46.1% of patients. In other patients, antiepileptic drugs used previously were withdrawn mainly to their low clinical efficacy and poor tolerability. The duration of the study was 12 weeks. The efficacy was assessed by the number of patients with seizures reductions of 50%. The positive therapeutic response was found in 93.2% of patients who completed the trial, and the complete reduction of seizures was achieved in 34.9%. There were also positive changes in the seizure duration, frequency of consciousness change and other post seizure phenomena. The low frequency and intensity of adverse effects during the treatment with trileptal was observed: there were 93 adverse effects in 60 patients included in the trial; 3 (3.2%) of these effects were considered as severe (dizziness in one patient, sleepiness in two patients). The adverse effects disappeared without any additional treatment.